RAFT Polymerization

RAFT Polymerization
RAFT Polymerization
Methods, Synthesis and Applications
Volume 1
Edited by
Graeme Moad
Ezio Rizzardo
RAFT Polymerization
Methods, Synthesis and Applications
Volume 2
Edited by
Graeme Moad
Ezio Rizzardo
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v
Contents
Volume 1
Preface xv
Acknowledgements xvii
1 Overview of RAFT Polymerization 1

Graeme Moad and Ezio Rizzardo
References 5
2 Terminology in Reversible Deactivation Radical

Polymerization (RDRP) and Reversible
Addition–Fragmentation Chain Transfer (RAFT)
Polymerization 15
Graeme Moad
2.1 Terminology for Reversible Deactivation Radical Polymerization
(RDRP) 15
2.2 Terminology in Reversible Addition–Fragmentation Chain Transfer
(RAFT) Polymerization 18
2.3 Terminology That Is Not Ratified by IUPAC 24
References 24
3 How to Do a RAFT Polymerization 25

Almar Postma and Melissa Skidmore
3.1 Introduction 25
3.2 IP Landscape 29
3.3 General Experimental Conditions 29
3.3.1 Initiator 32
3.3.2 Solvent 32
3.3.3 Temperature 32
3.3.4 Pressure 33
3.4 RAFT Polymerization of Styrene 33
3.4.1 Experimental Procedures for the RAFT Polymerization of Styrene 34
vi Contents
3.5 RAFT Polymerization of Methacrylates and Acrylates 37

3.5.1 Methacrylates 38
3.5.2 Acrylates 38
3.5.3 Experimental Procedures for the RAFT Polymerization of
Methacrylates 39
3.5.4 Experimental Procedures for the RAFT Polymerization of Acrylates 41
3.6 RAFT Polymerization of Acrylamides and Methacrylamides 43
3.6.1 Methacrylamides 44
3.6.2 Acrylamides 44
3.6.3 Experimental Procedures for the RAFT Polymerization of Acrylamides
and Methacrylamides 45
3.7 RAFT Polymerization of Vinyl Esters and Vinyl Amides 46
3.7.1 Experimental Procedures for the RAFT Polymerization of Vinyl Esters
and Vinyl Amides 47
3.8 Copolymers 48
3.8.1 Experimental Procedures for RAFT Copolymers 49
3.9 Block Copolymers 50
3.9.1 Experimental Procedures for RAFT Block Copolymers 51
3.10 Conclusion 53
References 54
4 Kinetics and Mechanism of RAFT Polymerizations 59

Michael Buback
4.1 Introduction 59
4.2 Ideal RAFT Polymerization Kinetics 60
4.3 Pulsed Laser Experiments in Conjunction with EPR Detection 61
4.4 Quantum Chemical Calculations of the RAFT Equilibrium 65
4.5 Xanthate-, Trithiocarbonate- and Dithiobenzoate-Mediated
Polymerizations 66
4.5.1 General Aspects of Actual RAFT Polymerizations 66
4.5.2 Xanthates 69
4.5.3 Trithiocarbonates 72
4.5.4 Dithiobenzoates 76
4.5.5 The ‘Missing Step’ Reaction 77
4.5.6 Kinetic Analysis of Dithiobenzoate-Mediated BA Polymerizations 85
4.5.7 Quantum Chemical Calculations for the CIP* – CPDB Model System 87
4.5.8 Dithiobenzoate-Mediated MMA Polymerizations and Model
Systems 88
4.6 Summary of Results and Concluding Remarks 89
References 91
5 RAFT Polymerization: Mechanistic Considerations 95

John F. Quinn, Graeme Moad, and Christopher Barner-Kowollik
5.1 Introduction 95
5.2 Role of the R Group 96
Contents vii
5.2.1 Chain Transfer and Leaving Group Ability 96

5.2.2 Measurement of the Chain Transfer Constant 97
5.2.3 Mechanistic Implications for Block Copolymer Synthesis 103
5.2.4 Re-Initiation and Initialization 105
5.2.5 R Group Stability and Implications for Chain Transfer Kinetics 109
5.2.6 Differential Leaving Group Ability and Mechanistic Discrimination 109
5.3 Role of the Z Group 112
5.3.1 The Z Group and Radical Addition to the Thiocarbonyl 112
5.3.2 The Z-Group and Side Reactions 114
5.3.3 Manipulating Z to Dictate Reactivity: ‘Switchable’ RAFT Agents 116
5.3.4 The Z-Group and Reaction Kinetics 118
5.3.5 Intermediate Radical Termination 119
5.3.6 Slow Fragmentation of the Intermediate Radical 123
5.3.7 Stability of the Z Group During Reaction 126
5.4 Light Effects on the Rate of Polymerization 130
5.5 Conclusion 131
References 132
6 Quantum Chemical Studies of RAFT Polymerization 139

Michelle L. Coote
6.1 Introduction 139
6.2 Methodology 140
6.2.1 Electronic Structure Calculations 140
6.2.2 Kinetics and Thermodynamics 143
6.2.3 Solvent Effects 147
6.2.4 Accuracy and Outstanding Challenges 147
6.3 Computational Modelling of RAFT Kinetics 152
6.3.1 Simplified Models for Theory and Experiment 153
6.3.2 Side Reactions 156
6.3.3 Computational Model Predictions 159
6.3.4 Ab initio Kinetic Modelling 165
6.4 Structure–Reactivity Studies 167
6.4.1 Fundamental Aspects 167
6.4.2 Structure–Reactivity in Practical RAFT Systems 171
6.4.3 RAFT Agent Design 176
6.5 Outlook 180
Abbreviations 180
References 181
7 Mathematical Modelling of RAFT Polymerization 187

Porfirio López-Domínguez, Iván Zapata-González, Enrique Saldívar-Guerra,
and Eduardo Vivaldo-Lima
7.2 Deterministic Modelling Techniques (DMTs) 188
7.2.1 Method of Moments (MM) 188
viii Contents
7.2.1.1 Homogeneous Systems 190

7.2.1.2 Heterogeneous Systems 194
7.2.2 Diffusion-Controlled or CL-Dependent Coefficients 196
7.2.3 Calculation of Full Molecular Weight Distributions 198
7.2.3.1 Explicit Integration Methods 199
7.2.3.2 Probability-Generating Function 201
7.2.3.3 Calculations Using the Predici® Software 201
7.3 Stochastic Modelling Techniques (SMTs) 204
7.3.1 Monte Carlo 204
7.3.1.1 Homogeneous Systems 205
7.3.1.2 Heterogeneous Systems 205
7.4 Hybrid Methods 206
7.5 Specific or Novel Polymerization Processes 206
7.5.1 Semibatch Polymerization 206
7.5.2 Polymerizations in CSTRs/PFR 208
7.5.3 Branched Copolymerizations 209
7.5.4 Microwave-Assisted (MA) RAFT Polymerization 210
7.6 Closing Remarks 211
Acknowledgments 212
References 212
8 Dithioesters in RAFT Polymerization 223

Graeme Moad
8.2 Mechanism of RAFT Polymerization with Dithioester Mediators 224
8.2.1 Transfer Coefficients of Dithioesters 226
8.2.2 RAFT Equilibrium Coefficients with Dithioesters 230
8.3 Choice of RAFT Agents 230
8.3.1 Aromatic Dithioesters (Z = Aryl or Heteroaryl) 233
8.3.2 Functional Aromatic Dithioesters (Z = Aryl or Heteroaryl) 235
8.3.3 Bis-aromatic Dithioesters (Z = Aryl or Heteroaryl) 235
8.3.4 Aliphatic Dithioesters (Z = Alkyl or Aralkyl) 236
8.3.5 Bis-aliphatic Dithioesters (Z = Alkyl or Aralkyl) 237
8.4 Synthesis of Dithioester RAFT Agents 237
8.5 Monomers for Dithioester-Mediated RAFT Polymerization 239
8.5.1 1,1-Disubsituted Monomers 239
8.5.1.1 Methacrylates 239
8.5.1.2 Methacrylamides 240
8.5.1.3 Other 1,1-Disubsituted Monomers 240
8.5.2 Monosubstituted MAMs 240
8.5.2.1 Acrylates 240
8.5.2.2 Acrylamides 273
8.5.2.3 Styrenics 275
8.5.2.4 Diene Monomers 278
8.5.3 1,2-Disubstituted MAMs 279
Contents ix
8.5.4 Monosubstituted IAMs and LAMs 279

8.5.5 Monomers with Reactive Functionality 279
8.5.6 Macromonomers 280
8.6 Cyclopolymerization 287
8.7 Ring-Opening Polymerization 287
8.8 RAFT Crosslinking Polymerization 288
8.9 RAFT Self-condensing Vinyl Polymerization 292
8.10 RAFT-Single-Unit Monomer Insertion (RAFT-SUMI) into
Dithioesters 292
8.11 Dithioesters in Mechanism-Transformation Processes 295
8.11.1 Ring-Opening Polymerization (ROP) 295
8.11.2 Ring-Opening Metathesis Polymerization (ROMP) 296
8.11.3 Atom Transfer Radical Polymerization (ATRP) 296
8.11.4 Nitroxide-Mediated Polymerization (NMP) 297
8.12 Thermally Initiated RAFT Polymerization with Dithioesters 298
8.13 Photoinitiated RAFT with Dithioesters 299
8.14 Redox-Initiated RAFT with Dithioesters 300
8.15 Reaction Conditions and Side Reactions of Dithioesters 300
8.16 RAFT Emulsion/Miniemulsion Polymerization Mediated by
Dithioesters 301
8.17 Dithioester Group Removal/Transformation 302
8.17.1 Dithioester Group Removal by Reaction with Nucleophiles 302
8.17.2 Dithioester Group Removal by Radical-Induced Reactions 303
8.17.2.1 Radical-Induced Coupling/Disproportionation 303
8.17.2.2 Radical-Induced Reduction 306
8.17.3 Dithioester Group Removal by Oxidation 306
8.17.4 Dithioester Group Removal by Thermolysis 309
8.17.5 Electrocyclic Reactions of Dithioesters 310
8.17.6 Boronic Acid Cross-Coupling 311
8.17.7 Conclusions and Outlook 311
Abbreviations 313
References 318
9 Trithiocarbonates in RAFT Polymerization 359

Graeme Moad
9.2 Mechanism of RAFT Polymerization with Trithiocarbonate
Mediators 359
9.2.1 Transfer Coefficients for Trithiocarbonates in RAFT
Polymerization 362
9.2.2 RAFT Equilibrium Coefficients for Trithiocarbonates 367
9.3 Choice of Homolytic Leaving Group R for Trithiocarbonate RAFT
Agents 367
9.3.1 Homolytic Leaving Group ‘R’ for 1,1-Disubsituted MAMs 368
9.3.2 Homolytic Leaving Group ‘R’ for Monosubstituted MAMs 369
x Contents
9.3.3 Homolytic Leaving Group ‘R’ for IAMs and LAMs 369
9.3.4 Macro-leaving Group ‘R’ for Block Copolymer Synthesis 369
9.4 Choice of Activating Group ‘Z’ for Trithiocarbonate RAFT Agents 370
9.5 Symmetric Trithiocarbonates 370
9.5.1 Bis-trithiocarbonates 370
9.6 Non-symmetric Trithiocarbonates 378
9.7 Functional Trithiocarbonates 379
9.8 Synthesis of Trithiocarbonates 408
9.9 Polymer Syntheses with Trithiocarbonates 409
9.9.2 Methacrylamides 424
9.9.3 Other 1,1-Disubstituted Monomers 424
9.9.4 Acrylates 424
9.9.5 Acrylamides 424
9.9.6 Styrenics 425
9.9.7 Diene Monomers 425
9.9.8 Other Monosubstituted Monomers (MAMs, IAMs, LAMs), Vinyl
Monomers 425
9.9.9 Monomers with Reactive Functionality 426
9.10 Macromonomers 426
9.12 Radical Ring-Opening Polymerization 428
9.14 RAFT Self-condensing Vinyl Polymerization 430
9.15 RAFT-Single-Unit Monomer Insertion (RAFT-SUMI) into
Trithiocarbonates 430
9.16 Trithiocarbonates in Mechanism Transformation Processes 433
9.16.3 Ring-Opening Opening Alkyne Metathesis Polymerization
(ROAMP) 435
9.16.4 Cationic Polymerization 435
9.16.5 Anionic Polymerization 435
9.16.6 Nitroxide Mediated Polymerization (NMP) 435
9.17 Photoinitiated RAFT with Trithiocarbonates 436
9.18 Redox-Initiated RAFT with Trithiocarbonates 436
9.19 RAFT Emulsion/Miniemulsion/Dispersion Polymerization Mediated by
Trithiocarbonates 437
9.20 Reaction Conditions and Side Reactions of Trithiocarbonates 438
9.21 Trithiocarbonate Group Removal/Transformation 439
9.21.1 Trithiocarbonate Group Removal by Radical-Induced Coupling 439
9.21.2 Trithiocarbonate Group Removal by Radical-Induced
Disproportionation 442
9.21.3 Trithiocarbonate Group Removal by Radical-Induced Reduction 443
Contents xi
9.21.4 Trithiocarbonate Group Removal by Reaction with Nucleophiles 444

9.21.5 Trithiocarbonate Group Removal by Thermolysis 444
9.21.6 Trithiocarbonate Group Removal by Oxidation 446
9.22 Conclusions and Outlook 446
Abbreviations 447
References 452
10 Xanthates in RAFT Polymerization 493

Mingxi Wang, Jean-Daniel Marty, and Mathias Destarac
10.2 Synthesis of RAFT/MADIX Agents 493
10.2.1 Reaction of a Xanthate Salt with an Alkylating Agent 500
10.2.2 Reaction with Xanthogen Disulfides 500
10.2.3 Xanthates Used as Precursors to Provide New Xanthates 500
10.3 Experimental Conditions 504
10.3.1 Initiation 504
10.3.1.1 Thermal Initiators 504
10.3.1.2 UV or Visible Light 504
10.3.1.3 60 Co γ-ray Irradiation 505
10.3.1.4 Redox Initiation 505

10.3.2 Polymerization Conditions 506
10.3.2.1 High-Pressure Polymerization 506
10.3.2.2 Heterogeneous Polymerizations 506
10.4 Kinetics 507
10.5 Monomers 508
10.5.1 Styrenics 508
10.5.2 Acrylates and Acrylamides 508
10.5.4 Vinyl Esters 510
10.5.5 S-Vinyl Monomers 510
10.5.6 Vinyl Phosphonic Acid 511
10.5.7 N-Vinyl Monomers 511
10.5.8 Halo-olefins 512
10.5.9 Ethylene 513
10.5.10 Cyclic Ketene Acetals (CKAs) 513
10.5.11 Diallyl Monomers 514
10.6 Macromolecular Architectures 514
10.6.1 End-Functional Homopolymers/Statistical Copolymers 515
10.6.2 Block Copolymers 516
10.6.3 Gradient Copolymers 519
10.6.4 Cyclic Copolymers 519
10.6.5 Graft/Comb/Brush Copolymers 520
10.6.6 Star Polymers 521
10.6.7 Hyperbranched Polymers/Polymer Gels 524
10.7 Methodologies for Xanthate End-Group Removal 525
xii Contents
10.7.1 Nucleophilic Reaction (Aminolysis/Hydrolysis/Ionic Reduction) 525

10.7.2 Oxidation 526
10.7.3 Thermolysis 527
10.7.4 Radical-Induced Reduction 528
10.8 Industrial Applications of RAFT/MADIX Polymerization 529
10.9 Conclusion 530
References 531
11 Dithiocarbamates in RAFT Polymerization 549

Graeme Moad
11.2 Dithiocarbamate Transfer Constants 552
11.3 Dithiocarbamates and RAFT Polymerization 554
11.4 Monomers for RAFT Polymerization 555
11.4.1 1,1-Disubstituted MAMs (Methacrylates) 555
11.4.2 Monosubstituted MAMs (Acrylates, Acrylamides, Styrenes) 572
11.4.3 LAMs, IAMs (Vinyl Monomers) 572
11.5 Synthesis of Dithiocarbamate RAFT Agents 575
11.5.1 Method A – Reaction of a Carbodithioate Anion with an Alkylating
Agent 575
11.5.2 Method B – Reaction of a Dithiochloroformate or a
Thiocarbonyl-bis-imidazole with a Nucleophile 577
11.5.3 Method C – Addition of a Dithioic Acid Across an Olefinic Double
Bond 578
11.5.4 Method D – Radical-induced Decomposition of a Thiuram
Disulfide 578
11.5.5 Method E – Ketoform Reaction 580
11.5.6 Method F – Other Methods 580
11.5.7 Method G – Commercially Available 580
11.6 Activity of Dithiocarbamate RAFT Agents 580
11.6.1 Dithiocarbamate RAFT Agents with Balanced Activity 582
11.6.2 Switchable Dithiocarbamate RAFT Agents 583
11.6.3 Dithiocarbamates as Mediators of Cationic Polymerization 585
11.6.4 Dithiocarbamate R Substituents 585
11.6.5 Prediction of Dithiocarbamate Activity 585
11.7 Dithiocarbamates in RAFT Emulsion Polymerization 587
11.8 Dithiocarbamates in Mechanism-Transformation Processes 587
11.9 Dithiocarbamate Group Removal/Transformation 588
11.9.1 Dithiocarbamate Group Removal by Radical-Induced Coupling 588
11.9.2 Dithiocarbamate Group Removal by Radical-Induced
Disproportionation 588
11.9.3 Dithiocarbamate Group Removal by Radical-Induced Reduction 589
Contents xiii
11.9.4 Dithiocarbamate Group Removal by Reaction with

Nucleophiles 589
11.9.5 Dithiocarbamate Group Removal by Thermolysis 590
11.9.6 Dithiocarbamate Group Removal by Oxidation 591
11.9.7 Dithiocarbamate Group Removal by Other Methods 591
′
11.10 Dithiocarbamate Z Z′′ NC(=S)S groups 591
11.11 Conclusions 593
Acknowledgements 593
Abbreviations 593
References 595
12 Photo RAFT Polymerization 611

Robert Chapman, Kenward Jung, and Cyrille Boyer
12.2 Photoinitiation 612
12.3 Photoiniferter Polymerizations 613
12.3.1 Catalyst-Free Photoiniferter 614
12.3.2 Photoredox Catalysis 617
12.3.2.1 PET–RAFT with Ir/Ru 618
12.3.2.2 PET–RAFT with Porphyrins 619
12.3.2.3 Metal-Free Photocatalysts 622
12.4 Applications 625
12.4.1 Single Unit Monomer Insertion (SUMI) 625
12.4.2 Wavelength Orthogonal Polymerization 628
12.4.3 High-Throughput Polymer Libraries 629
12.4.4 Hydrogels and 3D Printing 633
12.4.5 Live Cell Graft Polymerizations 634
References 636
Volume 2
13 Redox-Initiated RAFT Polymerization and (Electro)chemical

Activation of RAFT Agents 647
Francesca Lorandi, Marco Fantin, and Krzysztof Matyjaszewski
14 Considerations for and Applications of Aqueous RAFT

Polymerization 679
Alexander W. Fortenberry, Charles L. McCormick, and Adam E. Smith
15 RAFT-Mediated Polymerization-Induced Self-Assembly

(PISA) 707
Franck D’Agosto, Muriel Lansalot, and Jutta Rieger
xiv Contents
16 RAFT-Functional End Groups: Installation and

Transformation 753
Andrew B. Lowe and Elena Dallerba
17 Sequence-Encoded RAFT Oligomers and Polymers 805

Joris J. Haven, Jeroen De Neve, and Tanja Junkers
18 Synthesis and Application of Reactive Polymers via RAFT

Polymerization 829
Martin Gauthier-Jaques, Hatice Mutlu, Heba Gaballa, and Patrick Theato
19 RAFT Crosslinking Polymerization 873

Patricia Pérez-Salinas, Porfirio López-Domínguez, Alberto Rosas-Aburto,
Julio César Hernández-Ortiz, and Eduardo Vivaldo-Lima
20 Complex Polymeric Architectures Synthesized through RAFT

Polymerization 933
Thomas G. Floyd, Satu Häkkinen, Matthias Hartlieb, Andrew Kerr, and
Sébastien Perrier
21 Star Polymers by RAFT Polymerization 983

Stephanie Allison-Logan, Fatemeh Karimi, Mitchell D. Nothling,
and Greg G. Qiao
22 Surface and Particle Modification via RAFT Polymerization: An

Update 1017
Julia Pribyl and Brian C. Benicewicz
23 High-Throughput/High-Output Experimentation in RAFT

Polymer Synthesis 1051
Carlos Guerrero-Sanchez, Roberto Yañez-Macias, Miguel Rosales-Guzmán,
Marco A. De Jesus-Tellez, Claudia Piñon-Balderrama, Joris J. Haven,
Graeme Moad, Tanja Junkers, and Ulrich S. Schubert
24 An Industrial History of RAFT Polymerization 1077

Graeme Moad
25 Cationic RAFT Polymerization 1171

Mineto Uchiyama, Kotaro Satoh, and Masami Kamigaito
Index 1195
v
Contents
Volume 1
Preface xv
Acknowledgements xvii

2 Terminology in Reversible Deactivation Radical

Polymerization 15
Graeme Moad
3 How to Do a RAFT Polymerization 25

4 Kinetics and Mechanism of RAFT Polymerizations 59

Michael Buback
5 RAFT Polymerization: Mechanistic Considerations 95

John F. Quinn, Graeme Moad, and Christopher Barner-Kowollik
6 Quantum Chemical Studies of RAFT Polymerization 139

Michelle L. Coote
7 Mathematical Modelling of RAFT Polymerization 187

Porfirio López-Domínguez, Iván Zapata-González, Enrique Saldívar-Guerra,
and Eduardo Vivaldo-Lima
8 Dithioesters in RAFT Polymerization 223

Graeme Moad
vi Contents
9 Trithiocarbonates in RAFT Polymerization 359

Graeme Moad
10 Xanthates in RAFT Polymerization 493

Mingxi Wang, Jean-Daniel Marty, and Mathias Destarac
11 Dithiocarbamates in RAFT Polymerization 549

Graeme Moad
12 Photo RAFT Polymerization 611

Robert Chapman, Kenward Jung, and Cyrille Boyer
Volume 2
13 Redox-Initiated RAFT Polymerization and (Electro)chemical

Activation of RAFT Agents 647
13.2 Redox Initiation 648
13.3 Chemical Activation of RAFT Agents 656
13.4 Electrochemical Activation of RAFT Agents 660
13.4.1 Electrochemistry of RAFT Agents 661
13.4.2 Direct and Mediated Electro-reduction of RAFT Agents 665
13.4.2.1 Organic Mediators for eRAFT Polymerizations 667
13.4.2.2 Activation of RAFT Agents via Electro-reduction of ATRP Catalysts 668
13.5 Electro-reduction of Radical Initiators 670
13.6 Conclusions and Perspectives 673
Acknowledgement 673
References 673
14 Considerations for and Applications of Aqueous RAFT

Polymerization 679
Alexander W. Fortenberry, Charles L. McCormick, and Adam E. Smith
14.2 Chain Transfer Agents 679
14.2.1 Hydrolysis of the CTA 680
14.2.2 Aminolysis 681
14.3 Initiation 684
14.3.1 Initiation via Azo-containing Species 684
14.3.2 Photochemical Initiation 685
14.3.2.1 Externally Initiated aRAFT Photopolymerization 685
14.3.2.2 Initiator-Free aRAFT Photopolymerization 686
14.3.2.3 PET-RAFT Photopolymerizations 688
14.4 Deoxygenation Methods 690
14.4.1 PET-RAFT 690
Contents vii
14.4.2 Enzyme-Catalyzed Deoxygenation 691

14.4.2.1 Initiation by Thermal Initiation 691
14.4.2.2 Enzymatic Initiation Systems 693
14.5 Polymerization-Induced Self-assembly 696
14.6 Grafting from Biomolecules 699
References 701
15 RAFT-Mediated Polymerization-Induced Self-Assembly

(PISA) 707
Franck D’Agosto, Muriel Lansalot, and Jutta Rieger
15.2 History/Origin of PISA 709
15.3 PISA Process 710
15.3.1 Emulsion, Dispersion, and Precipitation Polymerizations: The Reference
Processes 710
15.3.2 Main Parameters at Play for a Successful PISA at a Glance 712
15.3.2.1 MacroRAFT Type 712
15.3.2.2 Initiation in RAFT-PISA 712
15.3.2.3 Chemical Nature of the Blocks 713
15.3.3 PITSA, PICA, PIESA, and PIHSA: Different Acronyms However All
Boiling Down to PISA 714
15.3.4 PISA-Inspired Synthesis of Surfactant-Free Latexes 715
15.4 Reactive/Functional Nano-objects 716
15.4.1 Via the RAFT Agent: Functionalization of the α-End of the Shell
Polymer 717
15.4.2 Via the Solvophilic Block: Functionalization Along the Shell
Polymer 718
15.4.2.1 A Variety of Functions 718
15.4.2.2 Surface Functionalization by Sugar Moieties and Amino Acids 719
15.4.2.3 Fluorinated Shells 720
15.4.2.4 PISA and CO2 721
15.4.3 Via the Solvophobic Block: Core Functionalization 722
15.4.3.1 Fluoroparticles 722
15.4.3.2 Core-crosslinking 723
15.4.3.3 Adding a Function Allowing Degradation of the Particle Core 725
15.4.3.4 CO2 -sensitive Particles 725
15.5 Control over the Particle Morphology 726
15.5.1 From Spherical to Anisotropic Block Copolymer Particles 726
15.5.2 Main Parameters that Impact the Particle Morphology 728
15.5.2.1 Varying the Molar Mass 729
15.5.2.2 Varying the Chemical Nature of the Solvophobic Block 729
15.5.2.3 Varying the Topology of the Shell or the Core 730
15.5.2.4 Varying the Solvent Quality 731
15.5.2.5 PISA in Aqueous Media: Varying pH and/or Ionic Strength 731
15.5.2.6 Varying the Block Copolymer Architecture via the RAFT Agent 732
viii Contents
15.5.3 Strategies to Stir Specific Morphologies 733

15.5.3.1 Using PICA 733
15.5.3.2 Using Mesogenic Monomers (PIHSA) 733
15.5.3.3 Using Ionic Complexes (PIESA) and Hydrogen-Bonding Units 734
15.5.3.4 Hierarchical Assembly Between Particles 735
15.5.4 Post-polymerization Morphological Transitions/Chain
Reorganization 735
15.5.4.1 Temperature 735
15.5.4.2 pH 736
15.5.4.3 ‘Reactive’ Groups 736
15.5.4.4 Light 737
15.5.4.5 Oxygen 738
Abbreviations 741
References 742
16 RAFT-Functional End Groups: Installation and

Transformation 753
16.2 Functionalization and Transformation of RAFT Polymers via the
R-group 757
16.3 Thiocarbonylthio End Group Removal and Transformation 762
16.3.1 Desulfurization of RAFT (Co)Polymers 763
16.3.1.1 Thermolysis 763
16.3.1.2 Radical-Mediated Reduction 765
16.3.1.3 Addition–Fragmentation Coupling 766
16.3.1.4 Radical-Induced Oxidation 768
16.3.2 Heteroatom Diels–Alder Chemistry 769
16.3.3 Generation and Application of Macromolecular Thiols 772
16.3.3.1 Radical Thiol–Ene Reaction 775
16.3.3.2 Radical Thiol–Yne Reaction 776
16.3.3.3 Catalyzed Thiol-Michael Additions 777
16.3.3.4 Thiol-Isocyanate Modification 780
16.3.3.5 Thiol-Epoxy Ring Opening 782
16.3.3.6 Thiol-Halo Substitution 783
16.3.3.7 Disulfide Reactions 787
16.3.3.8 Miscellaneous Examples of End Group Transformation and
Applications 790
Contents ix
16.4 Summary 793

References 794
17 Sequence-Encoded RAFT Oligomers and Polymers 805

References 825
18 Synthesis and Application of Reactive Polymers via RAFT

Polymerization 829
Martin Gauthier-Jaques, Hatice Mutlu, Heba Gaballa, and Patrick Theato
18.2 N-Hydroxysuccinimide (NHS) 830
18.3 Pentafluorophenyl (PFP) Ester and Its Derivatives 832
18.4 p-Nitrophenyl Esters and Their Derivatives 835
18.5 Miscellaneous Activated Ester Functional Group Transformations 836
18.6 Acetone Oxime (AO) 836
18.7 Salicylic Acid (SA) 837
18.8 p-Dialkylsulfonium Phenoxy Ester (DASPE) 837
18.9 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) 838
18.10 Di(Boc)-Acrylamide (DBAm) 838
18.11 Acyl Chloride 839
18.12 Alkyl Halide 839
18.13 Trichlorotriazine (TCT) 840
18.14 Isocyanate (NCO) 840
18.15 Azlactone 842
18.16 Anhydride 842
18.17 Thiolactone 843
18.18 Thiol Exchange (Disulphide)/Michael Addition/Thiol–Ene 843
18.19 Epoxide 843
18.20 Diels–Alder Cycloaddition 845
18.21 Triazolinedione 845
18.22 Carbonyl Groups and their Derivatives 846
18.23 Copper-Catalysed Azide–Alkyne Cycloaddition (CuAAC) 847
18.24 Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC) 848
18.25 Nitrone– and Nitrile Oxide–Alkyne Cycloadditions
(SPANOC/SPANC) 848
18.26 Cross-coupling Reactions 848
18.27 Boronic Acid/Diol Condensation 849
18.28 Multicomponent Reactions (MCR) 849
18.29 Metal–Ligand Coordination 850
18.30 Bioapplications of Reactive Polymers 850
18.31 Drug Delivery 851
18.32 Bio-conjugation 855
18.33 Surface/Particle Modification 859
x Contents
18.34 Conclusion and Outlook 864

References 864
19 RAFT Crosslinking Polymerization 873

Patricia Pérez-Salinas, Porfirio López-Domínguez, Alberto Rosas-Aburto,
Julio César Hernández-Ortiz, and Eduardo Vivaldo-Lima
19.2 Structure and Characteristics of Polymer Networks 875
19.3.1 Synthesis Pathways to Obtain Polymer Networks 877
19.3.2 RAFT Controllers Used in the Synthesis of Polymer Networks 879
19.4 Synthesis of Polymer Networks by RAFT Copolymerization of
Vinyl/Multivinyl Monomers in Supercritical Carbon Dioxide as Green
Solvent 898
19.5 Modelling of Polymer Network Formation 904
19.5.1 Background on Modelling of Crosslinking and RAFT 906
19.5.2 Trifunctional Polymer Molecule Modelling Approach 907
19.5.3 Multifunctional Polymer Molecule Modelling Approach 910
19.5.4 Kinetic Random Branching Theory (KRBT) 915
References 918
20 Complex Polymeric Architectures Synthesized through RAFT

Polymerization 933
Thomas G. Floyd, Satu Häkkinen, Matthias Hartlieb, Andrew Kerr, and
Sébastien Perrier
20.2 RAFT Synthesis of Block Copolymers 933
20.2.1 Block Copolymer by Sequential Polymerization Steps 934
20.2.1.1 Choice of CTA 935
20.2.1.2 Block Order 937
20.2.1.3 Polymer Livingness 938
20.2.1.4 Initiation System 941
20.2.1.5 Further Considerations 942
20.2.1.6 Multiblock Copolymers 942
20.2.2 Block Copolymers by Chain Extension of a Pre-functionalized
MacroCTA 943
20.2.3 Block Copolymers by Conjugation of Two Polymeric Chains 944
20.2.3.1 Block Copolymer Synthesis Through Click Chemistry 945
20.2.3.2 Supramolecular Block Copolymers 947
20.2.4 General Guidelines 948
20.3 Gradient Copolymers 948
20.4 Cyclic Polymers 949
20.5 Star-Shaped Polymers 950
Contents xi
20.5.1 Methods to Produce Star-Shaped Copolymers 950

20.5.1.1 Divergent Synthesis of Star (Co)Polymers 950
20.5.1.2 Convergent Synthesis of Star Polymers by RAFT Polymerization 953
20.5.2 Classification by Composition 955
20.6 Graft Polymers 956
20.6.1 Grafting Through 958
20.6.2 Grafting Onto 959
20.6.3 Grafting From 960
20.7 Hyperbranched Polymers 964
20.7.1 Self-condensing Vinyl Polymerization 964
20.7.2 Copolymerization of Multifunctional Monomers 966
20.7.3 Alternative Methods of Hyperbranched Synthesis 967
20.8 Conclusion 968
References 969
21 Star Polymers by RAFT Polymerization 983

Stephanie Allison-Logan, Fatemeh Karimi, Mitchell D. Nothling,
and Greg G. Qiao
21.1 Star Polymers 983
21.2 Synthesis of Star Polymers via RAFT Polymerization 985
21.2.1 Core-first Approach 985
21.2.1.1 Z-group Approach 987
21.2.1.2 R-group Approach 988
21.2.1.3 Developments in Synthesis 991
21.2.2 Arm-first Approach 994
21.2.2.1 Developments in Synthesis 996
21.2.3 Grafting-to Approach 1002
21.3 Application of Star polymers 1002
21.3.1 Star Polymers in Biomedical Applications 1003
21.3.2 Star Polymers in Other Applications 1004
21.3.2.1 Emulsion Stabilization 1006
21.3.2.2 Advanced Materials 1007
21.4 Conclusion 1010
References 1010
22 Surface and Particle Modification via RAFT Polymerization: An

Update 1017
Julia Pribyl and Brian C. Benicewicz
22.2 Complex Brush Architectures 1020
22.3 Bioconjugation and Stimuli-responsive Polymer Brushes 1027
22.4 Advanced Composites 1030
xii Contents
22.5 Shaped Polymer-Grafted Particles 1039

22.6 Conclusion 1042
References 1043
23 High-Throughput/High-Output Experimentation in RAFT

Carlos Guerrero-Sanchez, Roberto Yañez-Macias, Miguel Rosales-Guzmán,
Marco A. De Jesus-Tellez, Claudia Piñon-Balderrama, Joris J. Haven,
Graeme Moad, Tanja Junkers, and Ulrich S. Schubert
23.2 Fundamental Experimentation and Limitations of HT/HO-E in RAFT
23.3 HT/HO-E Kinetic Investigations 1053
23.4 Utilization of HT/HO-E for the RAFT Synthesis of Polymer
Libraries 1056
23.5 Applications of RAFT Polymer Libraries in Nanomedicine and Drug
Delivery Systems 1059
23.5.1 Applications of RAFT Polymer Libraries as Antimicrobial Agents 1064
Abbreviations 1067
References 1069
24 An Industrial History of RAFT Polymerization 1077

Graeme Moad
24.2 Macromonomer RAFT Polymerization 1077
24.3 Thiocarbonylthio-RAFT Polymerization 1082
24.3.1 Development of RAFT Polymerization 1086
24.3.2 RAFT Emulsion Polymerization 1097
24.3.3 Synthesis of Stars and Nano- or Microgels by RAFT
Polymerization 1137
24.3.4 RAFT Applications 1137
24.3.5 RAFT Thiocarbonylthio-End-Group Removal/Transformation 1137
Abbreviations 1141
References 1141
25 Cationic RAFT Polymerization 1171

25.2 Background and Overview of Cationic RAFT Polymerizations 1172
25.2.1 Living Cationic Polymerization and Mechanism 1172
25.2.2 Overview of Cationic RAFT Polymerizations and Comparison to Radical
RAFT Polymerizations 1173
Contents xiii
25.3 Design of Cationic RAFT or DT Polymerizations 1175

25.3.1 RAFT or DT Agents for Cationic Polymerizations 1175
25.3.2 Initiators, Cationogens, or Catalysts for Cationic RAFT or DT
Polymerizations 1179
25.3.3 Monomers for Cationic RAFT or DT Polymerizations 1182
25.4 Design of Well-Defined Polymers by Cationic RAFT or DT
Polymerizations 1184
25.4.1 End-Functionalized Polymers 1184
25.4.2 Block Copolymers 1185
25.4.3 Star Polymers 1189
25.5 Summary and Outlook for Cationic RAFT or DT Polymerizations 1190
Abbreviations 1191
References 1191
Index 1195
xv
Preface
This volume is intended to provide a detailed synopsis of the current state of RAFT
(reversible addition fragmentation chain transfer) polymerization. It is an update of
the 2008 Handbook of RAFT Polymerization and of the review series ‘Living Radical
Polymerization by the RAFT Process’ published over the period 2005–2012 in the
Australian Journal of Chemistry.
RAFT polymerization has been a success, there are now more than 10 000 pub-
lications that relate to the understanding, development, and/or application of the
technique, and the rate of publication shows no signs of waning. Commercial suc-
cess is more difficult to judge. A search reveals over 1000 patent families. On the
other hand, there are few examples of actual RAFT products. Maybe commercial
implementation will increase now that the first RAFT patents have reached the end
of their enforceable life.
Although some might argue that RAFT is now a mature technique, there are still
significant efforts striving for a more complete understanding of the mechanism and
scope of the process. It is our hope that by compiling this work and by highlighting
recent achievements in RAFT chemistry, we will inspire further research and further
drive the ever-increasing range of applications.
Clayton, Victoria, Australia Graeme Moad and Ezio Rizzardo

September 2021
xvii
Acknowledgements
The editors are extremely grateful to Caroline Bray, Guoxin Li, Catherine Moad, and
Lisa Strover for proofreading the various chapters and to CSIRO for allowing sub-
stantial time to be spent on this exercise.
1
Overview of RAFT Polymerization

CSIRO Manufacturing, Research Way, Clayton, VIC 3168, Australia
The first announcement of RAFT (reversible addition–fragmentation chain

transfer), polymerization making use of thiocarbonylthio transfer agents as a means
of controlling the outcome of radical polymerization was made at the IUPAC Word
Polymer Congress Macro 98 by Dr Ezio Rizzardo just over 21 years ago in July 1998.
The first publication on RAFT polymerization detailing the work at CSIRO was
published shortly thereafter [1]. The paper in Macromolecules [1] that announced
the RAFT process, is currently the most highly cited paper in that journal.
RAFT polymerization had been disclosed in a CSIRO/DuPont patent that was pub-
lished in January 1998 [2]. A patent describing the parallel development of MADIX
(MAcromolecule Design by Interchange of Xanthates – RAFT with xanthate trans-
fer agents) at Rhodia was published in December 1998 [3]. That first RAFT patent
[2] was, by 2005, one of the most highly cited patents in the field of chemistry and
related science, and the patent literature now abounds with a still-increasing num-
ber of RAFT-related inventions (Figure 1.1). However, commercial success stories
associated with RAFT polymerization and other reversible-deactivation radical poly-
merization (RDRP) are few [4]. With the first RAFT patents having reached the
end of their enforceable life, we might now envisage an upsurge in commercial
applications.
The further development of RAFT was chronicled in a series of reviews that
appeared in the Australian Journal of Chemistry in 2005 [5], 2006 [6], 2009 [7], and
2012 [8]. Since that time reviews of RAFT polymerization have targeted specific
application areas or have been otherwise limited in scope. A number of perspectives
have recently appeared to mark the 20th anniversary of the discovery of RAFT
polymerization [9–11].
The year 2008 saw the publication of the Handbook of RAFT Polymerization that
comprised 12 chapters from major players in the field at the time [12]. The 10 years
leading up to the handbook had seen a revolution in the field of radical polymer-
ization, which can, in large part, be attributed to the invention of RAFT and other
RDRP methods. Many of the same authors who contributed to that handbook have
also provided chapters for the present work.
RAFT Polymerization: Methods, Synthesis and Applications, First Edition.
Edited by Graeme Moad and Ezio Rizzardo.
© 2022 WILEY-VCH GmbH. Published 2022 by WILEY-VCH GmbH.
2 1 Overview of RAFT Polymerization
12 000
Total RAFT
10 000 Journal
Patent
Cumulative publications
8000
6000
4000
2000
0
2000 2005 2010 2015
Year
Figure 1.1 Cumulative publications relating to RAFT polymerization for the period
1998–2019 based on a ScifinderTM substructure search on the major classes of RAFT agent
carried out in February 2020 on the RAFT agent structures and the terms ‘RAFT’ and
‘MADIX’ (in the case of xanthates).
Publications relating to RAFT polymerization show no signs of abating. The

present work is intended as a survey of developments in RAFT polymerization
focusing on the last 10 years.
RAFT polymerization is a form of RDRP and can impart living characteristics (low
molar mass dispersity, high-end group fidelity, ability to synthesize complex archi-
tectures) to radical polymerization. The technique owes its success to the wide range
of tolerated functionality and polymerization conditions, and to the vast range of
monomers whose (co)polymerization can be successfully controlled.
In 2008, at the time the RAFT Handbook was published, one factor seen as signifi-
cant in holding back the exploitation of RAFT polymerization was that RAFT agents
were not commercially available [13]. This situation has now been redressed [14].
It has often been pointed out that to achieve the highest level of control over
polymerization, one needs to select the RAFT agent for the monomer(s) being poly-
merized. A dizzying array of RAFT agents, Z—C(=S)S—R, varying in the activating
(Z) and reinitiating (R) substituents, are now available commercially or are able to
be synthesized [15]. However, with just two RAFT agents, e.g. a trithiocarbonate, for
more activated monomers such as styrenes and (meth)acrylates, and a xanthate or
a dithiocarbamate, for less activated monomers such as vinyl esters or vinyl amides,
one can achieve acceptable control over the full monomer spectrum [16]. Moreover,
by using a switchable RAFT agent or a RAFT agent with balanced activity, e.g. a
1H-pyrazole-1-carbodithioate [17, 18], one can achieve only slightly compromised
control with just one RAFT agent.
1000 12 000
Total RAFT Total RAFT
Aromatic dithioester 10 000 Aromatic dithioester

800
Trithiocarbonate Trithiocarbonate
Cumulative publications
Xanthate 8000 Xanthate
600
Publications
Dithiocarbamate Dithiocarbamate
6000
400
4000
200
2000
0 0
2000 2005 2010 2015 2000 2005 2010 2015
Year Year
Figure 1.2 Publication rate for RAFT polymerization using different classes of RAFT agent
for the period 1998–2019. Includes both patent and open literature publications. Based on
a ScifinderTM substructure search carried out in February 2020 on the RAFT agent structures
and the terms ‘RAFT’ and ‘MADIX’ (in the case of xanthates). The total RAFT number relates
to a search on the terms ‘RAFT polymerization’ or ‘reversible addition fragmentation chain
transfer’.
In the following text we mention the chapters of this work by topic and refer to
chapters of the 2008 Handbook of RAFT Polymerization on similar topics.
We commence with a chapter on terminology in RDRP and RAFT polymerization
[19]. Then we go back to the basics and provide a beginner’s guide on How to Do a
RAFT polymerization [14].
There are four chapters concerning the detailed kinetics and mechanism of the
RAFT process: Kinetics and Mechanism of RAFT Polymerizations [20], RAFT Poly-
merization, Mechanistic Considerations [21], Mechanisms, Quantum Studies of RAFT
Polymerization [22], and Mathematical Modelling of RAFT Polymerization [23]; these
concern the detailed kinetics and mechanism of the RAFT process and the ongoing
efforts to enhance our understanding of the process (2008 chapters [24, 25]).
The next four chapters provide a critical survey of the four major classes of RAFT
agents, namely, dithioesters [26], trithiocarbonates [27], xanthates [28], and dithio-
carbamates [29] as regards activity as RAFT agents, polymerization mechanisms,
and their application in polymer synthesis (2008 chapters [16, 30, 31]). The year
2008 marked the point in time at which trithiocarbonates became the most popular
RAFT agents (Figure 1.2).
There are two chapters concerning the more recent developments in pro-
cesses for initiating RAFT polymerization. Overview of Photoregulated Reversible
Addition–Fragmentation Chain Transfer (RAFT) Polymerization [32], Redox-Initiated
RAFT Polymerization, and (Electro)Chemical Activation of RAFT Agents [33].
Further two chapters relate specifically to RAFT polymerization in aqueous solu-
tion or in heterogeneous medium and to polymerization-induced self-assembly:
Considerations for and Applications of Aqueous RAFT Polymerization [34], RAFT-
Mediated Polymerization-Induced Self-Assembly (PISA) (2008 chapters [35, 36]) [37].
Three chapters concern the synthesis of functional polymers, sequence-defined

polymers, and RAFT end-group transformation. RAFT Functional End Groups:
Installation and Transformation [38], Sequence-Encoded RAFT Oligomers and Poly-
mers [39], Synthesis and Application of Reactive Polymers via RAFT Polymerization
(2008 chapter [40]) [41].
We then go into detail on the other aspects of polymer architecture with chapters
on RAFT Crosslinking Polymerization [42], Complex Polymeric Architectures Synthe-
sized Through RAFT Polymerization [43], Star Polymers by RAFT Polymerization [44],
Surface and Particle Modification via RAFT Polymerization: An update (2008 chapters
[45–47]).
Two chapters relate to application areas. An Industrial History of RAFT Polymer-
ization [48] describes the development of RAFT by reference to the patent literature
and points to where RAFT is being applied in industry (2008 chapters [49, 50]).
The application of high throughput robotic platforms to RAFT polymerization as
an aid to shortcut the process of selecting reaction conditions and to create poly-
mer libraries for screening purposes is discussed in High Throughput/High Output
Experimentation in RAFT Polymer Synthesis [51].
A final chapter demonstrates that the RAFT process is not applicable only to rad-
ical polymerization and details the recent work on Cationic RAFT Polymerization
[52].
It is our hope that by compiling and highlighting recent achievements in RAFT
chemistry, we will inspire further research and further drive the ever-increasing
range of applications.
It should be stated that there is no lack of recent review material relating to
RAFT polymerization and its application. At least 30 reviews have been published
since 2017 specifically on RAFT polymerization (non-English language reviews are
not included in this list). These include overviews and perspectives [9–11, 53, 54],
polymerization-induced self-assembly (PISA) [55*, 56–58], monomers from
renewable resources [59], polymer brushes [60], therapeutics and bioapplications
[61–63], star polymers for bioapplications [64], hydrogels for drug delivery [65],
organic/inorganic nanohybrids for bioapplications [66], gold nanoparticles [67],
3D-printing [68], stimuli-responsive polymers [69], conjugated diene monomers
[70], single-unit monomer insertion (RAFT-SUMI) [71], redox initiation [72],
hydroxyl radical initiation [73], photoRAFT [74], externally regulated polymer-
ization [75], initiation with ionizing radiation [76], dithiocarbamate RAFT agents
[77]* , optoelectronic applications [78], and graft copolymers by transfer-to [79].
An asterisk (* ) indicates that an update to the review appears in this volume.
Earlier reviews on RAFT polymerization have been summarized previously
[5–8, 69].
There are additionally many reviews on radical or RDRP methods more generally
that contain substantial content on RAFT polymerization or RAFT applications.
The more than 50 reviews published since 2017 include reviews on ultrahigh
molar mass polymers [80, 81], self-condensing vinyl polymerization [82], complex
architectures by copolymerization of multi-vinyl monomers [83], nanoparticles
by surface-initiated polymerization [84], synthesis of multi-block copolymers
References 5
[85], PISA [86–89], biosensors [90, 91], hydrogels [92], biopolymer conjugates
[93–95], glycopolymers for bioapplications [96, 97], phosphonium polymers for
bioapplications [98], stimuli-responsive polymers in bioapplications [99–101],
oligonucleotide-based nanomaterials [102], star polymers for bioapplications
[103, 104], biocatalytic initiation [105, 106], alkylborane initiators [107], the use
of Fenton chemistry for initiation [108], dialkyldiazene initiation [109], influ-
ence of external fields on radical polymerization [110], polymerization of alkyl
2-cyanoacrylates [111], semi-fluorinated (meth)acrylates [112], terpenes [113],
rosin-derived monomers [114], polymers with pedant fatty acid chains [115],
lignin-derived polymers [116], chitosan-derived polymers [117], graphene-derived
polymers [118], functionalization of carbon nanotubes [119], cyclopolymerization
for sequence-defined polymers [120], PhotoRDRP [121–124], thermoresponsive
polymer ionic liquids [125], polyhedral oligomeric silsesquioxane (POSS)-hybrids
[126], 3D-printing [127], porous polymers [128], combination or RAFT or
atom-transfer-radical polymrerization (ATRP) with ring-opening polymerization
[129], metal-free RDRP [130], cyclic polymers [131], end-group modification [132],
and metallopolymers [133].
References
1 Chiefari, J., Chong, Y.K., Ercole, F. et al. (1998). Macromolecules 31: 5559–5562.
https://doi.org/10.1021/ma9804951.
2 Le, T.P., Moad, G., Rizzardo, E., and Thang, S.H. (1998). Polymerization with
living characteristics (DuPont/CSIRO). WO9801478A1.
3 Corpart, P., Charmot, D., Biadatti, T., Zard, S., and Michelet, D. (1998). Block
polymer synthesis by controlled radical polymerization (Rhodia Chimie).
WO9858974A1.
4 Destarac, M. (2018). Polym. Chem. 9: 4947–4967. https://doi.org/10.1039/
C8PY00970H.
5 Moad, G., Rizzardo, E., and Thang, S.H. (2005). Aust. J. Chem. 58: 379–410.
https://doi.org/10.1071/CH05072.
9 Matyjaszewski, K. (2020). Macromolecules 53: 495–497. https://doi.org/10.1021/
acs.macromol.9b02054.
10 Moad, G. and Rizzardo, E. (2020). Polym. Int. 69: 658–661. https://doi.org/10
.1002/pi.5944.
11 Perrier, S. (2017). Macromolecules 50: 7433–7447. https://doi.org/10.1021/acs
.macromol.7b00767.
12 Barner-Kowollik, C. (ed.) (2008). Handbook of RAFT Polymerization. Weinheim:

Wiley-VCH. https://doi.org/10.1002/9783527622757.
13 Barner-Kowollik, C. (2008). Introduction. In: Handbook of RAFT Polymerization
(ed. C. Barner-Kowollik), 1–4. Weinheim: Wiley-VCH. https://doi.org/10.1002/
9783527622757.ch1.
14 Postma, A. and Skidmore, M. (2022). How to do a RAFT polymerisation. In:
RAFT Polymerization: Materials, Synthesis and Applications (eds. G. Moad and
E. Rizzardo), 25–58. Weinheim: Wiley-VCH.
15 Keddie, D.J., Moad, G., Rizzardo, E., and Thang, S.H. (2012). Macromolecules
45: 5321–5342. https://doi.org/10.1021/ma300410v.
16 Rizzardo, E., Moad, G., and Thang, S.H. (2008). RAFT polymerization in bulk
monomer or in (organic) solution. In: Handbook of RAFT Polymerization (ed.
C. Barner-Kowollik), 189–234. Weinheim: Wiley-VCH. https://doi.org/10.1002/
9783527622757.ch6.
17 Gardiner, J., Martinez-Botella, I., Kohl, T.M. et al. (2017). Polym. Int. 66:
1438–1447. https://doi.org/10.1002/pi.5423.
18 Gardiner, J., Martinez-Botella, I., Tsanaktsidis, J., and Moad, G. (2016). Polym.
Chem. 7: 481–492. https://doi.org/10.1039/C5PY01382H.
19 Moad, G. (2022). Terminology in reversible deactivation radical polymerization
(RDRP) and reversible addition-fragmentation chain transfer (RAFT) polymer-
ization. In: RAFT Polymerization: Materials, Synthesis and Applications (eds. G.
Moad and E. Rizzardo), 15–24. Weinheim: Wiley-VCH.
20 Buback, M. (2022). Kinetics and mechanism of RAFT polymerizations. In:
21 Quinn, J.F., Moad, G., and Barner-Kowollik, C. (2022). RAFT polymerization:
mechanistic considerations. In: RAFT Polymerization: Materials, Synthesis and
Applications (eds. G. Moad and E. Rizzardo), 95–138. Weinheim: Wiley-VCH.
22 Coote, M.L. (2022). Quantum-chemical studies of RAFT polymerization. In:
23 López-Domínguez, P., Zapata-González, I., Saldívar-Guerra, E., and
Vivaldo-Lima, E. (2022). Mathematical modeling of RAFT polymerization.
In: RAFT Polymerization: Materials, Synthesis and Applications (eds. G. Moad
and E. Rizzardo), 187–222. Weinheim: Wiley-VCH.
24 Moad, G. and Barner-Kowollik, C. (2008). The mechanism and kinetics of
the RAFT process: overview, rates, stabilities, side reactions, product spec-
trum and outstanding challenges. In: Handbook of RAFT Polymerization (ed.
9783527622757.ch3.
25 Coote, M.L., Krenske, E.H., and Izgorodina, E.I. (2008). Quantum-chemical
studies of RAFT polymerization: methodology, structure-reactivity correla-
tions and kinetic implications. In: Handbook of RAFT Polymerization (ed.
9783527622757.ch2.
References 7
26 Moad, G. (2022). Dithioesters in RAFT polymerization. In: RAFT Polymeriza-

tion: Materials, Synthesis and Applications (eds. G. Moad and E. Rizzardo),
223–370. Weinheim: Wiley-VCH.
27 Moad, G. (2022). Trithiocarbonates in RAFT polymerization. In: RAFT Polymer-
ization: Materials, Synthesis and Applications (eds. G. Moad and E. Rizzardo),
28 Wang, M., Marty, J.-D., and Destarac, M. (2022). Xanthates in RAFT polymer-
29 Moad, G. (2022). Dithicarbamates in RAFT polymerization. In: RAFT Polymer-
30 Zard, S.Z. (2008). The radical chemistry of thiocarbonylthio compounds: an
overview. In: Handbook of RAFT Polymerization (ed. C. Barner-Kowollik),
151–187. Weinheim: Wiley-VCH. https://doi.org/10.1002/9783527622757.ch5.
31 Taton, D., Destarac, M., and Zard, S.Z. (2008). Macromolecular design by
interchange of xanthates: background, design, scope and applications. In: Hand-
book of RAFT Polymerization (ed. C. Barner-Kowollik), 373–421. Weinheim:
Wiley-VCH. https://doi.org/10.1002/9783527622757.ch10.
32 Chapman, R., Jungb, K., and Boyer, C. (2022). Overview of photoregulated
reversible addition-fragmentation chain transfer (RAFT) polymerization. In:
33 Lorandi, F., Fantin, M., and Matyjaszewski, K. (2022). Redox initiated RAFT
polymerization and (electro)chemical activation of RAFT agents. In: RAFT
Polymerization: Materials, Synthesis and Applications (eds. G. Moad and
34 Fortenberry, A.W., McCormick, C.L., and Smith, A.E. (2022). Considerations for
and Applications of Aqueous RAFT Polymerization. In: RAFT Polymerization:
Materials, Synthesis and Applications (eds. G. Moad and E. Rizzardo), 679–706.
Weinheim: Wiley-VCH.
35 Lowe, A.B. and McCormick, C.L. (2008). RAFT polymerization in homogeneous
aqueous media: initiation systems, RAFT agent stability, monomers and poly-
mer structures. In: Handbook of RAFT Polymerization (ed. C. Barner-Kowollik),
235–284. Weinheim: Wiley-VCH. https://doi.org/10.1002/9783527622757.ch7.
36 Urbani, C.N. and Monteiro, M.J. (2008). RAFT-mediated polymerization
in heterogeneous systems. In: Handbook of RAFT Polymerization (ed. C.
Barner-Kowollik), 285–314. Weinheim: Wiley-VCH. https://doi.org/10.1002/
9783527622757.ch8.
37 D’Agosto, F., Lansalot, M., and Rieger, J. (2022). RAFT-mediated
polymerization-induced self-assembly (PISA). In: RAFT Polymerization: Mate-
rials, Synthesis and Applications (eds. G. Moad and E. Rizzardo), 707–752.
38 Lowe, A.B. and Dallerba, E. (2022). RAFT functional end-groups: installa-

tion and transformation. In: RAFT Polymerization: Materials, Synthesis and
39 Haven, J.J., Neve, J.D., and Junkers, T. (2022). Sequence-encoded RAFT
oligomers and polymers. In: RAFT Polymerization: Materials, Synthesis and
40 Barner, L. and Perrier, S. (2008). Polymers with well-defined end groups via
RAFT – synthesis, applications and postmodifications. In: Handbook of RAFT
Polymerization (ed. C. Barner-Kowollik), 455–482. Weinheim: Wiley-VCH.
https://doi.org/10.1002/9783527622757.ch12.
41 Gauthier-Jaques, M., Mutlu, H., Gaballa, H., and Theato, P. (2022). Synthe-
sis and application of reactive polymers via RAFT polymerization. In: RAFT
Polymerization: Materials, Synthesis and Applications (eds. G. Moad and
42 Pérez-Salinas, P., López-Domínguez, P., Rosas-Aburto, A. et al. (2022). RAFT
crosslinking polymerization. In: RAFT Polymerization: Materials, Synthesis and
43 Floyd, T.G., Häkkinen, S., Hartlie, M. et al. (2022). Complex polymeric archi-
tectures synthesised through RAFT polymerization. In: RAFT Polymerization:
44 Allison-Logan, S., Karimi, F., Nothling, M.D., and Qiao, G.G. (2022). Star
polymers by RAFT polymerization. In: RAFT Polymerization: Materials, Syn-
thesis and Applications (eds. G. Moad and E. Rizzardo), 983–1016. Weinheim:
Wiley-VCH.
45 Stenzel, M.H. (2008). Complex architecture design via the RAFT process:
scope, strengths and limitations. In: Handbook of RAFT Polymerization (ed.
9783527622757.ch9.
46 Li, Y., Schadler, L.S., and Benicewicz, B.C. (2008). Surface and particle modifi-
cation via the RAFT process: approach and properties. In: Handbook of RAFT
Polymerization (ed. C. Barner-Kowollik), 423–453. Weinheim: Wiley-VCH.
https://doi.org/10.1002/9783527622757.ch11.
47 Pribyl, J. and Benicewicz, B.C. (2022). Surface and particle modification via
RAFT polymerization: an update. In: RAFT Polymerization: Materials, Synthe-
sis and Applications (eds. G. Moad and E. Rizzardo), 1017–1050. Weinheim:
Wiley-VCH.
48 Moad, G. (2022). An industrial history of RAFT polymerization. In: RAFT
Polymerization: Materials, Synthesis and Applications (eds. G. Moad and E.
Rizzardo), 1077–1158. Weinheim: Wiley-VCH.
49 Junkers, T., Lovestead, T.M., and Barner-Kowollik, C. (2008). The RAFT process
as a kinetic tool: accessing fundamental parameters of free radical polymeriza-
tion. In: Handbook of RAFT Polymerization (ed. C. Barner-Kowollik), 105–149.
Weinheim: Wiley-VCH. https://doi.org/10.1002/9783527622757.ch4.
References 9
50 Favier, A., de Lambert, B., and Charreyre, M.-T. (2008). Toward new mate-
rials prepared via the RAFT process: from drug delivery to optoelectronics?
In: Handbook of RAFT Polymerization (ed. C. Barner-Kowollik), 483–535.
Weinheim: Wiley-VCH. https://doi.org/10.1002/9783527622757.ch13.
51 Guerrero-Sanchez, C., Yañez-Macias, R., Rosales-Guzmán, M. et al. (2022).
High throughput / high output experimentation in RAFT polymer synthesis. In:
52 Uchiyama, M. and Kamigaito, M. (2022). Cationic RAFT polymerization. In:
53 Haven, J.J., Hendrikx, M., Junkers, T. et al. (2018). Elements of RAFT nav-
igation. RAFT 20 years later. RAFT-synthesis of uniform, sequence-defined
(co)polymers. In: Reversible Deactivation Radical Polymerization: Mech-
anisms and Synthetic Methodologies, ACS Symposium Series 1284 (eds.
K. Matyjaszewski, H. Gao, B.S. Sumerlin and N.V. Tsarevsky), 77–103. Wash-
ington, DC: American Chemical Society. https://doi.org/10.1021/bk-2018-1284
.ch004.
54 McCombie, S.W., Quiclet-Sire, B., and Zard, S.Z. (2018). Tetrahedron 74:
4969–4979. https://doi.org/10.1016/j.tet.2018.03.042.
55 D’Agosto, F., Rieger, J., and Lansalot, M. (2020). Angew. Chem. Int. Ed. 59:
8368–8392. https://doi.org/10.1002/anie.201911758.
56 Wang, X. and An, Z. (2019). Macromol. Rapid Commun. 40: 1800325. https://doi
.org/10.1002/marc.201800325.
57 Palmiero, U.C., Singh, J., and Moscatelli, D. (2018). Curr. Org. Chem. 22:
1285–1296. https://doi.org/10.2174/1385272822666180322123124.
58 Zhou, J., Yao, H., and Ma, J. (2018). Polym. Chem. 9: 2532–2561. https://doi.org/
10.1039/C8PY00065D.
59 Hatton, F.L. (2020). Polym. Chem. https://doi.org/10.1039/C9PY01128E.
60 Caykara, T. (2018). Polymer brushes by surface-mediated RAFT polymeriza-
tion for biological functions. In: Polymer and Biopolymer Brushes, vol. 1 (eds.
O. Azzaroni and I. Szleifer), 97–121. Hoboken, NJ: Wiley. https://doi.org/10
.1002/9781119455042.ch3.
61 Daniselson, A.P., Dougherty, M.L., Falatach, R. et al. (2018). Biocatalytic
polymerization, bioinspired surfactants, and bioconjugates using RAFT poly-
merization. In: Reversible Deactivation Radical Polymerization: Materials and
Applications, ACS Symposium Series 1285 (eds. K. Matyjaszewski, H. Gao, B.S.
Sumerlin and N.V. Tsarevsky), 219–232. American Chemical Society. https://doi
.org/10.1021/bk-2018-1285.ch012.
62 Xin, X. and John, J.R. (2018). Curr. Drug Deliv. 15: 1084–1086. https://doi.org/10
.2174/1567201815666180220100733.
63 Delaittre, G., Beloqui, A., Gil Alvaradejo, G. et al. (2018). Chem. Ing. Tech. 90:
1331–1331. https://doi.org/10.1002/cite.201855430.
64 Hu, J., Qiao, R., Whittaker, M.R. et al. (2017). Aust. J. Chem. 70: 1161–1170.
65 Xian, C., Yuan, Q., Bao, Z. et al. (2020). Chin. Chem. Lett. 31: 19–27. https://doi
.org/10.1016/j.cclet.2019.03.052.
66 Huang, X., Hu, J., Li, Y. et al. (2019). Biomacromolecules 20: 4243–4257. https://
doi.org/10.1021/acs.biomac.9b01158.
67 Pereira, S., Barros-Timmons, A., and Trindade, T. (2018). Polymers 10: 189.
https://doi.org/10.3390/polym10020189.
68 Zhang, Z., Corrigan, N., Bagheri, A. et al. (2019). Angew. Chem. Int. Ed. 58:
69 Moad, G. (2017). Polym. Chem. 8: 177–219. https://doi.org/10.1039/
C6PY01849A.
70 Moad, G. (2017). Polym. Int. 66: 26–41. https://doi.org/10.1002/pi.5173.
71 Xu, J. (2019). Macromolecules 52: 9068–9093. https://doi.org/10.1021/acs
.macromol.9b01365.
72 Reyhani, A., McKenzie, T.G., Fu, Q., and Qiao, G.G. (2019). Aust. J. Chem. 72:
479–489. https://doi.org/10.1071/CH19109.
73 McKenzie, T.G., Reyhani, A., Nothling, M.D., and Qiao, G.G. (2018). Hydroxyl
radical activated RAFT polymerization. In: Reversible Deactivation Radical
Polymerization: Mechanisms and Synthetic Methodologies, ACS Symposium
Series 1284 (eds. K. Matyjaszewski, H. Gao, B.S. Sumerlin and N.V. Tsarevsky),
307–321. American Chemical Society. https://doi.org/10.1021/bk-2018-1284
.ch014.
74 Figg, C.A. and Sumerlin, B.S. (2018). Aqueous visible-light RAFT polymeriza-
tions and applications. In: Reversible Deactivation Radical Polymerization: Mate-
rials and Applications, ACS Symposium Series 1285 (eds. K. Matyjaszewski,
H. Gao, B.S. Sumerlin and N.V. Tsarevsky), 43–56. American Chemical Society.
https://doi.org/10.1021/bk-2018-1285.ch003.
75 Shanmugam, S., Boyer, C., and Matyjaszewski, K. (2018). Recent develop-
ments in external regulation of reversible addition fragmentation chain transfer
(RAFT) polymerization. In: Reversible Deactivation Radical Polymerization:
Mechanisms and Synthetic Methodologies, ACS Symposium Series 1284 (eds.
K. Matyjaszewski, H. Gao, B.S. Sumerlin and N.V. Tsarevsky), 273–290. Ameri-
can Chemical Society. https://doi.org/10.1021/bk-2018-1284.ch012.
76 Barsbay, M. and Güven, O. (2020). Radiat. Phys. Chem. 169: 107816. https://doi
.org/10.1016/j.radphyschem.2018.04.009.
77 Moad, G. (2019). J. Polym. Sci., Part A: Polym. Chem. 57: 216–227. https://doi
.org/10.1002/pola.29199.
78 Tian, X., Ding, J., Zhang, B. et al. (2018). Polymers 10: 318. https://doi.org/10
.3390/polym10030318.
79 Foster, J.C., Radzinski, S.C., and Matson, J.B. (2017). J. Polym. Sci., Part A:
Polym. Chem. 55: 2865–2876. https://doi.org/10.1002/pola.28621.
80 An, Z. (2020). ACS Macro Lett. 9: 350–357. https://doi.org/10.1021/acsmacrolett
.0c00043.
81 Fang, J., Yan, K., and Luo, Y. (2018). Synthesis of well-defined polystyrene
with molar mass exceeding 500 kg/mol by RAFT emulsion polymerization. In:
Reversible Deactivation Radical Polymerization: Materials and Applications, ACS
References 11
Symposium Series 1285 (eds. K. Matyjaszewski, H. Gao, B.S. Sumerlin and N.V.
Tsarevsky), 81–106. Washington, DC: American Chemical Society. https://doi
.org/10.1021/bk-2018-1285.ch005.
82 Wang, X. and Gao, H. (2017). Polymers 9: 188. https://doi.org/10.3390/
polym9060188.
83 Gao, Y., Zhou, D., Lyu, J. et al. (2020). Nat. Rev. Chem. 4: 194–212. https://doi
.org/10.1038/s41570-020-0170-7.
84 Mocny, P. and Klok, H.-A. (2020). Prog. Polym. Sci. 100: 101185. https://doi.org/
10.1016/j.progpolymsci.2019.101185.
85 Beyer, V.P., Kim, J., and Becer, C.R. (2020). Polym. Chem. 11: 1271–1291.
https://doi.org/10.1039/C9PY01571J.
86 Mane, S.R. (2020). New J. Chem. 44: 6690–6698. https://doi.org/10.1039/
C9NJ05638F.
87 Penfold, N.J.W., Yeow, J., Boyer, C., and Armes, S.P. (2019). ACS Macro Lett. 8:
1029–1054. https://doi.org/10.1021/acsmacrolett.9b00464.
88 Chen, S.-l., Shi, P.-f., and Zhang, W.-q. (2017). Chin. J. Polym. Sci. 35: 455–479.
https://doi.org/10.1007/s10118-017-1907-8.
89 Gurnani, P. and Perrier, S. (2020). Prog. Polym. Sci. 102: 101209. https://doi.org/
10.1016/j.progpolymsci.2020.101209.
90 Hu, Q., Gan, S., Bao, Y. et al. (2020). J. Mater. Chem. B 8: 3327–3340. https://doi
.org/10.1039/C9TB02419K.
91 Kim, S. and Sikes, H.D. (2020). Polym. Chem. 11: 1424–1444. https://doi.org/10
.1039/C9PY01801H.
92 Ida, S. (2019). Polym. J. 51: 803–812. https://doi.org/10.1038/s41428-019-0204-5.
93 Messina, M.S., Messina, K.M.M., Bhattacharya, A. et al. (2020). Prog. Polym. Sci.
100: 101186. https://doi.org/10.1016/j.progpolymsci.2019.101186.
94 Wang, Y. and Wu, C. (2018). Biomacromolecules 19: 1804–1825. https://doi.org/
10.1021/acs.biomac.8b00248.
95 Sui, B., Cheng, C., and Xu, P. (2019). Adv. Ther. 2: 1900062. https://doi.org/10
.1002/adtp.201900062.
96 Van Bruggen, C., Hexum, J.K., Tan, Z. et al. (2019). Acc. Chem. Res. 52:
1347–1358. https://doi.org/10.1021/acs.accounts.8b00665.
97 Pramudya, I. and Chung, H. (2019). Biomater. Sci. 7: 4848–4872. https://doi.org/
10.1039/C9BM01385G.
98 Loczenski Rose, V., Mastrotto, F., and Mantovani, G. (2017). Polym. Chem. 8:
353–360. https://doi.org/10.1039/C6PY01855F.
99 Sponchioni, M., Palmiero, U.C., and Moscatelli, D. (2019). Mater. Sci. Eng., C
102: 589–605. https://doi.org/10.1016/j.msec.2019.04.069.
100 Nagase, K. and Okano, T. (2018). Thermoresponsive polymer brushes for ther-
mally modulated cell adhesion and detachment. In: Polymer and Biopolymer
Brushes, vol. 1 (eds. O. Azzaroni and I. Szleifer), 361–375. Hoboken, NJ: Wiley.
https://doi.org/10.1002/9781119455042.ch12.
101 Taylor, M.J., Tomlins, P., and Sahota, T.S. (2017). Gels 3: 4. https://doi.org/10
.3390/gels3010004.
102 Sun, H., Yang, L., Thompson, M.P. et al. (2019). Bioconjugate Chem. https://doi
.org/10.1021/acs.bioconjchem.9b00166.
103 Yang, D.-P., Oo, M.N.N.L., Deen, G.R. et al. (2017). Macromol. Rapid Commun.
38: 1700410. https://doi.org/10.1002/marc.201700410.
104 Khor, S.Y., Quinn, J.F., Whittaker, M.R. et al. (2019). Macromol. Rapid Com-
mun. 40: 1800438. https://doi.org/10.1002/marc.201800438.
105 Pollard, J. and Bruns, N. (2018). Biocatalytic ATRP. In: Reversible Deactivation
Radical Polymerization: Mechanisms and Synthetic Methodologies, ACS Sym-
posium Series 1284 (eds. K. Matyjaszewski, H. Gao, B.S. Sumerlin and N.V.
Tsarevsky), 379–393. American Chemical Society. https://doi.org/10.1021/bk-
2018-1284.ch019.
106 Rodriguez, K.J., Gajewska, B., Pollard, J. et al. (2018). ACS Macro Lett. 7:
107 Lv, C., Du, Y., and Pan, X. (2020). J. Polym. Sci. 58: 14–19. https://doi.org/10
.1002/pola.29477.
108 Reyhani, A., McKenzie, T.G., Fu, Q., and Qiao, G.G. (2019). Macromol. Rapid
Commun. 40: 1900220. https://doi.org/10.1002/marc.201900220.
109 Moad, G. (2019). Prog. Polym. Sci. 88: 130–188. https://doi.org/10.1016/j
.progpolymsci.2018.08.003.
110 Zhou, Y.-N., Li, J.-J., Wu, Y.-Y., and Luo, Z.-H. (2020). Chem. Rev. 120:
2950–3048. https://doi.org/10.1021/acs.chemrev.9b00744.
111 Duffy, C., Zetterlund, P.B., and Aldabbagh, F. (2018). Molecules 23: 465. https://
doi.org/10.3390/molecules23020465.
112 Gong, H., Gu, Y., and Chen, M. (2018). Synlett 29: 1543–1551 (1543 pp). https://
doi.org/10.1055/s-0036-1591974.
113 Kamigaito, M. and Satoh, K. (2017). Sustainable vinyl polymers via controlled
polymerization of terpenes. In: Sustainable Polymers from Biomass (eds. C.
Tang and C.Y. Ryu), 55–90. Weinheim: Wiley-VCH. https://doi.org/10.1002/
9783527340200.ch4.
114 Wang, J., Liu, S., Yu, J. et al. (2017). Rosin-derived monomers and their
progress in polymer application. In: Sustainable Polymers from Biomass (eds.
C. Tang and C.Y. Ryu), 103–149. Weinheim: Wiley-VCH. https://doi.org/10
.1002/9783527340200.ch6.
115 Yuan, L., Wang, Z., Trenor, N.M., and Tang, C. (2017). Preparation and applica-
tions of polymers with pendant fatty chains from plant oils. In: Sustainable
Polymers from Biomass (eds. C. Tang and C.Y. Ryu), 181–207. Weinheim:
Wiley-VCH. https://doi.org/10.1002/9783527340200.ch8.
116 Ganewatta, M.S., Lokupitiya, H.N., and Tang, C. (2019). Polymers 11: 1176.
117 Cheaburu-Yilmaz, C.N., Karavana, S.Y., and Yilmaz, O. (2017). Curr. Org. Synth.
14: 785–797. https://doi.org/10.2174/1570179414666161115150818.
118 Eskandari, P., Abousalman-Rezvani, Z., Roghani-Mamaqani, H. et al. (2019).
Adv. Colloid Interface Sci. 273: 102021. https://doi.org/10.1016/j.cis.2019.102021.
References 13
119 Abousalman-Rezvani, Z., Eskandari, P., Roghani-Mamaqani, H., and

Salami-Kalajahi, M. (2020). Adv. Colloid Interface Sci. 278: 102126. https://
doi.org/10.1016/j.cis.2020.102126.
120 Pasini, D. and Nitti, A. (2020). Eur. Polym. J. 122: 109378. https://doi.org/10
.1016/j.eurpolymj.2019.109378.
121 Junkers, T. and Laun, J. (2018). Controlled reversible deactivation radical pho-
topolymerization. In: Photopolymerisation Initiating Systems (eds. J. Lalevée and
J.-P. Fouassier), 244–273. Cambridge: The Royal Society of Chemistry. https://
doi.org/10.1039/9781788013307-00244.
122 Buss, B.L. and Miyake, G.M. (2018). Chem. Mater. 30: 3931–3942. https://doi
.org/10.1021/acs.chemmater.8b01359.
123 Burridge, K.M., Wright, T.A., Page, R.C., and Konkolewicz, D. (2018). Macro-
mol. Rapid Commun. 39: 1800093. https://doi.org/10.1002/marc.201800093.
124 Shanmugam, S., Xu, J., and Boyer, C. (2017). Macromol. Rapid Commun. 38:
1700143. https://doi.org/10.1002/marc.201700143.
125 Yu, J.R., Zuo, Y., and Xiong, Y.B. (2018). Thermo-responsive poly(ionic liquid)
nanogels prepared via one-step cross-linking copolymerization. In: Polymer-
ized Ionic Liquids (ed. A. Eftekhari), 202–224. Cambridge: The Royal Society of
Chemistry. https://doi.org/10.1039/9781788010535-00202.
126 Chen, F., Lin, F., Zhang, Q. et al. (2019). Macromol. Rapid Commun. 40:
127 Bagheri, A. and Jin, J. (2019). ACS Appl. Polym. Mater. 1: 593–611. https://doi
.org/10.1021/acsapm.8b00165.
128 Zhu, J., Yang, C., Lu, C. et al. (2018). Acc. Chem. Res. 51: 3191–3202. https://doi
.org/10.1021/acs.accounts.8b00444.
129 Palmiero, U.C., Sponchioni, M., Manfredini, N. et al. (2018). Polym. Chem. 9:
4084–4099. https://doi.org/10.1039/C8PY00649K.
130 Kreutzer, J. and Yagci, Y. (2018). Polymers 10: 35. https://doi.org/10.3390/
polym10010035.
131 Chang, Y.A. and Waymouth, R.M. (2017). J. Polym. Sci., Part A: Polym. Chem.
55: 2892–2902. https://doi.org/10.1002/pola.28635.
132 Lunn, D.J., Discekici, E.H., Read de Alaniz, J. et al. (2017). J. Polym. Sci., Part
A: Polym. Chem. 55: 2903–2914. https://doi.org/10.1002/pola.28575.
133 Zhao, L., Liu, X., Zhang, L. et al. (2017). Coord. Chem. Rev. 337: 34–79. https://
doi.org/10.1016/j.ccr.2017.02.009.
15
Terminology in Reversible Deactivation Radical

Polymerization
Graeme Moad
2.1 Terminology for Reversible Deactivation Radical

Polymerization (RDRP)
In this chapter, we consider the terminology used to describe reversible deactivation

radical polymerization (RDRP) and reversible addition–fragmentation chain
transfer (RAFT) polymerization. RDRP [1] is a recently introduced term to describe
what, until 2010, had been known under various terms that include living rad-
ical polymerization, controlled radical polymerization, controlled/living radical
polymerization, quasi-living radical polymerization, pseudo-living polymerization,
mediated polymerization, and some others.
The decade prior to 2010 had seen controversy over the use of the terms ‘liv-
ing’ and ‘controlled’ for describing radical polymerizations that show some living
characteristics [2–7]. The IUPAC recommendation that a living polymerization is ‘a
chain polymerization from which irreversible chain transfer and irreversible chain
termination (deactivation) are absent’ precluded the use of the term ‘living’ when
describing any form of radical process [8]. In any polymerization that involves rad-
icals as the propagating species, some termination is inevitable even if the products
are not always readily detected. With respect to other forms of polymerization, it
is acceptable to use the term that describes a dominant reaction mechanism and
characteristics of the process, even if side reactions occur or are possible.
The use of the adjective ‘controlled’ by itself, without some explanation, to
designate these polymerizations is also contrary to IUPAC recommendations. The
term, controlled polymerization, should only be used when the particular aspect
of polymerization that is being controlled has been specified. The word should
not be used in an exclusive sense to mean a particular form of polymerization
since it has an established, much broader usage. The construct ‘controlled living
polymerization’ would seem acceptable when used to refer to those living poly-
merizations whose outcomes are defined by controlling the reaction conditions or
other features, but the adjective ‘controlled’ must not be used to specify systems as
having a lesser degree of livingness. Terms such as ‘pseudo-living’ and ‘quasi-living’
Table 2.1 IUPAC recommendations on terminology for reversible deactivation radical polymerization (RDRP).
Term Definition Notes References
controlled Term indicating control of a certain Note 1: The expression “controlled polymerization” is sometimes used to [1, 8]
polymerization kinetic feature of a polymerization or describe a radical or ionic polymerization in which reversible deactivation
structural aspect of the polymer of the chain carriers is an essential component of the mechanism,
molecules formed, or both. interrupting the propagation to secure control of one or more kinetic
features of the polymerization or one or more structural aspects of the
macromolecules formed, or both.
Note 2: The expression controlled radical polymerization is sometimes used
to describe a radical polymerization conducted in the presence of reagents
that lead to, e.g., atom-transfer radical polymerization (ATRP), nitroxide-
[aminoxyl] mediated polymerization (NMP), or reversible-addition-
fragmentation chain transfer (RAFT) polymerization.
Note 3: Generally, the adjective “controlled” should not be used without
specifying the particular kinetic or structural feature that is subject to
control.
living Chain polymerization in which chain Note 1: In many cases, the rate of chain initiation is fast compared with [1, 8]
polymerization termination and irreversible chain the rate of chain propagation, so that the number of kinetic-chain carriers
transfer are absent. is essentially constant throughout the reaction. This is not a necessary
condition for living polymerization.
Note 2: In a living polymerization, the reversible (temporary) deactivation
of active sites can take place (see reversible chain deactivation).
Note 3: In a living polymerization, all the macromolecules formed possess
the potential for further growth.
Note 4: Use of the adjectives “pseudo-living”, “quasi-living”, and
“immortal” is discouraged.
reversible- Chain polymerization, propagated by Note 1: The abbreviated term “controlled radical polymerization” shall be [1]
deactivation radicals that are deactivated reversibly, permitted, provided that its context (i.e., the nature of the control) is
radical bringing them into active-dormant specified at the first occurrence.
polymerization, equilibria of which there might be more Note 2: Names containing the word “living” are discouraged. Definition
RDRP than one. 84 in the Kinetics document [8] stipulates that chain termination and
controlled irreversible chain transfer must be absent if a polymerization is to be
reversible- regarded as living. Examples of discouraged terms include “living radical
deactivation polymerization”, “controlled/living polymerization” and “quasi-living
radical polymerization”.
polymerization
Note 3: Atom-transfer radical polymerization, reversible-addition-
fragmentation chain-transfer polymerization, and polymerization
mediated by an aminoxyl (or similarly acting substance) all fall into this
polymerization category.
Note 4: When the equilibria are established rapidly compared to the rate
of propagation, the process may show many of the observable
characteristics associated with living polymerization. One consequence of
rapid equilibration is that it may become possible to exert control over the
shape of the chain-length distribution, prepare polymers of low dispersity
(i.e., polymers with a high degree of uniformity), and extend chains to
form block copolymers, the block lengths of which are of low dispersity,
by the sequential addition of monomers. Although some termination is
inevitably taking place, the equilibrium between the remaining
propagating radicals and dormant species is maintained.
18 2 Terminology in RDRP and RAFT
are also discouraged by IUPAC [1, 8]. It has been stated that the definition of living
polymerization ‘tolerates no restrictive adjectives implying something close to but
not strictly living’ [5] (Table 2.1).
2.2 Terminology in Reversible Addition–Fragmentation

Chain Transfer (RAFT) Polymerization
Much of the terminology used to describe RAFT polymerization is illustrated in the

simplified mechanism shown in Scheme 2.1. Initiation, propagation, and termina-
tion are the same as in radical polymerization (Table 2.2).
Initiation
Initiating radical Unimer Propagating radical
primary radical radical active polymer
Monomer
A2 A P1 Pn
(Conventional)
initiator
Initialization (pre-equilibrium)
Dead polymer Intermediate
Dead species
radical
Termination termination Termination MacroRAFT agent
RAFT agent
kadd kβ dormant polymer
Active polymer Pn + R X R X Pn R + Pn X
k –add k –β Initiating radical
Intermediate
Propagation
primary radical
Initiation Monomer
Monomer
P1
Propagation (main equilibrium)
Dead polymer Intermediate Dead polymer
radical
termination
MacroRAFT agent
Termination
Termination kadd k –add dormant polymer
Active polymer Pn + Pm X Pm X Pn Pm + Pn X
k –add kadd
Intermediate
Propagation Propagation
Monomer Monomer
Termination
Termination
Pn + Pn
Primary radical termination
Dead polymer
Pn + A
Pn + R
Scheme 2.1 Simplified mechanism for reversible addition–fragmentation chain transfer

(RAFT) polymerization with initiation by a conventional initiator (A2 ), e.g. a dialkyldiazene.
Source: Figure adapted from Moad, Chemistry of Radical Polymerization, © Elsevier 2021.
Table 2.2 IUPAC recommendations on terminology for reversible addition–fragmentation chain transfer (RAFT) polymerization.
chain deactivation Conversion of a chain carrier into Note 1: Chain deactivation, unlike chain termination, may be [8]
an inactive species. reversible; see reversible chain deactivation.
Note 2: The reverse of chain deactivation is chain reactivation.
chain initiation (in a Chemical reaction in which Note: The recommended symbol for the rate constant for chain [8]
chain polymerization) initiating species add to monomer initiation in a polymerization is ki .
initiation to form chain carriers.
chain propagation (in a Chemical reaction between a chain Note 1: The recommended symbol for the rate constant for chain [8]
chain polymerization) carrier and a monomer that results propagation in a homopolymerization is kp .
propagation in the growth of a polymer chain
Note 2: For chain propagation in copolymerization, see
and the regeneration of at least one
cross-propagation.
chain carrier.
chain reactivation Conversion of an inactive chain [8]
chain activation into a chain carrier.
chain termination (in Chemical reaction in which a Note 1: The recommended symbol for the rate constant or [8]
a chain chain carrier is converted coefficient for chain termination in a homopolymerization is kt .
polymerization) irreversibly into a non-propagating Note 2: The term “chain deactivation” is often used to stress that, in
irreversible chain species without the formation of a contrast to chain termination, the formation of non-propagating
deactivation, new chain carrier. species may be reversible; see chain deactivation and reversible
termination chain deactivation.
Note 3: See also combination, cross-termination,
disproportionation, and spontaneous termination.
chain transfer (in a Chemical reaction occurring Note 1: See also intermolecular chain transfer, intramolecular [8]
chain polymerization) during a chain polymerization in chain transfer, and backbiting.
transfer which an active center is Note 2: The recommended symbol for the rate constant of chain
transferred from a growing transfer in a homopolymerization is ktr .
macromolecule or oligomer
molecule to another molecule or to
another site on the same molecule.
(continued)
Table 2.2 (Continued)
chain-transfer agent Substance able to react with a Note: In a polymerization, the common occurrence is that a new [8]
transfer agent chain carrier by a reaction in chain carrier of lower molar mass is generated.
which the original chain carrier is
deactivated and a new chain
carrier is generated.
chain-transfer In a homopolymerization, rate [8]
constant, Ctr constant for chain transfer, ktr ,
divided by the rate constant for
chain propagation, kp , i.e.,
Ctr = ktr /kp .
degenerative chain Chain transfer reaction that [8]
transfer generates a new chain carrier and a
degenerate chain new chain-transfer agent with the
transfer same reactivity as the original
chain carrier and chain-transfer
agent.
degradative chain Chain-transfer reaction that [8]
transfer generates a new chain carrier of
much lower reactivity than that of
the original chain carrier.
degenerate-transfer Controlled reversible-deactivation Note: Examples of DT-active groups include those mentioned [1]
radical polymeri- radical polymerization in which below under reversible-addition-fragmentation chain-transfer
zation, DTRP the deactivation of the radicals polymerization, iodine (iodine transfer polymerization, ITP) and
involves degenerative transfer (DT) certain derivatives of Te, As, Sb, or Bi.
of a group (or atom).
dormant polymer Temporarily deactivated chain [1]
chain carrier.
initiating species Species to which monomer adds to Note 1: An initiating species may be formed from an initiator or be [8]
start chain polymerization. the initiator itself.
Note 2: In radical polymerization, initiating species formed directly
from an initiator are called primary radicals.
initiator Substance introduced into a Note: In contrast to a catalyst, an initiator is consumed in the [8]
reaction system in order to cause reaction.
chain initiation.
initiator efficiency, f Number of growing chains Note 1: In a radical polymerization, the rate of radical production [8]
initiated divided by the number of from an initiator that provides two similar radicals is 2kd f , where
active centers generated from kd is the rate constant for initiator decomposition.
initiator molecules. Note 2: In some texts, the initiator efficiency is defined as the
fraction of radicals that escapes the cage (see cage effect).
primary radical (in a Radical that is formed from an Note 1: A primary radical may be formed by the action of heat, [8]
chain polymerization) initiator or monomer molecule irradiation or electrode charge transfer.
and that is capable of initiating Note 2: The recombination of primary radicals and their reactions
polymerization. with other species may lead to reduced initiator efficiency.
Note 3: The term “primary radical” is also used to designate a
radical centered on a primary carbon atom, for example, an ethyl
radical.
See secondary radical.
secondary radical (in a Radical formed by the rearrange- Note: The term “secondary radical” is also used to designate a [8]
chain polymerization) ment or fragmentation of a radical centered on a secondary carbon atom, e.g., a 2-propyl
primary radical that is capable of radical.
initiating a polymerization. See primary radical.
(continued)
reversible-addition- Degenerate-transfer radical Note 1: Examples of RAFT agents include certain dithioesters, [1]
fragmentation polymerization in which chain trithiocarbonates, xanthates (dithiocarbonates), and
chain-transfer activation and chain deactivation dithiocarbamates.
polymerization involve a degenerative Note 2: RAFT with xanthates is also known as MADIX
RAFT polymerization, chain-transfer process which (macromolecular design by interchange of xanthate).
RAFT occurs by a two-step
addition-fragmentation
mechanism.
reversible chain Deactivation of a chain carrier in a Note 1: The temporarily deactivated species created in this process [1]
deactivation chain polymerization, reversibly are often described as dormant.
converting an active center into an Note 2: Reversible deactivation often involves reversible
inactive one and then, within the combination or reversible chain transfer.
average lifetime of a growing
macromolecule, regenerating an
active center on the same original
carrier.
Table 2.3 Additional terminology for reversible addition–fragmentation chain transfer (RAFT) polymerization.
Term Definition Notes
blocking efficiency (in RAFT Fraction of an initial macroRAFT agent converted to a block
polymerization) copolymer in the course of RAFT polymerization.
initialization (in RAFT Process for conversion of an initial RAFT agent to a macroRAFT
polymerization) agent
initialization efficiency (in Fraction of an initial RAFT agent converted to a macroRAFT agent Note: when the initial RAFT agent is a
RAFT polymerization) in the course of RAFT polymerization. macroRAFT agent the term blocking
efficiency may be used.
intermediate (in RAFT Transient intermediate formed by radical addition to a RAFT agent
polymerization) or macroRAFT agent
intermediate radical Termination reaction where one reactant is the intermediate formed
termination by radical addition to a RAFT agent or macroRAFT agent.
reversible addition- (a) A transfer agent that provides chain transfer by a reversible
fragmentation chain transfer addition-fragmentation mechanism
agent (b) Reagent that reacts by addition to give an intermediate that
RAFT agent fragments to provide a product which is in itself a RAFT agent.
macroRAFT agent (a) RAFT agent formed during RAFT polymerization comprising
one or more monomer units.
(b) RAFT agent formed by end-functionalization of a preformed
polymer or oligomer.
SUMI-RAFT agent A macroRAFT agent that comprises only one unit of monomer.
unimer RAFT agent
thiocarbonylthio RAFT agent RAFT agent where the reactive double bond is a thiocarbonyl double
bond.
macromonomer RAFT agent RAFT agent where the reactive double bond is a carbon-carbon
double bond
unimer Species derived from a single monomer unit
24 2 Terminology in RDRP and RAFT
2.3 Terminology That Is Not Ratified by IUPAC

The terms below are commonly encountered in describing RAFT polymerization
but are not defined in the current IUPAC document. These terms may form part
of a proposed IUPAC document Terminology for Chain Polymerization currently in
preparation [9] (Table 2.3).
References
1 Jenkins, A.D., Jones, R.I., and Moad, G. (2010). Pure Appl. Chem. 82: 483–491.
https://doi.org/10.1351/PAC-REP-08-04-03.
2 Matyjaszewski, K. and Mueller, A.H.E. (1997). Polym. Prepr. (Am. Chem. Soc., Div.
Polym. Chem.) 38 (1): 6–9.
3 Ivan, B. (2000). Polym. Prepr. (Am. Chem. Soc., Div. Polym. Chem.) 41 (2): 6a–12a.
4 Howell, B.A. (2000). Polym. Mater. Sci. Eng. 83: 578.
5 Quirk, R.P. and Lee, B. (1992). Polym. Int. 27: 359–367. https://doi.org/10.1002/pi
.4990270412.
6 Darling, T.R., Davis, T.P., Fryd, M. et al. (2000). J. Polym. Sci., Part A: Polym.
Chem. 38: 1706–1708. https://doi.org/10.1002/(SICI)1099-0518(20000515)38:10
<1706::AID-POLA20>3.0.CO;2-5.
7 Darling, T.R., Davis, T.P., Fryd, M. et al. (2000). J. Polym. Sci., Part A: Polym.
Chem. 38: 1709. https://doi.org/10.1002/(SICI)1099-0518(20000515)38:10
<1709::AID-POLA30>3.0.CO;2-W.
8 Penczek, S. and Moad, G. (2008). Pure Appl. Chem. 80: 2163–2193. https://doi.org/
10.1351/pac200880102163.
9 Anon. (2014). Chemistry International 32 (4): 24–24. https://doi.org/10.1515/ci.2010
.32.4.24.
25
How to Do a RAFT Polymerization

CSIRO Manufacturing, Bayview Avenue, Clayton, VIC 3168, Australia
3.1 Introduction
Reversible addition–fragmentation chain transfer (RAFT) polymerization is one of

the most versatile methods for providing living characteristics to radical polymer-
ization. RAFT polymerization provides the ability to control polymerization of most
monomers polymerizable by radical polymerization.
In an ideal living polymerization, all chains are initiated at the beginning of the
process, grow at a similar rate, and survive the polymerization (there is no irre-
versible chain transfer or termination). If initiation is rapid with respect to propa-
gation the molecular weight distribution is very narrow, and chains can be extended
by the provision of further monomer. In a radical polymerization all chains cannot
be simultaneously active. In RAFT polymerization, the majority of living chains are
maintained in a dormant form. A rapid equilibrium between active (propagating
radicals) and dormant chains (macroRAFT agents) ensures that all chains grow at
a similar rate. Under these conditions, molecular weights can increase linearly with
conversion and molecular weight distributions can be very narrow.
The reactions associated with RAFT equilibria (Scheme 3.1) are in addition to
those that occur during conventional radical polymerization (i.e. initiation, propa-
gation, and termination). The RAFT agent is a transfer agent and does not suppress
termination. Retention of the thiocarbonylthio groups in the polymeric product is
responsible for the living character of RAFT polymerization. RAFT polymerization
can be used in the synthesis of well-defined homo-, gradient, diblock, triblock, and
star polymers and more complex architectures including microgels and polymer
brushes (Figure 3.1).
The best way to understand the power of RAFT polymerization is to sim-
ply perform a conventional radical polymerization and then perform the same
polymerization and add an appropriately selected RAFT agent (see Table 3.1,
Figure 3.2) to it. Nearly all conventional radical polymerizations and, in particular,

26 3 How to Do a RAFT Polymerization
R must be a good homolytic leaving group and good initiating species
Reactive double bond
S Z
kadd kβ
R R′ R S Z
R′ Z S R′ R
k–add S S k–β
S
Z modifies the addition and fragmentation rates
Scheme 3.1 Mechanism for reversible addition–fragmentation chain transfer (RAFT).
End-functional Di-end-functional Telechelic Gradient copolymer
X Y X X X
Graft copolymer AB diblock ABA triblock ABC triblock
Star Dendritic polymer/hyperbranched
Figure 3.1 Polymer architectures amenable to RAFT polymerization.
solvent-based radical polymerizations, can easily become RAFT polymerizations;

the same solvents, initiators, and reaction temperatures can be used. It should be
noted that for optimal control of the RAFT process, it is important to pay attention
to factors such as initiator concentration and RAFT agent selection. Standard
ratios of reagents are [initiator]/RAFT/[monomer] = [1]/[4–10]/[2000–5000]. One
starting point may be to choose the conditions such that the target molecular
weight is ∼10% of that which would have been obtained in the absence of the RAFT
agent. The molecular weight can be predicted using Eq. (3.1) or, if initiator-derived
chains are significant, Eq. (3.2); M n(calc) is the predicted molecular weight, X is the
monomer conversion, mM and mRAFT are molecular weights of the monomer and
the RAFT agent respectively, and [M] and [RAFT] are the initial concentrations of
the monomer and RAFT agent respectively. In Eq. (3.2), M n(calc) is the predicted
molecular weight, mM and mRAFT are the molecular weights of the monomer and
the RAFT agent respectively, [M]0 and [M]f are the concentrations of the monomer
at the start and end of the reaction respectively, [RAFT]0 is the concentration of the
RAFT agent at the start of the reaction, [I]0 and [I]f are the concentrations of the
initiator at the start and end of the reaction respectively, mRAFT is the molecular
3.1 Introduction 27
Table 3.1 A list of selected commonly used RAFT agents with their suitability for various monomer
types: A excellent control of molecular weight with low dispersities (<1.1); B excellent control of
molecular weight with moderate dispersities; C good control of molecular weight with high
dispersities (>1.3); X not suitable.
Vinyl Vinyl
Styrenes Acrylate Methacrylates Acrylamides Methacrylamides esters amides
R1 O H H O O
R O N N
R R R
R2 O O R N R
O O O H
RAFT agent
S A A A A A X X
S
S A A A A A X X
S CN
S B B X B X X X
S
S B B X B X X X
S S
S B B X B X X X
C12H25 OH
S S
5 O
O S B B X B X X X
OH
HO S S
6 O
S CN A A A A A X X
C12H25 OH
S S
O
7
O S CN A A A A A X X
OH
HO S S
8 O
S A A X A X B B
N
H3C N S CN
CH3
9
Vinyl Vinyl
Styrenes Acrylate Methacrylates Acrylamides Methacrylamides esters amides
R1 O H H O O
R O N N
R R R
R2 O O R N R
O O O H
S NC A A C C C B B
N
H3C N S
CH3
10
S NC A A B B B B B
N
H3C N S
CH3
Cl
11
S X X X X X A A
N S CN
12
Source: Table adapted Rizzardo et al. [1]. © John Wiley and Sons.
Z group
O
Me N N
Me Me
Ph >> SMe > N > N ~ Me ~ N > N >> N > OPh > OEt ~ N ~ N > N(Et)2
Cl
NH+ N
MAM MMA, HPMA
MAM St, MA, Am, AN
IAM NVC
LAM VAc, NVP
R group
CH3 CH3 H H CH3 CH3 CH3 CH3 H CH3 H H

CN ~ Ph > Ph ~ Ph > COOEt >> CH2 CH3 ~ CN ~ Ph > CH3 ~ CN ~ Ph
CH3 CH3 CN CO2H CH3 CH3 CH3 H CH3 CH3 H H
MAM MMA, HPMA

MAM St, MA, Am, AN
LAM VAc, NVP, NVC
Figure 3.2 Guidelines for the selection of RAFT agents for various polymerizations. For Z,
addition rates decrease and fragmentation rates increase from left to right. For R,
fragmentation rates decrease from left to right. Dashed line indicates partial control (i.e.
control of molar mass but poor control over dispersity or substantial retardation in the case
of VAc, NVC, or NVP). AN - acrylonitrile, HPMA - N-(2-hydroxypropyl)methacrylamide,
Am - acrylamide. Source: Figure adapted from Moad et al. [2]. © CSIRO and Gardiner et al.
[3]. © Society of Chemical Industry.
weight of the RAFT agent, d is the number of chains produced from radical–radical
termination, and f is the initiator efficiency [2].
( )
[M]0
Mn (calc) = X mM + mRAFT (3.1)
[RAFT]0
[M]0 − [M]f
Mn (calc) = mM + mRAFT (3.2)
[RAFT]0 + df ([I]0 − [I]t )
3.2 IP Landscape
There is now no barrier to scale up RAFT polymerization procedures as RAFT

agents are now commercially available in gram to ton quantities through Boron
Molecular, http://www.boronmolecular.com/raftmonotable, in smaller quantities
from chemical suppliers such as STREM, Merck (Sigma-Aldrich), and FUJIFILM
Wako Pure Chemical Corporation, and due to the expiration of a number of the
foundation patents there is increased freedom to utilize RAFT technology. At the
time of printing, if a user is polymerizing a monomer using traditional RAFT
agents such as 1–7 or 12, using traditional manufacturing methods described in
WO/98/01478 or WO/99/31144, then the user may, after making their own assess-
ment, make RAFT-based polymers without seeking a licence from CSIRO, and in
any field. If the user is polymerizing a monomer using any new and improved RAFT
agents such as 8–11 protected by CSIRO-held patents, such as those stemming from
the published applications (WO/2010/083569, WO/2016/197187, WO/2016/054689,
and WO/2017/035570) then they will need to seek a licence directly from CSIRO,
or by buying the RAFT agents from a licenced commercial supplier subject to a
label licence. A summary of the current field restrictions and patent coverage of
commonly used RAFT agents is provided in Table 3.2. The label licence sets out
the conditions for use of the RAFT agents 8–11 and allows the end user to use the
RAFT agents for applications outside specifically listed electronics fields. This is
because DuPont still holds commercial interest in a few electronic fields and thus
users will require pre-approval from DuPont in those fields. Purchasing of RAFT
agents from a research supplier may still require a licence from CSIRO, depending
on the RAFT agents and the polymerization method adopted and the functionality
or end use that is anticipated.
3.3 General Experimental Conditions
In the laboratory, solvents are generally of analytical reagent grade and distilled
before use. To remove inhibitors and for further purification, monomers are
filtered through neutral or basic alumina (70–230 mesh), fractionally distilled
under reduced pressure, and redistilled under reduced pressure immediately
prior to use. Initiators such as azobisisobutyronitrile VAZO-64® (AIBN) and
1,1′ -azobis(cyclohexanenitrile) VAZO-88® (ACHN) are purified by crystallization
Table 3.2 Summary of field restrictions for commonly used RAFT agents.
Electronic field
RAFT agent Patent restriction
S WO/98/01478 Expired
S
S CN
2
S
S S
4
C12H25 OH
S S
O
5
O S WO/98/01478 Expired
OH
HO S S
6 O
S CN WO/98/01478 Expired
C12H25 OH
S S
O
7
O S CN WO/2017/035570 Yes
OH
HO S S
8 O
S WO/2016/197187 Yes
N
H3C N S CN
CH3
9
S NC WO/2016/197187 Yes
N
H3C N S
CH3
10
S NC WO/2016/054689 Yes
N
H3C N S
CH3
Cl
11
N S CN
12
Table 3.3 Bulk RAFT polymerization of un-purified

commercial MMA with 4-cyano-4-(((dodecylthio)
carbonothioyl)thio)pentanoic acid 7 under various
degassing methods (10 g MMA, 20 mg 7, 5 mg AIBN at
80 ∘ C for time specified) [2].
Time Conversion
Atmosphere (h) (%) M n a) Ð
Freeze–evacuate 1.5 93 100 000 1.25

N2 flush 1.5 87 90 000 1.25
In airb) 1.5 26 38 000 1.38
In airb) 3.0 88 112 000 1.26
a) GPC molecular weight in PSt equivalents.

b) No degassing.
Source: Moad et al. [2]. © CSIRO.
from chloroform/methanol. These precautions allow for reproducibility in a

laboratory setting, but are not necessary for successful RAFT polymerization;
un-purified monomers and initiators will work effectively, and small adjustments
to the amount of initiator may be needed to account for impurities or incomplete
degassing. The effects of these factors are exemplified for methyl methacrylate
(MMA) with the bulk RAFT polymerization of un-purified commercial MMA
with the RAFT agent 4-cyano-4-(((dodecylthio)carbonothioyl)thio)pentanoic acid
7 under various degassing methods; it is seen that all polymerizations provide
narrow molecular weight distributions and molecular weight control. However,
polymerizations with no degassing give substantial retardation. All polymerizations
yield a lower-than-expected molecular weight, which is attributed to the use of
un-purified monomer (and molecular weights are in polystyrene equivalents); see
Table 3.3, [2]. In the laboratory, freeze–evacuate–thaw cycles are often used to degas
polymerization solutions; bubbling or flushing with nitrogen produces very similar
results, as exemplified in Table 3.3. Different monomer systems or experimental
setups could provide considerably different outcomes to these results for MMA
RAFT polymerization.
RAFT polymerization provides the ability to control the polymerization of most
monomers polymerizable by conventional radical polymerization. These include
(meth)acrylates, (meth)acrylamides, acrylonitrile, styrenes, dienes, and vinyl
monomers. It is tolerant of unprotected functionality in the monomer and the
solvent (e.g. OH, NR2 , COOH, CONR2 , SO3 H). The process is compatible with a
wide range of reaction conditions (e.g. bulk, organic or aqueous solution, emulsion,
miniemulsion, suspension).
The polymerization conditions for RAFT polymerization (bulk or solution) are
generally the same as for conventional radical polymerization. Sections 3.3.1–3.3.4
describe the generic requirements for RAFT polymerization, outside of conventional
radical polymerization, that are helpful in achieving favourable outcomes.
3.3.1 Initiator
For polymerizations under RAFT control, careful attention must be paid to the
selection and concentration of radical initiators, with the initiator concentration or
radical generation chosen such that there is an acceptable rate of polymerization
and a low level of radical–radical termination (dead chains). Prolonged polymer-
ization times should be avoided; once full monomer conversion is achieved further
exposure to the generated radical can result in dead chains and unwanted radical
side reactions.
Conventionally, thermal initiators are used as a radical source (e.g. AIBN,
azobis(4-cyanopentanoic acid) [ACPA], dibenzoyl peroxide, potassium peroxydisul-
fate). However, polymerizations can be initiated with any source of radicals – redox
[4, 5], UV and visible [6–9], and γ sources [10–15].
Styrene can self-initiate above 100 ∘ C without the need for an external source of
radicals [16].
It should be noted that some initiators (e.g. peroxides and peroxydisulfates) may
oxidize RAFT agents and RAFT end-groups [17].
3.3.2 Solvent
The RAFT process is compatible with a wide range of solvents, functional groups,
and reaction media, mirroring conventional radical polymerization conditions.
These include common organic solvents, protic solvents (alcohols, water [18–21],
ionic liquids [22]), and supercritical carbon dioxide [23, 24]. Functional groups
to be avoided include primary amines. Care should also be taken in polar media,
increasing pH, and when using Lewis acids as RAFT agents can show hydrolytic
sensitivity [25–27]. From this, we can infer a trend indicating that the sensitivity is
highest with dithiobenzoates, lower with trithiocarbonates or aliphatic dithioesters,
and the lowest with dithiocarbamates [25–28].
3.3.3 Temperature
RAFT polymerizations have been performed from below ambient up to 140 ∘ C.
Higher temperatures provide higher propagation rates, allowing a higher conversion
to be achieved in a shorter period of time. Greater RAFT agent transfer constants
and fragmentation rate constants of the intermediates can also be achieved at
higher temperatures. In line with this, there is some data to show that narrower
molecular weight distributions and reduction in retardation with dithiobenzoates
can be obtained at higher temperatures [29].
RAFT agents and RAFT polymer end-groups are known to be unstable at high
temperatures for prolonged times [30–35]. In some cases, the RAFT agent is less
stable than the resulting polymer end-group, at elevated temperatures. Under those
conditions it is best to tailor the polymerization to have fast RAFT agent consump-
tion to the more stable RAFT polymer.
3.3.4 Pressure
High pressure conditions (1–5 kbar) reduce radical–radical termination and increase
propagation, allowing for the formation of higher molecular weight polymers at
higher polymerization rates [36–39].
The following sections will outline how RAFT polymerization of styrenes
(Section 3.4), (meth)acrylates (Section 3.5), (meth)acrylamides (Section 3.6), and
vinyl monomers (Section 3.7) can be achieved under various conditions and detail
the appropriate experimental methodology for the construction of block copolymers
(Section 3.8) using RAFT polymerization.
3.4 RAFT Polymerization of Styrene

Styrene was one of the first monomers used to demonstrate the RAFT process [40].
We demonstrated the effect on molecular weight and dispersity with the addition
of 2-phenyl-2-propyl benzodithioate 1 to a conventional radical polymerization. It
was shown that thermal polymerization of styrene at 110 ∘ C for 16 hours resulted
in a 72% conversion to polystyrene of M n = 323 700 and Ð = 1.74, whereas in the
presence of 1.47 × 10−2 M 1, polystyrene of M n = 30 900 and Ð = 1.05 was obtained in
53% yield (Figure 3.3). The lower conversion in the presence of the dithio compound
is most likely due to a reduction in the gel effect brought about by the formation of a
lower molecular weight polymer. Since this initial work, it has been shown that with
lower concentrations of RAFT agents such as 1 or 2-cyano-2-propyl benzodithioate
2 (<0.03 M) the rates of polymerization for styrene and MMA do not vary greatly
from that expected in the absence of RAFT agent and appear independent of the
particular dithiobenzoate [41–43].
Styrene is a secondary more activated monomer (2∘ MAM). Good control
over RAFT polymerization of styrene and styrenic derivatives requires a RAFT
agent suitable for 2∘ MAMs (see Table 3.1). RAFT agents that are suitable for the
Conventional
(a)
Mn = 323 700 Mw /Mn = 1.74
RAFT
(b) Mn = 30 900 Mw /Mn = 1.05
30 35 40 45 50 55 60
GPC elution time (min)
Figure 3.3 Comparison of conventional and RAFT polymerization. (a) Thermal polymeri-
zation of styrene at 110 ∘ C. (b) Thermal polymerization of styrene at 110 ∘ C in the presence
of 1.47 × 10−2 M of 2-phenyl-2-propyl benzodithioate 1. Source: Rizzardo et al. [40]. © John
Wiley and Sons.
B OH
O S O O
O O O
Si HN
F F
S
F F O
F
13 14 15 16
N N
O C
S
Si(CH3)3 N
S
N
17 18 19 20
Figure 3.4 Examples of functional styrenic monomers amenable to RAFT polymerization.
polymerization of styrene are primary, secondary, and tertiary dithiobenzoates

(Z = Ph), trithiocarbonates (Z = S-R′ ), and pyrazole dithiocarbamates (Z = N-R′ N).
RAFT agents that are ineffective for the controlled polymerization of styrene are
dithiocarbamates (Z = N-R′ 2 ) and xanthates (Z = O-R′ ). The RAFT polymerization
of styrene can be done in bulk, solution, emulsion, or dispersion. RAFT polymer-
ization has been carried out successfully on a number of functional styrenes as
depicted in Figure 3.4. These include monomers that contain bulky pendant groups
13 [44], active ester or similar functionality (14, 15) [45, 46], boroxole functionality
16 [47], or alkyne 17 [48] functionality. Many of the functional styrenes have been
used to prepare polymers for optoelectronic use (18, 19) [49, 50]. Isocyanate or
isothiocyanate functionality 20 [48] is compatible with RAFT polymerization;
however, some care must be taken in the selection of the RAFT agent and other
components of the polymerization medium such that they do not also contain other
functionalities that are inherently reactive (such as carboxy) [51].
3.4.1 Experimental Procedures for the RAFT Polymerization of Styrene

Bulk polymerization of styrene in the presence of 2-phenyl-2-propyl benzodithioate 1
at 100 ∘ C. A stock solution of styrene 25 ml and 1 (200 mg) was prepared and 5 ml
was transferred to four separate ampoules; the ampoules were degassed with three
O OH
S S S
C12H25 OH C4H9 C4H9
S S S S CN S S
O
21 22 23
S S S
CN HO OH O
S S S O S
O O O
24 26
25
S CN S N S
OH R
S N S CN N S
O
27 28 29 R = CH2CN
30 R = CH(CH3)CO2CH3
S S S
O O
O S N S O S
OH O
31 32 33
Figure 3.5 Selection of RAFT agents described in experimental procedures. RAFT agents
also appear in Tables 3.1 and 3.2.
Table 3.4 Molecular weight/conversion data for the

bulk thermal polymerization of styrene at 100 ∘ C in the
presence 1 (0.029 M).
Time Conversion M n(Calc)

(h) (%) M n a) (g mol−1 )b) Ð
2 4.3 1 500 1 300 1.12

6 14.3 5 700 4 500 1.08
20 40.0 13 800 12 500 1.08
64 81.0 25 200 25 300 1.12
a) GPC molecular weight in PSt equivalents.

b) Calculated molecular weight using Eq. (3.1), (g mol−1 ).
Source: Rizzardo et al. [40]. © John Wiley and Sons.
freeze–evacuate–thaw cycles, sealed, and heated at 100 ± 1 ∘ C for the periods of

time indicated in Table 3.4. The excess monomer and solvent were removed by
evaporation at ambient temperature under vacuum and the residues analyzed
directly by GPC; see Table 3.4 [40].
Initial work into RAFT-mediated styrene emulsion polymerization demonstrated
a major limitation of the RAFT process, due to the lack of colloidal stability,
suggesting that RAFT agent transportation was problematic. The success in

all RAFT emulsion polymerization depends strongly on the choice of RAFT
agent and polymerization conditions. This is attributed in part to the slow
transportation of the RAFT agent between the droplet phase and the particle
phase and in part to the way in which molecular weight distributions evolve
during RAFT polymerization. Successful heterogeneous RAFT experiments
rely on rapid co-localizing of the RAFT agent with the particulate phase. In the
past, these emulsion polymerizations have been successfully achieved through
starve-feeding of the emulsion, seeded particle approach, and later via an
amphiphilic macroRAFT approach. These can be performed via multistep pro-
cesses, use amphiphilic macroRAFT agents, and/or make use of miniemulsion or
seeded emulsion techniques (a summary of the development of RAFT emulsion
polymerization [52] and discussion on emulsion polymerization are captured in
chapter 15 on this book [53] and its corresponding publication [54]).
Emulsion polymerization of styrene in the presence of RAFT agent 3 at 80 ∘ C.
A five-neck reaction vessel equipped with a condenser, thermocouple, and
mechanical stirrer was charged with water (75 g) and sodium dodecyl sulfate
(3 g of 10% aqueous solution). The solution was heated at 80 ∘ C for 40 minutes
while purging with nitrogen. ACPA (211 mg) and benzyl dithiobenzoate (3)
(228 mg) in styrene (4.7 g) were then added. Further styrene (39.2 g, 0.2 ml min−1 )
and initiator (211 mg in 24 g of 1% [w/w] aqueous sodium dodecyl sulfate,
0.089 ml min−1 ) were added by syringe pumps. After completion of the feeds,
the reaction was held at 80 ∘ C for 90 minutes. The polymerization was sampled
periodically to establish conversion and for GPC analysis. Final polymerization
results (>99%, M n = 53 200; Ð = 1.37) [41].
Surfactant-free emulsion polymerization of styrene in the presence of poly(N,N-dime-
thylacrylamide PDMAm-macroRAFT agent at 80 ∘ C: PDMAm-macroRAFT agent.
Polymerization of 4.0 g of N,N-dimethylacrylamide DMAm (2.0 mol l−1 ) was
carried out in 16 ml of 1,4-dioxane with ACPA (5.7 mg, 1.0 × 10−3 mol l−1 ) and
S,S′ -bis(α,α′ -dimethyl-α′′ -acetic acid)-trithiocarbonate 25 (74 mg, 1.0 × 10−2
mol l−1 ); a small amount (242 mg, 0.13 mol l−1 ) of 1,3,5-trioxane was added as
an internal reference for determination of the monomer consumption by 1 H
NMR spectroscopy. The solution was poured in a septum-sealed flask, purged for
30 minutes with nitrogen in an ice bath, and heated to 80 ∘ C in a thermostatted
oil bath under stirring, for 13 minutes. The polymerization was quenched by
immersion of the flask in iced water. The polymer was recovered by two precipi-
tations in petroleum ether and dried under reduced pressure (47%, M n = 10 700,
Ð = 1.09).
Emulsion polymerization of styrene. The aqueous emulsion polymerization of
styrene was performed at 80 ∘ C at a stirring speed of 375 rpm, using an initial
monomer concentration of 1.1 mol l−1 latex (11 wt% with respect to the total
latex) and a macroRAFT/initiator molar ratio of 5 : 1. In a typical experiment,
323 mg of poly(N,N-dimethylacrylamide) macroRAFT agent (M n = 10 700;
3.8 × 10−3 mol l−1 ) was dissolved in 7.39 ml of deionized water. Then, 0.5 ml of
a stock solution of ACPA in water (concentration of 4.4 g l−1 neutralized by
3.5 M equivalent of sodium bicarbonate (NaHCO3 )) and 1.01 g (9.7 × 10−3 mol) of
styrene was added. After deoxygenation by bubbling with nitrogen for 30 minutes,
the septum-sealed flask containing the reaction mixture was immersed in an oil
bath thermostatted at 80 ∘ C for four hours. The polymerizations were quenched
by immersion of the sample vials in iced water and conversion was determined
by gravimetry (83%, M n = 39 600; Ð = 1.73) [55].
Surfactant-free emulsion polymerization of styrene in the presence of poly(ethylene
oxide) (PEO) macroRAFT agent. PEO-MacroRAFT Agent – A solution
of 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid 21 (1.82 g,
5 × 10−3 mol), N,N ′ -dicyclohexylcarbodiimide (DCC) (1.03 g, 5 × 10−3 mol),
and 4-(dimethylamino)pyridine (DMAP) (0.06 g, 5 × 10−4 mol) in 40 ml of
anhydrous tetrahydrofuran (THF) was introduced under nitrogen atmosphere
in a flask containing 5 g of dried α-methoxy ω-hydroxy poly(ethylene oxide)
(MPEO) (2.5 × 10−3 mol). The esterification reaction proceeded under stirring
at room temperature for 120 hours. The polymer was recovered by precipitation
of the mixture in cold diethyl ether. After filtration, the product was dried
under vacuum at 40 ∘ C and stored at 5–8 ∘ C (90%, M n = 2420 g mol−1 [NMR];
end-functionality: >95%). The macroRAFT agent can also be obtained commer-
cially at several molecular weights, as a trithiocarbonate or dithiobenzoate, and
with two different R leaving groups from suppliers such as Merck/Sigma Aldrich.
Emulsion polymerization of styrene. Surfactant-free batch emulsion polymerization
of styrene was conducted in the presence of PEO-TTC [styrene]0 /[PEO-TTC]0
= 145. In a typical experiment, 0.18 g PEO-TTC (0.073 mmol) was dissolved in
7.63 g of deionized water. Then, 1.04 g of styrene (10.0 mmol) was added to the
solution in a 25 ml septum-sealed flask. An aqueous stock solution of ACPA
was prepared (10 mg ml−1 ) and neutralized by NaHCO3 (3.5 M equivalents with
respect to ACPA). Finally, 0.48 ml of this solution (ACPA: 0.017 mmol) was added
to the reaction mixture, deoxygenated by bubbling with nitrogen for 30 minutes
at 3 ∘ C, and then immersed in an oil bath thermostatted at 80 ∘ C for 23 hours
(67%, M n = 12 200; Ð = 1.16, Dz = 260 nm (0.16) dispersity, N p = 9.7 × 1012
(glatex −1 )) [56].
3.5 RAFT Polymerization of Methacrylates and Acrylates

The choice of RAFT agent is critical in the success of the polymerization; this is
particularly important in relation to methacrylates. Figure 3.1 provides a general
summary of how to select the appropriate RAFT agent for particular monomers.
Note should be made of the dashed lines in the chart, particularly in relation to the
choice of R group for methacrylate polymerization. Although some control might
be achieved with these monomer/RAFT agent combinations, the molecular weight
distribution may be broad or there may be substantial retardation or prolonged
inhibition. Aromatic dithioesters such as 1 and 2 are among the most active RAFT
agents and have general utility in the polymerization of methacrylates and acrylates.
However, these RAFT agents may give retardation particularly when used in high
concentrations and are more sensitive to hydrolysis and decomposition induced by

Lewis acids [57]. The RAFT polymerization of acrylates and methacrylates can be
carried out in bulk, solution, emulsion, or dispersion polymerization. RAFT agents
that are ineffective for the controlled polymerization of acrylates and methacrylates
are dithiocarbamates and xanthates.
3.5.1 Methacrylates
Methacrylates are tertiary more activated monomers (3∘ MAMs). Good control over
RAFT polymerization of methacrylates requires a RAFT agent suitable for 3∘ MAMs
(Table 3.1, Figure 3.5). Methacrylates can only be homopolymerized in the pres-
ence of 3∘ dithiobenzoates (Z = Ph), trithiocarbonates (Z = S-R′ ), and some pyrazole
dithiocarbamates (Z = N-R′ N). RAFT agents that are ineffective for the controlled
polymerization of methacrylates are 2∘ dithiobenzoates (Z = Ph), trithiocarbonates
(Z = S-R′ ), pyrazole dithiocarbamates (Z = N-R′ N), dithiocarbamates (Z = N-R′ 2 ),
and xanthates (Z = O-R′ ).
A wide range of methacrylate monomers have been successfully polymerized
under RAFT reaction conditions to produce polymers of controlled molecular
weight and low dispersity. These include 2-(acetoacetoxy)ethyl methacrylate,
2-aminoethyl methacrylate (hydrochloride), allyl methacrylate, cholesteryl
methacrylate, butyl methacrylate, t-butyldimethylsilyl methacrylate, (diethylene
glycol monomethyl ether)methacrylate, 2-(diethylamino)ethyl methacrylate,
(ethylene glycol monomethyl ether)methacrylate, 2-hydroxyethyl methacry-
late, hexyl methacrylate, isobutyl methacrylate, dodecyl methacrylate, methyl
methacrylate, methacryloyloxyethyl phosphorylcholine, (poly(ethylene gly-
col)monomethyl ether)methacrylate, pentafluorophenyl methacrylate, and
2-(trimethylammonium)ethyl methacrylate, as well as a variety of less com-
mon functional acrylate and methacrylate monomers (depicted in Figure 3.3),
demonstrating that steric bulk 34 [58], a variety of functional groups including
glycomonomers 35 [59], protected thiol 36 [60, 61], ferrocenyl 37 [62], isocyanate
38 [63], ketal 39 [64], and oleyl-based monomers 40 [44] are compatible with the
RAFT polymerization process.
3.5.2 Acrylates
Acrylates are 2∘ MAMs. Good control over RAFT polymerization of acrylates
requires a RAFT agent suitable for more activated monomers (MAMs) (see
Table 3.1, Figure 3.5). Acrylates can be polymerized in the presence of the fol-
lowing classes of primary, secondary, and tertiary RAFT agents: dithiobenzoates
(Z = Ph), trithiocarbonates (Z = S-R′ ), and pyrazole dithiocarbamates (Z = N-R′ N).
RAFT agents that are ineffective for the controlled polymerization of acrylates are
dithiocarbamates (Z = N-R′ 2 ) and xanthates (Z = O-R′ ). The best control is with
the use of trithiocarbonates, aliphatic dithioester, or activated dithiocarbamates.
Dithiobenzoates can impart good control under conditions where low reaction
temperatures or high RAFT agent concentrations are avoided, or retardation and
inhibition will be observed.
O O O O O O
O OH O O O
OH
HO OH S NCO
S
N
Fe
34 35 36 37 38
O
O
O O
O
O
S
O
S
O
O
O
O
O
41
39 40
Figure 3.6 Examples of functional methacrylate and acrylate monomers amenable to

RAFT polymerization.
A wide range of acrylate monomers with a variety of functional groups and

steric bulk have been successfully polymerized under RAFT control to produce
polymers of controlled molecular weight and low dispersity. These include
2-(acryloyloxy)ethyl phosphate, butyl acrylate (BA), 3-chloropropyl acrylate, dode-
cyl acrylate, di(ethylene glycol) 2-ethylhexyl ether acrylate, 2-(dimethylamino)ethyl
acrylate, ethyl acrylate, ethoxyethyl acrylate, ethyl α-acetoxyacrylate, 2-ethylhexyl
acrylate, isobornyl acrylate, methyl acrylate, propargyl acrylate, (poly(ethylene
glycol) monomethyl ether)acrylate, t-butyl acrylate (tBA), and disulfide linker 41
[65] to list but a few (Figure 3.6).
3.5.3 Experimental Procedures for the RAFT Polymerization

of Methacrylates
Solution polymerization of MMA at 90 ∘ C in the presence of 4-cyano-4-(((dodecylthio)
carbonothioyl)thio)pentanoic acid 7. An aliquot (2 ml) of a stock solution com-
posed of MMA (14 ml), ACHN (9.8 mg), and benzene (6 ml) was added to each of a
series of ampoules containing weighed amounts of 7. The contents were degassed,
Table 3.5 Molecular weights and molar mass dispersities for

PMMA formed by polymerization of MMA (6.55 M) with ACHN
(0.0018 M) as initiator and RAFT agent 7 for six hours at 90 ∘ C [66].
[RAFT]0 M n(Calc) Conversion

(M × 102 ) M n a) (g mol−1 )b) Ð (%)
19.92 2 870 3 000 1.18 80

9.96 5 040 5 600 1.14 80
4.95 9 940 10 400 1.12 79
2.48 21 800 22 600 1.13 91
1.24 41 100 45 300 1.14 >99
0.61 80 900 80 100 1.13 >99
0.32 126 000 125 000 1.15 >99
a) Calculated from Eq. (3.2) (d = 1.67 for PMMA with ACHN) [42]
and f is the initiator efficiency (taken as 0.5). It was calculated
from the known value of kd (kd = 2.53 × 10−5 M−1 s−1 at 90 ∘ C for
ACHN) [67, 68].
b) GPC molecular weight: PMMA molecular weights are based on
use of a Universal calibration and Mark–Houwink–Sakaruda
parameters of K = 11.4 × 108 g l−1 , 𝛼 = 0.716 (PMMA) and
K = 9.44 × 108 g l−1 , 𝛼 = 0.719 (polystyrene) [69].
Source: Moad et al. [66]. © Elsevier.
the ampoules sealed, and heated at 90 ∘ C for six hours. The polymer was isolated
by exhaustive evaporation of monomer or precipitation in methanol and conver-
sions were determined gravimetrically. Molecular weight and conversion data are
shown in Table 3.5 [66].
Solution polymerization of methyl methacrylate at 100 ∘ C in the presence of 2-cyano-
butan-2-yl 4-chloro-3,5-dimethyl-1H-pyrazole-1-carbodithioate 11. A solution con-
taining MMA (0.64 mL, 3.5 M), 1,1′ -azobis(cyclohexanenitrile) (ACHN) (2.58 mg,
0.005 M), 11 (14.2 mg, 0.03 M), trioxane (10 mg; internal standard) and acetoni-
trile (1.36 mL) was prepared in a 5 mL microwave vial. The resulting mixture
was degassed, sealed and heated at 100 ∘ C by microwave irradiation for 4 h.
The volatiles were removed in vacuo to give poly(MMA) (72%, M n = 8,400;
Ð = 1.34) [3].
Solution polymerization of 6-O-methacryloyl mannose (MAMan) glycomonomer 35 in
the presence of 2-phenyl-2-propyl benzodithioate 1 at 70 ∘ C. In a round-bottom flask
1.0 g (4.028 mmol) MAMan, 5.59 mg (0.020 mmol) 1, and 0.66 mg (0.004 mmol)
AIBN were dissolved in 10 ml N,N-dimethylacetamide (DMAc), sealed with a sep-
tum, and degassed by bubbling with nitrogen for several minutes. The flask was
heated at 70 ∘ C in an oil bath for 180 minutes. Polymer purification was performed
by precipitating the polymer in methanol, followed by freeze-drying from water
(73%, M n = 42 500; Ð = 1.23) [70].
Solution polymerization of MMA with 2-cyano-2-propyl benzodithioate 2 at 60 ∘ C.
AIBN (4.4 mg, 2.67 × 10−5 mol) and 2 (11.8 mg, 5.342 × 10−5 mol) were weighed
into a 25 ml Schlenk tube inside a glove box. Nitrogen-purged MMA (2 ml,

18.69 mmol) and dry toluene (0.7 ml) were then added to the Schlenk tube and
immediately frozen on a liquid N2 bath. The solution was degassed with three
freeze–pump–thaw cycles using N2 and warmed to room temperature and then
heated at 60 ∘ C for 20 hours. The polymer sample was collected on precipitation
from excess hexane, which was dried in a vacuum oven (93%, M n = 25 900;
M n(calc) = 32 700 g mol−1 ; Ð = 1.20) [71].
Solution polymerization MMA in the presence of 2-cyano-2-propyl benzodithioate 2
at 70 ∘ C. MMA (5.00 ml, 4.67 × 10−2 mol) was placed in a Schlenk tube along
with 2 (1.03 × 10−1 g, 4.68 × 10−4 mol) and AIBN (7.68 × 10−3 g, 4.68 × 10−5 mol)
with a ratio of [MMA]:[2]:[AIBN] = 1000 : 10 : 1. The reagents were dissolved
in acetonitrile (9.36 ml) and the Schlenk tube was sealed and subjected to four
freeze–pump–thaw cycles. After the last cycle the tube was refilled with dry nitro-
gen and the Schlenk tube was placed in a preheated oil bath (70 ∘ C) for 16 hours.
The polymer was collected by precipitation into a cold mixture of methanol
and water (75 : 25) and dried under vacuum. The traces of monomers were
removed by Soxhlet extraction for four hours in methanol to obtain a pink solid
of poly(methyl methacrylate) (PMMA) (conversion = 70%, M n (NMR) = 7230;
M n (GPC) = 7600; Ð = 1.09) [72].
Solution polymerization of benzyl methacrylate (BnMA) in the presence of 2-phenyl-
2-propyl benzodithioate 1 at 70 ∘ C. 1 (81.6 mg, 0.30 mmol), AIBN (9.8 mg,
0.06 mmol), and benzyl methacrylate BnMA (3.172 g, 18.00 mmol) were dis-
solved in 7 ml of anisole in a Schlenk tube. The solution was degassed with N2
for 30 minutes. The tube was sealed with a rubber septum and immersed in
a water bath that was preheated at 70 ∘ C for the times specified in Table 3.6.
Aliquots were withdrawn at determined time intervals and analyzed by 1 H
NMR spectroscopy and GPC with N,N-dimethylformamide (DMF) as a mobile
phase for monitoring the degree of polymerization of BnMA. After six hours, the
polymerization was quenched by immersing the tube into liquid nitrogen and
opening to the air. The reaction mixture was diluted with THF and precipitated
three times with hexane before being vacuum dried to obtain a pink powder of
the PBnMA homopolymer [73].

of Acrylates
Solution polymerization of n-butyl acrylate in the presence of 2-cyano-2-propyl ben-
zodithioate 2 at 60 ∘ C. A solution containing butyl acrylate (2.0 g), 2 (17.3 mg), and
AIBN (0.5 mg) was placed in an ampoule, degassed with three freeze–evacuate–
thaw cycles, sealed, and heated at 60 ∘ C for 16 hours. Removal of the volatiles
under reduced pressure provided a pink polymer (0.5 g, 25% conversion,
M n = 6200, Ð = 1.07). A similar procedure can be used in the presence of
2-cyano-propan-2-yl butyl trithiocarbonate 22: butyl acrylate (2.0 g), 22 (72.8 mg),
and AIBN (5.1 mg) were degassed and heated at 60 ∘ C for 16 hours, with 95%
conversion, M n = 6800; Ð = 1.07 [74].
Table 3.6 RAFT polymerization of BnMA using 1 as a

chain transfer agent.
Time Conversion
(min) (%)a) M n(GPC) b) Ð
90 40 3000 1.16
180 68 3800 1.21
270 83 4300 1.22
360 89 4800 1.17
a) NMR.
b) Poly(ethylene oxide) (PEO) equivalents.
Source: Data from Wei et al. [73].
Surfactant-free batch emulsion polymerization of n-butyl acrylate at 70 ∘ C in the

presence of PEO-TTC. 0.1670 g PEO-TTC (0.069 mmol) (see Section 3.4.1) was
dissolved in 7.63 g of deionized water, and 1.28 g of n-butyl acrylate (10.0 mmol)
was added to the solution in a 25 ml septum-sealed flask. An aqueous stock
solution of ACPA was prepared (10 mg ml−1 ) and neutralized by NaHCO3 (3.5 M
equivalents with respect to ACPA). Finally, 0.48 ml of this solution (ACPA:
0.017 mmol) was added to the reaction mixture, deoxygenated by bubbling with
nitrogen for 30 minutes at 3 ∘ C, and then immersed in an thermostatted oil
bath at 70 ∘ C for seven hours (M n = 22 200; Ð = 1.26; 96%; Dz = 200 nm (0.16)
dispersity; N p = 3.3 × 1013 (glatex −1 )) [56].
Solution polymerization of 3,5-dibromobenzyl acrylate in the presence of S,S-dibenzyl
trithiocarbonate 4 at 70 ∘ C. 3,5-Dibromobenzyl acrylate (2.8 g; 0.0087 mol), 4
(0.1626 g; 5.6 × 10−4 mol), and AIBN (0.0184 g; 1.12 × 10−4 mol) in THF (5 ml)
were degassed with argon for 15 minutes. The reaction flask was sealed under
high vacuum pressure and then immersed into an oil bath preheated to 70 ∘ C.
After five hours, the reaction was quenched by placing the flask in liquid
nitrogen, and the reaction mixture was diluted with THF and precipitated into
acetone (300 ml). The polymer was collected by filtration to give a yellow powder
(1.68 g; 60.0%; M n = 2200; Ð = 1.3) [75].
Solution polymerization of 2-ethylhexyl acrylate in the presence of S,S-dibenzyl
trithiocarbonate 4 at 70 ∘ C. 2-Ethylhexyl acrylate (10.07 g; 0.054 mol), 4 (0.58 g;
2.0 × 10−3 mol), and AIBN (0.065 g; 4.0 × 10−4 mol) in THF (10 ml) were purged
with argon for 30 minutes and immersed into an oil bath preheated to 70 ∘ C.
After six hours, the reaction was quenched in liquid nitrogen, and the mixture
was diluted with acetone and precipitated into cold methanol/water (50 : 50;
300 ml). The polymer was collected by decantation and dried, to give a viscous
yellow oil (yield = 6.54 g; 65%; M n = 3700; Ð = 1.2) [74].
Solution polymerization of octadecyl acrylate in the presence of S,S-dibenzyl trithiocar-
bonate 4 at 70 ∘ C. Octadecyl acrylate (10 g; 0.0308 mol), 4 (0.580 g; 2.0 × 10−3 mol),
and AIBN (0.0656 g; 4.0 × 10−4 mol) in THF (10 ml) were purged with argon for
20 minutes and immersed into an oil bath preheated to 70 ∘ C. After five hours,
the reaction was quenched in liquid nitrogen, and the mixture was diluted with
THF and precipitated into methanol (300 ml). The polymer was filtered off to give
a yellow powder (yield = 5.9 g; 59%, M n = 9100, Ð = 1.3) [75].
Solution polymerization of oligo(ethylene glycol) acrylate (M n = 480 g mol−1 ) (OEGA-
480) in the presence of 2-(butylthiocarbonothioylthio)propanoic acid 23 at 70 ∘ C. A
mixture of 480 mg of OEGA480 (1 mmol), 29.8 mg of 23 (0.125 mmol), and 2 mg of
AIBN (0.013 mmol) were dissolved in 2 ml absolute ethanol in a capped vial lead-
ing to a final monomer concentration of 0.5 mol l−1 . The reaction mixture was
bubbled with argon for half an hour. The reaction solution was placed in a pre-
heated oil bath at 70 ∘ C. After five hours, the mixture was cooled to ambient tem-
perature. The solution was precipitated into cold diethyl ether (92%; M n = 3600;
Ð = 1.15) [76].
Solution polymerization of acrylic acid (AA) in the presence of 2-dodecylsulfanyl-thio-
carbonylsulfanyl-2-methylpropionic acid 21 at 80 ∘ C. Acrylic acid (AA) (7.20 g,
0.1 mol), 24 (364 mg, 1 mmol), THF (8.0 ml), and AIBN (16.4 mg, 0.1 mmol) with
the molar ratio of AA/24/AIBN 1000 : 10 : 1 were added to a 25 ml polymerization
vial with a magnetic stirring bar. After three freeze–evacuate–thaw cycles, the
vial was sealed under high vacuum and placed in an oil bath at 80 ∘ C while
stirring. After two hours, the vial was cooled to room temperature by placing
in an ice/water bath and opened. Poly(acrylic acid) (PAA) was obtained by
the precipitation of polymerization mixture into excess diethyl ether under
filtration and vacuum drying at room temperature overnight (61%; M n = 4400;
Ð = 1.13) [77].
Redox-initiated solution polymerization of t-butyl acrylate (tBA) in the presence of
2-dodecylsulfanyl-thiocarbonylsulfanyl-2-methylpropionic acid 21 at −5 ∘ C. tBA
(0.64 g, 5 mmol), 24 (18.2 mg, 0.05 mmol), ascorbic acid (17.6 mg, 0.1 mmol),
and dioxane (5.0 ml) were added into a 25 m, round-bottom flask equipped with
a magnetic stirring bar. Another portion of dioxane was added until the total
solution volume was 9.0 ml. The flask was sealed with a rubber septum, and the
mixture was purged with nitrogen for 30 minutes at 10 ∘ C. A dioxane solution of
cumene hydroperoxide (1.0 ml, 50 mM) was injected into the reaction mixture.
The flask was subsequently kept in the chamber of a cryoreactor (DHJF-4002,
Greatwall Scientific Industry & Trade Co. Lt., China) at −5 ∘ C for 32 hours. The
polymerization was stopped by rapid cooling in liquid nitrogen for a fixed dura-
tion. After the polymerization was stopped, the reaction mixture was precipitated
in a large excess of methanol/H2 O (2/1, v/v) at −20 ∘ C, followed by purification
by further precipitation and drying under vacuum at room temperature (94%;
M n = 10 900; Ð = 1.05) [78].
3.6 RAFT Polymerization of Acrylamides

and Methacrylamides
Acrylamides and methacrylamides are MAMs. RAFT polymerization of acry-
lamides and methacrylamides requires a RAFT agent suitable for MAMs (see
Table 3.1, Figure 3.5); these include dithiobenzoates (Z = Ph), trithiocarbonates

(Z = S-R′ ), and pyrazole dithiocarbamates (Z = N-R′ N). RAFT agents that are
ineffective for the controlled polymerization of acrylamides are dithiocarbamates
(Z = N-R′ 2 ) and xanthates (Z = O-R′ ). The RAFT polymerization of acrylamides
and methacryamides can be carried out in bulk, solution, or by emulsion poly-
merization. RAFT homo- and copolymerization resulting in controlled molecular
weight and low dispersity have been achieved for a variety of acrylamides and
methacrylamides.
3.6.1 Methacrylamides
The choice of RAFT agent for polymerization of methacrylamides is subject to
similar constraints as mentioned for the methacrylates. In particular, the ‘R’ group
should be selected so as to be a good leaving group with respect to the propagating
radical. Methacrylamides are 3∘ MAMs. Good control over RAFT polymerization
of methacrylamides requires a RAFT agent suitable for 3∘ MAMs (Table 3.1,
Figure 3.5). Methacrylamides can only be homopolymerized in the presence of 3∘
dithiobenzoates (Z = Ph), trithiocarbonates (Z = S-R′ ), and some pyrazole dithio-
carbamates (Z = N-R′ N). RAFT agents that are ineffective for the controlled poly-
merization of methacrylamides are 2∘ dithiobenzoates (Z = Ph), trithiocarbonates
(Z = S-R′ ), pyrazole dithiocarbamates (Z = N-R′ N), dithiocarbamates (Z = N-R′ 2 ),
and xanthates (Z = O-R′ ). Polymerization of commercially sourced methacrylamides
including N-(2-aminoethyl)methacrylamide (hydrochloride), N-(3-aminopropyl)
methacrylamide (hydrochloride), N-(2-hydroxypropylmethacrylamide), and many
functionalized methacrylamides such as zwitterionic monomer, carboxybetaine
methacrylamide 42 [65], and hydrazide 43 [79] have been successfully reported.
3.6.2 Acrylamides
The attributes for RAFT polymerization of acrylates that we have previously
discussed generally also apply to acrylamides polymerizations and thus require
RAFT agents suitable for MAMs (see Table 3.1, Figure 3.5). Enhanced rates of
polymerization are achieved under aqueous conditions and in the presence of
Lewis acids. Polymerization of commercially sourced acrylamides including acry-
lamide, N,N-dimethylacrylamide, 2-acrylamido-2-methylpropane-1-sulfonic
acid sodium salt, N-benzylacrylamide, N-cyclohexylacrylamide, diacetone
acrylamide, N,N-diethylacrylamide, N-(2-(dimethylamino)ethyl)acrylamide,
N-isopropylacrylamide, N-octylacrylamide, and many functionalized acry-
lamides such as anionic bisphosphonate monomers 44 [80], 3[2-(N-methyl
acrylamido)ethyldimethylammonio]propanesulfonate 45 [81], or amino function-
ality 46 [82] have been successfully reported (Figure 3.7).
NH
O NH O
O O
O HN SO3
N CO2 NH
5 O
NH
P OCH3
O
O O N
N O OCH2(CH3)3
P OCH3
NH
O
HN
O
(H3C)3CO
42 43 44 45 46
Figure 3.7 Examples of functional methacrylamide and acrylamide monomers amenable

to RAFT polymerization.

of Acrylamides and Methacrylamides
Solution polymerization of N-(2-hydroxypropyl)methacrylamide HPMA in the
presence of 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid 27 at 70 ∘ C.
Polymerization was performed directly in an acetic acid buffer at pH 5.2,
(0.27 nmol l−1 acetic acid and 0.73 mol l−1 sodium acetate), initial monomer con-
centration ([M]0 ) of 1 M, and feed ratio of [HPMA]0 /[CTA]0 /[AIBN]0 = 40/1/0.2.
HPMA (0.716 g, 0.005 mol), 27 (34.5 mg, 1.23 × 10−4 mol), ACPA (6.9 mg,
2.46 × 10−5 mol), and acetic buffer (5 ml) were mixed. The reaction mixture
was purged with nitrogen in an ice bath for 30 minutes. It was then placed in
an oil bath at 70 ∘ C for six hours. The polymerization solution was dialyzed
against water for three hours to remove salt (water was changed hourly) and then
freeze-dried. The solid was dissolved in ethanol and the polymer was precipitated
in diethyl ether. The precipitation was repeated twice. The product was dried in
vacuo to yield a pink powder (70%; M n = 8200; Ð = 1.04) [83].
Aqueous solution polymerization of N-[3-aminopropyl]methacrylamide (APMA)
in the presence of 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid 27 at 70 ∘ C.
The polymerization was performed directly in acetate buffer (pH = 5, 0.27 mol l−1
acetic acid and 0.73 mol l−1 sodium acetate) with an initial monomer concentration
[M]0 = 1.8 M. (Note that the buffer system was used to maintain the hydrochloride
salt form of the monomer during polymerization.) The initial [M]0 /[CTA]0 was 200,
while the CTA to initiator ratio was 5 : 1. The homopolymerization was conducted by
dissolving APMA (0.97 g, 5.4 mmol), 27 (7.6 mg, 0.027 mmol), and V-501 (1.51 mg,
0.0054 mmol) in a 25 ml round-bottom flask and diluting the resulting mixture to a
final volume of 3 ml with the acetate buffer. The reaction solution was purged with
nitrogen for 45 minutes and subsequently placed in a water bath at 70 ∘ C. The poly-
merization was allowed to proceed for 60 minutes before being quenched by rapid
cooling in liquid nitrogen. The poly(N-[3-aminopropyl]methacrylamide (PAPMA)
was then purified by dialysis against deionized water followed by lyophilization

(31%; M n = 15 000; Ð = 1.08) [84].
Solution polymerization of N,N-dimethylacrylamide (DMAm) in the presence of
cyanomethyl 3,5-dimethyl-1H pyrazole-1-carbodithioate 6 at 100 ∘ C. A solution
containing DMA (0.618 ml, 3 M), ACHN (2.93 mg, 0.006 M), 6 (12.68 mg, 0.03 M),
trioxane (10 mg; internal standard), and acetonitrile (1.4 ml) was prepared in a
5 ml microwave vial. The resulting mixture was degassed, sealed, and heated
at 100 ∘ C by microwave irradiation for one hour. The volatiles were removed in
vacuo to give poly(DMA) (99%; M n = 12 100; Ð = 1.07) [70].
Solution polymerization of NIPAm in the presence of cyanomethyl 4-cyano-4-(dode-
cylsulfanylthiocarbonyl) sulfanyl pentanoic acid 7 at 60 ∘ C. Into a flask were placed
2 g (17.7 mmol) of NIPAm, 54 mg (0.134 mmol) of 7, and 2.2 mg (13.4 μmol) of
AIBN in 4 g p-dioxane. The flask was purged with N2 for 30 minutes and heated at
60 ∘ C for 12 hours, followed by precipitation into pentane. The product was dried
under vacuum, dialyzed against DI water at 4 ∘ C, and freeze-dried (M n = 15 700;
Ð = 1.01; dn/dc of 0.074) [85].
Solution polymerization of acrylamide in the presence of 2-(1-carboxy-1-methylethyl-
sulfanylthio carbonylsulfanyl)-2-methylpropionic acid 25 at 70 ∘ C. Acrylamide
(15.4 g, 0.217 mol), 25 (76.6 mg, 0.271 mmol), and V-501 (15.2 mg, 0.0542 mmol)
were added to a 250 ml round-bottom flask equipped with a magnetic stirring
bar. Dimethyl sulfoxide was added until the total solution volume was 108.5 ml.
The flask was sealed with a rubber septum, and the contents were purged with
nitrogen for 60 minutes. The flask was subsequently immersed in a water bath
preheated to 70 ∘ C, and the polymerization proceeded for four hours before being
quenched by rapid cooling with liquid nitrogen. The polymer was then purified
by direct precipitation into 20 times excess of acetone (M n = 36 200 g mol−1 ;
Ð = 1.25) [86].
Solution polymerization of N,N-diethylacrylamide in the presence of 2-cyano-2-propyl
benzodithioate 2 at 80 ∘ C. N,N-Diethylacrylamide (13.3 g, 104 mmol), 2 (0.582 g,
2.66 mmol), and AIBN (76 mg, 0.463 mmol) were mixed in a round-bottom
flask equipped with a magnetic stir bar. The resulting homogeneous solution
was stirred at room temperature while being purged with N2 for a period of
one hour. The flask was then immersed in a preheated oil bath at 80 ∘ C for
2.5 hours. The polymerization was quenched by exposure to air while cooling
the flask with ice. THF (8.0 ml) was then added to the flask to dilute the
monomer/polymer mixture. The polymer was isolated by precipitation (×2) into
hexane (600 ml) followed by Buchner filtration and drying in vacuo, yielding
8.7 g of poly(N,N-diethylacrylamide) (65%; M n = 1790; Ð = 1.06) [87].
3.7 RAFT Polymerization of Vinyl Esters and Vinyl

Amides
Most vinyl ester and vinyl amide monomers are secondary less activated monomers
(LAMs) with the exception of 2-vinyl-4,4-dimethylazlactone (VDMA), which
3.7 RAFT Polymerization of Vinyl Esters and Vinyl Amides 47
F
O N O HO P OH O S O
O F O
47 48 49 50
Figure 3.8 Examples of functional vinylic monomers amenable to RAFT polymerization.
behaves as a 2∘ MAM. Good control over RAFT polymerization of vinyl esters

and vinyl amides requires a RAFT agent suitable for 2∘ LAMs. Primary, sec-
ondary, and tertiary pyrazole dithiocarbamates (Z = N-R′ N), dithiocarbamates
(Z = N-R′ 2 ), and xanthates (Z = O-R′ ) RAFT agents give good control over the
homopolymerization of vinyl ester and vinyl amide (see Table 3.1, Figure 3.5).
RAFT agents that are not suitable for the polymerization of vinyl ester and vinyl
amide are dithiobenzoates (Z = Ph) and trithiocarbonates (Z = S-R′ ). Vinyl ester
and vinyl amide polymerizations are generally carried out in solution. RAFT
homo- and copolymerization resulting in controlled molecular weight and low
dispersity have been achieved for a variety of vinyl esters including vinyl acetate,
vinyl butyrate, and vinyl benzoate (VAc, VB, VBz), N-vinyl amides and imides
such as N-vinylcaprolactam and N-vinylpyrrolidone, N-vinyl heteroaromatics
such as 4-vinylimidazole, vinylsulfonates such as 1-butyl ethenesulfonate and
neopentyl ethenesulfonate, vinylphosphonic acid, protected amino functionality
47 [88], phosphonic acid functionality 48 [89], haloolefins 49 [90] and sulfonic
acid-containing monomers 50 [91]. The polymerization of N-vinylpyrrolidone
(NVP) in aqueous media was reported as problematic due to the sensitivity of the
macroRAFT agent with a terminal NVP unit to hydrolysis. It has recently been
shown that this problem can be overcome by conducting the polymerization at
ambient temperature with redox initiation [92] (Figure 3.8).
3.7.1 Experimental Procedures for the RAFT Polymerization of Vinyl

Esters and Vinyl Amides
Solution polymerization of N-vinylcarbazole (NVC) in the presence of cyanomethyl
phenyl(pyridin-4-yl)carbamodithioate 29 at 60 ∘ C. A stock solution containing
29 (24.3 mg), NVC (2.12 g), AIBN (8.3 mg), and 1,4-dioxane to a volume of 5 ml
was prepared in a volumetric flask. The reaction mixture was transferred to an
ampoule, degassed by three repeated freeze–evacuate–thaw cycles, and sealed.
The ampoule was heated at 60 ∘ C for 20 hours (95%; M n = 16 900; Ð = 1.19) [93].
Solution polymerization of vinyl acetate in the presence of O-ethyl S-(1-methoxy-
carbonylethyl) dithiocarbonate (Rhodixan A1) 26 at 60 ∘ C. A mixture of vinyl
acetate (2.8 g, 3.2 × 10−2 mol), AIBN (8 mg, 0.049 mmol), and 26 (97 mg,
0.47 mmol) in ethyl acetate (2.9 g) was degassed by four freeze–pump–thaw
cycles, backfilled with argon, sealed, and placed in an oil bath at 60 ∘ C. After
15 hours, the reaction was stopped by cooling in liquid nitrogen. The polymer
was dried in vacuo (M n = 6050 g mol−1 ; Ð = 1.61) [94].
Solution polymerization of vinyl benzoate in the presence of ethylxanthogenacetic

acid (EXGA) 31 at 70 ∘ C. A stock solution was prepared of vinyl benzoate (1.90 g,
12.8 mmol), 31 (23.1 mg, 0.128 mmol), AIBN (4.2 mg, 0.026 mmol), and anisole
(0.45 ml). An aliquot (1 ml) was sealed in a 10 ml microwave vial equipped with a
magnetic stir bar. The resulting solution was purged with nitrogen for 20 minutes.
The reaction vial was placed in the cavity of the microwave instrument, and the
temperature was programmed to 70 ∘ C. After 48 minutes, the polymerization
was quenched by ceasing the microwave irradiation, removing the vial from
the instrument, rapidly cooling the vial in an ice water bath, and exposing the
reaction solution to air (41%; M n = 7300 g mol−1 ; Ð = 1.26) [95].
Solution polymerization of N-vinylphthalimide (NVPI) 47 in the presence of benzyl
1H-pyrrole-1-carbodithioate 32 at 60 ∘ C. 47 (0.174 g, 1.0 mmol), 32 (4.7 mg,
0.020 mmol), AIBN (1.6 mg, 0.010 mmol), and DMF (0.5 ml) were placed in a dry
glass ampoule equipped with a magnetic stirring bar; the solution was degassed
by three freeze–evacuate–thaw cycles. After the ampoule was flame-sealed under
vacuum, it was stirred at 60 ∘ C for 24 hours. The characteristic yellow colour
remained during the polymerization. The reaction was stopped by rapid cooling
with liquid nitrogen. The polymer obtained was purified by precipitation from a
DMF solution into a large excess of diethyl ether, and the resulting product was
dried at room temperature under vacuum to yield poly(NVPI) as a white powder
(84%; M n = 7300; Ð = 1.29) [88].
Redox initiated solution polymerization of N-vinylpyrrolidone (NVP) in the presence
of O-ethyl-S-(1-methoxycarbonyl)ethyldithiocarbonate (Rhodixan A1) 26 at room
temperature. 26 (122 mg, 5.8 × 10−4 mol), NVP (5 g, 4.5 × 10−2 mol), distilled water
(2.5 ml), and tert-butyl hydroperoxide (85 mg, 6.6 × 10−4 mol) were placed in a
15 ml Schlenk flask. The polymerization mixture was degassed by purging with
ultrahigh-purity argon for 20 minutes. Ascorbic acid (115 mg, 6.5 × 10−4 mol) was
added under a stream of argon. The reaction was stopped after 24 hours at room
temperature (97%; M n = 14 600 g mol−1 ; Ð = 1.30) [92].
3.8 Copolymers
Copolymerization under RAFT control allows for the polymer chains to all have a
similar composition. As polymer chains grow throughout the copolymerization, the
compositional drift of the monomers are captured within the chain structure, unlike
with conventional radical copolymerizations, where the polymers are generally not
homogeneous in composition.
Gradient, alternating, statistical, and pseudo-block copolymers can be synthe-
sized in a batch type polymerization by choosing the appropriate reactivity ratio of
monomer pairs.
The choice of RAFT agent for a successful copolymerization is not based on the
requirement for all monomers to be amenable to its control. Examples of good con-
trol over molecular weight and narrow molecular weight distributions for vinylic
monomers copolymerized with acrylates using trithiocarbonates exist provided the
3.8 Copolymers 49
monomer that is amenable to homopolymerization with the chosen RAFT agent,

in the monomer pair, does not deplete during the copolymerization. Alternatively,
a RAFT agent that can control both monomer pairs, such as the pyrazole carbod-
ithioate class chain transfer agents 9–11, can be used.
3.8.1 Experimental Procedures for RAFT Copolymers

Preparation of poly(N,N-dimethylacrylamide-covinyl acetate) using cyanomethyl
3,5-dimethyl-1H-pyrazole-1-carbodithioate 9 at 100 ∘ C. A solution containing
DMA (0.010 ml, 0.048 M), VAc (0.553 ml, 3 M), ACHN (5.86 mg, 0.012 M),
9 (20.28 mg, 0.048 M), and ethyl acetate (1.437 ml) was prepared in a 5 ml
microwave vial. The resulting mixture was degassed, sealed, and heated at 100 ∘ C
via microwave irradiation for 12 hours. The volatiles were removed in vacuo to
give poly(DMA-co-VAc) at 55% conversion (>99% of DMA and 54% VAc), with
M n = 4700; Ð = 1.23 [70].
Preparation of poly(methyl methacrylate-co-trimethylsilyl methacrylate-co-4-(tert-
butyldimethylsilyloxy)styrene 13) p(MMA-co-TMS-MA-co-TBDMS-OS) with
2-cyano-2-propyl benzodithioate 2 at 60 ∘ C. Polymerizations were carried out
in a Schlenk tube. MMA (1.90 g, 19 mmol), TMS-MA (1.58 g, 11 mmol), 13
(0.6 g, 2.6 mmol), 2 (0.015 g, 0.07 mmol), and AIBN (0.9 mg, 0.006 mmol) were
dissolved in anisole (4 ml) and the reaction mixture was degassed by three
freeze–pump–thaw cycles. The polymerizations were conducted under argon
atmosphere for 20.5 hours at a constant temperature of 70 ∘ C. The reaction was
stopped by freezing the Schlenk tube in liquid nitrogen. The reaction mixture
was then slowly precipitated in n-hexane, the polymer was filtered off, and dried
under vacuum. GPC (eluent: THF, RI, polystyrene [PSt]-standards): M n = 30 700;
Ð = 1.13 [96].
Preparation of poly(triphenylmethyl methacrylate 34-co-methacrylic acid) with
2-phenyl-2-propyl benzodithioate 1 at 60 ∘ C. In a 50 ml round-bottom flask were
placed toluene (5.40 ml), 34 (4.41 ml of 1.36 M solution in toluene), MAA (0.51 ml,
6.01 mmol), 1,2,3,4-tetrahydronaphthalene (0.48 ml) as an internal standard, and
toluene solutions of AIBN (0.60 ml of 100 mM solution in toluene) and 1 (0.60 ml
of 200 mM solution in toluene) at room temperature. The total volume of the
reaction mixture was 12.0 ml. Immediately after mixing, the solution was evenly
charged in six glass tubes and the tubes were sealed by flame under nitrogen
atmosphere. The tubes were immersed in a thermostatic oil bath at 60 ∘ C. In
predetermined intervals, the polymerization was terminated by cooling the
reaction mixtures in liquid N2 . Monomer conversion was determined from the
concentration of residual monomer measured by 1 H NMR spectroscopy against
the internal standard. The quenched reaction solutions were evaporated to dry
to give poly(MAA-grad-TrMA). Details of the polymerization results are given in
Table 3.7; [58].
Preparation of poly(methacrylic acid)-co-(oleyl methacrylate 40) (PMAoa 8.0 mol%)
with 4-cyano-4-(((dodecylthio)carbonothioyl)thio)pentanoic acid 7 at 60 ∘ C. RAFT
agent 7 (26.30 mg, 11.7 mmol), Vazo 68 (3.60 mg, 13.0 mmol), MMA (1.01 g,
12.0 mmol), and 40 (0.44 g, 1.29 mmol) were combined with 1,4-dioxane (3.0 ml)
Table 3.7 RAFT copolymerization of

triphenylmethyl methacrylate 34 and methacrylic
acid using 1 as a chain transfer agent.
Time Conversion
(h) (34/MAA%)a) M n(GPC) b) Ð
3 3/18 5 300 1.16

10 41/81 7 100 1.21
150 88/100 10 100 1.22
a) NMR.
b) PMMA equivalents.
Source: Data from Ishitake et al. [58].
in an ampoule. The solution was degassed with four freeze–pump–thaw cycles,

flame-sealed, and transferred to a temperature-controlled oil bath at 60 ∘ C
for seven hours. The polymerization was then quenched by rapid cooling in
liquid nitrogen. The monomer/polymer mixture was twice precipitated from a
workable dioxane/THF mixture into diethyl ether/hexane (3 : 1). The polymer
was recovered by filtration and dried under suction (1.24 g; 85%; M n = 25 200;
Ð = 1.19 [Molecular weight of methylated polymer obtained using THF, GPC
calibrated with PMMA standards]) [44].
Preparation of poly(N-isopropylacrylamide (80%)-co-sodium methacrylate (10%)-co-
N-cyclohexylacrylamide (10%)) p(NIPAm-co-NaMA-co-CA) with S,S′ -bis(𝛼,𝛼 ′ -
dimethyl-𝛼 ′′ -acetic acid)-trithiocarbonate 25 at 60 ∘ C. NIPAm (1.488 g, 13.1 mmol),
sodium methacrylate (0.142 g, 1.3 mmol), and N-cyclohexylacrylamide
(0.209 g, 1.3 mmol) were dissolved in methanol (20 ml) in a polymeriza-
tion tube fitted with a septum cap. The mixture was degassed by bub-
bling nitrogen through it for 30 minutes. 25 (74.4 mg, 0.26 mmol) and
2,2′ -Azobis(2-methylpropionamidine)dihydrochloride V-50 (23.8 mg, 0.08 mmol)
were then added and the mixture was heated to 60 ∘ C for 48 hours. The solvent
was evaporated, the residue dissolved in THF, and precipitated into pentane, and
then left to dry to give a pale yellow powder (M n = 3800; Ð = 1.31) [80].
3.9 Block Copolymers

The order of constructing the blocks of a block copolymer is very important. The
propagating radical for the first formed block must be a good homolytic leaving
group with respect to that of the second block. For example, in the synthesis of
a methacrylate–acrylate or methacrylate–styrene diblock, the methacrylate block
must be prepared first. The styrene or acrylate propagating radicals are very poor
leaving groups with respect to methacrylate propagating radicals. For the construc-
tion of polyMAM-block-polyLAM, the block comprising MAM needed to be syn-
thesized first. This sequence is necessary because polyLAM propagating radicals
are poor radical leaving groups with respect to polyMAM propagating radicals, and
3.9 Block Copolymers 51
consequently, polyLAM macroRAFT agents can have very low transfer constants in
MAM polymerization.
Attempts to synthesize PSt-block-PVAc or other PSt-block-polyLAM starting
from a PSt macroRAFT may require a different strategy to other polyMAM-block-
polyLAM synthesis. It has been shown that attempts to synthesize PSt-block-PVAc
or other PSt-block-polyLAM starting from a PSt macroRAFT agent (prepared with
methyl 2-[methyl(4-pyridinyl)carbamothioylthio]propionate 30) using the RAFT
polymerization conditions (initiator:RAFT agent ∼ 1 : 10) that had proved success-
ful for other polyMAM-block-polyLAM or PSt-block-polyMAM gave no significant
yield of polymer after an extended reaction period (>four hours) [97]. As it has been
observed that it is possible to synthesize low molecular weight PSt-block-poly(methyl
acrylate) (PMA) and PMA-block-PVAc, [98] the copolymerization of a mixture of
MA and VAc in the presence of the PSt macroRAFT in its deprotonated form allows
for the synthesis of PSt-MA-VAc (PSt-block-P(MA-grad-VAc)-block-PVAc) [99].
3.9.1 Experimental Procedures for RAFT Block Copolymers

Preparation of poly(methyl methacrylate)-b-poly(n-butyl acrylate) using 2-cyano-2-
propyl benzodithioate 2 at 70 ∘ C. MMA (15 g, 150 mmol), 2-cyano-2-propyl ben-
zodithioate 2 (0.0664 g, 0.300 mmol), AIBN (0.0123 g, 0.075 mmol), and toluene
(6.46 g, 30 wt%) were mixed together, degassed, and heated at 70 ∘ C under N2
for six hours and the reaction quenched in ice (55%, M n = 28 800 g mol−1 ,
Ð = 1.09). PMMA homopolymer (M n = 28 800 g mol−1 , Ð = 1.09, 0.3370 g,
0.0117 mmol), BA (1.4998 g, 11.7 mmol), AIBN (0.0004 g, 0.0023 mmol), and
30 wt% toluene (0.78 g) were mixed together, degassed, and heated at 70 ∘ C for
90 minutes, and the reaction quenched in ice after precipitation in cold methanol
to give PMMA-PBA block copolymer (44% [BA]; M n = 77 300 g mol−1 ; Ð = 1.37)
[100].
Preparation of poly(methyl acrylate)-b-poly(N-vinylcarbazole) using methyl 2-(methyl
(pyridin-4-yl)carbamothioylthio)propanoate 30 at 60 ∘ C. A stock solution (I) of
AIBN (8.5 mg) in acetonitrile (25 ml) was prepared. A stock solution (II) of 30
(47.6 mg, 0.0353 M) and p-toluenesulfonic acid (38.0 mg, 0.04 M) in acetonitrile
(5.0 ml) was prepared. Aliquots of stock solution (I) (1.0 ml), stock solution
(II) (2.0 ml), and methyl acrylate (2.0 ml) were transferred to ampoules that
were degassed by three repeated freeze–evacuate–thaw cycles and sealed. The
ampoule was heated at 60 ∘ C for seven hours. The volatiles were removed in
vacuo to give poly(methyl acrylate) (87.3%; M n = 31 100; Ð = 1.08). A stock
solution (I) consisting of the poly(methyl acrylate) (prepared as above) (1.67 g;
M n = 31 100; Ð = 1.08) and N,N-dimethylaminopyridine (10.0 mg) in acetonitrile
(10 ml) was prepared. A stock solution (II) of AIBN (10 mg) in acetonitrile
(5 ml) was prepared. NVC (0.5 g), stock solution (I) (2.0 ml), stock solution (II)
(1.0 ml), and acetonitrile (1.0 ml) were transferred into a test tube ampoule,
which was degassed by three repeated freeze–evacuate–thaw cycles, and sealed.
The ampoule was heated at 60 ∘ C for 16 hours. The volatiles were removed in
vacuo to give poly(methyl acrylate)-b-poly(N-vinylcarbazole) (almost complete
conversion of N-vinylcarbazole based on 1 H-NMR spectroscopy) with GPC result

M n = 48 000; Ð = 1.33 [98].
Preparation of poly(N,N-dimethylacrylamide)-b-poly(vinyl acetate) using cyanomethyl
3,5-dimethyl-1H-pyrazole-1-carbodithioate 9 at 100 ∘ C. A solution contain-
ing DMA (0.309 ml, 1.5 M), ACHN (1.47 mg, 0.003 M), and cyanomethyl
3,5-dimethyl-1H-pyrazole-1-carbodithioate 9 (12.68 mg, 0.03 M) in acetonitrile
was prepared in a 5 ml microwave vial. The resulting mixture was degassed,
sealed, and heated at 100 ∘ C via microwave irradiation for one hour (98%,
M n = 5800, Ð = 1.05). The vial cap was removed and VAc (0.553 ml) and
ACHN (1.47 mg) were added. The vial was again sealed, degassed, and heated
at 100 ∘ C via microwave irradiation for 24 hours. The volatiles were removed in
vacuo to give poly(DMA)-block-poly(VAc) at >99% conversion of DMA and 55%
conversion of VAc, with M n = 8500; Ð = 1.24 [70].
Preparation of poly(vinyl pivalate)-b-poly(vinyl acetate) (PVPv-b-PVAc) using methyl
(isopropoxycarbonothioyl)sulfanyl acetate 33 at 100 ∘ C. 33 (46.1 mg, 0.21 mmol,
9.9 mM) and AIBN (3.8 mg, 0.023 mmol, 1.1 mM) were dissolved in freshly
distilled vinyl pivalate (VPv) (21.2 ml, 143 mmol). The reaction was sealed,
degassed by freeze–pump–thaw cycles (×3), and heated to 60 ∘ C for three hours.
The reaction was removed from the heating bath and cooled under running water
to terminate the polymerization. Excess vinyl pivalate monomer was removed
under reduced pressure, and the resulting solids were freeze-dried from benzene
in vacuo (22.5%, M n = 14 800 g mol−1 (GPC-LS), Ð = 1.28 (PSt Standards)).
The PVPv-macroRAFT agent (0.5 g, 0.034 mmol) was dissolved in VAc (6.3 ml,
68.3 mmol); residual AIBN present in the macro-chain transfer agent was used
as the sole source of initiator. The reaction was degassed by freeze–pump–thaw
cycles (×3), sealed, and heated to 60 ∘ C for 3.5 hours. The reaction was removed
from the heating bath and cooled under running water to terminate the reaction.
Excess vinyl acetate monomer was removed by rotary evaporation. The resulting
solid polymer was freeze-dried from benzene in vacuo (6.8%; M n(NMR) = 24 800;
50.4 mol% VAc; Ð = 1.33 [PSt standards]) [101].
Preparation of polystyrene-b-poly(vinyl acetate) (PSt-b-PVAc) using methyl 2-((methyl
(pyridin-4-yl)carbamothioyl)thio)propanoate 30 at 70 ∘ C. A solution compris-
ing ACHN (12.2 mg), 30 (94.5 mg), p-toluenesulfonic acid (TsOH) (60.2 mg),
and styrene (5 ml) was transferred to an ampoule that was degassed by three
freeze–evacuate–thaw cycles, sealed, and then heated at 90 ∘ C for six hours. To
avoid unwanted cationic polymerization of styrene, it is important that TsOH is
not added directly to the styrene monomer. The ampoule was cooled, opened,
and the polymerization mixture evaporated to dryness in vacuo. The residue was
taken up in chlorobenzene and evaporated under vacuum several times until no
styrene signals were detectable by 1 H NMR spectroscopy. The residue (2-PSt-H+ )
was dissolved in dichloromethane and percolated through a carefully crushed
and dried sodium carbonate bed. The colour of the solution changed from yellow
to colourless. Removal of the solvent gave the PSt macroRAFT (18%, M n = 1850,
Ð = 1.22). A solution of PSt macroRAFT agent (18%; M n = 1850; Ð = 1.22; 0.030 g;
0.01 M), AIBN (1.4 mg, 0.005 M), and VAc (1.4 g) was transferred to an ampoule
3.10 Conclusion 53
Table 3.8 Preparation of poly(N-(2-hydroxypropyl)

methacrylamide)-b-poly(benzyl methacrylate) using
a PBnMA macro-RAFT agent.
Time Conversion
(h) (%)a) M n(GPC) b) Ð
9 20 7 700 1.22
14 30 9 000 1.23
17 36 10 800 1.22
30 61 19 200 1.26
a) NMR.
b) M n in poly(ethylene oxide) (PEO) equivalents.
Source: Data from Wei et al. [73]
that was degassed by three freeze–evacuate–thaw cycles and sealed. The ampoule
was heated at 70 ∘ C for eight hours, and the volatiles were removed in vacuo
(100%; M n = 73 600; Ð = 1.95) [97].
Synthesis of poly(N-(2-hydroxypropyl)methacrylamide)-b-poly(benzyl methacrylate)
PHPMA-b-PBnMA in the presence of PBnMA macro-CTA at 70 ∘ C. PBnMA
(see Section 3.5.3) was used as the macro chain transfer agent (macro-CTA).
PBnMA macro-CTA (M n = 4800; Ð = 1.17) (500 mg, 0.05 mmol), AIBN (1.6 mg,
0.01 mmol), and HPMA (1.432 g, 10 mmol) were dissolved in 4.0 ml of DMAc.
The solution was degassed with N2 for 30 minutes, and the polymerization was
carried out at 70 ∘ C for the times specified in Table 3.8. Aliquots were withdrawn
at determined time intervals and analyzed by 1 H NMR spectroscopy and GPC
with DMF as a mobile phase for monitoring the degree of polymerization (DP) of
HPMA. The reaction mixture was diluted with DMF and precipitated three times
from DMF/diethyl ether before being dried in vacuum [73].
3.10 Conclusion
Since its first report in 1998 [18], RAFT polymerization has become a tool adopted
by the broader scientific community and it is utilized by not only polymer chemists
but also synthetic chemists, material engineers, bioengineers, medicinal chemists,
and nanotechnologists, generating a plethora of materials with enormous structural
complexity and variation in areas ranging from microelectronics, batteries, plas-
tic solar cells, lubricants, surface modifiers, emulsion stabilizers, paints, adhesives,
cosmetics, polymer therapeutics, biosensors, and more. With the lapsing of the foun-
dation patents, a range of versatile RAFT agents now being commercially available
in a variety of quantities, and industry having shown that scaling up of RAFT agents
and polymers is feasible, [102] the time is ripe for scientists to explore the RAFT poly-
merization technology as a simple tool for the production of complex and functional
materials.
References
1 Rizzardo, E., Moad, G., and Thang, S.H. (2009). Encyclopedia of Polymer Science
and Technology. Wiley. https://doi.org/10.1002/0471440264.pst564.
1438–1447. https://doi.org/10.1002/pi.5423.
4 Carmean, R.N., Becker, T.E., Sims, M.B., and Sumerlin, B.S. (2017). Chem 2:
93–101. https://doi.org/10.1016/j.chempr.2016.12.007.
5 Martin, L., Gody, G., and Perrier, S. (2018). Reversible Deactivation Radical Poly-
merization: Materials and Applications, ACS Symposium Series 1285, 57–79.
American Chemical Society. https://doi.org/10.1021/bk-2018-1285.ch004.
6 Quinn, J.F., Barner, L., Barner-Kowollik, C. et al. (2002). Macromolecules 35:
7620–7627. https://doi.org/10.1021/ma0204296.
7 Lewis, R.W., Evans, R.A., Malic, N. et al. (2018). Polym. Chem. 9: 60–68. https://
doi.org/10.1039/C7PY01752A.
8 You, Y.-Z., Hong, C.-Y., Bai, R.-K. et al. (2002). Macromol. Chem. Phys. 203:
477–483. https://doi.org/10.1002/1521-3935(20020201)203:3<477::Aid-macp477>
3.0.Co;2-m.
9 Lu, L., Zhang, H., Yang, N., and Cai, Y. (2006). Macromolecules 39: 3770–3776.
https://doi.org/10.1021/ma060157x.
10 Bai, R.-K., You, Y.-Z., and Pan, C.-Y. (2001). Macromol. Rapid Commun. 22:
315–319. https://doi.org/10.1002/1521-3927(20010301)22:5<315::Aid-marc315>
3.0.Co;2-o.
11 Bai, R.-K., You, Y.-Z., Zhong, P., and Pan, C.-Y. (2001). Macromol. Chem. Phys.
202: 1970–1973. https://doi.org/10.1002/1521-3935(20010601)202:9<1970::
Aid-macp1970>3.0.Co;2-q.
12 Quinn, J.F., Barner, L., Davis, T.P. et al. (2002). Macromol. Rapid Commun. 23:
717–721. https://doi.org/10.1002/1521-3927(20020801)23:12<717::Aid-marc717>
3.0.Co;2-i.
13 Barner, L., Quinn, J.F., Barner-Kowollik, C. et al. (2003). Eur. Polym. J. 39:
449–459. https://doi.org/10.1016/S0014-3057(02)00247-1.
14 Zhou, Y., Zhu, J., Zhu, X., and Cheng, Z. (2006). Radiat. Phys. Chem. 75:
485–492. https://doi.org/10.1016/j.radphyschem.2005.10.012.
15 Millard, P.-E., Barner, L., Stenzel, M.H. et al. (2006). Macromol. Rapid Com-
mun. 27: 821–828. https://doi.org/10.1002/marc.200600115.
16 Chiefari, J., Mayadunne, R.T.A., Moad, C.L. et al. (2003). Macromolecules 36:
2273–2283. https://doi.org/10.1021/ma020883+.
17 Vana, P., Albertin, L., Barner, L. et al. (2002). J. Polym. Sci., Part A: Polym.
Chem. 40: 4032–4037. https://doi.org/10.1002/pola.10500.
https://doi.org/10.1021/ma9804951.
19 McCormick, C.L. and Lowe, A.B. (2004). Acc. Chem. Res. 37: 312–325. https://
doi.org/10.1021/ar0302484.
References 55
20 Lowe, A.B. and McCormick, C.L. (2002). Aust. J. Chem. 55: 367–379. https://doi
.org/10.1071/CH02053.
21 Fortenberry, A.W., McCormick, C.L., and Smith, A.E. (2022). RAFT Polymer-
ization: Materials, Synthesis and Applications (eds. G. Moad, S.H. Thang and
E. Rizzardo). Weinheim: Wiley-VCH. https://doi.org/10.1000/000000000.chxx.
22 Perrier, S., Davis, T.P., Carmichael, A.J., and Haddleton, D.M. (2002). Chem.
Commun.: 2226–2227. https://doi.org/10.1039/B206534G.
23 Arita, T., Beuermann, S., Buback, M., and Vana, P. (2005). Macromol. Mater.
Eng. 290: 283–293. https://doi.org/10.1002/mame.200400274.
24 Arita, T., Beuermann, S., Buback, M., and Vana, P. (2004). e-Polymers 003
https://doi.org/10.1515/epoly.2004.4.1.20.
25 Thomas, D.B., Convertine, A.J., Hester, R.D. et al. (2004). Macromolecules 37:
1735–1741. https://doi.org/10.1021/ma035572t.
26 Albertin, L., Stenzel, M.H., Barner-Kowollik, C., and Davis, T.P. (2006). Polymer
47: 1011–1019. https://doi.org/10.1016/j.polymer.2005.12.069.
27 Mertoglu, M., Laschewsky, A., Skrabania, K., and Wieland, C. (2005). Macro-
molecules 38: 3601–3614. https://doi.org/10.1021/ma048268o.
28 Moad, G., Rizzardo, E., and Thang, S.H. (2016). Reference Module in Materials
Science and Materials Engineering. Elsevier. https://doi.org/10.1016/B978-0-12-
803581-8.01349-7.
29 Chiefari, J. and Rizzardo, E. (2002). Handbook of Radical Polymerization (eds.
K. Matyjaszewski and T.P. Davis), 629–690. https://doi.org/10.1002/0471220450
.ch12.
30 Liu, Y., He, J., Xu, J. et al. (2005). Macromolecules 38: 10332–10335. https://doi
.org/10.1021/ma0513970.
31 Xu, J., He, J., Fan, D. et al. (2006). Macromolecules 39: 3753–3759. https://doi
.org/10.1021/ma060184n.
32 Postma, A., Davis, T.P., Moad, G., and O’Shea, M.S. (2005). Macromolecules 38:
5371–5374. https://doi.org/10.1021/ma050402x.
33 Chong, B., Moad, G., Rizzardo, E. et al. (2006). Aust. J. Chem. 59: 755–762.
34 Postma, A., Davis, T.P., Li, G. et al. (2006). Macromolecules 39: 5307–5318. doi:
10.1021/ma0604338.
35 Postma, A., Davis, T.P., Evans, R.A. et al. (2006). Macromolecules 39: 5293–5306.
https://doi.org/10.1021/ma060245h.
36 Monteiro, M.J., Bussels, R., Beuermann, S., and Buback, M. (2002). Aust. J.
Chem. 55: 433–437. https://doi.org/10.1071/CH02079.
37 Rzayev, J. and Penelle, J. (2004). Angew. Chem. Int. Ed. 43: 1691–1694. https://
doi.org/10.1002/anie.200353025.
38 Arita, T., Buback, M., and Vana, P. (2005). Macromolecules 38: 7935–7943.
https://doi.org/10.1021/ma051012d.
39 Arita, T., Buback, M., Janssen, O., and Vana, P. (2004). Macromol. Rapid Com-
40 Rizzardo, E., Chiefari, J., Chong, B.Y.K. et al. (1999). Macromol. Symp. 143:
291–307. https://doi.org/10.1002/masy.19991430122.
41 Moad, G., Chiefari, J., Chong, Y.K. et al. (2000). Polym. Int. 49: 993–1001.
https://doi.org/10.1002/1097-0126(200009)49:9<993::Aid-pi506>3.0.Co;2-6.
42 Chong, Y.K., Krstina, J., Le, T.P.T. et al. (2003). Macromolecules 36: 2256–2272.
43 Moad, G., Chiefari, J., Mayadunne, R.T.A. et al. (2002). Macromol. Symp.
182: 65–80. https://doi.org/10.1002/1521-3900(200206)182:1<65::Aid-masy65>
3.0.Co;2-e.
44 Hosta-Rigau, L., Chandrawati, R., Saveriades, E. et al. (2010). Biomacro-
molecules 11: 3548–3555. https://doi.org/10.1021/bm101020e.
45 Nilles, K. and Theato, P. (2011). Polym. Chem. 2: 376–384. https://doi.org/10
.1039/C0PY00261E.
46 Espeel, P., Goethals, F., Stamenović, M.M. et al. (2012). Polym. Chem. 3:
1007–1015. https://doi.org/10.1039/C2PY00565D.
47 Kim, H., Kang, Y.J., Kang, S., and Kim, K.T. (2012). J. Am. Chem. Soc. 134:
4030–4033. https://doi.org/10.1021/ja211728x.
48 Roth, P.J. and Theato, P. (2011). Non-Conventional Functional Block Copolymers,
ACS Symposium Series 1066, 23–37. American Chemical Society. https://doi
.org/10.1021/bk-2011-1066.ch003.
49 Häussler, M., Lok, Y.P., Chen, M. et al. (2010). Macromolecules 43: 7101–7110.
https://doi.org/10.1021/ma1008572.
50 Chen, M., Häussler, M., Moad, G., and Rizzardo, E. (2011). Org. Biomol. Chem.
9: 6111–6119. https://doi.org/10.1039/C1OB05276D.
51 Flores, J.D., Shin, J., Hoyle, C.E., and McCormick, C.L. (2010). Polym. Chem. 1:
213–220. https://doi.org/10.1039/B9PY00294D.
52 Stace, S.J., Vanderspikken, J., Howard, S.C. et al. (2019). Polym. Chem. 10:
53 D’Agosto, F., Lansalot, M., and Rieger, J. (2022). RAFT Polymerization: Mate-
rials, Synthesis and Applications (Chapter 15) (eds. G. Moad, S.H. Thang and
E. Rizzardo). Weinheim: Wiley-VCH. https://doi.org/10.1000/000000000.chxx.
54 D’Agosto, F., Rieger, J., and Lansalot, M. (2020). Angew. Chem. Int. Ed. 59:
55 Rieger, J., Zhang, W., Stoffelbach, F., and Charleux, B. (2010). Macromolecules
43: 6302–6310. https://doi.org/10.1021/ma1009269.
56 Rieger, J., Stoffelbach, F., Bui, C. et al. (2008). Macromolecules 41: 4065–4068.
https://doi.org/10.1021/ma800544v.
57 Chong, Y.K., Moad, G., Rizzardo, E. et al. (2007). Macromolecules 40:
9262–9271. https://doi.org/10.1021/ma071100t.
58 Ishitake, K., Satoh, K., Kamigaito, M., and Okamoto, Y. (2012). Polym. Chem. 3:
1750–1757. https://doi.org/10.1039/C1PY00401H.
59 Pfaff, A., Barner, L., Müller, A.H.E., and Granville, A.M. (2011). Eur. Polym. J.
47: 805–815. https://doi.org/10.1016/j.eurpolymj.2010.09.020.
60 Wong, L., Kavallaris, M., and Bulmus, V. (2011). Polym. Chem. 2: 385–393.
https://doi.org/10.1039/C0PY00256A.
61 Jia, Z., Liu, J., Boyer, C. et al. (2009). Biomacromolecules 10: 3253–3258. https://
doi.org/10.1021/bm900817a.
References 57
62 Herfurth, C., Voll, D., Buller, J. et al. (2012). J. Polym. Sci., Part A: Polym. Chem.
63 Moraes, J., Maschmeyer, T., and Perrier, S. (2011). J. Polym. Sci., Part A: Polym.
64 Syrett, J.A., Haddleton, D.M., Whittaker, M.R. et al. (2011). Chem. Commun. 47:
1449–1451. https://doi.org/10.1039/C0CC04532B.
65 Ting, S.R.S., Min, E.H., Zetterlund, P.B., and Stenzel, M.H. (2010). Macro-
molecules 43: 5211–5221. https://doi.org/10.1021/ma1004937.
66 Moad, G., Chong, Y.K., Postma, A. et al. (2005). Polymer 46: 8458–8468. https://
doi.org/10.1016/j.polymer.2004.12.061.
67 Overberger, C.G., Biletch, H., Finestone, A.B. et al. (1953). J. Am. Chem. Soc.
75: 2078–2082. https://doi.org/10.1021/ja01105a017.
68 Moad, G. and Solomon, D.H. (2005). The Chemistry of Radical Polymerization,
2e (eds. G. Moad and D.H. Solomon), 49–166. Amsterdam: Elsevier Science Ltd.
https://doi.org/10.1016/B978-008044288-4/50022-4.
69 Hutchinson, R.A., McMinn, J.H., Paquet, D.A. et al. (1997). Ind. Eng. Chem.
Res. 36: 1103–1113. https://doi.org/10.1021/ie9604031.
71 Jana, S., Parthiban, A., and Chai, C.L.L. (2011). J. Polym. Sci., Part A: Polym.
72 Yhaya, F., Binauld, S., Callari, M., and Stenzel, M.H. (2012). Aust. J. Chem. 65:
1095–1103. https://doi.org/10.1071/CH12158.
73 Wei, C., Wu, K., Li, J. et al. (2012). Macromol. Chem. Phys. 213: 557–565.
https://doi.org/10.1002/macp.201100607.
74 Chen, M., Moad, G., and Rizzardo, E. (2009). J. Polym. Sci., Part A: Polym.
75 Bivigou-Koumba, A.M., Görnitz, E., Laschewsky, A. et al. (2010). Colloid.
Polym. Sci. 288: 499–517. https://doi.org/10.1007/s00396-009-2179-9.
76 Krieg, A., Pietsch, C., Baumgaertel, A. et al. (2010). Polym. Chem. 1: 1669–1676.
https://doi.org/10.1039/C0PY00156B.
77 He, W.-D., Sun, X.-L., Wan, W.-M., and Pan, C.-Y. (2011). Macromolecules 44:
3358–3365. https://doi.org/10.1021/ma2000674.
78 Sun, X.-L., He, W.-D., Pan, T.-T. et al. (2010). Polymer 51: 110–114. https://doi
.org/10.1016/j.polymer.2009.11.014.
79 Chytil, P., Etrych, T., Kříž, J. et al. (2010). Eur. J. Pharm. Sci. 41: 473–482.
https://doi.org/10.1016/j.ejps.2010.08.003.
80 Tominey, A.F., Liese, J., Wei, S. et al. (2010). Beilstein J. Org. Chem. 6: 66.
https://doi.org/10.3762/bjoc.6.66.
81 Flores, J.D., Xu, X., Treat, N.J., and McCormick, C.L. (2009). Macromolecules 42:
4941–4945. https://doi.org/10.1021/ma900517w.
82 Liang, M., Lin, I.C., Whittaker, M.R. et al. (2010). ACS Nano 4: 403–413.
https://doi.org/10.1021/nn9011237.
83 Boyer, C., Granville, A., Davis, T.P., and Bulmus, V. (2009). J. Polym. Sci., Part
84 Alidedeoglu, A.H., York, A.W., Rosado, D.A. et al. (2010). J. Polym. Sci., Part A:
85 Nash, M.A., Yager, P., Hoffman, A.S., and Stayton, P.S. (2010). Bioconjugate
Chem. 21: 2197–2204. https://doi.org/10.1021/bc100180q.
86 Thomas, D.B., Convertine, A.J., Myrick, L.J. et al. (2004). Macromolecules 37:
8941–8950. https://doi.org/10.1021/ma048199d.
87 Harvison, M.A., Davis, T.P., and Lowe, A.B. (2011). Polym. Chem. 2: 1347–1354.
88 Maki, Y., Mori, H., and Endo, T. (2007). Macromol. Chem. Phys. 208: 2589–2599.
89 Blidi, I., Geagea, R., Coutelier, O. et al. (2012). Polym. Chem. 3: 609–612.
https://doi.org/10.1039/C2PY00541G.
90 Girard, E., Marty, J.-D., Ameduri, B., and Destarac, M. (2012). ACS Macro Lett.
1: 270–274. https://doi.org/10.1021/mz2001143.
91 Mori, H., Kudo, E., Saito, Y. et al. (2010). Macromolecules 43: 7021–7032.
https://doi.org/10.1021/ma100905w.
92 Guinaudeau, A., Mazières, S., Wilson, D.J., and Destarac, M. (2012). Polym.
Chem. 3: 81–84. https://doi.org/10.1039/C1PY00373A.
93 Keddie, D.J., Guerrero-Sanchez, C., Moad, G. et al. (2012). Macromolecules 45:
4205–4215. https://doi.org/10.1021/ma300616g.
94 Girard, E., Tassaing, T., Marty, J.-D., and Destarac, M. (2011). Polym. Chem. 2:
95 Roy, D. and Sumerlin, B.S. (2011). Polymer 52: 3038–3045. https://doi.org/10
.1016/j.polymer.2011.04.051.
96 Riedel, M., Stadermann, J., Komber, H. et al. (2011). Eur. Polym. J. 47: 675–684.
https://doi.org/10.1016/j.eurpolymj.2010.10.010.
97 Benaglia, M., Chen, M., Chong, Y.K. et al. (2009). Macromolecules 42:
9384–9386. https://doi.org/10.1021/ma9021086.
98 Benaglia, M., Chiefari, J., Chong, Y.K. et al. (2009). J. Am. Chem. Soc. 131:
6914–6915. https://doi.org/10.1021/ja901955n.
99 Moad, G., Benaglia, M., Chen, M. et al. (2011). Non-conventional Functional
Block Copolymers, ACS Symposium Series 1066, 81–102. American Chemical
Society. https://doi.org/10.1021/bk-2011-1066.ch007.
100 Sriprom, W., James, M., Perrier, S., and Neto, C. (2009). Macromolecules 42:
3138–3146. https://doi.org/10.1021/ma9004428.
101 Lipscomb, C.E. and Mahanthappa, M.K. (2009). Macromolecules 42: 4571–4579.
102 Perrier, S. (2017). Macromolecules 50: 7433–7447. https://doi.org/10.1021/acs
.macromol.7b00767.
59
Kinetics and Mechanism of RAFT Polymerizations

Michael Buback
Georg-August-University Goettingen, Faculty of Chemistry, Institute of Physical Chemistry,
Tammannstrasse 6, 37077 Goettingen, Germany
4.1 Introduction
the leading methods for producing polymers of controlled size and architecture.
To take full advantage of this powerful strategy, the RAFT mechanism needs to be
understood and the relevant rate coefficients should be accurately known to enable
simulation of polymerization kinetics and product properties and to adequately
select RAFT agents for specific monomer systems and reaction conditions. Because
of its chain transfer nature, the concentration of radicals during RAFT polymeriza-
tion under ideal conditions is not affected by the superimposed RAFT equilibrium.
As a consequence, monitoring of polymerization rate as well as analysis of polymer
size provides no clear mechanistic picture. In particular, such problems occur with
RAFT polymerizations mediated by dithiobenzoates (DTBs). These systems exhibit
strong anomalies, such as induction periods with virtually no polymerization
taking place, and significant rate retardation over the entire course of the reaction
as compared to conventional radical polymerization, i.e. reactions without RAFT
agent under otherwise identical conditions.
Two completely different mechanisms have been used to interpret rate retarda-
tion during DTB-mediated polymerizations [1]. One model, which traces back to
Monteiro and de Brouwer [2], assumes intermediate radical termination (IRT), i.e.
reaction of the intermediate radical species, produced by addition of a propagating
radical to the RAFT agent, with another radical species including the possibility of
self-termination of intermediate radicals. The other model adopts slow fragmenta-
tion (SF) of the intermediate radical as the cause for retardation [3].
Monomer conversion vs. time data for DTB-mediated RAFT polymerizations may
be fitted by these two limiting mechanisms. The fragmentation rate coefficients of
the intermediate radical associated with the two models, however, may differ by
more than 6 orders of magnitude [4], which is a nightmare for kineticists.
Objections against the SF model result from electron paramagnetic resonance
(EPR) evidence on the measured intermediate radical concentrations, which are
60 4 Kinetics and Mechanism of RAFT Polymerizations
orders of magnitude below the values predicted using the SF model [5]. The IRT
model can account for the experimentally observed low intermediate radical con-
centration, but was unable to explain the absence of significant amounts of products
from irreversible termination, i.e. three-arm star species, among the products of
acrylate polymerizations [6, 7]. Investigations into styrenic systems demonstrated
that such three-arm stars are stable at typical polymerization temperatures [8].
The controversial situation with DTB-mediated RAFT polymerizations has been
addressed by a task group of IUPAC Polymer Division in 2006 [4]. More recent
investigations are contained in Moad’s thorough review [1], in which he concludes
that the evidence for IRT being the primary cause for retardation in DTB-mediated
RAFT polymerizations appears overwhelming. The SF model should thus not be
applied towards the analysis of polymerizations mediated by DTBs. Recent ab initio
studies [9] have demonstrated that the earlier quantum chemical calculations,
which appeared to provide support for the SF model, need revision in the case of
DTB systems. The present study addresses the application of the single pulse-pulse
laser polymerization-electron paramagnetic resonance (SP-PLP-EPR) method
towards the analysis of RAFT kinetics and mechanism. Pulsed-laser polymeriza-
tion (PLP) is almost instantaneously induced by a laser single pulse (SP), which
decomposes a photoinitiator. The subsequent time evolution of intermediate and of
propagating radicals is measured by online EPR spectroscopy with a time resolution
of microseconds. As radical species are directly monitored, the method is perfectly
suited for detailed analysis of conventional and reversible deactivation (controlled)
radical polymerizations [10]. Moreover, products from the reaction of DTB model
systems have been analysed to clarify the mechanism.
In Section 4.2, aspects of ideal RAFT polymerization kinetics are outlined.
Section 4.3 illustrates the SP-PLP-EPR technique. Section 4.4 briefly addresses
the recently applied quantum chemical procedure [9]. Section 4.5 deals with
RAFT polymerizations mediated by one xanthate, two trithiocarbonates, and one
dithiobenzoate as well as with RAFT-related model systems with a focus on the
anomalies seen in the case of dithiobenzoate RAFT agents.
4.2 Ideal RAFT Polymerization Kinetics

The RAFT kinetic scheme encompasses the well-known steps of conventional rad-
ical polymerization, i.e. initiation, propagation, termination, and transfer processes
[1], onto which the reactions associated with the RAFT equilibrium are superim-
posed. As can be seen from Scheme 4.1, two such RAFT equilibria may be distin-
guished. One refers to the pre-equilibrium period, where a small radical species (P∗m )
adds with rate coefficient kad,1 to the RAFT agent 1, R—S—C(=S)—Z, to yield the
intermediate radical 2. Species 2 may either fragment back, with rate coefficient k𝛽,1 ,
or may fragment with rate coefficient k𝛽,2 to produce a macroRAFT agent 3, with the
leaving group Pm being specific for the polymerizing monomer. After consumption
of 1, rapid exchange of radicals P∗m and P∗n occurs via the polymeric intermediate
radical 4, which, in what follows, will be referred to as INT* . The chain lengths of
the radicals P∗m and P∗n should be close to each other and should gradually increase
during the course of polymerization. Upon ignoring the early RAFT polymerization
period and a potential chain length dependence of the addition and fragmentation
rate coefficients, the main equilibrium, with rate coefficients kad and k𝛽 , may provide
an adequate representation of the RAFT process. The main equilibrium is charac-
terized by the equilibrium constant K eq = kad /k𝛽 , which is a measure of the stability
of the intermediate radical.
S S kad,1 S S kβ,2 ∗
∗ S S
Pm + R Pm R Pm + R
Z kβ,1 Z kad,2 Z
1 2 3
S S kad S S kβ S S
∗ +
Pm Pn Pm Pn Pm + P∗n
Z kβ Z kad Z
4
Scheme 4.1 Pre-equilibrium and main equilibrium RAFT processes.
More detailed studies take primary addition steps into account by which initiator-
derived radicals R* add to the monomer producing the growing monomer-specific
radicals P∗m . Moreover, termination reactions, by combination or disproportiona-
tion, may occur between R* , P∗m , P∗n , and the intermediate radicals 2 and 4. A further
process, the so-called ‘missing step’ [11], that refers to the reaction of the product
from cross-combination of 4 and P∗m with a radical P*, will be presented below, as
this reaction is not part of the ideal RAFT polymerization kinetics.
4.3 Pulsed Laser Experiments in Conjunction with EPR

Detection
As rate measurements and studies into polymer molar mass distributions are
not diagnostic with respect to the RAFT mechanism, PLP techniques in con-
junction with online EPR spectroscopy are particularly helpful for elucidating
mechanistic details [10]. In addition to the analysis of RAFT kinetics [12, 13],
the SP-PLP-EPR method has been successfully applied towards the analysis of
chain-length-dependent termination [14] and of backbiting processes [15] as well
as towards the detailed analysis of atom transfer radical polymerization (ATRP)
[16] and of organometallic-mediated radical polymerization (OMRP) [17].
An important advantage of photoinitiation by laser pulses relates to externally
triggering the amount of photoinitiator-derived primary radicals. Within the
SP-PLP-EPR experiment an intense burst of such primary radicals is almost instan-
taneously produced, and the type and concentration of radicals is subsequently
measured by quantitative EPR spectroscopy. The beauty of the method consists
of the combination of instantaneous production of a high radical concentration,
mostly up to 10−5 mol l−1 , with the sensitive time-resolved EPR spectroscopic
detection of the decay of radical concentrations to values as low as 10−8 mol l−1 , in
both organic and aqueous solutions. Moreover, as a consequence of the extremely
short laser pulse used for initiation, no further primary radicals are produced during
the period of time-resolved EPR detection of radicals after firing the laser pulse at
t = 0.
In the situation where the leaving radical of the RAFT agent is identical in chem-
ical reactivity to the monomer radical, a particularly simple EPR spectroscopic sit-
uation is created with only two types of radicals being present, INT* and P∗m . Most
of the SP-PLP-EPR investigations reported here take advantage of this strategy. The
primary photoinitiator-derived radicals are not seen in most cases, as they add too
rapidly to the monomer or to the RAFT agent.
The components of the SP-PLP-EPR setup are illustrated in Figure 4.1. More
details are given in Ref. [18]. The sample contained in a quartz tube of 5 mm outer
and 4 mm inner diameter is placed into the EPR cavity and is irradiated by UV laser
pulses through a grid. The EPR signal intensity is measured as a function of time t
after applying the laser pulse. The spectrometer and the laser are synchronized by
a pulse generator. Signal intensity is calibrated for absolute radical concentration
against a 2,2,6,6-tetramethylpiperidine-1-yl-oxyl (TEMPO) solution at conditions
as close as possible to the ones of the actual polymerization, e.g. in butyl acrylate
(BA)/toluene solution. First, the double integral of the EPR spectrum is calibrated
against the TEMPO solution. Secondly, the peak signal intensity at a fixed magnetic
field is calibrated against the double integral of the full EPR spectrum, as detailed,
e.g. in Ref. [19]. It should be noted that all components of the setup in Figure 4.1
are commercially available.
In an early SP-PLP-EPR study into RAFT kinetics, the concentration of
INT* was measured for S,S′ -bis(methyl-2-propionate)trithiocarbonate (BMPT,
Setup:
Sample
PC
Cavity:
Cavity
Sample tube
UV laser
Pulse generator
Grid
Illuminated area
Figure 4.1 SP–PLP–EPR setup entirely consisting of commercially available

instrumentation; for more details see Ref. [18].
Scheme 4.2)-mediated butyl acrylate (2 mol l−1 BA in toluene) polymerization

at −30 ∘ C [12]. The left-hand part of Figure 4.2 shows normalized EPR peak
intensities measured at the field position of maximum intensity, H fix , of INT* with
a microsecond time resolution after firing the laser pulse. This data illustrates
that, after applying the intense laser pulse of nanosecond width onto the system
consisting of a photoinitiator, a monomer, and a RAFT agent, the addition of
primary radicals R* (or R − (BA)∗n ) to the RAFT agent occurs at a very fast rate.
Crude kinetic analysis of the initial reaction period reveals that kad is above
105 l mol−1 s−1 [12, 19]. The extended millisecond time range of the experiment
is depicted in the right-hand part of Figure 4.2. As with most other experi-
ments, 2-methyl-1-[4-(methylthio)phenyl]-2-morpholin-4-ylpropan-1-one (MMMP,
Scheme 4.2) was used as the photoinitiator. The early SP-PLP-EPR-type study in
Figure 4.2 demonstrates that this RAFT intermediate radical, INT* , is very rapidly
formed, but is not long-lived and decays quickly.
O
O O
S S
O O N
S S O
(a) BMPT (c) MMMP
O
S S
O
S
(b) EPPT
Scheme 4.2 (a) S,S ′ -Bis(methyl 2-propionate) trithiocarbonate (BMPT), (b) S-(methyl
2-propionate) S ′ -propyl trithiocarbonate (EPPT), and (c) 2-methyl-1-[4-(methylthio)phenyl]-
2-morpholin-4-ylpropan-1-one (MMMP) [20].
1.0
0.8
I(Hfix)/I0(Hfix)
0.6
0.4
Kinetic fit
0.2 –30 °C
30 °C
0.0 60 °C
0 2 × 10–3 5 × 10–3 0 0.05 0.10 0.15

t(s)
Figure 4.2 Time evolution, after applying a single laser pulse at t = 0, of the normalized
EPR signal at the field position Hfix of the EPR peak maximum for INT* in BMPT-mediated
BA polymerizations (C BMPT = 4.1 × 10−3 mol l−1 , C BA = 2.0 mol l−1 in toluene) [12].
O Figure 4.3 SP-PLP-EPR traces of

Bu INT* and P* species after applying a
O laser single pulse, at t = 0, during a
P∗ trithiocarbonate-mediated BA
polymerization (1.5 M in toluene
ld solution) at −40 ∘ C [20].
c fie
eti
INT ∗ gn
Ma
Time
Pm
S · S
Pm
S
INT ∗
Within the SP-PLP-EPR experiments described below, absolute concentrations are

monitored for both propagating and intermediate radicals. As representative results,
data for a trithiocarbonate-mediated BA RAFT polymerization at −40 ∘ C are illus-
trated in Figure 4.3 [20]. The EPR spectrum, which consists of the four-line spectrum
of secondary BA radicals and of the EPR singlet component associated with INT*, is
displayed along the magnetic field axis. The time evolution of both species is mon-
itored at the magnetic field position of the maxima of the BA radical, P*, and of
the INT* component, respectively. PREDICI® fitting of the experimental radical con-
centration vs. time traces using literature data for the rates of propagation and of
chain-length-dependent termination provides the rate coefficients kad and k𝛽 with
an assumption only being required for the size of the cross-termination rate coeffi-
cient, kt,cross , i.e. for the reaction rate of the INT* species with a propagating radical.
The SP-PLP-EPR method is laborious in that calibration of the individual radicals
is required under conditions as close as possible to the ones of the RAFT polymer-
ization experiment. Thus, within a second EPR-based experiment, the ratio of the
double integrals of the deconvoluted individual EPR spectra is measured. This ratio
is identical to the ratio of INT* to P* concentrations, CINT∗ ∕CP∗ . Thus, no EPR cali-
bration is required for accessing the ratio CINT∗ ∕CP∗ which has been determined for
several initial RAFT agent concentrations under quasi-stationary conditions during
continuous laser pulsing, typically at a repetition rate of 20 Hz. The slope of the plot
of the ratio of the two double integrals, i.e. of the two radical concentrations, vs. the
0
initial RAFT agent concentration, CRAFT , yields K eq = kad /k𝛽 according to Eq. (4.1):
CINT∗ ∕CP∗ = kad ∕k𝛽 ⋅ CRAFT = Keq ⋅ CRAFT (4.1)
As pointed out by Kwak et al. [5], Eq. (4.1) is valid when cross-termination and
INT* self-termination rates are negligible compared to the addition and fragmenta-
tion rates. This requirement is fulfilled in most cases but needs to be checked for each
4.4 Quantum Chemical Calculations of the RAFT Equilibrium 65
system. The method via Eq. (4.1) is applied within kinetic studies into monomer-free
model systems, where growing radicals Pm ∗ are absent. The SP-PLP-EPR experiment,
on the other hand, is used during RAFT polymerizations, i.e. in the presence of the
monomer. As BA was the monomer under investigation, the polymerizations (1.5 M
BA in toluene) were carried out at −40 ∘ C to avoid mid-chain radical formation,
which would result in unnecessary complications due to the occurrence of a sec-
ond type of growing radicals, such as mid-chain radicals produced from secondary
radicals by backbiting [21]. With the xanthate, trithiocarbonate, and dithiobenzoate
RAFT agents under investigation, the leaving group has been selected such as to
be chemically identical to an acrylate radical. PREDICI treatment of these systems is
enormously simplified, as only Pm ∗ and INT* need to be considered.
The RAFT agent should weakly absorb at the laser wavelength, 𝜆 = 351 nm, and
should be stable towards laser irradiation. By exposing the RAFT agents dissolved in
toluene to UV irradiation, it was confirmed that the RAFT concentration decreases
by no more than 1% even upon applying sequences of laser pulses as used within
the quasi-stationary experiments. That these laser sequences do not affect RAFT
agent performance has been demonstrated for trithiocarbonate-mediated bulk BA
polymerizations, in which the number average molar mass has been found to lin-
early increase with the degree of monomer conversion, at least up to 40% conversion,
while dispersity remains below 1.3 [19, 22].
4.4 Quantum Chemical Calculations of the RAFT

Equilibrium
Only a brief account of the method will be given, as the strategy used by the Mata
group in carrying out the recent RAFT-related quantum chemical calculations is
presented in more detail elsewhere [9].
Local pair natural coupled cluster (DLPNO-CCSD(T)) calculations have been
applied in a tailored conjugate method, including basis set extrapolation and
solvation effects. Thus, molecular systems of sizes that otherwise would be beyond
reach can be treated. Use is made of the close-range character of dynamic elec-
tronic correlation, constructing a smaller set of configurations on the basis of
local occupied and virtual orbital spaces. This allows for the inclusion of higher
order correlation effects, as canonical wave function methods scale with system
size.
The structures were optimized in solution at the B3LYP-D3/def2-TZVP (with
Becke-Jones damping of the D3 correction) level of theory [23, 24]. The zero-point
vibrational energy corrections, and thermal corrections to enthalpy and entropy,
were computed at the same level. Solvent effects of toluene were included via a
continuum solvation model, i.e. the Conductor-like Polarizable Continuum Model
(CPCM) [25]. The electronic energies for each species were refined through a
conjugate expression, summarized as
[ ]
Eel = E CC∕TZ + ΔCBS + ΔSolv (4.2)
The electronic energy at the DLPNO-CCSD(T)/cc-pVTZ level of theory [26],

E[CC/TZ], has thus been adjusted by two terms: ΔCBS includes a complete basis
set extrapolation using the cc-pVDZ and cc-pVTZ basis sets [27]. Solvent effects
are taken into account by ΔSolv, which refers to the difference in an MP2/cc-pVTZ
calculation with and without the CPCM solvation model.
The calculations were carried out with the ORCA 4.0 program package [9]. The
equilibrium constant K eq of the RAFT reaction was calculated from the reaction free
energy, ΔGr :
( )Δn
Keq (T) = C0 e−ΔGr ∕RT (4.3)
where T is the absolute temperature, C0 is the standard unit of concentration, which
is 1 mol l−1 for the solution phase, Δn is the change in moles upon reaction, and R
is the universal gas constant.
4.5 Xanthate-, Trithiocarbonate- and

Dithiobenzoate-Mediated Polymerizations
4.5.1 General Aspects of Actual RAFT Polymerizations
According to ideal kinetics, the RAFT polymerization rate is identical to that of a
conventional radical polymerization carried out under otherwise same conditions.
Minor differences may occur, as the chain length distribution of radicals in conven-
tional radical polymerization and in RAFT polymerization will mostly be different,
which affects the rate of chain-length-dependent termination [28]. Clear rate reduc-
tions with RAFT polymerizations are assigned to inhibition in the early reaction
period and to retardation in the subsequent range up to high degrees of monomer
conversion. In addition, several avoidable causes of retardation may occur, such as
the presence of air, impurities, instability of the RAFT agent, and a poor choice
of the initiator [1]. The latter effect is part of the initialization process, which has
been thoroughly investigated by Klumperman and colleagues [29, 30]. Initialization
refers to the period during which the initial RAFT agent is consumed. Within this
time interval several addition steps need to be considered, i.e. the addition of initia-
tor fragments I*, of leaving radicals R*, and of propagating radicals P* to the RAFT
agent and to the monomer, followed by fragmentation reactions of the so-obtained
products. The very low rate of monomer consumption during initialization is pri-
marily determined by slow addition of the leaving group R*. Moreover, termination
reactions of the multitude of radical species may play a role. The rather complex
kinetic situation has been carefully analysed by Klumperman and his group [29].
The complexity of the initial period may be reduced by selecting the leaving radi-
cal R* such as to be identical to the primary radical from initiator decomposition. A
significant simplification is reached by selecting R* such that it is chemically equiv-
alent to the monomer-specific propagating radical P*. Moreover, using macroRAFT
agents such that R* is an oligomeric radical based on the monomer under investi-
gation leads to further simplification in that no initialization period occurs and the
4.5 Xanthate-, Trithiocarbonate- and Dithiobenzoate-Mediated Polymerizations 67
system immediately enters the main equilibrium situation (unless avoidable causes
of retardation come into play).
The initialization period is determined by the type of initiator and of the RAFT
agent, in particular, the competition of the I* and R* addition rates to the monomer
and to the primary RAFT agent, the fragmentation rates of the products from these
early addition reactions, and the termination reactions of the different kinds of small
radicals formed in the initial period of the RAFT reaction. The initialization period is
over as soon as the primary RAFT agent R—S—C(=S)—Z is consumed and has been
converted at least into single monomer RAFT adduct species, I—M—S—C(=S)—Z
or R—M—S—C(=S)—Z without producing polymers with the degree of polymer-
ization exceeding unity. While initialization may be largely modified and even com-
pletely avoided, retardation occurs up to high degrees of monomer conversion.
Both initialization and retardation effects may be very pronounced in the case of
dithiobenzoate RAFT agents. During initialization, the polymerization rate may
be very low or even negligible. In the subsequent time range, polymerization is
retarded and remains at a reduced level. The situation is illustrated in Figure 4.4
for BA polymerizations at 70 ∘ C mediated by cumyl dithiobenzoate (CDB),
cyano-iso-propyl dithiobenzoate (CPDB), and ethyl-S-thiobenzoyl-2-thiopropionate
(ETTP, see Scheme 4.3a) at two RAFT agent concentrations: 1.5 × 10−3 mol l−1
(open symbols) and 2.0 × 10−2 mol l−1 (half-filled symbols) [13].
The dotted line in Figure 4.4 represents monomer conversion vs. time data for
conventional radical polymerization, i.e. without RAFT agent. At the lower RAFT
agent concentration (1.5 × 10−3 mol l−1 ), no inhibition occurs, but some retardation
does. As can be seen from the slope of the conversion vs. time data, this retarda-
tion is almost the same for the three dithiobenzoates but depends on the RAFT
agent concentration. At 2.0 × 10−2 mol l−1 (full symbols in Figure 4.4), extended
inhibition occurs for CDB-mediated polymerization. This strong effect is assigned
to the low addition rate to the monomer of the resonance-stabilized cumyl radi-
cal produced by the fragmentation of 2 (Scheme 4.1). This pre-equilibrium effect
is considerably smaller with the two other dithiobenzoates, where ethyl acrylate
Figure 4.4 Inhibition as well

as rate retardation during RAFT
polymerizations of BA at 70 ∘ C 0.3
mediated by ETTP (squares),
Monomer conversion
CPDB (triangles) and CDB

(circles) as well as without RAFT 0.2
agent (dotted line); AIBN
(1.5 × 10−3 mol l−1 ) was the
initiator; the RAFT agent
concentrations were 0.1
1.5 × 10−3 mol l−1 (open
symbols) and 2.0 × 10−2 mol l−1
(half-filled symbols) [13].
0.0
0 50 100 150 200
t (min)
O O
S S
BuO OBu
O
S S
O
O O
ETTP S S
BuO OBu
S S
O O
S S
CDB BuO OBu
CN
S S
O O
S S
CPDB BuO OBu
(a) INT∗
F
S F F
O
O
S O P
O
O O
(b)
Scheme 4.3 (a) Dithiobenzoate RAFT agents under investigation (left) and resonance
structures (right) of the common INT* species under main equilibrium conditions of BA
polymerization. (b) EDTCP (ethyl 2-[1-diethoxyphosphoryl-2,2,2-trifluoroethoxythio
carbonylsulfanyl] propionate).
and cyano-isopropyl radicals, respectively, are released from 2. The addition of a

cumyl radical to BA, under otherwise identical conditions, is by about a factor of
700 slower than the addition of a butyl acrylate propagating radical to BA (i.e. dur-
ing homopropagation) [31, 32]. This factor reduces to about 10 for the addition of
the cyano-isopropyl radical to BA [33].
In the case of ETTP, the reinitiation efficiency of ethyl acrylate radicals is sup-
posed to be very fast. As a consequence, no inhibition occurs. In the initial stage
of RAFT polymerizations, the rate is essentially determined by the addition of the
leaving radical R* to the monomer [34]. Along these lines, Moad [1] concluded that
retardation in the initial period is associated with the R group, whereas retardation
after consumption of the initial RAFT agent is determined by the Z group. In order
to avoid inhibition, it appears recommendable to use RAFT agents with R* being
a good leaving group and also a good (re)initiating radical. In the case of poorly
initiating R*, termination reactions come into play, which may heavily reduce the
polymerization rate.
As can be seen from the RHS of Scheme 4.3a, the resonance-stabilized INT*
species for BA polymerizations mediated by the three dithiobenzoates ETTP, CDB,
and CPDB are identical. Thus it comes as no surprise that, after passing the initial
stage, the slopes of the monomer conversion vs. time correlations in Figure 4.4 are
more or less identical under main equilibrium conditions.
The main equilibrium rates, given by the slope of the straight lines in
Figure 4.4, are lower than those for the associated conventional BA polymer-
izations by a factor of 10 for CRAFT = 1.5 × 10−3 mol l−1 and by a factor of 140 for
CRAFT = 2.0 × 10−2 mol l−1 . The subsequent text exclusively refers to the main
equilibrium situation, which is associated with pronounced and unavoidable
retardation in most dithiobenzoate-mediated RAFT polymerizations. Initial inhi-
bition may be shortened or even avoided by sensibly selecting the RAFT agent,
whereas retardation is observed throughout the course of the polymerization [1].
Initialization will not be further addressed, as excellent reviews are available on this
topic [1, 29, 30].
Retardation is weak or even negligible with xanthate and trithiocarbonate RAFT
polymerizations, but may be strong with dithiobenzoate-mediated BA polymeriza-
tions. These large effects will be used to illustrate and unravel the mechanism behind
this kinetic behaviour, which has been under debate for a long time.
4.5.2 Xanthates
The SP-PLP-EPR technique has been applied towards BA polymerizations in a
solution of toluene at −40 ∘ C with EDTCP being the xanthate/MADIX agent [35].
MADIX is the acronym for Macromolecular Design via the Interchange of Xanthates.
RAFT and MADIX processes are identical with MADIX referring to the specific
case of the Z moiety in Z—C(=S)—S—R being OR.
EDTCP was selected, because phosphor and/or fluorine atoms disfavour conjuga-
tion between the C=S double bond and the electron pair on the oxygen atom and
thus enhance reactivity. Moreover, EDTCP carries a leaving group that is chemically
close to the propagating radical in BA polymerization. Thus the addition rate coeffi-
cients to monomer have been assumed to be identical for the EDTCP-derived radical
and for the propagating radical. The reverse reaction, i.e. the fragmentation step,
is also assumed to be identical for species produced by the two addition reactions.
Fragmentation of intermediate radicals may occur via two pathways: In addition to
normal β-scission, the alkoxy group may be split. The latter reaction may however
be ignored at −40 ∘ C [35], as confirmed by subjecting product samples to end-group
analysis by mass spectrometry [36]. These experiments provided no indication of the

polymer (oligomer) from re-initiation by the Z-group.
The concentrations of INT* and P* were measured at the magnetic field positions
of the characteristic peak maxima via time-resolved EPR after firing an intense laser
pulse at time t = 0 [35]. For deducing absolute radical concentrations, calibration of
the setup with the stable radical TEMPO has been carried out. The entire three-step
calibration procedure is detailed elsewhere [37].
To enhance signal-to-noise quality, up to 20 radical concentration vs. time traces
were co-added in the case of INT* and up to 200 for P*. Illustrated in Figure 4.5
is the so-obtained time evolution of P* and INT* concentrations. The data on the
RHS of Figure 4.5 demonstrates that INT* exhibits maximum concentration imme-
diately after firing the laser pulse, which indicates rapid addition of the primary
MMMP-derived radical to EDTCP. The experimental traces were fitted to a simple
kinetic scheme via the parameter estimation module of the program package PREDICI
version 6.4.6 on an Intel Core Duo, 1.87 GHz computer [35]. The scheme encom-
passes initiation, propagation, chain-length-dependent termination, the individual
RAFT pre- and main equilibrium steps as well as cross-termination of the inter-
mediate radical. As radical chain length i increases linearly with time t after firing
the laser pulse at t = 0, this variation has been included into the PREDICI simula-
tion using the independently determined chain-length-dependent termination rate
coefficients kt (i,i) for reaction of two BA radicals, both of chain length i [15]. The
primary radical concentration, CR0 , which is instantaneously produced at t = 0, and
the rate coefficient for addition of the initiator-derived radical to the RAFT agent
kad,1 (Scheme 4.1), were obtained by fitting the early maximum of the experimental
CINT* and CP* traces. The rate coefficient for addition of the first monomer molecule
to the radical fragment from initiator decomposition was assumed to be ki = 10 × kp .
The selection of the parameters CR0 , ki as well as kad,1 does not significantly affect the
fitting of kad and k𝛽 , as the importance of these parameters is restricted to the very
initial part of the radical concentration vs. time traces (see Figure 4.2).
10
CINT∗ (mol l−1 10−7)
6
CP∗ (mol l−1 10−6)
4 6
4
2
2
0 0
0.00 0.02 0.04 0.06 0.08 0.00 0.02 0.04 0.06 0.08
Time (s) Time (s)
(a) (b)
Figure 4.5 Comparison of simulated and experimental concentration vs. time traces for
the propagating (LHS) and the intermediate (RHS) radicals in a BA polymerization
(1.5 mol l−1 in toluene) at −40 ∘ C with EDTCP being the RAFT agent (2.1 × 10−2 mol l−1 ) and
MMMP the photoinitiator (1.0 × 10−2 mol l−1 ) [35].
With the exception of the rate coefficient for the reaction of INT* with P*, kt,cross ,
the parameters required for PREDICI simulation of the measured radical concentra-
tion vs. time traces are known from separate experiments. Simulations under exten-
sive variation of kt,cross between 0 (SF model) and kt revealed that kt,cross has no
significant impact on the CINT* and CP* vs. time traces with EDTCP-mediated BA
polymerization. The associated change of k𝛽 is by less than a factor of 2. This weak
impact of kt,cross is not surprising in view of the low INT* concentration, which
decays with a half-life of about 1 ms.
The excellent PREDICI fit of the experimental curves in Figure 4.5 is achieved
with kt,cross ≈ 0.5 ⋅ kt (i,i). From experiments at −40 ∘ C and two EDTCP concentra-
tions, the following mean values are obtained: kad = (2.5 ± 0.1) × 104 l mol−1 s−1
and k𝛽 = (2.3 ± 0.3) × 103 s−1 , corresponding to an equilibrium constant of
K eq = (11.1 ± 1.2) l mol−1 .
The second EPR-based method, via Eq. (4.1), where pulse-periodic initiation is
used to create quasi-stationary radical concentrations for various initial RAFT agent
concentrations, has also been applied. Shown in Figure 4.6 is an EPR spectrum mea-
sured during an EDTCP-mediated BA polymerization at −40 ∘ C. The individual EPR
bands for INT* and P* were fitted to the overall band [35].
From CINT* /CP* measured at different initial EDTCP concentrations, the RAFT
equilibrium constant is obtained as K eq = (12.0 ± 0.2) l mol−1 , i.e. in almost perfect
agreement with the value from the SP-PLP-EPR experiment. The low K eq value is
consistent with the poor control observed in xanthate-mediated acrylate polymer-
izations. The value refers to main equilibrium conditions, which has been checked
by SEC analysis of polymer samples after pulse-periodic irradiation.
The kinetic studies were not carried out under conditions of effective polymeriza-
tion control, but were directed towards the determination of rate coefficients. Thus,
it was of primary importance to select xanthate concentrations such that accurate
rate coefficients are obtained. The stationary method via Eq. (4.1) does not require
calibration for absolute radical concentration. On the other hand, the SP-PLP-EPR
method, which needs such calibration, is far more powerful, as individual kad and
P∗ Experiment
INT∗
Simulation
5G
Figure 4.6 Section of the EPR spectrum used for CINT∗ ∕CP∗ determination; black line: EPR
spectrum recorded during laser-induced polymerization of BA (1.5 mol l−1 in toluene) in the
presence of EDTCP (2.1 × 10−2 mol l−1 ) at −40 ∘ C; pulse repetition rate: 20 Hz; sweep time:
42 seconds; grey line: simulated EPR spectrum on the basis of the separately measured
hyperfine coupling constants of INT* and P* species. The field positions used for monitoring
INT* and P* concentrations during the SP-PLP-EPR experiment are indicated by the arrows.
Table 4.1 Summary of the addition rate coefficients k ad and fragmentation rate coefficients
k 𝛽 deduced from SP-PLP-EPR experiments on BA polymerized in toluene solution at −40 ∘ C.
RAFT agent/ k ad
monomer in (l mol−1 s−1 ) k 𝜷 (s−1 ) K eq (l mol−1 ) K eq (l mol−1 )
toluene SP-PLP-EPR SP-PLP-EPR SP-PLP-EPR via Eq. (4.1)
EDTCP/BA (2.5 ± 0.1) × 104 2300 ± 300 11.1 ± 1.2 12.0 ± 0.2
6 4
BMPT/BA (4.1 ± 0.9) × 10 45 ± 5 (9.0 ± 3.0) × 10 (7.0 ± 0.2) × 104
EPPT/BA (3.4 ± 0.3) × 106 140 ± 40 (2.6 ± 0.8) × 104 (2.6 ± 0.1) × 104
6 5
ETTP/BA (1.4 ± 0.4) × 10 4.7 ± 1.5 (3.4 ± 0.6) × 10 (2.3 ± 0.6) × 105
Also listed in the Table 4.1 are the equilibrium constants K eq , from SP-PLP-EPR and from EPR
experiments according to the procedure via Eq. (4.1).
k𝛽 values are accessible. Moreover, the model assumption rtcross ≪ r ad , r 𝛽 underlying

Eq. (4.1) does not need to be made, but the applicability of Eq. (4.1) may be checked
on the basis of individual rate coefficients from the SP-PLP-EPR studies.
RAFT-related rate coefficients and RAFT equilibrium constants for several
xanthates have been estimated by Coote et al. [38], although not for the special
EDTCP agent. Quantum chemical calculations indicate that the addition of prop-
agating radicals to xanthates is much slower than to dithioesters. This is indeed
what the SP-PLP-EPR studies say: The addition rate coefficient of BA-type radicals
to xanthates is approximately 2 orders of magnitude smaller than the associated
numbers for addition to trithiocarbonates and to dithiobenzoates (see Section 4.6
and Table 4.1).
4.5.3 Trithiocarbonates
Rate coefficients kad and k𝛽 have been measured via the SP-PLP-EPR method for
BA polymerizations mediated by S-(methyl 2-propionate) S′ -propyl trithiocarbon-
ate EPPT, see Scheme 4.2) and by S,S′ -bis(methyl 2-propionate) trithiocarbonate
(BMPT, see Scheme 4.2) [20].
Intermediate and propagating radical concentrations, CINT* and CP* , measured
during EPPT-mediated BA polymerizations at −40 ∘ C, are shown in Figure 4.7. As
compared to the situation with EDTCP, the INT* lifetime is extended from about
1 ms (Figure 4.5) to around 50–100 ms (Figure 4.7), but is approximately 1 order of
magnitude smaller than the INT* lifetime with dithiobenzoate-mediated BA poly-
merizations at −40 ∘ C [13]. The radical concentration vs. time profiles were fitted
to the kinetic scheme presented in the Supporting Information associated with Ref.
[20], which has also been used for simulating EDTCP-mediated BA polymerization.
It is again assumed that kprein = kp and ki = 10 × kp , that kt,cross exhibits the same chain
length dependence as kt i,i (see Section 4.5.2), and that kad as well as k𝛽 are identical
for the leaving group R* and for the propagating radical P*. The propagation rate
coefficient kp and the chain-length-dependent termination rate coefficient for BA
kti,i were again taken from the literature.
Figure 4.7 Comparison of Experiment

simulated and experimental
CP∗ (mol l−1 10−5)

concentration vs. time profiles for 1.0
Simulation with kt, cross =
propagating and for intermediate
radicals during BA polymerization 0
(1.5 mol l−1 in toluene) at −40 ∘ C 0.5 0.75⋅kt
with EPPT being the RAFT agent
kt
(5.0 × 10−5 mol l−1 ) and MMMP
being the photoinitiator 0.0
(1.0 × 10−2 mol l−1 ). The (a) 0.00 0.02 0.04 0.06 0.08
simulations were carried out
adopting different values for the
1.5

cross-termination coefficient k t,cross ,
which was implemented as a
chain-length-dependent quantity 1.0
[20].
0.5
0.0
0.0 0.1 0.2 0.3 0.4
(b) Time (s)
Figure 4.7 compares the experimental and simulated radical concentration vs.
time traces for an EPPT-mediated BA polymerization at −40 ∘ C. To check for the
impact of cross-termination, kt,cross has been varied between 0 and kt i,i . The fits of CP*
and CINT* vs. time obtained for these very different cross-termination coefficients sit
upon each other, indicating that kt,cross has only negligible influence on the time evo-
lution of the intermediate and propagating radical concentrations after laser pulsing
at t = 0.
PREDICI simulation of the SP-PLP-EPR traces in Figure 4.7 yields the mean values of
addition and fragmentation rate coefficients at −40 ∘ C as (3.4 ± 0.3) × 106 l mol−1 s−1
and (1.4 ± 0.4) × 102 s−1 , respectively, which results in K eq = (2.6 ± 0.8) × 104 l mol−1
for a solution in toluene. In view of the low temperature, kad and k𝛽 are both large
and they are almost insensitive towards the size of kt,cross , as is presented in more
detail in Ref. [20].
SP-PLP-EPR traces of CINT* and CP* measured during BMPT-mediated BA poly-
merization at −40 ∘ C are shown in Figure 4.8. Adequate fits are obtained adopt-
ing kt,cross to be between 0 and 0.2 × kt i,i . Towards higher kt,cross , the CINT* vs. time
curve can still be well fitted, but the decay of CP* becomes faster than is experimen-
tally observed. A slower cross-termination with three-armed INT*s, as compared to
two-armed INT*s, is assigned to steric hindrance. The half-life of INT* for BMPT is
about three times larger than that with the ‘2-arm’ intermediate radical occurring
in EPPT-mediated polymerization (Figure 4.7). Since the BMPT-derived INT* car-
ries three arms (chains), a 3D treatment should, in principle, be used. To avoid the
associated extensive numerical effort, the reactions involving a three-arm intermedi-
ate radical were translated into a one-dimensional problem. The implementation of
the associated kinetic scheme into PREDICI is detailed in the Supporting Information
associated with Ref. [20].
3 Experiment Figure 4.8 Comparison of

CP∗ (mol l−1 10−5) simulated and experimental
Simulation with kt, cross = concentration vs. time profiles for
2 propagating and intermediate
0
radicals in BA polymerization
1
0.1⋅kt (1.5 mol l−1 in toluene) at −40 ∘ C
with BMPT being the RAFT agent at
0.2⋅kt
3.5 × 10−5 mol l−1 and MMMP at
0 1.0 × 10−2 mol l−1 the photoinitiator.
(a) 0.00 0.02 0.04 0.06 0.08 The simulations were carried out for
3 different sizes of the
(chain-length-dependent)
cross-termination rate coefficient,
2
k t, cross [20].
0
0.0 0.5 1.0 1.5 2.0 2.5
(b) Time (s)
The RAFT-related rate coefficients deduced from the SP-PLP-EPR data for
BMPT-mediated BA polymerization at −40 ∘ C are kad = (4.1 ± 0.9) × 106 l mol−1 s−1
and k𝛽 = (45 ± 5) s−1 . These numbers result in K eq = (9.0 ± 3.0) × 104 l mol−1 . The
addition of a growing radical to BMPT is thus close to the one for addition of a
BA radical to EPPT, whereas fragmentation is slower, by about a factor of 3. This
reduction is assigned to delocalization of the radical functionality over three sulfur
atoms with BMPT rather than over two sulfur atoms with EPPT.
In addition, the procedure according to Eq. (4.1) has been used for deducing K eq
via the CINT* /CP* ratios obtained from the EPR spectra [20]. The ratios obtained
for BMPT are plotted vs. RAFT agent concentration in Figure 4.9. The slope of
the straight line passing through the origin yields K eq = (7.0 ± 0.2) × 104 l mol−1 at
−40 ∘ C, which is remarkably close to the number from the SP-PLP-EPR technique.
To check for a potential chain length dependence of K eq , the stationary EPR experi-
ments for EPPT were carried out for the monomeric RAFT agent of chain length i = 1
as well as for two pre-polymerized EPPT-type RAFT agents of initial mean chain
3 Figure 4.9 Ratio of intermediate radical

and propagating radical concentrations,
CINT∗ ∕CP∗ , plotted vs. BMPT concentration
2 for BA polymerizations (1.5 mol l−1 in
CINT∗/CCP∗
toluene) at −40 ∘ C using MMMP

(1.0 × 10−2 mol l−1 ) as the photoinitiator [20].
1
0
0 1 2 3 4
CBMPT (mol l−1 10−5)
t=0
i EPPT = 1
0.4 t=0
i EPPT = 17
t=0
i EPPT = 38
CINT∗/CP∗
0.3
0.2
0.1
0.0
0.0 0.5 1.0 1.5
CEPPT (mol l−1 10−5)
Figure 4.10 Ratio of intermediate radical and propagating radical concentrations,

CINT∗ ∕CP∗ , plotted vs. EPPT concentration for BA polymerizations (1.5 mol l−1 in toluene) at
−40 ∘ C using MMMP (1.0 × 10−2 mol l−1 ) as the photoinitiator. The EPR experiments under
stationary conditions were carried out with monomeric (iEPPT = 1 at t = 0) and macroRAFT
agents (iEPPT = 17 at t = 0 and iEPPT = 38 at t = 0). The slope of the straight-line fit
corresponds to K eq = (2.6 ± 0.1) × 104 l mol−1 [20].
lengths 17 and 38, respectively. The measured CINT* /CP* ratios for the monomeric
and macroRAFT agents are plotted vs. RAFT agent concentration in Figure 4.10. The
resulting equilibrium constant, K eq = (2.6 ± 0.1) × 104 l mol−1 , applies to the three
EPPT-type RAFT agents that differ considerably in size. This finding indicates that
either K eq is not chain length dependent or the main equilibrium situation is very
rapidly reached with monomeric EPPT. The K eq value of EPPT-mediated BA poly-
merization at −40 ∘ C obtained via the stationary approach (Eq. (4.1)) is in perfect
agreement with the value deduced by the SP-PLP-EPR technique. For BMPT, the K eq
values from the two EPR-based techniques are slightly apart, (7.0 ± 0.2) × 104 l mol−1
(via Eq. (4.1)) and (9.0 ± 3.0) × 104 l mol−1 (from SP-PLP-EPR), but agree within the
limits of experimental accuracy, suggesting that the kinetic scheme underlying the
PREDICI simulation of the time-resolved traces adequately represents BA polymeriza-
tions mediated by these trithiocarbonates.
K eq of BMPT is slightly above K eq for EPPT, which may be due to the reduced
fragmentation rate of the ‘three-arm’ intermediate radical. The K eq values for the
two trithiobenzoates are about 3 orders of magnitude larger than the xanthate K eq .
Within the limits of experimental accuracy, the rate coefficients for addi-
tion of propagating BA radicals to trithiocarbonates at −40 ∘ C are the same:
(4.1 ± 0.9) × 106 l mol−1 s−1 for BMPT and (3.4 ± 0.3) × 106 l mol−1 s−1 for EPPT.
This result fits the ab initio estimate provided by Coote et al. of kad being typically
in the range 105 to 107 l mol−1 s−1 [38]. The fragmentation rate coefficients k𝛽 of the
INT* species are (140 ± 40) s−1 for EPPT and (45 ± 5) s−1 for BMPT. These values for
−40 ∘ C indicate fast fragmentation.
Fragmentation rate coefficients from ab initio estimates are not available so far.
However, the ab initio value of K eq = 1.4 × 104 l mol−1 reported by the Coote group
for BMPT-mediated methyl acrylate polymerization in toluene at −30 ∘ C, which is
close to the numbers from the EPR methods, suggests that also the k𝛽 values from
SP-PLP-EPR should be consistent with the earlier ab initio data [39]. In view of the
minor differences in monomer type and temperature, the agreement of K eq from

SP-PLP-EPR with the equilibrium constant deduced from the earlier ab initio calcu-
lations appears very satisfactory.
The recent ab initio estimates carried out for conditions as used within the
SP-PLP-EPR experiments yield K eq = 3.1 × 105 and 3.9 × 103 l mol−1 for BA poly-
merizations at −40 ∘ C mediated by BMPT and EPPT, respectively [9]. Within
an accuracy of about 1 order of magnitude, these ab initio data agree with the
experimental values and are relatively close to the number from the earlier K eq
estimates for BMPT-mediated methyl acrylate polymerization in toluene at −30 ∘ C
as provided by the Coote group [39]. It is gratifying to note that the earlier ab
initio procedure allows for estimating adequate numbers of K eq in the case of
trithiocarbonates and probably also with xanthates. The same is not true for
dithiobenzoate-mediated polymerizations, where the early predictions yield K eq
data, which are several orders of magnitude larger than the data measured via the
EPR-based techniques.
4.5.4 Dithiobenzoates
The mechanism of RAFT polymerizations mediated by DTBs, C6 H5 C(=S)—SR, has
been controversially discussed for a long time. The observed retardation has been
assigned to either SF of the INT* species or to IRT, i.e. cross-termination of INT*
with propagating radicals P*. Retardation due to these two limiting mechanisms may
be illustrated by Scheme 4.4, which refers to main equilibrium conditions. Both reac-
tion of INT* with P* and slow fragmentation of INT* reduce P* concentration and
thus may give rise to retardation.
S S S S
P P P
kad
+ P ∗
kβ
Radical (P*) INT∗
Scheme 4.4 Main equilibrium situation with dithiobenzoate-mediated RAFT

polymerizations.
Both models can account for the observed retardation, but at the expense of the
associated fragmentation rate coefficient k𝛽 differing by several orders of magnitude.
Adopting kt,cross to be either zero (SF model) or to occur at a comparable rate to
conventional termination via IRT has enormous consequences for k𝛽 , as has been
illustrated in the IUPAC dilemma paper on DTB-mediated RAFT kinetics and mech-
anisms [4]. Upon using the SF model with kt,cross = 0, styrene polymerizations at
60 ∘ C mediated by CDB result in a k𝛽 value of about 3 × 10−2 s−1 and in K eq being
around 1.6 × 107 l mol−1 . Applying the IRT model with kt,cross = kt to the experimen-
tal styrene RAFT data results in a k𝛽 value of about 1 × 105 s−1 and in K eq around 80.
Early ab initio studies into this system provided high K eq , e.g. 7.3 × 106 l mol−1 , for
the cumyl radical —S=C(Ph)SCH3 system at 30 ∘ C, which was used as an argument

in favour of the slow fragmentation model. The SF mechanism is however unable
to explain the measured low INT* concentrations, whereas the IRT mechanism can
provide this explanation but, with acrylates being polymerized, is in conflict with
the observed extremely low yield of the three-arm star product.
In an attempt to stay with part of the SF picture, Konkolewicz et al. assumed
that termination may occur by fast cross-termination of INT* with propagating rad-
icals of chain lengths up to i = 3, whereas cross-termination with larger propagating
radicals is extremely slow [40]. Short radicals undergoing termination would not sig-
nificantly affect the overall molecular mass and thus could account for the absence of
three-arm star material. However, as pointed out by Moad [1], this model extension
is not consistent with experimental findings. Termination of intermediate radicals
exclusively with very short propagating radicals is in conflict with Monte Carlo sim-
ulations of the contact probability between radical chain ends and various positions
on star-branched chains with up to six arms [41]. In addition, the termination rate
being fast for very small radicals and being negligible at radical chain lengths above
i = 3 would be associated with a highly unusual chain length dependence of the
termination rate coefficient. Thus, even with the modification of IRT exclusively
occurring with very small radicals, the SF picture provides no adequate explana-
tion of retardation with DTB-mediated acrylate polymerization. As a consequence,
the IRT model must be considered as the preferred one, in particular, as Geleen and
Klumperman have found that small amounts of three-arm star and four-arm star
species were produced even during DTB-mediated BA polymerization [42].
4.5.5 The ‘Missing Step’ Reaction

To resolve the mechanistic puzzle of three-arm star material being more or less
absent in dithiobenzoate-mediated acrylate polymerizations despite IRT taking
place, the ‘missing step’ reaction has been introduced as a follow-up reaction
of a propagating radical with the star-shaped product Pk –Int from irreversible
cross-termination of INT* and P* (Scheme 4.5) [11].
S S
Pi Pj
kt,cross
P*k +
.
Pk Int
4 5
Scheme 4.5 Cross-termination reaction [11].
Under main equilibrium conditions, the macroINT* (or polyINT*) species 4 con-
trols polymerization. Resonance structures of 4 are depicted in Scheme 4.6 [11].
Extended delocalization of radical functionality is associated with enhanced sta-
bility compared to the situation with xanthate and trithiocarbonate RAFT agents.
Another consequence of delocalization is the occurrence of a plethora of isomeric
S S S S S S S S S S
Pi Pj Pi Pj Pi Pj Pi Pj Pi Pj
= 4
Scheme 4.6 Resonance structures of the macroINT* species 4 [11].
products Pk –Int (Scheme 4.7), as Pk∗ may add at different sites of 4 (see Scheme 4.6).
The chain lengths i and j are close to each other in the case of well-controlled RAFT
polymerization. Delocalization of the radical functionality, in particular into the para
position of the phenyl ring, reduces problems associated with steric hindrance for
radical–radical reactions between macroINT* and Pk∗ .
Pj Pi S S Pk Pk
Pi Pk Pj Pi Pj
S S S S S S S S S S
Pi Pj Pi Pj Pi Pj
Pk Int = or or or or or
Pk Pk
5
Pk
Scheme 4.7 Examples of the Pk –Int species 5 produced by reaction of 4 with propagating
radicals Pk∗ [11].
The ‘missing step’ reaction, as introduced in Ref. [11], is illustrated in Scheme 4.8
for one out of the multitude of cross-termination products 5. The propagating rad-
ical Pl reacts with 5 to yield the combination product, Pl –Pk , as in conventional
termination. Basically, a growing radical picks up a radical moiety from P–Int. The
reaction may occur by combination, as illustrated in Scheme 4.8, but also by dispro-
portionation. The basic signature of the ‘missing step’ in acrylate polymerizations
consists of the transformation of a highly reactive growing radical, P*, and a labile
cross-combination product 5 into a stable termination product, by combination or
disproportionation, and a resonance-stabilized macroRAFT intermediate radical 4.
Because of the multitude of potential P–Int species, a variety of ‘missing step’ reac-
tions may occur, although with different rate coefficients ktr,Int .
S S
Pi Pj S S
Pi Pj
ktr,Int
∗ + Pl P k
.
Pl +
Pk
5 4
Scheme 4.8 ‘Missing step’ reaction illustrated for one out of a multitude of Pi –Int
cross-termination products 5.
The occurrence of the ‘missing step’ reaction may be verified by NMR product
analysis. In addition, by-products of benzyl dithiobenzoate-mediated styrene poly-
merization have provided support for such a process [43]. The mechanism of the
‘missing step’ has not yet been studied in detail. Potential pathways are illustrated
in Scheme 4.9. According to the upper option, Pl picks up the Pk moiety from the
six-membered ring. The pathway in the lower part of Scheme 4.9 suggests that Pl
first adds to a double bond of the six-membered ring prior to the release of Pl –Pk and
the formation of INT* by bond rearrangement.
S S S S
Pi Pj Pi Pj
+ P*l
Pk Pk P*l
− Pl –Pk
S S S S
Pi Pj Pi Pj
·
·
− Pl –Pk
S S S S
Pi Pj Pi Pj
+ P*l ·
Pl
Pk Pk
Scheme 4.9 Two examples of potential ‘missing step’ pathways [44].
Within a third pathway (not shown in Scheme 4.9), the radical P∗l may abstract
the H atom at the para position of the phenyl ring producing a radical species with
extended delocalization of radical functionality. Subsequent fragmentation yields a
macroRAFT species with the Pk moiety at the para position. The observation of such
ring-substituted RAFT components serves as a safe criterion for the occurrence of
‘missing step’ processes (see Section 4.5.5).
The enormous driving force behind the ‘missing step’ reaction (Scheme 4.8)
has been demonstrated by quantum chemical calculations [44]. This step may
be very fast, with ktr,Int even approaching kad [11]. With the ‘missing step’ being
included into the kinetic scheme, the absence of three-arm star products in
dithiobenzoate-mediated acrylate polymerizations is adequately understood. The
impact of the ‘missing step’ reaction depends on the specific monomer and thus
on the type of propagating radicals. At typical polymerization temperatures, the
three-arm star combination product, Pk –Int, has been reported to be stable with
styrenic systems [8]. The styrene radical may be resonance-stabilized to such an
extent that no significant reaction with P–Int occurs. In acrylate polymerizations
mediated by dithiobenzoates, the ‘missing step’ however is fully in action and will
result in the production of dead polymer Pi − Pk (or Pi + Pk ).
As detailed in Ref. [11], including the ‘missing step’ into the ideal RAFT kinetic
scheme allows for adequately simulating the time evolution of monomer conversion,
as well as of INT* and P–Int concentrations. The kinetic scheme subjected to the
PREDICI simulation is presented in Scheme 4.10 with a ‘missing step’ (MS) being
added in bold.
kd
(a) Initiator ⎯⎯→ f × (I∗ + I∗)
10 × kp
(b) I∗ + M ⎯⎯⎯→ P∗
kp
(c) P∗ + M ⎯⎯→ P∗
k
(d) P ∗ + P∗ ⎯⎯→
t
P
kad
(e) P∗ + macroRAFT Int∗
kβ
kt,cross
(f) P∗ + Int∗ ⎯⎯⎯→ P–Int
ktr,Int
(MS) Pl –Int + Pk∗ ⎯⎯⎯→ Int∗ + Pl ─ Pk
Scheme 4.10 Kinetic scheme underlying the PREDICI simulations with the ‘missing step’
(MS) being included; (a) initiator decomposition with efficiency f , (b) monomer addition to
the initiator fragment, I*, (c) propagation, (d) termination, (e) reversible reaction of a growing
radical with 3 to produce species 4, and (f) cross-termination to yield 5.
The ‘missing step’ neither affects the conversion vs. time profile nor the time evo-
lution of the concentration of the macroRAFT intermediate 4. The latter finding
ensures effective RAFT control during the course of the polymerization. With the
rate coefficient of the ‘missing step’ ktr,Int approaching the addition rate coefficient
kad the amount of (normal) termination product Pi –Pk largely exceeds that of P–Int,
i.e. of the primary product from IRT.
In Figure 4.11, the overall impact of the ‘missing step’ is illustrated [11]. The
intermediate radical 4 undergoes two successive irreversible reactions, one with
rate coefficient kt,cross , to yield the cross-termination product 5, and a second one,
with rate coefficient ktr,Int , which produces 4 back. The overall process resembles
a catalytic cycle by which two propagating radicals P* react to a conventional
termination product with the concentration of the intermediate macroRAFT radical
remaining unchanged.
With acrylates, the strong driving force of the ‘missing step’ may give rise to
hydrogen abstraction from the cross-termination product P–Int. Star–star coupling
reactions of two intermediate macroRAFT radicals may occur as well [11]. Perhaps
follow-up processes of products from such reactions need to be additionally
considered, as should the chain-length-dependent and conversion-dependent rate
coefficients be. Examination of these effects requires very detailed and accurate
studies into DTB-mediated RAFT kinetics. The extended scheme, including the
‘missing step’, should be applied towards all systems for which the macroRAFT
Figure 4.11 Catalytic cycle of radical termination kt,cross

mediated by a dithiobenzoate intermediate radical
[11]. + Pk∗
S S
Pi Pj Pk -Int
. 5
4
ktr,Int
+ Pl∗
Pl Pk
intermediate is relatively stable, i.e. also with substituted dithiobenzoates and with
dithionaphthoate-type RAFT agents. It appears advisable to use the expanded
kinetic scheme even for RAFT polymerizations, where INT* is high in energy
and fragmentation rate is very fast. Under such conditions, the ‘missing step’ will
however be of minor relevance.
Clear evidence for ‘missing step’ reactions has been deduced from NMR
analysis of products from reactions of the model system phenylethyl radical
(PE*)–phenylethyl dithiobenzoate (PEDB) [45], which contains only two relevant
types of radicals, PE* and INT*, with PE* resembling a styrenic radical. The
initiator meso-1,2-bis(1-phenylethyl)diazene (PEDA) serves as the source of PE*,
but is not a suitable photoinitiator. Only at and above 110 ∘ C, PEDA reacts (in
toluene solution) with two 2,3-butane-2,3-diyldibenzenes (BDDBs), i.e. with the
diastereomers produced by PE* dimerization. Towards lower temperatures a side
product occurs, which most likely is tris(1-phenylethyl)amine [45]. The product
mixture from the reaction at 110 ∘ C of PEDA and PEDB in toluene was analysed on
the basis of the comprehensive set of reactions depicted in Scheme 4.11, including
cross-termination (IV) and ‘missing step’ reactions (V). Products from other
cross-termination reactions at 110 ∘ C have not been found. Steps (I) through (III) in
Scheme 4.11 refer to initiator decomposition, to dimerization of the PE*, and to the
RAFT equilibrium, respectively.
The solid product from the PEDA–PEDB reaction at 110 ∘ C contains 23% CT1, 44%
PEDB, 3% PEDBMS , and 30% BDDB [45]. The occurrence of the ‘missing step’ reac-
tion is demonstrated by the product 1-phenylethyl-4-(1-phenylethyl)benzodithioate
(PEDBMS ) that has been identified by 1 H and 13 C NMR spectroscopy. The high
concentration of CT1 suggests that this cross-termination product is relatively
stable against attack of resonance-stabilized PE*. The latter finding is consistent
with the observation of the Fukuda group that three-arm star material may occur
in dithiobenzoate-mediated styrene polymerization [8].
Moreover, the ratio of radical concentrations, CINT* /CPE* , was EPR-spectroscopi-
cally measured during the reaction of PEDA and PEDB in toluene at 110 ∘ C. The
overlapping EPR bands were deconvoluted via the separately measured EPR spec-
tra of the individual components [45]. Analysis via Eq. (4.1) of the CINT* /CPE* data,
which were back-extrapolated towards t = 0, yields K eq = (30.7 ± 3.0) l mol−1 . Adopt-

ing a typical size for kad of around 1 × 106 l mol−1 s−1 results in a fragmentation rate
coefficient of about k𝛽 = 3.2 × 104 s−1 , which demonstrates fast fragmentation. Goto
et al. reported a value of k𝛽 ≈ 6.5 × 104 s−1 for polystyryl dithiobenzoate-mediated
styrene polymerization at 40 ∘ C [46]. This number is close to k𝛽 = 1.8 × 104 s−1 deter-
mined for polystyryl dithiobenzoate-mediated styrene polymerization at 60 ∘ C by the
same group [8].
The occurrence of ‘missing step’ reactions has also been shown for the
cyano-iso-propyl radical (CIP*)–CPDB system [47, 48]. Azobis-iso-butyronitrile
was the source of CIP*. The initiation process, the mutual reactions of the CIP
radicals, and the RAFT equilibrium steps are listed as reactions I–IV in Ref. [48].
Scheme 4.12 just contains the mechanistically relevant cross-termination (Va and
Vb), H-shift (VI), and ‘missing step’ (VIIa and VIIb) reactions. The numbering of
the equations in Scheme 4.12 does not fit to the numbers in Scheme 4.11, but refers
to the notations I to IV of Scheme 1 in [48].
The reaction of CPDB and azobis-iso-butyronitrile (AIBN) in toluene solution at
80 ∘ C yields 71% CPDB and 15% tetramethyl succinonitrile (from CIP* dimerization)
together with the cross-termination products CT1 (3%) and CT3 (8%) as well as 3%
of the ‘missing step’ product CPDBMS . The components CT1, CT3, and CPDBMS
kd
(I) N N 2 + N2
PEDA PE
. kt
(II) 2
BDDB
. S S kad S .S
(III) +
kβ
PEDB INT*
. S .S ktcross
(IVa) + S S
CT1
Scheme 4.11 Kinetic scheme for the model system PE*–PEDB reacting in toluene at
110 ∘ C; PEDA: meso-1,2-bis(1-phenylethyl)diazene; PE*: phenylethyl radical; BDDB:
2,3-butane-2,3-diyldibenzene; PEDB: 1-phenylethyl dithiobenzoate; INT*: RAFT
intermediate radical; CT1: cross-termination product 1; CT2: cross-termination product 2;
INT2*: ring-substituted intermediate radical; PEDBMS : ring-substituted PEDB.
. + S S ktcross2 S S
(IVb)
. H
INT*
CT2
S S S .S
+
. kMS1
+
H
(Va)
H
CT2 INT2*
kad kβ
S S
+
.
PEDBMS
S S
+
. kMS2 S .S +
(Vb)
H
INT* BDDB
CT2
kad kβ
S S
+
.
PEDB
Scheme 4.11 (Continued)

S . S
CN
(Va)
NC CN
+ . CN
ktcross1 NC S S
CN
INT∗
CT1
CN
S S
(Vb) NC
. CN
+ . CN
ktcross2
S H CN
H NC CT2
INT∗
CN CN
S H CN kH-shift S
(VI) H CN
S S
NC NC
CT2 CT3
CN CN
(VIIa)
S H CN
+ . CN
kMS1
.
S
CN +
H
CN
S S
NC CT2 NC INT2∗
kad kβ
CN
S + . CN
CN
S
CPDBMS
CN CN
CN
(VIIb)
S H CN
+ . CN
kMS2
.
S
+
S S
CN
NC CT2 NC
INT∗ TMSN
kad kβ
CN
S + . CN
CPDB
Scheme 4.12 Kinetic scheme for the model system CIP*–CPDB; CT1: cross-termination
product 1; CT2: cross-termination product 2; CPDBMS ; ‘missing step’ product.
have been confirmed by 1 H and 13 C NMR spectroscopy [48]. The cross-termination

product CT2 is absent, most likely due to the lower stability of this compound,
which exhibits no delocalization of the radical functionality over the cyclic moiety.
Aromaticity may be reached by the H-shift reaction of CT2 to yield CT3. CT2
may undergo a ‘missing step’ reaction (MS1) to form INT2*, which fragments to
the observed product CPDBMS . A second ‘missing step’ process (MS2, Eq. (VIIb))
produces CPDB back; see Eq. (VIIb).
4.5.6 Kinetic Analysis of Dithiobenzoate-Mediated BA Polymerizations

SP-PLP-EPR experiments have been carried out on ETTP-mediated BA polymeriza-
tions (1.5 M in toluene) at −40 ∘ C and ETTP concentrations between 7.4 × 10−6 and
2.6 × 10−5 mol l−1 [13]. For the stationary experiments a sweep time of 1.3 seconds
was selected, during which less than 1% ETTP was consumed by the UV irradiation.
Since ETTP bears an acrylate-type leaving group, again only two kinds of radicals
need to be considered.
From the EPR band for the INT* and P* signals measured at different initial ETTP
concentrations, the RAFT equilibrium constant has been estimated via Eq. (4.1) to be
K eq = (2.3 ± 0.6) × 105 l mol−1 at −40 ∘ C [13]. The experimental number averages of
molar mass, M n > 700 g mol−1 , indicate that main equilibrium conditions apply. The
K eq value is about 1 order of magnitude larger than the one for BA polymerization
mediated by trithiocarbonates [49] and is about 4 orders of magnitude larger than
K eq for BA polymerized in the presence of xanthates [35].
The individual rate coefficients, kad and k𝛽 , were determined via SP-PLP-EPR
monitoring of CINT∗ and of CP∗ . In Figure 4.12, the measured time dependences of
INT* and P* concentration are shown.
The data on the RHS of Figure 4.12 demonstrate that the resonance-stabilized
BA-ETTP* intermediate decays on a time scale of a few seconds with a half-life of
about one second. The decay of INT* suggested by the SF model, which is illustrated
2.0
Experiment
8
Simulation
CP∗ (mol l−1 10−6)
Slow fragmentation model

1.5
6
1.0
4
Experiment
2 0.5 Simulation
0 0.0
0.00 0.02 0.04 0.06 0.08 0 2 4 6 8
(a) Time (s) (b) Time (s)
Figure 4.12 Experimental and simulated concentration vs. time traces for propagating and
intermediate radicals during a butyl acrylate polymerization (1.5 mol l−1 in toluene) at
−40 ∘ C. The initial ETTP and MMMP concentrations were 2.0 × 10−5 and 1.0 × 10−2 mol l−1 ,
respectively. The full grey lines represent the PREDICI simulations, which are based on the
kinetic parameters and the kinetic scheme detailed in Ref. [13].
by the dashed line, would be far too slow to be consistent with experiment. Thus,
slow fragmentation is additionally demonstrated to be an unlikely explanation for
retardation in DTB-mediated acrylate polymerizations. The SF model would predict
a half-life of more than 10 seconds at 60 ∘ C [50], which corresponds to a half-life
of several hours at −40 ∘ C. The analysis of the experimental radical concentration
vs. time traces has been carried out via PREDICI (version 6.4.6 on an Intel Core
Duo, 1.87 GHz computer) applying the rather simple kinetic scheme mentioned
above and detailed in Ref. [35]. The scheme encompasses initiation, propaga-
tion, chain-length-dependent termination as well as chain-length-dependent
cross-termination of INT*. It is again assumed that the addition and the fragmen-
tation rate coefficients of the ETTP-derived radical species are identical to the
associated rate coefficients of BA radicals. Moreover, the leaving group is assumed
to add to a monomer molecule, and thus to re-initiate, as does a propagating radical,
i.e. kprein = kp . The propagation rate coefficient kp and the chain-length-dependent
termination rate coefficient kt (i,i) are known from the literature [37]. The initiation
rate coefficient was again assumed to be ki = 10 × kp . The primary free-radical
concentration CR0 has been obtained by fitting the maxima of the experimental
CINT* /CP* traces. The selection of the parameters CR0 , ki and of the addition rate
coefficient of P* to the primary RAFT agent kad,1 (Scheme 4.1) does not significantly
affect the kad and k𝛽 values from PREDICI fitting of the SP-PLP-EPR data.
No independently measured number is currently available for the cross-
termination rate coefficient. Kwak et al. estimated kt,cross to be around 0.5 × kt [8].
To check for the impact of cross-termination, parameter estimates have again been
carried out for various sizes of relative cross-termination rate, Ccross = kt,cross /kt ,
with Ccross being varied from zero to unity [13]. Other than with the xanthate and
trithiocarbonate RAFT agents, very low values of kt,cross , i.e. of Ccross approaching
zero, which would correspond to the SF model, do not allow for adequate fit of the
radical concentration vs. time traces in Figure 4.12.
Best fits of the CINT* and CP* vs. time traces were obtained for 0.2 × kt < kt,cross < 0.3
× kt . Thus kt,cross = 0.25 × kt was used within the simulations. This number indicates
fast cross-termination. Fitting of the CINT* and CP* vs. time traces in Figure 4.12
results in kad = (1.4 ± 0.4) × 106 l mol−1 s−1 and k𝛽 = (4.7 ± 1.5) s−1 , respectively.
These coefficients yield K eq = kad /k𝛽 = (3.4 ± 0.6) × 105 l mol−1 in close agreement
with K eq = (2.3 ± 0.6) × 105 l mol−1 , as obtained from the measured ratios of INT*
to P* concentrations (see above). The two EPR-based equilibrium constants are sev-
eral orders of magnitude smaller than the K eq value obtained via the earlier ab initio
methods for radical–dithiobenzoate systems extrapolated to −40 ∘ C [38, 51].
The kad and k𝛽 values from SP-PLP-EPR may also be used to check whether the
reaction conditions of the stationary experiments allow for reasonable estimates of
K eq via Eq. (4.1). This procedure results in r t,cross , the rate of cross-termination, being
indeed negligible compared to the addition and fragmentation rates, r ad and r 𝛽 .
Both pulsed laser experiments demonstrate that the SF model cannot account for
the experimental results of ETTP-mediated BA polymerization. With this system as
well as with CDB- and CPDB-mediated BA polymerization, IRT occurs in conjunc-
tion with subsequent ‘missing step’ reactions. As the major support for the SF model
with DTB-mediated RAFT polymerizations has emerged from the early quantum
chemical calculations, it appears mandatory to have a look at such estimates by
applying advanced quantum chemical methods [9].
4.5.7 Quantum Chemical Calculations for the CIP* – CPDB Model

System
The earlier and the actual quantum chemical estimates of K eq for DTB RAFT agents
are compared with the example of the CIP* + CPDB system in equilibrium with
the associated CIP–CPDB* species. The actual quantum chemical calculations
for the CIP*–CPDB system yield K eq = 1.0 l mol−1 in an environment of toluene
at 70 ∘ C [9]. This number is affected by the quality of estimating the entropy
penalty upon formation of the intermediate radical. Although the impact of the
applied approximations is still heavily disputed, K eq in a solution of toluene is
expected to be accurate within at least 1–2 orders of magnitude. The value of
K eq = 1.0 l mol−1 is far below the gas-phase value for 70 ∘ C obtained by the earlier
calculations: K eq = 2.35 × 105 l mol−1 [52]. After correction for the experimental
solution conditions, by using COSMO-RS solvation energies, the resulting literature
K eq = 2.31 × 104 l mol−1 is still significantly above K eq of the recent ab initio estimate
and of the EPR-based experiment. A discrepancy of about 2 orders of magnitude
remains even after an additional correction for solvation effects [53].
The ratio of the radical concentrations, CCPDB* /CCIP* , measured via EPR with CIP*
being produced by thermal decomposition of AIBN yields K eq = (9 ± 1) l mol−1 for
a toluene environment at 70 ∘ C [47]. This value agrees within the limits of accuracy
with K eq = 1.0 l mol−1 as obtained from the actual quantum chemical estimates.
The experimental reaction enthalpy and entropy are however not in close agreement
with the associated data from the recent ab initio calculations. This discrepancy may
be due to side reactions that are not adequately taken into account within the exper-
iments carried out over a wide temperature range.
Of particular relevance is the mismatch between the earlier and the recent ab ini-
tio calculations, because strong support for the SF model has evolved on the basis
of the earlier ab initio data [50]. As the correction for the molecular environment is
not trivial, it appears recommendable to directly compare K eq for identical condi-
tions, i.e. for the gas phase at 70 ∘ C. These numbers are estimated from the earlier
[52] and from the recent [9] quantum chemical calculations to be K eq = 2.35 × 105
and 0.29 l mol−1 , respectively. The earlier quantum chemical method thus yields an
equilibrium constant for the same dithiobenzoate system, which is about 6 orders of
magnitude larger than both the experimental value and the number from the actual
ab initio calculations. The level of theory used for describing the highly delocalized
radicals appears to be the prime reason for the large mismatch in K eq . In the ear-
lier quantum chemical approach, the system has been divided into parts that were
treated at different levels of theory, i.e. the delocalized species has been subjected
to the G3(MP2)-RAD level. Within the recent calculations, the entire system has
been treated at the higher level of DLPNO-CCSD(T). Another factor to be considered
is the lack of dispersion corrections in the earlier studies. The results indicate that
higher level calculations than used for the earlier studies are required in case of the
dithiobenzoate RAFT systems with extended delocalization of radical functionality.
4.5.8 Dithiobenzoate-Mediated MMA Polymerizations and Model

Systems
That dithiobenzoate RAFT agents do not necessarily induce retardation [1] can be
seen from CPDB-mediated methyl methacrylate (MMA) bulk polymerizations stud-
ied at 60 ∘ C and pressures of up to 2000 bar. Upon varying CPDB concentration
up to 2.0 × 10−2 mol l−1 , only minor retardation is observed. As polymers of lower
molar mass are produced towards higher CRAFT , this retardation may be assigned
to the chain length dependence of the termination rate coefficient [54]. High pres-
sure increases polymerization rate but has no effect on dispersity. Irrespective of the
applied pressure, the molar mass dispersity (Ð) of the poly(MMA) samples gener-
ated by the CPDB-mediated reaction lie on a single line, with Ð decreasing towards
higher degrees of monomer conversion.
In addition, RAFT polymerizations of MMA mediated by 2-methyl methacryl
dithiobenzoate (MMADB) have been studied via stationary EPR experiments using
MMMP as the photoinitiator [55]. The ratio of INT* to MMA* concentrations was
measured at different initial MMADB concentrations using the same deconvolution
strategy as applied towards the PE*–PEDB and CIP*–CPDB systems. The ratio
CINT* /CMMA* decreases with polymerization time t, which indicates considerable
cross-termination. The CINT* /CMMA* data were thus back-extrapolated to t = 0, i.e.
to the situation of the accurately known initial RAFT agent concentration. Analysis
via Eq. (4.1) yields K eq = (4.4 ± 0.4) × 103 l mol−1 as the mean value for −40 ∘ C. This
number is by about 2 orders of magnitude below K eq of dithiobenzoate-mediated
BA polymerization.
Owing to the strong overlap of the EPR signals for INT* and P*, the SP-PLP-EPR
method cannot be applied towards the measurement of individual kad and k𝛽 for
dithiobenzoate-mediated MMA polymerization. Thus Sidoruk et al. used literature
data for kad and Ea (kad ) to estimate 2.5 × 104 and 6.4 × 104 l mol−1 s−1 as the lower and
upper values, respectively, of kad at −40 ∘ C [55]. From the above K eq , the fragmen-
tation rate coefficient k𝛽 is obtained via these kad values to be 5.2 s−1 < k𝛽 < 13.5 s−1 ,
which is close to k𝛽 = 6 s−1 for DTB-mediated BA polymerization [13]. Thus, frag-
mentation rate provides no conclusive argument as to whether retardation occurs, as
retardation is absent with DTB-mediated MMA polymerization, but is strong with
acrylate polymerizations. The low addition rate, however, appears to significantly
contribute to the absence of retardation with DTB-mediated MMA polymerizations.
It is known that MMA radicals add at a lower rate to the C=S double bond [56].
Relatively low kad reduces K eq and results in a lower CINT* , which is similar to the
situation with xanthate-mediated BA polymerization.
Further studies have been carried out on the model system MMA*–MMADB.
Large concentrations of MMA* were produced by thermal decomposition of the
initiator dimethyl-2,2′ -azobis-(2-methylpropionate) (AIBME) [55]. Among the prod-
ucts of the AIBME plus MMADB reaction in toluene at 66 ∘ C is 27% of the ‘missing
4.6 Summary of Results and Concluding Remarks 89
step’ product MMADBMS (2-methylmethacryl-4-[2-methylmethacryl]benzodithi-

oate). This fraction reduces to 13% at 127 ∘ C. Such amounts of ‘missing step’ product
are far above the ones observed with the CIP*–CPDB and PE*–PEDB systems.
The amount of MMADBMS (Scheme 4.13) also largely exceeds that of the
cross-termination product CT1 (2% at 66 ∘ C and 3% at 127 ∘ C, Scheme 4.14), which
indicates that cross-termination of MMA* with INT* at the para position of the
phenyl group is favoured over MMA* attack at the carbon atom between the two
sulfur atoms.
O
S S
O
Scheme 4.13 Structure of the ‘missing step’ product MMADBMS from reaction of AIBME
with MMADB.
O O
O O
S S
O O
Scheme 4.14 Structure of the cross-termination product CT1 (dimethyl 2,2′ -(3methoxy-
2,2-dimethyl-3-oxo-1-phenylpropane-1,1-diyl)bis(sulfanediyl)bis(2-methylpropanoate)).
The analysis of the products from the MMA*–PEDB reaction thus pro-
vides additional evidence for the occurrence of ‘missing step’ processes with
dithiobenzoate-mediated polymerizations.
4.6 Summary of Results and Concluding Remarks
Pulsed laser experiments carried out in conjunction with the highly time-resolved
quantitative monitoring of radical concentrations via EPR spectroscopy allow
for detailed investigations into the kinetics of radical polymerizations. The
two EPR-based methods illustrated above are perfectly suited for the in-depth
understanding of the RAFT polymerization mechanism.
Data obtained for butyl acrylate polymerizations mediated by one xanthate

(EDTCP), two trithiocarbonates (BMPT and EPPT), and one dithiobenzoate (ETTP)
in toluene solution at −40 ∘ C are summarized in Table 4.1. Given in the first three
columns are the addition rate coefficient kad , the fragmentation rate coefficient
k𝛽 , both from SP-PLP-EPR, and the resulting equilibrium constant K eq . Listed in
column 4 is K eq deduced via the EPR-based method according to Eq. (4.1).
The rate coefficients for addition of propagating BA radicals to trithiocar-
bonate and to dithiobenzoate RAFT agents, at −40 ∘ C, are close to each other:
(4.1 ± 0.9) × 106 l mol−1 s−1 for BMPT, (3.4 ± 0.3) × 106 l mol−1 s−1 for EPPT, and
(1.4 ± 0.4) × 106 l mol−1 s−1 for ETTP, in agreement with the result from early ab
initio calculations that predict the kad of most RAFT agents to be in the range
105 –107 l mol−1 s−1 [38]. Xanthate kad differs from this behaviour, as the reactivity
of the thiocarbonyl bond is reduced due to interaction with the oxygen lone pair,
which significantly lowers kad , e.g. to (2.5 ± 0.1) × 104 l mol−1 s−1 for EDTCP at
−40 ∘ C. Associated with the lower xanthate kad is the higher fragmentation rate
coefficient: k𝛽 = 2300 ± 300 (Table 4.1). The two rate coefficients and the resulting
low equilibrium constant indicate low INT* concentrations, which account for the
absence of significant cross-termination reactions and thus of retardation.
With all four RAFT-mediated BA polymerizations, the two types of experimental
K eq values are close to each other (Table 4.1). The earlier quantum chemical calcu-
lations provide good estimates for trithiocarbonate-mediated polymerizations and
probably also for xanthate systems, but need revision in the case of DTB-mediated
polymerizations, where the radical functionality is delocalized over the phenyl moi-
ety. The failure is demonstrated by comparison of the earlier and most recent quan-
tum chemical calculations for the CIP*–CPDB system. Under ostensibly the same
conditions, i.e. for the gas phase at 70 ∘ C, the K eq values from the earlier calculations
are about 6 orders of magnitude larger than the actual quantum chemical calcula-
tions (and above the experimental value).
The values in column 2 of Table 4.1 demonstrate that it is essentially k𝛽 that
causes the differences between K eq of the trithiocarbonate and dithiobenzoate
RAFT agents. Adopting a typical activation energy for EA (k𝛽 ) of 50 kJ mol−1 , the
experimental rate coefficients for −40 ∘ C result in k𝛽 values, which are about 4
orders of magnitude larger at a polymerization temperature of 60 ∘ C. The entire set
of k𝛽 values in Table 4.1 thus is clearly indicative of fast fragmentation. The numbers
that have been reported on the basis of the SF model for dithiobenzoate-mediated
polymerizations at 60 ∘ C [4, 50] are in the range of about 10−2 s−1 , which is not
consistent with the EPR results deduced from quantitative online monitoring of the
relevant radical species.
As kad is associated with a weak temperature dependence, i.e. with an activation
energy EA (kad ) probably even below 10 kJ mol−1 , the equilibrium constants for the
trithiocarbonates and the dithiobenzoate in Table 4.1 correspond to K eq values in the
range 1–100 l mol−1 at around 60 ∘ C.
The SP-PLP-EPR method unambiguously demonstrates that the IRT model, in
conjunction with ‘missing step’ reactions, provides an adequate representation of
the entire body of experimental observations for dithiobenzoate-mediated RAFT
References 91
polymerizations. It should also be noted that Suzuki et al. measured rates of

dithiobenzoate-mediated styrene polymerization in bulk and in miniemulsion and
found significantly higher rates with the miniemulsion polymerization [57]. The
authors conclude that the experimental observation cannot be simulated with the
SF model, but may be adequately understood via the IRT model assuming relatively
high k𝛽 and high kt,cross . This result is in full agreement with the EPR-based data.
Mechanisms of radical polymerization processes that are in conflict with EPR evi-
dence should be considered with extreme care or, even better, should be discarded.
The K eq value for ETTP-mediated BA polymerization from SP-PLP-EPR,
K eq = 3.4 × 105 l mol−1 at −40 ∘ C, is above K eq of trithiocarbonates. This difference
mainly results from k𝛽, which, for ETTP, is 1 order of magnitude smaller than
the number for BMPT and a factor of 30 smaller than the EPPT value (Table 4.1).
Under conditions of similar kad , slower fragmentation thus appears to be the
essential reason behind the significant rate retardation observed in the case of
dithiobenzoate-mediated polymerizations.
To summarize, via SP-PLP-EPR experiments the debate on the RAFT mechanism
with dithiobenzoate-mediated polymerizations, SF vs. IRT, can be safely decided in
favour of the IRT model. The argument raised against IRT that three-arm star mate-
rial is absent in the product mixture from RAFT polymerization is invalidated by
introducing the ‘missing step’. This reaction has been overlooked for a long time, but
has now been confirmed by observation of reaction products that are unambiguously
due to this ‘missing step’. However, even after solving the main controversy with
DTB-mediated polymerizations, further work remains to be done: The SP-PLP-EPR
technique should be applied towards the measurement of addition and fragmenta-
tion rate coefficients for a variety of RAFT agents and monomers and within a wider
range of temperatures.
References
1 Moad, G. (2014). Macromol. Chem. Phys. 215: 9–26.

2 Monteiro, M.J. and de Brouwer, H. (2001). Macromolecules 34: 349–352.
3 Barner-Kowollik, C., Quinn, J.F., Morsley, D.R., and Davis, T.P. (2001). J. Polym.
Sci. Part A Polym. Chem. 39: 1353–1365.
4 Barner-Kowollik, C., Buback, M., Charleux, B. et al. (2006). J. Polym. Sci. Part A
Polym. Chem. 44: 5809–5831.
5 Kwak, Y., Goto, A., Tsujii, Y. et al. (2002). Macromolecules 35: 3026–3029.
6 Ah Toy, A., Vana, P., Davis, T.P., and Barner-Kowollik, C. (2004). Macromolecules
37: 744–751.
7 Feldermann, A., Ah Toy, A., Davis, T.P. et al. (2005). Polymer 46: 8448–8457.
8 Kwak, Y., Goto, A., and Fukuda, T. (2004). Macromolecules 37: 1219–1225.
9 Werner, M., Oliveira, J.C.A., Meiser, W. et al. (2020). Macromol. Theory Simul.
29: 2000022. https://doi.org/10.1002/mats.202000022.
10 Buback, M., Kattner, H., and Schroeder, H. (2016). Macromolecules 49:
3193–3213.
11 Buback, M. and Vana, P. (2006). Macromol. Rapid Commun. 27: 1299–1305.

12 Buback, M., Hesse, P., Junkers, T., and Vana, P. (2006). Macromol. Rapid Com-
mun. 27: 182–187.
13 Meiser, W., Barth, J., Buback, M. et al. (2011). Macromolecules 44: 2474–2480.
14 Buback, M., Egorov, M., Junkers, T., and Panchenko, E. (2004). Macromol. Rapid
Commun. 25: 1004–1009.
15 Barth, J., Buback, M., Hesse, P., and Sergeeva, T. (2010). Macromolecules 43:
4023–4031.
16 Soerensen, N., Barth, J., Buback, M. et al. (2012). Macromolecules 45: 3797–3801.
17 Schroeder, H. and Buback, M. (2015). Macromolecules 48: 6108–6113.
18 Kattner, H. (2016). Radical polymerization kinetics of non-ionized and
fully-ionized monomers studied by pulsed-laser EPR. Doctoral Thesis, University
of Goettingen.
19 Buback, M., Junkers, T., and Vana, P. (2006). Pulsed-laser initiated RAFT poly-
merization. In: Controlled/Living Radical Polymerization, ACS Symposium Series.
944 (ed. K. Matyjaszewski), 455–472.
20 Meiser, W., Buback, M., and Sidoruk, A. (2013). Macromol. Chem. Phys. 214:
2108–2114.
21 Willemse, R.X.E., van Herk, A.M., Panchenko, E. et al. (2005). Macromolecules
38: 5098–5103.
22 Meiser, W. (2012). Investigation of the kinetics and mechanism of RAFT poly-
merization via EPR spectroscopy. Doctoral Thesis, University of Goettingen.
23 Weigend, F. and Ahlrichs, R. (2005). Phys. Chem. Chem. Phys. 7: 3297–3305.
24 Grimme, S., Antony, J., Ehrlich, S., and Krieg, H. (2010). J. Chem. Phys. 132:
154104.
25 Takano, Y. and Houk, K.N. (2005). J. Chem. Theory Comput. 1: 70–77.
26 Woon, D.E. and Dunning, T.H. (1993). J. Chem. Phys. 98: 1358–1371.
27 Saitow, M., Becker, U., Riplinger, C. et al. (2017). J. Chem. Phys. 146: 164105.
28 Barner-Kowollik, C. and Russell, G.T. (2009). Prog. Polym. Sci. 34: 1211–1259.
29 McLeary, J.B., Tonge, M.P., and Klumperman, B. (2006). Macromol. Rapid Com-
mun. 27: 1233–1240.
30 McLeary, J.B., Calitz, F.M., McKenzie, J.M. et al. (2006). Macromolecules 37:
2383–2394.
31 McManus, N.T., Penlidis, A., and Dube, M.A. (2002). Polymer 43: 1607–1614.
32 Coote, M.L. and Davis, T.P. (1999). Macromolecules 32: 4290–4298.
33 Fischer, H. and Radom, L. (2001). Angew. Chem. Int. Ed. 40: 1340–1371.
34 Klumperman, B., van den Dungen, E.T.A., Heuts, J.P.A., and Monteiro, M.J.
(2010). Macromol. Rapid Commun. 31: 1846–1862.
35 Meiser, W., Buback, M., Barth, J., and Vana, P. (2010). Polymer 51: 5977–5982.
36 Buback, M., Frauendorf, H., Guenzler, F., and Vana, P. (2007). Polymer 48:
5590–5598.
37 Barth, J., Buback, M., Hesse, P., and Sergeeva, T. (2009). Macromol. Rapid Com-
mun. 30: 1969–1974.
38 Coote, M.L., Krenske, E.H., and Izgorodina, E.I. (2006). Macromol. Rapid Com-
mun. 27: 473–497.
References 93
39 Lin, C.Y. and Coote, M.L. (2009). Aust. J. Chem. 62: 1479–1483.
40 Konkolewicz, D., Hawkett, B.S., Gray-Weale, A., and Perrier, S. (2008). Macro-
molecules 41: 6400–6412.
41 Froehlich, M.G., Vana, P., and Zifferer, G. (2007). J. Chem. Phys. 127:
1649061–1649067.
42 Geleen, P. and Klumperman, B. (2007). Macromolecules 40: 3914–3920.
43 Moad, G., Chong, Y.K., Mulder, R. et al. (2009). New features of the mech-
anism of raft polymerization. In: Controlled/Living Radical Polymerization:
Progress in RAFT, DT, NMP & OMRP, ACS Symposium Series, vol. 1024 (ed.
K. Matyjaszewski), 3. Washington: American Chemical Society.
44 Buback, M., Janssen, O., Oswald, R. et al. (2007). Macromol. Symp. 248: 158–167.
45 Meiser, W., Buback, M., Ries, O. et al. (2013). Macromol. Chem. Phys. 214:
924–933.
46 Goto, A., Sato, K., Tsujii, Y. et al. (2001). Macromolecules 34: 402–408.
47 Meiser, W. and Buback, M. (2011). Macromol. Rapid Commun. 32: 1490–1494.
49 Barth, J., Buback, M., Meiser, W., and Vana, P. (2010). Macromolecules 43: 51–54.
50 Feldermann, A., Coote, M.L., Stenzel, M.H. et al. (2004). J. Am. Chem. Soc. 126:
15915–15923.
51 Coote, M.L. (2005). J. Phys. Chem. A 109: 1230–1239.
52 Coote, M.L., Izgorodina, E.I., Krenske, E.H. et al. (2006). Macromol. Rapid Com-
mun. 27: 1015–1022.
53 Junkers, T., Barner-Kowollik, C., and Coote, M.L. (2011). Macromol. Rapid Com-
mun. 32: 1891–1898.
54 Buback, M., Meiser, W., and Vana, P. (2009). Aust. J. Chem. 62: 1484–1487.
55 Sidoruk, A., Buback, M., and Meiser, W. (2013). Macromol. Chem. Phys. 214:
1738–1748.
56 Chong, Y.K., Krstina, J., Le, T.P. et al. (2003). Macromolecules 36: 2256–2272.
57 Suzuki, K., Nishimura, Y., Kanematsu, Y. et al. (2012). Macromol. React. Eng. 6:
17–23.
95
RAFT Polymerization: Mechanistic Considerations

John F. Quinn 1,2 , Graeme Moad 3 , and Christopher Barner-Kowollik 4
1
Monash University (Parkville Campus), Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy
and Pharmaceutical Sciences, 381 Royal Parade, Parkville Victoria 3052, Australia
2
Monash University (Clayton Campus), Department of Chemical Engineering, Faculty of Engineering,
Wellington Road, Clayton, Victoria 3800, Australia
3
4
Queensland University of Technology, School of Chemistry and Physics, Faculty of Science, Gardens Point
Campus, Brisbane, QLD 4001, Australia
5.1 Introduction
The development of polymerization with reversible addition–fragmentation transfer

(RAFT) [1] has enabled the synthesis of an extraordinary array of polymers with
well-defined molecular weight and readily functionalizable end-groups [2–5]. For
any given monomer, the utility of RAFT as a tool for controlling polymer properties
is highly dependent on the choice of RAFT agent, which in turn requires under-
standing the mechanism by which RAFT polymerization proceeds. In its simplest
form, the mechanism involves processes that are inherent to any radical polymeriza-
tion: initiation, propagation, chain transfer, and termination. However, in the case of
RAFT, the chain transfer step proceeds via a reversible addition–fragmentation pro-
cess [6], and the polymeric product formed is itself a RAFT agent (see Scheme 5.1).
R S S kadd IMm S S R kβ IMm S S

+ IMm + R
Initial chain transfer
Z k–add Z k–β Z
(1)
kiR
Initiation via expelled R R + M RMn
Where R . >>> I .
Reversible addition- RMm S S kaddP RMm S S MnR k-addP RMn S S

fragmentation chain + RMn + RMm
transfer k–addP kaddP
Z Z Z
(2)
Scheme 5.1 Processes unique to RAFT polymerization: initial chain transfer of a small
molecule ‘RAFT agent’; initiation of new polymer chains via the expelled group R; and
reversible addition–fragmentation chain transfer of the macromolecular transfer agent
formed. The majority of chains are initiated via the R group where R⋅ > > I.

96 5 RAFT Polymerization: Mechanistic Considerations
The first reported RAFT polymerization involved the use of methacrylate

macromonomers [7, 8]. However, in the vast majority of reports the employed
chain transfer agent is a thiocarbonylthio compound, although other species such
as selenocarbonylseleno compounds [9–11] are also used. Importantly, not every
thiocarbonylthio compound is compatible with every monomer, and, as such,
there is an imperative to understand the attributes of the chain transfer agent that
render it applicable for a particular monomer. Copolymerization introduces further
complications to the mechanism [12].
One of the simplest forms of a chain transfer agent that reacts by RAFT (i.e. a
so-called RAFT agent) is depicted below:
S S
R
Z
Depending on the identity of Z, the RAFT agent may be a dithioester,

trithiocarbonate, xanthate, or dithiocarbamate. Each of these categories of
RAFT agents has been the subject of extensive research, and specific chapters in
this text are dedicated to each [13–16]. There are also more exotic examples wherein
dithiobenzoic acid [17] and bis(thionaphthoyl)disulfide [18] have been employed
to yield RAFT agents in situ, although these are typically accompanied by long
induction times and reduced rates of polymerization for reasons that will become
evident. Both the groups R and Z impact on the suitability of the RAFT agent for
application in RAFT polymerization with a particular monomer. The roles of R and
Z are considered in more detail below.
5.2 Role of the R Group

5.2.1 Chain Transfer and Leaving Group Ability
The R group in the general structure R—S—(C=S)Z is – at its most basic level – a
good homolytic leaving group relative to the propagating radical that is itself capable
of efficiently initiating polymerization. The leaving group ability of R can be charac-
terized via the transfer constant (Ctr ):
ktr
Ctr = (5.1)
kp
i.e. the ratio of the rate coefficient for chain transfer (ktr ) to the propagation rate
coefficient (kp ).
In actuality, the efficiency of a RAFT agent is determined by the values of two
transfer constants, Ctr (=ktr /kp ) and C−tr (=k−tr /ki ). The rate coefficient for chain
transfer (ktr ) for a RAFT agent is given by Eq. (5.2), with the value of ktr depending
on the rate of addition of the propagating radical (Pn ⋅) to the RAFT agent and a
partition coefficient (𝜙), which describes the partitioning of intermediate radical (1)
between the starting materials and the products – see Scheme 5.1.
[ ]
k𝛽
ktr = kadd 𝜙 = kadd (5.2)
k−add + k𝛽
The radical (R⋅ ) expelled from the transfer agent is also partitioned between adding
to the monomer and reacting with the macromolecular RAFT agent. The rate coef-
ficient associated with this reaction (k−tr ) is thus defined as shown in Eq. (5.3).
[ ]
k−add
k−tr = k−𝛽 (1 − 𝜙) = k−𝛽 (5.3)
k−add + k𝛽
A high chain transfer constant is associated with good leaving group ability and,
provided that the R group can efficiently initiate further polymer chains, polymers
with narrow molecular weight distribution are formed. In cases where the transfer
constant is low, the RAFT agent is consumed more slowly and as a result the bulk
of the chains are not initiated at the same time. In such situations it is possible to
apply the methods used for measuring transfer coefficients for conventional chain
transfer agents. As such, it is prudent at this point to include some description of the
various methods for determining these constants.
5.2.2 Measurement of the Chain Transfer Constant

Mayo reported the first equation for determination of the chain transfer constant
in 1943 [19]. This initial report was associated with the specific scenario of chain
transfer to solvent. By observing that the degree of polymerization (X n ) in the poly-
merization of styrene could be determined by dividing the rate of chain growth by
the total rate of chain termination (including chain transfer to solvent, termination
by disproportionation, and chain transfer to monomer) at low conversion (i.e. where
the relative concentrations of monomer and solvent remain constant), Mayo devel-
oped the following expression:
[ ]
kp Pn ⋅ [M]
Xn = [ ] [ ]2 [ ] (5.4)
ktr Pn ⋅ [S] + kt Pn ⋅ + ktr(M) Pn ⋅ [M]
After taking the reciprocal and using steady-state approximation to remove the
term [Pn ⋅ ] from the equation, this reduces to
√
1 ktr [S] ki kt + ktr(M)
= + (5.5)
Xn kp [M] kp
With no added chain transfer agent (i.e. in this case solvent), the first term on the
RHS reduces to zero, and therefore the second term represents the inverse of degree
of polymerization in the absence of added chain transfer agent. Thus, the equation
can be recast as
1 [S] 1
= Ctr + (5.6)
Xn [M] Xn0
where X n0 is the degree of polymerization achieved in the absence of chain transfer
agent and Ctr is the chain transfer constant, as defined above in Eq. (5.1). Provided
that the value for kp is known, ktr can also be accessed via this method. Although
initially derived to describe chain transfer to the solvent, this equation is also used
to describe the chain transfer constant for added chain transfer agents. One of the
key limitations of the Mayo method for determining the chain transfer constant
is that the degree of polymerization must be known to a high degree of accuracy,

and therefore the method is susceptible to error associated with size exclusion chro-
matography (SEC) measurements. Specifically, determination of X n via SEC is often
relative, and the computed value for X n is sensitive to small variations in the base-
line. To overcome this limitation, Gilbert and Clay proposed an alternative approach
[20], wherein the chain transfer constant is determined via the gradient of a plot
of the natural logarithm of the number chain length distribution (CLD) in the high
chain length region against the ratio of the chain transfer agent (CTA) and monomer
concentrations (Eq. (5.7)).
⟨ ⟩ [ ⋅]
d ln yn [CTA] kt P n
= Ctr + (5.7)
dn [M] kp [M]
where in yn is the number fraction of dead polymer molecules with chain length n.
This approach has the advantage of being much less susceptible to variations in the
baseline of the measured CLD. Subsequent work by G. Moad and C. L. Moad [21] has
shown that applying this equation to those chain lengths having the highest signal
to noise ratio for the number CLD (i.e. the top 80% of the number CLD) enables
determination of Ctr values to a high degree of accuracy.
It is important to note that both the Mayo method and the ln(CLD) method require
data for low monomer and transfer agent conversions, and as such rapid consump-
tion of the transfer agent and efficient re-initiation renders these approaches unsuit-
able for estimating the Ctr for the most effective RAFT agents. Further, since the orig-
inal method of Mayo does not contemplate the polymeric product of chain transfer
also behaving as a chain transfer agent, there are limitations in applying these meth-
ods to RAFT systems (e.g. C−tr is assumed to be zero, which is unlikely for reactive
RAFT agents such as trithiocarbonates and dithiobenzoates). Nevertheless, these
methods have been applied to estimate the chain transfer constant in RAFT poly-
merizations where the rate of chain transfer is sufficiently low (e.g. where Ctr < 2).
In situations where the chain transfer constant is higher, other approaches need to
be employed.
In early publications on polymerization with RAFT mediated by thiocarbonylthio
compounds, Moad and coworkers [22] proposed the application of another classi-
cal method, known as the Walling method [23] or the O’Brien method [24], (but
which could also be attributed to Mayo and coworkers [25]) for evaluating the trans-
fer coefficient. This approach involves evaluating the relative consumption of the
transfer agent and monomer and enables estimation of the chain transfer constant
via Eq. (5.8):
d [CTA] [CTA]
= Ctr (5.8)
d [M] [M] + Ctr [CTA] + C−tr [macroCTA]
where [CTA] is the concentration of the chain transfer agent and [macroCTA] is the
concentration of the polymeric RAFT agent formed, Ctr = ktr /kp and C−tr = k−tr /ki .
This expression takes into account the consumption of the transfer agent due to the
reactivity of both propagating radicals and the expelled radical formed by homolytic
cleavage of the intermediate radical (R⋅ ). Provided that the rate of reaction of the
group R⋅ to the transfer agent is negligible (not always a fair assumption, see Section
5.2.4) and the chains are sufficiently long, this equation reduces to
d [CTA] [CTA]
≈ Ctr (5.9)
d [M] [M]
By rearranging and integrating
[CTA] [M]
d [CTA] d [M]
≈ Ctr (5.10)
∫[CTA]0 [CTA] ∫[M]0 [M]
ln [CTA] − ln [CTA]0 ≈ Ctr ln [M] − ln [M]0 (5.11)
ln [CTA] ≈ Ctr ln [M] + constant (5.12)
As such, a plot of ln[CTA] and ln[M] will yield the chain transfer constant as the
gradient, i.e.
d (ln [CTA])
Ctr ≈ (5.13)
d (ln [M])
An example of the use of Eq. (5.2) with parameter estimation by kinetic simu-
lation is given in Figure 5.1. The Ctr and C−tr for PhC(=S)SC(CH3 )2 Ph in methyl
methacrylate (MMA) polymerization were estimated as 25 and 450, respectively.
–2
–4
–6
In(CTA)
–8
–10
–12
1.9 2.0 2.1 2.2
In(MMA)
Figure 5.1 Double log plot of chain transfer agent concentration against monomer
concentration for polymerization of methyl methacrylate in the presence of
PhC(=S)SC(CH3 )2 Ph (CTA). Data are for bulk MMA polymerization at 60 ∘ C with
azobisisobutyronitrile as the initiator in the concentration range 0.0005–0.04 M and with
0.0058 M ( ) or 0.029 M ( ) PhC(=S)SC(CH3 )2 Ph as RAFT agent. Lines are those predicted by
Eq. (5.1) with C tr = 25 and C −tr = 450. Source: Adapted with permission from Chong et al.
[22]. © 2003, American Chemical Society.
Note that use of the simplified expression (5.6) gives an apparent transfer constant
of 5.9. Equation (5.6) is recommended only for giving an approximate ranking in the
case of more active RAFT agents where a series of experiments are conducted under
similar conditions (of [RAFT agent]0 and [M]0 ).
One of the challenges of this approach is employing a method to simply determine
the conversion of the chain transfer agent, as these are typically present in low con-
centrations. Moad has also proposed an elegant method for determining the amount
of residual chain transfer by comparing the calculated and experimental molecular
weights via the relationship:
[M]0 −[M]t
[CTA]0 − [CTA]t [CTA]0 Xn (calcd)
Conv (CTA) = = [M]0 −[M]t
= (5.14)
[CTA]0 Xn (found)
[CTA]0 −[CTA]t
where X n (calcd) is the expected number-average degree of polymerization

assuming complete conversion of the chain transfer agent and X n (found) is the
number-average degree of polymerization determined experimentally. It may be
beneficial to correct X n (calcd) by considering those radicals derived from the
initiator in addition to those from the R group of the transfer agent. This may be
achieved using the expression
[M]0 − [M]t
Xn (calcd) = ( ) (5.15)
[CTA]0 − df [I]0 − [I]t
wherein d is the number of chains produced from radical–radical reaction, f is the
initiator efficiency, and [I]0 − [I]t can be calculated via the exponential decay of the
initiator using kd , the rate constant for initiator decomposition:
( )
[I]0 − [I]t = [I]0 1 − e−kd t (5.16)
In cases where the initiator concentration and radical flux are low such that the
number of initiator-derived chains is negligible, this term may be ignored.
It is implicit in the derivation of the Mayo, lnCLD, and Walling methods that
the value C−tr is zero. However, in the case of more active RAFT agents it is well
understood that this is not the case. Nevertheless, the Walling method applied to
data obtained under a consistent set of reaction conditions may still be employed
to obtain a qualitative ranking of RAFT agent activity via apparent transfer con-
stants. However, the values of Ctr may be underestimated by several orders of
magnitude.
As an example, the Walling approach, or conventional Mayo analysis, has been
applied to a series of dithioesters with systematic variation of the R group structure
(see Table 5.1). The value of the chain transfer constant broadly correlates with the
homolytic leaving group ability of the R group with respect to propagating methacry-
lyl radicals. Based on these and other observations, it can be considered that steric
factors, polar effects, and the stability of the radical R⋅ , all contribute to the trans-
fer constant and therefore the effectiveness of the RAFT agents. Significantly, the R
group is shown to have little impact on the rate of addition to the thiocarbonyl group.
In a number of examples, such as the polymerization of styrene using benzyl
dithiobenzoate as a chain transfer agent, a significant narrowing of molecular
Table 5.1 Transfer constants of

various dithiobenzoates in MMA
polymerization at 60 ∘ C.
R group Cs
CH3 5.9
C
CH3
CH3 6.6
Cl C
CH3
CH3 6.8
H3C C
CN
CH3 1.7
H3C C
CO2Et
CH3 CH3 0.4

H2
H3C C C C
CH3 CH3
CH3 0.03
H3C C
CH3
Source: Data are taken from

Walling [23].
weight distribution occurs as the polymerization progresses. This behaviour is

caused by the initial transfer agent being consumed relatively slowly. While this
enables estimation of the chain transfer constant, to get a low dispersity at low
conversions the initial RAFT agent must be quickly consumed. This illustrates
the difficulty associated with the estimation of chain transfer constants for highly
efficient RAFT agents.
The value of the chain transfer constant for the initial transfer step may also be
estimated by other methods. For instance, in cases where the polymerization pro-
ceeds with the so-called ‘hybrid RAFT polymerization behaviour’ (i.e. a rapid initial
increase in the degree of polymerization followed by a linear evolution of molecu-
lar weight with conversion), Barner-Kowollik and coworkers proposed a method to
determine Ctr via SEC measurements. This approach relies on the expression
kp [M]0
kadd,0 = ( inst ) (5.17)
Xn − 1 [CTA]0 𝜙
wherein kadd,0 is the rate coefficient for the addition of the propagating polymer radi-
cal to the chain transfer agent, kp is the propagation rate coefficient, Xninst is the initial
degree of polymerization, and 𝜙 is the probability of fragmentation in favour of the
products [26]. In the case of the initial chain transfer step with an agent that primar-
ily fragments to expel the radical R⋅ , the value of 𝜙 = 1 and therefore kadd,0 = ktr,0 ,
and the expression can be rearranged to give [27]

[M]0
Xninst = +1 (5.18)
Ctr,0 [CTA]0
As such, a plot of the degree of polymerization of the initially formed polymer vs.
[M]0 /[CTA]0 can be used to deduce Ctr as the reciprocal of the gradient. While the
afore-mentioned methods for determining the Ctr are readily applicable to the initial
transfer step, their application to the main RAFT equilibrium is difficult for practi-
cal reasons (such as the difficulty in accurately determining concentration changes
for the macroCTA). As a result, approaches for determining Ctr for the main RAFT
equilibrium have also been developed, many of which have been derived from treat-
ment of degenerative chain transfer. For example, Goto, Fukuda and coworkers pro-
posed a method that employs very low concentrations of macroCTA relative to the
monomer [28]. Under these conditions, the larger number of monomer units added
per activation–deactivation cycle enables resolution of the chain extended polymer
from the macroCTA in the SEC chromatograms. By using the relative peak areas cor-
responding to the macroCTA and chain extended polymer, it is possible to estimate
a value for the activation rate coefficient kact via the expression
S0
ln = kact t (5.19)
S
where S0 and S are the concentrations for macroCTA and chain extended polymer
respectively. As such plotting the natural logarithm of the ratio of the SEC peak areas
for the macroCTA and the polymer at various times vs. time will yield kact as the
gradient. This can in turn be used to determine ktr via the expression
kact = kex [P⋅ ] (5.20)
wherein kex = ktr /2 (since Ctr = C−tr ). As such, by plotting kact against Rp /[M], Ctr
can be extracted via the gradient.
Goto and Fukuda have also proposed determination of the chain transfer constant
in degenerative chain transfer via analysis of the dispersity. In this case, the disper-
sity factor Y (i.e. Y = Ð − 1) is related to the chain transfer constant via the following
expression: [29]
[ ( )]−1 ( )
1 x
Y− = Ctr (5.21)
Xn 2−x
where x is the fractional conversion. This expression has been further extended to
account for conventional initiation and termination reactions [30]. Nevertheless,
Eq. (5.21) (and its extended version) does not consider possible transfer reactions
with the initial chain transfer agent, and as such it is only valid in situations where
the RAFT agent is consumed relatively quickly (i.e. monomer conversions below
a small percentage). Moreover, the method is strictly only applicable to macroCTA
where the Ctr values for the initial and product RAFT agents are the same (because
they differ only in chain length). As such, the application of this method to provide a
transfer constant for an initial RAFT agent in a polymerization is at best debatable.
However, the method has proved useful when used to rank the activity of RAFT
agents in a series of polymerizations conducted under similar conditions. A further

issue with this methodology is the accuracy of experimentally determined dispersity
measurements.
Values of transfer coefficients can also be estimated via kinetic simulation using
either numerical integration [31] or Monte Carlo methods [32]. In these cases, the
values are chosen in order to fit the experimental data. For a range of values of C−tr
that may cover orders of magnitude, it is often possible to choose a value of C−tr such
that a satisfactory fit is obtained. This may account for the wide range of values that
appear in the literature for certain systems (e.g. for the 2-phenylprop-2-yl dithioben-
zoate mediated polymerization of styrene) [33] and serves to emphasize that these
values should be treated with caution.
While methods for describing degenerative chain transfer can be applied to deter-
mine the chain transfer coefficients in RAFT polymerization, such approaches do
not provide values for the isolated addition and fragmentation rate coefficients. To
address this, Buback and coworkers have recently proposed an approach for deter-
mination of the addition–fragmentation equilibrium coefficient K eq using electron
paramagnetic resonance (EPR) spectroscopy [34]. Specifically, these researchers pro-
posed determination of the ratio of the propagating macroradicals and intermediate
radical species, which could then be combined to estimate K eq via the expression
kadd [Int]eq [Int]

Keq = = ⋅ = ⋅ (5.22)
kfrag [P ]eq [P]eq [P ] [P]
wherein kadd is the rate constant for addition, kfrag is the rate constant for fragmen-
tation, and [Int] is the intermediate radical concentration; [P⋅ ] is the total concen-
tration of macroradicals, [P] is the total concentration of deactivated chains, and the
suffix ‘eq’ denotes equilibrium. By combining this EPR approach with pulsed laser
initiation the decay of [Int] and [P⋅ ] with time can be determined, provided that the
EPR is suitably calibrated to determine both radical populations [35]. Subsequent fit-
ting of the resulting decay curves using a modelling package such as Predici® enables
the values for kadd and kfrag to be estimated. This approach is described in some detail
in the chapter by Buback [36].
For a comprehensive treatment of methods available to estimate the chain trans-
fer constants in RAFT polymerization (including others not described here), the
reader is referred to the recent review on the topic by Barner-Kowollik, D’hooge,
and coworkers [27].
5.2.3 Mechanistic Implications for Block Copolymer Synthesis

The need for the R group to be an effective homolytic leaving group has important
implications for block copolymer synthesis. In general, there is a requirement that
the first synthesized block yields a superior homolytic polymeric leaving group; this
is essential to enable radical addition of the second monomer to the first block. In
situations where the first synthesized block is a poor leaving group with respect to
the radical derived from the second monomer, block formation will be minimal, and
Case I R(M1)n S S I(M2)m S S

+ I(M2)m· + R(M1)n·
Poor leaving
group wrt Z Z
propagating
radical
M2
Poor block
formation
Case II R(M1)n S S I(M2)m S S

+ I(M2)m· + R(M1)n·
Good leaving
group wrt Z Z
propagating
radical
M2
Effective block
formation
Scheme 5.2 Formation of block copolymers via RAFT. Where the polymeric radical from
the first formed block is an inferior leaving group to those radicals formed from the second
monomer, fragmentation occurs principally in the direction of the starting reactants, leading
to minimal block formation (case 1). When the polymeric radical from the first formed block
is a good leaving group relative to radicals formed from the second monomer, blocks can
readily form via addition of the second monomer to the expelled polymer radical (case 2).
a significant proportion of the macromolecular chain transfer agent will be present

in the product (Scheme 5.2).
It is also important that the R⋅ radical is a very good initiating radical. If addi-
tion to the monomer is slow, poor blocking efficiencies may be observed, along with
by-products from the self-reaction of R⋅ (see Section 5.2.4).
Despite the general requirement for high transfer constants of the initially
formed macromolecular chain transfer agent to enable block formation via RAFT,
there are a small number of exceptions to this rule in the literature. Moad et al.
demonstrated the successful synthesis of poly(styrene-block-methyl methacry-
late) (P[Sty-block-MMA]) wherein the polystyrene block was synthesized first
by employing starved-feed emulsion polymerization [37]. They applied the same
approach to prepare polystyrene by RAFT emulsion polymerization with a xanthate
RAFT agent [37]. These authors had previously shown that starved-feed conditions
could be employed to make low dispersity polymers and block copolymers from
macromonomer RAFT agents [8]. As such, an initial block of polystyrene was
prepared by RAFT emulsion using benzyl dithioacetate as the RAFT agent to reach
a conversion >99%; MMA was then added by slow addition at a rate commensurate
with the rate of polymerization, thereby maintaining the very low concentration
of monomer relative to the chain transfer agent. This approach overcame the
limitation imposed on the monomer order of addition by the low Ctr of the
polystyryl macromolecular chain transfer agent. The methodology takes advantage
of compartmentalization effects to limit the extent of termination. This approach
has also recently been exploited by Haddleton and coworkers [38] to prepare
multiblock polymers using unsaturated methacrylate oligomers as non-sulfurous
reversible addition–fragmentation chain transfer agents. It has also been used to

prepare low-dispersity poly(methyl methacrylate) (PMMA) with xanthate RAFT
agents [39]. In principle, other agents with low transfer constants could also be
potentially applied in this manner. The observations made in these experiments
also provided the basis for the use of RAFT polymerization in the rapid synthesis of
multiblock copolymers by the ‘nanoreactor concept’ [40–42].
Barner-Kowollik and coworkers have also previously reported on a system where
the chain transfer kinetics of the initial agent differs substantially from that of the
formed macromolecular transfer agent [43] (Figure 5.2a) and this example illumi-
nates the potential implications of inappropriately chosen conditions/reagents for
RAFT polymerization. Cumyl phenyldithioacetate (CPDA) functions effectively as
a RAFT agent for the bulk polymerization of styrene initiated by azobisisobutyroni-
trile (AIBN) at 60 ∘ C, with the formation of polymers having controlled molecular
weight and linear evolution of molecular weight with conversion. However, applica-
tion of the same agent with MMA yields remarkably different behaviour. Specifically,
the initial chain transfer reaction is sufficiently slow with respect to propagation that
at low conversions (i.e. low yields of polymeric transfer agent), behaviour approx-
imating classical chain transfer is observed. However, as the CPDA is consumed,
the emergence of a second ‘living’ distribution becomes evident (Figure 5.2b), with
the distribution returning to being unimodal and shifting clearly to higher molecu-
lar weight at higher conversions (Figure 5.2c). Significantly, the excess of CPDA at
low conversions enables the chain transfer constant to be determined via the Mayo
method. In this case, Cs values of 4.1, 3.8, and 3.9 (corresponding to ktr of 1324,
1645, and 2219 l mol−1 s−1 ) were determined at 25 ∘ C, 35 ∘ C, and 45 ∘ C, respectively,
enabling calculation of the activation energy for the transfer reaction as 26 kJ mol−1 .
This approach, based on chromatographic analysis, is similar to that used by Fukuda
and coworkers [28] to estimate Ctr for macroRAFT agents (macroCTA).
5.2.4 Re-Initiation and Initialization

The choice of transfer agent for a particular monomer is also influenced by the suit-
ability of R for reinitiating polymerization. In general, the rate of addition of R to
the monomer should be greater than the propagation rate (i.e. the rate constant for
addition of the group R to monomer should exceed the propagation rate coefficient
[kiR > kp ]). Importantly, the factors that tend to make R a suitable homolytic leaving
group (and thus provide an adequate rate of chain transfer) also tend to reduce the
rate of addition of R to the monomer. As such, a balance needs to be found between
the leaving group ability of the R group and its propensity to add to the monomer.
Helpful data for the rate of addition of several R group candidates are readily avail-
able in the literature [44, 45]. A selection of these data is included in Table 5.2 [46].
For the polymerization of styrenic and methacrylate monomers R groups such
as 2-cyanoprop-2-yl and 2-phenylprop-2-yl are generally suitable, as the rate of
addition of these radicals to the corresponding monomers is sufficiently fast.
However, for polymerization of monomers such as N-vinylpyrrolidone and vinyl
acetate the rate of addition of 2-cyanoprop-2-yl and 2-phenylprop-2-yl groups is
(i)
S S S S
Pn + Pn +
(a)
(ii)
S S S S
Pn Pm
Pm + + Pn
(b)
12
10
Relative response
0
3 4 5 6 7
log M
0.9
0.8
Increasing conversation
0.7
Relative response
0.6
0.5
0.4
0.3
0.2
0.1
0
3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0
(c) log M
Figure 5.2 (a) Chain transfer reactions for (i) cumyl phenyldithioacetate and (ii) poly
(methyl methacrylyl) phenyldithioacetate. (b) Evolution of molecular weight distributions in
a cumyl phenyldithioacetate mediated (bulk) polymerization of MMA at 60 ∘ C. The initial
RAFT agent concentration was close to 3.7 × 10−3 mol l−1 and the initiator (AIBN)
concentration was 2.6 × 10−3 mol l−1 . The area under each distribution is scaled relative to
monomer conversions of 3.1%, 6.2%, 9.6%, 13.3%, 16.7%, and 22.3%, respectively. (c)
Evolution of molecular weight distributions in a cumyl phenyldithioacetate mediated (bulk)
polymerization of MMA at 60 ∘ C. The initial RAFT agent and initiator (AIBN) concentrations
are as above. The areas under the individual curves are all normalized. The additional two
distributions correspond to overall monomer conversions of 57% and 82%, respectively.
Source: Taken from Barner-Kowollik et al. [43]. © 2001, American Chemical Society.
Table 5.2 Estimated monomer addition rate coefficients for initiator-derived radicals (k i )
at 60 ∘ C.
Rate coefficienta) (103 M−1 s−1 )

(CH3 )2 CH2 (CH3 )2 (CH3 )2
CH2 CN CCN (CO2 R) C(COR) (CH3 )3 C PhCH2 CPh k p b)
MMA 790 3.3 2600 9.7 950 8.3 7.8 1.2

Styrene 1160 4.9 4000c) 13.5 220 4.7 3.8 0.34
MA 410 0.87 1130 3.4 1500 2.0 2.6 28
AN 410 4.1 1220 7.0 6330 8.7 6.5 3d)
VAcc) 70 0.086 1700 0.092 12.0 0.10 e) 8.3
a) Addition rate coefficient based on the activation parameters suggested by Fischer and Radom
[44] and their recommended log (A/M1 s1 ) of 8.5 for primary radicals and 7.5 for tertiary
radicals [46].
b) IUPAC recommended values of propagation rate coefficients in bulk monomer [47]. Value
indicated is based on the absolute rate constants reported by Fischer and Radom [44] and the
literature cited therein.
c) Note that for VAc the reported activation energies are not consistent with the rate constants
from which they were derived.
d) Polymer Handbook [48] – value typical for organic solvents.
e) No data available.
Source: Moad [46]. © Wiley-VCH.
slower, leading to long inhibition times. Instead, for these monomers R groups such
as cyanomethyl are preferable. Importantly, suitability of a R group for styrene and
methacrylates does not immediately translate to suitability for acrylates and acry-
lamides, and this is certainly the case for 2-cyanoprop-2-yl and 2-phenylprop-2-yl
radicals. These add relatively slowly to acrylamides and acrylates, and as such there
are better candidates for the R group in the polymerization of these monomers
(e.g. leaving groups that approximate the structure of acrylates). It is worth noting
that R groups that have lower re-initiation efficiency may also preferentially add
to the thiocarbonylthio group, giving a symmetrical intermediate radical. For
monomers for which the thiocarbonyl is highly activated to radical addition (e.g.
dithiobenzoates or trithiocarbonates), this preferential addition of the R group to
the RAFT agent may occur to a significant extent, exacerbating rate retardation and
in some cases leading to complete inhibition of polymerization (e.g. for the poly-
merization of vinyl acetate in the presence of 2-phenylprop-2-yl dithiobenzoate).
This demonstrates that the choice of R group for a given monomer cannot be made
completely in isolation: the Z group will also influence the extent to which R will
efficiently re-initiate polymerization or preferentially add to the CTA. If the latter
reaction is sufficiently dominant then no polymerization at all may be observed.
Further, in the RAFT oligomerization of acrylamides (e.g. N,N-dimethylacryl-
amide [DMAm]) mediated by tertiary cyanoalkyl trithiocarbonates it is possible to
detect the product from combination of R radicals in amounts predicted by kinetic
simulation, indicating that this is a cause of retardation [49].
100
100
90 CD CSD
Percentage dithiobenzoate species

90
80 CS2D
Percentage dithiobenzoates
80 Total dithiobenzoates
70
70 AD AD ASD
60 AS2D
60 ASD
AS2D 50
50
Total dithiobenzoates 40
40
30
30
20
20
10
10
0
0
0 50 100 150 200 250 0 50 100 150 200 250
(a) Time (minutes) (b) Time (minutes)
Figure 5.3 (a) Relative concentrations of methyl protons of dithiobenzoate species vs.
time in the radical polymerization of styrene in the presence of cyanoisopropyl dithio-
benzoate using AIBN as an initiator at 70 ∘ C. The reaction mixture includes 3.56 × 10−3 mol
of C6 D6 , 6.75 × 10−5 mol of AIBN, 2.40 × 10−3 mol of styrene, 4.84 × 10−4 mol of 2-cyano-
prop-2-yl dithiobenzoate. Source: Taken from McLeary et al. [50]. © 2004, Royal Society of
Chemistry. (b) Relative concentrations of the methyl protons of the dithiobenzoate species
vs. time in the radical polymerization of styrene in the presence of 2-phenylprop-2-yl
dithiobenzoate using azobis(isobutyronitrile) as an initiator at 84 ∘ C. The reaction mixture
includes 2.99 × 10−3 mol of C6 D6 , 6.30 × 10−5 mol of azobis(isobutyronitrile),
2.46 × 10−3 mol of styrene, and 3.68 × 10−4 mol of cumyl dithiobenzoate. Source: Taken
from McLeary et al. [51]. © 2005, American Chemical Society.
In cases where the R group (and the adduct of the R group with a single added
monomer group) undergoes rapid reaction with the thiocarbonyl preferentially
to propagation, the result is an ‘initialization’ period in which the predominant
species formed is the single monomer unit adduct (Figure 5.3a) [50]. Only after the
complete consumption of the initial chain transfer agent will chains with higher
degree of polymerization start to form. Initial studies in this area focused on the
polymerization of styrene using 2-cyanoprop-2-yl dithiobenzoate as a transfer agent
and AIBN as the initiator: in this case, the initiator-derived radicals and expelled
radical R are identical ((CH3 )2 (CN)C⋅) [52]. Subsequent work has investigated
more complex situations in which the radical R and initiator fragments are distinct
(Figure 5.3b) [51]. The same phenomenon, which was called selective initialization,
is observed with most monomers when effective RAFT agents are used. Importantly,
these phenomena can impact the reaction kinetics, with the process of initialization
proposed as an explanation for the inhibition periods observed in certain RAFT
polymerizations.
Selective initialization is also observed in the case of both thermally initiated and
photo-induced electron/energy transfer (PET)–RAFT of N,N-dimethylacrylamide
with tertiary cyanoalkyl RAFT agents [53, 54]. In this case, (i) the rate of addition
of R⋅ to monomer is rate determining; (ii) R⋅ is a much better homolytic leaving
group than the propagating species; and (iii) the transfer constant is such that on
average less than one monomer is added per activation cycle. Thus, R⋅ adds to the
monomer, but the resulting species RM. immediately reacts with the initial RAFT
agent to expel R⋅ . As soon as the initial RAFT agent is consumed, polymerization
accelerates dramatically.
5.2.5 R Group Stability and Implications for Chain Transfer Kinetics

Changes to the R group that occur on storage may alter the chemical identity of the
agent and therefore the Ctr , and thus lead to significantly poorer performance in
mediating polymerization. Fuchs and Thurecht recently observed that RAFT agents
in which the R group includes both a nitrile moiety and carboxylic acid may hydrol-
yse on storage, resulting in conversion of the nitrile to an amide moiety (Scheme 5.3)
[55]. This alteration was accompanied by a significant decrease in Ctr (from 16.7 to
2.5 for the dodecyl trithiocarbonate) for polymerization of MMA. This decrease in
Ctr was accompanied by a concomitant decrease in suitability for controlling MMA
polymerization, with the molecular weight distribution (MWD) shown to broaden
significantly. As the 4-cyanopentanoic acid R group is frequently employed in RAFT
polymerization the potential impact of these reactions cannot be ignored. That being
said, the chemistry requires water and our own observations show that the problem
of decomposition in storage can be largely avoided by ensuring that the RAFT agent
is maintained in a dry state. Additionally, the pathway seems to be less of an issue
with the corresponding dithiobenzoate.
5.2.6 Differential Leaving Group Ability and Mechanistic

Discrimination
RAFT polymerization can be achieved using a variety of different initiation sources,
including thermal autoinitiation of the monomer (e.g. polymerization of styrene
at >100 ∘ C) [56], addition of a thermally labile initiator such as an azo-initiator or
organic peroxide [28], redox initiation [57], or by applying ionizing radiation either
with [58] or without [59] an added photoinitiator. Interestingly, early reports on
the application of thiocarbonylthio compounds to control polymerization under
ionizing radiation (e.g. γ radiation or ultraviolet radiation) attributed the observed
behaviour to differing mechanisms. Specifically, the observed behaviour was
attributed to either (i) a photoiniferter mechanism in which the radiation causes
homolytic cleavage of the C—S bond, liberating the thiocarbonylthiyl radical,
which reversibly terminates the propagating polymer chains [60, 61]; or (ii) a RAFT
mechanism analogous to that operative with thermal initiation [62]. In order to
discriminate between the two mechanisms, Quinn et al. applied a methodology that
exploited the differing leaving group ability of 1-phenylethyl and 2-cyanoprop-2-yl
groups with respect to polymethacrylyl radicals [63]. Under a photoiniferter
mechanism, both 1-phenylethyl and 2-cyanoprop-2-yl dithiobenzoates ought to
show living radical behaviour, as both the 1-phenylethyl and 2-cyanoprop-2-yl
groups would initiate the polymerization of MMA upon cleavage of the C—S bond,
thus yielding propagating polymer chains that could be reversibly terminated by
the thiocarbonylthiyl radicals. On the other hand, where a RAFT mechanism is
operative only the 2-cyanoprop-2-yl dithiobenzoate ought to show living behaviour
with MMA, as the 1-phenylethyl dithiobenzoate would not undergo sufficient chain
transfer to have all chains initiated concurrently (see Figure 5.4a). This methodology
was applied to both 𝛾-initiated and UV-initiated polymerization and, in both cases,
H
O H H
H H O H
N N N
O H H O O
O
S S H S S S S
Z O Z O Z O
S S S
Ctr(MMA) = 16.7
H H
O NH2 O H
O NH2 O HO N O
S S S S S S
Z OH Z O Z O
S S S
Ctr(MMA) = 2.5
Scheme 5.3 Proposed acid-catalysed cyano-hydrolysis mechanism for 4-cyanopentanoic acid dodecyltrithiocarbonate. Source: Adapted from Fuchs et al.
[55]. © American Chemical Society.
CH3 CH3
O O O O
CH3 CH3 CH3 CH3
H2 H2
O O S S CN S S CN C S S + CN
C
H2 CH3 CH3
+ CH3 CH3 CH3
C
CH3
CH3
CH3 CH3 O O
CH3
S S H2
O O S S
C
H2 H
C + CH3 H
CH3
1.0 1.0
Normalized RI response
120 min
0.8 120 min 0.8 240 min
240 min 360 min
360 min
480 min
480 min
0.6 0.6 960 min
1440 min
0.4 0.4
0.2 0.2
0.0 0.0
4.5 5.0 5.5 6.0 6.5 7.0 2.5 3.0 3.5 4.0 4.5 5.0
(a) log M
(b) log M
1.0
0.8 120 min

240 min
360 min
0.6 480 min
0.4
0.2
0.0
4.5 5.0 5.5 6.0 6.5 7.0

(c) log M
Figure 5.4 (a) Initial chain transfer reaction for RAFT polymerization of MMA using
dithiobenzoates with either 2-cyanoprop-2-yl or 1-phenylethyl groups, showing the impact
of leaving group ability on the initial chain transfer step. (b) Evolution of molecular weight
distribution with time for the polymerization of methyl methacrylate at T = 23 ∘ C mediated
with a 1-phenylethyl dithiobenzoate ([PEDB] = 8.2 mmol l−1 ), (b) 2-cyanoprop-2-yl
dithiobenzoate ([CPDB] = 8.1 mmol l−1 ), and (c) dibenzyl trithiocarbonate
([DBTC] = 7.6 mmol l−1 ). Source: Adapted from Quinn et al. [63]. © Wiley Periodicals, Inc.
it was demonstrated that the principal mechanism behind the observed living
behaviour was RAFT rather than reversible termination (see Figure 5.4b for an
example of gamma-initiated living polymerization). These studies demonstrate that
by exploiting the inherent consequences of an operative RAFT mechanism, it is
possible to discriminate between conflicting explanations of living behaviour under
ionizing radiation.
5.3 Role of the Z Group

5.3.1 The Z Group and Radical Addition to the Thiocarbonyl
The principal role of the Z group in RAFT polymerization is to dictate the reactiv-
ity of the thiocarbonyl group toward propagating polymer radicals. As such, it is
essential that the Z group is properly chosen for the particular monomer being poly-
merized. Representative Z-groups, and some of the classes of monomer for which
they are suitable, are given in Table 5.3.
Early research by Moad and coworkers examined the suitability of a series of
thiocarbonylthio compounds for mediating the polymerization of styrene thermally
initiated at 110 ∘ C [88]. The series in question (Scheme 5.4) employed benzyl R
groups, which were previously shown to be a satisfactory homolytic leaving group
for mediating the polymerization of styrene. It was demonstrated that those agents
Table 5.3 Main classes of transfer agents suitable for RAFT polymerization and example
monomers.
Class General structure Examples Suitable monomers
Dithioester S S Z1 = Ph, naphthyl, Styrene [64]

R
phenanthryl, CH3 , CH2 Ph, Acrylates [65]
Z1
substituted Ph
Methacrylates [66]
Acrylamides [67]
Methacrylamides [68]
Acrylonitrile [69]
Vinylpyridine [70]
Trithiocarbonates S S Z1 = CH3 , (CH2 )n CH3 Styrenics [71]
R
CH2 Ph, (CH2 )n COOH Acrylates [72]
S
Z1
Methacrylates [73]
Acrylamides [74]
Methacrylamides [75]
Acrylonitrile [76]
Dithiocarbamates S S Z1 = Z2 = CH2 CH3 , Ph, Styrenics [77]
R
N Z1 –Z2 = pyrrolo, Acrylates [78]
Z1 Z2 phthalimido, pyrrolidono Methacrylates [79]
Acrylamides [80]
Vinyl esters [81]
N-vinyl pyrrolidone [82]
Xanthates S S Z1 = CH2 CH3 , Ph Styrene [83]
R
O
Acrylates [84]
Z1
Acrylamides [85]
Vinyl esters [86]
N-vinyl pyrrolidone [87]
F
S S S S F F
S
S > S S > S = N S >
F O S
F
O S S S S
= N S > O S > O S > N S
Scheme 5.4 Order of chain transfer efficiency for various thiocarbonylthio compounds with benzylic leaving groups. The presented order reflects the C tr
measured in polymerization of styrene at 110 ∘ C. Source: Data from Chiefari et al. [88]. © American Chemical Society.
for which zwitterionic canonical forms were possible (i.e. alkyl xanthates and
N,N-dialkyldithiocarbamates; see Scheme 5.5) demonstrated the least favourable
chain transfer kinetics in styrene polymerization. This was attributed to the inter-
action of the lone pair on the N or O with the thiocarbonyl, reducing the double
bond character of the C=S and increasing the lowest unoccupied molecular orbital
(LUMO) (and highest occupied molecular orbital [HOMO]). These factors were
considered to reduce the reactivity of the thiocarbonyl toward radical addition.
Importantly, the introduction of substituents that can delocalize the electrons
on the N (and therefore restore the double bond character to the thiocarbonyl)
can result in effective RAFT agents for styrene polymerization. Examples include
dithiocarbamates incorporating pyrrolo, pyrridinolo, and phenyl substituents.
S S
(a)
O S O S
S S
(b)
N S N S
Scheme 5.5 Zwitterionic canonical forms of (a) xanthates and (b) N,N-dialkyldithio-
carbamates. Source: Adapted from Chiefari et al. [88]. © American Chemical Society.
5.3.2 The Z-Group and Side Reactions

Although not effective as RAFT agents for the polymerization of styrene and other
more activated monomers (MAMs) (such as methacrylates), O-alkyl xanthates and
N,N-dialkylcarbamates have been shown to be highly effective at mediating the
polymerization of vinyl acetate. This is because the reactivity of the thiocarbonyl is
suitable for the highly reactive propagating poly(vinyl acetate) radical, and the req-
uisite fragmentation reaction is also suitably facile. In a recent innovation, Monteil
and coworkers have demonstrated the application of certain O-alkyl xanthates in
the polymerization of ethylene via a RAFT process [89]. By employing a suitable
combination of solvent (dimethyl carbonate, DMC) and pressure (200 bar), these
authors were able to prepare polyethylene with defined molecular weight and
end-groups from which chain extension was possible. In this case, so-called side
fragmentation was possible. Specifically, a proportion of the fragmentation occurs
at the O–CH2 yielding a polymer that incorporates a mid-chain backbone carbonyl
(Scheme 5.6). Of course, these carbonyls are not active to radical addition and as
such the chains formed via side fragmentation are no longer able to propagate,
resulting in the so-called dead chains.
Importantly, the level of side fragmentation can be significantly reduced by
employing an aromatic xanthate (methyl 2-(phenoxycarbonothioylthio)acetate)
instead of an alkyl xanthate (Figure 5.5a) [90]. However, these agents induced
Main addition-fragmentation equilibrium
S O S O S O
PE PE +
+ PE PE
S S S
PE PE
S O
PE Side fragmentation
+ Et
S (irreversible)
PE
Scheme 5.6 Side fragmentation in the RAFT-mediated polymerization of ethylene using

O-alkyl xanthates. Source: Adapted from Dommanget et al. [89]. © Wiley Periodicals, Inc.
RAFT At 70 °C and 200 bar

Refractive index
Conventional
(no CTA/
RAFT)
100 1000 10 000 100 000

Molar mass (g mol–1)
At 80 °C and 80 bar
RAFT
Refractive index
Conventional
(no CTA/RAFT)
100 1000 10 000 100 000

Molar mass (g mol–1)
Figure 5.5 (a) Molecular weight distributions of polyethylene produced in a conventional

system (no CTA/RAFT) after one hour and in the presence of methyl 2-(phenoxycarbon-
othioylthio)acetate after one, two, three, four, five, and six hours. At six hours, the
appearance of a high molecular weight species can be observed. (b) Molecular weight
distributions of polyethylene produced in a conventional system (no CTA/RAFT) after four
hours and in the presence of methyl 2-(4-methoxyphenoxycarbonothioylthio)acetate after
2, 4, 7, and 16 hours. Source: Taken from Wolpers et al. [90]. © Wiley Periodicals, Inc.
significant retardation to the polymerization, attributed to cross-termination of

the intermediate radical with a propagating polyethyl radical. Moreover, there is
a significant proportion of material formed with high molecular weight, which
the authors attributed to the occurrence of conventional radical (i.e. non-RAFT)
polymerization. This was postulated to occur as a result of the dispersion behaviour
of the formed polymer in supercritical DMC. As a result, the formation of dead
polymer is not avoided by this structural adjustment. Interestingly, the authors
were able to significantly reduce the proportion of high molecular weight material
by lowering the pressure at which the polymerization was conducted from 200 to
80 bar (Figure 5.5b). Moreover, RAFT polymerization of polyethylene could also be
achieved with a high degree of livingness by employing various dithiocarbamates
as the chain transfer agent. Although the molecular weight distributions achieved
were relatively broad (Ð > 1.5), the preservation of chain end functionality for
polyethylene (PE) synthesized using the dithiocarbamates was superior to both
alkyl and aromatic xanthates. These results demonstrate that the quest for low
dispersity does not necessarily lead to the best outcome: in this case, the higher
dispersity PE with higher chain end fidelity will be more useful for the preparation
of subsequent block copolymers than lower dispersity PE with compromised chain
end fidelity.
5.3.3 Manipulating Z to Dictate Reactivity: ‘Switchable’ RAFT Agents

The need to employ different RAFT agents for less activated monomers (LAMs) and
more activated monomers (MAMs) has motivated the development of the so-called
switchable RAFT agents that can be used to prepare block copolymers incorporating
segments of polymerized LAM and MAM (polyMAM-block-polyLAM). As noted
above, the zwitterionic canonical forms of N,N-dialkyldithiocarbamates have been
associated with the unsuitability of those RAFT agents for the polymerization
of MAMs. In order to abolish the zwitterionic character of the canonical form
and hence retain the double bond character of the thiocarbonyl, Benaglia et al.
proposed the preparation of a series of N-(4-pyridinyl)-N-methyldithiocarbamates
that can be protonated via the pyridinyl group (Scheme 5.7) [91]. Protonation via
a stoichiometric amount of a strong acid (such as trifluoromethanesulfonic acid
or 4-toluenesulfonic acid) leads to a non-zwitterionic canonical form and hence
suitability of the agent for polymerization of MAMs such as styrene, MMA, and
MA (depending on the nature of the R group employed). By adding a stoichio-
metric amount of a base such as N,N-dimethylaminopyridine the protonation is
reversed, restoring the zwitterionic character of the canonical form and render-
ing the agent suitable for polymerization of LAMs. By using this methodology,
poly(MMA)-block-poly(VAc) and poly(methyl acrylate [MA])-block-(N-vinyl car-
bazole [NVC]) were successfully synthesized. Subsequent investigations have
extended this approach to include poly(MAM)-block-poly(LAM) examples such as
polystyrene (PS)-block-poly(VAc) [92], poly(DMAm)-block-poly(NVC) [93], poly
(DMAm)-block-poly(VAc), poly(DMAm)-block-poly(N-vinyl pyrrolidone [NVP]),
and more sophisticated structures such as PS-block-poly(MA)-block-poly(VAc) and
PS-block-poly(MA-grad-VAc)-block-poly(VAc). Importantly, the reactivity of these

agents to radical addition can be modulated via variation of the non-pyridinyl N
substituent, thereby enabling application of these agents with a wide variety of
different monomers.
S S
+
N N
RAFT
S R S R
Controls
N N VAc, NVP, NVC
+
Base H
S S
+
N N
RAFT
S R S R
Controls
N N
+ MMA, MA, S
H H
Scheme 5.7 Application of N-(4-pyridinyl)-N-methyldithiocarbamates for RAFT

polymerization of LAMs and MAMs. Source: Adapted from Benaglia et al. [91]. © American
Chemical Society.
Gardiner and coworkers have reported an alternative family of dithiocarbamates

wherein the reactivity is broadly similar to that of protonated N-(4-pyridinyl)-N-
methyldithiocarbamates (Scheme 5.8) [94]. Specifically, 3,5-dimethyl-1H-pyrazole-
1-carbodithioates were applied successfully in the polymerization of N,N-dimethyla-
crylamide, methyl acrylate, methyl methacrylate, styrene, and vinyl acetate. Except
for MMA, Ð < 1.2 was attainable provided that the R group was chosen appropriately
for the monomer under study. In comparison to N-(4-pyridinyl)-N-methyldithio-
carbamates, 3,5-dimethyl-1H-pyrazole-1-carbodithioates gave greater retardation
in the polymerization of vinyl acetate, which was attributed to the stability of the
intermediate formed by addition to the RAFT agent, and the consequent effect on
side reactions involving that radical. The higher dispersities observed in the poly-
merization of MMA (Ð > 1.4) were indicative of a relatively low value of Ctr for the
tertiary 3,5-dimethyl-1H-pyrazole-1-carbodithioates employed at 100 ∘ C (Ctr ≈ 3.7).
As noted earlier, low dispersities (e.g. Ð < 1.1 with X n of 150 at 75% conversion)
would require a Ctr of >20. 3,5-Dimethyl-1H-pyrazole-1-carbodithioates were
also deployed in the copolymerization of MMA with styrene and DMA. Provided
there was sufficient comonomer present in the system the dispersities achieved
were lower than the corresponding homopolymerizations using MMA. While
N-(4-pyridinyl)-N-methyldithiocarbamates require protonation or deprotonation of
the pyridyl group in order to facilitate preparations of block copolymers of LAMs
and MAMs, 3,5-dimethyl-1H-pyrazole-1-carbodithioates could be used successfully
without the need to alter the solution pH. Specifically, poly(DMA) macromolecular
chain transfer agent was successfully employed to prepared a block copolymer
with VAc, with relatively low dispersities observed where the ratio of VAc to DMA
units in the macroCTA was 1 : 1 (Ð < 1.3: higher dispersity was observed when the
amount of VAc was increased). Importantly, in this series of experiments the blocks
prepared are more appropriately described as quasi-blocks, as the initial macroCTA
was not purified before chain extension. As such, the second block is strictly a
copolymer. Nevertheless, the resulting MWDs are essentially monomodal with
limited evidence of terminated product or high molecular weight PVAc (Figure 5.6).
Importantly, whether by the use of 3,5-dimethyl-1H-pyrazole-1-carbodithioates
or N-(4-pyridinyl)-N-methyldithiocarbamates, the use of RAFT enables the
preparation of sophisticated block structures that are not readily accessible via
other reversible deactivation radical polymerization (RDRP) techniques such
as nitroxide-mediated polymerization or atom transfer radical polymerization,
highlighting the utility of RAFT polymerization. Moreover, the development of
these agents highlights how mechanistic insights can drive judicious design of
transfer agent structure.
Scheme 5.8 Relative activity of dithiocarbamate ‘ZC(=S)S–’ groups in RAFT

polymerization. MAM – more activated monomer, LAM – less activated monomer. Source:
Taken from Gardiner et al. [94]. © Royal Society of Chemistry.
5.3.4 The Z-Group and Reaction Kinetics

RAFT agents in which the Z-group is phenyl (i.e. dithiobenzoates) have been asso-
ciated with significant kinetic effects. For example, such agents have been observed
to cause significant inhibition of polymerization [95], particularly at lower tempera-
tures [96]. Moreover, the polymerization of styrene has been shown to proceed with
a rather reduced rate relative to the homopolymerization of styrene under equiv-
alent conditions in the absence of a RAFT agent. Such rate retardation has also
been observed in the polymerization of (meth)acrylates [97] and (meth)acrylamides
[98]. Based on initial investigations into the polymerization of styrene in the pres-
ence of various dithiobenzoates, Monteiro and de Brouwer [99] and Barner-Kowollik
Normalised intensity
Normalised intensity
103 104 105 103 104 105
(a) Molar mass (PMMA equivalents) (b) Molar mass (PMMA equivalents)
Figure 5.6 Molecular weight distributions for poly(N,N-dimethylacrylamide) macro-RAFT

agent prepared with (a) 2-cyanobutanyl-2-yl 3,5-dimethyl-1H-pyrazole-1-carbodithioate or
(b) cyanomethyl (3,5-dimethyl-1H-pyrazole)-carbodithioate ( ) and the derived
poly(N,N-dimethylacrylamide)-block-poly(vinyl acetate) ( ). The large peak with apparent
molar mass < 103 poly(MMA) equivalents is a ‘salt peak’ associated with the LiBr/DMAc SEC
eluent. Source: Taken from Gardiner et al. [94]. © Royal Society of Chemistry.
et al. [100] postulated explanations for these observed phenomena, both employing
simulations to support the observed evolution of conversion with time. Specifically,
Monteiro and de Brouwer postulated that rate retardation could be attributed to
termination of the intermediate radical formed during chain equilibration, while
Barner-Kowollik et al. suggested that slow fragmentation of the intermediate radical
was a suitable explanation. These initial studies on the topic precipitated a substan-
tial subsequent work aimed at elucidating not only the origins of rate retardation
observed in the dithiobenzoate-mediated polymerization of styrene, but also the
phenomenon of rate retardation in RAFT polymerization more generally. Given that
dithiobenzoates are important agents for mediating the polymerization of various
monomers and typically give rise to very low dispersities, there was substantial moti-
vation for understanding the origin of these effects, leading to the establishment of
an IUPAC working group in 2005 ‘Towards a Holistic Mechanistic Model for RAFT
Polymerizations: Dithiobenzoates as Mediating Agents’, which published a situa-
tion paper in 2006 [101] and an update in 2014 [102]. Although retardation has
primarily been associated with the Z group, it is important to remember that – as
noted above – improper choice of the R group may also lead to significant kinetic
effects including inhibition. Moreover, such R group originating kinetic effects can
be potentially exacerbated by the use of dithiobenzoates (i.e. Z = Ph).
5.3.5 Intermediate Radical Termination

In their initial report, Monteiro and de Brouwer observed a concentration-dependent
decrease in the overall rate of reaction when methyl 2-methyl-2-((phenylcarbono-
thioyl)thio)propanoate was added to mediate the polymerization of styrene
initiated by AIBN at 80 ∘ C. They postulated that the loss of intermediate radicals via
termination with another radical species (Scheme 5.9) was a possible reason for the
observed retardation.
Pj
S S S S
Pm Pn Pm Pn
+ Pj
Scheme 5.9 Intermediate radical termination as proposed by Monteiro and de Brouwer

[99]. Source: Modified from Monteiro and de Brouwer [99].
Application of the intermediate radical termination model enabled simulation

of experimental conversion–time data for styrene polymerization in toluene at
80 ∘ C initiated using AIBN. Good agreement was obtained between the simulated
and experimental data, and the simulated intermediate radical concentrations for
this system are consistent with those measured previously by the CSIRO group,
once allowance is made for the different reaction conditions and temperature
[103]. Previous work from Monteiro’s laboratory demonstrated that irradiation
of a dithiobenzoate-terminated polymer with ultraviolet radiation could lead to
a proportion of the sample trebling in molecular weight, an observation consis-
tent with possible reaction of the intermediate radical with another polymeric
radical [104]. The general feasibility of such a reaction was firmly established in
a model system using polystyryl bromide and polystyryl dithiobenzoate, wherein
the polystyryl radical was produced from PSt–Br by the catalytic reaction of a
CuBr/Me6 TREN complex [105]. Subsequent studies by Kwak et al. examined the
reaction between 1-phenylethyl dithiobenzoate and 1-phenylethyl bromide and
demonstrated that, in addition to bimolecular coupling at the bis-thiosubstituted
benzylic carbon, reaction was also possible at the ortho and para positions on the
phenyl ring (Scheme 5.10) [106]. Moreover, the structures formed were shown to be
stable at both 60 and 100 ∘ C for 24 hours, indicating that the reaction is likely to be
essentially irreversible at polymerization temperatures.
Despite these findings, attempts to identify the three-armed star formed by
bimolecular intermediate radical termination in a polymerizing system either spec-
troscopically or chromatographically have generally been unsuccessful [107, 108].
If intermediate termination is potentially operational, the quantity of the generated
star polymer should exceed the amount of conventionally terminated polymer by
at least 1 order of magnitude, as the intermediate radical concentration exceeds
the propagating species concentration under both the fast and slow fragmentation
scenarios substantially [107]. Such quantities of three-armed star polymers have
never been identified. To address this, a number of solutions have been proposed
to demonstrate why the terminated intermediate radical may not necessarily be
identified.
S S
+ Br
S S
S S S S
H
H
Scheme 5.10 Model compounds prepared in the study of Kwak et al. [106] demonstrating
that radical reactions with the RAFT intermediate can potentially occur at the ortho and
para positions of the phenyl ring of the dithiobenzoate. Source: Modified from Kwak et al.
[106].
Vana and Buback proposed that the three-armed star formed via intermedi-
ate radical termination might itself be reactive, resulting in re-liberation of the
intermediate radical and dead polymer, which is essentially analogous to that
formed via termination of propagating chains (Scheme 5.11) [109]. Inclusion of
this so-called ‘missing step’ enables simulation of conversion–time profiles that
+ P
k
S S
Pi Pj
Pk Int
+ P
l
Pk Pl
S S S S S S S S S S
Pi Pj Pi Pj Pi Pj Pi Pj Pi Pj
=
Scheme 5.11 (a) Reaction of the three-armed star formed via intermediate radical
termination with a propagating radical: the so-called ‘missing step’ of the RAFT mechanism.
(b) Resonance structures of the intermediate radical formed when polymerization is
mediated with a dithiobenzoate. Source: Adapted from Buback and Vana [109]. © Wiley
Periodicals, Inc.
show concentration-dependent rate retardation, but which also give intermediate

radical concentrations consistent with those observed experimentally. Subsequent
investigations using (i) 1-phenylethyl dithiobenzoate and a source of 1-phenylethyl
radicals [110] and (ii) 2-cyanoprop-2-yl dithiobenzoate and AIBN [111] have
demonstrated the experimental feasibility of these reactions.
An alternative explanation for the absence of obvious three-armed star fractions
in systems where there is significant retardation was proposed by Konkolewicz et al.
[112]. This proposal suggests that to the extent that intermediate radical termination
This theory
1.2 Expt Barnel–Kowollik et al.
Theory Barnel–Kowollik et al.
4h 8h 12 h 24 h
1
Normalized distribution
0.8
0.6
0.4
0.2
0.0
3 3.2 3.4 3.6 3.8 4 4.2 4.4 4.6 4.8 5
(a) log M
Theory
1.2 Experiment
2h 9h 24 h
1
Normalized distribution
0.8
0.6
0.4
0.2
0
2.5 3 3.5 4 4.5 5
(b) log M
Figure 5.7 (a) Comparison between the molecular weight distributions suggested by the
theory of Konkolewicz et al. and the experimental molecular weight distribution of
Barner-Kowollik et al. for 2-phenylprop-2-yl dithiobenzoate. (b) Comparison between the
theoretical and experimental molecular weight distributions for [CPDB] = 1.42 × 10−2 mol/l
with samples taken at 2, 9, and 24 hours. Source: Taken from Konkolewicz et al. [112].
© 2009 American Chemical Society.
occurs, it does so primarily via termination with short radicals (i.e. with initiator
fragments or oligomeric chains wherein the number of added monomer units is two
or less) [113]. Implementation of this model enabled accurate prediction of the con-
version, molecular weight, and dispersity as a function of time (Figure 5.7). More-
over, the low molecular weight of the species reacting with the intermediate radical
means that there was no appreciable formation of polymer with triple the molecu-
lar weight of the main population, and hence the model was able to rationalize the
failure to identify and isolate appreciable quantities of the three-armed star expected
via intermediate radical termination.
Subsequently, Ting et al. tested the hypothesis of Konkolewicz et al. by employing
a macromolecular initiator and macromolecular chain transfer agent (polystyryl
dithiobenzoate) in the polymerization of styrene [114]. In this system there
were no short radicals present, and hence if there is validity to the explanation of
Konkolewicz et al. then a wholly macromolecular system should exhibit diminished
retardation compared to one in which short chains are introduced (e.g. via a con-
ventional azo-initiator). This was indeed the case, at least up to approximately
40% conversion, after which there was minimal difference in the rate of polymer-
ization between the macromolecular and small molecule initiators (Figure 5.8).
As such these experiments provide a level of confirmation for Konkolewicz’s
model, although the discrepancy at higher conversions indicates that there is still
more to learn in order to develop a complete understanding of rate retardation in
dithiobenzoate-mediated polymerization.
5.3.6 Slow Fragmentation of the Intermediate Radical

Slow fragmentation of the intermediate radical has also been proposed as the origin
of rate retardation in dithiobenzoate-mediated polymerization [100, 115]. Under this
explanation, β-scission of the intermediate is sufficiently slow as to effectively pro-
vide a radical sink, reducing the propagating radical concentration and thus leading
to a reduced rate of polymerization. While a slow fragmentation model was suc-
cessfully employed to model the evolution of conversion, molecular weight, and
0.0014
0.000 40
Conventional/VPE-601 Conventional/AIBN
0.0012
0.000 35 MacroCDB/VPE-601 MacroCDB/AIBN
CDB/VPE-601 CDB/AIBN
Conversion rate (min−1)
Conversion rate (min−1)
0.000 30 0.0010
0.000 25 0.0008
0.000 20
0.0006
0.000 15
0.0004
0.000 10
0.0002
0.000 05
0.000 00 0.0000
0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50
(a) Fractional conversion (b) Fractional conversion
Figure 5.8 Styrene conversion rates (min−1 ) vs. fractional conversion for the systems (a)
VPE-601, macroCDB/VPE-601, and CDB/VPE-601 and (b) AIBN, macroCDB/AIBN, and
CDB/AIBN at [St]/[RAFT agent] = 1226 (except when RAFT agent is not present). Source:
Taken from Ting et al. [114]. © 2011, American Chemical Society.
dispersity as a function of time, the predicted concentrations of the intermediate

radical greatly exceed those that have been measured via EPR [97, 116]. Neverthe-
less, despite these differences in the observed intermediate radical concentrations,
there have been a number of experiments and calculations that support the slow
fragmentation hypothesis. For example, Coote et al. have computed equilibrium
coefficients (K = kaddR /k−addR ) for 2-cyanoprop-2-yl dithiobenzoate-mediated poly-
merization that were consistent with potential rate retardation via slow fragmenta-
tion [117], although these values were substantially higher than those determined
previously by McLeary et al. [118] Klumperman and coworkers found a similar value
of K as Coote et al. within 1 order of magnitude (i.e. 104 vs. 105 ) and suggested that
perhaps the slow fragmentation and intermediate radical termination explanations
were not as irreconcilable as had been previously claimed. Nevertheless, these high
values of K are still in contrast to EPR determinations by Meiser and Buback, and as
such the need for further mechanistic elucidation remains [119, 120].
In addition to the theoretical calculations in support of slow fragmentation,
Davis and coworkers conducted an interesting ‘radical storage’ experiment to
demonstrate the existence of a long-lived radical sink in the 2-phenylprop-2-yl
dithiobenzoate-mediated polymerization of styrene (Figure 5.9a) [121]. In this case,
a solution of the transfer agent in styrene was irradiated at ambient temperature
with γ-radiation for 18 hours, and then isolated from the γ-source for a predeter-
mined ‘waiting’ period of 10–60 minutes. The solution was then heated to 60 ∘ C
for 22 hours. In contrast to control samples that were not irradiated, all irradiated
samples (regardless of the waiting time) polymerized when heated to 60 ∘ C to
conversions between 5% and 6%. Moreover, a sample of pure styrene (i.e. without
any added chain transfer agent) polymerized to less than 2%. Taken together, these
results are highly suggestive of a hidden radical sink in the dithiobenzoate/styrene
system. Moreover, kinetic simulation using the commercial Predici® simulation
package indicated that by using the intermediate radical termination model as the
exclusive source of rate retardation there should be no radical sink in the system
(unless one of the formed species is in fact reversible) (Figure 5.9b): this stands in
contrast to the slow fragmentation model where the radical concentration decreases
more slowly (Figure 5.9c). These results cannot be reconciled with the work of
Kwak et al. (see Section 5.3.5), who demonstrated that model low molecular weight
stars formed via 1-phenylethyl dithiobenzoate are chemically inert at 60 ∘ C. As
such, there are clearly peculiarities of the 2-phenylprop-2-yl system that remain
unelucidated.
The experimental evidence thus shows that intermediate radical termination can,
in principle, be operational and is favoured by slow fragmentation. Undoubtedly,
fragmentation of dithiobenzoate-derived intermediates is slow compared to other
RAFT intermediate radicals – with equilibrium constants up to 104 –105 depending
on the type of equilibrium, with possibly lower equilibrium constants for the main
equilibrium driven by the fact that the fragmentation rate of polymer chains with
defined cleave points is strongly entropic and thus chain length dependent, as estab-
lished by Barner-Kowollik et al. [122] Further, it is this sluggish fragmentation that
enhances the chances of intermediate radical termination reactions [99].
18 h ambient 10 – 60 min ambient 22 h 60 °C
CDB Intermediate Polymer

styrene styrene intermediate
styrene
twait
T1
T1 T2
No polymer formation No polymer formation 5– 7% conversion

to polymer
8 8 8
7 7 7
Response/mV
Response/mV
Response/mV
6 6 6
5 5 5
4 4 4
3 3 3
2 2 2
1 1
1
0 0
–1 0
–1
18 20 22 24 26 28 30 32 34 18 20 22 24 26 28 30 32 34 18 20 22 24 26 28 30 32 34
Retention volume/mL Retention volume/mL Retention volume/mL
(a)
4.0 × 10–9 0.0006

Initiation switched off
3.5 × 10–9
0.0005
–9
3.0 × 10
CIntermediate (mol l )
–1
CIntermediate (mol l )
–1
0.0004
2.5 × 10–9
–9
2.0 × 10 0.0003
–9
1.5 × 10
0.0002
–9
1.0 × 10
0.0001
5.0 × 10–10
0.0 0.0000
0 120 240 360 480 600 720 840 960 1080 1200 1320 1440 0 120 240 360 480 600 720 840 960 1080 1200 1320 1440
Time (min) Time (min)
(b) (c)
Figure 5.9 (a) Experimental procedure used to probe 2-phenylprop-2-yl dithiobenzoate-

mediated styrene polymerizations for the formation of intermediate species. The lower part
of the scheme gives examples of molecular weight distributions typical for each sequence
step (the large peak at 32 minutes is due to monomer in the reaction mixture). These
clearly demonstrate the absence or presence of a polymer peak. (b) Simulated intermediate
macroRAFT radical concentration vs. time profile for a CDB-mediated styrene bulk
polymerization at 60 ∘ C using the RAFT mechanism with irreversible intermediate
macroRAFT radical termination. The following set of rate coefficients was used:
k tr = 5 × 105 l mol−1 s−1 , k t = 1 × 108 l mol−1 s−1 , k p = 340 l mol−1 s−1 , k add = 4 × 106 l
mol−1 s−1 , k frag = 1 × 105 s−1 , and k t, intermediate = 1 × 108 l mol−1 s−1 . Initiation by 𝛾-radiation
was simulated using decomposition of an initiator with a decomposition rate coefficient of
5.2 × 10−6 s−1 and an initial concentration of 3.5 × 10−3 mol l−1 . At t = 18 hours, this
concentration was set to zero to represent removal of the 𝛾-source. (c) Simulated
intermediate macroRAFT radical concentration vs. time profile for a CDB-mediated styrene
bulk polymerization at 60 ∘ C using the RAFT mechanism without intermediate radical
termination and the following set of rate coefficients: k tr = 3.5 × 105 l mol−1 s−1 ,
k t = 4 × 108 l mol−1 s−1 , k p = 340 l mol−1 s−1 , k add = 5.4 × 105 l mol−1 s−1 , and
k frag = 3.3 × 10−2 s−1 . The dotted line indicates the point in time where the initiation was
switched off. Initiation by 𝛾-radiation was simulated by decomposition of an initiator with a
decomposition rate coefficient of 5.2 × 10−6 s−1 and an initial concentration of
3.5 × 10−3 mol l−1 . At t = 18 hours, this concentration was set to zero to simulate removal of
the γ-source. Source: Adapted from Barner-Kowollik et al. [121]. © Wiley Periodicals, Inc.
As noted above, numerous approaches have been applied to reconcile the slow
fragmentation and intermediate radical termination models, including the postula-
tion of reversible intermediate radical termination occurring on the phenyl moiety
[109] and termination exclusively via short radicals [112, 113]. While such reactions
might support both the observed conversion–time profiles and radical concentra-
tions, observation of the postulated structures spectroscopically or chromatographi-
cally remains challenging. It is worth noting that significant rate retardation during
RAFT polymerization is principally observed in a limited set of circumstances: the
application of relatively slow-propagating monomers with RAFT agents having thio-
carbonyl groups that are highly activated to radical addition. In this respect, rate
retardation can generally be overcome by selecting a more suitable RAFT agent such
as a trithiocarbonate, for which rate retardation is less of an issue.
5.3.7 Stability of the Z Group During Reaction

One of the issues noted in the course of investigating the observed rate retar-
dation in 2-phenylprop-2-yl dithiobenzoate-mediated polymerization of styrene
was the potential instability of the RAFT agent, and the resulting presence of
degradation products capable of inhibiting and/or retarding polymerization [123].
Specifically, the use of RAFT agent purified via column chromatography was
shown to give noticeably different kinetics than that purified via high performance
liquid chromatography (HPLC), with the former leading to significantly longer
inhibition periods and slower overall rate of polymerization for both styrene
and 2-hydroxyethyl methacrylate. Importantly, it was observed that storage of
2-phenylprop-2-yl dithiobenzoate at −20 ∘ C for three months led to a substantial
reduction in the rate of polymerization of styrene compared to polymerizations
using a RAFT agent that was stored for only one week. These results are significant
in that they highlight the sensitivity of RAFT reactions to potential impurities in
the chain transfer agent.
In light of these observations regarding the stability of 2-phenylprop-2-yl
dithiobenzoate, it is worth considering the potential for degradation of the thio-
carbonylthio moiety in the course of a polymerization reaction. Clearly, in order
to retain control of the polymerization throughout the duration of the reaction,
it is important that the macromolecular chain transfer agent formed is suitably
stable in the polymerization medium. This becomes particularly important in the
scenario that the polymerization is conducted in a protic solvent such as water,
ethanol, or methanol, or wherein the monomer can potentially react with the thio-
carbonylthio moiety (e.g. monomers containing a nucleophile). McCormick and
coworkers demonstrated the successful polymerization of a number of monomers
in water using dithiobenzoates [124–126], illustrating that hydrolysis of these CTAs
is sufficiently slow under polymerization conditions to avoid obvious impacts
on the molecular weight distribution. One notable exception occurs in the case
of acrylamide, which has been demonstrated to be rather pH sensitive [127].
Specifically, these authors observed that when the polymerization was conducted
at pH = 7.0 there was a total loss of control, with high molecular weights observed
12 h
RI Signal
8h
4h
2h
10 12 14 16 18 20
(a) Elution volume (ml)
24 h
12 h
RI Signal
8h
4h
2h
10 12 14 16 18 20
(b) Elution volume (ml)
Figure 5.10 (a) Aqueous size exclusion chromatograms (refractive index [RI] detection) for
the polymerization of acrylamide at pH = 7 in the presence of sodium
2-(2-thiobenzoyl-sulfonylpropionylamino)ethanesulfonate (STPE). Two hours: no polymer
observed; four hours: all colour bleached from reaction medium, Mn = 24 900 g mol−1 ,
Ð = 1.09, conversion = 6%; 8 hours: Mn = 114 000 g mol−1 , Ð = 1.87, conversion = 32%;
12 hours: Mn = 239 000 g mol−1 , Ð = 2.98, conversion = 70%. (b) Successful RAFT
polymerization of acrylamide with STPE in an acetic acid/sodium acetate buffer showing
the evolution of molecular weight with time (2 hours: Mn = 5300 g mol−1 , Ð = 1.15,
conversion = 3%; 4 h: Mn = 9790 g mol−1 , Ð = 1.05, conversion = 9%; 8 hours:
Mn = 13 700 g mol−1 , Ð = 1.04, conversion = 11%; 12 hours: Mn = 18 600 g mol−1 , Ð = 1.06,
conversion = 18%; 24 hours: Mn = 28 900 g mol−1 , Ð = 1.26, conversion = 28%). Source:
Adapted with permission from Thomas et al. [127]. © 2003, American Chemical Society.
at polymerization times beyond four hours (Figure 5.10a). This was accompanied
by loss of the CTA’s characteristic colour, consistent with degradation of the
RAFT agent. In contrast, by conducting the polymerization in acetate buffer
at pH = 5.0 it was possible to achieve much lower molecular weights, which
increased linearly with conversion (Figure 5.10b). The inability to control the
polymerization at pH = 7.0 was attributed to hydrolysis of acrylamide under these
conditions, liberating ammonia as a by-product. Reaction of the liberated ammonia
with the thiocarbonylthio moiety yielded (i) low molecular weight thioamide
and (ii) thiol-terminated polymer. The loss of thiocarbonylthio groups abolished
the RAFT equilibrium, leading to high molecular weight polyacrylamide. These

results illustrate the possibility of reactions between the solvent and/or monomer
interfering with the RAFT process and compromising the observed control over the
polymerization. This is particularly important in aqueous systems, although the
impact of other protic solvents such as methanol and ethanol cannot be discounted.
In an extension of this study, Thomas et al. predicted the rates of dithioben-
zoate end-group hydrolysis for the synthesis of polyacrylamide and poly(sodium
2-acrylamido-2-methylpropanesulfonate) (AMPS), and determined the impact of
these reactions on the proportion of living and dead chains across the duration of
the polymerization [128]. In the case of acrylamide, hydrolysis of the monomer
yielding aqueous ammonia required the additional consideration of aminolysis
on the thiocarbonylthio end-group. The proportion of living and dead chains for
acrylamide and AMPS are given in Figure 5.11a,b, respectively. The number of
(Living chains) (Living chains)

Chain concentration (mol l–1)
0.0025 0.014
(Dead chains) (Dead chains)
Chain concentration (mol l–1)
0.012
0.0020
0.010 tind
0.0015 0.008
0.006
0.0010
0.004
0.0005
0.002
0.0000 0.000
0 250 500 750 1000 1250 0 50 100 150 200 250
(a) Time (min) (b) Time (min)
25 000 35 000
With hydrolysis With hydrolysis
No hydrolysis 30 000 No hydrolysis
20 000
25 000
MW (g mol–1)
MW (g mol–1)
15 000
20 000
10 000 15 000
10 000
5 000
5 000
0 0
0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.0 0.2 0.4 0.6 0.8
(c) Conversation (d) Conversion
Figure 5.11 Theoretically predicted concentrations of living and dead chain ends for (a)
acrylamide polymerization at pH = 5.5, 70 ∘ C, and (b) AMPS polymerization at pH = 7, 70 ∘ C.
Molecular weights as a function of conversion for (c) acrylamide polymerization at pH = 5.5,
70 ∘ C, and (d) AMPS polymerization at pH = 7, 70 ∘ C. Molecular weights with and without
hydrolysis were calculated utilizing Eqs. (5.10) and (5.8) from D. B. Thomas et al.,
Macromolecules 2004, respectively. (For acrylamide polymerizations t ind = 0 min,
k p * = 0.36 × 10−5 s−1 , k a,macro = 0, [NH3 ] = 0.02 M, k hyd,CTP = 1.8 × 10−5 s−1 , and
k hyd,macro = 0.44 × 10−5 s−1 ; for AMPS polymerizations t ind = 51 min, k p * = 12 × 10−5 s−1 ,
k a,macro = 0.6, [NH3 ] = 0, k hyd,CTP = 2.5 × 10−5 s−1 , and k hyd,macro = 0.2 × 10–5 s−1 .) Source:
Taken from Thomas et al. [128]. © 2004, American Chemical Society.
dead chains is noticeably higher in the case of acrylamide polymerization for

two principle reasons: (i) the RAFT polymerization of acrylamide under these
conditions is sufficiently slow as to allow more extensive hydrolysis before the
polymerization is completed; and (ii) the added impact of aminolysis serves to
accentuate the loss of thiocarbonylthio end-group during the polymerization. The
loss of RAFT end-group during the reaction leads to an increase in the ratio of
[M]/[CTA], thereby leading to higher molecular weights than would be observed if
all CTA moieties remained intact. This manifests as an increasing departure from
theoretical molecular weight as higher conversions are reached (Figure 5.11c,d).
Again, the impact is most noticeable for acrylamide polymerization where the
slower rate of polymerization and more significant loss of thiocarbonylthio
end-group due to hydrolysis and aminolysis lead to substantial departures from
theoretical molecular weight at higher conversions. Altogether, these results
demonstrate the importance of solvent choice for RAFT polymerization. The use of
solvents that lead to any loss of thiocarbonylthio end-group during polymerization
can, in turn, result in substantial departures from the theoretical molecular weight.
This will be exacerbated by long polymerization times, and, as such, adjustment of
conditions to maximize the rate of polymerization relative to the rate of hydrolysis
will generally be an effective strategy for overcoming this issue.
The polymerization of monomers that incorporate a nucleophile represent a fur-
ther challenge. Nucleophiles such as amines and hydroxide are well known to react
with thiocarbonylthio groups and have been extensively used in the quantitative
removal of the end-groups formed during RAFT polymerization. As such, polymer-
izing monomers that incorporate such groups is difficult, and frequently involves the
use of protecting groups such as tert-butoxycarbonyl (BOC). Nevertheless, there have
been examples in which primary amine-containing monomers such as 2-aminoethyl
methacrylate (AEMA) have been successfully polymerized by controlling the pH
and temperature of the reaction medium, thereby minimizing the potential for
aminolysis of the RAFT end-group (or various other side reactions of the monomer
and polymer chains, for that matter). Specifically, Morgan and coworkers have
demonstrated that by maintaining the pH at 5.2 and polymerizing at 50 ∘ C using
VA-044 as the initiator it was possible to prepare poly(AEMA) with good control over
molecular weight and relatively narrow molecular weight distribution (Figure 5.12)
Figure 5.12 Aqueous size exclusion

chromatograms (with RI detection) for
the homopolymerization of
2-aminoethyl methacrylate (AEMA) at Increasing polymerization
RI Signal
50 ∘ C showing the detector response time

as a function of elution volume.
Source: Taken from Alidedeoglu et al.
[129]. © Wiley Periodicals, Inc.
6.0 6.5 7.0 7.5 8.0 8.5 9.0

Elution volume (ml)
[129]. This has been achieved with sufficient efficiency as to enable the synthesis of
block copolymers with N-(2-hydroxypropyl)methacrylamide (HPMAm).
5.4 Light Effects on the Rate of Polymerization

Several groups [130] have observed that trithiocarbonate and other RAFT agents
can be used to mediate the polymerization of acrylates and acrylamides under
visible light (e.g. 𝜆 = 460 nm) [131] without the addition of a photoinitiator or
catalyst. A lower yield of by-products was attributed to selective excitation of the
forbidden n → π* electronic transition. In photoinitiated RAFT, once radicals are
generated the normal RAFT mechanism becomes operative and is responsible for
the control. The observations of higher selectivity with blue light photoinitiation
motivated a subsequent study of the effect of visible light on the stability of several
trithiocarbonates [132]. Notably, trithiocarbonates with tertiary cyanoalkyl R
groups, such as 2-cyanoprop-2-yl, were shown to degrade faster under visible light
than those with secondary R groups. Moreover, these agents were shown to lead
to faster initiation of polymerization for MA under blue light, with no discernible
inhibition or initialization period observed under these conditions. In contrast,
those trithiocarbonates secondary leaving groups were far more stable under
blue light (as assessed using UV–visible spectrophotometry) and gave significant
inhibition periods (c. 4–6 hours). However, despite these long inhibition periods,
the resulting polymers displayed excellent end-group fidelity, which was attributed
to the superior stability of the secondary thiocarbonylthio group under the blue
light source. The results indicate that in the case of trithiocarbonate-mediated poly-
merization initiated under blue light, lengthy inhibition periods do not necessarily
compromise the end-group fidelity of the resulting polymer. Even so, despite the
inherent instability of the tertiary leaving group under blue light, low-dispersity
polymers were still successfully obtained due to the rapid polymerization of the
monomer relative to the rate of loss of the end-group under these conditions.
The inhibition periods observed in these experiments are most likely related to
trace amounts of air or impurities in the RAFT agents. These cause inhibition until
they are consumed, with the length of inhibition period dependent on the rate of
radical photogeneration and the level of impurities. Because the radical concentra-
tions are very low, it does not require much impurity to cause a substantial inhibi-
tion period. With tertiary trithiocarbonates the rate of photogeneration of radicals
is significantly higher than that with secondary trithiocarbonates. This means that
inhibition periods will be shorter. Also, because of the higher radical concentrations
generated, cross-termination reactions (between R⋅ or ZCS2 − ) are more likely both
in the presence and absence of monomer.
A further interesting consequence of trithiocarbonate activation via the forbidden
n → π* electronic transition under visible light is that trithiocarbonate-mediated
RAFT polymerizations tend to be accelerated under fluorescent laboratory lighting
(see Figure 5.13) [133]. This phenomenon has been observed for both methyl
methacrylate and methyl acrylate where a chain transfer agent incorporating a
5.5 Conclusion 131
1.4
H (Fume hood light ON)

1.2
D (Dark)
A (Ambient with fume hood light OFF)
1.0 Control (no AIBN)
In ([M]0 /[M]t)
0.8
0.6
0.4
0.2
0.0
0 1 2 3 4 5 6 7 8
Reaction time (h)
Figure 5.13 RAFT reaction of MMA with 4-cyano-4-((dodecylthio)carbonothio)pentanoic

acid and 0.05 equiv of AIBN under various lighting conditions at 70 ∘ C. Source: Taken from
da M. Costa et al. [133]. © American Chemical Society.
4-cyanopentanoic acid leaving group is employed. Notably, the effect of lighting is

quite dramatic in these experiments. Moreover, R groups incorporating a pendant
nitrile on the α-carbon are extremely commonly used in RAFT polymerization,
and as such caution should be exercised where such R groups are combined with a
trithiocarbonate Z group. This insight highlights the need for tightly controlling all
reaction variables in order to ensure that results can be readily reproduced and are
not compromised by variations in laboratory lighting, either with time or between
sites.
Further examples and details of visible light photoinititated RAFT polymerization
can be found in the chapter of Chapman et al. [130] and in the chapters relating to
specific RAFT agents.
5.5 Conclusion
While there are certain elements of the RAFT mechanism that have been discussed
in the literature, overall the mechanism of RAFT polymerization is well understood.
Those areas where there has been significant debate have generally been related to a
very narrow class of chain transfer agents (dithiobenzoates) that – although highly
useful – are by no means the only choice for conducting the RAFT polymerization of
most monomers. In the choice of chain transfer agent there is, of course, a necessity
to ensure that R and Z groups are appropriate for the monomer being polymerized,
and that the solvent, temperature, and initiation source are suitable. As such, a basic
mechanistic understanding of RAFT is essential for good experimental planning.
Within the last decade, there have been some important advances that have exploited
the mechanistic understanding of RAFT to design new, more versatile chain transfer
agents. In particular, the development of the so-called switchable RAFT agents that
are suitable for both LAMs and MAMs is a significant advance. These agents have
enabled the synthesis of new and interesting materials that are substantially more
complicated to make via other techniques. Moreover, the advance in understanding
of side reactions such as side fragmentation in the case of xanthates, and the devel-
opment of approaches that can minimize these reactions have enabled RAFT to be
applied to the simplest yet most challenging of monomers, ethylene [89, 90, 134].
Further exploration into the intricacies of the RAFT mechanism will undoubtedly
yield new insights – insights that will likely unlock even more opportunities for
applying the most versatile, widely applicable, and robust of the RDRP techniques:
The RAFT process.
References
6 Moad, C.L., Moad, G., Rizzardo, E., and Thang, S.H. (1996). Macromolecules 29:
7717–7726.
7 Krstina, J., Moad, C.L., Moad, G. et al. (1996). Macromol. Symp. 111: 13–23.
8 Krstina, J., Moad, G., Rizzardo, E. et al. (1995). Macromolecules 28: 5381–5385.
9 Zhang, Z., Zhu, J., Zhou, N. et al. (2013). J. Polym. Sci., Part A: Polym. Chem.
51: 2606.
10 Zhu, J., Zhang, Z., Pan, X. et al. (2013). J. Polym. Sci., Part A: Polym. Chem. 51:
3159.
11 Matioszek, D., Brusylovets, O., Wilson, D.J. et al. (2013). J. Polym. Sci., Part A:
Polym. Chem. 51: 4361–4368.
12 Feldermann, A., Ah Toy, A., Phan, H. et al. (2004). Polymer 45: 3997.
tion: Materials, Synthesis and Applications (eds. G. Moad and E. Rizzardo).
Weinheim: Wiley-VCH. 223–370.
ization: Materials, Synthesis and Applications (eds. G. Moad and E. Rizzardo).
Moad and E. Rizzardo). Weinheim: Wiley-VCH. 495–550.
16 Moad, G. (2022). Dithiocarbamates in RAFT polymerization. In: RAFT Polymer-
ization: Materials, Synthesis and Applications (eds. G. Moad and E. Rizzardo).
17 Nguyen, D.H. and Vana, P. (2006). Aust. J. Chem. 59: 549.
References 133
18 Zhu, J., Zhu, X., and Zhou, D. (2004). J. Macromol. Sci. Part A: Pure Appl.
Chem. 41: 827.
19 Mayo, F.R. (1943). J. Am. Chem. Soc. 65: 2324–2329.
20 Clay, P.A. and Gilbert, R.G. (1995). Macromolecules 28: 552–569.
21 Moad, G. and Moad, C.L. (1996). Macromolecules 29: 7727–7733.
23 Walling, C. (1948). J. Am. Chem. Soc. 70: 2561–2564.
24 O’Brien, J.L. and Gornick, F. (1955). J. Am. Chem. Soc. 77: 4757–4763.
25 Gregg, R.A., Alderman, D.M., and Mayo, F.R. (1948). J. Am. Chem. Soc. 70:
3740–3743.
26 Theis, A., Feldermann, A., Charton, N. et al. (2005). Macromolecules 38: 2595.
27 Derboven, P., Van Steenberge, P.H.M., Reyniers, M.F. et al. (2016). Macromol.
Theory Simul. 25: 104–115.
28 Goto, A., Sato, K., Tsujii, Y. et al. (2001). Macromolecules 34: 402–408.
29 Goto, A. and Fukuda, T. (2004). Prog. Polym. Sci. 29: 329–385.
30 Gao, X. and Zhu, S. (2011). J. Appl. Polym. Sci. 122: 497.
31 Vana, P., Davis, T.P., and Barner-Kowollik, C. (2002). Macromol. Theory Simul.
11: 823–835.
32 Drache, M., Schmidt-Naake, G., Buback, M., and Vana, P. (2005). Polymer 46:
8483–8493.
33 Barner-Kowollik, C., Coote, M.L., Davis, T.P. et al. (2003). J. Polym. Sci. Part A
Chem. 41: 2828–2832.
34 Barth, J., Buback, M., Meiser, W., and Vana, P. (2010). Macromolecules 43:
51–54.
E. Rizzardo). Weinheim: Wiley-VCH.
37 Moad, G., Chiefari, J., Chong, Y.K. et al. (2000). Polym. Int. 49: 993.
38 Engelis, N.G., Anastasaki, A., Nurumbetov, G. et al. (2017). Nat. Chem. 9:
171–178.
39 Destarac, M., Matioszek, D., Vila, X. et al. (2018). How can xanthates control
the RAFT polymerization of methacrylates? In: ACS Symposium Series 1284
(eds. K. Matyjaszewski, H. Gao, B.S. Sumerlin and N.V. Tsarevsky), 291–305.
Washington, DC: American Chemical Society.
40 Khan, M., Guimarães, T.R., Zhou, D. et al. (2019). J. Polym. Sci., Part A, Polym.
Chem. 57 (18): 1938–1946.
41 Guimaraes, T.R., Khan, M., Morrow, I.C. et al. (2019). Macromolecules 52 (8):
2965–2974.
42 Clothier, G.K.K., Guimarães, T.R., Khan, M. et al. (2019). ACS Macro Lett. 8 (8):
989–995.
43 Barner-Kowollik, C., Quinn, J.F., Nguyen, T.L.U. et al. (2001). Macromolecules
34: 7849.
44 Fischer, H. and Radom, L. (2001). Angew. Chem. Int. Ed. 40: 1340.

2e. Oxford, UK: Elsevier.
46 Moad, G. (2017). Macromol. Chem. Phys. 218 (19): 1700381.
47 (a) Beuermann, S., Buback, M., Davis, T.P. et al. (1997). Macromol. Chem.
Phys. 198: 1545–1560.(b) Buback, M., Gilbert, R.G., Hutchinson, R.A. et al.
(1995). Macromol. Chem. Phys. 196: 3267–3280.(c) Buback, M., Kurz, C.H., and
Schmaltz, C. (1998). Macromol. Chem. Phys. 199: 1721–1727.(d) Hutchinson,
R.A., Paquet, D.A. Jr., and McMinn, J.H. (1995). DECHEMA Monogr. 131:
467–492.
48 Kamachi, M. and Yamada, B. (1999). Elements of RAFT navigation. In: Polymer
Handbook, 4e (eds. J.I. Brandrup, H. Edmund, A. Grulke, Eric, et al.). Wiley.
49 Zhou, Y., Zhang, Z., Reese, C. et al. (2020). Macromol. Rapid Commun. 41 (1):
1900478.
50 McLeary, J.B., McKenzie, J.M., Tonge, M.P. et al. (2004). Chem. Commun. (17):
1950–1951.
3151–3161.
2383–2394.
53 Haven, J.J., Hendrikx, M., Junkers, T. et al. (2018). Reversible deactivation
radical polymerization: mechanisms and synthetic methodologies. In: ACS
Symposium Series 1284 (eds. K. Matyjaszewski, H. Gao, B.S. Sumerlin and N.V.
Tsarevsky), 77–103. Washington, DC: American Chemical Society.
54 Aerts, A., Lewis, R.W., Zhou, Y. et al. (2018). Macromol. Rapid Commun. 39:
55 Fuchs, A.V. and Thurecht, K.J. (2017). ACS Macro Lett. 6: 287–291.
56 Liu, C.H. and Pan, C.Y. (2007). Polymer 48: 3679.
57 Reyhani, A., McKenzie, T.G., Ranji-Burachaloo, H. et al. (2017). Chem. Eur. J.
23: 7221.
58 Zhao, J.C., Lalevee, J., Lu, H.X. et al. (2015). Polym. Chem. 6: 5053.
7620.
60 You, Y.Z., Hong, C.Y., Bai, R.K. et al. (2002). Macromol. Chem. Phys. 20: 477.
61 Bai, R.K., You, Y.Z., and Pan, C.Y. (2001). Macromol. Rapid Commun. 22: 315.
62 Quinn, J.F., Barner, L., Rizzardo, E., and Davis, T.P. (2002). J. Polym. Sci., Part
A: Polym. Chem. 40: 19.
63 Quinn, J.F., Barner, L., Davis, T.P. et al. (2002). Macromol. Rapid Commun. 23:
717.
64 Whittaker, M.R., Goh, Y.K., Gemici, H. et al. (2006). Macromolecules 39: 9028.
65 Grover, G.N., Alconcel, S.N.S., Matsumoto, N.M., and Maynard, H.D. (2009).
Macromolecules 42: 7657.
66 Lima, V., Jiang, X.L., Brokken-Zijp, J. et al. (2005). J. Polym. Sci., Part A: Polym.
Chem. 43: 959.
67 Favier, A., Charreyre, M.T., Chaumont, P., and Pichot, C. (2002). Macro-
molecules 35: 8271.
References 135
68 York, A.W., Scales, C.W., Huang, F.Q., and McCormick, C.L. (2007). Biomacro-
molecules 8: 2337.
69 Tang, C.B., Kowalewski, T., and Matyjaszewski, K. (2003). Macromolecules 36:
8587.
70 Zheng, G.H. and Pan, C.Y. (2006). Macromolecules 39: 95.
71 Mayadunne, R.T.A., Rizzardo, E., Chiefari, J. et al. (2000). Macromolecules 33:
243.
72 Wood, M.R., Duncalf, D.J., Findlay, P. et al. (2007). Aust. J. Chem. 60: 772.
73 Zhang, W.J., D’Agosto, F., Dugas, P.Y. et al. (2013). Polymer 54: 2011.
74 Convertine, A.J., Ayres, N., Scales, C.W. et al. (2004). Biomacromolecules 5:
1177.
75 Hong, C.Y. and Pan, C.Y. (2006). Macromolecules 39: 3517.
76 Spoerl, J.M., Ota, A., Beyer, R. et al. (2014). J. Polym. Sci., Part A: Polym. Chem.
52: 1322.
6977–6980.
78 Zhou, Y., Zhu, X., Cheng, Z., and Zhu, J. (2007). J. Appl. Polym. Sci. 103: 1769.
79 Chong, Y.K., Moad, G., Rizzardo, E. et al. (2007). Macromolecules 40: 9262.
80 Sun, X.L., He, W.D., Li, J. et al. (2008). J. Polym. Sci., Part A: Polym. Chem. 46:
6950.
81 Hornung, C.H., Guerrero-Sanchez, C., Brasholz, M. et al. (2011). Org. Process.
Res. Dev. 15: 593.
82 Jana, S. and Parthiban, A. (2011). Macromol. Chem. Phys. 212: 790.
83 Destarac, M., Bzducha, W., Taton, D. et al. (2002). Macromol. Rapid Commun.
23: 1049.
84 Wood, M.R., Duncalf, D.J., Rannard, S.P., and Perrier, S. (2006). Org. Lett. 8:
553.
85 Taton, D., Wilczewska, A.Z., and Destarac, M. (2001). Macromol. Rapid Com-
mun. 22: 1497.
86 Postma, A., Davis, T.P., Li, G. et al. (2006). Macromolecules 39: 5307.
87 Wan, D.C., Satoh, K., Kamigaito, M., and Okamoto, Y. (2005). Macromolecules
38: 10397.
2273–2283.
89 Dommanget, C., D’Agosto, F., and Monteil, V. (2014). Angew. Chem. Int. Ed. 53:
6683.
90 Wolpers, A., Bergerbit, C., Ebeling, B. et al. (2019). Angew. Chem. Int. Ed. 58:
14295.
91 Benaglia, M., Chiefari, J., Chong, Y.K. et al. (2009). J. Am. Chem. Soc. 131: 6914.
92 Moad, G., Benaglia, M., Chen, M. et al. (2011). Block copolymer synthesis
through the use of switchable RAFT agents. In: Non-conventional functional
block copolymers, ACS Symposium Series, vol. 1066 (eds. P. Theato, A.F.M.
Kilbinger and E.B. Coughlin), 81. Washington, D.C.: American Chemical
Society.

6738.
Chem. 7: 481.
95 Perrier, S., Barner-Kowollik, C., Quinn, J.F. et al. (2002). Macromolecules 35:
8300.
96 Quinn, J.F., Rizzardo, E., and Davis, T.P. (2001). Chem. Commun.: 1044.
97 Chernikova, E.V., Tarasenko, A.V., Garina, E.S., and Golubev, V.B. (2008).
Polym. Sci., Ser. A 50: 353.
98 Scales, C.W., Vasilieva, Y.A., Convertine, A.J. et al. (2005). Biomacromolecules 6:
1846.
99 Monteiro, M.J. and de Brouwer, H. (2001). Macromolecules 34: 349–352.
Sci., Part A: Polym. Chem. 39: 1353.
101 Barner-Kowollik, C., Buback, M., Charleux, B. et al. (2006). J. Polym. Sci. Part
102 Moad, G. (2014). Macromol. Chem. Phys. 215: 9–26.
103 Hawthorne, D.G., Moad, G., Rizzardo, E., and Thang, S.H. (1999). Macro-
molecules 32: 5457.
104 de Brouwer, H., Schellekens, M.A.J., Klumperman, B. et al. (2000). J. Polym.
105 Kwak, Y., Goto, A., and Fukuda, T. (2004). Macromolecules 37: 1219.
106 Kwak, Y., Goto, A., Komatsu, K. et al. (2004). Macromolecules 37: 4434.
107 Feldermann, A., Ah Toy, A., Davis, T.P. et al. (2005). Polymer 46: 8448–8457.
108 Ah Toy, A., Vana, P., Davis, T.P., and Barner-Kowollik, C. (2004). Macro-
molecules 37: 744–751.
109 Buback, M. and Vana, P. (2006). Macromol. Rapid Commun. 27: 1299.
110 Meiser, W., Buback, M., Ries, O. et al. (2013). Macromol. Chem. Phys. 214: 924.
111 Meiser, W. and Buback, M. (2012). Macromol. Rapid Commun. 33: 1273.
molecules 41: 6400.
113 Konkolewicz, D., Hawkett, B.S., Gray-Weale, A., and Perrier, S. (2009). J. Polym.
114 Ting, S.R.S., Davis, T.P., and Zetterlund, P. (2011). Macromolecules 44: 4187.
115 Feldermann, A., Coote, M.L., Davis, T.P. et al. (2004). J. Am. Chem. Soc. 126:
15915–15923.
116 Tonge, M.P., Calitz, F.M., and Sanderson, R.D. (2006). Macromol. Chem. Phys.
207: 1852.
mun. 27: 473.
mun. 27: 1233.
1738.
120 Meiser, W. and Buback, M. (2011). Macromol. Rapid Commun. 32: 1490.
References 137
121 Barner-Kowollik, C., Vana, P., Quinn, J.F., and Davis, T.P.J. (2002). Polym. Sci.
Part A: Chem. 40: 1058–1063.
122 Pahnke, K., Brandt, J., Gryńova, G. et al. (2016). Angew. Chem. Int. Ed. 55:
1514–1518.
123 Plummer, R., Goh, Y.K., Whittaker, A.K., and Monteiro, M.J. (2005). Macro-
molecules 38: 5352–5355.
124 Sumerlin, B.S., Donovan, M.S., Mitsukami, Y. et al. (2001). Macromolecules 34:
6561–6564.
125 Donovan, M.S., Lowe, A.B., Sumerlin, B.S., and McCormick, C.L. (2002).
Macromolecules 35: 4123–4132.
126 Donovan, M.S., Sumerlin, B.S., Lowe, A.B., and McCormick, C.L. (2002).
127 Thomas, D.B., Sumerlin, B.S., Lowe, A.B., and McCormick, C.L. (2003). Macro-
molecules 36: 1436–1439.
1735–1741.
129 Alidedeoglu, A.H., York, A.W., McCormick, C.L., and Morgan, S.E. (2009). J.
Polym. Sci. Part A. Chem. 47: 5405–5415.
130 Chapman, R., Jung, K., and Boyer, C. (2022). Overview of photoregulated
Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization. In:
E. Rizzardo). Weinheim: Wiley-VCH.
131 McKenzie, T.G., Fu, Q., Wong, E.H.H. et al. (2015). Macromolecules 48:
3864–3872.
132 McKenzie, T.G., da M. Costa, L.P., Fu, Q. et al. (2016). Polym. Chem. 7:
4246–4253.
133 da M. Costa, L.P., McKenzie, T.G., Schwarz, K.N. et al. (2016). ACS Macro Lett.
5: 1287–1292.
134 Busch, M., Roth, M., Davis, T.P. et al. (2007). Aust. J. Chem. 60: 788–793.
139
Quantum Chemical Studies of RAFT Polymerization

Michelle L. Coote
Australian National University, ARC Centre of Excellence in Electromaterials Science, Research School of
Chemistry, Canberra 2601, Australia
6.1 Introduction
Quantum chemistry allows one to predict, from first principles, the energetics
of chemical reactions. One can also use the calculations to visualize the electron
density and how the atoms rearrange along a reaction path. This information can be
used to elucidate reaction mechanisms, make first principles predictions of kinetics
and thermodynamics, and provide insights into the origin of structure–reactivity
trends. Quantum chemistry is particularly useful for complicated multi-step
processes such as reversible addition−fragmentation chain transfer (RAFT) poly-
merization [1] because, on the one hand, information about the kinetics and
structure–reactivity trends are essential in choosing optimal RAFT agents and
reaction conditions, and because, on the other hand, there is no experimental
method for directly measuring the individual rate coefficients.
Unsurprisingly then there have been several quantum chemical studies of the
RAFT process, addressing mechanistic issues, structure–reactivity analysis, reagent
design, and first principles predictions of rate coefficients. Chapter 2 in the first
edition of this book reviewed the early studies of this process [2], which were also
summarized in Ref. [3]. Herein, we recap these early studies, while also providing
an update on more recent work. We begin with a description of the types of methods
that are used and discuss their accuracy and their outstanding problems. We then
show how computational chemistry can be used to clarify and improve models for
reaction kinetics, and indeed how computational calculations can be used directly
in kinetic simulations to predict the macroscopic outcome of a process. Finally, we
examine the RAFT process at a deeper mechanistic level, using computational data
to model and explain structure–reactivity trends and show how these insights can
be applied to the practical problem of RAFT agent design.

140 6 Quantum Chemical Studies of RAFT Polymerization
6.2 Methodology
In order to select reliable yet cost-effective theoretical procedures, assessment
studies are performed. In essence, one takes a small prototypical example of the
class of chemical reaction under study and calculates the geometries, frequen-
cies, barriers, enthalpies, rate coefficients, and other properties at a variety of
levels of theory, ranging from the extremely accurate but highly computationally
intensive to those that are computationally inexpensive but potentially subject
to very large errors. For each type of property, one compares the results at the
lower levels of theory with the highest level results and (where possible) also
with reliable gas-phase experimental data. For the case of addition–fragmentation
processes, assessment studies have been performed for the prototypical reac-
tions ⋅CH3 + S=C(R)R′ → CH3 SC⋅(R)R′ (R, R′ = H, CH3 ) [4] and also the more
RAFT-related systems, R′ SC(Z)=S + ⋅R → R′ SC⋅(Z)SR (various combinations of
R, R′ = CH3 , CH2 CH3 , CH2 CN, C(CH3 )2 CN, CH2 COOCH3 , CH(CH3 )COOCH3 ,
CH2 OCOCH3 , CH2 Ph, CH(CH3 )Ph, and Z = CH3 , H, Cl, CN, CF3 , NH2 , Ph, CH2 Ph,
OCH3 , OCH2 CH3 , OCH(CH3 )2 , OC(CH3 )3 , F) [5]. In addition, the accuracy of
the harmonic oscillator approximation [6, 7] and the applicability of standard
(rather than variational) transition state theory have been explored [6]. Finally,
solution-phase calculations on small-molecule models have been compared directly
with the corresponding experimental data for the same systems [8]. On the basis
of these studies, the following guidelines for performing theoretical calculations
are suggested.
6.2.1 Electronic Structure Calculations

For simple systems, it is possible to conduct reliable geometry optimizations and
frequency calculations for the stationary species (i.e. the reactants and products)
in the RAFT process at relatively low levels of theory, such as B3-LYP/6-31G(d) or
HF/6-31G(d) [4]. For example, provided the energies are calculated at a consistent
level of theory, the reaction enthalpies for ⋅CH3 + S=CRR′ (R, R′ = H, CH3 ) vary
by less than 1 kJ mol−1 , regardless of whether low levels such as B3-LYP/6-31G(d)
or HF/6-31G(d) or higher levels such as CCSD(T)/6-311+G(d,p) are used for the
geometry optimizations [4]. Likewise, provided the recommended scale factors
are used [9], the zero-point vibrational energy (and hence the frequency cal-
culations) at these lower levels of theory agrees to within 1–2 kJ mol−1 of the
CCSD(T)/6-311+G(d,p) calculations [4]. These earlier studies were performed on
simple systems that do not involve significant non-covalent interactions and at a
time when dispersion-corrected density functional theory (DFT) methods were not
readily available. It is now well recognized that if intra- or inter-molecular hydrogen
bonding and/or other non-covalent interactions are important, DFT methods that
take account of dispersion either through corrections or parameterization should
be used in place of Hartree–Fock (HF) or non-dispersion-corrected DFT methods
such as B3-LYP [10].
6.2 Methodology 141
Regardless of whether dispersion is included, for transition structures extra

precautions are required. In particular, DFT methods significantly flatten the poten-
tial energy surface and overestimate the length of the forming bond in the transition
state, finding transition structures that are too early. HF fares somewhat better, but
does underestimate the forming bond length, finding transition structures that are
too late. To address this problem, the transition structures should be corrected to
higher levels of theory via IRCmax [4]. In the IRCmax method [11, 12], one calcu-
lates the minimum energy path of the chemical reaction at a low level of theory,
and then calculates single-point energies along this reaction path at a higher level
of theory, such as RMP2/6-311+G(3df,2p). The IRCmax transition structure is then
identified as that species corresponding to the maximum point of the minimum
energy path, as calculated at the higher level of theory. In essence, one optimizes
the most sensitive part of the geometry optimization (i.e. the reaction coordinate)
at the higher level of theory, at a fraction of the cost of a full geometry optimization
at that level. For the case of radical addition to C=S bonds, the IRCmax transition
structures have forming bond lengths within less than 0.05 Å, and provide reaction
barriers within 1 kJ mol−1 of those obtained using full geometry optimizations at
the CCSD(T)/6-311+G(d,p) level [4].
In contrast to geometries and frequencies, accurate calculations of the energetics
of these types of chemical reactions require very high levels of theory. Ideally, such
calculations should be performed using W1 theory or better. W1 aims to approximate
coupled cluster energies [URCCSD(T)] with an infinite basis set via extrapolation,
and includes corrections for core correlation and relativistic effects [13]. It has been
shown to deliver ‘kJ accuracy’ when assessed against a large test set of gas-phase
experimental data [13] and has performed well in assessment studies for the pro-
totypical system ⋅CH3 + S=CH2 [4] as well as other types of radical reactions such
as radical addition to C=C bonds [14] and hydrogen atom abstraction [15]. Unfor-
tunately, such calculations are computationally very intensive and currently only
practicable for up to approximately six to eight non-hydrogen atoms. The G3 and G4
families of methods provide a lower cost alternative to W1. Like W1, they attempt
to approximate coupled cluster energies with a large basis set, but achieve this via
additivity approximations at the MP2 and/or MP4 levels of theory. As a result, they
are less expensive than W1 but also less reliable. They have been shown to deliver
‘kcal accuracy’ when assessed against a large test set of experimental thermochem-
ical data [16, 17] and to provide good agreement with W1 for a variety of radical
reactions [14, 15]. For the specific problem of radical addition to C=S double bonds,
G3-methods provide excellent agreement with W1 for the forward reaction barriers;
for reaction enthalpies, the errors are slightly larger (c. 10 kJ mol−1 ) but are likely
to be reasonably systematic for a class of reactions and therefore suitable for study-
ing substituent effects [4]. Nonetheless, they are also currently too computationally
intensive for all but the simplest RAFT systems, being currently only feasible for
systems of up to approximately 17 non-hydrogen atoms.
For practical RAFT systems, lower cost procedures are necessary and unfortu-
nately these procedures can be subject to large errors. In particular, most DFT
methods comprehensively fail, even when modelling the qualitative trends let alone
quantitative kinetics and thermodynamics of addition–fragmentation processes [5].
Moreover, this failing has also been observed for other radical reactions such as
R—X bond dissociation reactions (R = Me, Et, i-Pr, t-Bu; X = H, CH3 , OCH3 , OH,
F) [18], propagation rate coefficients [19], and even simple closed-shell systems
such as the cyclization energies of alkenes [20] and alkane isomerization energies
[21, 22]. Restricted open-shell second order Møller–Plesset perturbation theory
(RMP2), which is slightly more expensive than DFT but can still be practically
applied to relatively large systems, has been shown to fare much better than DFT.
It generally provides reasonable absolute values (within 10 kJ mol−1 ) and excellent
relative values (within 4 kJ mol−1 or better) for the barriers and enthalpies of the
addition–fragmentation processes [4, 5] as well as a variety of other radical reactions
[14, 15, 18, 19]. However, it breaks down when the attacking radical is substituted
with a group (such as phenyl or CN) that delocalizes the unpaired electron, with
errors of over 15 kJ mol−1 being reported in some cases [5, 6]. Since such radicals are
common in practical RAFT systems, this severely compromises the utility of RMP2.
Given these problems, we have designed an alternative approach that is based on
our own N-layered integrated molecular orbital + molecular mechanic (ONIOM)
procedure of Morokuma and coworkers [23]. In the ONIOM method, one first
defines a ‘core’ section of the reaction that, in the very least, contains all forming
and breaking bonds and would preferably include the principal substituents
attached to them. In forming the core system, deleted substituents are replaced
with ‘link atoms’ (typically hydrogens), chosen so that the core system provides a
good chemical model of the reaction centre. One then calculates the core system at
both a high level of theory and a lower level; the ‘full system’ is calculated at only
the lower level. The full system at the high level of theory is then approximated
as the sum of (i) the core system at the high level and (ii) the substituent effect
measured at the low level of theory. The approximation is valid if the low level of
theory measures the substituent effect accurately; this in turn depends upon the
level of theory chosen, and the way in which the core system is defined.
For the RAFT systems, we know from above that W1 provides accurate abso-
lute values of barriers and enthalpies, and G3(MP2)-RAD provides excellent relative
values. For small systems, such as reaction (6.1), the W1 enthalpy could thus be
approximated as the sum of the W1 enthalpy for the core reaction (6.2), and the
difference in the G3(MP2)-RAD enthalpies for (6.1) and (6.2).
⋅
CH2 Ph + S=C(CH3 )SCH3 → PhCH2 SC⋅ (CH3 )SCH3 (6.1)
⋅
CH3 + S=CH2 → CH3 SCH⋅2 (6.2)
For larger systems, where G3(MP2)-RAD calculations are not currently feasible,
we add an additional ‘ONIOM-layer’ in which the full system is calculated using
RMP2/6-311+G(3df,2p), the core system is calculated using G3(MP2)-RAD, and
the ‘inner core’ is studied at W1. For example, one could approximate the W1
enthalpy for reaction (6.3) as the sum of the W1 value for the inner core (6.2),
the G3(MP2)-RAD difference for the core (6.1), and the inner core (6.2), and the
6.2 Methodology 143
RMP2/6-311+G(3df,2p) difference for the full (6.3) and core (6.1) systems.
⋅
CH(Ph)CH2 C(CH3 )2 CN + S=C(CH2 )SC(CH3 )2 Ph
→ (CH3 )2 C(CN)CH2 CH(Ph)SC⋅ (CH2 Ph)SC(CH3 )2 Ph (6.3)
The ONIOM procedure provides an accurate alternative to high-level calculations
on the full system, provided that the lower level of theory measures the substituent
effects accurately. While the RMP2/6-311+G(3df,2p) method normally provides
excellent relative values of barriers and enthalpies, it does break down in situations
where the unpaired electron is highly delocalized. It is therefore extremely impor-
tant to partition the full and core systems carefully, such that the delocalized radical
is treated at the G3(MP2)-RAD level of theory and the RMP2/6-311+G(3df,2p)
method is used only to measure remote substituent effects. Based on a careful
assessment study, the following general guidelines are suggested [5] for partitioning
the core and full systems: in the addition–fragmentation reaction (6.4), a suitable
core system should include all α-substituents on the attacking radical R⋅ but could
replace the R′ group with a methyl substituent and, if necessary, also replace the Z
group with a methyl substituent.
⋅
R + S=C(Z)SR′ → RSC⋅ (Z)SR′ (6.4)
Even when the Z group is itself a substituent capable of delocalizing the unpaired
electron in the RAFT-adduct radical, its replacement with CH3 in the core system
does not introduce substantial error [5]. This is presumably because the radical
is already highly delocalized by the thiyl groups (which are of course included in
both the core and inner core systems), and the additional delocalization by the Z
substituent is not as significant as in an ordinary carbon-centred radical [24]. This
ONIOM-based procedure allows one to study quite large RAFT systems (c. 30–40
non-hydrogen atoms) with kcal accuracy [5]. Similar performance has also been
demonstrated for a range of other radical reactions including the bond dissociation
energy (BDEs) of a range of organic compounds, propagation, hydrogen and
halogen atom transfer reactions, and radical ring opening [25].
6.2.2 Kinetics and Thermodynamics

Having obtained the geometries, energies, and frequencies of the reactants, prod-
ucts, and transition structures, it is possible to calculate the rates k(T) and equilib-
rium constants K(T) of chemical reactions, using the standard textbook formulae
[26, 27].
kB T ( ∘ )1−m (−𝛥G‡ ∕RT) k T ( )1−m Q‡
= 𝜅 (T) B c∘ e(−𝛥E ∕RT)
‡
k (T) = 𝜅 (T) c e
h h 𝛱Qi
reactants
(6.5)
⎛ ΠQj ⎞
( )𝛥n ( ∘ )𝛥n ⎜ products ⎟ (−𝛥E∕RT)
K (T) = c∘ e(−𝛥G∕RT) = c ⎜ ⎟e (6.6)
⎜ ΠQ ⎟
⎜ i
⎟
⎝ reactants ⎠
In these formulae, 𝜅(T) is the tunnelling correction factor, T is the temperature

(K), kB is Boltzmann’s constant (1.380658 × 10−23 J mol−1 K−1 ), h is Planck’s con-
stant (6.6260755 × 10−34 J s), c∘ is the standard unit of concentration (mol l−1 ), R is
the universal gas constant (8.3142 J mol−1 K−1 ), m is the molecularity of the reac-
tion and Δn the change in moles upon reaction, Q‡ , Qi , and Qj are the molecu-
lar partition functions of the transition structure, reactant I, and product j respec-
tively, ΔG‡ is the Gibbs free energy of activation, 𝛥G is the Gibbs free energy of
reaction, ΔE‡ the 0 K, zero-point energy corrected energy barrier for the reaction,
and ΔE is the 0 K, zero-point energy corrected energy change for the reaction. The
value of c∘ depends on the standard-state concentration assumed in calculating the
thermodynamic quantities (and translational partition function). For example, if
these quantities were calculated for 1 mol of an ideal gas at 333.15 K and 1 atm, then
c∘ = P/RT = 0.0365971 mol l−1 . The tunnelling coefficient 𝜅(T) corrects for quantum
effects in motion along the reaction path [28–31]. Whilst tunnelling is important in
certain chemical reactions such as hydrogen abstraction, it is negligible (i.e. 𝜅 ≈ 1) for
the addition of carbon-centred radicals to thiocarbonyl compounds at typical poly-
merization temperatures (such as 333.15 K) because the masses of the rearranging
atoms are large and the barriers for the reactions are relatively broad [6].
The molecular partition functions and their associated thermodynamic functions
(i.e. enthalpy, H and entropy, S) can be calculated using the standard textbook
formulae [26, 27], based on the statistical thermodynamics of an ideal gas under
the harmonic oscillator/rigid rotor approximation. These formulae require knowl-
edge of the point group, multiplicity, geometry, and vibrational frequencies of
each species; the accuracy of the results depends upon both the accuracy of the
calculated geometries and frequencies and the validity of the harmonic oscilla-
tor/rigid rotor approximation. As noted above, the geometries and frequencies are
well described with dispersion-corrected DFT methods, provided that transition
structures are corrected via IRCmax and frequencies are scaled by appropriate
scale factors. However, the use of the harmonic oscillator/rigid rotor approxi-
mation can lead to errors of 1–2 orders of magnitude in both the kinetics and
thermodynamics of the addition–fragmentation equilibrium [6, 7]. To address this
problem, the partition functions for the low-frequency torsional modes (<300 cm−1 )
should instead be treated as hindered internal rotations. Full details of these
calculations are published elsewhere [6, 32], but a short description is provided
below.
For each low-frequency torsional mode, one first calculates the full rotational
potential V(𝜃). This can be calculated at a relatively low level of theory, such as
B3-LYP/6-31G(d), and is performed as a relaxed (rather than frozen) scan in steps
of 10∘ through 360∘ . The potential is then fitted with a Fourier series of up to 18
terms, so that it can be interpolated to a finer numerical grid (typically 300 points
instead of 36). The corresponding energy levels are found by numerically solving
the one-dimensional Schrödinger equation (6.7) for a rigid rotor [33–35].
h2 𝜕 2 Ψ
− + V (𝜃) Ψ = 𝜀Ψ (6.7)
8𝜋lr 𝜕𝜃 2
6.2 Methodology 145
The reduced moment of inertia (I r ) is calculated using the equation for I 2,3 , as
defined by East et al. [36]. The resulting energy levels 𝜀i are then summed to obtain
the partition function at the specified temperature, as follows:
( )
1 ∑ 𝜀
Qint rot = exp − i (6.8)
𝜎int i kB T
where 𝜎 int is the symmetry number associated with that rotation. It should be noted
that, in this method, the low-frequency torsional modes have been approximated
as one-dimensional rigid rotors, while in practice these modes can be coupled with
another. However, a study of coupled internal rotations in another radical addition
reaction (ethyl benzyl radical addition to ethene) indicated that the errors incurred
in using a one-dimensional treatment are relatively minor, particularly when com-
pared with the errors incurred under the harmonic oscillator approximation [37].
By treating low-frequency torsional modes as 1D-hindered internal rotations,
one is effectively averaging contributions from conformations that are within a
single bond rotation of the starting geometry. Provided that this starting geometry
is the global minimum conformation for that species, this normally captures all
of the energetically relevant conformers and no further Boltzmann averaging is
needed. To find the global minimum, one needs to perform a conformational
search because procedures for optimizing geometries only find the nearest local
minimum structure. The best way to do this is to start with an optimized geometry,
and generate starting structures by rotating bonds in increments of 120∘ (or 180∘ if
cis–trans isomerization is being considered). All combinations of such bond rota-
tions should in principle be considered, which means that the number of structures
to be optimized increases rapidly with system size. Even a simple radical adduct of
methacrylate dimer with S=C(SCH2 CH3 )SC(CH3 )C(O)OCH3 has over 1.4 million
different conformers and, even if one assumes all esters to be cis, there are still well
over 150 000 structures to optimize in a complete conformational search. Given
this bottleneck, many different types of conformational searching algorithms have
been designed –ranging from fully stochastic methods to semi-systematic methods
and genetic algorithms. The semi-systematic algorithm energy-directed tree search
(EDTS) [38] was designed and benchmarked specifically for tackling this problem
for oligomeric polymerization reactions, including RAFT polymerization. The algo-
rithm reduces the scaling from 3n to 2n (where n is the number of rotatable bonds) in
the worst-case scenario, making it suitable for systems that are too big for complete
conformational searches but still small enough for chemically accurate electronic
structure calculations. Benchmarking on large systems (e.g. containing as many as
80 000 conformers) showed that the algorithm consistently found the global min-
imum, or a structure with an energy within 1 kcal mol−1 of it, with the calculation
of a manageable number of species (a few hundreds at most, usually less) [38].
The other key aspect to conformational searching is the choice of quantity upon
which to base the search. Early studies used the electronic energies from gas-phase
geometry optimizations [3]. However, follow-up studies of radical propagation kinet-
ics showed that this could give incorrect results in systems displaying intramolecular
non-covalent interactions such as hydrogen bonding [39]. On the one hand, such
interactions lead to lower electronic energies in the gas phase and hence searches
that are based on gas-phase electronic energies tend to find hydrogen-bonded con-
formations. However, these interactions also lead to lower entropy, which raises
the Gibbs free energies at relevant reaction temperatures. Moreover, the energetic
importance of hydrogen bonding is also reduced in solution compared with the gas
phase, and solvation also tends to favour non-hydrogen-bonded conformations. The
net effect of these two factors is that the lowest solution-phase Gibbs free energy
conformations tend to be more open and differ from the hydrogen-bonded confor-
mations obtained when electronic energies are used. Indeed, several studies have
shown that the inclusion of solvent effects is crucial in conformational searching
when non-covalent interactions such as hydrogen bonding are important [40, 41].
Methods for modelling solvent effects are discussed in Section 6.2.3.
In evaluating the rate coefficients, the method for identifying the transition
structure is also important. Standard geometry optimization algorithms identify the
transition structure as a first order saddle point in the potential energy surface, that
is, as the structure having the maximum internal energy (E) along the minimum
energy path. However, ideally the rate calculations should be performed using the
structure having the maximum Gibbs free energy (G). At non-zero temperatures,
E and G are non-equal and thus the geometries corresponding to their maximum
values are not necessarily equivalent. The corresponding methods for calculating
the rate coefficients are known as standard transition state theory and variational
transition state theory, respectively [31]. Variational transition state theory is more
accurate but also more expensive, as it entails the calculation of the energies and
partition functions not just at the transition structure but at several points along the
minimum energy path. In practice, for reactions with significant energy barriers, the
differences between transition state theory and variational transition state theory
are relatively minor, and the lower cost standard method can be used. However, for
barrierless reactions (and also for some low-barrier reactions), variational effects
can become important.
Radical addition to the sulfur atom of a C=S double bond is typically a fast
reaction, having a low or even negative barrier (ΔE‡ ) in most cases. The positive
Gibbs free energy barrier results from opposing enthalpic and entropic effects [6].
In other words, both ΔE and ΔH decrease along the reaction coordinate but −TΔS
increases and its opposing interaction leads to the maximum in ΔG. Under these
circumstances, one might have expected variational effects to be very important for
these systems. However, in an assessment study for the prototypical RAFT systems
R⋅ + S=C(Z)SCH3 (R = CH3 , CH2 Ph, CH2 COOCH3 , C(CH3 )2 CN; Z = CH3 , Ph,
CH2 Ph), it was found that provided the transition structures were corrected via
IRCmax, the use of variational transition state theory had little or no effect on the
reaction barriers [6]. The effects on the entropies and hence reaction rates were
somewhat larger (up to a factor of 16) in the case of the ⋅CH3 addition reactions,
but for the reaction of the substituted radicals (which are more indicative of real
polymerization systems), they remained relatively small (c. a factor of 2). Thus,
while variational transition state theory should always be used when possible for
6.2 Methodology 147
these systems, standard transition state theory may be adopted for large systems
without incurring significant additional error.
6.2.3 Solvent Effects

The methodology described thus far is designed to reproduce chemically accurate
values of the rate and equilibrium constants for gas-phase systems; however,
the majority of RAFT polymerizations occur in solution. The development of
cost-effective methods for treating the solvent in chemical reactions is an ongoing
area of research [42, 43]. The simplest and most computationally efficient methods
are continuum models, in which each solute molecule is embedded in a cavity
surrounded by a dielectric continuum of permittivity 𝜀 [43]. Some of the more
sophisticated continuum models, such as the ab initio conductor-like solvation
model (COSMO) [44] and the polarizable continuum model (PCM) [45], also
include terms for the non-electrostatic contributions of the solvent, such as dis-
persion, repulsion, and cavitation. Continuum models are designed to reproduce
bulk or macroscopic behaviour, and can fare extremely well in certain applications
such as the calculation of the solvation free energies [46], redox potentials [47],
and pK a values [48] of various organic molecules. However, the results obtained
using continuum models are highly sensitive to the choice of cavities (which are
typically parameterized to reproduce the free energies of solvation for a set of small
organic molecules), and the choice of appropriate cavities for weakly bound species
such as transition structures can be problematic [46]. Moreover, their accuracy can
suffer if there are explicit solute–solvent interactions such as complex formation
and hydrogen bonding [49]. Although this problem can be overcome by including
a small number of explicit solvent molecules in the ab initio calculation, as in a
cluster-continuum model [50], this adds significantly to the cost of the calculation.
Such explicit solute–solvent interactions might be expected to be particularly
important when studying aqueous-phase polymerizations of monomers capable of
undergoing strong hydrogen-bonding interactions (such as acrylic acid).
The impact of solvent effects on both the quantitative results and the qualitative
trends is clear in Figure 6.1, which compares the effect of chain length (n) on the
equilibrium constant (K; l mol−1 ) at 298.15 K for a model trithiocarbonate-mediated
polymerization of acrylamide and a model dithiobenzoate-mediated polymerization
of methyl methacrylate in the gas phase and bulk solution. [40] In both cases, but
particularly the acrylamide, the inclusion of solvent affects the trends and quantita-
tive results by as much as 7 orders of magnitude. Nonetheless, while this shows that
solvent effects are crucial, they can to a large extent be captured accurately with con-
tinuum solvation models, as evident in a range of benchmarking studies for small
molecule and polymeric systems [8, 51, 52].
6.2.4 Accuracy and Outstanding Challenges

Normally, one might establish the accuracy of ab initio calculations through compar-
ison with reliable experimental data. However, in the case of the RAFT process this
15 H3C
CH3 CH2
H2C Kn S S
S C
12 R CH2 CH + R CH2 CH
n C
S S n S H CH3
C C C
H2N O CH H2N O
H3C O C
C HO O
9
OH
log K (l mol–1)
HC CH3
R
6 O C
OH H 3C
R = C CN
3 H 3C
–3
–6
0 1 2 3
(a) n
16
14 CH3 CH3
H3C
CH3 H3C C CH3 CH3 C CH
S S Kn S S 3
12 R CH2 C C C
n + R CH2 C n
C C
O O O O
CH3 CH3
10
log K (l mol–1)
H 3C
R = C CH3
8
H 3C
2 H3C
R = C CN
H3C
0
0 1 2 3
(b) n
Figure 6.1 The effect of chain length (n) on the equilibrium constant (K; l mol−1 ) at
298.15 K for (a) a model trithiocarbonate-mediated polymerization of acrylamide and (b) a
model dithiobenzoate-mediated polymerization of methyl methacrylate. In each case, solid
lines are in bulk solution, dashed lines in the gas phase, circles indicate reactions where R
is the initiator fragment (i.e. C(CH3 )2 CN), and square points indicate reactions where R is the
leaving group of the RAFT agent (i.e. CH(CH3 )COOH and C(CH3 )3 and respectively) [40].
6.2 Methodology 149
is difficult as there is no model-free manner in which to measure experimentally

the rates and equilibrium constants of the individual addition–fragmentation pro-
cesses. Even if one makes the assumption that addition and fragmentation are chain
length independent beyond the dimer stage, a complete kinetic model would be
needed to contain in excess of 100 adjustable parameters (see Scheme 6.1 [53]). As
a result, various simplifications and approximations are made in obtaining experi-
mental measurements, and these are a potential source of error. Alternative exper-
imental measurements for ostensibly the same system can differ by several orders
of magnitude, and choosing the ‘correct’ experimental value for comparison with
the theoretical data is problematic. For example, although there is excellent agree-
ment between the calculated equilibrium constant of 4.2 × 106 l mol−1 (the originally
reported value of 7.3 × 106 l mol−1 [54] corrected to W1-theory) for cumyl dithioben-
zoate (CDB)-mediated polymerization of styrene at 303.15 K and the experimental
values (1.06 × 107 l mol−1 ) obtained from model-fitting to low-conversion kinetic
data [54], both the experimental and theoretical values are in conflict with those
estimated from electron paramagnetic resonance (EPR) data (8 × 101 l mol−1 ) albeit
under different polymerization conditions [55].
Nonetheless, there is greater consensus amongst the various experimental groups
with regard to measurements of the rate constant for addition to the RAFT agent, and
the values obtained thus far (c. 106 l mol−1 s−1 ) also appear to be relatively insensitive
to the nature of the dithioester and attacking radical (see for example Table 3.2 of
Chapter 3 of Ref. [56]). These experimental values are in excellent agreement with
the theoretical calculations for related small radicals; for example, the calculated
values for addition of R⋅ to S=C(CH3 )SCH3 are 1.2 × 106 and 3.8 × 106 l mol−1 s−1 for
the typical R groups C(CH3 )2 CN and CH(Ph)CH3 , although slightly faster values are
obtained (c. 107 –108 ) for more reactive small radical species (such as CH2 COOCH3
and CH(CH3 )OCOCH3 ) [3].
Support for the accuracy of the computational predictions was also pro-
vided in a kinetic modelling study of the initialization period in cyanoisopropyl
dithiobenzoate-mediated polymerization of styrene [57]. In this work, ab initio
predictions of the equilibrium constants for the first eight addition–fragmentation
reactions of the RAFT process were combined with reliable experimental values of
the rate coefficient for radical addition to the RAFT agent and the rate coefficients
for initiation, propagation, and termination in styrene homopolymerization. These
parameters were then used to predict, without any additional model fitting, the
overall monomer conversion and individual concentration profiles of the low
molecular weight thiocarbonyl compounds formed during the early stages of the
process. These ab initio predictions showed excellent agreement with previously
measured experimental data (obtained under the same reaction conditions used in
the kinetic simulation), despite the fact that no adjustable fit parameters were used
(see Figure 6.2 [57]). This work will be discussed in more detail in Section 6.3.4.
Other strategies have also been used for testing the accuracy of the theoretical
calculations. To begin with, we recall that the levels of theory have been selected on
the basis of assessment studies, and their accuracy established through comparison
with high levels of theory, which in turn have been benchmarked against gas-phase
S
[1] R· + ZC R S CS R
SR Z
+ S S S S
I· ZC R I + ZC [29]
[2] SR C R·
Z S I
S S
[3] I–M · + ZC R S CSM I R·
+ ZC I [30]
SR Z SM
S M S S
[4] I–M M· + ZC R C SM I R· + ZC M I [31]
SR Z SM
S S S R S
[5] R M· + ZC R C M R· + ZC R [32]
SR Z SM
S S
R M M· + ZC R C S M MR +
S
Z C MR [33]
[6] SR Z R·
SM
S M
–M M M· + ZC
S R CSM M S
[7] Z R· + Z C MM [34]
SR SM
S S S
[8] I· + ZC I C I
S I Z
+ S S S I S
I–M· ZC I C M I· + ZC I [35]
[9] S I Z SM
S S
I–M M· + ZC I S C SMM I I· + ZC M I [36]
[10] S I Z SM
S S
R M· + ZC I S C SMR + ZC R
[11] S I Z I· [37]
SM
M
R M M· + ZC
S I S C SM R +
S
Z C MR
[12] S I Z I· [38]
SM
M
ZC
S I S C SM M S
–M M M· + I· + Z C MM
[13] S I Z SM [39]
S I
I–M· + ZC I MS C M
S I
[14] SM Z
S I S
I–M M· + ZC I M S C S MM I I–M· + ZC M I [40]
[15] SM Z SM
S I S S R S
R M· + ZC I M C M + ZC R [41]
[16] SM Z I–M·
SM
I
+ ZC
S
I MS S M
C M R +
S
[17] R M M· I–M· Z C MR [42]
SM Z SM
S I M S C S MM M S
–M M M· + ZC I I–M· + Z C MM
[18] SM Z [43]
SM
+ S I MM S C S M M I
I–M M· ZC M I
[19] SM Z
S
M I I MM S C S M R S
R M· + ZC I–M M· + ZC R [44]
[20] SM Z SM
S I MM S C S MM R S
R M M· + ZC M I I–M M· + Z C MR [45]
[21] SM Z SM
S M S S MM S
ZC M I I M C M
[22] –M M M· + Z I–M M· + Z C MM [46]
SM SM
S R S R S
[23] R M· + ZC R M C M
SM Z
S R S S M S
R M M· + ZC R M C M R + Z C MR [47]
[24] R M·
SM Z SM
S R M S C S M MM S
[25] –M M M· + ZC R R M· + Z C MM
SM Z SM [48]
S R MM S C S M M R
[26] R M M· + ZC MR
SM Z
S M S S M S
ZC MR R M C M M
[27] –M M M· + Z R M M· + Z C MM [49]
SM SM
S M S S M
–M M M· + Z C MM M M C M M
[28] Z
SM
Scheme 6.1 Set of addition–fragmentation reactions to be included in a complete RAFT

reaction scheme if chain length effects extend to the trimer stage [53].
6.2 Methodology 151
0.8
IRAFT
IMRAFT
0.7 IMMRAFT experiment
0.6
Concentration (mol l–1)
0.5
0.4
Ab initio predictions
0.3
0.2
0.1
0.0
0 5 000 10 000 15 000 20 000
Time (s)
Figure 6.2 Experimental (McCleary et al. [58], symbols) and simulated (Coote et al. [57],
lines) evolutions of the initial RAFT agent (cyanoisopropyl dithiobenzoate, IRAFT, full line),
and the RAFT agents having one monomer unit (IMRAFT, dashed line) and two monomer
units (IMMRAFT, dotted line) inserted. The concentrations of the reagents were
C 0 IRAFT = 0.736 mol l−1 , C 0 AIBN = 0.10 mol l−1 , C 0 Styrene = 3.65 mol l−1 , and C 0 C6D6 = 5.4 mol l−1
and the temperature was 70 ∘ C.
thermochemical data [4–6]. On the basis of these assessment studies, it is concluded

that the selected procedures can model the absolute barriers and enthalpies for
radical addition C=S double bonds to within approximately 4 kJ mol−1 . It is also pos-
sible to benchmark the calculations against (relatively model-free) solution-phase
experimental data for related small systems. For example, Scaiano and Ingold
[59] have studied the addition of tert-butyl radicals to di-tert-butyl thioketone via
laser flash photolysis, obtaining an equilibrium constant of 1.2 × 106 l mol−1 at
25 ∘ C. This is in very good agreement with the corresponding theoretical value
(7.9 × 105 l mol−1 ) [60], the latter being slightly lower due to the neglect of the
solvent in the calculations. Moreover, more recent benchmarking studies in which
the solvent is taken into account do reproduce the experiment very well for addition
reactions to dithioesters [8, 51, 52].
The computational methodology can also be benchmarked against experimental
data for polymeric systems for the case of the propagation rate coefficients. Although
not chemically identical to an addition–fragmentation reaction, a propagation reac-
tion is still a radical addition reaction and has the advantage that reliable experi-
mental data can be obtained using pulsed laser polymerization (PLP) [61]. A com-
putational study of the propagation of vinyl chloride and acrylonitrile yielded values
within a factor of 2 of the experimental polymeric values, and demonstrated that the
rate coefficient for the polymeric propagating species was adequately modelled using
the corresponding rate coefficient for the dimer [19]. Further studies of a wider range
of monomers are currently underway, but it does seem that ‘chemical accuracy’ is
now attainable.
Despite this success, a number of challenges remain. In particular, as noted above,

the treatment of solvent effects is not yet satisfactory, and larger errors might be
expected for solvent-sensitive systems such as acrylic acids. It should also be stressed
that the above methodology is not suitable for studying the diffusion-controlled ter-
mination processes. In principle, one could calculate the chemically controlled com-
ponent of the termination reaction using computational chemistry, and this could
be extremely helpful in some situations. For example, there is currently a debate
about whether the RAFT-adduct radical is capable of undergoing termination [54,
55, 62–70]; establishing whether the chemically controlled component is fast or slow
would be an important contribution to this debate. However, the above methodol-
ogy, which makes use of methods with single-reference wavefunctions, is not likely
to be suitable for studying the transition structure of a radical–radical process. Unfor-
tunately, multireference methods are considerably more computationally intensive
and further work is needed to identify reliable low-cost alternatives for such systems.
Even in the case of the addition–fragmentation reaction, the computational
cost of the calculations remains an issue. Although the ONIOM-based approach
facilitates the calculation of accurate energetics for relatively large systems,
other computational bottlenecks are now emerging. Larger systems (such as the
reactions of dimer radicals with RAFT agents) have a high degree of confor-
mational complexity, and finding the minimum energy conformations of these
species can be computationally very demanding. We currently identify these
via a complete conformational search; that is, we optimize geometries for every
(non-unique) conformation about every bond (or forming bond) in the molecule
(or transition structure). For example, in a relatively simple species such as
(CH3 )2 C(Ph)–CH2 –CH(Ph)–S–C⋅(Ph)–S–C(CH3 )2 Ph, we might need to consider
324 possible conformations. Inserting just one extra styryl unit increases the number
of possible conformers to 2916 and the calculations rapidly become impractical. To
address this problem, as noted above we have developed a more efficient algorithm
for exploring conformational space called the Energy-Directed Tree Search [38].
Preliminary indications are that it is possible to find the global minimum reliably
at a cost of approximately 10% of a full search for typical RAFT systems, but further
savings would be desirable. A related computational bottleneck stems from the
need to treat the low-frequency torsional modes as hindered internal rotations. As
explained above, this entails the calculation of full rotational potentials (typically
36 geometry optimizations) for each mode considered. This too can rapidly become
computationally infeasible, and strategies for reducing this computational expense
are currently being investigated. Nonetheless, despite these problems, it is now
possible to perform accurate calculations on systems that are large enough (c. 30–40
non-hydrogen atoms) to be of relevance to practical polymerization systems.
6.3 Computational Modelling of RAFT Kinetics

One of the main advantages of a computational approach to studying RAFT poly-
merization kinetics is the ability to determine the rate and equilibrium constants of
individual reactions directly, without having to fit a kinetic model to data. This is
particularly useful for complex processes such as RAFT because the kinetic models
for these processes potentially can contain more adjustable parameters than can
practically be estimated from the available experimental data. For example, as
noted above, even if we make the assumption that the addition–fragmentation equi-
librium becomes chain length independent beyond the dimer stage, a ‘complete’
kinetic model for the process would need to contain 49 addition rate coefficients
and 49 fragmentation rate coefficients (see Scheme 6.1 [53]), in addition to various
re-initiation rate coefficients, and the usual initiation, propagation, termination,
and transfer coefficients. Since this is impractical, experimental studies typically
make simplifying assumptions – such as replacing all 98 rate coefficients by just 2 or
4 – and these assumptions are a potential source of error. In particular, such simpli-
fications are likely to affect the description of subtle yet important effects such as the
concentration profiles of the various species during the early stages of the process
[58, 71].
Computational chemistry can assist the kinetic modelling of RAFT in a number
of ways. Firstly, it is possible to study the effects of chain length and other remote
substituents on the addition–fragmentation equilibria. This information can be
used to identify which simplifying assumptions are justifiable in a kinetic model,
and thereby assist experimental studies. The same information can also be used to
assist the computational studies by identifying which remote substituents can be
replaced with smaller groups without affecting the calculated results. Secondly, it is
possible to use computational chemistry to establish whether side reactions (such as
alternative fragmentation pathways) are likely to be operative in particular systems,
and thus whether they need to be taken into account in the kinetic modelling
schemes. Finally, it is possible to calculate the rate and equilibrium constants for
many of the early reactions in the RAFT process, and thereby help minimize the
number of adjustable parameters that need to be measured experimentally. Indeed,
provided suitable small models for the polymeric reactions can be designed, it is
possible in principle to calculate all chemically controlled rate coefficients for a
RAFT process, so as to evaluate the performance of new RAFT agents prior to
experimental studies.1 These aspects are now examined in turn.
6.3.1 Simplified Models for Theory and Experiment

Both theoretical and experimental studies of radical polymerization processes
rely heavily on the fact that in a chemically controlled reaction, the effects of
substituents diminish rapidly with their distance from the reaction centre. From
an experimental perspective, it allows one to treat the reactions of species differing
only in their remote substituents as identical, thereby reducing the number of
adjustable parameters in kinetic models. From a theoretical perspective, it allows
one to replace these unimportant remote substituents with smaller chemical groups,
1 One would need to use experimental data for the diffusion controlled termination rate
coefficients but these could be obtained from a single homopolymerization polymerization of the
specified monomer in the absence of RAFT agent.
thereby reducing the computational cost of the calculations. For example, in free
radical copolymerization, the reactivity of the propagating radical is determined
solely by the nature of its terminal and penultimate units, and is independent of
the chemical composition of the remainder of the polymer chain [72]. As a result,
kinetic models for copolymerization need only to consider the propagation reactions
of four types of propagating radicals instead of thousands, while computational
studies can determine the radical and monomer reactivity ratios using dimers
as chemical models of the propagating species. This has been confirmed in both
experimental [73, 74] and theoretical [19] studies of the homopropagation rate
coefficients, which indicate that the rate coefficients have largely converged to their
long chain limit at the dimer radical stage and completely converged well before
the decamer stage.
In the RAFT process, there are two key areas where simplifications to kinetic
and theoretical studies are desirable. In the generic addition–fragmentation process
R⋅ + S=C(Z)SR′ , it is important to discover whether the kinetics and thermodynam-
ics are affected by the nature of the ‘attacking group’ (R⋅) and the ‘non-participating
group’ (R′ ) and, if so, at what point the remote substituent effects become negligible.
Recent experimental [1, 75, 76] and theoretical [6, 7, 24, 53, 77, 78] studies of the
effects of substituents on the RAFT process indicate that the kinetics and thermo-
dynamics are extremely sensitive to the nature of the attacking radical and the Z
group of the RAFT agent (S=C(Z)SR′ ). For example, the equilibrium constant (at
333.15 K) for ⋅CH3 addition to S=C(CH3 )SCH3 increases by approximately 6 orders
of magnitude when the CH3 Z group is replaced with a phenyl substituent, and
decreases by 7 orders of magnitude when the methyl attacking group is replaced
with the initiating radical derived from 2,2′ -azobis(isobutyronitrile) (AIBN),
⋅C(CH3 )2 CN [7]. It is therefore essential that reactions differing in the nature
of their Z groups and/or the primary substituents of their R groups are treated
as being kinetically distinct. The influence of the R′ is less significant and some
simplifications are possible. For example, the calculated equilibrium constants
for ⋅CH3 addition to S = C(CH3 )SR′ for R′ = CH2 X, CH(CH3 )X, and C(CH3 )2 X
and X = H, CH3 , CN, Ph, COOCH3 , OCOCH3 range over 3 orders of magnitude
(see Table 6.1) [53]. However, this effect is mainly steric in origin, with the bulky
R′ -groups destabilizing the thiocarbonyl compound to a greater extent than the
more flexible RAFT-adduct radical. As a result, the K values for individual classes of
monosubstituted, disubstituted, and trisubstituted R′ groups fall into much smaller
ranges and, depending on the nature of the monomer and initial R′ group, it may
be possible to ignore the effect of R′ in some kinetic models.
Given that the R, Z and, to some extent, the R′ groups all affect the addition–
fragmentation equilibrium, it is not surprising that the addition–fragmentation
equilibrium is also affected by the chain length of the R and R′ groups. Figure 6.1
above shows the effects of chain length (n) on the equilibrium constant (K; l mol−1 )
at 298.15 K for a model trithiocarbonate-mediated polymerization of acrylamide
and a model dithiobenzoate-mediated polymerization of methyl methacrylate [40].
Figure 6.3 below shows the effects of chain length (n) on the equilibrium constants
for addition of styryl radicals of varying chain lengths, (NC)C(CH3 )2 –(CH2 CHPh)n ⋅
Table 6.1 Effect of R′ on the calculated enthalpies (ΔH), entropies (ΔS), and equilibrium
constants (K)a) at 333.15 K for the model RAFT reaction,
⋅CH3 + S=C(CH3 )SR′ → CH3 SC⋅(CH3 )SR′ .
X R′ = CH2 X R′ = CH(CH3 )X R′ = C(CH3 )2 X

−𝚫H −𝚫S K −𝚫H −𝚫S K −𝚫H −𝚫S K
H 76.0 149.0 3.8 × 107

CH3 79.9 138.6 1.8 × 107 81.8 146.2 1.7 × 107 94.3 145.3 1.7 × 109
8 8
CN 92.9 161.5 1.8 × 10 93.2 163.2 1.5 × 10 102.4 146.4 2.9 × 1010
7 8
Ph 87.8 166.4 1.5 × 10 89.9 151.0 1.8 × 10 104.5 153.3 2.9 × 1010
COOCH3 90.0 168.1 3.3 × 107 97.1 175.4 1.8 × 108 97.5 158.6 1.4 × 109
7 9
OCOCH3 92.0 166.3 8.1 × 10 99.5 167.2 1.1 × 10 106.3 153.1 6.1 × 1010
a) ΔH (kJ mol−1 ), ΔS (J mol−1 K−1 ) and K (l mol−1 ). The original data reported in Ref. [53] was
re-calculated at the W1-ONIOM//B3-LYP/6-31G(d) level of theory in conjunction with the
harmonic oscillator approximation and taken from Ref. [3].
1.00E + 15
1.00E + 12
1.00E + 09
K
1.00E + 06
1.00E + 03
1.00E + 00
0 1 2 3 4
n
Figure 6.3 The effect of chain length (n) on the equilibrium constant (K; l mol−1 ) at
333.15 K for the addition of (NC)C(CH3 )2 –(CH2 CHPh)n ⋅ to S=C(Ph)SCH3 (○) and addition of
CH3 ⋅ to S=C(Ph)S—(CH(Ph)CH2 )n —C(CH3 )2 CN (●) [3].
(n = 0, 1, 2, 3), to S=C(Ph)SCH3 , and the addition of ⋅CH3 radicals to the

corresponding macroRAFT agents, S=C(Ph)S–(CHPhCH2 )n –C(CH3 )2 CN [53].
From Figures 6.1 and 6.3 it is clear that chain length effects in the early stages
of the RAFT process, and chain length effects on the attacking radical R⋅ (in
R⋅ + S=C(Z)SR′ ) are significant and variable. In general, however, they appear to
have converged by the n = 3 trimer species. In the case of the RAFT agent sub-
stituent R′ chain length effects appear to be much less significant and converge after
n = 1. In other words, in the early stages of the reaction, chain length effects in the
attacking radical, and to a lesser extent the RAFT agent substituent, are significant
and neglecting them leads a serious over-simplification of the initialization kinetics.
Based on the currently available computational results, it seems reasonable to
suppose that reactions of the various primary species (R⋅ and I⋅), unimeric radicals
(I–M⋅ and R–M⋅), dimeric radicals (R–M–M⋅ and I–M–M⋅), and the remaining
longer chain species do need to be treated as being kinetically distinct.
Beyond the trimer, chain length effects on the reaction energies appear to have
converged; however, entropic chain length effects cannot be ruled out. Such chain
length effects are known to converge rapidly in reactions such as propagation,
which involve a polymeric species adding to a small molecule to produce a poly-
meric species of similar size. However, RAFT reactions can involve a polymeric
species adding to a polymeric RAFT agent to produce a species that is significantly
larger than either. In those situations, entropic effects converge much more slowly
and this could account for the few orders of magnitude discrepancy between
small-molecule RAFT equilibrium constants (by theory or experiment) [79] and the
corresponding experimental equilibrium constants for the addition of polymeric
species to polymeric RAFT constants [80]. Regardless, a ‘complete’ kinetic model
of the addition–fragmentation kinetics would thus resemble at least that provided
in Scheme 6.1, and would contain far too many unknown parameters for fitting to
experimental data alone. As will be seen below, computational chemistry offers the
prospect of reducing the number of unknown parameters by providing direct cal-
culations of the relevant values for the early small-molecule reactions of the RAFT
process, leaving the estimation of a smaller number of parameters corresponding to
the longer chain radicals to experiment.
6.3.2 Side Reactions

In designing an appropriate kinetic model for RAFT polymerization, it is also nec-
essary to determine whether additional side reactions need to be incorporated into
the kinetic scheme. In principle, one could use computational chemistry to find all
possible side reactions of a process from first principles. However, this would entail
the calculation of a complete multi-dimensional potential energy surface for the
chemical system, followed by molecular dynamics simulations for a wide variety
of possible trajectories. Unfortunately, this is currently too computationally inten-
sive for practical RAFT systems. However, it is possible to study specific postulated
side reactions and test whether they are likely to occur. For example, if hydrogen
abstraction reactions involving the RAFT-adduct radical were suspected to be a prob-
lem in certain polymerization systems, one could calculate rate coefficients for the
various possible reactions (i.e. abstraction of the different hydrogen atoms on the
monomer, polymer, RAFT agent, and so forth). By comparing their rates with the
normal β-scission reaction, one could thereby establish which (if any) of the possible
abstraction reactions were likely to be competitive.
For example, computational chemistry was used to show that competitive
β-scission of the C—O bond of the alkoxy group in xanthate-mediated polymer-
ization of vinyl acetate was important [81]. Rate coefficients (333.15 K) for both
the normal β-scission of the vinyl acetate radical and the side reaction were
calculated for a series of model RAFT-adduct radicals, CH3 SC⋅(OZ′ )SCH2 OCOCH3
for Z′ = Me, Et, i-Pr, and t-Bu (see Scheme 6.2) [3]. It was shown that for the
Z′ = Me, Et, and i-Pr systems, the normal β-scission reaction is favoured and this
is consistent with the experimental observation that these systems display normal
RAFT behaviour. In contrast, for the t-Bu case, the side reaction is preferred, and
this provided a suitable explanation for the experimentally observed inhibition in
this system. In general, it would be worth considering this side reaction when the
Z′ substituent of the xanthate is a good radical leaving group (such as t-Bu) and/or
the propagating radical is a poor leaving group (as in vinyl acetate or ethylene
polymerization).
CH3
S S Normal
H3C C CH2OCOCH3 β-scission S S
C + CH2OCOCH3
O
Z′ O
Z′
Alkoxy Z′ kβ Alkoxy kβ Normal Ratio

β-scission CH3
S O Me 3.2 × 104 2.3 × 105 1.4 × 10–1
C + Z′
Et 3.5 1.7 ×105 1.2 × 10–5
S i-Pr 1.6 × 102 6.8 × 102 2.4 × 10–1
CH2OCOCH3
t-Bu 2.1 × 105 1.7 × 102 1.2 × 103
Scheme 6.2 Competitive β-scission processes in xanthate-mediated polymerization of

vinyl acetate [3].
Other side reactions might also be conceivable under certain circumstances,

although their feasibility is yet to be confirmed computationally. As noted above,
there is some debate as to whether the RAFT-adduct radical is capable of under-
going irreversible and/or reversible termination reactions (see Scheme 6.3) to
any significant extent in normal polymerizing RAFT systems [54, 55, 62–70, 82].
Recently Buback and coworkers used DFT calculations to study the thermodynam-
ics of several of these steps, showing that they are thermodynamically feasible [82].
However, calculations of the corresponding rate coefficients would be required to
identify which, if any, of the reactions in Scheme 6.3 are capable of out-competing
the β-scission reaction of the intermediate radical under normal polymerization
conditions. Although computational quantum chemistry is not currently capable
of predicting diffusion-controlled rate coefficients, computational calculations
could nonetheless be used to calculate the chemically controlled component of the
termination rate and establish a lower bound to the termination rate coefficient.
To this end, work is currently underway to identify cost-effective multireference
methods for studying such systems.
Another side reaction that is worth considering is the attack of the propagating
radical at the carbon centre (rather than the sulfur centre) of the C=S bond to
produce a sulfur-centred radical. Studies of radical addition to simple thiocarbonyl
compounds indicate that this side reaction is actually thermodynamically preferred,
though it is kinetically less favourable by 1–2 orders of magnitude [4, 83]. This is
Z
S S
2
S S (a)
Z S S
Z
S S
Z (b)
S S
+
Z
S S
+ (c)
Z
S S
S S S S S S
2
(d)
S S
S S
S S
S S
S S
(e)
S S
Scheme 6.3 Possible reversible and irreversible termination reactions of the RAFT-adduct radical.
due in part to the greater steric hindrance at the carbon centre and in part to
the stronger early bonding interaction when attack occurs at sulfur (see below)
[83]. In RAFT systems, the steric hindrance at the carbon centre is yet greater,
and the kinetic preference for addition at carbon should normally be very small.
Nonetheless, given that addition to the RAFT agent occurs many thousands of times
during the lifetime of the propagating radical, even a low relative rate of addition at
carbon might be sufficient to affect the polymerization kinetics in certain systems.
Other side reactions that have been suggested include reaction of the RAFT-adduct
radical with the monomer (i.e. copolymerization), the syn-elimination of tertiary
R-groups (as the corresponding alkenes) at elevated temperatures, and reactions
with oxygen impurities [1, 84]. Computational studies of these and other pathways
could help establish their feasibility and clarify their mechanism. Finally, while it is
unlikely in the context of normal RAFT conditions, decomposition of RAFT-based
polymers has also been studied both experimentally and computationally [85, 86].
6.3.3 Computational Model Predictions

Provided calculations are performed at an appropriately high level of theory, compu-
tational chemistry can be used to determine the rates and equilibrium constants for
the individual reactions in a RAFT polymerization. The resulting values can then be
used to study structure–reactivity trends, reduce the number of adjustable param-
eters in a kinetic analysis of experimental data, or, ultimately, predict the kinetic
behaviour of a RAFT polymerization system from first principles. Table 6.2 shows a
compilation of the main equilibrium constants that have been reported to date [3].
Owing to their greater computational expense, the reaction rates for RAFT systems
have been less widely studied. However, the rate coefficients have been reported for
a number of small model systems and these are provided in Table 6.3 [3]. Owing to
the significant errors that occur at low levels of theory, only high-level ab initio val-
ues are included in these tables. However, where possible, the original calculations
were improved to the W1-ONIOM level of theory and re-calculated at a consistent
temperature (333.15 K) [3]. Values obtained under the harmonic oscillator approxi-
mation are reported for all systems and where possible the more accurate hindered
rotor values are also reported.
The data confirm that the equilibrium constants (and thus the addition–
fragmentation kinetics) are dependent upon the nature of the attacking radical
and the RAFT agent. In a practical RAFT system it is not valid to treat all of the
possible reactions as having the same rates. Thus, for example, when calculated at
a uniform level of theory, the equilibrium constant for addition of a styryl radical
to RAFT agents of the form S=C(Ph)SCH(CH3 )2 vary from 2.9 × 105 to 3.6 × 109 ,
depending on whether styryl is modelled as a unimer with an H end-group, a
C(CH3 )2 CN end-group, a C(CH3 )2 Ph end-group, or as a dimer with an H end-group.
This explains why simplified models do not appear to be capable of describing
the initialization period in RAFT systems; indeed, as will be shown below, once
these effects are taken into account excellent agreement between the experimental
data and model predictions is obtained [57, 91]. Chain length effects may also
Table 6.2 Effect of R, Z, and R′ on the calculated equilibrium constants (K)a) at 333.15 K for the model RAFT reaction, ⋅R + S=C(Z)SR′ → RSC⋅(Z)SR′ .
R⋅ K(HO) K(HR) R⋅ K(HO) K(HR)
CH(CH3 )CN Z = CH3 2.9 × 100 CH2 COOCH3 Z = CH3 6.0 × 103 6.7 × 104
R′ = CH3 R′ = CH3
C(CH3 )2 CN (AIBN) Z = CH3 1.2 × 10−1 9.6 × 10−1 Z = Ph 4.1 × 107
R′ = CH3 R′ = CH3
Z = Ph 1.5 × 103 2.6 × 104 Z = CH2 Ph 1.1 × 104
R′ = CH3 ′
R = CH3
Z = CH2 Ph 1.3 × 100 Z = CH3 8.6 × 104
R′ = CH3 R′ = CH2 COOCH3
Z = Ph 1.1 × 105 7.4 × 104 Z=F 2.1 × 101
R′ = CH(CH3 )2 R′ = CH3
Z=F 9.4 × 10−4 CH(CH3 )COOCH3 Z = CH3 3.5 × 102
R′ = CH3 (MA) R′ = CH3
Z = CN 1.4 × 107 Z = CH3 1.5 × 103
R′ = CH3 R′ = CH2 CN
Z = OCH3 3.8 × 10−6 Z = Ph 1.0 × 106 5.6 × 106
′
R = CH3 R′ = CH3
Z = Ph 1.1 × 105 Z = Ph 5.9 × 106 3.6 × 107
R′ = C(CH3 )2 CN R′ = CH(CH3 )2
CH2 CH3 Z = CH3 1.8 × 106 C(CH3 )2 COOCH3 Z = CH3 4.3 × 100
R′ = CH3 R′ = CH3
CH(CH3 )2 Z = CH3 4.7 × 105 CH2 OCOCH3 Z = CH3 1.3 × 106
R′ = CH3 R′ = CH3
C(CH3 )3 Z = CH3 1.5 × 105 Z=F 2.3 × 103
R′ = CH3 R′ = CH3
Z=F 4.1 × 103 Z = CN 4.5 × 1014
R′ = CH3 R′ = CH3
CH2 Ph Z = CH3 2.7 × 100 2.8 × 102 Z = OCH3 5.6 × 100
′ ′
R = CH3 R = CH3
Z = Ph 2.8 × 105 Z = OCH2 CH3 1.7 × 101
R′ = CH3 R′ = CH3
Z = CH2 Ph 4.1 × 101 Z = OCH(CH3 )2 7.8 × 101
R′ = CH3 R′ = CH3
Z=F 2.9 × 10−3 Z = OC(CH3 )3 3.7 × 102
R′ = CH3 ′
R = CH3
Z = CN 1.5 × 109 CH(CH3 )OCOCH3 Z = CH3 9.6 × 105 5.0 × 107
R′ = CH3 (VA) R′ = CH3
Z = OCH3 5.3 × 10−5 Z = OCH3 1.3 × 100 1.5 × 101
R′ = CH3 R′ = CH3
CH(CH3 )Ph (STY) Z = CH3 1.1 × 100 5.1 × 101 Z=F 2.0 × 103 3.4 × 104
′
R = CH3 R′ = CH3
Z = Ph 1.5 × 105 3.4 × 106 C(CH3 )2 OCOCH3 Z = CH3 6.6 × 104
R′ = CH3 R′ = CH3
Z = Ph 2.9 × 105 6.6 × 105 CH(CH3 )COOH Z = CH3 2.0 × 101
R′ = CH(CH3 )2 (AA) R′ = CH3
Z = Ph 6.5 × 107 Z=F 2.1 × 10−1 1.9 × 100
R′ = C(CH3 )2 CN R′ = CH3
Z=F 1.0 × 10−3 8.8 × 10−3 Z = N-Pyrrole 1.2 × 102
R′ = CH3 R′ = CH3
(continued)
R⋅ K(HO) K(HR) R⋅ K(HO) K(HR)
Z = OCH3 1.1 × 10−5 1.8 × 10−4 CH(CH3 )CONH2 Z = CH3 8.0 × 102
R′ = CH3 (AM) R′ = CH3
C(CH3 )2 Ph (Cumyl) Z = CH3 6.9 × 10−2 Z=F 1.2 × 100 7.9 × 100
R′ = CH3 R′ = CH3
Z = Ph 2.4 × 103 4.6 × 104 Z = N-Pyrrole 4.1 × 103
R′ = CH3 R′ = CH3
Z = Ph 1.3 × 105 2.5 × 105 AIBN-STY Z = Ph 1.1 × 105
R′ = CH(CH3 )2 R′ = CH3
Cumyl-STY Z = Ph 1.3 × 107 Z = Ph 1.2 × 106
R′ = CH3 R′ = CH(CH3 )2
Z = Ph 8.7 × 107 Z = Ph 2.3 × 109
R′ = CH(CH3 )2 R′ = C(CH3 )2 CN
Cumyl-STY-STY Z = Ph 2.8 × 108 AIBN-STY-STY Z = Ph 7.4 × 107
R′ = CH3 R′ = CH3
STY-STY Z = Ph 2.2 × 108 Z = Ph 1.8 × 1011
R′ = CH3 R′ = C(CH3 )2 CN
Z = Ph 3.6 × 109 STY-STY-STY Z = Ph 2.5 × 108
R′ = CH(CH3 )2 R′ = CH3
a) Equilibrium constants K (l mol−1 ) calculated at the W1-ONIOM//B3-LYP/6-31G(d) level of theory in conjunction with the harmonic oscillator (HO)
approximation and, where data were available, also the hindered rotor (HR) model. The original electronic structure data were taken from previous studies
[5, 7, 24, 53, 54, 78, 81, 87–89] and corrected to the W1-ONIOM level in Ref. [3] using W1 calculations [4] for the core reaction. For most systems, a two-layer
ONIOM approach was possible in which the inner core was calculated at W1 and the rest of the system at G3(MP2)-RAD. For a limited number of larger systems
(such as reactions in which Z = Ph and reactions of dimer radicals with various substrates), a three-layer ONIOM approach was used in which the outer layer was
calculated at RMP2/6-311+G(3df,2p).
Table 6.3 Calculated addition (k add ), fragmentation (k frag ), and equilibrium (K) constantsa) at 333.15 K for the Model RAFT reaction,
⋅R + S=C(Z)SCH3 → RSC⋅(Z)SCH3 .
R⋅ Z k add (HO) k add (HR) k frag (HO) k frag (HO) K (HO) K (HR)
CH3 CH3 9.6 × 105 1.7 × 106 9.6 × 10−2 3.4 × 10−2 1.0 × 107 4.9 × 107
Ph 4.2 × 107 7.7 × 107 2.5 × 10−4 7.2 × 10−6 1.7 × 1011 1.1 × 1013
CH2 Ph 2.6 × 106 1.2 × 107 1.4 × 10−2 1.7 × 10−3 1.9 × 108 7.3 × 109
OCH3 1.2 × 104 1.4 × 103 8.2 × 100
OCH2 CH3 3.1 × 104 8.2 × 102 3.8 × 101
OCH(CH3 )2 3.4 × 104 5.6 × 102 6.1 × 101
OC(CH3 )3 3.2 × 104 1.8 × 102 1.8 × 102
5 6 5 4
CH2 Ph CH3 6.6 × 10 3.9 × 10 1.2 × 10 1.4 × 10 5.6 × 100 2.8 × 102
CH(CH3 )Ph CH3 7.5 × 105 3.8 × 106 6.8 × 105 7.5 × 104 1.1 × 100 5.1 × 101
F 2.3 × 105 1.8 × 106 2.3 × 108 2.1 × 108 1.0 × 10−3 8.8 × 10−3
OCH3 6.2 × 103 4.4 × 104 5.8 × 108 2.5 × 108 1.1 × 10−5 1.8 × 10−4
7 8 4 3 3
CH2 COOCH3 CH3 5.7 × 10 1.7 × 10 1.1 × 10 2.5 × 10 5.2 × 10 6.8 × 104
C(CH3 )2 CN CH3 4.5 × 105 1.2 × 106 3.7 × 106 1.2 × 106 1.2 × 10−1 9.6 × 10−1
CH2 OCOCH3 OCH3 1.3 × 106 2.3 × 105 5.6 × 100
OCH2 CH3 2.8 × 106 1.7 × 105 1.7 × 101
OCH(CH3 )2 5.2 × 104 6.8 × 102 7.8 × 101
OC(CH3 )3 6.2 × 104 1.7 × 102 3.7 × 102
CH(CH3 )OCOCH3 CH3 6.3 × 107 4.2 × 108 6.7 × 101 8.4 × 100 9.6 × 105 5.0 × 107
8 8 4 4 3
F 1.5 × 10 5.6 × 10 7.5 × 10 1.7 × 10 2.0 × 10 3.4 × 104
OCH3 3.9 × 106 5.0 × 107 3.0 × 106 3.3 × 106 1.3 × 100 1.5 × 101
−1 −1 −1 −1
a) Rate coefficients for addition (l mol s ) and fragmentation (s ) and equilibrium constants (l mol ) calculated at the W1-ONIOM//B3-LYP/6-31G(d) level of
theory in conjunction with the harmonic oscillator approximation (HO) and, where data were available, also the hindered rotor model (HR). The original
electronic structure data were taken from previous studies [6, 81, 89, 90] and corrected to the W1-ONIOM level in Ref. [58] using W1 calculations [4] for the core
reaction. Reactions of ⋅CH3 radical and ⋅CH2 OCOCH3 radical with the xanthates were studied via standard transition state theory; all other reactions were
studied via variational transition state theory.
help explain the large discrepancies in the experimental values for the rates and
equilibrium constants in CDB-mediated polymerization that are obtained by fitting
simplified models to experimental data, though it seems likely that additional
factors (such as missing side reactions) may be required to resolve the problem
fully [80].
Secondly, although the equilibrium constants vary considerably, this variability
arises mainly in the fragmentation reaction. For most substituents, the addition rate
coefficients fall into a relatively narrow range (105 –107 l mol−1 s−1 ). In these cases,
it may be reasonable to treat all (or most) of the possible addition reactions in a spe-
cific process as having the same rate coefficients, provided the rates of their reverse
fragmentation reactions are allowed to vary. However, there are a few important
exceptions. In particular, the addition of propagating radicals to xanthates is typi-
cally much slower than to dithioesters (Z = alkyl, aryl) unless the propagating radical
is highly reactive (as in vinyl acetate polymerization). As a result of their slow addi-
tion rate, monomers with stable propagating radicals (such as styrene) are not nor-
mally well controlled by xanthates. Moreover, within the xanthate reactions them-
selves, there is a large variation in the addition rate coefficient depending on whether
the propagating radical is capable of undergoing H-bonding interactions with the
alkoxy group of xanthate in the transition structure (see Section 6.4.1). Indeed, this
H-bonding interaction may be partially responsible for the success of xanthates in
controlling vinyl acetate. In this regard, it is worth noting that the xanthates have
been less successful in controlling ethylene polymerization, another system in which
the propagating radical is relatively unstable but for which the H-bonding interac-
tion is absent. From Table 6.3, it is seen that even for the methyl radical, which might
reasonably be expected to be more reactive than the ethyl propagating species, the
addition rate coefficient for the xanthate agent is relatively low (c. 104 l mol−1 s−1 ).
Finally, the data indicate that slow fragmentation of the RAFT-adduct radi-
cal can help explain the experimentally observed inhibition periods in cumyl
dithiobenzoate-mediated polymerizations [54]. Kinetic studies indicate that rate
retardation is likely to be significant when K is greater than or equal to approxi-
mately 106 l mol−1 [92]. The equilibrium constants for addition of unimers of methyl
acrylate (3.6 × 107 ) and dimers (3.6 × 109 ) of styrene satisfy this condition, while
that for addition of cumyl (2.5 × 105 ) and the styrene unimer (6.6 × 105 ) lie within
the level of possible error. In contrast, fragmentation of ⋅C(CH3 )2 CN from the
RAFT-adduct radical is not predicted to be retarded (7.4 × 104 ), consistent with the
experimental observation [93] that cyanoisopropyl dithiobenzoate does not display
a significant inhibition period. On the basis of Table 6.2, other retarded processes
would include the fragmentation reactions of the RAFT-adduct radicals bearing a
cyano Z group, and the fragmentation of ethyl radicals and vinyl acetate radicals
from the adduct radicals of dithioesters. Table 6.2 also correctly predicts that in
the case of vinyl acetate this rate retardation is relieved when xanthates are used
instead. They also indicate that similar success is likely with fluorodithioformates
(Z = F), the new computationally designed class of RAFT agents [87]. In this way,
such simple calculations can be used to evaluate quickly whether a polymerization
is likely to be successful.
6.3.4 Ab initio Kinetic Modelling

It is clear from both computational and experimental studies of RAFT kinetics
that simplified kinetic models in which side reactions and chain length effects are
ignored are not capable of providing an adequate description of all aspects of the
RAFT process [80]. However, kinetic models in which these effects are properly
taken into account would contain too many unknown adjustable parameters
for fitting to experimental data. As noted above, computational chemistry offers
a potential solution to this problem by allowing for the rates and equilibrium
constants of the individual steps to be calculated independently. The calculated
values could be used to reduce the number of fit parameters in the kinetic model
to more manageable levels or, ultimately, replace the fit parameters altogether.
In the latter case, one would have a truly ab initio kinetic modelling tool that
could allow for predictions of the macroscopic properties of the polymerization
process without recourse to experimental fit parameters.1 Such predictions could
be compared directly with experimental data so as to provide a sensitive test of a
kinetic model’s validity. Moreover, having identified a suitable kinetic model, ab
initio kinetic modelling could then be used to test new RAFT agents and optimize
reaction conditions prior to experiment.
Proof of principle for ab initio kinetic modelling was provided for cyanoisopropyl
dithiobenzoate-mediated polymerization of styrene at 70 ∘ C in the presence of
the initiator AIBN [57]. Based on computational studies of the chain length
dependence of the addition–fragmentation reaction, a kinetic model that included
a chain-length-dependent fragmentation reaction was constructed using modelling
software PREDICI® [94]. In this model, chain length effects in the attacking radical
were included up to the trimer stage and chain length effects in the macroRAFT
agent, which were found to be considerably smaller, were considered only up to
the unimer stage (see Scheme 6.4). Equilibrium constants (at 70 ∘ C) were then
calculated for the eight kinetically distinct addition–fragmentation reactions and
used in conjunction with the chain-length-independent experimental value for the
addition rate coefficient so as to obtain the corresponding chain-length-dependent
fragmentation rate coefficients. These were combined with reliable experimental
data for the initiation, propagation, and termination reactions, as taken from
styrene homopolymerization experiments. A kinetic simulation of the process
was then performed using identical reaction conditions to those in an earlier
experiment on the same system [58]. The concentration profiles obtained for the
low molecular weight thiocarbonyl compounds formed during the early stages
of the reaction, together with the corresponding experimental data, are shown in
Figure 6.2 [57]. The predicted and measured rates of overall monomer conversion
were also compared [57]. As noted above, there is excellent agreement between
the ab initio kinetic simulation and the experimental data despite the fact that no
model fitting of any kind was performed, and hence the model and calculations are
sufficiently accurate for predictive purposes. Further confirmation of this accuracy
was recently provided in an ab initio kinetic modelling study of 2-cyano-2-propyl
dodecyl trithiocarbonate-mediated polymerization of styrene [95]. Ab initio kinetic
I. Initiation
· · · ·
(la) Initiator I (lb) I + M I–M (I–M· = P1)
II. RAFT equilibria

S
+ S · S
I· Z C I C I
S I
Z
S S · S
+ I
I–M · Z C I C M
S I
Z
S S · S M
+ Z C I C M I
I–M–M ·
S I Z
S S · S M
I C M M
M–M–M · + Z C
S I Z
S
+ Z C S · S
I· –M C I
S M–
Z
S S · S
+ I
I–M · Z C –M C M
S M–
Z
S S · S M
I–M–M · + Z C –M C M I
S M –
Z
S S · S M
–M C M M
M–M–M · + Z C
S M– Z
III. Propagation
· Monomer · ·
(lIIa) Pm Pm+1 (Note: Pm includs I–M·, I–MM· and I–MMM·)
V. Termination
· + P1·
(Va) P1 P2
(Vb) Pn· ·
+ Pm Pn+m n=m=i
Scheme 6.4 Reaction scheme for ab initio kinetic modelling of cyanoisopropyl

dithiobenzoate-mediated polymerization of styrene in the presence of AIBN.
modelling is now a practical possibility for studying RAFT polymerization and the
scope of its potential applications can be expected to expand further with increasing
computer power.
6.4 Structure–Reactivity Studies

Computational quantum chemistry also has an important role to play in providing
an underlying understanding of the reaction mechanism and structure–reactivity
trends. At one level, computational chemistry can be used as a tool for determining
the rate or equilibrium constants of the individual addition–fragmentation processes
for a variety of RAFT agent and monomer combinations. In this regard, it offers
a complementary approach to experimental techniques, which are better suited to
measuring more practical quantities, such as the extent of control or the apparent
chain transfer constant. At a deeper level, computational chemistry can also offer
convenient access to additional mechanistic information, such as the geometries,
charges, and spin densities, and to other relevant energetic quantities, such as radi-
cal stabilization energies of the adduct radical. This information can greatly assist in
the interpretation of the structure–reactivity trends. Based on both ab initio calcula-
tions and experimental approaches, there is now a very good understanding of why
C=S double bonds are so effective at addition–fragmentation reactions, and how the
RAFT agent substituents affect this process. In what follows, these fundamental and
practical aspects are summarized in turn, and we then show how this information
can be used to design optimal RAFT agents.
6.4.1 Fundamental Aspects

A key aspect to controlling free radical polymerization by RAFT is the establishment
of an addition–fragmentation equilibrium in which there is rapid exchange between
the propagating species and the dormant macroRAFT agent. This in turn entails that
both the addition of the propagating radical to the RAFT agent and the fragmenta-
tion of the resulting RAFT-adduct radical (which is effectively the reverse reaction)
are sufficiently fast. In radical addition to C=C bonds this is normally quite diffi-
cult to achieve. Typically, if addition is fast, the reaction is highly exothermic and
fragmentation is too slow. If instead the addition reaction is not very exothermic,
then fragmentation becomes relatively facile but addition is then too slow. Although
some success has been achieved with macromonomers [96], alkenes are not gener-
ally suitable as practical RAFT agents. The question then arises: why are compounds
containing C=S bonds so much more effective, and are there any other types of dou-
ble bond that would serve the same purpose?
To understand the high reactivity of thiocarbonyl RAFT agents, it is helpful to
examine a simple curve-crossing model analysis of prototypical radical additions
to C=S and C=C bonds [83]. The curve-crossing model was developed by Pross
and Shaik [97–99] as a theoretical framework for explaining barrier formation in
chemical reactions. The basic idea is to think of a chemical reaction as comprising
a rearrangement of electrons, accompanied by a rearrangement of nuclei (i.e.

a geometric rearrangement). We can then imagine holding the arrangement of
electrons constant in its initial configuration (which we call the reactant config-
uration), and examining how the energy changes as a function of the geometry.
Likewise, we could hold the electronic configuration constant in its final form (the
product configuration), and again examine the variation in energy as a function
of the geometry. If these two curves (energy vs. geometry) are plotted, we form a
‘state correlation diagram’. The overall energy profile for the reaction, which is also
plotted, is formed by the resonance interaction between the reactant and product
configurations (and any other low-lying configurations). State correlation diagrams
allow for a qualitative explanation for how the overall energy profile of the reaction
arises and can then be used to provide a graphical illustration of how variations in
the relative energies of the alternative valence bond (VB) configurations affect the
barrier height.
In radical addition to double bonds (X=Y), the principal VB configurations that
may contribute to the ground-state wavefunction are the four lowest doublet config-
urations of the three-electron three-centre system formed by the initially unpaired
electron at the radical carbon (R) and the electron pair of the π bond in X=Y (A)
[100].
+ – – + (6.9)
C X–Y C X –Y C X= Y C X= Y
RA RA3 R+A– R–A+
The first configuration (RA) corresponds to the arrangement of electrons in the

reactants, the second to that of the products (RA3 ), and the latter two (R+ A− and
R− A+ ) to possible charge transfer configurations. The state correlation diagram
showing (qualitatively) how the energies of these configurations should vary as a
function of the reaction coordinate is provided in Figure 6.4 [3]. In plotting this
figure we have arbitrarily designated the R+ A− configuration to be lower in energy
than the R− A+ configuration.
In the early stages of the reaction, the reactant configuration (RA) is the lowest
energy configuration and dominates the reaction profile. This is due to the stabi-
lizing influence of the bonding interaction in the π bond of the RA configuration,
which is an anti-bonding interaction in the RA3 configuration. However, as the reac-
tion proceeds, the C· · ·X=Y distance decreases and the unpaired electron on the
radical is able to interact with the X=Y species. This growing interaction destabi-
lizes the RA configuration but stabilizes the RA3 configuration due to the increasing
bonding interaction in the forming C· · ·X bond (which is an anti-bonding inter-
action in the RA configuration). As the relative energies of the RA and RA3 con-
figurations converge, the increasing interaction between the alternative configura-
tions stabilizes the ground-state wavefunction, with the strength of the stabilizing
interaction increasing as the energy difference between the alternate configurations
decreases. It is this mixing of the reactant and product configurations that leads
to the avoided crossing, and accounts for barrier formation. Beyond the transition
Figure 6.4 State correlation diagram for

radical addition to double bonds [3]. R–A+
R+A–
Energy
RA3
RA
Reaction coordinate
structure, the product configuration is lower in energy and dominates the wavefunc-
tion. The charge transfer configurations of the isolated reactants and the isolated
products are high in energy, but in the vicinity of the transition structure they are
stabilized via favourable Coulombic interactions and can sometimes be sufficiently
low in energy to interact with the ground-state wavefunction. In those cases, the
transition structure is further stabilized, and (if one of the charge transfer configu-
rations is lower than the other) the mixing is reflected in the degree of partial charge
transfer between the reactants.
Using this state correlation diagram, in conjunction with simple VB arguments,
the curve-crossing model can be used to predict the qualitative influence of vari-
ous energy parameters on the reaction barrier [97–99]. In particular, the barrier is
lowered by an increase in the reaction exothermicity (see Figure 6.5a), a decrease in
the RA–RA3 separation in the reactants and/or products (see Figure 6.5b), and/or a
Figure 6.5 State correlation diagrams

showing the qualitative effect on the
barrier height of (a) increasing the
exothermicity; (b) decreasing the
singlet–triplet excitation gap; and (c)
decreasing the relative energy of one of
the charge transfer configurations [3].
(a) (b) (c)

decrease in the relative energies of one or both of the charge transfer configurations,
provided that these are sufficiently low in energy to contribute to the ground-state
wavefunction (see Figure 6.5c). Of these parameters, the reaction exothermicity is
of course directly accessible from ab initio molecular orbital calculations. For the
radical addition reactions, the RA–RA3 separation is related to the singlet–triplet
excitation gap of the alkene or thiocarbonyl species. The relative importance of the
charge transfer configurations can be assessed on the basis of the energy for charge
transfer between the isolated reactants, and can be further assessed by examining
the actual extent of charge transfer in the transition structures.
With these simple principles in hand, it then becomes obvious why thiocarbonyls
make much more effective RAFT agents than alkenes. As is well known, the π bond
of a thiocarbonyl is much weaker than that of an alkene, due to the poorer overlap
between the p–π orbitals of the (third row) S atom and the (second row) C atom [101].
This reduced π bond strength is reflected in a greatly reduced singlet–triplet gap for
the thiocarbonyl species, and hence in lower barriers and earlier transition struc-
tures for radical addition [83]. Indeed, unless there is substantial stabilization of the
C=S bond (via, for example, resonance with lone pair donor substituents at carbon),
radical addition to C=S bonds is typically barrierless (i.e. ΔH ‡ ≈ 0), the free energy
barrier (i.e. ΔG‡ > 0) arising merely due to the opposing enthalpic and entropic
effects [6]. Conversely, in the reverse direction, the transition state is very late and
almost completely dominated by the reaction exothermicity (i.e. ΔH ‡ ≈ ΔH).
The low singlet–triplet gap explains not only why dithioesters are generally
very reactive to radical addition but also how it is possible to manipulate the
RAFT agent substituents so as to ensure that fragmentation is also sufficiently
fast. The curve-crossing model predicts that the barrier is affected by the reaction
enthalpy: the less exothermic the reaction, the greater the barrier. Indeed, in the
absence of any additional factors (such as steric or polar effects), the well-known
Evans–Polanyi rule [102] (ΔH ‡ = αΔH) will hold. In radical addition to C=C bonds,
this raises a problem. If one wishes to promote the fragmentation reaction, one
needs to make the addition reaction less exothermic but, in doing so, this raises
the barrier to radical addition. In radical addition to C=S bonds this is also the
case, but there is an important difference. Owing to the early transition structures,
the influence of the exothermicity on the addition reaction is greatly reduced (i.e.
the proportionality constant α is much smaller), and there is much greater scope
for manipulating the reverse fragmentation reaction without compromising the
addition rate.
The dominant influence of the triplet configuration of the π bond also helps to
explain the regioselectivity of the radical addition reaction. As explained above, rad-
ical addition to the carbon centre of the C=S bond is actually the thermodynamically
preferred reaction, although in practice addition occurs at S due to kinetic factors
[4, 83]. The spin density is considerably greater on S than on C in the triplet configu-
ration of the thiocarbonyl, and there is thus a much stronger early bonding interac-
tion when addition occurs at this site. Although the preference for attack at sulfur is
countered by the reduced exothermicity, the early transition structure ensures that
influence of the triplet configuration dominates.
Finally, it is worth exploring whether compounds containing other types of double

bonds would be suitable in RAFT processes. In particular, dithiophosphinate esters
have been proposed as possible alternative RAFT agents [103]. In such systems, the
propagating radical would add to the sulfur centre of the P=S bond, generating a
phosphoranyl radical (instead of a carbon-centred radical) as the intermediate.
•
Pn S S S • S S S R•
+ P R Pn P R P Pn +
M Z Z Z′ Z Z′ M
Z′
(6.10)
Although there is some experimental indication that styrene polymerization
can be controlled using S=P(SCH(CH3 )Ph)3 and S=P(Ph)2 SCH(CH3 )Ph [103], the
observed control was by no means perfect and there was clear evidence of hybrid
behaviour. Computationally, it was shown that radical addition to the P=S bonds
of dithiophosphinate esters was considerably less reactive and less exothermic than
addition to the corresponding C=S compounds [104]. This is due in part to the lower
inherent stabilization energy of its phosphoranyl radical product and in part to its
stronger double bond [104]. Indeed, unlike the C=S double bond of dithioesters,
the P=S bond has a significant ionic character (i.e. a large resonance contribution
from P+ –S− ), which generally renders it less susceptible to radical addition (unless
the attacking radical is highly electrophilic). On this basis, it was concluded that
dithiophosphinate esters are likely to have only limited applicability as RAFT
agents, and would be most suited to the control of electrophilic monomers [104].
More recent studies have also explored the potential of Se-based RAFT agents
[105]. Theoretical studies suggest that identically substituted dithio- and diseleno-
carbamate RAFT agents will have similar reactivity but that diselenocarbamate
RAFT agents are more likely to undergo intermediate radical termination as a result
of the enhanced stability of the intermediate radical. These results have been backed
by experimental studies on the same systems [105]. The suitability of other types of
compounds has yet to be explored computationally; however, studies of prototypical
systems have revealed that C=C, C=O, and C≡C bonds all have significantly larger
singlet–triplet gaps than the corresponding C=S bonds [83, 106]. As a result, they
are less reactive to radical addition than C=S bonds, and less likely to function as
effective RAFT agents.
6.4.2 Structure–Reactivity in Practical RAFT Systems

Notwithstanding the high reactivity of C=S bonds, the precise nature of the other
substituents (R and Z) in a RAFT agent S=C(Z)SR is critical to a controlled polymer-
ization. The degree of control that can be achieved is reliant on the propensity for
addition of the propagating radical Pn ⋅ to the C=S bond, and the subsequent ability of
Pn ⋅ to be released from the RAFT-adduct radical. Both of these depend on the steric
and electronic properties of R and Z. As a result of numerous experimental studies
[1], there now exists a broad understanding of how effective a given R or Z group
is for a certain class of polymerization. For example, polymerizations of styrene,
acrylates, or methacrylates are well controlled by dithioester RAFT agents having
simple alkyl or aryl Z groups, whereas the polymerization of vinyl acetate is not. For
vinyl acetate, control can be achieved with xanthates (Z = OR) or dithiocarbamates
(Z = NR2 ). Equally, it is known [75] that a RAFT agent having R = benzyl would be
suitable for polymerization of methyl acrylate, but not for polymerization of methyl
methacrylate: the tertiary R group C(CH3 )2 Ph is necessary in the latter case.
Building on the wealth of structure–reactivity data now available from experimen-
tal studies, computational chemistry adds a powerful tool that allows these trends
to be explained, and this in turn has predictive power. Our computational investiga-
tions have been founded on the observation that despite the mechanistic complexity
of RAFT polymerization, the effects of R and Z can in large part be understood by
considering simplified versions of the chain transfer reaction (Eq. (6.11)).
S SR PnS • SR PnS S
• + +
Pn C C C R• (6.11)
Z Z Z
To begin with, it is clear from Table 6.3 that as expected on the basis of the
considerations detailed in Section 6.4.1, the fragmentation rate constants gen-
erally follow the same order as the fragmentation enthalpies. A useful analysis
of structure–reactivity relationships can therefore be carried out on the basis of
the thermodynamic parameters. Moreover, the analysis can be further simplified
through the use of isodesmic reactions to separate and rank the effects of R and Z
[78]. First of all, the fragmentation efficiency associated with a particular Z group
is measured by the enthalpy change (ΔH frag ) for the reaction CH3 SC⋅(Z)SCH3 +
S=C(H)SCH3 → CH3 SC⋅(H)SCH3 + S=C(Z)SCH3 . Next, the chain transfer effi-
ciency for a given R group is measured by the enthalpy change (ΔH CT ) for the
reaction CH3 ⋅ + S=C(CH3 )SR → S=C(CH3 )SCH3 + R⋅. The stabilities of RAFT
agents with different Z groups are compared by considering the enthalpies of
the reactions S=C(Z)SCH3 + CH4 → S=C(H)SCH3 + CH3 Z, while the stabil-
ities of RAFT agents with different R groups are compared by the reactions
S=C(CH3 )SR + CH3 SH → S=C(CH3 )SCH3 + RSH. The well-known quantity, rad-
ical stabilization energy (RSE) [24, 107], is used to estimate the stabilities of the
radical species.
In the overall chain transfer reaction (Eq. (6.11)), the effect of Z involves both the
RAFT agent (and the polyRAFT agent) and the intermediate RAFT-adduct radi-
cal. One must therefore consider each addition–fragmentation step separately. In
Figure 6.6, a variety of Z groups are ranked in the order of increasing fragmentation
efficiency −ΔH frag . Shown on the same graph are the stabilities of the two relevant
Z-containing species: the RAFT agent and the RAFT-adduct radical. The fragmen-
tation efficiencies span a range of 100 kJ mol−1 , making it clear that the choice of Z
is critical. We have suggested [78] that in considering the effects of Z, RAFT agents
may be divided into three broad classes based on their values of ΔH frag . In one class
are the agents with Z groups favouring fragmentation (Z = OR or NR2 ), in the sec-
ond are those with low fragmentation efficiencies (Z = CN, Ph, or CF3 ), and in the
third are those with moderate efficiencies (Z = SR, and modified OR or NR2 ). As
will be discussed below, the different classes are of varying utility depending on the
monomer of interest.
120 Stability of RAFT agent

RSE of RAFT-adduct radical
100 –ΔHfrag
80
60
Energy (kJ mol–1)
40
20
0 Z
H
Cl
Imidazole-N
Bn
SEt
Pyrrole-N
Me
SMe
F
NH2
OEt
OMe
MMe2
NEt2
OCH(CF3)P(O)(OMe)2
OCH2)CF3
OtBu
OCH(Me)P(O)(OMe)2
OiPr
–20
CF3
Ph
–40
CN
–60
Figure 6.6 Effect of Z group on fragmentation efficiency, RAFT agent stability, and
RAFT-adduct radical stability [3].
For the RAFT agents (and polyRAFT agents), there are two main ways in which
Z affects stability. First, lone pair donor Z groups such as OR, NR2 , and SR enhance
stability through delocalization of electron density into the C=S bond as shown in
Eq. (6.12).
S SR S SR (6.12)
C C
Z Z
Second, RAFT agents are destabilized by σ-withdrawal. This property can be

clearly seen with the RAFT agents that have Z = CN or CF3 . Within this stability
scheme, the positions of several Z groups are worthy of note. For example, the
groups Z = pyrrole and Z = imidazole confer much less stabilization on a RAFT
agent than do aliphatic amino groups such as NMe2 . This is consistent with the
notion that incorporating the nitrogen lone pair into an aromatic system reduces
the capacity for electron delocalization according to Eq. (6.12) [108].
For RAFT-adduct radicals, the effects of Z are somewhat more complicated.
Here, a major increase in stability is gained if Z is a π-acceptor group such as CN
or Ph. Stabilization by π-acceptor groups is common for carbon-centred radicals,
and in RAFT-adduct radicals the effect can be enhanced because the lone pair
donor SR groups can engage in captodative effects. In principle, the presence of
a lone pair donor Z group should be an alternative stabilizing feature (as in other
carbon-centred radicals), but in RAFT-adduct radicals this is not always borne
out. We have shown [24] that the delocalization of electron density from an SR
group onto a carbon radical centre places the unpaired electron into a higher
energy orbital, making further delocalization onto a second SR group much less
favourable. A RAFT-adduct radical has two lone pair donor SR groups even before
Z is considered, and the capacity for a third interaction involving a lone pair donor
Z group is therefore small. Only when Z is a stronger lone pair donor than SR
will there be enhanced stabilization. Making the situation more complicated,
RAFT-adduct radicals are strongly destabilized by σ-withdrawal (as demonstrated
when Z = F), which means that only those Z groups for which lone pair donation
is stronger than σ-withdrawal (and stronger than the lone pair donation by a SR
group) will confer enhanced stabilization. In Figure 6.6, the only Z groups that
satisfy both criteria are the simple amino groups NR2 (R = H, Me, Et). The alkoxy
groups, although being strong lone pair donors, are unable to enhance stability
because of their strong σ-withdrawing character.
Considering next the effects of R, we have found that it is usually sufficient to
consider the overall chain transfer equilibrium without giving separate attention to
the individual steps. Several earlier computational studies have also adopted this
approach. For example, semi-empirical methods have been used to show that the
chain transfer efficiency of dithiobenzoate RAFT agents varied with R in the order
CH2 COOEt < CH2 COOH < CH(Me)COOEt [109]. A related study [77] on a wide
range of R groups using DFT reached similar conclusions, suggesting that chain
transfer is affected by both steric and polar effects. The overall chain transfer equi-
librium is, of course, a competition between the radicals R⋅ and Pn ⋅ for adding to
the C=S bond. In most cases, the position of the equilibrium is determined mainly
by the relative stabilities of the radicals R⋅ and Pn ⋅: the group whose release from
the RAFT-adduct radical is favoured is the one whose RSE is greatest. The values
of ΔH CT for a range of common R groups are shown in order of increasing chain
transfer propensity in Figure 6.7, together with the stabilities of the relevant RAFT
agents and radicals R⋅.
Considering first the R⋅ radicals, the RSEs can be largely explained on the basis of
factors normally associated with stability in carbon-centred radicals [110]. Thus, the
presence of π-acceptor groups (such as CN or Ph) as α-substituents within R leads to
enhanced stability, as does the capacity for hyperconjugative interactions provided
by α-CH3 substituents. On the other hand, in the RAFT agents, the presence of
α-CH3 groups or π-acceptor α-substituents in R results in destabilization. Here,
methylation primarily induces unfavourable steric interactions. The π-acceptor
groups destabilize the RAFT agents by reducing the capacity for delocalization of
the sulfur lone pair onto the double bond (Eq. (6.13)).
(6.13)
S S S S
C R C R
Z Z
The steric and electronic properties of R therefore influence chain transfer in two
reinforcing ways – one effect on the RAFT agent and the opposite effect on the R⋅
radical. These combined effects render the commonly used R groups CH(CH3 )Ph,
80 Stability of RAFT agent

RSE of R•
–ΔHCT
60
40
Energy (kJ mol–1)
20
0 R
CH(Me)OCOMe
CH(Me)COOMe
CH(Me)CONH2
C(Me)2COOMe
C(Me)2CONH2
CH(Me)COOH
–20
CMe2OCOMe
C(Me)2COOH
CH2OCOMe
CH2COOMe
CH2CONH2
CH(Me)CN
CH2COOH
CH(Me)Ph
C(Me)2CN
CH(Me)Cl
C(Me)2Ph
C(Me)2Cl
CH2CN
CH2Cl
Bu
Me
Bn
Pr
Et
–40
t
i
Figure 6.7 Effect of R on RAFT agent stability, R⋅ stability, and chain transfer efficiency [3].
C(CH3 )2 CN, and C(CH3 )2 Ph very good leaving group radicals. However, it is not
correct to assume that a well-controlled polymerization will result if one simply
chooses the best leaving group R = C(CH3 )2 Ph. If R⋅ is too stable compared with
the monomer, then the subsequent re-initiation step is disfavoured, and polymeriza-
tion will not proceed past the stage of the unimeric RAFT agent. When faced with a
new polymerization, a sensible initial approach would therefore be first to take into
account the stability of the propagating radical (which is roughly measured by the
stability of the monomeric radicals shown in Figure 6.7, and could be better mea-
sured using calculations on the dimers), and then to choose an R group for which R⋅
is only slightly more or less stable than M⋅.
The simplifications involved in deriving the structure–reactivity relationships just
described are accompanied, of course, by a number of exceptional cases. One impor-
tant case is where a system does not obey the usual correlation between kinetics
and thermodynamics. For example, by using computational investigations, we have
found [81] that in the xanthate-mediated polymerization of vinyl acetate, the rate
constant for fragmentation of the RAFT-adduct radical CH3 SC⋅(Z)SCH2 OCOCH3
(Z = OCH3 ) is 3 orders of magnitude larger than that for the radical where Z = Ot Bu.
This result cannot solely be due to the steric effect of Z, however, because for the
related RAFT-adduct radicals CH3 SC⋅(Z)SCH3 the rate constants for Z = OCH3
and Z = Ot Bu are nearly identical. The source of the discrepancy lies instead in
a hydrogen-bonding interaction in the transition state for the fragmentation of
CH3 SC⋅(OCH3 )SCH2 OCOCH3 . A close contact takes place between the carbonyl
oxygen and an OCH3 hydrogen, leading to significant stabilization, whereas no
analogous interactions take place for the other three species.
A breakdown of the structure–reactivity trends can also occur if there are
synergistic interactions between the groups R, Z, and Pn . For example, we have
shown [24] that fragmentation of electron-withdrawing R groups is enhanced by
a homoanomeric effect in which the withdrawal of electron density from sulfur
towards the R group reduces the ability of sulfur to donate electron density to
the radical centre. If the R group contains a 𝜋-acceptor substituent, this induces
an altered CS–R conformation in which the unpaired electron is delocalized
into a CS–R anti-bonding orbital. This not only weakens the S—R bond but is
accompanied by a strengthening of the S—Pn bond in compensation. As a result,
altered chain transfer efficiencies arise that would not have been predicted on the
basis of R⋅ stabilities alone. Moreover, the homoanomeric interaction is further
modulated by the nature of Z: for example, a fluorine substituent in the Z position
can inhibit the effect of a π-acceptor-containing R group [88]. This example and
the vinyl acetate example given above emphasize the importance of conducting
specific computational or experimental investigations once one has selected a range
of candidate RAFT agents for a particular application.
Going beyond structure–reactivity trends within the RAFT itself, computational
studies have also aimed at developing linear free energy relationships for multiple
families of controlled radical polymerization processes, including RAFT, atom trans-
fer radical polymerization (ATRP), and nitroxide-mediated polymerization (NMP)
[111]. This work employed the ionization energy (IE) of the attacking radical and
the electron affinity (EA) of the control agent as polar descriptors, Tolman’s cone
angle of the attacking radical as a steric descriptor, and the RSE of the attacking radi-
cal and the highest occupied molecular orbital–lowest unoccupied molecular orbital
(HOMO–LUMO) gap of the control agent as resonance descriptors. Apart from pro-
viding a predictive relationship for the R—X bond energy of any control agent, the
linear free energy relationship also allows for general observations about the rela-
tive role of polar, steric, and resonance effects in the various processes. Specifically,
it was shown that RAFT is equally dominated by resonance, steric, and polar effects,
while ATRP is dominated by steric and polar effects and NMP by resonance and
steric effects. Other studies have analysed trends in RAFT agent reactivity in terms
of HOMO–LUMO gaps [112, 113] (Figure 6.8).
6.4.3 RAFT Agent Design

The ultimate goal of computational studies of RAFT polymerization is to design
new and improved RAFT agents to tackle any specific control problem. One could
envisage a two-stage approach in which one first utilizes the structure–reactivity
relationships to select promising combinations of substituents, and then tests the
candidate RAFT agents with direct calculations using model propagating radicals.
Having established computationally that a certain RAFT agent was likely to be suc-
cessful, one could then pursue experimental testing.
BDFE [R–X] = – 20.8 θ[R] – 9.73 IP[R] – 1.10 RSE[R] + 192 θ[X] + 57.4 EA[X] – 62.0 resonance[X] + 250
4.5
BDFE
4.0
Weak bond Strong bond
3.5
3.0 θ[R]
2.5 Bulky Small
2.0
θ[X]
1.5
Bulky Small
1.0
0.5 IP[R]
0.0 Hard to donate e– Easy to donate e–
–0.5
Cl
Br
SC(CH3)=S
SC(OCH3)=S
SC(SCH3)=S
SC(NEt2)=S
SC(Ph)=S
SC(F)=S
TEMPO
PROXYL
DBN
TMIO
EA[X]
Hard to accept e– Easy to accept e–
RSE[R]
Stable radical Unstable radical
ATRP RAFT NMP Resonance[X]

[X] EA[X] Resonance[X] Stable radical Unstable radical
Figure 6.8 Steric (𝜃), polar (ionization potential [IP], EA), and resonance contributions to the various R–X BDFEs (bond dissociation free energy) in model
RAFT, NMP, and ATRP reactions [111].
The kinetic requirements of a successful RAFT agent are now fairly well
understood: it should have a reactive C=S bond (kadd high) but the interme-
diate radical should undergo fragmentation at a reasonable rate (typically
K = kadd /kβ < 106 l mol−1 ); the R group should fragment preferentially from the
intermediate radical in the pre-equilibrium but also be capable of re-initiating
polymerization; and there should be no side reactions [1, 92]. Computational
data shown in Tables 6.2 and 6.3 and in Figures 6.5 and 6.6 can assist in choos-
ing RAFT agents that satisfy these criteria. For example, if one predicted that a
propagating radical was relatively stable, then in order to provide good control, its
addition to the C=S bond would need to be fast enough to compete with addition
to monomer. One could then select a Z group that destabilized the C=S bond,
promoting addition (i.e. ΔH frag in Figure 6.6 is large). In contrast, if one predicted
that the propagating radical was relatively unstable, then it would be necessary
to ensure that the propagating radical did not become trapped for too long as the
RAFT-adduct radical. In this case, one would choose a Z group that destabilized the
RAFT-adduct radical relative to the C=S compound (i.e. ΔH frag is small). Amongst
substituents displaying acceptable ΔH frag values, one could further optimize control
by choosing the Z-group that gave the lowest RAFT agent stability, and hence the
fastest addition rates. Likewise, one could use ΔH CT values (as in Figure 6.7) to
choose the R group – an optimal group usually having a ΔH CT value marginally
lower than that of the model propagating radical. Having selected candidate RAFT
agents on the basis of the simplified isodesmic measures, they could then be tested
computationally through direct calculation of the addition–fragmentation kinetics
in more realistic model systems.
There is a growing interest in using computational calculations as a basis for
RAFT agent design. Matyjaszewski and Poli [77] and Patten and coworkers [109]
have advocated the use of calculated chain transfer energies (Eq. (6.11)) as a basis
for choosing appropriate R groups for specified monomers; Matyjaszewski et al.
[77, 114, 115] and Tordo and coworkers [116] have applied similar strategies to
atom transfer radical polymerization and NMP, respectively. Building on this work,
the first computationally designed class of RAFT agents, the fluorodithioformates
(S=C(F)SR or ‘F-RAFT’), was proposed [87]. These were designed as multi-purpose
RAFT agents capable of controlling monomers with stable propagating radicals
and also those with unstable propagating radicals. Other current RAFT agents
for unstable monomers promote fragmentation of the propagating radicals by
stabilizing the thiocarbonyl product of fragmentation (i.e. the RAFT agent). As
a result, they are not sufficiently reactive for controlling monomers with stable
propagating radicals. In contrast, F-RAFT promotes fragmentation by destabilizing
the RAFT-adduct radical without deactivating the C=S bond of the RAFT agent.
The fluorine Z-group achieves this through its strong σ-withdrawing capacity,
which contributes a destabilizing influence to both the radical and the C=S bond,
and helps to counterbalance the stabilizing influence of its lone pair donor capacity.
It can be seen in Figure 6.6 that the stability of the fluorinated RAFT agent is
comparable to other dithioesters, and much lower than that of the xanthates.
On this basis, it is predicted that the RAFT agent is sufficiently reactive for
controlling stable propagating radicals, and the calculated addition rate coefficients
(1.8 × 106 l mol−1 s−1 for a styrene unimer adding to CH3 SC(F)=S at 333.15 K)
seem to confirm this [89]. Although the reduced stability renders fragmentation
less facile, this is counterbalanced to some extent by the reduced stability of the
RAFT-adduct radical. As a result, the equilibrium constant for fragmentation of a
model vinyl acetate radical (3.4 × 104 l mol−1 at 333.15 K) [89], though higher than
that for xanthates, is still considerably lower than the threshold above which rate
retardation occurs (c. 106 l mol−1 [92]). The computational calculations thus predict
that F-RAFT should function as a multi-purpose RAFT agent.
Experimental testing has already indicated that benzyl fluorodithioformate is
capable of controlling styrene polymerization, although testing of vinyl acetate
(and indeed other ‘unstable’ monomers such as ethylene) is still under way [88].
For these monomers, RAFT agents with alternative leaving groups are required;
benzyl fluorodithioformate is not likely to be suitable for controlling vinyl acetate
polymerization, due to the slow rate of re-initiation by the benzyl leaving group.
Instead, based on further computational calculations [89], we predict that a RAFT
agent with a CH2 CN leaving group would be more suitable. With successful prac-
tical applications such as this, it is clear that computational quantum chemistry is
showing promise as a kinetic tool for studying complicated radical polymerization
processes such as RAFT.
More recent RAFT agent design endeavours include the design of a metal-free
Dissociative Electron Transfer Reversible Addition–Fragmentation Chain Transfer
Polymerization (DET–RAFT) method, which avoids both conventional radical
initiators and photo-redox processes, for the polymerization of different monomer
families near room temperature. It is based on the use of inorganic sulfites in
combination with common RAFT agents and was shown to be successful for a
wide range of monomers [117]. In another work, a joint experimental–theoretical
study showed that cyanomethyl methyl(phenyl)carbamodithioate (CMPCD) was
found to be an efficient RAFT agent enabling the controlled/living polymer-
ization of vinyl chloride [118], while another showed that 2-(2-cyanopropanyl
dithiobenzoate) is suitable for 2-acetamidoacrylic acid [119]. More generally, a
theoretical study showed that the sulfonyl radical would be effective as a universal
leaving group for RAFT polymerization [120], while a joint theory–experiment
study showed that strongly electron-deficient sulfonyldithioformate-based RAFT
agents could function as building blocks for hetero Diels–Alder reactions [121].
Another theoretical–experimental study used theory and experiment to demon-
strate that 4-halogeno-3,5-dimethyl-1H-pyrazole-1-carbodithioates have broad
applicability [122] while others examined the synthesis of block copolymers
based on 2-vinyl-4,4-dimethyl-5-oxazolone [123], or poly(vinylidine fluoride)
(PVDF)-b-PVAc [124]. Finally, recent theoretical work has explained the mecha-
nism by which sequence-controlled and stereospecific oligomers are synthesized
via alternating radical chain growth and sequential photoinduced RAFT single unit
monomer insertion [125].
6.5 Outlook
While the key methodological guidelines for studying RAFT processes were
established over a decade ago, improvements in computer power have made these
methods more widely accessible and applicable to a broad range of systems. At the
same time, the crucial role of entropy in polymeric RAFT equilibria and solvent
effects has been revealed, further improving the accuracy and applicability of
computational studies. This maturing of the methodology has been accompanied
by developments in structure–reactivity studies to the extent that it is now possible
to select RAFT agents for a given process on the basis of simple computational
descriptors, and several successful examples of RAFT agent have been published as
a result. While challenges remain, the use of computational chemistry as a useful
complementary tool in RAFT agent design is now well established.
Abbreviations
AIBN α,α′ -azobis(isobutyronitrile)

ATRP atom transfer radical polymerization
BDE bond dissociation energy
B3-LYP A DFT method with the Becke’s B3 exchange and the correlation
functional of Lee, Yang, and Parr
CDB cumyl dithiobenzoate
COSMO ab initio conductor-like solvation model
DFT density functional theory
EPR electron paramagnetic resonance spectroscopy
G3 Gaussian-3; a family of high-level composite methods, e.g. G3, G3B3,
G3(MP2)
G3-RAD a family of G3 methods designed for radical chemistry, e.g.
G3(MP2)-RAD
HF Hartree–Fock
HOMO highest occupied molecular orbital
LUMO lowest unoccupied molecular orbital
MP2 second order Møller–Plesset perturbation theory
NMP nitroxide-mediated polymerization
ONIOM our own N-layered integrated molecular orbital + molecular mechanic
PCM polarizable continuum model; a method for incorporating solvent
effects
PLP pulsed laser polymerization
RAFT reversible addition–fragmentation chain transfer
VB valence bond (theory)
W1 Wiezmann-1; a high-level composite method
References 181
References
studies of raft polymerization: methodology, structure-reactivity correla-
tions and kinetic implications. In: Handbook of Raft Polymerization (ed. C.
Barner-Kowollik), 5–49. Weinheim, Germany: Wiley-VCH.
mun. 27: 473–497.
4 Coote, M.L., Wood, G.P.F., and Radom, L. (2002). J. Phys. Chem. A 106:
12124–12138.
5 Izgorodina, E.I. and Coote, M.L. (2006). J. Phys. Chem. A 110: 2486–2492.
7 Coote, M.L. (2004). Macromolecules 37: 5023–5031.
8 Chernikova, E., Golubev, V., Filippov, A. et al. (2010). Polym. Chem. 1:
1437–1440.
9 Scott, A.P. and Radom, L. (1996). J. Phys. Chem. 100: 16502–16513.
10 Grimme, S., Hansen, A., Brandenburg, J.G., and Bannwarth, C. (2016). Chem.
Rev. (9): 5105–5154.
11 Malick, D.K., Petersson, G.A., and Montgomery, J.A. (1998). J. Chem. Phys. 108:
5704–5713.
12 Schwartz, M., Marshall, P., Berry, R.J. et al. (1998). J. Phys. Chem. A 102:
10074–10081.
13 Martin, J.M.L. and Parthiban, S. (2001). W1 and W2 theories and their vari-
ants: thermochemistry in the kJ/mol accuracy range. In: Quantum Mechanical
Prediction of Thermochemical Data (ed. J. Cioslowski), 31–65. Dordrecht, The
Netherlands: Kluwer-Academic.
14 Gómez-Balderas, R., Coote, M.L., Henry, D.J., and Radom, L. (2004). J. Phys.
Chem. A 108: 2874–2883.
16 Henry, D.J., Parkinson, C.J., and Radom, L. (2002). J. Phys. Chem. A 106:
7927–7936.
17 Henry, D.J., Sullivan, M.B., and Radom, L. (2003). J. Chem. Phys. 118:
4849–4860.
18 Izgorodina, E.I., Coote, M.L., and Radom, L. (2005). J. Phys. Chem. A 109:
7558–7566.
19 Izgorodina, E.I. and Coote, M.L. (2006). Chem. Phys. 324: 96–110.
20 Check, C.E. and Gilbert, T.M. (2005). J. Org. Chem. 70: 9828–9834.
21 Grimme, S. (2006). Angew. Chem. Int. Ed. 45: 4460–4464.
22 Wodrich, M.D., Corminboeuf, C., and Schleyer, P.v.R. (2006). Org. Lett. 8:
3631–3634.
23 Vreven, T. and Morokuma, K. (2003). Theor. Chem. Acc. 109: 125–132.
24 Coote, M.L. and Henry, D.J. (2005). Macromolecules 38: 1415–1433.
25 Izgorodina, E.I., Brittain, D.R.B., Hodgson, J.L. et al. (2007). J. Phys. Chem. A
111: 10754–10768.
26 Atkins, P.W. (1990). Physical Chemistry, 4e. Oxford: Oxford University Press.
27 These formulae are described in full inCoote, M.L. (2004). Encyclopedia of
Polymer Science and Technology (ed. J.I. Kroschwitz), 319–371. New York, NY:
Wiley.
28 Bell, R.P. (1980). The Tunnel Effect in Chemistry, 276. London and New York:
Chapman and Hall.
29 Truhlar, D.G., Isaacson, A.D., Skodje, R.T., and Garrett, B.C. (1982). J. Phys.
Chem. 86: 2252–2261.
30 Truhlar, D.G. and Garrett, B.C. (1989). J. Am. Chem. Soc. 111: 1232–1236.
31 See for example: Truhlar, D.G., Garrett, B.C., and Klippenstein, S.J. (1996). J.
Phys. Chem. 100: 12771–12800.
32 Lin, C.Y., Izgorodina, E.I., and Coote, M.L. (2008). J. Phys. Chem. A 112:
1956–1964.
33 Nordholm, S. and Bacskay, G.B. (1976). Chem. Phys. Lett. 42: 253–258.
34 Heuts, J.P.A., Gilbert, R.G., and Radom, L. (1996). J. Phys. Chem. 100:
18997–19006.
35 Heuts, J.P.A., Gilbert, R.G., and Radom, L. (1995). Macromolecules 28:
8771–8781.
36 East, A.L.L. and Radom, L. (1997). J. Chem. Phys. 106: 6655.
37 Van Speybroeck, V., Van Neck, D., and Waroquier, M. (2002). J. Phys. Chem. A
106: 8945–8950.
38 Izgorodina, E.I., Lin, C.Y., and Coote, M.L. (2007). Phys. Chem. Chem. Phys. 9:
2507–2516.
39 Lin, C.Y., Izgorodina, E.I., and Coote, M.L. (2010). Macromolecules 43: 553–560.
41 Haworth, N.L., Wang, Q., and Coote, M.L. (2017). J. Phys. Chem. A 121:
5217–5225.
42 Voth, G.A. and Hochstrasser, R.M. (1996). J. Phys. Chem. 100: 13034–13049.
43 Tomasi, J. (2004). Theor. Chem. Acc. 112: 184–203.
44 Barone, V. and Cossi, M. (1998). J. Phys. Chem. A 102: 1995–2001.
45 Miertus, S., Scrocco, E., and Tomasi, J. (1981). J. Chem. Phys. 55: 117.
46 Takano, Y. and Houk, K.N. (2005). J. Chem. Theory Comput. 1: 70–77.
47 Marenich, A.V., Ho, J., Coote, M.L. et al. (2014). Phys. Chem. Chem. Phys. 16:
15068–15106.
48 Magill, A.M., Cavell, K.J., and Yates, B.F. (2004). J. Am. Chem. Soc. 126:
8717–8724.
49 Ho, J. and Coote, M.L. (2009). J. Chem. Theory Comput. 5: 295–306.
50 Pliego, J.R. Jr., and Riveros, J.M. (2001). J. Phys. Chem. A 105: 7241–7247.
52 Junkers, T., Barner-Kowollik, C., and Coote, M.L. (2011). Macromol. Rapid
Commun. 32: 1891–1898.
53 Izgorodina, E.I. and Coote, M.L. (2006). Macromol. Theory Simul. 15: 394–403.
References 183
54 Feldermann, A., Coote, M.L., Stenzel, M.H. et al. (2004). J. Am. Chem. Soc. 126:
15915–15923.
55 Kwak, Y., Goto, A., and Fukuda, T. (2004). Macromolecules 37: 1219–1225.
the raft process: overview rates stabilities side reactions product spectrum
and outstanding challenges. In: Handbook of Raft Polymerization (ed. C.
Barner-Kowollik), 51–104. Weinheim Germany: Wiley-VCH.
57 Coote, M.L., Izgorodina, E.I., Krenske, E.H. et al. (2006). Macromol. Rapid
Commun. 27: 1015–1022.
2382–2394.
59 Scaiano, J.C. and Ingold, K.U. (1976). J. Am. Chem. Soc. 98: 4727–4732.
60 Ah Toy, A., Chaffey-Millar, H., Davis, T.P. et al. (2006). Chem. Commun.:
835–837.
61 Olaj, O.F., Bitai, I., and Hinkelmann, F. (1987). Makromol. Chem. 188: 1689.
62 Wang, A.R., Zhu, S., Kwak, Y. et al. (2003). J. Polym. Sci. A 41: 2833–2839.
63 Barner-Kowollik, C., Coote, M.L., Davis, T.P. et al. (2003). J. Polym. Sci., Part A:
Polym. Chem. 41: 2828–2832.
64 Calitz, F.M., McLeary, J.B., McKenzie, J.M. et al. (2003). Macromolecules 36:
9687–9690.
65 de Brouwer, J.A.M., Schellekens, M.A.J., Klumperman, B. et al. (2000). J. Polym.
Sci. A 19: 3596.
66 Kwak, Y., Goto, A., Komatsu, K. et al. (2004). Macromolecules 37: 4434–4440.
67 Ah Toy, A., Vana, P., Davis, T.P., and Barner-Kowollik, C. (2004). Macro-
68 Prescott, S.W., Ballard, M.J., Rizzardo, E., and Gilbert, R.G. (2005). Macro-
molecules 38: 4901–4912.
69 Feldermann, A., Ah Toy, A., Stenzel, M.H. et al. (2005). Polymer 46: 8448–8457.
70 Venkatesh, R., Staal, B.B.P., Klumperman, B., and Monteiro, M.J. (2004). Macro-
molecules 37: 7906–7917.
3151–3161.
72 Coote, M.L. and Davis, T.P. (1999). Prog. Polym. Sci. 24: 1217–1251.
73 Zetterlund, P., Busfield, W., and Jenkins, I. (1999). Macromolecules 32:
8041–8045.
74 Deady, M., Mau, A.W.H., Moad, G., and Spurling, T.H. (1993). Makromol.
Chem. 194: 1691.
2273–2283.
77 Matyjaszewski, K. and Poli, R. (2005). Macromolecules 38: 8093–8100.
78 Krenske, E.H., Izgorodina, E.I., and Coote, M.L. (2006). An ab initio guide to
structure-reactivity trends in reversible addition fragmentation chain transfer
(RAFT) polymerization. In: Controlled/Living Radical Polymerization: From
Synthesis to Materials, ACS Symposium Series, vol. 944 (ed. K. Matyjaszewski),

406–420. Washington, DC: American Chemical Society.
79 Pahnke, K., Brandt, J., Gryn’ova, G. et al. (2016). Angew. Chem. Int. Ed. 55:
1514–1518.
80 Barner-Kowollik, C., Buback, M., Charleux, B. et al. (2006). J. Polym. Sci. A 44:
5809–5831.
81 Coote, M.L. and Radom, L. (2004). Macromolecules 37: 590–596.
82 Buback, M., Janssen, O., Oswald, R. et al. (2007). Macromol. Symp. 248:
158–167.
83 Henry, D.J., Coote, M.L., Gómez-Balderas, R., and Radom, L. (2004). J. Am.
Chem. Soc. 126: 1732–1740.
84 Zard, S.Z. (2006). Aust. J. Chem. 59: 663–668.
85 Altintas, O., Riazi, K., Lee, R. et al. (2013). Macromolecules 46: 8079–8091.
86 Desmet, G.B., D’hooge, D.R., Sabbe, M.K. et al. (2016). J. Org. Chem. 81:
11626–11634.
87 Coote, M.L. and Henry, D.J. (2005). Macromolecules 38: 5774–5779.
88 Theis, A., Stenzel, M.H., Davis, T.P. et al. (2005). Aust. J. Chem. 58: 437–441.
89 Coote, M.L., Izgorodina, E.I., Cavigliasso, G.E. et al. (2006). Macromolecules 39:
4585–4591.
90 Coote, M.L. and Radom, L. (2003). J. Am. Chem. Soc. 125: 1490–1491.
mun. 27: 1233–1240.
92 Vana, P., Davis, T.P., and Barner-Kowollik, C. (2002). Macromol. Theory Simul.
11: 823–835.
93 Perrier, S., Barner-Kowollik, C., Quinn, J.F. et al. (2002). Macromolecules 35:
8300–8306.
94 Wulkow, M. (1996). Macromol. Theory Simul. 5: 393–416.
95 Desmet, G.B., Rybel, N.D., Steenberge, P.H.M.V. et al. (2018). Macromol. Rapid
Commun. 38: 1700403.
97 Pross, A. and Shaik, S.S. (1983). Acc. Chem. Res. 16: 363.
98 Pross, A. (1985). Adv. Phys. Org. Chem. 21: 99–196.
99 Shaik, S.S. (1985). Prog. Phys. Org. Chem. 15: 197–337.
101 Schmidt, M.W., Truong, P.H., and Gordon, M.S. (1987). J. Am. Chem. Soc. 109:
5217–5227.
102 Evans, M.G. (1947). Disc. Faraday Soc. 2: 271–279.
103 Gigmes, D., Bertin, D., Marque, S. et al. (2003). Tetrahedron Lett. 44: 1227–1229.
104 Hodgson, J.L., Green, K.A., and Coote, M.L. (2005). Org. Lett. 7: 4581–4584.
105 Matioszek, D., Mazières, S., Brusylovets, O. et al. (2019). Macromolecules 52:
3376–3386.
106 Gómez-Balderas, R., Coote, M.L., Henry, D.J. et al. (2003). J. Phys. Chem. A 107:
6082–6090.
107 The use of radical stabilization energies (RSEs) to compare the stabilities of
two radicals R⋅ and R′ ⋅ is only meaningful if the discrepancy between the R–H
References 185
and R′ –H bond strengths is negligible. In the case of carbon-centered radicals

this assumption is normally reasonable but minor discrepancies can arise due
to non-canceling steric or polar interactions in the closed shell compounds.
More generally, in other types of radical, such as phosphoranyl radicals, this
assumption can break down altogether. For a more detailed discussion of this
problem, see for example:Hodgson, J.L. and Coote, M.L. (2005). J. Phys. Chem.
A 109: 10013–10021, and references cited therein.
6977–6980.
109 Farmer, S.C. and Patten, T.E. (2002). J. Polym. Sci., Part A: Polym. Chem. A40:
555–563.
110 Coote, M.L., Lin, C.Y., Beckwith, A.L.J., and Zavitsas, A.A. (2010). Phys. Chem.
Chem. Phys. 12: 9597–9610.
111 Lin, C.Y., Marque, S.R.A., Matyjaszewski, K., and Coote, M.L. (2011). Macro-
molecules 44: 7568–7583.
112 Rodríguez-Sanchez, I., Zaragoza-Contreras, E.A., and Glossman-Mitnik, D.
(2010). J. Mol. Model. 16: 95–105.
113 Rodríguez-Sanchez, I., Zaragoza-Contreras, E.A., and Glossman-Mitnik, D.
(2009). J. Mol. Model. 15: 1133–1143.
114 Gillies, M.B., Matyjaszewski, K., Norrby, P.-O. et al. (2003). Macromolecules 36:
8551–8559.
115 Singleton, D.A., Nowlan, D.T. III, Jahed, N., and Matyjaszewski, K. (2003).
116 Marsal, P., Roche, M., Tordo, P., and de Sainte Claire, P. (1999). J. Phys. Chem.
A 103: 2899–2905.
117 Maximiano, P., Mendonça, P.V., Costa, J.R.C. et al. (2016). Macromolecules 49:
1597–1604.
118 Abreu, C.M.R., Mendonca, P.V., Serra, A.C. et al. (2012). Macromolecules 45:
2200–2208.
119 Dedeoglu, B., Ugur, I., Degirmenci, I. et al. (2013). Polymer 54: 5122–5132.
120 Gryn’ova, G., Guliashvili, T., Matyjaszewski, K., and Coote, M.L. (2013). Aust. J.
Chem. 66: 308–313.
121 Nebhani, L., Sinnwell, S., Lin, C.Y. et al. (2009). J. Polym. Sci. A Polym. Chem.
47: 6053–6071.
1438–1447.
123 Pascual, S., Blin, T., Saikia, P.J. et al. (2010). J. Polym. Sci., Part A: Polym. Chem.
48: 5053–5062.
124 Guerre, M., Rahaman, S.M.W., Améduri, B. et al. (2016). Polym. Chem. 7:
6918–6933.
125 Huang, Z., Noble, B.B., Corrigan, N. et al. (2018). J. Am. Chem. Soc. 140:
13392–13406.
187
Mathematical Modelling of RAFT Polymerization

Porfirio López-Domínguez 1 , Iván Zapata-González 2 , Enrique Saldívar-Guerra 3 ,
and Eduardo Vivaldo-Lima 1
1 Universidad Nacional Autónoma de México, Facultad de Química, Departamento de Ingeniería Química,
Circuito Exterior S/N, Ciudad Universitaria, Coyoacán, Ciudad de México, CP 04510, México
2
Cátedras CONACYT-Tecnológico Nacional de México/Instituto Tecnológico de Tijuana, Centro de Graduados
e Investigación Química, CONACYT, AP 1166, Tijuana 22430, Baja California, México
3 Centro de Investigación en Química Aplicada, CIQA, Boulevard Enrique Reyna 140, Saltillo, Coahuila 25100,
México
7.1 Introduction
The first reports on modelling of reversible addition–fragmentation chain transfer
(RAFT) polymerization appeared soon after the process was disclosed in the open
literature [1–11]. Modelling and simulation of reversible deactivation radical poly-
merization (RDRP) processes, including RAFT polymerization, have been achieved
by using several numerical approaches. The method of moments (MMs), kinetic
Monte Carlo (kMC) simulations, and the software Predici® have been used in many
literature reports [11–14]. Application of these numerical techniques to RAFT poly-
merization includes mainly (i) the synthesis of homopolymers with narrow molar
mass distributions (MMDs) or molecular weight distributions (MWDs) [2–5], (ii) the
synthesis of polymer networks by crosslinking/branching reactions of vinyl/divinyl
monomers [15–19], (iii) microwave-assisted radical polymerization (RP) [20, 21], (iv)
copolymers with controlled chain composition distributions via semibatch reactor
operation [22, 23], (v) dispersion polymerizations in supercritical carbon dioxide
(scCO2 ) [24], (vi) continuous stirred tank reactors [2, 25], and (vii) miniemulsion
polymerization [26–28].
When some RAFT agents, such as dithiobenzoates, are used in radical polymer-
izations, the so-called retardation effect (reduced polymerization rate) is important
[29, 30]. The ‘slow fragmentation’ (SF) [3] and the ‘intermediate radical termina-
tion’ (IRT) [31] models have been proposed to account for the retardation effect.
Both models can satisfactorily describe the available experimental data on polymer-
ization rate (Rp ) and evolution of molecular weights (MWs) by fitting their corre-
sponding kinetic rate constants representing addition (kadd = ka ), fragmentation
(kbd = kb ), and cross-termination (ktir , only in IRT model) reactions. As a conse-
quence, there is a difference of six orders of magnitude between the estimated kinetic
188 7 Mathematical Modelling of RAFT Polymerization
rate constants for the fragmentation reaction, kb ≈ 10−2 – 10−1 s−1 for the SF model
and kb ≈ 103 – 105 l mol−1 s−1 for the IRT model [29, 32]. Other kinetic models for
RAFT polymerization consider some additional reactions between the participating
species [29, 33–36].
7.2 Deterministic Modelling Techniques (DMTs)

Deterministic modelling techniques (DMTs) are based on first principles: kinetic
laws and initial conditions. The model comprises the solution of a system of
equations describing mass balances derived from the polymerization scheme and
kinetic hypotheses for a given reactor type, in which the full information is available
throughout the solution trajectory. In this type of models, random variations must
be excluded from the calculations. The most popular modelling approach in this
category is the method of moments, but recently new DMTs have been developed
with the purpose of providing calculation of the full MWD with relatively low
computer processing time, involving chain-length (CL)-dependent kinetic rate
constants and multidimensional approaches for non-linear polymer molecules
produced in common steps, such as addition–fragmentation, cross-termination,
branching, or crosslinking.
7.2.1 Method of Moments (MM)

The MM in the context of polymerization kinetic modelling has been used for over
65 years [37, 38]. This statistical-kinetic technique has become a fundamental and
powerful tool in the modelling of polymerization processes. Specifically, in RAFT
polymerization, this versatile deterministic method has been continuously used in
the development of mathematical models for the analysis of kinetic theories, such
as the so-called IRT [4, 31, 39], missing step theory (MST) [36], intermediate radical
termination with oligomers (IRTO) [40, 41], and SF [32, 41], for estimation of
kinetic rate coefficients [42, 43], design of polymers with well-defined microstruc-
tures [44], and design of monomer feeding policies [45]. The polymerization
processes addressed include homogenous and heterogeneous media, different reac-
tor operating configurations (batch [46], semibatch [22, 47], and continuous [25]),
homo- and copolymerization systems [48], as well as linear and non-linear chain
polymer product architectures (crosslinking [15, 17] and branching [18, 49]). The
main advantages of the MM are simplicity and important dimensional reduction of
the mathematical system, resulting in reliable predictions of average characteristics,
such as number (M n ), weight (M w ), and z-(M z ) average molecular weights, molar
mass dispersity (Ð), end-group functionality (EGF), and selectivity (S).
The first step in the application of the technique is the derivation of the popula-
tion balance equations (PBEs) for each type and length of polymer molecule species
involved in the polymerization scheme, as shown in Table 7.1 for RAFT homopoly-
merization of vinyl monomers, where M is the monomer, I is the initiator, AB is
Table 7.1 Polymerization scheme for RAFT polymerization.
Step Equation
(f )kd
Initiation I −−−−→ 2R•in
ki
R•in + M −−−−→ R•1
ki
Re-initiation B• + M −−−−→ R•1
kp
Propagation R•m + M −−−−→ R•m+1
kadd kbd
−−−−−→ −−−−→
Reversible chain transfer to the RAFT agent R•m + AB k-add Rm A• B k−bd Rm A + B•
(pre-equilibrium) ←−−−−− ←−−−−−
ka kb
−−−−→ −−−−→
Chain equilibration (main equilibrium) R•m + Rn A k−a Rm A• Rn k−b Rm A + R•n
←−−−−− ←−−−−
ktir
Intermediate radical termination Rp A• Rq + R•r −−−−→ Rp Rq Rr
ktc
Termination by combination R•m + R•n −−−−→ Pm+n
ktd
Termination by disproportionation R•m + R•n −−−−→ Pm + Pn
the RAFT agent, and R•in is a primary radical. Then, the PBEs are transformed into
moment equations by multiplying them by the summation of chain length to the
given moment order power, for all chain sizes. This results in a finite system of
‘i’ ordinary differential equations (ODEs) for each polymer species, where i is the
moment order.
For illustration purposes, let us consider a simple representation of RAFT poly-
merization. For simplicity, only four types of polymer molecules are considered:
(i) living polymer radicals (R•m ), (ii) intermediate polymer radicals (1 and 2 arms:
Rm A• B and Rm A• Rn , respectively), (iii) dormant polymer molecules (Rm A), and (iv)
dead polymer molecules (Pm or Pm Pn Pt ). Definitions for the i-th moment of polymer
radicals, intermediate polymer radicals, and dormant and dead polymer molecules
are provided in Eqs. (7.1)–(7.4), respectively:
∑
∞
[ ]
Yi = mi R•m ; m = 0, 1, 2, … (7.1)
m=1
∑∑
∞ ∞
[ ]
Fi,j = mi nj Rm A•Rn ; n, m = 0, 1, 2, … (7.2)
m=1 n=1
∑
∞
[ ]
i
Zi = m Rm A ; m = 0, 1, 2, … (7.3)
m=1
∞
∑ [ ]
Qi = mi Pm ; m = 0, 1, 2, … (7.4)
m=1
The following step is to transform the PBEs into moment equations by multiply-
ing them by chain length raised to the order moment being considered and then
applying the summation operator over all chain lengths. This is equivalent to apply-
ing the operators defined by Eqs. (7.1)–(7.4) to the PBEs. This procedure leads to
Eqs. (7.5)–(7.8) for the zeroth, first, and second order moments for each polymer
species.1
dYi ( ) ( ) ( )
= 2fkd [I] + 𝛽i + k-a + kb Fi,0 − ka + k-b Y0 Zi − ktd + ktc Y0 Yi − ktir Yi F0,0
dt
(7.5)
dFi,j ( ) ( )
= ka + k-b Y0 Zi − k-a + kb Fi,0 − ktir Yi F0,0 (7.6)
dt
dZi ( ) ( )
= − ka + k-b Y0 Zi + k-a + kb Fi,0 (7.7)
dt
dQi
= ktd Y0 Yi + 𝜀tc + ktir Yi F0,0 (7.8)
dt
i = 0, 1, 2.
Average properties are related to moments through the expressions given by
Eqs. (7.9)–(7.13)1 :
( )
1
Xn = (7.9)

( 0)
2
Xw = (7.10)
1
( )
3
Xz = (7.11)
2
X
Ð= w (7.12)
Xn
Y0 + 12 F0,0 + Z0
EGF = (7.13)
0
where i denotes the i-th bulk moment, as defined in Eq. (7.14).2
i = Yi + Fi + Zi + Qi (7.14)
0 , 1 , and 2 are total polymer concentration, total monomer units incorporated
into polymer molecules, and total second order moment, respectively. X n (also
denoted as DPn ) and X w are number- and weight- average degree of polymerization
or chain length. If these averages are multiplied by monomer MW, Mn and Mw are
obtained. A detailed description of the general methodology and its application to
RAFT polymerization can be found in the literature [13, 50, 51].
7.2.1.1 Homogeneous Systems

The MM has been used in a good number of contributions on RAFT polymeriza-
tion of vinyl monomers carried out in bulk and solution [31–64]. As is well known,
kinetic theories aimed at describing the RAFT mechanism, to account mainly for
the strong retardation effect observed in dithiobenzoate-mediated polymerizations,
1 𝛽 i and 𝜀tc (termination by combination term) are defined in Ref. [11].

2 F i is a defined by the i-th moment; F 0 = 0.5F 0, 0 , F 1 = F 1, 0 , F 2 = F 2, 0 + F 1, 1 .
have been debated intensely in the literature [30, 33, 52]. The MM has been essential
to gain a first overall understanding of the kinetic mechanism involved in RAFT
polymerization. By using this method, it is possible to compare predictions of the
four theories: IRT, SF, IRTO, and MST. MM models can in principle be used to dis-
criminate among the existent theories available to explain controversial phenomena
in RAFT polymerization, such as the retardation effect, if adequate model discrimi-
nation techniques are used [43].
A summary of the kinetic behaviour and selectivity between growing and inter-
mediate chains predicted by each theory is shown in Figure 7.1. Although all the
aforementioned theories result in similar predictions of polymer species concentra-
tions, polymerization rate, and average molecular weight properties, the selectivity
of growing radicals displays strong discrepancies, by orders of magnitude, between
SF and the other theories (see Figure 7.1d).
The IRT theory postulated by Monteiro and de Brouwer [31] introduced
the so-called three-arm star polymer molecule (Pm Pn Pt ) into the kinetic
scheme. This theory was studied by Wang and Zhu [4]. They proposed that
the addition–fragmentation step (main equilibrium reaction in Table 7.1) can be
simplified to what is shown in Eq. (7.15), resulting in a reduction of the number of
rate coefficients.
ka kb
R•m + Rn A −−→ Rm A• Rn −−→ Rm A + R•m (7.15)
The model of Wang and Zhu allowed capturing low levels in the concentration
of intermediate radicals, F 0 , close to those exhibited by polymer radicals, and the
build-up of dead polymer (Q0 ) in the system, as observed in Figure 7.1c. The model
was adapted to include SF theory (kb = 10−2 s−1 and ktir = 0), in which a low value
of kb generated high concentration levels of intermediate radicals [32], as observed
in Figure 7.1c.
A comprehensive comparative study between IRT, SF, and a simple model based
on direct reversible chain transfer (absence of the intermediate radical species),
using a self-developed code for the MM equations and the PrediciTM software, was
carried out by Pallares et al. [11]. They observed that simulations based on the
complete polymerization scheme proposed by CSIRO for RAFT polymerization
and calculations carried out using Eq. (7.14) produced the same results. However,
calculations based on the simpler third model were qualitatively correct, but
quantitatively deviated from experimental data. Using the MM, Monteiro simulated
all the possible reaction events [39], including those involving primary radicals
produced by the initiator and chain transfer agent (AB), and the formation of
four-arm star polymers through intermediate–IRT, as described in Eq. (7.16). The
scenarios considered in their parametric analysis included the presence of poor
leaving groups, slow re-initiation of primary radicals (B• ), inhibition, and kinetic
characteristics of IRT and SF. However, the introduction of Eq. (7.16) did not
improve the performance behaviour of the model.
kiRR
Rm A• Rn + Rs A• Rt −−−−→ Rm Rn A − ARs Rt
m = 1, 2, … ; n = 1, 2, … ; s = 1, 2, … ; t = 1, 2, … (7.16)
IRT SF IRTO MST

Conversion
0.00 0.25 0.50 0.75 1.00
1.0 1.0 500 1.5
400 1.4
0.9
Conversion
300 1.3
EGF
DPn
0.5 Ð
200 1.2
0.8
100 1.1
0.0 0.7 0 1.0

0 10 20 30 0.0 0.5 1.0
(a) t (h) (b) Conversion
SF IRT IRTO MST SF0

100 SF0
–2 Z0 Z0 Z0 Z0 SF0
10
Q0 SY0 SY0&SF0
Selectivity
10–3 Q0
Total concentration (mol l )
–1
F0 Q0
10–4
Q0 10–1 SY0
10–5
5.8 × 10–5
10–6
5.6 × 10–5 RY0
G0 SY0 =
–7 SY0
10 Y0, F0 5.4 × 10–5 RY0 + RF0
Y0, F0 Y0, F0 5.2 × 10–5
Y0 SF0 = 1 – SY0
10–8
–5
5 × 10
0.0 0.5 1.0 0.0 0.5 1.0
(c) Conversion (d) Conversion
Figure 7.1 Evolution of average characteristics using different kinetic theories: (a)
conversion and EGF vs. time; (b) X n and Ð vs. conversion; (c) total polymer concentration
(zeroth moment) vs. conversion; and (d) selectivity of growing (Y 0 ) and intermediate (F 0 )
polymer radicals vs. conversion. Kinetic rate constants: for IRT, k b = 1 × 104 s−1 ,
k tir = 1 × 107 s−1 ; SF: k b = 5 × 10−1 s−1 , and k tir = 0; for IRTO, k b = 1 × 104 s−1 , k tir = 1 × 107 ;
and for MST, k b = 1 × 104 s−1 , k tir = 1 × 107 s−1 ; k tMS = 1 × 107 s−1 . Other kinetic rate
constants are considered as in Ref. [41], or [53] for MST. [M]0 : [AB]0 : [I]0 = 500 : 1 : 05.
Konkolewicz et al. proposed the IRTO theory [34], where radicals involved in
cross-termination are limited to small sizes, as shown in Eq. (7.17), thus resulting
in the elimination of three-arm star products without affecting the general kinetic
behaviour. This is illustrated in Figure 7.1.
ktir
Rm A• Rn + R•t −−−→ Rm Rn Rt m = 1, 2, … ; n = 1, 2, … ; t = 1, 2, … (7.17)
Zapata-González et al. reported another comparative study between IRT, SF, and
IRTO by using the MM and also carried out calculations of full MWDs [41]. They
analysed the validity of the quasi steady-state approximation (QSSA) for polymer
radicals (R⋅ m ) and intermediate polymer radicals (Rm A• Rn ). They found that the
QSSA hypothesis is adequate for both types of polymer radicals in IRT and IRTO.
However, it turned out that the QSSA was invalid in SF for Rm A• Rn , due to the high
stability and accumulation of these species. They also observed that the standard
one-dimensional implementation of the RAFT polymerization scheme in PrediciTM
does not generate adequate predictions of second and higher order moments [46].
Buback and Vanna introduced an additional step into the RAFT polymerization
scheme shown in Eq. (7.18), under MST [33]. This step consists of the regeneration
of two-arm intermediate polymer radicals through a chain transfer reaction between
three-arm polymer stars and living polymer radicals. Zapata-González et al. [36]
modelled this modified version of MST, using the MM and experimental data of
styrene (Sty) and butyl acrylate (BA) RAFT polymerizations reported in the liter-
ature. They found that the model provides adequate descriptions of both systems.
ktMS
Rm Rn Rt + R•s −−−−→ Rm A• Rn + Rs Rt
m = 1, 2, … ; n = 1, 2, … ; s = 1, 2, … ; t = 1, 2, … (7.18)
Recently, Masoumi et al. developed a sequential Bayesian Monte Carlo model dis-
crimination technique applied to the case of RAFT polymerization [43]. Two rival
models based on the MM (chain equilibration step as represented in Table 7.1 vs.
the reduced expression shown in Eq. (7.15)) were compared. It was found that Mn
seems to be the best output for model discrimination purposes. The Bayesian tech-
nique proved to be capable of discriminating rival RAFT models. However, the lim-
ited experimental data usually available (e.g. conversion, Mn and Ð as shown in
Figure 7.1a,b) does not allow to fully analyse the zones where rival models differ,
and no definite answer as to which theory is best has yet been obtained [43].
A kinetic approach known as degenerative chain transfer model [54, 55] greatly
reduces the complexity of the mathematical representation of RAFT polymerization.
The model neglects the contribution of intermediate species in the kinetic scheme
and the addition–fragmentation step is substituted by a degenerative chain trans-
fer step, given by Eq. (7.19). A mathematical model based on that approach allowed
calculations of X n , Ð, and the transfer coefficient Ctr [56]. One of the three mod-
els studied by Pallares et al., the simplest one, had the same structure but it was
reversible [11].
ktr(main)
R•m + Rn A −−−−−−→ Rm A + R•n (7.19)
Monteiro [9] carried out a parametric sensitivity analysis of a RAFT copolymer-

ization system using a general model where the retardation effect was negligible. He
used a degenerative chain transfer model and a semibatch process. He found that
the effect of Ctrs on X n was negligible but it strongly affected Ð.
Targeting tailored-designed products and microstructure control can be achieved
through semibatch and continuous processes. A comprehensive modelling study
focused on the RAFT polymerization of methyl methacrylate (MMA) in different
reactor configurations (batch, semibatch, single continuous stirred tank reactor
(CSTR), and a series of CSTRs) was reported by Zhang and Ray [2, 57]. The model
that they developed was generated from a general polymerization scheme using
2-cyanopropan-2-yl 1H-pyrrole-1-carbodithioate as RAFT agent. They included
diffusion-controlled effects by using the so-called Ross–Laurence gel effect factor
correlation [58]. They found that as the number of CSTR reactors was increased,
both monomer conversion and X n increased but Ð decreased. Higher values of
Ð than those generated in the analogous batch mode were observed. Although
semibatch polymerization turned out to be quite robust, exhibiting the best charac-
teristics to produce polymer with controlled microstructures and high productivity
levels, proper selection of thermal initiator and RAFT agent for optimal operation
were required. Wang et al. [59] carried out a comprehensive study on semibatch
RAFT copolymerization of vinyl monomers. They modelled a generic system with
kinetic parameters corresponding to dithiobenzoate RAFT agents. They focused
on optimizing feed policies for control of copolymer composition distributions
(CCDs). Their model was based on an IRT polymerization scheme. Constant
copolymer composition throughout the polymerization was obtained, in contrast
to batch processes, but reduced polymerization rate and higher Ð were obtained
as a consequence of the use of a semicontinuous process. These results were more
pronounced in systems with larger differences between reactivity ratios. Ye et al.
[60] developed mathematical models for calculation of chain length, chain length
sequences, and their distributions. They included the Ross–Laurence gel effect
correlation in their model. They validated their model by comparison against
experimental data of RAFT polymerization of MMA. Jiang et al. [45] synthesized
copolymers of Sty/BA with uniform CCDs and narrow MWDs by semibatch RAFT
copolymerization using model-based optimized monomer feeding policies. Other
studies on the effect of reactor configuration and operation on polymerization rate
and molecular weight development in RAFT polymerization include the use of plug
flow tubular reactors (PFTR) [61] and series of CSTR and PFTR reactors, both with
backmixing [25].
Although most modelling studies on RAFT polymerization use dithiobenzoates as
RAFT agents, other controllers have also been studied. Zhou et al. [62] presented a
modelling study on RAFT polymerization using xanthates. Jiang et al. [18] modelled
the copolymerization of Sty and BA using a trithiocarbonate RAFT agent. Ulitin et al.
[63–65] also considered trithiocarbonate RAFT agents in the modelling of RAFT
homopolymerizations of Sty and BA. All these models assumed an IRT scheme to
account for the retardation effect.
7.2.1.2 Heterogeneous Systems

Polymerizations carried out as heterogeneous processes are advantageous since they
provide high polymerization rates, easy of separation, and good temperature control.
In these systems, two phases are usually present, due to the low or null solubility
of the polymers produced: solvent-rich (continuous) and polymer-rich (dispersed)
phases. The kinetic study of heterogeneous polymerization processes is rather com-
plex since mass transport of the involved species between continuous and dispersed
phases must be considered in addition to polymerization kinetics.
Emulsion Polymerization In conventional emulsion polymerization (EP), the recipe

includes water, monomers, surfactant, and a water-soluble initiator. Recently,
several alternatives to surfactants have been proposed. In polymerization-induced
self-assembly (PISA), a water-soluble macroRDRP agent is used to produce block
copolymers [66].
The copolymerization of Sty and BA using 3-benzyltrithiocarbonyl propionic
acid (BCPA) and potassium persulfate (KPS) has been conducted as miniemulsion
polymerization in batch and semibatch processes [67]. The method of moments
and the pseudo-kinetic rate constants method were employed to calculate X n and
Ð. The experimental data corresponding to RAFT batch copolymerization were
used to estimate the RAFT kinetic constants. The model captured well the effect
of comonomer content on total monomer conversion, copolymer composition,
diameter of unswollen particles, and the number of particles per volume.
Dispersion Polymerization Dispersion polymerizations carried out in supercrit-

ical carbon dioxide (scCO2 ) are important since scCO2 is a good solvent for
polar/non-polar compounds and has a relatively low critical point. Block copoly-
mers can be produced in scCO2. A one-pot synthesis can be implemented: monomer
A is first polymerized to full conversion in the presence of a RAFT agent; monomer
B is then fed using a high-performance liquid chromatography (HPLC) pump [68].
The RAFT polymerization of Sty using S-thiobenzoyl thioglycolic acid (TBTGA)
and 2,2′ -azobis(2-methylpropionitrile) (AIBN) in scCO2 at 80 ∘ C and 300 bar was
studied using two modelling approaches [69]. In the first approach (Model A), the
‘complete’ model for RAFT polymerization [11] was used to describe the polymeriza-
tion kinetics in the continuous and dispersed phases. Three stages were considered
in this approach. Monomer and solvent concentrations in each phase were approxi-
mated by using semi-empirical partition equations. The second modelling approach
(Model B) was developed in the PrediciTM software [24] using the ‘Q-type’ approach
for each phase (see Section 7.2.3.3 in this chapter). Mass transfer between the con-
tinuous and dispersed phases for the components included in the reaction mixture
was modelled using Predici’s ‘phase exchange’ step. Migration of radicals from the
continuous to the dispersed phase was modelled using Predici’s ‘k(s)-termination’
step. Four cases were addressed by Jaramillo et al. [70]. Case 1 represented a con-
ventional case (no RAFT agent included in the reacting mixture) while Cases 2–4
contained increasing amounts of a RAFT agent. Both approaches described well the
experimental data of monomer conversion vs. time, as well as M n and Ð vs. conver-
sion for Case 1. A linear relationship between M n and conversion was obtained, as
observed in Figure 7.2. However, both models predicted wider differences in M n and
higher values of Ð for Cases 2–4.
Suspension Polymerization Although suspension polymerization has not been used

as a common operation mode for RAFT polymerizations, a few studies have been
reported [71–76]. However, no reports on modelling of polymerization kinetics or
particle size distribution calculations for RAFT polymerizations carried out in sus-
pension are available to the best of our knowledge.
1 12 000
Case 1 Case 3 Model A
Case 2 Case 4 Model B Case 2 Model A
2
10 000 Case 3 Model B
0.8 Case 4
8 000
Conversion
0.6 3
Mπ
6 000
0.4
4 000 4
0.2 2 000
0
0 0 0.2 0.4 0.6
0 10 20 30
(a) Time (h) (c) Conversion
8
Case 1
7 Model A
105 Model B
6
5
Mn
Ð
4
104
3
Case 1
Model A 2
Model B
1
103
0 0.2 0.4 0.6 0.8 0 0.2 0.4 0.6 0.8
(b) Conversion (d) Conversion
4
Case 2
3.5 Case 3
Case 4
Model A
2
3 Model B
2.5
Ð
2
3
1.5
4
1
0 0.2 0.4 0.6

(e) Conversion
Figure 7.2 Comparison of Models A and B (see text) against experimental data of
(a) monomer conversion against time, (b) Mn against conversion (Case 1), (c) Mn against
conversion (Cases 2–4), (d) Ð against conversion (Case 1), and (e) Ð against conversion
(Cases 2–4). Source: Reproduced with permission from López-Domínguez et al. [69].
© 2018, John Wiley & Sons.
7.2.2 Diffusion-Controlled or CL-Dependent Coefficients

It is well established that termination and, to a lesser extent, propagation reactions
in conventional RP are diffusion controlled [77, 78]. The intensity of the effect varies
with conversion and the average molecular weight of the polymer being produced.
It was suggested in early studies on RDRP that some reactions in these systems
could also become diffusion controlled at certain reaction conditions, especially at
moderate to high conversions, including the activation and deactivation reactions
[79, 80]. Diffusional limitations in RDRP in general have been reviewed by D’hooge
et al. [81]. Additionally, it is known that the termination coefficient in RP is chain
length dependent [78] and it has been reported that the propagation kinetic rate
coefficient (kp ) is CL dependent for the first 10 propagation steps [77, 81]. Since the
first mathematical models on RAFT polymerization were published, some authors
introduced expressions for diffusion control effects (DCE) on kinetic rate constants
in some of the reaction steps. As mentioned in Section 7.2.1.1, Zhang and Ray [2]
used the Ross–Laurence correlation [58] in their modelling of RAFT polymerization
of MMA, using MM, to take into account DCE in the termination and propaga-
tion reactions. They justified the use of the same DCE correlations applicable to
RP by assuming that the onset of the auto-acceleration effect (inflexion point in a
conversion vs. time plot) would occur at a conversion at which the average chain
length of the polymer being produced would be sufficiently long, above the entan-
glement chain length of poly(MMA) (around 100). No DCE were considered in the
kinetic rate constants for reactions involving RAFT agents or macroRAFT dormant
polymer molecules, based on the argument that those kinetic rate constants (e.g.
∼104 l mol−1 s−1 for the forward addition reaction) are much lower than typical ter-
mination rate constants (∼107 l mol−1 s−1 ).
Wang and Zhu [5] were apparently the first to introduce the concept of DCE for
the addition step in RAFT polymerization (equivalent to the deactivation step in
systems exhibiting the persistent radical effect). They argued that in RDRP systems
the deactivation kinetic coefficient is usually orders of magnitude higher than the
corresponding one for activation and, therefore, the deactivation reaction was more
prone to show DCE. They used free-volume theory to incorporate DCE. They found
that DCE in termination tends to improve molecular weight control, while the oppo-
site occurs for DCE in the addition step. Jiang et al. [48] studied the effects of chain
transfer to monomer and solvent reactions on the RAFT copolymerization of Sty
and BA. They found that these reactions can have significant effects on M n and Ð.
They used the MM with free volume theory-based semi-empirical expressions for
diffusion-controlled termination. De Rybel et al. [14] introduced DCE expressions
for the initiation, termination, addition, fragmentation, and cross-termination steps
in an MM-based model for RAFT polymerization of Sty using 2-cyanopropan-2-yl
dodecyl carbonotrithioate and AIBN at 80 ∘ C.
Other approaches for modelling of DCE are available. For instance, Johnston-Hall
and Monteiro [55] used an expression previously developed by them [82, 83] for
chain-length- (l) and conversion (x)-dependent termination kinetic rate constants
(ktl,l (x)) for the modelling of RAFT and RP of MMA using 2-cyanopropan-2-yl
dithiobenzoate and AIBN) at 80 ∘ C. The addition step of the RAFT polymerization
scheme was also conversion and CL dependent while propagation kinetic rate
constants were only CL dependent. They used two modelling approaches, MM
and solution of the full MWD, obtaining good agreement with experimental data.
Konkolewicz et al. [34, 40] used an IRTO model where DCE were considered by
using a chain-length (l)-dependent termination kinetic rate constant. The effect of
chain length on kt depended on the size regime. Two size regimes were considered;
in the regime of relatively short chains, ktXn = kt1 Xn−α , where X n is number average
chain length and 𝛼 is a power-law exponent; a similar expression was used for
longer chains. The modelling approach that they used is described in more detail in
Section 7.4. Lovestead et al. [84] developed a RAFT model designed to estimate the
termination kinetic rate constant between two chains of disparate (short-long, s, l)

lengths, kts,l . Their model was applied to a theoretical study on RAFT polymerization
of Sty at 80 ∘ C. Peklak et al. [10, 85] modelled the RAFT polymerization of MMA
including DCE in bimolecular reactions of the RAFT polymerization scheme. The
kinetic rate constants depended on conversion and chain length, and contained
two contributions, chemical and diffusional. The diffusional portion was based on
free volume theory. In one case [85], they favourably compared their model pre-
dictions against experimental data of RAFT polymerization of MMA using cumyl
dithiobenzoate (C-DB) and AIBN at 70 ∘ C. In a second paper [10], they compared
two models with different levels of detail: one taking into account diffusional
limitations based on average chain lengths, and the other using the complete MWD
and accounting individually for each pair of interacting chains of different lengths.
In spite of their initial expectations, significant differences in their calculations
(conversion, MWD dispersity) were obtained. More recently, Devlaminck et al.
[42] modelled the macromolecular design by interchange of xanthates (MADIX)
polymerization of Sty and Sty/BA using (O-ethyl xanthate)-2-ethyl propionate as
RAFT agent. They used a hybrid modelling approach (see Section 7.4 for details).
The termination kinetic rate constant was assumed to be CL dependent. DCE in the
other kinetic rate coefficients were neglected. Recently, De Rybel et al. [44] used a
deterministic approach to test the validity of the quasi-steady-state approximation
for polymer radicals in a RAFT polymerization scheme where the termination
kinetic rate constant considered DCE. Model predictions were compared against
experimental data of RAFT polymerization of Sty using 2-cyano-2-propyl dodecyl
trithiocarbonate and 2,2-azobis(2-methylpropionitrile). DCE on all the reactions
involving polymer molecules in the RAFT copolymerization of hydroxyethyl
methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) were required
in order to adequately describe experimental data of polymerization rate, molecular
weight development, gel fraction, and swelling index evolution with a model based
on MM and a multifunctional approach [16, 17] (see Chapter 19 of this handbook
for further details).
7.2.3 Calculation of Full Molecular Weight Distributions

It is well known that the end-use properties of polymers are directly correlated to
their MWDs [86]. It is therefore important to calculate full MWDs and not only aver-
ages. The solution of the mathematical system of kinetic equations derived from a
given polymerization scheme is a challenge. A few models based on analytical solu-
tions of the full MWD in RAFT polymerization systems that reduce such difficult
task have been developed [34, 55, 87, 88]. De Rybel et al. [44] compared calculations
of full MWDs carried out using the so-called extended model (based on assumed
Flory-Schulz and Poisson distributions) against calculations obtained using a rig-
orous solution of the full MWD for a RAFT polymerization system. The resulting
distribution of macroradicals calculated with both methods differed strongly, but
the average properties had good agreement, depending on the gel regime. Devlam-
inck et al. [42] analysed the MADIX polymerization of Sty. The MWD obtained for
8
Experimental
7 Model
4.0
10–5 mass fraction [–]
6 8h
3.0
5
m2Cm
4 2.0
3 13 h 1.0
2 0
0.3
1 0.2
0 0.1
100 101 102 103 0 400 500 600
100 200 300
(a) i [–] (b) Chain length (m)
400 2.5
63% r=t
2
Chain length arm 3 (t)
300 53%
Mass fraction (10–2)
43%
1.5
32%
200
22% 1
100 11%
0.5
0
100 200 300 400 100 200 300 400 500
(c) Chain length arm 1 (r), r = s

(d) Chain length (m)
Figure 7.3 (a) Comparison between experimental (solid lines) and simulated (dashed lines)
mass chain-length distributions (CLDs) at eight hours of reaction in the MADIX polymeri-
zation of Sty. Source: Reproduced with permission from Devlaminck et al. [42]. © 2017,
Royal Society of Chemistry. (b) 3-D plot of the total MWD in dithiobenzoate-mediated
polymerization for the SF model where C m is concentration of polymer with total chain
length m. Source: Reproduced with permission from Zapata-González et al. [41]. © 2011,
John Wiley & Sons. (c) Contour plot of evolution of the bivariate population of three-arm
star species in MST; the labels denote conversion (mol%). Source: Reproduced with
permission from Zapata-Gonzalez et al. [36]. © 2018, Elsevier. (d) Comparison of experimen-
tal (red dotted line) and simulated (black solid line) number mass chain length distribution
of trithiocarbonate-mediated polymerization of Sty; conversions: 0.1, 0.3, and 0.6, left to
right. Source: Reproduced with permission from De Rybel et al. [44]. © 2018, Elsevier.
this process was a Flory–Schulz distribution, which can be considered as a special

case of RAFT polymerizations, as shown in Figure 7.3a.
7.2.3.1 Explicit Integration Methods

PBEs derived from RAFT polymerization schemes, such as that shown in Table 7.1,
result in very large systems of ODEs (106 –108 equations), which are usually stiff
[89]. Numerical implicit integration methods (which require the inversion of the
Jacobian matrix of the system) are often required to integrate stiff ODE systems
[90]. Derboven et al. [91] used this technique to describe a RAFT polymerization
scheme based on a degenerative chain transfer model. The use of this technique
for larger systems, such as the entire RAFT system, may become computationally
prohibitive. On the other hand, it is possible to take advantage of the different
dynamics exhibited by the polymer species present in this type of system. The
QSSA can be used for the subset of ODEs describing the fast dynamic species
(growing and intermediate radicals). These ODEs can then be transformed into
algebraic equations. In this way, the remaining ODEs with reduced stiffness can be
easily solved by using an inexpensive explicit integration numerical method (such
as Euler, Heun, Runge–Kutta, etc.), which does not require the Jacobian matrix
inversion. The coupled algebraic equations system for the fast species is solved in a
sequential, explicit, and computationally inexpensive way. Two methodologies for
calculation of full MWDs using these concepts have been reported: the so-called
reduced stiffness by QSSA (RSQSSA) [92], and the extended RSQSSA method [44].
RSQSSA has been used for comparison of calculations of full MWDs in RAFT
polymerization systems using dithiobenzoate RAFT agents, considering IRT, SF,
and IRTO RAFT models [41]. Unimodal MWDs were predicted for IRT and IRTO
RAFT models. The dormant species was the most abundant, as expected. Two-arm
polymer intermediates (Rm A• Rn ) were modelled as polymer molecules with 2-D
distributions. Average chain lengths about twice the length of dormant polymer
molecules, but of very low concentrations, were predicted by the model. In contrast,
bimodal MWDs were predicted for RAFT polymerizations based on the SF model
(see Figure 7.3b). These bimodal MWDs result from combination of populations
of low molecular weight dormant polymer and high molecular weight two-arm
intermediate polymer. The calculations obtained by using the RSQSSA technique
were compared against calculations obtained using PrediciTM [44]. MWDs calculated
using both techniques for growing, dormant, and dead polymer species (1-D species)
completely overlapped. However, calculations of MWDs for two-arm intermediates
(2-D species) differed significantly. The RSQSSA technique uses a full 2-D treatment
of the polymer two-arm adduct population. It contains complete information about
interconnectivity of all length combinations for the two arms. In the PrediciTM
implementation, the introduction of two 1-D distributions serves as chain length
memory for two polymer molecules tethered to the two-arm polymer intermediates.
The interconnectivity information seems to be lost in the PrediciTM model.
In another research contribution, a kinetic analysis of the MST using the RSQSSA
method was carried out [36]. The MST involves 2- and 3-D polymer species (two-arm
intermediates and three-arm star polymers [Eq. 7.17]), giving rise to a very large sys-
tem of ODEs (2.7 × 107 equations). The model predictions agreed well with the aver-
age molecular weight reported in the literature for polymerizations of Sty and MA,
and with concentrations of two-arm intermediate polymer molecules measured by
electron paramagnetic resonance (EPR) spectroscopy. Unimodal MWDs predicted
by the model corresponded to dormant polymer molecules and two-arm intermedi-
ate polymer molecules with symmetrical chain lengths in both arms. The maximum
concentration of three-arm star polymers corresponded to symmetrical structures,
namely molecules with equal chain lengths (m = n = t), as observed in Figure 7.3c.
However, as also observed in Figure 7.3c, unexpected polymer star molecules with
broad arm MWDs were also produced by cross-termination. The extended RSQSSA
model used for MWD calculations considered diffusion-controlled termination. It
is observed in Figure 7.3d that good agreement between calculated and experimen-
tal MWDs is obtained for the RAFT polymerization of Sty using 2-cyano-2-propyl
dodecyl trithiocarbonate as RAFT agent [44].
7.2.3.2 Probability-Generating Function

The probability-generating function (PGF) of a discrete distribution Rj , which for the
purposes of this chapter represents the concentration of polymer species of length j,
is defined by the transformation indicated in Eq. (7.20), where s is a number in the
unit circle of the complex domain.
∑
∞
PGF (s, t) = sj Rj (t) (7.20)
j=1
It is possible to calculate full MWDs in polymerization processes by using the PGF.

The technique consists of transforming the system of equations representing mass
balances of the polymer species into the generating function domain. This transfor-
mation results in a system of ODEs. These equations are then numerically solved and
discrete points of the full MWD are transformed back to the chain length domain by
numerical inversion of the PGF. In some simple cases, an analytical inversion is also
possible. Although the technique has been applied to a good number of polymer-
ization systems [93] since its first use in this field back in 1955 [94], only a couple
of contributions from the same group have used it for calculation of full MWDs
in RAFT polymerization [95, 96]. In one of these contributions [95], three RAFT
kinetic models (SF, IRT, and IRTO) were evaluated by using the PGF technique. In
the case of intermediate two-arm adduct, a 2-D distribution is obtained. The method
favourably compares in computation time with direct integration of the full set of
ODEs [41]. However, a drawback of the technique is that spurious numerical oscil-
lations appear at the tail of the distribution, at large molecular weights, due to the
inversion procedure (see Figure 7.4).
7.2.3.3 Calculations Using the Predici® Software

The Predici® software of CiT has been used to model RAFT polymerization pro-
cesses. The basic steps used for modelling of RAFT polymerization are listed in
Table 7.2. The main equilibrium between active and dormant polymers is described
by introducing two polymer populations, Q1 (m) and Q2 (n) (Q-type approach), which
keep track of the size of the two-arm adduct [97, 98].
A model implementation in PrediciTM , based on the SF model, was used to
study the RAFT polymerization of tert-butyldimethylsilyl methacrylate using
2-cyanopropan-2-yl dithiobenzoate and AIBN, in toluene, at 70 ∘ C [99]. The
propagation kinetic rate constant kp for this system was estimated by pulsed laser
polymerization (PLP)–size exclusion chromatography (SEC) experiments. The
bimolecular termination kinetic rate constant kt was fitted from experimental
data of conversion vs. time without RAFT agent. The cases with RAFT agent
0.02 IRT theory
0.012 SF theory
0.0175
0.01
Weight fraction 0.015
Weight fraction
0.008 0.0125
0.006 0.01
0.0075
0.004
0.005
0.002 0.0025
0 0
0 100 200 300 400 500 0 100 200 300 400 500
(a) Chain length (b) Chain length
0.0225 IRTO theory

0.02
0.0175
Weight fraction
0.015
0.0125
0.01
0.0075
0.005
0.0025
0
0 100 200 300 400 500
(c) Chain length
Figure 7.4 MWDs for the RAFT polymerization of Sty obtained by the PGF (symbols) and by direct integration (solid lines). Initial molar concentrations of
[AB] : [I] : [M] = 0.01 : 0.005 : 5. (a) SF theory, (b) IRT theory, and (c) IRTO theory. Source: Reproduced with permission from Fortunatti et al. [95]. © 2018,
John Wiley & Sons.
Table 7.2 Steps used in PrediciTM for kinetic modelling of RAFT polymerization.
Kinetic
Reaction Step name Step pattern coefficient
Initiation and first Initiation (rad) I → 2Rin • f , kd

propagation Rin • + M → R • (1)
First propagation of Initiation (anion) B• + M → R • (1) ki
leaving group
Propagation Propagation R• (m) + M → R• (m + 1) kp
RAFT Elemental R•in + AB → Rin A• B kadd
pre-equilibrium Elemental Rin A• B → R•in + AB kbd
Change
R (m) + AB → RA B(m)
• •
kadd
Change
RA• B(m) → R• (m) + AB kbd
Change RA• B(m) → RA(m) + B• kbd
Change RA(m) + B• → RA• B(m) kadd
Addition D-termination R• (m) + RA(n) → Q1 (m) + Q2 (n) ka
Fragmentation Change Q1 (m) → RA(m) kb
Change Q1 (m) → R• (m) kb
Change Q2 (n) → RA(n) kb
Change Q2 (n) → R (n)
•
kb
Intermediate radical Condensation R• (r) + Q1 (q) → T(r + q) ktir
termination Condensation R• (r) + Q2 (q) → T(r + q) ktir
Termination Termination by R• (n) + R• (m) → P(n + m) ktc
combination/ R• (n) + R• (m) → P(n) + P(m) ktd
disproportionation
Termination of small Change R•in + R• (n) → P (n) kt
radicals Change B• + R• (n) → P(n) kt
Elemental B• + B• → BB kt
were used to estimate all the addition and fragmentation kinetic rate constants
(kadd = ka = 1.80 × 104 l mol−1 s−1 and kbd = kb = 2.0 × 10−2 s−1 ). Very good agree-
ment between experimental data and calculated profiles of monomer conversion vs.
time, RAFT agent consumption, as well as Mw and Ð vs. conversion, was obtained.
The model used also described well the effect of initiator concentration. A short
induction period, probably induced by slow fragmentation of the one-arm adduct
in the pre-equilibrium, was observed.
The RAFT polymerization of Sty using 1,1′ -azobis(cyclohexanecarbonitrile) as
initiator and 2-[(phenylthioxomethyl)thio]-acetic acid as RAFT agent (RAFT agent
with relatively poor leaving group), conducted in batch and discrete semibatch
modes under bulk and solution (toluene) conditions, at 90 ∘ C, was studied by
Hlalele et al. [100]. The Q-type PrediciTM modelling approach was used to model
RAFT polymerizations in batch and semibatch modes. In the case of semibatch
operating mode, a fraction of the total monomer (∼14% w/w) was polymerized
at the early stages of polymerization, yielding low-dispersity RAFT oligomers;
thereafter, the remaining monomer was added in a single shot to complete the
reaction. As a result, narrower molar mass distributions, with reduced amounts
of low molar mass oligomers, were obtained. Lower Ð values were obtained as
monomer feed time of the remaining monomer was delayed. Also, it was shown
that the fraction of polymer molecules retaining EGF reached similar values to
the fraction of polymer molecules obtained when using a RAFT agent with a good
living group after 30% monomer conversion.
The polymerization kinetics of BA, using S-thiobenzoyl-2-thiopropionate and
𝛼-methyl-4(methylmercapto)-𝛼-morpholinopropiophenone, was studied in toluene
at −40 ∘ C ([101]. Two ) experimental methods were used to estimate the equilibrium
ka
constant Keq = k : single fast EPR scanning, during (pseudo)stationary pho-
b
topolymerization, which results in K eq = (2.3 ± 0.6) × 105 l mol−1 ; and microsecond
time-resolved EPR, which leads to K eq = (3.4 ± 0.6) × 105 l mol−1 . In the second
method, the propagating (R•m ) and intermediate (Rm A• Rn ) radical concentrations
were monitored after applying the laser pulse. The experimental profiles were
subsequently used to estimate the fragmentation kinetic rate constant, leading to
kb = 3.1 × 104 s−1 . The addition–fragmentation equilibrium constant was estimated
using a kinetic model developed in PrediciTM that considered the occurrence of
k
intermediated radical termination. The best fit was attained with Ccross = ktir = 0.25.
t
7.3 Stochastic Modelling Techniques (SMTs)
Stochastic or random processes are based on the theory of probability. They are a
collection of random variables indexed by time. Contrary to DMTs, in which there
is a unique solution for the analysed system, in SMTs some degree of uncertainty is
present even if the initial conditions are known. The process can evolve in multiple
ways (often infinite) and, therefore, there are multiple solutions of the system. One
event is selected between the whole range of possibilities depending on the type of
SMT used. The most popular SMT in polymer reaction engineering (PRE) is kMC.
7.3.1 Monte Carlo

In this algorithm, initially proposed by Ulam and von Neumann during the Man-
hattan Project and later modified by Gillespie [102, 103] (in the so-called kMC), the
events are selected according to probabilities calculated from macroscopic or micro-
scopic parameters [104]. Comprehensive reviews on kMC have been published in the
literature [104, 105]. In addition, both aspects, computation time and solution preci-
sion, are determined by the initial number of molecules in the analysed system. One
of the advantages of kMC, compared to DMTs, is the more detailed microstructural
information of the polymer chains provided by kMC.
7.3 Stochastic Modelling Techniques (SMTs) 205
7.3.1.1 Homogeneous Systems

Drache et al. [7] carried out the RAFT polymerization of methyl acrylate using C-DB
as RAFT agent, at 80 ∘ C. They also simulated the system using a kMC model based on
IRT theory. Good agreement between model predictions and experimental data was
obtained. Pre-equilibrium and main equilibrium steps were included in the RAFT
polymerization scheme. The MWDs calculated with the model showed good agree-
ment with SEC measurements. They also modelled the RAFT polymerization of Sty
using benzyl dithiobenzoate (Bz-DB), 1-phenylethyl dithiobenzoate (PhEt-DB), and
C-DB, at 120 ∘ C, via Monte Carlo simulations [106, 107]. Drache et al. [108] pre-
sented a software program based on a kMC algorithm (mcPolymer) capable of mod-
elling RAFT polymerizations, even in parallel programming environments. In fact,
parallel programing has been demonstrated to be a remarkable strategy to decrease
computation time in kMC models, presenting the same level of performance (run-
ning times) as the PrediciTM software for versions not including kMC [109].
Prescott et al. [110] described the influence of CL-dependent kinetic rate constants
related to reactions that involve radicals, dormant and dead polymer molecules
in both homogeneous and heterogeneous systems. They used a kMC modelling
technique with pseudo-random number generators. Their results showed that the
presence of dormant species of large chain lengths led to increased lifetimes for
polymer radicals since reduced termination kinetic rate constants and zero–one
kinetic behaviour were inapplicable to RAFT emulsion polymerization. They also
studied the radical loss observed in the RAFT emulsion polymerization of Sty
using 2-phenylpropan-2-yl phenyldithioacetate (PPPDTA) as RAFT agent [111].
The system did not show a retardation effect. Nuclear magnetic resonance (NMR)
analyses did not show the presence of three-arm star polymer molecules, or build-up
of intermediate polymer radicals. Monte Carlo simulations suggested that radical
loss is mainly due to termination between two large polymer radical molecules.
Other contributions on the use of kMC method for modelling of homogeneous
RAFT polymerizations include a discussion on discrimination between IRT and
SF theories by the addition of an alkoxyamine [112]; analysis of theories for RAFT
polymerization using the Julia programming language [113]; fitting of kinetic rate
constants by using IRT including Eq. (7.15) and all possible reactions with primary
radicals [114]; and modelling of the RAFT polymerization Sty at 110 ∘ C, including
self-initiation in the polymerization Scheme [1].
7.3.1.2 Heterogeneous Systems

Tobita has modelled miniemulsion RAFT polymerizations using a kMC technique
based on the ‘competition technique’, which resulted in a faster execution code [27,
115–117]. In his first contribution, he compared IRT and SF theories. In the former
theory polymerization rate significantly increased when particle size (Dp ) decreased.
In contrast, an almost negligible increase in polymerization rate was observed as
Dp decreased, when the second model was used [27]. However, calculated MWDs
were inaccurate due to an improper account of the repetition of active periods. In a
subsequent publication, he considered the overall connection probability to account
for the ‘repetition of active periods’ effect in a proper manner [115]. He derived
expressions for Dp in RAFT miniemulsion polymerization [116]. Additionally, based

on previous RAFT model discrimination proposals using the Monte Carlo approach
[117], a series of poly(styryl dithiobenzoate)-mediated RAFT miniemulsion poly-
merizations of Sty were carried out at 60 ∘ C. The experimental results agreed well
with calculated profiles using IRT theory, in which polymerization rate increased
when Dp decreased [118]. Another contribution on RAFT miniemulsion polymer-
ization included the study of droplet nucleation [119].
7.4 Hybrid Methods

Modelling methods that combine deterministic and stochastic or probabilistic tech-
niques are explored and discussed in this section. Several Monte Carlo simulation
studies that obtain information from deterministic models expressed as systems of
ODEs have been used to model radical polymerization processes (see for instance
[120, 121]). However, very few of such studies have focused on the modelling of
RAFT polymerization. The use of these combined techniques is intended to reduce
the computation time of standard Monte Carlo algorithms.
The modelling technique used by Konkolewicz et al. [34, 40] in the development
of their IRTO model can be considered a hybrid one. They used a basic deterministic
model to describe the evolution of conversion, average molecular weights, and dis-
persity, resulting in a low dimensionality system of ODEs; however, the full MWD
was described by using a probabilistic approach. Each of the polymer distributions
(dormant, living, and dead polymer) was described by using probabilistic deriva-
tions, arguably to avoid direct integration of a large set of ODEs (one equation for
each chain size). However, one of the individual polymer populations, the dead poly-
mer distribution, was obtained by accumulating the previous distribution to that of
the newly formed dead polymer molecule in a discrete time interval, which is equiv-
alent to a numerical integration of the corresponding equations. Probabilities for the
full MWD were updated at each time interval by taking updated kinetic information
from the solution of the system of ODEs representing the basic model.
In the modelling work of Devlaminck et al. [42] for the MADIX polymerization
of Sty and copolymerization of Sty/BA, two approaches were used. A simple deter-
ministic model employing a variation of the MM was applied for the calculation of
conversion and average polymer properties (averages of the MWD and average chain
end-functionality). On the other hand, a modified version of Gillespie’s kMC method
was used to describe detailed copolymer composition microstructure.
7.5 Specific or Novel Polymerization Processes
7.5.1 Semibatch Polymerization

Polymerization rate in batch radical copolymerization depends on (co)monomers
and polymer radical current concentrations. Their concentration profiles are gov-
erned by the initial quantities charged to the reactor. In semibatch reactors, on the
7.5 Specific or Novel Polymerization Processes 207
other hand, the addition to the reactor of one or more reactants is dosified, in order
to modify/improve product quality, according to the reactants feeding policy.
Mole balances for the components present in semibatch copolymerization reactors
are given by Eq. (7.21), where Cm , Rm , Qm , MWm , 𝜌m , and V are the concentration,
consumption rate, molar feeding flow rate, molar mass and density for component
m, and volume, respectively. The change in volume for the reacting mixture con-
tained in the reactor is given by the sum of solvent feeding flow rate, F s , feeding flow
rate for component m, and the term related to the difference in densities between
comonomers 𝜌m and polymer 𝜌p , as shown in Eq. (7.22).
( )
d Cm V Q MWm
= Rm V + m (7.21)
dt 𝜌m
( )
dV ∑ Qm MWm ∑ 1 1
= Fs + + m VRm MWm − (7.22)
dt m
𝜌m 𝜌m 𝜌p
Total monomer conversion and cumulative copolymer composition (CFm ) are cal-
culated using Eqs. (7.23) and (7.24), respectively.
∑ ( )
m Vo Cm0 + ∫ Qm dt − VCm
x= ∑ ( ) for m = A and B (7.23)
m Vo Cm0 + ∫ Qm dt
Vo Cm0 + ∫ Qm dt − VCm
CFm = ∑ ( ) for m = A and B (7.24)
m V0 Cm0 + ∫ Qm dt − VCm
Semibatch reactors are often used to control cumulative copolymer composition,

CFm , and/or component m number average sequence length, SLn, m [122–124].
In binary copolymerization of comonomers A and B, the monomer that reacts
faster, say B, is usually fed following a semibatch feeding policy. The initial amount
of comonomer B charged to the reactor can be calculated from the Mayo–Lewis
equation, Eq. (7.25) and (7.26), where f A and f B are the unreacted molar fractions
of monomer A and monomer B, respectively. F A and F B are the instantaneous
copolymer compositions of monomer A and monomer B, respectively.
r1 fA2 + fA fB
FA = (7.25)
r1 fA2 + 2fA fB + r2 fB2
FB = 1 − FA (7.26)
The addition of comonomer B, QB , in a time interval Δt should satisfy a given
relationship between instantaneous copolymer composition and the number
average chain length (X n ), given by F m = f (X n ), for m = A or B, in order to obtain
the desired CFm vs. conversion profile. Different composition profiles can be
designed; for instance, uniform, linear gradient or tanh gradient, as defined in
Eq. (7.27)–(7.30), where Rp, m is the monomer m consumption rate and X n, targeted is
the targeted number average chain length.
Rp,A
FA = , FB = 1 − FA (7.27)
Rp,A + Rp,B
Uniform ∶ Fm = 0.5 (7.28)
Xn
Linear gradient ∶ Fm = (7.29)
Xn,targeted
( )
1 1 Xn 1
tan h gradient ∶ Fm = + tan h𝜆 − (7.30)
2 2 Xn,targeted 2
Wang et al. theoretically demonstrated that the synthesis of copolymers with con-
trolled copolymer compositions (uniform and gradient) is possible through semi-
batch operation during the copolymerization [59]. They carried out their calcula-
tions using the terminal model and the MM [59]. They compared the composition
performance of two cases, namely batch and semibatch RAFT copolymerization of
two monomers (A and B), assuming hypothetical values for the kinetic rate con-
stants, and addressed two sets of reactivity ratios (r A = 2, (10) and r B = 10, (0.1),
respectively). In a subsequent publication [22], they studied the semibatch copoly-
merization of Sty and BA using benzyl dithioisobutyrate (BDIB) and AIBN, at 70 ∘ C.
The feeding flow rate of comonomer B was controlled by a metering pump pro-
grammed with the optimal profile. Their experimental data agreed well with the
predicted profiles (an implicit penultimate model was used) of monomer conversion,
CFm , M n , and Ð for a targeted uniform composition of CFA = 0.25 and a linear gra-
dient semibatch policy. This group also studied the semibatch copolymerization of
St/BA using BDIB and 1,1′ -azobis(cyclohexane carbonitrile) (ACC) at 88 ∘ C, yielding
uniform, linear gradient, and tan h gradient copolymers, as well as triblock copoly-
mers with linear gradient mid-block composition profiles [23].
Constant and linear gradient copolymer composition, CFm , and constant number
average sequence length, SLn , profiles for the copolymerization of MMA (monomer
A) with a hypothetical monomer (denoted as B) of higher propagation rate, using
AIBN and 2-cyanopropan-2-yl 1H-pyrrole-1-carbodithioate at 60 ∘ C, were obtained
by using a chain model coupled to a sequence model, both derived by Ye and Schork
[60]. The proposed models were based on the MM for calculation of average proper-
ties. The presence of intermediate radicals was neglected. Two sets of reactivity ratios
were investigated, r A = 0.5 (0.1) and r B = 2 (10), respectively. Copolymers with con-
Xn
stant composition, F A = 0.5, linear gradient, FB = 1000 , and constant number average
sequence length, SLn, A = 3 or SLn, B = 3, were attained by adjusting the feeding flow
rate of monomer B.
7.5.2 Polymerizations in CSTRs/PFR

The effect of backmixing on the RAFT polymerization of a hypothetical monomer
carried out in a tubular reactor was addressed using two modelling approaches:
a train of CSTR-in-series (train of 1, 3, 5, and 10 reactors), and a recycle model
(1–99% recycling) [25]. A hypothetical ratio of [M] : [AB] : [I] = 1000 : 2 : 1 and a
space–time of 30 hours were assumed. The increase of backmixing (lower number
of CSTR-in-series or higher recycling percentage) resulted in a decrease of monomer
conversion, shorter chain lengths, and broader molar mass distributions. It was
found that Mn of dead polymer molecules was independent of backmixing, but
the concentration of dead polymer molecules decreased due to lower bimolecular
7.5 Specific or Novel Polymerization Processes 209
termination rates. Simulations generated with both models were similar in terms
of monomer conversion. However, monomer conversion was predicted to be
higher at the beginning of the polymerization when the recycle model was used.
Polymerization rate decreased afterwards.
The copolymerization of two hypothetical monomers, identified as A and B in
continuous reactors, with assumed reactivity ratios of r A = 2 and r B = 0.5, was
studied using the MM [125]. Three reactor configurations were addressed: single
CSTR, CSTR-PFR-CSTR trains, and PFR-CSTR-PFR trains, with a residence time
of 𝜏 = 20 000 s for each reactor. Lower conversions, lower X n , and higher Ð were
attained in the CSTRs. In contrast, the use of plug flow reactors (PFRs) resulted in
higher conversions, higher X n , and lower Ð. Copolymer compositions and sequence
length averages were calculated for each case. Compositional drift was observed
only in PFRs.
7.5.3 Branched Copolymerizations

The RAFT emulsion copolymerization of 1,3-butadiene and acrylonitrile (AN)
using KPS and 2-(((dodecylsulfanyl)carbonothioyl)sulfanyl)propanoic acid
(DoPAT) in water at 45–55 ∘ C was modelled using PrediciTM [126]. A high ratio
of [AB]0 : [I]0 was required to produce copolymers with low Ð values. Although
branching was neglected in the model, polymerization rate, expressed as conversion
vs. time, was adequately described. Since the predictions of molecular weight
development were underestimated with the model, a correction to account for
branching, using an additional exponent to the theoretical M n,th , was implemented,
as shown in Eq. (7.31).
1+x
Mn = Mn,thb + MRAFT (7.31)
A value of xb = 0.065 fitted M n , the experimental data, well at different RAFT
agent concentrations. A two-stage temperature operation was also considered in
order to reduce the observed inhibition periods. The first polymerization stage pro-
ceeded at 55 ∘ C and lasted four hours; the temperature was then lowered to 45 ∘ C.
Hyperbranched polymers with narrow MWDs can be synthesized using RAFT
agents with single double bonds, as observed in Figure 7.5.
The modelling of hyperbranching polymerization has been achieved with
application of the segment model, modified for inclusion of branch trackers
[127]. Three copolymerizations using 4-vinylbenzyl 1H-imidazole-4-carbodithioate
(RAFT agent) and AIBN were addressed: acrylamide/acrylic acid, acrylonitrile/
methacrylic acid, and ethylene/Sty. The system acrylamide/acrylic acid yielded
Figure 7.5 4-vinylbenzyl S

1H-imidazole-4-carbodithioate.
S
N
NH
hyperbranched polymers with low dispersities (X n ≈ 15 000, Ð≈1) whereas the

other cases produced low X n , indicating that hyperbranched structures were not
obtained.
The MM has been applied to the synthesis of hyperbranched polymers from
N-isopropylacrylamide (NIPAm) using 4-vinylbenzyl 1H-imidazole-4-carbodithio-
ate and AIBN at 65 ∘ C, in dioxane [128]. A mathematical model consider-
ing inhibition and retardation was developed. Three experimental cases were
addressed: [M] : [AB] : [I] = 100, 150, 200 : 1 : 0.5. Calculated Ð values of 1.2–1.4 and
branch points of 0.4–0.6 were obtained, indicating the formation of well-defined
hyperbranched copolymers.
The PrediciTM software of CiT was used to calculate R group molar mass distribu-
tions of star polymerizations [129]. The RAFT equilibrium was modelled using the
Q-approach while star chain lengths were calculated as the addition of their arms.
7.5.4 Microwave-Assisted (MA) RAFT Polymerization

Organic chemistry syntheses carried out in the presence of microwave irradiation
(MI) offer faster heating and polymerization rates, compared to conventional heat-
ing [130]. The phenomena observed in microwave-activated radical polymerizations
can be explained by what are known as ‘thermal effects’ (TE) or ‘microwave effects’
(ME) conceptual approaches. The former accounts for temperature gradients
reached within the reaction mixture due to lack of optimal temperature monitoring
and control. The resulting elevated temperatures directly affect polymerization rate
and molar mass development. In the case of ME, one or more reactions are affected;
these reactions reach unusually high kinetic rate constant values. Alternatively, ME
may be caused by side reactions that greatly affect the evolution of the reaction. It
is recommended to use optic fibre sensors to accurately measure reactor temper-
ature profiles and to help assess what causes the increases in polymerization rate
[131, 132].
Mathematical models for different microwave-assisted polymerization situations,
including microwave-assisted reversible addition–fragmentation chain transfer
(MA-RAFT) polymerization of vinyl monomers, based on ME, TE, or combinations
of both, have been proposed by Vivaldo-Lima’s group [20, 21, 133–137]. Three
main models have been used: (i) microwave-induced generation of radicals from
monomer (a ME approach, identified as Model 1); (ii) non-isothermal polymeriza-
tion (TE approach, identified as Model 2); and (iii) a specific reaction or a small
set of reactions that proceed much faster (a type of ME, identified here as Model
3). An example of Model 1, where monomeric radicals (M•r ) are generated from
monomer (M) due to microwave irradiation, is shown in Table 7.3. This approach
was first proposed by Aldana-García et al. to describe the emulsion polymerization
of Sty in water with sodium dodecyl sulphate as surfactant and KPS as initiator at
50 and 70 ∘ C [133]. The model was tested with several experimental cases under
conductive heating (CH) and MI obtaining fairly good predictions. This approach
has also been used in the study of RDRP systems [20, 21, 134–137].
Table 7.3 Implementation of Model 1 in Predici.
Kinetic
Reaction Step in Predici Pattern coefficient
Microwave-induced Elemental M → 2M•r kir

generation of radicals
First propagation Initiation (anion) M + M•r → P (1) ki
Propagation Propagation M + P(s) → P(s + 1) kp
In Model 2 all the kinetic rate constants depend on temperature, kj (T). If actual
temperature profiles are not known, predefined profiles, T(t), can be assumed. This
approach has been explored in the modelling of other RDRP cases [134–137].
Hernández-Ortiz et al. reported the first study on MA-RAFT polymerization of
Sty by application of the MM [20]. They addressed eight cases with and without ini-
tiator (AIBN) under conventional and microwave heating at 60, 72, and 98 ∘ C, using
2-cyanopropan-2-yl naphthalene-1-carbodithioate (CPDN) as RAFT agent. The
cases under conventional heating were used to fit the kinetic rate constants associ-
ated to the addition–fragmentation reactions. They used Model 1 for the cases under
MI. It was found that their approach described reasonably well the experimental
data, although Mn was overestimated at low conversions and Ð was overestimated
in all cases. The model captured well the faster polymerization rate in MA RAFT
polymerizations.
Zetterlund et al. modelled the MA-RAFT polymerization of Sty by implementing
Models 1–3 in the Predici software. They used 2-cyanopropan-2-yl dithiobenzoate
(CPDB) as the RAFT agent and AIBN as the initiator at 60 ∘ C [21]. Regarding the
implementation of Model 2, they assumed that the system reached temperatures
of 80 and 100 ∘ C. The propagation and first addition to RAFT agent reactions were
assumed to be enhanced by MI in Model 3. The best results were obtained with
Model 3 where kinetic rate coefficients kp and kadd were increased by one order of
magnitude.
7.6 Closing Remarks
The modelling and simulation of RAFT polymerization of vinyl monomers has

been achieved by using several numerical approaches. A large number of research
reports are based on the method of moments, kMC simulations, and the software
Predici. The cases modelled include synthesis of homopolymers with narrow
molar mass distributions, synthesis of polymer networks by crosslinking/branching
reactions of vinyl/divinyl monomers, microwave-assisted polymerizations, synthe-
sis of copolymers with controlled chain composition distributions via semibatch
operation modes, dispersion polymerizations carried out in supercritical carbon
dioxide, continuous stirred tank reactors, and miniemulsion polymerizations.
The use of modelling tools has been useful in the design of materials and processes
based on RAFT polymerization. There are still issues to be addressed, but research
efforts are already targeted at them.
Acknowledgments
Financial support from the following sources is gratefully acknowledged: (i)

Consejo Nacional de Ciencia y Tecnología (CONACYT, México), Project CB 239364
granted to E.V.-L., Project CB 256358 granted to E.S.-G., Project ‘Cátedras’ 707
granted to I.Z-G., and a PhD scholarship granted to P.L.-D.; (ii) DGAPA-UNAM,
Projects PAPIIT IG100718, IV100119 and sabbatical PASPA support to E.V.-L.;
and (iii) Facultad de Química-UNAM, research funds granted to E. V.-L. (PAIP
5000-9078).
References
1 Li, L., He, J., and Yang, Y. (2000). Monte Carlo simulation on living radical
polymerization with RAFT process. Chem. J. Chinese U. 21 (7): 1146–1148.
2 Zhang, M. and Ray, W.H. (2001). Modeling of “living” free-radical polymeriza-
tion with RAFT chemistry. Ind. Eng. Chem. Res. 40 (20): 4336–4352.
3 Barner-Kowollik, C., Quinn, J.F., Morsley, D.R. et al. (2001). Modeling
the reversible addition – fragmentation chain transfer process in cumyl
dithiobenzoate-mediated styrene homopolymerizations: assessing rate coef-
ficients for the addition – fragmentation equilibrium. J. Polym. Sci., Part A:
Polym. Chem. 39 (9): 1353–1365.
4 Wang, A.R. and Zhu, S. (2003). Modeling the reversible addition –
fragmentation transfer polymerization process. J. Polym. Sci., Part A:
Polym. Chem. 41 (11): 1553–1566.
5 Wang, A.R. and Zhu, S. (2003). Effects of diffusion-controlled radical reactions
on RAFT polymerization. Macromol. Theory Simul. 12 (2–3): 196–208.
6 Luo, Y.W. (2003). Monte Carlo simulations for the very beginning of RAFT
seeded emulsion polymerization. Chem. J. Chinese U. 24 (10): 1926–1928.
7 Drache, M., Schmidt-Naake, G., Buback, M. et al. (2005). Modeling RAFT poly-
merization kinetics via Monte Carlo methods: Cumyl dithiobenzoate mediated
methyl acrylate polymerization. Polymer 46 (19): 8483–8493.
8 Theis, A., Feldermann, A., Charton, N. et al. (2005). Living free radical
polymerization (RAFT) of dodecyl acrylate: chain length dependent termi-
nation, mid-chain radicals and monomer reaction order. Polymer 46 (18):
6797–6809.
9 Monteiro, M.J. (2005). Modeling the molecular weight distribution of block
copolymer formation in a reversible addition – fragmentation chain transfer
mediated living radical polymerization. J. Polym. Sci., Part A: Polym. Chem.
43 (22): 5643–5651.
References 213
10 Peklak, A.D. and Butte, A. (2006). Modeling of diffusion limitations in bulk

RAFT polymerization. Macromol. Theory Simul. 15 (7): 546–562.
11 Pallares, J., Jaramillo-Soto, G., Flores Cataño, C. et al. (2006). A comparison
of reaction mechanisms for reversible addition – fragmentation chain transfer
polymerization using modeling tools. J. Macromol. Sci. Part A Pure Appl. Chem.
43 (9): 1293–1322.
12 Mastan, E., Li, X., and Zhu, S. (2015). Modeling and theoretical development in
controlled radical polymerization. Prog. Polym. Sci. 45: 71–101.
13 Zhou, Y.-N. and Luo, Z.-H. (2016). State-of-the-art and progress in method of
moments for the model-based reversible- deactivation radical polymerization.
Macromol. React. Eng. 10 (6): 516–534.
14 De Rybel, N., Van Steenberge, P.H.M., Reyniers, M.-F. et al. (2017). An update
on the pivotal role of kinetic modeling for the mechanistic understanding and
design of bulk and solution RAFT polymerization. Macromol. Theory Simul.
26 (1): 1600048.
15 Hernández-Ortiz, J.C., Vivaldo-Lima, E., Dubé, M.A. et al. (2014). Modeling
of network formation in reversible addition-fragmentation transfer (RAFT)
copolymerization of vinyl/divinyl monomers using a multifunctional polymer
molecule approach. Macromol. Theory Simul. 23 (3): 147–169.
16 Espinosa-Pérez, L., Hernández-Ortiz, J.C., López-Domínguez, P. et al. (2014).
Modeling of the production of hydrogels from hydroxyethyl methacrylate and
(Di)ethylene glycol dimethacrylate in the presence of RAFT agents. Macromol.
React. Eng. 8 (8): 564–579.
17 López-Domínguez, P., Hernández-Ortiz, J.C., Barlow, K.J. et al. (2014). Model-
ing the kinetics of monolith formation by RAFT copolymerization of styrene
and divinylbenzene. Macromol. React. Eng. 8 (10): 706–722.
18 Jiang, J., Wang, W., Li, B., and Zhu, S. (2017). Modeling and experimentation of
RAFT solution copolymerization of styrene and butyl acrylate, effect of chain
transfer reactions on polymer molecular weight distribution. Macromol. React.
Eng. 11: 1700029. doi:https://doi.org/10.1002/mren.201700029.
19 Oliveira, D., Dias, R.C.S., and Costa, M.R.P.F.N. (2016). Modeling RAFT
gelation and grafting of polymer brushes for the production of molecularly
imprinted functional particles. Macromol. Symp. 370 (1): 52–65.
20 Hernández-Ortiz, J.C., Jaramillo-Soto, G., Palacios-Alquisira, J. et al. (2010).
Modeling of polymerization kinetics and molecular weight development in the
microwave-activated RAFT polymerization of styrene. Macromol. React. Eng.
4 (3–4): 210–221.
21 Zetterlund, P.B. and Perrier, S. (2011). RAFT polymerization under microwave
irradiation: toward mechanistic understanding. Macromolecules 44 (6):
1340–1346.
22 Sun, X., Luo, Y., Wang, R. et al. (2007). Programmed synthesis of copolymer
with controlled chain composition distribution via Semibatch RAFT copolymer-
ization. Macromolecules 40 (4): 849–859.
23 Sun, X., Luo, Y., Wang, R. et al. (2008). Semibatch RAFT polymerization for
producing ST/BA copolymers with controlled gradient composition profiles.
AlChE J. 54 (4): 1073–1087.
24 Jaramillo-Soto, G., Castellanos-Cárdenas, M.L., García-Morán, P.R. et al. (2008).

Simulation of RAFT dispersion polymerization in supercritical carbon dioxide.
Macromol. Theory Simul. 17 (6): 280–289.
25 Bitsch, B., Barner-Kowollik, C., and Zhu, S. (2011). Modeling the effects of reac-
tor backmixing on RAFT polymerization. Macromol. React. Eng. 5 (1): 55–68.
26 Butté, A., Storti, G., and Morbidelli, M. (2001). Miniemulsion living free radical
polymerization by RAFT. Macromolecules 34 (17): 5885–5896.
27 Tobita, H. and Yanase, F. (2007). Monte Carlo simulation of controlled/living
radical polymerization in emulsified systems. Macromol. Theory Simul. 16 (4):
476–488.
28 Altarawneh, I.S., Gomes, V.G., and Srour, M.S. (2008). The influence of
xanthate-based transfer agents on styrene emulsion polymerization: mathe-
matical Modeling and model validation. Macromol. React. Eng. 2 (1): 58–79.
29 Barner-Kowollik, C., Buback, M., Charleux, B. et al. (2006). Mechanism and
kinetics of dithiobenzoate-mediated RAFT polymerization. I. The current
situation. J. Polym. Sci., Part A: Polym. Chem. 44 (20): 5809–5831.
30 Moad, G. (2014). Mechanism and kinetics of dithiobenzoate-mediated RAFT
polymerization - status of the dilemma. Macromol. Chem. Phys. 215 (1): 9–26.
31 Monteiro, M.J. and De Brouwer, H. (2001). Intermediate radical termination
as the mechanism for retardation in reversible addition-fragmentation chain
transfer polymerization. Macromolecules 34 (3): 349–352.
32 Wang, A.R., Zhu, S., Kwak, Y. et al. (2003). A difference of six orders of
magnitude: a reply to “the magnitude of the fragmentation rate coefficient”.
J. Polym. Sci., Part A: Polym. Chem. 41 (18): 2833–2839.
33 Buback, M. and Vana, P. (2006). Mechanism of dithiobenzoate-mediated RAFT
polymerization: a missing reaction step. Macromol. Rapid Commun. 27 (16):
1299–1305.
34 Konkolewicz, D., Hawkett, B.S., Gray-Weale, A. et al. (2008). RAFT polymeriza-
tion kinetics: combination of apparently conflicting models. Macromolecules 41
(17): 6400–6412.
35 Li, C., He, J., Liu, Y. et al. (2012). Probing the RAFT process using a model
reaction between alkoxyamine and dithioester. Aust. J. Chem. 65 (8): 1077–1089.
36 Zapata-Gonzalez, I., Saldivar-Guerra, E., and Licea-Claverie, A. (2017). Kinetic
modeling of RAFT polymerization via dithiobenzoate agents considering the
missing step theory. Chem. Eng. J. 326: 1242–1254.
37 Bamford, C.H. and Tompa, H. (1953). On the calculation of molecular weight
distributions from kinetic schemes. J. Polym. Sci. 10 (3): 345–350.
38 Bamford, C.H. and Tompa, H. (1954). The calculation of molecular weight
distributions from kinetic schemes. Trans. Faraday Soc. 50: 1097–1115.
39 Monteiro, M.J. (2005). Design strategies for controlling the molecular weight
and rate using reversible addition-fragmentation chain transfer mediated living
radical polymerization. J. Polym. Sci., Part A: Polym. Chem. 43 (15): 3189–3204.
40 Konkolewicz, D., Hawkett, B.S., Gray-Weale, A. et al. (2009). RAFT polymeriza-
tion kinetics: how long are the cross-terminating oligomers? J. Polym. Sci., Part
A: Polym. Chem. 47 (14): 3455–3466.
References 215
41 Zapata-González, I., Saldívar-Guerra, E., and Ortiz-Cisneros, J. (2011). Full

molecular weight distribution in RAFT polymerization. New mechanistic
insight by direct integration of the equations. Macromol. Theory Simul. 20 (6):
370–388.
42 Devlaminck, D.J.G., Van Steenberge, P.H.M., De Keer, L. et al. (2017). A
detailed mechanistic study of bulk MADIX of styrene and its chain extension.
Polym. Chem. 8 (45): 6948–6963.
43 Masoumi, S., Duever, T.A., Penlidis, A. et al. (2018). Model discrimination
between RAFT polymerization models using sequential Bayesian methodology.
Macromol. Theory Simul. 27 (5): 1800016.
44 De Rybel, N., Van Steenberge, P.H.M., Reyniers, M.-F. et al. (2018). How chain
length dependencies interfere with the bulk RAFT polymerization rate and
microstructural control. Chem. Eng. Sci. 177: 163–179.
45 Jiang, J., Wang, W.-J., Li, B.-G. et al. (2018). Tailoring uniform copolymer com-
position distribution via policy II RAFT solution copolymerization of styrene
and butyl acrylate. Macromol. React. Eng. 12 (4): 1800014.
46 Zapata-González, I., Saldívar-Guerra, E., Flores-Tlacuahuac, A. et al. (2012).
Efficient numerical integration of stiff differential equations in polymerisation
reaction engineering: computational aspects and applications. Can. J. Chem.
Eng. 90 (4): 804–823.
47 Wang, D., Li, X., Wang, W.-J. et al. (2012). Kinetics and Modeling of semi-batch
RAFT copolymerization with hyperbranching. Macromolecules 45 (1):
28–38.
48 Jiang, J., Wang, W.-J., Li, B.-G. et al. (2017). Modeling and experimentation of
RAFT solution copolymerization of styrene and butyl acrylate, effect of chain
transfer reactions on polymer molecular weight distribution. Macromol. React.
Eng. 11 (6): 1700029.
49 Pinto, M.A., Li, R., Immanuel, C.D. et al. (2008). Effects of reversible addition
fragmentation transfer (RAFT) on branching in vinyl acetate bulk polymeriza-
tion. Ind. Eng. Chem. Res. 47 (3): 509–523.
50 Hutchinson, R.A. (2005). Free-radical polymerization: homogeneous. In:
Handbook of Polymer Reaction Engineering (eds. T. Meyer and J. Keurentjes),
51 Mastan, E. and Zhu, S. (2015). Method of moments: a versatile tool for
deterministic modeling of polymerization kinetics. Eur. Polym. J. 68:
139–160.
52 Klumperman, B., van den Dungen, E.T.A., Heuts, J.P.A. et al. (2010).
RAFT-mediated polymerization-a story of incompatible data? Macromol. Rapid
Commun. 31 (21): 1846–1862.
53 Magallanes, A.R. (2019). Computational study of RAFT polymerization, explor-
ing the effect of retardation. Instituto Tecnologico de Tijuana. Bachelor Thesis,
filed 26 November 2019 and issued 26 November 2019.
54 Goh, Y.-K. and Monteiro, M.J. (2006). Novel approach to tailoring molecular
weight distribution and structure with a difunctional RAFT agent. Macro-
molecules 39 (6): 4966–4974.
55 Johnston-Hall, G. and Monteiro, M.J. (2007). Kinetic Modeling of “living” and

conventional free radical polymerizations of methyl methacrylate in dilute and
gel regimes. Macromolecules 40 (20): 7171–7179.
56 Gao, X. and Zhu, S. (2011). Modeling analysis of chain transfer in reversible
addition-fragmentation chain transfer polymerization. J. Polym. Sci., Part A:
Polym. Chem. 112 (1): 497–508.
57 Zhang, M. and Ray, W.H. (2002). Modeling of “living” free-radical polymer-
ization processes. I. Batch, semibatch, and continuous tank reactors. J. Appl.
Polym. Sci. 86 (7): 1630–1662.
58 Ross, R.T. and Laurence, R.L. (1976). Gel effect and free volume in the bulk
polymerization of methyl methacrylate. AlChE Symp. Ser. 160: 1974–1974.
59 Wang, R., Luo, Y., Li, B. et al. (2006). Design and control of copolymer com-
position distribution in living radical polymerization using semi-batch feeding
policies: a model simulation. Macromol. Theory Simul. 15 (4): 356–368.
60 Ye, Y. and Schork, F.J. (2009). Modeling and control of sequence length distri-
bution for controlled radical (RAFT) copolymerization. Ind. Eng. Chem. Res. 48
(24): 10827–10839.
61 Zhang, M. and Ray, W.H. (2002). Modeling of “living” free-radical polymeriza-
tion processes. II. Tubular reactors. J. Appl. Polym. Sci. 86 (5): 1047–1056.
62 Zhou, Y.-N., Guan, C.-M., and Luo, Z.-H. (2010). Kinetic modeling of two-step
RAFT process for the production of novel fluorosilicone triblock copolymers.
Eur. Polym. J. 46 (11): 2164–2173.
63 Ulitin, N.V., Nasyrov, I.I., Deberdeev, T.R. et al. (2012). Kinetic approach to
modeling the radical polymerization of styrene in the presence dibenzyl trithio-
carbonate. Russ. J. Phys. Chem. B 6 (6): 752–760.
64 Ulitin, N.V. and Oparkin, A.V. (2014). Kinetic modeling of Pseudoliving free
radical styrene polymerization occurring via reversible addition – fragmentation
chain transfer. Theor. Found. Chem. Eng. 48 (4): 434–443.
65 Ulitin, N.V., Tereshenko, K.A., Deberdeev, T.R. et al. (2015). Pseudolive radical
polymerization of butyl acrylate in the presence of trithiocarbonates: model-
ing the kinetics and regulation of the molecular mass characteristics of the
polymer. Theor. Found. Chem. Eng. 49 (1): 79–87.
66 Velasquez, E., Rieger, J., Stoffelbach, F. et al. (2016). Surfactant-free
poly(vinylidene chloride) latexes via one-pot RAFT-mediated aqueous poly-
merization. Polymer 106: 275–284.
67 Li, X., Wang, W.-J., Weng, F. et al. (2014). Targeting copolymer composition
distribution via model-based monomer feeding policy in semibatch RAFT
mini-emulsion copolymerization of styrene and butyl acrylate. Ind. Eng. Chem.
Res. 53 (18): 7321–7332.
68 Jennings, J., Beija, M., Kennon, J.T. et al. (2013). Advantages of block copoly-
mer synthesis by RAFT-controlled dispersion polymerization in supercritical
carbon dioxide. Macromolecules 46 (17): 6843–6851.
69 López-Domínguez, P., Jaramillo-Soto, G., and Vivaldo-Lima, E. (2018). A mod-
eling study on the RAFT polymerization of vinyl monomers in supercritical
carbon dioxide. Macromol. React. Eng. 12 (4): 1800011.
References 217
70 Jaramillo-Soto, G., García-Morán, P.R., Enríquez-Medrano, F.J. et al. (2009).

Effect of stabilizer concentration and controller structure and composition on
polymerization rate and molecular weight development in RAFT polymeriza-
tion of styrene in supercritical carbon dioxide. Polymer 50 (21): 5024–5030.
71 Biasutti, J.D., Davis, T.P., Lucien, F.P. et al. (2005). Reversible
addition–fragmentation chain transfer polymerization of methyl methacrylate in
suspension. J. Polym. Sci., Part A: Polym. Chem. 43 (10): 2001–2012.
72 Nguyen, T.L.U., Farrugia, B., Davis, T.P. et al. (2007). Core-shell microspheres
with surface grafted poly(vinyl alcohol) as drug carriers for the treatment
of hepatocellular carcinoma. J. Polym. Sci., Part A: Polym. Chem. 45 (15):
3256–3272.
73 Cunningham, M.F. (2008). Controlled/living radical polymerization in aqueous
dispersed systems. Prog. Polym. Sci. 33 (4): 365–398.
74 Zhang, Y., Ding, J., and Gong, S. (2013). Preparation of molecularly imprinted
polymers for vanillin via reversible addition-fragmentation chain transfer sus-
pension polymerization. J. Appl. Polym. Sci. 128 (5): 2927–2932.
75 Gonçalves, M.A.D., Pinto, V.D., Costa, R.A.S. et al. (2013). Stimuli-responsive
hydrogels synthesis using free radical and RAFT polymerization. Macromol.
Symp. 333 (1): 41–54.
76 Oliveira, M., Barbosa, B.S., Nele, M. et al. (2014). Reversible
addition–fragmentation chain transfer polymerization of vinyl acetate in bulk
and suspension systems. Macromol. React. Eng. 8 (6): 493–502.
77 Odian, G. (2004). Principles of Polymerization, 4e. Hoboken, NJ, N: Wiley.
2e. San Diego, CA: Elsevier.
79 Shipp, D.A. and Matyjaszewski, K. (1999). Kinetic analysis of con-
trolled/“living” radical polymerizations by simulations. 1. The importance of
diffusion-controlled reactions. Macromolecules 32 (9): 2948–2955.
80 Delgadillo-Velazquez, O., Vivaldo-Lima, E., Quintero-Ortega, I.A. et al. (2002).
Effects of diffusion-controlled reactions on atom-transfer radical polymerization.
AlChE J. 48 (11): 2597–2608.
81 D’hooge, D.R., Reyniers, M.-F., and Marin, G.B. (2013). The crucial role of dif-
fusional limitations in controlled radical polymerization. Macromol. React. Eng.
7 (8): 362–379.
82 Johnston-Hall, G., Stenzel, M.H., Davis, T.P. et al. (2007). Chain length depen-
dent termination rate coefficients of methyl methacrylate (MMA) in the gel
regime: accessing ktii using reversible addition-fragmentation chain transfer
(RAFT) polymerization. Macromolecules 40 (8): 2730–2736.
83 Vana, P., Davis, T.P., and Barner-Kowollik, C. (2002). Easy access to
chain-length-dependent termination rate coefficients using RAFT polymer-
ization. Macromol. Rapid Commun. 23 (16): 952–956.
84 Lovestead, T.M., Theis, A., Davis, T.P. et al. (2006). Accessing the chain length
dependence of the termination rate coefficient for disparate length radicals via
reversible addition fragmentation chain transfer chemistry: a theoretical study.
Macromolecules 39 (15): 4975–4982.
85 Peklak, A.D., Butte, A., Storti, G. et al. (2005). Gel effect in the bulk reversible
addition – fragmentation chain transfer polymerization of methyl methacry-
late: modeling and experiments. J. Polym. Sci., Part A: Polym. Chem. 44 (3):
1071–1085.
86 Read, D.J., Auhl, D., Das, C. et al. (2011). Linking models of polymerization
and dynamics to predict branched polymer structure and flow. Science 333
(6051): 1871–1874.
87 Tobita, H. (2006). Fundamental molecular weight distribution of RAFT poly-
mers. Macromol. React. Eng. 2 (5): 371–381.
88 Harrisson, S. (2018). Distribution of an ideal deactivation radical radical poly-
merization deactivation polymerization. Polymers 10 (8): 887–887.
89 Enright, W.H., Hull, T.E., and Lindberg, B. (1975). Comparing numerical meth-
ods for stiff systems of O.D.E.s. BIT 15: 10–48.
90 Byrne, D. and Hindmarsh, A.C. (1987). Siff ODE solvers: a review of corning
attractions. J. Comput. Phys. 70 (1): 1–62.
91 Derboven, P., Van Steenberge, P.H.M., Vandenbergh, J. et al. (2015). Improved
livingness and control over branching in RAFT polymerization of acrylates:
could microflow synthesis make the difference? Macromol. Rapid Commun. 36
(24): 2149–2155.
92 Saldívar-Guerra, E., Infante-Martínez, R., Vivaldo-Lima, E. et al. (2010).
Returning to basics: direct integration of the full molecular-weight distribu-
tion equations in addition polymerization. Macromol. Theory Simul. 19 (6):
151–157.
93 Dotson, N.A., Galván, R., Laurence, L.R. et al. (1996). Polymerization Process
Modeling. New York, NY: Wiley-VCH.
94 Howe, J.P. (2004). Method of integrating the rate equations for free radical initi-
ated. J. Chem. Phys. 23 (5): 899–902.
95 Fortunatti, C., Sarmoria, C., and Brandolin, A. (2014). Modeling of RAFT poly-
merization using probability generating functions. Detailed prediction of full
molecular weight distributions and sensitivity analysis. Macromol. React. Eng. 8
(12): 781–795.
96 Fortunatti, C., Sarmoria, C., Brandolin, A. et al. (2014). Prediction of the full
molecular weight distribution in RAFT polymerization using probability gener-
ating functions. Comput. Chem. Eng. 66: 214–220.
97 Vana, P., Davis, T.P., and Barner-Kowollik, C. (2002). Kinetic analysis of
reversible addition fragmentation chain transfer (RAFT) polymerizations: condi-
tions for inhibition, retardation, and optimum living polymerization. Macromol.
Theory Simul. 11 (8): 823–835.
98 Wulkow, M., Busch, M., Davis, T.P. et al. (2004). Implementing the reversible
addition–fragmentation chain transfer process in PREDICI. J. Polym. Sci., Part
A: Polym. Chem. 42 (6): 1441–1448.
99 Nguyen, N.M., Margaillan, A., Pham, T.Q. et al. (2018). RAFT polymerization
of tert-butyldimethylsilyl methacrylate: kinetic study and determination of rate
coefficients. Polymers 10 (2): 224.
References 219
100 Hlalele, L., Pfukwa, R., and Klumperman, B. (2017). Simulation studies of the
discrete semi-batch RAFT–mediated polymerization of styrene using a RAFT
agent with relatively poor leaving group. Eur. Polym. J. 95: 596–605.
101 Meiser, W., Barth, J., Buback, M. et al. (2011). EPR measurement of fragmenta-
tion kinetics in dithiobenzoate-mediated RAFT polymerization. Macromolecules
44 (8): 2474–2480.
102 Gillespie, D.T. (1977). Exact stochastic simulation of coupled chemical reac-
tions. J. Phys. Chem. 81 (25): 2340–2361.
103 Gillespie, D.T. (2001). Approximate accelerated stochastic simulation of chem-
ically reacting systems approximate accelerated stochastic simulation of
chemically reacting systems. J. Chem. Phys. 115 (4): 1716–1733.
104 Brandão, A.L.T., Soares, J.B.P., Pinto, C. et al. (2015). When polymer reaction
engineers play dice: applications of Monte Carlo models in PRE. Macromol.
Theory Simul. 9 (3): 141–185.
105 Meimaroglou, D. and Kiparissides, C. (2014). Review of Monte Carlo meth-
ods for the prediction of distributed molecular and morphological polymer
properties. Ind. Eng. Chem. Res. 53 (22): 8963–8979.
106 Drache, M. and Schmidt-Naake, G. (2007). RAFT polymerization – investigation
of the initialization period and determination of the transfer coefficients.
Macromol. Symp. 259 (1): 397–405.
107 Drache, M. and Schmidt-Naake, G. (2008). Initialization of RAFT agents with
different leaving groups – determination of the transfer coefficients. Macromol.
Symp. 271 (1): 129–136.
108 Drache, M. and Drache, G. (2012). Simulating controlled radical polymeriza-
tions with mcPolymer – A Monte Carlo approach. Polymers 4 (3): 1416–1442.
109 Chaffey-Millar, H., Stewart, D., Chakravarty, M.M.T. et al. (2007). A parallelised
high performance Monte Carlo simulation approach for complex polymerisation
kinetics. Macromol. Theory Simul. 16 (6): 575–592.
110 Prescott, S.W. (2003). Chain-length dependence in living/controlled free-radical
polymerizations: physical manifestation and Monte Carlo simulation of
reversible transfer agents. Macromolecules 36 (25): 9608–9621.
111 Prescott, S.W., Ballard, M.J., Rizzardo, E. et al. (2005). Radical loss in
RAFT-mediated emulsion polymerizations. Macromolecules 38 (11): 4901–4912.
112 Ao, Y., He, J., Han, X. et al. (2007). Kinetic analysis of the cross reaction
between dithioester and alkoxyamine by a Monte Carlo simulation. J. Polym.
Sci., Part A: Polym. Chem. 45 (3): 374–387.
113 Pintos, E., Sarmoria, C., Brandolin, A. et al. (2016). Modeling of RAFT polymer-
ization processes using an efficient Monte Carlo algorithm in Julia. Ind. Eng.
Chem. Res. 55 (31): 8534–8547.
114 Ganjeh-Anzabi, P., Hadadi-Asl, V., Salami-Kaljahi, M. et al. (2012). A new
approach for Monte Carlo simulation of RAFT polymerization. Iran. J. Chem.
Chem. Eng. 31 (3): 75–84.
115 Tobita, H. (2010). Modeling controlled/living radical polymerization kinetics:
bulk and miniemulsion. Macromol. React. Eng. 4 (11–12): 643–662.
116 Tobita, H. (2011). Threshold particle diameters in miniemulsion

reversible-deactivation radical polymerization. Polymers 3 (4): 1944–1971.
117 Tobita, H. (2013). On the discrimination of RAFT models using miniemulsion
polymerization. Macromol. Theory Simul. 22 (8): 399–409.
118 Suzuki, K., Kanematsu, Y., Miura, T. et al. (2014). Experimental method to
discriminate RAFT models between intermediate termination and slow frag-
mentation via comparison of rates of miniemulsion and bulk polymerization.
Macromol. Theory Simul. 23: 136–146.
119 Luo, Y. and Yu, B. (2005). Monte Carlo simulation of droplet nucleation in
RAFT free radical miniemulsion polymerization. Polym. Plast. Technol. Eng.
43 (5): 1299–1321.
120 Paper, F., Tripathi, A.K., and Sundberg, D.C. (2015). A hybrid algorithm for
accurate and efficient Monte Carlo simulations of free-radical polymerization
reactions. Macromol. Theory Simul. 24 (1): 52–64.
121 Neuhaus, E., Herrmann, T., Vittorias, I. et al. (2014). Modeling the polymeric
microstructure of LDPE in tubular and autoclave reactors with a coupled deter-
ministic and stochastic simulation approach. Macromol. Theory Simul. 23 (7):
415–428.
122 Kozub, D.J. and MacGregor, J.F. (1992). Feedback control of polymer quality in
semi-batch copolymerization reactors. Chem. Eng. Sci. 47 (4): 929–942.
123 Arzamendi, G. and Asua, J.M. (1989). Monomer addition policies for copolymer
composition control in semicontinuous emulsion copolymerization. J. Appl.
Polym. Sci. 38: 2019–2036.
124 Saldívar, E. and Ray, W.H. (1997). Control of semicontinuous emulsion copoly-
merization reactors. AlChE J. 43 (8): 2021–2033.
125 Zargar, A. and Schork, F.J. (2009). Design of copolymer molecular architecture
via design of continuous reactor systems for controlled radical polymerization.
Ind. Eng. Chem. Res. 48 (9): 4245–4253.
126 Hlalele, L., D’hooge, D.R., Dürr, C.J. et al. (2014). RAFT-mediated ab initio
emulsion copolymerization of 1,3-butadiene with acrylonitrile. Macromolecules
47 (9): 2820–2829.
127 Zargar, A., Chang, K., Taite, L.J. et al. (2011). Mathematical modeling of hyper-
branched water-soluble polymers with applications in drug delivery. Macromol.
React. Eng. 5 (9–10): 373–384.
128 Kim, S.Y., Van Dyke, R., Chang, K. et al. (2015). Modeling of highly branched
water-soluble polymers with applications to drug delivery model extensions and
validation. Macromol. React. Eng. 9 (6): 545–555.
129 Chaffey-Millar, H., Busch, M., Davis, T.P. et al. (2005). Advanced computational
strategies for modelling the evolution of full molecular weight distributions
formed during multiarmed (star) polymerisations. Macromol. Theory Simul. 14
(3): 143–157.
130 De la Hoz, A. and Loupy, A. (2012). Microwaves in Organic Synthesis, 3e.
References 221
131 Herrero, M.A., Kremsner, J.M., and Kappe, C.O. (2008). Nonthermal microwave
effects revisited: on the importance of internal temperature monitoring and agi-
tation in microwave chemistry. J. Organomet. Chem. 73 (1): 36–47.
132 Kappe, C.O. (2013). How to measure reaction temperature in microwave-heated
transformations. Chem. Soc. Rev. 42 (12): 4977–4990.
133 Aldana-García, M.A., Palacios, J., and Vivaldo-Lima, E. (2005). Modeling of the
microwave initiated emulsion polymerization of styrene. J. Macromol. Sci. Part
A Pure Appl. Chem. 42 (9): 1207–1225.
134 López-Domínguez, P. and Vivaldo-Lima, E. (2013). Analysis of the microwave
activated atom transfer radical polymerization of methyl methacrylate and
styrene using modeling tools. Macromol. React. Eng. 7 (9): 463–476.
135 López-Domínguez, P., Olvera-Mancilla, J., Palacios-Alquisira, J. et al. (2018).
Kinetic modeling of vinyl acetate telomerization catalyzed by metal transition
complexes under thermal and microwave heating. J. Macromol. Sci. Part A Pure
Appl. Chem. 55 (3): 231–242.
136 Hernández-Meza, J.J., Jaramillo-Soto, G., García-Morán, P.R. et al. (2009).
Modeling of polymerization kinetics and molecular weight development in
the microwave-activated nitroxide-mediated radical polymerization of styrene.
Macromol. React. Eng. 3 (2–3): 101–107.
137 Xie, Z.-K., Guo, J.-K., and Luo, Z.-H. (2018). Assessment of microwave effect
on polymerization conducted under ARGET ATRP conditions. Macromol. React.
Eng. 12 (1): 1700032.
223
Dithioesters in RAFT Polymerization

Graeme Moad
8.1 Introduction
S S R
Z
1a Z = Aryl
1b Z = Alkyl
Aromatic dithioesters 1a, which include the dithiobenzoates, are one of the most
widely reported classes of RAFT agents with close to 3000 ScifinderTM entries relat-
ing to papers or patents showing structure 1a in the context of RAFT polymerization
between 1998 and 2020 (Figure 8.1). They are the most used RAFT agents for mediat-
ing the polymerization of methacrylates and methacrylamides where they can offer
better control over molar mass and molar mass distribution, and higher end-group
fidelity than other classes of RAFT agents (i.e. trithiocarbonates, xanthates, and
dithiocarbamates). Consistent with their high activity as RAFT agents, they also tend
to be more reactive in other contexts. This means that the dithioester end-groups are
more readily removed or transformed. This can be advantageous, or even essential,
in some biomedical [1, 2] and optoelectronic applications [3] where the presence of
the dithioester end-groups can present issues. However, poor end-group stability can
be detrimental to polymerization kinetics and can impact adversely on some poly-
mer properties. Methods for RAFT end-group transformation are discussed in the
chapter by Lowe and Dallerba [4]. For further specific information on dithioesters,
see Section 8.17.
Even though aliphatic dithioesters (1b) are also described in the first papers and
patents concerning RAFT polymerization, they have been seldom exploited, with
there being less than 250 Scifinder reports of structure 1b in the context of RAFT
polymerization (Figure 8.1). They (1b) have significantly lower activity as RAFT
agents than the aromatic dithioesters (1a), but they are also less prone to side reac-
tions and cause less retardation than the aromatic dithioesters.

224 8 Dithioesters in RAFT Polymerization
(a) 500 Figure 8.1 Publication rate of

papers on RAFT
Aromatic dithioester polymerization using various
Aliphatic dithioester classes of RAFT agents
400
provided as (a) publications
Trithiocarbonate
per year and (b) cumulative
Xanthate publications for the period
Publications (yr)
300 1998–2019. The data includes

Dithiocarbamate
both patent and open
literature publications and is
200 based on ScifinderTM
substructure searches carried
out in February 2020 on the
indicated structures refined
100 with the terms ‘RAFT’ and
‘MADIX’ (in the case of
xanthates).
0
2000 2005 2010 2015
Year
(b) 5000
Aromatic dithioester
4000 Aliphatic dithioester
Trithiocarbonate
Xanthate
Publications
3000
Dithiocarbamate
2000
1000
0
2000 2005 2010 2015
Year
8.2 Mechanism of RAFT Polymerization with Dithioester

Mediators
The sequence of addition–fragmentation equilibria that comprise RAFT polymer-

ization [5] is shown in Scheme 8.1. This scheme shows the RAFT agent as an ideal
transfer agent. In these circumstances, as in any radical polymerization with an ideal
chain transfer agent, the kinetics of RAFT polymerization should not be affected by
the presence of the RAFT agent, notwithstanding effects attributable to the differ-
ent molar mass of the reacting species (e.g. chain length dependent termination).
Termination occurs at a rate dictated by the radical concentration and, when an

exogenous initiator is used, the number of chains that undergo termination must
ultimately match the number of chains generated by initiation processes. It follows
that living characteristics will only be imparted when the molar mass of the polymer
formed is substantially lower than that which would be formed under similar condi-
tions in the absence of a RAFT agent. Thus, for good control, the number of polymer
molecules formed with RAFT agent-derived ends should far exceed the number of
dead chains formed by termination.
Initiation
M M
initiator I• Pn•
Reversible chain transfer/propagation

kadd kβ
Pn• + S S R Pn S • S R Pn S S + R
•
k–add k–β
Z Z Z
M
kp 1 2 3
Reinitiation
M M M
•
R• R M• Pm
ki
Chain equilibration/propagation
Pm• kaddP P S k–addP P •
+ S S Pn m • S Pn m S S + Pn
k–addP kaddP
Z Z Z
M M
kp 3 4 3 kp
Termination
•
kt
Pn• + Pm dead polymer
Scheme 8.1 Mechanism of RAFT polymerization with exogenous initiator.
While the basics of the mechanism have not changed from that described in
the first paper [5] and patent [143], the finer details of the mechanism of RAFT
polymerization mediated by dithiobenzoates have been the subject of intense study
over the past 20 years. Of concern have been the factors that cause retardation, the
stability of the various intermediates, and the extent to which those intermediates
might undergo side reactions such as intermediate radical termination. In 2006
an IUPAC task group, ‘Towards a Holistic Mechanistic Model for RAFT Polymer-
izations: Dithiobenzoates as Mediating Agents’, published a ‘dilemma paper’ [7]
that surveyed the then literature on polymerization with dithiobenzoate RAFT
agents and summarized the evidence for and against the various mechanisms for
retardation.
There were four major views expressed:
(a) That intermediate radical fragmentation (of species 2 and/or 4 in Scheme 8.1)
was slow such that this process, by itself, was responsible for retardation.
(b) That intermediate radical fragmentation would not by itself cause retardation
but was nonetheless sufficiently slow such that side reactions, such as inter-
mediate radical termination by self-reaction or cross-reaction with other radi-
cal species, competed with fragmentation, consumed active chains, and thereby
caused retardation.
(c) That reinitiation by the expelled radical R⋅ was rate determining, causing ini-
tialization to be slow. For example, there is clear evidence for this when R⋅ is
2-cyano-2-propyl and the monomer is an acrylate or an acrylamide [8].
(d) That apparent retardation was caused by extraneous factors not directly related
to the RAFT process, such as mitigation of auto-acceleration caused by the gel
or Trommsdorff effect, ineffective degassing, or impurities in the RAFT agent(s)
and other components of the polymerization medium.
Combinations of the above were also canvassed.

In 2014, the ‘dilemma paper’ [7] was followed by a paper summarizing devel-
opments in the mechanistic understanding that had occurred during the period
2006–2013 [9]. That period had seen the original paper [7] being well cited and a
doubling of the publication rate of papers concerning dithiobenzoate RAFT agents
(Figure 8.1). The period also saw publications on the use of dithiobenzoates in
controlling polymerization of acrylates, acrylamides, and styrenes significantly
diminish as a fraction of the total RAFT papers, mainly in favour of trithiocarbonate
RAFT agents [10–13]. The latter are generally more readily synthesized [14], are
less sensitive to hydrolysis and many other forms of degradation, and significantly,
polymerizations with these reagents generally display much less or (often) no
discernible retardation.
The 2014 review [9] came to the conclusion that, once the extraneous factors, i.e.
explanations (c) and (d) above, were eliminated, the experimental evidence was
overwhelmingly in favour of intermediate radical termination as the most likely
cause of retardation in polymerizations of more activated monomers (MAMs).
Nonetheless, debate on the importance of intermediate radical termination and
intermediate stability in dithiobenzoate-mediated RAFT polymerization con-
tinues [15–20]. Further discussion on kinetics and retardation mechanisms in
RAFT polymerization will be found in the chapters by Buback [21] and Quinn
et al. [22].
8.2.1 Transfer Coefficients of Dithioesters

The activity of a RAFT agent is determined by the values of two transfer coefficients,
Ctr (=ktr /kp ) and Ctr (=k−tr /k−𝛽 ). The chain transfer rate coefficient (ktr ) for a RAFT
agent is given by Eq. (8.1). The value of ktr depends on the rate of addition of the
propagating radical (Pn •) to the RAFT agent and a partition coefficient (𝜙), which
describes the partitioning of the intermediate radical (2) between the starting mate-
rials and products – refer to Scheme 8.1:
[ ]
k𝛽
k−add + k𝛽
The transfer agent-derived radical (R• ) is also partitioned between adding to the
monomer and reacting with the macroRAFT agent (3). The rate coefficient associ-
ated with this reaction (k−tr ) is defined in Eq. (8.2).
[ ]
k−add
k−tr = k−𝛽 𝜙𝛽 = k−𝛽 (8.2)
k−add + k𝛽
Methods used for measuring the transfer coefficients for conventional (irre-
versible) transfer agents can be used to estimate Ctr when the value of Ctr is low
(e.g. <1). However, these methods, which include an assumption that C−tr is zero,
will underestimate Ctr (Table 8.1). It is recommended that these values should be
called apparent transfer coefficients Ctr app . For dithiobenzoates, actual values of Ctr
may be higher than Ctr app by several orders of magnitude [23, 34]. A dependence of
Ctr app on the RAFT agent concentration and/or on monomer conversion provides
an indication that the reverse reaction is important.
The situation is simplified for macroRAFT agents in homopolymerization, where,
notwithstanding the effects of chain length, the forward and reverse reactions are the
same (Ctr = C−tr ) and the partition coefficient 𝜙 is 0.5 (Table 8.2).
Methods for determining transfer coefficients of RAFT agents (Ctr app , Ctr , or C−tr )
are described elsewhere in this volume [22]. However, one method of transfer con-
stant estimation requires special mention. The expression for dispersity for polymer-
ization with degenerative chain transfer (Eq. (8.3)) [39] can be rearranged to provide
a qualitative estimate of the transfer constant (Ctr ) (Eq. (8.4)).
( )
1 2−x 1
Ð=1+ + (8.3)
Xn x Ctr
where X n is the number average degree of polymerization and x is the monomer
conversion.
( )/( )
2−x 1
Ctr = Ð−1− (8.4)
x Xn
Strictly, the Dispersity method is only applicable to macroRAFT agents where the
Ctr values for the initial and product RAFT agent are the same (because they differ
only in chain length). Nonetheless, we have applied Eq. (8.4) to provide a ranking of
Ctr values for aromatic dithioesters [ZC(=S)—C(CH3 )2 CN] in MMA polymerization.
The estimates will be lower than the actual values. The data of Benaglia et al. [40]
for low (5–10%) monomer conversion was used to generate Figure 8.2. The presence
of ortho-substituents (b, c, e, g; blue shading in Figure 8.2) significantly reduces
the activity of dithiobenzoate RAFT agents. The presence of para substituents (d,
f, I, n; magenta shading) has little effect on activity. Perfluoro- (l) and bis-meta
electron-withdrawing substituents (j, k; red shading) enhance activity. The pyridyl
analogues (h, m; green shading) show significantly enhanced activity, substantially
Table 8.1 Transfer coefficients of dithioester RAFT agents Z—C(=S)S—R in RAFT polymerization.
RAFT agenta) Z R Monomer T (∘ C) C tr app b) C tr C −tr Methodc) References
5 Ph C(CH3 )2 (Ph) MMA 60 6.6 56 2500 W/K [23]

6 Ph C(CH3 )2 (CN) MMA 60 6.8 25 450 W/K [23]
11a Ph C(CH3 )2 (CO2 Et) MMA 60 1.7 — — W [23]
11a Ph C(CH3 )2 C(CH3 )3 MMA 60 0.4 — — W [23]
12 Ph C(CH3 )3 MMA 60 0.03 — — W [23]
5 Ph CH(CH3 )(Ph) MMA 60 0.15 — — W [23]
21 Ph CH2 Ph MMA 60 < 0.03 — — W [23]
5 Ph C(CH3 )2 (Ph) St 60 — 2000 10000 K [23]
21 Ph CH2 Ph MA 60 105 — — W [23]
70 PhCH2 C(CH3 )2 (CO2 Et) MA 60 70 — — K [24]
6 Ph C(CH3 )2 (CN) MMA 80 40 — — W [25]
6 Ph C(CH3 )2 (CN) tBDMSMA 70 9.3 — — K [26]
9 Ph C(CH3 )(CN)CH2 CH2 CO2 H MMA 80 > 50 — — W [25]
12 Ph C(CH3 )3 MMA 80 0.7 — — M [25]
17 Ph CH(Ph)(CH3 ) MMA 60 — 40-280 9900 W [27]
21 Ph CH2 Ph MMA 80 0.2 — — M [25]
6 Ph C(CH3 )2 (CN) MPEGMA 65 9.1 — — W [28]
7 Ph C(CH3 )(C2 H5 )(CN) DEGMA 70 0.5 — — W [29]
7 Ph C(CH3 )(C2 H5 )(CN) MPEGMA 70 0.5 — — W [29]
5 Ph C(CH3 )2 (Ph) St 120 — 2037 34 K [30]
17 Ph CH(CH3 )(Ph) St 120 — 3331 4173 K [30]
21 Ph CH2 Ph St 120 — 92 1057 K [30, 31]
21 Ph CH2 Ph St 60 190 — — W [32]
24 Ph CH2 CO2 H St 90 6 — — M [33]
— Ph C(CH3 )2 (CONH2 ) VAc 95 4 — — B [33]
a) Initial RAFT agent used in polymerization.

b) Published values of transfer coefficients that are based on a model that does not allow for partitioning of the intermediate radicals and/or the reversibility of chain
transfer are considered as apparent transfer coefficients (see text).
c) Method used: M – Mayo method, W – Walling method, K – kinetic simulation, B – M n (0) method. Refer to the chapter by Quinn et al. [22] and to the cited papers
for a detailed of the description of the methods.
For a full list of abbreviations, see the Abbreviations section.
S S
S TsO– S
+
N HN m
h
500 S S S
NC
S CF3 S S
CN j k
400 S S S S CF3 o S
S S S S S
H3CO COH3 F F S
b c e gF F
S p
300 S S S
F
F
F S
I
app S S S S
Ctr H3CO d F f NC i
n
200 S
S
a
100
0
a b c d e f g h i j k l m n o p
Figure 8.2 Values of apparent transfer coefficients (C tr app ) for aromatic dithioesters
[ZC(=S)S—C(CH3 )2 CN] in MMA polymerization estimated by the Dispersity method.
more so if protonated. The finding that para-substituents have relatively little effect
on the activity of dithiobenzoates is supported by other studies [41].
8.2.2 RAFT Equilibrium Coefficients with Dithioesters

The properties of RAFT agents are often discussed in terms of the values of the
equilibrium coefficients (K = kadd /k−add ) associated with radical addition to a thio-
carbonylthio compound [21, 42]. Rate coefficients (kadd ) for addition reported for
aromatic dithioesters 1b are ∼106 M−1 s−1 (Table 8.3). A high equilibrium coefficient
implies a low fragmentation rate for the radical adduct and an increased likelihood
for retardation and/or side reaction involving this species.
Methods for evaluating the equilibrium coefficients and implications concerning
retardation in RAFT processes are described elsewhere in this volume [21, 47].
8.3 Choice of RAFT Agents
The criteria for an effective RAFT polymerization can be summarized as follows

(Scheme 8.1, Figure 8.3): [6]
● The initial RAFT agents (1) and the macroRAFT agent (3) should have a reactive
C=S double bond (high kadd ).
● The intermediate radicals (2) and (4) should fragment rapidly (high k𝛽 , weak S—R
bond in the intermediate) and give no side reactions.
● The intermediate (2) should partition in favour of products (k𝛽 ≥ k−add ).
● The expelled radicals (R• ) must efficiently reinitiate polymerization (ki > kp ).
Table 8.2 Transfer coefficients of dithioester macroRAFT agents Z—C(=S)S—Pn in RAFT

polymerization.
Z Pn Monomer T (∘ C) C tr app a) C tr Methodb) References
Ph PMMA MMA 60 140 140 C [35, 36]

Ph PMMA BA 60 482 — C [36]
Ph PBA MMA 60 5 — C [36]
Ph PBA BA 60 ∼ 248 ∼ 248 C [36]
Ph PMMA MMA 80 > 500 — W [25]
Ph PSt St 40 — ∼ 6000 C [35]
Ph PSt St 60 > 103 — W [32]
Ph PAA AA 70 8.3 — K [37]
PhCH2 PMMA MMA 60 11 11 W [36]
PhCH2 PMMA BA 60 205 — W [36]
PhCH2 PBA MMA 60 2.6 — W [36]
PhCH2 PBA BA 60 116 116 W [36]
(CH3 )2 CH PSt St 60 42 42 W [36]
(CH3 )2 CH PSt BA 60 54 — W [36]
(CH3 )2 CH PBA St 60 50 — W [36]
(CH3 )2 CH PBA BA 60 59 59 W [36]
CH3 PSt St 60 — 180 C [35]
CH3 PSt St 40 — 220 C [38]
CH3 PSt MMA 40 — 0.83 C [38]
CH3 PMMA St 40 — 420 C [38]
CH3 PMMA MMA 40 — 40 C [38]
a) For macroRAFT agents in homopolymerization, it is assumed that Ctr app = Ctr = C−tr .
b) Method used: W – Walling method, K – kinetic simulation, C – chromatography. Refer to the
chapter by Quinn et al. [22] and the cited papers for further details.
Weak single bond
R′ • + S S R kaddR R′ S • S R
k–addR
Reactive Z Z
double bond
R,R′ are free radical
leaving groups (R • must
Z modifies addition and
also be able to reinitiate
fragmentation rates
polymerization)
Figure 8.3 Structural features of thiocarbonylthio RAFT agent and the intermediate
formed on radical addition. Source: Moad et al. [6]. Copyright 2005, CSIRO.
Table 8.3 Values of the RAFT equilibrium coefficients with dithioesters.
RAFT agenta) Z R Monomer/radical T (∘ C) k add (M−1 s−1 ) k −add (s−1 ) K eq (M−1 ) Methodb) References
20 Ph--- PBA BA −40 1.4 × 106 4.7 3.4 × 105 EPR2 [43]
20 Ph--- PBA BA −40 — — 2.3 × 105 EPR1 [43]
70 — — 75
6 Ph--- 60 — — 13 EPR1 [44]
70 — — 9
CN CN
90 — — 5.1
100 — — 4.6
11b Ph--- 70 — — 10.8 EPR1 [45]
90 — — 7.1
CO2CH3 CO2CH3
100 — — 5.6
110 — — 2.6
12 Ph--- 20 5 × 106 8 × 10−3 6(±4) × 108 EPR3 [46]
12 Ph--- 20 — — 4.5 × 108 Theory [46]
a) Initial RAFT agent used.

b) EPR1 – direct determination of radical concentrations by electron paramagnetic resonance spectroscopy; EPR2 – measurement of radical concentrations vs. time
in SP-PLP-EPR (single pule-pulsed laser photolysis-electron paramagnetic resonance) experiments and PredeciTM simulation of experimental data; EPR3 – spin
trapping experiments; theory – ab initio calculations.
8.3.1 Aromatic Dithioesters (Z = Aryl or Heteroaryl)

RAFT polymerizations making use of the more common (most used or commercially
available) aromatic dithioesters and a few others chosen for their relevance to the
text are shown in Table 8.4. We consider functional dithioesters and bis-dithioesters
separately below.
The tertiary aralkyl or cyanoalkyl dithiobenzoates, e.g. 5–9 (Table 8.4) are much
used (Figure 8.4) for synthesizing polymers based on 1,1-disubsituted monomers,
namely, methacrylates (e.g. MMA) or methacrylamides (e.g. HPMAm). This can be
understood in terms of these RAFT agents offering the highest transfer coefficients
in polymerizations of these monomers and thence the lowest dispersities and highest
end-group fidelity (cf. Figure 8.5). Retardation when preparing such polymers with
X n > 50 appears minimal. Auto-acceleration is also minimal [23].
However, the aromatic dithioesters are more sensitive to nucleophilic attack and
more prone to hydrolysis, for example, when employed in aqueous media [557, 558].
Issues of RAFT agent stability can give rise to a conversion plateau, for example, in
the polymerization of HPMAm in aqueous solution. An advantage of the aromatic
dithioesters is that they are more reactive in end-group transformation/removal
reactions post-RAFT polymerization (Section 8.17).
The tertiary alkoxycarbonylalkyl dithiobenzoates, e.g. 11, are considerably
less active than 5–9 and offer, at best, poor control over polymerization of
1,1-disubsituted monomers. Primary, secondary and unsubstituted tertiary
alkyl dithiobenzoates do not provide significant control polymerization of
1,1-disubsituted monomers in a batch process. These dithiobenzoates are those
preferred for mediating polymerization of monosubstituted monomers.
Dithiobenzoates typically give some retardation in polymerizations of acrylates
and acrylamides and this can be pronounced particularly when targeting low molar
(a) 250 (b) 250

Ph (CO2R)CR2
Ar CNCR2
200 200 PhCR2
All
Publications (yr)
Publications (yr)
150 150
100 100
50 50
0 0
2000 2005 2010 2015 2000 2005 2010 2015
Year Year
Figure 8.4 Rate of journal publication on aryl dithioesters 1a in the period 1998–2019
based on a ScifinderTM search carried out in January 2020. The key word ‘RAFT’ was used to
exclude references that do not relate to RAFT polymerization. For the situation (a) where Z
is phenyl or aryl and R is any alkyl, and (b) where Z is aryl and R is carboxyalkyl, cyanoalkyl,
aralkyl, or any alkyl.
(a) S S S S S
S
S S
S S S SH SH
> ~ > S >>>
+HN
N ~ > ~ H3C S
S
EWG EDG
(b) CN CO2CH3
CN CO2CH3 CN CO2CH3 CO2CH3 CN
MMA, HPMAm (disubstituted MAMs)
MA, BA, DMAm, NIPAm, AN, St (monosubstituted MAMs)
VAc, NVP, NVC (monosubstituted LAMs or IAMs)
Figure 8.5 (a) Effect of ZC(=S)— group and (b) R group on the activity of dithioesters ZC(=S)SR in RAFT polymerization. Activity increases from right to
left. Source: Figure 8.5b is adapted with permission from Moad [757]. Copyright 2019, John Wiley & Sons. Note that dithioesters are not generally useful
in mediating polymerization of LAMs. MAM, more activated monomer; LAM, less activated monomer; IAM, intermediate activated monomer; AN,
acrylonitrile; BA, butyl acrylate; DMAm, N,N-dimethylacrylamide; HPMAm, N-(2-hydroxypropyl)methacrylamide; MA, methyl acrylate; MMA, methyl
methacrylate; NIPAm, N-isopropylacrylamide; NVC, N-vinylcarbazole; NVP, N-vinylpyrrolidone; St, styrene; VAc, vinyl acetate; EDG, electron-donating
group; EWG, electron-withdrawing group.
mass polymers. Note, however, that dithiobenzoates are, nonetheless, suitable for
RAFT single unit monomer insertion (SUMI), where higher transfer coefficients are
desirable and propagation is not desirable [172].
The tertiary aralkyl or cyanoalkyl dithiobenzoates are not the preferred RAFT
agents for use when preparing low molar mass polymers based on acrylates and
acrylamides because reinitiation by ‘R’ is rate determining. This is likely to be an
additional cause of retardation.
8.3.2 Functional Aromatic Dithioesters (Z = Aryl or Heteroaryl)

A wide variety of functional RAFT agents have been reported. Many of these are
listed in Table 8.5 (p 251), however, this list should not be considered as compre-
hensive. Carboxy-functional RAFT agents (9, 15, 19, 24) are included in Table 8.4.
RAFT monomers (or dithioester inimers) are shown in Table 8.22. Many of the listed
RAFT agents were used as precursor to other functional RAFT agents, macroRAFT
agents, or to RAFT functional surfaces. Surface-initiated RAFT polymerization to
prepare modified surfaces and particles is covered in detail in the chapter by Pribyl
and Benicewicz [646].
The lists can be considered as indicative of tolerated functionality. Unfortunately,
in many papers the quantitative characterization that would enable a rigorous evalu-
ation of the effectiveness of the various chemistries is sometimes lacking. The alkyne
functionality present in RAFT agents such as 37, 38, 40, or 41 is potentially reactive
under the conditions used for RAFT polymerization and it is desirable to protect with
a trimethylsilyl group as in 39 [587]. The synthesis of reactive polymers by RAFT
polymerization is described in the Chapter by Gauthier-Jaques et al. [647].
Another application of functional RAFT agents is in mechanism-transformation
processes (Section 8.11). Thus, hydroxyl-functional RAFT agents (e.g. 25 or 27) can
-
be used in ROP-T-RAFT (Section 8.11.1), while those with appropriate alkene func-
-
tionality (e.g. 45 or 46) can be used in ROMP-T-RAFT (Section 8.11.2).
8.3.3 Bis-aromatic Dithioesters (Z = Aryl or Heteroaryl)

Some bis-dithioesters are shown in Table 8.6. These bis-RAFT agents are precursors
to telechelics and to symmetric triblock (and potentially higher order block) copoly-
mers. Multi-dithioesters, which are precursors to star polymers, are not directly con-
sidered in this document. Star polymer synthesis is dealt with in the chapter by
Allison-Logan et al. [673].
‘R-connected’ bis-dithioesters can be used to form BAB triblocks by sequential
monomer addition (Scheme 8.2). The dithioester groups are retained at the chain
ends. The product is telechelic. ‘Z-connected’ bis-dithioesters can be used to form
ABA triblocks by sequential monomer addition (Scheme 8.3). The dithioester
groups are retained with the structure. If the dithioester groups are cleaved AB
blocks are formed. This form of bis-dithioester is, in this context, analogous to a
trithiocarbonate.
S S S S
Monomer A
R R
Z S S Z Z S S Z
RAFT
Monomer B S S
R
Z S S Z
Initiator
Scheme 8.2 RAFT polymerization mediated by a ‘R-connected’ bis-dithioester to form a

BAB triblock.
S S Monomer A S S
R R R R
S Z S RAFT S Z S
Monomer B S S
R R
RAFT S Z S
Scheme 8.3 RAFT polymerization mediated by a ‘Z-connected’ bis-dithioester to form an

ABA triblock.
8.3.4 Aliphatic Dithioesters (Z = Alkyl or Aralkyl)

For aliphatic dithioesters, the most common Z groups are methyl and phenylmethyl
(Figure 8.6a), while the most common R group is benzyl or substituted benzyl. A few
papers relate to dithioesters where R is cyanomethyl or carboxymethyl (Figure 8.6b).
Aliphatic dithioesters 1b have transfer coefficients approximately an order of mag-
nitude lower than those of similar aromatic dithioesters 1a (Table 8.2). As such, they
(a) 20 (b) 20
Me CNCR2
PhCH2 PhCR2
(CH3)2CH (CO2R)CR2
15 15
Publications (yr)
Publications (yr)
10 10
5 5
0 0
2000 2005 2010 2015 2000 2005 2010 2015
Year Year
Figure 8.6 Rate of journal publication on aliphatic dithioesters 1b in the period

1998–2019 based on a ScifinderTM search carried out in January 2020. The key word ‘RAFT’
was used to exclude references that do not relate to RAFT polymerization. For the situation
(a) where Z is phenylmethyl, isopropyl or methyl and R is any alkyl, and (b) where Z is any
alkyl and R is carboxyalkyl, cyanoalkyl, or aralkyl.
8.4 Synthesis of Dithioester RAFT Agents 237
are not generally suitable for forming low-dispersity polymers in polymerizations of

1,1-disubstituted monomers, such as methacrylates, in batch RAFT polymerization.
Thus, they are little used for such monomers (Table 8.7, p 260). The issue of low
transfer coefficients has been addressed through the use of a starved-feed addition
protocol [48].
With appropriate choice of R, the transfer coefficients of aliphatic dithioesters
1b are, nonetheless, suitable for producing low-dispersity polymers from monosub-
stituted MAMs (e.g. styrenes, acrylates). There was early interest (2000–2010) in
aliphatic dithioesters 1b in circumstances where a RAFT agent with lower activity
than an aromatic dithioester was advantageous. For example, in polymerizations
of monosubstituted MAMs, aliphatic dithioesters 1b give no or substantially less
retardation than the corresponding aromatic dithioesters 1a with the same R [48].
Another example is RAFT emulsion or miniemulsion polymerization, where the use
of a less active RAFT agent avoids retardation [48, 698, 723] and issues associated
with colloidal instability caused by the formation of a large population of very short
chains (the phenomenon known as superswelling) [699].
More recently, these issues have also been addressed with the use of trithiocar-
bonate RAFT agents [13], which can have similar properties and are more readily
available or more easily synthesized.
8.3.5 Bis-aliphatic Dithioesters (Z = Alkyl or Aralkyl)

Examples of bis-aliphatic dithioesters are shown in Table 8.8.
8.4 Synthesis of Dithioester RAFT Agents

The methods most commonly exploited for the synthesis of (low molar mass)
dithioester RAFT agents are listed below. The method of choice is dependent on
the structure of the specific RAFT agent, the amount required, the toxicity and
ease of handling of reagents, and a variety of other factors. A critical review of
synthetic methods for RAFT agent synthesis was published in 2012 [14] and the
major methods are summarized in Scheme 8.4. Within this chapter further details
are provided only for the few methods that require further comment or have seen
development since that time. For examples of the methods, refer to The RAFT agent
synthesis column in Tables 8.4–8.8.
A. Reaction of a carbodithioate salt with an alkylating agent.
This is the most popular method of synthesizing dithioesters with primary and
secondary R (e.g. 13–21 and 23) [14].
B. Addition of a dithioacid across an olefinic double bond.
The reaction between a dithioacid and an olefinic double bond that leads to
Markovnikov adducts with electron-rich alkenes and to Michael adducts with
electron-poor alkenes was reported in 1972 [727]. Only the former are gener-
ally useful as RAFT agents. The reaction has been widely used for the synthesis
of dithioester RAFT agents from styrene derivatives and simple alkenes. The
G. Single-unit F. Transesterification
monomer insertion (SUMI) (thiol exchange by
S reaction of a
dithioester with a thiol)
R′
Z S S
A. Reaction of R′
a carbodithioate RSH Z S
salt with an R″
alkylating agent
D. Thionation
S S O (thiation) of a
CS2 RX LR
R R thioloester or
Z Z S Z S Z S
R″ another substrate
R
S
R′ R R′
S Z S
S S
Z SH E. Radical-
Z S S Z
B. Addition of a induced ester
dithioacid across exchange
C. Radical-
an olefinic
induced
double bond
decomposition
of a bis(thioacyl)
disulfide
Scheme 8.4 Major methods for dithioester RAFT agent synthesis. RX, alkylating agent; LR,
Lawesson’s reagent. For details on individual processes, refer to Ref. [14].
reaction, which is considered an ene reaction, has been studied using molecular
orbital calculations [728].
C. Radical-induced decomposition of a bis(thioacyl) disulfide.
This is the most popular method of synthesizing dithioesters with tertiary
R-containing electron-withdrawing substituents (e.g. 6–11) [14].
D. Thionation (Thiation) of a thioloester or another substrate.
A recent paper shows that dithioesters can be prepared in good to excellent yields
by reaction of a thiol, RSH, with the desired acid chloride, Z(C=O)Cl, in the pres-
ence of triethylamine followed by thionation with Lawesson’s reagent [505].
E. Radical-induced ester exchange.
F. Transesterification (thiol exchange by reaction of a dithioester with a thiol).
G. SUMI, see Section 8.10.
H. Esterification or amidation (carbodiimide)
A common method of dithioester macroRAFT agent synthesis involves ester-
ification (Steglich esterification) or amidation of a carboxy-functional RAFT
agent with a hydroxy- or amino-functional polymer. An example is the forma-
tion of a poly(3-hexylthiophene) (P3HT) macroRAFT agent by amidation of a
carboxy-functional RAFT agent with an amino-functional polymer (Scheme 8.5)
[729]. The reaction with amines is usually rapid and proceeds in high yield. The
reaction of the amine with the carbodiimide adduct is very much faster than
any reaction between the amine and the dithioester. The reaction of an alcohol
with a DCC adduct is slower, requires a catalyst, and can give variable yields. It
is important that each of the substrates is rigorously dried.
S
C6H13 S DCC
CHCl3 C6H13
S NH2 S
H S S
S N
n HO2C H H O
S n
C6H13
C6H13
Scheme 8.5 Formation of a P3HT macroRAFT agent by N,N′ -dicyclohexylcarbodiimide

(DCC)-mediated amidation of a carboxy-functional RAFT agent.
I. Esterification (acid chloride).

J. Esterification (Mitsunobu reaction).
K. Esterification (other).
L. Active ester–amine reaction or active ester–thiol reaction.
M. Other methods.
N. Commercial availability
The indicated RAFT agents were commercially available at the time of writing
[43, 44].
8.5 Monomers for Dithioester-Mediated RAFT

Polymerization
Polymer syntheses by RAFT polymerization mediated by the more common
dithioesters are surveyed in Tables 8.4–8.6 (aromatic dithioesters) and Tables 8.7
and 8.8 (aliphatic dithioesters). Some of the more exotic monomers mentioned in
these tables are also included in the tables that follow. They include 1,1-disubsituted
MAMs in Section 8.5.1, which include methacrylates (Table 8.9, Section 8.5.1.1),
methacrylamides (Table 8.10, Section 8.5.1.2), and other 1,1-disubstituted
monomers (Table 8.11, Section 8.5.1.3); monosubstituted MAMs in Section
8.5.2, which include acrylates (Table 8.12, Section 8.5.2.1), acrylamides (Table 8.13,
Section 8.5.2.2), styrene derivatives (Table 8.14, Section 8.5.2.3), and diene
monomers (Section 8.5.2.4); 1,2-disubsituted MAMs in Section 8.5.3; and monosub-
stituted less activated monomers (LAMs) in Section 8.5.4 (Table 8.15). Monomers
from all of these classes that additionally contain other reactive functionality appear
in Section 8.5.5 (Table 8.16, p 281).
There is substantial interest in RAFT polymerization of various bio-related or sus-
tainably sourced monomers, which include those derived from amino acids [750],
such as acrylamides 217–224 and glycomonomers, such as methacrylates 130–139,
acrylates 189–190, methacrylamides 170–174 and 176–177, acrylamides 213–216,
and styrenes 236–237.
8.5.1 1,1-Disubsituted Monomers

8.5.1.1 Methacrylates
Dithiobenzoates are the most used RAFT agents for mediating RAFT polymer-
ization of methacrylates. The achievement of low dispersities requires that the
dithiobenzoate R group is a good leaving group with respect to the methacrylate
propagating radical. Methacrylates mentioned in Tables 8.2–8.4 include AAEMA,

AEMA, AMA, CMA, BMA, BDSMA, DEGMA, DMAEMA, EOEMA, HEMA, HMA,
iBMA, LMA, MAEP, MMA, MOEMA, MPC, MPEGMA, PFPMA (262), TMAEMA,
TMAPMA, and TPMMA (see Abbreviations), those in Table 8.9 (p 263), and those
in Table 8.16 (see Section 8.5.5, p 279). The monomers in Table 8.9 are grouped by
application.
8.5.1.2 Methacrylamides
Many examples are appearing on RAFT (co)polymerization of HPMAm,
particularly with respect to various bioapplications [1]. Other examples of
methacrylamide monomers recently used in RAFT polymerization are the
primary amino-functional monomers, AEMAm and APMAm, the tertiary
amino-functional monomers DEAPMAm and DMAPMAm, those shown
in Table 8.10, and the functional methacrylamides included in Table 8.16 (see
Section 8.5.5, p 279). The choice of RAFT agent for polymerization of methacry-
lamides is subject to similar constraints as mentioned for the methacrylates. In
particular, the ‘R’ group of the initial RAFT agent should be selected so as to be
a good leaving group with respect to the propagating radical. The RAFT agents
preferred include dithiobenzoate 9, and derivatives 32 and 33, which are chosen for
their solubility in aqueous media under the conditions used.
8.5.1.3 Other 1,1-Disubsituted Monomers

Other 1,1-disubstituted monomers that have been used in dithioester-mediated
RAFT (co)polymerization include itaconates (DBI, DEHI and 287, Table 8.16(f), see
Section 8.5.5, p 279), the methylenebutyrolactones (182–184), and the itaconimide
derivative (185, Table 8.11).
8.5.2 Monosubstituted MAMs

Attaining low molar mass dispersities in RAFT polymerization of monosubstituted
MAMs requires a RAFT agent suitable for MAMs. Dithioesters are generally suit-
able in this context. It is also important that the homolytic leaving group R of the
dithioester is a good initiating radical such that addition of the R radical is not rate
determining (i.e. ki should be greater than kp – refer Scheme 8.1). For example, the
rate of addition of 2-cyano-2-propyl radical is rate determining in polymerization of
acrylates and acrylamides. This can cause retardation or an inhibition period, espe-
cially in circumstances where low mass is targeted.
8.5.2.1 Acrylates
Acrylates mentioned in this survey include AEP, BA, CPA, DA, DEHEA, DMAEA,
EA, EAA, EEA, EHA, iBoA, MA, PA, (poly(ethylene glycol)monomethyl ether)
acrylate (PEGA), tBA, those in Table 8.12, and those in Table 8.16 (see Section 8.5.5,
p 279).
(continued on page 273)

Table 8.4 RAFT polymerizations with popular or commercially available aromatic

dithioesters.
RAFT agent Synthesisa) Polymerizations b)
S B [48, 49] Methacrylates: AAEMA [52] AEMA [53]

N [50, 51] BMA [5] BzMA [54, 55] DMAEMA [5,
56–58] HEMA [58] GMA [59] GMA [60]
S
LMA [61] MAA [62, 63] MMA [5, 23, 54,
64–74] MMA [75] MMA [60] MMA
[76–78] MPEGMA [79–81] MAEP [52]
PFPMA [82] POSSMA [83] tBMA [84]
2-Phenylpropan-2-yl benzodithioate tBDMSMA [85] TFPMA [86] (TPMMA)
5 [85, 87, 88] TPSiMA [85] 82 [89, 90] 88
[91] 91 [92] 96 [93] 97 [93] 297 [85] 299
[85] 301 [85] 302 [85] 303 [85] 109 [94]
112 [95] 113 [96] 114 [97, 98] 115 [97] 120
[99] 120 [100] 130 [101] 132 [102] 251
[103] 282 [104]
Other 1,1-disubstituted MAMs: (DBI) [105,
106] 185 [106] 313 [107] 326 [108]
Acrylates: (MA) [109] MA [23, 110–114]
MA [114] BA [43, 48] (BA) [60]
Acrylamides: Am [115] DMAm [56, 80,
116] NIPAm [56, 117, 118] 205 [119] 206
[120] 205 [121] 223 [80]
Styrenes: CMS [122] St [5, 23, 35, 48, 56,
70, 71, 122–130] (St) [75, 131–136] St [76,
78] PFPVB [137] PVS [137] tBDMSOS
[138] 2VP [139] 4VP [139] 228 [140] 225
[141] 226 [141] 268 [142] 269 [90] 271
[142] 272 [142] 273 [142] 274 [142] 325
[143] 330 [144]
Vinyls: (NVP) [145]
Copolymers: MMA/HEMA [5]
MMA/BDSMA [146] MMA/EGDMA
[147] MMA/4VP [148] (MAA/TPMMA)
[88] (MAA/104) [88] DEGMA/MPEGMA
[149] DMAEMA/POSSMA/150a [150]
MMA/LMA [79] tBMA/DMAEMA/80
[151] St/AcS [152] St/CMS [122] St/AN
[5, 58] 4VP/EGDMA [153] BA/327 [154]
St/MAH [58, 155] St/DVB [156]
BMA/TMSEMA [157] DMAEMA/96 [93]
DMAEMA/323 [158]
Blocks: AEMA-b-166 [53] BzMA-b-MAA
[54] BzMA-b-DMAEMA [54]
BzMA-b-HPMAm [55] MMA-b-St [54]
MMA-b-DMAEMA [73] (St-b-DMAEMA)
[129] MMA-b-St [23] (St-b-MMA) [23]
St-b-MeS [23] St-b-DMAm [23]
DEGMA/MPEGMA-b-DMAPMAm [149]
LMA-b-BzMA/339 [61] MMA-b-AN [72]
(continued)
RAFT agent Synthesisa) Polymerizationsb)
MMA-b-St [74] MMA-b-St [76]

MMA-b-BMA [77] MPEGMA-b-MMA
[79] MPEGMA-b-241 [81]
LMA/MMA-b-MPEGMA [79] 114-b-95
[98] 251-b-MPEGMA [103] 282-b-BzMA
[104] AAEMA-b-AEP [52]
AAEMA-b-MAEP [52]
MAEP-b-AAEMA [52] TFPMA-b-tBA
[86] St-b-CMS [122] St-b-NIPAm [127]
St-b-HEMA/DMAEMA [49] 225-b-265
[141] 226-b-265 [141] 269-b-82 [89]
120-b-St [99] DMAm-b-223 [80]
MPEGMA-b-223 [80] 88-b-MPEGMA
[91] POSSMA-b-4VP [83] POSSMA-b-St
[83] POSSMA-b-St-b-4VP [83]
2VP-b-4VP [139] St-b-MAH [71]
326-b-BA [108]328 [159] 96-b-St [93]
97-b-St [93] GMA-b-POSSMA [59]
S A [48] Methacrylates: BMA [163] BMA [164]
C [160–162] DMAEMA [165] EOEMA [166] GMA
[167, 168] HFBMA [169] (iBMA) [170]
S E [23]
LMA [171] (MMA) [172] MMA [11, 23,
CN N 25, 68, 160, 173–187] MMA [188] MMA
2-Cyanopropan-2-yl benzodithioate [189] MPEGMA [28, 190–192]
PDFOMA [193] tBDMSMA [26, 187,
6 194] TPSiMA [194] 79 [168, 195–198]
301 [194] 100 [199] 101 [200] 108 [201]
109 [94] 117 [202] (119) [203] 122 [204]
123 [205] 124 [205] 128 [206] 141 [207]
144 [208] 145 [209–211] 146b [212] 149
[213] 151 [214] 153 [186] 158 [215] 163
[216] 164 [216] 165 [216] 182 [217] 184
[217] 252 [218] 253 [218] 257 [219] 258
[220] 319 [221] 324 [194]
Acrylates: BA [36, 43, 183, 222] HFBA
[223] MA [23, 113, 183] iBoA [183] 190
[224] 197 [224] 192 [208] 193 [225]
Acrylamides: DEAm [226, 227] NIPAm
[228, 229] NIPAm [172]
Styrenes: tBOS [230] St [128, 174, 181,
222, 227, 231] (St) [132] St [172] 242
[232] 231 [233] 240 [234] 348 [235]
Dienes: Cp [236, 237] Cp [236] (Ip) [238]
Ip [239]
Vinyls: VBz [5]
Others: AN [240, 241] iPOx [242]
(continued)
Copolymers: AMA/MMA [243]

DMAEMA/118 [244]
DMAEMA/DEAEMA [245]
IPhMA/MMA [246] LMA/258 [220]
MMA/92 [246] MMA/90 [246]
(MMA/254) [243] MAA/MPEGMA [28]
HEMAm/MPEGMA/MPEGMAm [247]
MMA/149b [248] MMA/282 [249–251]
MMA/BA/tBDMSMA [187] BzMA/282
[251] tBA/283 [250] MMA/TMSMA
[252] MMA/TMSMA/tBDMSOS [252]
MMA/110 [253] MMA/111 [253]
MMA/146a/252 [254] MMA/146b/252
[254] MMA/146c/252 [254] AA/287
[255] DMAm/287 [255] 288/287
[255]NMS/HPMAm [256] iPOx/NIPAm
[242] HMA/163 [216] LMA/163 [216]
HMA/165 [216] LMA/165 [216]
MMA/199 [257] MA/199 [257] MA/200
[257] MA/202 [257] St/MAH [155, 210,
258] St/230 [259] MMA/BA [36]
MMA/119 [203]
HEMAm/PEGMA/TEGMAm [247]
107/NAS
Blocks: BMA-b-162 [260] BMA-b-243
[163] BMA-b-DFHMA [164]
MMA-b-BA/199 [261] MMA-b-153 [186]
DMAEMA/DEAEMA-b-DMAEMA
[245] EOEMA-b-DMAm [166]
EOEMA-b-NAM [166] LMA-b-EGDMA
[171] LMA-b-EGDMA-b-DMAEMA
[171] MMA-b-162 [262]
MMA-b-BA/tBDMSMA [187]
MPEGMA-b-NMS [191]
MPEGMA-b-NMS-b-94
[191]/tBDMSMA-b-BA/MMA [187]
79-b-HPMA [168, 195] 79-b-BzMA [198]
79-b-HPMA [168, 195] 79-b-MOEMA
[196] 79-b-80 [197] 101-b-HEMA [200]
128-b-129 [206] 146b-b-152 [212]
151-b-146b [214] 190-b-197 [224]
197-b-190 [224] MMA/TMSMA-b-PFS
[252] MMA/TMSMA/tBDMSOS-b-PFS
[252] PDFOMA-b-THPOS [193]
141-b-152 [207] 145-b-St/MAH [210]
145-b-227 [211] St-b-St/307 [231]
GMA-b-PFS [167] MMA-b-S [174]
HFBMA-b-BMA [169] MMA-b-BA [175]
NIPAm-b-DEAm [228] tBOS-b-St [230]
St-b-MAH [172] St-b-(NIPAm) [172]
231-b-240-b-AA [233] 122-b-93 [204]
123-b-93 [205] 124-b-93 [205]
(continued)
S C [263] Methacrylates: MAA [264, 265] BMA

N [50] [266] BzMA [266] DEGMA [264,
267] DMAEMA [266] EOEMA [264]
S MMA [266, 268, 269] MPEGMA
CN [264] 167 [270] 147 [271] 81 [272]
2-Cyanobutan-2-yl benzodithioate 253 [273] 317 [274]
Acrylates: BzA [266] EEA [275] EHA
7
[266] MA [266] tBA [266]
Copolymers: MAA/AA [265]
95/MMA [276]
DMAEMA/MPEGMA [277]
DEGMA/MPEGMA [29]
DEGMA/150b [278]
DEGMA/MPEGMA/150b [278]
MMA/253 [273] MAA/MPEGMA
[264] MMA/DMAEMA [279]
Blocks: MAA-b-AA [265]
DEGMA-b-DMAEMA [267]
MMA-b-DMAEMA [279]
MMA-b-253 [273]
S C [40] Methacrylates: MMA [40]
N
S
CN
2-Cyano-4-methylpentan-2-yl benzodithioate
8
S C [2, 161, Methacrylates: AEMA [53, 283–285]

CO2H 263, BMA [286] BMA [287] DEAEMA
280–282] [288–290] DEGMA [291] DMAEMA
S [5, 292–295] DMAEMA [296]
N
CN DPAEMA [297] GMA [296] LMA
4-Cyano-4- [61, 294] MAA [25, 291, 298–303]
((phenylcarbonothioyl)thio)pentanoic acid MMA [287, 304–315] MMA [296]
9 MPC [316, 317] MPEGMA [295, 297,
318–323] MPEGMA [309] PFBEMA
[324] PFHEMA [324] PFOEMA [324]
PFPMA [325–329] POSSMA [330]
TFEMA [287] TPSiMA [331] VBTAC
[282, 332–336] 79 [337, 338] 83 [339]
84 [340] 100 [199] 114 [341] 131
[289, 342] 132 [102] 133 [101, 343]
134 [344] 135 [345] 137 [344, 346]
139 [347] 140 [348] 143 [349] 157
[350] 158 [351] 160 [298] 161 [298]
162 [352] 169 [353] 277 [354–356]
284 [357] 281 [358] 285 [357] 315
[359, 360]
(continued)
Acrylates: DMAEA [361] HFBA [362] NAS

[363] HA [364] MA [365, 366] MA [367] PFPA
[329] 190 [368] 284 [357] 285 [357]
Methacrylamides: APMAm [284, 369, 370]
DMAPAm [369] HPMAm [302, 371, 372]
HPMAm [308] 170 [373] 173 [373] 174 [347]
175 [374] 176 [375] 177 [375] 179 [298] 293
[376, 377] 294 [377]
Acrylamides: AEMAm [370, 377] Am [378]
AMPS [379, 380] DMAm [381] DMAm [367]
NIPAm [365, 382–384] NIPAm [367] 178 [385]
211 [386] 217 [387]
Styrenes: St [137, 348, 388] St [367] (PFPVS)
[137] SSO3 Na [5, 389] 273 [142] (274) [142]
(304) [390]
Other MAM: AN [391] AN [392]
Vinyls: (NVP) [393]
Copolymers: MAA/MPEGMA [28] MAA/142
[394] MMA/257 [395] PFPMA/LMA [326]
PFPMA/PFPA [329] MMA/PFPMA [396]
MPEGMA/PFPMA [396] MPEGMA/251 [397]
MPC/138 [316] MPC/170 [316] MPC/171 [316]
158/157 [351] 159/[2]278 [398] AEMAm/172
[370] APMAm/172 [370] HPMAm/284 [399]
HPMAm/APMAm [400] EOEMA/186 [401]
MPEGMA/207 [401] HPMAm/APMAm [402]
HPMAm/181 [403] tBMA/280 [404]
BMA/308/PEGDMA [405] 309/EGDA [406]
PEGA/MAH [407]
Blocks: 79-b-HPMA [337] 140-b-DEAm [348]
143-b-MMA [349] 158-b-157 [351] AMPS-b-217
[379, 380] AEMA-b-HPMAm [284, 285]
131-b-HEMA-bNIPAm [342] DEAEMA-b-131
[289] DMAEMA-b-HEMA [292]
DMAEMA/MPEGMA [321]
DMAEMA-b-BzMA/239 [290]
DMAEMA-b-BzMA-b-PFHEMA [408]
(DMAEMA+MPEGMA)-b-DMAEA/346 [295]
DMAEMA-b-168 [293] DMAEMA-b-148 [294]
LMA-b-148 [294] LMA-b-BzMA/339 [61]
LMA-b-BzMA/340 [61] MMA-b-162 [409–411]
MPEGMA-b-148 [412] MPEGMA-b-DMAEMA
[321] MPEGMA-b-VBTAC [334]
MPEGMA-b-276 [413] PFPMA-b-TEGMA
[328] TEGMA-b-PFPMA [328] AEMAm-b-172
[370] APMAm-b-172 [370]
HPMAm-b-DMAPMAm [371] 178-b-HPMAm
[385] St-b-PFPVS [137] St-b-DEAm [348]
(continued)
APMAM-b-NIPAm [69, 376]

MAA-b-DFHMA [299] BMA-b-MPC
[286] P DEGMA-b-265 [291]
MAA-b-MMA [303] MMA-b-MAA [54]
MMA-b-St [54] MMA-b-265 [291]
DMAm-b-211 [386]
DMAEMA-b-NIPAm [288]
DPAEMA-b-MPEGMA
MPEGMA/AMPS [319, 320]
MPEGMA-b-AMPS [319, 320]
MPEGMA-b-252 [318] 84-b-286 [340]
262-b-LMA [325] 294-b-293 [377]
134-b-BMA [344] 137-b-DMAEMA
[344] 137-b-BA [344] 139-b-174 [347]
160-b-MAA [298] MAA-b-160 [298]
MAA-b-161 [298] MMA-b-160 [298]
MMA-b-161 [298]
DMAm-b-NIPAm/260 [381]
NIPAm-b-295 [384] NIPAm/293 [377]
MPC/294 [377] 277-b-HPMAm [354]
HPMAm/APMAm-b-DMAPMAm [402]
HPMAm/181-b-280 [403] St-b-265 [388]
156-b-DEAm [317] 156-b-VBA [317]
156-b-157 [317] 156-b-234 [317]
157-b-HPMA [350] 170-b-AEMAm
[373] 170-b-MPC [373] 173-b-AEMAm
[373] 173-b-APMAm [373]
APMAm-b-173 [373] 179-b-Am [298]
VBTAC-b-233 [335] NAS-b-Am [363]
POSSMA-b-PFOEMA [330]
162-b-NIPAm [352] PEGA/MAc-b-St
[407]
C [414] Methacrylates: BMA [415] DMAEMA
[415] GMA [416] GMA [415] MMA
S [366, 414, 417–421] MMA [422] MMA
[415, 423] MPEGMA [424] MPEGMA
[415, 425] PEMA [426] 105 [427] 106
S
[427] 116 [428] 121 [429]
CN
Others: (AN) [430] AN [431, 432]
2-Cyanopropan-2-yl naphthalene-1-
carbodithioate Styrenes: St [129, 433, 434] 4VP [415]
10 Copolymers: MMA/102 [435] St/NMMI
[436] St/NPrMI [436]
Blocks: MMA-b-S [414] GMA-b-St [437]
116-b-MMA [428] 116-b-St [428]
(St-b-DMAEMA) [129]
(continued)
S A [23] Methacrylates: MMA [23, 45, 68, 74]

C [438] Acrylates: 312 [439]
S R N Styrenes: St [23, 438, 440] (St) [133]
O Dienes: Cp [441]
O Copolymers: PEGMA/95 [442]
Alkyl 2-methyl-2- (AA/MMA) [443] 4VP/BA [444]
((phenylcarbonothioyl)thio)propanoate Blocks: MMA-b-St [74] St-b-Cp [441]
11a R = C2H5
b R = CH3
S D [23, Methacrylates: (MMA) [23, 25, 449, 450]

445, 446] Acrylates: AA [451] BA [449] EHA [448]
S F Acrylamides: DEAm [452] tBAm [453]
[446–448] DEAm [449] DMAm [449, 454] NAM
tert-Butyl benzodithioate N [447, 453] NIPAm [449, 450]
12 Styrenes: St [23] St [455, 456] AcS [457]
Vinyls: (VAc) [458] (NVP) [393]
Copolymers: BA/S [459] VCl2/MA [446,
460]
DMA/NAS [454] NAM/NAS [447, 461,
462]
Blocks: EHA-b-MA [448, 463]
DMA-b-(DMA/NAS) [454]
tBAm-b-NAM [453] DMAm/NAS [464]
NAM-b-tBAm [453] NAM/NAS-b-NAM
[461]
A [41] Methacrylates: MMA [41] MMA [188]

S Acrylates: BA [41] tBA [41]
Styrenes: AcS [41] St [41]
S
CN
Cyano(phenyl)methyl benzodithioate
13
A [41] Methacrylates: MMA [188] 256 [465]

S Acrylates: BA [41]
Styrenes: St [41]
S Blocks: 256-b-MMA [465]
CN
Cyano(phenyl)methyl naphthalene-2-
carbodithioate
14
(continued)
A [466] HA [364]
S N
S
OH
O
2-Phenyl-2-
((phenylcarbonothioyl)thio)acetic acid
15
A [467] Methacrylates: MMA [438, 450, 467]

S
C [438] Acrylates: BA [468] HA [364] MA [467]
N tBA [469–471] 194 [472]
S Acrylamides: NIPAm [450, 473]
OR
Styrenes: St [438, 467] 4VP [474]
O
Copolymers: DMAEMA/331 [475]
Alkyl 2-phenyl-2-
((phenylcarbonothioyl)thio)acetate
DMAEMA/332 [475] DMAEMA/332
[475] DMAEMA/335 [475] HEMA/331
16a R = CH3 [475] HEMA/332 [475] HEMA/332
b R = C2H5 [475] HEMA/335 [475]
MAA/MPEGMA [476] MMA/154 [477]
MMA/155 [477] MMA/331 [475]
MMA/332 [475] MMA/333 [475]
MMA/334 [475] MMA/335 [475]
St/CMS [478] St/2VP [479] St/228 [480]
Blocks: MMA-b-NIPAm [450] THPA-b-S
[481] THPA-b-St/255 [482] tBA-b-194
[469–471] 194-b-SSO3 Na [472]
NIPAm-b-194 [473] 4VP-b-194 [474]
A [483] Methacrylates: (MMA) [23]

S B [23] Acrylates: AA [5] BA [23, 54] MA [54]
D [445] PEGA [483, 484]
S Styrenes: St [129, 485, 486] (St) [131] 237
N
[487] 232 [488]
1-Phenylethyl benzodithioate Copolymers: St/EVE [489] (St/MAH)
17 [489] BP/MAH [490] St/Bd [143]
(St/Bd) [491]
Blocks: BA-b-AA [54] MA-b-EA [54]
(St-b-DMAEMA) [129] St-b-MAH [486]
S A [492] Others: AN [492]

C [438] Copolymers: AN/BP [493]
S
CN
1-Cyanoethyl benzodithioate
18
(continued)
RAFT agent Synthesisa) Polymerizations b)
S A [494, Acrylates: AA [37] DEGA [496]

495] Acrylamides: NAA [495] NAM [494,
S N 495] NAPi [495] NIPAm [497]
OH Styrenes: St [497]
O Blocks: NAM-b-NAPi [495]
NAM-b-NAA [495] St-b-NIPAm
2-((Phenylcarbonothioyl)thio)propanoic acid
[497]
19 (used to prepare other functional
RAFT agents) [495, 498]
S A [43, 497, Acrylates: BA [43, 500] PEGA [484]

499] Acrylamides: NIPAm [499]
S C [438] Styrenes: St [500, 501] VBPDE [502]
OR F [446] Copolymers: MA/BP [503]
O N SSO3 Na/MPEGMA [504] VCl2 /MA
[446]
Alkyl
2-((Phenylcarbonothioyl)thio)propanoate Blocks: VBPDE-THPFDA [502]
20a R = C2H5
b R = CH3
S A [23] Methacrylates: (MMA) [23, 25]

D [445, Acrylates: AA [506, 507] BA [5, 23,
S
505] 508] BA [509] HEA [510] MA [23]
F [446] (MA) [511] PEGA [512] 219 [513]
N Acrylamides: DEAm [514] DMAm
[515] NIPAm [516] 218 [517] 219
[518, 519] 221 [519, 520] 220 [80,
Benzyl benzodithioate
517] 222 [519] 223 [80, 521] 224
21 [522] 236 [523]
Others: (NVPI) [524]
Styrenes: St [23, 31, 32, 54, 69, 128,
507, 508, 515, 525, 526] PFPVS [137]
PVS [137] 236 [523] 337 [527–529]
(338) [527] 267 [530] 306 [531]
Vinyls: (VAc) [458] (NVP) [393]
(NES) [532] (BES) [532]
Copolymers: MAA/EGDMA [533]
MAA/MA [534] MMA/337 [528]
AA/St [506, 507] BA/337 [528]
tBA/St [506] AN/337 [528] (St/Bd)
[491] St/MAH [535, 536] St/337
[528] 4VP/337 [528] MAH/329 [537]
VCl2/MA [446] (DVE/MAH) [538]
Blocks: HEA-b-336 [510]
PEGA-b-NIPAm [512]
(PFPVS-b-PSt) [137] (255-b-EA)
[531] 219-b-229 [513] 220-b-223 [80]
St-b-MeS [54] St-b-DMAm [54]
(St-b-DMAm) [515] St-b-4VP [525]
(continued)
S M [539] Acrylates: iBoA [540] tBA [541, 542]

135 [543]
N S Styrenes: St [540, 544, 545] (St) [131]
268 [142] 272 [142] 273 [142]
Copolymers: AN/Bd [546] St/AN
[546]
Benzyl pyridine-2-carbodithioate
22
S A [547] Acrylates: DEGMA [548] (MA) [549]

N Vinyls: (NVC) [550]
S
CN
Cyanomethyl benzodithioate
23
S N Methacrylates: (MAA) [551] (MMA)

[449]
S Acrylates: BA [449] HA [364]
OH Styrenes: (St) [33]
O Acrylamides: Am [552] (DEAm)
2-((Phenylcarbonothioyl)thio)acetic acid [449] (DMAm) [449] (NIPAm) [449,
551, 553] 215 [552]
24
Dienes: (Cp [237])
Copolymers: St/DVB [443, 554, 555]
m/215 [552] Am/214 [552]
Blocks: (NIPAm-b-NAS) [553]
(NIPAm-b-MAA) [551]
a) Details of RAFT agent synthesis. The letter (A–N) indicates the synthetic method used – see
Section 8.4.
b) Monomers used. Polymerizations leading to block copolymers are designated as A-b-B. The
first mentioned monomer (A) was polymerized first, and the polymer formed was used as a
macroRAFT agent in polymerization of the second mentioned monomer (B), etc. Those
leading to gradient or statistical copolymers are designated as A/B. The following apply:
Purple – crosslinking polymerization. Block copolymers prepared by crosslinking
polymerization will be arm-first stars. Red – photoinitiated polymerization. Orange – SUMI.
Bold Orange – PhotoSUMI. Green – redox RAFT. Blue Italics – heterogeneous polymerization
(emulsion, miniemulsion, dispersion). If the monomer(s) appear in parentheses, a relatively
broad molar mass distribution (Ð > 1.4), significant retardation/inhibition, and/or other issues
were encountered.
Table 8.5 Functional dithioester RAFT agents.
Hydroxyl Synthesisa) Polymerizationsb)
S OH C [23, 161] Methacrylates: BMA [559]

N DMAEMA [560, 561] MMA [5, 23,
559, 560] MMA [188]
S
Acrylates: HA [364]
CN
Acrylamides: NIPAm [382]
25
Styrenes: St [562, 563]
Blocks:
-
RAFT-T-ROP: MMA-b-CL [564]
BMA-b-CL [564] tBMA-b-CL [564]
MMA-b-VL [564]
BMA-b-VL [564] tBMA-b-VL [564]
S O H [102] Methacrylates: 132 [102]
OH Blocks: 132-b-BA [102]
S O
CN
26
S C [23, 565] Methacrylates: (MMA) [23]

O Copolymers: NIPAm/DMAm
[566–569]
S
-
ROP-T-RAFT: NIPAm/DMAm-b-CL
HN [566, 569] NIPAm/DMAm-b-LA
OH [566, 568]
27
A [364] Acrylates: HA [364]

S
OH
S
O
O
28
Protected primary amine

A [364] Acrylates: HA [364]
S O
HN
S O
NH
O
29
(continued)
Active ester
O C [570] Styrenes: 270 [572]
C/H
[571–573]
S O N
H [574–578]
S O O N
CN
30
S D [579]
O O
S
O N
O
31
S O H [580] Methacrylamides: HPMAm [372]

S (used to prepare other functional
S N RAFT agents) [365, 580–583]
CN S
32
F F C/H [584] Methacrylates: tBMA [585] DEGMA

[584, 585] LMA [69, 584] MMA
[584] MPEGMA [69, 584]
S O F Methacrylamides: NIPMAm [584]
S O F F
CN
33
Azide
N3 H [586] Methacrylates: MMA [586]
S O
S O
CN
34
(continued)
N3 H [587–589] Methacrylates: APMA [589]

DMAEMA [590, 591] MMA [591]
S O
Acrylamides: DMAm [588] NIPAm
[592]
Styrenes: St [587, 588, 591–593] 2VP
S O
[594] 4VP [591]
CN Blocks: DMAm-b-St [588]
35 St-b-DMAm [588] St-b-MAH [592]
N3 C,H [595] Styrenes: St [595]

S O
S O
CN
36
Alkyne
H [586, 589, Methacrylates: AEMA [599] APMA
594, [589] BMA [586] TESPMA [594] 98
596–598] [598] 140 [597, 600]
S O
Blocks: PEGA-b-TMSPA/191 [601]
140-b-MPEGMA [600]
S O
CN
37
L [585] Methacrylates: tBMA [585] MMA

[585] DEGMA [585]
S HN
S O
CN
38
Si(CH3)3 H [587] Methacrylates: 133 [602]

Styrenes: St [587]
S O
S O
CN
39
(continued)
S A [592] Styrenes: St [592]

Blocks: St-b-MAH-b-NIPAm [592]
S
O
O
40
S - Blocks: THPA-b-S [481]

Ph
S
O
O
41
Alkene
H [603] Copolymers: DEGMA/HEMA [603]
S O
S O
CN
42
Dibromomaleimide
Br M [604, 605] Acrylamides: DMAm [604] NIPAm
[604, 605]
Br
O
S N
O
S
CN
43
Thiolactone
S O O C [606] Styrenes: St [606]
S
S HN
CN
44
(continued)
ROMP monomer
H [607, 608] Methacrylates: MMA
[607, 608]
Acrylates: MA [608]
S O
Styrenes: St [608]
Copolymers: 4HS/NPMI
S O
[609]
CN -
RAFT-T-ROMP
45 [607–609]
O H [610] -
ROMP-T-RAFT [610,
611]
N
S O
O
S O
CN
46
Protected maleimide
O H [612–614] Methacrylates: MMA
[612–616]NMA [615]
N O
S O
O
S O
CN
47
O H [603, 617] Methacrylates: MPC

S O N [617]
O Copolymers:
S O O DEGMA/HEMA [603]
CN
48
Poly(dimethylsiloxane)
S O H [618] Copolymers: MMA/150b
[618] BMA/150b [618]
HMA/150b [618]
S O O
Si Si
CN n
49
(continued)
S O H [619] Methacrylates: DMAEMA [619]

O
Blocks: DMAEMA-b-HEMA [619]
S O
CN O Si Si C4H9
n
50
Poly(ethylene glycol)
S O H [620] Methacrylates: BzMA [54]
DMAEMA [321, 621] HEMA [622]
TMAEMA [623] 126 [624]
S O
Acrylates: BA [620]
CN O
Styrenes: St [54] St [621, 625] 2VP
n [626]
51 Copolymers: St/DVB [627]
Blocks: DMAEMA-b-St [621]
2VP-b-St [626]
S O L [54] Styrenes: St [54]
S HN
CN O
n
52
H [628] Methacrylates: MMA [628]

Blocks: MMA-b-St [628]
S
O
S O
O n
53
S K [449] Methacrylates: (MMA) [449]

O Acrylates: BA [449]
S O Acrylamides: (DMAm) [449]
O n (NIPAm) [449]
54
(continued)
Lipid
S O H [629] Methacrylates:
DMAEMA [629]
S O [mixture of fatty alcolols]
CN
55
a) Details of RAFT agent synthesis. The letter (A–N) indicates the method(s) used – see Section
8.4.
b) See footnote ‘b’ of Table 8.4. In the case of bis-RAFT agents, sequential polymerization of two
monomers will yield a triblock copolymer.
Table 8.6 Bis-dithioester RAFT agents.
‘R’-connected
S S B [49, Methacrylates: BMA [54,
648–651] 652] DMA [648] DMAEMA
S S [649–654] TFEMA [654]
MMA [54, 648, 655] 80 [656]
56
1,4-Phenylenebis(propane-2,2-diyl) dibenzodithioate Acrylates: AA [649] BA [652]
Acrylamides: NAM [447]
Styrenes: S [649, 652]
Copolymers:
HEMA/DMAEMA [49]
Blocks: BMA-b-MMA [54]
BMA-b-St [54]
DMAEMA-b-BMA [652]
DMAEMA-b-BA [652]
DMAEMA-b-S [652]
HEMA/DMAEMA-b-St [49]
MMA-b-HEMA
[54]MMA-b-154 [655]
MMA-b-154/MMA [655]
80-b-85 [656]
S B [49, 657] Methacrylates: MPC [657]
S
Copolymers:
S DMAEMA/HEMA [49]
S Blocks:
DMAEMA/HEMA-b-St [49]
57
1,3-Phenylenebis(propane-2,2-diyl) dibenzodithioate
(continued)
S O CN H [106] Methacrylates: PEGMA [658]

O S
S
TEGMA [659]
O
CN O S Other: (DEHI) [106] DBI [106]
58
Ethane-1,2-diyl bis(4-cyano-4-((phenylcarbonothioyl)thio)pentanoate) Blocks: PEGMA-b-Am/AN
[658] DBI-b-185 [106]
S O CN H [398] Acrylamides: 212 [398]

O S
S O 2
CN O S
59
S O CN H [660–662] Methacrylates: MMA [660, 661]

O S 169 [663]
S O n
CN O S Acrylates: BA [660]
60 Styrenes: St [660, 661] SSO3 Na
[301, 662] 2VP [661]
Blocks: MMA-b-St [661]
MMA-b-St-b-2VP [661]
MMA-b-2VP [661]
MMA-b-2VP-b-St [661]
MMA-b-EGDMA [660]
BA-b-EGDA [660] St-b-DVB
[660] St-b-2VP [661] 2VP-b-St
[661]
S O H [664] Blocks: 125/290-b-87-b-MPC
S [664]
S O S
CN
CN
O S
O S
61
CN
H [665] Methacrylates: DMAEMA [665]
S O
O S
S O n
CN O S
62
(continued)
S O O S H [666] Methacrylates: TMSEMA [666]

S O O S Blocks: TMSEMA-b-86 [666]
CN CN
63
S O A [386] Acrylamides: DMAm [386]

HN
S S Blocks: DMAm-b-211 [386]
NH
O S
64
S A [555, 648] Acrylates: tBA [667]

S Acrylamides: NIPAm [653]
S Styrenes: St [648, 668]
SSO3 Na [669] CMS [670]
S
65 Copolymers: DA/ODA
[555]
Blocks: tBA-b-St [667]
SSO3 Na-b-NIPAm/MBAm
[669] CMS-b-St [670]
ODA/DA-b-St [555]
‘Z’-connected
S
S
S
66
S D [672] Acrylates: tBA [672]

S
Blocks: tBA-b-St [672]
S
S
67
a) Details of RAFT agent synthesis. The letter (A–N) indicates the synthetic method used – see
Section 8.4.
Table 8.7 RAFT agents and RAFT polymerizations – aliphatic dithioester RAFT agents
(Z = alkyl or aralkyl).
S B [674, 675] Methacrylates: (MMA) [675, 676]

Acrylates: AA [677] BA [678] MA
S [113, 183, 679] BA [183, 677, 679]
HPA [677] 187 [680] (204) [681]
Styrenes: St [682–684] St
[685–687] MeS [677]
68
2-Phenylpropan-2-yl 2-phenylethanedithioate
Copolymers: Bd/AN [688]
BP/NPMI [689] St/307 [690]
Blocks: MMA-b-AA [675]
MMA-b-AA-b-MMA/BA [675]
S B [691] Acrylates: AEP [52] MA [691] BA
[36, 509] (BA) [509] TFPA [86]
Acrylamides: DEAm [692]
S
NIPAm [693–695]
Styrenes: AcS [696] St [697] St
[698–702] PFS [86]
69 Blocks: St-b-St/Bd [700]
1-Phenylethyl 2-phenylethanedithioate St-b-Bd-b-St [700]
Copolymers: St/MAH [703]
BP/MAH [490] DMAm/180 [704]
S A [24] Acrylates: MA [24, 705, 706] BA
[705] DA [705]
Copolymers: MA/BP [503]
S
CO2CH3
70
Methyl 2-((2-phenylethane-
thioyl)thio)propanoate
S A [683] Acrylamides: NIPAm [693,

707–711]
Styrenes: St [712–714] St [701,
S
715]
Dienes: Bd [715] Cp [441]
Other MAM: MMBL [716]
71 Copolymers: St/MAH [713]
Benzyl 2-phenylethanedithioate St/MMBL [716] MMA/BA [36]
BP/NPMI [689] BP/NMMI [689]
BP/NEMI [689] St/Bd [715]
Blocks: St-b-(St/Bd) [714, 715,
717] St-b-(St/MAH) [713]
St-b-Bd-b-St [718] (St/MAH)-b-St
[713] St/MAH-b-St/Bd [719, 720]
NIPAm-b-MAA [711]
TFPA-b-tBA [86] PFS-b-tBA [86]
(continued)
S B [509] Acrylates: BA [509] (BA) [509]
72
2-Phenylpropan-2-yl 2-
methylpropanedithioate
S — Acrylates: BA [500]
S
O
O
73
Ethyl 2-((2-methylpropane-
S A [721] Acrylates: BA [36, 509, 721] BA

D [505] [509] Styrenes: St [721]
Copolymers: St/BA [721, 722]
S
MAA/EGDMA [533]
74
Benzyl 2-methylpropanedithioate
S D [505] Acrylates: BA [5, 48]

S Blocks: St-b-MMA [48]
75
Benzyl ethanedithioate
8.4.
b) See footnote ‘b’ of Table 8.4. If the monomer(s) appear in parentheses, a relatively broad molar
mass distribution (Ð > 1.4), significant retardation/inhibition, and/or other issues were
encountered.
Table 8.8 RAFT agents and RAFT polymerizations – bis-dithioester RAFT agents (Z = alkyl
or aralkyl).
‘R’-connected
A [724] Styrenes: St [724]
S
S
S
S
76
S S B [712] Styrenes: St [712]
S S
77
S B [712, 725] Styrenes: St [712,

725, 726]
S
S
78
8.4 Synthesis of RAFT Agents.
Table 8.9 Methacrylate monomers subjected to RAFT polymerization.
O O O O O
O O O O O
HO OH O O O O O
81 [272] 82 [89, 90]
79 GMMA
80 SKMA 83 [339]
O O O
O O O O
O
O O
O N N
C7H15
84 86
OCH3 87
85 [656]
Metallo-monomers
O O O O
O O O O
O O N N
O O
N
Ru
Rh+ PF6–
N N N
88 [91] Ni
N N
O O 91
Ru2+
N N
C6H13O OC6H13
N
89
90 [246]
(continued)
Ligating monomers
O O O O
O O O O
(CH2)6
O
O O
O O
O O
O
95
O
N N O
N N N N
94
92 [246] 93 [730]
Boron, sulfonate, phosphonate, and phosphate-containing monomers
O O O
O O O
(CH2)10 (CH2)10
O
N N N N S
B B K + O
O
F F
98
96 [93, 731]
Ph Ph
97 [93]
O O O O
O O O O
O
P O
O O P
O O
P O OH
OH O O
HO P
100 O
99 MAEP 101 O
102
(continued)
Bulky monomers
O O O O O
O O
O O O
Ph
HO 107
106 [427]
TPMMA 104 [88] 105 [427]
103 [87]
Monomers containing aziridine or thiirane functionality
O O
O O
S
N 109 [94]
108 [201]
Dye monomers
O O
O O
O O O
O
(CH2)2 (CH2)2
O N O O N O
N O
N N
N O
S
S
111 [253] N O NH
110 [253]
112 [95]
113 [96]
(continued)
O O O O
O O O O
(CH2)6
O O
N O
N O
C8H17O
114 N
N N
N
OH
117 [202]
115 [97] 116 [428]
O O O O
O O O O
N
O
N N
O
S
O N
N
OH N
S
O
N(CH3)2 121 [429]
O 119 [203] S
118 [244, 732]
120 [99]
O O O
O O
O O O
12 12 12
O O O
N
N
S
122
N
125
124
123
(continued)
O O O O
O O 6
O
H13Oc6
O
O Oc6H13
R N Oc6H13
126
O H13Oc6
O H13Oc6
129
NO2
127 R = benzyl, isopropyl
O O
H13Oc6
Oc6H13
Oc6H13
H13Oc6
H13Oc6
128
Glycomonomers
O
O O O
O
O O
O
O
O H O OH
O
O O O
HO
O O HO
O O O
O H OH
131 [289, 342] O
133 [101]
130 [101] O
132 [102]
(continued)
HO
O
O O HO O O
O O HO
HN OH OH
O O OH
HO HO O O
HO HO HN O
OH HO
OH
OH OCH3 OH
134 [344] 135 [345] 137 [344]
O
O
136 [343]
O
O
O O NH
OH O N O
O
OH
HO
NH
HO
OH
O HO OH
138 [316] 139 [347]
Liquid crystalline monomers
O O O O O O O O
2O 6O
O O
O O
O O
142 [394]
143
140
141 [207]
(continued)
O
O O O O O O
O
6 O nO
OC6H13
144
OCH3 CN OC6H13
145 146a n = 2 147 [271]

146b n = 6
146c n = 8
O O
O O O O
O O
11 O 6 O
N N
N
N
N N
N N
C4H9
OCH3
148
R R 151
149 150a R = H
R = CN, OCH3 150b R = NO2
(continued)
O
O O
6 N N
N
N N
N
N Cl
CN N
152 [207] N N
153 [186]
Dendrons
O
O O
O
HN O
HN O
O
O
O O
O O
CF3 CF3
CONH2 CONH2
155 [477]
154 [477]
Betaines
O O O O
O O O O
O N N
O N
P
O O
CO2–
158 –O
2C
SO3–
N 159
157 [317, 350]
156 [286, 317] DMAPS
MPC
(continued)
Ionic liquid monomers
O O O
O O O
Br– X–
Br–
N N
N
N N
N
160 [298]
161 [298]
162
Amine/ammonium functional
O O
O O N
O
O
N N O
N N
N
163 [216]
165 [216]
N
164 [216]
O O O O
O O O O
I– N C7H15
N NH O
S
167 [270] 168 Li+ O
N–
O
166 S
O
CF3
169
Table 8.10 Methacrylamide derivatives subjected to RAFT polymerization.
HN O HN O
OH HO OH OH
O
OH OH
HO O
NH HO NH
HO HO
OH
OH OH
O O
170 [316] 171 [316]
O O
NH NH
OH OH
OH OH
HO HO
NH NH
HO HO
OH OH
O O
172 [370] 173 [373]
OH
O
HO C8H17O HN O
HO
HN OH
OC8H17
O
174 [347]
C8H17O
175
HN HN O O
O
OH HN
O OH
HO
O
HO O
OH HO
O N
176 HO
OH
177
CO2–
178 [385]
(continued)
O O
HN O
HN Br– HN
N
N
NH
179 [298] O
OH HO2C
N N
OH
180
N N
CO2H
CO2H
181
Table 8.11 Other 1,1-disubsituted monomers subjected to RAFT polymerization.
O
O O O O O N
O O
182 183 MMBL 184
185
(continued from page 240)
Many acrylate esters commonly undergo chain transfer to polymers during poly-
merization, leading to branched and even gelled polymers. It has been reported
that the extent of branching is higher for conventional radical polymerization than
for RDRP (ATRP, RAFT, NMP) [751, 752]. Explanation for this has been proposed
in terms of the differences in the concentrations of short-chain radicals between
RDRP and conventional radical polymerization and in terms of radical life times (the
time between chain activation and deactivation) being of the same order of magni-
tude or shorter than the time required for the conformational change required for
intermolecular hydrogen atom transfer [753]. On this basis, the process might be
anticipated to be less prevalent with dithiobenzoates than with less active RAFT
agents. However, this hypothesis has not been tested.
8.5.2.2 Acrylamides
Attaining low dispersities with RAFT polymerization of acrylamides requires a
RAFT agent suitable for MAMs. Acrylamides include Am, DEAm, DMAm, NIPAm,
Table 8.12 Acrylate monomers subjected to RAFT polymerization.
O O O
O O O
O O
O O
O
O
NH2
186 [733]
187 [680]
Solketal O
acrylate P
HO
Ph
188 [734]
O
O OH O
O OH O O O O
HO HO
O
OH
PhCH2O
189 [345] O
PhCH2O O
190 [224]
OC6H13
192
191 [601]
O
O O O O O
O O
11 O
nO
O O
CN
193
CN
194
CA
196 n = 1 [348]
195
[735] 197 n = 2 [224]
198 n = 4 [736]
(continued)
OCH3 O
O
O O
OCH3 O
199 [261]
OCH3
200 [257]
O
O
O O
OCH3
O O
O
O
OCH3
201 [257] OCH3
202 [257]
O O
O O
N
Fe
N
O
204 [681]
N
NO2
203 [737]
NAM (see Abbreviations), those listed in Table 8.13, and those in Table 8.16 (see
Section 8.5.5, p 279).
8.5.2.3 Styrenics
Styrenic monomers subjected to dithiobenzoate-mediated RAFT polymerization
include AcS, AMS, CMS, HMS, 4HS, MeS, PFS, SSO3 Na, St, tBDMSOS, tBOS,
Table 8.13 Acrylamide derivatives subjected to RAFT polymerization.
O O
O
HN HN N
O NH
N
N N
HN O O O
208 NAA
206 [120]
205 [119] 207 [401]
O O O O
NH NH N N
HO2C HO3S N N
CO2–
209 [738] 210 SO3–
AMPS 212
211
OH
HO O
O
HN HO
OH HO O
OH O
O NHAc
OH N
H
213 [739]
214 [552]
OH
OH O
O HN
HO
HO O
O
O
O O
O
O
N
H
215 [552] 216 [740, 741]
O O O O
HO2C NH HO2C N H3CO2C N N

HO2C
217 218 [517] 219 [513]

OH
220 [80]
O O O O
HO2C NH H3CO2C NH HO2C NH NH

O
NH HN
CO2H
221 [519, 742] 222
224
223 [80]
Table 8.14 Styrene derivatives subjected to RAFT polymerization.
OCH3
N O O
N
O
226 [141]
225 [141] 228 [140, 480]
O O
OCH3
227
N
O N N O
N
229 [513] N
O O
O O
230 [259] 231 232 [488]
N N
N
233 235
234 [317, 743]
(continued)
CHO
O O
O O
O O
O O
O O
O O
239
236 [523] 237 [487]
238 [235]
Br
S O
240 [235] Br
acenapthylene 241 O C4H9
P
C4H9
O C4H9
Fe
([Co(Sal)2]2–)0.5
242 [232] 243 [163]
N N+
Cl–
O N– O
VBTAC S S
CF3 CF3
244 OO
245 [744]
THPOS (see Abbreviations), those listed in Table 8.14, and those included in
Table 8.16 (see Section 8.5.5, p 279). Rates of RAFT polymerization of styrenes are
relatively slow and may be slower when mediated by aromatic dithioesters. Much
has been written on the potential retardation mechanisms [7, 9, 22, 754].
8.5.2.4 Diene Monomers

RAFT polymerization of diene monomers generally requires a more active RAFT
agent and the use of higher reaction temperatures to obtain good control and a
reasonable rate of polymerization (e.g. 125 ∘ C). RAFT homopolymerizations of Bd
and Ip in solution are slow [755].
Table 8.15 Monosubstituted LAMs and IAMs (vinyl monomers).
O N N N
O O S
O S O
O
248 [745] 249 [745]
250 [745]
246 NES [532] 247 BES [532]
There are conflicting results for RAFT polymerization of Ip mediated by 6 at

120 ∘ C, with one report indicating that the dithiobenzoate was unstable [238], and
the other indicating reasonable control [239]. It was noted that low molar mass was
targeted in the latter experiment. Another difference was the use of DCP vs. AIBN
as initiator respectively.
8.5.3 1,2-Disubstituted MAMs

1,2-Disubsituted MAMs used in dithioester-mediated RAFT polymerization
include MAH and the maleimide derivatives, NPMI, NEMI, NMMI, and NPrMI.
These monomers are not used in homopolymerization but are used in RAFT
copolymerization and in RAFT-SUMI (Section 8.10) to form end-functional
polymers.
8.5.4 Monosubstituted IAMs and LAMs

The monosubstituted LAMs and intermediate activated monomers (IAMs), such as
the vinyl esters (e.g. VAc), the N-vinyl amides and imides (e.g. NVP), the N-vinyl het-
eroaromatics (e.g. NVC, 248–250), and the halo-olefins (e.g. VC) generally require
the use of a RAFT agent more suited for those classes of monomers (usually a xan-
thate [756] or an appropriate dithiocarbamate [556, 757]).
Thus, substantial retardation is seen with the dithiobenzoates in the polymerization
of VAc [458], BES, and NES [532], and the vinyl aromatics NVC [550] and 248–250
[745]. Intermediate radical termination is a likely cause of the retardation with
these systems. However, poor R group selection may also be an issue. For example,
benzyl radical is slow to add to LAMs (e.g. VAc, NVP) [758].
8.5.5 Monomers with Reactive Functionality

There is a need for processes for polymer modification after RAFT polymerization
(the so-called polymer analogous reactions) that ideally proceed with quantitative
yield under mild reaction conditions. The reactive functionality may be present on
the Z or R groups of the RAFT agent (Section 8.3.2) or in the monomers. Monomers
used in this context can be incorporated in blocks to serve as a precursor to a
polymer brush, or they may be copolymerized to provide sites for the attachment
of functionality or for crosslinking. Examples of functional monomers used in

dithiobenzoate-mediated RAFT polymerization are shown in Table 8.16, p 279.
Many papers are concerned with the combination of RAFT and azide–alkyne
1,3-dipolar cycloaddition. There are some issues with the use of azides and alkynes
in radical polymerization, which extend to RAFT polymerization. Alkynes are
not completely unreactive towards radicals. Thus, alkyne-functional monomers
(Table 8.16(a)) are often protected as the silyl ether and used in that form. The azido
group of azido-functional monomers (Table 8.16(b)) may undergo cycloaddition
reaction with electron-deficient monomers (e.g. (meth)acrylates, acrylamides) and
this may occur during polymerization [759]. The extent of this side reaction can be
mitigated by the use of lower reaction temperatures and shorter reaction times.
Active ester monomers that have been subject to RAFT polymerization are shown
in Table 8.16(c). Thialactones and azlactones, which are used similarly, are shown
in Table 8.16(d). The active ester groups undergo facile reaction with primary or
secondary amines. They may also react with alcohols, thiols, and other nucleophiles.
A potential issue is that nucleophilic reagents may also react with dithioester groups.
The rate of reaction of primary amines with active esters is generally more facile than
that with a dithioester group to the extent that end-group removal is only observed
when an excess of the amine is used.
Methacrylate ester 282 and acrylate 283 (Table 8.16(e)) also contain xanthate func-
tionality. The xanthate functionality with ‘R’ = primary alkyl appears essentially
inert as a RAFT agent during copolymerizations of MMA and tBA, respectively,
mediated by 6. The monomers were used as precursor to thiol functionality following
transformation of the xanthate groups in the product copolymers.
Primary or secondary amine (or hydrazine) functionality is reactive towards
dithioester functionality and must be protected during RAFT polymerization
(Table 8.16(f)). Commonly the tert-butyloxycarbonyl (BOC) protecting group is
used. However, simple protonation is also effective as a protection strategy.
Several papers have explored polymerization of monomers containing isocyanate
functionality; see Table 8.16(h) [231, 390, 531]. RAFT polymerization and the thio-
carbonylthio group are compatible with isocyanate functionality. However, some
care must be taken in the selection of the RAFT agent to ensure that it does not
contain any other functionality that is inherently reactive towards isocyanates (such
as carboxy) [390].
It is possible to use monomers that contain initiator functionality for other forms
of RDRP such as ATRP (Table 8.16(i)) or NMP (Table 8.16(j)) – refer also Section 8.11.
8.5.6 Macromonomers
RAFT polymerization of macromonomers provides a route to comb polymers and
a method for including arms in stars. References to the use of the macromonomers
shown in Table 8.17 in RAFT polymerization with dithioesters can be found
in Table 8.4. The end-groups of macromonomers remote from the double bond
(continued on page 287)

Table 8.16 Monomers with reactive functionality.
(a) Alkyne
O O
O O O O
O O
(H3C)3Si 254
(H3C)3Si 252 [218, 318] 253 [746] PA
251 [103] Si(CH3)3
255 [531]
(b) Azide
O
O O O O HN
O O O N3 O
N3
N3 N3
260 [381]
256 [465] 259 [747]
258 [220]
N3
257 [219]
(c) Active ester
O O O
O O F
O O O
O O N
F F
N O
O F F 264
NO2
262 NAS [583]
261 263 [89, 90]
NMS PFPMA [326–329]
O O
O F O O
O
F F O O
N
F F
F F CF3SO3– S
265 [141, 291, 388] 267 [530]
PFPA [329, 748] 266 [749] F F
F
268 PFPVB [137]
(continued)
O S OF O O
O F
O O O N O
O N O
F F
F
270 [572]
269 PFPVS [137] 271 [142]
O O O O
Cl O O
Cl
N
N
Cl Cl
N
Cl Br
272 [142] 273 [142] 274 [142]
(d) Thialactone, azlactone
N
O
O
O S O 276
HN
S
O
275
(continued)
(e) Protected thiol (2-pyridyldisulfide, thioacetyl, xanthate)
O O
O O O O O O O
O O HN O O
6
S S
S
S
S N S S S
O OC2H5
S O N S S
N N 281 OC2H5 283
S 282
279
277 S 280
N
278
(f) Protected amine or hydrazide
C4H9
O
O O O
O O O
H O
N
O O
O O
O O O
HN HN HN
HN
O O O
O (H3C)3CO
(H3C)3CO (H3C)3CO
(H3C)3CO
285 286 287a R = C3H7
284
287b R = C4H9
O O
O O
HN HN
O HN
6
HN 5
O O
NH
NH (H3C)3CO NH
O
O HN
OC(CH3)3 290 O
OC(CH3)3
289 (H3C)3CO
288
291
(continued)
O
O O O HN
O HN HN
N
N Cl
Cl Cl Cl N
NH3 NH3 NH3
292 AEMA H3N 294 AEMAm 295 [384]
293 APMAm
(g) Silyl ether
O O O
O O O
Si Si Si
O
Si 297
298 tBDMSMA 299
296 tBDMSOS
O
O O O O
O O O Si
Si Si Si
303
300 TPSiMA 301
302
(h) Isocyanate or isothiocyanate
O
O O
O
N N N
C C
N S C
O C 306 O
304 O
307
305
(continued)
(i) ATRP initiator

O
O O
O Cl
O O O O O O
O
O O
Br O O
O
O O O O
O O
O S
Br Cl
O S HO
Br
Br
310 311 312 313
308 O
O
Br
309
(j) NMP initiator
O
O
O N
314
Table 8.17 Macromonomers subjected to RAFT polymerization.
O O O O
H H H H
N N N N
O N N OH
H
O O O
Peptide
macromonomer
315
O
O O
O
O n
N
O
PEGMA (MPEGMA) n
316
Poly(2-ethyl-2-oxazoline)
macromonomer [274]
317
O
O
O O
O
n N
PEGA (MPEGA) O
n
318
Poly(2-cyclopropyl-2-oxazoline)
macromonomer [221]
319
O O
O
O
n N OH
O n
PEG macromonomer O
320 PCL macromonomer
321
O
O
O
O Si
O O Si
Si Si
O O
O O
Si Si
O
Si O Si O
O
POSSMA
322
(continued)
8.7 Ring-Opening Polymerization 287
S O
O N
N
O
O
Si Si Si Si
n O O O
C6H13C6H13 m n
Polyfluorene macromonomer [158] PDMS macromonomer

324
323
(continued from page 280)
are often not explicitly specified. Those based on poly(ethylene glycol) (PEG) (e.g.
316-320) are almost invariably the monomethyl ether but in a few cases, may be the
monoethyl ether or simply hydroxy.
8.6 Cyclopolymerization
Examples of monomers used in dithioester-mediated RAFT cyclopolymerization
or cyclocopolymerization are provided in Table 8.18 (p 288). Details of the RAFT
agents used will be found in Table 8.4. There appear to be no specific constraints on
cyclopolymerization imposed by the RAFT process.
Dithiobenzoates are not generally suitable for mediating the polymerization of
ketene acetals, which are LAMs. However, RAFT copolymerizations of 339 and
BMDO (340) with methacrylates are controlled [61].
Monomers such as DEGMA or DSDMA (344) do not undergo efficient cyclopoly-
merization. However, RAFT crosslinking copolymerizations with DEGMA or
DSDMA (344) have been explored to ascertain the extent of the intermolecu-
lar branching and intramolecular cyclization (cyclopolymerization) that occur
[283, 760].
8.7 Ring-Opening Polymerization

RAFT ring-opening polymerization provides a simple method of forming polymers
with readily cleavable linkages, i.e. esters, thioesters, and/or disulfides, into the
carbon–carbon backbone of a polymer chain (Table 8.19) [475]. The monomers
331–335 were copolymerized with MMA, DMAm, and HEMA.
Dithiobenzoates are not generally suitable for mediating the polymerization of
ketene acetals, which are LAMs. However, RAFT copolymerizations of 339 and
BMDO (340) with methacrylates are controlled [61].
Table 8.18 Monomers used in experiments on dithioester-mediated RAFT

cyclopolymerization.
EtO2C CO2Et tBuO2C CO2tBu
O O O O
O
EtO2C CO2Et 326 [108]
325 [143] O O
O
327 [154]
O O
O O
O O O O
HN NH
O O N
O O O
n
329 [538] O
330 [144]
328 [159]
8.8 RAFT Crosslinking Polymerization
Crosslinking monomers are used both in the synthesis of hyperbranched polymers

(sometimes called microgels) and polymer networks. Crosslinking monomers
include DEGDMA, EGDMA, TEGDMA, EGDA, HDDA, TEGDA, MBAm, and DVB
and the multiolefinic monomers in Table 8.20. Use of monomers such as 343, with
an acetal linkage, or 344–346, with disulfide linkages, results in the formation of
degradable crosslinks, which can be important in controlled release applications.
The crosslinks can also be cleaved to allow for polymer analysis.
Use of a macroRAFT agent to mediate RAFT crosslinking polymerization provides
a mechanism for forming arm-first stars. The use of the hyperbranched polymers
formed by RAFT crosslinking polymerization to mediate further RAFT polymeriza-
tion provides core-first stars. Details of these processes are provided in the Chapters
by Floyd et al. [767] and Allison-Logan et al. [673] Examples of both processes are
included in Table 8.4 and are indicated by purple highlighting.
Model co-networks, so called because the distance between crosslinks is relatively
well defined, can be formed by RAFT crosslinking polymerizations mediated by a
Table 8.19 Monomers used in experiments on dithioester-mediated RAFT ring opening polymerization.
O O O O
O S O
O
S O
S Si S S S
S O S
O
O O S O
O O O O
331
332 O 334 [475] 335 [475]
333 [475]
O O O O
339 [61] 340

336 [761]
Cl Br BMDO
337 [527, 761] 338 [527]
Table 8.20 Crosslinking monomers.
O OH
O O O
O n O
O O
O O O
n
O OH
341 [762] 342 [762]
O
O O
O O S O
O S
O O O
343 [763] DSDMA 344 [632, 763, 764]
O O
H
S O S N
O S N S
H
O O
DSDA 345 [765] DSDAm 346 [748, 766]
O OH
H
N
N
H
OH O
347 [766]
348
Table 8.21 Preparation of model co-networks by RAFT polymerization with ‘R’-connected bis-macroRAFT agents.
Initial RAFT Agent Monomers X-linkera) Comment Application References
56 BMA EGDMA bis-MacroRAFT agent Model co-networks [768]

DMAEMA prepared in first step
56 BA EGDMA bis-MacroRAFT agent Model (co)networks [652]
BMA prepared in first step
DMAEMA
St
56 TFEMA EGDMA bis-MacroRAFT agent Model (co)networks [654]
56 DMAEMA EGDMA bis-MacroRAFT agent Model (co)networks [769]
MAA prepared in first step
60 MMA EGDMA bis-MacroRAFT agent Model (co)networks [660]
BA EGDA prepared in first step
St
S DMAEMA EGDMA bis-MacroRAFT agent Model (co)networks with [644]

MMA prepared in first step hydrolytically degradable
O O crosslinks
S
CN O
2
a) Crosslinker.
bis-macroRAFT agent [644, 652, 654, 660, 768, 769]. Examples of co-networks made
using bis-dithiobenzoates are shown in Table 8.21.
8.9 RAFT Self-condensing Vinyl Polymerization
RAFT self-condensing vinyl polymerization provides a method of preparing

dithioester-functional hyperbranched polymers that can be precursors to core-first
star polymers. The topic has been reviewed [770, 771] and details of the process
are covered in the Chapters by Floyd et al. [767] and Allison-Logan et al. [673]
Examples of dithioester RAFT monomers (sometimes called inimers) are shown
in Table 8.22 (p 293). These polymerizations comprise copolymerization of the
RAFT monomer to form a hyperbranched structure. A second RAFT step or ‘block
synthesis’ then results in adding arms to produce a core-crosslinked star.
There are two forms of hyperbranched core that can be formed depending on
whether the double bond of the inimer RAFT agent is located on ‘Z’ or ‘R’. Most
inimer RAFT agents (349–352, Table 8.22) possess a double bond as part of the
homolytic leaving group R. When the double bond is on ‘Z’ (as in 353), dithioester
group cleavage should provide a linear polymer [644]. The RAFT agents 350a and
b contain a cleavable disulfide linkage that also enables the hyperbranched core to
be decomposed.
8.10 RAFT-Single-Unit Monomer Insertion (RAFT-SUMI)

into Dithioesters
RAFT-SUMI into trithiocarbonates and dithiobenzoates was originally developed as

a method of synthesizing functional RAFT agents or macroRAFT agents. The topic
has been reviewed by Xu [772] and Haven et al. [773]. See also the chapter in the
present volume on sequence-encoded RAFT oligomers and polymers [774].
Successful SUMI requires a RAFT agent with Ctr such that, on average, there
is ≪1 monomer inserted per activation cycle (i.e. kp [M] ≪ ktr [RAFT agent]) and
is facilitated by ki ≫ kp , by k𝛽 ≫k−add , (refer to Scheme 8.1), and by low relative
monomer concentrations (i.e. stoichiometric with RAFT agent). These same
factors are responsible for the selective initialization phenomenon first reported by
McLeary, Klumperman, and coworkers and appear general for RAFT polymeriza-
tion with more effective RAFT agents (those with high Ctr ). They reported data for
dithiobenzoates 5 and 6 with St [775, 776], St/MAH [155], and MA [113]. Similar
findings were reported by Moad et al. [128], who found selective initialization in St
polymerization with dithiobenzoates 5 and 6 (where R is cumyl or 2-cyanoprop-2-yl,
respectively) but not with 22 (R is benzyl). The finding was attributed to the much
lower Ctr of 22 in St polymerization that allows multiple additions of St in an
activation cycle. It was also shown that selective initialization is, not unexpectedly,
favoured by a high RAFT agent/monomer ratio [128].
8.10 RAFT-Single-Unit Monomer Insertion (RAFT-SUMI) into Dithioesters 293
Table 8.22 RAFT monomers for self-condensing vinyl polymerization.
RAFT monomer Synthesisa) Polymerizationsb)
a [630, 631] 349a/St [630]

349a/130 [631]
S S
O
CN b [631] 349b/216 [631]
O
O
R O
349
a R = CH3
bR=H
a [632] 350a/DMAEMA
[632]
350a/GMA/
copolymer [633]
350a/GMA/
S S copolymer-b-
GPMA/MPEGMA
O [633]
CN
S O
O S b [634] 350b/GMA [635]
R O 350b/GMA/
MPEGMA [636]
350
a R = CH3 350b/GMA/
bR=H MPEGMA-b-
MPEGMA [636]
350b/320/321 [634]
A [637] 351/AA [638]

351/St [637, 639]
351/DMAEA [640]
351
(continued)
A [641] 352/NIPAm [641,

642] 352/NIPAm/79
[642, 643]
352/NIPAm/79/126
[643]
352/NIPAm-b-79
[642]
S
N
S
N
352
A [644, 645] 353/St [644, 645]

353/4VP [644]
353/2VP [644]
353/St-b-4VP [644]
353/St-b-2VP [644]
S 353/4VP-b-St [644]
353/2VP-b-St [644]
S
353
a) Refer Section 8.4.

b) Homopolymers and statistical copolymer will typically be hyperbranched. For A-b-B block
copolymers, block A will be a hyperbranched core and block B will be the arms of core-first
stars.
The SUMI process is simplified with the use of monomers that either do
not propagate or are slow to propagate. The SUMI of MAH has been used for
end-functionalization of PSt prepared with 17 [486], or PMMA-dithiobenzoate
prepared with 5 [71], with a succinic anhydride unit (Scheme 8.6).
In 2004, Chen et al. [233] applied SUMI in the synthesis of light-harvesting poly-
mers when they prepared new dithiobenzoate macroRAFT agents by selectively
inserting a single unit of various styrene derivatives.
A complication in SUMI initiated with an added initiator is the formation of prod-
ucts from the reaction of the initiator-derived radicals with the monomer. One way
of resolving this problem is to ensure that the initiator-derived radicals are identical
to the RAFT agent ‘R’ group [172, 777]. This is the case for a first SUMI step when a
dialkyldiazene of structure R—N=N—R is used as the initiator. The issue can also be
resolved by the use of SUMI with direct photoinitiation or PET-RAFT-SUMI when
radicals are generated directly from the precursor RAFT agent [367]. Xu et al. [367]
O O
O
O O O
S S
S THF 70 °C
S
n n
O O
O
O O O
S
S
S BPO dioxane 100 °C

O O n O O n S
Scheme 8.6 Examples of chain-end functionalization by RAFT-SUMI of MAH into a

dithiobenzoate macroRAFT agent.
have demonstrated selective PET-RAFT-SUMI for insertion of St, BA, MA, DMAm,
and NIPAm into dithiobenzoate 9.
8.11 Dithioesters in Mechanism-Transformation

Processes
Block, star, or graft copolymers comprising segments formed by RAFT and other
processes (other RDRP, RDP, living polymerizations) can be combined through the
use of dual initiator-RAFT agents [778–780] and/or through the use of orthogonally
reactive monomers, which enable such functionalities to be combined in situ. The
-
term RAFT-T-‘process’ -
(RAFT first) or ‘process’-T-RAFT (other process first) was
-
coined [778] to describe such processes, where T is short for transformation. We do
not focus on examples (of which there are many) of transformation of end-functional
polymers to polymers with dithioester functionality by end-group modification or
where RAFT-synthesized polymers are linked to other end-functional polymers in
this section.
Dithioester-mediated RAFT polymerization can often be successfully conducted
in the presence of the initiator functionality used in other RDRP methods (e.g.
alkoxyamines for NMP, alkyl halides for ATRP). However, the high reactivity of
dithiobenzoates in radical polymerization means that the converse is seldom true.
8.11.1 Ring-Opening Polymerization (ROP)

Hydroxy-functional dithioesters (e.g. 25–28) allow sequential or, in a few
cases, simultaneous hydroxy-initiated ring-opening polymerization (ROP) and
dithioester-mediated RAFT polymerization. Examples of ROP-T-RAFT - (ROP step
-
first) and RAFT-T-ROP (RAFT first) are shown in Table 8.5 (p 251).
There are also many examples in the literature of the use of end functional poly-
mers, which are converted to a macroRAFT agent to form a block copolymer by
RAFT polymerization. Examples include the PDMS macroRAFT agents 49 and 50

(Table 8.5), where the PMDS can be formed by ROP of a cyclic siloxane, and PEG
macroRAFT agents, where the PEG might be formed by ROP of ethylene oxide but
is most often obtained commercially.
8.11.2 Ring-Opening Metathesis Polymerization (ROMP)

Many of the 1,2-disubsituted olefins commonly used as monomers for ROMP appear
inert under the conditions used for RAFT polymerization. Thus, dithiobenzoates can
contain a norbornene group (45, Table 8.5), and the RAFT-synthesized polymers
formed with these RAFT agents can be used as a precursor to brush polymers by
-
ROMP in a RAFT-T-ROMP -
process [607–609]. ROMP-T-RAFT (ROMP first) making
use of dithioester 46 has also been described [611].
8.11.3 Atom Transfer Radical Polymerization (ATRP)

Many RAFT agents have been used as pseudo-halides in ATRP. There are also
examples of photo-redox processes or PET-RAFT involving dithioesters, which can
-
be considered under the umbrella of RAFT-T-ATRP. Some of these are mentioned
in Section 8.14.
ATRP initiators can be converted to RAFT agents by activation in the presence
of a bis-dithioacyl disulfide. This process is an example of Method C (Section
8.4) [438, 781]. The process has been applied both in the synthesis of low
molar mass RAFT agents and for the transformation of ATR-synthesized poly-
mers into macroRAFT agents. The process has been called atom transfer radical
addition−fragmentation (ATRAF). For dithioesters, the reported yields are generally
high (82−92%) [438, 781], but lower yields were observed for dithiocarbamate (65%)
and xanthates (43%) [438].
ATRP (alkyl halide) initiators (and ATRP conditions for activation) can also be
used to initiate dithioester-mediated RAFT polymerization. In this, the RAFT agents
or macroRAFT agents may also act as pseudo-halide ATRP initiators; the precise
mechanism of the concurrent ATRP/RAFT process is not always clear [782].
In the absence of an ATRP activator or catalyst, ATRP alkyl halide initiators
are typically inert. Thus, RAFT polymerization can be used to form polymeric
architectures containing ATRP initiator functionality, which can subsequently
be activated by addition of the ATRP activator. For example, graft (bottlebrush)
-
and star polymers were prepared by RAFT-T-ATRP. The process involved RAFT
polymerization to form a polymer based on the monomer bearing pendant ATRP
initiator functionality, which was subsequently used in growing arms on the
RAFT-synthesized core/backbone. Examples of monomers containing ATRP initia-
tor functionality (sometimes known as ATRP inimers) are provided in Table 8.16(i)
and examples of their use appear in Table 8.4. For clarity of mechanism and to
ensure product purity, it may be desirable to remove the RAFT end-group before
commencing the ATRP step.
8.11.4 Nitroxide-Mediated Polymerization (NMP)

-
Various processes for implementing RAFT-T-NMP have been described [778–780].
The ESARA process (Exchange of Substituents between [macro]Alkoxyamines
and [macro]RAFT Agents) [579] allows exchange of homolytic leaving groups
between alkoxyamines and (macro)RAFT agents; the pathways are illustrated
in Scheme 8.7 for the case of formation of a PSt–SG1 macro-alkoxyamine from
the macroRAFT agent PSt–DB. The radical derived from the initial alkoxyamine
[(CH3 )2 Ċ(CO2 H) – MAMA] must be able to displace the PSt R group of the macro-
RAFT agent. The desired outcome is favoured by choosing a temperature such that
the initial alkoxyamine (MAMA–SG1) is labile (i.e. undergoes reversible C—O
bond homolysis) and the product alkoxyamine (PSt-SG1) is stable. The kinetics of
the cross-reaction between alkoxyamines and dithioesters has been studied by He
and coworkers [783, 784].
O O O
O O O
P N Δ P N P N
O
O O O
O O n
Ph Ph Ph
O OH n
MAMA-SG1 Ph Ph Ph PSt-SG1
O OH
S S
R R
S S
S S
R R
S S
n
Ph Ph Ph
O OH
S S
S R S
R n
Ph Ph Ph
O OH
PSt-DB
Scheme 8.7 Potential reaction pathways during an ESARA process used to form a macro
alkoxyamine (PSt–SG1) from a macroRAFT agent (PSt–DB).
The one-way transformation of an alkoxyamine NMP initiator to a dithiobenzoate

RAFT agent by heating the NMP initiator with dibenzoyl disulfide has been also
been demonstrated [785].
Dual RAFT agent/NMP-initiators can be synthesized directly or formed in situ by
RAFT copolymerization of an NMP inimer (e.g. 314, Table 8.16(j)) [786, 787].
8.12 Thermally Initiated RAFT Polymerization

with Dithioesters
RAFT polymerization requires a source of free radicals. Historically, this has taken
the form of an added thermal initiator, most often a dialkyldiazene. The use of
dialkyldiazenes in RAFT polymerization has been described in a recent review
[8]. However, in principle, almost any radical source might be used. Thus, radicals
might be generated thermally from an added initiator, the monomer, or the RAFT
agent, by UV–visible irradiation, electrochemically, or by any other process.
Two important considerations to bear in mind in choosing a radical source are
that (a) the initiator-derived radicals, when different from the RAFT agent ‘R’ radi-
cal, will limit the end group fidelity since there will be a mixture of initiator-derived
and RAFT agent-derived chain-ends formed, and (b) for every radical generated by
initiation, one must ultimately be consumed whether by termination, initiator inef-
ficiency or some other process.
When using an added thermal initiator, it is possible to estimate the maximum
fraction of living chains (L) using expression (8.5) or (8.6) [6].
[RAFT]0
L= ([ ] [ ]) (8.5)
[RAFT]0 + df A2 0 − A2 t
[RAFT]0
= [ ] ( ) (8.6)
[RAFT]0 + df A2 0 1 − e−kd t
([ ] [ ])
where [RAFT]0 is the initial transfer agent concentration, df A2 0 − A2 t =
[ ] ( )
df A2 0 1 − e−kd t is the number of initiator derived chains, d is the number of
chains produced in a radical–radical termination event (1 < d < 2, e.g. d ∼ 1.67
in MMA and d ∼ 1.2 in styrene polymerization [788]), f is the initiator efficiency
(0 < f < 1), [A2 ]0 is the initial initiator concentration, kd is the rate coefficient of
initiator disappearance, and t is the reaction time.
A guideline for achieving control proposed in the first RAFT patent [5, 143] was
that conditions should be chosen such that the amount of initiator decomposed was
<10 mol% of the amount of RAFT agent. This would ensure an end-group fidelity of
>80% and most likely >90%, depending on the initiator efficiency and the mode of
termination.
It is important that the initiator-derived radical is a good homolytic leaving
group with reference to the R group of both the initial RAFT agent and the product
macroRAFT agent; otherwise, the RAFT agent can be converted to a relatively
stable ‘by-product’. For example, AIBMe was found to be a poor initiator choice
in MMA polymerization [64] mediated by dithioester 6 since the initiator-derived
RAFT agent (11b) has a low transfer coefficient both with respect to 6 and the
PMMA macroRAFT agent [64]. The initiator-derived RAFT agent 11b was observed
to accumulate during the experiment.
Most peroxide initiators can be successfully used in RAFT polymerization
with dithioesters as long as conditions are such that the initiator-derived radicals
react with monomer rather than with the RAFT agent. Rate coefficients ki for
8.13 Photoinitiated RAFT with Dithioesters 299
oxygen-centred radicals adding to monomer [758, 789] are typically substantially

higher than those for tertiary alkyl radicals adding to monomer [790].
8.13 Photoinitiated RAFT with Dithioesters

RAFT photoinitiation was foreshadowed and claimed in the first RAFT patent
in 1998 [143]. However, this document contained no examples of photoinitia-
tion whether direct or with the use of photoinitiators. A process equivalent to
photo-SUMI (into xanthates) was first reported by Delduc et al. [791] in 1988.
For additional information on photoinitiated RAFT processes making use of
dithioesters, the reader is referred to the chapter of Chapman et al. [792] and
other recent reviews [793]. Examples of photoinitiated RAFT polymerization
and photo-SUMI are indicated in Table 8.4 (entries in Red and Bold Orange,
respectively).
Dithioesters have been used in photoinitiated RAFT polymerization. The π → π
transition appears at ∼295 nm (𝜀 ∼ 15 000). The forbidden n → π transition for
primary and secondary dithioesters appears at ∼510 nm (𝜀 ∼ 100) and is red-shifted
to ∼530 nm for tertiary dithioesters [794]. The use of direct photoinitiation or
PET-RAFT appears to give less by-products than conventionally initiated (with
a thermal initiator) RAFT polymerization. Additionally, the use of visible light
irradiation (excitation of the n → π transition) appears to result in fewer issues than
does the use of UV light [66, 795–797]. This is attributed to a lower incidence of
side reactions. However, the specific side reactions have not been defined and it is
not clear whether the process is more selective for the desired C—S bond scission
(Scheme 8.8) or whether higher selectivity is simply a consequence of lower radical
concentrations. The occurrence of termination will lead to an excess of ZC(=S)S
radicals, which may retard radical generation.
Initiation
S S R kactR S S• + R •
Z kdeactR Z
S S Pn kactP S S• + Pn•
Z kdeactP Z
Scheme 8.8 Mechanism for initiation of RAFT polymerization without an exogenous

initiator.
The mechanism for radical generation by direct photoinitiation is described by

the two reactions shown in Scheme 8.8. As with systems with an exogenous initia-
tor (Scheme 8.1), termination occurs at a rate dictated by the radical concentration.
While it might be considered that reversible deactivation steps shown in Scheme 8.8
could, by themselves, provide a mechanism for control (one analogous to Otsu’s
iniferter process [798]), to achieve low dispersities at low conversions, the dominant
control mechanism must be RAFT. The use of photoinitiation does not turn off the
activity of dithioesters as RAFT agents.
At least four forms of photoinitiated RAFT polymerization should be considered:
(i) polymerizations conducted in the presence of an added photoinitiator; (ii) direct
photoinitiation when the dithioester dissociates into radicals by photocleavage of the
C—S single bond; and PET (photo-induced energy or electron transfer) RAFT that
might involve either (iii) photosensitization or a (iv) photo-redox process. Examples
of photoinitiated RAFT polymerization are highlighted in the Table 8.4. However, we
do not distinguish the form of photoinitiation there. Catalysts used in PET-RAFT of
MMA with dithiobenzoate 9 include Ru(bpy)3 Cl2 [304], Ir(ppy)3 [304], and Eosin-Y
[305] with blue light, ZnTPP with yellow light [799], and TPP [306] and ZnTPP [306]
with red light (refer Table 8.4).
8.14 Redox-Initiated RAFT with Dithioesters

In this section, we consider RAFT polymerization initiated by a redox process involv-
ing the RAFT agent. We do not consider RAFT polymerization initiated by redox
initiators. The redox properties of dithioesters and redox/electrochemical initiation
are detailed in the chapter by Lorandi et al. [800] and so a detailed discussion will not
be given in this chapter. The electrochemical behaviour of dithioesters is described
by Strover et al. [801].
Examples of redox-RAFT are identified in Table 8.4 (entries in Green). At least two
forms of direct redox-initiated RAFT can be distinguished, (i) where the RAFT agent
behaves as a pseudo-halide in an ATRP-type mechanism [76, 77, 423, 425, 802], and
(ii) involving electron transfer to the RAFT agent with formation of a radical anion
intermediate. The latter process has been called dissociative electron-transfer RAFT
polymerization (DET-RAFT) [296, 803].
A report of ‘ATRP’ of MMA mediated by Cu(II) dithiobenzoate as activator,
PMDETA as ligand, and with AIBN initiator at 100 ∘ C should also be considered
here [804]. In this and many other cases, the mechanism has not been fully
established [415, 805].
8.15 Reaction Conditions and Side Reactions

of Dithioesters
The mechanism of RAFT with dithioesters and other RAFT agents and complicating
side reactions have been briefly mentioned above and are described in greater detail
in the chapters by Buback [21] and Quinn et al. [22] Some specific situations have
been discussed elsewhere in this chapter.
Low conversion initiator efficiencies in RAFT polymerization appear to be the
same as in conventional radical polymerization [128]. Conversion plateaus, where
the conversion of monomer to polymer reaches a limiting value, are sometimes
observed in RAFT polymerization. These can have a number of causes, which
8.16 RAFT Emulsion/Miniemulsion Polymerization Mediated by Dithioesters 301
include decomposition of the RAFT agent (or other species) during polymerization
to form compound(s) that inhibit polymerization (for dithioester examples see
[9, 806, 807]), exhaustion of the initiator, and reduced initiator efficiencies at high
monomer conversions.
It is known that initiator efficiencies for dialkyldiazenes reduce dramatically with
conversion for higher monomer conversions [8]. This can cause rates of initiation
drop to near zero at high monomer conversion. Polymerization cannot then be con-
tinued and cannot be simply restarted by addition of further initiator. Conversion
plateaus in RAFT polymerization may, in part, be attributed to the fact that dialkyl-
diazenes are the most commonly used initiators.
Although many RAFT polymerizations can be carried out in the presence of air to
still yield low-dispersity polymers, they, nonetheless, show sensitivity to air and it is
clear that rigorous degassing is critical in any study of RAFT polymerization kinetics
[6, 9]. Depending on the monomer and the particular RAFT agent, the presence of air
can cause retardation, an inhibition period, and/or loss of RAFT agent, all of which
can lead to the degree of control being reduced. RAFT polymerization mediated by
aromatic dithioesters such as dithiobenzoates may be more air sensitive than that
with most other RAFT agents (e.g. aliphatic dithioesters, trithiocarbonates) because
of the longer lifetimes of the intermediate radicals.
8.16 RAFT Emulsion/Miniemulsion Polymerization

Mediated by Dithioesters
Examples of heterogeneous polymerization are identified in Table 8.4 (entries
in Blue). RAFT emulsion polymerizations commencing with low-molar mass
dithioesters were first reported by CSIRO in the initial RAFT papers [5, 48] and
patents [143]. The reported processes were starved-feed (also known as semi-batch)
emulsion polymerizations and successfully provided low-dispersity polymers (e.g.
Ðm < 1.2). The conditions used were similar to those successfully used in forming
low-dispersity block polymers with the so-called macromonomer RAFT agents
[808, 809]. The starved-feed protocol was used because initial attempts to form
low-dispersity polymers by ab initio batch emulsion RAFT polymerization with
dithiobenzoates had failed [9].
Monteiro and coworkers studied RAFT emulsion polymerization in greater depth
and found that the direct use of more active RAFT agents (in particular, cumyl
dithiobenzoate, 5) in a batch ab initio process was generally unsuccessful and the
polymerizations were characterized by substantial retardation or inhibition, poor
latex stability, and broad or multimodal molar mass distributions. Luo and Cui [810]
proposed an explanation for the lack of success in RAFT emulsion polymerization
with dithioesters in terms of ‘super swelling’ caused by the presence of the high
concentrations of short oligomers that are formed early in the polymerization,
which is characteristic of an efficient RDRP. They found that the problem could be
mitigated, though not fully resolved, through the use of very high concentrations of
conventional surfactants and/or by the use of non-ionic surfactants [701].
Several groups reported that less active (low transfer constant) RAFT agents such
as the aliphatic dithioesters, 68, 69, or 75, could be used to conduct a successful batch
ab initio emulsion polymerization [698, 811]. This avoided the formation of high
concentrations of short oligomers at low monomer conversions. However, the level
of control achievable was then compromised in that polymers with low molar mass
dispersity were not formed (Ðm usually >2).
Most recent studies on RAFT emulsion polymerization with dithioesters have
been based on the use of amphiphilic macroRAFT agents usually in the context of
polymerization-induced self-assembly (PISA). PISA is discussed in the Chapter of
D’Agosto et al. [812].
8.17 Dithioester Group Removal/Transformation

The presence of a dithioester group in RAFT-synthesized polymers means that these
polymers are likely to be coloured. The colour may range from violet through red
(aromatic dithioesters including dithiobenzoates) to orange (aliphatic dithioesters).
This may provide a reason for end-group removal.
Dithiobenzoate RAFT agents and macroRAFT agents have also been found to very
effectively quench the fluorescence of coumarone derivatives and acenaphthylene
units [235, 813, 814]. No such quenching was observed for polymers from which
the dithioester end-group had been removed [235, 813]. Thus, the thiocarbonylthio
groups are often removed from polymers used in optoelectronic applications.
In their review, Fairbanks et al. [2] reported that some toxicity can be observed
for polymers formed with dithiobenzoate RAFT agents for high concentrations of
polymers but also pointed out that most applications call for concentrations that are
well below the toxicity threshold. Nonetheless, for many biomedical applications
it is considered desirable to avoid any unforeseen issues by removing the thiocar-
bonylthio functionality. Fortunately, dithioester chain ends may be easily removed
by a variety of techniques to leave the RAFT-synthesized polymer with no intrinsic
toxicity attributable to the mechanism of polymerization.
There are also many other circumstances when it may be desirable to transform a
dithioester group to achieve a desired functionality or for use in a subsequent process
post-RAFT polymerization. Methods for end-group transformation are discussed in
detail in the chapter by Lowe and Dallerba [4]. Earlier reviews on end-group trans-
formation may also be consulted [815–817]. In this chapter, we focus on methods
that are used for dithioester end-group transformation.
8.17.1 Dithioester Group Removal by Reaction with Nucleophiles

RAFT-synthesized polymers are an often-used source of polymers comprising thiol
chain ends. The thiocarbonylthio group of RAFT-synthesized polymers reacts with
nucleophiles to provide a thiol end [250, 818]. A theoretically estimated order
of reactivity of thiocarbonylthio groups towards primary amine nucleophiles is
dithioate ≥ dithiobenzoate > xanthate ≥ trithiocarbonate ≫ dithiocarbamates [818]
(this order can be modified by substituents). Nucleophilic reactants used in this

context include primary and secondary amines, thiols, hydroxide, azide, and
hydride reducing agents, borohydride (examples of most of these are provided in
Table 8.23).
Various side reactions can complicate thiol formation. These include disulfide for-
mation by oxidative coupling and intramolecular thiolactone formation. The side
reactions depend strongly on reaction conditions and can be mitigated by trapping
the thiol end-group in situ, for example, through a thio-Michael adduct [174, 229]
or the methyl or other disulfide [822].
The reaction of dithioesters with thiols has been used as a method of RAFT agent
synthesis by thiol exchange. (Method F, Section 8.4) [827]. The method was applied
in the synthesis of 12, 20, and 21 (refer Table 8.4). Dithiobenzoates and polymers
with dithionenzoate ends react with cysteine or homocystine to form a polymer with
a thiol end-group and release hydrogen sulfide (Scheme 8.9) [505, 824].
8.17.2 Dithioester Group Removal by Radical-Induced Reactions

Various radical-induced processes for thiocarbonylthio group removal, which
include radical-induced coupling, radical-induced disproportionation, and
radical-induced reduction are described in the chapter on trithiocarbonates [13]
and will not be described in detail here.
The processes involve generation of radicals, usually from an exogenous
initiator, and conversion of the macroRAFT agent to propagating species by
radical addition–fragmentation, which can then terminate by radical–radical
reaction (giving radical-induced coupling or radical-induced disproportionation)
or by irreversible chain transfer (to give radical-induced reduction) – refer to
Scheme 8.10.
8.17.2.1 Radical-Induced Coupling/Disproportionation

Radical-induced coupling as a method of end-group removal was introduced by
Perrier et al. [828] and involves heating a RAFT-synthesized polymer with a very
large excess (typically ∼20 molar equiv) of a radical initiator. The method has been
successfully applied to many dithioesters and is most effective for polymers with
a terminal methacrylate unit. Most often, the initiator used is a dialkyldiazene
such as AIBN, although other initiators can be used. Some examples are provided
in Table 8.24. Additional examples are reported in the Chapter by Lowe and
Dallerba [4].
While dithiobenzoate end-group removal for polymers with a terminal methacry-
late unit appears generally efficient when using 20 molar equiv of dialkyldiazene,
variable results have been reported for polymers with a terminal St or acrylate unit,
with removal efficiencies being as low as <30% even though reaction conditions
appear generally similar (Table 8.24).
Undecyl radicals (from LPO) are poor radical leaving groups and their addition to
the dithioester thiocarbonyl is irreversible. However, a pronounced bimodal molec-
ular weight distribution was seen when using LPO alone, indicating that the undecyl
Table 8.23 Dithioester end-group transformation by reaction with nucleophiles.
Terminal
monomera) Zb) Reagent(s)c) Trapping, etc.d) Comment References
St Ph NaBH4 — — [485]
St Ph NaBH4 /PBu3 Acrylates In situ thiol-ene [174]
BA Npth NaN3 DTT Sequential [819]
St Ph Ethylamine Zn/CH3 CO2 H Sequential [645]
St Ph Propylamine/ Acrylates In situ thiol-ene [174]
PBu3
St Ph Propylamine — — [485]
St Ph Hexylamine/ — Subsequently [649]
NaHSO3 used in disulfide
formation
St Ph Hydrazine No disulfide [820]
hydrate formation
St/StOAc Ph Hydrazine — Simultaneous [152]
hydrate ester cleavage
StSO3 Na Ph NaBH4 In situ reaction [821]
with gold
surface
St/2VP Ph Hexylamine/ — — [479]
Na2 S2 O4
MMA Ph hexylamine/ — Subsequently [559]
Na2 S2 O4 used in thiol-ene
MMA Ph Hexylamine — Conditions to [468]
favour disulfide
formation
MMA Ph Propylamine MTS In situ trapping [822]
MMA Ph NaN3 DTT Sequential [819]
LMA Ph Propylamine/ — — [608]
Na2 S2 O4
DMAEMA Ph Hexylamine/ — Subsequently [649]
formation
MAA Ph NaOH — [823]
e)
HPMA Ph Hydroxypro- — [823]

e)
pylamine
MPEGMA Ph Hydrazine — [323]

MPEGMA Ph Cysteine With release of [824]
H2 S
AA Ph Hexylamine/ — Subsequently [649]
formation
(continued)
Terminal
monomera) Zb) Reagent(s)c) Trapping, etc.d) Comment References
BA Npth NaN3 DTT Sequential [819]

MA Ph Hydrazine No disulfide [820]
hydrate formation
MA Ph Hexylamine Et3 N/MBP Thio-bromo [365]
Et3 N/EBiB ‘click’
PEGA Ph Butylamine Subsequently [484]
used in thiol-ene
PEGMA Ph Cysteine With release of [2, 824]
H2 S
NIPAm Ph NaBH4 — Gold [416]
nanoparticles
NIPAm Ph LiB(C2 H5 )3 H — Subsequently [382]
used in thiol-ene
NIPAm Ph Octylamine/ AMA In situ thiol-ene [229]
DMPP
NIPAm Ph Ictylamine/ PA In situ thiol-ene [229]
DMPP
NIPAm Ph Hexylamine Et3 N/MBP Thio-bromo [365]
Et3 N/EBiB ‘click’
DEAm Ph Hexylamine/ TMPTA In situ thiol-ene [226]
DMPP
DMAm Ph Hydrazine [116]
DMAm Ph NaBH4 In situ reaction [821, 825]
with gold
surface
AMPS Ph NH3 — Kinetic study [558]
AN Ph Propylamine/ MTS Thiol trapped as [826]
MTS disulfide
a) Monomer unit adjacent to thiocarbonylthio group.

b) Z group of macroRAFT agent. Npth = 2-naphthyl.
c) Nucleophile/reducing agent: DMPP – dimethylphenylphosphine.
d) Reagent used to trap initially formed thiol: DTT, dithiothreitol; EBiB, ethyl
2-bromoisobutyrate; TMPTA, trimethylolpropane triacrylate; MBP, methyl
2-bromopropionate; MTS, methyl methanethiolsulfonate (S-methyl methanesulfonothioate).
e) During conversion of RAFT-synthesized poly(pentafluorophenyl methacrylate) to
poly(methacrylic acid) (by reaction with NaOH) or a poly(N-alkylmethacrylamide) (by
reaction with a primary amines; such as 2-hydroxypropylamine). Conversion efficiency to
thiol end-group was determined as >80%.
S
S
H2S N
S CN
n CO2H CO2H
HS
O O HS CN
NH2 n
m
O O
O
PEGA-DB m PEGA-SH
Scheme 8.9 Transformation of polymers with dithiobenzoate end-group (PEGA-DB) with

cysteine to form polymer with a thiol end-group (PEGA-SH) and release hydrogen sulfide.
radical is unable to trap the propagating radicals efficiently. A combination of LPO

and AIBN was found to completely remove the thiocarbonylthio end-groups of PSt
and PBA without formation of a bimodal molecular weight distribution [222].
It is important to note, if using this process to prepare end-functional polymers,
that reaction of (for example) 2-cyano-2-propyl radicals with propagating radicals
may involve disproportionation as well as combination. For example, the combi-
nation/disproportionation ratio for 2-cyano-2-propyl reacting with PSt propagating
radical is reported as 0.61.
8.17.2.2 Radical-Induced Reduction

Examples of radical-induced reduction of dithioesters are provided in Table 8.25.
The comments on the process provided in the Chapter on trithiocarbonates [13] are
relevant here and do not require elaboration.
8.17.3 Dithioester Group Removal by Oxidation

Examples of dithioester-group removal by oxidation are provided in Table 8.26. Li
et al. [70] found that dithiobenzoates are slowly converted to thiobenzoates on heat-
ing with an initiator (usually AIBN) under air in an inert solvent (benzene), in some
cases with replacement of ‘R’ with an initiator-derived radical. This process may
complicate end-group removal by radical-induced coupling.
On the other hand, heating under air with initiator in THF solvent provides a poly-
mer with hydroperoxide end-groups, which can be reduced to hydroxyl end-groups
[159, 720].
RAFT end-groups can be readily removed by reaction with hydrogen peroxide
[5, 833–836]. The process has been demonstrated for dithiobenzoates [834, 836],
trithiocarbonates [834, 835], and xanthates [833]. The processes reportedly [833,
834] lead to the thiocarbonylthio group being replaced with a hydroxyl group
though the exact mechanism has not yet been established or the end-group struc-
ture experimentally confirmed. It is known that low-molar mass dithiobenzoates
(e.g. 21) undergo reaction with alkaline hydrogen peroxide to form benzoic acid
[837], with the benzyl group being converted (initially) to the thiolate anion.
Initiator I•
S S Pn I S • S Pn I S S
Radical addition– + Pn•
fragmentation I• +
Z
Z Z
S S Pn S S•
hν or Δ
Photoiniferter process + Pn•
Z Z
Radical-induced coupling Pn• + I• Pn I
Radical-induced disproportionation Pn• + I• Pn = + I H
Termination Pn• + •
Pn Pn Pn
Pn• + Pn• Pn H + Pn =
[H]
Radical-induced reduction Pn• Pn H
Scheme 8.10 Dithioester group (Z = aryl or alkyl) removal by radical-induced reaction pathways including radical-induced coupling, radical-induced
disproportionation, and radical-induced reduction.
Table 8.24 Dithioester group removal by radical-induced reactions (coupling or

disproportionation).
Terminal
monomer [Initiator] Temperature % ends
ZCS2 a) unit Initiator [RAFT]b) (∘ C/h)c) removedd) References
S St AIBN 20 80/2.5 100 [828]

Ph
S
S St AIBN 20 80/4 28 [222]
Ph
S
S St AIBN 100 80/4 80 [222]
Ph
S
S St LPOe) 2 80/4 100 [222]
Ph
S
S St AIBN+LPO 20+2 80/4 100 [222]
Ph
S
S PEGA/ ACHN 20 80/2.5 100 [828]
Ph DMAEA
S
S MA ACPA 20 80/2.5 100 [828]
Ph
S
S BA AIBN 30 80/4 27 [222]
Ph
S
S BA AIBN + LPO 20 + 2 80/4 100 [222]
Ph
S
S MMA AIBN 20 80/2.5 100 [828]
Ph
S
S MMA/ AIBN 20 80/2.5 100 [396]
Ph PFPMA
S
S MMA Et3 B/O2 5 25/1 min 100 [829]
Ph
S
S PEMA AIBN 60/48 100 [426]
Npth
S
a) ZCS2 group of macroRAFT agent. Npth = 2-naphthyl.
b) Mole ratio of initiator to RAFT synthesized polymer.
c) Temperature/reaction time.
d) Percentage of end-groups removed.
e) Bimodal molar mass distribution observed.
Table 8.25 Dithioester group removal by radical-induced reduction.
Dithioester
group Polymer Initiator Reagenta) comment References
S MMA h𝜈 (365 nm) EPHP [830]

Ph
S
S St LPO, BPO iPrOH Bimodal MMDb) [125]
Ph
S
S St ACHN EPHP [125]
Ph
S
S St AIBN C12 H25 SH/Ph3 SiH Incomplete [831]
Ph
S
S St TPO/h𝜈 C12 H25 SH/Ph3 SiH [831]
Ph
S
S St h𝜈 (365 nm) C12 H25 SH/Ph3 SiH [831]
Ph
S
a) ZCS2 group of macroRAFT agent.
b) iPrOH, isopropanol; EPHP, N-ethylpiperidine hypophosphate.
c) Bimodal molar mass distribution.
8.17.4 Dithioester Group Removal by Thermolysis

Legge et al. [838] examined the stability of a range of RAFT agents (includ-
ing dithiobenzoates 9 and 15) by thermogravimetric analysis and reported that
dithiobenzoates are significantly more thermally stable than similar trithiocarbon-
ates, xanthates, or dithiocarbamates.
Chong et al. [178] studied the use of thermolysis as a means of end-group removal
for PMMA-dithiobenzoate and PMMA-trithiocarbonate. For the dithiobenzoate,
end-group loss by a Chugaev mechanism occurred at 180–220 ∘ C to leave a poly-
mer with an unsaturated chain end that had little change in molecular weight
from the precursor polymer. These findings were confirmed in general terms
by Bressy et al. [839], Katsikas et al. [173], Bekanova et al. [840], and Bressy
et al. [839] also examined the thermal stability of poly(tert-butyldimethylsilyl
methacrylate)-dithiobenzoate. The PMMA ‘macromonomer’ formed is more stable
to (further) weight loss than that formed by conventional radical polymerization,
but noticeably less stable than the polymer formed from PMMA-dithiobenzoate
Table 8.26 Dithioester group removal by oxidation.
Product
Polymer Z Reagent Comment end-group References
MA Ph tBuOOH sulfine intermediate —(C=O)SPh [110]

MMA, acrylates Ph Air AIBN, THF solvent –OOH [183, 832]
MMA, St Ph Air AIBN, benzene —(C=O)SPh [70]
MMA Ph(CH3 )2 Air THF, acid SHa) [181]
St Ph H2 O2 — –OH [833]
a) Presumed end-group [181].
after end-group removal by aminolysis (with thiol end-group) [648] or sequential

aminolysis and thio-Michael reaction [559].
PMMA-dithiobenzoate is reported to be relatively unstable when heated in
solution at ≥100 ∘ C. Xu et al. [841] reported that PMMA with dithiobenzoate ends
degrades at substantially lower temperature than found in the abovementioned
work [178]. Factors that might lead to PMMA appearing less stable include the
presence of residual initiator (left over from polymer synthesis), exposure to light
during thermolysis, or metal contamination in the sample.
8.17.5 Electrocyclic Reactions of Dithioesters

The hetero-Diels–Alder reaction involving thiocarbonyl group as heterodienophile
provides a route to dihydrothiopyrans [842, 843]. The cycloaddition is facilitated by
α-electron-withdrawing substituents and is catalysed by Lewis and Brønsted acids.
Barner-Kowollik and coworkers demonstrated this chemistry for RAFT agents and
macroRAFT agents with electron-withdrawing ‘Z’ (2-pyridyl (e.g. 22), phosphonate,
and phenylsulfonyl) and suitable dienes (Scheme 8.11) [540, 544, 844–851]. The pro-
cess has been used in the synthesis of block copolymers [540, 543, 546, 563, 844],
star polymers [544, 546, 844, 847], graft copolymers [851], and modified surfaces
[848, 849]. To achieve acceptable rates, the reaction is typically catalysed by trifluo-
roacetic acid [844].
Aliphatic diazo-compounds undergo a facile 1,3-dipolar cycloaddition with
electron-deficient thiocarbonyl dipolarophiles [852, 853]. Low-molar mass
RAFT-synthesized PMMA with dithiobenzoate ends undergoes facile reaction
R R S N
S N
S S
O O
Scheme 8.11 Hetero-Diels–Alder process with 2-pyridyl dithioester as dienophile.

with diazomethane as indicated by immediate decolourization and a quantitative

doubling of molar mass [182]. Higher molar mass PMMA-dithiobenzoates are also
rapidly decolourized by diazomethane to provide a product with a bimodal molar
mass distribution. The proposed mechanism is shown in Scheme 8.12. Historically,
diazomethane has been widely used to methylate carboxylic acid functionality, e.g.
in polymers containing acrylic or methacrylic acid units [854]. In another study,
methylation of PAA-dithiobenzoate with trimethylsilyldiazomethane provided a
PMA with ∼30% thiol chain end plus other undefined chain ends [855]. Under sim-
ilar conditions, trithiocarbonates were found to either not react with diazomethane
(PMMA) [182] or to give complex mixtures (PAA or PMA) [855].
Z S
Pn
N A
S N N S A
S B B
CH2 N
Z S Z S Z
Z S
Pn S Pn Pn Pn S
Z′ S Qn S
S
Qn Z′
Z
S
Pn S
Scheme 8.12 Proposed pathways for reaction of a dithioester with diazomethane by

1,3-dipolar cycloaddition. A = B is another dipolarophile.
8.17.6 Boronic Acid Cross-Coupling

A copper-promoted cross-coupling reaction between thiocarbonylthio end-groups
(of PSt-dithiobenzoate) and arylboronic acids has been reported [74]. The method
was effective with styrenics (PSt-dithiobenzoate, PPFS-dithiobenzoate) but failed
with PMMA-dithiobenzoate (prepared with 16b). A strategy comprising SUMI
of styrene into the PMMA-dithiobenzoate to introduce a terminal styrene unit
as shown in Scheme 8.13 enabled successful cross-coupling and provided >95%
end-group replacement [74].
8.17.7 Conclusions and Outlook

This chapter was intended as a critical survey of the synthesis, properties, and
application of dithioester RAFT agents of general structure ZC(=S)SR. Aromatic
OCH3
RAFT-SUMI
S S
St
S AIBN 80 °C 2 h S
O O n O O n
OCH3
OCH3
(HO)2 B
Cu(BF4)2·H2O·EtOAc
80 °C 16 h O O n
>95%
Scheme 8.13 Sequential SUMI of styrene (St) and copper-promoted cross-coupling for transformation of PMMA-dithiobenzoate by cross-coupling.
Abbreviations 313
dithioesters (Z = aryl), specifically, dithiobenzoates, reported in the initial pub-

lications on RAFT polymerization, dominated the early literature and remain
amongst the most popular RAFT agents. This can be attributed to the better control
offered by the dithiobenzoates over molar mass, molar mass distribution, and
end-group fidelity with respect to most other RAFT agents, in the polymerization
of 1,1-disbustituted monomers. Aromatic dithioesters are less suited for mediating
RAFT polymerization of monosubstituted monomers, where their use is often
associated with significant retardation, side reactions, and other factors that limit
control. Aliphatic dithioesters (Z = alkyl or substituted alkyl) were also described in
the first patents and publications on RAFT but have seen relatively little use. They
are substantially less active than the aromatic dithioesters but also tend to give less
side reactions and less retardation.
Abbreviations
Abbreviations are listed alphabetically by the abbreviated term. In general abbrevi-
ations of methacrylates end with ‘MA’ methacrylamides end with ‘MAm’ acrylates
end with ‘A’ acrylamides end with ‘Am’ or begin with ‘NA’ (for N-acryloyl). Except
as indicated below the prefix ‘P’ is an abbreviation for ‘poly()’, thus PBA is an abbre-
viation for poly(butyl acrylate).
AA acrylic acid
AAEMA 2-(acetoacetoxy)ethyl methacrylate
AcS 4-acetoxystyrene
AEMA 2-aminoethyl methacrylate (hydrochloride)
AEMAm N-(2-aminoethyl)methacrylamide (hydrochloride)
AEP 2-(acryloyloxy)ethyl phosphate
AIBN azobis(isobutyronitrile) [2,2′ -azobis(2-methylpropionitrile)]
ACHN 1,1′ -azobis(1-cyclohexanenitrile)
ACPA 4,4′ -azobis(4-cyanopentanoic acid)
AIBMe azobis(methyl isobutyrate) [dimethyl
2,2′ -azobis(2-methylpropionate)]
Am acrylamide
AMA allyl methacrylate
AMPS 2-acrylamido-2-methylpropanesulfonic acid sodium salt (AMPS)
AMS α-methylstyrene
AN acrylonitrile
APMAm N-(3-aminopropyl)methacrylamide (hydrochloride)
ATRP atom-transfer radical polymerization
BA butyl acrylate
BAm N-butylacrylamide
Bd butadiene
BES 1-butyl ethenesulfonate (247)
BMA butyl methacrylate
BzAm N-benzylacrylamide
BDSMA t-butyldimethylsilyl methacrylate

BP β-pinene
BzMA benzyl methacrylate
ClPEA 2-chloropropionyloxyethyl acrylate
BPO benzoyl peroxide
CHAm N-cyclohexylacrylamide
CCT catalytic chain transfer
CHMA cyclohexyl methacrylate
CL ε-caprolactone
CMS 4-(chloromethyl)styrene
CMA cholesteryl methacrylate
Cp chloroprene
CPA 3-chloropropyl acrylate
Ð or Ðm molar mass dispersity = ratio of mass average to number average
molar mass [856]
DA dodecyl acrylate
DTT dithiothreitol
DAAm diacetone acrylamide (N-(1,1-dimethyl-3-oxobutyl)acrylamide)
DADMAC diallyldimethylammonium chloride
Dc 1-decene
DBI dibutyl itaconate
DCC N,N ′ -dicyclohexylcarbodiimide
DEAm N,N-diethylacrylamide
DEAEMA 2-(diethylamino)ethyl methacrylate
DEAPMAm N-(3-(diethylamino)propyl)methacrylamide (hydrochloride)
DEGA (diethylene glycol monomethyl ether) acrylate
DEGDMA diethylene glycol dimethacrylate
DEGMA (diethylene glycol monomethyl ether) methacrylate
DEHEA di(ethylene glycol) 2-ethylhexyl ether acrylate
DEHI di-2-ethylhexyl itaconate
DFHMA dodecafluoroheptyl methacrylate
DFHMA decafluoroheptyl methacrylate
DMA dodecyl methacrylate
DMAm N,N-dimethylacrylamide
DMAEA 2-(dimethylamino)ethyl acrylate
DMAEAm N-(2-(dimethylamino)ethyl)acrylamide
DMAEMA 2-(dimethylamino)ethyl methacrylate
DMAPMAm N-(3-(dimethylamino)propyl)methacrylamide (hydrochloride)
DPAEMA 2-(diisopropylamino)ethyl methacrylate
DSDMA disulfide dimethacrylate (344)
DVB divinylbenzene
DVE divinyl ether
EA ethyl acrylate
EAA ethyl 2-acetoxyacrylate
E ethene
EEA ethoxyethyl acrylate
Abbreviations 315
EGDA ethylene glycol diacrylate

EGDMA ethylene glycol dimethacrylate
EHA 2-ethylhexyl acrylate
EOEMA 2-ethoxyethyl methacrylate
EtOAc ethyl acetate
EVC N-ethyl-3-vinylcarbazole
EVE ethyl vinyl ether
EWG electron-withdrawing group
GMA glycidyl methacrylate
GMMA glycerol monomethacrylate (79)
GPMAm N-3-guanidinopropyl)methacrylamide
HA hexyl acrylate
HDDA hexane-1,6-diol diacrylate
HEA 2-hydroxyethyl acrylate
HEMA 2-hydroxyethyl methacrylate
HEMAm N-(2-hydroxyethyl)methacrylamide
HFBA 2,2,3,4,4,4-hexafluorobutyl acrylate
HFBMA 2,2,3,4,4,4-hexafluorobutyl methacrylate
HMA hexylmethacrylate
HMS 4-(hydroxymethyl)styrene
HPA hydroxypropyl acrylate (mixture of isomers)
HPMA 2-hydroxypropyl methacrylate
HPMAm N-(2-hydroxypropyl)methacrylamide
4HS 4-hydroxystyrene
IAM intermediate activated monomer (includes N-vinyl monomers such
as NVC)
iBoA isobornyl acrylate
iBMA isobutyl methacrylate
Ip isoprene
IPhMA 4-iodophenyl methacrylate
iPOx 2-Isopropenyl-2-oxazoline
LA lactic acid
LAM less activated monomer (includes vinyl monomers such as VAc and
NVP)
LMA dodecyl (lauryl) methacrylate
Lim limonene
LPO dodecanoyl peroxide (lauroyl peroxide)
LR Lawesson’s reagent
MA methyl acrylate
MAA methacrylic acid
MAc maleic acid
MADIX Macromolecular Design by Interchange of Xanthate
MAEP 2-(methacryloyloxy)ethyl phosphate (99)
MAH maleic anhydride
MAM more activated monomer (includes styrenes, acrylates, acrylamides)
MAN methacrylonitrile
MBAm methylene-bis-acrylamide
MeS 4-methylstyrene
MMA methyl methacrylate
MMBL γ-methyl-α-methylene-χ-butyrolactone (183)
MOEMA 2-methoxyethyl methacrylate
MPC methacryloyloxyethyl phosphorylcholine (156)
MPEGMA (poly(ethylene glycol) monomethyl ether) methacrylate
MPEGMAm (poly(ethylene glycol) monomethyl ether) methacrylamide
MVK methyl vinyl ketone
NAA N-acryloylazocane (208)
NAM N-acryloylmorpholine
NAPM N-acryloyl-L-proline methyl ester
NAPAM N-acryloyl-L-phenylalanine methyl ester
NAPi N-acryloylpiperidine
NAP N-acryloylpyrrolidine
NAS N-acryloyloxysuccinimide (264)
NEMI N-ethylmaleimide
NES neopentyl ethenesulfonate (246)
NIPAm N-isopropylacrylamide
NMA 2-(naphthalen-2-yloxy)ethyl methacrylate
NMMI N-methylmaleimide
NMP aminoxyl-(nitroxide-) mediated polymerization
NPMI N-phenylmaleimide
NPrMI N-propylmaleimide
NMS N-methacryloyloxysuccinimide (261)
NVC N-vinylcarbazole
NVP N-vinylpyrrolidone
NVPI N-vinylphthalimide
OAm N-octylacrylamide
ODA octadecyl acrylate
PAm N-propylacrylamide
PA propargyl acrylate
PAA α-propylacrylic acid (2-methylenepentanoic acid)
PDFOMA pentadecylfluorooctyl methacrylate
PDMS poly(dimethylsiloxane)
PE polyethylene
PEG poly(ethylene glycol) monomethyl ether
PEGA (poly(ethylene glycol) monomethyl ether) acrylate
PEGDMA poly(ethylene glycol) dimethacrylate
PEGMA poly(ethylene glycol) methacrylate
PEMA 2-phenylethyl methacrylate
PEO poly(ethylene oxide)
PFPMA pentafluorophenyl methacrylate
PET-RAFT photo-induced electron or energy transfer-RAFT
PFBEMA 2-(perfluorobutyl)ethyl methacrylate
Abbreviations 317
PFHEMA 2-(perfluorohexyl)ethyl methacrylate

PFPVB pentafluorophenyl 4-vinylbenzoate
PFOEMA 2-(perfluorooctyl)ethyl methacrylate
PFPVS pentafluorophenyl 4-vinylbenzenesulfonate
PFS 2,3,4,5,6-pentafluorostyrene
Ph phenyl
PLA poly(lactic acid)
PMA propargyl methacrylate
PMVE perfluoro(methyl vinyl ether)
POSSMA isobutyl polyhedral oligomeric silsesquioxane methacrylate (322)
PVK phenyl vinyl ketone
PVS phenyl 4-vinylbenzenesulfonate
P3HT poly(3-hexylthiophene)
RDRP reversible deactivation radical polymerization
ROMP ring-opening metathesis polymerization
ROP ring-opening polymerization
SKMA solketal methacrylate (80)
SSO3 Na sodium styrene-4-sulfonate
St styrene
SUMI single unit monomer insertion
T- transformation
tBAm N-tert-butylacrylamide
tBA tert-butyl acrylate
tBDMSOS 4-(tert-butyldimethylsilyloxy)styrene (296)
tBDMSMA tert-butyldimethylsilyl methacrylate (298)
tBMA tert-butyl methacrylate
tBOS 4-(tert-butoxy)styrene
TEGDA triethylene glycol diacrylate
TEGMA (triethylene glycol monomethyl ether) methacrylate
TEGDMA triethylene glycol dimethacrylate
TEGMAm triethylene glycol monomethyl ether methacrylamide
[N-(2,5,8,11-tetraoxatridecan-13-yl)methacrylamide]
TESPMA 3-(triethoxysilyl)propyl methacrylate
TFEMA 2,2,2-trifluoroethyl methacrylate
TFPMA 2,2,3,3-tetrafluoropropyl methacrylate
TFPA 2,2,3,3-tetrafluoropropyl acrylate
THF tetrahydrofuran
THPA tetrahydropyran acrylate
THPFDA 1,1,2,2-tetrahydroperfluorodecyl acrylate
THPOS 3-(2-tetrahydropyranyloxy)styrene
TMAEMA 2-(trimethylammonium)ethyl methacrylate
TMAPMA 3-(trimethylamonium)propyl methacrylate
TMSEA 2-(trimethylsilyloxy)ethyl acrylate
TMSEMA 2-(trimethylsilyloxy)ethyl methacrylate
TMSMA trimethylsilyl methacrylate

TMSPA 3-(trimethylsilyl)propyl acrylate
TPMMA triphenylmethyl methacrylate (103)
TPO diphenyl(2,4,6-trimethylbenzoyl)phosphine
TPSiMA triisopropylsilyl methacrylate (300)
VAc vinyl acetate
VB vinyl butyrate
VBA 4-vinylbenzaldehyde
VBPDE vinylbenzylphosphonic acid diethylester
VBSC 4-vinylbenzenesulfonyl chloride
VBDA (4-vinylbenzyl)dimethylamine
VBTAC (vinylbenzyl)trimethylammonium chloride
VBTPC (4-vinylbenzyl)trimethylphosphonium chloride
VBz vinyl benzoate
VCl2 vinylidene chloride
VF2 vinylidene fluoride
Vim 4-vinylimidazole
VL γ-valerolactone
VPv vinyl pivalate
2VP 2-vinylypyridine
4VP 4-vinylpyridine.
References
1 Boyer, C., Bulmus, V., Davis, T.P. et al. (2009). Chem. Rev. 109: 5402–5436.
https://doi.org/10.1021/cr9001403.
2 Fairbanks, B.D., Gunatillake, P.A., and Meagher, L. (2015). Adv. Drug Deliv. Rev.
91: 141–152. https://doi.org/10.1016/j.addr.2015.05.016.
3 Moad, G., Chen, M., Häussler, M. et al. (2011). Polym. Chem. 2: 492–519.
https://doi.org/10.1039/c0py00179a.
https://doi.org/10.1021/ma9804951.
7 Barner-Kowollik, C., Buback, M., Charleux, B. et al. (2006). J. Polym. Sci., Part
9 Moad, G. (2014). Macromol. Chem. Phys. 215: 9–26. https://doi.org/10.1002/
macp.201300562.
243–245. https://doi.org/10.1021/ma991451a.
References 319
11 Rizzardo, E., Chen, M., Chong, B. et al. (2007). Macromol. Symp. 248: 104–116.
https://doi.org/10.1002/masy.200750211.
12 Moad, G., Li, G., Pfaendner, R. et al. (2006). RAFT copolymerization and
its application to the synthesis of novel dispersants/intercalants/exfoliants
for polymer-clay nanocomposites. Some interesting results from RAFT
(co)polymerization. In: Controlled/Living Radical Polymerization. From Syn-
thesis to Materials, ACS Symposium Series, vol. 944 (ed. K. Matyjaszewski),
514–532. Washington, DC: American Chemical Society. https://doi.org/10.1021/
bk-2006-0944.ch035.
45: 5321–5342. https://doi.org/10.1021/ma300410v.
15 Ranieri, K., Delaittre, G., Barner-Kowollik, C., and Junkers, T. (2014). Macro-
mol. Rapid Commun. 35: 2023–2028. https://doi.org/10.1002/marc.201400518.
16 Fortunatti, C., Sarmoria, C., Brandolin, A., and Asteasuain, M. (2014). Macro-
mol. React. Eng. 8: 781–795. https://doi.org/10.1002/mren.201400020.
17 Chernikova, E.V., Golubev, V.B., Filippov, A.N., and Garina, E.S. (2015). Polym.
Sci., Ser. C 57: 94–109. https://doi.org/10.1134/S1811238215010026.
18 De Rybel, N., Van Steenberge, P.H.M., Reyniers, M.-F. et al. (2017). Macromol.
Theory Simul. 26: 1600048. https://doi.org/10.1002/mats.201600048.
19 Devlaminck, D.J.G., Van Steenberge, P.H.M., Reyniers, M.-F., and D’hooge, D.R.
(2019). Polymers 11: 320. https://doi.org/10.3390/polym11020320.
20 Zapata-Gonzalez, I., Saldivar-Guerra, E., and Licea-Claverie, A. (2017). Chem.
Eng. J. 326: 1242–1254. https://doi.org/10.1016/j.cej.2017.06.051.
24 Theis, A., Feldermann, A., Charton, N. et al. (2005). Macromolecules 38:
2595–2605. https://doi.org/10.1021/ma047476d.
Polym. Sci., Ser. A 50: 353–364. https://doi.org/10.1134/S0965545X08040019.
26 Nguyen, M.N., Margaillan, A., Pham, Q.T., and Bressy, C. (2018). Polymers 10:
224. https://doi.org/10.3390/polym10020224.
27 Han, X., Fan, J., He, J. et al. (2007). Macromolecules 40: 5618–5624. https://doi
.org/10.1021/ma070220y.
28 Rinaldi, D., Hamaide, T., Graillat, C. et al. (2009). J. Polym. Sci., Part A: Polym.
29 Pietsch, C., Fijten, M.W.M., Lambermont-Thijs, H.M.L. et al. (2009). J. Polym.
Sci., Part A: Polym. Chem. 47: 2811–2820. https://doi.org/10.1002/pola.23363.
30 Drache, M. and Schmidt-Naake, G. (2008). Macromol. Symp. 271: 129–136.

Polym. Sci., Ser. A 48: 1046–1057. https://doi.org/10.1134/S0965545X06100051.
33 Uzulina, I., Kanagasabapathy, S., and Claverie, J. (2000). Macromol. Symp. 150:
33–38. https://doi.org/fp9hp3.
2273–2283. https://doi.org/10.1021/ma020883+.
35 Goto, A., Sato, K., Tsujii, Y. et al. (2001). Macromolecules 34: 402–408. https://
doi.org/10.1021/ma0009451.
36 Gao, J., Luo, Y., Wang, R. et al. (2009). Polymer 50: 802–809. https://doi.org/10
.1016/j.polymer.2008.12.014.
37 Konkolewicz, D., Siauw, M., Gray-Weale, A. et al. (2009). J. Phys. Chem. B 113:
7086–7094. https://doi.org/10.1021/jp900684t.
38 Kubo, K., Goto, A., Sato, K. et al. (2005). Polymer 46: 9762–9768. https://doi
.org/10.1016/j.polymer.2005.08.045.
39 Goto, A. and Fukuda, T. (2004). Prog. Polym. Sci. 29: 329–385. https://doi.org/10
.1016/j.progpolymsci.2004.01.002.
40 Benaglia, M., Rizzardo, E., Alberti, A., and Guerra, M. (2005). Macromolecules
38: 3129–3140. https://doi.org/10.1021/ma0480650.
41 Li, C.Z. and Benicewicz, B.C. (2005). J. Polym. Sci., Part A: Polym. Chem. 43:
1535–1543. https://doi.org/10.1002/pola.20658.
(2010). Macromol. Rapid Commun. 31: 1846–1862. https://doi.org/10.1002/marc
.200900907.
https://doi.org/10.1002/marc.201100228.
1738–1748. https://doi.org/10.1002/macp.201300247.
46 Chernikova, E., Golubev, V., Filippov, A. et al. (2010). Polym. Chem. 1:
1437–1440. https://doi.org/10.1039/C0PY00245C.
48 Moad, G., Chiefari, J., Krstina, J. et al. (2000). Polym. Int. 49: 993–1001.
https://doi.org/10.1002/1097-0126(200009)49:9<993::AID-PI506>3.0.CO;2-6.
49 Guice, K.B., Marrou, S.R., Gondi, S.R. et al. (2008). Macromolecules 41:
4390–4397. https://doi.org/10.1021/ma8003746.
50 Strem Chemicals. http://www.strem.com/uploads/resources/documents/raft.pdf
(accessed 28 April 2009).
51 Grajales, S. (ed.) (2012). Controlled Radical Polymerization Guide. St. Louis, MO:
Sigma-Aldrich.
References 321
52 Suzuki, S., Whittaker, M.R., Grondahl, L. et al. (2006). Biomacromolecules 7:

3178–3187. https://doi.org/10.1021/bm060583q.
53 He, L., Read, E.S., Armes, S.P., and Adams, D.J. (2007). Macromolecules 40:
4429–4438. https://doi.org/10.1021/ma070670q.
54 Chong, Y.K., Le, T.P.T., Moad, G. et al. (1999). Macromolecules 32: 2071–2074.
https://doi.org/10.1021/ma981472p.
55 Wei, C., Wu, K., Li, J. et al. (2012). Macromol. Chem. Phys. 213: 557–565.
56 Rizzardo, E., Chiefari, J., Mayadunne, R.T.A. et al. (2000). Synthesis of
defined polymers by reversible addition fragmentation chain transfer. In: Con-
trolled/Living Radical Polymerization, ACS Symposium Series, vol. 768 (ed. K.
Matyjaszewski), 278–296. Washington, DC: American Chemical Society. https://
doi.org/10.1021/bk-2000-0768.ch020.
57 Hotchkiss, J.W., Lowe, A.B., and Boyes, S.G. (2007). Chem. Mater. 19: 6–13.
https://doi.org/10.1021/cm0622912.
58 Fan, D.Q., He, J.P., Xu, J.T. et al. (2006). J. Polym. Sci., Part A: Polym. Chem. 44:
2260–2269.
59 Xu, Y., Chen, J., Huang, J. et al. (2016). High Perform. Polym. 29: 1148–1157.
https://doi.org/10.1177/0954008316671792.
60 Cao, H., Wang, G., Xue, Y. et al. (2019). ACS Macro Lett. 8: 616–622. https://doi
.org/10.1021/acsmacrolett.9b00320.
61 Guégain, E., Zhu, C., Giovanardi, E., and Nicolas, J. (2019). Macromolecules 52:
3612–3624. https://doi.org/10.1021/acs.macromol.9b00161.
62 Zheng, C., Zhou, Y., Jiao, Y., and Zhang, H. (2019). Macromolecules 52:
63 Zheng, C., Zhou, Y., and Zhang, H. (2020). ACS Appl. Polym. Mater. 2: 220–233.
https://doi.org/10.1021/acsapm.9b00766.
64 Moad, G., Chiefari, J., Moad, C.L. et al. (2002). Macromol. Symp. 182: 65–80.
https://doi.org/dnhr7s.
65 Johnston-Hall, G., Theis, A., Monteiro, M.J. et al. (2005). Macromol. Chem.
Phys. 206: 2047–2053. https://doi.org/10.1002/macp.200500354.
67 Peklak, A.D., Butte, A., Storti, G., and Morbidelli, M. (2006). J. Polym. Sci., Part
9262–9271. https://doi.org/10.1021/ma071100t.
69 Roth, P.J., Kessler, D., Zentel, R., and Theato, P. (2009). J. Polym. Sci., Part A:
70 Li, C., He, J., Zhou, Y. et al. (2011). J. Polym. Sci., Part A: Polym. Chem. 49:
71 Sasso, B., Dobinson, M., Hodge, P., and Wear, T. (2010). Macromolecules 43:
7453–7464. https://doi.org/10.1021/ma1011683.
72 Serrano, J.M., Liu, T., Khan, A.U. et al. (2019). Chem. Mater. 31: 8898–8907.
https://doi.org/10.1021/acs.chemmater.9b02918.
73 Hu, L., Wang, Y., Yin, Q. et al. (2019). J. Appl. Polym. Sci. 136: 47972. https://
doi.org/10.1002/app.47972.
74 Golf, H., O’Shea, R., Braybrook, C. et al. (2018). Chem. Sci. 9: 7370–7375.
https://doi.org/10.1039/C8SC01862F.
75 Apostolovic, B., Quattrini, F., Butté, A. et al. (2006). Helv. Chim. Acta 89:
1641–1659. https://doi.org/10.1002/hlca.200690163.
76 Kwak, Y., Nicolay, R., and Matyjaszewski, K. (2008). Macromolecules 41:
6602–6604. https://doi.org/10.1021/ma801502s.
77 Nicolaÿ, R., Kwak, Y., and Matyjaszewski, K. (2010). Angew. Chem. Int. Ed. 49:
78 Kwak, Y., Yamamura, Y., and Matyjaszewski, K. (2010). Macromol. Chem. Phys.
211: 493–500. https://doi.org/10.1002/macp.200900509.
79 Kim, Y., Pourgholami, M.H., Morris, D.L., and Stenzel, M.H. (2011). Macromol.
Biosci. 11: 219–233. https://doi.org/10.1002/mabi.201000293.
80 Mori, H., Takahashi, E., Ishizuki, A., and Nakabayashi, K. (2013). Macro-
molecules 46: 6451–6465. https://doi.org/10.1021/ma400596r.
81 Lo, C.-T., Watanabe, Y., Murakami, D. et al. (2019). Macromol. Rapid Commun.
82 Eberhardt, M. and Théato, P. (2005). Macromol. Rapid Commun. 26: 1488–1493.
83 Xu, Y., Chen, M., Xie, J. et al. (2013). React. Funct. Polym. 73: 1646–1655.
https://doi.org/10.1016/j.reactfunctpolym.2013.09.008.
84 Cazares-Cortes, E., Baker, B.C., Nishimori, K. et al. (2019). Macromolecules 52:
85 Ishitake, K., Satoh, K., Kamigaito, M., and Okamoto, Y. (2011). Macromolecules
44: 9108–9117. https://doi.org/10.1021/ma202155b.
86 Suzuki, S., Whittaker, M.R., Wentrup-Byrne, E. et al. (2008). Langmuir 24:
13075–13083. https://doi.org/10.1021/la802300q.
87 Ishitake, K., Satoh, K., Kamigaito, M., and Okamoto, Y. (2009). Angew. Chem.
Int. Ed. 48: 1991–1994. https://doi.org/10.1002/anie.200805168.
88 Ishitake, K., Satoh, K., Kamigaito, M., and Okamoto, Y. (2012). Polym. Chem. 3:
89 Li, R.C., Hwang, J., and Maynard, H.D. (2007). Chem. Commun.: 3631–3633.
https://doi.org/10.1039/b709304g.
90 Hwang, J.Y., Li, R.C., and Maynard, H.D. (2007). J. Controlled Release 122:
279–286. https://doi.org/10.1016/j.jconrel.2007.04.010.
91 Yan, Y., Zhang, J., Qiao, Y. et al. (2013). Macromolecules 46: 8816–8823. https://
doi.org/10.1021/ma402039u.
92 Yan, Y., Deaton, T.M., Zhang, J. et al. (2015). Macromolecules 48: 1644–1650.
https://doi.org/10.1021/acs.macromol.5b00471.
93 Nagai, A., Kokado, K., Miyake, J., and Chujo, Y. (2009). Macromolecules 42:
5446–5452. https://doi.org/10.1021/ma900840y.
94 de Sordi, M.L.T., Ceschi, A., Petzhold, C.L., and Muller, A.H.E. (2007). Macro-
95 Jiang, J., Leng, B., Xiao, X. et al. (2009). Polymer 50: 5681–5684. https://doi.org/
10.1016/j.polymer.2009.10.003.
References 323
96 Zhao, P., Jiang, J., Leng, B., and Tian, H. (2009). Macromol. Rapid Commun. 30:
1715–1718. https://doi.org/10.1002/marc.200900318.
97 Zhao, P., Ling, Q.D., Wang, W.Z. et al. (2007). J. Polym. Sci., Part A: Polym.
98 Papagiannouli, I., Demetriou, M., Krasia-Christoforou, T., and Couris, S. (2014).
RSC Adv. 4: 8779–8788. https://doi.org/10.1039/C3RA46132G.
99 Islam, M.S., Qiao, Y., Tang, C., and Ploehn, H.J. (2015). ACS Appl. Mater. Inter-
faces 7: 1967–1977. https://doi.org/10.1021/am507751m.
100 Qiao, Y., Islam, M.S., Han, K. et al. (2013). Adv. Funct. Mater. 23: 5638–5646.
https://doi.org/10.1002/adfm.201300736.
101 Pfaff, A., Barner, L., Müller, A.H.E., and Granville, A.M. (2011). Eur. Polym. J.
102 Gallagher, J.J., Hillmyer, M.A., and Reineke, T.M. (2015). ACS Sustain. Chem.
Eng. 3: 662–667. https://doi.org/10.1021/sc5008362.
103 Withey, A.B.J., Chen, G., Nguyen, T.L.U., and Stenzel, M.H. (2009). Biomacro-
molecules 10: 3215–3226. https://doi.org/10.1021/bm901050x.
104 Teulère, C. and Nicolaÿ, R. (2017). Polym. Chem. 8: 5220–5227. https://doi.org/
10.1039/C7PY00875A.
105 Szablan, Z., Toy, A.A., Terrenoire, A. et al. (2006). J. Polym. Sci., Part A: Polym.
106 Satoh, K., Lee, D.-H., Nagai, K., and Kamigaito, M. (2013). Macromol. Rapid
Commun. https://doi.org/10.1002/marc.201300638.
107 Ding, A., Xu, J., Gu, G. et al. (2017). Sci. Rep. 7: 12601. https://doi.org/10.1038/
s41598-017-12710-y.
108 Erkoc, S. and Acar, A.E. (2008). Macromolecules 41: 9019–9024. https://doi.org/
10.1021/ma801492a.
109 Arita, T., Beuermann, S., Buback, M., and Vana, P. (2005). Macromol. Mater.
Eng. 290: 283–293. https://doi.org/10.1002/mame.200400274.
110 Vana, P., Albertin, L., Barner, L. et al. (2002). J. Polym. Sci., Part A: Polym.
111 Toy, A.A., Vana, P., Davis, T.P., and Barner-Kowollik, C. (2004). Macromolecules
37: 744–751. https://doi.org/10.1021/ma035244t.
112 McLeary, J.B., McKenzie, J.M., Tonge, M.P. et al. (2004). Chem. Commun.:
1950–1951. https://doi.org/10.1039/b404857a.
113 van den Dungen, E.T.A., Matahwa, H., McLeary, J.B. et al. (2008). J. Polym. Sci.,
Part A: Polym. Chem. 46: 2500–2509. https://doi.org/10.1002/pola.22582.
114 Elsen, A.M., Nicolaÿ, R., and Matyjaszewski, K. (2011). Macromolecules 44:
1752–1754. https://doi.org/10.1021/ma200263w.
8941–8950. https://doi.org/10.1021/ma048199d.
116 Li, S., Nie, H., Gu, S. et al. (2019). ACS Macro Lett. 8: 783–788. https://doi.org/
10.1021/acsmacrolett.9b00371.
117 Ganachaud, F., Monteiro, M.J., Gilbert, R.G. et al. (2000). Macromolecules 33:
6738–6745. https://doi.org/10.1021/ma0003102.
118 Mertoglu, M., Garnier, S., Laschewsky, A. et al. (2005). Polymer 46: 7726–7740.
https://doi.org/10.1016/j.polymer.2005.03.101.
119 Tao, Y., Satoh, K., and Kamigaito, M. (2011). Macromol. Rapid Commun. 32:
120 Wan, D.C., Pu, H.T., and Yang, G.J. (2007). Chin. Chem. Lett. 18: 1141–1144.
https://doi.org/10.1016/j.cclet.2007.07.037.
121 Wan, D.C., Satoh, K., and Kamigaito, M. (2006). Macromolecules 39: 6882–6886.
https://doi.org/10.1021/Ma0615654.
122 Save, M., Manguian, M., Chassenieux, C., and Charleux, B. (2005). Macro-
molecules 38: 280–289. https://doi.org/10.1021/ma048487+.
124 Arita, T., Buback, M., and Vana, P. (2005). Macromolecules 38: 7935–7943.
125 Chong, Y.K., Moad, G., Rizzardo, E., and Thang, S.H. (2007). Macromolecules
40: 4446–4455. https://doi.org/10.1021/ma062919u.
molecules 41: 6400–6412. https://doi.org/10.1021/ma800388c.
127 Yi, F. and Zheng, S. (2009). Polymer 50: 670–678. https://doi.org/10.1016/j
.polymer.2008.11.038.
128 Moad, G., Chong, Y.K., Mulder, R. et al. (2009). New features of the mecha-
nism of RAFT polymerization. In: Controlled/Living Radical Polymerization.
Progress in RAFT, NMP & OMRP, ACS Symposium Series, vol. 1024 (ed. K.
Matyjaszewski), 3–18. Washington, DC: American Chemical Society https://doi
.org/10.1021/bk-2009-1024.ch001.
129 Bai, Y.X., Liu, Y.B., Li, Y.F., and Zhang, Q. (2012). Polym. Adv. Technol. 23:
581–587. https://doi.org/10.1002/pat.1928.
130 Monteiro, M.J. and de Brouwer, H. (2001). Macromolecules 34: 349–352. https://
doi.org/10.1021/ma001484m.
131 Nozari, S. and Tauer, K. (2005). Polymer 46: 1033–1043. https://doi.org/10.1016/
j.polymer.2004.11.039.
132 Tsavalas, J.G., Schork, F.J., de Brouwer, H., and Monteiro, M.J. (2001). Macro-
molecules 34: 3938–3946. https://doi.org/10.1021/ma001888e.
133 Monteiro, M.J., Hodgson, M., and De Brouwer, H. (2000). J. Polym. Sci., Part A:
Polym. Chem. 38: 3864–3874. https://doi.org/10.1002/1099-0518(20001101)38:21
<3864::aid-pola30>3.0.co;2-3.
137 Nilles, K. and Theato, P. (2011). Polym. Chem. 2: 376–384. https://doi.org/
10.1039/C0PY00261E.
References 325
138 Takeshima, H., Satoh, K., and Kamigaito, M. (2020). J. Polym. Sci. 58: 91–100.
https://doi.org/10.1002/pola.29453.
139 Convertine, A.J., Sumerlin, B.S., Thomas, D.B. et al. (2003). Macromolecules 36:
4679–4681. https://doi.org/10.1021/ma034361l.
140 Dong, Z.M., Liu, X.H., Lin, Y., and Li, Y.S. (2008). J. Polym. Sci., Part A: Polym.
141 Zorn, M. and Zentel, R. (2008). Macromol. Rapid Commun. 29: 922–927. https://
doi.org/10.1002/marc.200800165.
142 Nilles, K. and Theato, P. (2009). J. Polym. Sci., Part A: Polym. Chem. 47:
living characteristics (DuPont/CSIRO), WO9801478A1.
144 Zou, L., Liu, J.a., Zhang, K. et al. (2013). J. Polym. Sci., Part A: Polym. Chem.
145 Bilalis, P., Pitsikalis, M., and Hadjichristidis, N. (2006). J. Polym. Sci., Part A:
146 Bressy, C., Nguyen, M.N., Tanguy, B. et al. (2010). Polym. Degrad. Stab. 95:
1260–1268. https://doi.org/10.1016/j.polymdegradstab.2010.03.017.
147 Lin, F.-Y., Yan, M., and Cochran, E.W. (2019). Macromolecules 52: 7005–7015.
148 Jin, C., Zhang, T., Wang, L. et al. (2014). RSC Adv. 4: 45890–45894. https://doi
.org/10.1039/C4RA09347J.
149 Tian, H.-Y., Yan, J.-J., Wang, D. et al. (2011). Macromol. Rapid Commun. 32:
150 Xu, Y., Cao, J., Li, Q. et al. (2018). RSC Adv. 8: 16103–16113. https://doi.org/10
.1039/C8RA01660G.
151 Kaur, B., D’Souza, L., Slater, L.A. et al. (2011). Macromolecules 44: 3810–3816.
https://doi.org/10.1021/ma200357u.
152 Lee, C.-U., Roy, D., Sumerlin, B.S., and Dadmun, M.D. (2010). Polymer 51:
1244–1251. https://doi.org/10.1016/j.polymer.2010.01.033.
153 Pan, G., Zu, B., Guo, X. et al. (2009). Polymer 50: 2819–2825. https://doi.org/10
.1016/j.polymer.2009.04.053.
154 Chan, Y., Bulmus, V., Zareie, M.H. et al. (2006). J. Controlled Release 115:
155 van den Dungen, E.T.A., Rinquest, J., Pretorius, N.O. et al. (2006). Aust. J.
156 Norisuye, T., Morinaga, T., Tran-Cong-Miyata, Q. et al. (2005). Polymer 46:
157 Adelmann, R., Mela, P., Gallyamov, M.O. et al. (2009). J. Polym. Sci., Part A:
158 Deng, C. and Ling, J. (2016). Macromol. Rapid Commun. 37: 1352–1356. https://
doi.org/10.1002/marc.201600188.
159 Ochiai, B., Ootani, Y., and Endo, T. (2008). J. Am. Chem. Soc. 130: 10832–10833.
https://doi.org/10.1021/ja801491m.
160 Milovanovic, M.B., Avramovic, M., Katsikas, L., and Popovic, I.G. (2010). J.
Serb. Chem. Soc. 75: 1711–1719. https://doi.org/10.2298/jsc100628082m.
161 Thang, S.H., Chong, Y.K., Mayadunne, R.T.A. et al. (1999). Tetrahedron Lett. 40:
2435–2438. https://doi.org/10.1016/S0040-4039(99)00177-X.
162 Bouhadir, G., Legrand, N., Quiclet-Sire, B., and Zard, S.Z. (1999). Tetrahedron
Lett. 40: 277–280. https://doi.org/10.1016/S0040-4039(98)02380-6.
163 Shi, Z., May, A.W., Kohno, Y. et al. (2017). J. Polym. Sci., Part A: Polym. Chem.
164 Qinghua, Z., Xiaoli, Z., Fengqiu, C. et al. (2007). J. Polym. Sci., Part A: Polym.
165 Sahnoun, M., Charreyre, M.T., Veron, L. et al. (2005). J. Polym. Sci., Part A:
166 Hawkins, G., Zetterlund, P.B., and Aldabbagh, F. (2015). J. Polym. Sci., Part A:
167 Gudipati, C.S., Tan, M.B.H., Hussain, H. et al. (2008). Macromol. Rapid Com-
168 Blanazs, A., Madsen, J., Battaglia, G. et al. (2011). J. Am. Chem. Soc. 133:
16581–16587. https://doi.org/10.1021/ja206301a.
169 Zhou, X., Ni, P., Yu, Z., and Zhang, F. (2007). J. Polym. Sci., Part A: Polym.
170 Rojas, R., Harris, N.K., Piotrowska, K., and Kohn, J. (2009). J. Polym. Sci., Part
171 Kitiri, E.N., Varnava, C.K., Patrickios, C.S. et al. (2018). J. Polym. Sci., Part A:
172 Moad, G., Guerrero-Sanchez, C., Haven, J.J. et al. (2014). RAFT for the control
of monomer sequence distribution – single unit monomer insertion (SUMI)
into dithiobenzoate RAFT agents. In: Sequence-Controlled Polymers: Synthesis,
Self-assembly and Properties, vol. 1170 (eds. J.-F. Lutz, M. Ouchi, M. Sawamoto
and T. Meyer), 133–147. Washington, DC: ACS Symposium Series, American
Chemical Society. https://doi.org/10.1021/bk-2014-1170.ch009.
173 Katsikas, L., Avramovic, M., Cortes, R.D.B. et al. (2008). J. Serb. Chem. Soc. 73:
915–921. https://doi.org/10.2298/JSC0809915K.
174 Spruell, J.M., Levy, B.A., Sutherland, A. et al. (2009). J. Polym. Sci., Part A:
175 Sriprom, W., James, M., Perrier, S.b., and Neto, C. (2009). Macromolecules 42:
3138–3146. https://doi.org/10.1021/ma9004428.
176 Johnston-Hall, G., Stenzel, M.H., Davis, T.P. et al. (2007). Macromolecules 40:
2730–2736. https://doi.org/10.1021/ma062405v.
177 Johnston-Hall, G. and Monteiro, M.J. (2007). Macromolecules 40: 7171–7179.
179 Puttick, S., Irvine, D.J., Licence, P., and Thurecht, K.J. (2009). J. Mater. Chem.
19: 2679–2682. https://doi.org/10.1039/b817181p.
References 327
180 Gerstel, P. and Barner-Kowollik, C. (2011). Macromol. Rapid Commun. 32:

181 Jana, S., Parthiban, A., and Chai, C.L.L. (2011). J. Polym. Sci., Part A: Polym.
182 Chen, M., Moad, G., and Rizzardo, E. (2011). Aust. J. Chem. 64: 433–437.
183 Dietrich, M., Glassner, M., Gruendling, T. et al. (2010). Polym. Chem. 1:
634–644. https://doi.org/10.1039/b9py00273a.
184 Yhaya, F., Binauld, S., Callari, M., and Stenzel, M.H. (2012). Aust. J. Chem. 65:
1095–1103. https://doi.org/10.1071/CH12158.
185 Perevyazko, I.Y., Vollrath, A., Pietsch, C. et al. (2012). J. Polym. Sci., Part A:
186 Xue, X., Yang, J., Huang, W. et al. (2015). React. Funct. Polym. 96: 61–70.
187 Nguyen, M.N., Pham, Q.T., Le, V.D. et al. (2018). Asian J. Chem. 30: 1125–1130.
https://doi.org/10.14233/ajchem.2018.21217.
188 Gregory, A.M., Thurecht, K.J., and Howdle, S.M. (2008). Macromolecules 41:
1215–1222. https://doi.org/10.1021/ma702017r.
189 Fu, Q., Ruan, Q., McKenzie, T.G. et al. (2017). Macromolecules 50: 7509–7516.
190 Ng, Y.-H., di Lena, F., and Chai, C.L.L. (2011). Polym. Chem. 2: 589–594.
191 Huynh, V.T., Binauld, S., de Souza, P.L., and Stenzel, M.H. (2012). Chem. Mater.
24: 3197–3211. https://doi.org/10.1021/cm301556b.
192 Bebis, K., Jones, M.W., Haddleton, D.M., and Gibson, M.I. (2011). Polym. Chem.
2: 975–982. https://doi.org/10.1039/C0PY00408A.
193 Wang, C., Li, X., and Deng, H. (2019). ACS Macro Lett. 8: 368–373. https://doi
194 Pavlović, D., Lafond, S., Margaillan, A., and Bressy, C. (2016). Polym. Chem. 7:
195 Blanazs, A., Ryan, A.J., and Armes, S.P. (2012). Macromolecules 45: 5099–5107.
https://doi.org/10.1021/ma301059r.
196 Brotherton, E.E., Hatton, F.L., Cockram, A.A. et al. (2019). J. Am. Chem. Soc.
141: 13664–13675. https://doi.org/10.1021/jacs.9b06788.
197 Jesson, C.P., Cunningham, V.J., Smallridge, M.J., and Armes, S.P. (2018). Macro-
molecules 51: 3221–3232. https://doi.org/10.1021/acs.macromol.8b00294.
198 Cunningham, V.J., Alswieleh, A.M., Thompson, K.L. et al. (2014). Macro-
molecules 47: 5613–5623. https://doi.org/10.1021/ma501140h.
199 Canniccioni, B., Monge, S., David, G., and Robin, J.-J. (2013). Polym. Chem. 4:
200 Solimando, X., Catel, Y., Moszner, N. et al. (2020). Polym. Chem. 11: 3237–3250.
https://doi.org/10.1039/D0PY00337A.
201 de Sordi, M.L.T., de Oliveira da Silva, E., Ceschi, M.A., and Petzhold,
C.L. (2011). React. Funct. Polym. 71: 648–654. https://doi.org/10.1016/j
.reactfunctpolym.2011.02.005.
202 Li, S.J., Lin, M.N., Lu, J., and Liang, H. (2009). Macromolecules 42: 1258–1263.
https://doi.org/10.1021/ma802236s.
203 Li, D., Zhu, J., Cheng, Z. et al. (2009). React. Funct. Polym. 69: 240–245. https://
doi.org/10.1016/j.reactfunctpolym.2009.01.008.
204 Li, C.H., Ng, A.M.C., Mak, C.S.K. et al. (2012). ACS Appl. Mater. Interfaces 4:
74–80. https://doi.org/10.1021/am201561g.
205 Lo, K.C., Hau, K.I., and Chan, W.K. (2018). Nanoscale 10: 6474–6486. https://
doi.org/10.1039/C7NR09670D.
206 Ban, J., Pan, L., Shi, B., and Zhang, H. (2018). New J. Chem. 42: 13581–13588.
https://doi.org/10.1039/C8NJ02568A.
207 Zhu, Y., Zhou, Y., Chen, Z. et al. (2012). Polymer 53: 3566–3576. https://doi.org/
10.1016/j.polymer.2012.05.063.
208 Bin, N., Yongbin, L., Yujie, L. et al. (2015). New J. Chem. 39: 6568–6577. https://
doi.org/10.1039/C5NJ01315A.
209 Hao, X.J., Heuts, J.P.A., Barner-Kowollik, C. et al. (2003). J. Polym. Sci., Part A:
210 Hao, X., Stenzel, M.H., Barner-Kowollik, C. et al. (2004). Polymer 45:
211 Xie, H.-L., Liu, Y.-X., Zhong, G.-Q. et al. (2009). Macromolecules 42: 8774–8780.
https://doi.org/10.1021/ma9017668.
212 Zhu, Y. and Wang, X. (2013). Dyes and Pigments 97: 222–229. https://doi.org/10
.1016/j.dyepig.2012.12.014.
213 Cao, H.Z., Zhang, W., Zhu, J. et al. (2008). Express Polym. Lett. 2: 589–601.
https://doi.org/10.3144/expresspolymlett.2008.71.
214 Zhao, Y., Qi, B., Tong, X., and Zhao, Y. (2008). Macromolecules 41: 3823–3831.
https://doi.org/10.1021/ma8000302.
215 Shrivastava, S. and Matsuoka, H. (2016). Colloid Polym. Sci. 294: 879–887.
https://doi.org/10.1007/s00396-016-3839-1.
216 Yu, B. and Lowe, A.B. (2009). J. Polym. Sci., Part A: Polym. Chem. 47:
217 Trotta, J.T., Jin, M., Stawiasz, K.J. et al. (2017). J. Polym. Sci., Part A: Polym.
218 Quemener, D., Le Hellaye, M., Bissett, C. et al. (2008). J. Polym. Sci., Part A:
219 Li, Y. and Benicewicz, B.C. (2008). Macromolecules 41: 7986–7992. https://doi
.org/10.1021/Ma801551z.
220 Rayeroux, D., Travelet, C., Lapinte, V. et al. (2017). Polym. Chem. 8: 4246–4263.
221 Bloksma, M.M., Weber, C., Perevyazko, I.Y. et al. (2011). Macromolecules 44:
4057–4064. https://doi.org/10.1021/ma200514n.
223 Chakrabarty, A. and Singha, N.K. (2013). J. Colloid Interface Sci. 408: 66–74.
https://doi.org/10.1016/j.jcis.2013.07.031.
References 329
224 Liu, Y., Wang, Y., Zhuang, D. et al. (2012). J. Colloid Interface Sci. 377: 197–206.
225 Li, Y., Zhao, J., Chen, L. et al. (2019). React. Funct. Polym. 134: 112–120.
226 Chan, J.W., Yu, B., Hoyle, C.E., and Lowe, A.B. (2008). Chem. Commun.:
4959–4961. https://doi.org/10.1039/b813438c.
228 Ge, Z., Cai, Y., Yin, J. et al. (2007). Langmuir 23: 1114–1122. https://doi.org/10
.1021/la062719b.
229 Yu, B., Chan, J.W., Hoyle, C.E., and Lowe, A.B. (2009). J. Polym. Sci., Part A:
230 Tanaka, S., Nishida, H., and Endo, T. (2009). Macromolecules 42: 293–298.
https://doi.org/10.1021/ma801431a.
232 Shi, M., Li, A.-L., Liang, H., and Lu, J. (2007). Macromolecules 40: 1891–1896.
233 Chen, M., Ghiggino, K.P., Mau, A.W.H. et al. (2004). Macromolecules 37:
5479–5481. https://doi.org/10.1021/ma049037k.
234 Chen, M., Ghiggino, K.P., Thang, S.H. et al. (2005). J. Org. Chem. 70:
1844–1852. https://doi.org/10.1021/jo047899d.
235 Chen, M., Ghiggino, K.P., Rizzardo, E. et al. (2008). Chem. Commun.:
1112–1114. https://doi.org/10.1039/b716471h.
236 Ozoe, S. (2009). Chloroprene-based block copolymer, soapless polychloro-
prene latexes, and processes for producing same (Tosoh Corporation, Japan),
US20090036608A1.
237 Pullan, N., Liu, M., and Topham, P.D. (2013). Polym. Chem. 4: 2272–2277.
https://doi.org/10.1039/c3py21151g.
238 Jitchum, V. and Perrier, S. (2007). Macromolecules 40: 1408–1412. https://doi
.org/10.1021/ma061889s.
239 Li, J., El harfi, J., Howdle, S.M. et al. (2012). Polym. Chem. 3: 1495–1501.
240 Liu, X.H., Li, Y.G., Lin, Y., and Li, Y.S. (2007). J. Polym. Sci., Part A: Polym.
241 An, Q., Qian, J., Yu, L. et al. (2005). J. Polym. Sci., Part A: Polym. Chem. 43:
242 Weber, C., Neuwirth, T., Kempe, K. et al. (2011). Macromolecules 45: 20–27.
https://doi.org/10.1021/ma2021387.
243 Perez-Baena, I., Asenjo-Sanz, I., Arbe, A. et al. (2014). Macromolecules 47:
8270–8280. https://doi.org/10.1021/ma5017133.
244 He, J., Tremblay, L., Lacelle, S., and Zhao, Y. (2011). Soft Matter 7: 2380–2386.
https://doi.org/10.1039/C0SM01383H.
245 Wright, D.B., Patterson, J.P., Pitto-Barry, A. et al. (2015). Polym. Chem. 6:
2761–2768. https://doi.org/10.1039/C4PY01782J.
246 Breul, A.M., Schäfer, J., Friebe, C. et al. (2012). Macromol. Chem. Phys. 213:
247 Lossada, F., Jiao, D., Yao, X., and Walther, A. (2020). ACS Macro Lett. 9: 70–76.
https://doi.org/10.1021/acsmacrolett.9b00997.
248 Cao, H., Zhu, J., Zhang, W. et al. (2010). e-Polymers https://doi.org/10.1515/
epoly.2010.10.1.534.
249 Nicolaÿ, R. (2011). Macromolecules 45: 821–827. https://doi.org/10.1021/
ma202344y.
250 Le Neindre, M., Magny, B., and Nicolay, R. (2013). Polym. Chem. 4: 5577–5584.
https://doi.org/10.1039/C3PY00754E.
251 Kröger, A.P.P., Boonen, R.J.E.A., and Paulusse, J.M.J. (2017). Polymer 120:
253 Menzel, R., Breul, A., Pietsch, C. et al. (2011). Macromol. Chem. Phys. 212:
254 Berndt, A., Pospiech, D., Jehnichen, D. et al. (2015). ACS Appl. Mater. Interfaces
7: 12339–12347. https://doi.org/10.1021/am5069479.
255 Himmelsbach, A., Schneider-Chaabane, A., and Lienkamp, K. (2019). Macro-
mol. Chem. Phys. 220: 1900346. https://doi.org/10.1002/macp.201900346.
256 Yanjarappa, M.J., Gujraty, K.V., Joshi, A. et al. (2006). Biomacromolecules 7:
1665–1670. https://doi.org/10.1021/bm060098v.
257 Sriprom, W., Neel, M., Gabbutt, C.D. et al. (2007). J. Mater. Chem. 17:
1885–1893. https://doi.org/10.1039/b617865k.
258 Smith, A.A.A., Autzen, H.E., Laursen, T. et al. (2017). Biomacromolecules
https://doi.org/10.1021/acs.biomac.7b01136.
259 Zhou, D., Zhu, X.L., Zhu, J., and Cheng, Z.P. (2008). Polymer 49: 3048–3053.
260 Yamane, M., Fadil, Y., Tokuda, M. et al. (2020). Macromol. Rapid Commun.:
261 Sriprom, W., Neto, C., and Perrier, S. (2010). Soft Matter 6: 909–914. https://doi
.org/10.1039/b920133e.
262 Tokuda, M., Yamane, M., Thickett, S.C. et al. (2016). Soft Matter 12: 3955–3962.
https://doi.org/10.1039/C6SM00269B.
263 Rizzardo, E., Thang, S.H., and Moad, G. (1999). Synthesis of dithioester
chain-transfer agents and use of bis(thioacyl) disulfides or dithioesters as
chain-transfer agents in radical polymerization. (CSIRO), WO9905099.
264 Becer, C.R., Hahn, S., Fijten, M.W.M. et al. (2008). J. Polym. Sci., Part A: Polym.
266 Fijten, M.W.M., Paulus, R.M., and Schubert, U.S. (2005). J. Polym. Sci., Part A:
267 Kostiainen, M.A., Pietsch, C., Hoogenboom, R. et al. (2011). Adv. Funct. Mater.
21: 2012–2019. https://doi.org/10.1002/adfm.201002597.
References 331
268 Fijten, M.W.M., Meier, M.A.R., Hoogenboom, R., and Schubert, U.S. (2004). J.
Polym. Sci., Part A: Polym. Chem. 42: 5775–5783. https://doi.org/10.1002/pola
.20346.
269 Paulus, R.M., Becer, C.R., Hoogenboom, R., and Schubert, U.S. (2009). Aust. J.
270 Janoschka, T., Teichler, A., Krieg, A. et al. (2012). J. Polym. Sci., Part A: Polym.
271 Pavlov, G.M., Breul, A.M., Hager, M.D., and Schubert, U.S. (2012). Macromol.
Chem. Phys. 213: 904–916. https://doi.org/10.1002/macp.201100653.
272 Van Camp, W. and Du Prez, F.E. (2006). ACS Symp. Ser. 944: 171–184. https://
doi.org/10.1021/bk-2006-0944.ch013.
273 Krieg, A., Becer, C.R., Hoogenboom, R., and Schubert, U.S. (2009). Macromol.
Symp. 275–276: 73–81. https://doi.org/10.1002/masy.200950109.
274 Weber, C., Becer, C.R., Hoogenboom, R., and Schubert, U.S. (2009). Macro-
275 Hoogenboom, R., Schubert, U.S., Van Camp, W., and Du Prez, F.E. (2005).
Macromolecules 38: 7653–7659. https://doi.org/10.1021/ma050906v.
276 Ulbricht, C., Becer, C.R., Winter, A., and Schubert, U.S. (2010). Macromol.
Rapid Commun. 31: 827–833. https://doi.org/10.1002/marc.200900787.
277 Fournier, D., Hoogenboom, R., Thijs, H.M.L. et al. (2007). Macromolecules 40:
915–920. https://doi.org/10.1021/ma062199r.
278 Pietsch, C., Hoogenboom, R., and Schubert, U.S. (2009). Angew. Chem. Int. Ed.
48: 5653–5656. https://doi.org/10.1002/anie.200901071.
279 Hoogenboom, R., Fijten, M.W.M., Paulus, R.M., and Schubert, U.S. (2006). ACS
Symp. Ser. 944: 473–485. https://doi.org/10.1021/bk-2006-0944.ch032.
280 Grande, C.D., Tria, M.C., Jiang, G. et al. (2011). React. Funct. Polym. 71:
938–942. https://doi.org/10.1016/j.reactfunctpolym.2011.05.013.
281 Esteves, A.C.C., Hodge, P., Trindade, T., and Barros-Timmons, A.M.M.V. (2009).
J. Polym. Sci., Part A: Polym. Chem. 47: 5367–5377. https://doi.org/10.1002/pola
.23586.
282 Mitsukami, Y., Donovan, M.S., Lowe, A.B., and McCormick, C.L. (2001). Macro-
283 Li, Y.T. and Armes, S.P. (2009). Macromolecules 42: 939–945. https://doi.org/10
.1021/ma802750x.
284 Alidedeoglu, A.H., York, A.W., Rosado, D.A. et al. (2010). J. Polym. Sci., Part A:
285 Alidedeoglu, A.H., York, A.W., McCormick, C.L., and Morgan, S.E. (2009). J.
.23590.
286 Chu, H., Liu, N., Wang, X. et al. (2009). Int. J. Pharm. 371: 190–196. https://doi
.org/10.1016/j.ijpharm.2008.12.033.
287 Zhu, Y. and Egap, E. (2020). Polym. Chem. 11: 1018–1024. https://doi.org/10
.1039/C9PY01604J.
288 Smith, A.E., Xu, X., Abell, T.U. et al. (2009). Macromolecules 42: 2958–2964.
289 Liu, L., Zhang, J., Lv, W. et al. (2010). J. Polym. Sci., Part A: Polym. Chem. 48:
290 Huo, M., Ye, Q., Che, H. et al. (2017). Macromolecules 50: 1126–1133. https://
doi.org/10.1021/acs.macromol.6b02499.
291 Meuer, S., Oberle, P., Theato, P. et al. (2007). Adv. Mater. 19: 2073–2078. https://
doi.org/10.1002/adma.200602516.
292 Samsonova, O., Pfeiffer, C., Hellmund, M. et al. (2011). Polymers 3: 693–718.
293 Lechuga-Islas, V.D., Festag, G., Rosales-Guzmán, M. et al. (2020). Eur. Polym. J.
124: 109457. https://doi.org/10.1016/j.eurpolymj.2019.109457.
294 Guan, S., Wen, W., Yang, Z., and Chen, A. (2020). Macromolecules 53: 465–472.
295 Teo, J., McCarroll, J.A., Boyer, C. et al. (2016). Biomacromolecules 17:
2337–2351. https://doi.org/10.1021/acs.biomac.6b00185.
297 Hu, Y.Q., Kim, M.S., Kim, B.S., and Lee, D.S. (2007). Polymer 48: 3437–3443.
298 Vijayakrishna, K., Jewrajka, S.K., Ruiz, A. et al. (2008). Macromolecules 41:
6299–6308. https://doi.org/10.1021/ma800677h.
299 Xu, S. and Liu, W. (2008). J. Fluorine Chem. 129: 125–130. https://doi.org/10
.1016/j.jfluchem.2007.09.008.
300 Pelet, J.M. and Putnam, D. (2009). Macromolecules 42: 1494–1499. https://doi
.org/10.1021/ma801433g.
301 Yokoyama, Y. and Yusa, S.-i. (2013). Polym. J. 45: 985–992. https://doi.org/10
.1038/pj.2013.2.
303 Farooq, U., Upadhyaya, L., Shakeel, A. et al. (2020). J. Membr. Sci. 611: 118181.
https://doi.org/10.1016/j.memsci.2020.118181.
304 Xu, J., Jung, K., and Boyer, C. (2014). Macromolecules 47: 4217–4229. https://
doi.org/10.1021/ma500883y.
305 Xu, J., Shanmugam, S., Duong, H.T., and Boyer, C. (2015). Polym. Chem. 6:
306 Shanmugam, S., Xu, J., and Boyer, C. (2015). J. Am. Chem. Soc. 137: 9174–9185.
https://doi.org/10.1021/jacs.5b05274.
307 Cheng, B.-F., Wang, L.-H., and You, Y.-Z. (2016). Macromol. Res. 24: 811–815.
https://doi.org/10.1007/s13233-016-4106-5.
308 Corrigan, N., Xu, J., and Boyer, C. (2016). Macromolecules 49: 3274–3285.
309 Wu, C., Chen, H., Corrigan, N. et al. (2019). J. Am. Chem. Soc. 141: 8207–8220.
310 Jiang, J., Ye, G., Wang, Z. et al. (2018). Angew. Chem. Int. Ed. 57: 12037–12042.
https://doi.org/10.1002/anie.201807385.
References 333
311 Theriot, J.C., Miyake, G.M., and Boyer, C.A. (2018). ACS Macro Lett. 7:
312 Wang, G.-X., Liu, M.-s., Liang, E., and He, B. (2018). J. Polym. Res. 25: 70.
https://doi.org/10.1007/s10965-018-1459-9.
313 Hakobyan, K., Gegenhuber, T., McErlean, C.S.P., and Müllner, M. (2019).
Angew. Chem. Int. Ed. 58: 1828–1832. https://doi.org/10.1002/anie.201811721.
314 Thum, M.D., Wolf, S., and Falvey, D.E. (2020). J. Phys. Chem. A. https://doi.org/
10.1021/acs.jpca.0c02678.
315 Zhu, Y., Liu, Y., Miller, K.A. et al. (2020). ACS Macro Lett. 9: 725–730. https://
doi.org/10.1021/acsmacrolett.0c00232.
316 Bhuchar, N., Deng, Z., Ishihara, K., and Narain, R. (2011). Polym. Chem. 2:
317 Yu, B., Lowe, A.B., and Ishihara, K. (2009). Biomacromolecules 10: 950–958.
https://doi.org/10.1021/bm8014945.
318 Zhang, X., Lian, X., Liu, L. et al. (2008). Macromolecules 41: 7863–7869. https://
doi.org/10.1021/ma801405j.
319 Bouhamed, H., Boufi, S., and Magnin, A. (2007). J. Colloid Interface Sci. 312:
279–291. https://doi.org/10.1016/j.jcis.2007.03.060.
320 Bouhamed, H., Boufi, S., and Magnin, A. (2009). J. Colloid Interface Sci. 333:
321 Venkataraman, S., Ong, W.L., Ong, Z.Y. et al. (2011). Biomaterials 32:
2369–2378. https://doi.org/10.1016/j.biomaterials.2010.11.070.
322 Shen, W., Chang, Y., Liu, G. et al. (2011). Macromolecules 44: 2524–2530.
https://doi.org/10.1021/ma200074n.
323 Tucker, B.S., Stewart, J.D., Aguirre, J.I. et al. (2015). Biomacromolecules 16:
324 Huo, M., Li, D., Song, G. et al. (2018). Macromol. Rapid Commun. 39: 1700840.
325 Barz, M., Tarantola, M., Fischer, K. et al. (2008). Biomacromolecules 9:
3114–3118. https://doi.org/10.1021/bm800684b.
326 Allmeroth, M., Moderegger, D., Biesalski, B. et al. (2011). Biomacromolecules 12:
2841–2849. https://doi.org/10.1021/bm2005774.
327 Gibson, M.I., Danial, M., and Klok, H.-A. (2011). ACS Comb. Sci. 13: 286–297.
https://doi.org/10.1021/co100099r.
328 Nuhn, L., Hirsch, M., Krieg, B. et al. (2012). ACS Nano 6: 2198–2214. https://
doi.org/10.1021/nn204116u.
329 Chua, G.B.H., Roth, P.J., Duong, H.T.T. et al. (2012). Macromolecules 45:
1362–1374. https://doi.org/10.1021/ma202700y.
330 Zhang, K., Li, X., Zhao, Y. et al. (2016). Prog. Org. Coat. 93: 87–96. https://doi
.org/10.1016/j.porgcoat.2016.01.005.
331 Wald, S., Wurm, F.R., Landfester, K., and Crespy, D. (2016). Polymers 8: 303.
332 Meng, S., Liu, Y., Yeo, J. et al. (2020). Colloid Polym. Sci. https://doi.org/10
.1007/s00396-020-04637-0.
333 Marras, A.E., Vieregg, J.R., Ting, J.M. et al. (2019). Polymers 11: 83. https://doi
.org/10.3390/polym11010083.
334 Haladjova, E., Mountrichas, G., Pispas, S., and Rangelov, S. (2016). J. Phys.
Chem. B 120: 2586–2595. https://doi.org/10.1021/acs.jpcb.5b12477.
335 Mitsukami, Y., Hashidzume, A., Yusa, S.-i. et al. (2006). Polymer 47: 4333–4340.
336 Baussard, J.-F., Habib-Jiwan, J.-L., Laschewsky, A. et al. (2004). Polymer 45:
337 Li, Y. and Armes, S.P. (2010). Angew. Chem. Int. Ed. 49: 4042–4046. https://doi
.org/10.1002/anie.201001461.
338 Sun, L., Hong, L., and Wang, C. (2016). Macromol. Rapid Commun. 37:
339 Jia, Z., Liu, J., Davis, T.P., and Bulmus, V. (2009). Polymer 50: 5928–5932.
340 Datta, L.P., De, D., Ghosh, U., and Das, T.K. (2018). Polymer 138: 103–112.
341 Grande, C.D., Tria, M.C., Jiang, G. et al. (2011). Macromolecules 44: 966–975.
342 Luo, Y., Liu, L., Wang, X. et al. (2012). Soft Matter 8: 1634–1642. https://doi
.org/10.1039/C1SM06412F.
343 Kitano, H., Hayashi, A., Takakura, H. et al. (2009). Langmuir 25: 9361–9368.
https://doi.org/10.1021/la9008625.
344 Cameron, N.R., Spain, S.G., Kingham, J.A. et al. (2008). Faraday Discuss. 139:
359–368. https://doi.org/10.1039/b717177c.
345 Albertin, L. and Cameron, N.R. (2007). Macromolecules 40: 6082–6093. https://
doi.org/10.1021/ma070967o.
346 Spain, S.G. and Cameron, N.R. (2011). Polym. Chem. 2: 1552–1560. https://doi
.org/10.1039/C1PY00030F.
347 Pearson, S., Allen, N., and Stenzel, M.H. (2009). J. Polym. Sci., Part A: Polym.
348 Boissé, S., Rieger, J., Di-Cicco, A. et al. (2009). Macromolecules 42: 8688–8696.
https://doi.org/10.1021/ma9018137.
349 Krishnasamy, V., Qu, W., Chen, C. et al. (2020). Macromolecules https://doi.org/
10.1021/acs.macromol.9b02264.
350 Doncom, K.E.B., Warren, N.J., and Armes, S.P. (2015). Polym. Chem. 6:
7264–7273. https://doi.org/10.1039/C5PY00396B.
351 Lim, J., Matsuoka, H., Yusa, S.-i., and Saruwatari, Y. (2019). Langmuir 35:
1571–1582. https://doi.org/10.1021/acs.langmuir.8b02952.
352 Karjalainen, E., Chenna, N., Laurinmäki, P. et al. (2013). Polym. Chem. 4:
353 Olmedo-Martínez, J.L., Porcarelli, L., Alegría, Á. et al. (2020). Macromolecules
https://doi.org/10.1021/acs.macromol.0c00703.
354 Jia, Z., Wong, L., Davis, T.P., and Bulmus, V. (2008). Biomacromolecules 9:
3106–3113. https://doi.org/10.1021/bm800657e.
References 335
355 Wong, L., Boyer, C., Jia, Z. et al. (2008). Biomacromolecules 9: 1934–1944.
https://doi.org/10.1021/bm800197v.
356 Wong, L., Kavallaris, M., and Bulmus, V. (2011). Polym. Chem. 2: 385–393.
357 Bauri, K., Roy, S.G., Pant, S., and De, P. (2013). Langmuir 29: 2764–2774.
https://doi.org/10.1021/la304918s.
358 Hrsic, E., Zografou, I., Schulte, B. et al. (2013). Polymer 54: 495–504. https://doi
.org/10.1016/j.polymer.2012.11.059.
359 Fernandez-Trillo, F., Dureault, A., Bayley, J.P.M. et al. (2007). Macromolecules
40: 6094–6099. https://doi.org/10.1021/ma070527x.
360 Fernández-Trillo, F., Van Hest, J.C.M., Thies, J.C. et al. (2009). Adv. Mater. 21:
55–59. https://doi.org/10.1002/adma.200801986.
361 Li, Z., Serelis, A.K., Reed, W.F., and Alb, A.M. (2010). Polymer 51: 4726–4734.
362 Koiry, B.P., Moukwa, M., and Singha, N.K. (2013). J. Fluorine Chem. 153:
137–142. https://doi.org/10.1016/j.jfluchem.2013.04.005.
363 Gujraty, K.V., Yanjarappa, M.J., Saraph, A. et al. (2008). J. Polym. Sci., Part A:
364 Cortez-Lemus, N.A., Salgado-Rodríguez, R., and Licea-Claveríe, A. (2010). J.
.24082.
365 Xu, J., Tao, L., Boyer, C. et al. (2010). Macromolecules 43: 20–24. https://doi.org/
10.1021/ma902154h.
366 Wang, J., Rivero, M., Muñoz Bonilla, A. et al. (2016). ACS Macro Lett. 5:
367 Xu, J., Shanmugam, S., Fu, C. et al. (2016). J. Am. Chem. Soc. 138: 3094–3106.
368 Zhuang, D., Nie, J., and Yang, J. (2011). J. Polym. Sci., Part A: Polym. Chem. 49:
369 Tran, J.D., Mikulec, S.N., Calzada, O.M. et al. (2020). Macromol. Chem. Phys.
221: 1900397. https://doi.org/10.1002/macp.201900397.
370 Ahmed, M. and Narain, R. (2011). Biomaterials 32: 5279–5290. https://doi.org/
10.1016/j.biomaterials.2011.03.082.
371 Kirkland-York, S., Zhang, Y., Smith, A.E. et al. (2010). Biomacromolecules 11:
1052–1059. https://doi.org/10.1021/bm100020x.
372 Tao, L., Liu, J., Xu, J., and Davis, T.P. (2009). Org. Biomol. Chem. 7: 3481–3485.
https://doi.org/10.1039/B907061C.
373 Deng, Z., Ahmed, M., and Narain, R. (2009). J. Polym. Sci., Part A: Polym.
Chem. 47: 614–627.
374 Manning, K.B., Shtukenberg, A.G., Nichols, S.M. et al. (2015). J. Polym. Sci.,
375 Adharis, A., Vesper, D., Koning, N., and Loos, K. (2018). Green Chem. 20:
476–484. https://doi.org/10.1039/C7GC03023A.
376 Li, Y., Lokitz, B.S., and McCormick, C.L. (2006). Angew. Chem. Int. Ed. 45:
377 Deng, Z.C., Bouchekif, H., Babooram, K. et al. (2008). J. Polym. Sci., Part A:
378 Kanayama, N., Shibata, H., Kimura, A. et al. (2009). Biomacromolecules 10:
805–813. https://doi.org/10.1021/bm801301b.
379 Kellum, M.G., Smith, A.E., York, S.K., and McCormick, C.L. (2010). Macro-
molecules 43: 7033–7040. https://doi.org/10.1021/ma100983p.
380 Kellum, M.G., Harris, C.A., McCormick, C.L., and Morgan, S.E. (2011). J.
.24524.
381 Jiang, X.Z., Zhang, J.Y., Zhou, Y.M. et al. (2008). J. Polym. Sci., Part A: Polym.
382 Shan, J., Zhao, Y., Granqvist, N., and Tenhu, H. (2009). Macromolecules 42:
2696–2701. https://doi.org/10.1021/ma802482e.
383 Isoda, K., Kanayama, N., Miyamoto, D. et al. (2011). React. Funct. Polym. 71:
384 Zhou, Y., Jiang, K., Chen, Y., and Liu, S. (2008). J. Polym. Sci., Part A: Polym.
385 Rodriguez-Emmenegger, C., Schmidt, B.V.K.J., Sedlakova, Z. et al. (2011).
Macromol. Rapid Commun. 32: 958–965. https://doi.org/10.1002/marc
.201100176.
386 Donovan, M.S., Lowe, A.B., Sanford, T.A., and McCormick, C.L. (2003). J.
.10658.
387 Lokitz, B.S., Convertine, A.J., Ezell, R.G. et al. (2006). Macromolecules 39:
8594–8602. https://doi.org/10.1021/ma061672y.
388 Zorn, M., Meuer, S., Tahir, M.N. et al. (2008). J. Mater. Chem. 18: 3050–3058.
https://doi.org/10.1039/b802666a.
389 Barsbay, M., Guven, O., Davis, T.P. et al. (2009). Polymer 50: 973–982. https://
doi.org/10.1016/j.polymer.2008.12.027.
391 Kopeć, M., Krys, P., Yuan, R., and Matyjaszewski, K. (2016). Macromolecules 49:
392 He, J.-Y. and Lu, M. (2019). J. Macromol. Sci., Part A: Pure Appl. Chem. 56:
443–449. https://doi.org/10.1080/10601325.2019.1581575.
393 Chernikova, E., Terpugova, P., Filippov, A. et al. (2009). Russ. J. Appl. Chem. 82:
1882–1889. https://doi.org/10.1134/s1070427209100267.
394 Chandrawati, R., Städler, B., Postma, A. et al. (2009). Biomaterials 30:
395 Li, J. and Benicewicz, B.C. (2013). J. Polym. Sci., Part A: Polym. Chem. 51:
396 Alex, J., González, K., Kindel, T. et al. (2020). Biomacromolecules https://doi
.org/10.1021/acs.biomac.0c00096.
397 Stals, P.J.M., Cheng, C.-Y., van Beek, L. et al. (2016). Chem. Sci. 7: 2011–2015.
https://doi.org/10.1039/C5SC02319J.
References 337
398 Chien, H.-W., Xu, X., Ella-Menye, J.-R. et al. (2012). Langmuir 28: 17778–17784.
https://doi.org/10.1021/la303390j.
399 Chytil, P., Etrych, T., Kríz, J. et al. (2010). Eur. J. Pharm. Sci. 41: 473–482.
400 York, A.W., Huang, F., and McCormick, C.L. (2010). Biomacromolecules 11:
505–514. https://doi.org/10.1021/bm901249n.
401 Rossi, N.A.A., Zou, Y., Scott, M.D., and Kizhakkedathu, J.N. (2008). Macro-
molecules 41: 5272–5282. https://doi.org/10.1021/ma800606k.
402 York, A.W., Zhang, Y., Holley, A.C. et al. (2009). Biomacromolecules 10:
936–943. https://doi.org/10.1021/bm8014768.
403 Luo, Q., Xiao, X., Dai, X. et al. (2018). ACS Appl. Mater. Interfaces 10:
1575–1588. https://doi.org/10.1021/acsami.7b16345.
404 Ju, Y., Xing, C., Wu, D. et al. (2017). Chem. Eur. J. 23: 3366–3374. https://doi
.org/10.1002/chem.201604843.
405 Cuthbert, J., Zhang, T., Biswas, S. et al. (2018). Macromolecules 51: 9184–9191.
406 Liu, Y., Kang, G., Sun, L. et al. (2020). ACS Appl. Polym. Mater. 2: 263–272.
https://doi.org/10.1021/acsapm.9b00786.
407 Ohshio, M., Mizoue, Y., Shiino, D. et al. (2020). Polym. J. 52: 189–197. https://
doi.org/10.1038/s41428-019-0278-0.
408 Huo, M., Zeng, M., Li, D. et al. (2017). Macromolecules 50: 8212–8220. https://
409 Du, C., Ma, X., Li, J., and Wu, C. (2017). J. Appl. Polym. Sci.: 134. https://doi
.org/10.1002/app.44751.
410 Meek, K.M., Sharick, S., Ye, Y. et al. (2015). Macromolecules 48: 4850–4862.
411 Ye, Y., Choi, J.-H., Winey, K.I., and Elabd, Y.A. (2012). Macromolecules 45:
7027–7035. https://doi.org/10.1021/ma301036b.
412 Guan, S. and Chen, A. (2020). ACS Macro Lett. 9: 14–19. https://doi.org/10
.1021/acsmacrolett.9b00868.
413 Zhu, Y., Quek, J.Y., Lowe, A.B., and Roth, P.J. (2013). Macromolecules 46:
6475–6484. https://doi.org/10.1021/ma401096r.
414 Zhu, J., Zhu, X.L., Cheng, Z.P. et al. (2002). Polymer 43: 7037–7042. https://doi
.org/10.1016/S0032-3861(02)00655-9.
415 Gu, Y., Zhao, J., Liu, Q. et al. (2015). Polym. Chem. 6: 359–363. https://doi.org/
10.1039/C4PY01248H.
416 Zhu, M.-Q., Wang, L.-Q., Exarhos, G.J., and Li, A.D.Q. (2004). J. Am. Chem. Soc.
126: 2656–2657. https://doi.org/10.1021/ja038544z.
417 Zhou, Y., Zhu, J.A., Zhu, X.L., and Cheng, Z.P. (2006). Radiat. Phys. Chem. 75:
485–492. https://doi.org/10.1016/j.radphyschem.2005.10.012.
418 Zhang, Z.B., Zhu, X.L., Zhu, J. et al. (2006). J. Polym. Sci., Part A: Polym. Chem.
419 Zhang, Z., Wang, W., Cheng, Z. et al. (2010). Macromolecules 43: 7979–7984.
https://doi.org/10.1021/ma101379r.
420 Zhang, Z., Wang, W., Xia, H. et al. (2009). Macromolecules 42: 7360–7366.
421 Wang, H., Chang, T., Li, X. et al. (2016). Nanoscale 8: 14950–14955. https://doi
.org/10.1039/C6NR04459J.
422 Tu, K., Xu, T., Zhang, L. et al. (2017). RSC Adv. 7: 24040–24045. https://doi.org/
10.1039/C7RA03103C.
423 Zhang, Z., Zhang, W., Zhu, X. et al. (2007). J. Polym. Sci., Part A: Polym. Chem.
424 Chen, L., Chen, B., Liu, X. et al. (2016). J. Mater. Chem. B 4: 3377–3386. https://
doi.org/10.1039/C6TB00315J.
425 Pan, J., Miao, J., Zhang, L. et al. (2013). Polym. Chem. 4: 5664–5670. https://doi
.org/10.1039/C3PY00671A.
426 Hirosawa, K., Fujii, K., Ueki, T. et al. (2016). Macromolecules 49: 8249–8253.
427 Sohn, H.-S., Cha, S.-H., Lee, W.-K. et al. (2011). Macromol. Res. 19: 722–728.
https://doi.org/10.1007/s13233-011-0705-3.
428 Zhang, Y., Cheng, Z., Chen, X. et al. (2007). Macromolecules 40: 4809–4817.
https://doi.org/10.1021/ma070257i.
429 Sun, B., Zhu, X.L., Zhu, H. et al. (2007). Macromol. Chem. Phys. 208:
430 Xu, Y., Sun, J., Chen, H. et al. (2015). J. Polym. Sci., Part A: Polym. Chem. 53:
431 Huang, Z., Zhang, L., Cheng, Z., and Zhu, X. (2017). Polymers 9: 4. https://doi
.org/10.3390/polym9010004.
432 Zhang, S., Yin, L., Wang, J. et al. (2017). Polymers 9: 26. https://doi.org/10.3390/
polym9010026.
433 Zhu, J., Zhu, X.L., Zhou, D., and Chen, J.Y. (2003). e-Polymers 3: 576–586.
https://doi.org/10.1515/epoly.2003.3.1.576.
434 Hernández-Ortiz, J.C., Jaramillo-Soto, G., Palacios-Alquisira, J., and
Vivaldo-Lima, E. (2010). Macromol. React. Eng. 4: 210–221. https://doi.org/
10.1002/mren.200900047.
435 Tian, C., Xu, T., Zhang, L. et al. (2016). RSC Adv. 6: 34659–34665. https://doi
.org/10.1039/C6RA02809H.
436 Ji, Y., Zhang, L., Gu, X. et al. (2017). Angew. Chem. Int. Ed. 56: 2328–2333.
437 Kim, S.-M., Han, S.S., Kim, A.Y. et al. (2015). J. Nanosci. Nanotechnol. 15:
7866–7870. https://doi.org/10.1166/jnn.2015.11216.
3738–3742. https://doi.org/10.1021/ma9005389.
439 Fu, Z., Tao, W., and Shi, Y. (2008). J. Polym. Sci., Part A: Polym. Chem. 46:
440 Zheng, G.H. and Pan, C.Y. (2006). Macromolecules 39: 95–102. https://doi.org/10
.1021/ma0517897.
441 Hui, J., Dong, Z., Shi, Y. et al. (2014). RSC Adv. 4: 55529–55538. https://doi.org/
10.1039/c4ra08715a.
References 339
442 Li, Z., Li, D., Wang, L. et al. (2019). Polymer 168: 16–20. https://doi.org/10.1016/
j.polymer.2019.02.004.
443 Sui, X., Fu, Z., and Shi, Y. (2011). J. Appl. Polym. Sci. 121: 1860–1865. https://
doi.org/10.1002/app.33589.
444 Sievers, M., Namyslo, J.C., Lederle, F., and Hübner, E.G. (2018). Express Polym.
Lett. 12: 556–568. https://doi.org/10.3144/expresspolymlett.2018.46.
445 Sudalai, A., Kanagasabapathy, S., and Benicewicz, B.C. (2000). Org. Lett. 2:
3213–3216. https://doi.org/10.1021/ol006407q.
446 Severac, R., Lacroix-Desmazes, P., and Boutevin, B. (2002). Polym. Int. 51:
1117–1122. https://doi.org/10.1002/pi.932.
447 Favier, A., Charreyre, M.T., Chaumont, P., and Pichot, C. (2002). Macro-
448 Houillot, L., Bui, C., Save, M. et al. (2007). Macromolecules 40: 6500–6509.
https://doi.org/10.1021/ma0703249.
449 Seifert, D., Kipping, M., Adler, H.K.P., and Kuckling, D. (2007). Macromol.
Symp. 254: 386–391. https://doi.org/10.1002/masy.200750856.
450 Tang, T., Castelletto, V., Parras, P. et al. (2006). Macromol. Chem. Phys. 207:
1718–1726.
451 Ladaviere, C., Dorr, N., and Claverie, J.P. (2001). Macromolecules 34: 5370–5372.
452 Zhang, X., Oddon, M., Giani, O. et al. (2010). Macromolecules 43: 2654–2656.
https://doi.org/10.1021/ma9025916.
453 de Lambert, B., Charreyre, M.-T., Chaix, C., and Pichot, C. (2007). Polymer 48:
454 Marcelo, G., Martinho, J.M.G., and Farinha, J.P.S. (2013). J. Phys. Chem. B 117:
3416–3427. https://doi.org/10.1021/jp312198k.
455 Saikia, P.J., Lee, J.M., Lee, B.H., and Choe, S. (2007). J. Polym. Sci., Part A:
456 Butte, A., Storti, G., and Morbidelli, M. (2001). Macromolecules 34: 5885–5896.
https://doi.org/10.1021/ma002130y.
457 Kanagasabapathy, S., Sudalai, A., and Benicewicz, B.C. (2001). Macromol.
Rapid Commun. 22: 1076–1080. https://doi.org/10.1002/1521-3927(20010901)
22:13<1076::AID-MARC1076>3.0.CO;2-K.
458 Chernikova, E., Yulusov, V., Mineeva, K. et al. (2011). Polym. Sci., Ser. B 53:
437–447. https://doi.org/10.1134/s1560090411070025.
459 Chernikova, E.V., Morozov, A.V., Kaziev, M.B. et al. (2007). Polym. Sci., Ser. A
49: 962–974. https://doi.org/10.1134/s0965545x07090027.
460 Lacroix-Desmazes, P., Severac, R., and Boutevin, B. (2002). ACS Symp. Ser. 854:
570–585. https://doi.org/10.1021/bk-2003-0854.ch039.
461 Favier, A., D’Agosto, F., Charreyre, M.-T., and Pichot, C. (2004). Polymer 45:
462 Relogio, P., Bathfield, M., Haftek-Terreau, Z. et al. (2013). Polym. Chem. 4:
2968–2981. https://doi.org/10.1039/C3PY00059A.
463 Raust, J.-A., Houillot, L., Save, M. et al. (2010). Macromolecules 43: 8755–8765.
464 Lou, X., Zhang, G., Herrera, I. et al. (2007). Angew. Chem. Int. Ed. 46:
465 Li, Y., Yang, J.W., and Benicewicz, B.C. (2007). J. Polym. Sci., Part A: Polym.
466 Legge, T.M., Slark, A.T., and Perrier, S. (2007). Macromolecules 40: 2318–2326.
https://doi.org/10.1021/ma061372g.
467 Perrier, S., Takolpuckdee, P., Westwood, J., and Lewis, D.M. (2004). Macro-
molecules 37: 2709–2717. https://doi.org/10.1021/ma035468b.
468 Gemici, H., Legge, T.M., Whittaker, M. et al. (2007). J. Polym. Sci., Part A:
469 Lee, H.-G., Munir, S., and Park, S.-Y. (2016). ACS Appl. Mater. Interfaces 8:
470 Seo, J., Song, M., Jeong, J. et al. (2016). ACS Appl. Mater. Interfaces 8:
471 Lee, D.-Y., Seo, J.-M., Khan, W. et al. (2010). Soft Matter 6: 1964–1970. https://
doi.org/10.1039/B926461B.
472 Omer, M., Islam, M.T., Khan, M. et al. (2014). Macromol. Res. 22: 888–894.
https://doi.org/10.1007/s13233-014-2112-z.
473 Khan, W., Seo, J.-M., and Park, S.-Y. (2011). Soft Matter 7: 780–787. https://doi
.org/10.1039/C0SM00758G.
474 Omer, M. and Park, S.-Y. (2014). Anal. Bioanal. Chem. 406: 5369–5378. https://
doi.org/10.1007/s00216-014-7900-y.
475 Paulusse, J.M.J., Amir, R.J., Evans, R.A., and Hawker, C.J. (2009). J. Am. Chem.
Soc. 131: 9805–9812. https://doi.org/10.1021/ja903245p.
476 Krivorotova, T., Vareikis, A., Gromadzki, D. et al. (2010). Eur. Polym. J. 46:
546–556. https://doi.org/10.1016/j.eurpolymj.2009.12.001.
477 Seo, M., Beck, B.J., Paulusse, J.M.J. et al. (2008). Macromolecules 41: 6413–6418.
https://doi.org/10.1021/ma8009678.
478 Kim, S., Lee, B., Kim, S. et al. (2010). Macromol. Chem. Phys. 211: 1188–1195.
479 Kim, B.J., Bang, J., Hawker, C.J. et al. (2007). Langmuir 23: 12693–12703.
https://doi.org/10.1021/la701906n.
480 Campos, L.M., Killops, K.L., Sakai, R. et al. (2008). Macromolecules 41:
7063–7070. https://doi.org/10.1021/ma801630n.
481 O’Reilly, R.K., Joralemon, M.J., Hawker, C.J., and Wooley, K.L. (2006). J. Polym.
482 O’Reilly, R.K., Joralemon, M.J., Hawker, C.J., and Wooley, K.L. (2006). Chem.
Eur. J. 12: 6776–6786. https://doi.org/10.1002/chem.200600467.
Macromolecules 42: 7657–7663. https://doi.org/10.1021/ma901036x.
484 Chang, C.-W., Bays, E., Tao, L. et al. (2009). Chem. Commun.: 3580–3582.
https://doi.org/10.1039/b904456f.
485 Nishi, H. and Kobatake, S. (2008). Chem. Lett. 37: 630–631. https://doi.org/10
.1246/cl.2008.630.
References 341
486 Feng, X.S. and Pan, C.Y. (2002). Macromolecules 35: 4888–4893. https://doi.org/
10.1021/ma020004j.
487 Xiao, N.-Y., Li, A.-L., Liang, H., and Lu, J. (2008). Macromolecules 41:
2374–2380. https://doi.org/10.1021/ma702510n.
488 Fu, Q., Cheng, L.L., Zhang, Y., and Shi, W.F. (2008). Polymer 49: 4981–4988.
489 Tinsley, J.F., Jahnke, J.P., Adamson, D.H. et al. (2009). Energy Fuels 23:
2065–2074. https://doi.org/10.1021/ef800651d.
490 Wang, Y., Ai, Q., and Lu, J. (2015). J. Polym. Sci., Part A: Polym. Chem. 53:
491 Senyek, M.L., Kulig, J.J., and Parker, D.K. (2002). Dibenzyltrithiocarbonate
molecular weight regulator for emulsion polymerization of butadiene and
styrene (Goodyear Tire & Rubber), US6369158B1.
492 Tang, C., Kowalewski, T., and Matyjaszewski, K. (2003). Macromolecules 36:
8587–8589. https://doi.org/10.1021/ma034942a.
493 Li, A.L., Wang, Y., Liang, H., and Lu, J. (2006). J. Polym. Sci., Part A: Polym.
494 D’Agosto, F., Hughes, R., Charreyre, M.-T. et al. (2003). Macromolecules 36:
621–629. https://doi.org/10.1021/ma025646l.
495 Jo, Y.S., van der Vlies, A.J., Gantz, J. et al. (2008). Macromolecules 41:
1140–1150. https://doi.org/10.1021/ma071710t.
496 Kumar, S., Deike, S., and Binder, W.H. (2018). Macromol. Rapid Commun. 39:
497 Liu, Y., Tu, W., and Cao, D. (2010). Ind. Eng. Chem. Res. 49: 2707–2715. https://
doi.org/10.1021/ie901143p.
498 Dong, S., Sun, W., Wang, D. et al. (2019). Macromol. Rapid Commun. 40:
499 Seno, R. and Kobatake, S. (2015). Dyes Pigm. 114: 166–174. https://doi.org/10
.1016/j.dyepig.2014.11.010.
500 Li, D., Luo, Y., Li, B.-G., and Zhu, S. (2008). J. Polym. Sci., Part A: Polym. Chem.
501 Ladaviere, C., Lacroix-Desmazes, P., and Delolme, F. (2009). Macromolecules 42:
70–84. https://doi.org/10.1021/ma8013788.
502 Ribaut, T., Oberdisse, J., Annighofer, B. et al. (2011). J. Phys. Chem. B 115:
836–843. https://doi.org/10.1021/jp108888x.
503 Wang, Y., Li, A.-L., Liang, H., and Lu, J. (2006). Eur. Polym. J. 42: 2695–2702.
504 Christman, K.L., Vazquez-Dorbatt, V., Schopf, E. et al. (2008). J. Am. Chem. Soc.
130: 16585–16591. https://doi.org/10.1021/ja803676r.
505 Cerda, M.M., Newton, T.D., Zhao, Y. et al. (2019). Chem. Sci 10: 1773–1779.
https://doi.org/10.1039/C8SC04683B.
506 Vishnevetskii, D.V., Plutalova, A.V., Yulusov, V.V. et al. (2015). Polym. Sci., Ser.
B 57: 197–206. https://doi.org/10.1134/S1560090415030094.
507 Chernikova, E.V., Zaitsev, S.D., Plutalova, A.V. et al. (2018). RSC Adv. 8:
14300–14310. https://doi.org/10.1039/C8RA00048D.
508 Chen, C.-L., Lo, Y.-H., Lee, C.-Y. et al. (2010). Inorg. Chem. Commun. 13:
603–605. https://doi.org/10.1016/j.inoche.2010.02.013.
509 Luo, Y.W., Liu, B., Wang, Z.H. et al. (2007). J. Polym. Sci., Part A: Polym. Chem.
510 Mori, H. and Tanaka, H. (2011). Macromol. Chem. Phys. 212: 2349–2359.
511 Hua, D.B., Ge, X.P., Bai, R.K. et al. (2005). Polymer 46: 12696–12702.
512 Han, D.-H. and Pan, C.-Y. (2008). J. Polym. Sci., Part A: Polym. Chem. 46:
513 Mori, H. and Okabayashi, S. (2009). React. Funct. Polym. 69: 441–449. https://
514 Wu, M., Zhang, H., and Liu, H. (2019). Polym. Bull. 76: 825–848. https://doi
.org/10.1007/s00289-018-2411-1.
515 Wong, K.H., Davis, T.P., Barner-Kowollik, C., and Stenzel, M.H. (2007). Polymer
516 Roohi, F. and Titirici, M.M. (2008). New J. Chem. 32: 1409–1414. https://doi.org/
10.1039/b800851e.
517 Mori, H., Kato, I., Matsuyama, M., and Endo, T. (2008). Macromolecules 41:
5604–5615. https://doi.org/10.1021/ma800181h.
518 Mori, H., Iwaya, H., Nagai, A., and Endo, T. (2005). Chem. Commun.:
4872–4874. https://doi.org/10.1039/b509212d.
519 Mori, H., Sutoh, K., Iwaya, H. et al. (2006). Controlled synthesis of amino
acid-based polymers by reversible addition fragmentation chain transfer
polymerization. In: Controlled/Living Radical Polymerization. From Synthe-
sis to Materials, Controlled/Living Radical Polymerization, vol. 944 (ed. K.
doi.org/10.1021/bk-2006-0944.ch036.
520 Mori, H., Matsuyama, M., Sutoh, K., and Endo, T. (2006). Macromolecules 39:
4351–4360. https://doi.org/10.1021/ma052756u.
521 Singh, P., Srivastava, A., and Kumar, R. (2014). Polym. Int. 63: 633–645. https://
doi.org/10.1002/pi.4549.
522 Yonenuma, R., Ishizuki, A., Nakabayashi, K., and Mori, H. J. Polym. Sci., Part
A: Polym. Chem. https://doi.org/10.1002/pola.29531.
523 Wang, J., Zhu, X.L., Cheng, Z.P. et al. (2007). J. Polym. Sci., Part A: Polym.
524 Maki, Y., Mori, H., and Endo, T. (2007). Macromol. Chem. Phys. 208: 2589–2599.
525 Li, H., Shen, H., Pei, C. et al. (2019). ChemCatChem 11: 3882–3891. https://doi
.org/10.1002/cctc.201900626.
526 Mettry, M., Hess, A.E., Goetting, I. et al. (2019). J. Vac. Sci. Technol., A 37:
020923. https://doi.org/10.1116/1.5080119.
527 Mori, H., Tando, I., and Tanaka, H. (2010). Macromolecules 43: 7011–7020.
https://doi.org/10.1021/ma100820z.
References 343
528 Mori, H., Masuda, S., and Endo, T. (2008). Macromolecules 41: 632–639. https://
doi.org/10.1021/ma0714262.
529 Mori, H., Masuda, S., and Endo, T. (2006). Macromolecules 39: 5976–5978.
https://doi.org/10.1021/ma0612879.
530 Metz, N. and Theato, P. (2007). Eur. Polym. J. 43: 1202–1209. https://doi.org/10
.1016/j.eurpolymj.2007.01.009.
531 Roth, P.J. and Theato, P. (2011). ACS Symp. Ser. 1066: 23–37 (3 pp). https://doi
.org/10.1021/bk-2011-1066.ch003.
533 Xu, S., Li, J., and Chen, L. (2011). Talanta 85: 282–289. https://doi.org/10.1016/j
.talanta.2011.03.060.
534 Zamyshlyayeva, O.G., Ionychev, B.N., Frolova, A.I. et al. (2019). Russ. J. Appl.
Chem. 92: 775–786. https://doi.org/10.1134/S1070427219060077.
535 Han, J., Silcock, P., McQuillan, A.J., and Bremer, P. (2008). Colloid Polym. Sci.
286: 1605–1612. https://doi.org/10.1007/s00396-008-1934-7.
536 Zhu, M.Q., Wei, L.H., Li, M. et al. (2001). Chem. Commun.: 365–366.
https://doi.org/10.1039/B009815I.
537 Jia, Y.-g., Liu, L.-y., Lei, B. et al. (2011). Macromolecules 44: 6311–6317. https://
doi.org/10.1021/ma201247d.
538 Serbin, A.V., Karaseva, E.N., Dunaeva, I.V. et al. (2011). Polym. Sci., Ser. B 53:
116–124. https://doi.org/10.1134/s1560090411030079.
539 Abrunhosa, I., Gulea, M., and Masson, S. (2004). Synthesis 2004: 928–934
(928 pp). https://doi.org/10.1055/s-2004-822311.
540 Inglis, A.J., Sinnwell, S., Stenzel, M.H., and Barner-Kowollik, C. (2009). Angew.
Chem. Int. Ed. 48: 2411–2414. https://doi.org/10.1002/anie.200805993.
541 Goldmann, A.S., Tischer, T., Barner, L. et al. (2011). Biomacromolecules 12:
1137–1145. https://doi.org/10.1021/bm101461h.
542 Kumar, J., Bousquet, A., and Stenzel, M.H. (2011). Macromol. Rapid Commun.
32: 1620–1626. https://doi.org/10.1002/marc.201100331.
543 Glassner, M., Delaittre, G., Kaupp, M. et al. (2012). J. Am. Chem. Soc. 134:
7274–7277. https://doi.org/10.1021/ja301762y.
544 Inglis, A.J., Sinnwell, S., Davis, T.P. et al. (2008). Macromolecules 41: 4120–4126.
https://doi.org/10.1021/ma8002328.
545 Alberti, A., Benaglia, M., Guerra, M. et al. (2005). Macromolecules 38:
7610–7618. https://doi.org/10.1021/ma050652d.
546 Dürr, C.J., Hlalele, L., Kaiser, A. et al. (2013). Macromolecules 46: 49–62.
https://doi.org/10.1021/ma302017c.
547 Previero, A. and Pechere, J.-F. (1970). Biochem. Biophys. Res. Commun. 40:
549–556. https://doi.org/10.1016/0006-291X(70)90937-X.
548 Niu, X., Ran, F., Chen, L. et al. (2016). Langmuir 32: 4297–4304. https://doi
.org/10.1021/acs.langmuir.6b00562.
549 Christmann, J., Ibrahim, A., Charlot, V. et al. (2016). ChemPhysChem 17:
2309–2314. https://doi.org/10.1002/cphc.201600034.
550 Keddie, D.J., Guerrero-Sanchez, C., and Moad, G. (2013). Polym. Chem. 4:
3591–3601. https://doi.org/10.1039/c3py00487b.
551 Yang, C. and Cheng, Y.L. (2006). J. Appl. Polym. Sci. 102: 1191–1201. https://doi
.org/10.1002/app.24415.
552 Toyoshima, M. and Miura, Y. (2009). J. Polym. Sci., Part A: Polym. Chem. 47:
553 Quan, C.-Y., Wu, D.-Q., Chang, C. et al. (2009). J. Phys. Chem. C 113:
11262–11267. https://doi.org/10.1021/jp902637n.
554 Jaramillo-Soto, G. and Vivaldo-Lima, E. (2012). Aust. J. Chem. 65: 1177–1185.
555 Wang, S., Vajjala Kesava, S., Gomez, E.D., and Robertson, M.L. (2013). Macro-
557 Fortenberry, A.W., McCormick, C.L., and Smith, A.E. (2022). Considerations for
and applications of aqueous RAFT polymerization. In: RAFT Polymerization:
1735–1741. https://doi.org/10.1021/ma035572t.
560 Coulembier, O., Lohmeijer, B.G.G., Dove, A.P. et al. (2006). Macromolecules 39:
5617–5628. https://doi.org/10.1021/ma0611366.
561 Zheng, Y., Turner, W., Zong, M. et al. (2011). Macromolecules 44: 1347–1354.
https://doi.org/10.1021/ma1027092.
562 Inglis, A.J., Pierrat, P., Muller, T. et al. (2010). Soft Matter 6: 82–84.
https://doi.org/10.1039/B920806M.
563 Inglis, A.J., Stenzel, M.H., and Barner-Kowollik, C. (2009). Macromol. Rapid
Commun. 30: 1792–1798. https://doi.org/10.1002/marc.200900363.
564 Yu, Y., Li, G., Kang, H., and Youk, J. (2012). Colloid Polym. Sci. 290: 1707–1712.
https://doi.org/10.1007/s00396-012-2788-6.
565 Kinoshita, K., Takami, T., Mori, Y. et al. (2017). J. Polym. Sci., Part A: Polym.
566 Li, W., Li, J., Gao, J. et al. (2011). Biomaterials 32: 3832–3844. https://doi.org/10
.1016/j.biomaterials.2011.01.075.
567 Akimoto, J., Nakayama, M., Sakai, K., and Okano, T. (2009). Biomacromolecules
10: 1331–1336. https://doi.org/10.1021/bm900032r.
568 Akimoto, J., Nakayama, M., Sakai, K., and Okano, T. (2008). J. Polym. Sci., Part
569 Akimoto, J., Nakayama, M., Sakai, K. et al. (2013). Polym. J. 45: 233–237.
https://doi.org/10.1038/pj.2012.108.
570 Bathfield, M., D’Agosto, F., Spitz, R. et al. (2006). J. Am. Chem. Soc. 128:
2546–2547. https://doi.org/10.1021/ja057481c.
References 345
571 Zheng, Q. and Pan, C.Y. (2005). Macromolecules 38: 6841–6848.

https://doi.org/10.1021/ma050455e.
572 Aamer, K.A. and Tew, G.N. (2007). J. Polym. Sci., Part A: Polym. Chem. 45:
573 Yang, H., Liang, F., Wang, X. et al. (2013). Macromolecules 46: 2754–2759.
574 Yuan, K., Li, Z.F., Lu, L.L., and Shi, X.N. (2007). Mater. Lett. 61: 2033–2036.
https://doi.org/10.1016/j.matlet.2006.08.010.
575 Yuan, K., Lu, L.-L., Li, Z.-F., and Shi, X.-N. (2008). Chin. J. Chem. 26:
1929–1934. https://doi.org/10.1002/cjoc.200890346.
576 Warren, N.J., Rosselgong, J., Madsen, J., and Armes, S.P. (2015). Biomacro-
molecules 16: 2514–2521. https://doi.org/10.1021/acs.biomac.5b00767.
577 Sun, P., Zhang, Y., Shi, L., and Gan, Z. (2010). Macromol. Biosci. 10: 621–631.
https://doi.org/10.1002/mabi.200900434.
578 Gurbuz, N., Demirci, S., Yavuz, S., and Caykara, T. (2011). J. Polym. Sci., Part A:
579 Favier, A., Luneau, B., Vinas, J. et al. (2009). Macromolecules 42: 5953–5964.
https://doi.org/10.1021/ma9006939.
580 Li, C., Han, J., Ryu, C.Y., and Benicewicz, B.C. (2006). Macromolecules 39:
3175–3183. https://doi.org/10.1021/ma051983t.
581 Liu, J., Yang, W., Zareie, H.M. et al. (2009). Macromolecules 42: 2931–2939.
582 Xu, J., Tao, L., Liu, J. et al. (2009). Macromolecules 42: 6893–6901. https://doi
.org/10.1021/ma901290a.
583 Xu, J., Tao, L., Boyer, C. et al. (2011). Macromolecules 44: 299–312. https://doi
.org/10.1021/ma102386j.
584 Roth, P.J., Wiss, K.T., Zentel, R., and Theato, P. (2008). Macromolecules 41:
8513–8519. https://doi.org/10.1021/ma801681b.
585 Wiss, K.T. and Theato, P. (2010). J. Polym. Sci., Part A: Polym. Chem. 48:
586 Li, Y. and Benicewicz, B.C. (2007). Polym. Prepr. (Am. Chem. Soc., Div. Polym.
Chem.) 48: 524–525.
587 Quemener, D., Davis, T.P., Barner-Kowollik, C., and Stenzel, M.H. (2006).
Chem. Commun.: 5051–5053. https://doi.org/10.1039/b611224b.
588 Gondi, S.R., Vogt, A.P., and Sumerlin, B.S. (2007). Macromolecules 40: 474–481.
589 Mendonça, P.V., Serra, A.C., Popov, A.V. et al. (2014). React. Funct. Polym. 81:
590 Hanisch, A., Schmalz, H., and Müller, A.H.E. (2012). Macromolecules 45:
8300–8309. https://doi.org/10.1021/ma3017579.
591 Ye, Y.-S., Chen, Y.-N., Wang, J.-S. et al. (2012). Chem. Mater. 24: 2987–2997.
https://doi.org/10.1021/cm301345r.
592 Shi, G.Y., Tang, X.Z., and Pan, C.Y. (2008). J. Polym. Sci., Part A: Polym. Chem.
593 Goldmann, A.S., Quemener, D., Millard, P.E. et al. (2008). Polymer 49:
594 Zhang, K., Gao, L., and Chen, Y. (2010). Polymer 51: 2809–2817. https://doi.org/
10.1016/j.polymer.2010.04.042.
595 Zhu, J., Zhu, X., Kang, E.T., and Neoh, K.G. (2007). Polymer 48: 6992–6999.
{Goldmann, 2008 #1001}
596 Cha, Y., Jarrett-Wilkins, C., Rahman, M.A. et al. (2019). ACS Macro Lett. 8:
597 Zhou, F., Li, Y., Jiang, G. et al. (2015). Polym. Chem. 6: 6885–6893. https://doi
.org/10.1039/C5PY01003A.
598 Lorenz, M., Vogg, S., Finkelstein, P. et al. (2019). Macromol. Mater. Eng. 304:
1900311. https://doi.org/10.1002/mame.201900311.
599 Alidedeoglu, A.H., Harris, C.A., Martinez-Castro, N. et al. (2010). ACS Symp.
Ser. 1053: 113–129 (6 pp). https://doi.org/10.1021/bk-2010-1053.ch006.
600 Zhou, F., Zhang, Z., Jiang, G. et al. (2016). Polym. Chem. 7: 2785–2789. https://
doi.org/10.1039/C6PY00545D.
601 Müllner, M., Schallon, A., Walther, A. et al. (2010). Biomacromolecules 11:
390–396. https://doi.org/10.1021/bm901099p.
602 Ting, S.R.S., Granville, A.M., Quemener, D. et al. (2007). Aust. J. Chem. 60:
405–409. https://doi.org/10.1071/CH07089.
603 Arslan, M., Aydin, D., Degirmenci, A. et al. (2017). ACS Omega 2: 6658–6667.
https://doi.org/10.1021/acsomega.7b00787.
604 Long, S., Tang, Q., Wu, Y. et al. (2014). React. Funct. Polym. 80: 15–20. https://
605 Tang, Q. and Zhang, K. (2015). Polym. Int. 64: 1060–1065. https://doi.org/10
.1002/pi.4906.
606 Stamenović, M.M., Espeel, P., Baba, E. et al. (2013). Polym. Chem. 4: 184–193.
https://doi.org/10.1039/C2PY20751F.
607 Li, A., Ma, J., Sun, G. et al. (2012). J. Polym. Sci., Part A: Polym. Chem. 50:
608 Patton, D.L. and Advincula, R.C. (2006). Macromolecules 39: 8674–8683.
609 Su, L., Heo, G.S., Lin, Y.-N. et al. (2017). J. Polym. Sci., Part A: Polym. Chem. 55:
610 Zhang, J., Pellechia, P.J., Hayat, J. et al. (2013). Macromolecules 46: 1618–1624.
https://doi.org/10.1021/ma4000013.
611 Qiao, Y., Islam, M.S., Yin, X. et al. (2015). Polymer 72: 428–435. https://doi.org/
10.1016/j.polymer.2015.02.011.
612 Müller, R., Feuerstein, T.J., Trouillet, V. et al. (2018). Chem. Eur. J. 24:
18933–18943. https://doi.org/10.1002/chem.201803966.
613 Jiang, Y., Lu, H., Dag, A. et al. (2016). J. Mater. Chem. B 4: 2017–2027. https://
doi.org/10.1039/C5TB02576A.
614 Jiang, Y., Liang, M., Svejkar, D. et al. (2014). Chem. Commun. 50: 6394–6397.
https://doi.org/10.1039/C4CC00616J.
References 347
615 Zhao, J., Zhou, Y., Zhou, Y. et al. (2016). Polym. Chem. 7: 1782–1791. https://doi
.org/10.1039/C5PY01861G.
616 Lederhose, P., Abt, D., Welle, A. et al. (2018). Chem. Eur. J. 24: 576–580. https://
doi.org/10.1002/chem.201705393.
617 Chang, D. and Olsen, B.D. (2016). Polym. Chem. 7: 2410–2418. https://doi.org/
10.1039/C5PY01894C.
618 Spiridon, M.C., Demazy, N., Brochon, C. et al. (2020). Macromolecules 53:
619 Qin, X., Li, Y., Zhou, F. et al. (2015). Appl. Surf. Sci. 328: 183–192. https://doi
.org/10.1016/j.apsusc.2014.12.019.
620 Guo, J., Poros-Tarcali, E., and Perez-Mercader, J. (2019). Chem. Commun. 55:
621 dos Santos, A.M., Pohn, J., Lansalot, M., and D’Agosto, F. (2007). Macromol.
622 Ma, Y., Zhao, Y., Bejjanki, N.K. et al. (2019). ACS Nano 13: 8890–8902. https://
doi.org/10.1021/acsnano.9b02466.
623 Zhou, W., Wang, J., Ding, P. et al. (2019). Angew. Chem. Int. Ed. 58: 8494–8498.
624 Hu, C., Dong, B., and Liu, L. (2019). J. Polym. Sci., Part A: Polym. Chem. 57:
625 Martins dos Santos, A., Le Bris, T., Graillat, C. et al. (2009). Macromolecules 42:
946–956. https://doi.org/10.1021/ma802117h.
626 Bharatiya, B., Yusa, S.-I., Aswal, V. et al. (2011). Bull. Soc. Chem. Soc. Jpn. 84:
1227–1233. https://doi.org/10.1246/bcsj.20110184.
627 Zheng, Q., Zheng, G.-H., and Pan, C.-Y. (2006). Polym. Int. 55: 1114–1123.
https://doi.org/10.1002/pi.2089.
628 Bang, J., Kim, S.H., Drockenmuller, E. et al. (2006). J. Am. Chem. Soc. 128:
7622–7629. https://doi.org/10.1021/ja0608141.
629 El Asmar, A., Morandi, G., and Burel, F. (2019). Macromolecules 52: 9160–9167.
630 Wei, Z., Hao, X., Kambouris, P.A. et al. (2012). Polymer 53: 1429–1436. https://
doi.org/10.1016/j.polymer.2012.02.011.
631 Wei, Z., Hao, X., Gan, Z., and Hughes, T.C. (2012). J. Polym. Sci., Part A: Polym.
632 Tao, L., Liu, J., Tan, B.H., and Davis, T.P. (2009). Macromolecules 42: 4960–4962.
633 Hu, X., Liu, G., Li, Y. et al. (2015). J. Am. Chem. Soc. 137: 362–368. https://doi
.org/10.1021/ja5105848.
634 Zhang, M., Liu, H., Shao, W. et al. (2013). Macromolecules 46: 1325–1336.
https://doi.org/10.1021/ma3025283.
635 Li, C., Liu, H., Tang, D., and Zhao, Y. (2015). Polym. Chem. 6: 1474–1486.
636 Zheng, L., Wang, Y., Zhang, X. et al. (2018). Bioconjugate Chem. 29: 190–202.
https://doi.org/10.1021/acs.bioconjchem.7b00699.
637 Heidenreich, A.J. and Puskas, J.E. (2008). J. Polym. Sci., Part A: Polym. Chem.
638 Shallcross, L., Roche, K., Wilcock, C.J. et al. (2017). J. Mater. Chem. B 5:
6027–6033. https://doi.org/10.1039/C7TB00144D.
639 Heidenreich, A.J., Puskas, J.E., Schappacher, M. et al. (2012). J. Polym. Sci., Part
640 Zhang, M., Liu, H., Shao, W. et al. (2012). Macromolecules 45: 9312–9325.
641 Carter, S., Hunt, B., and Rimmer, S. (2005). Macromolecules 38: 4595–4603.
642 Carter, S., Rimmer, S., Sturdy, A., and Webb, M. (2005). Macromol. Biosci. 5:
373–378. https://doi.org/10.1002/mabi.200400218.
643 Hopkins, S., Carter, S., Swanson, L. et al. (2007). J. Mater. Chem. 17: 4022–4027.
https://doi.org/10.1039/B708415C.
644 Rikkou-Kalourkoti, M. and Patrickios, C.S. (2012). Macromolecules 45:
7890–7899. https://doi.org/10.1021/ma3012416.
645 Wang, Z.M., He, J.P., Tao, Y.F. et al. (2003). Macromolecules 36: 7446–7452.
https://doi.org/10.1021/ma025673b.
sis and Applications (eds. G. Moad and E. Rizzardo), 1017–1050. Weinheim:
Wiley-VCH.
648 Patton, D.L., Mullings, M., Fulghum, T., and Advincula, R.C. (2005). Macro-
molecules 38: 8597–8602. https://doi.org/10.1021/ma051035s.
649 You, Y.-Z., Manickam, D.S., Zhou, Q.-H., and Oupicky, D. (2007). Biomacro-
molecules 8: 2038–2044. https://doi.org/10.1021/bm0702049.
650 You, Y.-Z., Manickam, D.S., Zhou, Q.-H., and Oupický, D. (2007). J. Controlled
Release 122: 217–225. https://doi.org/10.1016/j.jconrel.2007.04.020.
651 You, J.-O., Guo, P., and Auguste, D.T. (2013). Angew. Chem. Int. Ed. 52:
652 Achilleos, M., Krasia-Christoforou, T., and Patrickios, C.S. (2007). Macro-
molecules 40: 5575–5581. https://doi.org/10.1021/ma070614p.
653 You, Y.-Z., Zhou, Q.-H., Manickam, D.S. et al. (2007). Macromolecules 40:
8617–8624. https://doi.org/10.1021/ma071176p.
654 Pafiti, K.S., Loizou, E., Patrickios, C.S., and Porcar, L. (2010). Macromolecules
43: 5195–5204. https://doi.org/10.1021/ma100552v.
655 Park, N., Seo, M., and Kim, S.Y. (2012). J. Polym. Sci., Part A: Polym. Chem. 50:
656 Huang, K., Canterbury, D.P., and Rzayev, J. (2010). Macromolecules 43:
6632–6638. https://doi.org/10.1021/ma100971w.
References 349
657 Harvey, A.C., Madsen, J., Douglas, C.W.I. et al. (2016). Biomacromolecules 17:
658 Fu, W. and Zhao, B. (2016). Polym. Chem. 7: 6980–6991. https://doi.org/10.1039/
C6PY01517D.
659 Zhu, K., Zhu, Z., Zhou, H. et al. (2017). Chin. Chem. Lett. 28: 1276–1284.
660 Achilleos, M., Legge, T.M., Perrier, S., and Patrickios, C.S. (2008). J. Polym. Sci.,
661 Pafiti, K.S., Patrickios, C.S., Abetz, C., and Abetz, V. (2013). J. Polym. Sci., Part
662 Peng, Z., Wang, D., Liu, X., and Tong, Z. (2007). J. Polym. Sci., Part A: Polym.
663 Porcarelli, L., Aboudzadeh, M.A., Rubatat, L. et al. (2017). J. Power Sources 364:
191–199. https://doi.org/10.1016/j.jpowsour.2017.08.023.
664 Su, X., Ma, B., Hu, J. et al. (2018). Bioconjugate Chem. 29: 4050–4061. https://
doi.org/10.1021/acs.bioconjchem.8b00671.
665 Zhu, C., Zheng, M., Meng, F. et al. (2012). Biomacromolecules 13: 769–778.
https://doi.org/10.1021/bm201693j.
666 Shi, Y., Zhu, W., Yao, D. et al. (2014). ACS Macro Lett. 3: 70–73. https://doi.org/
10.1021/mz400619g.
667 Banerjee, R., Maiti, C., Dutta, S., and Dhara, D. (2015). Polymer 59: 243–251.
668 Samakande, A., Sanderson, R.D., and Hartmann, P.C. (2009). Eur. Polym. J. 45:
669 Li, J., Cong, H., Li, L., and Zheng, S. (2014). ACS Appl. Mater. Interfaces 6:
13677–13687. https://doi.org/10.1021/am503148v.
670 Banerjee, R., Maiti, S., and Dhara, D. (2014). Green Chem. 16: 1365–1373.
https://doi.org/10.1039/C3GC41722K.
671 Delfanne, I. and Levesque, G. (1989). Macromolecules 22: 2589–2592. https://doi
.org/10.1021/ma00196a007.
672 Dureault, A., Taton, D., Destarac, M. et al. (2004). Macromolecules 37:
5513–5519. https://doi.org/10.1021/ma030420j.
673 Allison-Logan, S., Karimi, F., Nothling, M.D., and Qiao, G.G. (2022). Star
polymers by RAFT polymerization. In: RAFT Polymerization: Materials, Syn-
Wiley-VCH.
674 Barner-Kowollik, C., Quinn, J.F., Nguyen, T.L.U. et al. (2001). Macromolecules
34: 7849–7857. https://doi.org/10.1021/ma010349m.
675 Sontakke, T.K. and Jagtap, R.N. (2013). J. Dispersion Sci. Technol. 34: 1575–1584.
https://doi.org/10.1080/01932691.2012.756377.
676 Yao, L., Rong, M.Z., Zhang, M.Q., and Yuan, Y.C. (2011). J. Mater. Chem. 21:
9060–9065. https://doi.org/10.1039/C1JM10655D.
677 Becer, C.R., Groth, A.M., Hoogenboom, R. et al. (2008). QSAR Comb. Sci. 27:
977–983. https://doi.org/10.1002/qsar.200720159.
678 Zhou, G.T. and Ma, Y. (2008). Chem. Lett. 37: 850–851. https://doi.org/10.1246/
cl.2008.850.
679 Lovestead, T.M., Hart-Smith, G., Davis, T.P. et al. (2007). Macromolecules 40:
4142–4153. https://doi.org/10.1021/ma0701484.
680 Haehnel, A.P., Stach, M., Chovancova, A. et al. (2014). Polym. Chem. 5:
682 Gruendling, T., Hart-Smith, G., Davis, T.P. et al. (2008). Macromolecules 41:
1966–1971. https://doi.org/10.1021/ma702163v.
683 Johnston-Hall, G., Harjani, J.R., Scammells, P.J., and Monteiro, M.J. (2009).
Macromolecules 42: 1604–1609. https://doi.org/10.1021/ma802795j.
684 Johnston-Hall, G. and Monteiro, M.J. (2008). Macromolecules 41: 727–736.
https://doi.org/10.1021/ma702569m.
685 Szkurhan, A.R., Kasahara, T., and Georges, M.K. (2006). J. Polym. Sci., Part A:
molecules 35: 5417–5425. https://doi.org/10.1021/ma011840g.
molecules 38: 4901–4912. https://doi.org/10.1021/ma047373v.
688 Kaiser, A., Brandau, S., Klimpel, M., and Barner-Kowollik, C. (2010). Macromol.
689 Wang, Y., Chen, Q., Liang, H., and Lu, J. (2007). Polym. Int. 56: 1514–1520.
https://doi.org/10.1002/pi.2294.
690 Barner, L., Pereira, S., Sandanayake, S., and Davis, T.P. (2006). J. Polym. Sci.,
691 Quinn, J.F., Rizzardo, E., and Davis, T.P. (2001). Chem. Commun.: 1044–1045.
https://doi.org/10.1039/B101794M.
692 Matsumoto, M., Wakabayashi, R., Tada, T. et al. (2016). Macromol. Chem. Phys.
693 Biswas, C., Mitra, K., Singh, S. et al. (2015). Colloid Polym. Sci. 293: 1749–1757.
https://doi.org/10.1007/s00396-015-3562-3.
694 Biswas, C.S., Mitra, K., Singh, S., and Ray, B. (2016). J. Chem. Sci. 128: 415–420.
https://doi.org/10.1007/s12039-016-1033-0.
695 Biswas, C.S., Wu, Y., Wang, Q. et al. (2017). J. Rheol. 61: 1345–1357. https://doi
.org/10.1122/1.5006807.
696 Chaffey-Millar, H., Hart-Smith, G., and Barner-Kowollik, C. (2008). J. Polym.
697 Fujii, S., Yokoyama, Y., Nakayama, S. et al. (2018). Langmuir 34: 933–942.
https://doi.org/10.1021/acs.langmuir.7b02670.
698 Lansalot, M., Davis, T.P., and Heuts, J.P.A. (2002). Macromolecules 35:
7582–7591. https://doi.org/10.1021/ma012214m.
699 Luo, Y.W., Wang, R., Yang, L. et al. (2006). Macromolecules 39: 1328–1337.
700 Wang, Z., Zhang, Q., Zhan, X. et al. (2016). J. Polym. Res. 23: 253. https://doi
.org/10.1007/s10965-016-1152-9.
References 351
701 Urbani, C.N., Nguyen, H.N., and Monteiro, M.J. (2006). Aust. J. Chem. 59:
728–732. https://doi.org/10.1071/CH06231.
702 Hartmann, J., Urbani, C., Whittaker, M.R., and Monteiro, M.J. (2006). Macro-
703 Sirohi, S., Singh, D., Nain, R. et al. (2015). RSC Adv. 5: 34377–34382. https://doi
.org/10.1039/C4RA16988C.
704 García-Peñas, A., Biswas, C.S., Liang, W. et al. (2019). Polymers 11: 991. https://
doi.org/10.3390/polym11060991.
705 Theis, A., Stenzel, M.H., Davis, T.P., and Barner-Kowollik, C. (2006). Obtaining
chain length dependent termination rate coefficients via thermally initiated
reversible addition fragmentation chain transfer experiments. In: Con-
trolled/Living Radical Polymerization, ACS Symposium Series, vol. 944, 486–500.
American Chemical Society. https://doi.org/10.1021/bk-2006-0944.ch033.
706 Lovestead, T.M., Davis, T.P., Stenzel, M.H., and Barner-Kowollik, C. (2007).
Macromol. Symp. 248: 82–93. https://doi.org/10.1002/masy.200750209.
707 Katsumoto, Y. and Kubosaki, N. (2008). Macromolecules 41: 5955–5956. https://
doi.org/10.1021/ma800881r.
708 Yusa, S.-i., Fukuda, K., Yamamoto, T. et al. (2007). Langmuir 23: 12842–12848.
https://doi.org/10.1021/la702741q.
709 Biswas, C.S., Patel, V.K., Vishwakarma, N.K. et al. (2011). Macromolecules 44:
5822–5824. https://doi.org/10.1021/ma200735k.
710 Shimoaka, T., Rikiyama, K., Katsumoto, Y., and Hasegawa, T. (2013). Anal.
Bioanal. Chem. 405: 9411–9418. https://doi.org/10.1007/s00216-013-7400-5.
711 Alam, M., Keiko, H., Yusa, S., and Nakashima, K. (2014). Colloid Polym. Sci.
292: 1611–1617. https://doi.org/10.1007/s00396-014-3205-0.
712 Whittaker, M.R., Goh, Y.-K., Gemici, H. et al. (2006). Macromolecules 39:
9028–9034. https://doi.org/10.1021/ma061070e.
713 Yao, Z., Zhang, J.-S., Chen, M.-L. et al. (2011). J. Appl. Polym. Sci. 121:
1740–1746. https://doi.org/10.1002/app.33816.
714 Wang, Z.X., Zhang, Q.H., Yu, Y.T. et al. (2010). Chin. Chem. Lett. 21: 1497–1500.
715 Wei, R., Luo, Y., and Li, Z. (2010). Polymer 51: 3879–3886. https://doi.org/10
.1016/j.polymer.2010.06.023.
716 Qi, G.G., Nolan, M., Schork, F.J., and Jones, C.W. (2008). J. Polym. Sci., Part A:
717 Wang, Z., Zhang, Q., Zhan, X. et al. (2013). J. Polym. Res. 20: 1–13. https://doi
.org/10.1007/s10965-013-0288-0.
718 Wei, R., Luo, Y., Zeng, W. et al. (2012). Ind. Eng. Chem. Res. 51: 15530–15535.
https://doi.org/10.1021/ie302067n.
719 Yu, Y., Zhang, Q., Wang, Z. et al. (2012). J. Macromol. Sci., Part A: Pure Appl.
Chem. 49: 60–66. https://doi.org/10.1080/10601325.2012.630946.
720 Yu, Y., Zhang, Q., Zhan, X., and Chen, F. (2013). J. Appl. Polym. Sci. 127:
2557–2565. https://doi.org/10.1002/app.37785.
721 Sun, X.Y., Luo, Y.W., Wang, R. et al. (2007). Macromolecules 40: 849–859.
722 Sun, X., Luo, Y., Wang, R. et al. (2008). AIChE J. 54: 1073–1087. https://doi.org/
10.1002/aic.11446.
723 Nozari, S., Tauer, K., and Ali, A.M.I. (2005). Macromolecules 38: 10449–10454.
724 Schmid, C., Weidner, S., Falkenhagen, J., and Barner-Kowollik, C. (2012).
Macromolecules 45: 87–99. https://doi.org/10.1021/ma2022452.
725 Goh, Y.-K. and Monteiro, M.J. (2006). Macromolecules 39: 4966–4974. https://doi
.org/10.1021/ma060395s.
726 Johnston-Hall, G. and Monteiro, M.J. (2009). Influence of molecular weight dis-
tribution (MWD) on kt and the onset of the gel effect using the RAFT-CLD-T
method. In: Controlled/Living Radical Polymerization: Progress in RAFT, DT,
NMP & OMRP, ACS Symposium Series, vol. 1024, 19–35. American Chemical
727 Oae, S., Yagihara, T., and Okabe, T. (1972). Tetrahedron 28: 3203–3216. https://
doi.org/10.1016/S0040-4020(01)93661-0.
728 Chiacchio, M.-A., Legnani, L., Caramella, P. et al. (2018). Tetrahedron 74:
5627–5634. https://doi.org/10.1016/j.tet.2018.07.056.
729 Rajaram, S., Armstrong, P.B., Kim, B.J., and Frechet, J.M.J. (2009). Chem. Mater.
1775–1777. https://doi.org/10.1021/cm900911x.
730 Tam, W.Y., Mak, C.S.K., Ng, A.M.C. et al. (2009). Macromol. Rapid Commun.
731 Nagai, A., Kokado, K., Miyake, J., and Chujo, Y. (2009). J. Polym. Sci., Part A:
732 He, J., Yan, B., Tremblay, L., and Zhao, Y. (2010). Langmuir 27: 436–444.
https://doi.org/10.1021/la1040322.
733 Huang, Y., Hou, T., Cao, X. et al. (2010). Polym. Chem. 1: 1615–1623. https://doi
.org/10.1039/C0PY00165A.
734 Hua, D., Tang, J., Jiang, J., and Zhu, X. (2009). Polymer 50: 5701–5707. https://
doi.org/10.1016/j.polymer.2009.09.074.
735 He, S.-J., Zhang, Y., Cui, Z.-H. et al. (2009). Eur. Polym. J. 45: 2395–2401.
736 Zhang, X., Boisse, S., Bui, C. et al. (2012). Soft Matter 8: 1130–1141. https://doi
.org/10.1039/C1SM06598J.
737 Tao, L., Kaddis, C.S., Loo, R.R.O. et al. (2009). Chem. Commun.: 2148–2150.
https://doi.org/10.1039/b822799c.
4941–4945. https://doi.org/10.1021/ma900517w.
739 Min, E.H., Ting, S.R.S., Billon, L., and Stenzel, M.H. (2010). J. Polym. Sci., Part
740 Gody, G., Boullanger, P., Ladaviere, C. et al. (2008). Macromol. Rapid Commun.
741 Jiang, X., Ahmed, M., Deng, Z., and Narain, R. (2009). Bioconjugate Chem. 20:
994–1001. https://doi.org/10.1021/bc800566f.
742 Mori, H., Matsuyama, M., and Endo, T. (2009). Macromol. Chem. Phys. 210:
References 353
743 Zhang, H., Deng, J., Lu, L., and Cai, Y. (2007). Macromolecules 40: 9252–9261.
https://doi.org/10.1021/ma071287o.
744 Maksym, P., Tarnacka, M., Bielas, R. et al. (2020). Polymer 192: 122262. https://
doi.org/10.1016/j.polymer.2020.122262.
745 Maki, Y., Mori, H., and Endo, T. (2007). Macromolecules 40: 6119–6130. https://
doi.org/10.1021/ma062839q.
746 Semsarilar, M., Ladmiral, V., and Perrier, S.b. (2010). Macromolecules 43:
1438–1443. https://doi.org/10.1021/ma902587r.
747 Li, G., Zheng, H., and Bai, R. (2009). Macromol. Rapid Commun. 30: 442–447.
748 Boyer, C., Whittaker, M., and Davis, T.P. (2011). J. Polym. Sci., Part A: Polym.
749 Kakuchi, R. and Theato, P. (2012). Macromolecules 45: 1331–1338. https://doi
.org/10.1021/ma202175z.
750 O’Reilly, R.K. (2010). Polym. Int. 59: 568–573. https://doi.org/10.1002/pi.2830.
751 Ahmad, N.M., Charleux, B., Farcet, C. et al. (2009). Macromol. Rapid Commun.
752 Ballard, N. and Asua, J.M. (2018). Prog. Polym. Sci. 79: 40–60. https://doi.org/10
.1016/j.progpolymsci.2017.11.002.
753 Reyes, Y. and Asua, J.M. (2011). Macromol. Rapid Commun. 32: 63–67. https://
doi.org/10.1002/marc.201000375.
9783527622757.ch3.
755 Bar-Nes, G., Hall, R., Sharma, V. et al. (2009). Eur. Polym. J. 45: 3149–3163.
.org/10.1002/pola.29199.
https://doi.org/10.1002/1521-3773(20010417)40:8<1340::AID-ANIE1340>3.0.CO;
2-%23.
759 Ladmiral, V., Legge, T.M., Zhao, Y.L., and Perrier, S. (2008). Macromolecules 41:
6728–6732. https://doi.org/10.1021/ma8010262.
760 Rosselgong, J. and Armes, S.P. (2012). Macromolecules 45: 2731–2737. https://
doi.org/10.1021/ma3002609.
761 Nakabayashi, K., Tsuda, A., Otani, H., and Mori, H. (2015). React. Funct. Polym.
86: 52–59. https://doi.org/10.1016/j.reactfunctpolym.2014.11.004.
762 Leung, D. and Bowman, C.N. (2012). Macromol. Chem. Phys. 213: 198–204.
763 Syrett, J.A., Haddleton, D.M., Whittaker, M.R. et al. (2011). Chem. Commun. 47:
764 Luzon, M., Boyer, C., Peinado, C. et al. (2010). J. Polym. Sci., Part A: Polym.
766 Ferreira, J., Syrett, J., Whittaker, M. et al. (2011). Polym. Chem. 2: 1671–1677.
767 Floyd, T.G., Häkkinen, S., Hartlie, M. et al. (2022). Complex polymeric archi-
tectures synthesised through RAFT polymerization. In: RAFT Polymerization:
768 Krasia, T.C. and Patrickios, C.S. (2006). Macromolecules 39: 2467–2473. https://
doi.org/10.1021/ma051747i.
769 Pafiti, K.S., Philippou, Z., Loizou, E. et al. (2011). Macromolecules 44:
5352–5362. https://doi.org/10.1021/ma200668v.
770 Alfurhood, J.A., Bachler, P.R., and Sumerlin, B.S. (2016). Polym. Chem. 7:
polym9060188.
.macromol.9b01365.
773 Haven, J.J., Hendrikx, M., Junkers, T. et al. (2018). Elements of RAFT nav-
(co)polymers. In: Reversible Deactivation Radical Polymerization: Mecha-
nisms and Synthetic Methodologies, ACS Symposium Series, vol. 1284 (eds.
K. Matyjaszewski, H. Gao, B.S. Sumerlin and N.V. Tsarevsky), 77–103. Wash-
ington, DC: American Chemical Society. https://doi.org/10.1021/bk-2018-1284
.ch004.
2383–2394. https://doi.org/10.1021/ma035478c.
777 Houshyar, S., Keddie, D., Moad, G. et al. (2012). Polym. Chem. 3: 1879–1889.
https://doi.org/10.1039/C2PY00529H.
778 Guo, X., Choi, B., Feng, A., and Thang, S.H. (2018). Macromol. Rapid Commun.
779 Kermagoret, A. and Gigmes, D. (2016). Tetrahedron 72: 7672–7685. https://doi
.org/10.1016/j.tet.2016.07.002.
780 Pearson, S., St. Thomas, C., Guerrero-Santos, R., and D’Agosto, F. (2017). Polym.
Chem. 8: 4916–4946. https://doi.org/10.1039/C7PY00344G.
References 355
781 Wager, C.M., Haddleton, D.M., and Bon, S.A.F. (2004). Eur. Polym. J. 40:
782 Kwak, Y., Nicolay, R., and Matyjaszewski, K. (2009). Aust. J. Chem. 62:
1384–1401.
783 Ao, Y., He, J., Han, X. et al. (2007). J. Polym. Sci., Part A: Polym. Chem. 45:
784 Li, C., He, J., Liu, Y. et al. (2012). Aust. J. Chem. 65: 1077–1089. https://doi.org/
10.1071/CH12152.
785 Petton, L., Ciolino, A.E., Stamenović, M.M. et al. (2012). Macromol. Rapid Com-
786 Zehm, D., Laschewsky, A., Liang, H., and Rabe, J.P. (2011). Macromolecules 44:
9635–9641. https://doi.org/10.1021/ma2015613.
787 St Thomas, C., Maldonado-Textle, H., Rockenbauer, A. et al. (2012). J. Polym.
788 Moad, G. and Solomon, D.H. (2006). Propagation. In: The Chemistry of
Radical Polymerization, 167–232. Oxford: Elsevier. https://doi.org/10.1016/
B978-008044288-4/50023-6.
789 Moad, G. (2017). Macromol. Chem. Phys. 218: 1700381. https://doi.org/10.1002/
macp.201700381.
790 Moad, G. and Solomon, D.H. (2006). Initiation. In: The Chemistry of Radi-
cal Polymerization, 49–166. Oxford: Elsevier. https://doi.org/10.1016/B978-
008044288-4/50022-4.
791 Delduc, P., Tailhan, C., and Zard, S.Z. (1988). J. Chem. Soc., Chem. Commun.:
308–310. https://doi.org/10.1039/C39880000308.
793 Li, S., Han, G., and Zhang, W. (2020). Polym. Chem. 11: 1830–1844. https://doi
.org/10.1039/D0PY00054J.
794 Skrabania, K., Miasnikova, A., Bivigou-Koumba, A.M. et al. (2011). Polym.
Chem. 2: 2074–2083. https://doi.org/10.1039/C1PY00173F.
795 McKenzie, T.G., Fu, Q., Uchiyama, M. et al. (2016). Adv. Sci. 3: 1500394.
https://doi.org/10.1002/advs.201500394.
797 Xu, J., Shanmugam, S., Corrigan, N.A., and Boyer, C. (2015). Catalyst-free vis-
ible light-induced RAFT photopolymerization. In: Controlled Radical Polymer-
ization: Mechanisms, ACS Symposium Series, vol. 1187 (eds. K. Matyjaszewski,
B.S. Sumerlin, N.V. Tsarevsky and J. Chiefari), 247–267. American Chemical
798 Otsu, T. (2000). J. Polym. Sci., Part A: Polym. Chem. 38: 2121–2136. https://doi.
org/10.1002/(SICI)1099-0518(20000615)38:12<2121::AID-POLA10>3.0.CO;2-X.
799 Upadhya, R., Murthy, N.S., Hoop, C.L. et al. (2019). Macromolecules 52:
801 Strover, L.T., Cantalice, A., Lam, J.Y.L. et al. (2019). Macro Lett. 8: 1316–1322.
802 Nicolaÿ, R. and Kwak, Y. (2012). Isr. J. Chem. 52: 288–305. https://doi.org/10
.1002/ijch.201100124.
803 Lorandi, F., Fantin, M., Shanmugam, S. et al. (2019). Macromolecules 52:
804 Liu, X.-h., Li, H.-n., Zhang, F.-j. et al. (2016). Polymer 107: 170–176. https://doi
.org/10.1016/j.polymer.2016.11.019.
805 Jiang, H., Pan, X., Li, N. et al. (2017). React. Funct. Polym. 111: 1–6. https://doi
.org/10.1016/j.reactfunctpolym.2016.12.007.
806 Nejad, E.H., Castignolles, P., Gilbert, R.G., and Guillaneuf, Y. (2008). J. Polym.
807 David, G., Asri, Z.E., Rich, S. et al. (2009). Macromol. Chem. Phys. 210: 631–639.
https://doi.org/10.1021/ma00119a034.
809 Krstina, J., Moad, C.L., Moad, G. et al. (1996). Macromol. Symp. 111: 13–23.
810 Luo, Y.W. and Cui, X.F. (2006). J. Polym. Sci., Part A: Polym. Chem. 44:
811 Monteiro, M.J., Sjöberg, M., van der Vlist, J., and Göttgens, C.M. (2000). J.
Polym. Sci., Part A: Polym. Chem. 38: 4206–4217. https://doi.org/dwkfgw.
812 D’Agosto, F., Lansalot, M., and Rieger, J. (2022). RAFT-mediated polymerz-
iation-induced self-assembly (PISA). In: RAFT Polymerization: Materials, Syn-
Wiley-VCH.
813 Farinha, J.P.S., Relogio, P., Charreyre, M.-T. et al. (2007). Macromolecules 40:
4680–4690. https://doi.org/10.1021/ma070444g.
814 Kitchin, A.D., Velate, S., Chen, M. et al. (2007). Photochem. Photobiol. Sci. 6:
853–856. https://doi.org/10.1039/b702811c.
815 Harvison, M.A., Roth, P.J., Davis, T.P., and Lowe, A.B. (2011). Aust. J. Chem. 64:
992–1006. https://doi.org/10.1071/CH11152.
816 Moad, G., Rizzardo, E., and Thang, S.H. (2011). Polym. Int. 60: 9–25. https://doi
.org/10.1002/pi.2988.
817 Willcock, H. and O’Reilly, R.K. (2010). Polym. Chem. 1: 149–157. https://doi
.org/10.1039/b9py00340a.
11626–11634. https://doi.org/10.1021/acs.joc.6b01844.
819 Wu, Y., Zhou, Y., Zhu, J. et al. (2014). Polym. Chem. 5: 5546–5550.
https://doi.org/10.1039/c4py00732h.
820 Shen, W., Qiu, Q., Wang, Y. et al. (2010). Macromol. Rapid Commun. 31:
References 357
821 Sumerlin, B.S., Lowe, A.B., Stroud, P.A. et al. (2003). Langmuir 19: 5559–5562.
822 Roth, P.J., Kessler, D., Zentel, R., and Theato, P. (2008). Macromolecules 41:
8316–8319. https://doi.org/10.1021/ma801869z.
823 Gibson, M.I., Fröhlich, E., and Klok, H.-A. (2009). J. Polym. Sci., Part A: Polym.
824 Urquhart, M.C., Dao, N.V., Ercole, F. et al. (2020). ACS Macro Lett. 9: 553–557.
https://doi.org/10.1021/acsmacrolett.0c00066.
825 Lowe, A.B., Sumerlin, B.S., Donovan, M.S., and McCormick, C.L. (2002). J. Am.
Chem. Soc. 124: 11562–11563. https://doi.org/10.1021/ja020556h.
826 Carlson, J.S., Hill, M.R., Young, T., and Costanzo, P.J. (2010). Polym. Chem. 1:
827 Leon, N.H. and Asquith, R.S. (1970). Tetrahedron 26: 1719–1725. https://doi
.org/10.1016/s0040-4020(01)93022-4.
828 Perrier, S., Takolpuckdee, P., and Mars, C.A. (2005). Macromolecules 38:
2033–2036. https://doi.org/10.1021/ma047611m.
829 Alagi, P., Hadjichristidis, N., Gnanou, Y., and Feng, X. (2019). ACS Macro Lett.
8: 664–669. https://doi.org/10.1021/acsmacrolett.9b00357.
830 Carmean, R.N., Figg, C.A., Scheutz, G.M. et al. (2017). ACS Macro Lett. 6:
831 Uchiyama, M., Satoh, K., and Kamigaito, M. (2019). Chem. Commun. 55:
5327–5330. https://doi.org/10.1039/C9CC00900K.
832 Gruendling, T., Dietrich, M., and Barner-Kowollik, C. (2009). Aust. J. Chem. 62:
806–812. https://doi.org/10.1071/CH09080.
833 Pfukwa, R., Pound, G., and Klumperman, B. (2008). Polym. Prepr. (Am. Chem.
Soc., Div. Polym. Chem.) 49: 117–118.
834 Jesson, C.P., Pearce, C.M., Simon, H. et al. (2017). Macromolecules 50: 182–191.
835 Zhang, T. and Palasz, P.D. (2017). Thiocarbonylthio-free RAFT polymers and
the process of making the same (Henkel), WO2017027557A1.
836 Vega-Rios, A. and Licea-Claverie, A. (2011). J. Mex. Chem. Soc. 55: 21–32.
https://doi.org/10.29356/jmcs.v55i1.848.
837 Grellepois, F. and Portella, C. (2008). Synthesis 2008: 3443–3446 (3443 pp).
https://doi.org/10.1055/s-0028-1083190.
838 Legge, T.M., Slark, A.T., and Perrier, S. (2006). J. Polym. Sci., Part A: Polym.
839 Bressy, C., Ngo, V.G., and Margaillan, A. (2013). Polym. Degrad. Stab. 98:
840 Bekanova, M.Z., Neumolotov, N.K., Jablanović, A.D. et al. (2019).
Polym. Degrad. Stab. 164: 18–27. https://doi.org/10.1016/j.polymdegradstab
.2019.03.017.
841 Xu, J., He, J., Fan, D. et al. (2006). Macromolecules 39: 3753–3759.
842 Metzner, P. (1999). Top. Curr. Chem. 204: 127–181.
https://doi.org/10.1007/3-540-48956-8_2.
843 Heuzé, B., Gasparova, R., Heras, M., and Masson, S. (2000). Tetrahedron Lett.
41: 7327–7331. https://doi.org/10.1016/S0040-4039(00)01221-1.
844 Sinnwell, S., Inglis, A.J., Davis, T.P. et al. (2008). Chem. Commun.: 2052–2054.
https://doi.org/10.1039/b718180a.
845 Sinnwell, S., Synatschke, C.V., Junkers, T. et al. (2008). Macromolecules 41:
7904–7912. https://doi.org/10.1021/ma8013959.
846 Sinnwell, S., Lammens, M., Stenzel, M.H. et al. (2009). J. Polym. Sci., Part A:
847 Sinnwell, S., Inglis, A.J., Stenzel, M.H., and Barner-Kowollik, C. (2008). Macro-
848 Nebhani, L., Sinnwell, S., Inglis, A.J. et al. (2008). Macromol. Rapid Commun.
849 Nebhani, L., Gerstel, P., Atanasova, P. et al. (2009). J. Polym. Sci., Part A: Polym.
850 Nebhani, L., Sinnwell, S., Lin, C.Y. et al. (2009). J. Polym. Sci., Part A: Polym.
851 Bousquet, A., Boyer, C., Davis, T.P., and Stenzel, M.H. (2010). Polym. Chem. 1:
852 Huisgen, R., Kalvinsch, I., Li, X., and Mloston, G. (2000). Eur. J. Org. Chem.
2000: 1685–1694. https://doi.org/10.1002/(sici)1099-0690(200005)2000:9<1685:
:aid-ejoc1685>3.0.co;2-6.
853 Mlostoń, G., Urbaniak, K., Gulea, M. et al. (2005). Helv. Chim. Acta 88:
2582–2592. https://doi.org/10.1002/hlca.200590198.
854 Katchalsky, A. and Eisenberg, H. (1951). J. Polym. Sci. 6: 145–154. https://doi
.org/10.1002/pol.1951.120060202.
855 López-Pérez, L., Maldonado-Textle, H., Elizalde-Herrera, L.E. et al. (2019). Poly-
mer 168: 116–125. https://doi.org/10.1016/j.polymer.2019.02.025.
856 Gilbert, R.G., Hess, M., Jenkins, A.D. et al. (2009). Pure Appl. Chem. 81:
351–353. https://doi.org/10.1351/PAC-REC-08-05-02.
359
Trithiocarbonates in RAFT Polymerization

Graeme Moad
9.1 Introduction
Since 2008, trithiocarbonates, R—S(C=S)SR′′ (Figure 9.1), have been the most
popular form of transfer agents employed in radical polymerization with reversible
addition–fragmentation chain transfer (RAFT polymerization) (Figure 9.2). This
can be attributed to their broad applicability in controlling the polymerization of,
in particular, MAMs, and their ready commercial availability or ease of synthesis.
Trithiocarbonates can provide a good balance between high activity, and low
retardation and incidence of side reactions. The use of thiocarbonates as RAFT
agents was described in 1998 in the first patents on RAFT polymerization [1, 2]
and the first open-literature publications concerning their application in RAFT
polymerization appeared in 2000 [3, 4].
With appropriate selection of the substituents, trithiocarbonates provide good con-
trol (i.e. low dispersity, predicted M n , high end-group fidelity) over RAFT polymer-
ization of most MAMs [5]. Retardation is generally very low or not observable when
targeting M n > 3000 [6]. Some retardation is observed when preparing lower molar
mass polymers [7]. Good control can also be observed for the IAM, N-vinylcarbazole
(NVC) [8]. However, trithiocarbonates are not well suited for polymerization where
all the monomers are LAMs, such as vinyl esters or vinyl amides, where strong retar-
dation or inhibition is usually observed [5].
9.2 Mechanism of RAFT Polymerization

with Trithiocarbonate Mediators
In general terms, the mechanism or trithiocarbonate-mediated RAFT polymeriza-
tion is analogous to that involving other thiocarbonylthio RAFT agents (dithioesters,
xanthates, or dithiocarbamates). However, we need to distinguish two classes of
trithiocarbonates, known as the non-symmetric and symmetric RAFT agents that
comprise one or two good homolytic leaving groups, respectively.

360 9 Trithiocarbonates in RAFT Polymerization
Weak single bond
R' + S S R kaddR R' S S R

k-addR
Reactive S S
R" R"
double bond R,R' are free radical leaving
groups (R˙ must also be able to
R"S (Z) modifies addition
reinitiate polymerization). For
and fragmentation rates
symmetical trithiocarbonates, R"
also has these properties
Figure 9.1 Structural features of trithiocarbonate RAFT agents and the intermediate
formed on radical addition.
500
Trithiocarbonate
Alkyl trithiocarbonate
400
Aromatic dithioester
Aliphatic dithioester
Xanthate
300
Publications
Dithiocarbamate
200
100
0
2000 2005 2015 2015
Year
Figure 9.2 Publication rate for RAFT polymerization using different classes of RAFT
agents. Includes both patent and open literature publications. Based on a ScifinderTM
substructure search carried out in February 2020 on the RAFT agent structures and the
terms ‘RAFT’ and ‘MADIX’ (in the case of xanthates). The term ‘trithiocarbonate’ includes all
symmetric and non-symmetric trithiocarbonates. The term ‘alkyl trithiocarbonate’ embraces
only non-symmetric trithiocarbonates where SR′′ is a primary alkyl group of structure S-CH3
or S-CH2 CH2 -alkyl.
The mechanism of RAFT polymerization with non-symmetric trithiocarbonate

RAFT agents (R′′ SC(=S)SR, 1 in Scheme 9.1), where R⋅ is a good homolytic leaving
group and R′′ ⋅ is a poor homolytic leaving group with respect to the propagating
species (Pn ⋅), is described by the usual RAFT mechanism [9]. Examples of R′′ , which
are poor homolytic leaving groups with respect to MAM propagating species, are
primary alkyl (e.g. SR′′ = SC12 H25 ) and aryl. In the case of these RAFT agents, the
trithiocarbonate functionality is always retained as the ω-chain-end.
9.2 Mechanism of RAFT Polymerization with Trithiocarbonate Mediators 361
Intiation
∙ M M
initiator I Pn
Initialization or pre-equilibrium
Reversible chain transfer / Propagation
∙ + S kadd kβ ∙
Pn S R Pn S S R Pn S S + R
k–add k–β
S S S
R′′ R′′ R′′
M
kp
1 2 3
Reintiation
M M M
∙ ∙ ∙
R R M Pm
ki
Main equilibrium
Chain equilibration / Propagation
∙
Pm + S S Pn
kaddP Pm S S Pn
k–addP P S S +
∙
Pn
m
k–addP kaddP
S S S
R′′ R′′ R′′
M M
kp kp
3 4 3
Termination
∙ ∙
kt
Pn + Pm dead polymer
Scheme 9.1 Mechanism of RAFT polymerization with non-symmetric trithiocarbonates

and R′′ is a poor homolytic leaving group.
In the case of symmetric trithiocarbonates (RSC(=S)SR, 5 in Scheme 9.2), where

both R substituents are good homolytic leaving groups, further reactions must be
added as shown in Scheme 9.2. The product will usually retain the trithiocarbonate
functionality located centrally within the polymer chain.
If the homolytic leaving group ability for the R substituent of the initial RAFT
agent 5 is significantly lower than that of the propagating species Pn ⋅, the trithio-
carbonate functionality will not be centrally located at least for low monomer con-
versions [10–12]. In extreme cases, the mechanism, may be better represented by
Scheme 9.1.
All radical species formed during RAFT polymerization, including I⋅, R⋅, and the
various intermediates (e.g., 2, 4, 6, 8 or 10), may undergo termination by combi-
nation or disproportionation. However, rates of fragmentation for the intermediates
formed by radical addition to the trithiocarbonates are usually sufficiently rapid that
there is a low probability of intermediate radical termination in RAFT polymeriza-
tion of MAMs.
The initiating species I⋅ can also react by RAFT with any RAFT agent or macro-
RAFT agent. This reaction assumes greater importance in polymerizations to give
lower molar mass polymers and at high monomer conversions when the ratio of
monomer to RAFT agent is low. The process is of particular importance or concern
in single-unit monomer insertion (SUMI) experiments (Section 9.15) [13, 14].
Initiator-derived by-products can be largely avoided when the initiating radicals are
generated directly from the RAFT agent, e.g. in PhotoRAFT, photoinduced electron
Intiation
∙ M ∙ M M ∙
initiator I I M Pn
ki kp kp
Initialization or pre-equilibrium
Reversible chain transfer / Propagation ∙ ∙
+ R + R
kadd1 Pn S S R kβ S S kadd2 Pn S S R kβ2
S S R Pn Pn S S
k–add1 k–β k–add2 k–β2
S S S S S
R R R Pm Pm
+ P∙n + P∙m
M M
kp kp
5 6 7 8 9
Reintiation
∙ M ∙ M M
R R M ∙
kiR kp kp Pm
Main equilibrium
∙ k ∙
Po S S Pn addP2 Po S S Pn k–addP2 Po S S + Pn
k–addP2 kaddP2
S S S
M Pm Pm Pm M
kp kp
9 10 9
Termination
kt
∙ ∙
Pn + Pm dead polymer
Scheme 9.2 Mechanism of RAFT polymerization with symmetric trithiocarbonates.
or energy transfer-RAFT (PET-RAFT, Section 9.17 and the Chapter 12 of Chapman

et al. [15]), eRAFT or redox RAFT (Section 9.18 and the Chapter 13 of Lorandi
et al. [16]).
9.2.1 Transfer Coefficients for Trithiocarbonates in RAFT

Polymerization
The efficiency of an initial RAFT agent, such as the non-symmetric trithio-
carbonate 1, is determined by the values of two transfer coefficients, Ctr
(= ktr /kp ) and C−tr (= k−tr /ki ). The rate coefficient for chain transfer (ktr ) for a
RAFT agent is then given by Eq (9.1), where the value of ktr depends on the rate
of addition of the propagating radical (Pn ⋅) to the RAFT agent and a partition
coefficient (𝜙) that describes the partitioning of the intermediate radical (9.2)
between the starting materials and products – refer to Scheme 9.1:
[ ]
k𝛽
k-add + k𝛽
The transfer agent-derived radical (R⋅) is also partitioned between adding to the
monomer and reacting with the macroRAFT agent (9.3). The rate coefficient asso-
ciated with this reaction (k−tr ) is defined as shown in Eq. (9.2).
[ ]
k−add
k−tr = k−𝛽 (1 − 𝜙) = k−𝛽 (9.2)
k−add + k𝛽
9.2 Mechanism of RAFT Polymerization with Trithiocarbonate Mediators 363
S S S
O S S S
S S S
HO2C CO2H
O X
11 12 13
Figure 9.3 Structures of some trithiocarbonates referred to in Table 9.1 (others appear in
subsequent tables).
The high reactivity of trithiocarbonates towards radical addition means that C−tr
is unlikely to be zero.
For the case of symmetric RAFT agents we should consider a second set of trans-
fer coefficients Ctr2 (= ktr2 /kp ) and C−tr2 (= k−tr2 /ki ) relating to loss of the second R
leaving group where the rate coefficients ktr2 and k−tr2 might be defined as shown in
Eqs. (9.3) and (9.4) (assuming no dependence on Pn ).
[ ]
k𝛽2
ktr2 = kadd2 𝜙2 = kadd2 (9.3)
k−add2 + k𝛽2
[ ]
( ) k−add2
k−tr2 = k−𝛽2 1 − 𝜙2 = k−𝛽2 (9.4)
k−add2 + k𝛽2
Little is known about values of Ctr2 and C−tr2 and they are generally assumed
to be the same as Ctr and C−tr, respectively, where R and R′′ are the same. For
RAFT homopolymerization, there should, in most circumstances, be no distinction
between the propagating species attached to an intermediate.
Note that for macroRAFT agents in homopolymerization, or if the properties of R⋅
are the same as those of Pn ⋅, kβ = k−add and ktr = k−tr = kadd /2.
A listing of apparent transfer coefficients (Ctr app ) for trithiocarbonates is provided
in Table 9.1 (see also Figure 9.3). The methods for determining apparent transfer
coefficients (Ctr app ) of trithiocarbonates include the Mayo method (M in Table 9.1),
the walling method (W) [20, 30–34], the dispersity method (D) [35, 36], and the
M n (0) method [37] (B). Details of these methods are provided elsewhere in this vol-
ume [29]. It is implicit in the derivation of each of these methods that the value of C−tr
for the initial RAFT agent is zero. For the more active trithiocarbonates this assump-
tion cannot be justified and the actual values of Ctr may be higher than Ctr app by as
much as several orders of magnitude. Nonetheless, data obtained under a consistent
set of polymerization conditions may still be relied on for a qualitative ranking of
RAFT agent activity.
A method of evaluating transfer coefficients Ctr and C−tr , which is applicable when
the transfer coefficients are high, involves an evaluation of the usage of transfer agent
as a function of monomer conversion for several different initial RAFT agent con-
centrations (Method K in Table 9.1) [34, 38]. Values of transfer coefficients estimated
by kinetic simulation are numbers chosen to fit the experimental data. For a range of
values of C−tr that may span orders of magnitude, it is often possible to choose a value
of C−tr such that a fit is obtained [13]. This may account for very different values that
Table 9.1 Transfer coefficients for initial trithiocarbonates in RAFT polymerization.
RAFT agent Z (R′ S) R Monomera) T (∘ C) C tr app b) C tr C -tr Methodc) References
14 (CH3 )2 (CO2 H)CS (CH3 )2 (CO2 H)C⋅ St 70 25.2 — — M [17]

11 PhC(=O)CH2 S PhC(=O)CH2 ⋅ St 70 19 — — M [17]
13 CH2 (CO2 H)CH2 S CH2 (CO2 H)CH2 ⋅ St 70 4.3 — — M [17]
63 CH2 (CO2 H)CH2 S CH3 ĊH(CO2 H) St 70 13.9 — — M [17]
48 CH2 (CO2 H)CH2 S (CH3 )2 (CO2 H)C⋅ St 70 20.2 — — M [17]
75 C12 H25 S PhCH2 ⋅ St 110 9.4 — — W [18]
40 C12 H25 S (CH3 )2 Ċ(CN) St 70 — 1875 1.6 K [13]
40 C12 H25 S (CH3 )2 Ċ(CN) St 80 128 0.23 K [19]
40 C12 H25 S (CH3 )2 Ċ(CN) NIPAm 70 — 1850 10 K [13]
22 PhCH2 S PhCH2 ⋅ St 110 18 — — W [20]
12 4-(MeO)PhS PhCH2 ⋅ St 110 11.6 — — W [18]
12 PhS PhCH2 ⋅ St 110 12.4 — — W [18]
12 4-FPhS PhCH2 ⋅ St 110 18.5 — — W [18]
12 3,4-F2 PhS PhCH2 ⋅ St 110 19.5 — — W [18]
12 4-ClPhS PhCH2 ⋅ St 110 18.4 — — W [18]
12 3,4-Cl2 PhS PhCH2 ⋅ St 110 17.4 — — W [18]
12 2,3,4,5,6-Cl5 PhS PhCH2 ⋅ St 110 18.7 — — W [18]
12 4-pyS PhCH2 ⋅ St 110 22.2 — — W [18]
12 3,5-(CF3 )2 PhS PhCH2 ⋅ St 110 23.0 — — W [18]
24 PhCH(CN)C(S)S(CH2 )4 S PhĊH(CN) St 70 — 72 0 K [21]
24 PhCH(CN)C(S)S(CH2 )4 S PhĊH(CN) MMA 70 — 43 377 K [21]
24 PhCH(CN)C(S)S(CH2 )4 S PhĊH(CN) GMA 70 — 23 255 K [21]
22 PhCH2 S PhCH2 ⋅ OFPA 80 14 — — W [22]
— PHCH2 CH2 S (CH3 )Ċ(CN)(C2 H4 CO2 H) MMA 75 21.1 — — D [23]
44 C12 H25 S (CH3 )Ċ(CN)(C2 H4 CO2 H) MMA 75 16.7 — — D [23]
40 C12 H25 S (CH3 )2 Ċ(CN) TFPMA 70 1.6 — — W [24]
44 C12 H25 S (CH3 )Ċ(CN)(C2 H4 CO2 H) TFPMA 70 3.2 — — W [24]
— PhCH2 CH2 S (CH3 )Ċ(CONH2 )(C2 H4 CO2 H) MMA 75 4.3 — — D [23]
— C12 H25 S (CH3 )Ċ(CONH2 )(C2 H4 CO2 H) MMA 75 2.5 — — D [23]
— CH(CH3 )(CO2 Et)S (CH3 )ĊH(CO2 Et) MA 60 112 — — B [25, 26]
— CH(CH3 )(CO2 Et)S (CH3 )ĊH(CO2 Et) BA 60 98 — — B [26, 27]
— CH(CH3 )(CO2 Et)S (CH3 )ĊH(CO2 Et) DA 60 98 — — B [26, 28]
a) For a full list of monomer abbreviations see Abbreviations.

b) Published values of transfer coefficients that are based on a model that does not allow for partitioning of the intermediate radicals and/or the reversibility of chain
transfer are considered as apparent transfer coefficients [29]. Caution should be used when comparing values obtained in different studies under different
conditions.
c) Method used: M, Mayo method; W, Walling method; K, Kinetic simulation; D, Dispersity method; B, M n (0) method.
Table 9.2 Values of the RAFT equilibrium coefficient for trithiocarbonates.
RAFT agenta) Z (R′ S) R Monomer/radical T (∘ C) k add (M−1 /s) k -add (s−1 ) K eq (M−1 ) Methodb) References
4
19 O P(MA) MA −30 — — 1.4 × 10 Theory [41]
S
O
19 O P(BA) BA −40 4 × 106 45 8 × 104 EPR [42]

S
O
73 S P(BA) BA −40 — — 1.0 × 104 EPR [43]

67 S P(BA) BA −40 3.4 × 106 1.4 × 102 2.6 × 104 EPR [42]
40 C12H25S St 70 1 × 107 2 × 104 500 Kinetics [13]
CN
40 C12H25S NIPAm 70 1 × 107 1 × 103 1 × 104 Kinetics [13]
CN
40 C12H25S 70 1 × 104 4 × 103 2.5 Kinetics [13]
Ph CN
40 C12H25S 70 1 × 104 5 × 103 2 Kinetics [13]
CN
iC3H7NH O
40 C12H25S 70 1 × 104 2 × 104 0.5 Kinetics [13]

CN CN
40 C12H25S 70 1 ×104 2 ×104 0.5 Kinetics [13]
CN CN
23 S 25 2.2 × 105 2 × 10−2 1.1 × 107 EPR [44]
23 S 20 — — 5.3 × 104 Theory [44]
22 Ph S Ph 20 — — 1.1 Theory [44]
23 Ph S Ph 20 — — 4.34 × 103 Theory [44]
a) Initial RAFT agent used.

b) EPR, determination of radical concentrations; Theory, ab initio calculations; Kinetics, kinetic simulation.
9.3 Choice of Homolytic Leaving Group R for Trithiocarbonate RAFT Agents 367
appear in the literature for the given systems (e.g. styrene with 40) [13, 19] and serves
to emphasize that all values of Ctr and C−tr should be treated circumspectly.
9.2.2 RAFT Equilibrium Coefficients for Trithiocarbonates

The properties of RAFT agents are often discussed in terms of the value of the equi-
librium coefficients (K = kadd /k−add ) associated with radical addition to a thiocar-
bonylthio compound [39, 40].
For all RAFT agents, including trithiocarbonates, addition rates decrease and
fragmentation rates increase in the series where R is bulkier, where R becomes
more electron withdrawing, and where R becomes more stable. It is found that
addition rates decrease and fragmentation rates increase in the series where
R is primary > secondary > tertiary, and where the alpha substituent on R is
CN ∼ Ph > CO2 alkyl > CONalkyl2 > alkyl. Penultimate unit effects are significant
such that a propagating species generally adds slower and fragments faster than a
unimeric model.
Rates of addition reported for trithiocarbonates are high, in the range
104 –107 M−1 /s (Table 9.2). However, the amount of experimental data is lim-
ited. A higher equilibrium coefficient implies a low fragmentation rate for the
radical adduct and an increased likelihood for retardation and/or side reaction
involving this species. It is generally believed that for trithiocarbonate-mediated
polymerization of MAMs, fragmentation rates for R are sufficiently fast that side
reactions involving the intermediate radicals are unlikely.
Methods for determining equilibrium coefficients for RAFT processes are
described elsewhere in this volume [40, 45]. Rate coefficients for addition kadd and
fragmentation kβ or k−add (not distinguished) have been measured via the single
pulse-pulsed laser photolysis-electron paramagnetic resonance (SP-PLP-EPR)
method for butyl acrylate (BA) polymerizations mediated by the non-symmetric
trithiocarbonate, ethyl 2-(((ethylthio)carbonothioyl)thio)propanoate (67), and the
symmetric trithiocarbonate, dimethyl 2,2′ -(thiocarbonylbis(sulfanediyl))diprop-
ionate (19) [42].
Fitting the time evolution of products vs. time in SUMI experiments by numerical
integration of the differential equations can allow estimation of values of the rate
coefficients for addition and fragmentation [13]. However, the uncertainties inher-
ent in this method are high. K values have also been estimated through the use of
molecular orbital calculations [44].
9.3 Choice of Homolytic Leaving Group R

for Trithiocarbonate RAFT Agents
The trithiocarbonate homolytic leaving groups R (and R′ ) need to be chosen for
compatibility with the monomer(s) to be polymerized. The criteria for selection are
mentioned in Chapter 3 in this volume [29] and guidelines to R group selection are
provided in Figure 9.4b [5, 46]. These guidelines do not differ from those that apply
in the cases of dithioesters [36], xanthates [47], or dithiocarbamates [36, 48, 878]
with the main requirements ensuring control being as follows:
(a) S S S S
S S S S S S S S
CH2
Alkyl
EWG EDG
(b) CO2CH3
CN
Figure 9.4 (a) Effect of R′ SC(=S)— group on non-symmetric trithiocarbonates

[R′ SC(=S)SR] and (b) R group on activity of symmetric or non-symmetric trithiocarbonates
(R′ SC(=S)SR or RSC(=S)SR) in RAFT polymerization. Activity increases from right to left.
Source: Figure 4b from [48]. © John Wiley and Sons. MAM, more activated monomer; LAM,
less activated monomer; IAM, intermediate-activated monomer; AN, acrylonitrile; BA, butyl
acrylate; DMAm, N,N-dimethylacrylamide; HPMAm, N-(2-hydroxypropyl)methacrylamide;
MA, methyl acrylate; MMA, methyl methacrylate; NIPAm, N-isopropylacrylamide; NVC,
N-vinylcarbazole; NVP, N-vinylpyrrolidone; St, styrene; VAc, vinyl acetate, EDG,
electron-donating group; EWG, electron-withdrawing group.
● The radical R⋅ should be a good homolytic leaving group relative to the propagating
radicals generated (ideally k𝛽 ≥ k−add ).
● The rate coefficient for reinitiation by R⋅ (kiR ) should be greater than or equal to the
propagation rate coefficient (kp ). Otherwise, there may be some retardation and
there is a likelihood of by-products from self-reaction of R⋅ . Values for R⋅ adding
to common monomers are known [29, 49–51].
Additional criteria may be the ease of synthesis or commercial availability, com-

patibility (e.g. stability, solubility) with the reaction conditions, and the presence or
ease of transformation/removal of functionality.
9.3.1 Homolytic Leaving Group ‘R’ for 1,1-Disubsituted MAMs

Tertiary cyanoalkyl R (e.g. in trithiocarbonates 37–45) are among the best homolytic
leaving groups and are currently the preferred R groups for 1,1-disubsituted MAMs,
such as methacrylates or methacrylamides, when low dispersities are required. Note,
however, that the nitrile group of trithiocarbonates with a 4-cyanopentanoic acid R
group may hydrolyse during storage under moist conditions to form a less active
trithiocarbonate (see Section 9.20) [52].
Alternative R for 1,1-disubsituted MAMs are 1-aryl-1-cyanomethyl (R = –CHPh
(CN), e.g. 24, 53) [53] or 1-aryl-1-carboxymethyl (R = –CHPh(CO2 X) with X = H
or alkyl, e.g. 54–59) [3]. These R substituents are good homolytic leaving groups.
Rate coefficients for addition of these R⋅ to the monomer may be sufficiently low
to cause an inhibition period, particularly when low molar masses are targeted. An
9.3 Choice of Homolytic Leaving Group R for Trithiocarbonate RAFT Agents 369
advantage of these trithiocarbonates with a secondary R is that they are more readily
synthesized by method A (refer Section 9.8).
2-Carboxyprop-2-yl radicals are relatively poor homolytic leaving groups with
respect to propagating radicals derived from 1,1-disubsituted MAMs, such as
methyl methacrylate (MMA). Use of trithiocarbonates comprising such R (i.e.
R = –C(CH3 )2 (CO2 X) with X = H or alkyl as in 14–17 or 47–51) [54] provides
molar mass control and allows block synthesis, but relatively high dispersities
(typically > 1.3) are obtained with 1,1-disubsituted MAMs. Moreover, transfer
coefficients are such that, in a batch polymerization, the initial RAFT agent may
not be fully consumed until high monomer conversions.
9.3.2 Homolytic Leaving Group ‘R’ for Monosubstituted MAMs

Trithiocarbonates with R = tertiary cyanoalkyl (54-59) can be successfully used in
polymerizations of monosubstituted MAMs. However, rates of addition to monomer
may be rate determining during the initialization stage of polymerization with acry-
lates and acrylamides [55], which manifests as an inhibition period, or period of slow
polymerization.
Trithiocarbonates with R = 2-carboxyprop-2-yl (R = –C(CH3 )2 (CO2 X) with X = H
or alkyl, e.g. 14–17, 47–51) [54] or 1-carboxyethyl (R = –CH(CH3 )(CO2 X) with X = H
or alkyl, e.g. 19, 20, 62–70) are well suited for use with monosubstituted MAMs.
One of the most versatile R substituents, suited to most 1-substituted MAMs and
LAMs, is the cyanomethyl group (e.g. 41) [8, 56]. Cyanomethyl trithiocarbonates are
not suitable for 1,1-disubsituted MAMs. The phthalimidomethyl trithiocarbonates
(e.g. 21, 25, 70) are suitable for 1-substituted MAMs and LAMs, but these RAFT
agents have low solubility in many solvents [10, 57].
Trithiocarbonates with R = 1-phenylethyl (e.g. 20, 60, 61), benzyl (e.g. 22, 71-75),
or tertiary alkyl (e.g. 23) are suitable for mediating RAFT polymerizations of most
monosubstituted MAMs.
9.3.3 Homolytic Leaving Group ‘R’ for IAMs and LAMs

Trithiocarbonates are not generally suitable for IAMs or LAMs. When used, marked
retardation or inhibition is typical. However, the cyanomethyl trithiocarbonate is
suitable (even preferred) for NVC polymerization. It has been possible to conduct
efficient PET-RAFT-SUMI of VAc or limonene into macro-trithiocarbonates with a
terminal maleimide unit [58].
9.3.4 Macro-leaving Group ‘R’ for Block Copolymer Synthesis

The same factors used in selecting the trithiocarbonate ‘R’ suggest guidelines
for the preferred order for incorporating monomers in the synthesis of a block
copolymer by sequential monomer addition. Thus, 1,1-disubstituted monomers
must generally be incorporated before monosubstituted monomers; MAMs before
IAMs before LAMs; monomers with electron-deficient double bonds before those
with electron-rich double bonds.
In specific circumstances, the influence of these guidelines can be relaxed by using
copolymerization, by implementing starved-feed monomer addition protocol [29],
or through the use of PET-RAFT or direct photoinitiation [59].
9.4 Choice of Activating Group ‘Z’ for Trithiocarbonate

RAFT Agents
The effectiveness of a RAFT agent depends on the monomer being polymerized

and is determined by the properties of the radical leaving group R and the group
Z, which can be chosen to activate or deactivate the thiocarbonyl double bond of
the RAFT agent (1) and modify the stability of the various intermediate radicals 2, 4
(Scheme 9.1) 6, 8, and 10 (Scheme 9.2).
Two main classes of trithiocarbonate RAFT agents are distinguished. The
symmetrically substituted dialkyl trithiocarbonates (Tables 9.3, 9.4). and 9.7) have
2 equiv homolytic leaving groups. The non-symmetrically substituted trithiocar-
bonates (Tables 9.6 and 9.8) have one good homolytic leaving group (R) and a
substituent (R′′ ), which is not a leaving group under polymerization conditions
and is almost always primary alkyl. Aryl trithiocarbonates (R′′ is aryl) are also
effective in this context and show higher transfer coefficients than similar RAFT
agents where R′′ is primary alkyl (Figure 9.4) [18]. However, they are not readily
available.
9.5 Symmetric Trithiocarbonates
One of the attractions of symmetric trithiocarbonates is that they enable [2] the
one-step synthesis of ABA triblock (or, more correctly, AB—SC(=S)S—BA triblock)
copolymers as illustrated in Scheme 9.3 [3]. The same applies to Z-connected,
bis-trithiocarbonates (Section 9.5.1). A potential disadvantage is that the trithio-
carbonate group generally ends up near the centre of the chain (see Section 9.2)
meaning that the chain is likely to be cleaved into two on trithiocarbonate group
removal/transformation (Section 9.21).
9.5.1 Bis-trithiocarbonates
A wide variety of bis-trithiocarbonates have been described. Some examples are
listed in Table 9.4 (connected by the Z substituent) and Table 9.5 (connected by the
R substituent).
Z-connected bis-trithiocarbonates with two good homolytic leaving groups (R)
are functionally equivalent to symmetric trithiocarbonates in that the trithiocarbon-
ate groups are retained in the centre of the macromolecule (Scheme 9.3). For these
Table 9.3 RAFT polymerizations with symmetrically substituted trithiocarbonate RAFT

agents.
RAFT agent Synthesisa) Polymerizationsb), c)
S F [60, 61] Methacrylates: BAMA [62]

S N MMA [63] (MMA) [54] MMA
S CO2H [64] ODMA [65] (TFPMA)
HO2C [24] 176 [66]
2,2′-(thiocarbonylbis(sulfanediyl))bis(2-methylpropanoic acid)
Acrylates: AA [54, 67–70] AA
[71, 72] BA [54, 73–76] EA
14
[54] HEA [54, 77] MA
[76, 78, 79] MEA [80, 81]
MMA [82]
Acrylamides: Am [83, 84]
DMAm [77, 83, 85] (DMAm)
[85] NIPAm
[60, 67, 69, 86–90] NIPAm
[91] 228 [92] 230 [79] MBAm
[93, 94] PBAm [93] BBAm
[93]
Styrenes: St [17, 54, 95–97]
4VP [98] 2VP [99] 2VP [100]
Other MAM: AN [101, 102]
356 [103]
Vinyls: NVP [104]
Copolymers:
MAA/CHAm/NIPAm [105]
MAA/BzAm/NIPAm [105]
MAA/NIPAm/239 [105]
MAA/OAm/NIPAm [105]
MAA/NIPAm/234 [105]
TEGDMA/365 [61]
HPMAm/351 [106]
NIPAm/327 [107]
TMAPMA/PEGMA/NIPAm
[108] (PEGMA/199) [109]
(PEGMA/225) [109]
AEMA/180/185 [110]
(DMAm/MEA) [80, 81]
AA/AN [111] AA/St [112]
AN/Am [102]
AEMA/185/248 [110] HPMA
copolymer [113]
NIPAm/tBAm [114]
NIPAm/234 [105] NIPAm/239
[105]
(continued)
Blocks:
MMA-b-(PEGMA/NIPAm)
[63] ODMA-b-NIPAm [65]
176-b-GMA [66]
(NVP-b-MMA) [115, 116]
AA-b-EA [54] AA/St-b-NVP
[112] EHA-b-EA [54]
DMAm-b-228 [92]
DMAm-b-228-b-NIPAm [92]
NIPAm-b-DMAm [87]
NIPAm-b-Am [90]
2VP-b-EA [99] St-b-AA [54]
St-b-tBA/TMSPMA [96]
(MEA-b-DMAm) [80, 81]
NIPAm/TBAm-b-DMAm/
AA [114]
NIPAm/TBAm-b-DMAm/
NAS [114] NIPAm-b-ODA
[89] St-b-NIPAm [97]
St-b-4VP [98] 230-b-MA [79]
S A [11] Methacrylates: MMA [11]

S O Acrylates: BA [117] tBA
S [117] 206 [118]
O O
Styrenes: St [117] 4VP
O
[117, 119]
dimethyl 2,2′-(thiocarbonylbis(sulfanediyl))bis(2-methylpropanoate)
15 Other: AN [101, 120]
Blocks: 206-b-214 [118, 121]
4VP-b-214 [119, 122]
S F/J [123] Acrylates: BA [123]

S O Styrenes: St [123]
S
O O
O
dimethyl 2,2′-(thiocarbonylbis(sulfanediyl))bis(2-methylpropanoate)
16
S F [124] Methacrylates: (MMA) [125]
S O Acrylates: BA [91, 125] tBA
Ph S Ph [91, 124–126] MEA
O O [91, 124, 126] HEA [91] MA
O [91, 125]
dibenzyl 2,2′-(thiocarbonylbis(sulfanediyl))bis(2-methylpropanoate)
Aacrylamides: Am [125]
17
DMAm [91, 124, 126]
(DMAm) [125] NIPAm
[91, 124, 126] (NIPAm)
[125]
(continued)
Blocks: AA-b-BA [72]

AA-b-EA [72] AA-b-TFEA
[72] AA-b-HFBA [72]
DMAm-b-BA [91]
DMAm-b-MEA [91]
DMAm-b-NIPAm [91]
S A [127–129] Acrylates: HEA [91] MA [91]

HO S Acrylamides: DMAm [91]
S NAM [129] NIPAm [130]
O OH NIPAm [91]
O
Vinyls: (VAc) [91]
2,2′-(thiocarbonylbis(sulfanediyl))dipropionic acid
18 Copolymers: AA/BA [128]
St/MAH [127]
Blocks: AA/BA-b-MMA/BA
[128] DMAm-b-BA [91]
NAM-b-250 [129]
S A [101] Acrylates: BA [42, 117] MA

O S [41] tBA [117] 206 [118]
S Styrenes: St [117] 4VP [117]
O O
Other: AN [101, 102]
O
dimethyl 2,2′-(thiocarbonylbis(sulfanediyl))dipropionate
Copolymers: AN/Am [102]
19 Blocks: 206-b-214 [118]
S H [91] Acrylates: HEA [91] MA [91]

O S Acrylamides: NIPAm [91]
Ph S Ph
O O
O
dibenzyl 2,2′-(thiocarbonylbis(sulfanediyl))dipropionate
S A [131–133] Acrylates: AA [134] tBA [135]
S Styrenes: St [3, 132, 136]
S
Blocks: St-b-BA [3] St-b-BEA
[136] St-b-EA [132]
bis(1-phenylethyl) carbonotrithioate
20
O S A [10] Styrenes: St [10, 137]
S
N S O
N
O O
bis((1,3-dioxoisoindolin-2-yl)methyl) carbonotrithioate
21
(continued)
S A [101, 131, Acrylates: AA [141–143] AdA

S 133, 138] [144] BA [117, 145–147] DMAEA
S B [139] [148] MA [139, 145] iBoA [145]
ODA [149] 2EHA [149] PEGA
M [140]
[150] tBA [117, 145, 151] OFPA
N [22] 206 [118]
dibenzyl carbonotrithioate
Acrylamides: Am [83, 152]
22
Styrenes: CMS [153] St [3, 117,
143, 145, 147, 149, 154–156] St [4]
tBS [149] 4VP [117]
Other MAM: AN [101, 102, 157]
Vinyls: NVP [158] (VAc) [146]
Copolymers: MAA/MA [159]
AA/St [142, 143] tBA/St [142]
Bd/AN [160] DVE/MAH
[161, 162] St/AA [163]
St/MAH/NVP [164, 165] AN/Am
[102] (St/AA) [166] 186/PEGA
[167] 186/AMPS [167] 186/329
[167]
Blocks: PEGA-b-CIPEA [150]
ODA-b-NIPAm [149]
2EHA-b-NIPAm [149]
(BA-b-VAc) [146] St-b-NIPAm
[149] tBS-b-NIPAm [149]
OFPA-b-AA [22] OFPA-b-tBA
[22] AdA-b-THFA [144]
St-b-NIPAm [156] St/AA-b-St
[163] DVE/MAH-b-St [161, 162]
206-b-214 [118] (St/AA-b-BA)
[166]
S A Acrylates: BA [117] tBA [117] 211

S M [140] [168] 211-b-214 [168]
S Styrenes: St [117] (4VP) [117]
di-tert-butyl carbonotrithioate Vinyls: VAc [146] (NVP) [158]
23 Blocks: (VAc-b-BA) [146]
a) The letter A-N refers to the method of RAFT agent synthesis. Refer to Section 9.8.
b) Purple – crosslinking polymerization. Red – photoinitiated polymerization.
Italics – heterogeneous polymerization. A-b-B blocks in most cases will be triblocks of
structure AB—SC(=S)S—BA.
c) For a full list of monomer abbreviations, see Abbreviations section.
Table 9.4 RAFT polymerizations with symmetrically substituted, Z-connected,

bis-trithiocarbonate RAFT agents.
S CN
A [21] Methacrylates:
MMA [21]
S S
S S GMA [21]
CN S Styrenes: St [21]
butane-1,4-diyl bis(cyano(phenyl)methyl) bis(carbonotrithioate) Blocks:
24 MMA-b-GMA
[21]
GMA-b-MMA
[21]
O A [10] Styrenes: St
S O [10, 137]
N S S
S S N
O S
O
butane-1,4-diyl bis((1,3-dioxoisoindolin-2-yl)methyl) bis(carbonotrithioate)

25
A [169] Acrylates: tBA
[169]
S S S S
Styrenes: St [169]
S S
dibenzyl pentane-1,5-diyl bis(carbonotrithioate)
26
b) The A-b-B blocks will in most cases be ABA triblocks (Scheme 9.3).
S S S S
Monomer A
R R R R
S S R′′ S S RAFT S S R′′ S S
n n
S S
Monomer B
R R
S S R′′ S S
RAFT
n
Trithiocarbonate group
removal/transformation 2R
X
Scheme 9.3 Process of RAFT polymerization with symmetric trithiocarbonates (n = 0) or

R′′ -connected bis-trithiocarbonates (n = 1) showing how the trithiocarbonate groups are
retained in the centre of the product macromolecule (R is a homolytic leaving group, R′′ is a
poor homolytic leaving group). The process provides a route to ABA triblocks. The group X
formed on trithiocarbonate group removal/transformation depends on the process used.
Source: Adapted with permission from Moad et al. [46]. Copyright 2013, Royal Society of
Chemistry.
Table 9.5 RAFT polymerizations with symmetrically substituted, R-connected,

bis-trithiocarbonate RAFT agents.
S A [169] Acrylamides: NIPAm [149]
S SC3H7
C3H7S S
S
1,4-phenylenebis(methylene) dipropyl bis(carbonotrithioate)
27
S A [170] Acrylates: BA [171] 216 [171]

S SC4H9
Acrylamides: DMAm [170]
C4H9S S Blocks: DMAm-b-NIPAm
[170]
S
1,4-phenylenebis(methylene) dibutyl bis(carbonotrithioate)
28
S A Acrylates: tBA [169]

S SC12H25
C12H25S S
S
1,4-phenylenebis(methylene) didodecyl bis(carbonotrithioate)
27
S A [173]
S SC18H37
C18H37S S
S
1,4-phenylenebis(methylene) dioctadecyl bis(carbonotrithioate)
30
S A [174] Acrylates: tBA [174] CIPEA

C4H9S CO2CH3 [150]
S Blocks: tBA-b-AA/tBA [174]
CO2CH3 CIPEA-b-PEGA [150]
S
S
SC4H9
dimethyl 2,6-bis(((butylthio)carbonothioyl)thio)heptanedioate
31
S A [174] Acrylates: BA
C2H5S CO2CH3 [175]
S Blocks: BA-b-361
CO2CH3 [175]
S
S
SC2H5
dimethyl 2,6-bis(((ethylthio)carbonothioyl)thio)heptanedioate
32
O S 177 Styrenes: St
C12H25S S O [176]
O S SC12H25
Blocks:
S O
St-b-MA/ODA
hexane-1,6-diyl bis(2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoate)
[176]
33
CN H [177] Methacrylates:
O S DMAEMA [177]
SC12H25 Blocks:
O S DMAEMA-b-
PEGMA [177]
S O
C12H25S
S O
CN
butane-1,4-diyl bis(4-cyano-4-(((dodecylthio)carbonothioyl)thio)pentanoate)
34
CN H [178] Methacrylates:
O S DMAEMA [178]
SC12H25 Blocks:
O S DMAEMA-b-292
S [178]
S DMAEMA-b-292-
S O b-HPMAm [178]
C12H25S
S O
CN
disulfanediylbis(ethane-2, 1-diyl) bis(4-cyano-4-(((dodecylthio)carbonothioyl)thio)pentanoate)
35
b) The A-b-B blocks shown will in most cases be BAB triblocks (Scheme 9.4).
c) For a full list of abbreviations, see Abbreviations section.
S S S S
Monomer A
R R
R′′S S S SR′′ R′′S S S SR′′
RAFT
Monomer B S S
R
RAFT R′′S S S SR′′
Trithiocarbonate group
removal/transformation R
X X
Scheme 9.4 Process of RAFT polymerization with R-connected bis-RAFT agents (R is a

homolytic leaving group, R′′ is a not a homolytic leaving group) to form telechelic BAB
triblocks. The groups X formed on trithiocarbonate-group removal/transformation depend
on the process used. Source: Adapted from [46]. Copyright 2013, Royal Society of Chemistry.
structures, the molar mass will be approximately halved on trithiocarbonate group

removal/transformation.
With R-connected bis-trithiocarbonates, the trithiocarbonate groups are retained
as end-groups (Scheme 9.4). As with non-symmetric trithiocarbonates, there will be
little change of molar mass on trithiocarbonate group removal/transformation since
the polymer chain is maintained intact.
9.6 Non-symmetric Trithiocarbonates

There is little data on the dependence of kadd values or transfer coefficients for
non-symmetric trithiocarbonate RAFT agents 1 on the particular R′′ S (or Z)
substituent. When R′′ is primary alkyl, it is generally assumed that the activity is
independent of chain length and the presence of remote functionality on R′′ . The
frequently encountered R′′ substituents are CH3 , C2 H5 , CH2 CH2 CO2 H, CH2 CH2 Ph,
C3 H7 , C4 H9, and C12 H25 (Figure 9.5). The most common R′′ substituent is C12 H25 .
This can be attributed to the relatively low volatility of dodecylmercaptan and the
consequent relatively low odour of the RAFT agent and the derived polymers. The
trithiocarbonates where R′′ is C2 H5 or CH2 CH2 CO2 H are commonly used where
aqueous solubility is required.
For styrene polymerization with aryl benzyl trithiocarbonates 12, there is a clear
trend for RAFT agent activity to increase with the electron-withdrawing qualities of
the aryl substituents (Table 9.1) [18]. This observation is in line with other observa-
tions of enhanced activity for RAFT agents with electron-withdrawing Z.
While the R′′ S substituent may have little effect on RAFT agent activity, it does
influence the properties of the polymer formed. For example, despite making up
only a very small fraction of the polymer (M n > 20 K), the terminal groups (C2 H5
vs. C12 H25 ) have been shown to have a significant influence on both the confor-
mation and assembly of PNIPAm and its analogues below the critical temperature
(Table 9.6) [553].
(a) (b)
160 200
all all
140
CH3
CH3
150 C2H5
120 C2H5 C4H9
C4H9 C12H25
100
Publications
Publications
C12H25 sym
80 100
60
40 50
20
0 0
2000 2005 2010 2015 2000 2005 2010 2015
Year Year
(c)
100
all
CH3
80 C2H5
C4H9
C12H25
sym
60
Publications
CH2CH2CO2H
40
20
0
2000 2005 2010 2015
Year
Figure 9.5 Publication rate for RAFT polymerization for the three most popular forms of
trithiocarbonate where the homolytic leaving group is (a) t-cyanoalkyl (e.g. 36–45), (b)
t-carboxyalkyl (e.g. 47–51), and (c) benzyl (e.g. 71–75) with various S–R′′ groups as
indicated (sym = symmetrical trithiocarbonate). Includes both patent and open literature
publications. Based on a ScifinderTM Search on the RAFT agent substructure and the term
‘RAFT’ conducted in June 2020.
9.7 Functional Trithiocarbonates

A wide variety of functional RAFT agents have been reported. Examples appear
in Table 9.7 (based on symmetric trithiocarbonates) and Table 9.8 (non-symmetric
trithiocarbonates). This list should not be considered as comprehensive.
Carboxy-functional RAFT agents are included in Tables 9.5 and 9.6. Trithio-
carbonates containing polymerizable double bonds (known as trithiocarbonate
inimers) are shown in Table 9.21.
These RAFT agents are used in the synthesis of other RAFT agents and in prepar-
ing RAFT functional surfaces. Surface-initiated RAFT polymerization to prepare
modified surfaces and particles is covered in detail in the Chapter 22 by Pribyl and
Benicewicz [731].
Table 9.6 RAFT polymerizations with non-symmetric trithiocarbonate RAFT agents.
S C Other: 361 [175]

C4H9S Copolymers: BzMA/Lim/NPMI [179]
S 197/NPMI [180]
Ph
butyl (2-cyanopropan-2-yl) carbonotrithioate
36
S C Methacrylates: MMA [3, 181–183]

H3CS Acrylates: MA [3] tBA [184]
S
CN
Copolymers: tBA/AcS [154] tBA/AcS/St [154]
2-cyanopropan-2-yl methyl carbonotrithioate
37 Blocks: tBA-b-AcS [154] tBA-b-AcS-b-St [154]
S C [186] Methacrylates: DMAEMA [187] TrMA [186]

C2H5S Acrylamides: 222 [188]
S
Other: 198 [189] 359 [190] 361 [175]
CN
Copolymers: HPMAm/194 [191]
2-cyanopropan-2-yl ethyl carbonotrithioate
BzMA/Lim/NPMI [179]
38
Blocks: DMAEMA-b-BzMA [187]
S A [192] Methacrylates: BMA [193] HxMA [193]

C4H9S C [193] HpMA [193] MMA [192] OMA [193] 159
S [194]
CN Acrylates: BA [195]
butyl (2-cyanopropan-2-yl) carbonotrithioate Methacrylamides: 191 [196]
39 Styrenes: St [195] 251 [197] 254 [197] 255
[197]
Copolymers: BMA/HxMA [193] BMA/OMA
[193] BMA/LMA [193] NPMI/Lim [198]
251-b-254 [197] 251-b-255 [197] 254-b-251
[197]
S C [199, 200] Methacrylates: BMA [201] FMA [202] GMA

C12H25S N [203] MMA [199, 204–206] MMA [207]
S ODMA [65] tBMA [208] TFPMA [24] 169
CN
[209] 330 [210]
2-cyanopropan-2-yl dodecyl carbonotrithioate Acrylates: HEA [211] BA [212] MA [213] MA
40 [212, 214] 358 [215]
Methacrylamides: BzMAm [216] PhMAm
[216]
Acrylamides: DMAm [217] LAm [218]
MPAm [217] NAM [217] NIPAm [13] NIPAm
[13, 217]
Styrenes: St [13, 219, 220] St [13] 274 [221]
278 [222] 258 [223] 356 [224]
Vinyls: NVC [8] 285 [225] 289 [226]
(continued)
Copolymers: MAA/MA [159]

tBMA/NIPAm [227] tBMA/343 [200]
HPMAm/297 [228] St/GMA [229]
PEGA/DA/AMPS [230] St/DVB [231]
DMAm/MBAm [217] NAM/MBAm
[217] NAM/PIPBAm [217]
MPAm/MBAm [217] NIPAm/PIPBAm
[217] DMAm/NAM [217]
DMAm/NIPAm [217] St/277 [232]
NIPAm/AN [233] CMS/266 [217, 234]
Blocks: BMA-b-MMA [201]
GMA-b-310 [203, 235]
ODMA-b-NIPAm [65]
tBMA/DMAEMA [208]
TFPMA-b-MAA [24] TFPMA-b-MA
[24] TFPMA-b-GMA [24] BA-b-222
[236] St/DVB-b-VPBA [231]
St/DVB-b-DVPP [231] St-b-NIPAm
[13] 258-b-305 [223]
S C Methacrylates: DEAEMA [239, 241]

C2H5S CO2H [237–240] DMAEMA [238, 242, 243] PEGMA
S [244–247] 299 [248]
CN Acrylates: (339) [249]
4-cyano-4-(((ethylthio)carbonothioyl)thio)pentanoic acid Methacrylamides: HPMAm [250]
41 Acrylamides: DMAm [85] DMAm [85]
HPMAm [251, 252] 193 [251] 223
[253]
Others: PAA [254] 288 [255]
Copolymers: MAA/PEGMA [245]
NIPAm/223 [253]
APMAm/DEAPMAm [256]
APMAm/DMAPMAm [256]
DEGMA/PEGMA/EGDMA [257]
DMAEMA/DEGMA [243]
HPMAm/APMAm [258]
HPMAm/350/352 [259]
Blocks: DEAEMA-b-NIPAm [241]
DMAEMA-b-NIPAm [260]
DMAEMA-b-AA/BMA/DMAEMA
[239] DMAEMA-b-PEGMA [243]
DMAEMA/DEGMA-b-PEGMA [243]
PEGMA/MAA-b-St [245, 261]
PEGMA/MAA-b-BzMA [262]
PEGMA/MAA-b-166 [263]
PAA-b-DMAm/313 [254]
DMAEMA-b-(PAA/BMA/DMAEMA)
[238, 242] HPMAm/APMAm-b-
HPMAm/DMAPMAm [258]
HPMAm-b-193 [251] PEGMA/155
[264]
(continued)
S Methacrylamides: DMAPMAm
C3H7S CO2H [265]
S Acrylates: AA [70]
CN Styrenes: 4VP [266]
4-cyano-4-(((propylthio)carbonothioyl)thio)pentanoic acid
Copolymers: AA/BA [267]
42
Blocks: AA/BA-b-MMA/BA
[267] AA/BA-b-MA/BA [267]
AA/BA-b-MMA/BA/EGDA
[267] 4VP-b-St [266]
279-b-St-b-St/DEGDMA [266]
DMAPMAm-b-MMA [265]
DMAPMAm-b-BA [265]
DMAPMAm-b-MMA/BA [265]
S C [268] Methacrylates: HEMA [269]

C4H9S CO2H MAA [182] PEGMA [268–270]
S Acrylates: PEGA [270]
CN Methacrylamides: 191 [196]
4-(((butylthio)carbonothioyl)thio)-4-cyanopentanoic acid
Copolymers: PEGA/TFEA [271]
43
Blocks: PEGA-b-St [270]
PEGMA-b-St [270]
PEGA/TFEA-b-Sty/3VBA [271]
S C [272] Methacrylates: CMA [273]

C12H25S CO2H N DMAEMA [274] GMA [275]
S GMMA [276] MAA [277] MMA
CN
[275, 278] MMA [279] PEGMA
4-cyano-4-(((dodecylthio)carbonothioyl)thio)pentanoic acid
[280–282] PMA [283] TFPMA
44 [24] 150 [171] 168 [284] 176
[285] 319 [286] 320 [286] PAA
[277]
Acrylates: AA [54] BA [287] BA
[275] EAA [277] EA [54] HEA
[288] MA [288] PEGA [282] 217
[171] 241 [289]
DMAm [288] NAM [290]
NIPAm [287, 291] NIPAm [288]
tBAm [54] 222 [292] 309 [288]
Methacrylamides: 181 [293] 191
[196] 192 [196] 187 [196] 188
[196] 348 [294]
Styrenes: PFS [288] 276 [295]
Others: Bd [296] Ip [297, 298]
(continued)
Copolymers: tBMA/168 [284]

BMA/343/PEGDMA [299]
DMAEMA/PAA/DSDA [300]
DMAEMA/PEGMA/305 [301]
GMA/Ip [297, 298] HPMA/304
[302] IPMA/304 [302]
LMA/304 [303] MAA/MMA
[304] MAA/DFHA [305]
MMA/368 [306] MAA/364
[307] MMA/292 [308]
OeMA/MMA [273]
PEGMA/366 [281] 149/172/174
[272] 149/171/172/174 [309]
HDFDMA/168 [284]
HPMAm/304 [302]
NIPMAm/304 [302]
189/DEGDMA [310] AA/370
[307] Am/222 [311]
DMAm/305 [312] Bd/AN [296]
MMA/PEGDMA/384 [278]
MMA/383 [278] MMA/383/384
[278]
Blocks: MMA-b-BMA [279]
MMA-b-BA [275] 319-b-MMA
[286] 320-b-MMA [286]
NIPAm-b-DMAEAm [291]
DMAEMA-b-BzMA-b-253 [274]
GMMA-b-HPMA/DMAEMA/
AMA [276] PEGMA-b-GMA
[280] PEGMA-b-HPMA [282]
PEGA-b-HPMA [282]
PEGMA-b-GMA [280]
149/172/174-b-PFOEMA [272]
AA-b-EA [54] AA-b-St [54]
176-b-VCL/MBAm [285]
348-b-NIPAm [294]
348-b-PEGMA [294]
NAM-b-305/NAM [290, 313]
-
RAFT-T-ATRP:
BMA/343/PEGDMA-g-BA
[299] BA/345/PEGDA-g-OFPA
[299]
BMA/343/PEGDMA-g-BA
[299] BA/345/PEGDA-g-OFPA
[299]
S NC Methacrylates: PEGMA [314]

S CO2H Acrylamides: DMAm [315, 316]
S
Styrenes: St [58] CMS [58] tBS
HO2C CN [58]
4-(((2-carboxyethyl)thio)carbonothioyl)thio)-4-cyanopentanoic acid
45
(continued)
Copolymers: HEMA/PEGMA
[317]
MAA/DMAPMAm/tBMAm
[318]
Blocks: St-b-NPMI [58]
St-b-NPMI-b-VAc [58]
HEMA/PEGMA-b-LMA [317]
HEMA/PEGMA-b-176 [317]
S C [319] Methacrylates: DMAEMA

S CO2H [320, 321] GMMA [322, 323]
S LMA [324] MAA [325] ODMA
Ph CN
[326] 335 [327] 338 [319]
4-cyano-4-(((phenethylthio)carbonothioyl)thio)pentanoic acid Copolymers: MMA/353 [328]
46 PEGMA/158/DSDM [329]
Blocks: DMAEMA-b-BzMA
[320, 321] GMMA-b-HPMA
[323] GMMA-b-MAA [323]
GMMA-b-TFEMA [322]
LMA-b-MMA [324]
MAA-b-BMA [325]
MAA-b-BzMA [325]
ODMA-b-BzMA [326]
335-b-BzMA [327] 338-b-HPMA
[319] MMA/353-b-MMA [328]
PEGMA/158/DSDM-
b-PEGMA/TFEMA [329]
S F Arylates: MA [240]
C2H5S Styrenes: St [240] (339) [249]
S CO2H
Acrylamides: DMAm
[85, 92, 240, 330] DMAm [85]
2-(((ethylthio)carbonothioyl)thio)-2-methylpropanoic acid NIPAm [240, 331] 227 [332] 228
47 [92, 332] 233 [333] 246 [330]
Other: 355 [334] 359 [190]
Blocks: DMAm-b-228 [92]
DMAm-b-228-b-NIPAm [92]
DMAm-b-235-b-224 [335]
228-b-227 [332]
S F [73] Acrylates: BA [73]

S Acrylamides: DMAm [336, 337]
S CO2H BA [336]
HO2C Styrenes: St [17]
2-(((2-carboxyethyl)thio)carbonothioyl)thio)-2-methylpropanoic acid
Copolymers: AA/Am [338]
48 Am-b-AA [338] DMAm/242
[339] DMAm/243 [339]
DMAm/244 [339] HEAm/245
[340]
(continued)
Blocks: DMAm-b-NIPAm [336]

DMAm-b-MA [336] BA-b-MA
[336]
S A [192, Methacrylates: CHMA [341]

C4H9S 341–343] MMA [192] 159 [194]
S CO2H F Acrylamides: AMPS [346, 347]
[344–346] Vinyls: NVC [194]
2-(((butylthio)carbonothioyl)thio)-2-methylpropanoic acid
49 Copolymer: AMPS/HEAm
[346]
Blocks: AMPS-b-BA [347]
AMPS-b-St [347]
AMPS-b-HEAm [346]
(AMPS-b-HEAm)4 [346]
AMPS-b-NAM [346]
(AMPS-b-NAM)2 [346]
AMPS-b-MBAm [346]
AMPS-b-DVB [346]
AMPS-b-DEGDA [346]
S M [173]
C4H9S
S CO2CH3
methyl 2-(((butylthio)carbonothioyl)thio)-2-methylpropanoate
50
S F [348] Methacrylates: (BMA) [349]

C12H25S (BMA) [349] CMA [350] MMA
S CO2H [151, 351] (MMA) [351] ODMA
[352] (TFPMA) [24] 154 [353]
2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoate
296 [354, 355] 305 [356] 349
51 (DDMAT, Lubrizol CTA-acid) [357]
Acrylates: AA [358, 359] BA
[73] CA [360] tBA [361] tBA
[91] MA [362] PFOEA [363]
200 [364] 203 [365] 218 [366]
Acrylamides: BAm [367] DEAm
[367, 368] DMAm [367, 368]
DMAm [91] EMAm [367, 368]
NIPAm [367–371] PAm
[367, 371] DMAm [85, 372–374]
(DMAm) [85] MPAm [375]
NIPAm [291, 374, 376] 225
[377] 240 [378] 236 [379]
Others: MVK [380] PVK [380]
195 [381]
(continued)
Styrenes: St
[7, 349, 358, 382–385] St [386]
(St) [349] St [387] CMS [387]
HMS [387] PFS [388] tBS [99]
261 [387] 264 [389] 265 [390]
267 [391] 268 [392] 269 [392]
315 [393] 4VP [388, 394, 395]
2VP [100]
Dienes: Ip [396–398] 280 [396]
Other MAM: 310 [383, 399, 400]
Vinyls: (NVP) [401] NVP [104]
285 [225]
Copolymers: BMA/PEGMA/311
[402] CEMA/292/NIPAm [403]
PAA/NIPAm [404] AA/PEGA
[405, 406] BA/200 [364]
(tBMA/DMAEMA/147) [407]
HEA/PEGA [408] PA/PEGA
[408] DMAm/160 [372]
DMAm/PFS [409]
HADA/MADA/NLAA [410]
DMAm/314/323 [411]
HADM/MADM/NLAM [410]
172/tBA/St/AcS [412]
(BMA/BA) [349] (BMA/BA)
[349] (BMA/St) [349] (BMA/St)
[349] MAH/Dc [413]
MAH/Dc/VAc [413]
MAH/Dc/MA [413]
MAH/Dc/St [413]
EHA/PFOEA [363] St/DVB
[414] 4VP/295 [415] St/308
[416] BA/167 [417]
BA/167/EGDMA [417] St/156
[418] St/291 [418] St/161 [419]
St/342 [420] tBA/St/AcS/172
[412]
Blocks: ODMA-b-MMA [352]
AA-b-St [381, 386]
AA-b-St-b-MMBL/St [381]
St/308 [416] HEMA/Ip [396]
HEA/Ip [396]Ip/280 [396]
AA/PEGA-b-209 [405]
AA/PEGA-b-St [406] 203-b-BA
[365] 203-b-BA/St [365]
(203-b-St) [365] 349-b-St [357]
St/342-b-TEGA/293 [420]
AA/PEGA-b-210 [263] AA-b-St
[359] DMAm-b-NIPAm [372]
DMAm/160-b-NIPAm [372]
(continued)
DMAm/160-b-NIPAm/160 [372]
NIPAm-b-DMAEAm [291]
PFS-b-PFPVS [409] 4VP-b-PFS
[388] 4VP-b-St [394]
DMAm-b-MA [374]
DMAm-b-BA [374]
DMAm-b-NIPAm [374]
NIPAm-b-MA [374] NIPAm-b-BA
[374] NIPAm-b-DMAm [374]
240-b-NIPAm [378] (NVP-b-Ip)
[401] 331X-b-St [392] tBA-b-Ip
[361] tBA-b-St [361]
tBA-b-IP-b-tS [361] tBA-b-St-b-IP
[361] MA-b-NAS/MAM [362]
CMA-b-TMSEMA [350]
St/MAH-b-Ip [421]
St/MAH-b-X332X [392] Ip-b-St
[398] Ip-b-St-b-DMAm [398]
NVP-b-2VP [104] NIPAm/MAA
[422] NIPAm/PAA [422]
PAM-b-NIPAm [368, 371]
PAm-b-NIPAm-b-EMAm
[368, 371] NIPAm/NAS/X279X
[423] X320X-b-NIPAm [378]
St-b-CMS [387] St-b-310
[383–385] CMS-b-HMS [387]
4VP-b-Ss [395] 4VP-b-St [395]
St-b-CA [360] Ip-b-St [397]
MMBL/St [381] St-b-NIPAm
[424] 4VP/295-b-St [415]
PFOEA-b-HEA [363] 315-b-St
[393] St/156-b-NIPAm [418]
St/291-b-NIPAm [418]
St/161-b-NIPAm/156/291 [419]
S F [425] Styrenes: St [426]

C12H25S Other MAMs: 281 [427] 282 [427]
S CO2C4H9 283 [427] 284 [427]
Copolymers: St/MAH [428]
butyl 2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoate
Blocks: St-b-MAH [426]
52 (Lubrizol CTA-ester)
St-b-St/MAH [428]
A Methacrylates: MMA [53]

S
H3CS
S
CN
cyano(phenyl)methyl methyl carbonotrithioate
53
(continued)
A Methacrylates: MPC [431]

S [429, 430] Acrylates: BA [432] MA [3]
H3CS
Acrylamides: NIPAm [433–437]
S
OH Styrenes: St [3, 438] SSO3Na
O [439]
2-(((methylthio)carbonothioyl)thio)-2-phenylacetic acid Blocks:
54 MPC-b-DMAEMA/NIPAm
[431] NIPAm-b-DMAPMAm
[434] NIPAm-b-AA [435, 436]
NIPAm-b-SSO3Na [437]
SSO3Na-b-AA [439]
SSO3Na-b-NIPAm [439]
A Methacrylates: MMA [440]

S
H3CS
S
OCH3
O
methyl 2-(((methylthio)carbonothioyl)thio)-2-phenylacetate
55
A Acrylates: BA [175] MA [175]

S Other: 361 [175]
C2H5S
Blocks: BA-b-361 [175]
S
OCH3
MA-b-361 [175]
O
methyl 2-(((ethylthio)carbonothioyl)thio)-2-phenylacetate
56

S Acrylates: BA [441] MA [441]
C3H7S
S
OCH3
NIPAm [441]
O Styrenes: St [441]
methyl 2-phenyl-2-(((propylthio)carbonothioyl)thio)acetate
57
A [442] Methacrylates: MEMA [442]

S METAC [442]
C4H9S Copolymers: MEMA/METAC
S [442]
OCH3
O
methyl 2-(((butylthio)carbonothioyl)thio)-2-phenylacetate
58
(continued)
A Acrylates: 204 [444]

S [443, 444] Methacrylamides: 179 [443]
C12H25S
S
Styrenes: St [444]
OCH3 Copolymers: (St/204) [444]
O Blocks: (204-b-St) [444] St-b-204
methyl 2-(((dodecylthio)carbonothioyl)thio)-2-phenylacetate [444]
59
S A [445] Acrylates: BA [445] ODA [445]

C4H9S Copolymers: ODA/DMAEA
S [445] ODA/NVP [445]
ODA/PEGA [445]
Blocks: ODA-b-DMAEA [445]
butyl (1-phenylethyl) carbonotrithioate

60
S A [445] Acrylates: ODA [445]

C12H25S Acrylamides: 231 [356]
S Copolymers: ODA/DMAEA
[445] ODA/AN [445]
ODA/MAA [445] ODA/MEP
[445] ODA/MAH [445]
dodecyl (1-phenylethyl) carbonotrithioate ODA/MAH/MMA [445]
61 ODA/NVP [445] St/263 [446]
Blocks: St/263-b-NIPAm [446]
S A Acrylamides: Am [447]
C2H5S Other: 355 [334] 359 [190]
S
CO2H
2-(((ethylthio)carbonothioyl)thio)propanoic acid
62
S A Acrylates: AA [450] BA [73]

S [448, 449] Acrylamides: Am [83] Am [451]
S DMAm [452] NAM [453] 225
HO2C CO2H [377]
3-((((1-carboxyethyl)thio)carbonothioyl)thio)propanoic acid Styrenes: St [17] VBA [454] 275
63 [454] 276 [454]
Copolymers: MAA/DMAm
[455] AA/DMAm [455] AA/Am
[338] Am/DAAm [448]
(continued)
Blocks: DMAm-b-DAAm [452]

NAM-b-DMAm [453]
NAM-b-DMAm-b-DEAm [453]
NAM-b-DMAm-b-DEAm-b-
NAM-b-DMAm-b-DEAm [453]
NAM-b-HEAm-b-NIPAm-b-
NAM-b-HEAm-b-NIPAm [453]
S A Acrylates: AA [456, 458, 459] HEA

C4H9S [456, 457] [77] HEA [314] MA [460] tBA [460]
S
PEGA [461] PEGA [314]
CO2H Acrylamides: DEAm [314, 462]
DMAm [77, 457, 463] DMAm
2-(((butylthio)carbonothioyl)thio)propanoic acid
[314, 462] NIPAm [463, 464] NIPAm
64
[460, 462] 246 [461]
Copolymers: AA/BA [68, 128]
AA/PEGA [459] AA/260 [467]
EGDA/HEA [460] NIPAm/NVC
[468] NIPAm/182 [469]
NIPAm/183 [469]
NIPAm/184 [469]
Blocks: AA-b-BA [456, 458, 470]
AA-b-MA [456] AA-b-BA-b-St [456]
AA-b-St [470] AA/BA-b-MMA/BA
[128] AA-b-PEGA [459] DMAm
[471] DMAm-b-St [471] MA-b-HEA
[460] MA-b-PEGA [460]
DMAm-b-NIPAm [314] St-b-St/340
[465] St-b-tBDMSOS [466]
DMAm-b-PEGA [462] PEGA-b-BA
[461] PEGA-b-BA-b-BA [461]
246-b-BA [461] 246-b-BA-b-BA [461]
NIPAm-b-DMAm/310 [463]
S A [456, Methacrylamides: APMAm [473]

C12H25S 472, 473] Acrylates: AA [456, 473, 474] BA
S [148, 475] HEA [476] MA [476–478]
CO2H Styrenes: St [148] CMS [479]
2-(((dodecylthio)carbonothioyl)thio)propanoic acid Dienes: (Bd) [480] (Ip) [480] 215
65 [171] (DMAEA) [148]
Others: (DADMAC) [481] 152 [482]
Vinyls: 290 [483]
Copolymers: AA-b-BA [456] AN/Bd
[160] (AN/BD) [484] St/MAH [472]
tBA/360 [485] AN/Bd/296 [486]
(continued)
Blocks: (AA-b-TFEMA) [474]

AA-b-St [480] (AA-b-St-b-BD) [480]
(AA-b-St-b-Ip) [480] (AA-b-St-b-Ip)
[480] (AA-b-BA-b-St-b-BD) [480]
NIPAm/NVC-b-DMAEA [468]
NIPAm/EGDMA [487] NIPAm/DVB
[487] NIPAm/369 [487] 152-b-151
[482]
S A [488] Acrylates: BA [488]

C2H5S -
RAFT-T-Cationic Polymerization:
S (BA-b-IBVE) [488]
CO2C2H5
ethyl 2-(((ethylthio)carbonothioyl)thio)propanoate
66

C3H7S
S
CO2C2H5
ethyl 2-(((propylthio)carbonothioyl)thio)propanoate
67
S A [342, Acrylates: MA [492] DEGA [492]

C4H9S 489, 490] DMAEA [491] PEGA [493] tBA
S
[343, 491] [492, 494]
Acrylamides: DEAm [492] DMAm
CO2CH3
[492] HEAm [492, 495] NAM [492]
methyl 2-(((butylthio)carbonothioyl)thio)propanoate
NIPAm [489, 490, 494] 225 [494] 324
68 [494]
Copolymers: DMAEA/NIPAm [496]
BA/DMAEA/NIPAm [496]
DMAEA/NIPAm/St [496]
TEGA/199 [497] DMAm/NIPAm
[343, 498] Am/294 [499] NIPAm/St
[343, 500]
Blocks: PEGA-b-310/MBAm [493]
DMA/NIPAm-b-CS/St [498]
NIPAm-b-St [490] NIPAm/St-b-St
[500]
S A [199] Acrylates: AA [277] BA [199, 204]

C12H25S N HEA [501] PEGA [501] NAS [502]
S Acrylamides: DDAm [503] DEAm
CN [476] DMAm [476] NIPAm
cyanomethyl dodecyl carbonotrithioate [504, 505] NIPAm [476]
69 Styrenes: St [199] CMS [479] DMOS
[506] 4HS [309]
(continued)
Vinyls: NVC [8]

Other: 355 [334] 196 [507]
DADMAC [481]
Copolymers: Am/AN [508]
BA/208 [509] MA/VAc [510]
St/DVB [414] St/MAH [511]
Blocks: NIPAm-b-VBA [505]
DDAm-b-TPAm [503]
DMOS-b-St [506]
HEA-b-DMAEA/DEGDA [501]
PEGA-b-DMAEA/DEGDA [501]
NIPAm-b-St [489]
S A [10, 512] Acrylates: BA [57, 513]

C4H9S Acrylamides: DEAm [514]
S O DMAm [515] NIPAm
N [57, 513, 516]
O Styrenes: St [10, 137, 513]
Vinyls: (NVP) [57] 325 [517]
Copolymers: AA/PA
butyl ((1,3-dioxoisoindolin-2-yl)methyl) carbonotrithioate
[512, 518]AA/CPA [512]
70
S A Acrylates: BA [519]
C2H5S Acrylamides: DMAm [246]
S
Copolymers: PEGA/MEA [246]
Blocks:
PEGA/MEA-b-NIPAm/MBAm
benzyl ethyl carbonotrithioate [246] BA-b-NVP [519]
71 DMAm-b-NIPAm/MBAm [246]
S A [151] Acrylates: AA [520] PEGA [521]

S tBA [521] OBA [522] 213 [523]
S 207 [524] PEGA [525, 526]
HO2C Acrylamides: MAm [527] NIPAm
[521, 528, 529] 226 [530] 229
[530] 246 [531]
3-(((benzylthio)carbonothioyl)thio)propanoic acid
Styrenes: St [151, 527, 532] (St)
72
[533] (SSO3Na) [534] 257 [524]
262 [535]
Others: DADMAC [536] NVC
[524] NVPI [524] 238 [537]
Copolymers: HEA/202 [529]
PEGA/DEGA [521] 257 [524]
BA/157 [538] NVC/257 [524]
St/CMS [532] PEGA/PFPA [539]
(continued)
Blocks: AA-b-SSO3Na [520]

PEGA-b-NIPAm/293 [525]
OBA-b-MA-b-293 [522] 213-b-247 [523]
238-b-DMAm [537] (St-b-DMAm) [527]
PEGA-b-373 [521] PEGA-b-374 [521]
PEGA-b-371 [521] PEGA-b-373 [521]
tBA-b-374 [521] NIPAm-b-374 [521]
PEGA/DEGA-b-374 [521]
PEGA-b-MBAm/310 [526] 257-b-207
[524] NIPAm-b-HEA/292 [529]
-
RAFT-T-ATRP: St/CMS-g-MMA [532]

C3H7S Acrylamides: NiPAm [540]
S
Other MAM: 310 [541–543]
Copolymers: MA/360 [544] PEGA/360
[544] NIPAm/360 [544] DMAm/360
benzyl propyl carbonotrithioate [544] NMMI/360 [545] NPMI/360 [545]
73 NPFPMI/360 [545]
Blocks: 310-b-DMAm [542]
310-b-NIPAm [542]
S A Styrenes: St [546] 4VP [546]

C4H9S Dienes: Cp [547]
S
Other: NPMI [548]
Blocks: NPMI-b-Ind [548]
NPMI-b-Ind-b-NPMI [548]
benzyl butyl carbonotrithioate NPMI-b-Ind-b-NPMI-b-Ind [548]
74 NPMI-b-Ind-b-NPMI-b-Ind-b-NPMI
[548] St-b-4VP [546]
S A Acrylates: MA [460] 205 [549]

C12H25S Styrenes: St [18] St [550]
S
Dienes: Cp [547]
Other: 310 [541]
Copolymers: DEGA/PEGA/201 [551]
benzyl dodecyl carbonotrithioate PEA/PEGA/324 [552] PEA/PEGA/323
75 [552]
b) Purple – crosslinking polymerization. Block copolymers prepared by crosslinking
polymerization will be arm-first stars. Red – photoinitiated polymerization. Orange – SUMI.
Bold Orange – PhotoSUMI or photoinduced electron or energy transfer-single-unit monomer
insertion (PET-SUMI). Green – redox RAFT. Blue Italics – heterogeneous polymerization
(emulsion, miniemulsion, dispersion).
Table 9.7 RAFT polymerizations with functional trithiocarbonates derived from symmetric.
Hydroxyl
HO S A [554] -
ROP-T-RAFT:
O S OH LA-b-NIPAm
S [554]
O O
O
76
Active ester
S H [555] RAFT agent
S O O synthesis
S [555, 556]
HO2C O N
O
77
Protected maleimide
O S O I [557] Methacrylates:
O S O I/M [558] MMA [557]
O N S N O
O O
O O
78
Protected thiol
N H [559] Acrylates: PEGA
S N [559]
S S
O S S S
S
O O
O
79
protected aminoxy
O H [559] Acrylates: PEGA
NH O [559]
(H3C)3CO O S OC(CH3)3
O S O NH
S
O O
O
80
(continued)
Alkyne
S J [560, 561] Acrylamides:
O S O H [562] NIPAm
S [563, 565]
F,H [563]
O O RAFT agent
F, I [560,
81 synthesis [560–
564, 565]
562, 564, 566]
NMP initiator
J [567] Acrylates: AA
S [568] BA [567]
O S O Ph N
O S O
N Ph O O
82
ROAMP initiator
CF3 M [569] Acrylates: MA
S
R= CF3 [569]
S O
S RO O
O Mo O
RO OR
83
ROMP monomer
S S I [570] -
ROMP-T-RAFT
C12H25S O O SC12H25 [570]
S S
O O
84
b) For a full list of monomer abbreviations, see Abbreviations section.
Table 9.8 RAFT polymerizations with functional trithiocarbonates derived from

non-symmetric trithiocarbonates.
RAFT Agent Synthesisa) Polymerizationsb)
Hydroxyl
S H [571] Acrylates: MA [571]
C4H9S -
ROP-T-RAFT: CL [571] VL [572]
S
CL-b-MA [571] VL-b-MA [572]
O
O
OH
85
S A Methacrylates: (318) [574]

S [573, 574] Acrylates: 305 [575]
S
HO
Acrylamides: NIPAm [573] 301 [576]
Copolymers: Am/249 [577]
Blocks: 305-b-BA [575]
86
Am/249-b-NIPAm [577]
-
ROP-T-RAFT: CL [573, 578, 579] LA
[580] CL-b-HEMA [581] CL-b-St
[582] CL-b-DEGMA [579]
CL-b-PEGMA [583] CL-b-NIPAm
[579] CL-b-tBAm [579]
CL-b-179/362 [578]
(GA/LA-b-PEGMA) [584]
LA-b-NAM/NAS LA-b-Sty/DVB
[585]
S A [586] -
ROP-T-RAFT: LA [586–589] PDL
C12H25S [590] LA-b-THPA [586–588]
S LA-b-293 [589] PDL-b-EHA [590]
PDL-b-MA [590] PDL-b-NIPAm
[590]
OH
87
Active ester
S O O H Methacrylates: MMA [593] PEGMA
C2H5S [591, 592] [591]
S O N RAFT agent synthesis [592, 594–598]
CN
O
88
S O O H Methacrylamides: HPMAm [600]

C12H25S [599, 600] RAFT agent synthesis [599, 601–603]
S O N
CN
O
89
(continued)
S H [604] RAFT agent synthesis [604]

C4H9S O O
S
O N
O
90
S H Methacrylates: CMA [608]

C12H25S O O [605–607] Acrylates: DMAEA [609]
S
O N
Acrylamides: NIPAm [610]
Styrenes: [605]
O Blocks: CMA-b-DMAEMA [608]
91
St-b-DVB [605]
RAFT agent synthesis
[601, 606, 607, 611–623]
S H [592, Acrylates: HEA [624]
C4H9S 624–626] Copolymers: PEGMA/PFOEMA
S [627]
O O RAFT agent synthesis [592, 625, 626]
O N
92
S O F F H [592] RAFT agent synthesis [592]

C12H25S
S O F
CN
F F
S M [628] Methacrylamides: HPMAm [629]

C12H25S O F F Acrylates: OPA [628]
S
O F
Acrylamides: DMAm [630] HEAm
[464, 629, 631–633]
F F Styrenes: 252 [634]
S H Acrylates: HEA [624]

C4H9S [624, 625] RAFT agent synthesis [625, 635]
S
O
O F
F F
F F
93
(continued)
2-Mercaptothiazoline
S O H [636] Acrylates: PEGA [636]
C2H5S O RAFT agent synthesis [637]
S N
CN S
94
S O H [638] RAFT agent synthesis [638]

C3H7S O
S N
CN S
95
S O H [600] Methacrylamides: HPMAm [600]

C12H25S O
S N
CN S
96
Azlactone
S A [639] Acrylates: EA [639]
C12H25S Acrylamides: NIPAm [639]
S
Styrenes: St [639]
O
N
O
97
Trifluoroborate iminium
S A [640] Acrylamides: NIPAm [640]
C12H25S
S
N+
–
F3B
98
(continued)
Protected thiol
S H [604] Acrylamides: NIPAm [604]
C4H9S O Blocks: NIPAm-b-St [604]
S N
O S
S
99
S H [641] Styrenes: 272 [641]

C2H5S Copolymers: PEGMA/PFOEMA
S N [627]
O S S
O
100
S H Acrylates: DEGA [642] HEA [624]

C4H9S [462, 624] PEGA [643]
S N RAFT agent synthesis [462]
O S S
O
101
S I Acrylates: PEGA [526]

C12H25S Blocks: PEGA-b-MBAm/310 [526]
S N
O S S
O
102
S H [641] Styrenes: 272 [641]

C2H5S
S N
O S S
O
3
103
S H [644] Acrylates: PEGA [644]

C2H5S
S
O S N
O S
104
(continued)
S I [645] Acrylates: PEGA [645]

N S Blocks: PEGA-b-BA [645]
S
S S O
O
105
Thioketal
S O H [646] Acrylamides: DMAm [646]
S
S O OH
Ph CN S S
106
Protected amine
S K [606] Acrylamides: NIPAm [606]
C12H25S O RAFT agent synthesis [606]
S O
HN OC(CH3)3
NH
107
S M [606] RAFT agent synthesis [606]

C12H25S O
S
HN CF3CO2–
+
NH3
108
Alkyne
S O H Methacrylates: PEGMA [648]
C12H25S [647, 648] Copolymers:
S O PEGMA/317/dye/EGDMA [647]
CN
Blocks: PEGMA-b-DMAEMA/
109 TFEMA-b-368 [648]
S O H [649] Acrylamides: NIPAm [649]

C12H25S
S HN
CN
110
(continued)
S H [650] Methacrylates: 178 [650]

C12H25S O O Blocks: 178-b-175 [650]
S
HN N
111
S H Methacrylates: MMA [655] 321

C12H25S O [651–654] [656]
S Acrylates: tBA [657] EHA [657]
O DA [657] PEGA [657]
112
Acrylamides: NAM [658] NIPAm
[654, 659–661]
Styrenes: St [662, 663] tBOS [662]
4VP [348]
[651–653, 664–669]
S H [604] Acrylamides: NIPAm [604]
S
O
113
S A [539] Acrylates: PEGA [539, 670]

S Other MAM: 310 [671]
S Si(CH3)3
Copolymers: PEGA/PFPA/DSDA
HO2C O
[539] 310/PFPA [671]
O
Blocks: PEGA-b-PFPA/DSDAm
[539] PEGA-b-310/MBAm
310-b-PFPA [671]
S H [604] Acrylates: HEA [672] tBA [471]
C4H9S Acrylamides: DMAm [471]
S
Styrenes: CMS [673]
O
O
Blocks: CMS-b-St [673] tBA-b-St
[471] DMAm-b-St [471]
114
S H [486] Copolymers: AN/Bd [486]

C12H25S
S
O
O
115
(continued)
Azide
S O J [674] Methacrylates: MMA [674, 675]
C12H25S Vinyls: 310 [675]
S O N3
CN
116
S O H [676] Styrenes: St [676]

C12H25S
S O
CN O
n
N3
117
S I [677] Acrylates: PFPA [678]

C12H25S O N3 N Acrylamides: DMAm [677, 679]
S NEAm [679] NIPAm [680] (NIPAm)
O [681]
118 Styrenes: St [677] 2VP [682]
RAFT agent synthesis [683, 684]
S N3 A [685] 337 [685]
C12H25S
S
119
Dibromomaleimide
Br I [686] Acrylates: PEGA [686]
O
Br Blocks: PEGA-b-219
S N
C12H25S O
S
CN
120
Br J [687] RAFT agent synthesis [687]

Br
O
S N
C2H5S O
S
CN
121
(continued)
S M [688] Acrylates: BA [688] MA [688] TEGA

C 12 H 25 S [688]
Styrenes: St [688]
O
Br RAFT agent synthesis [689]
N
Br
O
122
Thiolactone
S K [604] Acrylamides: NIPAm [604]
S
HN
S
O
123
Carbonyl azide (transforms to isocyanate in situ)

S M [690] Methacrylates: MMA [690] Acrylates:
C12H25S O MA [690]
N3
Styrenes: St [690]
124
Protected maleimide/ROMP monomer

S H [691] Methacrylates: 176 [691]
C2H5S O O Acrylates: HPA [692]
S
O N O
Acrylamides: NIPAm [691, 693, 694]
Copolymers: MEA/DEGA [692]
O
125
S O I [695] Acrylamides: DEAm [695]

C2H5S O
S N O
O
O
126
(continued)
S O H Methacrylates: MMA [698]

C12H25S O [696, 697] Acrylamides: NIPAm [697, 699, 700]
S N O
Styrenes: St [696, 698, 700–702]
O
Copolymers: MMA/St [698]
O
127 -
RAFT-T-ROMP [696, 701]
S O H [703] Methacrylates: MMA [703]

C12H25S O Acrylates: BA [703]
S O
Styrenes: St [703]
CN N O
4 -
RAFT-T-ROMP [703]
O
128
S H [624] Acrylates: (HEA) [624]

C4H9S
S O
O O
O N O
O
129
Urazole (1,2,4-triazoline-3,5-dione precursor)

9 S O K [626] Acrylates: BA [626]
C4H9S
NH
S N
6 NH
NH
O O
130
Sulfonyl fluoride
S M [704] Methacrylates: (MMA) [704]
C4H9S Acrylates: tBA [704]
S
Styrenes: St [704]
O
S
O
F
131
(continued)
S A [705] Methacrylates: 177 [706]

S
Vinyls: NVP [705]
O
Si Blocks: 177-b-186 [706]
O
S
O
F
132
ATRP initiator
S O H [707] Acrylates: MA [707]
C4H9S O -
RAFT-T-ATRP: MA-b-MMA [707]
S
O Br
O
133
Norbornene (ROMP monomer)
S
H Acrylates: tBA [708, 711, 712]
C12H25S O
[708–710] Acrylamides: NAM [713]
S Styrenes: St [709–711, 714, 715]
O
Blocks: St-b-MA [714]
134 St-b-MA-b-tBA [714]
-
RAFT-T-ROMP [708–715]
H [716] Methacrylates: MMA [716]
S O Styrenes: St [716]
C12H25S
S O
CN
135
Alkoxysilane
A RAFT agent synthesis [441, 717]
S [441, 717]
S
S
(H3CO)3Si OCH3
O
136
(continued)
A [718] RAFT agent synthesis [718, 719]

S Si(OC2H5)3
S
S
O
O
137
t-Butyldimethsilyl (see also 132)

S C [720] Styrenes: St [720]
S
Si O S OH
11
CN
138
H [721] Acrylates: 220 [721] 221 [721]

S
C12H25S O Si
S O
O
O
Si
139
H [704] Acrylamides: NAM [704]

O Si
S
C4H9S
S
O
O
140
Poly(dimethylsiloxane)
S O H Methacrylates:
S [722, 723] BzMA [722, 723]
S O DMAEMA [723]
O
CN O Si Si C4H9 GMMA [723]
n
MMA [723]
141 TFEMA [723]
tBDMSMA [724]
Copolymers:
BMA/
tBDMSMA [724]
PEGMA/
TBSiMA [725]
PEGMA/
TPSiMA [725]
S H [726] Styrenes: St [726]
C12H25S O MeS [726] tBS
S [726]
O
O
O Si Si C4H9
n
142
S H [727] Acrylates:
C4H9S DMAEA [727]
S
O
O O Si Si C4H9
n
O
143
S H [728] Vinyls: NVP [728]

S
S
O
O O Si Si O
n
O
2
144
Peptide
S O M Methacrylates:
C12H25S [729, 730] BMA [730]
S HN peptide-NH2 DMAEMA [730]
CN PEGMA [730]
145 Blocks:
PEGA-b-BA [729]
b) Blue italics – heterogeneous polymerization (emulsion, miniemulsion, dispersion).
Purple – crosslinking polymerization. Red – photoinduced polymerization.
For a full list of monomer abbreviations, see Abbreviations section.
Functional RAFT agents also facilitate the synthesis of conjugates post-RAFT

polymerization. In this context, this summary can be used for guidance as to the
functionalities tolerated by the RAFT process. Unfortunately, in many papers
the quantitative characterization that would enable a rigorous evaluation of the
effectiveness of the various chemistries is lacking.
Azide functionality is best installed post-RAFT polymerization. It has been found
that azide functionality (e.g. from 118) is not completely stable to the conditions
used for RAFT polymerization [681]. The synthesis of reactive polymers by RAFT
polymerization is detailed in the Chapter 18 by Gauthier-Jaques et al. [732].
9.8 Synthesis of Trithiocarbonates
The methods most commonly exploited for the synthesis of (low molar mass)
trithiocarbonates are listed below. The method of choice is dependent on the
specific structure, the amount required, the toxicity and ease of handling of
reagents, and other factors. A critical review [5] of synthetic methods for RAFT
agent synthesis provides further details of the various methods listed below and
they will not be elaborated here. Two recent reviews on the synthesis of organic
trithiocarbonates have appeared [733, 734].
Procedures for RAFT agent synthesis referred to in Tables 9.3–9.8 are as follows:
A. Reaction of a carbodithioate salt with an alkylating agent.

A process for the synthesis of symmetrical trithiocarbonates from carbon
disulfide and various alkyl halides in dimethyl sulfoxide (DMSO) with 1 equiv
of CsOH.H2 O at 50 ∘ C [735]. The method has been used for 20 (PhCḢ(CH3 )Br,
60 minutes, 81%) and 22 (PhCH2 Cl, 45 minutes, 91%; PhCH2 Br, 30 minutes,
96%). No reaction was observed for the tertiary halides including Ph(CH3 )2 Br
or C(CH3 )3 Br.
B. Reaction of a dithiochloroformate or a thiocarbonyl-bis-imidazole with a nucle-
ophile.
C. Radical-induced decomposition of a bis(thioacyl)disulfide.
D. Radical-induced ester exchange.
E. Transesterification (thiol exchange by reaction of a dithioester with a thiol).
F. Ketoform reaction (used for the synthesis of carboxy functional RAFT agents).
G. Single-unit monomer insertion (SUMI).
RAFT-SUMI and PET-RAFT-SUMI are described in Section 9.15.
H. Esterification or amidation (carbodiimide)
I. Esterification (acid chloride)
J. Esterification (Mitsunobu reaction)
K. Active ester–amine reaction or active ester–thiol reaction
L. 1,3-Dipolar cycloaddition
M. Other methods
An imidazole-mediated process for the synthesis of symmetrical trithiocar-
bonates from carbon disulfide and various alkyl halides in wet DMSO or
N,N-dimethylformamide (DMF) has been described [140]. The method was

used for (22 (PhCH2 Cl, 4.5 hours, 92%; PhCH2 Br, 3.5 hours, 91%)) and 23
[C(CH3 )3 Br, 14 hours, 65%].
N. Commercially available.
9.9 Polymer Syntheses with Trithiocarbonates

The more common monomers subjected to RAFT polymerization with trithio-
carbonates are referred to using abbreviations (Section 9.23). The structures
of more exotic monomers are included in the tables that follow. They include
1,1-disubsituted monomers, namely, methacrylates (Table 9.9), methacrylamides
(Table 9.10), and others (Table 9.11), and monosubstituted monomers, namely,
acrylates (Table 9.12), acrylamides (Table 9.13), styrene derivatives (Table 9.14),
and vinyl monomers (Table 9.15). Monomers with reactive functionality appear in
Table 9.16. To assist in finding the trithiocarbonate RAFT agents that might best be
used for a specific monomer, some guidance is provided in the preamble section
before each table. Example polymerizations can be found in Tables 9.3–9.8 by
searching for the corresponding abbreviation or compound number. The monomer
numbers in Tables 9.3–9.8 are hyperlinked to the monomer structures in the online
version of this chapter.
There is substantial interest in RAFT polymerization of monomers derived from
renewable resources [763]. More commonly encountered monomers in this cate-
gory include those derived from amino acids [764], such as acrylamides (Table 9.12),
and glycomonomers, such as acrylates 204 and 205, methacrylamides 180–179, acry-
lamide 247, and styrene derivative 272.
9.9.1 Methacrylates
RAFT polymerization with trithiocarbonates has been successfully applied to
a very wide range of methacrylates. These include allyl methacrylate (AMA),
cholesteryl methacrylate (CMA, 165), butyl methacrylate (BMA), (diethylene glycol
monomethyl ether) methacrylate (DEGMA), (2-dimethylamino)ethyl methacry-
late (DMAEMA), 2-hydroxyethyl methacrylate (HEMA), lauryl methacrylate
(LMA), methyl methacrylate (MMA), (methacryloyloxy)ethyl phosphoryl-
choline (MPC), (polyethylene glycol monomethyl ether) methacrylate (PEGMA),
(3-trimethylaminonium)propyl methacrylate (TMAPMA) (for other examples see
Abbreviations), and those listed in Tables 9.9 and 9.16 (functional methacrylates).
Low D- in RAFT polymerization of methacrylates requires the use of a RAFT agent
with a suitably high transfer coefficient. This requires that the RAFT agent R group is
a good leaving group with respect to the methacrylate propagating radical. Amongst
the better RAFT agents for methacrylates are the tertiary cyanoalkyl trithiocarbon-
ates 37–45. Tertiary carboxy trithiocarbonates 47–51 provide control over molar mass
but D- is typically > 1.3 even at high monomer conversions. The 1-phenyl-1-carboxy
trithiocarbonates 54–59 can give good control, but often give some retardation due
to slow reinitiation, which is most noticeable for high RAFT agent concentrations.
Table 9.9 Methacrylate monomers subjected to RAFT polymerization.
O O O O
O O O O
HO OH O O S
O
glycerol monomethacrylate (GMMA) 148 [736] O
146 149
solketal methacrylate
147
Metallomonomers
O O
O NH
Fe O O
150 [171] Fe Co+PF6–

[171]
151 152
Ligating monomer
O O
O
O O O
6
O 6
O
O
O
NH N 155
N
Ph Ph
N N
N HN
153 [737]
Ph
154
(continued)
Dyes
O O NO2 O
O O O
O O
N O
O
O O 158
Br
156 157
O O O
O O O
O N
N
N
N
O
161
159
O
Liquid crystals 160
O
O O O O O O O O
O
5O
2O
O O O
4
O O
O O
O O
CMA
165 [739]
164 [738]
162 166 [263]
163 [404]
(continued)
O O O
O O
O O O
6
O
N
N
OC6H13
O
167
170 [740]
NC
168 OCH3
169
Bulky monomers
O O O O O
O O O
MADM 173 [741] 174

HO
172
HADM
171 [741]
Betaines, ionic liquids
O O O O
O O O O
–
5 Br
+
N
O +
N N
O–
P N
O
O
177 178
–
SO3
+
N
DMAPS
176
MPC
175
Table 9.10 Methacrylamide derivatives subjected to RAFT polymerization.
OH HO OH OH
O O
HO O
HN O HO O HN O
HO OH HO
NH OH OH
OH
OH
O HO 181
NH
HO
OH
O
179
180
OAc
OAc
OAc
O
OAc HN O HN O
OAc
OAc AcO HN O
O AcO O S
S S
AcO AcO 184
OAc OAc
182 183
O O O
HN O HN O
HN HN HN O
O O OCH3
O NH
NH NH
O O
OH
OCH3
OH
O
HN 186 N
189
N
NH
S 188
187
185 [110]
O O O O O
HN HN HN HN HN
O O
N NH NH
HN
NH
190 [742] N N H2N O
NH
193 [251]
192 H2N
191 194
Table 9.11 Other 1,1-disubstituted monomers subjected to RAFT polymerization.
O
O N N
O O O
MMBL
195 196
Lim
198
197
Table 9.12 Acrylate monomers subjected to RAFT polymerization.
O O O O O
O O O O O
O O
O
O O N
O O
O
200 201 202
199 203
O O O
O O O
O O
O
OAc O
OAc
O O
O O 4
AcO O N
N CN
OAc
204 [444] 205 N

CN
206 207
O O
O O
O O O O O
O
10
n O O O
O
4 O
O O O
N N
N
N N
OH
208
HO
CA
212 OH
211 213
209 n = 1
210 n = 4
(continued)
O O
O HN O
O O O
O
O
5 O Fe
O
O
Fe
217 [171] O
215 [171]
O Fe Co
O Ph Ph
Ph Ph
216 [171]
218 [171]
O
214
O O O
O O O
C2H5O
P
OCH3 OC2H5
P O O
H3CO C2H5O
O 220 P
OC2H5
219 O
221
Table 9.13 Acrylamide derivatives subjected to RAFT polymerization.
O O O
O
HN NH NH HN
HO2C
N
O 224 O
O
HN O
O
223 225
222 [188, 292]
O O O O
H3CO2C NH HO2C NH HO2C NH H3CO2C NH
226
227 228 229
O O O O
HO2C NH HO3CO2C NH N HO2C NH

CO2CH3
232
233 [333]
230 231
(continued)
O + O O
Na O
HN − N N HN NH
–
N+ O3S
N +
Na
N N SO3–
AMPS
234 [105] 235 +
237
N
–
O3S
236
O O
O O
OCH3
HN HN NH N
P +
O– Li N
O
O O
B
P + HO OH O
– Li
O
H3CO 240 [378]
O
NH 239 [105] O
O
Fe
238 [537]
241
O O O O
HN HN HN HN
O O O N
N
O O O N
NH NH H3CO NH
O
243
242 245
244
O O
HO
HN HN
HN O
OH O
OH OH
O O
O O
HO O OH O
HO
247 O
OH
246
248 [110, 743]
OH OH
O O
HO O
OH HN HO H
HO N
HO
OH O OH
O
HO N N O
OH N
250
249
Table 9.14 Styrene derivatives subjected to RAFT polymerization.
N
O
N
O O
251 Fe
252 [744]
253
N
S
N
254
N
O N
257 [197, 745]

O
N
258
N
S
N
S 256
C6H13
255
(continued)
acenaphthylene
260 N N
N
N
261 [387, 747]

N
259 [746] N N Ph
N N N
N
Ph
262 [535]
B OH
O
O O O
O
264 [389]
O
N 265 [390, 748]
N 266
263 [446]
F F F F F F
F F F F F F
O O O O
O
O
O
O
O
267 [391] 268 [392] 269 [392]
270 [749]
CHO + +
N N
O CI– OTf–
O O O
O OH 273 [92] 274
O
O O
O OH
O
OH
271 [750]
HO OH
OH
272 [641]
(continued)
N+
I–
+ +
+ Ph + N – –
CI N X
P P 279
CI– Ph CI–
Ph N N
275 276
277
278
Table 9.15 Vinyl derivatives subjected to trithiocarbonate-mediated RAFT polymerization.
Thioacrylates
O O O O
S S S S
281 283
282 284
Vinylsulfides
S S S
S N S N O N
N
286
285
287
Others
Br–
B N+
O
HN O
NH O N O
+ N
–
AcO
288 289
HN
290
291
Table 9.16 Monomers with reactive functionality used in trithiocarbonate-mediated RAFT

(co)polymerization.
(a) Alkyne
O O
O O HN
O
(H3C)3Si
(H3C)3Si 293 Si(CH3)3
Si(CH3)3
292 294
295
O
O O O
O HN
298 [753–755]
296 [751, 752] 297
(b) Azide
O
O
N3
299
(c) Active ester
O O
O O O HN
N
O O
O
N
O NAS O O
301 N
NMS O O
300 [756] O
302 [757] O O
N
O
NaO3S
303
(continued)
O
O O F
O F
F F
F F O O O S O F
F F F F O F
F F PFPA
PFPMA 305 F F F F
304 F F
PFPVB PFPVS
306 [409] 307 [409]
(d) Thialactone, azlactone

O
N O N
O
S
309 O
O S O
310
HN
S
O
308 [416]
(e) Protected thiol, hydrazide, or amino functionality
O O
O O O HN
O HN
S S
S S S S HN
S S N N
N N O OC(CH3)3
315 [393]
313 [758] 314
311 312 [254]
O O O O O
HN HN O O O
5 NH
O O
NH OC(CH3)3 O O O
HN O O O
317
O Ph
(H3C)3CO HN HN HN
O O O
316 [759]
(H3C)3CO (H3C)3CO (H3C)3CO
318 319 320
(continued)
O O O O
O HN HN HN
O
(H3C)3CO O
O NH 325
O
HN O
O O
O OC(CH3)3
HN
O (H3C)3CO 324
O 323
HN HN
(H3C)3CO O O OC(CH3)3
322
321 [656]
O
O O O HN O
O HN HN O
CI–
– + + +
CI NH3 CI
– CI– NH3 H3N NH
+
AEMA H3N AEMAm APAm
326 APMAm 328 329 330
327
(f) Silyl ether (see also TBSiMA, TPSiMA)
O O O O
O O O O
Si Si Si
O
Si
TPSiMA (H3C)3SiO Si OSi(CH3)3
tBDMSMA 334 OSi(CH3)3
tBDMSOS 332 TBSiMA
333 335
331
[760, 761]
(g) Protected aldehyde, protected sulfonate
O O
O O
O S O
O O SO3K
O
336 [760, 761] 338 [760, 761]
CF3
337
(continued)
(h) Isocyanate functionality
O
O O
O
N
N
C N
O C
C
O
339 [249] O
340 [465] 341 [465]
(i) ROMP monomer
342
(j) ATRP inimers
O O O
O O O O
O
O O O
O O O
O
Br Br CI
O
Br
344 [762] 345 346
343
(k) NMP inimers
O
O
O N
347
9.9.2 Methacrylamides
Many examples have appeared of RAFT (co)polymerization of HPMAm, particularly
with respect to various bioapplications [765]. Other examples of methacrylamide
monomers recently used in RAFT polymerization are the primary amino-functional
monomers, AEMAm (328) and APMAm (327), and the tertiary amino-functional
monomers, DEAPMAm, DMAPMAm, and those shown in Table 9.10. Various func-
tional methacrylamides appear in Table 9.16.
The choice of RAFT agent for polymerization of methacrylamides is subject to
similar constraints as mentioned for the methacrylates. In particular, the R group
should be selected to be a good leaving group with respect to the propagating radical.
9.9.3 Other 1,1-Disubstituted Monomers

Other 1,1-disubsitueted monomers that have been used in trithiocarbonate-mediated
RAFT (co)polymerization include derivatives of γ-butyrolactones (195) oxazoline
(196), maleimide (198) (Table 9.11). The sesquiterpene 197 [181] and limonene
(Lim) [180] are not readily homopolymerized but can be used as comonomers or in
SUMI experiments (Section 9.15) [58].
9.9.4 Acrylates
Acrylates include 2-(acryloyloxy)ethyl phosphate (AEP), butyl acrylate (BA),
3-chloropropyl acrylate (CPA), dodecyl acrylate (DA), (2-dimethylamino)-
ethyl acrylate (DMAEA), 2-ethylhexyl acrylate (EHA), isobornyl acrylate (iBoA),
methyl acrylate (MA), propargyl acrylate (PA), (polyethylene glycol monomethyl
ether) acrylate (PEGA), tert-butyl acrylate (tBA) (for other examples see Abbrevia-
tions), and those listed in Table 9.12.
Many acrylate esters have been shown to undergo intramolecular chain transfer to
polymer (backbiting) during polymerization leading to branched structures. It has
been reported that the extent of branching is higher for conventional radical poly-
merization than for RDRP (atom-transfer radical polymerization [ATRP], RAFT,
NMP) [766, 767]. A qualitative explanation was proposed in terms of the differences
in the concentrations of short-chain radicals between RDRP and conventional radi-
cal polymerization. Reys and Asua [768] have proposed an alternative explanation in
terms of radical life times (the time between chain activation and deactivation) being
of the same order of magnitude or shorter than the time required for the confor-
mation change necessary for intermolecular hydrogen atom transfer. Conventional
chain transfer agents (n-octanethiol) [769] and H-bonding solvents (n-butanol) [770]
also appear to reduce the extent of branching in conventional radical polymerization.
9.9.5 Acrylamides
Attaining low dispersities with RAFT polymerization of acrylamides requires a
RAFT agent suitable for MAMs. Acrylamides include acrylamide Am, 2-acrylamido-
2-methylpropane-1-sulfonic acid sodium salt (AMPS, 237), N-benzylacrylamide
BzAm, N-cyclohexylacrylamide CHAm, diacetone acrylamide DAAm, N,N-diethyl-
acrylamide DEAm, N,N-dimethylacrylamide DMAm, N-(2-(dimethylamino)ethyl)
acrylamide DMAEAm, N-isopropylacrylamide NIPAm, N-acryloylmorpholine

NAM and N-octylacrylamide OAm (for other examples see Abbreviations), and
those listed in Table 9.13.
9.9.6 Styrenics
Styrenic monomers used in RAFT polymerization include those listed in Table 9.14
plus, 4-acetoxystyrene (AcS), 4-chloromethylstyrene (CMS), 4-chlorostyrene (CS),
3,4-dimethoxystyrene (DMOS), 4-hydroxymethylstyrene (HMS), 4-methylstyrene
(MeS), 2,3,4,5,6-pentafluorostyrene (PFS), sodium 4-styrenesulfonate (SSO3Na),
4-(tert-butyldimethylsilyloxy)styrene (tBDMSOS), 4-tert-butylstyrene (tBS),
4-tert-butoxystyrene (tBOS), 4-hydroxystyrene (4HS), 295, 302, 306, 307, 308, 337,
341, 342 (see Section 9.9, Table 9.16). Good control over RAFT polymerization
of styrene and derivatives requires a RAFT agent suitable for MAMs. Many of
the styrenes in Table 9.14 have been used to prepare polymers for optoelectronic
applications. The advantage of the styrenic monomers over acrylic monomers in
this context is that the functionality is typically not attached through a potentially
labile ester or amide linkage.
9.9.7 Diene Monomers

RAFT polymerization of diene monomers, like other MAMs, generally requires
a more active RAFT agent. RAFT homopolymerizations of Bd and Ip in solution
are slow and generally require the use of higher reaction temperatures to obtain
good control and reasonable rate of polymerization (e.g. 125 ∘ C) [480]. Emulsion
(co)polymerization of the diene monomers (Bd, Ip, and Cp) mediated by trithiocar-
bonate RAFT agents is more facile even at low (near ambient) temperature and has
been extensively reported in the patent literature (Table 9.15) [771].
The RAFT copolymerization of Ip with hydroxy-functional monomers, HEMA,
HEA and 280, with trithiocarbonate (51) has been explored [396]. Diels–Alder
reaction of Ip with the (meth)acrylates was observed as a side reaction. The (meth)
acrylates are consumed preferentially to Ip, and thus their copolymers with Ip have a
gradient structure. The copolymer of Ip with diene 280 is a more random copolymer.
OH
280 [398]
9.9.8 Other Monosubstituted Monomers (MAMs, IAMs, LAMs), Vinyl

Monomers
Trithiocarbonates are not generally suited for mediating polymerization of LAMs.
A study on the use of benzyl and t-butyl trithiocarbonate and dithiobenzoate RAFT
agents for VAc polymerization has appeared [146]. Intermediate radical termination
was proposed to be a significant cause of retardation with these systems.
Trithiocarbonates are suited for controlling polymerization of IAMs such as NVC
[8] and S-vinylsulfides (285–287).
9.9.9 Monomers with Reactive Functionality

There is a need for processes that permit polymer modification post-RAFT polymer-
ization. So-called polymer analogous reaction make use of reactive functionality that
can be present on the Z or R groups of the RAFT agent or can be associated with the
monomer(s) [772]. The functionality must be inert to the conditions of polymeriza-
tion and yet polymerization must proceed on demand in quantitative yield under
mild reaction conditions.
Many papers consider the combination of RAFT and azide–alkyne 1,3-dipolar
cycloaddition. Some alkyne-functional monomers are listed in Table 9.16a; those
with azide functionality appear in Table 9.16b. Alkynes with a terminal C–H may
be reactive towards radicals and therefore are commonly protected as the silyl ether.
Azides react with election-deficient monomers and are most often incorporated
post-RAFT polymerization. Further detail can be found in the Chapter 18 Synthesis
and Application of Reactive Polymers via RAFT Polymerization [732].
‘Active ester’ monomers that have been subjected to RAFT polymerization are
shown in Table 9.16c. These active ester groups undergo facile reaction with sub-
strates containing primary amine functionality.
Several recent papers have explored polymerization of monomers containing
isocyanate functionality (Table 9.16h) [249, 465, 773]. RAFT polymerization and
the thiocarbonylthio group are compatible with isocyanate functionality. However,
some care must be taken in the selection of the RAFT agent and other components
of the polymerization medium such that they do not also contain any other
functionality that is inherently reactive (such as carboxy) [249].
ATRP inimers (Monomers with ATRP initiator functionality) include CMS and the
monomers shown in Table 9.16i [762, 774]. NMP inimers are shown in Table 9.16j.
Some applications of these inimers are described in Section 9.16.
9.10 Macromonomers
RAFT polymerization of macromonomers provides a route to comb polymers by a
‘grafting through’ process. RAFT-crosslinking copolymerization of macromonomers
is another route to arm-first stars. RAFT-SUMI of macromonomers into RAFT
agents is a route to macroRAFT agents. Some examples of macromonomers used
in trithiocarbonate-mediated RAFT polymerization are provided in Table 9.17.
Additionally, there are many examples of RAFT polymerization of PEG-based
macromonomers, PEGA, PEGMA, polyethylene gycol diacrylate (PEGDA), and
polyethylene gycol dimethacrylate (PEGDMA). The PVDF macromonomer
(353) was prepared by xanthate-mediated RAFT polymerization and end-group
modification [328].
9.11 Cyclopolymerization
Some of the monomers used in trithiocarbonate-mediated RAFT cyclopolymeriza-
tion are listed in Table 9.18. Attempted RAFT cyclopolymerization of DADMAC with
trithiocarbonate 69 has been reported [481]. While the polymerizations show some
Table 9.17 Macromonomers subjected to RAFT polymerization.
HN NH2
HN O
OH
O
O O O O O O
H H H O Si O Si
N N N O
N N N NH2 Si Si
H H H O O
O O O
OH O O
Si Si
Peptide macromonomer O Si
Si O O
348 O
POSSMA
349
O O
O O OH
H NH O HO
N
N NH2 N O
H H
O HN N H
F OH
H
NH2
351
12
Peptide macromonomer
350
O O
NH O
N O O S n
OH F F O
O O
H PVDF macromonomer
N NH2
N N 353
H H
O O
5
NH2
6
Peptide macromonomer
352
- > 1.5).
living character, conversions are generally low and dispersities are poor (D
Trithiocarbonates are not ideal for DADMAC, which is a LAM. A xanthate is more
appropriate for such monomers [775, 776].
- ) were observed for RAFT cyclopolymer-
Better results (high conversions, low D
ization of MAM 355 with trithiocarbonates 47, 63, or 69 [334]. RDRP cyclopolymer-
ization has been proposed as a method for precision synthesis of periodic polymers
[777, 778] in which monomer sequence, polymer molar mass, and dispersity
are simultaneously controlled. An example involves cyclopolymerization of 358
mediated by 40 [215]. High dilution conditions were required to avoid crosslinking.
A 1 : 2 mixture of divinyl ether (DVE) and maleic anhydride (MAH) with diben-
zyl trithiocarbonate was reported to undergo alternating RAFT cyclopolymerization
mediated by dibenzyl trithiocarbonate (22) to provide the polymer 354 as shown in
Scheme 9.5 [161, 162].
Table 9.18 Monomers subjected to RAFT cyclopolymerization.
H3CO2C
O
O O
N+ – O O HN
CI O O O
O N
DADMAC O S O O
O O N N
N
O Si O
Ph Ph NO2
356 [224] 358

355 357 [103]
O
O R
O MAH
O
R R O
DVE O O O
O
O
O O
O O O
O
R
MAH O O S
O O S
O O O O
n
2
Scheme 9.5 RAFT cyclocopolymerization of DVE/MAH.
9.12 Radical Ring-Opening Polymerization

Radical ring-opening polymerization (ROP) provides a simple method of form-
ing polymers with readily cleavable linkages, i.e. esters, thioesters, and/or
disulfides, into the carbon–carbon backbone of a polymer chain by radical poly-
merization [779]. Several ring-opening MAMs (359–361) that have been used in
trithiocarbonate-mediated RAFT (co)polymerization are listed in Table 9.19.
Trithiocarbonates are not generally suitable RAFT agents for mediating
the copolymerization of LAMs, such as the ketene acetals. However, RAFT
copolymerizations of monomers, such as BMDO (362) or 363 (Table 9.19) with
acrylates [780] or methacrylates [545, 578, 781] are effectively controlled.

Star synthesis by RAFT crosslinking polymerization is described in the Chapter 21
by Allison-Logan et al. [782] and the process will not be detailed here. Examples
making use of trithiocarbonates are highlighted in Tables 9.3 and 9.6 and examples
of multiolefinic monomers used in this process are included in Table 9.20. Network
Table 9.19 Monomers used in trithiocarbonate-mediated RAFT ring-opening

polymerization.
O
O O O O O O
O
O O S
S
O
O Pinocarvone
Ph 363
360 361
359 BMDO
362
Table 9.20 Examples of multiolefinic monomers used in RAFT Crosslinking polymerization

mediated by trithiocarbonates.
O O O O O O
O O
O O O O
O NH O S O
O 2
O O S
O O
O
O O
O
364 O O
O O
O O
O O
O
O
O HN
DSDM 369
367
368
O 2 O
O
O
365 366
O O O O O
O O HN HN
O
OH
HO
S NH S
O S
S
O
O 373
O NH
O
370 O O
O
HDDA N,N-bis(acryloyl)cystamine (DSDAm)

DSDA
371 374
372
For a full list of monomer abbreviations, see Abbreviations section.

formation by RAFT crosslinking polymerization has been reviewed by Moad [783]

and is covered in the Chapter 19 by Pérez-Salinas et al. [784].
The kinetics of network formation in RAFT polymerization of various acrylamide
monomers mediated by trithiocarbonate 40 was examined [217]. A process for gel
point normalization was developed, which was proposed to enable the targeting of
specific number and weight average molar masses in the synthesis of hyperbranched
polymers using RDRP. Applications of RAFT-synthesized polymer networks that
have made use of trithiocarbonate RAFT agents include networks for molecular
imprinting [307], monolithic flow reactors [231, 785], dynamic-covalent networks,
and self-healing materials [487].
Multiolefinic monomers used in the synthesis of microgels and polymer networks
include (diethylene glycol)dimethacrylate (DEGDMA), TEGDMA, ethylene glycol
dimethacrylate (EGDMA), HDDA, MBAm, PIPBAm, and DVB and compounds
365–374 (Table 9.20). Use of monomers such as 367, with an acetal linkage, and 368
and 374, with disulfide linkages, results in the formation of degradable crosslinks
that can be important in controlled release applications. The crosslinks can also
be cleaved to allow polymer analysis, for example, to determine arm length in star
synthesis.
9.14 RAFT Self-condensing Vinyl Polymerization

Self-condensing vinyl polymerization provides a method of hyperbranched polymer
synthesis. The first RAFT examples appear in the patent literature. The area has
recently been reviewed [786, 787]. Examples of trithiocarbonate RAFT monomers
(sometimes called inimers) are shown in Table 9.21. These polymerizations com-
prise copolymerization of the RAFT monomer to form a hyperbranched structure.
A second RAFT step or ‘block synthesis’ can then result in adding arms to produce a
core-crosslinked star. Star synthesis is dealt with in greater detail in the Chapter 21
by Allison-Logan et al. [782].
Examples of trithiocarbonate inimers in the synthesis of polymer networks are
contained in Table 9.22. These networks have an inbuilt mechanism for stress relief
and self-healing [800–804, 806].
9.15 RAFT-Single-Unit Monomer Insertion (RAFT-SUMI)

into Trithiocarbonates
RAFT-SUMI into trithiocarbonates and dithiobenzoates was originally developed
as a method of synthesizing functional RAFT agents or macroRAFT agents. Itera-
tive SUMI has also been explored as a method for synthesizing sequence-defined
oligomers. The area has recently been reviewed by Xu [807] and Haven et al. [14].
See also the Chapter 17 in the present volume on sequence-encoded RAFT oligomers
and polymers [808]. Many of the more recent examples of RAFT-SUMI into MAMs
have made use of trithiocarbonates [14, 58, 288, 315, 548, 809, 810].
9.15 RAFT-Single-Unit Monomer Insertion (RAFT-SUMI) into Trithiocarbonates 431
Table 9.21 RAFT monomers for self-condensing vinyl polymerization.
O C/H [788] 375/BMA/DEAEMA,

375/BMA/DEAEMA-b-312/
O DMAm [788]
S O
S
S O
CN
375
O C/H [789] 376/PEGMA/TFEMA [789]

376/PEGMA, PEGMA-b-St [790]
O
S O
C12H25S
S O
CN
376
O C/H [791] 377/HPMAm [791]
NH
S O
C4H9S
S O
CN
377
S A [574] 378/318 [574]

S
S
HO
378
S A [792] 379/MMA, 379/MA, 379/tBA, 379/St,

C3H7S 379/St-b-St, 379/St-b-379/tBA [792]
S
379/DMAEMA [793]
379/St, 379/CMS, 379/St-b-379/CMS,
379/CMS-b-Ip [794]
379 379/St, 379/St-b-tBA,
379/St-b-NIPAm, 379/St-b-DMAEA,
379/St-b-AA-b-NIPAm,
379/St-b-DMAEA-b-NIPAm [424]
379/PEGMA [795, 796]
S A [797, 798] 380/322, 380/322-b-380/DEGA/PEGA
C4H9S [798]
S
380/NIPAm [797]
380
(continued)
S M [799] 381/NIPAm, 381/NIPAm-b-276 [799]

C12H25S
–
S CO2
+
Bu2P
381
a) The letter in this column refers to the method of RAFT agent synthesis. Refer to Section 9.8.
b) Polymerizations comprise copolymerization of RAFT monomer to form a hyperbranched
structure. A second RAFT step or ‘block synthesis’ results in adding arms to produce a
core-crosslinked star.
Table 9.22 RAFT monomers for synthesis of combs and defined networks.
O J [800, 801] 382/MMA [800, 802] 382/BA

I [802] [803]
O
O 382/MMA-b-St [802]
S 382/BisGMA/TEGDMA [804]
O S
S
O
O O
O
382
O A/H [278] For examples, see Table 9.6

trithiocarbonate 44
O
O
S
O S
S
O
O O
O
383
S A/H [805] 384, 384-b-DMAm,

C4H9S 384/MMA, 384/MMA-b-MA
S [805]
O
O O See also under Table 9.6
O trithiocarbonate 44
384
a) The letter in this column refers to the method of RAFT agent synthesis. Refer to Section 9.8.
b) RAFT agent appears inert during polymerization of methacrylates. Red – photoinitiated
polymerization.
Further examples of RAFT SUMI include end-functionalization of macroRAFT

agents through SUMI of a functional monomer, such as MAH or a maleimide [811]
or an allyl monomer 325 (Scheme 9.6) [812], and the synthesis of macroRAFT
agents from macromonomers, for example, a P3HT macroRAFT agent as shown in
Scheme 9.7 or the RAFT functionalization of pendant methacrylate double bonds,
present in a molecular imprinted polymer formed by crosslinking copolymerization,
by SUMI into trithiocarbonate 47 [813].
HN
O O
HO HO
O O
S SC4H9 S SC4H9
N N
H H
S AIBN, 70 °C S
HN O n HN O HN
n
O O
OH OH
Scheme 9.6 Example of chain-end functionalization by RAFT-SUMI of allyl monomer 325

into a trithiocarbonate macro RAFT agent.
S
C4H9S
S
C6H13 C6H13 S
39 CN
S SC4H9
Br AIBN, 70 °C Br
S n S n
NC
Scheme 9.7 Example of formation of macroRAFT agents by RAFT-SUMI of a

macromonomer.
9.16 Trithiocarbonates in Mechanism Transformation

Processes
Block, star, or graft copolymers comprising segments formed by different mech-
anisms can be combined using post-polymerization modification techniques or
through the use of a dual initiator-RAFT agent [814, 815]. Of significance is the
orthogonality of the various processes. Trithiocarbonate-mediated RAFT poly-
merization can often be successfully conducted in the presence of the initiator
functionality used in other RDRP methods (e.g. alkoxyamines for NMP, alkyl
halides for ATRP). However, the converse is seldom true.
We do not consider examples (of which there are many) of transformation
of end-functional polymers to polymers with trithiocarbonate functionality by
end-group modification in this section.

Hydroxy-functional trithiocarbonates (e.g. 76, 86, or 87) allow sequential or, in some
cases, one-pot ROP and RAFT polymerization, Examples of ROP-T-RAFT - (ROP step
first) are provided in Tables 9.7 and 9.8 (ROP of lactones, e.g. caprolactone [CL],
lactic acid [LA], is compatible with retention of the trithiocarbonate functionality).
Examples of RAFT-T-ROP - (RAFT first) or simultaneous ROP and RAFT have also
been demonstrated [571].
Amine or ammonium functional RAFT agents (e.g. 108) might be used for
-
ROP-T-RAFT of, for example, N-carboxyanhydrides to form block copolymers
with peptides [606]. However, amine-functional RAFT agents may also cause
aminolysis of the RAFT agent. RAFT-T-ROP - has been carried out with RAFT
agents containing protected amine functionality (e.g. 107), which is deprotected
post-RAFT polymerization to enable RAFT-T-ROP. -
It is also possible to use thiol-functional polymers formed by end-group aminol-
ysis directly for initiating ROP of N-carboxyanhydrides in RAFT-T-ROP - [816]. The
success of this strategy depends on the stability of the terminal thiol.
End-group transformation by sequential aminolysis and thio-Michael addition to
APMAm can also be used to provide amine end-functionality for RAFT-T-ROP - of
N-carboxyanhydrides (Scheme 9.8) [252].
CN CN
RAFT HO2C S SC2H5 APMAm HO2C SH
41 n n
HPMAm S
O NH O NH
OH OH
O OCH2Ph
CN H CN H H
HO2C S N NH2 HO2C S N N H
n ROP n N
O O O H n
O NH O NH
OH OH
Scheme 9.8 Example of RAFT-T-ROP- involving RAFT polymerization of HPMAm mediated

by 41, followed by end-group transformation, by one-pot aminolysis, and thio-Michael
addition to APMAm, and amine-initiated ROP of an N-carboxyanhydride.

RAFT polymerization and ring-opening metathesis polymerization (ROMP) appear
orthogonal such that RAFT polymerization can be carried out in the presence
of some ROMP active monomers (1,2-disubstituted olefins) and ROMP can be
conducted in the presence of trithiocarbonate functionality. RAFT polymerization
mediated by a trithiocarbonate containing a norbornene group as a ROMP-active
but RAFT-inert monomer functionality to form macromonomers can be used to
form bottlebrush polymers in a ROMP ‘grafting through’ polymerization [708, 711].
A one-pot process for simultaneous ROMP and RAFT polymerization was also
-
described [817]. Examples of ROMP-T-RAFT (ROMP first) have also been reported
for the synthesis of triblock [570] and graft copolymers [818].
Examples of trithiocarbonates also containing ROMP monomer functional-
ity include 84 (cis-1,2-disubsituted double bond), 127 and 128 (furan protected
maleimide), and 134 and 135 (norbornene).
9.16.3 Ring-Opening Opening Alkyne Metathesis Polymerization

(ROAMP)
A reagent comprising both a molybdenum complex as initiator for ring-opening
alkyne metathesis polymerization (ROAMP) and trithiocarbonate functionality (83)
has been reported, which allowed sequential ROAMP and RAFT polymerization to
provide a poly(o-phenylene ethynylene)-block-poly(methyl acrylate) [569].
9.16.4 Cationic Polymerization

RAFT agents can be used to mediate both cationic and RAFT polymerization and
-
examples of cationic polymerization-T-RAFT can be found in the Chapter 25 by
Uchiyama and Kamigaito [819].
9.16.5 Anionic Polymerization

Trithiocarbonates can act as an initiator for the anionic ROP of thiiranes with
tetraphenylphosphonium chloride as catalyst [820, 821]. One-pot and sequential
polymerization processes were developed for polymers containing PDMAm (by
RAFT polymerization) and poly(methylthiarane) (by anionic ROP) segments [820].
9.16.6 Nitroxide Mediated Polymerization (NMP)

-
Processes for RAFT-T-NMP have been described in reviews on RDRP trans-
formation processes [814, 815]. These include the ESARA process in which
thiocarbonylthio and alkoxyamine groups are exchanged [822] and the use of
species that contain both RAFT agent and alkoxyamine initiator functionality [568].
9.16.7 Atom Transfer Radical Polymerization (ATRP)

Many RAFT agents can be used as pseudohalides in ATRP though trithiocarbonates
are seldom used in this context. There are also examples of what are believed to be
photo-redox processes that go under the umbrella of PET-RAFT (see Section 9.17).
The RAFT agent/ATRP initiator 133 was used first for PET-RAFT of MA, followed
by organo-ATRP of MMA, to form a low-dispersity PMA-b-PMMA [707]. The pentyl
methacrylate (PMA)–trithiocarbonate would not be expected to be an effective medi-
ator of MMA polymerization under the conditions used. However, the complete
orthogonality of the ATRP and RAFT steps is not fully established.
-
Graft (bottlebrush) and star polymers have been prepared by RAFT-T-ATRP. The
process involves RAFT (co)polymerization of an ATRP inimer, a monomer contain-
ing ATRP initiator functionality (Table 9.16i) [150, 200, 299, 823–825], to form a
polymer with pendant ATRP initiator moieties, which can then be used to grow
arms on the core/backbone by ATRP. For example, ATRP was used to add arms
to hyperbranched cores formed by RAFT crosslinking polymerization mediated by
trithiocarbonate 44 and that incorporate monomer 345 or 343 [299]. The chloro- or
bromo-compounds used as ATRP initiators are generally inert in RAFT polymeriza-
tion in the absence of an activator.
9.17 Photoinitiated RAFT with Trithiocarbonates
RAFT photoinitiation was foreshadowed and claimed in the first RAFT patent in
1998 [1]. However, this document contained no examples of photoinitiation whether
direct or with the use of photoinitiators. A process equivalent to photo-SUMI (into
xanthates) was first reported by Delduc et al. [826] in 1988. Trithiocarbonates
have been widely used in photoinitiated RAFT polymerization. The n → π tran-
sition for primary and secondary trithiocarbonates appears at ∼430 nm and is
red-shifted to ∼440 nm for tertiary trithiocarbonates [173]. The use of direct pho-
toinitiation or PET-RAFT appears to give fewer by-products than conventionally
initiated (with a thermal initiator) RAFT polymerization. Additionally, the use
of visible light irradiation appears to give rise to fewer issues than does UV light
[827–829].
At least four forms of photoinitiated RAFT polymerization should be considered:
(i) polymerizations conducted in the presence of an added photoinitiator; (ii) direct
photoinitiation when the trithiocarbonate dissociates into radicals by photocleavage
of the C—S single bond and PET (photo energy or electron transfer) RAFT, which
might involve either a (iii) photosensitization or a (iv) photo-redox process. There
is also a range of photo-redox processes [477]. Examples of photo-RAFT polymer-
ization are highlighted in Tables 9.3 and 9.6 with entries in Red (polymerization) or
Bold Orange (SUMI). However, we do not distinguish the form of photo-process
there and the reader should refer to the references cited.
For additional information on photoinitiated RAFT processes making use of
dithioesters the reader is referred to the Chapter 12 of Chapman et al. [15] and other
recent reviews [830].
9.18 Redox-Initiated RAFT with Trithiocarbonates
RAFT polymerization can be initiated by a redox process involving the RAFT

agent. The redox properties of various RAFT agents and their utility in
redox/electrochemical initiation are detailed in the Chapter 18 by Lorandi
et al. [16] and so a detailed discussion will not be given in this chapter.
9.19 RAFT Emulsion/Miniemulsion/Dispersion Polymerization Mediated by Trithiocarbonates 437
The electrochemical behaviour of trithiocarbonates has been described by

Strover et al. [831]. The major reduction peak moves to more cathodic potentials
in the series dithiobenzoates > trithiocarbonates > heteroaromatic dithiocarba-
mates > xanthates ∼ N-alkyl-N-aryldithiocarbamates generally paralleling the order
of activity as RAFT agents. The reduction peak for trithiocarbonates makes it most
suitable for direct or mediated eRAFT, in that it is suitably distant from that for redox
active monomers or other components of the electrochemical reaction medium.
Examples of redox-RAFT are identified in Table 9.6 (entries in Green). At least two
forms of direct redox-initiated RAFT can be distinguished, though not all have been
demonstrated for trithiocarbonates: (i) where the RAFT agent behaves as a pseudo-
halide in an ATRP-type mechanism [832–836], and (ii) involving electron transfer to
the RAFT agent with formation of a radical anion intermediate. The latter process
has been called dissociative electron-transfer RAFT (DET-RAFT) [837, 838].
9.19 RAFT Emulsion/Miniemulsion/Dispersion

Polymerization Mediated by Trithiocarbonates
Examples of heterogeneous polymerization are identified in Tables 9.3 and
9.6 (entries in blue italics). In 2000, Moad et al. [4] provided a first report of
trithiocarbonate-mediated RAFT emulsion polymerization. They compared the
efficacy of a series of benzylic RAFT agents in semi-batch RAFT emulsion poly-
merization of St. Except for the example using cumyl dithiobenzoate as mediator,
polymerization was rapid and little coagulum was observed. RAFT emulsion
polymerization mediated by the trithiocarbonate and xanthate provided molar
mass control but with Ð ∼ 2 (Table 9.23).
A significant advance in RAFT emulsion polymerization came with the devel-
opment of so-called ‘surfactant-free’ RAFT emulsion polymerization based on
amphiphilic macroRAFT agents [456, 458]. A recent review has summarized
the status of this method [839]. Most examples make use of trithiocarbonates.
Table 9.23 Molecular weight and conversion data obtained in semi-batch emulsion
polymerizations of styrene at 80∘ C in the presence of various RAFT agents.
RAFT agent Mn Ð % Conversion RAFT agent M n a) Ð % Conversion
S 39900 7.09 96 S 32400 1.98 >99

Ph Ph
S S
Ph Ph
S 53200 1.37 >99 S 31300 2.04 >99
Ph S
S S
Ph Ph
S 35600 1.38 >99 Control 132600 2.71 >99

O
S
Ph
a) Number average molar mass in polystyrene equivalents.

The process typically involves initial synthesis of a hydrophilic block, such as

propacrylic acid (PAA) [163, 456, 458], poly(N-acryloylpyrrolidine) [840], PEG
[841], poly(PEGA-co-HEAm) [842], or poly(DEGMA-co-HPMA-co-PEGMA) [843]
by solution RAFT polymerization followed by formation of a hydrophobic block
usually composed of the monomer being polymerized and which can be produced
in situ. An issue with this methodology is that the product is always a block
copolymer with the hydrophilic segment of the macroRAFT agent stoichiometri-
cally incorporated into the final product. The hydrophilic block can be important
to polymerization-induced self-assembly (PISA). In other cases, it comprises an
impossible-to-remove ‘impurity’ in the product.
Most recent studies on RAFT emulsion polymerization with dithioesters have
been based on the use of amphiphilic macroRAFT agents usual in the context of
PISA. PISA during RAFT dispersion polymerization has been extensively studied
by Armes and coworkers [844]. Many examples (for some examples see Table 9.6)
involve solution polymerization mediated by trithiocarbonate 46 followed by
dispersion polymerization. PISA is described in detail in the Chapter 15 by D’Agosto
et al. [845].
9.20 Reaction Conditions and Side Reactions

of Trithiocarbonates
One disadvantage of many trithiocarbonates is that thermal or hydrolytic decompo-
sition yields thiols that may be odorous. This issue can be mitigated by using trithio-
carbonates based on thiols with low volatility and provides a case for end-group
removal post-RAFT polymerization.
Trithiocarbonates are less prone to hydrolysis and reaction with nucleophiles than
dithioesters and they are probably the most used RAFT agents for polymerizations
conducted in aqueous media [52]. Nonetheless, it is desirable to conduct aqueous
polymerizations at lower temperatures (e.g. <50 ∘ C) [846] to minimize hydrolysis
(Scheme 9.9).
A
A
HN O O
S N
S
C12H25S S
+ S
C12H25S H
Scheme 9.9 Proposed mechanism for loss of trithiocarbonate functionality from

methacrylamide macroRAFT agents.
Trithiocarbonates containing a 4-cyanopentanoic acid group as R (reported for

R′′ = C2 H5 (41), C4 H9 (43), C12 H25 (44), or CH2 CH2 Ph) have been found to be
subject to a side reaction in which the nitrile substituent is converted to a primary
amide (Scheme 9.10) [23]. The process has not been reported for other tertiary
H
O
H H H
N N–
O O O O O NH2
S S + S
CO2H
R'S S R'S S R'S S
Scheme 9.10 Proposed mechanism for nitrile hydrolysis for trithiocarbonates with
R = 4-cyanopentanoic acid.
cyanoalkyl trithiocarbonates and is therefore thought to involve intramolecular

acid catalysis. This results in the nitrile being converted to an iminium salt that is
then hydrolysed to the amide by reaction with the water present in the sample. The
–CN → –CONH2 transformation has also been reported as a complication during the
synthesis of peptide RAFT agents based on 44 [730]. The process has not (yet) been
reported for other compounds containing the 4-cyanopentanoic acid group such as
similar dithioester RAFT agents or the initiator 4,4′ -azobis(2-cyanopentanoic acid)
(ACPA).
The rate of RAFT polymerization is enhanced with the use of ionic liquids as
the polymerization medium. Examples of such RAFT polymerizations mediated by
trithiocarbonates include the solution polymerization of BMA [201] and FMA [202]
and the dispersion polymerization of St [847].
Trithiocarbonate functionality in PAA has been shown to be unstable during
methylation with trimethylsilyldiazomethane undergoing a side reaction that
results in conversion of the trithiocarbonate to a thiol [70].
The sensitivity of RAFT polymerization to air or oxygen has long been a concern.
In high throughput experimentation a range of methods have been applied to alle-
viate the issue, which include freeze-thaw degassing [848] and enzyme degassing
[849, 850]. The PET-RAFT process with DMSO solvent has been found to be remark-
ably insensitive to air [476, 851–853]. The DMSO solvent imparts oxygen tolerance
through its ability to quench singlet oxygen generated by photosensitization.
9.21 Trithiocarbonate Group Removal/Transformation
Most of the methods described for removal or transformation of thiocarbonylthio

groups of RAFT-synthesized polymers [854–857] are applicable to polymers con-
taining trithiocarbonate groups. For polymers formed from symmetrical trithiocar-
bonates, removal of the thiocarbonylthio group will usually result in cleavage of the
polymer chain. A review of RAFT end-group transformation is provided in Chapter
16 by Lowe and Dallerba [856].
9.21.1 Trithiocarbonate Group Removal by Radical-Induced Coupling

Various radical-induced processes for trithiocarbonate group removal have been
developed including radical-induced coupling, radical-induced disproportionation,
and radical-induced reduction (Scheme 9.11). They involve initial conversion of the
macroRAFT agent to a propagating species either by radical addition–fragmentation
or by photo-induced C—S bond scission through a photoiniferter-like process. The
challenge in applying these methods is to find conditions that maximize the desired
pathway(s), particularly with respect to radical–radical termination.
Initiator ∙
I
S S Pn I S S Pn I S S Pn
+ P∙n
Radical addition-
fragmentation ∙ +
I S S S
R′′ R′′ R′′
S S Pn S S
hν or Δ ∙
Photoiniferter process + Pn
S S
R′′ R′′
∙ + I∙
Radical-induced coupling Pn Pn I
∙
Radical-induced disproportionation Pn + I∙ Pn= + I H
∙ + I∙
Pn Pn H + I=
∙ + P∙n
Termination Pn Pn Pn
∙ ∙
Pn + Pn Pn H + Pn=
Radical-induced reduction ∙ [H]

Pn H
Pn
Scheme 9.11 Trithiocarbonate group removal by various radical-induced reaction

pathways including radical-induced coupling, radical-induced disproportionation, and
radical-induced reduction. The ‘= ’ in ‘Pn = ’ or ‘I= ’ indicates unsaturation.
A method developed by Perrier et al. [440] involves heating a RAFT-synthesized

polymer with a large excess of a radical initiator (e.g. 20 molar equiv), most
often a dialkyldiazene such as AIBN. The method has been successfully applied
to many trithiocarbonates. For examples of trithiocarbonate group removal by
radical-induced coupling, see Table 9.24.
Several studies have explored the conditions required for thiocarbonylthio group
replacement by radical-induced coupling and how this depends on the macroRAFT
agent and initiator used [195, 205]. Side reactions include the reaction of propagating
species with other radicals (e.g. other propagating species, the RAFT intermedi-
ates). The reaction of propagating radicals with other radicals is usually shown as
combination and this appears to be the dominant pathway for methacrylate propa-
gating species and 2-cyano-2-propyl radicals. However, the process depends of the
radical source and the propagating species and may also involve disproportionation
(see Section 9.21.2).
End-group removal to produce a monomodal product from PMMA-trithio-
carbonate (C12 H25 S(C=S)— end) was found to require milder conditions (20-fold
excess AIBN, 80 ∘ C, 2.5 hours) than [2] that from PMMA-dithiobenzoate (at least
100-fold excess AIBN for 80 ∘ C, 2.5 hours) [205]. The relative ease of end-group
removal from the trithiocarbonate by this method was associated with the shorter
Table 9.24 Trithiocarbonate group removal by radical-induced coupling.
Terminal [Initiator] Temperature % ends

ZCS2 monomer Initiator [RAFT]a) (∘ C)b) removedc) References
S MMA AIBN 20 80 100 [440]

H3CS
S
S MMA AIBN 20, 40 80 100 [205]

C12H25S
S
S TFEMAd) LPO 7.5 70 100 [858]

S
S BA AIBN 20 80 25 [195]
C4H9S
S
S BA AIBN+LPO 20+2 80 100 [195, 267]

C4H9S
S
S HEA AIBN 20 70 100 [859]

C12H25S
S
S HPA AIBN 10 80 (100) [860]

C12H25S
S
S HPA BPO 10 80 100 [860]

C12H25S
S
S DAMEA/ AIBN 20 65 100 [861]

C12H25S TFEA
S
S HADA/ AIBN 20 60 100 [410]

C12H25S MADA/
S
NLAA
S NIPAm AIBN (20) (80) (100) [606]

C12H25S
S
S NIPAm AIBN (20) 80 (100) [862]

S
S
S NAM/NAS AIBN 400 80 (100) [362]

C12H25S
S
S DMAm AIBN (20) 80 (100) [862]

S
S
(continued)
Terminal [Initiator] Temperature % ends

ZCS2 monomer Initiator [RAFT]a) (∘ C)b) removedc) References
S St AIBN 20 80 (100) [440]

H3CS
S
S St AIBN 20 80 24 [195]
C4H9S
S
S St AIBN 100 80 64 [195]

C4H9S
S
S St AIBN+LPO 20+2 80 100 [195]

C4H9S
S
S St AIBN 20 80 ∼95 [10]

C4H9S
S
S St AIBN (20) 80 (100) [862]

S
S
a) Mole ratio of initiator to RAFT-synthesized polymer.

b) Temperature.
c) Percentage of end-groups removed. Where details of polymer characterization are not
provided the values appear in parentheses.
d) Nanoparticle dispersion.
lifetime of intermediate radicals formed by radical addition to the trithiocarbonate,

which reduced the complications from intermediate radical termination.
For polymers based on monosubstituted monomers (BA, St) the efficiency of
end-group removal by radical-induced coupling is significantly lower than for those
based on 1,1-disubstituted monomers (MMA) [195]. The problem relates to the
homolytic leaving group ability of the propagating species and is noticeable when
a dialkyldiazene, such as AIBN, is used as a radical source. Use of a dialkyldiazene
and a peroxide (lauroyl peroxide [LPO] or BPO) in combination is substantially
more effective than the use of a dialkyldiazene alone [195]. The peroxide-derived
radicals are poor homolytic leaving groups relative to the propagating radicals, while
the dialkyldiazene-derived radicals are more effective in trapping the propagating
species [195].
9.21.2 Trithiocarbonate Group Removal by Radical-Induced

Disproportionation
A method for removing thiocarbonylthio groups by radical-induced disproportion-
ation involves the use of a triakylborane (most often triethylborane) and oxygen to
Table 9.25 Trithiocarbonate-group removal by radical-induced disproportionation.
Trithiocarbonate
group Polymer Initiator Comment References
S St B(C2 H5 )3 /O2 Product is PSt-H plus some PSt-PSt. [863]

C12H25S Ethylene is also formed.
S
S MA B(C2 H5 )3 /O2 Product is PMA-H plus minor [863]
C12H25S products. Ethylene is also formed.
S
generate ethyl radicals that react with macroRAFT agents to produce a propagat-
ing species by irreversible addition–fragmentation [863]. These react with further
ethyl radicals mainly by disproportionation by H-transfer to the propagating species.
Smaller amounts of other chain ends may also be formed. The process appears to pro-
vide rapid and quantitative end-group removal. Examples of applying the method to
remove trithiocarbonate ends are shown in Table 9.25.
9.21.3 Trithiocarbonate Group Removal by Radical-Induced Reduction

Radical-induced reduction allows the thiocarbonylthio group of RAFT-synthesized
polymers to be replaced with a hydrogen atom (for example see Table 9.26)
[199, 866, 867]. The process involves treating a polymer with a radical source in the
presence of H-donor transfer agents, such as stannanes, silanes, or hypophosphites
[199]. The efficiency of end-group removal depends on the polymer, the hydrogen
atom donor, and the radical source. Peroxide initiators (LPO, BPO) appear generally
more effective than dialkyldiazenes such as AIBN [199]. This is attributed to the
peroxide-derived radicals being poor homolytic leaving groups and thus more
effective in displacing the propagating radicals from the RAFT intermediate.
However, the peroxide initiators are also prone to provide end-groups.
The effectiveness of hydrogen donors increases in the series toluene < 2-propanol
< triethylsilane < triphenylsilane ∼ tris(trimethylsilyl)silane < N-ethylpiperidine
hypophosphite < tributylstannane. With poor H-donors such as toluene or
2-propanol radical–radical reaction between propagating radicals competes with
reduction even when they are used in vast excess as the solvent for the reaction.
This is manifest in the products as bimodal molar mass distributions (PBA, PSt) or
unsaturated end-groups (PMMA) [199].
Photo-generation of radicals directly from the RAFT agent offers an alternative
to using conventional initiators and also solves a potential issue associated with the
formation of by-products derived from the initiator [78, 864, 865].
Cooperative reduction of trithiocarbonate groups making use of a thiol as a polar-
ity reversal catalyst in conjunction with a hydrosilane as the apparent reducing agent
is more effective. Thus a combination of C12 H25 SH and Ph3 SiH has been used [78].
The use of either reagent alone was less successful.
Table 9.26 Trithiocarbonate group removal by radical-induced reduction.
Trithiocarbonate group Polymer Initiator Reagenta) References
S BA, St BPO, LPO Toluene [199]

C12H25S
S
S BA BPO Toluene/iPrOH [199]
C12H25S
S
S MMA BPO Toluene/PrOH [199]
C12H25S
S
S MMA ACHN EPHP [199]
C12H25S
S
S MA, DMAm h𝜈 Bu3 SnH [864]
C12H25S
S
S MA AIBN or h𝜈 C12 H25 SH/Ph3 SiH [78]
C2H5S
S
S MA AIBN or h𝜈 C12 H25 SH/Ph3 SiH [78]
S
S
S tBA h𝜈 PTH-NBu3 -HCOOH [865]
C12H25S
S
a) EPHP, N-ethylpiperidine hypophosphate; PTH, 10-phenylphenothiazine.
9.21.4 Trithiocarbonate Group Removal by Reaction with Nucleophiles

The thiocarbonylthio end-group of RAFT-synthesized polymers can be removed by
reaction with nucleophiles to replace the RAFT-end with a thiol-end [868, 869].
The theoretically estimated order of reactivity of RAFT end-groups towards primary
amine nucleophiles is dithioacetate ≥ dithiobenzoate > xanthate ≥ trithiocarbonate
≫ dithiocarbamate [869]. For examples of removal of trithiocarbonate ends through
reaction with nucleophiles, see Table 9.27.
Often conversion of a trithiocarbonate group to a thiol end-group is preliminary
to use of the thiol end-group in a thio-Michael reaction or other chemistry [870].
9.21.5 Trithiocarbonate Group Removal by Thermolysis

Studies on the thermolysis of trithiocarbonates are summarized in Table 9.28. The
trithiocarbonate group can be thermally labile at temperatures >100 ∘ C when,
depending on substituents, it becomes susceptible to C—S bond homolysis and
direct (Chagaev-type) elimination (Schemes 9.12–9.14). Mechanisms for end-group
loss by thermolysis are discussed in reviews on end-group transformation [855].
The onset temperature also depends on reaction conditions (e.g. the medium and
the presence of radical sources).
Table 9.27 Trithiocarbonate group removal through reaction with nucleophiles.
Trithiocarbonate group Polymer Reagent (solvent)a) Comment References
S St HA/TEA (DMF) RT 12 h [220]

C12H25S
S
S NIPAm HA (CH2 Cl2 ) RT 24 h [540]
C3H7S
S
S St Pip (THF) Reflux 1 h [6]
S
S
S
S
S
S MA, DMAm, hydrazine hydrate RT 1–5 min [240]
C2H5S NIPAm, St (DMF) no disulfide
S
formation
S MA, DMAm, Butylamine (DMF) RT 1–20 h [240]
C2H5S NIPAm, St
S
a) HA, hexylamine; Pip, piperidine; RT, room temperature; TEA, triethylamine; THF,
tetrahydrofuran.
Table 9.28 End-group removal by thermolysis.
Trithiocarbonate group Polymer Temperature (∘ C) Comment References
S St, 4VP 165 In solution (DEG, [871]

C12H25S nitrobenzene) with
S Pn Cu(0) catalyst
S St 140 Z-attached stars [872]
S
S Pn
O
O
S St, BA 100–200 Mid-chain [873]
S trithiocarbonate
Pn S Pn
S St, BA 100–200 [873]

C12H25S
S Pn
S St, BA, St/BA [12]

S
Pn S Pn
S MA 220 End-group removal [185]

C12H25S in flow
S Pn
S St 220 End-group removal [185]

H3CS in flow
S Pn
S MMA 220 [183]

H3CS
S Pn
S MMA Comparison with [206]

C12H25S dithiobenzoate
S Pn
S S C4H9
H S S C4H9
S
Ei SH
+
Ph Ph Ph Ph
Scheme 9.12 Trithiocarbonate group loss by Chagaev elimination (e.g. PSt). Ei ,

electrocyclic intramolecular.
H
S S
C4H9 S S
C4H9
B B B S B B B
S
H
+ other products
B B B B B B
Scheme 9.13 Trithiocarbonate group loss by homolysis followed by backbiting and chain
scission (e.g. PBA). Multiple backbiting reactions may occur in succession.
S
S
Homolysis CS2
S S
S S (CH3S∙)
M M M M
Unzipping
–CH2 = C(CH3)M
R
Disproportionation M
+ other products
M
H
M
Scheme 9.14 Trithiocarbonate group loss by homolysis followed by unzipping (e.g. PMMA).
9.21.6 Trithiocarbonate Group Removal by Oxidation

Examples of trithiocarbonate group removal by oxidation are shown in Table 9.29.
[9, 874–877]. The process has been demonstrated for dithiobenzoates [874, 877],
trithiocarbonates [874, 875], and xanthates [876]. The processes reportedly
[874, 876] lead to the thiocarbonylthio group being replaced with a hydroxyl group
but the chemistry has not been established in most cases.
9.22 Conclusions and Outlook
This chapter provided a survey of the synthesis, reactions, and applications of

trithiocarbonates RAFT agents. Only the more common agents were included in
the detailed survey. Trithiocarbonates have some limitations. Dithioesters may offer
lower dispersities with 1,1-disubsituted MAMs. Xanthates and dithiocarbamates
Abbreviations 447
Table 9.29 Trithiocarbonate group removal by oxidation.
Trithiocarbonate group Polymer Reagent References
S HPMA H2 O2 [874]
S
S Pn
S AA/MA/EHA H2 O2 [875]
C12H25S
S Pn
may be more suited to mediating polymerization of LAMs. Nonetheless, trithiocar-

bonates are currently the most popular, and perhaps most versatile, form of RAFT
agent for mediating radical polymerization. Trithiocarbonates are also effective
as initiators in direct photoRAFT, in PET RAFT in redox RAFT, and in mediated
eRAFT. The trithiocarbonate group is generally stable under the conditions usually
used for radical polymerization yet is readily transformed post-RAFT polymeriza-
tion. We anticipate that the use of trithiocarbonates as RAFT agents will continue
to grow.
Abbreviations
Abbreviations are listed alphabetically by the abbreviated term. In general, abbrevi-
ations of methacrylates end with ‘MA’, methacrylamides end with ‘MAm’, acrylates
end with ‘A’. acrylamides end with ‘Am’ or begin with ‘NA’ (for N-acryloyl). Except
as indicated below the suffix ‘P’ is an abbreviation for ‘poly()’. Thus, poly(methyl
methacrylate) is abbreviated as PMMA. The abbreviations often reflect common
usage rather than IUPAC names. For some entries, alternative names are provided
within parentheses, and IUPAC names are provided within brackets.
AA acrylic acid
AcO− acetate
[4,4′ -(diazene-1,2-diyl)bis(4-cyanopentanoic acid)]
AcS 4-acetoxystyrene
AdA 1-adamantyl acrylate (202)
AEMA 2-aminoethyl methacrylate (or hydrochloride salt (326))
AEMAm N-(2-aminoethyl)methacrylamide
AEP 2-(acryloyloxy)ethyl phosphate
AIBN 2,2′ -azobis(2-methylpropionitrile)
[2,2′ -(diazene-1,2-diyl)bis(2-methylpropanenitrile)]
Am acrylamide
AMA allyl methacrylate
AMPS 2-acrylamido-2-methylpropane-1-sulfonic acid sodium salt (237)
AN acrylonitrile
APAm N-(2-aminopropyl)acrylamide
BA butyl acrylate
BAm N-butylacrylamide
Bd butadiene
BisGMA bisphenylglycidyl dimethacrylate [((propane-2,2-diylbis(4,1-
phenylene))bis(oxy))bis(2-hydroxypropane-3,1-diyl)
bis(2-methylacrylate)]
BMDO 5,6-benzo-2-methylene-1,3-dioxepane (362)
BPO benzoyl peroxide [benzoic peroxyanhydride]
BzAm N-benzylacrylamide
BzMAm N-benzylmethacrylamide
CEMA 2-chloroethyl methacrylate
CHAm N-cyclohexylacrylamide
CHMA cyclohexyl methacrylate
CIPEA 2-chloropropionyloxyethyl acrylate
CL caprolactone [oxepan-2-one]
CMA cholesteryl methacrylate (165)
CMS 4-chloromethylstyrene
Cp chloroprene
CPA 3-chloropropyl acrylate
CS 4-chlorostyrene
CTA chain transfer agent
DA dodecyl acrylate (lauryl acrylate)
DAAm diacetone acrylamide [N-(2-methyl-4-oxopentan-2-yl)acrylamide]
DADMAC diallyl dimethyl ammonium chloride (Table 9.18)
DDMAT 2-(Dodecylthiocarbonothioylthio)-2-methylpropanoic acid
(S-Dodecyl-S′ -(α,α′ -dimethyl-α′′ -acetic acid)trithiocarbonate) (51)
DEAEMA (2-diethylamino)ethyl methacrylate
DEGA (diethylene glycol monomethyl ether) acrylate
DEGDA (diethylene glycol) diacrylate
DEGDMA (diethylene glycol) dimethacrylate
DMAEA (2-dimethylamino) ethyl acrylate
DMAEAm N-(2-(dimethylamino)ethyl)acrylamide
DMAEMA (2-dimethylamino)ethyl methacrylate
DMAPMAm N-[3-(Dimethylamino)propyl]methacrylamide
DMF N,N-dimethylformamide
DMOS 3,4-dimethoxystyrene
DMSO dimethyl sulfoxide
DSDM disulfide dimethacrylate [bis(2-methacryloyloxy)ethyl disulfide
(368)]
Abbreviations 449
DSDAm disulfide diacrylamide (N,N-bis(acryloyl)cystamine (374))

DSDA disulfide diacrylate [bis(2-acryloyloxy)ethyl disulfide (372)]
DVB divinylbenzene
DVE divinyl ether
DVPP diphenyl(4-vinylphenyl)phosphane
EGDA ethylene glycol diacrylate
EGDMA ethylene glycol dimethacrylate
EMAm N-ethyl-N-methylacrylamide
ESARA exchange of substituents between (macro)alkoxyamines and
(macro)RAFT agents
FMA furfuryl methacrylate
EPR electron paramagnetic resonance spectroscopy
eRAFT electrochemically initiated RAFT polymerization
GA glycolic acid
GMMA glycerol monomethacrylate (146) (2,3-dihydroxypropyl
methacrylate)
HADA 3-hydroxy-1-adamantyl acrylate
HADM 3-hydroxy-1-adamantyl methacrylate (171)
HDDA hexanediol diacrylate (371)
HDFDMA 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl
methacrylate
HEAm N-(2-hydroxylethyl)acrylamide
HMS 4-hydroxymethylstyrene
HPMAm N-(2-hydroxylpropyl)methacrylamide
iAA isoamyl acrylate
iBoA isobornyl acrylate
IBVE isobutyl vinyl ether
Ind indene
Ip isoprene
IPMA isopropyl methacrylate
LA lactic acid (stereoisomers not distinguished)
LMA lauryl methacrylate [dodecyl methacrylate]
LAm N-laurylacrylamide [N-dodecylacrylamide]
LAM less activated monomer
Lim limonene
LPO lauroyl peroxide (dodecanoyl peroxide) [dodecanoic
peroxyanhydride]
MA methyl acrylate
MADA 2-methyl-2-adamantyl acrylate
MADIX macromolecular design by interchange of xanthates
MADM 2-methyl-2-adamantyl methacrylate (172)
MAM more activated monomer

MBAm methylene-bis-acrylamide
MEA 2-methoxyethyl acrylate
MEMA 2-methoxyethyl methacrylate
MEP 2-methacryloylethyl phosphate
MeS 4-methylstyrene
METAC [2-(methacryloyloxy)ethyl]trimethylammonium chloride
MMBL γ-methyl-α-methylene-γ-butyrolactone
[5-methyl-3-methylenedihydrofuran-2(3H)-one]
MPAm N-(3-methoxypropyl)acrylamide
MPC (methacryloyloxy)ethyl phosphorylcholine (175)
NAS N-acryloylsuccinimide
NEAm N-ethylacrylamide
NIPMAm N-isopropylmethacrylamide
NMP nitroxide-mediated polymerization [aminoxyl-mediated radical
polymerization]
NPFPMI N-perfluorophenylmaleimide
OAm N-octylacrylamide
OBA 3-oxobutyl acrylate
ODA octadecyl acrylate
ODMA octadecyl methacrylate
OeMA oleyl methacrylate
OFPA 2,2,3,3,4,4,5,5-octafluoropentyl acrylate
OPA 2-oxopropyl acrylate (acetonyl acrylate)
OTf- triflate [trifluoromethanesulfonate]
PA propargyl acrylate
PAA propacrylic acid [2-methylenebutanoic acid]
PAm N-propylacrylamide
PDL ω-pentadecalactone [oxacyclohexadecan-2-one]
PEA 2-phenylethyl acrylate
PEG poly(ethylene glycol)
PEGA (polyethylene glycol monomethyl ether) acrylate [includes OEGA
(oligoethylene glycol monomethyl ether) acrylate
PEGDA polyethylene glycol diacrylate
PEGDMA polyethylene glycol dimethacrylate
Abbreviations 451
PEGMA (polyethylene glycol monomethyl ether) methacrylate [also includes

OEGMA (oligoethylene glycol monomethyl ether) methacrylate
PET-RAFT photoinduced electron or energy transfer-RAFT
PET-SUMI photoinduced electron or energy transfer-single-unit monomer
insertion
PFOEA 2-(perfluorooctyl)ethyl acrylate
[3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl acrylate]
PFOEMA 2-(perfluorooctyl)ethyl methacrylate [3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,
10-heptadecafluorodecyl methacrylate]
PFPA perfluorophenyl acrylate (305)
PhMAm N-phenylmethacrylamide
PIPBAm 1,4-bis(acryloyl)piperazine
PLP pulsed laser photolysis
PMA pentyl methacrylate
RDRP reversible-deactivation radical polymerization
SSO3Na sodium 4-styrenesulfonate
St styrene
SUMI single-unit monomer insertion
tBAm N-tert-butylacrylamide
tBDMSMA tert-butyldimethylsilyl methacrylate (332)
tBDMSOS 4-(tert-butyldimethylsilyloxy)styrene (331)
tBOS 4-tert-butyloxystyrene
tBS 4-tert-butylstyrene
TBSiMA tributylsilyl methacrylate (333)
TEGA (tetraethylene glycol monomethyl ether) acrylate
TFEA 2,2,2-trifluoroethyl acrylate
TFPMA 2,2,3,3-tetrafluoropropyl methacrylate
THFA tetrahydrofurfuryl acrylate [(tetrahydrofuran-2-yl)methyl acrylate]
THPA tetrahydropyran-2-yl acrylate [tetrahydro-2H-pyran-2-yl acrylate]
TMAPMA (3-trimethylaminonium)propyl methacrylate
TPSiMA triisopropylsilyl methacrylate (334)
TrMA trityl methacrylate
VAc vinyl acetate
3VBA 3-vinylbenzaldehyde
VBA 4-vinylbenzoic acid
VPBA (4-vinylphenyl)boronic acid
VL γ-valerolactone [tetrahydro-2H-pyran-2-one]
4HS 4-hydroxystyrene
2VP 2-vinylpyridine
4VP 4-vinylpyridine
References
living characteristics. (DuPont/CSIRO), WO9801478A1.
2 Corpart, P., Charmot, D., Biadatti, T., et al. (1998). Block polymer synthesis by
controlled radical polymerization. (Rhodia Chimie), WO9858974A1.
243–245. https://doi.org/10.1021/ma991451a.
45: 5321–5342. https://doi.org/10.1021/ma300410v.
6 Moad, G., Chong, Y.K., Rizzardo, E. et al. (2005). Polymer 46: 8458–8468.
7 Gao, Y., Lv, L., Zou, G., and Zhang, Q. (2017). Macromol. Res. 25: 931–935.
https://doi.org/10.1007/s13233-017-5099-4.
https://doi.org/10.1021/ma9804951.
11 Chernikova, E.V., Terpugova, P.S., Baskakov, A.A. et al. (2010). Polym. Sci., Ser.
B 52: 119–128. https://doi.org/10.1134/S1560090410030012.
12 Chernikova, E.V., Plutalova, A.V., Garina, E.S., and Vishnevetsky, D.V. (2016).
Polym. Chem. 7: 3622–3632. https://doi.org/10.1039/C6PY00301J.
13 Houshyar, S., Keddie, D., Moad, G. et al. (2012). Polym. Chem. 3: 1879–1889.
14 Haven, J.J., Hendrikx, M., Junkers, T. et al. (2018). Elements of RAFT Nav-
(co)polymers. In: Reversible Deactivation Radical Polymerization: Mechanisms
and Synthetic Methodologies, vol. 1284 (eds. K. Matyjaszewski, H. Gao, B.S.
Sumerlin and N.V. Tsarevsky), 77–103. Washington, DC: ACS Symposium
Series, American Chemical Society. https://doi.org/10.1021/bk-2018-1284.ch004.
E. Rizzardo). Weinheim: Wiley-VCH, 611–646.
Rizzardo). Weinheim: Wiley-VCH, 647–678.
17 Ran, R., Chen, Z., and Wang, X.L. (2009). J. Appl. Polym. Sci. 111: 2011–2017.
https://doi.org/10.1002/app.29262.
References 453
18 Bicciocchi, E., Chong, Y.K., Giorgini, L. et al. (2010). Macromol. Chem. Phys.
19 De Rybel, N., Van Steenberge, P.H.M., Reyniers, M.-F. et al. (2018). Chem. Eng.
Sci. 177: 163–179. https://doi.org/10.1016/j.ces.2017.11.043.
2273–2283. https://doi.org/10.1021/ma020883+.
21 Strube, O.I., Nothdurft, L., Drache, M., and Schmidt-Naake, G. (2011). Macro-
mol. Chem. Phys. 212: 574–582. https://doi.org/10.1002/macp.201000572.
22 Grigoreva, A., Polozov, E., and Zaitsev, S. (2019). Colloid Polym. Sci. https://doi
.org/10.1007/s00396-019-04559-6.
23 Fuchs, A.V. and Thurecht, K.J. (2017). ACS Macro Lett. 6: 287–291. https://doi
24 Grigoreva, A., Polozov, E., and Zaitsev, S. (2020). J. Fluorine Chem. 232: 109484.
https://doi.org/10.1016/j.jfluchem.2020.109484.
25 Theis, A., Feldermann, A., Charton, N. et al. (2005). Macromolecules 38:
2595–2605. https://doi.org/10.1021/ma047476d.
9783527622757.ch3.
27 Theis, A., Feldermann, A., Charton, N. et al. (2005). Polymer 46: 6797–6809.
28 Buback, M., Hesse, P., Junkers, T., and Vana, P. (2006). Macromol. Rapid Com-
Applications (eds. G. Moad and E. Rizzardo). Weinheim: Wiley-VCH, 95–138.
30 Walling, C. (1948). J. Am. Chem. Soc. 70: 2561–2564. https://doi.org/10.1021/
ja01187a079.
31 O’Brien, J.L. and Gornick, F. (1955). J. Am. Chem. Soc. 77: 4757–4763. https://
doi.org/10.1021/ja01623a019.
32 Smith, W.V. (1946). J. Am. Chem. Soc. 68: 2059–2064. https://doi.org/10.1021/
ja01214a055.
33 Gregg, R.A., Alderman, D.M., and Mayo, F.R. (1948). J. Am. Chem. Soc. 70:
3740–3743. https://doi.org/10.1021/ja01191a058.
Weinheim: Wiley-VCH, 223–370.
37 Derboven, P., Van Steenberge, P.H.M., Reyniers, M.-F. et al. (2016). Macromol.
Theory Simul. 25: 104–115. https://doi.org/10.1002/mats.201500076.

(2010). Macromol. Rapid Commun. 31: 1846–1862. https://doi.org/10.1002/marc
.200900907.
41 Lin, C.Y. and Coote, M.L. (2009). Aust. J. Chem. 62: 1479–1483. https://doi.org/
10.1071/ch09269.
42 Meiser, W., Buback, M., and Sidoruk, A. (2013). Macromol. Chem. Phys. 214:
43 Barth, J., Buback, M., Meiser, W., and Vana, P. (2010). Macromolecules 43:
51–54. https://doi.org/10.1021/ma902111z.
44 Golubev, V.B., Filippov, A.N., Chernikova, E.V. et al. (2011). Polym. Sci., Ser. C
53: 14–26. https://doi.org/10.1134/s1811238211040023.
46 Moad, G., Rizzardo, E., and Thang San, H. (2013). Fundamentals of RAFT
polymerization. In: Fundamentals of Controlled/Living Radical Polymerization,
RSC Polymer Chemistry Series No. 4 (eds. N.V. Tsarevsky and B.S. Sumerlin),
205–249. Cambridge: Royal Society of Chemistry. https://doi.org/10.1039/
9781849737425-00205.
Moad and E. Rizzardo). Weinheim: Wiley-VCH, 495–550.
.org/10.1002/pola.29199.
49 Fischer, H. and Radom, L. (2001). Angew. Chem. Int. Ed. 40: 1340–1371. https://
doi.org/10.1002/1521-3773(20010417)40:8<1340::AID-ANIE1340>3.0.CO;2-%23.
50 Moad, G. (2017). Macromol. Chem. Phys. 218: 1700381. https://doi.org/10.1002/
macp.201700381.
52 Fortenberry, A.W., McCormick, C.L., and Smith, A.E. (2022). Considerations
for and applications of aqueous RAFT polymerization. In: RAFT Polymeriza-
Weinheim: Wiley-VCH, 679–706.
54 Lai, J.T., Filla, D., and Shea, R. (2002). Macromolecules 35: 6754–6756. https://
doi.org/10.1021/ma020362m.
macp.201300562.
References 455
56 Moad, G., Keddie, D., Guerrero-Sanchez, C. et al. (2015). Macromol. Symp. 350:
57 Postma, A., Davis, T.P., Li, G. et al. (2006). Macromolecules 39: 5307–5318.
https://doi.org/10.1021/ma0604338.
58 Xu, J., Fu, C., Shanmugam, S. et al. (2017). Angew. Chem. Int. Ed. 56:
59 Easterling, C.P., Xia, Y., Zhao, J. et al. (2019). ACS Macro Lett. 8: 1461–1466.
60 Chang, K., Dicke, Z.T., and Taite, L.J. (2012). J. Polym. Sci., Part A: Polym.
61 Leung, D. and Bowman, C.N. (2012). Macromol. Chem. Phys. 213: 198–204.
63 Qu, T., Wang, A., Yuan, J. et al. (2009). Colloids Surf., B 72: 94–100. https://doi
.org/10.1016/j.colsurfb.2009.03.020.
64 Ma, J., Yang, C., Luo, J. et al. (2012). J. Macromol. Sci., Part A 49: 321–329.
https://doi.org/10.1080/10601325.2012.662068.
65 Zhao, X. and Shan, G. (2019). Colloid Polym. Sci. 297: 1353–1363. https://doi
.org/10.1007/s00396-019-04556-9.
66 Chou, Y.-N., Venault, A., Cho, C.-H. et al. (2017). Langmuir 33: 9822–9835.
67 Millard, P.-E., Barner, L., Stenzel, M.H. et al. (2006). Macromol. Rapid Com-
68 Das, P., Zhong, W., and Claverie, J. (2011). Colloid. Polym. Sci.: 1–15. https://doi
.org/10.1007/s00396-011-2466-0.
69 Hart-Smith, G., Lovestead, T.M., Davis, T.P. et al. (2007). Biomacromolecules 8:
2404–2415. https://doi.org/10.1021/bm700526j.
70 López-Pérez, L., Maldonado-Textle, H., Elizalde-Herrera, L.E. et al. (2019). Poly-
mer 168: 116–125. https://doi.org/10.1016/j.polymer.2019.02.025.
71 Yu, L., Wei, Y., Tu, Y. et al. (2018). J. Polym. Sci., Part A: Polym. Chem. 56:
72 Huang, Z., Qiu, T., Xu, H. et al. (2018). Macromolecules 51: 7329–7337. https://
73 Wang, R., McCormick, C.L., and Lowe, A.B. (2005). Macromolecules 38:
9518–9525. https://doi.org/10.1021/ma050669w.
75 Jiang, X.L., Schoenmakers, P.J., van Dongen, J.L.J. et al. (2003). Anal. Chem. 75:
5517–5524. https://doi.org/10.1021/ac034556r.
76 Jiang, W., Lu, L., and Cai, Y. (2007). Macromol. Rapid Commun. 28: 725–728.
77 Reyhani, A., Ranji-Burachaloo, H., McKenzie, T.G. et al. (2019). Macromolecules
52: 3278–3287. https://doi.org/10.1021/acs.macromol.9b00038.
78 Uchiyama, M., Satoh, K., and Kamigaito, M. (2019). Chem. Commun. 55:
5327–5330. https://doi.org/10.1039/C9CC00900K.
79 Hendrich, M., Lewerdomski, L., and Vana, P. (2015). J. Polym. Sci., Part A:
Polym. Chem. https://doi.org/10.1002/pola.27753.
80 Haraguchi, K., Kubota, K., Takada, T., and Mahara, S. (2014). Biomacro-
molecules 15: 1992–2003. https://doi.org/10.1021/bm401914c.
81 Haraguchi, K., Takehisa, T., Mizuno, T., and Kubota, K. (2015). ACS Biomater.
Sci. Eng. 1: 352–362. https://doi.org/10.1021/acsbiomaterials.5b00079.
82 Liu, Y., Hu, X., Meng, M. et al. (2016). Chem. Eng. J. 302: 609–618. https://doi
.org/10.1016/j.cej.2016.05.097.
83 Lewis, R.W., Evans, R.A., Malic, N. et al. (2017). Polym. Chem. 8: 3702–3711.
8941–8950. https://doi.org/10.1021/ma048199d.
85 Sogabe, A., Flores, J.D., and McCormick, C.L. (2010). Macromolecules 43:
6599–6607. https://doi.org/10.1021/ma1008463.
86 Nuopponen, M., Kalliomaki, K., Laukkanen, A. et al. (2008). J. Polym. Sci., Part
87 Kirkland, S.E., Hensarling, R.M., McConaughy, S.D. et al. (2008). Biomacro-
molecules 9: 481–486. https://doi.org/10.1021/bm700968t.
88 Demirel, G., Rzaev, Z., Patir, S., and Piskin, E. (2009). J. Nanosci. Nanotechnol.
9: 1865–1871. https://doi.org/10.1166/jnn.2009.388.
89 Wu, J., Sun, X., Zhang, R. et al. (2016). Colloid Polym. Sci. 294: 1989–1995.
https://doi.org/10.1007/s00396-016-3958-8.
90 Díaz-Silvestre, S.E., St Thomas, C., Maldonado-Textle, H. et al. (2018). Colloid
Polym. Sci. 296: 1699–1710. https://doi.org/10.1007/s00396-018-4391-y.
91 Chen, M., Deng, S., Gu, Y. et al. (2017). J. Am. Chem. Soc. 139: 2257–2266.
92 Lokitz, B.S., Convertine, A.J., Ezell, R.G. et al. (2006). Macromolecules 39:
8594–8602. https://doi.org/10.1021/ma061672y.
93 Zhou, S., Zhang, D., Bai, L. et al. (2016). Polymers 8: 135. https://doi.org/10
.3390/polym8040135.
94 Zhang, Y., Wen, X., Shi, Y. et al. (2019). Ind. Eng. Chem. Res. 58: 1142–1149.
https://doi.org/10.1021/acs.iecr.8b04913.
95 Ran, R., Wan, T., Gao, T. et al. (2008). Polym. Int. 57: 28–34. https://doi.org/10
.1002/pi.2307.
96 Li, W., Thanneeru, S., Kanyo, I. et al. (2015). ACS Macro Lett. 4: 736–740.
97 Cetintas, M. and Kamperman, M. (2016). Polymer 107: 387–397. https://doi.org/
10.1016/j.polymer.2016.08.033.
98 Kajita, T., Tanaka, H., Noro, A. et al. (2019). J. Mater. Chem. A 7: 15585–15592.
https://doi.org/10.1039/C9TA01890E.
99 Noro, A., Matsushita, Y., and Lodge, T.P. (2008). Macromolecules 41: 5839–5844.
References 457
100 Luo, J., Li, M., Xin, M. et al. (2016). Macromol. Chem. Phys. 217: 1777–1784.
101 Chernikova, E., Poteryaeva, Z., Belyaev, S., and Sivtsov, E. (2011). Russ. J. Appl.
Chem. 84: 1031–1039. https://doi.org/10.1134/s1070427211060231.
102 Chernikova, E.V., Kishilov, S.M., Plutalova, A.V. et al. (2014). Polym. Sci., Ser. B
56: 553–565. https://doi.org/10.1134/s1560090414050029.
103 Li, C., Liu, H., and Li, Y. (2011). Macromol. Chem. Phys. 212: 1050–1055.
104 Bilalis, P., Pitsikalis, M., and Hadjichristidis, N. (2006). J. Polym. Sci., Part A:
105 Tominey, A.F., Liese, J., Wei, S. et al. (2010). Beilstein J. Org. Chem. 6: 66.
https://doi.org/10.3762/bjoc.6.66.
106 Liu, X.-M., Quan, L.-D., Tian, J. et al. (2008). Pharm. Res. 25: 2910–2919.
https://doi.org/10.1007/s11095-008-9683-3.
107 Deng, Z.C., Bouchekif, H., Babooram, K. et al. (2008). J. Polym. Sci., Part A:
108 Rossi, N.A.A., Jadhav, V., Lai, B.F.L. et al. (2008). J. Polym. Sci., Part A: Polym.
109 Rossi, N.A.A., Zou, Y., Scott, M.D., and Kizhakkedathu, J.N. (2008). Macro-
molecules 41: 5272–5282. https://doi.org/10.1021/ma800606k.
110 Jiang, X., Ahmed, M., Deng, Z., and Narain, R. (2009). Bioconjugate Chem. 20:
994–1001. https://doi.org/10.1021/bc800566f.
111 Zhao, C., Dolmans, L., and Zhu, X.X. (2019). Macromolecules 52: 4441–4446.
112 Ran, F., Nie, S., Li, J. et al. (2012). Macromol. Biosci. 12: 116–125. https://doi
.org/10.1002/mabi.201100249.
113 Wei, X., Wu, J., Zhao, G. et al. (2018). Mol. Pharm. 15: 3456–3467. https://doi
.org/10.1021/acs.molpharmaceut.8b00433.
114 Tamate, R., Takahashi, K., Ueki, T. et al. (2017). Biomacromolecules 18:
115 Pang, D.-X., Liu, W.-D., Li, T. et al. (2011). J. Appl. Polym. Sci. 119: 2953–2960.
116 Ran, F., Nie, S., Zhao, W. et al. (2011). Acta Biomater. 7: 3370–3381. https://doi
.org/10.1016/j.actbio.2011.05.026.
117 Vishnevetskii, D.V., Chernikova, E.V., Garina, E.S., and Sivtsov, E.V. (2013).
Polym. Sci., Ser. B 55: 515–525. https://doi.org/10.1134/s156009041308006x.
118 Bugakov, M.A., Boiko, N.I., Chernikova, E.V., and Shibaev, V.P. (2013). Polym.
Sci., Ser. B 55: 294–303. https://doi.org/10.1134/s1560090413050011.
119 Bugakov, M.A., Boiko, N.I., Chernikova, E.V. et al. (2018). Polym. Sci., Ser. C 60:
3–13. https://doi.org/10.1134/S1811238218010022.
120 Chernikova, E., Poteryaeva, Z., Belyaev, S. et al. (2011). Polym. Sci., Ser. B 53:
391–403. https://doi.org/10.1134/s1560090411070013.
121 Boiko, N.I., Bugakov, M.A., Chernikova, E.V. et al. (2015). Polym. Chem. 6:
122 Bugakov, M., Boiko, N., Abramchuk, S. et al. (2020). J. Mater. Chem. C 8:
1225–1230. https://doi.org/10.1039/C9TC06397H.
123 Bertrand, A., Chen, S., Souharce, G.g. et al. (2011). Macromolecules 44:
3694–3704. https://doi.org/10.1021/ma200540u.
124 Chen, M. and Johnson, J.A. (2015). Chem. Commun. 51: 6742–6745. https://doi
.org/10.1039/C5CC01562F.
125 Lamb, J.R., Qin, K.P., and Johnson, J.A. (2019). Polym. Chem. 10: 1585–1590.
https://doi.org/10.1039/C9PY00022D.
126 Chen, M., MacLeod, M.J., and Johnson, J.A. (2015). ACS Macro Lett. 4:
127 Harrisson, S. and Wooley, K.L. (2005). Chem. Commun.: 3259–3261. https://doi
.org/10.1039/b504313a.
128 Nguyen, D., Zondanos, H.S., Farrugia, J.M. et al. (2008). Langmuir 24:
2140–2150. https://doi.org/10.1021/la7027466.
129 Albertin, L., Wolnik, A., Ghadban, A., and Dubreuil, F. (2012). Macromol.
130 Lorenzo, M.M., Decker, C.G., Kahveci, M.U. et al. (2016). Macromolecules 49:
131 Srivastava, N., Saxena, M., and Shukla, M. (2019). Rasayan J. Chem. 12:
333–337. https://doi.org/10.31788/rjc.2019.1215038.
132 Tang, B., White, S.P., Frisbie, C.D., and Lodge, T.P. (2015). Macromolecules 48:
133 Chaturvedi, D., Mishra, N., Chaturvedi, A.K., and Mishra, V. (2008). Monats.
Chem. 139: 1467–1470. https://doi.org/10.1007/s00706-008-0956-7.
134 Ladaviere, C., Dorr, N., and Claverie, J.P. (2001). Macromolecules 34: 5370–5372.
135 Majonis, D., Herrera, I., Ornatsky, O. et al. (2010). Anal. Chem. (Washington,
DC, US) 82: 8961–8969. https://doi.org/10.1021/ac101901x.
136 Gu, Y. and Lodge, T.P. (2011). Macromolecules 44: 1732–1736. https://doi.org/10
.1021/ma2001838.
5371–5374. https://doi.org/10.1021/ma050402x.
138 Kiasat, A.R., Badri, R., and Sayyahi, S. (2008). Chin. Chem. Lett. 19: 1301–1304.
553–556. https://doi.org/10.1021/ol0525617.
140 Soleiman-Beigi, M. and Taherinia, Z. (2014). J. Sulfur Chem. 35: 470–476.
https://doi.org/10.1080/17415993.2014.919296.
141 Loiseau, J., Ladaviere, C., Suau, J.M., and Claverie, J. (2005). Polymer 46:
142 Vishnevetskii, D.V., Plutalova, A.V., Yulusov, V.V. et al. (2015). Polym. Sci., Ser.
B 57: 197–206. https://doi.org/10.1134/S1560090415030094.
143 Chernikova, E.V., Zaitsev, S.D., Plutalova, A.V. et al. (2018). RSC Adv. 8:
14300–14310. https://doi.org/10.1039/C8RA00048D.
References 459
144 Lu, W., Wang, Y., Wang, W. et al. (2017). Polym. Chem. 8: 5741–5748. https://doi
.org/10.1039/C7PY01225J.
634–644. https://doi.org/10.1039/b9py00273a.
146 Chernikova, E., Yulusov, V., Mineeva, K. et al. (2011). Polym. Sci., Ser. B 53:
437–447. https://doi.org/10.1134/s1560090411070025.
147 Chernikova, E.V., Terpugova, P.S., Garina, E.S., and Golubev, V.B. (2007). Polym.
Sci., Ser. A 49: 108–119.
148 Li, Z., Serelis, A.K., Reed, W.F., and Alb, A.M. (2010). Polymer 51: 4726–4734.
149 Bivigou-Koumba, A., Görnitz, E., Laschewsky, A. et al. (2010). Colloid. Polym.
Sci. 288: 499–517. https://doi.org/10.1007/s00396-009-2179-9.
150 Zehm, D., Laschewsky, A., Heunemann, P. et al. (2011). Polym. Chem. 2:
151 Skey, J. and O’Reilly, R.K. (2008). Chem. Commun.: 4183–4185. https://doi.org/
10.1039/b804260h.
152 Su, X.L., Zhao, Z.G., Li, H. et al. (2008). Eur. Polym. J. 44: 1849–1856. https://
doi.org/10.1016/j.eurpolymj.2008.03.012.
153 Couture, G. and Améduri, B. (2012). Eur. Polym. J. 48: 1348–1356. https://doi
.org/10.1016/j.eurpolymj.2012.03.020.
154 Bae, S.-k., Lee, S.-Y., and Hong, S.C. (2011). React. Funct. Polym. 71: 187–194.
155 Lefay, C., Glé, D., Rollet, M. et al. (2011). J. Polym. Sci., Part A: Polym. Chem.
156 Bivigou-Koumba, A.M., Kristen, J., Laschewsky, A. et al. (2009). Macromol.
157 Liu, X.H., Zhang, G.B., Lu, X.F. et al. (2006). J. Polym. Sci., Part A: Polym.
158 Chernikova, E., Terpugova, P., Filippov, A. et al. (2009). Russ. J. Appl. Chem. 82:
1882–1889. https://doi.org/10.1134/s1070427209100267.
159 Zamyshlyayeva, O.G., Ionychev, B.N., Frolova, A.I. et al. (2019). Russ. J. Appl.
Chem. 92: 775–786. https://doi.org/10.1134/S1070427219060077.
160 Kaiser, A., Brandau, S., Klimpel, M., and Barner-Kowollik, C. (2010). Macromol.
161 Serbin, A.V., Karaseva, E.N., Dunaeva, I.V. et al. (2011). Polym. Sci., Ser. B 53:
116–124. https://doi.org/10.1134/s1560090411030079.
162 Serbin, A., Karaseva, E., Chernikova, E. et al. (2010). Macromol. Symp. 296:
163 Freal-Saison, S., Save, M., Bui, C. et al. (2006). Macromolecules 39: 8632–8638.
164 Hu, Z.Q., Tao, M., and Zhang, Z.C. (2007). Colloids Surf., A 302: 307–311.
https://doi.org/10.1016/j.colsurfa.2007.02.049.
165 Hu, Z.Q. and Zhang, Z.C. (2006). Macromolecules 39: 1384–1390.
166 Mogami, H. and Mori, H. (2020). ACS Omega 5: 3678–3688. https://doi.org/10
.1021/acsomega.9b04282.
167 Na, H.-K., Kim, H., Son, J.G. et al. (2019). Appl. Surf. Sci. 483: 1069–1080.
https://doi.org/10.1016/j.apsusc.2019.04.059.
168 Shibaev, V., Ivanov, M., Boiko, N., and Chernikova, E. (2009). Dokl. Chem. 427:
183–185. https://doi.org/10.1134/s0012500809080011.
169 O’Reilly, R. and Hansell, C. (2009). Polymers 1: 3–15. https://doi.org/10.3390/
polym1010003.
170 Skrabania, K., Li, W., and Laschewsky, A. (2008). Macromol. Chem. Phys. 209:
172 Samakande, A., Sanderson, R.D., and Hartmann, P.C. (2009). Eur. Polym. J. 45:
173 Skrabania, K., Miasnikova, A., Bivigou-Koumba, A.M. et al. (2011). Polym.
Chem. 2: 2074–2083. https://doi.org/10.1039/C1PY00173F.
174 Schwabe, M., Rotzoll, R., Küchemann, S. et al. (2010). Macromol. Chem. Phys.
175 Miyaji, H., Satoh, K., and Kamigaito, M. (2016). Angew. Chem. Int. Ed. 55:
176 Fei, P. and Cavicchi, K.A. (2010). ACS Appl. Mater. Interfaces 2: 2797–2803.
https://doi.org/10.1021/am100481p.
177 Hinton, T.M., Guerrero-Sanchez, C., Graham, J.E. et al. (2012). Biomaterials 33:
178 Williams, E.G.L., Hutt, O.E., Hinton, T.M. et al. (2017). Biomacromolecules 18:
179 Ojika, M., Satoh, K., and Kamigaito, M. (2017). Angew. Chem. Int. Ed. 56:
180 Hashimoto, H., Takeshima, H., Nagai, T. et al. (2019). Polym. Degrad. Stab. 161:
9262–9271. https://doi.org/10.1021/ma071100t.
182 Rizzardo, E., Chen, M., Chong, B. et al. (2007). Macromol. Symp. 248: 104–116.
184 Lee, T.-Y., Lin, Y.-J., Yu, C.-Y., and Chang, J.-F. (2010). J. Appl. Polym. Sci. 118:
3245–3254. https://doi.org/10.1002/app.32610.
185 Hornung, C.H., Postma, A., Saubern, S., and Chiefari, J. (2014). Polymer 55:
186 Ishitake, K., Satoh, K., Kamigaito, M., and Okamoto, Y. (2009). Angew. Chem.
187 Zhang, B., Lv, X., Zhu, A. et al. (2018). Macromolecules 51: 2776–2784. https://
188 Tao, Y., Satoh, K., and Kamigaito, M. (2011). Macromol. Rapid Commun. 32:
References 461
189 Satoh, K., Lee, D.-H., Nagai, K., and Kamigaito, M. (2013). Macromol. Rapid
Commun. https://doi.org/10.1002/marc.201300638.
190 Huang, H., Sun, B., Huang, Y., and Niu, J. (2018). J. Am. Chem. Soc. 140:
10402–10406. https://doi.org/10.1021/jacs.8b05365.
191 Sivak, L., Subr, V., Tomala, J. et al. (2017). Biomaterials 115: 65–80. https://doi
.org/10.1016/j.biomaterials.2016.11.013.
192 Haridharan, N., Bhandary, R., Ponnusamy, K., and Dhamodharan, R. (2012). J.
.25890.
193 Fu, W., Bai, W., Jiang, S. et al. (2018). Macromolecules 51: 1674–1680. https://
194 Haridharan, N. and Dhamodharan, R. (2011). J. Polym. Sci., Part A: Polym.
196 Luo, C., Fu, W., Li, Z., and Zhao, B. (2016). Polymer 101: 319–327. https://doi
.org/10.1016/j.polymer.2016.08.091.
197 Häussler, M., Lok, P., Chen, M. et al. (2010). Macromolecules 43: 7101–7010.
https://doi.org/10.1021/ma1008572.
198 Satoh, K., Matsuda, M., Nagai, K., and Kamigaito, M. (2010). J. Am. Chem. Soc.
132: 10003–10005. https://doi.org/10.1021/ja1042353.
40: 4446–4455. https://doi.org/10.1021/ma062919u.
200 He, S., Chen, L., Cui, J. et al. (2019). J. Am. Chem. Soc. 141: 19708–19714.
201 Santha Kumar, A.R.S., Roy, M., and Singha, N.K. (2018). Eur. Polym. J. 107:
202 Singha, N.K., Pramanik, N.B., Behera, P.K. et al. (2016). Green Chem. 18:
6115–6122. https://doi.org/10.1039/C6GC01677D.
203 Lokitz, B.S., Wei, J., Hinestrosa, J.P. et al. (2012). Macromolecules 45: 6438–6449.
204 Moad, G., Rizzardo, E., and Thang, S.H. (2011). Strem Chem. 25: 2–10.
205 Bekanova, M.Z., Neumolotov, N.K., Jablanovic, A.D. et al. (2019). Polym. Sci.,
Ser. C 61: 186–197. https://doi.org/10.1134/S1811238219010028.
206 Bekanova, M.Z., Neumolotov, N.K., Jablanović, A.D. et al. (2019). Polym.
Degrad. Stab. 164: 18–27. https://doi.org/10.1016/j.polymdegradstab.2019.03
.017.
207 Fu, Q., McKenzie, T.G., Tan, S. et al. (2015). Polym. Chem. 6: 5362–5368.
208 Shieh, Y.-T., Yeh, Y.-C., and Cheng, C.-C. (2019). ACS Omega 4: 15479–15487.
https://doi.org/10.1021/acsomega.9b01728.
209 Kawatsuki, N., Shoji, H., Inada, Y. et al. (2014). Polym. J. 46: 85–88. https://doi
.org/10.1038/pj.2013.59.
210 Janoschka, T., Teichler, A., Krieg, A. et al. (2012). J. Polym. Sci., Part A: Polym.
211 Cazares-Cortes, E., Baker, B.C., Nishimori, K. et al. (2019). Macromolecules 52:
212 Zhu, Y. and Egap, E. (2020). Polym. Chem. 11: 1018–1024. https://doi.org/10
.1039/C9PY01604J.
213 De Neve, J., Haven, J.J., Harrisson, S., and Junkers, T. (2019). Angew. Chem. Int.
Ed. 58: 13869–13873. https://doi.org/10.1002/anie.201906842.
214 Fu, Q., Xie, K., McKenzie, T.G., and Qiao, G.G. (2017). Polym. Chem. 8:
215 Kametani, Y., Tournilhac, F., Sawamoto, M., and Ouchi, M. (2020). Angew.
216 Abel, B.A. and McCormick, C.L. (2016). Macromolecules 49: 465–474. https://
217 Mann, J.L., Rossi, R.L., Smith, A.A.A., and Appel, E.A. (2019). Macromolecules
52: 9456–9465. https://doi.org/10.1021/acs.macromol.9b02109.
218 Ebata, K., Hashimoto, Y., Ebara, K. et al. (2019). Polym. Chem. 10: 835–842.
219 Moad, G., Chong, Y.K., Mulder, R. et al. (2009). New features of the mecha-
nism of RAFT polymerization. In: Controlled/Living Radical Polymerization.
Progress in RAFT, NMP & OMRP, ACS Symposium Series, vol. 1024 (ed. K.
Matyjaszewski), 3–18. Washington, DC: American Chemical Society https://doi
.org/10.1021/bk-2009-1024.ch001.
220 Pei, M., Ko, J.S., Shin, H. et al. (2018). Macromol. Res. 26: 942–949. https://doi
.org/10.1007/s13233-018-6129-6.
221 Baddam, V., Aseyev, V., Hietala, S. et al. (2018). Macromolecules 51: 9681–9691.
222 Steinkoenig, J., Bloesser, F.R., Huber, B. et al. (2016). Polym. Chem. 7: 451–461.
223 Fokina, A., Lee, Y., Chang, J.H. et al. (2016). Adv. Mater. Interfaces 3: 1600279.
https://doi.org/10.1002/admi.201600279.
224 Ferri, N., Ozaydin, G.B., Zeffiro, A. et al. (2018). J. Polym. Sci., Part A: Polym.
225 Nakabayashi, K., Matsumura, A., Abiko, Y., and Mori, H. (2016). Macro-
226 Nishikawa, T. and Ouchi, M. (2019). Angew. Chem. Int. Ed. 58: 12435–12439.
227 Kametani, Y., Sawamoto, M., and Ouchi, M. (2018). Angew. Chem. Int. Ed. 57:
228 Yu, F., Wang, Y., Hang, Y. et al. (2019). J. Polym. Sci., Part A: Polym. Chem. 57:
229 Benvenuta-Tapia, J.J., Tenorio-López, J.A., and Vivaldo-Lima, E. (2018). Macro-
mol. React. Eng. 12: 1800003. https://doi.org/10.1002/mren.201800003.
230 Liu, R. and Lindsey, J.S. (2019). ACS Macro Lett. 8: 79–83. https://doi.org/10
231 Barlow, K.J., Hao, X., Hughes, T.C. et al. (2014). Polym. Chem. 5: 722–732.
https://doi.org/10.1039/c3py01015e.
References 463
232 Garmendia, S., Lawrenson, S.B., Arno, M.C. et al. (2019). Macromol. Rapid
233 Sayyar, S., Moskowitz, J., Fox, B. et al. (2019). J. Appl. Polym. Sci. 136: 47932.
234 Hou, J., Liu, Y., Liu, Y. et al. (2019). Chem. Eng. Sci. 201: 167–174. https://doi
.org/10.1016/j.ces.2019.02.033.
235 Kumar, R., Lokitz, B.S., Sides, S.W. et al. (2015). RSC Adv. 5: 21336–21348.
https://doi.org/10.1039/C5RA00974J.
236 Wang, S., Li, M., Zhang, H. et al. (2016). J. Polym. Sci., Part A: Polym. Chem. 54:
237 Liu, J., Setijadi, E., Liu, Y. et al. (2010). Aust. J. Chem. 63: 1245–1250. https://
doi.org/10.1071/ch1009110.1071/ch10.
238 Nelson, C.E., Gupta, M.K., Adolph, E.J. et al. (2012). Biomaterials 33:
239 Convertine, A.J., Benoit, D.S.W., Duvall, C.L. et al. (2009). J. Controlled Release
133: 221–229. https://doi.org/10.1016/j.jconrel.2008.10.004.
241 Smith, A.E., Xu, X., Kirkland-York, S.E. et al. (2010). Macromolecules 43:
1210–1217. https://doi.org/10.1021/ma902378k.
242 Convertine, A.J., Diab, C., Prieve, M. et al. (2010). Biomacromolecules 11:
2904–2911. https://doi.org/10.1021/bm100652w.
243 Wais, U., Chennamaneni, L.R., Thoniyot, P. et al. (2018). Polym. Chem. 9:
244 Liu, G., Qiu, Q., Shen, W., and An, Z. (2011). Macromolecules 44: 5237–5245.
245 Zhang, X., Boissé, S.p., Zhang, W. et al. (2011). Macromolecules 44: 4149–4158.
https://doi.org/10.1021/ma2005926.
246 Qiu, Q., Liu, G., and An, Z. (2011). Chem. Commun. 47: 12685–12687. https://
doi.org/10.1039/C1CC15679A.
247 Shen, W., Chang, Y., Liu, G. et al. (2011). Macromolecules 44: 2524–2530.
248 Crownover, E., Duvall, C.L., Convertine, A. et al. (2011). J. Controlled Release
155: 167–174. https://doi.org/10.1016/j.jconrel.2011.06.013.
250 Pan, X., Zhang, F., Choi, B. et al. (2019). Eur. Polym. J. 115: 166–172. https://doi
.org/10.1016/j.eurpolymj.2019.03.016.
251 Treat, N.J., Smith, D., Teng, C. et al. (2012). ACS Macro Lett. 1: 100–104.
https://doi.org/10.1021/mz200012p.
252 Holley, A.C., Ray, J.G., Wan, W. et al. (2013). Biomacromolecules 14: 3793–3799.
https://doi.org/10.1021/bm401205y.
253 Hou, Y., Guo, Y., Qian, S. et al. (2019). Polymer 167: 159–166. https://doi.org/10
.1016/j.polymer.2019.02.008.
254 Crownover, E.F., Convertine, A.J., and Stayton, P.S. (2011). Polym. Chem. 2:
255 Allen, M.H., Hemp, S.T., Smith, A.E., and Long, T.E. (2012). Macromolecules 45:
3669–3676. https://doi.org/10.1021/ma300543h.
256 Paslay, L.C., Abel, B.A., Brown, T.D. et al. (2012). Biomacromolecules https://doi
.org/10.1021/bm3007083.
257 Luzon, M., Boyer, C., Peinado, C. et al. (2010). J. Polym. Sci., Part A: Polym.
258 Parsons, K.H., Holley, A.C., Munn, G.A. et al. (2016). Polym. Chem. 7:
259 Johnson, R.N., Burke, R.S., Convertine, A.J. et al. (2010). Biomacromolecules 11:
3007–3013. https://doi.org/10.1021/bm100806h.
260 Smith, A.E., Xu, X., Savin, D.A., and McCormick, C.L. (2010). Polym. Chem. 1:
628–630.
261 Zhang, W., D’Agosto, F., Boyron, O. et al. (2011). Macromolecules 44: 7584–7593.
262 Zhang, X., Rieger, J., and Charleux, B. (2012). Polym. Chem. 3: 1502–1509.
263 Zhang, X., Boisse, S., Bui, C. et al. (2012). Soft Matter 8: 1130–1141. https://doi
.org/10.1039/C1SM06598J.
264 Huang, Z., Wang, R., Chen, Y. et al. (2019). J. Mater. Res. 34: 3011–3019.
https://doi.org/10.1557/jmr.2019.163.
265 Engström, J., Benselfelt, T., Wågberg, L. et al. (2019). Nanoscale 11: 4287–4302.
https://doi.org/10.1039/C8NR08057G.
266 Wang, H., Vendrame, L., Fliedel, C. et al. (2020). Macromolecules https://doi
.org/10.1021/acs.macromol.9b02582.
267 Pearson, S., Pavlovic, M., Augé, T. et al. (2018). Macromolecules 51: 3953–3966.
268 Klimkevicius, V. and Makuska, R. (2017). Eur. Polym. J. 86: 94–105. https://doi
.org/10.1016/j.eurpolymj.2016.11.026.
269 Klimkevicius, V., Steponaviciute, M., and Makuska, R. (2019). Eur. Polym. J.:
109356. https://doi.org/10.1016/j.eurpolymj.2019.109356.
270 Zhao, W., Gody, G., Dong, S. et al. (2014). Polym. Chem. 5: 6990–7003. https://
doi.org/10.1039/C4PY00855C.
271 Zhao, W., Ta, H.T., Zhang, C., and Whittaker, A.K. (2017). Biomacromolecules
18: 1145–1156. https://doi.org/10.1021/acs.biomac.6b01788.
272 Sheehan, M.T., Farnham, W.B., Okazaki, H. et al. (2008). Proc. SPIE 6923:
69232E/69231–69232E/69239. https://doi.org/10.1117/12.772115.
273 Hosta-Rigau, L., Chandrawati, R., Saveriades, E. et al. (2010). Biomacro-
274 Shi, P., Qu, Y., Liu, C. et al. (2016). ACS Macro Lett. 5: 88–93. https://doi.org/10
275 Cao, H., Wang, G., Xue, Y. et al. (2019). ACS Macro Lett. 8: 616–622. https://doi
References 465
276 Yu, L., Zhang, Y., Dai, X. et al. (2019). Chem. Commun. 55: 11920–11923.
https://doi.org/10.1039/C9CC05812E.
277 Riber, C.F., Andersen, A.H.F., Rolskov, L.A. et al. (2017). ACS Macro Lett. 6:
278 Shanmugam, S., Cuthbert, J., Flum, J. et al. (2019). Polym. Chem. 10:
279 Ma, Y. and Lodge, T.P. (2016). Macromolecules 49: 3639–3646. https://doi.org/10
.1021/acs.macromol.6b00315.
280 Dai, X., Yu, L., Zhang, Y. et al. (2019). Macromolecules 52: 7468–7476. https://
281 Pal, S., Brooks, W.L.A., Dobbins, D.J., and Sumerlin, B.S. (2016). Macro-
282 Zhang, Y., Yu, L., Dai, X. et al. (2019). ACS Macro Lett. 8: 1102–1109. https://
doi.org/10.1021/acsmacrolett.9b00509.
283 Nitschke, A., Riemann, L., Kollenbach, L. et al. Macromol. Chem. Phys.:
1900345. https://doi.org/10.1002/macp.201900345.
284 Concellón, A., Zentner, C.A., and Swager, T.M. (2019). J. Am. Chem. Soc. 141:
285 Saha, P., Kather, M., Banerjee, S.L. et al. (2019). Eur. Polym. J. 118: 195–204.
286 Kumar, S., Roy, S.G., and De, P. (2012). Polym. Chem. 3: 1239–1248. https://doi
.org/10.1039/C2PY00607C.
287 Hornung, C.H., Guerrero-Sanchez, C., Brasholz, M. et al. (2011). Org. Proc. Res.
Dev. 15: 593–601. https://doi.org/10.1021/op1003314.
288 Fu, C., Huang, Z., Hawker, C.J. et al. (2017). Polym. Chem. 8: 4637–4643.
289 Jiang, X., Li, R., Feng, C. et al. (2017). Polym. Chem. 8: 2773–2784. https://doi
.org/10.1039/C7PY00091J.
290 Gaballa, H. and Theato, P. (2019). Biomacromolecules 20: 871–881. https://doi
.org/10.1021/acs.biomac.8b01508.
291 Nash, M.A., Yager, P., Hoffman, A.S., and Stayton, P.S. (2010). Bioconjugate
Chem. 21: 2197–2204. https://doi.org/10.1021/bc100180q.
292 Asadujjaman, A., Ahmadi, V., Yalcin, M. et al. (2017). Polym. Chem. 8:
293 Rosencrantz, S., Tang, J.S.J., Schulte-Osseili, C. et al. (2019). Macromol. Chem.
Phys. 220: 1900293. https://doi.org/10.1002/macp.201900293.
294 Chen, C. and Thang, S.H. (2018). Polym. Chem. 9: 1780–1786. https://doi.org/10
.1039/C7PY01887H.
295 Biswas, Y., Maji, T., Dule, M., and Mandal, T.K. (2016). Polym. Chem. 7:
296 Enriquez-Medrano, F.J., Soriano-Corral, F., Acuna-Vazquez, P. et al. (2014). J.
Mex. Chem. Soc. 58: 194–201.
297 Rosales-Guzmán, M., Pérez-Camacho, O., Guerrero-Sánchez, C. et al. (2019).
ACS Comb. Sci. https://doi.org/10.1021/acscombsci.9b00110.
298 Contreras-López, D., Fuentes-Ramírez, R., Albores-Velasco, M. et al. (2018). J.

.29221.
299 Cuthbert, J., Martinez, M.R., Sun, M. et al. (2019). Macromol. Rapid Commun.
300 Blackburn, C., Tai, H., Salerno, M. et al. (2019). Eur. Polym. J. 120: 109259.
https://doi.org/10.1016/j.eurpolymj.2019.109259.
301 Li, L., Xu, Z., Sun, W. et al. (2020). J. Membr. Sci. 598: 117661. https://doi.org/
10.1016/j.memsci.2019.117661.
302 Heraud, C., Basuki, J., Hughes, T.C., and Mueller, M. (2019). Macromol. Rapid
303 Enke, M., Jehle, F., Bode, S. et al. (2017). Macromol. Chem. Phys. 218: 1600458.
304 Sun, Z. and Luo, Y. (2011). Soft Matter 7: 871–875. https://doi.org/10.1039/
C0SM00983K.
305 Chen, H. and Luo, Y. (2011). Macromol. Chem. Phys. 212: 737–743. https://doi
.org/10.1002/macp.201000664.
306 Liang, S., Li, X., Wang, W.-J. et al. (2016). Macromolecules 49: 752–759. https://
307 Gonzato, C., Pasetto, P., Bedoui, F. et al. (2014). Polym. Chem. 5: 1313–1322.
308 Prasher, A., Loynd, C.M., Tuten, B.T. et al. (2016). J. Polym. Sci., Part A: Polym.
309 Sheehan, M.T., Farnham, W.B., Chambers, C.R. et al. (2011). Proc. SPIE 7972
https://doi.org/10.1117/12.882960.
310 Sar, P., Roy, S.G., De, P., and Ghosh, S. Macromol. Mater. Eng.: 1900809. https://
doi.org/10.1002/mame.201900809.
311 Asadujjaman, A., Ahmadi, V., Michel Claude Franc, A., and Bertin, A. (2019).
J. Polym. Sci., Part A: Polym. Chem. 57: 2064–2073. https://doi.org/10.1002/pola
.29474.
312 Lin, S., Das, A., and Theato, P. (2017). Polym. Chem. 8: 1206–1216. https://doi
.org/10.1039/C6PY01996J.
313 Gaballa, H., Shang, J., Meier, S., and Theato, P. (2019). J. Polym. Sci., Part A:
314 Shanmugam, S., Xu, J., and Boyer, C. (2017). Macromolecules 50: 1832–1846.
1800240 (7 pp). https://doi.org/10.1002/marc.201800240.
316 Zhou, Y., Zhang, Z., Reese, C. et al. (2020). Macromol. Rapid Commun. 41:
317 Das, D., Gerboth, D., Postma, A. et al. (2016). Polym. Chem. 7: 6133–6143.
318 Weaver, L.G., Stockmann, R., Thang, S.H., and Postma, A. (2017). RSC Adv. 7:
31033–31041. https://doi.org/10.1039/C7RA04723A.
References 467
319 Semsarilar, M., Ladmiral, V., Blanazs, A., and Armes, S.P. (2011). Langmuir 28:
914–922. https://doi.org/10.1021/la203991y.
320 Farooq, U., Upadhyaya, L., Shakeel, A. et al. (2020). J. Membr. Sci. 611: 118181.
https://doi.org/10.1016/j.memsci.2020.118181.
321 Rubio, A., Desnos, G., and Semsarilar, M. (2018). Macromol. Chem. Phys. 219:
322 Hunter, S.J., Penfold, N.J.W., Chan, D.H. et al. (2020). Langmuir 36: 769–780.
323 Kim, Y.-Y., Fielding, L.A., Kulak, A.N. et al. (2018). Chem. Mater. 30:
7091–7099. https://doi.org/10.1021/acs.chemmater.8b02912.
324 Cornel, E.J., Smith, G.N., Rogers, S.E. et al. (2020). Soft Matter 16: 3657–3668.
https://doi.org/10.1039/C9SM02425E.
325 Cockram, A.A., Bradley, R.D., Lynch, S.A. et al. (2018). React. Chem. Eng. 3:
645–657. https://doi.org/10.1039/C8RE00066B.
326 Parker, B.R., Derry, M.J., Ning, Y., and Armes, S.P. (2020). Langmuir 36:
3730–3736. https://doi.org/10.1021/acs.langmuir.0c00211.
327 Rymaruk, M.J., O’Brien, C.T., Brown, S.L. et al. (2020). Macromolecules 53:
328 Guerre, M., Ameduri, B., and Ladmiral, V. (2016). Polym. Chem. 7: 441–450.
329 Wang, K., Peng, H., Thurecht, K.J. et al. (2016). Polym. Chem. 7: 1059–1069.
330 Das, P.K., Dean, D.N., Fogel, A.L. et al. (2017). Biomacromolecules 18:
331 Golden, A.L., Battrell, C.F., Pennell, S. et al. (2010). Bioconjugate Chem. 21:
1820–1826. https://doi.org/10.1021/bc100169y.
332 Lokitz, B.S., Stempka, J.E., York, A.W. et al. (2006). Aust. J. Chem. 59: 749–754.
333 Lokitz, B.S., York, A.W., Stempka, J.E. et al. (2007). Macromolecules 40:
6473–6480. https://doi.org/10.1021/ma070921v.
334 Huang, H., Wang, W., Zhou, Z. et al. (2019). J. Am. Chem. Soc. 141:
4941–4945. https://doi.org/10.1021/ma900517w.
336 Carmean, R.N., Figg, C.A., Becker, T.E., and Sumerlin, B.S. (2016). Angew.
338 Ouyang, L., Wang, L., and Schork, F.J. (2010). Macromol. Chem. Phys. 211:
339 Appel, E.A., Forster, R.A., Koutsioubas, A. et al. (2014). Angew. Chem. Int. Ed.
340 Coulston, R.J., Jones, S.T., Lee, T.-C. et al. (2011). Chem. Commun. 47: 164–166.
https://doi.org/10.1039/C0CC03250F.
341 Haridharan, N., Ponnusamy, K., and Dhamodharan, R. (2010). J. Polym. Sci.,
342 Bobrin, V.A., Chen, S.-P.R., Jia, Z., and Monteiro, M.J. (2018). Biomacro-
molecules 19: 4703–4709. https://doi.org/10.1021/acs.biomac.8b01558.
343 Bobrin, V.A. and Monteiro, M.J. (2015). J. Am. Chem. Soc. 137: 15652–15655.
344 Skrabania, K., Laschewsky, A., Berlepsch, H.v., and Böttcher, C. (2009). Lang-
muir 25: 7594–7601. https://doi.org/10.1021/la900253j.
345 Li, H., Bapat, A.P., Li, M., and Sumerlin, B.S. (2011). Polym. Chem. 2: 323–327.
https://doi.org/10.1039/C0PY00178C.
346 Bray, C., Peltier, R., Kim, H. et al. (2017). Polym. Chem. 8: 5513–5524. https://
doi.org/10.1039/C7PY01062A.
347 Gurnani, P., Bray, C.P., Richardson, R.A.E. et al. (2019). Macromol. Rapid Com-
348 Zhang, T., Wu, Y., Pan, X. et al. (2009). Eur. Polym. J. 45: 1625–1633. https://doi
.org/10.1016/j.eurpolymj.2009.03.016.
349 Stoffelbach, F., Tibiletti, L., Rieger, J., and Charleux, B. (2008). Macromolecules
41: 7850–7856. https://doi.org/10.1021/ma800965r.
350 Zhou, Y. and Kasi, R.M. (2008). J. Polym. Sci., Part A: Polym. Chem. 46:
19: 2679–2682. https://doi.org/10.1039/b817181p.
352 Chakrabarty, A. and Teramoto, Y. (2020). ACS Sustain. Chem. Eng. 8:
4623–4632. https://doi.org/10.1021/acssuschemeng.0c00687.
353 Cao, H., Qin, Y., Zhuo, C. et al. (2019). ACS Catal. 9: 8669–8676. https://doi
.org/10.1021/acscatal.9b02741.
354 Zhang, Y., He, H., Gao, C., and Wu, J. (2009). Langmuir 25: 5814–5824. https://
doi.org/10.1021/la803906s.
355 He, H., Zhang, Y., Gao, C., and Wu, J. (2009). Chem. Commun.: 1655–1657.
https://doi.org/10.1039/B821280E.
356 Moore, B.L. and O’Reilly, R.K. (2012). J. Polym. Sci., Part A: Polym. Chem. 50:
357 Mya, K.Y., Lin, E.M.J., Gudipati, C.S. et al. (2010). J. Phys. Chem. B 114:
9119–9127. https://doi.org/10.1021/jp102731e.
https://doi.org/10.1021/cm0622912.
359 He, W.-D., Sun, X.-L., Wan, W.-M., and Pan, C.-Y. (2011). Macromolecules 44:
3358–3365. https://doi.org/10.1021/ma2000674.
360 He, S.-J., Zhang, Y., Cui, Z.-H. et al. (2009). Eur. Polym. J. 45: 2395–2401.
361 Germack, D.S. and Wooley, K.L. (2007). Macromol. Chem. Phys. 208: 2481–2491.
362 Li, Y., Akiba, I., Harrisson, S., and Wooley, K.L. (2008). Adv. Funct. Mater. 18:
551–559. https://doi.org/10.1002/adfm.200700532.
References 469
363 Grignard, B., Jerome, C., Calberg, C. et al. (2007). J. Polym. Sci., Part A: Polym.
364 Boujioui, F., Damerow, H., Zhuge, F., and Gohy, J.-F. Macromol. Chem. Phys.:
365 Deane, O.J., Musa, O.M., Fernyhough, A., and Armes, S.P. (2020). Macro-
366 Hadadpour, M., Liu, Y., Chadha, P., and Ragogna, P.J. (2014). Macromolecules
47: 6207–6217. https://doi.org/10.1021/ma501323q.
367 Cao, Y., Zhu, X.X., Luo, J.T., and Liu, H.Y. (2007). Macromolecules 40:
6481–6488. https://doi.org/10.1021/ma0628230.
368 Cao, Y. and Zhu, X.X. (2007). Can. J. Chem. 85: 407–411. https://doi.org/10
.1139/V07-043.
369 An, Z.S., Shi, Q.H., Tang, W. et al. (2007). J. Am. Chem. Soc. 129: 14493–14499.
https://doi.org/10.1021/ja0756974.
370 Lai, J.J., Hoffman, J.M., Ebara, M. et al. (2007). Langmuir 23: 7385–7391.
https://doi.org/10.1021/la062527g.
371 Cao, Y., Zhao, N., Wu, K., and Zhu, X.X. (2009). Langmuir 25: 1699–1704.
https://doi.org/10.1021/la802971s.
372 He, J., Yan, B., Tremblay, L., and Zhao, Y. (2010). Langmuir 27: 436–444.
https://doi.org/10.1021/la1040322.
373 Diehl, C., Laurino, P., Azzouz, N., and Seeberger, P.H. (2010). Macromolecules
43: 10311–10314. https://doi.org/10.1021/ma1025253.
374 Roy, D., Ullah, A., and Sumerlin, B.S. (2009). Macromolecules 42: 7701–7708.
https://doi.org/10.1021/ma901471k.
375 Savelyeva, X., Li, L., and Marić, M. (2015). J. Polym. Sci., Part A: Polym. Chem.
376 Li, M., De, P., Li, H., and Sumerlin, B.S. (2010). Polym. Chem. 1: 854–859.
377 Sharma, N., Rajan, R., Makhaik, S., and Matsumura, K. (2019). ACS Omega 4:
12186–12193. https://doi.org/10.1021/acsomega.9b01409.
378 Roy, D., Cambre, J.N., and Sumerlin, B.S. (2009). Chem. Commun.: 2106–2108.
https://doi.org/10.1039/b900374f.
379 Rajan, R. and Matsumura, K. (2017). Macromol. Rapid Commun. 38: 1700478.
380 Cheng, C., Sun, G., Khoshdel, E., and Wooley, K.L. (2007). J. Am. Chem. Soc.
129: 10086–10087. doi: https://doi.org/10.1021/ja073541y.
381 Xu, S., Huang, J., Xu, S., and Luo, Y. (2013). Polymer 54: 1779–1785. https://doi
.org/10.1016/j.polymer.2013.02.007.
382 Potzsch, R., Fleischmann, S., Tock, C. et al. (2011). Macromolecules 44:
3260–3269. https://doi.org/10.1021/ma2000724.
383 Choi, J.W., Carter, M.C.D., Wei, W. et al. (2016). Macromolecules 49: 8177–8186.
384 Carter, M.C.D., Jennings, J., Speetjens, F.W. et al. (2016). Macromolecules 49:
385 Speetjens, F.W., Carter, M.C.D., Kim, M. et al. (2014). ACS Macro Lett. 3:
1178–1182. https://doi.org/10.1021/mz500654a.
386 Luo, Y., Wang, X., Li, B.-G., and Zhu, S. (2011). Macromolecules 44: 221–229.
387 Zhang, H., Deng, J., Lu, L., and Cai, Y. (2007). Macromolecules 40: 9252–9261.
https://doi.org/10.1021/ma071287o.
389 Kim, H., Kang, Y.J., Kang, S., and Kim, K.T. (2012). J. Am. Chem. Soc. 134:
4030–4033. https://doi.org/10.1021/ja211728x.
390 Dong, Z.M., Liu, X.H., Lin, Y., and Li, Y.S. (2008). J. Polym. Sci., Part A: Polym.
391 Ma, J., Cheng, C., Sun, G., and Wooley, K.L. (2008). Macromolecules 41:
9080–9089. https://doi.org/10.1021/ma802057u.
392 Ma, J., Cheng, C., and Wooley, K.L. (2009). Macromolecules 42: 1565–1573.
https://doi.org/10.1021/ma8024255.
393 Stadermann, J., Fleischmann, S., Messerschmidt, M. et al. (2009). Macromol.
394 Wan, W.-M. and Pan, C.-Y. (2010). Polym. Chem. 1: 1475–1484. https://doi.org/
10.1039/C0PY00124D.
395 Bozovic-Vukic, J., Manon, H.T., Meuldijk, J. et al. (2007). Macromolecules 40:
7132–7139. https://doi.org/10.1021/ma070789z.
396 Gramlich, W.M., Theryo, G., and Hillmyer, M.A. (2012). Polym. Chem. 3:
1510–1516.
397 Germack, D.S. and Wooley, K.L. (2007). J. Polym. Sci., Part A: Polym. Chem. 45:
398 Mulvenna, R.A., Prato, R.A., Phillip, W.A., and Boudouris, B.W. (2015). Macro-
mol. Chem. Phys. 216: 1831–1840. https://doi.org/10.1002/macp.201500201.
399 Lokitz, B.S., Messman, J.M., Hinestrosa, J.P. et al. (2009). Macromolecules 42:
9018–9026. https://doi.org/10.1021/ma9015399.
400 Kim, J.S., Sirois, A.R., Vazquez Cegla, A.J. et al. (2019). Bioconjugate Chem. 30:
1220–1231. https://doi.org/10.1021/acs.bioconjchem.9b00155.
401 Bartels, J.W., Billings, P.L., Ghosh, B. et al. (2009). Langmuir 25: 9535–9544.
https://doi.org/10.1021/la900753r.
402 Bickerton, S., Jiwpanich, S., and Thayumanavan, S. (2012). Mol. Pharm. 9:
3569–3578. https://doi.org/10.1021/mp3004226.
403 Ormategui, N., García, I., Padro, D. et al. (2012). Soft Matter 8: 734–740. https://
doi.org/10.1039/C1SM06310C.
404 Zhu, Y., Zhou, Y., Chen, Z. et al. (2012). Polymer 53: 3566–3576. https://doi.org/
10.1016/j.polymer.2012.05.063.
405 Boissé, S., Rieger, J., Di-Cicco, A. et al. (2009). Macromolecules 42: 8688–8696.
https://doi.org/10.1021/ma9018137.
406 Boisse, S., Rieger, J., Belal, K. et al. (2010). Chem. Commun. 46: 1950–1952.
https://doi.org/10.1039/B923667H.
References 471
407 Kaur, B., D’Souza, L., Slater, L.A. et al. (2011). Macromolecules 44: 3810–3816.
408 Grogna, M., Cloots, R., Luxen, A. et al. (2011). Polym. Chem. 2: 2316–2327.
409 Nilles, K. and Theato, P. (2011). Polym. Chem. 2: 376–384. https://doi.org/
10.1039/C0PY00261E.
410 Lou, Q., Kishpaugh, M.A., and Shipp, D.A. (2010). J. Polym. Sci., Part A: Polym.
411 Jackson, A.W. and Fulton, D.A. (2012). Macromolecules 45: 2699–2708. https://
doi.org/10.1021/ma202721s.
412 Li, H., Liu, J., Zheng, X. et al. (2016). J. Polym. Res. 23: 102. https://doi.org/10
.1007/s10965-016-0996-3.
413 Ma, J., Cheng, C., Sun, G., and Wooley, K.L. (2008). J. Polym. Sci., Part A:
414 Gonçalves, M.A.D., Pinto, V.D., Dias, R.C.S. et al. (2013). Macromol. Symp. 333:
415 Stadermann, J., Riedel, M., and Voit, B. (2013). Macromol. Chem. Phys. 214:
416 Espeel, P., Goethals, F., Stamenovic, M.M. et al. (2012). Polym. Chem. 3:
417 Ma, X., Lan, X., Wu, L. et al. (2020). Eur. Polym. J. 123: 109446. https://doi.org/
10.1016/j.eurpolymj.2019.109446.
418 Li, D., Jiang, J., Huang, Q. et al. (2016). Polym. Chem. 7: 3444–3450. https://doi
.org/10.1039/C6PY00490C.
419 Li, D., Munyentwali, A., Wang, G. et al. (2015). Dyes Pigm. 117: 92–99. https://
doi.org/10.1016/j.dyepig.2015.02.009.
420 Hansell, C.F. and O’Reilly, R.K. (2012). ACS Macro Lett. 1: 896–901. https://doi
.org/10.1021/mz300230c.
421 Germack, D.S., Harrisson, S., Brown, G.O., and Wooley, K.L. (2006). J. Polym.
422 Yin, X., Hoffman, A.S., and Stayton, P.S. (2006). Biomacromolecules 7:
1381–1385. https://doi.org/10.1021/bm0507812.
423 Rowe, M.D., Thamm, D.H., Kraft, S.L., and Boyes, S.G. (2009). Biomacro-
424 Sudo, Y., Kawai, R., Sakai, H. et al. (2018). Langmuir 34: 653–662. https://doi
425 Yodice, R., Johnson, J.R., Beebe, R.L. et al. (2014). Process for making sub-
stituted trithiocarbonate derivatives. (The Lubrizol Corporation, USA),
US8791286B2.
426 Moriceau, G., Gody, G., Hartlieb, M. et al. (2017). Polym. Chem. 8: 4152–4161.
427 Aksakal, S. and Remzi Becer, C. (2016). Polym. Chem. 7: 7011–7018. https://doi
.org/10.1039/C6PY01721E.
428 Moriceau, G., Tanaka, J., Lester, D. et al. (2019). Macromolecules 52: 1469–1478.
429 Yusa, S.-I., Endo, T., and Ito, M. (2009). J. Polym. Sci., Part A: Polym. Chem. 47:
431 Goto, F., Ishihara, K., Iwasaki, Y. et al. (2011). Polymer 52: 2810–2818. https://
doi.org/10.1016/j.polymer.2011.04.033.
432 Gemici, H., Legge, T.M., Whittaker, M. et al. (2007). J. Polym. Sci., Part A:
433 Iwasaki, Y., Sakiyama, M., Fujii, S., and Yusa, S.-i. (2013). Chem. Commun. 49:
7824–7826. https://doi.org/10.1039/C3CC44072A.
434 Khimani, M., Yusa, S., Nagae, A. et al. (2015). Eur. Polym. J. 69: 96–109. https://
doi.org/10.1016/j.eurpolymj.2015.05.027.
435 Yee, M.M., Tsubone, M., Morita, T. et al. (2016). J. Lumin. 176: 318–323. https://
doi.org/10.1016/j.jlumin.2016.02.043.
436 Khimani, M., Yusa, S.-i., Aswal, V.K., and Bahadur, P. (2019). J. Mol. Liq. 276:
47–56. https://doi.org/10.1016/j.molliq.2018.11.135.
437 Matsuoka, H., Moriya, S., and Yusa, S.-i. (2018). Colloid Polym. Sci. 296: 77–88.
https://doi.org/10.1007/s00396-017-4217-3.
doi.org/10.1021/bk-2000-0768.ch020.
439 Mizusaki, M., Endo, T., Nakahata, R. et al. (2017). Polymers 9: 367. https://doi
.org/10.3390/polym9080367.
2033–2036. https://doi.org/10.1021/ma047611m.
441 Zhao, Y. and Perrier, S. (2007). Macromolecules 40: 9116–9124. https://doi.org/
10.1021/ma0716783.
442 Klimkevicius, V., Graule, T., and Makuska, R. (2015). Langmuir 31: 2074–2083.
https://doi.org/10.1021/la504213t.
444 Escalé, P., Ting, S.R.S., Khoukh, A. et al. (2011). Macromolecules 44: 5911–5919.
445 Moad, G., Li, G., Pfaendner, R. et al. (2006). RAFT copolymerization and
its application to the synthesis of novel dispersants/intercalants/exfoliants
for polymer-clay nanocomposites. Some interesting results from RAFT
(co)polymerization. In: Controlled/Living Radical Polymerization. From Syn-
thesis to Materials, ACS Symposium Series, vol. 944 (ed. K. Matyjaszewski),
514–532. Washington, DC: American Chemical Society. https://doi.org/10.1021/
bk-2006-0944.ch035.
446 Cotanda, P., Lu, A., Patterson, J.P. et al. (2012). Macromolecules 45: 2377–2384.
https://doi.org/10.1021/ma2027462.
References 473
447 Lucius, M., Falatach, R., McGlone, C. et al. (2016). Biomacromolecules 17:
448 Ido, Y., Maçon, A.L.B., Iguchi, M. et al. (2017). Polymer 132: 342–352. https://
doi.org/10.1016/j.polymer.2017.10.057.
449 Cimen, D., Yildirim, E., and Caykara, T. (2015). J. Polym. Sci., Part A: Polym.
450 Ouyang, L., Wang, L., and Schork, F.J. (2011). Macromol. React. Eng. 5:
163–169. https://doi.org/10.1002/mren.201000050.
451 Qi, G., Eleazer, B., Jones, C.W., and Schork, F.J. (2009). Macromolecules 42:
3906–3916. https://doi.org/10.1021/ma802741u.
452 Parkinson, S., Hondow, N.S., Conteh, J.S. et al. (2019). React. Chem. Eng. 4:
852–861. https://doi.org/10.1039/C8RE00211H.
453 Kuroki, A., Martinez-Botella, I., Hornung, C.H. et al. (2017). Polym. Chem. 8:
454 Wang, R. and Lowe, A.B. (2007). J. Polym. Sci., Part A: Polym. Chem. 45:
455 Saubern, S., Nguyen, X., Nguyen, V. et al. (2017). Macromol. React. Eng. 11:
1600065. https://doi.org/10.1002/mren.201600065.
456 Ferguson, C.J., Hughes, R.J., Nguyen, D. et al. (2005). Macromolecules 38:
2191–2204. https://doi.org/10.1021/ma048787r.
457 Nai, Y.H., Jones, R.C., and Breadmore, M.C. (2013). Electrophoresis 34:
3189–3197. https://doi.org/10.1002/elps.201300288.
458 Ferguson, C.J., Hughes, R.J., Pham, B.T.T. et al. (2002). Macromolecules 35:
9243–9245. https://doi.org/10.1021/ma025626j.
461 Gurnani, P., Lunn, A.M., and Perrier, S. (2016). Polymer 106: 229–237. https://
doi.org/10.1016/j.polymer.2016.08.093.
462 Xu, J., Jung, K., Corrigan, N.A., and Boyer, C. (2014). Chem. Sci. 5: 3568–3575.
https://doi.org/10.1039/C4SC01309C.
463 Levere, M.E., Ho, H.T., Pascual, S., and Fontaine, L. (2011). Polym. Chem. 2:
464 Won, S., Hindmarsh, S., and Gibson, M.I. (2018). ACS Macro Lett. 7: 178–183.
466 Hur, Y.H., Song, S.W., Mays, J. et al. (2017). Mol. Syst. Des. Eng. 2: 589–596.
https://doi.org/10.1039/C7ME00085E.
467 Swift, T., Swanson, L., Geoghegan, M., and Rimmer, S. (2016). Soft Matter 12:
2542–2549. https://doi.org/10.1039/C5SM02693H.
468 Suchao-in, N., Chirachanchai, S., and Perrier, S. (2009). Polymer 50: 4151–4158.
469 von der Ehe, C., Rinkenauer, A., Weber, C. et al. (2016). Macromol. Biosci. 16:
470 Pham, B.T.T., Nguyen, D., Ferguson, C.J. et al. (2003). Macromolecules 36:
8907–8909. https://doi.org/10.1021/ma035175i.
471 Konkolewicz, D., Poon, C.K., Gray-Weale, A., and Perrier, S. (2011). Chem.
Commun. 47: 239–241. https://doi.org/10.1039/C0CC02429E.
472 Zhang, L., Fang, K., Fu, S. et al. (2012). J. Appl. Polym. Sci. 125: 915–921.
473 Gormley, A.J., Chapman, R., and Stevens, M.M. (2014). Nano Lett. 14:
6368–6373. https://doi.org/10.1021/nl502840h.
474 Chen, Y., Luo, W., Wang, Y. et al. (2012). J. Colloid Interface Sci. 369: 46–51.
475 Alb, A.M., Drenski, M.F., and Reed, W.F. (2009). J. Appl. Polym. Sci. 113:
190–198. https://doi.org/10.1002/app.29501.
476 Corrigan, N., Rosli, D., Jones, J.W.J. et al. (2016). Macromolecules 49: 6779–6789.
477 Kuhn, L.R., Allegrezza, M.L., Dougher, N.J., and Konkolewicz, D. (2020). J.
Polym. Sci. 58: 139–144. https://doi.org/10.1002/pol.20190343.
479 Tilley, A.J., Chen, M., Danczak, S.M. et al. (2012). Polym. Chem. 3: 892–899.
480 Bar-Nes, G., Hall, R., Sharma, V. et al. (2009). Eur. Polym. J. 45: 3149–3163.
481 Blinco, J.P., Greiner, A., Barner-Kowollik, C., and Agarwal, S. (2011). Eur.
Polym. J. 47: 111–114. https://doi.org/10.1016/j.eurpolymj.2010.10.025.
482 Yang, P., Pageni, P., Kabir, M.P. et al. (2016). ACS Macro Lett. 5: 1293–1300.
483 Ke, Y., Zhang, J., Xie, Y. et al. ChemSusChem https://doi.org/10.1002/cssc
.201902214.
484 Dürr, C.J., Emmerling, S.G.J., Kaiser, A. et al. (2012). J. Polym. Sci., Part A:
485 Smith, R.A., Fu, G., McAteer, O. et al. (2019). J. Am. Chem. Soc. 141:
486 Dürr, C.J., Emmerling, S.G.J., Lederhose, P. et al. (2012). Polym. Chem. 3:
487 Wilborn, E.G., Gregory, C.M., Machado, C.A. et al. (2019). Macromolecules 52:
488 Li, J., Kerr, A., Häkkinen, S. et al. (2020). Polym. Chem. https://doi.org/10.1039/
C9PY01785B.
489 Kessel, S., Urbani, C.N., and Monteiro, M.J. (2011). Angew. Chem. 123:
8232–8235. https://doi.org/10.1002/ange.201102651.
490 Kessel, S., Thakar, N., Jia, Z. et al. (2019). J. Polym. Sci., Part A: Polym. Chem.
References 475
491 Truong, N.P., Jia, Z., Burges, M. et al. (2011). Biomacromolecules 12: 1876–1882.
https://doi.org/10.1021/bm200219e.
492 Wu, C., Chen, H., Corrigan, N. et al. (2019). J. Am. Chem. Soc. 141: 8207–8220.
493 Duong, H.T.T., Jung, K., Kutty, S.K. et al. (2014). Biomacromolecules 15:
2583–2589. https://doi.org/10.1021/bm500422v.
494 Liang, M., Lin, I.C., Whittaker, M.R. et al. (2009). ACS Nano 4: 403–413.
https://doi.org/10.1021/nn9011237.
495 Kerr, A., Hartlieb, M., Sanchis, J. et al. (2017). Chem. Commun. 53:
11901–11904. https://doi.org/10.1039/C7CC07241D.
496 Tran, N.T.D., Jia, Z., and Monteiro, M.J. (2019). Ind. Eng. Chem. Res. 58:
21003–21013. https://doi.org/10.1021/acs.iecr.9b01991.
497 Zhang, Q., Vanparijs, N., Louage, B. et al. (2014). Polym. Chem. 5: 1140–1144.
498 Chen, S.-P.R., Jia, Z., Bobrin, V.A., and Monteiro, M.J. (2019). Biomacro-
molecules https://doi.org/10.1021/acs.biomac.9b01088.
499 Nagao, M., Fujiwara, Y., Matsubara, T. et al. (2017). Biomacromolecules 18:
500 Holdsworth, C.I., Jia, Z., and Monteiro, M.J. (2016). Polymer 106: 200–207.
501 Rolph, M.S., Pitto-Barry, A., and O’Reilly, R.K. (2017). Polym. Chem. 8:
502 Evans, C.M., Bridges, C.R., Sanoja, G.E. et al. (2016). ACS Macro Lett. 5:
503 Yamamoto, S., Miyashita, T., and Mitsuishi, M. (2017). RSC Adv. 7:
44954–44960. https://doi.org/10.1039/C7RA06788G.
504 Park, J., Kim, H., da Silveira, K.C. et al. (2019). Fuel 235: 1266–1274. https://doi
.org/10.1016/j.fuel.2018.08.036.
505 Brisson, E.R.L., Griffith, J.C., Bhaskaran, A. et al. (2019). J. Polym. Sci., Part A:
506 Kwak, J., Mishra, A.K., Lee, J. et al. (2017). Macromolecules 50: 6813–6818.
https://doi.org/10.1021/ma2021387.
508 Otsuka, C., Wakahara, Y., Okabe, K. et al. (2019). Macromolecules 52:
509 Savage, A.M., Walck, S.D., Lambeth, R.H., and Beyer, F.L. (2018). Macro-
510 Tselepy, A., Schiller, T.L., Harrisson, S. et al. (2018). Macromolecules 51:
511 Pavía-Sanders, A., Nissen, A., and O’Bryan, G. (2018). Macromol. Mater. Eng.
303: 1800278. https://doi.org/10.1002/mame.201800278.
512 Upadhyay, A.P., Sadhukhan, P., Roy, S. et al. (2014). RSC Adv. 4: 27135–27139.
https://doi.org/10.1039/C4RA02734E.
513 Jacobs, J., Gathergood, N., and Heise, A. (2013). Macromol. Rapid Commun. 34:
514 Rieger, J., Antoun, T., Lee, S.-H. et al. (2012). Chem. Eur. J. 18: 3355–3361.
https://doi.org/10.1002/chem.201101771.
515 Zhang, Z., Vanparijs, N., Vandewalle, S. et al. (2016). Polym. Chem. 7:
516 Wallyn, S., Zhang, Z., Driessen, F. et al. (2014). Macromol. Rapid Commun. 35:
517 Huang, Z. and Xu, J. (2013). Tetrahedron 69: 10272–10278. https://doi.org/10
.1016/j.tet.2013.10.031.
518 Kinnane, C.R., Such, G.K., and Caruso, F. (2011). Macromolecules 44:
1194–1202. https://doi.org/10.1021/ma102593k.
519 Nandy, K., Srivastava, A., Afgan, S. et al. (2020). Eur. Polym. J. 122: 109387.
https://doi.org/10.1016/j.eurpolymj.2019.109387.
520 Yap, H.P., Hao, X., Tjipto, E. et al. (2008). Langmuir 24: 8981–8990. https://doi
.org/10.1021/la8011074.
521 Ferreira, J., Syrett, J., Whittaker, M. et al. (2011). Polym. Chem. 2: 1671–1677.
522 Fu, C., Xu, J., Tao, L., and Boyer, C. (2014). ACS Macro Lett. 3: 633–638.
https://doi.org/10.1021/mz500245k.
523 Zhang, K., Jia, Y.-G., Tsai, I.H. et al. (2017). Biomacromolecules 18: 778–786.
524 Kim, Y., Lee, J., Kwon, W. et al. (2019). Polymer 178: 121584. https://doi.org/10
.1016/j.polymer.2019.121584.
525 Yhaya, F., Lim, J., Kim, Y. et al. (2011). Macromolecules 44: 8433–8445. https://
doi.org/10.1021/ma2013964.
526 Glass, J.J., Li, Y., De Rose, R. et al. (2017). ACS Appl. Mater. Interfaces 9:
527 Wong, K.H., Davis, T.P., Barner-Kowollik, C., and Stenzel, M.H. (2007). Polymer
528 Goldmann, A.S., Walther, A., Nebhani, L. et al. (2009). Macromolecules 42:
3707–3714. https://doi.org/10.1021/ma900332d.
529 Yhaya, F., Binauld, S., Kim, Y., and Stenzel, M.H. (2012). Macromol. Rapid
530 Yamano, T., Higashi, N., and Koga, T. (2020). Macromol. Rapid Commun.:
531 Adharis, A., Vesper, D., Koning, N., and Loos, K. (2018). Green Chem. 20:
476–484. https://doi.org/10.1039/C7GC03023A.
532 Lan, T., Yang, W., Peng, J. et al. (2014). Polym. Int. 63: 1691–1698. https://doi
.org/10.1002/pi.4693.
533 Köllisch, H., Barner-Kowollik, C., and Ritter, H. (2006). Macromol. Rapid. Com-
534 Barsbay, M., Guven, O., Davis, T.P. et al. (2009). Polymer 50: 973–982. https://
doi.org/10.1016/j.polymer.2008.12.027.
References 477
535 Wallyn, S., Lammens, M., O’Reilly, R.K., and Prez, F.D. (2011). J. Polym. Sci.,
536 Assem, Y., Chaffey-Millar, H., Barner-Kowollik, C. et al. (2007). Macromolecules
40: 3907–3913. https://doi.org/10.1021/ma0629079.
537 Kollisch, H.S., Barner-Kowollik, C., and Ritter, H. (2009). Chem. Commun.:
1097–1099. https://doi.org/10.1039/b818897a.
538 Jia, Y., Wang, S., Wang, W.-J. et al. (2019). Macromolecules 52: 7920–7928.
539 Li, Y., Beija, M., Laurent, S. et al. (2012). Macromolecules 45: 4196–4204.
540 Schweizerhof, S., Demco, D.E., Mourran, A. et al. (2017). Macromol. Chem.
Phys. 218: 1600495. https://doi.org/10.1002/macp.201600495.
541 Zhu, Y., Batchelor, R., Lowe, A.B., and Roth, P.J. (2016). Macromolecules 49:
542 Quek, J.Y., Zhu, Y., Roth, P.J. et al. (2013). Macromolecules 46: 7290–7302.
https://doi.org/10.1021/ma4013187.
6475–6484. https://doi.org/10.1021/ma401096r.
544 Bingham, N.M. and Roth, P.J. (2019). Chem. Commun. 55: 55–58. https://doi
.org/10.1039/C8CC08287A.
545 Spick, M.P., Bingham, N.M., Li, Y. et al. (2020). Macromolecules 53: 539–547.
546 Zhang, Y., Guan, T., Han, G. et al. (2019). Macromolecules 52: 718–728. https://
547 Ishigaki, Y. and Mori, H. (2018). Polymer 140: 198–207. https://doi.org/10.1016/j
.polymer.2018.02.025.
549 Ting, S.R.S., Gregory, A.M., and Stenzel, M.H. (2009). Biomacromolecules 10:
342–352. https://doi.org/10.1021/bm801123b.
550 Cheng, S., Ting, S.R.S., Lucien, F.P., and Zetterlund, P.B. (2012). Macromolecules
45: 1803–1810. https://doi.org/10.1021/ma202744f.
551 Wong, E.H.H., Lam, S.J., Nam, E., and Qiao, G.G. (2014). ACS Macro Lett. 3:
524–528. https://doi.org/10.1021/mz500225p.
552 Nguyen, T.-K., Lam, S.J., Ho, K.K.K. et al. (2017). ACS Infect. Dis. 3: 237–248.
https://doi.org/10.1021/acsinfecdis.6b00203.
553 Lang, X., Patrick, A.D., Hammouda, B., and Hore, M.J.A. (2018). Polymer 145:
554 You, Y., Hong, C., Wang, W. et al. (2004). Macromolecules 37: 9761–9767.
https://doi.org/10.1021/ma048444t.
555 He, P. and He, L. (2009). Biomacromolecules 10: 1804–1809. https://doi.org/10
.1021/bm9002283.
556 He, P., Zheng, W.M., Tucker, E.Z. et al. (2008). Anal. Chem. 80: 3633–3639.
https://doi.org/10.1021/ac702608k.
557 Zhao, J., Zhou, Y., Zhou, Y. et al. (2016). Polym. Chem. 7: 1782–1791. https://doi
.org/10.1039/C5PY01861G.
558 Lampley, M.W. and Harth, E. (2018). ACS Macro Lett. 7: 745–750. https://doi
559 Grover, G.N., Lee, J., Matsumoto, N.M., and Maynard, H.D. (2012). Macro-
molecules 45: 4958–4965. https://doi.org/10.1021/ma300575e.
560 Lian, X., Jin, J., Tian, J., and Zhao, H. (2010). ACS Appl. Mater. Interfaces 2:
2261–2268. https://doi.org/10.1021/am1003156.
561 Jin, J., Tian, J., Lian, X. et al. (2011). Soft Matter 7: 11194–11202. https://
doi.org/10.1039/C1SM06225E.
562 Cai, T., Yang, W.J., Zhang, Z. et al. (2012). Soft Matter 8: 5612–5620. https://doi
.org/10.1039/C2SM25368B.
563 Zhang, T., Zheng, Z., Ding, X., and Peng, Y. (2008). Macromol. Rapid Commun.
29: 1716–1720.
564 Wang, L., Zeng, K., and Zheng, S. (2011). ACS Appl. Mater. Interfaces 3:
898–909. https://doi.org/10.1021/am101258k.
565 Wang, J., Kang, Z., Qi, B. et al. (2014). RSC Adv. 4: 51510–51518. https://doi
.org/10.1039/C4RA07987F.
566 Jin, J., Zhang, M., Xiong, Q. et al. (2012). Soft Matter 8: 11809–11816. https://
doi.org/10.1039/C2SM26362A.
567 St Thomas, C., Maldonado-Textle, H., Cabello-Romero, J.N. et al. (2014). Polym.
Chem. 5: 3089–3097. https://doi.org/10.1039/C3PY01270K.
568 St Thomas, C., Cabello-Romero, J.N., Garcia-Valdez, O. et al. (2017). J. Polym.
569 von Kugelgen, S., Sifri, R., Bellone, D., and Fischer, F.R. (2017). J. Am. Chem.
Soc. 139: 7577–7585. https://doi.org/10.1021/jacs.7b02225.
570 Mahanthappa, M.K., Bates, F.S., and Hillmyer, M.A. (2005). Macromolecules 38:
7890–7894. https://doi.org/10.1021/ma051535l.
571 Fu, C., Xu, J., Kokotovic, M., and Boyer, C. (2016). ACS Macro Lett. 5: 444–449.
572 Fu, C., Xu, J., and Boyer, C. (2016). Chem. Commun. 52: 7126–7129. https://doi
.org/10.1039/C6CC03084J.
573 Hales, M., Barner-Kowollik, C., Davis, T.P., and Stenzel, M.H. (2004). Langmuir
20: 10809–10817. https://doi.org/10.1021/la0484016.
574 Mukherjee, I., Ghosh, A., Bhadury, P., and De, P. (2018). ACS Omega 3:
769–780. https://doi.org/10.1021/acsomega.7b01674.
575 Eissa, A.M., Abdulkarim, A., Sharples, G.J., and Cameron, N.R. (2016).
Biomacromolecules 17: 2672–2679. https://doi.org/10.1021/acs.biomac.6b00711.
576 Tsuji, S., Aso, Y., Ohara, H., and Tanaka, T. (2019). Polym. J. 51: 1015–1022.
https://doi.org/10.1038/s41428-019-0221-4.
577 Tanaka, T. and Okamoto, M. (2018). Polym. J. 50: 523–531. https://doi.org/10
.1038/s41428-018-0038-6.
578 Ganda, S., Jiang, Y., Thomas, D.S. et al. (2016). Macromolecules 49: 4136–4146.
References 479
579 Wang, J., Song, Y., Sun, P. et al. (2016). Langmuir 32: 2737–2749. https://doi
580 Samarajeewa, S., Shrestha, R., Li, Y., and Wooley, K.L. (2012). J. Am. Chem.
Soc. 134: 1235–1242. https://doi.org/10.1021/ja2095602.
581 Redondo, F.L., Ninago, M.D., de Freitas, A.G.O. et al. (2018). Int. J. Polym. Sci.
2018: 8252481 (15 pp pp). https://doi.org/10.1155/2018/8252481.
582 de Freitas, A.G.O., Trindade, S.G., Muraro, P.I.R. et al. (2013). Macromol. Chem.
583 Jiang, Y., Wong, S., Chen, F. et al. (2017). Bioconjugate Chem. 28: 979–985.
https://doi.org/10.1021/acs.bioconjchem.6b00698.
584 Saeed, A.O., Dey, S., Howdle, S.M. et al. (2009). J. Mater. Chem. 19: 4529–4535.
https://doi.org/10.1039/B821736J.
585 Seo, M., Murphy, C.J., and Hillmyer, M.A. (2013). ACS Macro Lett. 2: 617–620.
https://doi.org/10.1021/mz400192f.
586 Petzetakis, N., Dove, A.P., and O’Reilly, R.K. (2011). Chem. Sci. 2: 955–960.
https://doi.org/10.1039/C0SC00596G.
587 Sun, L., Petzetakis, N., Pitto-Barry, A. et al. (2013). Macromolecules 46:
9074–9082. https://doi.org/10.1021/ma401634s.
588 Li, Z., Sun, L., Zhang, Y. et al. (2016). ACS Macro Lett. 5: 1059–1064. https://doi
589 Li, Z., Zhang, Y., Wu, L. et al. (2019). ACS Macro Lett. 8: 596–602. https://doi
590 Pflughaupt, R.L., Hopkins, S.A., Wright, P.M., and Dove, A.P. (2016). J. Polym.
591 Chen, T., Xu, Z., Zhou, L. et al. (2019). Tetrahedron Lett. 60: 419–422. https://
doi.org/10.1016/j.tetlet.2018.12.051.
592 Larnaudie, S.C., Brendel, J.C., Jolliffe, K.A., and Perrier, S. (2016). J. Polym. Sci.,
593 Chen, T., Xu, Z., Zhou, L. et al. (2019). Mol. Catal. 474: 110422. https://doi.org/
10.1016/j.mcat.2019.110422.
594 Thankappan, H., Zelcak, A., Taykoz, D., and Bulmus, V. (2018). Eur. Polym. J.
595 Catrouillet, S., Brendel, J.C., Larnaudie, S. et al. (2016). ACS Macro Lett. 5:
596 Li, H., Yu, S.S., Miteva, M. et al. (2013). Adv. Funct. Mater. 23: 3040–3052.
https://doi.org/10.1002/adfm.201202215.
597 Benoit, D.S.W., Srinivasan, S., Shubin, A.D., and Stayton, P.S. (2011). Biomacro-
molecules 12: 2708–2714. https://doi.org/10.1021/bm200485b.
598 Duvall, C.L., Convertine, A.J., Benoit, D.S.W. et al. (2010). Mol. Pharm. 7:
468–476. https://doi.org/10.1021/mp9002267.
599 Bagheri, A., Arandiyan, H., Adnan, N.N.M. et al. (2017). Macromolecules 50:
600 Smith, A.A.A., Zuwala, K., Pilgram, O. et al. (2016). ACS Macro Lett. 5:
601 Oyeneye, O.O., Xu, W.Z., and Charpentier, P.A. (2015). RSC Adv. 5:
76919–76926. https://doi.org/10.1039/C5RA16193B.
602 Togashi, D., Otsuka, I., Borsali, R. et al. (2014). Biomacromolecules 15:
4509–4519. https://doi.org/10.1021/bm501314f.
603 Zammarelli, N., Luksin, M., Raschke, H. et al. (2013). Langmuir 29:
12834–12843. https://doi.org/10.1021/la402870p.
604 Jia, Z., Bobrin, V.A., Truong, N.P. et al. (2014). J. Am. Chem. Soc. 136:
5824–5827. https://doi.org/10.1021/ja500092m.
605 Han, D.H., Yang, L.P., Zhang, X.F., and Pan, C.Y. (2007). Eur. Polym. J. 43:
606 Zhang, X., Li, J., Li, W., and Zhang, A. (2007). Biomacromolecules 8: 3557–3567.
https://doi.org/10.1021/bm700729t.
607 Phillips, D.J., Prokes, I., Davies, G.-L., and Gibson, M.I. (2014). ACS Macro Lett.
3: 1225–1229. https://doi.org/10.1021/mz500686w.
608 Zong, W., Thingholm, B., Itel, F. et al. (2018). Langmuir 34: 6874–6886. https://
doi.org/10.1021/acs.langmuir.8b01073.
609 Fan, F., Wang, W., Holt, A.P. et al. (2016). Macromolecules 49: 4557–4570.
610 Zhang, J., Chen, W., Yu, L. et al. (2018). ACS Appl. Nano Mater. 1: 1513–1521.
https://doi.org/10.1021/acsanm.8b00017.
611 You, Y.-Z. and Oupický, D. (2007). Biomacromolecules 8: 98–105. https://doi.org/
10.1021/bm060635b.
612 Lv, W., Liu, L., Luo, Y. et al. (2011). J. Colloid Interface Sci. 356: 16–23. https://
doi.org/10.1016/j.jcis.2011.01.005.
613 Xing, T. and Yan, L. (2014). RSC Adv. 4: 28186–28194. https://doi.org/10.1039/
C4RA04423A.
614 Huang, X., Wang, S., Zhu, M. et al. (2015). Nanotechnology 26: 15705. https://
doi.org/10.1088/0957-4484/26/015705.
615 Montarnal, D., Delbosc, N., Chamignon, C. et al. (2015). Angew. Chem. Int. Ed.
616 Wang, S., Huang, X., Wang, G. et al. (2015). J. Phys. Chem. C 119: 25307–25318.
https://doi.org/10.1021/acs.jpcc.5b09066.
617 Oz, Y., Arslan, M., Gevrek, T.N. et al. (2016). ACS Appl. Mater. Interfaces 8:
618 Zhang, H., Chen, J., Zhang, X. et al. (2017). Biomacromolecules 18: 924–930.
619 Oyeneye, O.O., Xu, W.Z., and Charpentier, P.A. (2017). J. Polym. Sci., Part A:
620 Li, L., Zhang, T., Lü, J., and Lü, C. (2018). Appl. Surf. Sci. 454: 181–191. https://
doi.org/10.1016/j.apsusc.2018.05.157.
621 Duan, H., Yang, Y., Lü, J., and Lü, C. (2018). Nanoscale 10: 12487–12496.
https://doi.org/10.1039/C8NR02719F.
622 Li, B., Yuan, Z., Hung, H.-C. et al. (2018). Angew. Chem. Int. Ed. 57:
References 481
623 Erzina, M., Guselnikova, O., Postnikov, P. et al. (2018). Adv. Mater. Interfaces 5:
1801042. https://doi.org/10.1002/admi.201801042.
624 Vanparijs, N., Maji, S., Louage, B. et al. (2015). Polym. Chem. 6: 5602–5614.
https://doi.org/10.1039/C4PY01224K.
625 Lueckerath, T., Strauch, T., Koynov, K. et al. (2019). Biomacromolecules 20:
626 Vandewalle, S., Billiet, S., Driessen, F., and Du Prez, F.E. (2016). ACS Macro
Lett. 5: 766–771. https://doi.org/10.1021/acsmacrolett.6b00342.
627 Koda, Y., Terashima, T., Sawamoto, M., and Maynard, H.D. (2015). Polym.
628 Godula, K., Rabuka, D., Nam, K.T., and Bertozzi, C.R. (2009). Angew. Chem. Int.
629 Georgiou, P.G., Baker, A.N., Richards, S.-J. et al. (2020). J. Mater. Chem. B 8:
136–145. https://doi.org/10.1039/C9TB02004G.
630 Quan, W.-D., Pitto-Barry, A., Baker, L.A. et al. (2016). Chem. Commun. 52:
1938–1941. https://doi.org/10.1039/C5CC09095D.
631 Tomás, R.M.F., Martyn, B., Bailey, T.L., and Gibson, M.I. (2018). ACS Macro
632 Otten, L., Vlachou, D., Richards, S.-J., and Gibson, M.I. (2016). Analyst 141:
4305–4312. https://doi.org/10.1039/C6AN00549G.
633 Richards, S.-J. and Gibson, M.I. (2014). ACS Macro Lett. 3: 1004–1008. https://
doi.org/10.1021/mz5004882.
634 Mathias, F., Tahir, M.N., Tremel, W., and Zentel, R. (2014). Macromol. Chem.
635 De Vrieze, J., Van Herck, S., Nuhn, L., and De, B.G. (2020). Geest. Macromol.
Rapid Commun.: 2000034. https://doi.org/10.1002/marc.202000034.
636 Luo, X., Liu, J., Liu, G. et al. (2012). J. Polym. Sci., Part A: Polym. Chem. 50:
637 Cui, L., Wang, R., Ji, X. et al. (2014). Mater. Chem. Phys. 148: 87–95. https://doi
.org/10.1016/j.matchemphys.2014.07.016.
638 Huang, X., Appelhans, D., Formanek, P. et al. (2012). ACS Nano 6: 9718–9726.
https://doi.org/10.1021/nn3031723.
639 Ho, H.T., Leroux, F., Pascual, S. et al. (2012). Macromol. Rapid Commun. 33:
640 Schauenburg, D., Divandari, M., Neumann, K. et al. (2020). Angew. Chem. Int.
641 Mancini, R.J., Lee, J., and Maynard, H.D. (2012). J. Am. Chem. Soc. 134:
8474–8479. https://doi.org/10.1021/ja2120234.
642 Evgrafova, Z., Voigt, B., Baumann, M. et al. (2019). ChemPhysChem 20:
643 Song, Q., Yang, J., Hall, S.C.L. et al. (2019). ACS Macro Lett. 8: 1347–1352.
644 Heredia, K.L., Nguyen, T.H., Chang, C.W. et al. (2008). Chem. Commun.:
3245–3247. https://doi.org/10.1039/b804812f.
645 Liu, J., Bulmus, V., Barner-Kowollik, C. et al. (2007). Macromol. Rapid Com-
646 Mohammed, F., Ke, W., Mukerabigwi, J.F. et al. (2019). ACS Appl. Mater. Inter-
faces 11: 31681–31692. https://doi.org/10.1021/acsami.9b10950.
647 Zhao, Y., Houston, Z.H., Simpson, J.D. et al. (2017). Mol. Pharm. 14: 3539–3549.
https://doi.org/10.1021/acs.molpharmaceut.7b00560.
648 Wang, K., Peng, H., Thurecht, K.J. et al. (2014). Polym. Chem. 5: 1760–1771.
649 Le Bohec, M., Piogé, S., Pascual, S., and Fontaine, L. (2017). J. Polym. Sci., Part
650 Xu, G., Neoh, K.G., Kang, E.-T., and Teo, S.L.-M. (2020). ACS Sustain. Chem.
Eng. 8: 2586–2595. https://doi.org/10.1021/acssuschemeng.9b07836.
651 Ranjan, R. and Brittain, W.J. (2007). Macromol. Rapid Commun. 28: 2084–2089.
652 Ranjan, R. and Brittain, W.J. (2008). Macromol. Rapid Commun. 29: 1104–1110.
653 Li, S. and Gao, C. (2013). Polym. Chem. 4: 4450–4460. https://doi.org/10.1039/
C3PY00546A.
654 John, J.V., Chung, C.-W., Johnson, R.P. et al. (2016). Biomacromolecules 17:
655 Ma, W., Zhao, Y., Li, Y. et al. (2018). Appl. Surf. Sci. 435: 79–90. https://doi.org/
10.1016/j.apsusc.2017.10.190.
656 Guo, Y., van Beek, J.D., Zhang, B. et al. (2009). J. Am. Chem. Soc. 131:
11841–11854. https://doi.org/10.1021/ja9032132.
657 Nasrullah, M.J., Vora, A., and Webster, D.C. (2011). Macromol. Chem. Phys. 212:
658 Ramesh, K., Anugrah, D.S.B., and Lim, K.T. (2018). React. Funct. Polym. 131:
659 Huang, Y., Zhang, X.R., Ye, S. et al. (2019). Nanoscale 11: 13502–13510. https://
doi.org/10.1039/C9NR04664J.
660 Joubert, F., Musa, O., Hodgson, D.R.W., and Cameron, N.R. (2015). Polym.
661 Inglis, A.J., Pierrat, P., Muller, T. et al. (2010). Soft Matter 6: 82–84.
662 Meereboer, N.L., Terzić, I., Mellema, H.H. et al. (2019). Macromolecules 52:
663 Zhang, W. and Müller, A.H.E. (2010). Polymer 51: 2133–2139. https://doi.org/10
.1016/j.polymer.2010.03.028.
664 Xie, Y., Peng, C., Gao, Y. et al. (2017). J. Polym. Sci., Part A: Polym. Chem. 55:
665 Namvari, M., Biswas, C.S., Galluzzi, M. et al. (2017). Sci. Rep. 7: 44508. https://
doi.org/10.1038/srep44508.
666 Zigmond, J.S., Letteri, R.A., and Wooley, K.L. (2016). ACS Appl. Mater. Inter-
faces 8: 33386–33393. https://doi.org/10.1021/acsami.6b11112.
667 Zigmond, J.S., Pavía-Sanders, A., Russell, J.D., and Wooley, K.L. (2016). Chem.
Mater. 28: 5471–5479. https://doi.org/10.1021/acs.chemmater.6b02013.
References 483
668 Sudo, Y., Sakai, H., Nabae, Y. et al. (2015). Polymer 70: 307–314. https://doi.org/
10.1016/j.polymer.2015.06.035.
669 Zhou, J. and Hu, B. (2015). J. Appl. Polym. Sci.: 132. https://doi.org/10.1002/app
.42649.
670 Khor, S.Y., Hu, J., McLeod, V.M. et al. (2015). Nanomed.: Nanotechnol. Biol.
Med. 11: 2099–2108. https://doi.org/10.1016/j.nano.2015.08.001.
671 Li, Y., Duong, H.T.T., Jones, M.W. et al. (2013). ACS Macro Lett. 2: 912–917.
https://doi.org/10.1021/mz4004375.
672 Kakwere, H., Payne, R.J., Jolliffe, K.A., and Perrier, S. (2011). Soft Matter 7:
3754–3757. https://doi.org/10.1039/C0SM01237H.
673 Lim, J., Yang, H., Paek, K. et al. (2011). J. Polym. Sci., Part A: Polym. Chem. 49:
674 Nölle, J.M., Primpke, S., Müllen, K. et al. (2016). Polym. Chem. 7: 4100–4105.
675 Soto-Cantu, E., Lokitz, B.S., Hinestrosa, J.P. et al. (2011). Langmuir 27:
5986–5996. https://doi.org/10.1021/la2000798.
676 Caciagli, A., Zupkauskas, M., Levin, A. et al. (2018). Langmuir 34:
10073–10080. https://doi.org/10.1021/acs.langmuir.8b01828.
677 Gondi, S.R., Vogt, A.P., and Sumerlin, B.S. (2007). Macromolecules 40: 474–481.
678 Bajj, D.N.F., Tran, M.V., Tsai, H.-Y. et al. (2019). ACS Appl. Nano Mater. 2:
898–909. https://doi.org/10.1021/acsanm.8b02149.
679 Willersinn, J., Bogomolova, A., Cabré, M.B., and Schmidt, B.V.K.J. (2017).
Polym. Chem. 8: 1244–1254. https://doi.org/10.1039/C6PY02212J.
680 Li, S. and Schroeder, C.M. (2018). ACS Macro Lett. 7: 281–286. https://doi.org/
10.1021/acsmacrolett.8b00016.
681 Wilks, T.R., Bath, J., de Vries, J.W. et al. (2013). ACS Nano 7: 8561–8572.
https://doi.org/10.1021/nn402642a.
682 Terzic, I., Meereboer, N.L., Acuautla, M. et al. (2019). Macromolecules 52:
683 Liu, Z., Lu, G., Li, Y. et al. (2014). RSC Adv. 4: 60920–60928. https://doi.org/10
.1039/C4RA07825J.
684 Wu, L., Glebe, U., and Böker, A. (2017). Adv. Mater. Interfaces 4: 1700092.
https://doi.org/10.1002/admi.201700092.
685 Reichstein, P.M., Brendel, J.C., Drechsler, M., and Thelakkat, M. (2019). ACS
Appl. Nano Mater. 2: 2133–2143. https://doi.org/10.1021/acsanm.9b00108.
686 Qiao, R., Esser, L., Fu, C. et al. (2018). Biomacromolecules 19: 4423–4429.
687 Hua, Z., Keogh, R., Li, Z. et al. (2017). Macromolecules 50: 3662–3670. https://
688 Robin, M.P., Jones, M.W., Haddleton, D.M., and O’Reilly, R.K. (2011). ACS
Macro Lett. 1: 222–226. https://doi.org/10.1021/mz200164x.
689 Robin, M.P., Wilson, P., Mabire, A.B. et al. (2013). J. Am. Chem. Soc. 135:
2875–2878. https://doi.org/10.1021/ja3105494.
690 Gody, G., Rossner, C., Moraes, J. et al. (2012). J. Am. Chem. Soc. 134:
12596–12603. https://doi.org/10.1021/ja3030643.
691 Suguri, T. and Olsen, B.D. (2019). Polym. Chem. 10: 1751–1761. https://doi.org/
10.1039/C8PY01228H.
692 Chang, D., Lam, C.N., Tang, S., and Olsen, B.D. (2014). Polym. Chem. 5:
4884–4895. https://doi.org/10.1039/C4PY00448E.
693 Lam, C.N. and Olsen, B.D. (2013). Soft Matter 9: 2393–2402. https://doi.org/10
.1039/C2SM27459K.
694 Thomas, C.S., Glassman, M.J., and Olsen, B.D. (2011). ACS Nano 5: 5697–5707.
https://doi.org/10.1021/nn2013673.
695 Hirschbiel, A.F., Konrad, W., Schulze-Sünninghausen, D. et al. (2015). ACS
Macro Lett. 4: 1062–1066. https://doi.org/10.1021/acsmacrolett.5b00485.
696 Li, X., Prukop, S.L., Biswal, S.L., and Verduzco, R. (2012). Macromolecules 45:
7118–7127. https://doi.org/10.1021/ma301046n.
697 Hufendiek, A., Barner-Kowollik, C., and Meier, M.A.R. (2015). Polym. Chem. 6:
2188–2191. https://doi.org/10.1039/C5PY00063G.
698 Mah, A.H., Afzali, P., Qi, L. et al. (2018). Macromolecules 51: 5665–5675.
699 Li, X., ShamsiJazeyi, H., Pesek, S.L. et al. (2014). Soft Matter 10: 2008–2015.
https://doi.org/10.1039/C3SM52614C.
700 Wuest, K.N.R., Trouillet, V., Goldmann, A.S. et al. (2016). Macromolecules 49:
701 Pesek, S.L., Li, X., Hammouda, B. et al. (2013). Macromolecules 46: 6998–7005.
https://doi.org/10.1021/ma401246b.
702 Mitra, I., Li, X., Pesek, S.L. et al. (2014). Macromolecules 47: 5269–5276. https://
doi.org/10.1021/ma501070w.
703 Teo, Y.C. and Xia, Y. (2015). Macromolecules 48: 5656–5662. https://doi.org/10
704 Brendel, J.C., Martin, L., Zhang, J., and Perrier, S. (2017). Polym. Chem. 8:
705 Liu, W., Zhang, S., Liu, S. et al. (2019). Macromol. Rapid Commun. 40: 1900310.
706 Liu, W., Dong, Y., Liu, S. et al. (2019). Macromol. Rapid Commun. 40: 1900379.
707 Theriot, J.C., Miyake, G.M., and Boyer, C.A. (2018). ACS Macro Lett. 7:
708 Li, Z., Zhang, K., Ma, J. et al. (2009). J. Polym. Sci., Part A: Polym. Chem. 47:
709 Dalsin, S.J., Rions-Maehren, T.G., Beam, M.D. et al. (2015). ACS Nano 9:
12233–12245. https://doi.org/10.1021/acsnano.5b05473.
710 Radzinski, S.C., Foster, J.C., Chapleski, R.C. et al. (2016). J. Am. Chem. Soc.
138: 6998–7004. https://doi.org/10.1021/jacs.5b13317.
711 Li, Z., Ma, J., Cheng, C. et al. (2010). Macromolecules 43: 1182–1184. https://doi
.org/10.1021/ma902513n.
References 485
712 Yu, L., Martin, I.J., Kasi, R.M., and Wei, M. (2018). ACS Appl. Mater. Interfaces
10: 28440–28449. https://doi.org/10.1021/acsami.8b10234.
713 Alaboalirat, M., Qi, L., Arrington, K.J. et al. (2019). Macromolecules 52:
714 Li, Z., Ma, J., Lee, N.S., and Wooley, K.L. (2011). J. Am. Chem. Soc. 133:
1228–1231. https://doi.org/10.1021/ja109191z.
715 Mah, A.H., Mei, H., Basu, P. et al. (2018). Soft Matter 14: 6728–6736. https://doi
.org/10.1039/C8SM01127C.
716 Mei, H., Laws, T.S., Mahalik, J.P. et al. (2019). Macromolecules 52: 8910–8922.
717 Saito, K., Hirose, K., Okayasu, T. et al. (2013). RSC Adv. 3: 9752–9756. https://
doi.org/10.1039/C3RA41823E.
718 Ohno, K., Ma, Y., Huang, Y. et al. (2011). Macromolecules 44: 8944–8953.
719 Sabouri, H., Huang, Y., Ohno, K., and Perrier, S. (2015). Nanoscale 7:
19036–19046. https://doi.org/10.1039/C5NR06400G.
720 Kim, K., Ahn, J., Park, M. et al. (2019). Macromolecules 52: 7448–7455. https://
721 Baratha, K.V., Nourry, A., and Pilard, J.-F. (2015). Eur. Polym. J. 70: 317–330.
722 Lopez-Oliva, A.P., Warren, N.J., Rajkumar, A. et al. (2015). Macromolecules 48:
723 Rymaruk, M.J., Hunter, S.J., O’Brien, C.T. et al. (2019). Macromolecules 52:
724 Duong, T.H., Margaillan, A., and Bressy, C. (2019). Polym. Degrad. Stab. 164:
725 Guazzelli, E., Galli, G., Martinelli, E. et al. (2020). Polymer 186: 121954. https://
doi.org/10.1016/j.polymer.2019.121954.
726 Wadley, M.L. and Cavicchi, K.A. (2010). J. Appl. Polym. Sci. 115: 635–640.
727 Zhao, W., Fonsny, P., FitzGerald, P. et al. (2013). Polym. Chem. 4: 2140–2150.
https://doi.org/10.1039/C3PY21038C.
728 Guo, H., Liu, M., Xie, C. et al. (2020). Chem. Eng. J. 402: 126161. https://doi
.org/10.1016/j.cej.2020.126161.
729 Chen, C., Richter, F., Guerrero-Sanchez, C. et al. (2020). ACS Macro Lett. 9:
730 Chen, C., Kong, F., Wei, X., and Thang, S.H. (2017). Chem. Commun. 53:
10776–10779. https://doi.org/10.1039/C7CC05316A.
sis and Applications (eds. G. Moad and E. Rizzardo). Weinheim: Wiley-VCH,
1017–1050.

Rizzardo). Weinheim: Wiley-VCH, 829–872.
733 Kazemi, M., Shiri, L., and Kohzadi, H. (2015). Phosphorus, Sulfur Silicon Relat.
Elem. 190: 1398–1409. https://doi.org/10.1080/10426507.2014.993035.
734 Fallah-Mehrjardi, M. (2018). Monatsh. Chem. Chem. Mon. 149: 1931–1944.
https://doi.org/10.1007/s00706-018-2256-1.
735 Yousefi, A. (2015). J. Sulfur Chem. 36: 672–677. https://doi.org/10.1080/
17415993.2015.1079912.
736 Vestberg, R., Piekarski, A.M., Pressly, E.D. et al. (2009). J. Polym. Sci., Part A:
737 Tam, W.Y., Mak, C.S.K., Ng, A.M.C. et al. (2009). Macromol. Rapid Commun.
738 Zhou, Y., Ahn, S.-k., Lakhman, R.K. et al. (2011). Macromolecules 44:
3924–3934. https://doi.org/10.1021/ma102922u.
739 Chandrawati, R., Städler, B., Postma, A. et al. (2009). Biomaterials 30:
740 Pavlov, G.M., Breul, A.M., Hager, M.D., and Schubert, U.S. (2012). Macromol.
741 Sohn, H.-S., Cha, S.-H., Lee, W.-K. et al. (2011). Macromol. Res. 19: 722–728.
https://doi.org/10.1007/s13233-011-0705-3.
742 Xu, X., Smith, A.E., and McCormick, C.L. (2009). Aust. J. Chem. 62: 1520–1527.
743 Gody, G., Boullanger, P., Ladaviere, C. et al. (2008). Macromol. Rapid Commun.
744 Zorn, M. and Zentel, R. (2008). Macromol. Rapid Commun. 29: 922–927. https://
doi.org/10.1002/marc.200800165.
745 Chen, M., Haeussler, M., Moad, G., and Rizzardo, E. (2011). Org. Biomol. Chem.
9: 6111–6119. https://doi.org/10.1039/C1OB05276D.
746 Mao, J., Qi, X., Cao, X. et al. (2011). Chem. Commun. 47: 4228–4230. https://doi
.org/10.1039/C1CC10610D.
https://doi.org/10.1021/bm8014945.
748 Campos, L.M., Killops, K.L., Sakai, R. et al. (2008). Macromolecules 41:
7063–7070. https://doi.org/10.1021/ma801630n.
749 Wang, J., Zhu, X.L., Cheng, Z.P. et al. (2007). J. Polym. Sci., Part A: Polym.
750 Xiao, N.-Y., Li, A.-L., Liang, H., and Lu, J. (2008). Macromolecules 41:
2374–2380. https://doi.org/10.1021/ma702510n.
751 Zhang, X., Lian, X., Liu, L. et al. (2008). Macromolecules 41: 7863–7869. https://
doi.org/10.1021/ma801405j.
752 Quemener, D., Le Hellaye, M., Bissett, C. et al. (2008). J. Polym. Sci., Part A:
753 Cavalieri, F., Postma, A., Lee, L., and Caruso, F. (2009). ACS Nano 3: 234–240.
https://doi.org/10.1021/nn800705m.
References 487
754 Such, G.K., Tjipto, E., Postma, A. et al. (2007). Nano Lett. 7: 1706–1710. https://
doi.org/10.1021/nl070698f.
755 Such, G.K., Quinn, J.F., Quinn, A. et al. (2006). J. Am. Chem. Soc. 128:
9318–9319. https://doi.org/10.1021/ja063043+.
756 Yanjarappa, M.J., Gujraty, K.V., Joshi, A. et al. (2006). Biomacromolecules 7:
1665–1670. https://doi.org/10.1021/bm060098v.
758 Yan, J.-J., Hong, C.-Y., and You, Y.-Z. (2011). Macromolecules 44: 1247–1251.
https://doi.org/10.1021/ma102944k.
759 Chytil, P., Etrych, T., Kríz, J. et al. (2010). Eur. J. Pharm. Sci. 41: 473–482.
760 Hwang, J.Y., Li, R.C., and Maynard, H.D. (2007). J. Controlled Release 122:
761 Li, R.C., Hwang, J., and Maynard, H.D. (2007). Chem. Commun.: 3631–3633.
https://doi.org/10.1039/b709304g.
762 Seo, M., Shin, S., Ku, S. et al. (2010). J. Mater. Chem. 20: 94–102. https://doi
.org/10.1039/b914941d.
763 Hatton, F.L. (2020). Polym. Chem. https://doi.org/10.1039/C9PY01128E.
764 O’Reilly, R.K. (2010). Polym. Int. 59: 568–573. https://doi.org/10.1002/pi.2830.
765 Boyer, C., Bulmus, V., Davis, T.P. et al. (2009). Chem. Rev. 109: 5402–5436.
https://doi.org/10.1021/cr9001403.
766 Ahmad, N.M., Charleux, B., Farcet, C. et al. (2009). Macromol. Rapid Commun.
767 Ballard, N. and Asua, J.M. (2018). Prog. Polym. Sci. 79: 40–60. https://doi.org/10
.1016/j.progpolymsci.2017.11.002.
768 Reyes, Y. and Asua, J.M. (2011). Macromol. Rapid Commun. 32: 63–67. https://
doi.org/10.1002/marc.201000375.
769 Gaborieau, M., Koo, S.P.S., Castignolles, P. et al. (2010). Macromolecules 43:
5492–5495. https://doi.org/10.1021/ma100991c.
770 Liang, K., Hutchinson, R.A., Barth, J. et al. (2011). Macromolecules 44:
5843–5845. https://doi.org/10.1021/ma201391t.
772 Roth, P.J. and Theato, P. (2016). Polymer analogous reactions. In: Reference
Module in Materials Science and Materials Engineering. Elsevier 26 pages.
https://doi.org/10.1016/B978-0-12-803581-8.01420-X.
773 Roth, P.J. and Theato, P. (2011). ACS Symp. Ser. 1066: 23–37 (3 pp). https://doi
.org/10.1021/bk-2011-1066.ch003.
774 Rzayev, J. (2009). Macromolecules 42: 2135–2141. https://doi.org/10.1021/
ma802304y.
775 Destarac, M., Guinaudeau, A., Geagea, R. et al. (2010). J. Polym. Sci., Part A:
776 Simonova, Y.A., Topchiy, M.A., Filatova, M.P. et al. (2020). Eur. Polym. J. 122:
777 Pasini, D. and Takeuchi, D. (2018). Chem. Rev. 118: 8983–9057. https://doi.org/
10.1021/acs.chemrev.8b00286.
778 Pasini, D. and Nitti, A. (2020). Eur. Polym. J. 122: 109378. https://doi.org/10
.1016/j.eurpolymj.2019.109378.
779 Paulusse, J.M.J., Amir, R.J., Evans, R.A., and Hawker, C.J. (2009). J. Am. Chem.
Soc. 131: 9805–9812. https://doi.org/10.1021/ja903245p.
780 Ganda, S., Dulle, M., Drechsler, M. et al. (2017). Macromolecules 50: 8544–8553.
781 Jackson, A.W., Chennamaneni, L.R., and Thoniyot, P. (2020). Eur. Polym. J. 122:
782 Allison-Logan, S., Karimi, F., Nothling, M.D., and Qiao, G.G. (2022). Star poly-
mers by RAFT polymerization. In: RAFT Polymerization: Materials, Synthesis
and Applications (eds. G. Moad and E. Rizzardo). Weinheim: Wiley-VCH.
784 Pérez-Salinas, P., López-Domínguez, P., Rosas-Aburto, A. et al. (2022). RAFT
crosslinking polymerization. In: RAFT Polymerization: Materials, Synthesis and
785 Barlow, K.J., Bernabeu, V., Hao, X. et al. (2015). React. Funct. Polym. 96: 89–96.
786 Alfurhood, J.A., Bachler, P.R., and Sumerlin, B.S. (2016). Polym. Chem. 7:
polym9060188.
788 Wilson, J.T., Postma, A., Keller, S. et al. (2015). AAPS J. 17: 358–369. https://doi
.org/10.1208/s12248-014-9697-1.
789 Wang, K., Peng, H., Thurecht, K.J. et al. (2015). Biomacromolecules 16:
790 Chen, Y., Shi, Y., Liang, Y. et al. (2019). ACS Appl. Energy Mater. 2: 1608–1615.
https://doi.org/10.1021/acsaem.8b02188.
791 Alfurhood, J.A., Sun, H., Bachler, P.R., and Sumerlin, B.S. (2016). Polym. Chem.
7: 2099–2104. https://doi.org/10.1039/C6PY00111D.
792 Zhang, C., Zhou, Y., Liu, Q. et al. (2011). Macromolecules 44: 2034–2049.
https://doi.org/10.1021/ma1024736.
793 Zhao, J., Li, D., Han, H. et al. (2019). Langmuir 35: 2630–2638. https://doi.org/
10.1021/acs.langmuir.8b03231.
794 Liu, Y., Zhou, J., Hou, J. et al. (2019). ACS Appl. Polym. Mater. 1: 76–82. https://
doi.org/10.1021/acsapm.8b00058.
795 Zhuang, Y., Zhu, Q., Tu, C. et al. (2012). J. Mater. Chem. 22: 23852–23860.
https://doi.org/10.1039/C2JM34306A.
796 Zhuang, Y., Su, Y., Peng, Y. et al. (2014). Biomacromolecules 15: 1408–1418.
https://doi.org/10.1021/bm500018s.
797 Zhang, Y., Teo, B.M., Postma, A. et al. (2013). J. Phys. Chem. B 117:
10504–10512. https://doi.org/10.1021/jp407106z.
798 Ghosh Roy, S. and De, P. (2014). Polym. Chem. 5: 6365–6378. https://doi.org/10
.1039/C4PY00766B.
References 489
799 Chen, X., Liu, X., Miao, C. et al. (2018). Eur. Polym. J. 107: 229–235. https://doi
.org/10.1016/j.eurpolymj.2018.08.016.
800 Nicolaÿ, R., Kamada, J., Van Wassen, A., and Matyjaszewski, K. (2010). Macro-
801 Fenoli, C.R. and Bowman, C.N. (2014). Polym. Chem. 5: 62–68. https://doi.org/
10.1039/C3PY00709J.
802 Yu, L.-X., Zhuo, D., and Ran, R. (2013). Int. J. Polym. Mater. Polym. Biomater.
62: 749–754. https://doi.org/10.1080/00914037.2013.769237.
803 Amamoto, Y., Kamada, J., Otsuka, H. et al. (2011). Angew. Chem. Int. Ed. 50:
804 Park, H.Y., Kloxin, C.J., Abuelyaman, A.S. et al. (2012). Macromolecules 45:
5640–5646. https://doi.org/10.1021/ma300228z.
805 Shanmugam, S., Cuthbert, J., Kowalewski, T. et al. (2018). Macromolecules 51:
806 Fenoli, C.R., Wydra, J.W., and Bowman, C.N. (2014). Macromolecules 47:
907–915. https://doi.org/10.1021/ma402548e.
.macromol.9b01365.
809 Lin, S., Zhang, L., Huang, Z. et al. (2019). Macromolecules 52: 7157–7166.
810 Zhou, Y., Zhang, Z., Postma, A., and Moad, G. (2019). Polym. Chem. 10:
811 Henry, S.M., Convertine, A.J., Benoit, D.S.W. et al. (2009). Bioconjugate Chem.
20: 1122–1128. https://doi.org/10.1021/bc800426d.
812 Isahak, N., Gody, G., Malins, L.R. et al. (2016). Chem. Commun. 52:
813 Montagna, V., Haupt, K., and Gonzato, C. (2020). Polym. Chem. https://doi.org/
10.1039/C9PY01629E.
814 Guo, X., Choi, B., Feng, A., and Thang, S.H. (2018). Macromol. Rapid Commun.
.org/10.1016/j.tet.2016.07.002.
816 Zhang, X., Oddon, M., Giani, O. et al. (2010). Macromolecules 43: 2654–2656.
https://doi.org/10.1021/ma9025916.
817 Cheng, C., Khoshdel, E., and Wooley, K.L. (2007). Macromolecules 40:
2289–2292. https://doi.org/10.1021/ma0627525.
818 Li, L., Huang, J., and Zhang, Y. (2018). Macromol. Chem. Phys. 219: 1800217.
819 Uchiyama, M. and Kamigaito, M. (2022). Cationic RAFT polymerization. In:
RAFT Polymerization: Materials, Synthesis and Applications (eds. G. Moad, S.H.
Thang and E. Rizzardo). Weinheim: Wiley-VCH, 1159–1182.
820 Zhang, Z., Xia, L., Zeng, T.-Y. et al. (2019). Polym. Chem. 10: 2117–2125. https://
doi.org/10.1039/C9PY00230H.
821 Wang, C.-H., Fan, Y.-S., Zhang, Z. et al. (2019). Appl. Surf. Sci. 475: 639–644.
https://doi.org/10.1016/j.apsusc.2019.01.033.
https://doi.org/10.1021/ma9006939.
823 Bolton, J. and Rzayev, J. (2012). ACS Macro Lett. 1: 15–18. https://doi.org/10
.1021/mz200003j.
824 Bolton, J. and Rzayev, J. (2014). Macromolecules 47: 2864–2874. https://doi.org/
10.1021/ma500625k.
825 Cuthbert, J., Zhang, T., Biswas, S. et al. (2018). Macromolecules 51: 9184–9191.
826 Delduc, P., Tailhan, C., and Zard, S.Z. (1988). J. Chem. Soc., Chem. Commun.:
308–310. https://doi.org/10.1039/C39880000308.
827 McKenzie, T.G., Fu, Q., Uchiyama, M. et al. (2016). Adv. Sci. 3: 1500394.
https://doi.org/10.1002/advs.201500394.
829 Xu, J., Shanmugam, S., Corrigan, N.A., and Boyer, C. (2015). Catalyst-free
visible light-induced RAFT photopolymerization. In: Controlled Radical
Polymerization: Mechanisms, ACS Symposium Series, vol. 1187 (eds. K.
Matyjaszewski, B.S. Sumerlin, N.V. Tsarevsky and J. Chiefari), 247–267. Ameri-
can Chemical Society. https://doi.org/10.1021/bk-2015-1187.ch013.
830 Li, S., Han, G., and Zhang, W. (2020). Polym. Chem. https://doi.org/10.1039/
D0PY00054J.
831 Strover, L.T., Cantalice, A., Lam, J.Y.L. et al. (2019). Macro Lett. 8: 1316–1322.
832 Zhang, Z., Zhang, W., Zhu, X. et al. (2007). J. Polym. Sci., Part A: Polym. Chem.
6602–6604. https://doi.org/10.1021/ma801502s.
835 Nicolaÿ, R. and Kwak, Y. (2012). Israel J. Chem. 52: 288–305. https://doi.org/10
.1002/ijch.201100124.
.org/10.1039/C3PY00671A.
838 Lorandi, F., Fantin, M., Shanmugam, S. et al. (2019). Macromolecules 52:
839 Zhou, J., Yao, H., and Ma, J. (2018). Polym. Chem. 9: 2532–2561. https://doi.org/
10.1039/C8PY00065D.
840 Eggers, S. and Abetz, V. (2017). Polymers 9: 668. https://doi.org/10.3390/
polym9120668.
References 491
841 Rieger, J., Stoffelbach, F., Bui, C. et al. (2008). Macromolecules 41: 4065–4068.
842 Truong, N.P., Dussert, M.V., Whittaker, M.R. et al. (2015). Polym. Chem. 6:
843 Truong, N.P., Quinn, J.F., Anastasaki, A. et al. (2017). Polym. Chem. 8:
844 Penfold, N.J.W., Yeow, J., Boyer, C., and Armes, S.P. (2019). ACS Macro Lett. 8:
845 D’Agosto, F., Lansalot, M., and Rieger, J. (2022). RAFT-mediated
polymerization-induced self-assembly (PISA). In: RAFT Polymerization: Mate-
rials, Synthesis and Applications (eds. G. Moad and E. Rizzardo). Weinheim:
Wiley-VCH, 707–752.
846 Convertine, A.J., Lokitz, B.S., Lowe, A.B. et al. (2005). Macromol. Rapid
847 Zhou, H., Liu, C., Gao, C. et al. (2016). J. Polym. Sci., Part A: Polym. Chem. 54:
848 Guerrero-Sanchez, C., Keddie, D.J., Saubern, S., and Chiefari, J. (2012). ACS
Comb. Sci. 14: 389–394. https://doi.org/10.1021/co300044w.
849 Wang, M., Zhang, J., Guerrero-Sanchez, C. et al. (2019). ACS Comb. Sci. 21:
643–649. https://doi.org/10.1021/acscombsci.9b00082.
850 Liu, Z., Lv, Y., and An, Z. (2017). Angew. Chem. Int. Ed. 56: 13852–13856.
851 Gormley, A.J., Yeow, J., Ng, G. et al. (2018). Angew. Chem. Int. Ed. 57:
852 Ng, G., Yeow, J., Chapman, R. et al. (2018). Macromolecules 51: 7600–7607.
853 Judzewitsch, P.R., Corrigan, N., Trujillo, F. et al. (2020). Macromolecules 53:
.org/10.1039/b9py00340a.
855 Moad, G., Rizzardo, E., and Thang, S.H. (2011). Polym. Int. 60: 9–25. https://doi
.org/10.1002/pi.2988.
857 Lunn, D.J., Discekici, E.H., Read de Alaniz, J. et al. (2017). J. Polym. Sci., Part
858 Cornel, E.J., van Meurs, S., Smith, T. et al. (2018). J. Am. Chem. Soc. 140:
859 Karunakaran, R. and Kennedy, J.P. (2007). J. Polym. Sci., Part A: Polym. Chem.
860 Vo, C.-D., Rosselgong, J., Armes, S.P., and Tirelli, N. (2010). J. Polym. Sci., Part
861 Thurecht, K.J., Blakey, I., Peng, H. et al. (2010). J. Am. Chem. Soc. 132:
5336–5337. https://doi.org/10.1021/ja100252y.
862 Zhou, Y., Jiang, K., Song, Q., and Liu, S. (2007). Langmuir 23: 13076–13084.
https://doi.org/10.1021/la702548h.
865 Mattson, K.M., Pester, C.W., Gutekunst, W.R. et al. (2016). Macromolecules 49:
866 Destarac, M., Kalai, C., Wilczewska, A. et al. (2006). Various strategies for
the chemical transformation of xanthate-functional chain termini in MADIX
copolymers. In: Controlled/Living Radical Polymerization. From Synthesis to
Materials, ACS Symposium Series, vol. 944 (ed. K. Matyjaszewski), 564–577.
Washington, DC: American Chemical Society. https://doi.org/10.1021/bk-2006-
0944.ch038.
867 Tong, Y.-Y., Dong, Y.-Q., Du, F.-S., and Li, Z.-C. (2009). J. Polym. Sci., Part A:
870 Kakwere, H. and Perrier, S.b. (2009). J. Am. Chem. Soc. 131: 1889–1895. https://
doi.org/10.1021/ja8075499.
871 Zhang, X., Jiang, J., and Zhang, Y. (2016). J. Appl. Polym. Sci. 133: 43992.
872 Altintas, O., Abbasi, M., Riazi, K. et al. (2014). Polym. Chem. 5: 5009–5019.
873 Altintas, O., Riazi, K., Lee, R. et al. (2013). Macromolecules 46: 8079–8091.
the process of making the same. (Henkel), WO2017027557A1.
https://doi.org/10.29356/jmcs.v55i1.848.
878 Moad, G. (2022). Dithiocarbamates in RAFT polymerization. In: RAFT Poly-
merization: Materials, Synthesis and Applications (eds. G. Moad and E.
Rizzardo). Weinheim: Wiley-VCH.
493
10
Xanthates in RAFT Polymerization

Mingxi Wang 1,2 , Jean-Daniel Marty 1 , and Mathias Destarac 1
1
IMRCP, UMR 5623, Université de Toulouse, 118, route de Narbonne, F-31062, Cedex 9, Toulouse, France
2
College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi’an
Weiyang University Park, Xi’an, Shaanxi Province, 710021, China
10.1 Introduction
Reversible addition−fragmentation chain transfer polymerization (RAFT) recently
celebrated its 20th anniversary [1, 2]. In 1998, CSIRO disclosed the RAFT process
in a first patent [3] followed soon after by their seminal Macromolecules paper [4].
Owing to their too low transfer constants, xanthates were not claimed in their orig-
inal patent to be efficient RAFT agents [4]. Later the same year, Rhodia and CNRS
published a patent where xanthates were central to mediating a reversible chain
transfer process similar to RAFT [5]. They coined this process MADIX for Macro-
molecular Design by Interchange of Xanthates. The first paper came out in 2000
[6]. For the sake of clarity, we will use xanthate-mediated RAFT, or RAFT with xan-
thates, or just RAFT to describe MADIX throughout this document. Regardless of
these historical considerations, xanthate RAFT agents gained increasing attention
over the years and are today firmly established as best suited for the RAFT poly-
merization of non-conjugated monomers [7, 8]. A series of recent reviews address
various aspects of xanthate-mediated RAFT [2, 9–11].
This chapter will highlight the most recent developments in this field since our
chapter in the previous 2008 edition [12], covering areas such as xanthate synthesis,
polymerization kinetics and reaction conditions, range of monomers, macromolec-
ular architectures, xanthate end-group removal, and industrial applications.
10.2 Synthesis of RAFT/MADIX Agents
Synthetic methodologies to RAFT agents have been well reported and reviewed by
different groups [13–15]. Here we outline three main methods for preparing a variety
of xanthates (Table 10.1).

Table 10.1 Xanthates (ZOC(=S)SR) used as RAFT agents.
RAFT agenta) Synthesisa) Monomerb)
MeOOC S O A [16–19] CMS [20], n-BA [21], BDDA [22], EGDA [22], AA [17], AM [23], VAc [19, 24, 25],
C R2 VTFAc [26, 27], VTFBu [28], CF3 VAc [29], vinyl sulfonate ester derivatives [18, 30],
R1 S VDF [31–33], MDO [16, 34], DADMAC [35]
X0a: R1 = –CH3 , R2 = –CH2 CH3
X0b: R1 = –H, R2 = –CH2 CH3 A [19, 25] VAc [19, 25, 36, 37], ethylene [38]
X0c: R1 = –H, R2 = –CH3 A [38] VAc [36, 38, 39], ethylene [38]
X0d: R1 = –CH3 , A [16] MDO [16]
R2 = –CH(CH3 )2
X0e: R1 = –CH3 , R2 = –C4 H9
X0f: R1 = –CH3 ,
R2 = –Ph–O–CH3
R1 A [15, 34, 40–44] St [45, 46], BDDA [22], EGDA [22], DMA [44, 47], NIPAM [48], MMA [45], VAc [15, 42,
EtOOC S O 43, 49–52], VBu [51], S-vinyl sulfide derivatives [53], NVP [54, 55], NVPiP [56], NVTri
C B [45]
[41], NVPi [57], NVCbz [15, 54], N-vinylimidazolium salts [48]
R2 S
X1a: R1 = –H, R2 = –CH3
X1b: R1 = –CH3 , R2 = –CH3 A [40, 43, 49, 57] VAc [43, 49], NVPi [57]
X1c: R1 = –H, R2 = –H A [57] NVPi [57]
X1d: R1 = –H, R2 = –Ph A [55, 58] VAc [59], NVP [55, 58, 59]
Ph S O A [15, 18, 41, 48] St [60], DMA [61], NIPAM [48, 61], VAc [15, 19], vinyl sulfonate ester derivatives [18,
C R2 30], S-vinyl sulfide derivatives [53], NVP [58], NVCL [62], NVPi [57], NVCbz [15],
R1 S N-vinylimidazolium salts [48], N-vinylindole derivatives [63]
X2a: R1 = –CH3 , R2 = CH2 CH3
X2b: R1 = –H, R2 = –CH2 CH3 A [15, 18, 41] VAc [64, 65], NVCL [62], vinyl sulfonate ester derivatives [18, 30], S-vinyl sulfide
derivatives [53], NVPi [57], N-vinylindole derivatives [63]
X2c: R1 = –H, R2 = –CH(CH3 )2 A [15] VAc [15, 16], NVCbz [15]
O A [55, 66, 67] MA [67], DMA [67], MMA [67], VAc [67], NVP [55], NVP-b-VAc [66], VPA [68–70]
R1
S O
HO C R3
R2 S
X3a: R1 = –H, R2 = –CH3 ,
R3 = –CH2 CH3
X3b: R1 = –H, R2 = –H, A [71–73] VAc [71, 73], DADMAC [72]
R3 = –CH2 CH3
X3c: R1 = –H, R2 = –CH3 , A [74] n-BA-b-GMA [74]
R3 = –CH(CH3 )2
X3d: R1 = –H, R2 = –H, A [73] VAc [73]
R3 = –CH3
X3e: R1 = –H, R2 = –H,
R3 = –CH(CH3 )2
X3f: R1 = –H, R2 = –H,
R3 = –(CH2 )7 CH3
X3g: R1 = –H, R2 = –H, A [75]
R3 = –C(CH3 )3
S O C [58] NVP [58]
C
S
X4
S O A [75]
C
S
X5
(continued)
O A [76] VC [76]
HO S OEt NVP [77]
O C
S
X6
O A [78, 79] VAc [76]
C6F13 S OEt VC [76, 78]
O C
S
X7
O A [80, 81] VAc [80, 81]
S OEt MDO [34]
O C
R S
X8: R = –H or R = –CH3
O A [25, 82] St [82]
S OEt VAc [25, 82]
O C NVP [82]
R S
X9: R = –H or R = –CH3
R O S OEt A [19, 42] VAc [42]
C C VBz [42]
O S VPi [42]
X10: R = –H or R = –C(CH3 )3
A [83] EVE [84]
O S OEt
C
S
X11
O A [85] VAc [85, 86]
S OC4H9
N3 N C
H S
X12
A [87] VAc [87]
N3 S O
C O
S
X13
O B [55, 58] NVP [55, 58]
S OEt
HO C
CN S
X14
B [55] NVP [55]
S OEt
HO C
CN S
X15
O O A [88] VAc [88]
CI S OEt
HN N C
H S
X16
(continued)
S O B [7, 58, 63, 89, VAc [7, 90, 91]

C R 90] NVP [7, 55, 58, 89]
NC
S NVCbz [7]
X17a: R = –CH2 CH3 N-vinylindole derivatives [63] MMA [92]
X17b: R = –CH(CH3 )2
X17c: R = –CH2 CF3
O A [93] NVP [93]
O S OEt
N C
O S
O
X18
O A [94] NVP [94]
N S OEt
C
O S
X19
A [49] VAc [49]
S O NVP [95]
C
R1 S
R2
X20a: R1 = –H, R2 = –CH3
X20b: R1 = –CH3 , R2 = –H
N C [96, 97] VAc [96, 97]
N N
Ph NVP [96]
S OEt
C
S
X21
CF3 A [98] VDF [98]
S O
S
X22
S A [99] MA [99]
S
O
O
S
S
X23
S O A [82] NVP [82]
C C S O
O S C
R S
X24: R = –H or –CH3
A [100] NVP [100, 101]
O S S O NVCbz [102]
C C
S S
X25
a) The letter indicates the synthetic method used.

b) Monomer abbreviations and structures are shown in Table 10.2.
500 10 Xanthates in RAFT Polymerization
10.2.1 Reaction of a Xanthate Salt with an Alkylating Agent

The synthesis of xanthates is most commonly achieved by treating a xanthate salt
with an alkyl halide in conditions favourable to an SN 2 reaction. This method
was mainly used for the efficient preparation of xanthates containing primary and
secondary R groups, and yields were generally lower by substitution of tertiary
halides (40–60%) [40, 49]. Commercially available potassium O-ethyl xanthate
salt with structure EtO(C=S)S− K+ was by far the most considered [41, 42, 57].
Alternatively, xanthate salts can be produced by treatment of an alcohol precursor
with carbon disulfide in the presence of a strong base such as sodium or potassium
hydroxide [16, 40, 43, 49, 74, 103].
10.2.2 Reaction with Xanthogen Disulfides

Since xanthates bearing tertiary R leaving groups are more cumbersome to be pre-
pared via nucleophilic substitution of tertiary halides, Zard and coworkers [104] and
CSIRO [105] simultaneously reported the effective radical-induced decomposition of
a xanthogen disulfide by R group radicals derived from azo-initiators such as AIBN.
This method is now well established to produce S-tertiary xanthates in good yields
[58, 63, 104, 105]. It is also possible to use this chemistry to generate xanthates in
situ during polymerization [7, 89, 90].
Kwak et al. [45] reported a related atom transfer radical addition–fragmentation
process to synthesize various RAFT agents including xanthates (Scheme 10.1). The
process was accomplished using stoichiometric amounts of secondary or tertiary
alkyl halides and O-ethyl xanthogen disulfide in the presence of an atom transfer
radical polymerization (ATRP) catalyst and, optionally, Cu metal as a reducing
agent. Xanthate yields were lower (43%) compared with dithioesters (82–92%)
under similar conditions.
Addition
Atom transfer S S S
R
S
R X + Cu X/L
l
CuIIX2/L + R EtO S S OEt OEt
Cu(0)
Fragmentation
S
S OEt
Scheme 10.1 Atom transfer radical addition–fragmentation for the synthesis of xanthate
RAFT agents. Source: Adapted with permission from Kwak et al. [45]. Copyright 2009, John
Wiley & Sons.
10.2.3 Xanthates Used as Precursors to Provide New Xanthates

Functional xanthates can be derivatized into a variety of other xanthates of interest.
For instance, the Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition of S-propargyl
O-ethyl xanthate with phenyl azide yielded the triazolinyl xanthate X21 [96]. Owing
to the aromaticity of the triazole ring, the triazolinyl leaving group exhibits a similar
Table 10.2 Monomers compatible with the RAFT/MADIX process.
Monomer Abbreviations and structures
Styrenics St CMS
CH2CI
Acrylates MA n-BA EGDA BDDA

O O
O O
O O
O O
O O O
O
Acrylamides AM DMA NIPAM
O O O
H
N N N
H H
Methacrylates MMA
O
Vinyl esters VAc VBu VBr VPi

O O O Br
O
O O O
O
VBz VTFAc VTFBu CF3 VAc
O CF3 O CF3 O
O
O O CF3 O
O
(continued)
Monomer Abbreviations and structures
S-Vinyl monomers MES EES BES NES

O O O O
S O S O S O S O
O O O O
IPES PES TFES TCLES
O O O F O CI
F CI
S O S O S O S O
O O O F O CI
PVS CPVS DCPVS BPVS
CI
S S CI S Br
S CI
Vinyl phosphonic acid VPA

OH
P
OH
O
N-Vinyl monomers NVP NVCL NVPiP
O O O
N N N
NVTri NVPi NVCbz

O
N
N N N
N
O
PVI-Br EtOEVI-Br EHVI-Br
O
N + N + O N+
N –
N – N – O
Br Br Br
NVIn 2MNVIn 3MNVIn
N N
N
Vinyl ethers EVE IBVE HOVE

O O
O OH
Halo-olefins VDF PMVE TFE
H F F F F F
H F F OCF3 F F
CTFE HFP VC
F F F F H H
CI F F CF3 H CI
Miscellaneous Ethylene MDO BMDO DADMAC
H H O O
+
H H O O N
St, styrene; CMS, 4-chloromethylstyrene or 4-vinylbenzyl chloride; MA, methyl acrylate;, n-BA, n-butyl acrylate; EGDA, ethylene glycol diacrylate; BDDA,
1,4-butanediol diacrylate; AM, acrylamide; DMA, N,N-dimethylacrylamide; NIPAM, N-isopropylacrylamide; MMA, methyl methacrylate; VAc, vinyl acetate; VBu,
vinyl butyrate; VBr, vinyl bromobutanoate; VPi, vinyl pivalate; VBz, vinyl benzoate; VTFAc, vinyl trifluoroacetate; VTFBu, vinyl trifluorobutyrate; CF3 VAc,
1-(trifluoromethyl)vinyl acetate; MES, methyl ethenesulfonate; EES, ethyl ethenesulfonate; BES, 1-butyl ethenesulfonate; NES, neopentyl ethenesulfonate; IPES,
isopropyl ethenesulfonate; PES, phenyl ethenesulfonate; TFES, 2,2,2-trifluoroethyl ethenesulfonate; TCLES, 2,2,2-trichloroethyl ethenesulfonate; PVS, phenyl vinyl
sulfide; CPVS, 4-chlorophenyl vinyl sulfide; DCPVS, 2,4-dichlorophenyl vinyl sulfide; BPVS, 4-bromophenyl vinyl sulfide; VPA, vinylphosphonic acid; NVP,
N-vinylpyrrolidone; NVCL, N-vinylcaprolactam; NVPiP, N-vinylpiperidone; NVTri, N-vinyl-1,2,4-triazole; NVPi, N-vinylphthalimide; NVCbz, N-vinylcarbazole;
PNI-Br, 1-(3-phenylpropyl)-3-vinylimidazolium bromide; EtOEVI-Br, 1-(2-ethoxyethyl)-3-vinylimidazolium bromide; EHVI-Br,
1-(6-ethoxycarbonylhexyl)-3-vinylimidazolium bromide; NVIn, N-vinylindole; 2MNVIn, 2-methyl-N-vinylindole; 3MNVIn, 3-methyl-N-vinylindole; IBVE, isobutyl
vinyl ether; EVE, ethyl vinyl ether; HOVE, 2-hydroxylethyl vinyl ether; VDF, vinylidene fluoride; PMVE, perfluoro(methyl vinyl ether); TFE, tetrafluoroethylene;
CTFE, chlorotrifluoroethylene; HFP, hexafluoropropylene; VC, vinyl chloride; MDO, 2-methylene-1,3-dioxepane; BMDO, 5,6-benzo-2-methylene-1,3-dioxepane;
DADMAC, diallyldimethylammonium chloride.
performance to that of a benzyl leaving group, and hence has been confirmed as
an appropriate leaving group for RAFT polymerizations of N-vinylpyrrolidone
(NVP) and VAc (see footnote of Table 10.2 for the complete list of monomer
abbreviations) [96].
S-(tert-Butyl)-O-ethyl xanthate (X4) with high purity (>96%) and moderate yield
(55%) has been synthesized by thiol exchange between a thioglycolic acid-based xan-
thate and tert-butyl thiol [58].
10.3 Experimental Conditions

In this section, an overview of recent reports on various modes of initiation and poly-
merization processes involving xanthate RAFT agents is proposed.
10.3.1 Initiation
As with other classes of RAFT agents, the commonly used methods to generate
active radicals in RAFT polymerization with xanthates include (i) decomposition
of thermal initiators, (ii) UV or visible light irradiation, (ii) 60 Co γ-ray irradiation,
and (iv) redox initiation.
10.3.1.1 Thermal Initiators

The most common source of radicals for xanthate-mediated RAFT polymerization is
azo-type initiators. AIBN and other commercially available azo initiators [16] have
been selected according to their solubility and activation temperature.
Roy and Sumerlin [71] synthesized well-defined homopolymers and block
copolymers of vinyl esters via xanthate-mediated RAFT with AIBN initiator
under microwave heating. An unexplained enhancement of molecular weight
controllability without significant inhibition or retardation was observed.
10.3.1.2 UV or Visible Light

An attractive alternative method to generate radicals uses UV or visible light
to control the flux of radicals through simple ‘ON/OFF’ modulation of the
light irradiation. A first approach consists in direct homolysis of the xanthate
under irradiation, which plays a dual role of initiator and mediator. This strat-
egy avoids the introduction of external radical sources and metal complexes
into the polymerization, hence pushing back the limits in terms of molar mass
control [50, 106–110]. Another approach involves photoinitiators. Successful
RAFT polymerization of VAc has been demonstrated using X0b RAFT agent and
bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide as photoinitiator [111].
Boyer’s group reported the first RAFT polymerization based on a photoinduced
electron transfer (PET) process between a RAFT agent and the photoredox catalyst
fac-[Ir(ppy)3 ] under visible light irradiation [112, 113]. The proposed mecha-
nism with xanthate RAFT agents for the so-called PET-RAFT polymerization is
described in Scheme 10.2. Since then, a few xanthate/photoredox catalyst systems
10.3 Experimental Conditions 505
such as X0a/ZnTPP [103] and X3a/Bi2 O3 [67] have been applied to PET-RAFT
polymerization. Conveniently, PET-RAFT polymerization is oxygen tolerant and
can be carried out without the conventional degassing procedure [103].
PET
Ir(III)* RAFT Process

S S
S S
Visible (IV)
Pn S
Ir Pn + Pm S OEt Pn S OEt + Pm
OEt Light EtO S
M
M
(III)
Ir
Scheme 10.2 Proposed mechanism for xanthate-mediated PET-RAFT polymerization.

Source: Adapted with permission from Xu et al. [112]. Copyright 2014, John Wiley & Sons.
10.3.1.3 60
Co 𝛄-ray Irradiation
60 Co γ-ray irradiation as a source of active radicals has attracted increasing attention
over the years, since the first γ-ray-initiated RAFT polymerization of methyl acry-
late (MA) performed with five S-benzyl xanthates, including X2b [114]. Later, the
same group reported the RAFT polymerization of the same monomer with a cyclic
dixanthate (X23) at different temperatures (28, −30 and −76 ∘ C) [99]. Polymers with
well-controlled macromolecular characteristics were obtained. The lower the tem-
perature is, the better the control of the polymerization. Yu et al. [52] investigated
bulk RAFT polymerization of VAc with X1a at room temperature, and compared to
AIBN initiation at 60 ∘ C. Much lower dispersities and slightly better control of the
polymer regioregularity were found with γ-ray initiation, presumably mainly due
to differences in temperature. Segura et al. [91] reported miniemulsion polymeriza-
tion of VAc with X17a at room temperature. Controlled M n values with relatively
high dispersities (1.5 < Ð < 2.4) were obtained, for a process yielding stable latexes
produced with high rates and high conversions. Sütekin and Güven [17] also stud-
ied the γ-radiation-induced RAFT polymerization of AA in aqueous media and in
ethanol, using xanthate X0a. PAAs with controlled Mn and dispersities in the range
of 1.23–1.39 were synthesized. Wang et al. [115] investigated the xanthate-mediated
living/controlled radical copolymerization of hexafluoropropylene (HFP) and butyl
vinyl ether (BVE) at room temperature under 60 Co γ-ray irradiation. Xanthate X1b
was used to control the synthesis of poly(HFP-alt-BVE) [115] with dispersities close
to 1.3 up to M n of 35 000 g mol−1 . After that, the xanthate terminal was oxidized to
produce a fluoroalkyl sulfonic acid chain end.
10.3.1.4 Redox Initiation

Only one case of organosoluble redox initiating system (benzoyl peroxide/N,N-
dimethylaniline) under high pressure (5 kbar) was reported, for VAc polymerization
with X1a [49]. In contrast, numerous examples of aqueous redox initiators were
reported relatively recently. tert-Butylhydroperoxide (TBHP) in combination with
ascorbic acid (AsAc) allowed the RAFT polymerization of N-vinylcaprolactam
(NVCL) in water–ethanol mixtures with X0a [116] and that of NVP in pure
water at room temperature with the same xanthate [117]. Using xanthate X1a,
TBHP/AsAc initiated the polymerization-induced thermal self-assembly (PITSA)
of N-isopropylacrylamide (NIPAM) and pentafluorophenyl acrylate (PFPA) [44].
In association with sodium sulfite Na2 SO3 as reducing agent [118], TBHP initiated
the controlled RAFT polymerization of NVP in water, by maintaining pH under
basic conditions in order to avoid the formation of NVP hydration by-products.
The ammonium persulfate (APS)/sodium formaldehyde sulfoxylate (NaFS) redox
system was proved an excellent initiator for the aqueous polymerization of Am
[23, 119] and derivatives [119] with X0a at room temperature, or for comonomer
compositions comprising Am [120].
10.3.2 Polymerization Conditions

One of the major advantages of RAFT polymerizations is its compatibility with vari-
ous reaction conditions, as it only requires the introduction of a CTA to an otherwise
conventional-radical polymerization. In recent years, high-pressure polymerization
and the RAFT PISA process have attracted the attention of researchers.
10.3.2.1 High-Pressure Polymerization

The use of high-pressure conditions (several kbar) for radical polymerization
can increase the propagation rate coefficient kp by several orders of magnitude
and decrease the overall activation volumes [121]. Hence, high molecular weight
polymers can be obtained with accessible industrial polymerization processes.
Chen et al. [49] reported the use of high pressure (up to 5 kbar) for the synthesis
of high molecular weight PVAc (M n = 123 000 g mol−1 , Ð = 1.28) via RAFT poly-
merization at 35 ∘ C using X1a, X1b, and X20a CTAs. Under these conditions, the
polymerization rate was significantly increased (15.2 times) in comparison with
atmospheric pressure conditions. An induction period of four hours was observed,
and polymerizations were kept below 40% conversion in order to maintain an
acceptable level of control of M n and Ð. A decrease of efficiency in the order of
X1a > X1b > X20a was found.
10.3.2.2 Heterogeneous Polymerizations

Xanthate-mediated RAFT polymerization is compatible with all kinds of het-
erogeneous processes, in particular aqueous emulsion polymerization. Owing
to their inherently low transfer constant for conjugated monomers and suitably
limited solubility in water, xanthates were the first RAFT CTAs in early 2000s
to circumvent issues associated with particle nucleation and allow controlled
emulsion polymerization under ab initio conditions [122]. Since then, other
strategies such as seeded emulsion, miniemulsion, and microemulsion polymer-
izations using xanthates have been successfully carried out and recently reviewed
10.4 Kinetics 507
[123, 124]. RAFT-mediated PISA is a recent and very powerful process for preparing
block copolymer nanoparticles [125]. Recently, Binauld et al. [126] reported the
xanthate-mediated RAFT emulsion PISA of VAc in the presence of PNVP, PEG, and
poly(acryloylmorpholine) macro-CTAs, giving access to original surfactant-free
PVAc latexes in water. Siirilä et al. [127] reported the aqueous emulsion PISA
polymerization of NVCL with PEG-X1a above the thermal transition temperature
of PNVCL, producing larger vesicular morphologies than the most commonly found
spherical core–shell particles. In order to design waterborne physically crosslinked
thermoresponsive particles, a successful approach of the xanthate-mediated RAFT
PISA copolymerization of VAc and NVCL in emulsion with PEG-X1a was reported
[128]. Zhang et al. [129] synthesized poly(ionic liquid) (PIL) nanoparticles through
the aqueous RAFT PISA process of 3-n-dodecyl-1-vinylimidazolium bromide,
using PEG-X1a as macro-CTA. Vakili et al. [44] recently reported the preparation of
thermoresponsive crosslinked nanoobjects by aqueous PISA of PFPA starting from a
monomer-in-water emulsion or NIPAm, using a PDMA-X1a reactive stabilizer and
either redox or UV activation at room temperature. The synthesis of PVAc-b-PVDF
block copolymers was investigated by RAFT PISA in dispersion in dimethylcar-
bonate [130]. The presence of PVAc and PVDF homopolymer contaminants was
confirmed as a result of side reactions. New flake-like crystalline structures were
obtained, with morphologies presumably governed by the crystallization of the
PVDF block.
Two supercritical CO2 -(scCO2 ) soluble xanthate-terminated PVAc (PVAc-X0b and
PVAc-X0c) were reported by Pham et al. [36] for RAFT homopolymerization of VAc
and VPi in scCO2 . As expected for an efficient RAFT process, an increase in the ini-
tial loading of macroRAFT agent resulted in a decrease in both M n and dispersities
of PVAc, whereas the conversion was not affected (relatively low, <37%). Disper-
sities increased during polymerization for both VAc and VPi. The xanthate agent
with an ethoxy group (X0b) showed better controllability (with lower Ð value) than
that with a methoxy group (X0c). The reported process could be referred to as a dis-
persion RAFT PISA in scCO2 even though the authors did not address the nature
of the reaction medium during polymerization. Howdle and coworkers developed
X1a-RAFT PISA dispersion of NVP in scCO2 using statistical copolymers of VAc
with VBu [51] and VPi [131, 132] as macro-CTAs.
10.4 Kinetics
The different aspects of the kinetics of RAFT polymerization with xanthate
CTAs, including their structure–reactivity relationship [133–135], initialization
phenomenon [136], and computational studies of their addition–fragmentation
pathways [137], have been largely reported in the 2000s. Owing to their strong
σ-withdrawing character, alkoxy Z groups stabilize the intermediate RAFT radicals
to a limited extent. Hence fragmentation is fast, and consequently xanthates have a
very limited impact on the rate of polymerization in comparison with more reactive
RAFT agents.
The reactivity of xanthate X0a has been largely explored over the whole range
of monomers. Its chain transfer constant Ctr can vary by orders of magnitude
depending on the monomer. For non-conjugated monomers such as vinyl esters
[35], N-vinyl monomers [117, 138], S-vinyl monomers [18, 53], vinyl phosphonic
acid (VPA) [68, 92], diallyldimethylammonium chloride (DADMAC) [35], and
ethylene [38], a systematic good correlation between theoretical and experimental
M n in the early stages of polymerization reflected the high reactivity of X0a (Ctr
typically >10). In a few cases such as for NVP and VAc, the selective formation
of the O-ethyl xanthate/monomer 1 : 1 adduct prior to polymerization (so-called
initialization period) was evidenced [136]. The interchain transfer constant Cex can
be quite high and result in narrowly dispersed polymers such as for N-vinyl lactams
[138] and vinyl esters [35]. In contrast, relatively high dispersities for PVPA [92] and
PDADMAC [35] were attributed to a slow reversible transfer of the O-ethyl xanthate
end-group during polymerization. For conjugated monomers, the reactivity scale of
xanthate X0a is as follows: acrylamides > acrylates > styrenics ≫ methacrylates. For
substituted acrylamides (AMs), Ctr and Cex are in the two to five range, which allows
the formation of polyacrylamides with dispersities down to 1.2 in best cases [139].
Xanthates exhibit slightly lower reactivities for acrylate monomers; Ctr and Cex are
in the range of 1.5–2.0 for X0a, leading to dispersities generally between 1.5 and 1.8
[139]. O-Ethyl xanthates are poorly reactive for styrene and derivatives, with Ctr in
the 0.65–0.80 range [46, 133, 139] and reported Cex values of 0.65 [139] and 0.44 [46]
for St. Polymerization of methacrylates with O-ethyl xanthates is uncontrolled, as
illustrated by the very low Ctr values recently reported for this monomer (<0.1) [140].
10.5 Monomers
Xanthates RAFT agents can control a very broad range of monomers with highly
disparate reactivities, typically from ethylene to methacrylates under specific condi-
tions. A summary of compatible monomers is given in Table 10.2.
10.5.1 Styrenics
A limited number of recent studies deal with the use of xanthates in the polymer-
ization of styrene and derivatives because of their poor transfer ability. Devlaminck
et al. [46] recently reported a detailed study on X1a-mediated RAFT polymeriza-
tion of St in bulk and solution conditions by successfully combining experimental
and modelling analysis tools. Couture and Améduri [20] investigated the kinetics of
RAFT polymerization of 4-chloromethyl styrene (CMS) initiated by AIBN at 80 ∘ C in
the presence of xanthate X0a. M n decreased with constant high Ð values (≈1.8) dur-
ing the reaction, indicating that the polymerization is poorly controlled in a similar
fashion with St.
10.5.2 Acrylates and Acrylamides

RAFT polymerizations of acrylates and acrylamides with xanthate CTAs have been
widely studied. Mori and Tsukamoto [22] investigated RAFT polymerization of
10.5 Monomers 509
diacrylate derivatives having different spacers under dilute conditions by using

xanthates X0a and X1a and comparing with benzyl 1-pyrrolecarbodithioate of much
higher reactivity. Owing to their moderate reactivity, xanthates led to comparatively
faster polymerization rates, higher molecular weights, broader molecular weight
distributions, and crosslinked products in some cases. Reports of polymerization
of acrylamide monomers with xanthate RAFT agents include pioneering works
on AM by Taton et al. using X0a and a difunctional xanthate in aqueous media
[141], N,N-dimethylacrylamide (DMA) [47, 61, 67] and NIPAM [44, 61]. In all
cases, polymerizations led to controlled M n at high conversions and relatively
narrow molecular weight distributions (1.2 < Ð < 1.5). Yuan et al. [61] reported
the controlled synthesis of double hydrophilic block copolymers comprising either
PNIPAM or PDMA as neutral first block and poly(1-vinylimidazolium) ionic liquid
block using X2a CTA. Hakobyan et al. [67] and Carmean et al. [47] were interested
in the aqueous polymerization of DMA via PET-RAFT process with Bi2 O3 catalyst
using X3a, and by direct activation by UV light with X0a, respectively.
One of the most striking advances of the last decade in the field of RAFT polymer-
ization is the access to ultra-high molar molecular weight (UHMW, M n of typically
106 g mol−1 and above) polyacrylamides by the so-called aqueous RAFT gel poly-
merization process first reported by our group [119]. It involves the use of minute
amounts of redox initiator at low temperatures (10–25 ∘ C) for monomer concentra-
tions >10 wt.%. Under these reaction conditions, polymerizations reach completion
within a few hours while a physical gel is formed. Low-dispersity polymers (Ð < 1.2)
were obtained for controlled M n up to ∼106 g mol−1 for AM and DMA homopoly-
mers, AM/AMPS statistical copolymers, and a PNIPAM-b-DMA copolymer [119].
Inspired by this work, Mejia et al. [142] developed an adiabatic gel process to perform
polymerizations to a much higher volume and monomer concentration (from 2.0 to
3.47 M). They obtained controlled high molar mass P(AM-stat-AMPS) copolymers
up to 3 × 106 g mol−1 over the whole range of composition. Adiabatic and conven-
tional gel processes gave similar results. Alternatively, Sumerlin’s group reported a
photomediated-RAFT polymerization under conditions of gel polymerization with
xanthate X1a as the single source of radicals [109]. By doing so, well-defined PDMAs
were obtained using a UV light source. The molar masses reached 8.67 × 106 g mol−1
in less than five minutes of irradiation, and dispersities below 1.2 were achieved.
Thanks to well-defined polyacrylamides produced by RAFT gel polymerization
with X0a [119] the outcome and kinetics of competitive adsorption between low
and high molar mass chains of neutral PAM or partially hydrolyzed-PAM in aqueous
solution at the surface of siliceous materials were better understood [143, 144].
10.5.3 Methacrylates
The reactivity of O-ethyl xanthates in methacrylate polymerization is very low (Ctr
typically <0.1) [4, 92], hence no block copolymerization comprising a methacrylate
sequence is possible under classical RAFT batch polymerization conditions. At
best, a limited amount (up to ∼20 mol%) of methacrylate comonomer can be
statistically copolymerized in a controlled manner with a xanthate-compatible
monomer, e.g. an acrylate. Recently, Destarac et al. [92] adapted a semi-batch RAFT
emulsion polymerization strategy reported for methacrylate polymerization with

oligo(methacrylate) macromonomer CTAs [145] to fluorinated xanthate X17c of
similar reactivity. By keeping very low instantaneous methyl methacrylate (MMA)
concentrations, well-controlled PMMA latexes with controlled molar masses and
low dispersities (1.2 < Ð < 1.3) were obtained prior to chain extension with VAc,
leading to PMMA-b-PVAc copolymers.
10.5.4 Vinyl Esters

Xanthates are the most popular RAFT agents for controlling the polymerization of
vinyl esters [9], among which VAc was by far the most studied. The reactivity of
X0a-X0c [24, 25, 36–39], X1a [15, 42, 43, 49–52], X1b [43, 49], X1d [59], X2a [15],
X2c [15, 16], X3a [67], X3b [71, 73], X3d-X3f [73], X7-X10 [25, 42, 76, 80–82], X12
[85, 86], X13 [87], X16 [88], X17a [7, 90, 91], X20a [49], and X21 [96, 97] under
different conditions of VAc polymerization was examined by different groups. The
high reactivity of the propagating radical leads to a non-negligible fraction of side
reactions such as 1–2% head-to-head addition [146] and chain transfer to solvent,
monomer, and polymer, which explains limited RAFT control in terms of M n (typ-
ically <105 g mol−1 ) while maintaining low dispersities (Ð < 1.2). Other vinyl alky-
lates such as vinyl benzoate (VBz) [42], vinyl butyrate (VBu) [51], and vinyl pivalate
(VPi) [42, 131, 132, 147, 148] were also successfully polymerized with xanthates
(Table 10.2). Most of these studies aimed at improving the solubility of their copoly-
mers with VAc in scCO2 .
Using RAFT agent X0f, Hedir et al. [149] synthesized a series of thermoresponsive
poly(oligo(ethylene glycol) vinyl acetate)s (P(MeO2 VAc)s) with excellent control
over their molecular properties. Moreover, the statistical copolymerization of
MeO2 VAc with 2-methylene-1,3-dioxepane (MDO) cyclic ketene acetal (CKA)
enabled to independently control the thermal properties and degradation behaviour
of the resulting polymers.
Well-defined poly(fluorovinyl esters) from vinyl trifluoroacetate (VTFAc) [26, 27]
and vinyl trifluorobutyrate (VTFBu) [28] were synthesized via RAFT polymerization
using X0a as CTA. The solubility of PVTFBu and VTFAc/VAc statistical copolymers
in scCO2 was shown to be greatly enhanced compared to PVAc [26–28]. As PVT-
FAc is much more susceptible to hydrolysis than VAc, diblock copolymers of VAc
and VTFAc allowed the preparation of PVAc-PVOH diblock copolymers by selective
methanolysis. 1-(Trifluoromethyl)vinyl acetate (CF3 VAc) has been copolymerized
with VAc by X0a-mediated RAFT polymerization with a strong tendency towards
alternated microstructure [29]. By increasing the CF3 VAc molar fraction from 10%
to 50% in the feed, an increase of dispersities (1.2 < Ð < 1.7) was observed although
control over molecular weight was maintained (M n ∼ 4000 g mol−1 ).
10.5.5 S-Vinyl Monomers

Mori and his colleagues focused on S-vinyl monomers, including eight vinyl sul-
fonate ester derivatives (in Table 10.2) [18, 30]: methyl ethenesulfonate (MES), ethyl
10.5 Monomers 511
ethenesulfonate (EES), 1-butyl ethenesulfonate (BES), neopentyl ethenesulfonate

(NES), 2,2,2-trifluoroethyl ethenesulfonate (TFES), 2,2,2-trichloroethyl ethenesul-
fonate (TCLES), isopropyl ethenesulfonate (IPES), phenyl ethenesulfonate (PES);
and four S-vinyl sulfide derivatives (in Table 10.2) [53]: phenyl vinyl sulfide (PVS),
4-chlorophenyl vinyl sulfide (CPVS), 2,4-dichlorophenyl vinyl sulfide (DCPVS),
4-bromophenyl vinyl sulfide (BPVS). All the homopolymers exhibited relatively
narrow molecular weight distributions (1.3 < Ð < 1.7) and pre-determined molec-
ular weights when RAFT agent X0a was used. Block copolymerizations were
also successfully conducted via RAFT polymerization using PNIPAM-X0a [30] or
PNVCbz-X0a [18, 53] as macro-CTA, the synthesized block copolymers having
distinct thermoresponsive property [18, 30] or optoelectronic functionalities [53].
10.5.6 Vinyl Phosphonic Acid

VPA is a monomer of great interest due to the multiple properties of the corre-
sponding polymers associated with its strong diacid character. It had been a very
challenging candidate for RDRP due to its vinyl nature and unprotected phospho-
nic acid character, until Blidi et al. [68] first reported the controlled aqueous RAFT
polymerization of VPA using X3a under thermal initiation conditions. Using 31 P
NMR spectroscopy the authors established that transfer to X3a is fast compared to
propagation with early formation of xanthate-terminated oligomers. By means of a
X3a/VPA 1 : 1 adduct, it was shown by SEC and 31 P NMR spectroscopy that chain
growth proceeds with a relatively slow interchain transfer of the xanthate terminal
group, resulting in relatively high dispersities [68]. Destarac’s group tried to accel-
erate VPA polymerization by using microwave irradiation [70] or by adding metal
alkali hydroxides [69]. Microwave heating with X3a caused a threefold increase of
the initial rate of RAFT/MADIX aqueous polymerization compared with conven-
tional heating, with no visible impact on the macromolecular parameters of PVPA.
With metal alkali hydroxide additives, the use of 0.5 equiv NaOH relative to VPA led
to the fastest polymerizations, while 0.5 equiv KOH and NH4 OH provided a mod-
erate increase in rate coupled with a significant reduction in dispersity of the final
polymers [69].
10.5.7 N-Vinyl Monomers

A wide range of xanthates, including X1a, X1d, X2a, X3a, X4, X9, X14, X15,
X17a–X19, X21, X24, and X25, have been used for the polymerization of NVP
[7, 54, 55, 58, 82, 89, 93, 94, 100, 101, 150] either in bulk or in organic solvent with
thermal initiation. Pound et al. [55] evidenced several side reactions in RAFT poly-
merization of NVP, among which are hydration products of NVP at acidic pH and
elimination of the xanthate from the polymer chain end. The main lessons learnt
from this precious contribution was that control of pH when using aqueous media
and the application of low temperatures should lead to a decrease of undesired
reactions. Later, Guinaudeau et al. [117] reported successful aqueous RAFT poly-
merization of NVP under concentrated conditions at room temperature (pH = 6–7)
with TBHP/ascorbic acid as redox initiator. For the synthesis of NVP-based double
hydrophilic block copolymers under more dilute conditions, sodium sulfite was
used instead as reducing agent (pH ∼ 9) [117]. Very recently, Wang et al. [95]
reported RAFT polymerization of NVP under UV or visible light irradiation at room
temperature with xanthate X20b and without extra initiator or catalyst. Wan et al.
[62] and Beija et al. [138] reported the successful RAFT polymerization of NVCL,
respectively with X2a and X0a. Well-controlled statistical copolymers of NVP and
NVP of tunable LCST and hydrogel properties were effectively designed using X0a
[151]. The polymerization of several other N-vinyl monomers, N-vinylpiperidone
(NVPiP)/X1a [56], N-vinyl-1,2,4-triazole (NVTri)/X1a [41], N-vinylphthalimide
(NVPi)/X1b [57], N-vinylcarbazole (NVCbz)/X17a, and X25 [7, 108], was controlled
by RAFT polymerization.
Mori et al. [48] reported the RAFT polymerizations of a series of four
N-vinylimidazolium salts (Table 10.2) by using X1a and X2a as CTAs. The
polymerizations proceeded in a controlled fashion. Maki et al. [63] examined the
RAFT polymerization of three N-vinylindole derivatives: NVIn, 2MNVIn, and
3MNVIn (Table 10.2) with five different xanthates. Among them, X2a was the most
efficient (Ð = 1.20–1.40).
10.5.8 Halo-olefins
Recent years have witnessed a growing interest in the development of xanthate-
mediated RAFT to control the polymerization of vinylidene fluoride (VDF),
perfluoro(methyl vinyl ether) (PMVE), tetrafluoroethylene (TFE), chlorotriflu-
oroethylene (CTFE), and hexafluoropropene (HFP) and prepare well-defined
fluoropolymer-based architectures including end-functional [115, 152] and star
[153] polymers, statistical [79, 154, 155], alternated [115, 156], and block copolymers
[31, 83, 84, 98, 154, 157]. As VDF was the only fluoro-olefin of the series to be
homopolymerized in a controlled fashion by RAFT [32, 33, 154, 157], it will be the
only study described in this section. All the other works on various microstructures
and architectures will be developed in dedicated sections.
Guerre et al. [32] carried out a thorough study of the RAFT polymerization of
VDF using xanthate X0a in dimethylcarbonate. PVDF-X0a homopolymers with
DPn < 50 showed narrow molar mass distributions (Ð < 1.5), and were expected to
be used as macro-CTAs for preparing novel fluorinated architectures. It was found
that polymerizations suffer from several side reactions, among which are transfer
to solvent and reverse additions during propagation. The latter effect is responsible
for an accumulation of –CH2 –X chain ends during polymerization until –CF2 –X
terminal groups completely disappear. The authors defined this stage as the end
of RAFT control with conventional radical polymerization taking over, until they
demonstrated by means of NMR and DFT calculations that the reverse xanthate
adducts –CF2 CH2 –X can actually be reactivated by a small fraction of –CF2 CH2 ⋅
radicals present in the system [33]. Transfer to solvent contributed to the loss of
∼10% of xanthate terminal functionality with ∼90% of chains remaining potentially
reactive.
10.5 Monomers 513
Solution and aqueous miniemulsion of RAFT polymerizations of VC mediated

by fluorinated xanthate X7 were successfully conducted by Huang et al. [78].
The miniemulsion polymerization exhibits higher rate and broader molecular
weight distribution than solution polymerization. It was further reported that the
X7-terminated PVC can be reinitiated and extended by VAc and NVP in solution;
and the X7-terminated PVC can also be chain-extended by VAc in miniemulsion
polymerization to obtain PVC-b-PVAc diblock copolymers. Very recently, Coelho
and coworkers [158] reported the efficient low-temperature (30 ∘ C) RAFT polymer-
ization of VC in cyclopentyl methyl ether with xanthate X0b. Dispersities in the
1.2–1.3 range were obtained. Very small fractions of structural defects were revealed
by NMR spectroscopy. Successful chain extensions were performed with VAc and
NVCL to produce the corresponding diblock copolymers.
10.5.9 Ethylene
Dommanget et al. [38] reported the first example of RAFT polymerization of ethy-
lene in the presence of xanthates X0b and X0c as CTAs in dimethylcarbonate under
relatively mild conditions (70 ∘ C, P ≤ 200 bars). The livingness of the process was
confirmed by the linear increase of predicted molar masses vs. conversion and by
PE chain extension. A side fragmentation of the O-ethyl group was evidenced by 1 H
NMR, which limited control to low M n (∼2 K). Semicrystalline copolymers of ethy-
lene and vinyl acetate were further produced under mild conditions and exhibited
low contents of the VAc unit (<10%). In a later report [159], the O-fragmentation
was suppressed by the same group using aromatic xanthates X0f. The loss of living
chain ends was nevertheless detected via a mechanism based on cross-termination.
PEs with Ð = 1.2–1.3 were obtained for M n up to 1000 g mol−1 .
10.5.10 Cyclic Ketene Acetals (CKAs)

Ring-opening polymerization of CKAs by radical polymerization has attracted
increasing attention over the past years [160]. The widely studied MDO, a
seven-membered ring CKA (Table 10.2) for which the corresponding polymer
PMDO is identical to poly(ε-caprolactone), was successfully polymerized by RAFT
using xanthates [16, 161, 162]. Bell et al. [16] reported the controlled homopoly-
merization of MDO in the presence of X0a and X0d–X0f. The p-methoxyphenyl
xanthate X0f offers significantly enhanced control over molecular weight and
dispersity compared to other xanthates. In-depth investigation showed loss of the
xanthate functionality as a result of Z group fragmentation leading to the formation
of carbonodithioate groups (Scheme 10.3). Then the authors applied X0f to the
statistical copolymerization of VAc and MDO, all dispersities were within 1.3–1.5.
Hedir et al. successfully synthesized linear degradable copolymers P(MDO-co-VAc)
[162] and P(MDO-co-VBr) [161]. The bromine atom of the VBr units was converted
to an azide for further derivatization by alkyne–azide click coupling.
Hydrolytically degradable statistical copolymers of 5,6-benzo-2-methylene-1,3-
dioxepane (BMDO) (Table 10.2) with NVCL (Ð = 1.4–1.6) [163] and VAc (Ð < 1.26)
O
∙
P S S + Pm
O n
O
Z
Xanthate end-group functionality
kfrag1 kadd
O O
P S S P
O n O m
O
Z
kfrag2 Z
O O
P S S P
O n O m
O
Carbonodithioate mid-chain functionality
Scheme 10.3 Rearrangement and Z-group fragmentation occurring during the

polymerization of MDO in the presence of a xanthate. Source: Bell et al. 2015 [16] and
Xu et al. 2019 [34]. Adapted with permission of John Wiley & Sons. [16, 34].
[164] were achieved by RAFT polymerization with F BMDO up to 0.5 using X0b and
0.4 with X0a, respectively. In both, BMDO was found to be much more reactive
than its comonomer.
10.5.11 Diallyl Monomers

In the case of diallyl monomers, Assem et al. [72] first reported the RAFT/MADIX
cyclopolymerization of DADMAC in aqueous medium via RAFT process with
trithiocarbonates in 2007. Comparatively, the RAFT agent X3b was much less
efficient to control M n , despite unexpectedly giving low dispersities (Ð ≈ 1.12).
Soon after, our group [35, 92] investigated the aqueous DADMAC polymeriza-
tion at 50 ∘ C using a X0a-terminated AM oligomer of DPn = 7. Excellent control
of M n was observed with dispersities (1.8 < Ð < 2.2), which contradicted the works
of Assem et al. [72]. Based on a kinetic study using the SEC-peak resolution method,
it was concluded that Cex was quite low (1.5), which supported the existence of broad
molar mass distributions.
10.6 Macromolecular Architectures

Xanthate-mediated RAFT copolymerization is a versatile and powerful tool to design
and synthesize controlled copolymers with ‘complex’ macromolecular architectures,
including end-functional homopolymers/statistical copolymers, block copolymers,
gradient copolymers, cyclic polymers, graft/comb/brush copolymers, and star and

hyperbranched polymers (HPs). This section reviews the recent achievements in
macromolecular engineering with RAFT using xanthates.
10.6.1 End-Functional Homopolymers/Statistical Copolymers

Well-defined functional polymers can be obtained by using either a functionalized
monomer or a xanthate agent. Recently, Jia et al. [165] demonstrated the first
example of a lysine-based NVCL derivative and its RAFT copolymerization to afford
a sustainable and amino-functionalized PNVCL with thermo and pH dual-stimuli
responsiveness. Langlais et al. [166] designed two new thiolactone-based xanthates
from a single hydroxy thiolactone (Scheme 10.4), which were further used in the
RAFT polymerization of NVP, NVCL, VAc, and NIPAM. The efficiency of these
xanthates was evidenced through the successful synthesis of related functional
homopolymers of controlled M n and low dispersities (Ð < 1.22), bearing α-terminal
thiolactone groups. The thiolactone group at the end of the polymer chains was
post-modified with an amine-thiol-thiosulfonate strategy.
O O
Br Br
S O
O O O Br
S 8 S 8 OH S 8O
OH TL-OH TL-Br2
M-OH
O
Br
Br
O
O Br
S 8 O
– + TL-Br1
O S ,K – +
O S ,K
S S
O O
O OP N Cu(0)/ O
O S O O Me6Tren O S O
O 8 S S
8
O
S S
TL-XA1 TL-XA2
O
O O O
S 8 O N P
O O
TL-SG1
Scheme 10.4 Synthetic route to thiolactone-containing RDRP agents for controlled

polymerizations. Source: Adapted with permission from Langlais et al. [166]. Copyright
2018, John Wiley & Sons.
Post-polymerization modification (PPM) of functional polymers has also gained

the most attention these years. Chen et al. [167] have reported the synthesis of PVAc
with fluorescence properties via a combination of RAFT polymerization and ‘click’
chemistry. They first used an azido-functional xanthate to mediate RAFT polymer-
ization of VAc and give rise to azide-terminated PVAc. Then the resulting PVAc was
‘clicked’ with a fluorescent alkyne.
Etchenausia et al. [168] synthesized well-defined thermoresponsive amphiphilic

statistical copolymers based on NVCL and VAc by polymerization mediated by X1a
at 65 ∘ C. Copolymers with controlled molar masses and low dispersities (Ð < 1.3)
were produced over a wide range of monomer feed ratios. Reactivity ratio values
demonstrated that NVCL and VAc units are distributed homogeneously along the
copolymer chains.
Several types of statistical and alternated copolymers based on fluoro-olefins
using RAFT polymerization have been recently reported using xanthate
X0a, more precisely poly(VDF-stat-PMVE) [154], poly(VDF-stat-TCP) [79],
poly(VDF-stat-MAF-TBE) [155], and low-dispersity (Ð ∼ 1.1) poly(TFE-alt-iBuVE)
of low molar mass [156]. Another example of end-functional fluoropolymer
was reported by Guerre et al. [152] who synthesized a PVDF methacrylate
macromonomer by X0a-mediated RAFT polymerization of VDF followed by a
one-pot thio-Michael addition with 3-(acryloyl)-2-hydroxypropyl methacrylate.
10.6.2 Block Copolymers

Considerable strides were recently made in the synthesis of block copolymers
through sequential monomer addition using xanthate RAFT agents, especially from
some rarely reported monomers (e.g. VC [78], VDF [98, 154], VPA [72, 141], DAD-
MAC [35, 92], vinyl sulfonates [18, 30]). In addition, xanthate-capped poly(ethylene
oxide) [147, 169–178] and polysaccharides [179, 180] have been largely exploited by
a variety of research groups as precursors for the synthesis of block copolymers.
Some researchers focused on the investigation of the self-assembly properties
of amphiphilic [41, 54, 60, 181, 182] or double hydrophilic block copolymers
[61, 173, 183]. For example, Peng et al. [60] synthesized well-defined (Ð = 1.24)
amphiphilic PSt-b-PNVim block copolymers by sequential RAFT polymerization
using X2a as CTA. The size and morphology of the copolymer aggregates were
investigated by DLS and TEM. The copolymers assembled into uniform spheroidal
micelles with PSt as the dense core and PNVim as the loose corona in water. Mori
et al. [41] reported the controlled synthesis of amphiphilic PNVTri-b-PNVCbz block
copolymers by RAFT polymerization using X1a as CTA. The block copolymers
formed spherical micelles and inverse micelles depending on the nature of the
solvents (Scheme 10.5). Huang et al. [54] synthesized the two PNVCbz-b-PNVP
and PNVP-b-PNVCbz amphiphilic block copolymers via xanthate-mediated RAFT
polymerization by changing the order of monomer addition. The particle size
distributions of the prepared block copolymers were measured in several organic
solvents with different polarities. Depending on their composition, block copoly-
mer PNVCbz-b-PNVP formed micelles in methanol whereas PNVP-b-PNVCbz
formed larger aggregates and precipitates. Our group reported the synthesis of
PDMA-b-PVAc amphiphilic diblock copolymers and studied their solubility in
scCO2 using high-pressure IR spectroscopy [182]. The copolymer solubility was low
and further decreased on increasing the weight fraction of the PDMA block and/or
the total molecular weight of the polymer.
S O
R n
N RAFT N S
N N
N N In water
N-Vinyl- Poly(NVTri)
1,2,4-triazole Water-soluble polymer
S O
R n m
N N N S
N
N
Poly(NVTri)-b-Poly(NVCbz) In organic solvent
Scheme 10.5 Synthesis of amphiphilic block copolymer PNVTri-b-PNVCbz and their

self-assembly behaviour in selective solvents. Source: Reproduced with permission from
Mori et al. [41]. Copyright 2012, John Wiley & Sons.
Markiewicz et al. [173] reported the synthesis of PEO-b-PVPA diblock copoly-

mer in water and their use to stabilize iron oxide nanoparticles formed in situ.
Willersinn and Schmidt [180] studied the synthesis of pullulan-b-PNVP copolymer
from xanthate-capped pullulan. The well-defined copolymers were self-assembled
in water to form vesicles. After crosslinking with cystamine, vesicles became redox-
and pH-cleavable.
The assembly behaviour of thermoresponsive double hydrophilic [56, 183] and
amphiphilic [56, 184–187] block copolymers in aqueous media was also an impor-
tant centre of focus. Nguyen et al. [187] reported the behaviour of thermoresponsive
block copolymers of BA and N-alkylacrylamides in 1-ethyl-3-methylimidazolium
bis(trifluoromethylsulfonyl)imide ([C2 mim][NTf2 ]) ionic liquid. The polymers
exhibited double thermoresponsiveness with both upper critical solution tem-
perature (UCST) and lower critical solution temperature (LCST). For a given
molar mass, these temperatures can be easily controlled by choosing the PBA to
PNIPAM balance or by altering the polymer composition of the PNIPAM block by
copolymerizing NIPAM with hydrophobic N-tert-butylacrylamide (NtBuA).
Yuan et al. [61] synthesized PNIPAM-b-PIL double hydrophilic block copoly-
mers comprising a 1-vinylimidazolium-based poly(ionic liquid) segment via the
RAFT process using xanthate CTAs. Copolymers showed dual-stimuli-responsive
behaviour against changes in temperature and ionic strength in aqueous solution.
The combination of xanthate-mediated RAFT with other polymerization tech-
niques, such as ATRP [88, 97, 188–191], ring-opening polymerization (ROP) [76,
77, 85, 192–196], living cationic polymerization [197], or click coupling reactions
[85, 97, 181], are efficient approaches for the synthesis of block copolymers.
Kang et al. [77] synthesized well-defined PNVP-b-PCL amphiphilic block
copolymers at 30 ∘ C via the combination of ROP and RAFT polymerization in a
one-pot procedure using the hydroxyl-functional xanthate X6 as dual initiator. The
copolymers showed narrow molecular weight distributions (Ð < 1.2) and predicted
molar masses, indicating that the ROP and RAFT polymerization proceeded
independently in a controlled manner. The block copolymers could be labeled

fluorescently through a reaction with rhodamine B isothiocyanate in the same pot.
Numerous examples of block copolymers comprising one poly(fluoro-olefin)
sequence have emerged in recent literature. Guerre et al. [83] reported the first
block copolymerization of ethyl vinyl ether (EVE) with VDF via sequential cationic
and xanthate-mediated RAFT polymerization [84]. It was found that xanthate X11
gave moderate control for cationic radical polymerization of EVE (Ð ∼ 1.5) but
efficient cross-over for VDF polymerization by radical RAFT polymerization. The
same strategy was followed by the same authors who considered the combination
of nearly equimolar amounts of CTFE and EVE monomers for an alternated radical
RAFT polymerization step [83] (Scheme 10.6). It was demonstrated that block
copolymerization was much better controlled by performing cationic RAFT poly-
merization of EVE as first block (Scheme 10.6). Cationic RAFT polymerization of
EVE afforded PEVE macro-CTAs with high chain end fidelity and chain extension
Pathway 1 Pathway 2
F F Chain transfer agent: Chain transfer agent:

CTFE S
F Cl S
O O
EVE S O EVE S O
OCH2CH3 O OCH2CH3
RAFT radical RAFT cationic

polymerization polymerization
OF Cl S O
S O n
O n O O S
F FO S
P(CTFE-alt-EVE)-XA P(EVE)-XA
F F
RAFT cationic CTFE
EVE RAFT cationic F Cl
polymerization
OCH2CH3 polymerization EVE
OCH2CH3
OF Cl OF Cl
S O S O
O m O m
F FO n
O S F F On O S
P(CTFE-alt-EVE)-b-P(EVE)-XA P(EVE)-b-P(CTFE-alt-EVE)-XA
block copolymer block copolymer
OF Cl S O
S O n
O n O O S
F FO S
-CH-CTA (39%) Low CTA functionality -CH-CTA (>90%)

High CTA functionality -CH-OCH (<10%)
-CFCI-H (61%) Slow reactivation 3
OF OF Cl
Cl
S O S O
m O m
F On O
O n
F FO F S
O S
III-defined block copolymers Well-defined block copolymers
Scheme 10.6 Synthesis of P(CTFE-alt-EVE)-b-PEVE and PEVE-b-P(CTFE-alt-EVE) block

copolymers. Source: Adapted with permission from Guerre et al. [83]. Copyright 2018, John
Wiley & Sons.
reactions, resulting in well-defined PEVE-b-P(CTFE-alt-EVE) block copolymers

with low dispersities (Ð < 1.35).
Through a kinetic study, chain extension experiments, and DFT calculations,
Guerre et al. [157] demonstrated that PVDF-b-PVAc block copolymerization could
be carried out with fast reactivation of the –CH2 CF2 –X0a normal terminal adducts
and a slower but still possible activation of the –CF2 CH2 –X reverse adducts [157].
For PVDF-b-PNVP, block copolymerization was much less efficient with slower
activation of the normal PVDF-X0a chain ends, and no activation of the reverse
ones [157]. Later in 2018, Li et al. [31] reported the synthesis of PVDF-b-PNVP
copolymers and studied their self-assembly behaviour. Even though the block
copolymers self-assembled in water, it is likely that the control of block copoly-
merization remained limited. PVDF-b-PVAc and PVDF-b-(PVAc-alt-MAF-TBE)
(MAF-TBE = tert-butyl 2-trifluoromethacrylate) multiblock copolymers were
successfully synthesized using fluorinated cyclic xanthate X22 [98]. Amphiphilic
PDMA-b-PDVF and PDMA-b-P(VDF-stat-PMVE) copolymers were also prepared
using xanthate X0a [154].
10.6.3 Gradient Copolymers

Gradient copolymers are defined as containing at least one section of continuously
varying monomer composition [198]. Xanthates are particularly well suited for the
synthesis of spontaneous gradient copolymers, which can be formed in a one-pot
procedure when copolymerizing monomers of disparate reactivities by any kind of
controlled or living polymerization.
To date, only a few cases of spontaneous gradient copolymers have been reported
using xanthate-mediated RAFT polymerization [199–201]. This approach can lead
to ‘block-like’ structures with an initial region of nearly constant composition, a rel-
atively steep transitional region, and a final segment of homopolymer [199, 201].
Spontaneous block-like gradient copolymers synthesized by RAFT polymeriza-
tion with xanthates usually exhibit intriguing differences with block analogues. For
instance, our group [201] investigated the synthesis and self-assembly behaviour
of P(NIPAM-grad-VAc) amphiphilic gradient copolymers in water. 1 H NMR spec-
troscopy results suggested the formation of dynamic aggregates that respond rapidly
to changes in solubility, in contrast to the kinetically frozen aggregates formed by
block copolymers. Furthermore, they display a single, broad glass transition, as is
typically found for gradient copolymers. We also reported X0a-mediated RAFT poly-
merization of spontaneous amphiphilic gradient terpolymers of DMA, VPi, and VAc
[199]. The copolymers exhibited slightly lower cloud point pressures in scCO2 than
the corresponding diblock copolymers. Moreover, much more pronounced differ-
ences were established at the water/scCO2 interface, with larger critical aggregation
concentration (CAC), much faster adsorption kinetics and equilibration, and lower
surface tension for gradient copolymers compared to their diblock counterparts.
10.6.4 Cyclic Copolymers

Cyclic polymers have markedly different physicochemical characteristics from
their linear counterparts. In general, homo- or hetero-telechelic polymers are
synthesized by controlled/living polymerization, and click chemistry is then

employed to ring-close the linear precursors and prepare the corresponding
cyclic polymers. Tang et al. [202] and Li et al. [203] reported a strain-promoted
azide–alkyne cycloaddition (SPAAC) reaction for the ring closure of telechelic
polymers derived from xanthate-mediated RAFT polymerization of unconjugated
monomers. As shown in Scheme 10.7 [202], a functional xanthate agent bearing the
cyclopropenone-masked dibenzocyclooctyne and azide end-groups was designed to
polymerize VAc and NVP. The resultant linear precursors were then directly used to
prepare the corresponding cyclic polymers by the catalyst-free UV-induced SPAAC
ring-closure reaction, in air at room temperature.
O N3 N3 O S
O
S UV-light
O
S AIBN O
O
O O O
S O O O
Xanthate chain transfer agent 1 Linear polymers Cyclic polymers
Unconjugated vinyl monomers: VAc, NVP, etc.

Polymers: PVAc, PNVP, etc.
Scheme 10.7 Preparation of PVAc and PNVP cyclic polymers by RAFT polymerization and
light-induced SPAAC reaction. Source: Adapted with permission from Tang et al. [202].
Copyright 2015, John Wiley & Sons.
10.6.5 Graft/Comb/Brush Copolymers

Graft copolymers are comb-shaped copolymers, which generally consist of a linear
backbone of one composition and randomly distributed branches of another com-
position. Well-defined graft copolymers can be prepared via RAFT polymerization
using xanthate CTAs by either a grafting from or a grafting to process.
In the ‘grafting from’ process, the macromolecular backbone is chemically
modified in order to introduce xanthates. Atanase et al. [204] synthesized
PVAc-graft-PNVP copolymers of low grafting density and with a PVAc backbone
of constant length. In a first step, a series of P(VAc-co-VClAc) copolymers were
prepared by RAFT, followed by their functionalization with xanthate groups. Then
RAFT polymerization of NVP was performed from the xanthate-functional
backbone to yield the graft copolymers. Kashio et al. [205] reported the
xanthate-mediated RAFT graft polymerization of DMA, NIPAM, and acry-
loylmorpholine from a xanthate-modified polysilsesquioxane (PSQ) backbone.
No crosslinked product was formed during polymerizations. Amphiphilic
organic–inorganic hybrid polymers were achieved in this way, some of them show-
ing some thermoresponsiveness. Li et al. [206] prepared a series of well-defined
amphiphilic PAA-graft-PVAc copolymers according to a grafting from methodology.
tert-Butyl 2-((2-bromopropanoyloxy)-methyl)acrylate (tBBPMA) was successfully
polymerized via RAFT with a dithiobenzoate to obtain a well-defined homopoly-
mer backbone with narrow molecular weight distribution (Ð = 1.08), which was
subsequently converted into a xanthate-functional macro-CTA by substitution of
the pendant bromide groups with an O-ethyl xanthate salt. Then, well-defined
PtBA-graft-PVAc copolymers with narrow molecular weight distributions (Ð < 1.40)

were synthesized by RAFT polymerization of VAc. The final PAA-graft-PVAc
amphiphilic copolymers were obtained by selective acidic hydrolysis of the PtBA
backbone without affecting the PVAc side chains.
Dual ATRP/RAFT polymerization has also been applied to the preparation of
brush copolymers with block copolymer side chains. Nese et al. [207] synthe-
sized the well-defined PPXEM-graft-PVOAc linear molecular brushes using a
combination of ATRP and RAFT polymerization. A macro-chain transfer agent
poly(2-((2-ethylxanthatepropanoyl)oxy)ethyl methacrylate) (PPXEM) was pre-
pared through the esterification of carboxy-functional X3a and –OH groups of
poly(2-hydroxyethyl methacrylate) (PHEMA). PVAc side chains (DP = 50 and
60) were then grown from this macro-CTA to generate molecular brushes. It was
found that the longer spacer separating the xanthate moiety from the backbone
(7 vs. 3 atoms) was essential for the synthesis of the well-defined PVOAc side
chains. Two years later, the same authors [208] synthesized well-defined molecular
bottlebrushes with PNVP-b-PVAc block copolymer side chains using the same
procedure. The structure of the bottlebrushes PPXEM-graft-(PNVP-b-PVAc) was
confirmed by AFM where it was noted that relatively large amounts of linear
polymer chains were formed due to transfer reactions and new chains generated by
AIBN during the side chain growth.
The grafting to process has become a more efficient method for the preparation
of graft copolymers with the development of various click chemistries. However,
its combination with xanthate-mediated RAFT polymerization has been rarely
reported in the literature. Quémener et al. [86] achieved well-defined comb
copolymers of PVAc with low dispersities through the combination of RAFT
polymerization and CuAAC click reaction. As shown in Scheme 10.8, propargyl
methacrylate with its acetylene function protected with a silyl group was first
polymerized via a RAFT process and subsequently deprotected to afford a polymer
backbone where each repeated unit carries an alkyne functionality. In parallel, an
azido functional xanthate X12 was employed to prepare narrowly dispersed PVAc.
PVAc chains were finally grafted to the polymer backbone by CuAAC reaction to
afford comb-like graft copolymers with low dispersities (1.12 < Ð < 1.18). Using
the same CuAAC click coupling, Joubert et al. [209] successfully prepared graft
copolymers of hydroxyethyl cellulose (HEC) and a RAFT-derived polyacrylate
ionic liquid. Well-defined PILs of different DPn (10, 50, and 100) of relatively low
dispersity (Ð = 1.5 for PIL100 ) were first prepared via RAFT polymerization using an
alkyne-functional xanthate as transfer agent. The PIL chains were then coupled to
15 N-labeled azido-functionalized HEC, forming graft copolymers of HEC-graft-PILs
with different chain lengths and graft densities.
10.6.6 Star Polymers

In the context of RAFT polymerization, the two R-group and Z-group approaches,
involving two different types of multifunctional xanthates (Scheme 10.9), can be
employed for the synthesis of star-like polymers.
Monomer synthesis
Si
O
Si
O
OH O
CI Et2O
Protected propargyl metharylate M1
Et3N
H
O
H O
OH CI O
Unprotected propargyl metharylate M2
RAFT polymerization: Synthesis of backbone
S S CN
S S n
M1 or M2
CN O O
AIBN, toluene, 60 °C
R R = SiMe3(M1)
R = H(M2)
Deprotection of backbone
S S CN S S CN
n TBAF n
O O O
THF O
Si H
Synthesis of poly(vinyl acetate) branch
O VAc O
S O S O
N3 O N3 O n
60 °C
S O O S
Synthesis of poly(vinyl acetate) comb-like graft polymer via click reaction
Cul/DBU N N N N
N N N N N N N N
THF
N3
Scheme 10.8 Schematic representation of the general synthetic approach from monomer
synthesis to the preparation of the final PVAc comb-like graft polymer. Source: Adapted with
permission from Quémener et al. [86]. Copyright 2008, John Wiley & Sons.
O O
S O S O
C O C
O O 3
2 S
S
S O S
O C
O C O O O S O
4
S O S O
S O C
O C 3 4
2 S
S
X30 X31 X32 X33
S S S S
C C C C
O S COOEt O S COOEt O S COOMe O S Ph
3 4 4 4
X34 X35 X36 X37
Scheme 10.9 Representative multifunctional xanthates used in RAFT polymerization for

star polymer synthesis (R-group approach: X30-X33, Z-group approach: X34-X37).
A few examples of multifunctional xanthates (e.g. X30–X33) were designed to

grow star polymers by the R-group approach. This method has been effectively used
for AA [210], NVP [211, 212], NVCL [213], NVTri [214], NVCbz [215], and VEI-Br
[216]. Following the Z-group approach, star-like polymers of VAc [217, 218] and
NVCbz [215, 219] were synthesized using xanthates X34–X37. For an optimal design
of the star polymers, a suitable choice of the approach and xanthate structure is
required, depending on the nature of the monomer. For example, Mori et al. [215]
synthesized PNVCbz star polymers via RAFT using three different xanthate-type
CTAs: X30 for the R-group approach and two xanthates X36 and X37 having differ-
ent R leaving groups for the Z-group approach. The R-group approach was found to
be the most efficient for the synthesis of the four-arm PNVCbz stars having a low dis-
persity (Ð = 1.16) and controlled molecular weights. In the case of Z-group approach,
the results suggested that the R leaving group of xanthates had a clear effect on the
polymerization kinetics involving an induction period and retardation, but had no
significant influence on the controlled character of the polymerization. The con-
trolled character was affected by the R-group or Z-group approach, and the poly-
merization kinetics was independent of the difference in the approach. Well-defined
four-arm star PVDF was synthesized with tetrafunctional xanthate X30 [153] and
used as precursors for photo-crosslinked coatings. In addition to star homopoly-
mers, some star-like copolymers (statistical, block, …) [213–216, 220] have also been
achieved via RAFT polymerization mediated by different multifunctional xanthates.
Miktoarm star polymers [221–224] or the star polymers containing degradable
chains [192, 224–226] are of interest because of their unique properties and potential
application in many areas. However, their synthesis usually requires the combina-
tion of different polymerization or coupling methods, e.g. RAFT polymerization
associated with ATRP, NMP, ROP, SET-LRP or click chemistry. For instance, Zhang
et al. [222] synthesized the well-defined amphiphilic A2 B2 miktoarm star-block
copolymer (PAA)2 (PVAc)2 via the combination of SET-LRP and RAFT/MADIX
polymerization using xanthates. Hira et al. [225] prepared well-defined
four-arm star (PDLLA-b-PNVP)4 amphiphilic block copolymer that consists

of D,L-lactide (DLLA) via the combination of ROP and xanthate-mediated RAFT
polymerization.
Alternatively, a ‘coupling onto’ approach is also a possibility to prepare star-like
polymers, where a linear telechelic polymer is reacted with a preformed core
molecule containing complementary functionality. This approach until recently
had not received as much attention. For example, seven-armed star-like PNVP
polymers with a lysozyme core were obtained by coupling succinimidyl-terminated
PVP to the primary amine groups of the protein used as the core [93].
10.6.7 Hyperbranched Polymers/Polymer Gels

HPs [227] have attracted significant attention because of their characteristic topolog-
ical structure associated with their unique physical properties compared with those
of the corresponding linear polymers.
Poly et al. [228] reported the one-pot xanthate-mediated reversible crosslinking
copolymerization (RCC) process for PVAc nanogels with controlled constitutive
chain length using either a di- or a tri-functional crosslinker (divinyl adipate or
2,4,6-tris(allyloxy)-1,3,5-triazine, respectively). The use of xanthate X0a allowed
for the incorporation of large amounts of crosslinker without macrogel formation.
Significant intramolecular crosslinking (cyclization) favourably contributes to the
formation of such nanogels. Reactivation of the multiple xanthate end-groups
of the parent PVAc nanogels allowed for the synthesis of ‘second generation’
nanogels with core–shell structures. After this, Poly et al. applied their well-defined
PVAc nanogels for the fabrication of patterned porous surfaces. Schmitt et al.
[81] especially designed a polymerizable xanthate X8 (R = –CH3 ) for the one-step
synthesis of well-defined branched PVAc by self-condensing vinyl polymerization
(SCVP) based on a RAFT mechanism. The branching density as well as the length
of the branches could be efficiently tuned by adjusting either the concentration of
polymerizable functions C0 or the C0 /[X8]0 ratio. Additionally, xanthate X8 was also
homopolymerized to afford hyperbranched oligomers, which were subsequently
used as multifunctional CTA for the divergent synthesis of star-like PVAcs following
a chain extension procedure. Similarly the same year, Zhou et al. [80] synthesized
hyperbranched PVAc via the combination of SCVP and RAFT polymerization in the
presence of unsaturated X8 (R = –H). The average degree of branching and branch
length were readily tuned by the reaction stoichiometry.
Cong et al. [100] employed xanthate-mediated RCC/RAFT process from PNIPAM-
b-PNVP copolymers using xanthate X29 and N,N′ -methylenebisacrylamide (MBA)
as the crosslinker. Zheng and Zheng [178] synthesized PEO-b-PNIPAM copolymers
via RCC/RAFT polymerization using a xanthate-terminated PEO as macro-CTA
and MBA as the crosslinking agent. Song et al. [89] prepared PNIPAM-graft-PNVP
copolymer hydrogels in the presence of MBA as the crosslinking agent. In this
RAFT polymerization, the xanthate CTA was formed in situ via the reaction of
isopropylxanthic disulfide (DIP) with AIBN.
10.7 Methodologies for Xanthate End-Group Removal

Although RAFT/MADIX polymerization offers numerous advantages, in some cir-
cumstances, removal of the thiocarbonylthio terminal group is desirable. Concerns
with the end-group are linked to colour, their inherent reactivity, and especially
the thermal and chemical stability (which may generate low molar mass mal-
odorous or potentially toxic sulfur-based by-products), depending on applications.
Several methodologies to remove the thiocarbonylthio end-groups are reviewed by
Willcock and O’Reilly [229], Harvison et al. [230], and Moad et al. [9, 231, 232].
In this section, we specifically refer to xanthates. Four main kinds of chemical
modification of a xanthate group were reported in the literature: nucleophilic
reaction, oxidation, thermolysis, and radical-induced reduction (Scheme 10.10).
Pn SH
ct ion
c rea H
phili Pn OH or Pn
c leo O
Nu O
S O xidation Pn S OZ′ or Pn OH
Pn S OZ′
Thermolysis
Rad Pn SH
ical-
indu
ced
reac
tion
Pn H
Scheme 10.10 Modification of the xanthate group: a summary.
10.7.1 Nucleophilic Reaction (Aminolysis/Hydrolysis/Ionic Reduction)

The reduction of thiocarbonylthio end-groups into thiols by aminolysis, hydroly-
sis, or reaction with ionic reducing agents (e.g. borohydrides) is one of the most
commonly encountered end-group transformation of a RAFT polymer. In a recent
patent, Holbein et al. [233] synthesized a copolymer containing a metal-chelating
methacrylamido monomer and NVP via RAFT polymerization with xanthates as
CTAs. They successfully modified the thiocarbonylthio terminal groups into thiol
group using three separate methods, i.e. by aminolysis, by thermal treatment, and
using sodium borohydride as a mild reducing agent. Shimoni et al. [94] treated the
xanthate end-group of PNVP with hydrazine hydrate in methanol, and subsequently,
by reduction with sodium borohydride. Ellman’s reagent was allowed to react with
the thiol functionality for treatment with dithiothreitol (DTT) and used in biocon-
jugation (Scheme 10.11).
Wu et al. [234] reported a ‘universal’ and effective approach for removing thiocar-
bonylthio end-groups of RAFT-made polymers by the utilization of sodium azide in
Scheme 10.11 RAFT/MADIX polymerization of PNVP and end-group transformation.

Source: Adapted with permission from Shimoni et al. [94]. Copyright 2012, John Wiley &
Sons.
an open system at ambient temperature without deoxygenation. Through the exam-

ination with three different RAFT agents (including a xanthate) and four polymers
including PBA, PSt, PMMA and PVAc, it was concluded that the terminal thiocar-
bonylthio group was successfully converted to the thiol group by NaN3 via a nucle-
ophilic process (Scheme 10.12).
S S–
+ S
Nucleophilic H
Pn S Z Pn S Z Pn SH + N3 Z
Reaction N3
–
N3
‘Coupling’
Pn S S Pn
Scheme 10.12 Mechanism of the reaction by NaN3 via a nucleophilic process. Source:
Adapted with permission from Wu et al. [234]. Copyright 2014, John Wiley & Sons.
Pound et al. [235] reported that PNVP chain ends formed with xanthate RAFT
agents are susceptible to hydrolysis and can be converted to hydroxyl and aldehyde
end-groups under different conditions (Scheme 10.13) [235]. They took advantage
of this feature for the preparation of ω-aldehyde functional PNVP, and then coupled
the polymer to a model protein lysozyme via reductive amination.
10.7.2 Oxidation
Reaction with oxidizing agents, such as ozone (O3 ) and hydrogen peroxide
(H2 O2 ), is also an effective process for removing the xanthate end-groups from
O O
NC NC NC
N N H
n (a) H2O n (b) Δ n
O N S S O N OH O N O
Scheme 10.13 Modification of PNVP xanthate chain ends into hydroxyl and aldehyde
end-groups. Reagents and conditions: (a) distilled water (pH = 4–10), 40 ∘ C, 16 hours;
(b) 120 ∘ C, 1 mbar, 20 hours. Source: Adapted with permission from Pound et al.
[235]. Copyright 2008, John Wiley & Sons.
RAFT-synthesized polymers. For instance, two articles [236, 237] and a patent [238]
reported the ozonolysis of a xanthate, quantitatively forming the corresponding
polymer with a thionocarbonate end-group. The oxidation reaction was successfully
performed not only in solution but also on a poly(n-butylacrylate) latex. It is the
only reported effective technique for RAFT latexes without latex destabilization
[237]. A possible mechanism has been proposed (Scheme 10.14) [236].
O O
S S O O +
R Rʹ O3 O O
S O R Rʹ + –
S O S O S
R Rʹ
1 2 3 4
O O
H2O O3 O O
H2SO4 O S O S
S
O
5
Scheme 10.14 A possible mechanism for the ozonolysis of xanthate. Source: Adapted with
permission from Quiclet-Sire et al. [236]. Copyright 2010, John Wiley & Sons.
Pfukwa et al. [239] reported a facile method for directly transforming RAFT
end-groups into hydroxyl end-groups by using H2 O2 as the oxidizing agent. The
process was applied to PNVP with xanthate chain ends, which involves heating the
polymers in solution with H2 O2 at 60 ∘ C. The proposed mechanism is shown in
Scheme 10.15. However, the xanthate-terminated PNVP showed a tendency to take
part in side reactions during the end-group modification.
10.7.3 Thermolysis
If complete removal of the thiocarbonylthio group is required, the effective pro-
cesses are either thermolysis [240, 241] or radical-induced reaction (see Section
10.7.4). Thermolysis, usually carried out at temperatures higher than 150 ∘ C, is a
simple and powerful method to cleave the thiocarbonylthio groups and introduce
an alkene at the polymer chain end, but the dominant mechanism of reaction
Scheme 10.15 The mechanism for RAFT end-group removal by H2 O2 . Source: Adapted
with permission from Pfukwa et al. [239]. Copyright 2008, John Wiley & Sons.
depends on both the particular polymer and the type of thiocarbonylthio group. For
example, the high-temperature (∼ 180 ∘ C) thermolysis of polymers terminated with
O-alkyl xanthates possessing at least a β-hydrogen atom (e.g. O-isobutyl xanthate),
known as the Chugaev elimination, provides 2-butene and polymers with a thiol
end-group (Scheme 10.16) [240]. Applying this methodology, Langlais et al. [166]
used thiolactone-based xanthates (TL-Xa) in RAFT polymerization of NIPAM,
and the TL-PNIPAM-Xa polymers at the ω-end decomposed into TL-PNIPAM-SH
under thermolysis conditions through Chugaev elimination. The terminal thiol
group was unstable and led to thiolactonization with the penultimate NIPAM unit.
Postma et al. [242] studied the thermolysis of PVAc synthesized with a phtalilimido
xanthate. At 220 ∘ C, discolouration of the polymer was observed with concomitant
increase of the molar mass. It was concluded that thermal degradation may lead
to homolysis of C—S bond followed by radical coupling or decay by backbiting
followed by β-scission.
S O S O
+
Ph S Ph SH
H
SH O
+ C
Ph S
Scheme 10.16 Thermolysis of PSt with O-isobutyl xanthate end-group. Source: Adapted
with permission from Destarac et al. [240]. Copyright 2006, John Wiley & Sons.
10.7.4 Radical-Induced Reduction

Radical-induced reduction also allows the thiocarbonylthio end-group of
RAFT-synthesized polymers to be replaced with a hydrogen atom [243]. For
instance, our group reported the transformation of TL-PVP-Xa [166], PNIPAM-X0a
[244], and PVAc-X0a [182] into the corresponding hydrogen-terminated polymers
by radical reduction with lauroyl peroxide (LPO) in propan-2-ol.
10.8 Industrial Applications of RAFT/MADIX Polymerization 529
Hu et al. [172] used radical-induced reduction with tributylstannane (Bu3 SnH) as

the most effective H-donor to remove the xanthate end-groups from the homopoly-
mer PVNCbz.
Tong et al. [87] exposed the azido-functional PVAc with a xanthate end-group
to stoichiometric amounts of LPO in refluxing 2-propanol/THF as H-donors,
resulting in the complete replacement of the xanthate group by a hydrogen atom via
radical-induced reduction (Scheme 10.17). This method is ecologically superior to
the abovementioned using Bu3 SnH as the H-donor. And in this case, the peroxide
initiator LPO appears generally more effective in radical-induced reduction than
azo-type compounds such as AIBN, which is attributed to the peroxide-derived
radicals being more effective in displacing the propagating radicals than the
cyanoalkyl radical [243].
Scheme 10.17 (A) RAFT synthesis of N3 -PVAc and 𝜔-xanthate group removal. Reagents
and conditions: (a) VAc, AIBN, 80 ∘ C; (b) LPO, 2-propanol/THF, 80 ∘ C. Source: Adapted with
permission from Tong et al [87]. Copyright 2009, John Wiley & Sons.), and (B)
radical-induced reduction of xanthate end-groups. Source: Adapted with permission from
Chong et al. [243]. Copyright 2007, John Wiley & Sons.
Carmean et al. [47] also reported a novel photo-induced end-group removal

(PEGR) process, which provides a low temperature, initiator- and catalyst-free
method to efficient end-group modification in the presence of N-ethylpiperidine
hypophosphite (EPHP) as a H-donor. Under long-wave ultraviolet irradiation,
polymers with thiocarbonylthio end-groups derived from acrylamido, acrylic,
methacrylic, styrenic, and vinylpyrrolidone monomers undergo excitation and
photolytic cleavage to reveal an active macro-radical capable of irreversible
termination with a suitable hydrogen source. This straightforward method was
successfully demonstrated by the removal of a range of end-groups that com-
monly result from RAFT agents including xanthates among other classes of
thiocarbonylthio compounds. Under identical reaction conditions, PDMA-Xa
showed complete end-group removal to PDMA-H in eight hours and exhibited
a photolysis rate nearly six times more rapid than the PDMA analogue with
trithiocarbonate-terminated chains [47].
10.8 Industrial Applications of RAFT/MADIX

Polymerization
The industrial developments of reversible deactivation radical polymerization, and
RAFT polymerization in particular, have been recently reviewed [10]. RAFT process
can be seen as a conventional radical polymerization in the presence of a reversible

thiocarbonylthio chain transfer agent. Therefore, it can be implemented in classical
industrial polymerization reactors, under normal conditions of temperature and
pressure.
Rhodia Chimie (now part of Solvay) and the CNRS pioneered xanthate-mediated
RAFT (coined MADIX), based on O-ethyl-S-(1-methoxycarbonylethyl)dithiocarbo-
nate, which was registered under the trade name Rhodixan A1. They have joint
ownership in intellectual property on RAFT agent design, xanthate end-group
removal, and aqueous processes to produce ultra-high molar mass polymers or
controlled architectures based on NVP. In the 2000s, the first commercial success
with MADIX was Rhodibloc® RS, an amphiphilic block copolymer with improved
stabilizing properties for inverse emulsions, especially under high shear conditions.
Solvay’s Rhodibloc® FL fluid loss block copolymer additives for cementing appli-
cations for the Oilfield market were developed during the 2010s. These products
are effective in retaining water within slurries over a wide range of temperatures.
Rhodibloc® GC is a gas migration control agent that is based on styrene–butadiene
latex and a proprietary block copolymer surfactant. It is stable in cement slurries up
to 150 ∘ C. Over the last five years, Solvay Novecare developed MADIX micellar poly-
merization, a direct aqueous route to associative multiblock copolymers, by simply
adding a xanthate to a conventional micellar polymerization medium comprising
mainly hydrophilic monomers (most often a mixture of AM and AMPS), a small
amount of hydrophobic monomer (e.g. N-laurylmethacrylamide or t-Bu styrene),
and a surfactant. Thanks to an improved control of the copolymer microstructure,
molar mass, and dispersity over conventional processes, the multiblock amphiphilic
copolymers exhibit excellent rheological properties for extracting and fracturing
fluids or suspending agents in oil recovery applications, in particular in very
concentrated saline media.
The reactivity of Rhodixan A1 covers a very broad spectrum of monomers, nearly
all of them, with the exception of 1,1-disubstituted monomers such as methacrylates.
It is compatible with all kinds of reaction media, and based on the estimated cost
of the raw materials used for its synthesis, the extra cost associated with the use
of Rhodixan A1 in an industrial polymer should be much lower than for the other
classes of commercially available RAFT agents. For all these reasons, Rhodixan A1
and O-ethyl xanthates in general hold a strong position for the development of future
generations of complex polymer architectures at the industrial level.
10.9 Conclusion
Over the last decade, giant steps have been taken in the development of RAFT
polymerization with xanthates with a vast amount of academic literature and an
increasing number of industrial products. Today’s breadth and depth of knowledge
on xanthate RAFT agents is primarily due to their practicality: xanthates are easier
to synthesize and generate little or no retardation of polymerization compared
to the other classes of RAFT agents, and they are compatible with all kinds of
polymerization media and monomer reactivities. In particular, they can control
the polymerization of both conjugated and non-conjugated monomers, which
References 531
opens an infinite number of original options for block copolymer synthesis or more
complex microstructures, e.g. spontaneous gradient copolymers. Xanthates are best
known for their great ability to control RAFT polymerization of non-conjugated
monomers. Since the last edition of this handbook in 2008, a strong focus on
vinyl esters and N-vinyl monomers was observed and a great deal of important
monomers complemented the range of xanthate-compatible monomers for RAFT
polymerization, including VDF, vinyl sulfonates and sulfides, vinyl phosphonic
acid, diallyl(dimethylammonium chloride), CKAs, and ethylene. Novel strategies
for removal of the xanthate terminal group were proposed, such as UV light-induced
radical reduction and ozonolysis. In parallel, significant progress has been accom-
plished in the industrial development of MADIX technology by Solvay (Rhodia) for
aqueous formulation additives, using Rhodixan A1. Xanthates surely have some
surprises left for the future.
References
1 Moad, G. and Rizzardo, E. (2019). A 20th anniversary perspective on the life of

RAFT (RAFT coming of age). Polym. Int. https://doi.org/10.1002/pi.5944.
2 Perrier, S. (2017). 50th anniversary perspective: RAFT polymerization – a user
guide. Macromolecules 50 (19): 7433–7447.
3 Le, T.P., Moad, G., Rizzardo, E. et al. (2001). Polymerization with living charac-
teristics. WO Patent 1998001478A1, filed July 03, 1997 and issued December 12,
2001.
4 Chiefari, J., Chong, Y., Ercole, F. et al. (1998). Living free-radical polymeriza-
tion by reversible addition-fragmentation chain transfer: the RAFT process.
5 Corpart, P., Charmot, D., Biadatti, T. et al. (2007). Method for block polymer
synthesis by controlled radical polymerisation. WO Patent 1998058971A1, filed
June 23, 1998 and issued May 09, 2007.
6 Charmot, D., Corpart, P., Adam, H. et al. (2000). Controlled radical polymeriza-
tion in dispersed media. Macromol. Symp. 150 (1): 23–32.
7 Yan, Y., Zhang, W., Qiu, Y. et al. (2010). Universal xanthate-mediated controlled
free radical polymerizations of the “less activated” vinyl monomers. J. Polym.
8 Nakabayashi, K. and Mori, H. (2013). Recent progress in controlled radical
polymerization of N-vinyl monomers. Eur. Polym. J. 49 (10): 2808–2838.
9 Moad, G., Rizzardo, E., and Thang, S.H. (2012). Living radical polymerization
by the RAFT process–a third update. Aust. J. Chem. 65 (8): 985–1076.
10 Destarac, M. (2018). Industrial development of reversible-deactivation rad-
ical polymerization: is the induction period over? Polym. Chem. 9 (40):
4947–4967.
11 Moad, G. (2015). RAFT polymerization – then and now. In: Controlled Rad-
ical Polymerization: Mechanisms (eds. K. Matyjaszewski, B.S. Sumerlin,
N.V. Tsarevsky and J. Chiefari), 211–246. ACS Publications.
12 Taton, D., Destarac, M., and Zard, S.Z. (2008). Macromolecular design by inter-
change of xanthates: design, scope and applications. In: Handbook of RAFT
Polymerization, 1e (ed. C. Barner-Kowollik), 373–421. Wiley-VCH.
13 Lai, J.T. and Shea, R. (2006). Controlled radical polymerization by carboxyl-
and hydroxyl-terminated dithiocarbamates and xanthates. J. Polym. Sci., Part A:
Polym. Chem. 44 (14): 4298–4316.
14 Keddie, D.J., Moad, G., Rizzardo, E. et al. (2012). RAFT agent design and
synthesis. Macromolecules 45 (13): 5321–5342.
15 Skey, J. and O’Reilly, R.K. (2008). Facile one pot synthesis of a range of
reversible addition-fragmentation chain transfer (RAFT) agents. Chem. Com-
mun. (35): 4183–4185.
16 Bell, C.A., Hedir, G.G., O’Reilly, R.K. et al. (2015). Controlling the synthesis of
degradable vinyl polymers by xanthate-mediated polymerization. Polym. Chem.
6 (42): 7447–7454.
17 Sütekin, S.D. and Güven, O. (2018). Radiation-induced controlled polymeriza-
tion of acrylic acid by RAFT and RAFT-MADIX methods in protic solvents.
Radiat. Phys. Chem. 142: 82–87.
18 Mori, H., Kudo, E., Saito, Y. et al. (2010). RAFT polymerization of vinyl sul-
fonate esters for the controlled synthesis of poly(lithium vinyl sulfonate) and
sulfonated block copolymers. Macromolecules 43 (17): 7021–7032.
19 Tong, Y.-Y., Dong, Y.-Q., Du, F.-S. et al. (2008). Synthesis of well-defined
poly(vinyl acetate)-b-polystyrene by combination of ATRP and RAFT poly-
merization. Macromolecules 41 (20): 7339–7346.
20 Couture, G. and Améduri, B. (2012). Kinetics of RAFT homopolymerisation of
vinylbenzyl chloride in the presence of xanthate or trithiocarbonate. Eur. Polym.
J. 48 (7): 1348–1356.
21 Sistach, S., Beija, M., Rahal, V. et al. (2010). Thermoresponsive amphiphilic
diblock copolymers synthesized by MADIX/RAFT: properties in aqueous solu-
tions and use for the preparation and stabilization of gold nanoparticles. Chem.
Mater. 22 (12): 3712–3724.
22 Mori, H. and Tsukamoto, M. (2011). RAFT polymerization of diacrylate
derivatives having different spacers in dilute conditions. Polymer 52 (3):
635–645.
23 Barthet, C., Wilson, J., Cadix, A. et al. (2018). Influence of sodium dodecyl
sulfate on the kinetics and control of RAFT/MADIX polymerization of acry-
lamide. J. Polym. Sci., Part A: Polym. Chem. 56 (7): 760–765.
24 Wen, L., Wang, L., Fang, S. et al. (2018). Stabilization of CO2 -in-water
emulsions with high internal phase volume using PVAc-b-PVP and
PVP-b-PVAc-b-PVP as emulsifying agents. J. Appl. Polym. Sci. 135 (23): 46351.
25 Góis, J.R., Popov, A.V., Guliashvili, T. et al. (2015). Synthesis of functionalized
poly(vinyl acetate) mediated by alkyne-terminated RAFT agents. RSC Adv. 5
(111): 91225–91234.
26 Girard, E., Liu, X., Marty, J.-D. et al. (2014). RAFT/MADIX (co)polymerization
of vinyl trifluoroacetate: a means to many ends. Polym. Chem. 5 (3):
1013–1022.
References 533
27 Girard, E., Tassaing, T., Camy, S. et al. (2012). Enhancement of poly(vinyl

ester) solubility in supercritical CO2 by partial fluorination: the key role of
polymer-polymer interactions. J. Am. Chem. Soc. 134 (29): 11920–11923.
28 Liu, X., Coutelier, O., Harrisson, S. et al. (2014). Enhanced solubility of
polyvinyl esters in scCO2 by means of vinyl trifluorobutyrate monomer. ACS
Macro Lett. 4 (1): 89–93.
29 Girard, E., Tassaing, T., Ladavière, C. et al. (2012). Distinctive features of solu-
bility of RAFT/MADIX-derived partially trifluoromethylated poly(vinyl acetate)
in supercritical CO2 . Macromolecules 45 (24): 9674–9681.
30 Mori, H., Saito, Y., Takahashi, E. et al. (2012). Controlled synthesis of sul-
fonated block copolymers having thermoresponsive property by RAFT polymer-
ization of vinyl sulfonate esters. Polymer 53 (18): 3861–3877.
31 Li, L., Li, J., and Zheng, S. (2018). Poly(vinylidene fluoride)-block-poly(N-
vinylpyrrolidone) diblock copolymers: synthesis via sequential RAFT/MADIX
polymerization and self-assembly behavior. Polymer 142: 61–71.
32 Guerre, M., Campagne, B., Gimello, O. et al. (2015). Deeper insight into
the MADIX polymerization of vinylidene fluoride. Macromolecules 48 (21):
7810–7822.
33 Guerre, M., Rahaman, S.W., Améduri, B. et al. (2016). Limits of vinylidene fluo-
ride RAFT polymerization. Macromolecules 49 (15): 5386–5396.
34 Xu, P., Huang, X., Pan, X. et al. (2019). Hyperbranched polycaprolactone
through RAFT polymerization of 2-methylene-1,3-dioxepane. Polymers 11 (2):
318.
35 Destarac, M., Guinaudeau, A., Geagea, R. et al. (2010). Aqueous MADIX/RAFT
polymerization of diallyldimethylammonium chloride: extension to the synthe-
sis of poly (DADMAC)-based double hydrophilic block copolymers. J. Polym.
36 Pham, Q.L., Haldorai, Y., Kang, C. et al. (2014). Reversible addition-fragment-
ation chain transfer polymerization of vinyl acetate and vinyl pivalate in super-
critical carbon dioxide. Korean J. Chem. Eng. 31 (11): 2101–2107.
37 Dufils, P.E., David, G., Boutevin, B. et al. (2012). Phosphonate-terminated
poly(vinyl acetate) synthesized by RAFT/MADIX polymerization. J. Polym. Sci.,
Part A: Polym. Chem. 50 (10): 1997–2007.
38 Dommanget, C., D’Agosto, F., and Monteil, V. (2014). Polymerization of ethy-
lene through reversible addition–fragmentation chain transfer (RAFT). Angew.
Chem. Int. Ed. 53 (26): 6683–6686.
39 Jiang, B., Zhang, Q.H., Zhan, X.L. et al. (2009). The reversible addition-
fragmentation chain transfer (RAFT) miniemulsion polymerization of vinyl
acetate mediated by xanthate. Chin. Chem. Lett. 20 (6): 733–737.
40 Patel, V.K., Mishra, A.K., Vishwakarma, N.K. et al. (2010). (S)-2-(ethyl
propionate)-(O-ethyl xanthate) and (S)-2-(ethyl isobutyrate)-(O-ethyl
xanthate)-mediated RAFT polymerization of N-vinylpyrrolidone. Polym. Bull. 65
(2): 97–110.
41 Mori, H., Ishikawa, K., Abiko, Y. et al. (2012). Synthesis of triazole-based

amphiphilic block copolymers containing carbazole moiety by RAFT poly-
merization. Macromol. Chem. Phys. 213 (17): 1803–1814.
42 Lipscomb, C.E. and Mahanthappa, M.K. (2009). Poly(vinyl ester) block
copolymers synthesized by reversible addition-fragmentation chain transfer
polymerizations. Macromolecules 42 (13): 4571–4579.
43 Patel, V.K., Vishwakarma, N.K., Mishra, A.K. et al. (2012). (S)-2-(ethyl
propionate)-(O-ethyl xanthate) and (S)-2-(ethyl isobutyrate)-(O-ethyl
xanthate)-mediated RAFT polymerization of vinyl acetate. J. Appl. Polym. Sci.
125 (4): 2946–2955.
44 Vakili, M., Cunningham, V.J., Trebbin, M. et al. (2019). Polymerization-induced
thermal self-assembly of functional and thermo-responsive diblock copolymer
nano-objects via RAFT aqueous polymerization. Macromol. Chem. Phys. 220 (2):
1800370.
45 Kwak, Y., Nicolaÿ, R., and Matyjaszewski, K. (2009). A simple and effi-
cient synthesis of RAFT chain transfer agents via atom transfer radical
addition-fragmentation. Macromolecules 42 (11): 3738–3742.
46 Devlaminck, D.J., Van Steenberge, P.H., De Keer, L. et al. (2017). A detailed
mechanistic study of bulk MADIX of styrene and its chain extension. Polym.
Chem. 8 (45): 6948–6963.
47 Carmean, R.N., Figg, C.A., Scheutz, G.M. et al. (2017). Catalyst-free photoin-
duced end-group removal of thiocarbonylthio functionality. ACS Macro Lett.
6 (2): 185–189.
48 Mori, H., Yahagi, M., and Endo, T. (2009). RAFT polymerization of
N-vinylimidazolium salts and synthesis of thermoresponsive ionic liquid block
copolymers. Macromolecules 42 (21): 8082–8092.
49 Chen, J., Zhao, X., Zhang, L. et al. (2015). Reversible addition-fragmentation
chain transfer polymerization of vinyl acetate under high pressure. J. Polym.
50 Wang, J., Rivero, M., Muñoz-Bonilla, A. et al. (2016). Natural RAFT polymer-
ization: recyclable-catalyst-aided, opened-to-air, and sunlight-photolyzed RAFT
polymerizations. ACS Macro Lett. 5 (11): 1278–1282.
51 Lee, H., Terry, E., Zong, M. et al. (2008). Successful dispersion polymerization
in supercritical CO2 using polyvinylalkylate hydrocarbon surfactants synthe-
sized and anchored via RAFT. J. Am. Chem. Soc. 130 (37): 12242–12243.
52 Yu, H., Chen, Q., Zhang, Z. et al. (2012). 60 Co γ-irradiation-initiated RAFT poly-
merization of VAc at room temperature. React. Funct. Polym. 72 (2): 153–159.
53 Nakabayashi, K., Abiko, Y., and Mori, H. (2013). RAFT polymerization of
S-vinyl sulfide derivatives and synthesis of block copolymers having two distinct
optoelectronic functionalities. Macromolecules 46 (15): 5998–6012.
54 Huang, C.-F., Yoon, J.A., and Matyjaszewski, K. (2010). Synthesis of
N-vinylcarbazole-N-vinylpyrrolidone amphiphilic block copolymers by
xanthate-mediated controlled radical polymerization. Can. J. Chem. 88 (3):
228–235.
References 535
55 Pound, G., Eksteen, Z., Pfukwa, R. et al. (2008). Unexpected reactions associ-
ated with the xanthate-mediated polymerization of N-vinylpyrrolidone. J. Polym.
56 Ieong, N.S., Redhead, M., Bosquillon, C. et al. (2011). The missing
lactam-thermoresponsive and biocompatible poly(N-vinylpiperidone) polymers
by xanthate-mediated RAFT polymerization. Macromolecules 44 (4): 886–893.
57 Maki, Y., Mori, H., and Endo, T. (2007). Controlled RAFT polymerization of
N-vinylphthalimide and its hydrazinolysis to poly(vinyl amine). Macromol.
Chem. Phys. 208 (24): 2589–2599.
58 Klumperman, B. and Pound, G. (2009). Reversible addition fragmentation chain
transfer (RAFT) mediated polymerization of N-vinylpyrrolidone: RAFT agent
design. In: Controlled/Living Radical Polymerization: Progress in RAFT, DT, NMP
& OMRP (ed. K. Matyjaszewski), 167–179. ACS Publications.
59 Pound, G., Aguesse, F., McLeary, J.B. et al. (2007). Xanthate-mediated copoly-
merization of vinyl monomers for amphiphilic and double-hydrophilic block
copolymers with poly(ethylene glycol). Macromolecules 40 (25): 8861–8871.
60 Peng, C., Huang, K., Han, M. et al. (2013). Facile synthesis and catalytic activity
of well-defined amphiphilic block copolymers based on N-vinylimidazolium.
Polym. Adv. Technol. 24 (12): 1089–1093.
61 Yuan, J., Schlaad, H., Giordano, C. et al. (2011). Double hydrophilic diblock
copolymers containing a poly (ionic liquid) segment: controlled synthesis,
solution property, and application as carbon precursor. Eur. Polym. J. 47 (4):
772–781.
62 Wan, D., Zhou, Q., Pu, H. et al. (2008). Controlled radical polymerization of
N-vinylcaprolactam mediated by xanthate or dithiocarbamate. J. Polym. Sci.,
Part A: Polym. Chem. 46 (11): 3756–3765.
63 Maki, Y., Mori, H., and Endo, T. (2007). Xanthate-mediated controlled radical
polymerization of N-vinylindole derivatives. Macromolecules 40 (17): 6119–6130.
64 Congdon, T., Dean, B.T., Kasperczak-Wright, J. et al. (2015). Probing the
biomimetic ice nucleation inhibition activity of poly(vinyl alcohol) and compar-
ison to synthetic and biological polymers. Biomacromolecules 16 (9): 2820–2826.
65 Congdon, T., Shaw, P., and Gibson, M.I. (2015). Thermoresponsive,
well-defined, poly(vinyl alcohol) co-polymers. Polym. Chem. 6 (26): 4749–4757.
66 Fandrich, N., Falkenhagen, J., Weidner, S.M. et al. (2010). Characterization of
new amphiphilic block copolymers of N-vinyl pyrrolidone and vinyl acetate,
1–analysis of copolymer composition, end groups, molar masses and molar
mass distributions. Macromol. Chem. Phys. 211 (8): 869–878.
67 Hakobyan, K., Gegenhuber, T., McErlean, C.S. et al. (2019). Visible-light-driven
MADIX polymerisation via a reusable, low-cost, and non-toxic bismuth oxide
photocatalyst. Angew. Chem. Int. Ed. 58 (6): 1828–1832.
68 Blidi, I., Geagea, R., Coutelier, O. et al. (2012). Aqueous RAFT/MADIX poly-
merisation of vinylphosphonic acid. Polym. Chem. 3 (3): 609–612.
69 Seiler, L., Loiseau, J., Leising, F. et al. (2017). Acceleration and improved con-
trol of aqueous RAFT/MADIX polymerization of vinylphosphonic acid in the
presence of alkali hydroxides. Polym. Chem. 8 (25): 3825–3832.
70 Coutelier, O., Blidi, I., Reynaud, S. et al. (2015). Aqueous RAFT/MADIX poly-
merization of vinylphosphonic acid under microwave irradiation. In: Controlled
radical polymerization: Mechanisms (eds. N.V. Tsarevsky, B.S. Sumerlin, K.
Matyjaszewski and J. Chiefari), 283–294. ACS Publications.
71 Roy, D. and Sumerlin, B.S. (2011). Block copolymerization of vinyl ester
monomers via RAFT/MADIX under microwave irradiation. Polymer 52 (14):
3038–3045.
72 Assem, Y., Chaffey-Millar, H., Barner-Kowollik, C. et al. (2007). Con-
trolled/living ring-closing cyclopolymerization of diallyldimethylammonium
chloride via the reversible addition fragmentation chain transfer process.
73 Xiao, S., Xu, W.Z., and Charpentier, P.A. (2014). Bifunctional
2-(alkoxycarbonothioylthio) acetic acids for the synthesis of TiO2 -poly(vinyl
acetate) nanocomposites via RAFT polymerization. J. Polym. Sci., Part A: Polym.
Chem. 52 (5): 606–618.
74 Chambhare, S.U., Lokhande, G.P., and Jagtap, R.N. (2017). Effects of incor-
porated imine functionality and dispersed nano zinc oxide particles on
antimicrobial activity synthesized by RAFT polymerization. Polym. Bull. 74
(5): 1421–1439.
75 Chibber, B.A. (2010). Efficient method for partial sequencing of peptide/protein
using acid or base labile xanthates. US Patent 20100069252A1, filed October 30,
2006 and issued March 18, 2010.
76 Sun, Z., Choi, B., Feng, A. et al. (2019). Nonmigratory poly(vinyl
chloride)-block-polycaprolactone plasticizers and compatibilizers prepared
by sequential RAFT and ring-opening polymerization (RAFT-T-ROP). Macro-
molecules 52 (4): 1746–1756.
77 Kang, H.U., Yu, Y.C., Shin, S.J. et al. (2013). One-pot synthesis of
poly(N-vinylpyrrolidone)-b-poly(ε-caprolactone) block copolymers using a
dual initiator for RAFT polymerization and ROP. Macromolecules 46 (4):
1291–1295.
78 Huang, Z., Pan, P., and Bao, Y. (2016). Solution and aqueous miniemulsion
polymerization of vinyl chloride mediated by a fluorinated xanthate. J. Polym.
79 Kostov, G., Boschet, F., Buller, J. et al. (2011). First amphiphilic poly(vinylidene
fluoride-co-3, 3, 3-trifluoropropene)-b-oligo(vinyl alcohol) block copolymers as
potential nonpersistent fluorosurfactants from radical polymerization controlled
by xanthate. Macromolecules 44 (7): 1841–1855.
80 Zhou, X., Zhu, J., Xing, M. et al. (2011). Synthesis and characters of hyper-
branched poly(vinyl acetate) by RAFT polymeraztion. Eur. Polym. J. 47 (10):
1912–1922.
81 Schmitt, J., Blanchard, N., and Poly, J. (2011). Controlled synthesis of branched
poly(vinyl acetate)s by xanthate-mediated RAFT self-condensing vinyl
(co)polymerization. Polym. Chem. 2 (10): 2231–2238.
82 Patel, V.K., Vishwakarma, N.K., Mishra, A.K. et al. (2013). Synthesis of
alkyne-terminated xanthate RAFT agents and their uses for the controlled
References 537
radical polymerization of N-vinylpyrrolidone and the synthesis of its block

copolymer using click chemistry. J. Appl. Polym. Sci. 127 (6): 4305–4317.
83 Guerre, M., Uchiyama, M., Lopez, G. et al. (2018). Synthesis of
PEPE-b-P(CTFE-alt-EVE) block copolymers by sequential cationic and radical
RAFT polymerization. Polym. Chem. 9 (3): 352–361.
84 Guerre, M., Uchiyama, M., Folgado, E. et al. (2017). Combination of cationic
and radical RAFT polymerizations: a versatile route to well-defined poly(ethyl
vinyl ether)-block-poly(vinylidene fluoride) block copolymers. ACS Macro Lett.
6 (4): 393–398.
85 Mishra, A.K., Park, J., Joseph, K.V. et al. (2016). Synthesis and self-assembly
of amphiphilic and biocompatible poly(vinyl alcohol)-block-poly(l-lactide)
copolymer. Polymer 100: 28–36.
86 Quémener, D., Hellaye, M.L., Bissett, C. et al. (2008). Graft block copolymers of
propargyl methacrylate and vinyl acetate via a combination of RAFT/MADIX
and click chemistry: reaction analysis. J. Polym. Sci., Part A: Polym. Chem. 46
(1): 155–173.
87 Tong, Y.Y., Wang, R., Xu, N. et al. (2009). Synthesis of well-defined
azide-terminated poly(vinyl alcohol) and their subsequent modification via
click chemistry. J. Polym. Sci., Part A: Polym. Chem. 47 (18): 4494–4504.
88 Mishra, A.K., Choi, C., Maiti, S. et al. (2018). Sequential synthesis
of well-defined poly(vinyl acetate)-block-polystyrene and poly(vinyl
alcohol)-block-polystyrene copolymers using difunctional chloroamide-xanthate
iniferter. Polymer 139: 68–75.
89 Song, J., Yu, R., Wang, L. et al. (2011). Poly(N-vinylpyrrolidone)-grafted
poly(N-isopropylacrylamide) copolymers: synthesis, characterization and rapid
deswelling and reswelling behavior of hydrogels. Polymer 52 (10): 2340–2350.
90 Gu, Y., He, J., Li, C. et al. (2010). Block copolymerization of vinyl acetate and
vinyl neo-decanoate mediated by dithionodisulfide. Macromolecules 43 (10):
4500–4510.
91 Segura, T., Menes-Arzate, M., León, F. et al. (2016). Synthesis of narrow
molecular weight distribution polyvinyl acetate by gamma-rays initiated
RAFT/MADIX miniemulsion polymerization. Polymer 102: 183–191.
92 Destarac, M., Blidi, I., Coutelier, O. et al. (2012). Aqueous RAFT/MADIX
polymerization: same monomers, new polymers? In: Progress in Controlled Rad-
ical Polymerization: Mechanisms and Techniques (eds. K. Matyjaszewski, B.S.
Sumerlin and N.V. Tsarevsky), 259–275. ACS Publications.
93 McDowall, L., Chen, G., and Stenzel, M.H. (2008). Synthesis of seven-arm
poly(vinyl pyrrolidone) star polymers with lysozyme core prepared by
MADIX/RAFT polymerization. Macromol. Rapid Commun. 29 (20): 1666–1671.
94 Shimoni, O., Postma, A., Yan, Y. et al. (2012). Macromolecule functionalization
of disulfide-bonded polymer hydrogel capsules and cancer cell targeting. ACS
Nano 6 (2): 1463–1472.
95 Wang, Y.J., Wang, M.Q., Bai, L.J. et al. (2020). Facile synthesis of poly(N-vinyl
pyrrolidone) block copolymers with “more-activated” monomers by using
photoinduced successive RAFT polymerization. Polym. Chem. https://doi.org/10

.1039/c9py01763a.
96 Akeroyd, N., Pfukwa, R., and Klumperman, B. (2009). Triazole-based leaving
group for RAFT-mediated polymerization synthesized via the Cu-mediated
huisgen 1,3-dipolar cycloaddition reaction. Macromolecules 42 (8): 3014–3018.
97 Altintas, O., Speros, J.C., Bates, F.S. et al. (2018). Straightforward synthesis of
model polystyrene-block-poly(vinyl alcohol) diblock polymers. Polym. Chem. 9
(31): 4243–4250.
98 Banerjee, S., Patil, Y., Gimello, O. et al. (2017). Well-defined multiblock
poly(vinylidene fluoride) and block copolymers thereof: a missing piece of
the architecture puzzle. Chem. Commun. 53 (79): 10910–10913.
99 Hua, D., Ge, X., Tang, J. et al. (2007). Low-temperature controlled free-radical
polymerization of vinyl monomers in the presence of a novel cyclic dixanthate
under γ-ray irradiation. J. Polym. Sci., Part A: Polym. Chem. 45 (14): 2847–2854.
100 Cong, H., Li, L., and Zheng, S. (2013). Poly(N-isopropylacrylamide)-block-poly
(vinyl pyrrolidone) block copolymer networks: synthesis and rapid thermore-
sponse of hydrogels. Polymer 54 (4): 1370–1380.
101 Cong, H., Li, J., Li, L. et al. (2014). Thermoresponsive gelation behavior of
poly(N-isopropylacrylamide)-block-poly(N-vinylpyrrolidone)-block-poly(N-
isopropylacrylamide) triblock copolymers. Eur. Polym. J. 61: 23–32.
102 Xiang, Y., Cong, H., Li, L. et al. (2016). Poly(N-vinyl
pyrrolidone)-block-poly(N-vinyl carbazole)-block-poly(N-vinyl pyrrolidone)
triblock copolymers: synthesis via RAFT/MADIX process, self-assembly behav-
ior, and photophysical properties. J. Polym. Sci., Part A: Polym. Chem. 54 (12):
1852–1863.
103 Shanmugam, S., Xu, J., and Boyer, C. (2015). Exploiting metalloporphyrins for
selective living radical polymerization tunable over visible wavelengths. J. Am.
Chem. Soc. 137 (28): 9174–9185.
104 Bouhadir, G., Legrand, N., Quiclet-Sire, B. et al. (1999). A new practical synthe-
sis of tertiary S-alkyl dithiocarbonates and related derivatives. Tetrahedron Lett.
40 (2): 277–280.
105 Thang, S.H., Chong, Y.K., Mayadunne, R.T.A. et al. (1999). A novel synthesis
of functional dithioesters, dithiocarbamates, xanthates and trithiocarbonates.
Tetrahedron Lett. 40 (12): 2435–2438.
106 Khan, M.Y., Cho, M.-S., and Kwark, Y.-J. (2014). Dual roles of a xanthate as a
radical source and chain transfer agent in the photoinitiated RAFT polymeriza-
tion of vinyl acetate. Macromolecules 47 (6): 1929–1934.
107 Ding, C., Fan, C., Jiang, G. et al. (2015). Photocatalyst-free and blue
light-induced RAFT polymerization of vinyl acetate at ambient temperature.
Macromol. Rapid Commun. 36 (24): 2181–2185.
108 Poly, J., Cabannes-Boué, B., Hebinger, L. et al. (2015). Polymers synthesized by
RAFT as versatile macrophotoinitiators. Polym. Chem. 6 (31): 5766–5772.
109 Carmean, R.N., Becker, T.E., Sims, M.B. et al. (2017). Ultra-high molecular
weights via aqueous reversible-deactivation radical polymerization. Chem 2 (1):
93–101.
References 539
110 Uyar, Z., Turgut, F., Arslan, U. et al. (2019). Synthesis and characterization
of well-defined end-chain functional macrophotoinitiators of polystyrene
and polyacrylonitrile by RAFT/MADIX polymerization. Eur. Polym. J. 119:
102–113.
111 Ham, M.-k., HoYouk, J., Kwon, Y.-K. et al. (2012). Photoinitiated RAFT
polymerization of vinyl acetate. J. Polym. Sci., Part A: Polym. Chem. 50 (12):
2389–2397.
112 Xu, J., Jung, K., Atme, A. et al. (2014). A robust and versatile photoinduced liv-
ing polymerization of conjugated and unconjugated monomers and its oxygen
tolerance. J. Am. Chem. Soc. 136 (14): 5508–5519.
113 Shanmugam, S., Xu, J., and Boyer, C. (2014). Photoinduced electron
transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymer-
ization of vinyl acetate and N-vinylpyrrolidinone: kinetic and oxygen tolerance
study. Macromolecules 47 (15): 4930–4942.
114 Hua, D., Xiao, J., Bai, R. et al. (2004). Xanthate-mediated controlled/living
free-radical polymerization under 60 Co γ-ray irradiation: structure effect of
O-group. Macromol. Chem. Phys. 205 (13): 1793–1799.
115 Wang, P., Dai, J., Liu, L. et al. (2013). Xanthate-mediated living/controlled rad-
ical copolymerization of hexafluoropropylene and butyl vinyl ether under 60 Co
γ-ray irradiation and preparation of fluorinated polymers end-capped with a
fluoroalkyl sulfonic acid group. Polym. Chem. 4 (6): 1760–1764.
116 Van Nieuwenhove, I., Maji, S., Dash, M. et al. (2017). RAFT/MADIX polymer-
ization of N-vinylcaprolactam in water-ethanol solvent mixtures. Polym. Chem.
8 (16): 2433–2437.
117 Guinaudeau, A., Mazières, S., Wilson, D.J. et al. (2012). Aqueous RAFT/MADIX
polymerisation of N-vinyl pyrrolidone at ambient temperature. Polym. Chem.
3 (1): 81–84.
118 Guinaudeau, A., Coutelier, O., Sandeau, A. et al. (2013). Facile access to
poly(N-vinylpyrrolidone)-based double hydrophilic block copolymers by aque-
ous ambient RAFT/MADIX polymerization. Macromolecules 47 (1): 41–50.
119 Read, E., Guinaudeau, A., James Wilson, D. et al. (2014). Low temperature
RAFT/MADIX gel polymerisation: access to controlled ultra-high molar mass
polyacrylamides. Polym. Chem. 5 (7): 2202–2207.
120 Zhao, J., Yang, B., Mao, J. et al. (2018). A novel hydrophobic associative poly-
mer by RAFT-MADIX copolymerization for fracturing fluids with high thermal
stability. Energy Fuels 32 (3): 3039–3051.
121 Rzayev, J. and Penelle, J. (2004). HP-RAFT: a free-radical polymerization tech-
nique for obtaining living polymers of ultrahigh molecular weights. Angew.
Chem. 116 (13): 1723–1726.
122 Monteiro, M.J. and de Barbeyrac, J. (2001). Free-radical polymerization of
styrene in emulsion using a reversible addition−fragmentation chain transfer
agent with a low transfer constant: effect on rate, particle size, and molecular
weight. Macromolecules 34 (13): 4416–4423.
123 Zetterlund, P.B., Kagawa, Y., and Okubo, M. (2008). Controlled/living radical
polymerization in dispersed systems. Chem. Rev. 108 (9): 3747–3794.
124 Zetterlund, P.B., Thickett, S.C., Perrier, S. et al. (2015). Controlled/living rad-
ical polymerization in dispersed systems: An update. Chem. Rev. 115 (18):
9745–9800.
125 D’Agosto, F., Rieger, J., and Lansalot, M. (2019). RAFT-mediated
polymerization-induced self-assembly. Angew. Chem. Int. Ed. https://doi.org/
10.1002/anie.201911758.
126 Binauld, S., Delafresnaye, L., Charleux, B. et al. (2014). Emulsion polymeriza-
tion of vinyl acetate in the presence of different hydrophilic polymers obtained
by RAFT/MADIX. Macromolecules 47 (10): 3461–3472.
127 Siirilä, J., Häkkinen, S., and Tenhu, H. (2019). The emulsion polymerization
induced self-assembly of a thermoresponsive polymer poly(N-vinylcaprolactam).
Polym. Chem. 10 (6): 766–775.
128 Etchenausia, L., Khoukh, A., Lejeune, E.D. et al. (2017). RAFT/MADIX
emulsion copolymerization of vinyl acetate and N-vinylcaprolactam: towards
waterborne physically crosslinked thermoresponsive particles. Polym. Chem. 8
(14): 2244–2256.
129 Zhang, Q., Fu, M., Wang, C. et al. (2017). Preparation of poly(ionic liquid)
nanoparticles through RAFT/MADIX polymerization-induced self-assembly.
Polym. Chem. 8 (36): 5469–5473.
130 Guerre, M., Semsarilar, M., Godiard, F. et al. (2017). Polymerization-induced
self-assembly of PVAc-b-PVDF block copolymers via RAFT dispersion poly-
merization of vinylidene fluoride in dimethyl carbonate. Polym. Chem. 8 (9):
1477–1487.
131 Birkin, N.A., Arrowsmith, N.J., Park, E.J. et al. (2011). Synthesis and application
of new CO2 -soluble vinyl pivalate hydrocarbon stabilisers via RAFT polymerisa-
tion. Polym. Chem. 2 (6): 1293–1299.
132 Birkin, N.A., Wildig, O.J., and Howdle, S.M. (2013). Effects of poly(vinyl
pivalate)-based stabiliser architecture on CO2 -solubility and stabilising abil-
ity in dispersion polymerisation of N-vinyl pyrrolidone. Polym. Chem. 4 (13):
3791–3799.
133 Destarac, M., Brochon, C., Catala, J.-M. et al. (2002). Macromolecular design via
the interchange of xanthates (MADIX): polymerization of styrene with O-ethyl
xanthates as controlling agents. Macromol. Chem. Phys. 203 (16): 2281–2289.
134 Destarac, M., Bzducha, W., Taton, D. et al. (2002). Xanthates as chain-transfer
agents in controlled radical polymerization (MADIX): structural effect of the
O-alkyl group. Macromol. Rapid Commun. 23 (17): 1049–1054.
135 Destarac, M., Taton, D., Zard, S.Z. et al. (2003). On the importance of xanthate
substituents in the MADIX process. In: Advances in Controlled/Living Radical
Polymerization (ed. K. Matyjaszewski), 536–550. ACS Publications.
136 Pound, G., McLeary, J.B., McKenzie, J.M. et al. (2006). In-situ NMR spec-
troscopy for probing the efficiency of RAFT/MADIX agents. Macromolecules 39
(23): 7796–7797.
137 Coote, M.L., Krenske, E.H., and Izgorodina, E.I. (2006). Computational stud-
ies of RAFT polymerization–mechanistic insights and practical applications.
Macromol. Rapid Commun. 27 (7): 473–497.
References 541
138 Beija, M., Marty, J.-D., and Destarac, M. (2011). Thermoresponsive poly(N-vinyl
caprolactam)-coated gold nanoparticles: sharp reversible response and easy tun-
ability. Chem. Commun. 47 (10): 2826–2828.
139 Guinaudeau, A. (2010). Towards sustainability of RAFT/MADIX polymeriza-
tion: low temperature initiation and environmentally friendly reaction media.
PhD thesis. Université Toulouse III-Paul Sabatier.
140 Destarac, M., Matioszek, D., Vila, X. et al. (2018). How can xanthates con-
trol the RAFT polymerization of methacrylates? In: Reversible Deactivation
Radical Polymerization: Mechanisms and Synthetic Methodologies (eds.
K. Matyjaszewski, H. Gao, B.S. Sumerlin and N.V. Tsarevsky), 291–305. ACS
Publications.
141 Taton, D., Wilczewska, A.Z., and Destarac, M. (2001). Direct synthesis of double
hydrophilic statistical di- and triblock copolymers comprised of acrylamide and
acrylic acid units via the MADIX process. Macromol. Rapid Commun. 22 (18):
1497–1503.
142 Mejia, A., Rodriguez, L., Schmitt, C. et al. (2019). Synthesis and viscosimet-
ric behavior of poly(acrylamide-co-2-acrylamido-2-methylpropanesulfonate)
obtained by conventional and adiabatic gel process via RAFT/MADIX polymer-
ization. ACS Omega 4 (6): 11119–11125.
143 Bessaies-Bey, H., Fusier, J., Harrisson, S. et al. (2018). Impact of polyacry-
lamide adsorption on flow through porous siliceous materials: state of the art,
discussion and industrial concern. J. Colloid Interface Sci. 531: 693–704.
144 Bessaies-Bey, H., Fusier, J., Hanafi, M. et al. (2019). Competitive adsorption of
PAM and HPAM on siliceous material. Colloids Surf., A 579: 123673.
145 Krstina, J., Moad, G., Rizzardo, E. et al. (1995). Narrow polydispersity block
copolymers by free-radical polymerization in the presence of macromonomers.
146 Flory, P.J. and Leutner, F.S. (1948). Occurrence of head-to-head arrangements
of structural units in polyvinyl alcohol. J. Polym. Sci. 3 (6): 880–890.
147 Lipscomb, C.E. and Mahanthappa, M.K. (2011). Microphase separation
mode-dependent mechanical response in poly(vinyl ester)/PEO triblock copoly-
mers. Macromolecules 44 (11): 4401–4409.
148 Matioszek, D., Brusylovets, O., Wilson, D.J. et al. (2013). Reversible addition-
fragmentation chain-transfer polymerization of vinyl monomers with N,N-
dimethyldiselenocarbamates. J. Polym. Sci., Part A: Polym. Chem. 51 (20):
4361–4368.
149 Hedir, G.G., Arno, M.C., Langlais, M. et al. (2017). Poly(oligo(ethylene gly-
col) vinyl acetate)s: a versatile class of thermoresponsive and biocompatible
polymers. Angew. Chem. Int. Ed. 56 (31): 9178–9182.
150 Ilchev, A., Pfukwa, R., Hlalele, L. et al. (2015). Improved control through a
semi-batch process in RAFT-mediated polymerization utilizing relatively poor
leaving groups. Polym. Chem. 6 (46): 7945–7948.
151 Zhao, X.G., Coutelier, O., Nguyen, H.H. et al. (2015). Effect of copolymer com-
position of RAFT/MADIX-derived N-vinylcaprolactam/N-vinylpyrrolidone
statistical copolymers on their thermoresponsive behavior and hydrogel proper-

ties. Polym. Chem. 6 (29): 5233–5243.
152 Guerre, M., Ameduri, B., and Ladmiral, V. (2016). One-pot synthesis of
poly(vinylidene fluoride) methacrylate macromonomers via thia-michael addi-
tion. Polym. Chem. 7 (2): 441–450.
153 Lopez, G., Guerre, M., Améduri, B. et al. (2017). Photocrosslinked PVDF-based
star polymer coatings: an all-in-one alternative to PVDF/PMMA blends for
outdoor applications. Polym. Chem. 8 (20): 3045–3049.
154 Girard, E., Marty, J.-D., Ameduri, B. et al. (2012). Direct synthesis of vinylidene
fluoride-based amphiphilic diblock copolymers by RAFT/MADIX polymeriza-
tion. ACS Macro Lett. 1 (2): 270–274.
155 Patil, Y. and Ameduri, B. (2013). First RAFT/MADIX radical copolymeriza-
tion of tert-butyl 2-trifluoromethacrylate with vinylidene fluoride controlled by
xanthate. Polym. Chem. 4 (9): 2783–2799.
156 Puts, G., Venner, V., Améduri, B. et al. (2018). Conventional and RAFT copoly-
merization of tetrafluoroethylene with isobutyl vinyl ether. Macromolecules 51
(17): 6724–6739.
157 Guerre, M., Wahidur Rahaman, S.M., Améduri, B. et al. (2016). RAFT syn-
thesis of well-defined PVDF-b-PVAc block copolymers. Polym. Chem. 7 (45):
6918–6933.
158 Abreu, C.M.R., Rezende, T.C., Fonseca, A.C. et al. (2019). Polymerization of
vinyl chloride at ambient temperature using macromolecular design via the
interchange of xanthate: kinetic and computational studies. Macromolecules 53
(1): 190–202.
159 Wolpers, A., Bergerbit, C., Ebeling, B. et al. (2019). Aromatic xanthates
and dithiocarbamates for the polymerization of ethylene through reversible
addition-fragmentation chain transfer (RAFT). Angew. Chem. Int. Ed. 58 (40):
14295–14302.
160 Hill, M.R., Kubo, T., Goodrich, S.L. et al. (2018). Alternating radical
ring-opening polymerization of cyclic ketene acetals: access to tunable and
functional polyester copolymers. Macromolecules 51 (14): 5079–5084.
161 Hedir, G.G., Bell, C.A., O’Reilly, R.K. et al. (2015). Functional degradable
polymers by radical ring-opening copolymerization of mdo and vinyl bro-
mobutanoate: synthesis, degradability and post-polymerization modification.
Biomacromolecules 16 (7): 2049–2058.
162 Hedir, G.G., Bell, C.A., Ieong, N.S. et al. (2014). Functional degradable
polymers by xanthate-mediated polymerization. Macromolecules 47 (9):
2847–2852.
163 Andrei, M., Stănescu, P.O., Drăghici, C. et al. (2018). Synthesis and characteri-
zation of hydrolytically degradable poly(N-vinylcaprolactam) copolymers with
in-chain ester groups. Colloid. Polym. Sci. 296 (11): 1905–1915.
164 d’Ayala, G.G., Malinconico, M., Laurienzo, P. et al. (2014). RAFT/MADIX
copolymerization of vinyl acetate and 5,6-benzo-2-methylene-1,3-dioxepane.
References 543
165 Jia, F., Wang, S., Zhang, X. et al. (2016). Amino-functionalized

poly(N-vinylcaprolactam) derived from lysine: a sustainable polymer with
thermo and pH dual stimuli response. Polym. Chem. 7 (46): 7101–7107.
166 Langlais, M., Coutelier, O., and Destarac, M. (2018). Thiolactone-functional
reversible deactivation radical polymerization agents for advanced macromolec-
ular engineering. Macromolecules 51 (11): 4315–4324.
167 Chen, F., Cheng, Z., Zhu, J. et al. (2008). Synthesis of poly(vinyl acetate) with
fluorescence via a combination of RAFT/MADIX and “click” chemistry. Eur.
Polym. J. 44 (6): 1789–1795.
168 Etchenausia, L., Rodrigues, A.M., Harrisson, S. et al. (2016). RAFT copolymer-
ization of vinyl acetate and N-vinylcaprolactam: kinetics, control, copolymer
composition, and thermoresponsive self-assembly. Macromolecules 49 (18):
6799–6809.
169 Besada, L.N., Peruzzo, P., Cortizo, A.M. et al. (2018). Preparation, characteriza-
tion, and in vitro activity evaluation of triblock copolymer-based polymersomes
for drugs delivery. J. Nanopart. Res. 20 (3): 67.
170 Chen, K., Grant, N., Liang, L. et al. (2010). Synthesis of CO2 -philic
xanthate-oligo(vinyl acetate)-based hydrocarbon surfactants by RAFT polymer-
ization and their applications on preparation of emulsion-templated materials.
171 Pal, A. and Pal, S. (2018). Synthesis of triblock copolymeric micelle
based on poly(ethylene glycol) and poly(vinyl acetate) through reversible
addition-fragmentation chain transfer polymerization. J. Colloid Interface Sci.
524: 122–128.
172 Hu, N., Ji, W.-X., Tong, Y.-Y. et al. (2010). Synthesis of diblock copolymers
containing poly(N-vinylcarbazole) by reversible addition-fragmentation chain
transfer polymerization. J. Polym. Sci., Part A: Polym. Chem. 48 (20): 4621–4626.
173 Markiewicz, K.H., Seiler, L., Misztalewska, I. et al. (2016). Advantages
of poly(vinyl phosphonic acid)-based double hydrophilic block copoly-
mers for the stabilization of iron oxide nanoparticles. Polym. Chem. 7 (41):
6391–6399.
174 Willersinn, J., Drechsler, M., Antonietti, M. et al. (2016). Organized polymeric
submicron particles via self-assembly and cross-linking of double hydrophilic
poly(ethylene oxide)-b-poly(N-vinylpyrrolidone) in aqueous solution. Macro-
molecules 49 (15): 5331–5341.
175 Lee, S., Nam, J.H., Kim, Y.J. et al. (2011). Synthesis of PEO-based
glucose-sensitive block copolymers and their application for preparation of
superparamagnetic iron oxide nanoparticles. Macromol. Res. 19 (8): 827–834.
176 Jeon, H.J., Choi, S.-Y., Kim, K.M. et al. (2008). Synthesis of poly(ethylene
oxide)-based thermoresponsive block copolymers by RAFT radical polymer-
ization and their uses for preparation of gold nanoparticles. Colloids Surf., A
317 (1–3): 496–503.
177 Tong, Y.Y., Dong, Y.Q., Du, F.S. et al. (2009). Block copolymers of poly(ethylene
oxide) and poly(vinyl alcohol) synthesized by the RAFT methodology. J. Polym.
178 Zheng, Q. and Zheng, S. (2012). From poly(N-isopropylacrylamide)-block-poly

(ethylene oxide)-block-poly(N-isopropylacrylamide) triblock copolymer to
poly(N-isopropylacrylamide)-block-poly(ethylene oxide) hydrogels: synthesis and
rapid deswelling and reswelling behavior of hydrogels. J. Polym. Sci., Part A:
Polym. Chem. 50 (9): 1717–1727.
179 Lohmann, J., Houga, C., Driguez, H. et al. (2009). Hybrid block copolymers
incorporating oligosasaccharides and d synthetic blocks grown by controlled
radical polymerization. In: Controlled/living radical polymerization: Progress
in ATRP, ACS Symposium Series (ed. K. Matyjaszewski), 231–240. American
Chemical Society.
180 Willersinn, J. and Schmidt, B.V. (2018). Pure hydrophilic block copolymer vesi-
cles with redox- and pH-cleavable crosslinks. Polym. Chem. 9 (13): 1626–1637.
181 Muller, J., Marchandeau, F., Prelot, B. et al. (2015). Self-organization in water
of well-defined amphiphilic poly(vinyl acetate)-b-poly(vinyl alcohol) diblock
copolymers. Polym. Chem. 6 (16): 3063–3073.
182 Girard, E., Tassaing, T., Marty, J.-D. et al. (2011). Influence of macromolecular
characteristics of RAFT/MADIX poly(vinyl acetate)-based (co) polymers on
their solubility in supercritical carbon dioxide. Polym. Chem. 2 (10): 2222–2230.
183 Liang, X., Kozlovskaya, V., Cox, C.P. et al. (2014). Synthe-
sis and self-assembly of thermosensitive double-hydrophilic
poly(N-vinylcaprolactam)-b-poly(N-vinyl-2-pyrrolidone) diblock copolymers.
184 Özgüç, Ç., Helvac𝚤oğlu, E., Nugay, N. et al. (2013). Synthesis and characteriza-
tion of poly(N-isopropylacrylamide) and poly(vinyl acetate) diblock copolymers
via MADIX process. Macromol. Symp. 323 (1): 18–25.
185 Zhu, Z. and Sukhishvili, S.A. (2009). Temperature-induced swelling and
small molecule release with hydrogen-bonded multilayers of block copolymer
micelles. ACS Nano 3 (11): 3595–3605.
186 Destarac, M., Papon, A., Van Gramberen, E. et al. (2009). MADIX thermore-
sponsive amphiphilic block copolymers as stimulable emulsion stabilizers. Aust.
J. Chem. 62 (11): 1488–1491.
187 Nguyen, H.H., El Ezzi, M., Mingotaud, C. et al. (2016). Doubly
thermo-responsive copolymers in ionic liquid. Soft Matter 12 (13): 3246–3251.
188 Huang, C.-F., Hsieh, Y.-A., Hsu, S.-C. et al. (2014). Synthesis of poly
(N-vinyl carbazole)-based block copolymers by sequential polymerizations of
RAFT-ATRP. Polymer 55 (23): 6051–6057.
189 Petruczok, C.D., Barlow, R.F., and Shipp, D.A. (2008). Synthesis of
poly(tert-butyl acrylate-block-vinyl acetate) copolymers by combining ATRP and
RAFT polymerizations. J. Polym. Sci., Part A: Polym. Chem. 46 (21): 7200–7206.
190 Zhang, S., Luo, W., Yan, W. et al. (2014). Synthesis of a CO2 -philic poly(vinyl
acetate)-based cationic amphiphilic surfactant by RAFT/ATRP and its applica-
tion in preparing monolithic materials. Green Chem. 16 (9): 4408–4416.
191 Bao, L., Fang, S., Hu, D. et al. (2018). Stabilization of CO2 -in-water emulsions
by nonfluorinated surfactants with enhanced CO2 -philic tails. J. Supercrit.
Fluids 133: 163–170.
References 545
192 Mishra, A.K., Ramesh, K., Paira, T.K. et al. (2013). Synthesis and self-
assembly properties of well-defined four-arm star poly(ε-caprolactone)-b-poly(N-
vinylpyrrolidone) amphiphilic block copolymers. Polym. Bull. 70 (11):
3201–3220.
193 Mishra, A.K., Patel, V.K., Vishwakarma, N.K. et al. (2011). Synthesis of
well-defined amphiphilic poly(ε-caprolactone)-b-poly (N-vinylpyrrolidone)
block copolymers via the combination of ROP and xanthate-mediated RAFT
polymerization. Macromolecules 44 (8): 2465–2473.
194 Ramesh, K., Gundampati, R.K., Singh, S. et al. (2016). Self-assembly,
doxorubicin-loading and antibacterial activity of well-defined ABA-type
amphiphilic poly(N-vinylpyrrolidone)-b-poly(D, L-lactide)-b-poly (N-vinyl pyrroli-
done) triblock copolymers. RSC Adv. 6 (31): 25864–25876.
195 Pal, A. and Pal, S. (2017). Effect of Fe3 O4 NPs on micellization and
release behavior of CBABC-type pentablock copolymer. Polymer 133:
184–194.
196 Yu, Y.C., Shin, S.J., Ko, K.D. et al. (2013). One-pot synthesis of poly(vinyl
alcohol)-based biocompatible block copolymers using a dual initiator for ROP
and RAFT polymerization. Polymer 54 (21): 5595–5600.
197 Ma’Radzi, A.H., Sugihara, S., Toida, T. et al. (2014). Synthesis of polyvinyl alco-
hol stereoblock copolymer via the combination of living cationic polymerization
and RAFT/MADIX polymerization using xanthate with vinyl ether moiety. Poly-
mer 55 (21): 5332–5345.
198 Zhang, J., Farias-Mancilla, B., Destarac, M. et al. (2018). Asymmetric copoly-
mers: synthesis, properties, and applications of gradient and other partially
segregated copolymers. Macromol. Rapid Commun. 39 (19): 1800357.
199 Liu, X., Wang, M., Harrisson, S. et al. (2017). Enhanced stabilization of
water/scCO2 interface by block-like spontaneous gradient copolymers. ACS
Sustainable Chem. Eng. 5 (11): 9645–9650.
200 Guerrero-Sanchez, C., Harrisson, S., and Keddie, D.J. (2013). High-throughput
method for RAFT kinetic investigations and estimation of reactivity ratios in
copolymerization systems. In: Macromolecular Symposia, 38–46. Weinheim:
Wiley-VCH.
201 Yañez-Macias, R., Kulai, I., Ulbrich, J. et al. (2017). Thermosensitive sponta-
neous gradient copolymers with block-and gradient-like features. Polym. Chem.
8 (34): 5023–5032.
202 Tang, Q., Chen, J., Zhao, Y. et al. (2015). A ring-closure method for prepar-
ing cyclic polymers from unconjugated vinyl monomers. Polym. Chem. 6 (37):
6659–6663.
203 Li, Z., Qu, L., Zhu, W. et al. (2018). Self-accelerating click reaction for preparing
cyclic polymers from unconjugated vinyl monomers. Polymer 137: 54–62.
204 Atanase, L.I., Winninger, J., Delaite, C. et al. (2014). Reversible
addition-fragmentation chain transfer synthesis and micellar characteristics of
biocompatible amphiphilic poly(vinyl acetate)-graft-poly(N-vinyl-2-pyrrolidone)
copolymers. Eur. Polym. J. 53: 109–117.
205 Kashio, M., Sugizaki, T., Miyasaka, Y. et al. (2012). Graft polymerization of
acrylamide monomers from polysilsesquioxane containing xanthate groups.
Polym. J. 44 (12): 1214.
206 Li, Y., Zhang, Y., Yang, D. et al. (2009). Well-defined amphiphilic graft copoly-
mer consisting of hydrophilic poly(acrylic acid) backbone and hydrophobic
poly(vinyl acetate) side chains. J. Polym. Sci., Part A: Polym. Chem. 47 (22):
6032–6043.
207 Nese, A., Kwak, Y., Nicolaÿ, R. et al. (2010). Synthesis of poly(vinyl acetate)
molecular brushes by a combination of atom transfer radical polymerization
(ATRP) and reversible addition- fragmentation chain transfer (RAFT) polymer-
ization. Macromolecules 43 (9): 4016–4019.
208 Nese, A., Li, Y., Averick, S. et al. (2011). Synthesis of amphiphilic
poly(N-vinylpyrrolidone)-b-poly(vinyl acetate) molecular bottlebrushes. ACS
Macro Lett. 1 (1): 227–231.
209 Joubert, F., Yeo, R.P., Sharples, G.J. et al. (2015). Preparation of an antibacterial
poly(ionic liquid) graft copolymer of hydroxyethyl cellulose. Biomacromolecules
16 (12): 3970–3979.
210 Duan, S., Cai, S., Xie, Y. et al. (2012). Synthesis and characterization of a
multi-arm poly(acrylic acid) star polymer for application in sustained deliv-
ery of cisplatin and a nitric oxide prodrug. J. Polym. Sci., Part A: Polym. Chem.
50 (13): 2715–2724.
211 Johnson, I.J., Khosravi, E., Musa, O.M. et al. (2015). Xanthates designed for the
preparation of N-vinyl pyrrolidone-based linear and star architectures via RAFT
polymerization. J. Polym. Sci., Part A: Polym. Chem. 53 (6): 775–786.
212 Nguyen, T.L.U., Eagles, K., Davis, T.P. et al. (2006). Investigation of the influ-
ence of the architectures of poly(vinyl pyrrolidone) polymers made via the
reversible addition-fragmentation chain transfer/macromolecular design via
the interchange of xanthates mechanism on the stabilization of suspension
polymerizations. J. Polym. Sci., Part A: Polym. Chem. 44 (15): 4372–4383.
213 Cortez-Lemus, N.A. and Licea-Claverie, A. (2017). Preparation of a mini-library
of thermo-responsive star (NVCL/NVP-VAc) polymers with tailored properties
using a hexafunctional xanthate RAFT agent. Polymers 10 (1): 20.
214 Mori, H., Ishikawa, K., Abiko, Y. et al. (2013). Water-soluble
poly(N-vinyl-1,2,4-triazole) star and amphiphilic star block copolymers by
RAFT polymerization. Polymer 54 (8): 2001–2010.
215 Mori, H., Ookuma, H., and Endo, T. (2008). Poly(N-vinylcarbazole) star poly-
mers and amphiphilic star block copolymers by xanthate-mediated controlled
radical polymerization. Macromolecules 41 (19): 6925–6934.
216 Mori, H., Ebina, Y., Kambara, R. et al. (2012). Temperature-responsive
self-assembly of star block copolymers with poly(ionic liquid) segments. Polym.
J. 44 (6): 550–560.
217 Fleet, R., McLeary, J.B., Grumel, V. et al. (2007). Preparation of new mul-
tiarmed RAFT agents for the mediation of vinyl acetate polymerization.
Macromol. Symp. 255 (1): 8–19.
References 547
218 Zhang, S., Chen, K., Liang, L. et al. (2013). Synthesis of oligomer vinyl acetate
with different topologies by RAFT/MADIX method and their phase behaviour
in supercritical carbon dioxide. Polymer 54 (20): 5303–5309.
219 Mori, H., Ookuma, H., and Endo, T. (2007). Synthesis of star polymers based
on xanthate-mediated controlled radical polymerization of N-vinylcarbazole.
Macromol. Symp. 249–250 (1): 406–411.
220 Zheng, X., Ji, C., Liu, J. et al. (2018). Novel star polymers as chemically ampli-
fied positive-tone photoresists for KrF lithography applications. Ind. Eng. Chem.
Res. 57 (19): 6790–6796.
221 Qiu, Y., Zhang, W., Yan, Y. et al. (2010). Preparation of miktoarm star-block
copolymers PSn -b-PVAc4-n via combination of ATRP and RAFT polymerization.
222 Zhang, W., Zhang, W., Zhu, J. et al. (2009). Controlled synthesis of
pH-responsive amphiphilic A2 B2 miktoarm star block copolymer by combi-
nation of SET-LRP and RAFT polymerization. J. Polym. Sci., Part A: Polym.
Chem. 47 (24): 6908–6918.
223 Zhang, W., Zhang, W., Zhang, Z. et al. (2010). Thermo-responsive fluorescent
micelles from amphiphilic A3 B miktoarm star copolymers prepared via a com-
bination of SET-LRP and RAFT polymerization. J. Polym. Sci., Part A: Polym.
Chem. 48 (19): 4268–4278.
224 Ramesh, K., Thangagiri, B., Mishra, A.K. et al. (2018). AB2 -type miktoarm
poly(L -lactide)-b-poly(N-acryloylmorpholine) amphiphilic star block copolymers
as nanocarriers for drug delivery. React. Funct. Polym. 132: 112–119.
225 Hira, S.K., Ramesh, K., Gupta, U. et al. (2015). Methotrexate-loaded four-arm
star amphiphilic block copolymer elicits CD8+ T cell response against a highly
aggressive and metastatic experimental lymphoma. ACS Appl. Mater. Interfaces
7 (36): 20021–20033.
226 Xie, C., Zhang, P., Zhang, Z. et al. (2015). Drug-loaded pseudo-block copolymer
micelles with a multi-armed star polymer as the micellar exterior. Nanoscale 7
(29): 12572–12580.
227 Zheng, Y., Li, S., Weng, Z. et al. (2015). Hyperbranched polymers: advances
from synthesis to applications. Chem. Soc. Rev. 44 (12): 4091–4130.
228 Poly, J., Wilson, D.J., Destarac, M. et al. (2008). Synthesis of poly(vinyl acetate)
nanogels by xanthate-mediated radical crosslinking copolymerization. Macro-
mol. Rapid Commun. 29 (24): 1965–1972.
229 Willcock, H. and O’Reilly, R.K. (2010). End group removal and modification of
RAFT polymers. Polym. Chem. 1 (2): 149–157.
230 Harvison, M.A., Roth, P.J., Davis, T.P. et al. (2011). End group reactions of
RAFT-prepared (co)polymers. Aust. J. Chem. 64 (8): 992–1006.
231 Moad, G., Chong, Y., Postma, A. et al. (2005). Advances in RAFT polymer-
ization: the synthesis of polymers with defined end-groups. Polymer 46 (19):
8458–8468.
232 Moad, G., Rizzardo, E., and Thang, S.H. (2011). End-functional poly-
mers, thiocarbonylthio group removal/transformation and reversible
addition-fragmentation-chain transfer (RAFT) polymerization. Polym. Int. 60

(1): 9–25.
233 Holbein, B.E., Ang, M.T.C., Palaskar, D.V. et al. (2019). Polymeric metal chelat-
ing compositions and methods of preparing same for controlling growth and
activities of living cells and organisms. US Patent 20190169126A1, filed August
26, 2016 and issued June 6, 2019.
234 Wu, Y., Zhou, Y., Zhu, J. et al. (2014). Fast conversion of terminal thiocar-
bonylthio groups of RAFT polymers to “clickable” thiol groups via versatile
sodium azide. Polym. Chem. 5 (19): 5546–5550.
235 Pound, G., McKenzie, J.M., Lange, R.F. et al. (2008). Polymer-protein conju-
gates from ω-aldehyde endfunctional poly(N-vinylpyrrolidone) synthesised
via xanthate-mediated living radical polymerisation. Chem. Commun. 27:
3193–3195.
236 Quiclet-Sire, B. and Zard, S.Z. (2010). A convenient, high yielding cleavage of
the thiocarbonyl group in xanthates. ChemInform 31 (3): 543–544.
237 Matioszek, D., Dufils, P.E., Vinas, J. et al. (2015). Selective and quantitative
oxidation of xanthate end-groups of RAFT poly(N-butyl acrylate) latexes by
ozonolysis. Macromol. Rapid Commun. 36 (14): 1354–1361.
238 Zard, S., Sire, B., and Jost, P. (2009). Method for partial or total oxidation of
one or several thiocarbonylthio ends of a polymer obtained by radical polymeri-
sation controlled by reversible addition-fragmentation. US Patent 7473740B2,
filed October 22, 2003 and issued January 6, 2009.
239 Pfukwa, R., Pound, G., and Klumperman, B. (2008). Facile end group modifi-
cation of RAFT made polymers, by radical exchange with hydrogen peroxide.
Polym. Prepr. 49 (2): 117.
copolymers. In: Controlled/Living Radical Polymerization, ACS Symposium
Series, vol. 944 (ed. K. Matyjaszewski), 564–577. American Chemical Society.
241 Wilczewska, A.Z., Destarac, M., and Zard, S. et al. (2002). Method for synthesis
of polymers with thiol functions. WO2002090424A1, Rhodia Chimie, Fr.
242 Postma, A., Davis, T.P., Li, G. et al. (2006). RAFT polymerization with phthal-
imidomethyl trithiocarbonates or xanthates. On the origin of bimodal molecular
weight distributions in living radical polymerization. Macromolecules 39 (16):
5307–5318.
243 Chong, Y.K., Moad, G., Rizzardo, E., and Thang, S.H. (2007). Thiocarbonylthio
end group removal from RAFT-synthesized polymers by radical-induced reduc-
tion. Macromolecules 40 (13): 4446–4455.
244 Glaria, A., Beija, M., Bordes, R. et al. (2013). Understanding the role of ω-end
groups and molecular weight in the interaction of PNIPAM with gold surfaces.
Chem. Mater. 25 (9): 1868–1876.
549
11
Dithiocarbamates in RAFT Polymerization

Graeme Moad
11.1 Introduction
This review updates a review on the same topic that was originally published in
Journal of Polymer Science, Polymer Chemistry in 2019 [1]. Much of the text and many
of the figures and schemes are from that source [1].
Dithiocarbamates (Z′ Z′′ NC(=S)SR, IUPAC recommended term is car-
bamodithioate) are versatile RAFT agents. Their activity as a class spans a
continuum ranging from the most active to the least active of RAFT agents and
depends strongly on the substituents R and NZ′ Z′′ (Figure 11.1). In the initial RAFT
agent, R should be a good homolytic leaving group both in absolute terms and when
considered in relation to the propagating species. It must also be an effective initi-
ating radical for the monomers being polymerized. The substituents Z′ , Z′′ largely
determine the reactivity of the thiocarbonyl double bond towards radical addition
and the facility of intermediate fragmentation. Early work showed that depending
on Z′ , Z′′ , the attributes of good control (i.e. predicted molar mass, low dispersity (Ð),
little retardation, high end-group fidelity) could be obtained in the polymerization
of both more activated monomers (MAMs; (meth)acrylates, styrenes, acrylamides)
and less activated monomers (LAMs; vinyl esters, vinylamides, allyl monomers).
Dithiocarbamates with Z′ Z′′ NC(=S)S— appearing near the centre of Figure 11.1a
show capacity for controlling the polymerization of both MAMs and LAMs. For this
reason, they are said to have balanced activity. However, the activity of these RAFT
agents with respect to one or both monomer classes is compromised to some extent
[2–6] such that molar mass may be higher than predicted for low monomer conver-
sions, higher Ð (e.g. >1.3) is seen for 1,1-disubstituted MAMs (e.g. methyl methacry-
late [MMA]), and some retardation is observed with LAMs (e.g. vinyl acetate) and
intermediate activated monomers (IAMs) (e.g. N-vinylcarbazole [NVC]) [7].
Despite their versatility, dithiocarbamates have to date had limited impact as
RAFT agents. The publication rate in both the patent and open literature on
dithiocarbamate RAFT agents lags behind those relating to the use of xanthate
RAFT agents (those currently most popular for controlling polymerization of
550 11 Dithiocarbamates in RAFT Polymerization
High activity More suited for MAMs

only suited for MAMs (can be used for LAMs)
S S S S O S S S S
S S
N S N S N S N S N S N S N S N S
>> > > CI N S > N S > ~ >> >> >>
N N
N N N N
H H More suited for LAMs Lower acitivity
(can be used for MAMs) only suited for LAMs
(a)
CN CO2CH3
(b)
Figure 11.1 (a) Effect of Z′ Z′′ NC(=S)-group and (b) R group on activity of dithiocarbamates
Z′ Z′′ NC(=S)SR in RAFT polymerization. Activity increases from right to left. MAM, more
activated monomer; LAM, less activated monomer; IAM, intermediate activated monomer;
AN, acrylonitrile; BA, butyl acrylate; DMAm, N,N-dimethylacrylamide; HPMAm,
N-(2-hydroxypropyl)methacrylamide; MA, methyl acrylate; MMA, methyl methacrylate;
NIPAm, N-isopropylacrylamide; NVC, N-vinylcarbazole; NVP, N-vinylpyrrolidone; St, styrene;
VAc, vinyl acetate. Source: Moad [1]. © 2019, John Wiley and Sons.
LAMs – Figure 11.2) [8], and they lie substantially further behind those relat-
ing to the use of dithioesters [9] and trithiocarbonates (currently preferred for
MAMs – Figure 11.2) [10]. This can in large part be attributed to the lack of
commercial availability of dithiocarbamates with suitable activity for controlling
the polymerization of MAMs, which has only recently been addressed.
RAFT polymerization with dithiocarbamate RAFT agents should be distinguished
from radical polymerization performed with dithiocarbamate ‘iniferters’. The
carbon-sulfur bonds of N,N-dialkyldithiocarbamates and related compounds can
undergo reversible homolysis under irradiation with light of appropriate wavelength
to allow monomer insertion into the C—S bond. The N,N-dialkyldithiocarbamyl
radical is considered persistent, reacting with most monomers very slowly if at all.
Otsu developed this chemistry as a method of controlled polymerization. Their
first experiments in the field were reported in 1956–1957 [11, 12]. The monomer
insertion process with N,N-dialkyldithiocarbamates is, like nitroxide-mediated
polymerization (NMP) [13–16], a form of stable radical-mediated polymerization
(SRMP).
In 1982, Otsu et al. [17–19] proposed the concept of living radical polymeriza-
tion, now termed reversible-deactivation radical polymerization (RDRP) [16, 20].
They recognized that radical polymerizations might display living attributes
in the presence of reagents that are capable of reversibly deactivating active
chains (propagating radicals, Pn ⋅) such that the majority of living chains are
maintained in a dormant form (Pn –X). They also introduced the terms ‘initer’
500
Dithiocarbamate
Dithiocarbamate journal
Xanthate
400
Xanthate journal
Trithiocarbonate
Trithiocarbonate journal
Dithiobenzoate
300
Publications
Dithiobenzoate journal
200
100
0
2000 2005 2010 2015
Year
Figure 11.2 RAFT polymerization publication rate per annum. Includes both patent and
open literature publications (dashed lines) or just journal publications (solid lines). Based
on ScifinderTM Search carried out in May 2020 on the RAFT agent structures and the terms
‘RAFT’ or ‘reversible addition–fragmentation chain transfer’, and the term ‘MADIX’, in the
case of xanthates, and the term ‘iniferter’, in the case of dithiocarbamates.
(for initiator-terminator) and ‘iniferter’ (for initiator-transfer agent-terminator) to

describe the reagents used. A similar terminology (‘inifer’ [for initiator-transfer
agent]) had already been used by Kennedy et al. [21, 22] in describing cationic
polymerizations with reversible deactivation.
Otsu recognized that reversible chain transfer could contribute to living
characteristics. However, they, and others [23], soon demonstrated that the
N,N-dialkyldithiocarbamates they used had very low transfer constants in the
polymerizations of MAMs. Thiuram disulfide ‘iniferters’ have higher transfer
constants and are deserving of the name (Ctr (St, 60 ∘ C) = 0.29) [24]. However, they
are immediately transformed to less active N,N-dialkyldithiocarbamate end-groups
when used in polymerization.
Sulfur-centred radical-mediated polymerization making use of N,N-dialkyldithio-
carbamate photoiniferters or photoiniters has been reviewed by Sebenik [25], Otsu
and Matsumoto [26], and Otsu [19] with respect to the literature through 2000, and
more recently by Tasdelen and Yagci [27]. The ‘photoiniferter’ process as originally
conceived, whether with simple alkyl N,N-dialkyldithiocarbamates or with thiuram
disulfides, is not generally useful for the synthesis of well-defined polymers, though
recent examples of block [28] and star polymer syntheses [29–31] can be found.
The main current use of iniferter chemistry is in photoinitiated grafting from
particles or surfaces of various types with a significant number of publications from

just 2016–2018 [32–44]. The process of surface-initiated photoiniferter-mediated
polymerization (SI-PIMP) is compared with surface-initiated atom-transfer radical
polymerization (SI-ATRP), surface-initiated reversible addition-fragmentation
chain transfer polymerization (SI-RAFT), and surface-initiated nitroxide-mediated
polymerization (SI-NMP) in a recent review [45].
This said, there has been a marked upsurge in interest in photoinitiated RAFT
polymerization (mainly using trithiocarbonates or dithioesters) where radicals are
generated by direct or photosensitized photolysis of the RAFT agent [46–52], by what
can be recognized as Otsu’s photoiniferter mechanism, or through a photo-redox
process involving the RAFT agent. The last process, making use of a photosensitizer
or a photo-redox catalyst, is known as (photoinduced electron/energy transfer)
PET-RAFT [53–58].
Visible (blue) light-initiated RAFT polymerization with dithiocarbamates (where
Z′ Z′′ NC(=S)S– includes 126, 127, 128, 149, 150) has been reported [59]. There has
been debate about the relative importance of RAFT and the SRMP mechanisms in
providing control over polymerization. However, it is likely in most, if not all, cases
that when an effective (high transfer coefficient) RAFT agent is used, it is the RAFT
process that is dominant in providing low dispersities and good control [46, 55]. On
the other hand, when a poor RAFT agent for the monomer being polymerized is
used the iniferter mechanism may dominate [60].
11.2 Dithiocarbamate Transfer Constants
The efficiency of RAFT can be measured in terms of two transfer coefficients, Ctr
(=ktr /kp ) and C−tr (=k−tr /k−𝛽 ), where ktr and k−tr are given by Eqs. (11.1) and (11.2),
respectively. The value of ktr depends on the rate of addition of the propagating
radical (Pn ⋅) to the RAFT agent and a partition coefficient (𝜙) that describes the
partitioning of intermediate radical between starting materials and products – refer
to Scheme 11.1 for rate coefficient definitions.
For less active RAFT agents where Ctr ≤ 1, transfer constants for RAFT agents
may be determined with reasonable accuracy by the usual methods (e.g. the Mayo
method [61], the log CLD method [62], or the Walling method [63]) [64].
However, these methods, which include an implicit assumption that C−tr is zero,
will typically underestimate the actual Ctr and the values so obtained should be
called apparent transfer constants, Ctr app . While values of Ctr app obtained are useful
for ranking RAFT agents, it should be stressed that for more active RAFT agents, val-
ues of Ctr can be higher than Ctr app by several orders of magnitude [65, 66]. Further
details on the methods for determining transfer coefficients in RAFT polymerization
are provided in the Chapter by Quinn et al. [67].
11.2 Dithiocarbamate Transfer Constants 553
Photoinitiation
S S R kβ S
∙
R + R
∙
k–β
N N
Z' Z" Z' Z"
S S Pn
kβ S
∙
S + Pn
k–β
N N
Z' Z" Z' Z"
Initiation
∙ M ∙ M M ∙
intiator I I M Pn
ki ki kp
Initialization
Reversible chain transfer / Propagation
∙ + S kadd kβ ∙
Pn S R Pn S S R Pn S S + R
k–add k–β
N N N
Z' Z" Z' Z" Z' Z"
M
kp
Reintiation
M M M
∙ ∙ ∙
R R M Pm
kiR kp kp
Main euilibrium
∙ + S kaddP k–addR P S ∙
Pm S Pn Pm S S Pn m S + Pn
k–addP kaddR
N N N
M Z' Z" Z' Z" Z' Z"
M
kp kp
Termination
kt
∙ + ∙
Pn Pm dead polymer
Scheme 11.1 Major pathways in the mechanism of RAFT polymerization with

dithiocarbamates.
A listing of available transfer constants, Ctr app , for dithiocarbamates is provided

in Table 11.1 and values can be seen to span more than four orders of magnitude
depending on the substituents Z′ Z′′ NC(=S)S— and R.
[ ]
k𝛽
k−add + k𝛽
[ ]
k−add
k−tr = k−𝛽 (1 − 𝜙) = k−𝛽 (11.2)
k−add + k𝛽
Table 11.1 Estimates of apparent transfer coefficients (C tr app ) for dithiocarbamates

[Z′ Z′′ NC(=S)S—R] in RAFT polymerization.
Z′ ZNC(=S)S—a) R Monomerb) T (∘ C) C tr app Methodc) References
126 Ċ(CH3 )2 CN St 110 >50 W [65]

126 ĊH(CH3 )Ph St 85 81 M [68]
126 ĊH2 Ph St 110 11 W [65]
140 ĊH2 Ph St 110 1.6 W [65]
156 ĊH2 Ph St 80 0.009 W [65]
156 ĊH2 Ph St 60 0.0044 N [24]
156 ĊH2 Ph St 30 0.07 N [69]
156 ĊH2 PhĊH2 St 60 0.011 N [24]
127 Ċ(CH3 )2 CO2 Ra MMA 60 2.6 M [70, 71]
127 Ċ(CH3 )2 CO2 Et MMA 60 1.1 M [70, 71]
156 ĊH(CH3 )CO2 Bu BA 80 0.3 M [72]
138-H+ ĊH2 CN MA 70 12.5 W [73]
137-H+ ĊH2 CN MA 70 6.9 W [73]
138 ĊH2 CN MA 70 2.9 W [73]
137 ĊH2 CN MA 70 0.9 W [73]
138 ĊH2 CN NVC 60 56.0 W [73]
137 ĊH2 CN NVC 60 33.3 W [73]
138 ĊH2 CN VAc 70 124 W [73]
137 ĊH2 CN VAc 70 41.7 W [73]
a) For Structures refer to Table 11.17.

b) Monomer: St, styrene; MMA, methyl methacrylate; BA, butyl acrylate; MA, methyl acrylate;
NVC, N-vinylcarbazole; VAc, vinyl acetate.
c) Method used to determine transfer coefficient: M, Mayo method; [61, 64] N, not stated; W,
Walling method [63, 64]. Refer to Quinn et al. [67] for further details on methods.
d) R = (4-phenylazo)phenyl.
Source: Updated from Moad [1]. Copyright 2019, John Wiley & Sons.
11.3 Dithiocarbamates and RAFT Polymerization

The factors that influence the choice of RAFT agent for a particular polymeriza-
tion are detailed in previous reviews [74–78]. The effectiveness of a given RAFT
agent depends on the monomer being polymerized and is determined by the prop-
erties of the free radical leaving group R and the activating group Z (NZ′ Z′′ in the
case of dithiocarbamates). For effective RAFT polymerization (refer Scheme 11.1,
Figure 11.3) the following conditions should be met:
Reactive Weak single bond

double bond
kaddR
R′ · + S S R R′ S · S R
k–addR
N N
Z′ Z″ Z′ Z″
R,R′ are free radical leaving

Z′Z″N modifies addition groups (R · must also be able to
and fragmentation rates efficiently reinitiate polymerization)
Figure 11.3 Structural features of dithiocarbamate RAFT agents and the intermediate
formed by radical addition. Source: Moad [1]. Copyright 2019, John Wiley and Sons.
● The initial RAFT agents and the macroRAFT agent should have a suitably reactive
C=S double bond (high kadd ).
● The intermediate radicals should fragment rapidly and give no side reactions (high
kβ , weak S—R bond in intermediate).
● The intermediate should partition in favour of products (k𝛽 ≥ k−add ).
● The expelled radicals (R⋅) must efficiently reinitiate polymerization (ki > kp ).
RAFT polymerizations making use of the most commonly encountered dithio-
carbamate RAFT agents are summarized in Table 11.2. Switchable RAFT agents
are listed separately in Table 11.3. In the tables we indicate those dithiocarbamates
that are commercially available from sources such as Boron Molecular [227], Merck
(Sigma-Aldrich) [228, 229], or Strem Chemicals [230, 231].
11.4 Monomers for RAFT Polymerization

Polymer syntheses making use of dithiocarbamate RAFT agents are summarized in
the tables above. The only systems that require separate comment are mentioned
here or in the subsequent sections. Some of the more exotic monomers subjected to
RAFT polymerization are included in the tables that follow. They include methacry-
lates and other 1,1-disubstituted MAMs, (Table 11.4), acrylates and acrylamides
(Table 11.5), styrene derivatives (Table 11.6), and vinyl monomers and other LAMs
(Table 11.7).
11.4.1 1,1-Disubstituted MAMs (Methacrylates)

RAFT polymerization with dithiocarbamate RAFT agents has been successfully
applied to methacrylates, which include butyl methacrylate (BMA), tert-butyl
methacrylate (tBMA), (diethylene glycol monomethyl ether) methacrylate
(DEGMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), glycidyl methacry-
late (GMA), MAA, MMA, (poly(ethylene glycol)monomethyl ether)methacrylate
(sentence continued on p. 572)

Table 11.2 RAFT polymerization with dithiocarbamate RAFT agents.
(a) More active RAFT agents suitable for MAMs (1H-pyrrole-1-carbodithioates,

9H-carbazole-9-carbodithioates)
S D [65] Methacrylates: MMA [65, 79–81]
N Styrenes: PFS [82] St [65] 90 [83]
S CN Others: (65) [84]
1
2-cyanopropan-2-yl 1H-pyrrole-1-carbodithioate
S D [85] Methacrylates: MMA [85]

N
S CN
2
2-cyanobutan-2-yl 1H-pyrrole-1-carbodithioate
S A [86] Methacrylates: GMA [87]

N C [86, 87] Acrylamides: NIPAm [86, 88]
S Styrenes: St [87]
Copolymers: tBMA/DEGMA [87]
Blocks: tBMA/DEGMA-b-GMA
3 [87]
2-phenylpropan-2-yl 1H-pyrrole-1-carbodithioate

N Blocks: St-b-2VP [89]
S CO2C2H5 ATRP: St [90]
4
ethyl 2-((1H-pyrrole-1-carbonothioyl)
thio)-2-methylpropanoate
S A [91] Styrenes: St [68, 92]

N
S
5
1-phenylethyl 1H-pyrrole-1-carbodithioate
(continued)
S A [65] Methacrylates: MMAa) [93] 60

N G (Merck) [94] 61 [94]
S Acrylates: (AA) [95] MA
[93, 96–98] BA [99] EHA [99]
Acrylamides: NIPAm [88, 100]
70 [101] 71 [102, 103] 72 [104]
6
73 [104] 74 [105–107] 75 [107]
benzyl 1H-pyrrole-1-carbodithioate
76 [102] 77 [108] 83 [107, 109]
84 [102, 105, 107] 78 [110] 79
[110] 80 [111] 81 [111] 85
[102] 86 [112] 89 [113]
Styrenes: St [65, 98] (94) [114]
95 [115]
Dienes: (Cp) [116]
Others: (NES) [117] NVPI
[108, 118] (99–101) [119]
107–106 [120] (110–111) [121]
112 [122] 103 [123] 104 [123]
(NVC) [124]
Copolymers: NIPAm/NVPI
[125] NIPAm/102 [126]
(AA/ACE) [95] (DMAm/102)
[126] (MA/102) [126]
(MAH/103) [127]
(NMMI/103) [127]
(NPMI/103) [127] 94/CMS
[115] 94/St [128]
Blocks: MMA-b-Stc) [93]
MA-b-Stc) [93] 71-b-92
[103] St-b-74 [106] 76-b-74
[106] 76-b-83 [105] 76-b-84
[105] 83-b-84 [105] 83-b-78
[105] 83-b-79 [105] 86-b-
NIPAm [112] 103-b-NIPAm
[123] 104-b-NIPAm [123]
NVPI-b-74 [108] NVPI-b-77
[108]
S A [129] Acrylamides: NIPAm
N [95, 129–132]
S
7
4-vinylbenzyl 1H-pyrrole-1-carbodithioate
(continued)
D [133] Methacrylates: BMA [134]

S EMA [134] MMA [133, 135]
N Blocks: BMA-b-MMA [134]
S CN EMA-b-MA [134]
8
2-cyanopropan-2-yl 9H-carbazole-9-carbodithioate
CO2H D [133] Methacrylates: MMA [133]

S
N
S CN
9
4-((9H-carbazole-9-carbonothioyl)
thio)-4-cyanopentanoic acid
A [136] Methacrylates: MMA [136]

S Styrenes: St [136]
N
S
10
2-phenylpropan-2-yl 9H-carbazole-9-carbodithioate
A [50, 137] Methacrylates: MMA [50]

S (MMA) [137]
N Acrylates: BA [50] BAa) [50]
S CO2R MA [137, 138]
Styrenes: St [50]
Vinyls: NVC [50]
11a R=CH3
Blocks: MA-b-St [137]
11b R=C2H5
alkyl 2-((9H-carbazole-9-carbonothioyl)

S (MMA) [136, 139]
N Styrenes: St [136] (St) [139]
S
12
1-phenylethyl 9H-carbazole-9-carbodithioate
(continued)
A [136, Acrylates: BA [134, 142] BzA [144]

S 140–143] EA [134] EHA [134] MA [142, 143]
G PEGA [145] OA [142]
N
S Methacrylates: MMAe) [141] (MMA)
[136]
Styrenes: St [134, 136, 140, 142, 146]
CMS [147]
13 Blocks: BA-b-MA [134] BzA-b-MA
benzyl 9H-carbazole-9-carbodithioate [144] EA-b-MA [134] EHA-b-BA
[134] PEGA-b-St [145]
PEGA-b-St/DMAm [145] St-b-MA
[134] St-b-PVK [146] St-b-PVK-b-AA
[146] St-b-PVK-b-MA [146]
S F [148] St [148]
N
S
CN
N
+
C12H25SO4–
H3C
14
4-((((cyanomethyl)thio)carbonothioyl)
(methyl)amino)-1-methylpyridin-1-ium
dodecylsufonate
(b) RAFT agents with balanced activity suitable for MAMs and LAMs
(1H-pyrazole-1-carbodithioates, diphenylcarbamodithioates)
S A [91] Acrylates: (AA) [149]
N N B [149]
S
15
1-phenylethyl 1H-imidazole-1-
carbodithioate
S A Methacrylates: (MMA) [154]

N N [150–152] Acrylates: (AA) [149] MA
S B [153] [79, 97, 154–156] MA [59] 66
G [157, 158]
Styrenes: St [159, 160] 91
[154, 156, 160, 161]
16 Copolymers: MA/62 [161] St/62
benzyl 1H-imidazole-1-carbodithioate [161] MA/91 [161] St/91 [161]
96/MA [156] 97/MA [162]
Blocks: 66-b-St [158] St-b-96/MA
[156, 159]
(continued)
S A [59] Acrylates: MA [59]

N N
S
Ph
Ph Ph
18
4-(1,2,2-triphenylvinyl)benzyl 1H-
imidazole-1-carbodithioate
D [3] Methacrylates: (MMA) [3]

S
G Acrylates: MA [3]
N
S CN Acrylamides: DMAm [3]
N
Vinyls: VAc [3]
19
Copolymers: BA/CHPMA [164]
2-cyanobutan-2-yl 3,5-dimethyl-1H-
DMAm/VAc [164]
pyrazole-1-carbodithioate
D [2] Methacrylates: MMA [2]

S
CI G Acrylates: MA [2]
N
N S CN
Styrenes: St [2]
Vinyls: VAc [2]
20
2-cyanobutan-2-yl 4-chloro-3,5-
dimethyl-1H-pyrazole-1-carbodithioate

S
G Acrylates: MA [3]
N
S
Acrylamides: DMAm [3, 165]
N
CN Styrenes: St [3]
21 Vinyls: E [166] VAc [3]
cyanomethyl 3,5-dimethyl-1H- Copolymers: AA/BA [167]
pyrazole-1-carbodithioate Blocks: (AA/BA-b-MA) [167]
AA/BA-b-MA-b-MA/EGDA [167]
(continued)
A [3] Acrylates: MA [3]

S
F [168] Acrylamides: DMAm [3]
N
G Styrenes: St [163]
N S
Vinyls: VAc [3]
22
benzyl 3,5-dimethyl-1H-
pyrazole-1-carbodithioate

N
N S CO2C2H5
23
ethyl 2-((1H-pyrazole-1-carbonothioyl)
E [169] Acrylates: AA [169] BA [169]

S G Vinyls: (NVCL) [170]
N
S
CO2H
24
2-((diphenylcarbamothioyl)thio)-2-
methylpropanoic acid
A [4, 5] Acrylates: EA [6] MA [5] tBA [5]

S Styrenes: (St) [4, 5]
N CO2C2H5 Vinyls: VAc [6]
S Blocks: St-b-VAc [4, 5]
CO2C2H5
25
diethyl 2-((diphenylcarbamothioyl)
thio)malonate
A [171] Vinyls: NVP [171]

S
N
S
O
O
OH
26
2-hydroxyethyl 2-((diphenylcarbamothioyl)
thio)propanoate
(continued)
C [172] Vinyls: EVEf) [173] iBVEf) [172]

S Blocks: EVE-b-(EVE-alt-CTFE)
N [173]
S
O
27
1-isobutoxyethyl diphenylcarbamodithioate
G (Merck) Acrylates: (MA) [174]

S
N
S
CN
28
cyanomethyl
diphenylcarbamodithioate
O A [175] Methacrylates: (MMA) [175]

S Acrylates: MA [175]
N Acrylamides: NAM [175]
O
Vinyls: (VAc) [175]
29
1-phenylethyl 1,3-dioxo-1,3,4,7-
tetrahydro-2H-4,7-methanoisoindole-2-
carbodithioate
O A Methacrylates: (MMA) [175]

S [175, 176] Acrylates: BA [176]
N Styrenes: St [176]
S Vinyls: (VAc) [175]
O
-
ROMP-T-RAFT [176, 177]
30
benzyl 1,3-dioxo-1,3,4,7-tetrahydro-2H-4,7-
methanoisoindole-2-carbodithioate
(continued)
O A [153] Acrylates: (MA) [153]

N
S
O
31
benzyl 1,3-dioxoisoindoline-2-
carbodithioate
O A [65, 153] Acrylates: MA [98, 153, 178]

S Styrenes: (St) [65, 153]
N
S
32
benzyl 2-oxopyrrolidine-1-
carbodithioate
O A Acrylamides: 82 [88]
S Acrylates: AA [88, 179] MA [178]
N Others: 64 [88] (63) [180]
S
Blocks: AA-b-NIPAm [88, 179]
CN AA-b-64 [88]
33
1-cyanoethyl 2-oxopyrrolidine-1-
carbodithioate
O C [181] Vinyls: (iBVE)f) [172, 181]

S Blocks: EVE-b-(EVE/VAc) [181]
N
S
O
34
1-isobutoxyethyl 2-oxopyrrolidine-1-
carbodithioate
(continued)
(c) Less active RAFT agents suitable for LAMs (alkyl(aryl)carbamodithioates, dialkylcarbamodithioates)
D [182] Vinyls: VAc [182] E [182]
N S
n
S CO2CH3 CN
35
S A [5] Vinyls: VAc [5] NVP [183]

N
S
CO2C2H5
36
ethyl 2-((methyl(phenyl)carbamothioyl)
thio)propanoate
S A [184] Acrylates: (MA) [3] (MA) [174]

N G Dienes: (Cp) [185]
S Vinyls: E [166] HEVE [186] NVP [186]
CN VAc [2, 3, 53, 98, 186–191] VAc [189]
(VAc)e)[53] VC [190, 192] vinyl ethers
[186] iBVE [193] MOVE [193] 98 [194]
37
Blocks: (HEVE-b-VAc) [186]
cyanomethyl methyl(phenyl) (HEVE-b-NVP) [186] VAc-b-HEVE [186]
carbamodithioate
VAc-b-VC [190]
S
Acrylates: (MA) [175]
N
Acrylamides: (NAM) [175]
S
Styrenes: (St) [175]
CN
Vinyls: VAc [175]
38
cyanomethyl 1,3,3a,4,7,
7 a-hexahydro-2H-4,
7-methanoisoindole-
2-carbodithioate
S D [195] Methacrylates: (MMA) [79]

R′
Vinyls: (VAc) [28]
N
ATRP: DMAEMA [196] MMA [195–198]
R″ S
PEGMA [196] BA [196] tBA [196] St
CN [195–197, 199] VAc [196]
2-cyanopropan-2-yl
dialkylcarbamodithioate
39a R′ = R″ = CH3
39b R′ = R″ = C2H5
(continued)
S A [195, 200] Vinyls: VAc [28]

N D [200] ATRP: MMA [195, 197, 198, 201] St
E [200] [195, 197, 199]
S
Photoiniferter: HEMAd) [202]
CO2C2H5
HEMA-b-MMAd) [202]
40
ethyl 2-((diethylcarbamothioyl)
S A [203] Acrylates: (BA) [169] (EA) [169]

N E [169] Styrenes: (St) [169]
S Vinyls: (VAc) [169] NVCL [204]
CO2H Copolymers: BA/MAA/MMA/DAAm
41 [205]
2-((dimethylcarbamothioyl)
thio)-2-methylpropanoic acid
A [195] ATRP: MMA [195, 198]

S
N
S
CO2CH3
42
methyl 2-((diethylcarbamothioyl)
thio)-2-phenylacetate
S A [206] Vinyls: VAc [28] VAc g) [207]

N Bg) [207] Others: VF2 [206]
S D [208]
CO2R
alkyl 2-((diethylcarbamothioyl)
thio)propanoate
43a R = CH3
43b R = C2H5
S A [65] Vinyls: (VAc) [207]

N G (Merck) Styrenes: (St) [65, 79]
S
44
benzyl diethylcarbamodithioate
(continued)
S C [172] Vinyls: EVEf) [173, 206] iBVEf) [172]f)

HOStf) [172]
N
Blocks: EVE-b-(EVE-alt-CTFE) [173]
S
EVE-b-VF2 [206]
O
45
1-isobutoxyethyl
diethylcarbamodithioate
S C [209] Other: 113 [209]

N
S
O
O
46
methyl 3-((diethylcarbamothioyl)thio)-2-
methylpropanoate
a) Method of synthesis (the letters (A-G) correspond to the method of synthesis in Section 11.5).
b) Red – photoinitiated polymerization, italics – heterogeneous polymerization,
(parentheses) – little or poor control (e.g. molar mass substantially higher than predicted,
dispersity ≥1.4 and/or marked retardation). Refer to Abbreviations at the end of the chapter for
a full list of abbreviations.
c) Microfuidic reactor.
d) Photoinitiated process – SRMP mechanism likely to be dominant.
e) Photoinitiated process – RAFT mechanism likely to be dominant.
f) Cationic RAFT polymerization.
g) Ethyl ester.
Table 11.3 RAFT polymerization with switchable dithiocarbamate RAFT agents.
RAFT agent Synthesisa) Polymerizationsb), c) Switched RAFT agent Polymerizationsb)
X A [73] (MA) [73] NVC [73] VAc X MA [73]

[73] NVP [210] NIPAm [210]
S NIPAm-b-NVP [210] S
N N
S S
CN CN
N +N
cyanomethyl aryl(pyridin-4-yl) H
carbamodithioate 47a-H+ X = OCH3
47aX = OCH3 b-H+ X = H
b X=H c-H+ X = F
c X=F d-H+ X = CN
d X = CN cyanomethyl (4-chlorophenyl)
cyanomethyl (4-chlorophenyl) (pyridin-4-yl) carbamodithioate
(pyridin-4-yl)carbamodithioate
47d CTFE/EVE [211]
N A [73] (MA) [73] NVC [73] VAc N MA [73]

[73] NVP [210] S
S
N N
S S
CN CN
N +N
cyanomethyl di(pyridin-4-yl) H
carbamodithioate 48-H+
48
(continued)
S D [184] – S MMA [184]

N OCH3 N OCH3
S S
CN CN
N +N
2-cyano-4-metahoxy-4-methylpentan-2-yl H
methyl(pyridin-4-yl)carbamodithioate 49-H+
49
S D [184] E [166] (VIm) [212] S BMA [148]

N G MMA-b-VAc [184, 213],c N MMA
S iBVE [193] MOVE [193] S
[184, 213, 216]
MMA [148]
CN tBMA-b-NVP [214],c CN
PFS-b-NVP [215] tBMA [214] PFS
N +N
PFS-b-VAc [215] St-b-NVP [215] St [215]
2-cyanopropan-2-yl methyl(pyridin-4-yl) H
carbamodithioate [215] St-b-VAc [215]
50-H+
50
S G[227, 229]
N
S
CN
N
2-cyanobutan-2-yl methyl(pyridin-4-yl)
carbamodithioate
51
S O O G NVP [217, 218]
N
S O N
CN
N O
2,5-dioxopyrrolidin-1-yl 4-cyano-4-
((methyl(pyridin-4-yl)carbamothioyl)
thio)pentanoate
52
S A [184] E [166] MA [184, 213] S DMAm [220] St

N G NVC [184, 213] NVP N [184, 213, 219]
S [184, 213] MA-b-NVC S (NVC)
CO2CH3 [213],c St-b-VAc [184, 213]
CO2CH3
[184, 219],c St-b-MA
N +N
St-b-MA-grad-VAc [184, 219]
53 [184, 219],c H
53-H+
S A [184] E [166] BA [184, 213] VAc S BA [184, 213]

N G [184, 213, 216] VAc [148] N BA [148] DMAm
S VBz [148] NVP [210, 216] S [60, 220, 224] St
MA/VAc [221] NVP/VAc [148] NIPAm
CN CN
[222] DMAm-b-NVC [220] [216] St [216]
N +N
DMAm-b-NVP [220] Am/AN [223]
54 H
DMAm-b-VAc [220]
54-H+
Am/AN-b-NVP [223]
DMAm-b-MMA [60]
(continued)
– – – S BA [184]
N
S
CN
+ N
–
(TfO)3AI
54-Al(OTf)3
– – – S MA/VAc [221]
N
S
CN
+ N
–
(TfO)3Sc
54-Sc(OTf)3
S A [220] (DMAm) [220] S DMAm [220]

N N
S S
O OH O OH
O 4 + O 4
N N
55 H
55-H+
S HO A [225] NVP [225] VAc [225] S HO MA [225]
-
ROP-T-RAFT [225] DMAm [225]
N N
-
ROP-T-RAFT
S S
[225]
O O
N O + N O
56 H
56-H+
OH A [226] NVC [226] OH St [226]

OH
S S HO
N N
S S
O O
N O +N O
57 H
55-H+
S S G [227]
N N
S S
N N
58
a) Reference to method of synthesis (the letters (A-G) correspond to the method of synthesis in Section 11.5).
b) Red – photoinitiated polymerization italics – heterogeneous polymerization, (parentheses) – little or poor control (e.g. molar mass substantially higher than
predicted, dispersity ≥1.4 and/or marked retardation). Refer to Abbreviations at the end of the chapter for a full list of abbreviations.
c) For MAM-b-LAM, the RAFT agent was protonated for synthesis of MAM block and switched (neutralized) to make the LAM block.
Table 11.4 Methacrylate and other 1,1-disubstituted monomers subjected to RAFT

polymerization with dithiocarbamate RAFT agents.
O O
O O
O O O O
O O
HO OH
O O N3
59 HN O HN O
Glycerol monomethacrylate 62 [161]
O O
60 [94] 61 [94]
O
N N
O O
65 [84]
63 O
64 [88]
(PEGMA), and those listed in Table 11.4. Low dispersities require the use of a RAFT
agent with a suitably high transfer constant, which in turn requires that the ‘Z’ group
is suitable for MAMs and that the ‘R’ group is a good leaving group with respect to the
methacrylate propagating radical. The most suitable dithiocarbamate RAFT agents
in this context include those where Z is pyrrole (127), carbazole (128), or imidazole
(129) and switchable dithiocarbamates in their more active switched or protonated
form (137-H+ and 138-H+ ). The RAFT agents where Z is pyrazole (134–136) provide
higher dispersities but still give reasonable control.
11.4.2 Monosubstituted MAMs (Acrylates, Acrylamides, Styrenes)

Attaining low dispersities with RAFT polymerization of acrylates, acrylamides,
or styrenes requires a RAFT agent suitable for MAMs. Acrylates and acrylamides
include methyl acrylate (MA), butyl acrylate (BA), DEGMA, hexyl acrylate (HA),
Am, DMAm, NIPAm, N-acryloyl acrylamide (NAM), and those listed in Table 11.5,
which include a range of amino acid-based acrylamides [239]. Styrenes include
4-(chloromethyl)styrene (CMS), HOSt, St, 2VP, 4VP, and those in Table 11.6.
11.4.3 LAMs, IAMs (Vinyl Monomers)

Vinyl monomers in the present context include the vinyl esters (e.g. VAc, VBz, VPv),
the N-vinylamides (e.g. N-vinylcaprolactam [NVCL], N-vinylpyrrolidone [NVP]),
the N-vinyl heteroaromatics (e.g. Vim, NVC), the halo-olefins (vinyl chloride [VC],
VF2), the vinyl ethers, and the monomers in Table 11.7. Most of these monomers
are LAMs or IAMs and good control over homopolymerization requires use a RAFT
agent suited for that class of monomer, which is usually a xanthate or a less active
dithiocarbamate. Note, however, that good control over copolymerization of LAMs
Table 11.5 Acrylate and acrylamide derivatives subjected to RAFT polymerization with dithiocarbamate RAFT agents.
O
O O O
O O O O
O O
O O O
OAc HS + –
O O N Br
OAc
O
HO P OAc OAc 68 [232]
Ph
67 [232]
66 [157]
69 [233]
O O O O
O O O O
N N N N
OH O OH OH
70 [101, 104] HO HO
71 [103, 104]
72 [104] 73 [104]
O O O O
HO2C NH H3CO NH H3CO2C NH HO2C NH
74 [105–107] 75 [107]
CO2H
76 77 [108]
[102, 105, 106, 234]
(continued)
O O O O O
HO2C NH HO2C NH HO2C NH NH NH
O
OH OH H3CO2C
80 [111]
78 [110] 79 [110] 81 [111] 82 [88]
O O O O
HO2C NH HO2C NH H3CO2C NH NH
O
HN
83 [107, 109] 84 [102, 105, 107] 85 [102] CO2H
86 [112]
O O O
HN HN H3CO2C NH
O O O
O C(CH3)3 NH
(H3C)3C N O 88 [236]
O H 89 [113]
87 [235]
Table 11.6 Styrene derivatives subjected to RAFT polymerization with dithiocarbamate

RAFT agents.
OSi(C2H5)3
OSi(C2H5)3 O N
90 [83]
92 [103]
Si(CH3)3
93 [238]
91 [237]
CI
94 95 [115]
[114, 115, 128]
with MAMs can be obtained with more active RAFT agents suited to MAMs (e.g.
NVPI/NIPAm with 6 [125]). Also included in this section is vinylene carbonate
(1,3-dioxol-2-one, 113).
The polymerization of NVP in aqueous media was reported as problematic due to
the sensitivity of the macroRAFT agent with a terminal NVP unit to hydrolysis [210].
It has been shown for xanthate-mediated RAFT polymerization [240, 241] that this
problem might be overcome by conducting the polymerization at ambient tempera-
ture with redox initiation. We have found that for trithiocarbonate-mediated RAFT,
photoinitiation at 30 ∘ C provides low dispersities [242]. These methods are also likely
to be successful in dithiocarbamate-mediated RAFT polymerization of NVP.
11.5 Synthesis of Dithiocarbamate RAFT Agents

The methods most commonly exploited for the synthesis of dithiocarbamate RAFT
agents are listed below. The letters A-G correspond to those indicated in the Syn-
thesis columns of Tables 22.3 snf 22.3. The method of choice is dependent on the
structure of the desired RAFT agent, the amount required, the toxicity and ease of
handling of reagents, and other factors. A review of methods for RAFT agent syn-
thesis covering the literature through 2012 provides further details [78].
11.5.1 Method A – Reaction of a Carbodithioate Anion with an

Alkylating Agent
The preparation of RAFT agents, including dithiocarbamates, is most commonly
achieved by reaction of a carbodithioate anion with an alkylating agent (RX) for
Table 11.7 Vinyl monomers subjected to RAFT polymerization.
CI
O O O O
N + O S O
N –
96 [156, 159] N O
CI
97 [162] 98 [194]
NES [117]
O
N N N
N
99 [119] 100 [119] O

101 [119]
102 [126]
S S S S
O N
S N
N
N
103 [127] Br
104 [127] 105 [120]
106 [120]
S N S S
S
S N S N
107 [120] N
108 [120]
109 [120]
HN Si O O
N N
N N H Si NH
+N Si H O
+N HN
Si N 113 [209]
110 [121] O RH n
111 [121] 112

vinylcyclosil-
azane, R = H or
vinyl, n ∼ 20
[122]
NES, neopentyl ethenesulfonate.
which a general mechanism is shown in Scheme 11.2 (Table 11.8). Many variants
of this technique have been reported. The method generally provides high yields for
RAFT agents containing primary and secondary ‘R’ groups. However, RAFT agents
with tertiary ‘R’ groups are more difficult to prepare as nucleophilic substitution on
tertiary alkylating agents is relatively slow and elimination is often complicated.
S S
CS2 RX R
N N S N S
Scheme 11.2 Preparation of RAFT agents using carbodithioate salts.
The synthesis of dithiocarbamates often requires the use of a strong base, such
as sodium hydroxide [245–247] or sodium hydride [248–251], to promote formation
Table 11.8 Examples of syntheses of dithiocarbamates by alkylation of a carbodithioate

anion.
Entry ZH Base Halide Reaction conditionsa) Yield (%) References
4 Pyrrole NaH PhCH2 Br DMSO, 1 h 50 [65]

– Pyrrole NaOH Polystyrene-Brb) DMF, 24 h (100)c) [243]
– Pyrazole NaOH Polystyrene-Brb) DMF, 40 h (100)c) [244]
12 Carbazole NaH PhCH(CH3 )Br H2 O, 2 h 93 [136]
13 Carbazole NaH PhCH2 Br H2 O, 2 h 89 [136]
10 Carbazole NaH PhC(CH3 )2 Br H2 O, 2 h 69 [136]
– Carbazole NaH (CH3 )3 CBr H2 O, 2 h 76 [136]
11a Carbazole NaOH (CH3 )C(CO2 CH3 )Br DMSO, 24 h 42 [50]
a) Conditions for halide displacement step. DMSO, dimethyl sulfoxide; DMF,

N,N-dimethylformamide.
b) Bromine end-functional polystyrene.
c) Reaction assumed to be quantitative.
Table 11.9 Synthesis of 1-phenylethyl or benzyl dithiocarbamates.
Entry ZH Halide Reaction conditions Yield (%)
4 Imidazole (Ph)CH(CH3 )Br Acetone, K3 PO4, 4 h 78

— (i-Pr)2 NH PhCH2 Br Acetone, Cs2 CO3 , 10 min 61
— (Ph)(CH3 )NH PhCH2 Br Ethanol, Cs2 CO3 [252], 4 h 70
of the carbodithioate salt, although sodium N,N-diethyldithiocarbamate is commer-

cially available. Skey and O’Reilly [91] published on the synthesis of various RAFT
agents including dithiocarbamates. They found that the use of a non-nucleophilic
base (phosphate or cesium carbonate) and, typically, acetone as solvent provided
high yields. Dithiocarbamate examples are provided in Table 11.9.
Alkyl 1H-imidazole-1-carbodithioates can be prepared in high yield through the
reaction of imidazole and carbon disulfide and an alkylating agent [151]. However,
mixtures of the alkyl 1H-imidazole-1-carbodithioate and a symmetrical dialkyl
trithiocarbonate may be obtained with the proportion of the two being dependent
on the reaction conditions (cf. method B, Section 11.5.2) [152]. Anhydrous solvents
favour the exclusive formation of the 1H-imidazole-1-carbodithioate.
11.5.2 Method B – Reaction of a Dithiochloroformate or a

Thiocarbonyl-bis-imidazole with a Nucleophile
Benzyl [153] and 1-phenylethyl 1H-imidazole-1-carbodithioate [149] were prepared
by reaction of the appropriate mercaptan with thiocarbonyl-bis-imidazole
(Scheme 11.3). Perrier and coworkers [253] have shown that a range of
trithiocarbonates, dithiocarbamates, and xanthates can be prepared in moderate to
high yield by reaction of the 1H-imidazole-1-carbodithioate with the appropriate

thiol, amine, or thiol-derived nucleophile. A further example of this approach is the
synthesis of 43b (Scheme 11.3) [207].
S HS S R
N N N N S
N N
CH2CI2
RT
R = H or CH3, yield 54%
CO2C2H5
S S CO2C2H5 NH S CO2C2H5
HS
N N N S N S
N N N
Toluene KOH 46% yield
60 °C
Scheme 11.3 Preparation of dithiocarbamates from 1,1′ -thiocarbonyl diimidazole.
11.5.3 Method C – Addition of a Dithioic Acid Across an Olefinic

Double Bond
The reaction of dithioic acids with a variety of electron-rich alkenes has been shown
to provide very high yields of the required Markovnikov addition product [254]. The
olefins successfully used in this context include St, AMS, VAc, vinyl ethers and vinyl
sulfones. The process was used to synthesize cumyl 1H-pyrrole-1-carbodithioate (3)
[86, 87], and 27 [172], 34 [181] and 45 [172], derived by addition of the dithiocar-
bamic acid across the double bond of isobutyl vinyl ether (iBVE). Note that dithioic
acids, including dithiocarbamic acids [255], react with electron-deficient alkenes,
such as acrylates, by Michael addition.
11.5.4 Method D – Radical-induced Decomposition of a Thiuram

Disulfide
Radical-induced decomposition of thiuram disulfides by radicals derived from
azo-initiators is arguably the most effective technique for the synthesis of func-
tional tertiary RAFT agents (see Scheme 11.4 and Table 11.10, synthesis of
dithiocarbamate RAFT agents by reaction of dialkyldiazenes (R—N=N—R) with
bis(thioacyl)disulfides [ZC(=S)S]2 •) [256, 257, 260]. The method has been applied
CN
N
S N S
CN
S N
N S N S CN
EtOAc
S 70 °C, 24 h
Scheme 11.4 Synthesis of a tertiary RAFT agent from a thiuram disulfide.

Table 11.10 Synthesis of dithiocarbamate RAFT agents by reaction of dialkyldiazenes

(R—N=N—R) with bis(thioacyl) disulfides [ZC(=S)S]2 .
RAFT agent Z Initiatora) Reaction conditionsb) Yield (%)c) References
1 126 AIBN A 61 [65, 85, 256]

2 126 AMBN A 28 [85]
39a 155 AIBN B 93 [256, 257]
95
— 126 ACPA C 88 [258]
— 127 ACPA C 94 [259]
19 134 AMBN D Not stated [3]
20 134 AMBN D 73 [2]
a) AIBN, azobis(isobutyronitrile) (2,2′ -azobis(2-methylproionitrile)); AMBN,

2,2′ -azobis(2-methylbutyronitrile); ACPA, 4,4′ -azobis(4-cyanopentanoic acid).
b) Reaction conditions: A: degas, ethyl acetate, 70 ∘ C, 24 hours; B: reflux, benzene, 24 hours; C:
degas, ethyl acetate, 75 ∘ C, 18 hours; D: ethyl acetate, reflux, 20 hours.
c) Isolated yield after purification.
to each of most forms of RAFT agents including dithiocarbamates. The usual

radical source is an excess of an azo-compound initiator [256, 257, 260] and
the main contaminants in the product are the by-products of azo-compound
decomposition (e.g. tetramethylsuccinonitrile when azobis(isobutyronitrile)
(2,2′ -azobis(2-methylproionitrile)) (AIBN) is used).
The thiuram disulfide can be prepared by oxidation of the appropriate carbod-
ithioate salt with molecular iodine, which generally proceeds in quantitative yield
[260, 261]. Other methods that have been used with good effect include oxidation
of the carbodithioate salt with potassium ferricyanide [135, 258], p-toluenesulfonyl
chloride [262], or sodium chlorite [263].
Polymers with dithiocarbamate ends can be formed by radical polymerization in
the presence of a thiuram disulphide. This enables the synthesis of polymers that
might not be easily produced by RAFT polymerization. For example, the process
was used to prepare PMMA as shown in Scheme 11.5.
MMA
CN
N
S N
S N CN S N
N S n
S CH3CN CN CO2CH3 S
80 °C, 6 h
Scheme 11.5 Synthesis of a PMMA macroRAFT agent (35) from radical polymerization in
the presence of a thiuram disulfide.
A related process has been reported by Wager et al. [264] and Kwak et al. [208] in
which an atom-transfer radical polymerization (ATRP) initiator (a secondary or ter-
tiary alkyl halide and a copper catalyst) is used as the radical source. The latter group
termed the process atom-transfer radical addition–fragmentation (ATRAF) [208].
For dithioesters reported yields were generally high (82–92%) but significantly lower
yields were observed for dithiocarbamate (65%) and xanthate (43%) examples [208].
11.5.5 Method E – Ketoform Reaction

Lai et al. adapted the ketoform reaction [265] to prepare trithiocarbonates [266],
dithiocarbamates, and xanthates [169]. Their proposed mechanism involves ring
opening of a dichloroepoxide intermediate with a carbodithioate salt [265, 266]. Sub-
sequent hydrolysis of the acyl chloride formed provides the RAFT agent. Reaction of
a secondary amine, carbon disulfide, chloroform, a ketone, and sodium hydroxide
in the presence of a phase transfer catalyst (PTC) provides the dithiocarbamate in
good to high yield (Scheme 11.6, Table 11.11).
O
S R R′
R″ R CI
R″
NH + O + H CI N S CO2H
R′″ R′ CS2, NaOH,
CI R′″
PTC
Scheme 11.6 Synthesis of tertiary carboxyl-functional dithiocarbamates via the ketoform

reaction.
11.5.6 Method F – Other Methods

Some RAFT agents are prepared by modification of other dithiocarbamates. For
example, the pyrazole RAFT agent 22 was prepared by a base catalysed condensation
reaction between S-benzyl dithiocarbazate and 2,4-pentandione [168]. RAFT agent
14 was prepared from 54 by methylation and ion exchange (Scheme 11.7).
11.5.7 Method G – Commercially Available

A variety of dithiocarbamate RAFT agents are commercially available.
11.6 Activity of Dithiocarbamate RAFT Agents

The Z′ Z′′ N– group of dithiocarbamates [Z′ Z′′ NC(=S)SR] modifies both the rate of
addition of propagating radicals (Pn ⋅) to the thiocarbonyl and the rate of fragmen-
tation of the intermediate radical. The value of Ctr app can be ‘adjusted’ over some 4
orders of magnitude through manipulation of Z′ Z′′ N– (Table 11.1) [65].
O OCH2(CH2)10C
H3
I– O O–
+
S N CH3I S N SDS S N+
S N Acetone S N CH2CI2/H2O S N
N N N
89% 56%
Scheme 11.7 Synthesis of dithiocarbamate 54 from 14 by methylation and ion exchange.

Table 11.11 Examples of syntheses of tertiary carboxyl-functional dithiocarbamates via

the ketoform reaction [169].
Amine Ketone Product Yield (%)
Dimethylamine Acetone — 100

Dimethylamine 2-Butanone — 80
Dimethylamine Cyclohexanone — 85
Diethylamine Acetone 41 85
Diethylamine Cyclohexanone — 78
Diethylamine Acetophenone — 35
Diphenylamine Acetone 24 60
Diallylamine Cyclohexanone — 78
Diallylamine Acetone — 72
Morpholine Acetone — 85
Azepane Acetone — 85
Piperazine Acetone — 95
Piperazine 2-Butanone — 83
Piperazine 2-Pentanone — 65
1,4-Diazacycloheptane Acetone — 100
The most reactive RAFT agents include the dithioesters and trithiocarbonates
which have carbon or sulfur adjacent to the thiocarbonylthio group.
N,N-Dialkyldithiocarbamates have a lone pair on nitrogen adjacent to the thiocar-
bonyl, which can dramatically lower reactivity towards radical addition. Lower rate
coefficients for addition are predicted by molecular orbital calculations (vide infra)
[2, 65, 267, 268] and can be qualitatively understood in terms of the importance of
the zwitterionic canonical forms 114 and 115 (Figure 11.4). The interaction between
the lone pair and the C=S double bond both reduces the double bond character of
the thiocarbonyl group and stabilizes the RAFT agent relative to the intermediate
radical [65, 248, 268, 269]. Dithiocarbamates where the nitrogen lone pair is not as
available because it is part of an aromatic ring system, such as a pyrrole (in 117) or
carbazole, or where a carbonyl (in 120) is α to the nitrogen lone pair (Figure 11.4),
have reactivities closer to those of the dithioesters and trithiocarbonates [6, 65, 79].
In these cases, the importance of canonical forms such as 116 and 119 effectively
reduces the contribution of 118 and 121 respectively (Figure 11.4).
Propagating radicals with a terminal MAM unit are less reactive in radical addition
(lower kp , lower kadd ) and one of the more reactive RAFT agents is required for good
control. The poly(MAM) propagating radicals are also relatively good homolytic
leaving groups (higher k𝛽 , k−add ), and therefore, retardation solely due to slow
fragmentation is unlikely. The more active RAFT agents such as the dithioesters,
trithiocarbonates, and aromatic dithiocarbamates allow the preparation of
–
S S
R + R
N S N S
114 115
–
S S S
+ R R + R
– N S N S N S
116 117 118
– –
O S O S O S
+ R R + R
N S N S N S
119 120 121
Figure 11.4 Canonical forms of dithiocarbamates.
low-dispersity polymers from MAMs whereas the N-alkyl-N-aryldithiocarbamates

typically have lower transfer constants and provide poor control.
Propagating radicals with a terminal LAM unit are highly reactive in radical
addition (higher kp , higher kadd ). Thus, the N-alkyl-N-aryldithiocarbamates have
high transfer constants in LAM polymerization. However, the poly(LAM) propa-
gating radicals are relatively poor homolytic leaving groups (lower k𝛽 , lower k−add )
such that inhibition or retardation is likely with the more active RAFT agents, such
as the pyrrolocarbodithioates (117).
11.6.1 Dithiocarbamate RAFT Agents with Balanced Activity

Some dithiocarbamates show capacity for controlling the polymerization of both
MAMs and LAMs (see Table 11.2b and Figure 11.5). The activity of these inter-
mediate activity RAFT agents with respect to one or both monomer classes is
compromised [2–6] to the extent that while achieving control over molar mass
for both MAMs and LAMs, they provide higher dispersities with MAMs (most
noticeable, with methacrylates) and some retardation with LAMs (e.g. VAc).
Nonetheless, these RAFT agents allow most polymerizations to be controlled, and
may be the best choice when there is uncertainty about what to do. Their use can
allow the formation of poly(MAM)-block-poly(LAM).
Early work from the Rhodia group [6] showed that dithiocarbamates 122 and 123
with Z′ Z′′ N– as 5,5-dimethyloxazolidin-2-one (142) and an appropriate R group
provided control (i.e., molecular weights consistent with prediction, Ð < 1.2) over
the polymerization of MAMs (St, EA) and LAM (VAc). The Rhodia group also
reported the N,N-diphenyldithiocarbamate 124, which provided modest control
O S O O
O O S
O S
N S CN O
O O N S
N S
O O
O
122
123
124
Figure 11.5 Further examples of RAFT agents with balanced activity.
(Ð ∼ 1.4, molecular weights consistent with prediction) over the polymerizations

of both ethyl acrylate (EA) and VAc. Shipp and coworkers [4, 5] further explored
the use of 124 in BA, VAc, NVP, and vinyl laurate polymerization obtaining Ð ≤ 1.4
at higher conversions, and St, Ð ≤ 1.5 at higher conversions. They also used 124 to
synthesize poly(St)-block-poly(VAc) with Ð ≤ 1.4 [4].
The use of 1H-pyrazole-1-carbodithioates (133 refer Table 11.17) as RAFT agents
for controlling the polymerization of monosubstituted MAMs was first reported in a
series of patents issued to Symyx [270–276]. Subsequently, Babu and Dhamodharan
[89] successfully used 133 (R = benzyl) in the polymerization of styrene and
2-vinylpyridine. However, the full utility of the 1H-pyrazole-1-carbodithioates
as RAFT agents was not recognized until very recently when Gardiner et al.
[2, 3] demonstrated the 3,5-dimethyl-1H-pyrazole-1-carbodithioates (134–136)
in polymerizations of both MAMs and LAMs. Thus, the parent (19 and 20) and
the 4-chloro-(21) and 4-bromo derivatives gave low-dispersity (Ð ≤ 1.2) poly-
mers with monosubstituted MAMs, St, MA, and DMAm. Dithiocarbamate 21
provided a poly(MMA) with the anticipated molar mass and Ð as low as 1.3 at
high monomer conversion [2]. Low dispersities (Ð ≤ 1.2) and molar mass control
were also achieved for homo- and copolymerizations of the LAM, VAc, albeit
with some retardation [2, 3]. Low-dispersity poly(DMAm)-block-poly(VAc), a
poly(MAM)-block-poly(LAM), was also prepared.
11.6.2 Switchable Dithiocarbamate RAFT Agents

Stimuli-responsive, switchable, RAFT agents [73, 184, 210, 213, 219, 220, 277] can
be switched, potentially in situ, to allow good control over polymerization of either
MAMs or LAMs depending on the state of the switch. The primary motivation for
developing switchable RAFT agents was to provide a direct route to low-dispersity
poly(MAM)-block-poly(LAM). The N-methyl-N-(4-pyridinyl)dithiocarbamates, like
other N-aryl-N-alkyldithiocarbamates, control the polymerization of LAMs but are
not effective in controlling the polymerization of MAMs. With addition of stoichio-
metric strong acid, the switched N-methyl-N-(4-pyridinium)dithiocarbamates pro-
vide excellent control over the polymerization of MAMs. Protonation reduces the
importance of canonical forms, which contain two positive charges in proximity
(Figure 11.6).
S
N
S R
S H
N
S
S R
(Switch) N
+ S R
N H
Base
N
S
N H
S R
S
N N
S R
Figure 11.6 Canonical forms of N-(4-pyridinyl)-N-methyldithiocarbamate switchable RAFT

agents.
Lewis acids, such as aluminium triflate [184, 213] or scandium triflate [221], can
be used as switches with similar effect. These Lewis acids can be used to control
RAFT (co)polymerization of VAc, whereas protic acids would rapidly hydrolyse
macroRAFT agents with a terminal VAc unit to an aldehyde chain-end [221].
In applying such RAFT agents to prepare poly(MAM)-block-poly(LAM), the
block comprising the MAM generally needs to be synthesized first. This is
necessary because poly(LAM) propagating radicals are poor homolytic leaving
groups with respect to poly(MAM) propagating radicals and, consequently,
poly(LAM)-derived macroRAFT agents have very low transfer constants in MAM
polymerization. For example, attempts to synthesize poly(St)-block-poly(VAc) or
other poly(St)-block-poly(LAM) starting from a poly(St) macroRAFT agent gave
no significant yield of polymer for an extended period (>4 hours) corresponding
to the time needed to convert the initial macroRAFT agent [184, 219]. This was
attributed to the very low rate of polystyrene propagating radicals adding to VAc,
possibly compounded by the presence of trace amounts of styrene monomer in
the polystyrene macroRAFT agent (styrene is an inhibitor of VAc polymerization).
A solution to this difficulty involves forming an intermediate ‘block’ of poly(MA)
[184, 219]. Polystyrene propagating radicals give facile addition to MA, and MA
readily copolymerizes with VAc. The problems associated with ‘wrong way’ addition
may be circumvented through the use of starved-feed protocol (though this has not
been demonstrated for dithiocarbamates) [269] or through the use of photoinitiation
[60].
Switchable RAFT agents and their use in polymerization are summarized in
Table 11.3.
11.6.3 Dithiocarbamates as Mediators of Cationic Polymerization

RAFT-mediated cationic polymerization of vinyl ethers (e.g. iBVE) has been
described [172, 173, 181, 206]. Various RAFT agents were prepared. The best, as
judged by the precision of molar mass control and the low dispersity (Ð < 1.2) of
the polymers formed, were based on Z′ Z′′ NC(=S)S— 156 or 159 [172]. Dithiocar-
bamate 140 gave broader dispersities (Ð ∼ 1.8), which is attributed to the greater
ability of the Z′ Z′′ N– in 156 or 159 to stabilize a positive charge. Xanthates and
dithiocarbonates were also effective mediators in cationic RAFT polymerization.
The mechanism of cationic RAFT polymerization was proposed to be analogous
to that in radical RAFT polymerization. The RAFT end-groups are retained in the
product polymer enabling block copolymer synthesis by sequential cationic and then
radical RAFT polymerization.
Cationic RAFT polymerization is considered in more detail elsewhere in this vol-
ume [278].
11.6.4 Dithiocarbamate R Substituents

The R substituents of dithiocarbamates Z′ Z′′ NC(=S)S—R need to be chosen for com-
patibility with the monomer(s) to be polymerized. The radical R⋅ should be a good
initiating radical for at least one of the monomers comprising the feed. The rate of
addition of R⋅ to the monomer should be greater than the rate of propagation such
that initiation is not a rate-determining step. The radical R⋅ should also be a good
homolytic leaving group relative to the propagating radicals generated.
Guidelines to R group selection have been provided elsewhere [78, 279]. A sum-
mary is provided in Figure 11.1. The following are the points to note:
● Electron-rich benzyl and alkyl radicals add only slowly to most LAMs and RAFT
agents where R is benzyl and can cause potentially lengthy inhibition periods.
● A similar situation can apply with tertiary cyanoalkyl radicals. They are good
homolytic leaving groups, but their addition to the monomer may be rate deter-
mining in the initialization phase of polymerization where tertiary cyanoalkyl
RAFT agents are used with certain monomers, including acrylates, acrylamides,
and vinyl esters [280].
● One of the most versatile R substituents, being suited to most 1-substituted MAMs
and LAMs, is the cyanomethyl group [7, 277].
11.6.5 Prediction of Dithiocarbamate Activity

Both ab initio and semi-empirical methods have been employed in attempts to
explain or predict RAFT activity.
S
N Et2
S
S
N
S Ph,Me
N S
N Pyraz
S
ΔHfrag
N S
N CI-Pyraz
S
CI
S
N imid
N S
ΔHfrag
S RSE
N pyr ΔHstab
S
–60 –40 –20 0 20 40 60 80 100

–1
kJ mol
Figure 11.7 Values of ΔHfrag , ΔHstab , and RSE for dithiocarbamates derived from ab initio
calculations. Parameter values are taken from Gardiner et al. [2]. Source: Moad [1].
Extensive studies on RAFT agent activity using ab initio methods have been
performed by Coote and coworkers [2, 281, 282]. Calculated values of ΔH frag ,
ΔH stab , and the resonance stabilization energy (RSE) for dithiocarbamates [2]
are shown in Figure 11.7. ΔH frag provides a measure of the effect of the Z group
on the enthalpy of the fragmentation reaction, relative to a reference compound
with Z = H. The more exothermic the value, the more easily a given leaving group
will fragment. Typical values for known RAFT agents span nearly 100 kJ mol−1
with the most exothermic values being associated with O-alkyl xanthates and
N,N-dialkyldithiocarbamates. The most endothermic values are associated with
RAFT agents containing π-acceptor Z groups such as phenyl, which retard
fragmentation to the extent that they are only suitable when R is a very good
homolytic leaving group, such as the propagating radicals in styrene or MMA
polymerization.
The enthalpy of fragmentation for a fixed leaving group depends on how the Z
group stabilizes the RAFT agent and the RAFT-adduct radical. Decoupling these two
effects is important as it is the stabilization of the RAFT agent, rather than the adduct
radical, that has the most dramatic impact on kadd . The value of ΔHstab reflects the
effect of the Z group on the stability of the RAFT agent C=S bond. The stability of
the RAFT-adduct radical is measured using the standard RSE.
The data reported in Figure 11.7 [2] helps in understanding the difference in activ-
ity between N,N-dialkyl (155–159) or N-alkyl-N-aryl (152–154) and those where
the nitrogen is part of an aromatic ring system (126–136). However, discrimination
between the individual members of these classes or of these from those with inter-
mediate activity (137–140) is less obvious.
11.8 Dithiocarbamates in Mechanism-Transformation Processes 587
11.7 Dithiocarbamates in RAFT Emulsion

Polymerization
A process called vesicle-templated RAFT-based emulsion polymerization was exam-

ined by Rusli et al. [167]. The process made use of a P(AA-co-BA)-b-PMA-133 macro
RAFT agent.
Dithiocarbamates 156 would not be anticipated to provide good control, yet such a
RAFT agent (with R = 2-cyanoethyl) was reported to successfully mediate miniemul-
sion polymerization of EHA [283].
11.8 Dithiocarbamates in Mechanism-Transformation

Processes
Block, star, or graft copolymers comprising segments formed by RAFT and other
mechanisms (including other RDRP) can be combined through the use of dual
initiator-RAFT agents [284–286] or through the polymerization of reactively orthog-
-
onal monomers. The terminology RAFT-T-process -
(RAFT first) or process-T-RAFT
(other process first) was coined [284] to describe these processes, where the I charac-
ter is short for transformation. We do not consider transformation of end-functional
polymers formed by non-RAFT mechanisms to install dithiocarbamate functional-
ity or end linking of RAFT-synthesized polymers to other functional polymers in
this section.
Le Neindre et al. [287] in a study of thiocarbonyl and thioesters as protecting
groups for thiols found that a simple dithiocarbamate (156 with n-propyl as R) inhib-
ited the polymerization of acrylates and chain transfer was observed during styrene
polymerization. The result appears at odds with the findings that dithiocarbamates
156 are essentially inert in polymerizations of MAMs [65].

Dithiocarbamates comprising a primary hydroxy substituent allow preparation
of block copolymers by ROP-T-RAFT.- Examples of ring-opening polymeriza-
tion (ROP) in this context are acid catalysed ROP of ε-caprolactone (CL) or
trimethylenecarbonate (TMC) and base catalysed ROP of lactide (LA) making use
of 26 [171] (Table 11.2) or the switchable dithiocarbamate 56 [225] (Table 11.3). Use
-
of 56 allowed ROP-T-RAFT of ROP monomers with both MAMs (MA and DMAm)
and LAMs (VAc and NVP).

Many of the monomers for ring-opening metathesis polymerization (ROMP)
appear essentially inert under the conditions used for RAFT polymerization.
Thus, dithiocarbamates containing such functionality can be used as precursors
to ‘ene’ end-functional macro-dithiocarbamates and then of brush polymers in a

-
RAFT-T-ROMP ‘grafting-through’ process. The ene functionality of the dithio-
carbamates can also be polymerized by ROMP and brush copolymers formed
-
in a ‘grafting-from’ process by ROMP-T-RAFT. Dithiocarbamates used in such
-
RAFT-T-ROMP are 29, 30, and 38 (Table 11.2). Dithiocarbamate 30 has been used
-
in ROMP-T-RAFT.
11.8.3 Atom-Transfer Radical Polymerization (ATRP)

It is possible to convert ATRP (halide) initiators and macro-initiators to dithiocar-
bamates by ATRAF (Method D (Section 11.5.4)) [208, 264]. Dithiocarbamates have
been used a pseudohalide initiators in ATRP [288].
11.9 Dithiocarbamate Group Removal/Transformation

Most of the methods described for removal or transformation of thiocarbonylthio
end-groups of RAFT-synthesized polymers [289, 290] are applicable to polymers
with dithiocarbamate chain-ends. However, the N,N-dialkyldithiocarbamates (e.g.
156) and N-aryl-N-alkyldithiocarbamates (e.g. 153) have a significantly lower reac-
tivity towards radical addition or nucleophilic attack than dithiocarbamates, such
as the 1H-pyrrole-1-carbodithioates (126), and most other thiocarbonylthio-RAFT
agents (the dithioesters and the trithiocarbonates).
11.9.1 Dithiocarbamate Group Removal by Radical-Induced Coupling

A method developed by Perrier et al. [291] involves heating a RAFT-synthesized
polymer with a large excess of a radical initiator (e.g. 20 molar equiv), most often a
dialkyldiazene. The method has been successfully applied to 1H-pyrrole-1-carbo-
dithioates (126) [292]. Related chemistry, making use of organic peroxides, is
described in the patent literature [293]. Another method, also described in the
patent literature [273] that involves heating the RAFT-synthesized polymer with a
mixture of an initiator and a non-propagating monomer (e.g. a maleimide) appears
substantially more economical in initiator. For examples, see Table 11.12.
11.9.2 Dithiocarbamate Group Removal by Radical-Induced

Disproportionation
A method for removing thiocarbonylthio groups by what might be considered as
radical-induced disproportionation has been reported [191]. The process involves
use of triethylborane (or another triakylborane) and oxygen to generate ethyl
radicals that react with thiocarbonylthio groups to produce a propagating species by
irreversible addition–fragmentation. This reacts with further ethyl radicals mainly
by disproportionation with H-transfer to the propagating species. The process
appears rapid and quantitative (for end-group removal). Smaller amounts of other
11.9 Dithiocarbamate Group Removal/Transformation 589
Table 11.12 End-group removal by radical-induced coupling.
RAFT end-groupa) Polymerb) Initiatorb) Commentb) References
126 NIPAm ACPA 20×, 60 ∘ C, DMF [292]

129 St AIBN 20×, 80 ∘ C, toluene, 5 h [294]
134 NLA/EADA/HADA AIBMe/NPMI 4×, reflux, MEK, 2 h [273]
133 BA AIBN/NPMI 4×, reflux, MEK, 2 h [273]
134 tBA LPO 4×, reflux, toluene, 2 h [293]
a) Refer Table 11.17.

b) ACPA, 4,4′ -azobis(4-cyanopentanoic acid); NLA, 6-(5-hydroxynorbornane-2-carboxylic acid
lactone)yl acrylate; EADA, 2-[2-ethyladamantyl]acrylate; HADA,
1-[13-hydroxyadamantyl]acrylate; DMF, N,N-dimethylformamide; MEK, butan-2-one; tBA,
tert-butyl acrylate; NPMI, N-phenylmaleimide; LPO, dodecanoyl peroxide (lauroyl
peroxide). Refer to Abbreviations at the end of the chapter for a full list of abbreviations.
Table 11.13 End-group removal by radical-induced disproportionation.
RAFT end-groupa) Polymer Initiatorb) Comment References
152 VAc TEB/O2 Product is PVAc-H [191]

(80%)c) plus some PVAc-Etd)

b) TEB, triethylborane.
c) Disproportionation product.
d) Combination product.
chain-ends may also be formed. The application to removal of dithiocarbamate

ends is shown in Table 11.13.
11.9.3 Dithiocarbamate Group Removal by Radical-Induced Reduction

Radical-induced reduction allows the thiocarbonylthio group of RAFT-synthesized
polymers to be replaced with a hydrogen atom [261, 295, 296]. The process involves
reaction of the radicals formed by RAFT with a hydrogen atom donor such as a
stannane or a hypophosphite. Radical formation by heating the RAFT-synthesized
polymer with an added initiator can be inefficient with the dithiocarbamates. Photo-
generation of radicals directly from the RAFT agent offers an alternative, which also
solves the issue of initiator-derived products [292] (for examples, see Table 11.14).
11.9.4 Dithiocarbamate Group Removal by Reaction with Nucleophiles

Dithiocarbamate chain-ends are substantially less susceptible to nucleophilic attack
than most other RAFT end-groups (dithioesters, trithiocarbonates, xanthates)
[287, 297], which most likely accounts for variable results (for Examples see
Table 11.15). The theoretically estimated order of reactivity of RAFT end-groups
towards primary amine nucleophiles is dithioate ≥ dithiobenzoate > xanthate ≥
Table 11.14 End-group removal by radical-induced reduction.
RAFT end-groupa) Polymer Initiator Reagent References
156 Stb) h𝜈 Bu3 SnH [292]

126 88 AIBN EPHPc) [236]

b) Polymer formed by ATRP.
c) EPHP, N-ethylpiperidine hypophosphate.
Table 11.15 End-group removal by reaction with nucleophiles.
RAFT end-groupa) Polymer Reagent Comment References
127 MA EtNH2 /Zn Quantitative [143]

powder at 40 ∘ C, 72 h
140 AA-b-NIPAm NaOH/ Quantitative [179]
MeOH – EDTA at ambient
temperature,
3 days
b) St CH3 NH2 /H2 O Quantitative [176]
at ambient
temperature,
3 days
156 Model nBuNH2 No reaction [287]
compound at ambient
temperature,
<8 h

b) Bottlebrush polymer formed by ring-opening metathesis polymerization (ROMP) [176].
trithiocarbonate ≫ dithiocarbamate [297], where the dithiocarbamate is an

N,N-dimethyldithiocarbamate.
Partial end-group loss has been found to complicate aqueous size exclusion
chromatography of RAFT-synthesized polymers (e.g. DMAm prepared with 21).
The issue has been shown to stem from reaction with the azide salt present in the
eluent (0.2 M NaNO3 , 0.01 M Na3 PO4 , 200 ppm NaN3 , in water adjusted to pH 8).
The reaction produces a polymer with a thiol end.
11.9.5 Dithiocarbamate Group Removal by Thermolysis

Studies with model compounds (RAFT agents) show that dithiocarbamates are more
thermally stable than other RAFT agents, with N,N-dialkyldithiocarbamates being
stable under conditions where facile end-group elimination is seen for analogous
dithioesters, trithiocarbonate, and xanthates [298, 299]. Poly(MMA) formed with a
thiuram disulfide as thermal iniferter appeared relatively stable to thermolysis with
no mass loss to 300 ∘ C [300].
′
11.10 Dithiocarbamate Z Z′′ NC(=S)S groups 591
A series of experiments with polymers, polystyrene, poly(MMA), poly(NIPAm),

poly(NVP), and poly(VAc), prepared with a switchable, N-(4-pyridinyl)-N-methyl-
dithiocarbamate RAFT agent demonstrated successful end-group removal by
thermolysis for the polymers in either the switched (137) or the unswitched state
(137-H+ ) [216]. The nature of the chain-ends formed depends on the particular
polymer and in some cases remains to be clarified. Polymers based on LAMs were
stable relative to those based on MAMs. The non-protonated form of the end-group
was stable relative to the protonated form.
11.9.6 Dithiocarbamate Group Removal by Oxidation

[301–305]. The process has been demonstrated for dithiobenzoates [302, 305],
trithiocarbonates [303], and xanthates [304] and is also claimed to be effective with
dithiocarbamate chain-ends 137 and 134 [303]. The processes are claimed to lead to
the thiocarbonylthio group being replaced with a hydroxyl group [304]. Note that
hydrogen peroxide can also be used as a component of a redox initiating system for
RAFT polymerization [306–311], which must be understood in terms of the rate
of reaction of hydrogen peroxide with a RAFT end-group being very much slower
than that for reaction with a monomer under the reaction conditions.
11.9.7 Dithiocarbamate Group Removal by Other Methods

Thiocarbonylthio compounds have been shown to undergo copper-promoted
cross-coupling reaction with aryl boronic acids, which leads to replacement of the
thiocarbonylthio group with an aryl group (Scheme 11.8) [163]. The method is effec-
tive for polystyrene but leads to a complex mixture in the case of (meth)acrylates
(Table 11.16).
CN
S CN DCE, 80 °C, 20 h
N Cu(BF4)2·H2O
H3CO
N S
Ph n
Ph n (HO)2B
OCH3
Scheme 11.8 End-group transformation by copper-promoted cross-coupling DCE –

1,2-dichloroethane.
′
11.10 Dithiocarbamate Z Z′′ NC(=S)S groups
Table 11.17 provides a summary of Z′ Z′′ NC(=S)S groups in reported dithiocarba-
mate RAFT agents. Not all are mentioned in this chapter. For additional details on
those not mentioned, refer to our recent review [1].
Table 11.16 End-group removal by copper-promoted cross-coupling.
RAFT end-groupa) Polymer Reagent Comment References
134 St Complete end-group [163]

removal (Scheme 11.8)
134 MA Decomposition [163]
Table 11.17 Dithiocarbamate RAFT agent Z′ Z′′ NC(=S)S— groups.
Pyrole S Carbazole Imidazole S Triazole S

N S N N N
S N N S N S
125 S 127 128
126
Hydrazinyl F
F N S
S H S
N N N
N N S
S F H
S O
F
F 131
129
130
Pyrazole N S N S N S N S
N N N N
S S S S
132 CI Br
133 134 135
N-alkyl-N-pyridyl N-alkyl-N-pyridinium N-aryl-N-pyridyl N-aryl-N-pyridinium

S S
N S S
N
S N N
S
S S
N
N
136 H N N
H 137–
136–H+ 137
O O O O O
α-carbonyl S
S S S S
N N N O N O N
S S S S S
O 139 142
138 140 141
O O O C4H9O2C S C4H9O2C S
S S S N N
N N O N O N S S
S S S
CO2CH3
145 146 147
143 144
N,N-diaryl H
N
S S S
N N N
S S S
148
149 150
S S
N-aryl-N-alkyl N N S
S S N
S
153
151 152
S S S S S S
N,N-dialkyl N N O N N N N
S S S S S S
154 155 156 157 158
Source: Moad [1]. Copyright 2019, John Wiley and Sons.

Abbreviations 593
11.11 Conclusions
The use of dithiocarbamates Z′ Z′′ NC(=S)SR in RAFT polymerization has been

reviewed. Dithiocarbamates are an extremely versatile class of RAFT agents.
Through choice of substituents on nitrogen (Z′ , Z′′ ), the polymerization of
most monomer types can be controlled. Historically, it has been necessary
to choose one dithiocarbamate for controlling polymerization of MAMs (e.g.
1-pyrrolocarbodithioate) and another for LAMs, (e.g. N-alkyl-N-aryldithiocar-
bamate). It is now possible to have one dithiocarbamate that controls all monomer
classes (MAMs, LAMs, IAMs). Depending on the degree of control required, this
might be a RAFT agent with balanced activity (e.g. 1H-pyrazole-1-carbodithioates)
or a switchable RAFT agent (e.g. N-methyl-N-(4-pyridinyl)dithiocarbamate).
Acknowledgements
This review borrows heavily from and updates a review on the same topic published
in Journal of Polymer Science, Polymer Chemistry [1].
Abbreviations
Abbreviations are listed alphabetically by the abbreviated term. In general, abbre-

viations of methacrylates end with ‘MA’, methacrylamides end with ‘MAm’,
acrylates end with an ‘A’. acrylamides end with an ‘Am’ or begin with ‘NA’ (for
N-acryloyl). Except as indicated below the suffix ‘P’ is an abbreviation for ‘poly()’.
Thus, poly(methyl methacrylate) is abbreviated as PMMA.
AA acrylic acid
ACE acenaphthylene
AIBN azobis(isobutyronitrile) [2,2′ -azobis(2-methylproionitrile)]
ACHN 1,1′ -azobis(1-cyclohexanenitrile)
Am acrylamide
AMS α-methylstyrene [prop-1-en-2-ylbenzene]
AN acrylonitrile
BA butyl acrylate
BPO benzoyl peroxide
CEVE 2-chloroethyl vinyl ether
CL ε-caprolactone
CMS 4-(chloromethyl)styrene
CMS chloromethylstyrene
CTFE chlorotrifluoroethylene
Ð molar mass dispersity = ratio of mass average to number average

molar mass [312]
DAAm diacetone acrylamide
DCE 1,2-dichloroethane
DMAEMA 2-(dimethylamino)ethyl methacrylate
E ethylene
EA ethyl acrylate
EDTA ethylenediaminetetraacetic acid
EMA ethyl methacrylate
HA hexyl acrylate
HEVE 2-hydroxyethyl vinyl ether
HOSt 4-hydroxystyrene
HPMAm N-(2-hydroxylpropyl)methacrylamide
iBVE isobutyl vinyl ether
IAM intermediate activated monomer (IAMs include NVC)
Ip isoprene
LA lactide
LAM less activated monomer (LAMs include vinyl monomers such as VAc,
VC, NVP)
Lim limonene
LMA lauryl methacrylate (dodecyl methacrylate)
LPO dodecanoyl peroxide (lauroyl peroxide)
MA methyl acrylate
MADIX macromolecular design by interchange of xanthates
MAM more activated monomer (MAMs include styrenes, (meth)acrylates,
(meth)acrylamides)
MOVE 2-methoxyethyl vinyl ether
NAM N-acryloylacrylamide
NES neopentyl ethenesulfonate
NMP aminoxyl- (nitroxide-)mediated polymerization
NVCL N-vinylcaprolactam
References 595
PEGA (poly(ethylene glycol) monomethyl ether) acrylate
PEGMA (poly(ethylene glycol) monomethyl ether) methacrylate
PTC phase transfer catalyst
PVK phenyl vinyl ketone
RAFT reversible addition-fragmentation chain transfer
SDS sodium dodecyl sulfate
St styrene
TMC trimethylenecarbonate
VAc vinyl acetate
VBz vinyl benzoate
VC vinyl chloride
VF2 vinylidene fluoride
Vim 4-vinylimidazole
VPv vinyl pivalate
2VP 2-vinylypyridine
4VP 4-vinylpyridine
References
.org/10.1002/pola.29199.
1438–1447. https://doi.org/10.1002/pi.5423.
4 Dayter, L.A., Murphy, K.A., and Shipp, D.A. (2013). Aust. J. Chem. 66:
1564–1569. https://doi.org/10.1071/CH13375.
5 Malepu, V., Petruczok, C.D., Tran, T. et al. (2009). RAFT polymerization of
vinyl acetate, styrene and acrylates using N,N-dithiocarbamates. In: Con-
trolled/Living Radical Polymerization: Progress in RAFT, DT, NMP & OMRP,
ACS Symposium Series, vol. 1024 (ed. K. Matyjaszewski), 37–47. Washington,
DC: American Chemical Society https://doi.org/10.1021/bk-2009-1024.ch003.
6 Destarac, M., Charmot, D., Franck, X., and Zard, S.Z. (2000). Macromol. Rapid
Commun. 21: 1035–1039. https://doi.org/10.1002/1521-3927(20001001)21:
15<1035::AID-MARC1035>3.0.CO;2-5.

tion: Materials, Synthesis and Applications (eds. G. Moad and E. Rizzardo),
10 Moad, G. (2022). Trithiocarbonates in RAFT polymerization. In: RAFT
11 Otsu, T. (1956). J. Polym. Sci. 21: 559–561. https://doi.org/10.1002/pol.1956
.120219924.
12 Otsu, T. (1957). J. Polym. Sci. 26: 236–239. https://doi.org/10.1002/pol.1957
.1202611313.
13 Hawker, C.J., Bosman, A.W., and Harth, E. (2001). Chem. Rev. 101: 3661–3688.
https://doi.org/10.1021/cr990119u.
14 Moad, G. and Rizzardo, E. (2016). History of nitroxide-mediated polymeriza-
tion. In: Nitroxide Mediated Polymerization: From Fundamentals to Applications
in Materials (ed. D. Gigmes), 1–44. Cambridge: The Royal Society of Chemistry.
https://doi.org/10.1039/9781782622635-00001.
15 Gigmes, D. (ed.) (2016). Nitroxide Mediated Polymerization: From Fundamen-
tals to Applications in Materials Science. Cambridge: The Royal Society of
Chemistry. https://doi.org/10.1039/9781782622635.
16 Moad, G., Rizzardo, E., and Thang, S.H. (2008). Acc. Chem. Res. 41: 1133–1142.
https://doi.org/10.1021/ar800075n.
17 Otsu, T. and Yoshida, M. (1982). Makromol. Chem. Rapid Commun. 3: 127–132.
https://doi.org/10.1002/marc.1982.030030209.
18 Otsu, T., Yoshida, M., and Kuriyama, A. (1982). Polym. Bull. 7: 45–50. https://
doi.org/10.1007/BF00264156.
19 Otsu, T. (2000). J. Polym. Sci., Part A: Polym. Chem. 38: 2121–2136.
https://doi.org/10.1002/(SICI)1099-0518(20000615)38:12<2121::AID-POLA10>
3.0.CO;2-X.
20 Jenkins, A.D., Jones, R.I., and Moad, G. (2010). Pure Appl. Chem. 82: 483–491.
https://doi.org/10.1351/PAC-REP-08-04-03.
21 Kennedy, J., Chang, V.C., Smith, R., and Iván, B. (1979). Polym. Bull. 1:
575–580. https://doi.org/10.1007/bf00254487.
22 Kennedy, J.P. and Smith, R.A. (1980). J. Polym. Sci., Polym. Chem. Ed. 18:
1523–1537. https://doi.org/10.1002/pol.1980.170180509.
23 Nair, C.P.R. and Clouet, G. (1991). J. Macromol. Sci., Rev. Macromol. Chem.
Phys. C31: 311–340. https://doi.org/10.1080/15321799108021926.
24 Otsu, T., Matsunaga, T., Doi, T., and Matsumoto, A. (1995). Eur. Polym. J. 31:
67–78. https://doi.org/10.1016/0014-3057(94)00122-7.
25 Sebenik, A. (1998). Prog. Polym. Sci. 23: 875–917. https://doi.org/10.1016/S0079-
6700(98)00001-X.
26 Otsu, T. and Matsumoto, A. (1998). Controlled synthesis of polymers using the
iniferter technique: developments in living radical polymerization. In: Microen-
capsulation Microgels Iniferters (eds. S. DiMari, W. Funke, M.A. Haralson,
et al.), 75–137. Berlin, Heidelberg: Springer-Verlag. https://doi.org/10.1007/3-
540-69682-2_3.
References 597
27 Tasdelen, M.A. and Yagci, Y. (2013). Controlled/living radical polymerization

in the presence of iniferters. In: Fundamentals of Controlled/Living Radical
Polymerization (eds. N.V. Tsarevsky and B.S. Sumerlin), 78–111. Cambridge:
The Royal Society of Chemistry. https://doi.org/10.1039/9781849737425-00078.
28 Wang, M., Jiang, X., Luo, Y. et al. (2017). Polym. Chem. 8: 5918–5923. https://
doi.org/10.1039/C7PY01222E.
29 Yasuhide, N., Takeshi, M., Makoto, N. et al. (2005). Curr. Drug Deliv. 2: 53–57.
https://doi.org/10.2174/1567201052772825.
30 Nemoto, Y., Borovkov, A., Zhou, Y.-M. et al. (2009). Bioconjugate Chem. 20:
2293–2299. https://doi.org/10.1021/bc900283h.
31 Nakayama, Y. (2012). Acc. Chem. Res. 45: 994–1004. https://doi.org/10.1021/
ar200220t.
32 Gutiérrez-Climente, R., Gómez-Caballero, A., Halhalli, M. et al. (2016). J. Mol.
Recognit. 29: 106–114. https://doi.org/10.1002/jmr.2443.
33 Bonomi, P., Attieh, M.D., Gonzato, C., and Haupt, K. (2016). Chem. Eur. J. 22:
10150–10154. https://doi.org/10.1002/chem.201600750.
34 Fukui, Y., Sakai, D., and Fujimoto, K. (2016). Colloids Surf., B 148: 503–510.
https://doi.org/10.1016/j.colsurfb.2016.09.032.
35 Lv, Y.-K., Zhang, J., Li, M.-Z. et al. (2016). Anal. Methods 8: 3982–3989. https://
doi.org/10.1039/C6AY00417B.
36 Jing, L., Zhang, Q., Wang, Y., and Wei, T. (2016). Anal. Lett. 49: 1696–1710.
https://doi.org/10.1080/00032719.2015.1119838.
37 Gao, X., Hu, X., Guan, P. et al. (2016). RSC Adv. 6: 110019–110031. https://doi
.org/10.1039/C6RA24518H.
38 Salmi-Mani, H., Ait-Touchente, Z., Lamouri, A. et al. (2016). RSC Adv. 6:
88126–88134. https://doi.org/10.1039/C6RA14713E.
39 Ayadi, H., Mekhalif, T., Salmi, Z. et al. (2016). J. Appl. Polym. Sci. 133 https://
doi.org/10.1002/app.43694.
40 Wang, H., Wu, H., Lee, C.-J. et al. (2016). Langmuir 32: 6544–6550. https://doi
41 Ding, S., Hu, X., Guan, P. et al. (2017). J. Mater. Sci. 52: 8027–8040. https://doi
.org/10.1007/s10853-017-1005-x.
42 Gong, X., Tang, B., Liu, J.J. et al. (2017). Biosens. Bioelectron. 87: 858–864.
https://doi.org/10.1016/j.bios.2016.09.027.
43 Prete, M.C., Dos Santos, D.M., Effting, L., and Tarley, C.R.T. (2019). J. Chem.
Eng. Data https://doi.org/10.1021/acs.jced.8b01010.
44 García-Mutio, D., Gómez-Caballero, A., Gotiandia, A. et al. (2018). Electrochim.
Acta 279: 57–65. https://doi.org/10.1016/j.electacta.2018.05.075.
45 Zoppe, J.O., Ataman, N.C., Mocny, P. et al. (2017). Chem. Rev. 117: 1105–1318.
https://doi.org/10.1021/acs.chemrev.6b00314.
7620–7627. https://doi.org/10.1021/ma0204296.
47 Wang, H., Li, Q., Dai, J. et al. (2013). Macromolecules 46: 2576–2582. https://doi
.org/10.1021/ma400208j.
49 Xu, J., Shanmugam, S., Corrigan, N.A., and Boyer, C. (2015). Catalyst-free vis-
ible light-induced RAFT photopolymerization. In: Controlled Radical Polymer-
ization: Mechanisms, ACS Symposium Series, vol. 1187 (eds. K. Matyjaszewski,
B.S. Sumerlin, N.V. Tsarevsky and J. Chiefari), 247–267. American Chemical
50 Cabannes-Boue, B., Yang, Q., Lalevee, J. et al. (2017). Polym. Chem. 8:
51 Fu, C., Huang, Z., Hawker, C.J. et al. (2017). Polym. Chem. 8: 4637–4643.
52 Aerts, A., Lewis, R.W., Zhou, Y. et al. (2018). Macromol. Rapid. Commun. 39:
54 Figg, C.A., Hickman, J.D., Scheutz, G.M. et al. (2018). Macromolecules 51:
55 Xu, J., Fu, C., Shanmugam, S. et al. (2017). Angew. Chem. Int. Ed. 56:
56 Sivaprakash, S., Jiangtao, X., and Cyrille, B. (2016). Angew. Chem. Int. Ed. 55:
57 Seal, P., Xu, J., De Luca, S. et al. (2019). Adv. Theory Simul. 2: 1900038. https://
doi.org/10.1002/adts.201900038.
59 Liu, S., Cheng, Y., Zhang, H. et al. (2018). Angew. Chem. Int. Ed. 57:
60 Easterling, C.P., Xia, Y., Zhao, J. et al. (2019). ACS Macro Lett. 8: 1461–1466.
61 Mayo, F.R. (1948). J. Am. Chem. Soc. 70: 3689–3694. https://doi.org/10.1021/
ja01191a044.
62 Moad, G. and Moad, C.L. (1996). Macromolecules 29: 7727–7733. https://doi
.org/10.1021/ma960851k.
63 Walling, C. (1948). J. Am. Chem. Soc. 70: 2561–2564. https://doi.org/10.1021/
ja01187a079.
64 Moad, G. and Solomon, D.H. (2006). Chain transfer. In: The Chemistry of Rad-
ical Polymerization, 279–331. Elsevier: Oxford. https://doi.org/10.1016/B978-
008044288-4/50025-X.
2273–2283. https://doi.org/10.1021/ma020883+.
References 599
68 Altarawneh, I.S., Srour, M., and Gomes, V.G. (2007). Polym. Plast. Technol. Eng.
46: 1103–1115. https://doi.org/10.1080/03602550701557928.
69 Zaremskii, M.Y., Olenin, A.V., Garina, Y.S. et al. (1991). Polym. Sci. U.S.S.R. 33:
2036–2045. https://doi.org/10.1016/0032-3950(91)90104-X.
70 Wan, X., Zhang, Z., Zhu, X. et al. (2008). e-Polymers (1): 8. https://doi.org/10
.1515/epoly.2008.8.1.1028.
71 Wan, X., Zhu, X., Zhu, J. et al. (2007). J. Polym. Sci., Part A: Polym. Chem. 45:
72 Dika Manga, J., Tardi, M., Polton, A., and Sigwalt, P. (1998). Polym. Int. 45:
243–254. https://doi.org/10.1002/(SICI)1097-0126(199803)45:3<243::AID-PI913>
3.0.CO;2-U.
4205–4215. https://doi.org/10.1021/ma300616g.
77 Moad, G., Rizzardo, E., and Thang, S.H. (2008). Polymer 49: 1079–1131. https://
doi.org/10.1016/j.polymer.2007.11.020.
45: 5321–5342. https://doi.org/10.1021/ma300410v.
6977–6980. https://doi.org/10.1021/ma9906837.
9262–9271. https://doi.org/10.1021/ma071100t.
81 Zhang, M. and Ray, W.H. (2001). Ind. Eng. Chem. Res. 40: 4336–4352. https://
doi.org/10.1021/ie0009482.
82 ten Brummelhuis, N. and Weck, M. (2014). J. Polym. Sci., Part A: Polym. Chem.
83 Takeshima, H., Satoh, K., and Kamigaito, M. (2017). Macromolecules 50:
84 Miyaji, H., Satoh, K., and Kamigaito, M. (2016). Angew. Chem. Int. Ed. 55:
85 Chiefari, J., Mayadunne, R.T., Moad, G. et al. (2003). (du Pont/CSIRO),
US6642318B1.
86 Schilli, C., Lanzendoerfer, M.G., and Mueller, A.H.E. (2002). Macromolecules
35: 6819–6827. https://doi.org/10.1021/ma0121159.
87 Merican, Z., Schiller, T.L., Hawker, C.J. et al. (2007). Langmuir 23:
10539–10545. https://doi.org/10.1021/la702218b.
88 Schilli, C.M., Muller, A.H.E., Rizzardo, E. et al. (2003). RAFT Polymers:
novel precursors for polymer protein conjugates. In: Advances in Con-
trolled/Living Radical Polymerization, ACS Symposium Series, vol. 854
(ed. K. Matyjaszewski), 603–618. Washington, DC: American Chemical Society

89 Babu, R.P. and Dhamodharan, R. (2008). Polym. Int. 57: 365–371. https://doi
.org/10.1002/pi.2363.
90 Harihara, S.S., Prakash, B.R., and Dhamodharan, R. (2008). Macromolecules 41:
262–265. https://doi.org/10.1021/ma7021056.
91 Skey, J. and O’Reilly, R.K. (2008). Chem. Commun.: 4183–4185. https://doi.org/
10.1039/b804260h.
92 Altarawneh, I., Rawadieh, S., and Gomes, V.G. (2014). Des. Monomers Polym.
17: 430–437. https://doi.org/10.1080/15685551.2013.867566.
93 Hoang, P.H., Nguyen, C.T., Perumal, J., and Kim, D.-P. (2011). Lab Chip 11:
329–335. https://doi.org/10.1039/C0LC00321B.
94 Kumar, S., Roy, S.G., and De, P. (2012). Polym. Chem. 3: 1239–1248. https://doi
.org/10.1039/C2PY00607C.
95 Swift, T., Lapworth, J., Swindells, K. et al. (2016). RSC Adv. 6: 71345–71350.
https://doi.org/10.1039/C6RA13139E.
96 Luo, R. and Sen, A. (2007). Macromolecules 40: 154–156. https://doi.org/10
.1021/ma062341o.
97 Hua, D., Bai, R., Lu, W., and Pan, C. (2004). J. Polym. Sci., Part A: Polym.
doi.org/10.1021/bk-2000-0768.ch020.
99 Ishigaki, Y. and Mori, H. (2018). Polymer 140: 198–207. https://doi.org/10.1016/
j.polymer.2018.02.025.
100 Sun, X.-L., He, W.-D., Li, J. et al. (2008). J. Polym. Sci., Part A: Polym. Chem.
101 El-Newehy, M.H., Elsherbiny, A.S., and Mori, H. (2016). RSC Adv. 6:
72761–72767. https://doi.org/10.1039/C6RA14307E.
102 Mori, H., Sutoh, K., Iwaya, H. et al. (2006). Controlled synthesis of amino
acid-based polymers by reversible addition fragmentation chain transfer
polymerization. In: Controlled/Living Radical Polymerization. From Synthe-
sis to Materials, Controlled/Living Radical Polymerization, vol. 944 (ed. K.
doi.org/10.1021/bk-2006-0944.ch036.
103 Mori, H. and Okabayashi, S. (2009). React. Funct. Polym. 69: 441–449. https://
104 Mori, H., Kato, I., Matsuyama, M., and Endo, T. (2008). Macromolecules 41:
5604–5615. https://doi.org/10.1021/ma800181h.
References 601
107 El-Newehy, M.H., Elsherbiny, A.S., and Mori, H. (2013). J. Appl. Polym. Sci.
127: 4918–4926. https://doi.org/10.1002/app.37611.
108 Koseki, T., Kanto, R., Yonenuma, R. et al. (2020). React. Funct. Polym. 150:
104540. https://doi.org/10.1016/j.reactfunctpolym.2020.104540.
109 Mori, H., Matsuyama, M., Sutoh, K., and Endo, T. (2006). Macromolecules 39:
4351–4360. https://doi.org/10.1021/ma052756u.
110 Shoji, K., Nakayama, M., Koseki, T. et al. (2016). Polymer 97: 20–30. https://doi
.org/10.1016/j.polymer.2016.05.003.
111 Higashi, N., Sekine, D., and Koga, T. (2017). J. Colloid Interface Sci. 500:
112 Yonenuma, R., Ishizuki, A., Nakabayashi, K., and Mori, H. J. Polym. Sci., Part
A: Polym. Chem. https://doi.org/10.1002/pola.29531.
113 Mori, H., Takahashi, E., Ishizuki, A., and Nakabayashi, K. (2013). Macro-
https://doi.org/10.1021/ma0612879.
115 Nakabayashi, K., Tsuda, A., Otani, H., and Mori, H. (2015). React. Funct.
Polym. 86: 52–59. https://doi.org/10.1016/j.reactfunctpolym.2014.11.004.
116 Ishigaki, Y. and Mori, H. (2018). J. Appl. Polym. Sci. 135: 46008 (13pp pp).
118 Maki, Y., Mori, H., and Endo, T. (2007). Macromol. Chem. Phys. 208:
doi.org/10.1021/ma062839q.
120 Nakabayashi, K., Matsumura, A., Abiko, Y., and Mori, H. (2016). Macro-
121 Nakabayashi, K., Umeda, A., Sato, Y., and Mori, H. (2016). Polymer 96: 81–93.
122 Nguyen, C.T., Nghiem, Q.D., Kim, D.-P. et al. (2009). Polymer 50: 5037–5041.
123 Abiko, Y., Matsumura, A., Nakabayashi, K., and Mori, H. (2014). Polymer 55:
124 Mori, H., Ookuma, H., Nakano, S., and Endo, T. (2006). Macromol. Chem.
125 Maki, Y., Mori, H., and Endo, T. (2010). Macromol. Chem. Phys. 211:
doi.org/10.1021/ma801359y.
127 Abiko, Y., Matsumura, A., Nakabayashi, K., and Mori, H. (2015). React. Funct.
Polym. 93: 170–177. https://doi.org/10.1016/j.reactfunctpolym.2015.06.014.
https://doi.org/10.1021/ma0714262.
129 Plenderleith, R., Swift, T., and Rimmer, S. (2014). RSC Adv. 4: 50932–50937.
https://doi.org/10.1039/C4RA10076J.
130 Teratanatorn, P., Hoskins, R., Swift, T. et al. (2017). Biomacromolecules 18:
131 Sarker, P., Shepherd, J., Swindells, K. et al. (2011). Biomacromolecules 12: 1–5.
https://doi.org/10.1021/bm100922j.
132 Carter, S.R., England, R.M., Hunt, B.J., and Rimmer, S. (2007). Macromol.
Biosci. 7: 975–986. https://doi.org/10.1002/mabi.200700108.
133 Ruiwei, G. and Jianhua, Z. (2010). Acta Polym. Sin. 010: 691. https://doi.org/10
.3724/SP.J.1105.2010.09228.
134 Zhu, Y., Xue, Y., Li, X. et al. (2019). Polym. Chem. 10: 2073–2082. https://doi
.org/10.1039/C9PY00120D.
135 Liu, B., Deng, L., Guo, C. et al. (2012). J. Appl. Polym. Sci. 126: 740–748.
136 Zhang, J., Dong, A., Cao, T., and Guo, R. (2008). Eur. Polym. J. 44: 1071–1080.
137 Zhou, D., Zhu, X., Zhu, J. et al. (2007). J. Appl. Polym. Sci. 103: 982–988.
138 Zhou, Y., Zhu, X., Cheng, Z., and Zhu, J. (2007). J. Appl. Polym. Sci. 103:
1769–1775. https://doi.org/10.1002/app.25357.
139 Butte, A., Storti, G., and Morbidelli, M. (2001). Macromolecules 34: 5885–5896.
140 Brown, S.L., Konkolewicz, D., Gray-Weale, A. et al. (2009). Aust. J. Chem. 62:
1533–1536. https://doi.org/10.1071/CH09242.
141 Lalevée, J., Blanchard, N., El-Roz, M. et al. (2008). Macromolecules 41:
2347–2352. https://doi.org/10.1021/ma702406b.
142 Zhou, D., Zhu, X., Zhu, J. et al. (2006). e-Polymers (059): 6. https://doi.org/10
.1515/epoly.2006.6.1.755.
143 Guo, R., Wang, X., Guo, C. et al. (2012). Macromol. Chem. Phys. 213:
144 Guo, R., Yao, Y., Bai, S. et al. (2017). Polym. Chem. 8: 3560–3573. https://doi
.org/10.1039/C7PY00720E.
145 Guo, R., Liu, Y., Zhang, Y. et al. (2013). Macromol. Res. 21: 1127–1137. https://
doi.org/10.1007/s13233-013-1142-2.
146 Guo, R., Mei, P., Zhong, Q. et al. (2015). RSC Adv. 5: 31365–31374. https://doi
.org/10.1039/C5RA02863A.
147 Guo, J., Zhou, Y., Qiu, L. et al. (2013). Polym. Chem. 4: 4004–4009. https://doi
.org/10.1039/C3PY00460K.
149 Ladaviere, C., Dorr, N., and Claverie, J.P. (2001). Macromolecules 34:
5370–5372. https://doi.org/10.1021/ma010358v.
150 Brunhofer-Bolzer, G., Gabriel, M., Studenik, C.R., and Erker, T. (2015). Bioorg.
Med. Chem. 23: 4710–4718. https://doi.org/10.1016/j.bmc.2015.05.049.
References 603
151 Wang, Y.-Q., Ge, Z.-M., Hou, X.-L. et al. (2004). Synthesis 675–678. https://doi
.org/10.1055/s-2004-815972.
152 Soleiman-Beigi, M. and Taherinia, Z. (2014). J. Sulfur Chem. 35: 470–476.
https://doi.org/10.1080/17415993.2014.919296.
153 Chiefari, J., Mayadunne, R.T., Moad, G., et al. (2004). Polymerization process
with living characteristics and polymers made therefrom Polymerization pro-
cess with living characteristics and polymers made therefrom (E.I. Du Pont
De Nemours and Company, Commonwealth Scientific and Industrial Research
Organization), US6747111.
154 Zheng, H., Bai, W., Hu, K. et al. (2008). J. Polym. Sci., Part A: Polym. Chem. 46:
155 Hua, D., Cheng, K., Bai, R. et al. (2004). Polym. Int. 53: 821–823. https://doi
.org/10.1002/pi.1525.
156 Yu, Q., Hua, D., Ge, X. et al. (2006). Polymer 47: 6575–6580. https://doi.org/10
.1016/j.polymer.2006.07.049.
157 Hua, D., Tang, J., Jiang, J., and Zhu, X. (2009). Polymer 50: 5701–5707. https://
doi.org/10.1016/j.polymer.2009.09.074.
158 Hua, D., Tang, J., Jiang, J. et al. (2009). Macromolecules 42: 8697–8701. https://
doi.org/10.1021/ma9018334.
159 Yu, Q., Li, X., Tao, Y., and Cheng, G. (2012). Adv. Mater. Res. 356–360: 74–77.
https://doi.org/10.4028/www.scientific.net/AMR.356-360.74.
160 Yu, Q. and Li, X. (2012). Adv. Mater. Res. (Durnten-Zurich, Switz.) 482–484:
1886–1889. https://doi.org/10.4028/www.scientific.net/AMR.482-484.1886.
162 Li, G., Wang, H., Zheng, H., and Bai, R. (2010). J. Polym. Sci., Part A: Polym.
https://doi.org/10.1039/C8SC01862F.
164 Saubern, S., Nguyen, X., Nguyen, V. et al. (2017). Macromol. React. Eng. 11:
1600065. https://doi.org/10.1002/mren.201600065.
165 Lewis, R.W., Evans, R.A., Malic, N. et al. (2017). Polym. Chem. 8: 3702–3711.
166 Wolpers, A., Bergerbit, C., Ebeling, B. et al. (2019). Angew. Chem. Int. Ed. 58:
167 Rusli, W., Jackson, A.W., and Van Herk, A. (2018). Polymers 10: 774. https://doi
.org/10.3390/polym10070774.
168 Tarafder, M.T.H., Miah, M.A.J., Howlader, M.B.H. et al. (1989). J. Bangladesh
Chem. Soc. 2: 73–75.
169 Lai, J.T. and Shea, R. (2006). J. Polym. Sci., Part A: Polym. Chem. 44:
170 Wan, D., Zhou, Q., Pu, H., and Yang, G. (2008). J. Polym. Sci., Part A: Polym.
171 Shin, S.J., Yu, Y.C., Seo, J.D. et al. (2014). J. Polym. Sci., Part A: Polym. Chem.
172 Uchiyama, M., Satoh, K., and Kamigaito, M. (2015). Angew. Chem. Int. Ed. 54:
173 Guerre, M., Uchiyama, M., Lopez, G. et al. (2018). Polym. Chem. 9: 352–361.
174 Christmann, J., Ibrahim, A., Charlot, V. et al. (2016). ChemPhysChem 17:
175 Foster, J.C., Radzinski, S.C., Lewis, S.E. et al. (2015). Polymer 79: 205–211.
176 Radzinski, S.C., Foster, J.C., and Matson, J.B. (2015). Polym. Chem. 6:
177 Radzinski, S.C., Foster, J.C., Lewis, S.E. et al. (2017). Polym. Chem. 8:
178 Moad, G., Mayadunne, R.T.A., Rizzardo, E. et al. (2003). Kinetics and mech-
anism of RAFT polymerization. In: Advances in Controlled/Living Radical
Polymerization, ACS Symposium Series, vol. 854 (ed. K. Matyjaszewski),
520–535. Washington, DC: American Chemical Society https://doi.org/10
.1021/bk-2003-0854.ch036.
179 Kulkarni, S., Schilli, C., Grin, B. et al. (2006). Biomacromolecules 7: 2736–2741.
https://doi.org/10.1021/bm060186f.
https://doi.org/10.1021/ma2021387.
181 Aoshima, H., Uchiyama, M., Satoh, K., and Kamigaito, M. (2014). Angew.
182 Bergerbit, C., Farías-Mancilla, B., Seiler, L. et al. (2019). Polym. Chem. 10:
183 Ilchev, A., Pfukwa, R., Hlalele, L. et al. (2015). Polym. Chem. 6: 7945–7948.
184 Moad, G., Benaglia, M., Chen, M. et al. (2011). Block copolymer synthesis
through the use of switchable RAFT agents. In: Non-Conventional Functional
Block Copolymers, ACS Symposium Series, vol. 1066 (eds. P. Theato, A.F.M.
Kilbinger and E.B. Coughlin), 81–102. Columbus, OH: American Chemical
Society https://doi.org/10.1021/bk-2011-1066.ch007.
185 Pullan, N., Liu, M., and Topham, P.D. (2013). Polym. Chem. 4: 2272–2277.
https://doi.org/10.1039/c3py21151g.
186 Sugihara, S., Kawamoto, Y., and Maeda, Y. (2016). Macromolecules 49:
187 Hornung, C.H., Guerrero-Sanchez, C., Brasholz, M. et al. (2011). Org. Process
Res. Dev. 15: 593–601. https://doi.org/10.1021/op1003314.
188 Hornung, C.H., Nguyen, X., Kyi, S. et al. (2013). Aust. J. Chem. 66: 192–198.
189 Oliveira, M., Barbosa, B.S., Nele, M., and Pinto, J.C. (2014). Macromol. React.
Eng. 8: 493–502. https://doi.org/10.1002/mren.201300175.
190 Abreu, C.M.R., Maximiano, P., Guliashvili, T. et al. (2016). RSC Adv. 6:
7495–7503. https://doi.org/10.1039/C5RA21975B.
References 605
192 Abreu, C.M.R., Mendonça, P.V., Serra, A.C. et al. (2012). Macromolecules 45:
2200–2208. https://doi.org/10.1021/ma300064j.
193 Sugihara, S., Yoshida, A., Kono, T.-a. et al. (2019). J. Am. Chem. Soc. 141:
194 Olijve, L.L.C., Hendrix, M.M.R.M., and Voets, I.K. (2016). Macromol. Chem.
195 Kwak, Y. and Matyjaszewski, K. (2008). Macromolecules 41: 6627–6635. https://
doi.org/10.1021/ma801231r.
196 Fan, L., Jiang, H., Zhang, L. et al. (2015). RSC Adv. 5: 31657–31663. https://doi
.org/10.1039/C5RA03264D.
197 Zhang, Y., Schröder, K., Kwak, Y. et al. (2013). Macromolecules 46: 5512–5519.
198 Jiang, X., Wu, J., Zhang, L. et al. (2014). Macromol. Rapid Commun. 35:
199 Zhang, W., Zhu, X.L., Cheng, Z.P., and Zhu, J. (2007). J. Appl. Polym. Sci. 106:
230–237.
200 Guillaneuf, Y., Couturier, J.-L., Gigmes, D. et al. (2008). J. Org. Chem. 73:
4728–4731. https://doi.org/10.1021/jo800422a.
doi.org/10.1021/ma100850a.
202 Ishizu, K., Khan, R.A., Ohta, Y., and Furo, M. (2004). J. Polym. Sci., Part A:
203 Bertin, D., Couturier, J.L., Gigmes, D. et al. (2009). Method for prepar-
ing alkoxyamines by photolysis of dithiocarbamates (Arkema France),
WO2006111637A1.
204 Shao, L., Hu, M., Chen, L. et al. (2012). React. Funct. Polym. 72: 407–413.
205 Lubnin, A., O’Malley, K., Hanshumaker, D., and Lai, J. (2010). Eur. Polym. J.
206 Guerre, M., Uchiyama, M., Folgado, E. et al. (2017). ACS Macro Lett. 6:
207 Nomura, N., Shinoda, K., Takasu, A. et al. (2013). J. Polym. Sci., Part A: Polym.
3738–3742. https://doi.org/10.1021/ma9005389.
209 Kumru, B. and Bicak, N. (2015). RSC Adv. 5: 30936–30942. https://doi.org/10
.1039/C5RA02783G.
210 Stace, S.J., Moad, G., Fellows, C.M., and Keddie, D.J. (2015). Polym. Chem. 6:
7119–7126. https://doi.org/10.1039/C5PY01021G.
211 Jiang, K., Han, S., Ma, M. et al. (2020). J. Am. Chem. Soc. 142: 7108–7115.
https://doi.org/10.1021/jacs.0c01016.
212 Skouta, R., Wei, S., and Breslow, R. (2009). J. Am. Chem. Soc. 131:
15604–15605. https://doi.org/10.1021/ja9072589.
6914–6915. https://doi.org/10.1021/ja901955n.
214 Pan, X., Guo, X., Choi, B. et al. (2019). Polym. Chem. 10: 2083–2090. https://doi
.org/10.1039/C9PY00110G.
215 Rajput, F., Colantuoni, A., Bayahya, S. et al. (2018). J. Polym. Sci., Part A:
216 Stace, S.J., Fellows, C.M., Moad, G., and Keddie, D.J. (2018). Macromol. Rapid
Commun. 39: 1800228 (9 pp). https://doi.org/10.1002/marc.201800228.
217 Pan, G., Zu, B., Guo, X. et al. (2009). Polymer 50: 2819–2825. https://doi.org/10
.1016/j.polymer.2009.04.053.
218 Zheng, J., Wang, L., Zeng, X. et al. (2016). ACS Appl. Mater. Interfaces 8:
219 Benaglia, M., Chen, M., Chong, Y.K. et al. (2009). Macromolecules 42:
9384–9386. https://doi.org/10.1021/ma9021086.
6738–6745. https://doi.org/10.1021/ma200760q.
221 Tselepy, A., Schiller, T.L., Harrisson, S. et al. (2018). Macromolecules 51:
222 Kitov, P.I., Kotsuchibashi, Y., Paszkiewicz, E. et al. (2013). Org. Lett. 15:
5190–5193. https://doi.org/10.1021/ol402315n.
223 Palanisamy, A. and Sukhishvili, S.A. (2018). Macromolecules 51: 3467–3476.
224 Guerrero-Sanchez, C., Keddie, D.J., Saubern, S., and Chiefari, J. (2012). ACS
Comb. Sci. 14: 389–394. https://doi.org/10.1021/co300044w.
225 Dong, H., Zhu, Y., Li, Z. et al. (2017). Macromolecules 90: 9295–9306. https://
226 Liu, X., Chen, J.-Q., Zhang, M. et al. (2019). J. Polym. Sci., Part A: Polym.
227 BoronMolecular. RAFT Agents. https://www.boronmolecular.com/polymers/
raft-polymerisation-technology/ (accessed 6 December 2020).
228 Moad, G., Rizzardo, E., and Thang, S.H. (2010). Mater. Matters 5: 2–5.
229 Sigma-Aldrich. RAFT Agents. https://www.sigmaaldrich.com/materials-
science/material-science-products.html?TablePage=103936134 (accessed 6
December 2020).
230 Moad, G., Rizzardo, E., and Thang, S.H. (2011). Strem Chem. 25: 2–10.
231 Strem Chemicals. RAFT Agent. https://www.strem.com/catalog/family/RAFT+
Agent/ (accessed 6 December 2020).
232 An, J., Dai, X., Wu, Z. et al. (2015). Biomacromolecules 16: 2444–2454. https://
doi.org/10.1021/acs.biomac.5b00693.
233 Dai, X., Chen, X., Zhao, Y. et al. (2018). Biomacromolecules 19: 141–149.
234 Mori, H., Sutoh, K., and Endo, T. (2005). Macromolecules 38: 9055–9065.
https://doi.org/10.1021/ma0509558.
235 Hasegawa, U., van der Vlies, A.J., Simeoni, E. et al. (2010). J. Am. Chem. Soc.
132: 18273–18280. https://doi.org/10.1021/ja1075025.
References 607
236 Hasegawa, U. and van der Vlies, A.J. (2015). MedChemComm 6: 273–276.
https://doi.org/10.1039/C4MD00373J.
237 Stadermann, J., Fleischmann, S., Messerschmidt, M. et al. (2009). Macromol.
238 Mao, J., Qi, X., Cao, X. et al. (2011). Chem. Commun. 47: 4228–4230. https://
doi.org/10.1039/C1CC10610D.
239 Mori, H. and Endo, T. (2012). Macromol. Rapid Commun. 33: 1090–1107.
240 Destarac, M., Blidi, I., Coutelier, O. et al. (2012). ACS Symp. Ser. 1100: 259–275.
241 Guinaudeau, A., Mazieres, S., Wilson, D.J., and Destarac, M. (2012). Polym.
Chem. 3: 81–84. https://doi.org/10.1039/C1PY00373A.
242 Haven, J., Hendrikx, M., Danial, M. et al. (2021). Polym. Chem. (to be submit-
ted).
243 Zhang, S., Yin, L., Zhang, W. et al. (2016). Polym. Chem. 7: 2112–2120. https://
doi.org/10.1039/C6PY00012F.
244 Rajendran Prakash, B. and Raghavachari, D. (2012). J. Polym. Sci., Part A:
245 Hu, D. and Zheng, S. (2010). Polymer 51: 6346–6354. https://doi.org/10.1016/j
.polymer.2010.10.047.
246 Xue, X., Zhu, J., Zhang, Z. et al. (2010). Polymer 51: 3083–3090. https://doi.org/
10.1016/j.polymer.2010.04.052.
247 Chen, K., Grant, N., Liang, L. et al. (2010). Macromolecules 43: 9355–9364.
https://doi.org/10.1021/ma101182f.
248 Destarac, M., Bzducha, W., Taton, D. et al. (2002). Macromol. Rapid Commun.
249 Stamenović, M.M., Espeel, P., Camp, W.V., and Du Prez, F.E. (2011). Macro-
molecules 44: 5619–5630. https://doi.org/10.1021/ma200799b.
250 Nagai, A., Yoshii, R., Otsuka, T. et al. (2010). Langmuir 26: 15644–15649.
https://doi.org/10.1021/la102597y.
251 Jana, S. and Parthiban, A. (2011). Macromol. Chem. Phys. 212: 790–798. https://
doi.org/10.1002/macp.201000701.
252 Du, J., Willcock, H., Ieong, N.S., and O’Reilly, R.K. (2011). Aust. J. Chem. 64:
1041–1046. https://doi.org/10.1071/CH11131.
553–556. https://doi.org/10.1021/ol0525617.
254 Oae, S., Yagihara, T., and Okabe, T. (1972). Tetrahedron 28: 3203–3216. https://
doi.org/10.1016/S0040-4020(01)93661-0.
255 Xia, S., Wang, X., Ge, Z.-m. et al. (2009). Tetrahedron 65: 1005–1009. https://doi
.org/10.1016/j.tet.2008.11.084.
256 Thang, S.H., Chong, Y.K., Mayadunne, R.T.A. et al. (1999). Tetrahedron Lett.
40: 2435–2438. https://doi.org/10.1016/S0040-4039(99)00177-X.
257 Bouhadir, G., Legrand, N., Quiclet-Sire, B., and Zard, S.Z. (1999). Tetrahedron
Lett. 40: 277–280. https://doi.org/10.1016/S0040-4039(98)02380-6.
258 Wang, L. and Benicewicz, B.C. (2017). Raft agents and their use in the devel-
opment of polyvinylpyrrolidone grafted nanoparticles (University of South
Carolina), US9732169B2.
259 Sha, Y., Zhu, Q., Wan, Y. et al. (2016). J. Polym. Sci., Part A: Polym. Chem. 54:
260 Moad, G., Chong, Y.K., Rizzardo, E. et al. (2005). Polymer 46: 8458–8468.
40: 4446–4455. https://doi.org/10.1021/ma062919u.
262 Weber, W.G., McLeary, J.B., and Sanderson, R.D. (2006). Tetrahedron Lett. 47:
4771–4774. https://doi.org/10.1016/j.tetlet.2006.04.031.
263 Ramadas, K. and Srinivasan, N. (1995). Synth. Commun. 25: 227–234. https://
doi.org/10.1080/00397919508010811.
264 Wager, C.M., Haddleton, D.M., and Bon, S.A.F. (2004). Eur. Polym. J. 40:
265 Lai, J.T. (2002). Tetrahedron Lett. 43: 1965–1967. https://doi.org/10.1016/S0040-
4039(02)00159-4.
266 Lai, J.T., Filla, D., and Shea, R. (2002). Macromolecules 35: 6754–6756. https://
doi.org/10.1021/ma020362m.
267 Coote, M.L. and Henry, D.J. (2005). Macromolecules 38: 1415–1433. https://doi
.org/10.1021/ma047814a.
studies of RAFT polymerization: methodology, structure-reactivity correla-
tions and kinetic implications. In: Handbook of RAFT Polymerization (ed.
9783527622757.ch2.
270 Charmot, D., Chang, H.T., and Li, Y. (2002). Compounds useful for living-type
free radical polymerization (Symyx Technologies, Inc.), US6482909.
271 Charmot, D., Chang, H.T., and Huefner, P. (2002). Control agents for
living-type free radical polymerization, methods of polymerizing and polymers
with same (Symyx Technologies, Inc.), US6380335.
272 Chang, H.T., Charmot, D., and Li, Y. (2003). Compounds useful for living-type
free radical polymerization (Symyx Technologies, Inc.), US6518448.
273 Charmot, D. and Piotti, M. (2005). Removal of the thiocarbonylthio or thio-
phosphorylthio end group of polymers and further functionalization thereof
(Symyx Technologies, Inc.), US6919409.
274 Benoit, D., Safir, A., Chang, H.T. et al. (2008). Synthesis of photoresist poly-
mers (Symyx Technologies, Inc.), US7399806.
mers (Symyx Technologies, Inc.), US7250475.
276 Blokzijl, W., Carswell, R.J., Charmot, D. et al. (2007). Laundry treatment com-
positions comprising a polymer with a cationic and polydialkylsiloxane moiety
(Unilever Home & Personal Care USA Division of Conopco, Inc.), US7179777.
References 609
278 Uchiyama, M., Satoh, K., and Kamigaito, M. (2022). Cationic RAFT polymer-
279 Moad, G., Rizzardo, E., and Thang San, H. (2013). Fundamentals of RAFT
polymerization. In: Fundamentals of Controlled/Living Radical Polymerization,
RSC Polymer Chemistry Series No. 4 (eds. N.V. Tsarevsky and B.S. Sumerlin),
205–249. Cambridge: Royal Society of Chemistry https://doi.org/10.1039/
9781849737425-00205.
macp.201300562.
281 Krenske, E.H., Izgorodina, E.I., and Coote, M.L. (2006). An ab initio guide to
structure–reactivity trends in reversible addition fragmentation chain transfer
polymerization. In: Controlled/Living Radical Polymerization. From Synthesis
to Materials, ACS Symposium Series, vol. 944 (ed. K. Matyjaszewski), 406–420.
0944.ch028.
283 Ingale, R.P., Jagtap, R.N., and Adivarekar, R.V. (2016). J. Adhes. 92: 236–256.
https://doi.org/10.1080/00218464.2015.1022649.
284 Guo, X., Choi, B., Feng, A., and Thang, S.H. (2018). Macromol. Rapid. Com-
.org/10.1016/j.tet.2016.07.002.
286 Pearson, S., Thomas, C.S., Guerrero-Santos, R., and D’Agosto, F. (2017). Polym.
Chem. 8: 4916–4946. https://doi.org/10.1039/C7PY00344G.
288 Jiang, X., Liu, Y., Ding, M. et al. (2015). Macromol. Chem. Phys. 216:
.org/10.1039/b9py00340a.
290 Moad, G., Rizzardo, E., and Thang, S.H. (2011). Polym. Int. 60: 9–25. https://
doi.org/10.1002/pi.2988.
2033–2036. https://doi.org/10.1021/ma047611m.
293 Charmot, D., Chang, H.T., Wang, W., and Piotti, M. (2006).Cleaving and replac-
ing thio control agent moieties from polymers made by living-type free radical
polymerization (Symyx Technologies, Inc.), US7012119B2.
294 Zhang, W., Yan, Y., Zhu, X. et al. (2010). Macromol. React. Eng. 4: 264–271.
https://doi.org/10.1002/mren.200900056.
copolymers. In: Controlled/Living Radical Polymerization. From Synthesis to
Materials, ACS Symposium Series, vol. 944 (ed. K. Matyjaszewski), 564–577.
0944.ch038.
296 Tong, Y.-Y., Dong, Y.-Q., Du, F.-S., and Li, Z.-C. (2009). J. Polym. Sci., Part A:
298 Zhou, Y., He, J., Li, C. et al. (2011). Macromolecules 44: 8446–8457. https://doi
.org/10.1021/ma201570f.
300 Nair, C.P.R., Clouet, G., and Chaumont, P. (1989). J. Polym. Sci., Part A: Polym.
Chem. 27: 1795–1809. https://doi.org/10.1002/pola.1989.080270601.
https://doi.org/10.1021/ma9804951.
the process of making the same (Henkel), WO2017027557A1.
306 Danielson, A.P., Van Kuren, D.B., Lucius, M.E. et al. (2016). Macromol. Rapid
23: 7221–7226. https://doi.org/10.1002/chem.201701410.
308 Zhang, B., Wang, X., Zhu, A. et al. (2015). Macromolecules 48: 7792–7802.
310 Nothling, M.D., McKenzie, T.G., Reyhani, A., and Qiao, G.G. (2018). Macromol.
Rapid Commun. 39: 1800179. https://doi.org/10.1002/marc.201800179.
311 Wang, X.-H., Wu, M.-X., Jiang, W. et al. (2018). Macromolecules 51: 716–723.
312 Gilbert, R.G., Hess, M., Jenkins, A.D. et al. (2009). Pure Appl. Chem. 81:
351–353. https://doi.org/10.1351/PAC-REC-08-05-02.
611
12
PhotoRAFT Polymerization
Robert Chapman 1,2 , Kenward Jung 3 , and Cyrille Boyer 3
1
The University of Newcastle, Discipline of Chemistry, Callaghan, NSW 2308, Australia
2
UNSW Sydney, School of Chemistry, Centre for Advanced Macromolecular Design (CAMD), Sydney,
NSW 2052, Australia
3
UNSW Sydney, School of Chemical Engineering, Centre for Advanced Macromolecular Design (CAMD) and
the Australian Centre for Nanomedicine (ACN), Sydney, NSW 2052, Australia
12.1 Introduction
Light is a powerful stimulus providing users with the ability to control in real time
when (temporal) and where (spatial) reactions may occur [1, 2]. This powerful
capability comes hand in hand with surprising efficiency that is yet to be fully
harnessed for chemical syntheses. The rekindling of interest in photochemistry in
recent years, which could be attributed to the widespread proliferation of low-cost,
narrow-emission light sources, has resulted in the development of a wide range
of novel polymerization processes regulated by visible light [3]. By utilizing these
less energetic wavelengths, reaction conditions have become even milder, offering
new opportunities, particularly in the arena of bioapplications. Moreover, the
increased spectral real estate available from the broadening of the usable electro-
magnetic spectrum holds the promise of realizing orthogonal reactions using light
alone [4].
In addition to the intrinsic advantages of exerting spatio-temporal control,
reversible addition–fragmentation chain transfer (RAFT) photopolymerizations
have gained several interesting new capabilities. From the re-investigation of
iniferter chemistry under visible light to the application of photoredox catalysis, the
single biggest change is arguably the elimination of hazardous exogenous radical
initiators. This change alone significantly increases the safety and atom efficiency of
RAFT polymerizations. Additionally, the implementation of photoredox catalysis,
when paired with the appropriate co-agents, enables the facile removal of oxygen
in situ, thereby avoiding tedious and potentially costly deoxygenation procedures
(Figure 12.1). This chapter aims to provide a broad overview on the current state of
the art with regard to the use of light to mediate RAFT polymerizations.
612 12 PhotoRAFT Polymerization
O
O O O
O
O
N
Si Si N Zn N N N
N Mg
N O+ N N
N
–
O BF4
S
O
PTH Ir(ppy)3 MPP Pent ZnTPP BChl a
380 nm 460 nm 480 nm 635 nm 655 nm 850 nm
UV Visible IR
N
O O HN
O N CI N
O S S
O S CN N AI N
O
P Br Br N OH N N
10 S S
O O O HN
HO N
O OH
Br Br
TPO EY DTC CDTPA OBN AIPc

405 nm 460 nm 520 nm 530 nm 635 nm 850 nm
Figure 12.1 Representative chromophores used in light-regulated polymerizations. From

left to right, top then bottom, PTH, 10-phenylphenothiazine; Ir(ppy)3 ,
tris[2-phenylpyridinato-C2 ,N]iridium(III); MPP, 2,4,6-tris(p-methoxyphenyl)pyrylium
tetrafluoroborate; Pent, 6,13-bis(triisopropylsilylethynyl)pentacene; ZnTPP,
5,10,15,20-tetraphenyl-21H,23H-porphine zinc; BChl a, bacteriochlorophyll a; TPO,
(2,4,6-trimethylbenzoyl)diphenylphosphine oxide; EY, eosin Y; DTC, methyl
2-((9H-carbozole-9-carbonothioyl)thio)-2-methylpropanoate; CDTPA,
4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid; OBN, oil blue N; AlPc,
aluminium phthalocyanine. Source: Reproduced with permission from Corrigan et al.
12.2 Photoinitiation
Light can be used to drive RAFT polymerizations by the creation of a radical prop-
agating centre through energy transfer to one of the chemical components in the
system. The simplest mechanism involves creating the radical propagating centre
from an initiator, which is external to the RAFT process. This is known as pho-
toinitiation. Once the propagating centre is generated, the polymerization can be
controlled by a chain transfer (or RAFT) agent, which is not in itself photo-active.
Alternatively, the propagating centre can be formed from the RAFT agent itself, via
cleavage of the sulfur–carbon bond between the thiocarbonylthio group and the ‘R’
group of the chain transfer agent. This second mechanism has come to be known as
photoiniferter polymerization, because in these systems the same chemical species
acts as both the initiator of polymerization and a chain transfer agent (ini-fer) [5–7].
Photoinitiators have been adopted into RAFT systems from their widespread
application in conventional free radical polymerizations, particularly in the field
of 3D printing, where rapid polymerizations that can be triggered on demand at
room temperature are desirable. Common photoinitiators can be based either on
homolytic cleavage of an aromatic carbonyl compound such as benzoin ethers,
benzoin ketals, aceto-phenones, or acyl-phosphine oxides (type I photoinitiators) or
through bimolecular hydrogen abstraction of an aromatic ketone, benzophenone,
or quinone (type II photoinitiators). Type II systems require a second species,
typically an amine, to donate a proton to the excited photoinitiator. Most early type I
photoinitiators were only UV active, but the two-component type II systems enabled
longer wavelengths in the visible region. Addition of a third component, typically
an iodonium salt, to the photoinitiator and amine greatly enhances the speed of
initiation [8, 9]. While the precise mechanisms that drive the rate enhancement
are still debated in the literature, there is strong evidence that the iodonium salt
is able to both oxidize dye radicals back to their ground state for reinitiation and
participate itself in photolysis to generate a phenyl-based radical [9–11]. Regardless
of the mechanism, three-component (type III) systems such as these do offer a great
deal of versatility in the choice of dye, and therefore in the wavelengths of light
that can be used. Dyes based on various ketone xanthene, thioxanthene, xanthone,
thioxanthone, coumarin, ketocoumarin, thiazine, and merocyanine derivatives
have been used in type III systems [8, 9].
Mechanistically, RAFT polymerization initiated by a photoinitiator is no different
to one initiated by a thermal free radical initiator such as AIBN. The propagating cen-
tre is rapidly transferred across the chain transfer agent by conventional processes
and is terminated by combination or disproportionation. As in any RAFT process,
for a high degree of control it is important to ensure that the concentration of rad-
icals is low relative to the chain transfer agent, and this can be tuned both by the
intensity of the light and the concentration of the photoinitiator.
12.3 Photoiniferter Polymerizations
In contrast to photoinitiated systems, photoiniferter polymerizations generate a

radical from the RAFT agent directly, through cleavage of the sulfur–carbon bond
between the thioester and the ‘R’ group [12]. This can be done via direct energy
transfer, in which the light causes photolysis of the bond without any additional
sensitizer or photocatalyst (PC) (the so-called ‘catalyst-free’ photoiniferter systems;
see Scheme 12.1a) [12–15]. Although typically performed using high-intensity UV,
this approach has recently been reported in certain RAFT systems with visible light.
Regardless of the wavelength used, such a system will only undergo propagation
in the presence of light and will cease the moment the light is switched off. Alter-
natively, photoiniferter polymerization can be performed using a photocatalyst
(PC) to transfer either an electron or energy to the chain transfer agent via an
oxidative or reductive quenching cycle, promoting the photolysis of the RAFT agent
(Scheme 12.1b,c). In the oxidative cycle (Scheme 12.1b), the excited photocatalyst
PC* is oxidized to PC+⋅ as the chain transfer agent is reduced to (A–B)−⋅ . The PC+⋅ is
returned to the ground state by re-oxidizing the chain transfer agent (A–B)−⋅ back to
(A–B). In the reductive cycle (Scheme 12.1c), an electron donor (D) is added to the
system, which transfers an electron to the exited photocatalyst (PC* ) to form PC−⋅ ,
which then reduces the chain transfer agent to (A–B)−⋅ as it returns to its ground
state (PC). Both metal-based and non-metallic photocatalysts have been explored
for these processes and will be discussed in detail below.
A-Pn-B
hν PET
A-Pn-B
PC*
PC–
[A-Pn-B]–• B–+M P•n-A
M D
P•n-A+B• [A-Pn-B]* A-Pn-B hν PC+•+ [A-Pn-B]–• B–+M P•n-A
PET
D+•
PC*
PC
PC
(a) (b) PC = Photocatalyst (c) D = Electron donor
Scheme 12.1 Photomediated controlled/radical polymerization (photo-CRP). (a) Energy

transfer to induce bond cleavage, (b) photoredox-catalyzed electron transfer through an
oxidative cycle, and (c) photoredox-catalyzed electron transfer through a reductive cycle.
Source: Reproduced with permission from Shanmugam et al. [13]. Copyright 2017, John
Wiley & Sons.
12.3.1 Catalyst-Free Photoiniferter

There are a number of examples of dithiobenzoate [16], trithiocarbonate [17–23],
dithiocarbamate [24–26], xanthate [27, 28], and disulfide [29] chain transfer agents
that can be directly photolyzed using high-intensity UV light. This is possible due
to the strong absorbance of the thiocarbonylthio group in the 250–350 nm region.
Unfortunately, prolonged exposure to this high-energy source can lead to degra-
dation of the chain transfer agent and undesirable side reactions, resulting in loss
of control during the polymerization [16, 30–33]. The direct photolysis of trithio-
carbonate RAFT agents using visible light was first reported by the Boyer group
in 2015, who took advantage of a small amount of absorption in the spectrum of
trithiocarbonates at 400–500 nm, corresponding to the spin-forbidden n to 𝜋* tran-
sition [34]. Because the energy of the light is lower at this wavelength, less damage
to the RAFT agent and fewer side reactions were observed, leading to significantly
better control throughout the polymerization. In their original study, four different
RAFT agents, 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid
(CDTPA), 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT),
4-cyanopentanoic acid dithiobenzoate (CPADB), and 2-(n-butyltrithiocarbonate)
propionic acid (BTPA) (Figure 12.2), were employed in the polymerization of methyl
0.15 CDTPA
S CN
432 nm C12H25
433 nm S S CO2H
513 nm
449 nm
Intensity (a.u)
0.10 CPADB S CN
S CO2H
0.05
DDMAT
S
C12H25
S S CO2H
0.00 BTPA S
400 450 500 550 600 650 700 C4H9
S S CO2H
Wavelength (nm)
Figure 12.2 Absorption profiles of different RAFT agents in the visible spectrum. Source:
Adapted with permission from Xu et al. [34]. Copyright 2015, American Chemical Society.
acrylate (MA) and MMA under blue (𝜆max = 461 nm), green (𝜆max = 530 nm), and
red (𝜆max = 635 nm) irradiation.
Both MA and MMA polymerizations were able to proceed under blue light using
CDTPA and DDMAT, albeit after long inhibition periods. The polymerization
kinetics showed a gradual increase in the concentration of the propagating radical
with time, indicating that the photolysis of the carbon–sulfur bond is quite slow
[34]. The long inhibition periods were presumed to be due to the time taken to
establish the initial RAFT equilibrium, although later studies suggest that these are
more likely due to the consumption of oxygen or other impurities in the system
[35, 36]. The stability of the carbon–sulfur bond in the RAFT agent and in the
macroRAFT agent (after addition of the first few monomer units) is crucial to the
success of this approach. If the stability is too high, then polymerization will not
proceed. For this reason, under green light irradiation (which has a lower energy
than the blue light) only the MMA polymerizations with CDTPA, and not with
DDMAT, were able to proceed due to the lower carbon–sulfur bond dissociation
energy in CDTPA. Similarly, no conversion was observed in MA polymerizations
conducted under green light, due to the higher stability of the carbon–sulfur
bond in the MA macroRAFT agent after the first monomer insertion than in the
MMA analogue. No polymerization was observed in any of the examples under
red light, due to its low energy and the lack of any overlap of this wavelength
light with the RAFT agent absorption spectra. The approach is reasonably indis-
criminate to solvent or monomer functionality, and the polymerization of a range
of methacrylates including glycidyl methacrylate (GMA), dimethylaminoethyl
methacrylate (DMAEMA), and 2-hydroxyethyl methacrylate (HEMA) in solvents
such as N,N-dimethylformamide (DMF), acetonitrile (MeCN), dioxane, and toluene
has been shown for CDTPA under blue or green light [34]. The degradation of a
similar set of trithiocarbonate RAFT agents under blue light (𝜆max = 460 nm) was
studied in closer detail by Qiao and coworkers, who followed the 𝜋 to 𝜋* transition
of the thiocarbonyl at 305 nm during photolysis (Figure 12.3) [37]. RAFT agents
with low fragmentation rates, in which the leaving ‘R’ group forms a shorter lived
primary or secondary radical, were found to rapidly recombine. By contrast, RAFT
agents with a tertiary R group and higher rates of fragmentation degraded in
the UV–vis experiment. In the presence of monomer, photolysis of these tertiary
RAFT agents can lead to a successful RAFT polymerization. The approach is not
restricted to methacrylates, and Xiao and coworkers have shown that blue light
irradiation of DDMAT with no other photocatalysts can be used to polymerize
2-vinylpyridine in solvents such as ethanol, acetic ether, acetone, methanol, and
dimethyl sulfoxide (DMSO) [38]. Qiao and coworkers have extended the concept
to polymerize acrylates and acrylamides including MA, 2-hydroxyethyl acrylate
(HEA), oligo(ethyleneglycol) acrylate (OEGA), tert-butyl acrylate (tBA), and
N-isopropyl acrylamide (NIPAAm) using blue light irradiation of trithiocarbonate
RAFT agents [39, 40].
The absorption of the RAFT agent at 400–500 nm can be enhanced by the
introduction of N-carbazole onto the Z group of the RAFT agent, as shown recently
by Poly and coworkers (Figure 12.4a) [41]. This leads to significantly improved
S S
HO HO
TTC-1: S S 3 TTC-3: S S 11
O O
2.0 2.0
0
3h
6h 0
1.45 9h 1.45 3h
No change 6h
12 h
15 h 9h
12 h
Abs.
Abs.
1.0 1.0 15 h
0.5 0.5
0.0 0.0
300 350 400 450 300 350 400 450
(a) Wavelength (nm) (b) Wavelength (nm)
CN S S
TTC-4: HO
S S 11
TTC-6: S S 11
1.2 O 1.6
0 1.4 0
1.0 3h No change 3h
6h 1.2 6h
9h 9h
0.8 12 h 12 h
15 h
1.0
15 h
Abs.
Abs.
0.6 0.8
0.4 0.6
0.4
0.2
0.2
0.0 0.0
(c) 300 350 400 450 (d) 300 350 400 450
(A) Wavelength (nm) Wavelength (nm)
Fragmentation rates
CH3 CH3 H CH3 H H CH3 H H H
R: CN Ph Ph COOR´ CN Ph CH3 CN COOR´ Ph
CH3 CH3 CN CH3 CH3 CH3 CH3 H CH3 H
Photolytic degradation observed Degradation

not observed
(B)
Figure 12.3 UV–vis experiment for degradation of thiocarbonylthio compounds (TTC)

upon continuous irradiation (A) and fragmentation rates of RAFT agents (B). Source:
Reproduced with permission from McKenzie et al. [37]. Copyright 2016, Royal Society of
Chemistry.
kinetics and control over the photoiniferter polymerization in the visible region
without the need for any photocatalyst. While they only showed the success of this
approach on butyl acrylate, it could likely be extended to less active monomers
such as methacrylates and styrenics. Zhu and coworkers have shown similar results
using a xanthate ethyl 2-((phenoxycarbonothioyl)thio)propanoate, PXEP), under
purple led emission (𝜆max = 400 nm) for polymerization of butyl acrylate [42],
and with a napthalate-bearing RAFT agent (2-cyanoprop-2-yl-1-dithionaphthalate,
CPDN) for polymerization of MMA, MA, VAc, and NIPAAm under sunlight
(see Figure 12.4b,c) [43]. Oxygen tolerance was achieved in this second system
by the introduction of a Zn0.64 Fe2.36 O4 semiconductor, which could be removed
magnetically after polymerization.
S S S
O CN
N S O
O S S
O O
(a) DTC (b) PXEP (c) CPDN
Figure 12.4 Structures of some visible light catalyst-free photoiniferter RAFT agents.
(a) DTC [41], (b) PXEP [42], and (c) CPDN [43].
12.3.2 Photoredox Catalysis

The use of photoredox catalysis to drive RAFT polymerization, also known as pho-
toinduced electron/energy transfer (PET)–RAFT polymerization, follows a similar
iniferter mechanism to the catalyst-free approaches, through the formation of radi-
cals from the R group of the RAFT agent [34, 44]. However, in a photoredox catalysis
the processes of absorption (by the catalyst) and activation (of the RAFT agent) are
decoupled. Because photoredox catalysts possess superior photophysical character-
istics to the RAFT agent, more efficient RAFT activation yielding better control over
the polymerization is possible [45]. Furthermore, judicious selection of the catalyst
provides an avenue to extend the activation wavelength further away from the UV,
which not only provides milder reaction conditions but also affords opportunities
to incorporate latent chromophores, which would have been inevitably activated at
more energetic wavelengths [46, 47]. Because many photoredox catalysts also gen-
erate singlet oxygen, addition of a singlet oxygen quencher to the reaction can afford
the convenience of an oxygen-tolerant process [48].
An interesting discovery in the implementation of various photoredox catalysts
for PET–RAFT polymerization has been the apparent existence of RAFT agent
selectivity, as summarized in Table 12.1. The transition metal photoredox cat-
alyst fac-Ir(ppy)3 is capable of activating trithiocarbonates, dithiobenzoates,
and xanthates. At the other end of the spectrum, the metalloporphyrin,
5,10,15,20-tetraphenyl-21H,23H-porphine zinc (ZnTPP), has presented high
specificity towards trithiocarbonates, with poor or no activation of dithiobenzoates
and xanthates, respectively [49]. This discovery, in tandem with the specificity
of Pheophorbide a for a dithiobenzoate RAFT agent, enabled the preparation of
complex architectures, which is not possible using conventional RAFT approaches
[50]. While more instances of selectivity may exist, the narrow focus of many studies
leads this to be an underexplored aspect of PET–RAFT polymerization.
The ease of implementation aided by the availability of light sources has fuelled
the continued interest in the PET–RAFT process and new species are consistently
added to the growing list of compatible photocatalysts. Just as the seminal work
reported the implementation of fac-Ir(ppy)3 , which was first demonstrated for
visible light atom transfer radical polymerization (ATRP), phenothiazine and
phenazine organophotocatalysts have also been demonstrated as compatible with
the PET–RAFT process [51–53]. Heterogeneous catalysis of the PET–RAFT pro-
cesses appears to be increasing in frequency, attributable to the potential for facile
recycling in comparison to homogeneous photocatalysts [54–59]. This section aims
Table 12.1 RAFT agent compatibility of representative photoredox catalysts for

PET–RAFT polymerization.
RAFT agent compatibility
Photoredox catalyst Trithiocarbonate Dithiobenzoate Xanthate
fac-Ir(ppy)3 a) ✓✓✓ ✓✓✓ ✓✓✓

Ru(bpy)3 Cl2 b) ✓✓✓ ✓✓✓ ✘
Eosin Yc) ✓✓✓ ✓ ✘
ZnTPPd) ✓✓✓ ✘ ✘
✓✓✓: Excellent activation; ✓: Poor activation; ✘: Inability to activate.
a) Tris[2-phenylpyridinato-C2 ,N]iridium(III).
b) Tris(bipyridine)ruthenium(II) chloride.
c) 2′ ,4′ ,5′ ,7′ -Tetrabromofluorescein.
d) 5,10,15,20-Tetraphenyl-21H,23H-porphine zinc.
to provide an overview of the major families of photoredox catalysts compatible

with the PET–RAFT process with insight into their characteristic properties and
capabilities.
12.3.2.1 PET–RAFT with Ir/Ru

Inspired by the work of Hawker and Fors [60], the Boyer group introduced the
concept of PET–RAFT polymerization in 2014, using either fac-Ir(ppy)3 or the
water-soluble Ru(bpy)3 Cl2 as photocatalysts to activate RAFT polymerizations
[45, 61–63]. These catalysts were proposed to operate via an oxidative reduction
cycle (Scheme 12.1b). When excited under blue light irradiation (𝜆max = 460 nm) to
either Ir(III)* or Ru(III)* , both catalysts were able to reduce thiocarbonylthio RAFT
agents via electron transfer, cleaving the carbon–sulfur bond to produce the radical
leaving group (Pn ⋅ ) and either Ir(IV) or Ru(IV) (Scheme 12.2a). The propagating
centre can be deactivated back to the initial state by returning the electron to
the Ir(IV) or Ru(IV) species. More recent studies suggest that an energy transfer
process mediated by Dexter electron exchange was energetically more favourable
when compared to the electron transfer mechanism (Scheme 12.2b) [65, 66]. The
Ir(ppy)3 -catalyzed system was typified by the combination of fast rates and excellent
control, which enable the synthesis of high molecular weight polymers of up to
2 × 106 Da, and multiblock copolymers (up to 10 blocks) by repeated chain extension
reactions [45]. Furthermore, Ir(ppy)3 was demonstrated to be compatible with the
Lewis acid yttrium(III) trifluoromethanesulfonate (Y(OTf)3 ) to exert stereotactic
control over the polymerization without compromising the livingness [67]. High
degrees of isotacticity (>80%) was afforded by the complexation of Y(OTf)3 with
N,N-dimethylacrylamide in mixtures of methanol and toluene.
Although similar in catalytic activity, Ru(bpy)3 Cl2 presents additional advantages
of lower cost and a broader solubility range. Arising from its water solubility,
Ru(bpy)3 Cl2 provides well-controlled aqueous polymerizations, including the
Electron
transfer
PC*
RAFT process
S S
S Visible S Pn • + + Pm•
light PC+/– Pm S Z Pn S Z
Pn S Z S Z
M M
PC
(a)
Energy
transfer
PC*
RAFT process
S S
S Visible S Pn• + + Pm•
•
light Pm S Z Pn S Z
Pn S Z S Z
M M
PC
(b)
Scheme 12.2 Proposed mechanisms for photoinduced electron/energy transfer–reversible

addition–fragmentation chain transfer (PET–RAFT) polymerization in the presence of
photocatalyst: (a) electron transfer and (b) energy transfer mechanism. PC, photocatalyst.
Source: Reproduced with permission from Corrigan et al. [64]. Copyright 2016, Royal Society
of Chemistry.
ability to ‘graft-from’ bovine serum albumin with almost complete preservation of

the esterase activity [63]. Notably, these early studies revealed the interesting and
highly advantageous capability to perform polymerizations in the presence of air
[45, 62]. Polymerizations mediated by Ir(ppy)3 and Ru(bpy)3 Cl2 in the presence
of air differed from deoxygenated experiments only by the presence of an initial
induction period wherein it was proposed that ground-state oxygen (O2 ) was con-
verted to superoxide (O2 ⋅− ). In hindsight, the oxygen-tolerant capabilities of these
photocatalysts likely stems from the photosensitized conversion of ground-state
oxygen to singlet oxygen (1 O2 ) and subsequent trapping by the solvent DMSO [68].
12.3.2.2 PET–RAFT with Porphyrins

Following the successful implementation of the transition metal photoredox
catalysts, Ir(ppy)3 and Ru(bpy)3 Cl2 , a more economic species capable of operating
under longer wavelengths was sought. Inspired by the photosynthetic capabilities
of plants, chlorophyll was investigated for its ability to regulate the PET–RAFT
process. Chlorophyll a (Chl a) extracted from spinach leaves was demonstrated as a
capable photocatalyst enabling controlled polymerizations of (meth)acrylates and
(meth)acrylamides under blue (𝜆 = 430 nm) and red (𝜆 = 665 nm) lights [69]. The
crude extract of Chl a was also demonstrated as an equally capable photocatalyst
[70]. Except for a longer induction period in comparison to the purified Chl a,
the crude extract provided similarly excellent control over the polymerization,
with the additional advantage of degradation under prolonged light exposure.
Further extension of the activation wavelength was achieved through the use of
Bacteriochlorophyll a (Bachl a) [71]. Extracted from bacteria living in deep sea
vents, the far-red (𝜆 = 780 nm) and near-infrared (NIR) (𝜆 = 850 nm) absorptions
of Bachl a provided photo-regulated polymerizations at unprecedented wave-
lengths. Furthermore, the enhanced penetrative capabilities of NIR light enabled
polymerizations to proceed through translucent paper barriers.
Upon identification of chlorophyll as a photocatalyst capable of regulating the
PET–RAFT process, studies were initiated into the implementation of synthetic
metalloporphyrins. From an initial screening of Zn, Ni, Co, and Fe(III) metallated
tetraphenylporphyrins (TPPs), only ZnTPP was capable of activating trithio-
carbonate RAFT agents [49]. Critically, the broad absorption spectra of ZnTPP
enables polymerization under wavelengths that span from blue (𝜆 = 460 nm) to red
(𝜆 = 635 nm), with the highest rates occurring under yellow (𝜆 = 570 nm) light. In
comparison to the abovementioned chlorophyll photocatalysts, the significantly
superior photostability of ZnTPP, coupled with their superior singlet oxygen
generation, permits polymerizations under open air conditions (Scheme 12.3).
Oxygen tolerance in PET–RAFT is facilitated by the photosensitized for-
mation of 1 O2 , which can be subsequently trapped by the solvent, DMSO
(Scheme 12.3), or other singlet oxygen quenchers such as ascorbic acid, limonene,
or 9,10-dimethylanthracene [48, 72]. The ability to eliminate oxygen in this way
has enabled the relatively straightforward implementation of PET–RAFT in flow
[68]. Flow systems not only provide enhanced light penetration due to narrower
optical path lengths but also provide an avenue to facile scale up with the additional
capability of tailoring molecular weight distributions [73, 74].
3Σ
TTA 2 DMSO
1Δ 2 DMSO2
PET
ZnTPP*
RAFT process
S S
S Visible S Pn• + + Pm•
+
light ZnTPP /– Pm S Z Pn S Z
Pn S Z S Z
M M
ZnTPP
Scheme 12.3 Proposed mechanism for ZnTPP-mediated PET–RAFT polymerization in the

presence of oxygen. 3 Σ, ground state oxygen; 1 Δ, singlet oxygen; TTA, triplet–triplet
annihilation; DMSO, dimethyl sulfoxide; DMSO2 , dimethyl sulfone. Source: Reproduced with
permission from Corrigan et al. [68]. Copyright 2016, American Chemical Society.
As one of the most widely studied macrocycles, porphyrins as a class of

photocatalysts possess abundant avenues to vary their photophysical charac-
teristics. A donor–acceptor strategy was used to overcome the poor activation
of PET–RAFT polymerization in the presence of metal-free TPP [15]. By con-
jugating a RAFT agent via the Z-group functionality to a mono-hydroxylate
TPP, significantly faster polymerizations, in comparison to the use of free TPP,
were observed under green (𝜆 = 530 nm) and red (𝜆 = 635 nm) lights. Aqueous
polymerizations using a water-soluble zinc porphyrin have also been reported.
Zn(II) meso-tetra(4-sulfonatophenyl) porphyrin (ZnTPPS4− ) was shown to provide
well-controlled aqueous polymerizations under red (𝜆 = 635 nm) light at pH 8.6
[75]. However, with decreasing pH, the rate was observed to slow down, with
polymerization being suppressed at pH ∼ 3. This capability was used to demonstrate
a dual-gated activation system wherein polymerization could be reversibly paused
by turning off the light or acidifying the reaction mixture. Conversely, reactivation of
the polymerization required both resumption of irradiation and pH ∼ 7–8. Aqueous
PET–RAFT polymerizations utilizing ZnTPPS4− could also be made oxygen tolerant
via the addition of ascorbic acid as a singlet oxygen quencher [76].
More recently, the Boyer group reported a peculiar porphyrin photocatalyst, which
possessed the property of only facilitating polymerization in the presence of oxy-
gen [77]. Zinc(II) (2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetraphenylporphyrin)
(ZnOETPP), by virtue of its dense functionalization, adopts a distorted con-
formation, enabling the absorption of lower energy wavelengths in the far-red
(𝜆 = 685 nm) region. Surprisingly, polymerization only proceeds in the presence of
a tertiary amine species, such as triethylamine, and oxygen; polymerization was
suppressed in inert gases such as nitrogen or carbon dioxide. Conversely, in the
presence of pure oxygen, as opposed to air, the polymerization rate was observed
to accelerate. This capability was used to demonstrate a gas-gated polymeriza-
tion wherein the (de)activation could be readily switched by bubbling with the
appropriate gas (Figure 12.5).
As synthetic analogues of porphyrins, phthalocyanines are another class of
macrocycles that have been widely studied for their photoactive properties. In
addition to their more straightforward synthesis in comparison to porphyrins,
phthalocyanines are attractive for their strongly absorbing Q-band peak in the
far-red (𝜆 > 650 nm) region. However, due to their difficulty in forming 𝜋-cation
radicals compared to porphyrins, phthalocyanines are unable to directly reduce
the RAFT agent for PET–RAFT polymerization. Nevertheless, phthalocyanines
are attractive chromophores for enabling polymerizations mediated by NIR
wavelengths.
In an initial study, aluminium phthalocyanine (AlPc) was found to facilitate
polymerizations in the presence of the solvent N-methyl-2-pyrrolidone under red
and NIR (𝜆 = 780 and 850 nm) lights [78]. Radical generation was proposed to
occur via oxidation of axially ligated solvent molecules, which then propagated
under RAFT control. The activation of peroxides to generate radicals was recently
demonstrated to facilitate faster polymerizations under far-red (𝜆 = 680 nm) and
NIR (𝜆 = 780 and 850 nm) lights using AlPc and aluminium napthalocyanine
2.0 2.0
O2 Air CO2 Air
Air
1.5 N2 1.5
In ([M]0/[M]t)
In ([M]0/[M]t)
CO2
1.0 1.0
0.5 0.5
0.0 0.0
0 1 2 3 4 5 6 0 1 2 3 4 5 6 7
(a) Time (h) (b) Time (h)
2.0 2.0
Air N2 Air Air N2 Air
1.5 1.5
In ([M]0/[M]t)
In ([M]0/[M]t)
1.0 1.0
0.5 0.5
0.0 0.0
0 1 2 3 4 5 6 7 0 2 4 6 8 10 12 14
(c) Time (h) (d) Time (h)
Figure 12.5 Gas-controlled temporal control of ZnOETPP-mediated PET–RAFT

polymerization of methyl acrylate in DMSO. (a) Plot of ln([M]0 /[M]t ) in pure O2 , Air, N2 , and
CO2 ; ON/OFF control induced by injecting (b) CO2 or (c) N2 ; (d) demonstration of dual-gated
temporal control induced by both injecting N2 and switching the light ON/OFF. Source:
Reproduced with permission from Zhang et al. [77]. Copyright 2019, John Wiley & Sons.
(AlNc) respectively [79]. Critically, the efficiency of this initiation system facilitated
polymerizations through thick barriers such as paper (0.2 mm), chicken skin
(1.0 mm), and pig skin (15.0 mm). Furthermore, owing to their narrow absorptions,
these phthalocyanines could be combined with other photocatalysts possessing
complementary absorptions to enable more efficient utilization of broadband
emissions, such as sunlight, for concurrent macromolecule and organic synthesis
in segregated vessels (Figure 12.6).
12.3.2.3 Metal-Free Photocatalysts

Since the inception of the PET–RAFT process, a major research focus has been the
discovery and implementation of metal-free photocatalysts. Although undoubtedly
effective, the high cost of transition metal catalysts, together with their potential
toxicity, limits their wide-scale adoption or commercialization. To this end, a variety
of organo-photocatalysts, including 10-phenylphenothiazine (PTH) [51, 52, 80],
N,N-diaryl dihydrophenazines [53], bismuth oxide (Bi2 O3 ) [58], zinc oxide (ZnO)
[57], graphitic carbon nitride (g-C3 N4 ) [54, 81], and carbon dots [55] have been
successfully reported to mediate the PET–RAFT process. Most works pertaining to
Figure 12.6 (a) Scheme

depicting layered
photocatalysts in the order
(top to bottom) of fac-Ir(ppy)3 AM 1.5G
(𝜆max = 390 nm), eosin Y
(𝜆max = 540 nm), AlPc
Ir(ppy)3
(𝜆max = 678 nm), and AlNc
(𝜆max = 783 nm) irradiated by
simulated sunlight (AM 1.5G). EY
(b) Spectral comparison of
broadband solar emission (AM AIPc
1.5G) and the normalized
absorptions of the layered AINc
photocatalysts. (c) Comparison
of layered
(a)
photopolymerization kinetics 0
mediated simultaneously
I (W m–2 nm–1)
under a broadband solar
emission (AM 1.5G) by
different photocatalysts. 1
Source: Reproduced with
permission from Wu et al.
[79]. Copyright 2020, John
Wiley & Sons. 1.00 2
Ir(ppy)3
Normalized ε
0.75
EY
0.50 AIPc
AINc
0.25
0.00
400 500 600 700 800 900 1000
(b) Wavelength (nm)
1.5
Ir(ppy)3
EY
1.0 AIPc
In ([M0]/[Mt])
AINc
0.5
0.0
0 10 20 30 40
(c) Time (min)
metal-free PET–RAFT polymerizations have revolved around the use of xanthene

dyes, which are widely accessible and possess strong absorptions that extend further
into the visible spectrum in comparison to the aforementioned catalysts.
Of the xanthene dyes, Eosin Y (EY) has undoubtedly received the most attention
with regard to facilitating PET–RAFT polymerization under metal-free conditions
3Σ 1Δ DMSO
TTA DMSO2
S
HO
PET S S
PC* O
BTPA
S S S
S
PC•+ Pn• + Pm–S Z Pn–S Z + Pm•
Pn S Z hν
Z S
M RAFT M O N
PC
DMAm
(a) (c)
I I Br Br I I Br Br
Na+– Na+– O O
Na+–O O O Na+ –O O O O O O O
I I Br Br I I Br Br
O O O O
CI CI +
O– Na
+
O– Na
+ O– Na
+
O– Na
CI CI CI CI
Erythrosin B (EB) Eosin Y (EY) CI CI
(b) Rose Bengal (RB) Phloxine B (PB)
Scheme 12.4 (a) Proposed mechanism of oxygen-tolerant PET–RAFT polymerization

mediated by (b) xanthene dyes and (c) the model RAFT agent (BTPA) and monomer
(N,N-dimethylacrylamide). 3 Σ, ground-state oxygen; 1 Δ, singlet oxygen; TTA, triplet–triplet
annihilation; DMSO, dimethyl sulfoxide; DMSO2 , dimethyl sulfone. Source: Reproduced with
permission from Wu et al. [82]. Copyright 2018, American Chemical Society.
(Scheme 12.4) [83]. Mediated by blue (𝜆 = 460 nm) light, EY enabled activation of a
dithiobenzoate for the polymerization of methacrylates via an oxidative quenching
cycle. Critically, through the addition of a tertiary amine species, as a sacrificial
electron donor, the process is transformed into a reductive quenching cycle with
the ability to polymerize in the presence of oxygen. Further investigations into
the mechanism of EY-mediated PET–RAFT revealed that the direct photolysis of
trithiocarbonate RAFT agents can occur under blue light irradiation [84]. Control
over molecular weight was best achieved through the use of an oxidative pathway
under green light, which removed the potential activation of the trithiocarbonates
via the iniferter pathway.
Oxygen tolerance in xanthene-mediated PET–RAFT can also be accessed via
the addition of ascorbic acid. The use of EY or Rose Bengal in conjunction with
ascorbic acid can promote dark polymerization, wherein oxygen contained in
the reaction mixture is quickly converted into hydrogen peroxide during a short
exposure period (t = 5–45 minutes) [85]. Thereafter, the slow reduction of hydrogen
peroxide into hydroxyl radicals by ascorbic acid enables polymerization to occur
even in the absence of sustained light exposure. The same photochemistry has also
been exploited to enable controlled polymerizations at ultralow volumes under
sustained irradiation [86].
The aqueous solubility of xanthene dyes is an advantage that has been exploited for
the preparation of bioconjugates. Sumerlin and coworkers utilized EY in conjunc-
tion with a tertiary amine species to successfully graft water-soluble acrylates and
acrylamides from trithiocarbonate-functionalized lysozyme under blue light [87].
Notably, fast polymerizations were observed even at high dilutions, signifying the
efficiency of the polymerization mechanism. More recently, Weil and coworkers
pH 7.0 pH 5.0 pH 7.0 2.5 ON

1.2 OFF by HC1/N2
Absorbance
In ([M0]/[Mt])
HC1/N2 fume NaHCO3 2.0 ON by NaHCO3

0.8 1.5
1.0 BTPA-M
0.4
0.5
0.0 0.0
0 20 40 60 80 100 120 140 160 180 200 400 500 600 700
(a) Time (min) (b) Wavelength (nm)
Normalized w log M
2.0 Light OFF S5 S1
1.6 S2
In ([M0]/[Mt])
HC1/N2 0.8
1.2 HC1/N2 S4 S3
S2 S3 S4
0.8 S1 0.4 S5
NaHCO3
0.4 NaHCO3
0.0 0.0
0 120 240 360 480 600 720 840 960 3.5 4.0 4.5 5.0
(c) Time (min) (d) log M
Figure 12.7 pH-controlled temporal control of tetrabrominated benzoic fluorescein

(TBrFL)-mediated PET–RAFT polymerization of N,N-dimethylacrylamide in water and in the
presence of oxygen under green light. (a) Plot of ln([M]0 /[M]t ) wherein acidification (HCl
fumes) induces a colour-to-colourless transition to pause the polymerization. Reverting to
neutral pH via the addition of base (NaHCO3 ) reactivates the system by returning the colour
of the TBrFL photocatalyst. (b) Corresponding UV–vis spectra of the different
coloured/colourless states in (a). (c) Demonstration of temporal control exerted using both
pH and light. (d) Molecular weight distributions of samples taken during the kinetic
experiment presented in (c). Source: Adapted with permission from Wu et al. [89]. Copyright
2019, American Chemical Society.
reported DNA–polymer conjugates prepared by an approach that was mediated by

EY in conjunction with ascorbic acid [88]. However, poor control was noted and was
attributed to potential chain transfer reactions to the single-stranded DNA sequence.
With the successful application of EY, the effect of halogen substituents on the
photophysical and electrochemical properties of xanthene dyes in the context of
PET–RAFT polymerization was examined [82]. This theoretical framework paved
the way for the discovery of a xanthene catalyst with an accessible pH-switch
(Figure 12.7) [89]. Although commercially available xanthene dyes possess such
transitions, they usually occur at prohibitively acidic conditions (pH < 2). Under
neutral conditions (pH = 7) the ‘new’ photocatalyst retained its colour to enable
polymerization to proceed. However, under slightly acidic conditions (pH = 5),
the catalyst became colourless and therefore was unable to absorb the incident
wavelength, resulting in cessation of polymerization.
12.4 Applications
12.4.1 Single Unit Monomer Insertion (SUMI)

One of the advantages of photoRAFT over other forms of controlled radical poly-
merization is the access it enables to new types of polymers. Light is a very versatile
medium – it is possible to precisely control its delivery not only with respect to time
and space but also with respect to energy. Chemical processes can be selectively acti-
vated by light of different energies, enabling orthogonal reactions within a single
system to be controlled.
One area where this might become important is in the field of sequence-controlled
polymers. The ability to precisely define the monomer sequence in a polymer chain
has long been a dream of polymer chemists. Except for carbohydrates, such control
is present in all of nature’s macromolecules – DNA, RNA, and proteins – and is criti-
cal to their folding and function. From a tiny set of monomeric building blocks (just
5 nucleobases and 20 canonical amino acids) comes the entire function of biology
because of the precision with which their arrangement in the polymer chain can be
defined. Even a single out of place amino acid or nucleobase can lead to dramatic
changes to the conformational structure in solution. The complexity of protein syn-
thesis is possible thanks to the ribosome. This machine uses DNA to template the
position of amino acid monomers such that they react in the desired order to form
the protein chain. By contrast, controlled radical polymers are built in solution by a
stochastic process and even the most well-controlled systems show some dispersity
of molecular weight and architecture. It is very difficult to imagine how we might
build any molecular machinery that would mimic the ribosome in a radical poly-
merization given our current chemical toolkit.
A wide range of strategies for achieving sequence control in synthetic polymers
have been proposed, although it would be fair to say that no approach has been
completely successful to date [90]. Multiblock copolymers are one way to achieve
a form of sequence control in controlled radical polymerization. In this case, poly-
merization is performed with a single monomer at a relatively low target degree of
polymerization (perhaps 5–10 units) and driven to full monomer conversion before
addition of the next monomer. Reinitiation of the polymerization causes chain exten-
sion with this monomer, and after repetition of the process enough times a polymer
with a defined sequence of blocks can be obtained. Polymers with up to 21 blocks
have been demonstrated by a variety of controlled radical polymerization techniques
[91–98], including photoRAFT [99]. The order of units in the backbone comes from
the sequence of monomer addition. However, in the absence of any templating, con-
trolled radical polymerizations such as these will always be stochastic in nature, and
so the length of each block will always have a distribution. Worse than this, as the
length of each block is reduced, or the number of blocks increased, there will be a
growing proportion of polymer chains with missing blocks. The maths, as demon-
strated by Harrisson and coworkers, shows that even under ideal conditions 5% of
chains in each chain extension reaction will fail to reinitiate if the targeted block
length is equal to or less than 3, such that after 18 chain extensions the majority of
chains will be missing at least one block [100]. If the targeted block length is dou-
bled to 6, the situation is greatly improved, but 5% of chains will still be missing at
least one block after 20 chain extensions. One way around this problem is to isolate
the desired product from the stochastic mixture produced at each step, and although
the groups of both Hawker and Junkers have shown very workable methodologies
for this, the physical challenge of performing a purification at every step remains
[101, 102]. Another alternative is to build up polymers by sequential click reactions,
rather than via a radical polymerization, but even these often require intermediate
purification steps [103–106].
Even with only this brief background to the field, the power of single unit
monomer insertion (SUMI) reactions should become evident. In the ideal case,
such a reaction would cause the reinitiation of all chains but halt the reaction after
the first monomer addition to each chain. This would eliminate all distribution in
the system – every chain would have precisely one monomer unit attached and
could be reinitiated with the next desired monomer. In RAFT, the character of the
C—S bond on the R group side of the RAFT agent changes after addition of the first
monomer. Before activation, the sulfur is connected to the carbon of the R group,
and after addition of the first monomer it is connected to the monomer unit. This
should result in slightly different bond strength. If we use light rather than a free
radical initiator to activate this bond it should be possible to tune the energy of the
light to cause cleavage in the case of the RAFT agent, but not after addition of the
first monomer. This was first shown by the Boyer group in collaboration with Moad
and Hawker’s groups, using the PET–RAFT system (Figure 12.8).
Investigations were initiated by the discovery that the catalyst pheophorbide
a, which selectively activated the dithiobenzoate RAFT agent, CPADB, could not
facilitate the polymerizations of monomers that generated secondary propagating
radicals [50]. Rather, polymers were only formed in the presence of methacrylic
monomers, which generated tertiary propagating species. In the case of acrylate,
acrylamido, and styrenic monomers, it was found that the single unit adduct of the
RAFT agent could not be reactivated by the catalyst because of the change in C—S
bond strength from a tertiary carbon to a secondary carbon.
O
O St S S O
HO S S OH
HO S S CN S CDTPA-St HO
Green light CN S
CN S PMI (>99%) O
CDTPA CETPA
Ir(ppy)3
Blue light St Green light
VAc N O
O N O O O PMI Blue light
O ZnTPP
HO S S HO S S
Red light CN
CN O O S S VAc Red light
CDTPA-St-PMI
CDTPA-St-PMI-VAc Limonene (96%)
(79%) Ir(ppy)3
Blue light O O N O
S S OH
HO
N N O O N O CN O O S O
Ir N Zn N HO S S
N N N CN S
CDTPA-St-PMI-Lim CDTPA-St-PMI-VAc
Ir(ppy)3 ZnTPP (>99%) (73%)
(a) (b)
O N O O N O O O
N-Ethyl Vinyl acetate

O
maleimide (VAc)
3-Vinylbenzaldehyde O N O N-Benylmaleimide
(VBA) (EMI) (BMI)
Styrene (St) O CI
4-tert-Butyl
4-Methoxystyrene styrene 4-Vinylbenzyl
(MeOSt) chloride N-Phenylmaleimide (R)-(+)-Limonene
(tBuSt)
(C) (VBC) (PMI) (Lim)
Figure 12.8 Synthetic strategy for the preparation of sequence-defined trimers.

(a) Monofunctional trimer, (b) difunctional trimer, and (c) investigated monomers. Source:
Reproduced with permission from Xu et al. [107]. Copyright 2017, John Wiley & Sons.
Advancement to the preparation of trimers was made possible by adapting this

strategy to trithiocarbonate RAFT agents (Figure 12.8) [107]. The lability of the
tertiary C—S bond in CDTPA under green light provided a single unit monomer
adduct of styrenic monomers, which could not progress further due to the absence
of catalyst and low propagation rate constant of the monomer at room temperature.
Addition of the transition metal photoredox catalyst, fac-Ir(ppy)3 , could facilitate
reactivation of the single unit monomer adduct and in the presence of maleimido
monomers, which cannot homopolymerize, provided a dimeric species. Thereafter,
the C—S bond was reactivated by the metalloporphyrin, ZnTPP, to insert either
vinyl acetate or limonene as monomers that could not be polymerized by ZnTPP
and trithiocarbonates. In this manner, sequence-defined trimers were successfully
synthesized.
More recently, the reactivity of the radical generated from the PET process was
exploited for the preparation of pentamers [108]. Indene and maleimido monomers
incapable of homopolymerization were selected for an alternating insertion
strategy. Critically, due to the electron-accepting qualities of maleimides, prepa-
ration of a maleimido mono-adduct required the starting trithiocarbonate RAFT
agent to possess an electron-donating R group. Conversely, the electron-donating
capabilities of indene necessitated a trithiocarbonate RAFT agent possessing an
electron-accepting cyano-isopropyl R group. Successive PET-mediated cleavage by
the metalloporphyrin ZnTPP facilitated alternating insertions of maleimido and
indene monomers up to pentamers with the main limitation to achieving higher
lengths being the purification of the products for each addition step. Interestingly,
the insertion of the cyclic maleimido and indene monomers was found to be trans
only resulting in oligomers that were both sequence controlled and stereospecific.
12.4.2 Wavelength Orthogonal Polymerization

The broad range of catalyst families demonstrated for the PET–RAFT enables the
process to be activated by wavelengths along the entire visible electromagnetic spec-
trum and even into the NIR region. Arising from the narrow and distinct absorp-
tion spectra between different catalyst families and other chromophores, there is an
opportunity to perform orthogonal reactions in a single pot by utilizing two different
photocatalysts with distinct photophysical and photochemical characteristics.
One example is the photocatalyst pheophorbide a (PheoA), which has been
shown to selectively activate the dithiobenzoate RAFT agent CPADB in the
presence of trithiocarbonate BTPA during methacrylate PET–RAFT polymer-
izations under red light (𝜆max = 690 nm) [50]. The selectivity arises from the
secondary R-group of BTPA, which disfavours addition of the tertiary methacrylic
propagating radical-facilitated selective polymerization. This selectivity was
exploited to polymerize a trithiocarbonate-functionalized methacrylate monomer,
BTPEMA (2-(2-(n-butyltrithiocarbonate)-propionate)ethyl methacrylate) and
subsequently polymerize MA from the pendant trithiocarbonate functionalities
under green light (𝜆max = 530 nm) through ZnTPP, affording a graft copolymer
(PMMA-r-BTPEMA)-g-PMA in a single reaction vessel (Scheme 12.5).
O
CN
HO S
x y
O CN m
O O O O S
S
HO N N
Zn O
S P(MMA-r-BTPEMA)
N N O O
CPADB MMA O
S S
ZnTPP
Red light S
+ (690 nm) O
O Green light O
O NH N (530 nm) MA
O
N HN CN
O BTPEMA S
O HO x y
S S O O PheoA m
HO O O O O O O S
O OCH3
S
O P(MMA-r-BTPEMA)-g-PMA
O
S S
n
O O S
Scheme 12.5 Selective photoactivation of thiocarbonylthio compounds with SUMI

reactions and PET–RAFT polymerization. Source: Reproduced with permission from Xu
et al. [50]. Copyright 2016, American Chemical Society.
In another example, wavelength-orthogonal ring-opening polymerization

(ROP) and PET–RAFT polymerization was achieved through the combination
of a merocyanine-based photoacid and ZnTPP [109]. Specifically, merocyanine
undergoes photoinduced cyclization under blue light (𝜆 = 460 nm, 0.7 mW cm−2 )
to release a proton capable of catalyzing the ROP of cyclic esters. Combining this
blue light-mediated ROP with ZnTPP mediated PET–RAFT of acrylates enabled a
one-pot orthogonal polymerization that was switchable between ROP (blue light)
and PET–RAFT (red light).
The extended absorption and efficient photocatalysis of ZnTPP has invited
further investigation of its use in conjunction with orthogonally absorbing chro-
mophores. o-Nitrobenzyl functionalities are a common photo-protecting group
that undergo photocleavage under UV irradiation (300–365 nm), which prohibits
their usage in conjunction with most conventional photoinitiators. By employing
yellow (𝜆 = 560 nm) and red (𝜆 = 635 nm) light, ZnTPP successfully mediated
the PET–RAFT polymerization of o-nitrobenzyl methacrylate, enabling the facile
preparation of UV-sensitive polymers [46]. More recently, the water-soluble
ZnTPP analogue, zinc meso-tetra(N-methyl-4-pyridyl) porphine tetrachloride
(ZnTPMPyP), afforded successful polymerization of a coumarin-functionalized
methacrylamide under red light (𝜆 = 595 nm)-mediated dispersion conditions
[47]. Various morphologies such as micelles, worms, and vesicles were produced
via polymerization-induced self-assembly (PISA); the coumarin moieties in the
hydrophobic core enabled facile cross-linking under UV irradiation (𝜆 = 365 nm) to
fix the morphologies.
12.4.3 High-Throughput Polymer Libraries

In addition to enabling access to more complex polymers, photoRAFT techniques
are usually very practical methods for obtaining regular controlled radical polymers.
They can be performed at room temperature, and the temporal control afforded
by the light enables reactions to be turned off and on at will. Many of the photo-
catalytic systems discussed in this chapter enable polymerization in the presence
of oxygen and in volumes as low as 10–20 μl. All these features make photoRAFT
well suited to the preparation of high-throughput (HTP) polymer libraries. HTP
techniques have been used extensively to map out structure–function relationships
of small-molecule drug candidates in the pharmaceutical industry [110, 111]. The
potential chemical landscape for a small-molecule scaffold is often too vast, and the
biological interactions too complicated, to rationally design a drug from the ground
up. Computational methods and in silico screening have improved library design in
recent years, but this has been seen as a complement to, rather than a replacement
for, experimental screening [112]. HTP techniques have also been widely applied to
develop new materials, particularly in the fields of solar energy, batteries, inorganic
materials, catalysis, and nanomaterials [113, 114]. Polymers are natural candidates
for HTP techniques [115, 116]. HTP libraries of controlled radical polymers tradi-
tionally required glove box-bound automated synthesizers and dedicated degassed
solvent lines, severely limiting widespread adoption and use [117–121]. By contrast,
oxygen-tolerant polymerizations can be performed on multi-well plates in the open
atmosphere, enabling library synthesis in low volume (<40 μl) with simple auto-
mated pipetting systems [122]. This dramatically simplifies the process and removes
many of the technical barriers. PET–RAFT [123–126], eosin-Y [86], and a few other
photoRAFT systems [42, 127] have been used to prepare polymer libraries on well
plates without any degassing steps, and these have been applied to begin to map
out structure–property relationships for lectin-binding polymers [123], antimicro-
bial polymers [125–127], haemotoxic polymers [127], and in PISA [86]. We anticipate
that oxygen-tolerant photoRAFT techniques will be increasingly applied to investi-
gate structure–property relationships for controlled radical polymers in a wide range
of fields.
Take, for example, our own work studying lectin-binding polymers, which applied
a porphyrin-catalyzed PET–RAFT system to the synthesis of star-shaped polymer
libraries on 384 well plates [123]. By using zinc tetraphenyl porphyrin (ZnTPP) as
the photocatalyst, very high tolerance to oxygen was achieved. This is because of the
high quantum yield this catalyst has for the conversion of triplet to singlet oxygen,
which is subsequently trapped by the solvent (DMSO) as DMSO2 . While a few pre-
vious reports had shown oxygen-tolerant controlled/radical polymerization (CRP)
in water, none had worked in purely organic solvents [128–130]. Both of these fea-
tures are highly advantageous. (i) The high oxygen tolerance enables polymerization
at a wide range of DPs in very low volume and low concentrations without wor-
rying about effects from oxygen, and (ii) by working in DMSO rather than water
as a solvent we could prepare star-shaped polymers with reactive ester handles,
which had not been previously accessible. By post-polymerization modification of
these scaffolds bioactive functionality could be easily installed in a HTP manner.
We applied this system to prepare star-polymers functionalized with mannose to
probe the relationships between a polymers structure and its binding strength to the
lectin Concanavalin A (ConA); see Figure 12.9. This class of carbohydrate-binding
3O O
2 S
O S S CO2H
C12H25
1O S CN R1
2 DMSO
ZnTPP*
R
R2
Pn–S S S S
ZnTPP\ + Pn
Z Ph Z R R
N N ZnTPP
Ph Zn Ph R3
N N
RAFT
R
Ph
R R
R4
R R
S S
R= CO2H
S
Figure 12.9 Representation showing the ZnTPP polymerization mechanism and RAFT
agents used in the library design. Source: Reproduced with permission from Gormley Adam
et al. [123]. Copyright 2018, John Wiley & Sons.
proteins are important recognition units in the body, controlling cellular communi-
cation pathways, the binding of bacteria and viruses, and uptake of nanoparticles.
Our libraries showed that the polymer–protein binding affinity was the strongest for
the three-arm star polymers. It was found to increase with size (DP) relative to poly-
mer molarity, but relative to the total mannose concentration smaller polymers had
the stronger affinity.
HTP polymer libraries have also been recently applied in the development of
antimicrobial polymers. Such polymers are designed to break open the cell mem-
brane in order to destroy the cell and take advantage of the fact that most bacterial
membranes are more negatively charged than their mammalian equivalents for
their selectivity. Because they disrupt the membranes via a physical process and not
by blocking a receptor or the action of the ribosome, it is very difficult for bacteria
to develop resistance. It is hoped that this might enable the design of a new class
of drugs able to target multi-drug resistant strains. Most effective antimicrobial
polymers contain some mixture of hydrophobicity (which aids insertion into the
lipophilic membrane), some degree of positive charge (to target the negatively
charged membrane surface), and some degree of hydrophilicity (to enable overall
solubility in water). Their activity relies on the structural conformation they adopt
in solution, but unlike the antimicrobial peptides they aim to mimic [125], the rules
governing their conformational folding are not well understood.
In a recent work from the Boyer group, libraries of antimicrobial copolymers were
prepared using a HTP PET–RAFT approach to study the effect of polymer archi-
tecture and composition on gram-negative Pseudomonas aeruginosa, Acinetobacter
baumannii, and Escherichia coli; and gram-positive Staphylococcus aureus, as well
as Mycobacterium smegmatis [125, 126]. Haemolysis was performed as a control to
A H B H C H
N N N
NH2 OH
#1 O O O
Ref # Block organization PAO1 PA ATTC EC K12 AB ATCC SA ATCC
1 ABC
2 ABC
#4 3 ABC
4 AB
5 AB
#10 6 AB
7 AC-B
8 AC-B
9 AC-B
#12 10 AC-B-AC
11 B-AC-B
12 AC-B-AC-B-AC-B-AC-B
13 A-B
#15 14 A-B
15 A-BC
16 A-BC
17 A-BC
#22 18 A-BC-A
19 BC-A-BC
20 A-BC-A-BC
>256 μg.ml–1 21 A-BC-A-BC-A-BC-A-BC
#26
22 AB-C
23 AB-C
256 μg.ml–1
MIC concentration
24 AB-C
#31 25 AC-BC
128 μg.ml–1 26 AC-BC
27 AC-BC
28 A-B-C
64 μg.ml–1
#32 29 A-C-B
30 C-A-B
32 μg.ml–1 31 ABC
32 A-BC
Figure 12.10 Heat map of MICs for all polymers synthesized in this study where the
selection of polymer structures from each family is shown. The bacterial strains are Pseu-
domonas aeruginosa PAO1 and ATCC 27853 strains, Escherichia coli K12 strain, Acinetobacter
baumannii ATCC 19606 strain, and Staphylococcus aureus ATCC 29213 strain. Source: Reprod-
uced with permission from Judzewitsch et al. [125]. Copyright 2018, John Wiley & Sons.
determine the mammalian cell compatibility. In the first study, 32 polymers were
prepared with the same overall monomer composition but different architectures
(blocks vs. various mixtures of random copolymers) (Figure 12.10) [125]. Monomers
based on the amino acids lysine, phenylalanine, and serine were chosen to impart
cationic, hydrophobic, and hydrophilic character to the polymer respectively. Both
the antimicrobial and haemolytic activity were found to be dependent on the
distribution of monomers within blocks, and bacteria genus specificity could be
tuned via polymer block order and to a lesser extent via combined modulation
of polymer chain length. In the second study, the library was expanded to 120
polymers comparing three different amine functionalities across a range of com-
positional formulations [126]. Primary amines were found to work best against
gram-negative P. aeruginosa, while quaternary ammonium provided better activity
against M. smegmatis. Leveraging a slightly different photoRAFT system, originally
developed by Qiao and coworkers [131], the Gibson group have performed similar
studies towards the development of antimicrobial polymers [127]. Using a Gilson
Pipetmax 268 liquid-handling robot, they were able to prepare a library of 108
cationic statistical copolymers from DMAEMA and eight different co-monomers
S NC S S
O O + O O + n m
R NC S S S
10 Antimicrobial
10 OH O OO O
N HO N R
OH N
Variable unit
Haemotoxicity
Liquid-handling
robot
Parallel-library synthesis
Figure 12.11 Schematic showing the HTP RAFT synthesis of amine-containing

antimicrobial polymers in well-plates. Source: Reproduced with permission from Richards
with four concentrations of either hydrophobic or hydrophilic substituents (5, 10,

15, 20 mol%) in 96 well plates (Figure 12.11). The polymers were then screened for
antimicrobial and haemotoxic activity. Using automation and HTP size exclusion
chromatography (for polymer characterization) significantly streamlines both the
synthetic and analytical processes. A number of hits were identified, including one
copolymer with propylene glycol side chains, which showed significantly enhanced
antimicrobial activity.
These few examples give a taste for the power of HTP polymer chemistry, which
is only just beginning to be leveraged. Lessons learnt from combinatorial work in
the small-molecule space will be valuable moving forward. Even with HTP polymer
synthesis techniques it is impossible to sample the entirety of the available chemical
space, and so these need to be paired with some form of rational experimental design.
However, where structure–property relationships are not well defined they should
be very helpful in mapping out the key parameters.
12.4.4 Hydrogels and 3D Printing

Light is a very widely used medium for curing both hydrogels and 3D printed
materials. It is typically used either to photoinitiate a free radical polymerization
in the presence of a vinylic crosslinker or to catalyze click reactions between two
pre-prepared polymers, such as between a polyethylene glycol (PEG) dithiol and
multi-armed PEG-maleimide or PEG-norbornene. Compared to other sources of
initiation, light affords excellent spatial resolution, so polymerization can be driven
only in the desired voxels. It can trigger the rapid generation of large quantities of
radicals, enabling rapid curing times. In addition, because the wavelength can be so
finely tuned, orthogonal functionality can be very easily polymerized into the mate-
rial. For these reasons many 3D printers, whether extrusion or stereolithographic
in design, are already designed to be cured using light. Many researchers have
Monomer (M) and

crosslinker (CL)
Photoredox
Parent gel catalyst (PTH)
Ph Daughter gel
with iniferter N
=
groups:
S
(a)
Recombine
and SET Propagation
Cleaved network
strand with stable
PTH in solution +
TTC anion end R Cleaved network
Blue S S
strand with
LED Network Network Network + Network propagating
Light S S S S
+ end
Network strand with RAFT
TTC iniferter process
PTH radical cation
PTH* in solution Network Network
(b) SET and fragment
Figure 12.12 Polymer network structure from PRCG via photoredox catalysis using PTH
under blue light irradiation [132]. (a) Photoredox catalyzed growth (PRCG) of polymer gels,
(b) PRCG mechanism. Source: Reproduced with permission from Chen et al. [132]. Copyright
2017, American Chemical Society.
taken advantage of this to 3D print controlled polymer scaffolds using photoRAFT

systems, giving them access to highly functional and adaptable materials.
Johnson and coworkers were among the first to use a photoredox catalyst
to produce a ‘living’ hydrogel [132]. They prepared ‘parent’ hydrogels using
well-established strain-promoted azide–alkyne cycloaddition (SPAAC) chemistry,
from a four arm PEG-dibenzocyclooctyne (tetra-DBCO-PEG) and a bis-azide RAFT
agent (bis-N3 -thiocarbonylthio compound [TTC]). Because of the inclusion of
the RAFT agent within the network, when these parent gels were swollen with
monomer and the redox photocatalyst PTH [51, 133], the PTH could be used to
catalyze the controlled radical chain extension at the RAFT agent junctions to
expand the hydrogel network (Figure 12.12). By introducing additional crosslinker
monomers in this chain extension step the stiffness of the daughter hydrogel could
be modulated. The group were able to perform this chain extension using a range
of monomers including NIPAAm, OEGMA, and nBA. Daughter gels could also be
welded together through polymerization to afford self-healing gels, and gels with
spatially heterogeneous chemistries.
12.4.5 Live Cell Graft Polymerizations

The mild conditions provided by visible light-mediated RAFT polymerizations
have been attractive for the preparation of polymer-modified biomaterials. In par-
ticular, the modification of proteins with polymers via a grafting-from PET–RAFT
approach has been investigated in the works of Boyer and coworkers [63], Sumerlin
and coworkers [87], and Averick and coworkers [134]. More recently, the use of
Cell surface-initiated
PET-RAFT polymerization
Then 1 Monomers 2 and 3
Yeast cells CTA-modified yeast cells

Cell–polymer conjugates
H
N R
or
2 O
24
= S O
N H R = biotin, N3
N O H O N N
S S O 3
O N S O
O S N 3 H
O N O N O
O
SO Na
3 O O 1 3 O
O HO O 24
Figure 12.13 PET–RAFT mediated polymerization initiated from the surface of yeast cells.
Source: Reproduced with permission from Messina et al. [137]. Copyright 2020, Elsevier.
PET–RAFT was extended to the preparation of DNA–polymer conjugates and bioac-

tive peptide brush polymers [88, 135]. Save for the initial report by Boyer, which
utilized the transition metal catalyst Ru(bpy)3 Cl2 , the common thread among these
works has been the use of the xanthene dye, EY, as the photoredox catalyst. Its water
solubility, low cost, and availability make it an accessible photocatalyst that has been
proved to be effective for the preparation of biomaterials with preserved activities.
Perhaps the greatest demonstration of biocompatibility of EY-mediated
PET–RAFT was the modification of live cell surfaces by Soh and coworkers
[136]. PEG-based acrylamides were grafted-from Saccharomyces cerevisiae (Baker’s
yeast) cells using optimized conditions to generate polymer-grafted yeast cells in
under five minutes of blue LED (𝜆 = 465 nm, 5.0 mW cm−2 ) irradiation. Cleavage
of the attached polymers confirmed the controlled nature of the process. More
importantly, high viability of the modified yeast cells was confirmed by flow
cytometry together with an unchanged growth curve when compared to wild-type
cells. Following confirmation of the process’s remarkable biocompatibility, poly-
mer modification was extended to human Jurkat cells. Poor cell viability, which
was reasoned to occur from covalent modification, was rectified by utilizing a
lipid-modified RAFT agent that was inserted into the cell membrane and led to
polymer-modified mammalian cells with approximately 90% of the cells confirmed
as being metabolically active (Figure 12.13).
12.5 Conclusions and Outlook
The visible light-mediated regulation of RAFT processes has undoubtedly created

exciting new opportunities. The accessibility of low-cost and narrow-emission light
sources has inextricably fuelled its development and this availability will continue to
increase the proliferation of these techniques. The ability to stop and start reactions
at will in combination with easy access to oxygen tolerance no doubt makes for an
attractive proposition for non-specialists. In this vein, a critical area of investigation
is in the effective scale up of these light-mediated processes. Indeed, the longer
optical path lengths demanded by larger volumes result in inhomogeneities in

irradiation intensity, leading to broad molecular weight distributions and other
undesirable effects. The narrow optical path lengths offered by flow chemistry is a
potential answer to this problem and has the added benefit of enabling continuous
operation. Photoredox catalysis has emerged as an effective tool in regulating many
polymerizations. An ongoing area of research is undoubtedly the development of
more effective photocatalysts. Increasing the accessibility through decreased costs
and broader capabilities needs to be addressed for wide-scale proliferation of this
technology. Additionally, a route to facile catalyst recycling is another area that
must also be addressed. At the other end of the spectrum, photoredox catalysis has
unveiled the potential to exert more selective control over photopolymerizations,
enabling the realization of sequence control through SUMI reactions and the
potential for implementing orthogonal polymerizations in single pot by simply
switching between different wavelengths. In a relatively short period, a broad range
of catalysts with exciting properties have been discovered and hints at the potential
of what remains unseen. Considering these potential gains, the future is bright for
photopolymerizations.
References
1 Jung, K., Corrigan, N., Ciftci, M. et al. (2020). Designing with light: advanced
2D, 3D, and 4D materials. Adv. Mater. 32 (18): 1903850.
2 Chatani, S., Kloxin, C.J., and Bowman, C.N. (2014). The power of light in
polymer science: photochemical processes to manipulate polymer formation,
structure, and properties. Polym. Chem. 5 (7): 2187–2201.
3 Corrigan, N., Yeow, J., Judzewitsch, P. et al. (2019). Seeing the light: advanc-
ing materials chemistry through photopolymerization. Angew. Chem. 131 (16):
5224–5243.
4 Corrigan, N., Ciftci, M., Jung, K., and Boyer, C.A.J.M. (2019). Mediating reac-
tion orthogonality in polymer and materials science. Angew. Chem. Int. Ed. 59:
2–36.
5 Chen, M., Zhong, M., and Johnson, J.A. (2016). Light-controlled radical poly-
merization: mechanisms, methods, and applications. Chem. Rev. 116 (17):
10167–10211.
6 Zivic, N., Bouzrati-Zerelli, M., Kermagoret, A. et al. (2016). Photocatalysts in
polymerization reactions. ChemCatChem 8 (9): 1617–1631.
7 Dadashi-Silab, S., Doran, S., and Yagci, Y. (2016). Photoinduced electron trans-
fer reactions for macromolecular syntheses. Chem. Rev. 116 (17): 10212–10275.
8 Padon, K.S. and Scranton, A.B. (2000). A mechanistic investigation of a
three-component radical photoinitiator system comprising methylene blue,
N-methyldiethanolamine, and diphenyliodonium chloride. J. Polym. Sci., Part A:
Polym. Chem. 38 (11): 2057–2066.
9 Shao, J., Huang, Y., and Fan, Q. (2014). Visible light initiating systems for pho-
topolymerization: status, development and challenges. Polym. Chem. 5 (14):
References 637
10 Cook, W.D. and Chen, F. (2015). Polymer chemistry dimethacrylates with the
three component system. Polym. Chem. 6: 1325–1338.
11 Mousawi, A.A., Garra, P., Sallenave, X. et al. (2018). π-Conjugated
dithienophosphole derivatives as high performance photoinitiators for 3D
printing resins. Macromolecules 51 (5): 1811–1821.
12 Allegrezza, M.L., DeMartini, Z.M., Kloster, A.J. et al. (2016). Visible and sun-
light driven RAFT photopolymerization accelerated by amines: kinetics and
mechanism. Polym. Chem. 7 (43): 6626–6636.
13 Shanmugam, S., Xu, J., and Boyer, C. (2017). Photocontrolled living polymeriza-
tion systems with reversible deactivations through electron and energy transfer.
Macromol. Rapid Commun. 38 (13, SI): 1700143.
14 Skrabania, K., Miasnikova, A., Bivigou-Koumba, A.M. et al. (2011). Examining
the UV–vis absorption of RAFT chain transfer agents and their use for polymer
analysis. Polym. Chem. 2 (9): 2074–2083.
15 Xu, J., Shanmugam, S., and Boyer, C. (2015). Organic electron donor–acceptor
photoredox catalysts: enhanced catalytic efficiency toward controlled radical
polymerization. ACS Macro Lett. 4 (9): 926–932.
16 Quinn, J.F., Barner, L., Barner-Kowollik, C. et al. (2002). Reversible
addition–fragmentation chain transfer polymerization initiated with ultraviolet
radiation. Macromolecules 35 (20): 7620–7627.
17 Ran, R., Wan, T., Gao, T. et al. (2008). Controlled free radical photopolymeriza-
tion of styrene initiated by trithiocarbonate. Polym. Int. 57 (1): 28–34.
18 Zhou, H. and Johnson, J.A. (2013). Photo-controlled growth of telechelic poly-
mers and end-linked polymer gels. Angew. Chem. Int. Ed. 52 (8): 2235–2238.
19 Lu, L., Yang, N., and Cai, Y. (2005). Well-controlled reversible
addition–fragmentation chain transfer radical polymerisation under ultraviolet
radiation at ambient temperature. Chem. Commun. 42: 5287–5288.
20 Carmean, R.N., Becker, T.E., Sims, M.B., and Sumerlin, B.S. (2017). Ultra-high
molecular weights via aqueous reversible-deactivation radical polymerization.
Chem 2 (1): 93–101.
21 Singh, A., Kuksenok, O., Johnson, J.A., and Balazs, A.C. (2016). Tailoring the
structure of polymer networks with iniferter-mediated photo-growth. Polym.
Chem. 7 (17): 2955–2964.
22 Muthukrishnan, S., Pan, E.H., Stenzel, M.H. et al. (2007). Ambient temperature
RAFT polymerization of acrylic acid initiated with ultraviolet radiation in aque-
ous solution. Macromolecules 40 (9): 2978–2980.
23 You, Y.-Z., Hong, C.-Y., Bai, R.-K. et al. (2002). Photo-initiated living free radical
polymerization in the presence of dibenzyl trithiocarbonate. Macromol. Chem.
Phys. 203 (3): 477–483.
24 Lalevée, J., Blanchard, N., El-Roz, M. et al. (2008). New photoiniferters:
respective role of the initiating and persistent radicals. Macromolecules 41
(7): 2347–2352.
25 Yasutake, M., Andou, Y., Hiki, S. et al. (2004). Controlled radical polymer-
ization of vaporized vinyl monomers on solid surfaces under UV irradiation.
Macromol. Chem. Phys. 205 (4): 492–499.
26 Kwak, Y. and Matyjaszewski, K. (2010). Photoirradiated atom transfer rad-

ical polymerization with an alkyl dithiocarbamate at ambient temperature.
27 Khan, M.Y., Cho, M.-S., and Kwark, Y.-J. (2014). Dual roles of a xanthate as a
radical source and chain transfer agent in the photoinitiated RAFT polymeriza-
tion of vinyl acetate. Macromolecules 47 (6): 1929–1934.
28 Ham, M.-k., HoYouk, J., Kwon, Y.-K., and Kwark, Y.-J. (2012). Photoinitiated
RAFT polymerization of vinyl acetate. J. Polym. Sci., Part A: Polym. Chem. 50
(12): 2389–2397.
29 Lalevée, J., El-Roz, M., Allonas, X., and Fouassier, J.P. (2007). Controlled pho-
topolymerization reactions: the reactivity of new photoiniferters. J. Polym. Sci.,
Part A: Polym. Chem. 45 (12): 2436–2442.
30 Moad, G. and Barner-Kowollik, C. (2008). The mechanism and kinetics of the
RAFT process: overview, rates, stabilities, side reactions, product spectrum
and outstanding challenges. In: Handbook of RAFT Polymerization (ed. C.
Barner-Kowollik), 51–104. Wiley-VCH Verlag GmbH & Co. KGaA.
31 Zhang, H., Deng, J., Lu, L., and Cai, Y. (2007). Ambient-temperature RAFT
polymerization of styrene and its functional derivatives under mild long-wave
UV–vis radiation. Macromolecules 40 (26): 9252–9261.
32 Wang, H., Li, Q., Dai, J. et al. (2013). Real-time and in situ investigation of
“living”/controlled photopolymerization in the presence of a trithiocarbonate.
33 Lu, L., Zhang, H., Yang, N., and Cai, Y. (2006). Toward rapid and
well-controlled ambient temperature RAFT polymerization under UV–vis
radiation: effect of radiation wave range. Macromolecules 39 (11): 3770–3776.
34 Xu, J., Shanmugam, S., Corrigan, N.A., and Boyer, C. (2015). Catalyst-free visi-
ble light-induced RAFT photopolymerization. In: Controlled Radical Polymeriza-
tion: Mechanisms, ACS Symposium Series, vol. 1187 (eds. K. Matyjaszewski, B.S.
Sumerlin, N.V. Tsarevsky and J. Chiefari), 247–267. American Chemical Society.
35 McLeary, J.B., Calitz, F.M., McKenzie, J.M. et al. (2005). A 1H NMR investiga-
tion of reversible addition–fragmentation chain transfer polymerization kinetics
and mechanisms. Initialization with different initiating and leaving groups.
36 McLeary, J.B., Calitz, F.M., McKenzie, J.M. et al. (2004). Beyond inhibition: a
1H NMR investigation of the early kinetics of RAFT-mediated polymerization
with the same initiating and leaving groups. Macromolecules 37 (7): 2383–2394.
37 McKenzie, T.G., Costa, L.P.d.M., Fu, Q. et al. (2016). Investigation into the pho-
tolytic stability of RAFT agents and the implications for photopolymerization
reactions. Polym. Chem. 7 (25): 4246–4253.
38 Luo, J., Li, M., Xin, M. et al. (2016). Visible light induced RAFT polymerization
of 2-vinylpyridine without exogenous initiators or photocatalysts. Macromol.
Chem. Phys. 217 (16): 1777–1784.
39 McKenzie, T.G., Fu, Q., Wong, E.H.H. et al. (2015). Visible light mediated con-
trolled radical polymerization in the absence of exogenous radical sources or
catalysts. Macromolecules 48 (12): 3864–3872.
References 639
40 da M. Costa, L.P., McKenzie, T.G., Schwarz, K.N. et al. (2016). Observed pho-
toenhancement of RAFT polymerizations under fume hood lighting. ACS
Macro Lett. 5 (11): 1287–1292.
41 Cabannes-Boue, B., Yang, Q., Lalevee, J. et al. (2017). Investigation into the
mechanism of photo-mediated RAFT polymerization involving the reversible
photolysis of the chain-transfer agent. Polym. Chem. 8: 1760–1770.
42 Li, J., Ding, C., Zhang, Z. et al. (2016). Visible light-induced living radical poly-
merization of butyl acrylate: photocatalyst-free, ultrafast, and oxygen tolerance.
Macromol. Rapid Commun. 38 (13): 1600482.
43 Wang, J., Rivero, M., Muñoz Bonilla, A. et al. (2016). Natural RAFT polymer-
ization: recyclable-catalyst-aided, opened-to-air, and sunlight-photolyzed RAFT
polymerizations. ACS Macro Lett. 5 (11): 1278–1282.
44 Otsu, T. (2000). Iniferter concept and living radical polymerization. J. Polym.
46 Bagheri, A., Yeow, J., Arandiyan, H. et al. (2016). Polymerization of a pho-
tocleavable monomer using visible light. Macromol. Rapid Commun. 37 (11):
905–910.
47 Xu, S., Yeow, J., and Boyer, C. (2018). Exploiting wavelength orthogonal-
ity for successive photoinduced polymerization-induced self-assembly and
photo-crosslinking. ACS Macro Lett. 7 (11): 1376–1382.
48 Ng, G., Yeow, J., Xu, J., and Boyer, C. (2017). Application of oxygen tolerant
PET-RAFT to polymerization-induced self-assembly. Polym. Chem. 8 (18):
2841–2851.
49 Shanmugam, S., Xu, J., and Boyer, C. (2015). Exploiting metalloporphyrins for
selective living radical polymerization tunable over visible wavelengths. J. Am.
Chem. Soc. 137 (28): 9174–9185.
50 Xu, J., Shanmugam, S., Fu, C. et al. (2016). Selective photoactivation: from a
single unit monomer insertion reaction to controlled polymer architectures. J.
Am. Chem. Soc. 138 (9): 3094–3106.
51 Chen, M., MacLeod, M.J., and Johnson, J.A. (2015). Visible-light-controlled
living radical polymerization from a trithiocarbonate iniferter mediated by an
organic photoredox catalyst. ACS Macro Lett. 4 (5): 566–569.
52 Gong, H., Zhao, Y., Shen, X. et al. (2018). Organocatalyzed photocontrolled rad-
ical polymerization of semifluorinated (meth)acrylates driven by visible light.
Angew. Chem. Int. Ed. 57 (1): 333–337.
53 Theriot, J.C., Miyake, G.M., and Boyer, C.A. (2018). N,N-Diaryl dihy-
drophenazines as photoredox catalysts for PET-RAFT and sequential
PET-RAFT/O-ATRP. ACS Macro Lett. 7 (6): 662–666.
54 Fu, Q., Ruan, Q., McKenzie, T.G. et al. (2017). Development of a robust
PET-RAFT polymerization using graphitic carbon nitride (g-C3 N4 ). Macro-
molecules 50 (19): 7509–7516.
55 Jiang, J., Ye, G., Wang, Z. et al. (2018). Heteroatom-doped carbon dots (CDs) as
a class of metal-free photocatalysts for PET-RAFT polymerization under visible
light and sunlight. Angew. Chem. Int. Ed. 57 (37): 12037–12042.
56 Li, X., Li, J.L., Huang, W.G. et al. (2018). Metalloporphyrin-bound Janus
nanocomposites with dual stimuli responsiveness for nanocatalysis in living
radical polymerization. Nanoscale 10 (41): 19254–19261.
57 Liang, E., Liu, M.-s., He, B., and Wang, G.-X. (2018). ZnO as photocatalyst for
photoinduced electron transfer–reversible addition–fragmentation chain transfer
of methyl methacrylate. Adv. Polym. Technol. 37 (8): 2879–2884.
Visible-light-driven MADIX polymerisation via a reusable, low-cost, and
non-toxic bismuth oxide photocatalyst. Angew. Chem. Int. Ed. 58 (6): 1828–1832.
59 Zhu, Y. and Egap, E. (2020). PET-RAFT polymerization catalyzed by cad-
mium selenide quantum dots (QDs): grafting-from QDs photocatalysts to make
polymer nanocomposites. Polym. Chem. 11: 1018–1024.
60 Fors, B.P. and Hawker, C.J. (2012). Control of a living radical polymerization of
methacrylates by light. Angew. Chem. Int. Ed. 51 (35): 8850–8853.
61 Shanmugam, S., Xu, J., and Boyer, C. (2014). Photoinduced electron
transfer–reversible addition–fragmentation chain transfer (PET-RAFT) polymer-
ization of vinyl acetate and N-vinylpyrrolidinone: kinetic and oxygen tolerance
study. Macromolecules 47 (15): 4930–4942.
62 Xu, J., Jung, K., and Boyer, C. (2014). Oxygen tolerance study of photoinduced
electron transfer–reversible addition–fragmentation chain transfer (PET-RAFT)
polymerization mediated by Ru(Bpy)3 Cl2 . Macromolecules 47 (13): 4217–4229.
63 Xu, J., Jung, K., Corrigan, N.A., and Boyer, C. (2014). Aqueous photoinduced
living/controlled polymerization: tailoring for bioconjugation. Chem. Sci. 5 (9):
3568–3575.
64 Corrigan, N., Shanmugam, S., Xu, J., and Boyer, C. (2016). Photocatalysis in
organic and polymer synthesis. Chem. Soc. Rev. 45 (22): 6165–6212.
65 Christmann, J., Ibrahim, A., Charlot, V. et al. (2016). Elucidation of the key role
of [Ru(Bpy)3 ]2+ in photocatalyzed RAFT polymerization. ChemPhysChem 17
(15): 2309–2314.
66 Corrigan, N., Xu, J., Boyer, C., and Allonas, X. (2019). Exploration of the
PET-RAFT initiation mechanism for two commonly used photocatalysts.
ChemPhotoChem 3 (11): 1193–1199.
67 Shanmugam, S. and Boyer, C. (2015). Stereo-, temporal and chemical control
through photoactivation of living radical polymerization: synthesis of block and
gradient copolymers. J. Am. Chem. Soc. 137 (31): 9988–9999.
68 Corrigan, N., Rosli, D., Jones, J.W.J. et al. (2016). Oxygen tolerance in living
radical polymerization: investigation of mechanism and implementation in
continuous flow polymerization. Macromolecules 49 (18): 6779–6789.
69 Shanmugam, S., Xu, J., and Boyer, C. (2015). Utilizing the electron transfer
mechanism of chlorophyll a under light for controlled radical polymerization.
Chem. Sci. 6 (2): 1341–1349.
References 641
70 Wu, C., Shanmugam, S., Xu, J. et al. (2017). Chlorophyll a crude extract: effi-
cient photo-degradable photocatalyst for PET-RAFT polymerization. Chem.
Commun. 53 (93): 12560–12563.
71 Shanmugam, S., Xu, J., and Boyer, C. (2016). Light-regulated polymerization
under near-infrared/far-red irradiation catalyzed by bacteriochlorophyll a.
Angew. Chem. Int. Ed. 55 (3): 1036–1040.
72 Niu, J., Page, Z.A., Dolinski, N.D. et al. (2017). Rapid visible light-mediated con-
trolled aqueous polymerization with in situ monitoring. ACS Macro Lett. 6 (10):
1109–1113.
73 Corrigan, N., Almasri, A., Taillades, W. et al. (2017). Controlling molecular
weight distributions through photoinduced flow polymerization. Macro-
molecules 50 (21): 8438–8448.
74 Corrigan, N., Manahan, R., Lew, Z.T. et al. (2018). Copolymers with controlled
molecular weight distributions and compositional gradients through flow
75 Shanmugam, S., Xu, J., and Boyer, C. (2016). A logic gate for external regula-
tion of photopolymerization. Polym. Chem. 7 (42): 6437–6449.
76 Shanmugam, S., Xu, J., and Boyer, C. (2016). Aqueous RAFT photopolymeriza-
tion with oxygen tolerance. Macromolecules 49 (24): 9345–9357.
77 Zhang, L., Wu, C., Jung, K. et al. (2019). An oxygen paradox: catalytic use
of oxygen in radical photopolymerization. Angew. Chem. Int. Ed. 58 (47):
16811–16814.
78 Corrigan, N., Xu, J., and Boyer, C. (2016). A photoinitiation system for conven-
tional and controlled radical polymerization at visible and NIR wavelengths.
79 Wu, Z., Jung, K., and Boyer, C.A.J.M. (2020). Effective utilization of NIR
wavelengths for photo-controlled polymerization – penetration through thick
barriers and parallel solar syntheses. Angew. Chem. Int. Ed. 59 (5): 2013–2017.
80 Mattson, K.M., Pester, C.W., Gutekunst, W.R. et al. (2016). Metal-free removal
of polymer chain ends using light. Macromolecules 49 (21): 8162–8166.
81 Zhang, L., Ye, G., Huo, X. et al. (2019). Structural engineering of graphitic
carbon nitrides for enhanced metal-free PET-RAFT polymerizations in hetero-
geneous and homogeneous systems. ACS Omega 4 (14): 16247–16255.
82 Wu, C., Corrigan, N., Lim, C.-H. et al. (2019). Guiding the design of organic
photocatalyst for PET-RAFT polymerization: halogenated xanthene dyes.
83 Xu, J., Shanmugam, S., Duong, H.T., and Boyer, C. (2015).
Organo-photocatalysts for photoinduced electron transfer-reversible
addition–fragmentation chain transfer (PET-RAFT) polymerization. Polym.
Chem. 6 (31): 5615–5624.
84 Figg, C.A., Hickman, J.D., Scheutz, G.M. et al. (2018). Color-coding visible light
polymerizations to elucidate the activation of trithiocarbonates using eosin Y.
85 Shanmugam, S., Xu, J., and Boyer, C. (2017). Photoinduced oxygen reduction
for dark polymerization. Macromolecules 50 (5): 1832–1846.
86 Yeow, J., Chapman, R., Xu, J., and Boyer, C. (2017). Oxygen tolerant photopoly-
merization for ultralow volumes. Polym. Chem. 8 (34): 5012–5022.
87 Tucker, B.S., Coughlin, M.L., Figg, C.A., and Sumerlin, B.S. (2017).
Grafting-from proteins using metal-free PET–RAFT polymerizations under
mild visible-light irradiation. ACS Macro Lett. 6 (4): 452–457.
88 Lueckerath, T., Strauch, T., Koynov, K. et al. (2019). DNA–polymer conjugates
by photoinduced RAFT polymerization. Biomacromolecules 20 (1): 212–221.
89 Wu, C., Chen, H., Corrigan, N. et al. (2019). Computer-guided discovery
of a pH-responsive organic photocatalyst and application for pH and light
dual-gated polymerization. J. Am. Chem. Soc. 141 (20): 8207–8220.
90 Lutz, J.-F.F., Ouchi, M., Liu, D.R., and Sawamoto, M. (2013). Sequence con-
trolled polymers. Science 341 (6146): –1238149.
91 Carroll, D.R., Constantinou, A.P., Stingelin, N., and Georgiou, T.K. (2018). Scal-
able syntheses of well-defined pentadecablock bipolymer and quintopolymer.
Polym. Chem. 9 (25): 3450–3454.
92 Clothier, G.K.K., Guimarães, T.R., Khan, M. et al. (2019). Exploitation of
the nanoreactor concept for efficient synthesis of multiblock copolymers via
macroraft-mediated emulsion polymerization. ACS Macro Lett. 8 (8): 989–995.
93 Engelis, N.G., Anastasaki, A., Nurumbetov, G. et al. (2017). Sequence-controlled
methacrylic multiblock copolymers via sulfur-free RAFT emulsion polymeriza-
tion. Nat. Chem. 9 (2): 171–178.
94 Gody, G., Barbey, R., Danial, M., and Perrier, S. (2015). Ultrafast RAFT poly-
merization: multiblock copolymers within minutes. Polym. Chem. 6: 1502–1511.
95 Gody, G., Maschmeyer, T., Zetterlund, P.B., and Perrier, S. (2013). Rapid and
quantitative one-pot synthesis of sequence-controlled polymers by radical
polymerization. Nat. Commun. 4: 1–9.
96 Gody, G., Maschmeyer, T., Zetterlund, P.B., and Perrier, S. (2014). Pushing
the limit of the RAFT process: multiblock copolymers by one-pot rapid mul-
tiple chain extensions at full monomer conversion. Macromolecules 47 (10):
3451–3460.
97 Soeriyadi, A.H., Boyer, C., Nyström, F. et al. (2011). High-order multiblock
copolymers via iterative Cu(0)-mediated radical polymerizations (SET-LRP):
toward biological precision. J. Am. Chem. Soc. 133 (29): 11128–11131.
98 Anastasaki, A., Oschmann, B., Willenbacher, J. et al. (2017). One-pot syn-
thesis of ABCDE multiblock copolymers with hydrophobic, hydrophilic, and
semi-fluorinated segments. Angew. Chem. Int. Ed. 56 (46): 14483–14487.
99 Ng, G., Yeow, J., Chapman, R. et al. (2018). Pushing the limits of high through-
put PET-RAFT polymerization. Macromolecules 51 (19): 7600–7607.
100 Gody, G., Zetterlund, P.B., Perrier, S., and Harrisson, S. (2016). The limits of
precision monomer placement in chain growth polymerization. Nat. Commun.
7: 10514–10514.
101 Haven, J.J., De Neve, J.A., and Junkers, T. (2017). Versatile approach for the
synthesis of sequence-defined monodisperse 18- and 20-Mer oligoacrylates. ACS
Macro Lett. 6 (7): 743–747.
References 643
102 Lawrence, J., Lee, S.H., Abdilla, A. et al. (2016). A versatile and scalable strat-
egy to discrete oligomers. J. Am. Chem. Soc. 138 (19): 6306–6310.
103 Barnes, J.C., Ehrlich, D.J.C., Gao, A.X. et al. (2015). Iterative exponential
growth of stereo- and sequence-controlled polymers. Nat. Chem. 7 (10):
810–815.
104 Jiang, Y., Golder, M.R., Nguyen, H.V.T. et al. (2016). Iterative exponential
growth synthesis and assembly of uniform diblock copolymers. J. Am. Chem.
Soc. 138 (30): 9369–9372.
105 Espeel, P., Carrette, L.L.G., Bury, K. et al. (2013). Multifunctionalized
sequence-defined oligomers from a single building block. Angew. Chem. Int.
Ed. 52 (50): 13261–13264.
106 Martens, S., Van Den Begin, J., Madder, A. et al. (2016). Automated synthesis
of monodisperse oligomers, featuring sequence control and tailored functional-
ization. J. Am. Chem. Soc. 138 (43): 14182–14185.
107 Xu, J., Fu, C., Shanmugam, S. et al. (2017). Synthesis of discrete oligomers by
sequential PET-RAFT single-unit monomer insertion. Angew. Chem. Int. Ed. 56
(29): 8376–8383.
108 Huang, Z., Noble, B.B., Corrigan, N. et al. (2018). Discrete and stereospecific
oligomers prepared by sequential and alternating single unit monomer inser-
tion. J. Am. Chem. Soc. 140 (41): 13392–13406.
109 Fu, C., Xu, J., and Boyer, C. (2016). Photoacid-mediated ring opening polymer-
ization driven by visible light. Chem. Commun. 52 (44): 7126–7129.
110 Kodadek, T. (2011). The rise, fall and reinvention of combinatorial chemistry.
Chem. Commun. 47 (35): 9757–9763.
111 Schneider, G. (2018). Automating drug discovery. Nat. Rev. Drug Discovery 17
(February): 97–113.
112 Curtarolo, S., Hart, G.L.W., Nardelli, M.B. et al. (2013). The high-throughput
highway to computational materials design. Nat. Mater. 12 (3): 191–201.
113 Potyrailo, R., Rajan, K., Stoewe, K. et al. (2011). Combinatorial and
high-throughput screening of materials libraries: review of state of the art.
ACS Comb. Sci. 13 (6): 579–633.
114 Hook, A.L., Anderson, D.G., Langer, R. et al. (2010). High throughput methods
applied in biomaterial development and discovery. Biomaterials 31 (2): 187–198.
115 Audus, D.J. and De Pablo, J.J. (2017). Polymer informatics: opportunities and
challenges. ACS Macro Lett. 6 (10): 1078–1082.
116 Oliver, S., Zhao, L., Gormley, A.J. et al. (2019). Living in the fast lane – high
throughput controlled/living radical polymerization. Macromolecules 52 (1):
3–23.
117 Hoogenboom, R., Meier Michael, A.R., and Schubert Ulrich, S. (2003). Com-
binatorial methods, automated synthesis and high-throughput screening in
polymer research: past and present. Macromol. Rapid Commun. 24 (1): 15–32.
118 Hoogenboom, R. and Schubert Ulrich, S. (2003). The fast and the curious:
high-throughput experimentation in synthetic polymer chemistry. J. Polym. Sci.,
Part A: Polym. Chem. 41 (16): 2425–2434.
119 Hoogenboom, R. and Schubert, U.S. (2005). High-throughput synthesis equip-

ment applied to polymer research. Rev. Sci. Instrum. 76 (6): 062202.
120 Huiqi, Z., Richard, H., Michael, A.R.M., and Ulrich, S.S. (2005). Combinatorial
and high-throughput approaches in polymer science. Meas. Sci. Technol. 16 (1):
203.
121 Stefan, S., Meier, M.A.R., and Schubert, U.S. (2003). Instrumentation for com-
binatorial and high-throughput polymer research: a short overview. Macromol.
Rapid Commun. 24 (1): 33–46.
122 Yeow, J., Chapman, R., Gormley, A.J., and Boyer, C. (2018). Up in the air: oxy-
gen tolerance in controlled/living radical polymerisation. Chem. Soc. Rev. 47
(12): 4357–4387.
123 Gormley Adam, J., Yeow, J., Ng, G. et al. (2018). An oxygen-tolerant PET-RAFT
polymerization for screening structure–activity relationships. Angew. Chem. 130
(6): 1573–1578.
124 Yeow, J., Joshi, S., Chapman, R., and Boyer, C. (2018). A self-reporting pho-
tocatalyst for online fluorescence monitoring of high throughput RAFT
polymerization. Angew. Chem. Int. Ed. 57 (32): 10102–10106.
125 Judzewitsch, P.R., Nguyen, T.-K., Shanmugam, S. et al. (2020). Towards
sequence-controlled antimicrobial polymers: effect of polymer block order
on antimicrobial activity. Angew. Chem. Int. Ed. 59 (17): 4559–4564.
126 Judzewitsch, P.R., Zhao, L., Wong, E.H.H., and Boyer, C. (2019).
High-throughput synthesis of antimicrobial copolymers and rapid evaluation
of their bioactivity. Macromolecules 52 (11): 3975–3986.
127 Richards, S.-J., Jones, A., Thomás, R.M.F., and Gibson, M.I. (2018). Photochem-
ical ‘in-air’ combinatorial discovery of antimicrobial copolymers. Chem. Eur. J.
42 (52): 13758–13761.
128 Chapman, R., Gormley, A.J., Herpoldt, K.-l., and Stevens, M.M. (2014). Highly
controlled open vessel RAFT polymerizations by enzyme degassing. Macro-
molecules 47 (24): 8541–8547.
129 Chapman, R., Gormley, A.J., Stenzel, M.H., and Stevens, M.M. (2016). Combi-
natorial low-volume synthesis of well-defined polymers by enzyme degassing.
Angew. Chem. Int. Ed. 128 (14): 4576–4579.
130 Liu, Z., Lv, Y., and An, Z. (2017). Enzymatic cascade catalysis for the synthesis
of multiblock and ultrahigh-molecular-weight polymers with oxygen tolerance.
Angew. Chem. Int. Ed. 56 (54): 13852–13856.
131 Fu, Q., Xie, K., McKenzie, T.G., and Qiao, G.G. (2017). Trithiocarbonates as
intrinsic photoredox catalysts and RAFT agents for oxygen tolerant controlled
radical polymerization. Polym. Chem. 8 (9): 1519–1526.
132 Chen, M., Gu, Y., Singh, A. et al. (2017). Living additive manufacturing: trans-
formation of parent gels into diversely functionalized daughter gels made
possible by visible light photoredox catalysis. ACS Cent. Sci. 3 (2): 124–134.
133 Tumbleston, J.R., Shirvanyants, D., Ermoshkin, N. et al. (2015). Additive man-
ufacturing. Continuous liquid interface production of 3D objects. Science 347
(6228): 1349–1352.
References 645
134 Kovaliov, M., Allegrezza, M.L., Richter, B. et al. (2018). Synthesis of lipase poly-
mer hybrids with retained or enhanced activity using the grafting-from strategy.
Polymer 137: 338–345.
135 Sun, H., Choi, W., Zang, N. et al. (2019). Bioactive peptide brush polymers via
photoinduced reversible-deactivation radical polymerization. Angew. Chem. Int.
Ed. 58 (48): 17359–17364.
136 Niu, J., Lunn, D.J., Pusuluri, A. et al. (2017). Engineering live cell surfaces with
functional polymers via cytocompatible controlled radical polymerization. Nat.
Chem. 9 (6): 537–545.
137 Messina, M.S., Messina, K.M.M., Bhattacharya, A. et al. (2020). Preparation of
biomolecule-polymer conjugates by grafting-from using ATRP, RAFT, or ROMP.
Prog. Polym. Sci. 100: 101186.
647
13
Redox-Initiated RAFT Polymerization and (Electro)chemical

Activation of RAFT Agents
Carnegie Mellon University, Department of Chemistry, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA
13.1 Introduction

the leading techniques for the preparation of polymeric materials with precisely
controlled and complex architectures [1]. Typically, the polymerization control is
enabled via a degenerate transfer between propagating radicals and dormant species,
regulated by a chain transfer agent (CTA or RAFT agent). A distinct feature of RAFT
polymerization among other reversible deactivation radical polymerization (RDRP)
methods is the presence of sulfur-containing moieties as chain end-groups.
RAFT polymerizations are generally thermally initiated by conventional radical
initiators such as azobisisobutyronitrile (AIBN). Importantly, the use of thermal ini-
tiator causes the continuous generation of new chains throughout the polymeriza-
tion, which could lead to polymers with larger dispersity and lower functionality,
hampering the preparation of pure block copolymers.
The careful selection of the RAFT agent in correlation to the monomer activity
and polymerization conditions can minimize the formation of new chains, so that
block copolymers and polymers with more complex architectures can be accessed
[2]. Moreover, novel initiation systems that can minimize (or eliminate) the forma-
tion of new chains have been developed in the past decade [1c, f, 3]. These systems
employ (i) external molecules and/or stimuli that can generate radicals at ambient
temperature or (ii) direct activation of the RAFT agent to form radicals to start the
polymerization.
The latter approach has been vastly employed recently because of the increasing
interest in photo-induced polymerizations. Indeed, light can promote the dissocia-
tion of a CTA either directly, through a photoiniferter approach, or in the presence
of a photoredox catalyst, as in a photoinduced electron/energy transfer (PET)–RAFT
polymerization [4].
This chapter is focused on the chemical and electrochemical approaches towards
radical generation in RAFT systems. Chemical approaches such as the use of redox
initiators to generate radicals at low temperature [5], and the use of transition metal
648 13 Redox-Initiated RAFT Polymerization and (Electro)chemical Activation of RAFT Agents
complexes to directly activate CTAs [6], were first reported a decade ago. Recently,
these methods were extended to a Fenton–RAFT polymerization [7]. Moreover,
electrochemical stimuli have been applied to RAFT systems to electrochemically
reduce conventional radical initiators or RAFT agents, thus developing an elec-
trochemically mediated reversible addition–fragmentation chain transfer (eRAFT)
polymerization [8c, d].
13.2 Redox Initiation
The most relevant redox pairs used for initiating RAFT polymerizations are sum-
marized in Scheme 13.1, together with some monomers employed for the various
redox-initiated RAFT polymerizations.
Redox couple Monomers

Oxidant Reducing agent O O
O
O N O O
H MA MMA STY
O
O N3
N OH O O
O
BPO DMAN DAES O O N
APM PgA 2-VP
Na2S2O3 NaSO2CH2OH O O O
K2S2O8 HO O NH2 N N
O
KPS AM DMA H
NaAs NIPAM
HO O
Na+ – O OH O
O MEA
OOH OOH HO O O
O
CHP AsAc
HO N NVP
tBuOOH OH
HO
COOH
COOH
N N Fenton–RAFT
2+
H2O2 Fe Fe and
N N
Bio-Fenton–RAFT
Scheme 13.1 Redox couples employed to initiate RAFT polymerizations at room

temperature (or lower) and examples of monomers polymerized via redox-initiated RAFT
polymerization.
Room temperature RAFT polymerization of methyl acrylate (MA), methyl

methacrylate (MMA), and styrene (STY) was reported by Pan and coworkers
by exploiting a redox initiation system based on benzoyl peroxide (BPO) and
N,N′ -dimethylaniline (DMAN) [5]. The BPO/amine redox couple has been exten-
sively used to initiate free radical polymerizations [9]. Mechanistic studies showed
that amine-based radicals, benzoate anions, and benzoyloxy radicals are generated
as a consequence of a nucleophilic displacement on BPO by the amine [9b]. Then,
benzoyloxy radicals initiate the polymerizations, but amine radical cations can also
contribute to initiating polymer chains.
The RAFT polymerization of MA initiated by an equimolar amount of BPO
and DMAN at T = 25 ∘ C and with a target degree of polymerization (DP) 200
gave polymers with molecular weight (MW) matching theoretical values and low
- < 1.1), both in bulk or in tetrahydrofuran (THF) as a solvent, and
dispersities (D
using a dithiobenzoate (DB) or trithiocarbonate CTA. Short induction periods were
attributed to the slow fragmentation of the chain-CTA adduct. The redox-initiated
RAFT polymerization of MMA under similar conditions gave polymers with low
dispersity but with MW values higher than expected. In the case of STY, the reaction
temperature was raised to 35 ∘ C in bulk polymerizations to reach c. 50% conversion
in two to three days, with overall good control. Finally, a PSTY-b-PMA block copoly-
mer was prepared with no visible tailing in the gel permeation chromatography
(GPC) traces, confirming the livingness of the process and the negligible generation
of new chains during the polymerization.
The BPO/DMAN redox initiation system was also used for the RAFT polymer-
ization of the azide-containing monomer 4-azidophenyl methacrylate (APM) [10].
At room temperature, the redox-initiated RAFT polymerization of APM in bulk,
under similar conditions to the above described systems, reached c. 50% conver-
sion in 24 hours, giving a polymer with MW matching the theoretical value and
- = 1.19. The copolymerization of equimolar amounts of MA and APM reached 56%
D
conversion in 2.5 hours, yielding a low-dispersity statistical copolymer containing
about 30 mol% APM. Although azido groups are known to undergo a cycloaddi-
tion reaction to the C=C double bond of acrylates [11], this undesired reaction was
not observed at room temperature, thus highlighting the benefits of the redox ini-
tiation. Therefore, the same strategy was used to prepare block copolymers of MA
and 2-chloroallyl azide, which were further extended with a semi-fluorinated acry-
late monomer and then reacted with an alkyne-capped poly(ethylene glycol) via
‘click’ chemistry [12]. Similar procedures were adopted to fabricate, among others,
hydrophobic glass surfaces [12] and superhydrophobic cotton fibres [13].
Monomers containing acetylenic moieties are also prone to side reactions
during radical polymerizations. Therefore, the BPO/DMAN redox initiators have
been employed to prepare a MMA/propargyl acrylate (PgA) copolymer via RAFT
copolymerization at T = 25 ∘ C [14]. Well-defined P(MMA-co-PgA) copolymers were
then converted into intrachain cross-linked nanoparticles via ‘click’ reaction under
diluted conditions at room temperature.
Redox-initiated RAFT polymerization of 2-vinylpyridine (2-VP) at T = 25 ∘ C was
reported by using BPO but in the absence of an added reducing agent [15]. The
proposed interaction of BPO with the amine-containing monomer 2-VP led to the
formation of an intermediate adduct, followed by proton transfer and generation
of radicals. Furthermore, surface-initiated RAFT polymerization was successfully
paired to a redox initiation system, by using BPO together with 4-(diethylamino)
salicylaldehyde (DEAS) as a reducing agent. The latter was first attached onto the
surface of a nanoclay attapulgite (ATP). The functionalized ATP was subsequently
placed in a solution with BPO, MMA, and a dithiobenzoate CTA. Polymerization
conditions were tuned as to increase the grafting ratio of PMMA relative to hybrids,
which reached 47 wt%. The ATP@PMMA showed better solubility in organic sol-
vents compared to naked ATP [16].
A redox initiation system for room temperature aqueous RAFT polymerization
was developed by Bai et al. by using the redox couple potassium persulfate (K2 S2 O8 ,
KPS) – sodium thiosulfate (Na2 S2 O3 ) [17]. These species generate radicals according
to the reactions in Eqs. (13.1) and (13.2); moreover, for relatively high concentra-
tions of S2 O⋅−
3 , hydroxyl radicals are also generated (Eq. (13.3)), which initiate the
polymerization [9a].
⋅−
8 → 2SO4
S2 O2− (13.1)
⋅− ⋅−
8 + S2 O3 → 2SO4 + S2 O3 + SO4
S2 O2− 2− 2−
(13.2)
SO⋅−
4 + H2 O → HSO4 + HO
− ⋅
(13.3)
The redox-initiated RAFT polymerization of acrylamide (AM) and N-isopropy-

lacrylamide (NIPAM) was conducted in triple-distilled water in the presence of a
water-soluble trithiocarbonate CTA [17]. In the case of AM, a phosphate buffer was
employed to prevent hydrolysis of monomer and CTA. A control experiment proved
that the K2 S2 O8 –Na2 S2 O3 redox system was not able to oxidize the CTA at room
temperature. Almost quantitative conversion of NIPAM was obtained in six hours,
giving a polymer with M n = 4 × 104 g mol−1 , in agreement with the theoretical value,
and D- = 1.05. The chain extension of a PNIPAM macro(CTA) confirmed the preser-
vation of chain end functionalities. The redox-initiated RAFT polymerization of AM
was slower (88% conversion in 20 hours) but well controlled. By increasing the tem-
perature to 45 ∘ C, 80% conversion was reached in two hours, while retaining the
polymerization control.
Destarac and coworkers reported the redox-initiated aqueous RAFT/macromole-
cular design by interchange of xanthate (RAFT/MADIX) polymerization of various
acrylamides with a xanthate CTA at 10 ∘ C [18]. The redox initiator pair was com-
posed of ammonium persulfate as an oxidant and sodium formaldehyde sulfoxylate
dihydrate as a reducing agent. Homopolymers and block copolymers with M n up to
106 g mol−1 and D- < 1.32 were obtained, and quantitative monomer conversion was
observed within two hours, by using relatively high concentrations of monomers
and a very small amount of CTA (Figure 13.1).
Various aqueous dispersion RAFT polymerizations were carried out with redox
initiation systems based on persulfates, combined with a bisulfite or ascorbate salt as
a reducing agent [19]. By using a low concentration (0.02 mol% relative to monomer)
of KPS and sodium ascorbate (NaAs) in equimolar amount, RAFT dispersion poly-
merization of 2-methoxyethylacrylate (MEA) was carried out at T = 30 or 40 ∘ C with
a poly(ethylene glycol) methyl ether methacrylate (PPEGMA) as macro(CTA) [19b].
The dispersion polymerization was faster than a corresponding RAFT polymeriza-
tion in dimethylformamide (DMF) at T = 70 ∘ C with a conventional thermal ini-
tiator. PPEGMA-b-PMEA copolymers prepared in dispersed media showed lower
Mn,sec = 1.02 ×106 g mol–1 Mn,sec = 1.3 × 104 g mol–1
Ð = 1.51 Ð = 1.17
Mn,th = 2 ×105 g mol–1 P(NIPAM-block-DMA) PNIPAM-XA1
Mn,th = 4×105 g mol–1
Mn,th = 6 ×105 g mol–1
Mn,th =1 ×106 g mol–1
Xanthate free polym.
25 30
15 20 25
(a) Retention time (min)
(b) Retention time (min)
Figure 13.1 GPC traces of (a) PAM synthesized via redox-initiated RAFT/MADIX polymerization at T = 10 ∘ C and (b) PNIPAM-b-PDMA. Source: Adapted
with permission from Read et al. [18]. Copyright 2014, Royal society of chemistry.
dispersity compared to the one prepared in solution, likely because of the decreased
chain transfer to polymer at low temperatures.
The KPS/NaAs redox initiator system was also used for aqueous RAFT cryopoly-
merizations, in which the polymerization mixture was cooled at a temperature
lower than its freezing point, thus forming a heterogeneous system composed
of an ice phase and a monomer-containing liquid microphase [20]. Well-defined
homopolymers and copolymers of N,N-dimethylacrylamide (DMA) and NIPAM
were synthesized with a water-soluble trithiocarbonate CTA at −15 ∘ C. Cryogels
were also prepared by exploiting the porogenic effect of ice crystals in the poly-
merization medium and using a disulfide crosslinker to allow for a subsequent
chemical degradation. Redox-initiated RAFT cryopolymerization was extended to
organic solvents by using cumene hydroperoxide (CHP) and ascorbic acid (AsAc)
as redox initiators [21]. Well-controlled homo- and copolymerizations of several
acrylates and acrylamides have been reported in frozen 1,4-dioxane at −5 ∘ C.
The combination of organic hydroperoxides as oxidants and ascorbic acid as a
reducing agent has been used to initiate aqueous RAFT polymerization under var-
ious conditions. The RAFT/MADIX polymerization of N-vinyl pyrrolidone (NVP)
was reported in water at T = 25 ∘ C using tert-butyl hydroperoxide (tBuOOH) and
AsAc [22]. This redox couple enabled polymerization at a pH = 6.5, which decreased
the extent of side reactions between NVP and water compared to more acidic con-
ditions. At ambient temperature, the hydrolysis of terminal groups was success-
fully prevented [23], thus obtaining PVP and PAM-b-PVP block copolymer with
M n up to 1.2 × 104 g mol−1 and D - < 1.3. Perrier and coworkers used tBuOOH/AsAc
redox-initiated aqueous RAFT polymerization to synthesize multiblock copolymers
via a one-pot sequential monomer addition approach, without intermediate purifi-
cations [24]. Despite relatively high amounts of tBuOOH being used with monomers
owing to relatively low propagation rate constants, well-defined multiblock copoly-
mers (with 4–10 blocks) were prepared with different combinations of acrylates,
acrylamides, and acidic monomers. Minimal polymer branching and hydrolysis of
chain ends were observed by working at room temperature.
More recently, a Fenton reaction was exploited by Qiao and coworkers to develop
a catalytic redox initiation system for RAFT polymerization, which provided high
polymerization rates [7]. Typical Fenton’s reagents are ferrous ions (Fe2+ ) and H2 O2 ,
which in water generate oxidizing hydroxyl radicals through the reactions shown in
Eqs. (13.4) and (13.5) [7, 25]:
Fe2+ + H2 O2 −−−−→ Fe3+ + OH⋅ + OH− (13.4)
Fe3+ + H2 O2 −−−−→ Fe2+ + OH⋅2 + H+ (13.5)

OH⋅ is a non-specific highly reactive radical, which can therefore cause several unde-
sired reactions, particularly at high concentration of H2 O2 and Fe2+ .
The relative concentration of these two species was first optimized for the
Fenton–RAFT polymerization of DMA in water in the presence of a water-soluble
trithiocarbonate CTA. The optimal ratio of 3 : 1 [H2 O2 ]:[Fe2+ ] gave 85% monomer
conversion in only five minutes, yielding PDMA with MW matching the theoretical
value and D- = 1.04. Importantly, oxidation of Fe2+ to Fe3+ by oxygen or impurities

was carefully avoided because Fe3+ can inhibit the polymerization.
Control experiments in the absence of the Fenton’s reagents or the CTA, either
gave no monomer conversion or resulted in gelation, respectively. The target DP was
successfully increased from 50 to 400 by changing the molar ratio between monomer
and RAFT agent and increasing the amount of Fe2+ for higher DPs. A chain exten-
sion experiment and the aminolysis of the final polymer confirmed that the RAFT
end-group was not hydrolyzed by H2 O2 [26].
Poly(N-acryloylmorpholine) and poly(2-hydroxyethyl acrylate) with D - < 1.1 were
also prepared via Fenton–RAFT, reaching >60% conversion in one minute [7].
Furthermore, the Fenton–RAFT polymerization could be performed without tradi-
tional degassing: it was proposed that the Fenton reagents promoted the scavenging
of residual O2 through generation of singlet oxygen. Sequential additions of H2 O2
allowed for chemically degassing and temporally controlling the polymerization,
which stopped when all H2 O2 was consumed and restarted when a new batch was
added into the solution (Figure 13.2).
Nevertheless, because of their high and indiscriminate reactivity, the hydroxyl
radicals were rapidly consumed by many side reactions, often preventing to achieve
full monomer conversion. Therefore, a metered addition strategy was subsequently
developed, in which H2 O2 was fed into the system through a syringe pump, in
Sealed flask
O2
Chemical H2O2
H 2O 2 H degassing
2O
2
O2
2 min 1 min
O2
Fe
2+
Fe
2+
Fe2+
(a)
H2O2 H2O2 H2O2
100
Differential refractive index
2 min after 1 min after

second injection first injection
80 Mn = 25 700 Da Mn = 15 500 Da
Conversion (%)
Ð = 1.18 Ð = 1.09
60
40
20
0
0 1 2 3 4 5 6 7 8 20 22 24 26 28 30
(b) Reaction time (min) (c) Reaction time (min)
Figure 13.2 (a) Schematic of a Fenton–RAFT without traditional degassing: first, chemical
degassing by H2 O2 , followed by injection of new H2 O2 to start the polymerization;
(b) monomer conversions measured during sequential addition of H2 O2 ; (c) GPC
chromatograms at total reaction times of three and seven minutes (with c. 60% and >99%
conversion, respectively). Source: Reproduced with permission from Reyhani et al. [7].
order to control the radical concentration profile [27]. By using the Fenton–RAFT
of DMA with a water-soluble trithiocarbonate CTA as a model system, quantita-
tive and fast polymerization was obtained with relatively high concentrations of
Fenton’s reagents (e.g. [DMA]:[CTA]:[Fe2+ ]:[H2 O2 ] = 200 : 1 : 1 : 3). Decreasing the
concentrations of Fenton’s reagents and increasing the feeding time reduced the
polymerization rate but provided improved control. Induction periods observed for
relatively low doses of H2 O2 suggested that a threshold amount of H2 O2 was needed
to start the polymerization.
The control over MW, MW distribution, and dispersity did not depend on the feed-
ing strategy: indeed, the continuous supply of radicals served to reactivate the chains
trapped by the CTA, which was primarily responsible for the polymerization control.
Moreover, the polymer properties only slightly changed with a non-linear H2 O2 feed-
ing profile, suggesting that the radical concentration was approximately constant
because both the radical flux and the extent of side reactions increased with increas-
ing dosing rate.
Following these reports on Fenton–RAFT polymerization, a ‘solvent-initiated’
RAFT was proposed, in which ‘non-fresh’ THF and 1,4-dioxane were used
as both solvents and initiators for the RAFT polymerization of DMA and
N-acryloylpyrrolidine [28]. The authors proposed that a Fenton-like process
was occurring because of the presence of metal traces in the solvents, together
with the hydroperoxides that typically form over time by autoxidation reaction in
cyclic ether-based solvents. This process formed oxygen-centred radicals that could
abstract a hydrogen from another ether molecule, generating a carbon-centred
radical that could attack the C—S double bond of the CTA. Homo- and block
copolymers were obtained with acceptable control, when the estimated hydroper-
oxide content was <100 ppm. End-group analysis confirmed the presence of a few
chains initiated by ether-based radicals.
A Bio-Fenton–RAFT polymerization was reported by using haemoglobin (Hb)
as a source of iron and glucose oxidase (GOx) to enzymatically produce H2 O2 in
situ by catalyzing the reaction between O2 and glucose [29]. The Bio-Fenton–RAFT
polymerization of DMA with a trithiocarbonate CTA in a non-degassed flask was
slower than a Fenton–RAFT (i.e. with a Fe2+ salt) under otherwise similar con-
ditions. However, almost quantitative conversion was obtained in <8 hours, with
MW matching the theoretical value and D - < 1.1. Similar results were obtained with
different target DPs and acrylates or other acrylamides, paired with suitable CTAs.
Both commercial bovine Hb and bovine blood were successfully used as a Fe source,
with the polymerization rate depending on the actual concentration of red blood
cells.
A colorimetric assay showed that radicals were steadily, albeit relatively slowly,
generated after a short induction period. Therefore, the slow radical generation by
Hb was further exploited to prepare ultra-high molecular weight (UHMW) PDMA
by simply adjusting the [DMA]:[CTA] ratio [30]. Indeed, the synthesis of UHMW
polymers is based on enhancing the ratio between the rate of propagation and
termination [31]. The very low concentration of radicals in the Bio-Fenton–RAFT
of DMA drastically suppressed the termination reactions, thus enabling to obtain
S S
R HO OH
S Z S S UHMW polymers
Gluconic acid O2 O O
N O
GOx
Fenton S
reaction + R Z
S
D-Glucose H2O2 + FeII FeII + OH– + OH•
(A) H2O, r.t.
2+
5 [Fe2+]0 (mM) Polymerization time [Fe ]0 = 1.0 mM
5 min
0.0 15 min
Light scattering
4 0.1 30 min
ln [M]0/[M]t
1.0 45 min
3.0 60 min
3 10.0 75 min
2
Semi bio-Fenton RAFT
1
0
0 15 30 45 60 75 14 16 18 20 22 24 26 28 30
(a) Polymerization time (min) (b) Retention time (min)
1000 1.8
Mn,SEC/LS
Ð
Mn,SEC/LS (kg mol–1)
800 1.6
600
Mn,th. 1.4
Ð
400
1.2
200
1.0
0
0 20 40 60 80 100
(c) Conversion (%)
(B)
Figure 13.3 (A) Mechanism of semi-bio-Fenton RAFT polymerization. (B) (a)

Semi-logarithmic kinetic plot of semi-bio-Fenton RAFT polymerization of DMA with
different [Fe2+ ] and (b) GPC traces and (c) MW and dispersity evolution for the DMA
polymerization with [Fe2+ ] = 10−3 M. Other conditions: [GOx] = 250 nM, [D-glucose] = 0.1 M,
open-to-air vessel. Source: Adapted with permission from Reyhan et al. [30]. Copyright
2019, John Wiley & Sons.
PDMA with MW between 8.9 × 105 and 1.2 × 107 g mol−1 (M w values from static
light scattering measurements), in good agreement with theoretical values, in
48 hours.
Aiming to reduce the polymerization time, Hb was replaced with ammonium
ferrous sulfate (Semi Bio-Fenton RAFT, Figure 13.3). The concentration of Fe2+
was adjusted to reach almost quantitative conversion in two hours (Figure 13.3a).
Relatively high concentrations of Fe2+ led to precipitation of Fe(OH)3 and conse-
quently halting the polymerization because of the lack of Fe2+ in solution. The
livingness of the process was confirmed by two consecutive chain extensions
of a PDMA–macro(CTA) with DMA, providing a semi-triblock copolymer
with M w = 2.2 × 106 g mol−1 . The upper limit observed in the final M w (about
2 × 107 g mol−1 ) was attributed to the very low concentration of RAFT agent to
ensure the control when targeting DP > 200 000. Finally, the GOx/glucose system
was replaced with feeding H2 O2 through a syringe pump. By adjusting the feeding
rate to match the rate of radical generation in the enzymatic system, similar control
over the polymerization was achieved in a regularly degassed flask.
The enzymatic degassing by GOx was also combined with a redox initiation by
introducing in solution AsAc as a reducing agent for the H2 O2 generated by con-
sumption of the solubilized O2 . The redox couple initiated aqueous RAFT poly-
merizations of DMA in open air [32]. The use of enzymes as deoxygenating agents
and biocatalysts for RDRPs is gaining increasing attention [33]. Enzymatic cascades
were effectively used to initiate RAFT polymerizations under bio-relevant condi-
tions; however, discussion of enzyme-initiated RAFT polymerization is beyond the
scope of the present chapter.
13.3 Chemical Activation of RAFT Agents

Atom transfer radical polymerization (ATRP) is another powerful and versatile
RDRP technique [34, 35]. In ATRP, the dynamic equilibrium between propagating
radicals and dormant species is regulated by a transition metal catalyst, typically
a Cu complex with a polydentate amine ligand (L). The active catalyst, CuI L+ ,
reductively cleaves the carbon–halogen (C—X) bond in the initiator or dormant
species, thus generating propagating radicals and the deactivator XCuII L+ , which
reverts the radicals back to dormant species.
Because ATRP is based on a reversible deactivation mechanism, no external source
of radicals is required to initiate the polymerization, and thus no new chains are gen-
erated. This raised the question whether ATRP catalysts could activate alkyl pseu-
dohalides (i.e. RAFT agents) and how this reaction will affect the polymerization
mechanism. As a consequence, traditional ATRP catalysts have been combined with
CTAs both in the absence and presence of ATRP initiators, with the purpose of
avoiding the need of external radical sources, thus preventing the generation of new
chains during polymerizations [6]. Moreover, the synergistic interaction between
ATRP and RAFT can lead to improved control because of the deactivation/exchange
by both Cu(II) species and CTAs [36].
Several ATRP catalysts were initially used for the polymerization of STY and
MMA in the presence of various alkyl diethyldithiocarbamate (DC) species, which
served as RAFT agents and ATRP initiators as alkyl pseudohalides. Mechanistic
studies and end-group analysis showed that the process was a conventional ATRP
where the DC species acted as an alkyl pseudohalide initiator, and thus, DC-capped
chains were obtained (Scheme 13.2a) [37]. The trend in catalyst activity towards
DCs was different than towards conventional alkyl halide ATRP initiators. In
general, CuX/N,N,N ′ ,N ′′ ,N ′′ -pentamethyldiethylenetriamine (PMDETA) allowed
for better controlled polymerizations. Well-defined polymers were obtained in
<3 hours, at elevated temperatures and with an equimolar amount of Cu catalyst
ATRP with alkyl pseudohalide initiators

Termination
KATRP S S
•
NC EtOOC
Pn- DC + CuIL+ DC -CuIIL+ + Pn
S
S N N
+M
Propagation
(a) DC = dithiocarbamate anion
Concurrent ATRP/RAFT
O S O
+M +M O O
•
O S S O
Pn-S(CS)Z + Pm Pm-S(CS)Z + Pn• Br O O Br
II
DiBrTTC
+ Cu /L
Termination S
(b) + CuI/L
S
Dual concurrent ATRP/RAFT
CDB
Pm-Br Pn-Br
L: N N
Br-CuIIL+ CuIL+ Br-CuIIL+ CuIL+ N
N
N
C6H19 C6H19
PMDETA dNbpy
•
+ Pn-S(CS)Z Pm-S(CS)Z + Pn• +M
+M Pm N
+ CuII/L + CuII/L N N
Termination N
N
+ CuI/L + CuI/L N
N TPMA
N
(c) Me6TREN
Scheme 13.2 Mechanism of (a) ATRP with dithiocarbamates as alkyl pseudohalides;

(b) concurrent ATRP/RAFT; and (c) dual concurrent ATRP/RAFT (equilibria in grey marginally
contribute to the polymerization). On the right: examples of CTAs used in these processes.
Dashed square: structures of commonly used ATRP ligands.
and DC initiator. Electrochemical characterization showed that Cu/L complexes

with a coordinated DC group were reduced at more negative potentials than in
the case of coordinated Br− or Cl− ions. Thus, DC anions have strong affinity for
CuII L2+ and form more reducing Cu complexes. Because higher reducing power
typically results in higher ATRP activity, CuII L2+ complexes with DC anions could
result in faster polymerization; however, the strong interaction between DC− and
CuII L2+ could decrease the deactivation efficiency [38]. The combination of these
two aspects likely caused the different trend in polymerization control compared to
conventional ATRP with halide ions.
A first concurrent ATRP/RAFT was developed by using a dibromotrithiocarbon-
ate (DiBrTTC) initiator (Scheme 13.2b), CuBr/PMDETA, or CuBr/4,4′ -dinonyl-2,2′ -
bipyridine (dNbpy) as a catalyst and n-butyl acrylate (BA), MMA, and STY as
monomers under various conditions [39]. After polymerizations, aminolysis
and methanolysis of the polymers confirmed that chain growth occurred both
through the bromine chain end and the TTC moiety. However, because DiBrTTC
was an inefficient CTA in the RAFT polymerization of MMA, this result proved
that the Cu complexes could activate the TTC chain end similar to the case of
dithiocarbamates.
Dithioester CTAs could also be activated by Cu complexes [40]. Indeed, the

concurrent ATRP/RAFT of STY and MMA was reported by using cumyl dithioben-
zoate (CDB, Scheme 13.2) as alkyl pseudohalide. Well-defined PMMA, PSTY,
and PMMA-b-PSTY block copolymers were prepared in anisole at 80–100 ∘ C
with CuBr/PMDETA and CuBr/tris[2-(dimethylamino)ethyl]amine (Me6 TREN).
Polymerization rates increased when Cu(0) was added to regenerate the Cu(I)
activator from the accumulated Cu(II) species. High MW PMMA was prepared
by adjusting the [MMA]:[CDB] ratio and decreasing the amount of Cu catalyst
(0.1 equiv relative to CDB) in the presence of Cu(0) as a reducing agent, as in
activators regenerated by electron transfer (ARGET)–ATRP conditions. PMMA
with M n > 106 g mol−1 and D - < 1.3 was synthesized under similar conditions with
CuBr/tris(2-pyridylmethyl)amine (TPMA), Cu(0), and CDB [41]. Moreover, the
PMMA-b-PSTY block copolymer synthesized by concurrent ATRP/RAFT exhibited
higher retention of chain end functionality as compared to the same copolymer
prepared by RAFT polymerization with thermal initiation (Figure 13.4).
In order to better exploit the degree of control offered by the fast chain transfer
between propagating radicals and (macro)CTA, the concurrent ATRP/RAFT of STY
and MMA was also carried out with Cu complexes that are inefficient ATRP cata-
lysts [42]. Indeed, Cu(II) complexes with macrocyclic and anionic ligands are poor
deactivators in ATRP [38]. However, when combined with CDB, well-controlled con-
current ATRP/RAFT was observed under ARGET or conventional ATRP conditions.
The controlled polymerization of acrylate monomers required the development
of a dual concurrent ARGET–ATRP/RAFT (Scheme 13.2c), in which a conventional
PMMA-b-PSt
(by RAFT/V-40)
PMMA-SCSPh Conv = 50.1%
(by RAFT/V-40) Mn = 40 900, Mw/Mn = 1.32
Mn = 8800, Mw/Mn = 1.22
PMMA-b-PSt
PMMA-SCSPh (by RAFT/CuBr)
(by RAFT/CuBr) Conv = 48.4%
Mn = 8300, Mw/Mn = 1.23 Mn = 50 600, Mw/Mn = 1.20
103 104 105

Molecular weight
Figure 13.4 GPC traces of PMMA-S-C(S)-Ph macroinitiators (broken lines) and

PMMA-b-PSTY (right side, solid lines) synthesized via conventional RAFT polymerization
(red) and concurrent ATRP/RAFT (blue). Conditions: 50% STY in anisole, T = 80 ∘ C.
[STY]:[macroinitiator]:[V-40] = 1000 : 1 : 2 (RAFT), [STY]:[macroinitiator]:[CuBr2 ]:
[PMDETA]:[Cu(0)] = 1000 : 1 : 20 : 30 : 10 (concurrent ATRP/RAFT). Source: Reproduced with
permission from Kwak et al. [40]. Copyright 2008, American chemical society.
0.9
0.8
0.7
0.6
ln([M]0/[M])
0.5
0.4
0.3
50% ARGET
0.2 DP = 5000
DP = 500
0.1
0.0
0 5 10
(a) Time (h)
1.6
1.5
Mw/Mn
1.4
1.3
1.2
300 1.1
Mn (kg mol−1)
50% ARGET
DP = 5000
200 DP = 500
100
0
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
(b) Conversion
Figure 13.5 (a) Semi-logarithmic kinetic plots and (b) MW and dispersity evolution with
conversion of dual concurrent ATRP/RAFT at targeted DP = 5000 (black) and DP = 500 (red).
Conditions: 50 vol% MA in anisole, T = 50 ∘ C, [EBiB]:[CDB] = 1, [TPMA]:[CuBr2 ] = 3, and Cu(0)
wire (L = 20 cm, d = 1 mm). Source: Reproduced with permission from Elsen et al. [43].
Copyright 2011, American chemical society.
alkyl halide ATRP initiator was used together with a Cu catalyst, Cu(0), and a CTA
[43]. Well-defined PMA was obtained at both target DP 50 and 5000 (Figure 13.5).
Interestingly, by varying the molar ratio between ATRP initiator and CTA, it was
observed that higher amounts of CTA afforded slower polymerizations, but the pre-
pared polymers had lower dispersity, particularly at the early stage of the process.
Afterwards, it was reported that a dual concurrent ATRP/RAFT polymerization of
PEGMA in water was faster than in the absence of an ATRP initiator (i.e. concur-
rent ATRP/RAFT) [44]. This trend was observed at different temperatures (T = 30
and 90 ∘ C), with a 1 : 2 ratio between alkyl halide and CTA, and FeIII Cl3 ⋅H2 O/PPh3
as a catalyst.
A similar system composed of an alkyl halide and a dithiobenzoate CTA was used
in the presence of Cu wire and an amine ligand [36, 45]. Dimethylsulfoxide (DMSO)
was typically used as a solvent, and well-controlled room temperature polymeriza-

tions of STY, N-vinylcarbazole, and various methacrylates were demonstrated [46].
Noticeably, when the ratio between alkyl halide and CTA was decreased, polymer-
izations were slower and better controlled, similar to the dual concurrent system.
A transition-metal-free activation of RAFT agents was developed by employing
sodium sulfite salts, mainly sodium dithionite (Na2 S2 O4 ) [47]. The proposed reac-
tion mechanism (Scheme 13.3) involved (i) the thermal dissociation of dithionite
anions to SO2 − , (ii) the injection of one electron from SO2 − to the CTA, and (iii)
the dissociative electron transfer (DET) of the RAFT agent, which was reduced to
a radical anion that fragmented into a propagating radical and an anion. The latter
reaction was supported by density functional theory (DFT) computation of energy
states. The process was therefore called DET–RAFT polymerization.
S2O42– 2SO2– (1)
S – S –•
+ SO2 + SO2 (2)
S–R S–R
S +nM
+ R+ kp Pn• (3)
–
S
+nM S S–R S +nM

•
P• kp + + R+ kp
n
S–R (4)
S–Pn S–Pn
Scheme 13.3 Proposed mechanism of DET−RAFT polymerization using a dithiobenzoate

CTA and a dithionite salt.
Control experiments showed that Na2 S2 O4 could initiate the polymerization of
MMA in the absence of a CTA, but the process was extremely slow, and therefore,
its contribution in the presence of a CTA was neglected. In the DET–RAFT poly-
merizations of MMA using a dithiobenzoate CTA, the reaction rate was observed to
increase with increasing [Na2 S2 O4 ], but the match between theoretical and experi-
mental MW was poorly controlled. Several other methacrylates, as well as MA and
STY, were polymerized with good control, but the reactions required 3–10 days to
reach 36–53% monomer conversion.
13.4 Electrochemical Activation of RAFT Agents

Electrochemically triggered controlled polymerizations benefit from easily tunable
parameters, ‘green’ character, and in situ monitoring of polymerization systems [48].
In electrochemically mediated atom transfer radical polymerization (eATRP), elec-
trochemical stimuli (i.e. applied current or potential) are used to reduce the ATRP
deactivator, XCuII L+ , to the active catalyst CuI L+ , which reductively cleaves the
dormant species to generate propagating radicals [49]. However, by modifying the

stimulus (i.e. by applying an oxidative current/potential), all Cu species can be
converted to the XCuII L+ deactivator, thus stopping the polymerization on-demand.
Electrochemical oxidation of a CTA in the presence of a mediator has been recently
used to trigger controlled cationic polymerization of vinyl ethers [50]. In addition,
electrochemical reduction of CTAs or external radical initiators was explored as an
approach towards an electrochemically mediated RAFT polymerization.
13.4.1 Electrochemistry of RAFT Agents

The development of electrochemical methods to initiate and trigger RAFT polymer-
izations required a careful analysis of the redox properties of RAFT agents. The
library of available RAFT agents is vast, as well as the mechanistic information about
the performances of CTAs under polymerization conditions [1f]. Conversely, the
electrochemical properties of these species are nearly unexplored. The advent of
PET–RAFT has raised interest in measuring the redox potentials of RAFT agents in
order to pair them with suitable photoredox catalysts [4]. However, this brief analysis
concerned only a few RAFT agents.
More extensive electrochemical characterizations of some dithiobenzoates and
trithiocarbonates can be found in the literature of organic electrochemistry. Lund
and coworker and Savèant and coworkers conducted bulk electrolysis and voltam-
metric analysis of various thiocarbonylthio compounds, aiming to define the mech-
anism and the products of the electro-reduction of these species [51].
The dithiobenzoates analyzed by Lund and coworker had C6 H5 -C(S)-SR structure
with R = C6 H5 , 4-ClC6 H4 , C6 H5 CH2 , (CH3 )3 C, CH3 [51b]. In cyclic voltammetry
(CV), all these compounds exhibited a reduction signal with cathodic peak potential
Epc < −1 V vs. saturated calomel electrode (SCE) because of the reduction to the
corresponding radical anions [C6 H5 CSSR]⋅− . The CVs were conducted in DMF
on a platinum electrode. The cathodic peak was irreversible at a scan rate below
0.2 V s−1 , likely because of a rapid subsequent dimerization of the electro-generated
[C6 H5 CSSR]⋅− . The dimerization reaction was supported by the observation of a
negative shift of the Epc values when increasing the compounds’ concentration
(dEpc /d log C = −0.02 V decade−1 ). It should be noted that such a negative shift
was not observed for most commonly used RAFT agents in more recent analyses
[8b, d]. Constant potential electrolysis followed by chromatographic analysis
yielded diphenylacetylene and thiolates as most abundant products [51].
Similarly, the CVs of analyzed trithiocarbonates (RS-C(S)-SR with R = CH3 , C2 H5 ,
and (CH3 )2 CH) exhibited a cathodic peak because of the formation of [RSCSSR]⋅−
[51a, c]. The peak was irreversible at a scan rate <1 V s−1 on a mercury drop elec-
trode in DMF. The analysis of reduction products after constant potential electrolysis
showed that the initial compounds were further reacting with some products, in
overall complicated reduction mechanisms.
Although the compounds analyzed by Lund et al. were different from tradi-
tionally used RAFT agents, their study suggests that (i) the electro-reduction of
dithiobenzoates and trithiocarbonates generates their corresponding radical anions
Dithiobenzoates (DB)
S S S
CN
OH
S CN S S
O
DB-3CN DB-3Bz DB-3CN,A
Trithiocarbonates (T)
S S S S
CN
OH
10 S S CN 10 S S CN 10 S S 10 S S
O O
T12-1CN T12-3CN T12-3CN,A T12-2A
OH
S S S
OH
10 S S 2 S S S S
O
T12-3A T4-2Bz T-(2Bz)2
Dithiocarbamates (DC) Xanthate (X)

S S S S
O
N S CN N S CN N S CN O S
O
DCPh-1CN X-2E
DCPyr-1CN DCPyr-3CN
N N
Figure 13.6 Molecular structures of electrochemically characterized RAFT agents. Source:

Adapted with permission from Lorandi et al. [8b]. Copyright 2019, American chemical
society.
and (ii) the radical anions are unstable and involved in subsequent chemical
reactions.
Aiming to investigate compounds more relevant to RAFT polymerizations, we
recently performed a voltammetric analysis of the RAFT agents in Figure 13.6 [8b].
In order to facilitate the identification of structure–reactivity relationships, a unified
nomenclature is proposed to identify the CTAs. Considering their general structure
as Z-C(S)-SR (or Z(CS)SR), the RAFT agents were coded with a first group of char-
acters identifying the Z group, followed by a dash, followed by a second group of
characters identifying the R group (i.e. Z–R). The Z groups were subdivided into four
categories, namely, dithiobenzoates (DBs), trithiocarbonates (T), dithiocarbamates
(DC), and xanthates (X). For trithiocarbonates, the subscripts T4 and T12 indicated
a Z group with a butyl or a dodecyl alkyl chain, respectively. For dithiocarbamates,
DCPyr and DCPh indicated the presence of a pyridyl or a phenyl ring, respectively.
Concerning the R group, the numbers 1, 2, and, 3 identified primary, secondary, and
tertiary structures. Then, a superscript abbreviation indicated the nature of func-
tional groups present in the R fragment: CN = cyano, Bz = benzyl, A = acidic car-
boxyl group, and E = ester.
The CVs of the RAFT agents were conducted on a glassy carbon (GC) electrode
in DMF, and the general recorded pattern is shown in Figure 13.7. In agreement
with the observations of Lund et al., the cathodic peak in region A was attributed
to the generation of the radical anion [Z(CS)SR]⋅− . When the scan was extended
20
C
10
0
–10
–20
I (μA)
–30
–40
–50
–60 A
–70
B
–80
–3.0 –2.5 –2.0 –1.5 –1.0 –0.5 0.0 0.5 1.0 1.5
E vs. SCE (V)
Figure 13.7 Cyclic voltammetry of 2 × 10−3 M DB-3CN,A in DMF + 0.1 M Et4 NBF4 recorded
on a GC disk at scan rate = 0.2 V s−1 and T = 25 ∘ C. The letters A, B, and C denote regions
common to all RAFT agents in Figure 13.6. The dashed line represents an oxidative scan
not preceded by the reduction of the CTA, i.e. with initial potential −0.5 V vs. SCE. Source:
Reprinted with permission from Lorandi et al. [8b]. Copyright 2019, American chemical
society.
to more negative potentials, several peaks were recorded (region B), indicating that
the overall reduction process involved various reactions and products. Finally, when
reversing the scan, an anodic irreversible peak was observed in the potential range
0.3–0.5 V vs. SCE (region C). The peak was proposed to derive from the oxidation of
some thiolates (RS− ) to disulfides because RS− was observed as a reduction product
by Lund et al. and the oxidation of RS− was previously reported to occur at a similar
potential range.
All compounds, with the exception of T12 -2A and T12 -3A , exhibited one irre-
versible reduction peak at any tested scan rate (0.02–20 V s−1 ). This indicates that
the electro-generated [Z(CS)SR]⋅− was rapidly involved in one or more chemical
reactions, which prevented the observation of the oxidation signal for [Z(CS)SR]⋅−
when the scan direction was reversed. T12 -2A and T12 -3A exhibited two irreversible
reduction peaks, likely because of a ‘father–son’ interaction (i.e. the reaction of an
electro-generated product with the initial compound). Indeed, it was postulated
that the electro-generated [Z(CS)SR]⋅− was rapidly protonated by the carboxylic
group of the initial CTA molecule, and the resulting radical was further reduced at
the electrode (i.e. self-protonation reaction).
The onset potential (Eonset ) of the reduction of analyzed RAFT agents and the
corresponding Epc are listed in Table 13.1. Epc values decreased in the order:
dithiobenzoates > trithiocarbonates > dithiocarbamates ≈ xanthates. For each Z
group, Epc depended on the nature of the R group, with more positive values
observed for tertiary R groups, followed by secondary, then primary R groups.
Moreover, electron-withdrawing substituents in the R group shifted Epc to more
positive values because of the increased stability of the corresponding radicals. The
Table 13.1 Onset potential values for the reduction of electrochemically characterized
RAFT agents in DMF on a GC electrode, at T = 25 ∘ C.a)
RAFT agent E onset (V vs. SCE) E pc (V vs. SCE)
Dithiobenzoates DB-3CN −0.887 −1.000

DB-3Bz −1.044 −1.150
CN,A
DB-3 −0.826 −0.940
Trithiocarbonates T12 -1CN −0.987 −1.220
CN
T12 -3 −1.118 −1.092
T12 -3CN,1 −1.101 −1.050
A
T12 -2 −0.927 −1.338 (−1.691)
T12 -3A −1.216 −1.228 (−1.556)
T4 -2Bz −1.377 −1.500
Bz
T-(2 )2 −1.286 −1.437
Dithiocarbamates DCPyr -1CN −1.378 −1.513
CN
DCPyr -3 −1.285 −1.455
DCPh -1CN −1.716 −1.898
E
Xanthate X-2 −1.652 −1.812
a) 0.1 M Et4 NBF4 was used as a supporting electrolyte. 2 × 10−3 M CTA, scan rate = 0.2 V s−1 .
Eonset was measured as the intersection between the tangent to the baseline and the tangent to
the reduction peak. The quasi-reference electrode used in the study was composed of Ag|AgI|
(0.1 M n-Bu4 NBI in DMF). Ferrocene was used as an internal standard to refer the potential
values to SCE, according to the conversion factors in the literature [52].
Source: Lorandi et al. [8b]. © 2019, American chemical society.
observed trends were further confirmed by electrochemical characterizations of a

larger pool of RAFT agents [8d].
The solvent nature and electrode materials affected the voltammetric response of
the RAFT agents. In CH3 CN, the measured Epc values were generally 20–200 mV
more negative than in DMF. Electrode materials other than GC were partially
passivated during the reduction process, thus resulting in the Epc values shifting
to more negative potentials and poor reproducibility among consecutive potential
cycles. Indeed, different potential values and even reversible voltammetric signals
were previously reported for a few RAFT agents in different reports [4a, 53], likely
because of the poor reproducibility of this measurement on Pt electrodes. Therefore,
GC electrodes are recommended for electrochemical analysis of RAFT agents.
Bulk electrolysis of some RAFT agents performed at an applied potential
Eapp = Epc in the absence and presence of excess acid showed that (i) the C—S bond
between the Z(CS)S unit and the R group was reductively cleaved in accordance
with DFT analysis and (ii) reduction products reacted with initial compounds
(father–son and grandfather–grandson interactions) in a multistep reduction
process [8b, 54].
13.4.2 Direct and Mediated Electro-reduction of RAFT Agents

Common RAFT agents were observed to form short-lived radical anions upon elec-
trochemical reduction [8]. This means that the initial RAFT agent is irreversibly
lost after being electro-reduced. As a consequence, an eRAFT process in which rad-
icals are generated by directly reducing the RAFT agent at the electrode surface
(Scheme 13.4a) appears unlikely because the RAFT agent is invariably consumed,
thus challenging the polymerization control.
S M = monomer Z(CS)SPi = (macro)CTA

Pi = polymer chain Med = mediator
Pn
Z S
e–
• – S
S S S
Pm
Pn Z S Pn
Z S Z S–+ Pn• Z S + Pm•
(a) M M
S
Medox Pn
Z S
e–
•–
S
S S Pm S
Z S
Medred Pn Pn •
Z S Z S–+Pn• Z S + Pm
(b) M M
Mediators (organic):
CN NO2
NH N
NO2 N HN
3-Nitrobenzonitrile 2-Nitro-m-xylene
Tetraphenylporphyrin
(c) (TPP)
Scheme 13.4 Envisioned mechanisms of electrochemically mediated RAFT polymerization

via direct (a) and mediated (b) electrolysis of a CTA. (c) Organic molecules tested as
mediators for eRAFT polymerizations. Source: Adapted with permission from Lorandi et al.
[8b]. Copyright 2019, American chemical society.
The rather negative cathodic peak potentials of RAFT agents made necessary to
investigate the stability of other species in a RAFT system under the application of
such reducing potential values. CV of commonly employed monomers in RDRPs
showed that their reduction typically occurs at potential values more negative than
−1.7 V vs. SCE (in DMF, Table 13.2). Therefore, most monomers will be electrochem-
ically stable during the reduction of the vast majority of analyzed RAFT agents.
However, the direct electro-reduction of RAFT agents can produce a locally high
concentration of radicals in the proximity of the electrode surface. It was previously
Table 13.2 Cathodic peak and onset potential value for the reduction of common
monomers and standard reduction potentials of the corresponding radicals to carbanions
measured in DMF at T = 25 ∘ C.a)
𝛉
Monomer Eradical (V)b) E pc (V)c) E onset (V)d)
n-Butyl acrylate −0.63e) −2.18 −1.74

Methyl methacrylate −0.91 −2.28 −1.97
Styrene −1.53 −2.57 −2.23
a) 0.1 M Et4 NBF4 was used as supporting electrolyte, scan rate = 0.2 V s−1 . All potentials are
referred to SCE.
b) From [55].
c) Measured with 10 mM monomer.
d) Measured for 50 vol% monomer as the potential at the intersection between the tangent to the
baseline and the tangent to the reduction signal.
e) For methyl acrylate radical.
reported that the propagating radicals of common monomers are reduced to

carbanions at potentials more positive than the Epc of many RAFT agents [56]. In
particular, MA, MMA, and acrylonitrile radicals had standard reduction potentials
(Eθ ) between −0.63 and −0.91 V vs. SCE (Table 13.2). Consequently, if an eRAFT
polymerization of one of these monomers is attempted by applying a potential
Eapp = Epc (CTA), the propagating radicals formed near to the electrode surface will
be rapidly reduced to carbanions.
Radicals generated from similar monomers are expected to display similar reduc-
tion potentials. Only STY radicals (Eθ = −1.53 V vs. SCE) can be preserved during
the electro-reduction of dithiobenzoates or trithiocarbonates (i.e. the styryl radical
is reduced at more negative potentials than the CTAs). Nevertheless, a few eRAFT
polymerizations of STY via direct electro-reduction of dithiobenzoate or trithiocar-
bonate CTAs at various applied potentials resulted in slow reactions and polymers
with high dispersity [8b]. Voltammetric analysis before and after the polymeriza-
tions confirmed the consumption of the RAFT agents.
In brief, an eRAFT polymerization is hampered by (i) the very short lifetime of
[Z-C(S)-SR]⋅− and their involvement in side reactions and (ii) the reduction of prop-
agating radicals to carbanions occurring at similar or more positive potentials than
the reduction of many RAFT agents (Scheme 13.5).
Therefore, it appeared necessary to develop an alternative pathway towards
eRAFT polymerization. The use of a redox active mediator is a common strategy
to convert a heterogeneous electron transfer (ET) between the electrode and the
substrate of interest to a homogeneous ET occurring in solution (Scheme 13.4b).
In order to efficiently shuttle electrons from the electrode to the solution, (i) the
𝜃
reduction potential of the mediator (EMed ) should be more positive, but relatively
close to the one of the substrate, (ii) the ET between the electrode and mediator and
between the mediator and substrate must be fast, and (iii) the reduced mediator
should not participate in side reactions (e.g. coupling with radicals, reduction of
radicals to carbanions) [57].
Xanthates
Dithiocarbamates RAFT
Trithiocarbonates agents
Dithiobenzoates
–2.6 –2.4 –2.2 –2.0 –1.8 –1.6 –1.4 –1.2 –1.0 –0.8 –0.6 –0.4
Acrylates O E vs. SCE (V)
Methacrylates O O
Styrene
O
Z(CS)S-R
Z(CS)S– + R• [Z(CS)S-R]•– + e–
+ side reactions
Scheme 13.5 Reduction potential range of typical RAFT agents, monomers, and
propagating radicals measured by cyclic voltammetry in DMF at T = 25 ∘ C. Source: Reprinted
with permission from Lorandi et al. [8b]. Copyright 2019, American chemical society.
Typical mediators for electro-reduction reactions are aromatic hydrocarbons or

transition metal complexes. A few compounds from both these classes were tested
as mediators for eRAFT polymerizations.
13.4.2.1 Organic Mediators for eRAFT Polymerizations

Small-molecule aromatic hydrocarbons such as 3-nitrobenzonitrile and 2-nitro-m-
xylene (Scheme 13.4c) were tested as mediators for the eRAFT polymerization of
STY [8b]. The CV of these mediators showed reversible signals that were modified
after the addition of the RAFT agents DB-3Bz or T4 -2Bz . Indeed, the cathodic currents
of mediators’ signals increased in intensity while the anodic currents decreased,
indicating that mediators catalytically reduced the RAFT agents. However, negli-
gible conversion or poor control were observed in the polymerization of STY, at
𝜃
Eapp ≈ EMed .
This result was attributed to a coupling reaction between the radicals in solu-
tion and the radical anions derived from the small-molecule mediators. Therefore,
tetraphenylporphyrin (TPP, Scheme 13.4c) was tested as a mediator because of a
more bulky and conjugated structure. The eRAFT polymerization of acrylates in the
presence of TPP as a mediator and T12 -2A or T12 -3A RAFT agents at room tempera-
ture gave polymers with pre-determined molecular weight and low dispersity. The
mediator loading could be decreased to 0.01 mol% relative to the CTA. However, the
polymerizations were relatively slow (<20% conversion in six hours) and voltam-
metric analysis showed that the CTA was partially lost. Anthraquinone (AQ) was
subsequently tested as mediator for eRAFT polymerization, owing to its reversible
redox chemistry and efficient electron transfer to several RAFT agents [8c]. eRAFT
polymerizations of MMA in DMSO mediated by AQ reached > 60% conversions in
24 h at room temperature. The polymerization rate strongly decreased when tar-
geting high DP (200-400). Nevertheless, PMMA with low dispersity was obtained,
indicating that the identification of suitable mediators and reaction consitions can
broaden the scope of eRAFT polymerizations.
A mediated electrolysis of RAFT agents was exploited for electro-RAFT poly-

merization catalyzed by a redox-active coenzyme, the nicotinamide adenine
dinucleotide (NADH) [53]. The electro-reduction of NAD+ to NADH promoted
the reaction of the latter with a CTA, which could generate radicals to start the
polymerization. However, repeated attempts to reproduce this system by our
group gave no monomer conversion, possibly because the NADH molecule is not
sufficiently hindered to prevent coupling with generated radicals.
In summary, eRAFT polymerizations could be conducted through a mediated
electro-reduction of RAFT agents, in which suitable mediators were employed
to transfer electrons from the electrode surface to the CTA in solutions, thus
preventing the direct electro-reduction of the CTA and a high local concentration of
radicals at the electrode. Nevertheless, efforts should be devoted to find mediators
that efficiently and rapidly exchange electrons with the CTA, without being involved
in side reactions.
13.4.2.2 Activation of RAFT Agents via Electro-reduction of ATRP Catalysts

Transition metal complexes and particularly traditional ATRP catalysts can activate
RAFT agents, as described in Section 13.3 [6]. Because the active form of the cata-
lysts is the Cu(I) species, electrochemistry can be used to reduce an air-stable Cu(II)
precursor to the active Cu(I) [49], which can further reduce the CTA. As a result, the
Cu complex is a mediator for the electro-reduction of the RAFT agent.
The use of electrochemical stimuli to trigger ATRP with alkyl DC initiators
and (dual) concurrent ATRP/RAFT polymerization should provide several ben-
efits for these processes, as in the case of eATRP. In situ regeneration of the
active Cu(I) species, no need of chemical reducing agents and consequently no
by-products, diminished catalyst loadings, and facile temporal control are among
these advantages [48, 58].
Electrochemical tools have been successfully applied to reduce a Cu(II) complex
in the presence of a dithiocarbamate, thus developing an eATRP of MMA with an
alkyl pseudohalide initiator [59]. Preliminary CV showed that the reversible signal
of CuII (DC)2 /2,2′ -bipyridine (bpy) became catalytic after the addition of the RAFT
agent 1-cyano-1-methylethyl diethyldithiocarbamate (MANDC, Figure 13.8a). This
analysis proved that the Cu complexes could catalytically activate MANDC and
guided the selection of the Eapp values to be applied during the electrolysis. The
reduction potential of the Cu catalyst was 1.5 V more positive than the reduction of
MANDC, which therefore was not directly reduced during the electrolysis.
eATRPs of MMA with alkyl pseudohalides at T = 80 ∘ C were well-controlled giv-
ing polymers with expected MWs and D - < 1.4. The polymerization rate increased
with decreasing Eapp , as generally observed in eATRP. The Cu loading was success-
fully diminished to 500 ppm, while different DPs were targeted, showing an increase
in the polymerization rate with decreasing the target DP, as expected for an ATRP
process. Control experiments conducted in the dark and in the absence of a Cu cat-
alyst allowed to exclude that the polymerization proceeded through a photoiniferter
or a traditional RAFT mechanism, respectively. Finally, the retention of chain end
functionality was demonstrated by chain extending a PMMA–DC block with n-butyl
methacrylate (BMA) and STY. A clean shift towards higher MWs was observed in the
GPC traces (Figure 13.9).
40 II
CuII(DC)2/bpy Cu Br2/TPMA
10
+ MANDC + DDMAT (T12-3A)
0 CN S
S COOH
S N 0 C12H25
S S
I (μA)
I (μA)
–40
–10
–80
–20
–0.8 –0.6 –0.4 –0.6 –0.4 –0.2 0.0

(a) E vs. SCE (V) (b) E vs. SCE (V)
Figure 13.8 (a) CV of 4.7 × 10−3 M CuII (DC)2 /bpy in the absence and presence of
2.3 × 10−2 M MANDC in 50 vol% MMA in DMF + 0.1 M n-Bu4 NClO4 , T = 80 ∘ C. Source:
Adapted with permission from Wang et al. [59]. Copyright 2019, John Wiley & Sons. (b) CV
of 1.1 × 10−3 M CuII Br2 /TPMA in the absence and presence of 3.5 × 10−3 M DDMAT (T12 -3A ),
in 50 vol% BA in DMF + 0.1 M Et4 NBF4 , T = 50 ∘ C. Source: Adapted with permission from
Wang et al. [60]. Copyright 2018, John Wiley and Sons.
PMMA PMMA
PMMA- b -PBMA PMMA- b -PSty
103 104 105 103 104 105

(a) Molecular weight (b) Molecular weight
Figure 13.9 Chain extension from PMMA macroinitiators via (a) eATRP of BMA.
[BMA]:[PMMA-DC]:[Cu(DC)2 ]:[bpy] = 150 : 1 : 0.2 : 0.2, 50 vol% BMA in DMF + 0.1 M
n-Bu4 NClO4 , T = 80 ∘ C, E app = E pc,Cu , and (b) normal ATRP of STY.
[STY]:[PMMA-DC]:[CuBr]:[PMDETA] = 200 : 1 : 1 : 1, 50 vol% STY in DMF, T = 120 ∘ C. Source:
Adapted with permission from Wang et al. [59]. Copyright 2019, John Wiley & Sons.
A dual concurrent electrochemically mediated ATRP/RAFT was recently pro-

posed aiming to combine the ATRP/RAFT synergy with the electrochemical
triggering [60]. 2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT
or T12 -3A ) was selected as a CTA for the polymerization of BA at T = 50 ∘ C. The
CV of a typical ATRP catalyst, CuBr2 /TPMA, was not modified in the presence
of T12 -3A (Figure 13.8b), suggesting that the Cu complex could not activate the
CTA, thus excluding the possibility of an eATRP with T12 -3A as alkyl pseudohalide.
Therefore, a conventional ATRP initiator, ethyl α-bromoisobutyrate (EBiB), was
used to generate radicals, which were subsequently deactivated by both reacting
1.6
Mw/Mn
1.4
0.2 1.2
0.3
Eapp (V vs. Ag/Agl/l–)

ON ON ON
20 1.0
ln([M]0/[M])
0.2 0.4 15
Mn (×10–3)
0.6 10
0.1
5
OFF OFF
0.0 OFF 0.8
0
0 2 4 6 0 10 20 30
(a) Time (h) (b) Conversion (%)
Figure 13.10 Temporal control in dual concurrent eATRP/RAFT polymerization of BA.

(a) Polymerization kinetics and (b) MW and D - evolution with conversion. Conditions: 50 vol%
BA in DMF + 0.1 M Et4 NBF4 , T = 50 ∘ C. [BA]:[T12 -3A ]:[EBiB]:[CuBr2 ]:[TPMA] = 500 : 0.5 : 0.5 :
0.015 : 0.03, ‘ON’ E app = E pc,Cu , ‘OFF’ E app = E pc,Cu + 0.6 V. Source: Reproduced with permission
from Wang et al. [60]. Copyright 2018, John Wiley & Sons.
with the ATRP deactivator BrCuII TPMA+ and by degeneratively exchanging with
the CTA. Indeed, a control experiment in the absence of T12 -3A gave a four times
faster polymerization than with a 1/1 ratio of T12 -3A /EBiB. This indicates that
T12 -3A caused rate retardation in the polymerization, likely because of the slow
fragmentation of the macro(CTA) and in agreement with previous reports [43, 44].
The dual concurrent eATRP/RAFT gave PBA with MW matching the theoretical
values and D - < 1.20. By decreasing the T12 -3A /EBiB ratio, the polymerization rate
increased because of the smaller rate of retardation, as well as the higher radical
concentration. Interestingly, well-controlled polymerizations could be obtained with
as low as 10 ppm of Cu catalyst and 1% or 2% T12 -3A relative to EBiB, whereas in the
absence of T12 -3A , such a small amount of Cu complex was not enough to ensure an
efficient deactivation.
Finally, temporal control over the polymerization of BA was achieved by simply
tuning the applied potential (Figure 13.10). Indeed, the polymerization was effec-
tively switched off by applying a potential much more positive than the reduction of
the catalyst (Epc,Cu + 0.6 V) and then restarted by applying Eapp = Epc,Cu .
13.5 Electro-reduction of Radical Initiators
Another way to obviate the direct electro-reduction of a CTA at the electrode sur-
face is to electro-reduce a conventional radical initiator, such as to generate radicals
at room temperature. The electro-generated radicals can initiate the polymeriza-
tion in solution. Importantly, the reduction of the radical initiator must occur at
a more positive potential than the reduction of the RAFT agent, which otherwise
will be irreversibly consumed. This approach is similar to the redox-initiated RAFT
polymerization described in Section 13.2, with replacing the chemical redox process
with an electrochemical stimulus.
13.5 Electro-reduction of Radical Initiators 671
Two radical initiators, BPO and the diazonium salt 4-bromobenzenediazonium

tetrafluoroborate (BrPhN2 + ), were tested for the eRAFT polymerization of BA and
MMA (50 vol% monomer in DMF) [8a]. The reduction of BPO was investigated by
CV, showing an irreversible reduction peak with Epc,BPO = −0.83 V vs. SCE in DMF.
Two electrons are required for the reduction of a molecule of BPO, according to the
following equations [61]:
(RO)2 + e− ⇌ RO⋅ + RO− (13.6)
RO⋅ + e− ⇌ RO− (13.7)

The electro-generated radicals were stable enough to initiate a free radi-
cal polymerization of MMA in the absence of any RAFT agents. However,
the voltammetric signal of BPO strongly overlapped with the reduction sig-
nal of 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPAD or DB-3CN,A ,
Epc,DB-3CN,A = −1 V vs. SCE in DMF), which was selected as suitable CTA for the
polymerization of methacrylates. As a consequence, when the applied potential was
Eapp = Epc,BPO − 0.17 V, CPAD was also partially electro-reduced and MMA radicals
formed in the vicinity of the electrode were further reduced to carbanions. Indeed,
<5% conversion was obtained in 20 hours. Conversely, when Eapp = Epc,BPO + 0.34 V,
the reduction of BPO was inefficient and negligible conversion was observed after
20 hours. Finally, Eapp = Epc,BPO allowed to obtain PMMA with D - = 1.17, but the
process was relatively slow (22% conversion in 20 hours). The MW of PMMA
was 30% lower than expected, indicating that new chains were generated by the
electro-reduced BPO. Similar results were obtained for BA and T12 -3A as CTA
(Epc,T12-3A = −1.25 V vs. SCE in DMF).
The CV of the diazonium salt BrPhN2 + gave a reduction peak with Epc,BrPhN2 + =
−0.1 V vs. SCE, about 1 V more positive than DB-3CN,A (Figure 13.11a), thus
removing any limitations on the Eapp value. The reduction of BrPhN2 + gives highly
reactive bromophenyl radicals, which can quickly graft onto the electrode surface.
A free radical polymerization of BA was tested by reducing the diazonium salt
(Eapp = Epc,BrPhN2 + ) in the absence of a RAFT agent. A 75% conversion was reached
in 16 hours, proving that some BrPh⋅ could initiate the polymerization in the
solution instead of grafting onto the electrode.
The effect of the [T12 -3A ]:[BrPhN2 + ] ratio was analyzed for the eRAFT polymeriza-
tion of MMA conducted at Eapp = Epc,BrPhN2 + . A large amount of BrPhN2 + (10 equiv
relative to T12 -3A ) generated a high concentration of radicals; therefore, the poly-
merization was relatively fast but the control was limited. In contrast, when using
[T12 -3A ]:[BrPhN2 + ] = 1 : 1, the system reached 48% conversion in 20 hours, giving
PBA with MW matching the theoretical value and D - = 1.27. However, the rate was
strongly reduced after five hours, likely because initiating radicals grafted onto the
electrode surface, preventing the further reduction of the diazonium salt, as sup-
ported by the recorded current rapidly decaying to zero.
The ‘passivation’ of the electrode surface was overcome by working under gal-
vanostatic conditions, i.e. by applying a constant current to electro-reduce BrPhN2 + .
A galvanostatic approach requires a simpler electrochemical apparatus because
+
BrPhN2 0 CPAD
e– –5
I (μA)
–10 +
BrPhN2
–15
BrPh• + N2
–1.2 –0.8 –0.4 0.0 0.4
E vs. SCE (V)
S
S S
Pm
Pn • Z S Pn •
Z S + Pn Z S + Pm
(a) M M
2.0 Iapp (μA) 1.6
Ð
–200 1.2
1.5 –100 80
ln([M]0/[M])
–50
60
Mn (× 10–3)
1.0
40
0.5
20
0.0
0
0 2 4 6 8 10 0 20 40 60 80 100
(b) Time (h) (c) Conversion (%)
Figure 13.11 (a) Mechanism of eRAFT via electro-reduction of the diazonium salt BrPhN2 +
and CV of 10−3 M CPAD (DB-3CN,A ) + 10−3 M BrPhN2 + in DMF + 0.1 M Et4 NPF6 , T = 25 ∘ C,
scan rate = 0.1 V s−1 . (b) Semi-logarithmic kinetic plot and (c) MW and dispersity evolution
with monomer conversion during the galvanostatic eRAFT of 50 vol% BA in DMF + 0.1 M
Et4 NPF6 , [BA]:[T12 -3A ]:[BrPhN2 + ] = 500 : 1 : 1, T = 25 ∘ C. Source: Adapted with permission
from Wang et al. [8a]. Copyright 2017, American chemical society.
a common current generator and two electrodes can replace the conventional
potentiostat with a three-electrode set-up [48, 58]. Different applied current values
were tested (I app = −50, −100, and −200 mA). Faster polymerization was observed
with the highest I app (Figure 13.11b,c). However, the lowest current provided better
control, particularly a better match between theoretical and measured MW of PBA
because fewer new chains were generated during the eRAFT polymerization. This
method was also used to prepare a PBA-macro(CTA) that was successfully extended
with tert-butyl acrylate, yielding a well-defined block copolymer.
This redox initiation technique based on the electro-reduction of BrPhN2 +
was recently applied to a surface-initiated eRAFT polymerization (SI-eRAFT) in
order to prepare a biosensor for the electrochemical detection of protein kinase
(PK) activity [62]. It should be noted that a combination of electropolymerization
on a surface and RAFT agents was previously reported, where the presence of
RAFT agents was proved to promote the growth of a more uniform PNIPAM
film [63]. The fabrication of the biosensor via SI-eRAFT required the following
References 673
steps: (i) self-assembly of substrate peptides on the surface of an Au electrode,

(ii) site-specific phosphorylation of substrate peptides by PKs, (iii) anchoring a
CTA containing a –COOH group to the phosphorylated sites, and (iv) SI-eRAFT of
ferrocenyl methacrylate (FcMMA) initiated by BrPhN2 + . The effective grafting of
several ferrocenyl units allowed for strongly amplifying the detection signal of PK.
The biosensors tested with a model target showed a low detection limit by 1–2
orders of magnitude lower as compared to other detection methods. Indeed, the
latter are typically based on the (photoelectro)chemical detection of stoichiometric
reaction between phosphorylated sites and electroactive tags. Therefore, the eRAFT
polymerization served as a powerful amplification strategy. Moreover, the proposed
biosensor exhibited strong specificity for the model target, high reproducibility, and
long-term stability.
13.6 Conclusions and Perspectives

The development of novel initiation methods has brought several advantages
to RAFT polymerizations. Redox-initiated RAFT polymerizations, including
Fenton–RAFT and eRAFT via electro-reduction of radical generators, allow for the
preparation of (co)polymers at low temperatures, thus diminishing the extent of side
reactions and enabling to work under biological conditions. eRAFT polymerization
via electro-reduction of CTAs remains challenging because of the very negative
reduction potential of typical RAFT agents, which can be more negative than
the reduction potential of vinyl monomers. Thus, an effective eRAFT requires the
development of new efficient mediators. Chemical and electrochemical activation of
RAFT agents eliminate the issue of new chains generation during polymerizations.
Moreover, both ATRP and RAFT polymerization can benefit from the synergistic
interaction between the two processes. Therefore, these techniques can give access
to new functional and biocompatible materials.
Acknowledgement
The support from NSF (CHE 1707490) is gratefully acknowledged.
References
1 (a) Chiefari, J., Chong, Y.K., Ercole, F. et al. (1998). Macromolecules 31:
5559–5562. https://doi.org/10.1021/ma9804951. (b) Barner-Kowollik, C. (2008).
Handbook of RAFT Polymerization. Wiley. (c) Semsarilar, M. and Perrier, S.
(2010). Nat. Chem. 2: 811–820. https://doi.org/10.1038/Nchem.853. (d) Moad, G.,
Rizzardo, E., and Thang, S.H. (2012). Aust. J. Chem. 65: 985–1076. https://doi
.org/10.1071/CH12295. (e) Hill, M.R., Carmean, R.N., and Sumerlin, B.S. (2015).
Macromolecules 48: 5459–5469. https://doi.org/10.1021/acs.macromol.5b00342.
(f) Perrier, S. (2017). Macromolecules 50: 7433–7447. https://doi.org/10.1021/acs

.macromol.7b00767.
2 Destarac, M. (2011). Polym. Rev. 51: 163–187. https://doi.org/10.1080/15583724
.2011.568130.
3 McKenzie, T.G., Fu, Q., Uchiyama, M. et al. (2016). Adv. Sci. 3: 1500394. https://
doi.org/10.1002/advs.201500394.
4 (a) Xu, J., Jung, K., Atme, A. et al. (2014). J. Am. Chem. Soc. 136: 5508–5519.
https://doi.org/10.1021/ja501745g. (b) Xu, J., Shanmugam, S., Duong, H.T.,
and Boyer, C. (2015). Polym. Chem. 6: 5615–5624. https://doi.org/10.1039/
C4PY01317D.
5 Zheng, H.T., Bai, W., Hu, K.L. et al. (2008). J. Polym. Sci., Part A: Polym. Chem.
6 Kwak, Y., Nicolay, R., and Matyjaszewski, K. (2009). Aust. J. Chem. 62:
1384–1401. https://doi.org/10.1071/Ch09230.
8 (a) Wang, Y., Fantin, M., Park, S. et al. (2017). Macromolecules 50: 7872–7879.
https://doi.org/10.1021/acs.macromol.7b02005. (b) Lorandi, F., Fantin, M.,
Shanmugam, S. et al. (2019). Macromolecules 52: 1479–1488. https://doi.org/
10.1021/acs.macromol.9b00112. (c) Strover, L.T., Postma, A., Horne, M.D. and
Moad, G. (2020). Macromolecules. 53: 10315–10322. https://doi.org/10.1021/acs
.macromol.0c02392. (d) Strover, L.T., Cantalice, A., Lam, J.Y.L. et al. (2019). ACS
Macro Lett. 8: 1316–1322. https://doi.org/10.1021/acsmacrolett.9b00598.
9 (a) Sarac, A.S. (1999). Prog. Polym. Sci. 24: 1149–1204. https://doi.org/10.1016/
S0079-6700(99)00026-X. (b) Sideridou, I.D., Achilias, D.S., and Karava, O. (2006).
11 Li, Y., Yang, J.W., and Benicewicz, B.C. (2007). J. Polym. Sci. Pol. Chem. 45:
12 Li, G., Wang, H., Zheng, H., and Bai, R. (2010). J. Polym. Sci., Part A: Polym.
13 Zheng, H.T., Ye, X.D., Wang, H. et al. (2011). Soft Matter 7: 3956–3962. https://
doi.org/10.1039/c0sm01132k.
14 Sanchez-Sanchez, A., Asenjo-Sanz, I., Buruaga, L., and Pomposo, J.A. (2012).
Macromol. Rapid Commun. 33: 1262–1267. https://doi.org/10.1002/marc
.201200180.
15 Luo, J.X., Li, M.C., Xin, M.H., and Sun, W.F. (2015). Macromol. Chem. Phys. 216:
16 Yang, H., Xue, S., Pan, J. et al. (2016). RSC Adv. 6: 14120–14127. https://doi.org/
10.1039/C5RA25078A.
17 Bai, W., Zhang, L., Bai, R., and Zhang, G. (2008). Macromol. Rapid Commun. 29:
18 Read, E., Guinaudeau, A., Wilson, D.J. et al. (2014). Polym. Chem. 5: 2202–2207.
References 675
19 (a) Dos Santos, A.M., Le Bris, T., Graillat, C. et al. (2009). Macromolecules 42:
946–956. https://doi.org/10.1021/ma802117h. (b) Liu, G.Y., Qiu, Q., Shen, W.Q.,
and An, Z.S. (2011). Macromolecules 44: 5237–5245. https://doi.org/10.1021/
ma200984h.
20 Sun, X.L., He, W.D., Li, J. et al. (2009). J. Polym. Sci., Part A: Polym. Chem. 47:
21 Sun, X.L., He, W.D., Pan, T.T. et al. (2010). Polymer 51: 110–114. https://doi.org/
10.1016/j.polymer.2009.11.014.
22 Guinaudeau, A., Mazieres, S., Wilson, D.J., and Destarac, M. (2012). Polym.
Chem. 3: 81–84. https://doi.org/10.1039/c1py00373a.
23 Pound, G., Eksteen, Z., Pfukwa, R. et al. (2008). J. Polym. Sci., Part A: Polym.
24 Martin, L., Gody, G., and Perrier, S. (2015). Polym. Chem. 6: 4875–4886. https://
doi.org/10.1039/c5py00478k.
25 McKenzie, T.G., Reyhani, A., Nothling, M.D., and Qiao, G.G. (2018). Hydroxyl
radical activated RAFT polymerization. In: Reversible Deactivation Radical Poly-
merization: Mechanisms and Synthetic Methodologies (eds. K. Matyjaszewski, H.
Gao, B.S. Sumerlin and N.V. Tsarevsky), 307–321. American Chemical Society.
27 Nothling, M.D., McKenzie, T.G., Reyhani, A., and Qiao, G.G. (2018). Macromol.
Rapid Commun. 39: e1800179. https://doi.org/10.1002/marc.201800179.
28 Eggers, S. and Abetz, V. (2018). Macromol. Rapid Commun. 39: 1700683. https://
doi.org/10.1002/marc.201700683.
29 Reyhani, A., Nothling, M.D., Ranji-Burachaloo, H. et al. (2018). Angew. Chem.
30 Reyhani, A., Allison-Logan, S., Ranji-Burachaloo, H. et al. (2019). J. Polym. Sci.,
32 Lv, Y., Liu, Z., Zhu, A., and An, Z. (2017). J. Polym. Sci., Part A: Polym. Chem.
33 (a) Zhang, B., Wang, X., Zhu, A. et al. (2015). Macromolecules 48: 7792–7802.
https://doi.org/10.1021/acs.macromol.5b01893. (b) Liu, Z., Lv, Y., and An, Z.
(2017). Angew. Chem. Int. Ed. 56: 13852–13856. https://doi.org/10.1002/anie
.201707993. (c) Enciso, A.E., Fu, L., Russell, A.J., and Matyjaszewski, K. (2018).
(d) Enciso, A.E., Fu, L., Lathwal, S. et al. (2018). Angew. Chem. Int. Ed. 57:
34 Matyjaszewski, K. (2012). Macromolecules 45: 4015–4039. https://doi.org/10
.1021/ma3001719.
35 (a) Matyjaszewski, K. (2018). Adv. Mater. 30: e1706441. https://doi.org/10.1002/
adma.201706441. (b) Matyjaszewski, K. and Tsarevsky, N.V. (2014). J. Am. Chem.
Soc. 136: 6513–6533. https://doi.org/10.1021/ja408069v.
36 Harihara Subramanian, S., Prakash Babu, R., and Dhamodharan, R. (2008).

doi.org/10.1021/ma801231r.
38 Ribelli, T.G., Lorandi, F., Fantin, M., and Matyjaszewski, K. (2019). Macromol.
Rapid Commun. 40: e1800616. https://doi.org/10.1002/marc.201800616.
39 Nicolay, R., Kwak, Y., and Matyjaszewski, K. (2008). Macromolecules 41:
4585–4596. https://doi.org/10.1021/ma800539v.
6602–6604. https://doi.org/10.1021/ma801502s.
42 Kwak, Y., Yamamura, Y., and Matyjaszewski, K. (2010). Macromol. Chem. Phys.
43 Elsen, A.M., Nicolay, R., and Matyjaszewski, K. (2011). Macromolecules 44:
1752–1754. https://doi.org/10.1021/ma200263w.
.org/10.1039/C3PY00671A.
45 (a) Zhang, W., Zhang, W., Zhang, Z. et al. (2010). Macromol. Rapid Commun.
31: 1354–1358. https://doi.org/10.1002/marc.201000008. (b) Haridharan, N.,
Ponnusamy, K., and Dhamodharan, R. (2010). J. Polym. Sci., Part A: Polym.
46 (a) Haridharan, N. and Dhamodharan, R. (2011). J. Polym. Sci., Part A: Polym.
Chem. 49: 1021–1032. https://doi.org/10.1002/pola.24518. (b) Shen, Q., Zhang,
J., Zhang, S. et al. (2012). J. Polym. Sci., Part A: Polym. Chem. 50: 1120–1126.
48 Lorandi, F., Fantin, M., Isse, A.A., and Gennaro, A. (2018). Curr. Opin. Elec-
trochem. 8: 1–7. https://doi.org/10.1016/j.coelec.2017.11.004.
49 Magenau, A.J., Strandwitz, N.C., Gennaro, A., and Matyjaszewski, K. (2011). Sci-
ence 332: 81–84. https://doi.org/10.1126/science.1202357.
50 Peterson, B.M., Lin, S., and Fors, B.P. (2018). J. Am. Chem. Soc. 140: 2076–2079.
51 (a) Falsig, M. and Lund, H. (1980). Acta Chem. Scand. Ser. B 34: 545–549.
https://doi.org/10.3891/acta.chem.scand.34b-0545. (b) Falsig, M. and Lund,
H. (1980). Acta Chem. Scand. Ser. B 34: 585–590. https://doi.org/10.3891/acta
.chem.scand.34b-0585. (c) Falsig, M., Lund, H., Nadjo, L., and Saveant, J.M.
(1980). Acta Chem. Scand. Ser. B 34: 685–691. https://doi.org/10.3891/acta.chem
.scand.34b-0685.
52 Falciola, L., Gennaro, A., Isse, A.A. et al. (2006). J. Electroanal. Chem. 593:
47–56. https://doi.org/10.1016/j.jelechem.2006.02.003.
53 Sang, W., Xu, M.M., and Yan, Q. (2017). ACS Macro Lett. 6: 1337–1341. https://
References 677
54 Arévalo, M.C., Farnia, G., Severin, M.G., and Vianello, E. (1987). J. Electroanal.
Chem. Interfacial Electrochem. 220: 201–211. https://doi.org/10.1016/0022-
0728(87)85108-2.
55 Tang, W., Kwak, Y., Braunecker, W. et al. (2008). J. Am. Chem. Soc. 130:
10702–10713. https://doi.org/10.1021/ja802290a.
56 Bortolamei, N., Isse, A.A., and Gennaro, A. (2010). Electrochim. Acta 55:
8312–8318. https://doi.org/10.1016/j.electacta.2010.02.099.
57 Francke, R. and Little, R.D. (2014). Chem. Soc. Rev. 43: 2492–2521. https://doi
.org/10.1039/c3cs60464k.
58 Chmielarz, P., Fantin, M., Park, S. et al. (2017). Prog. Polym. Sci. 69: 47–78.
https://doi.org/10.1016/j.progpolymsci.2017.02.005.
59 Wang, Y., Fantin, M., and Matyjaszewski, K. (2019). J. Polym. Sci., Part A: Polym.
60 Wang, Y., Fantin, M., and Matyjaszewski, K. (2018). Macromol. Rapid Commun.
39: e1800221. https://doi.org/10.1002/marc.201800221.
61 Antonello, S., Musumeci, M., Wayner, D.D., and Maran, F. (1997). J. Am. Chem.
Soc. 119: 9541–9549. https://doi.org/10.1021/ja971416o.
62 Hu, Q., Kong, J., Han, D. et al. (2019). Anal. Chem. 91: 1936–1943. https://doi
.org/10.1021/acs.analchem.8b04221.
63 Bünsow, J., Mänz, M., Vana, P., and Johannsmann, D. (2010). Macromol. Chem.
679
14
Considerations for and Applications of Aqueous RAFT

Polymerization
Alexander W. Fortenberry 1 , Charles L. McCormick 2 , and Adam E. Smith 1
1
The University of Mississippi, Department of Chemical Engineering, University, MS 38677, USA
2
The University of Southern Mississippi, School of Polymer Science and Engineering, Hattiesburg,
MS 39406, USA
14.1 Introduction
Aqueous reversible addition–fragmentation chain transfer (aRAFT) polymerization

appeared in the original report detailing the reversible addition–fragmentation
chain transfer (RAFT) process in 1998 by Moad, Rizzardo, Thang, and coworkers
[1]. As part of their seminal work, the authors reported the RAFT polymerization
of sodium 4-styrenesulfonate (SS) directly in water using the water-soluble chain
transfer agent (CTA) 4-cyanopentanoic acid dithiobenzoate (CTP). Inspired by this
work, the McCormick group reported the first AB diblock copolymers directly in
water in 2001 [2]. Since these initial reports, aRAFT has been utilized to polymerize
a wide array of water-soluble monomers directly in aqueous media [3]. This chapter
will focus on considerations that must be taken into account in order to perform
well-controlled RAFT polymerizations directly in aqueous media, including
hydrolysis and aminolysis of CTAs in aqueous media, the types of initiation systems
utilized for aRAFT, and efforts to perform oxygen-tolerant aRAFT polymerizations.
The chapter will also discuss two applications of aRAFT, polymerization-induced
self-assembly (PISA), and the synthesis of protein–polymer and DNA–polymer
conjugates using ‘grafting from’ strategies.
14.2 Chain Transfer Agents
In the generally accepted RAFT mechanism (Scheme 14.1), the CTA reacts with a
growing polymer chain, Pn ⋅, and fragments to release the R⋅ radical, which is respon-
sible for the reinitiation of polymerization. Once the polymerization proceeds past
the pre-equilibrium, the polymerization enters the main equilibrium involving the
degenerative chain transfer of the thiocarbonylthio end group between propagating
chains. The exchange between active and dormant chains is established by the rapid
680 14 Considerations for and Applications of Aqueous RAFT Polymerization
fragmentation of the intermediate radical in both directions, allowing for the con-
trolled, intermittent addition of monomer to each growing polymer chain (Pm ⋅ and
Pn ⋅) with equal probability.
Initiation
kd •
Initiator 2I
I• + Monomer Pn•
Pre-equilibrium kβ
kadd • •
Pn• + S C S R Pn S C S R Pn S C S + R
k–add k–β
Z Z Z
Reinitiation
R• + Monomer Pm•
Main equilibrium
kadd • k–add
Pm• + S C S Pn Pm S C S Pn Pm S C S + Pn•
k–add kadd
Z Z Z
Monomer
Termination
kt1
I• R• Pn• Pm• Dead polymer
Scheme 14.1 The generally accepted RAFT polymerization mechanism.
A wide range of polymers and block copolymers have been prepared directly in
aqueous media utilizing water-soluble CTAs, some common examples of which
are shown in Figure 14.1. In addition to these small-molecule CTAs, water-soluble
macroCTAs can be chain extended with subsequent monomers to produce block
copolymers by aRAFT. One benefit of utilizing a macroCTA with regard to aRAFT
polymerization is that a macroCTA may have higher water solubility than the
small-molecule CTA based on the hydrophilicity of the polymer chain. In order to
take advantage of the economic and environmental benefits of utilizing aRAFT,
special attention must be paid to competing reactions such as hydrolysis and
aminolysis of the CTA that can affect the ability to produce well-defined polymers.
14.2.1 Hydrolysis of the CTA

Because thiocarbonylthio compounds are sulfur analogues of esters, it is not sur-
prising that they are susceptible to hydrolysis. In 2000, Levesque et al. examined the
effect of pH and temperature on thiocarbonylthio compounds [4]. In the study, they
varied the temperature from 20 to 35 ∘ C and the pH from 7.5 to 8.5 and found that
the rate of hydrolysis of the compounds increases with both increasing temperature
and increasing pH. Building on this work, the McCormick group performed the first
examination of the effects of hydrolysis and aminolysis of CTAs on aRAFT poly-
merization [5]. They examined the effects of temperature and pH on CTP and two
S CN S
S
S CO2H S S CO2H
HO2C S S CO2H
CTP CMP PMP
S S CN S
S S CO2H S S CO2H S S CO2H
BTPA CEP EMP
S
S CN
O
O S OH
S S CO2H
O
CPP
EMPA
Figure 14.1 Common CTAs utilized to enable the synthesis of well-defined polymers and
block copolymers using aRAFT polymerization. The acronym for each is shown below the
structure.
sodium 2-acrylamido-2-methylpropanesulfonate (AMPS) macroCTAs in water. The

hydrolysis of the CTA can be assumed to be zero order with respect to water because
water is present in large excess. The rate of CTA hydrolysis can be expressed in terms
of the apparent rate constant, khyd , and the CTA concentration as shown in Eq. (14.1).
d [CTA]
− = khyd [CTA] (14.1)
dt
Figure 14.2 shows the pseudo-first-order rate plots for the hydrolysis of CTP and
the two AMPS macroCTAs made using CTP [5]. It is evident from these plots that
the rates of hydrolysis of CTP and the two macroCTAs increase with increasing
pH, which is consistent with the findings of Levesque et al. [4]. Additionally, it is
important to note the sharp decrease in the rates of hydrolysis of the two macroC-
TAs compared to CTP with the larger of the macroCTAs (AMPS38 ) having the lowest
rate of hydrolysis of all three CTAs. Thomas et al. attributed this to the effect of steric
hindrance on the attack of water molecules on the dithioester moiety, which is anal-
ogous to the well-known steric effects observed for carboxylic ester hydrolysis [5].
14.2.2 Aminolysis
Thiocarbonylthio species are also susceptible to aminolysis by primary and
secondary amines present in solution. Levesque et al. studied the reaction of
thiocarbonylthio compounds with primary and secondary amines and found that
the reaction is first order with respect to the concentration of thiocarbonylthio
compounds and displays a second-order dependence with the amine concentration
[4, 6]. In their report, the McCormick group also examined the effect of aminolysis
on the stability of CTAs by exposing CTP to ammonia in buffered aqueous solutions
[5]. They analyzed the fraction of CTP remaining over a period of eight hours at
solution pH values of 5.5 and 7, where both hydrolysis and aminolysis may play
pH = 5.5
Figure 14.2 Pseudo-first-
0 order rate plots for the
pH = 7.0
pH = 9.0
hydrolysis of (a) CTP, (b)
pH = 10.0 AMPS38 , and (c) AMPS9 at
70 ∘ C. Source: Reprinted with
permission from Thomas
ln([CTP]/[CTP]0)
–1
et al. [5]. © 2004, American
Chemical Society.
–2
–3
0 5 10 15 20 25
(a) Time (h)
–1
ln([AMPS38]/[AMPS38]o)
–2 pH = 2.0
pH = 5.5
pH = 7.0
pH = 9.0
–3 pH = 10.0
0 5 10 15 20 25
(b) Time (h)
–1
ln([AMPS9]/[AMPS9]o)
–2 pH = 2.0
pH = 5.5
pH = 7.0
pH = 9.0
–3
pH = 10.0
0 5 10 15 20 25
(c) Time (h)
Figure 14.3 Fraction of CTP pH = 5.5

remaining in solution over time 1.0
pH = 7.0
under conditions, where both
hydrolysis and aminolysis may 0.8
lead to the disappearance of the
[CTP]/[CTP]o
thiocarbonylthio moiety. Source:
0.6
Reprinted with permission from
Thomas et al. [5]. © 2004,
American Chemical Society. 0.4
0.2
0.0
0 2 4 6 8
Time (h)
a role in the disappearance of the thiocarbonylthio moiety of CTP. As can be seen

from Figure 14.3, the CTP concentration decreases more rapidly at pH 7 than at a
pH of 5.5. The authors attributed this to the fact that at pH 5.5, only hydrolysis plays
a major role in the disappearance of the CTA moiety, while at pH 7, aminolysis also
leads to the disappearance of the CTA. The authors developed an expression to
model the CTA concentration over time as a function of hydrolysis and aminolysis,
Eq. (14.2).
d [CTA] [ ]2
− = khyd [CTA] + ka [CTA] NH3 (14.2)
dt
where ka is the aminolysis rate constant and [NH3 ] is the concentration of ammonia
in solution. Taking the rates of CTA hydrolysis and aminolysis into account,
Eq. (14.3) was developed to determine the theoretical molecular weight under
conditions where hydrolysis and aminolysis are occurring.
( [ ])
MMW [M]0 − M0 e−kp (t−tind )
∗
[M]n (t) = ( ) (14.3)

− k +k [NH ]2 (t−tind )
CTAind e hyd,macro a,macro 3
Because of the possible contribution of aminolysis in the destruction of the

CTA moiety, monomers containing primary and secondary amines were initially
thought to be precluded from direct polymerization by RAFT. However, Levesque
et al. demonstrated that the aminolysis of thiocarbonylthio compounds can be
significantly reduced by lowering the pH of the reaction media, thereby protonating
the amine-containing compounds [4, 6]. The McCormick group subsequently
demonstrated the ability to polymerize the primary amine containing monomer
N-(3-aminopropyl)methacrylamide (APMA) in a water/dioxane mix at a pH
between 4 and 5 using CTP [7] and from a poly(ethylene oxide) (PEO)-based
macroCTA directly in water (pH 4–5) with subsequent chain extension with
2-(diisopropylamino)ethyl methacrylate (DPAEMA) [8]. In both cases, good control
of the molecular weight and low dispersities were demonstrated.
In addition to the susceptibility of CTAs to hydrolysis via attack from water
molecules, certain monomers can also undergo hydrolysis and produce primary
and secondary amines, which can then react with the CTAs. Given the high
monomer-to-CTA ratio, the hydrolysis of even a few percent of this type of
monomer can result in complete loss of the thiocarbonylthio end groups and
hence loss of control of the polymerization. Thomas et al. examined the effect of
hydrolysis of acrylamide (AM) on the loss of CTA and found that by conducting the
polymerization under acidic conditions, the hydrolysis of AM could be minimized
sufficiently to allow for a well-controlled polymerization [5, 9].
14.3 Initiation
Because radicals are neither generated nor consumed in the main equilibrium of the
RAFT mechanism, RAFT polymerizations must be initiated by a source of radicals
[10]. Because RAFT polymerization is essentially a conventional radical polymeriza-
tion conducted in the presence of a CTA, initiation systems commonly employed in
radical polymerizations can also be employed in RAFT polymerizations. Common
examples include azo initiators, UV and γ irradiation, and redox initiation [3, 10, 11].
In RAFT polymerization, the initiators serve two purposes, to react with the CTA and
liberate the R⋅ to initiate chain growth and to replenish radicals lost to side reactions.
In order to maintain control of the polymerization, the CTA:initiator concentration
in most RAFT polymerizations is maintained at >10 because every pair of radicals
generated from the initiating species leads to a pair of radicals terminating to pro-
duce dead polymer impurities. In a well-designed RAFT polymerization, the fraction
of initiator derived chains will be less than 5% [3, 10].
14.3.1 Initiation via Azo-containing Species

Most early reports of RAFT polymerization utilize the homolytic cleavage of azo
compounds to initiate polymerization. In the early days of aRAFT polymerization,
initiation was almost exclusively done by the cleavage of azo-containing species at
elevated temperatures [1, 2, 12–16]. Examples of the water-soluble initiators used
for early reports of aRAFT are 4,4′ -Azobis(4-cyanopentanoic acid) (V-501) [1, 2, 12–
14, 16] and 2,2′ -azobis[2-methyl-N-(2-hydroxyethyl)propionamide] (VA-086) [15].
In 2005, Convertine et al. [17] were the first to report room temperature aRAFT
polymerization utilizing 2,2′ -Azobis(4-methoxy-2,4-dimethylpentanenitrile) (V-70)
as the thermal initiator. In this work, they employed 2-(1-carboxyl-1- methylethyl-
sulfanylthiocarbonylsulfanyl)-2-methylpropionic acid (CMP) as the CTA in
acidic solution and synthesized AM and N,N-dimethylacrylamide (DMA)
homopolymers at 25, 50, and 70 ∘ C. The polymerizations at 50 ∘ C were initiated by
2,2′ -azobis(N-(2-carboxyethyl)-2-methylpropionamidine) (VA-057) and the poly-
merizations at 70 ∘ C were initiated by V-501. They found that at temperatures up to
50 ∘ C, the trithiocarbonate functionality is stable and that above 50 ∘ C, CTA hydrol-
ysis becomes significant. They followed this work by synthesizing thermally respon-
sive AB and ABA block copolymers based on DMA and NIPAM in water at room
temperature utilizing 4,4′ -azobis[2-(imidazolin-2-yl)propane] dihydrochloride
14.3 Initiation 685
(VA-044) as the thermal initiator and CMP and S-ethyl-S′ -(α,α′ -dimethyl-α′′ -acetic
acid)-trithiocarbonate (EMP) as the CTAs [18].
Because of the increased rate of hydrolysis of the CTAs as described by Thomas
et al. [5], it is advantageous to conduct aRAFT polymerization at temperatures
below 50 ∘ C to obtain better control over the polymerization. Performing the
polymerizations at such temperatures also opens the door for potential in situ
functionalization of biological molecules under reaction conditions that do not
lead to denaturing. Because of these considerations, much work has been devoted
to investigating aRAFT photopolymerization at room temperature as discussed in
more detail in Section 14.3.2.
14.3.2 Photochemical Initiation

Visible light is an attractive initiation source in contrast to γ radiation (where sources
are not commonly available) and UV radiation (which can cause the photolysis of
CTA moieties leading to premature termination [19]). Visible light is also a low
energy irradiation source that minimizes damage to biomolecules and often does
not require high temperatures for polymerizations, which can reduce the rate of
CTA hydrolysis. These factors make visible light-mediated aRAFT polymerization
appealing for the synthesis of macromolecules for biological applications, and most
of the reports of aRAFT photopolymerization have been visible light mediated. As
Figg and Sumerlin described in their review on the topic [20], visible light mediated
aRAFT photopolymerization can be divided into roughly three categories: externally
catalyzed, catalyst-free, and photoinduced electron/energy transfer (PET)-RAFT.
14.3.2.1 Externally Initiated aRAFT Photopolymerization

Because aRAFT polymerization is another type of free radical polymerization,
it can be initiated photochemically via externally initiating species that absorb
light, fragment, and initiate RAFT polymerization. To our knowledge, the first
report of aRAFT photopolymerization appeared in 2009 when Shi et al. utilized
(2,4,6-trimethylbenzoyl) diphenylphosphine oxide (TPO) as the photoinitiator for
the EMP-mediated RAFT polymerization of poly(ethylene glycol) methyl ether
acrylate (PEGA) at 25 ∘ C in water [21]. They then chain extended PEGA macroCTAs
with 2-hydroxyethyl acrylate (HEA) in water to illustrate the living character of
the polymerization. They subsequently demonstrated the ability to copolymerize
acrylate-based monomers (N-(2-acryloyloxyethyl) pyrrolidone [NAP] and HEA)
in water under similar conditions [22]. The polymerizations exhibited a negligible
thermoactivating effect (the kinetic character of the polymerization did not change
much when performing the reaction at 7 ∘ C vs. 25 ∘ C) and periodic exposure to
visible light led to a corresponding repeatable periodic polymerization.
Much of the externally catalyzed aRAFT photopolymerization has been per-
formed utilizing sodium phenyl-2,4,6-trimethylbenzoyl phosphinate (SPTP) as the
water-soluble photoinitiator [23–29]. SPTP decomposes rapidly upon exposure to
UV or visible light irradiation, making it a useful initiator in such systems [23].
Much of this work was reported by the Tan and Zhang groups in their studies
of the room temperature photoinitiated polymerization-induced self-assembly

(photo-PISA) of N-(2-hydroxypropyl)methacrylamide (HPMA) with water-soluble
macroCTAs [23–26]. They reported the rapid formation of nanoparticles with
complex morphologies (i.e. spheres, worms, and vesicles) via aqueous dispersion
polymerization when exposed to sunlight or visible light and that the polymer-
izations could be controlled by turning on or off the light source [23–25]. They
subsequently performed kinetic studies to compare the rate of polymerization of
photoinitiated PISA to PISA initiated by V-501 at 70 ∘ C [26]. Figure 14.4 shows the
comparison of the photopolymerization of HPMA at 25 ∘ C and the V-501-initiated
polymerization of HPMA at 70 ∘ C using a water-soluble glycerol monomethacrylate
(GMA) macroCTA. They found that the rate of polymerization is much faster for
the photopolymerization because of the short half-life of SPTP under photolytic
conditions [26]. In addition, visible light-mediated room temperature aRAFT
polymerization utilizing SPTP as the photoinitiator has been utilized to synthesize
zwitterionic polyelectrolytes for their potential benefit in emerging biological
applications [27] and for the synthesis of stimuli-responsive cylindrical vesicular
nanotubes formed via hydrogen-bond driven PISA [28].
14.3.2.2 Initiator-Free aRAFT Photopolymerization

Most thiocarbonylthio compounds are able to initiate polymerization because of a
photoiniferter mechanism as they absorb light in the visible region between 380
and 525 nm because of the n → 𝜋* transition of the C=S bond [30]. As depicted
in Figure 14.5, initiation occurs via a homolytic C—S bond cleavage to generate a
carbon-centred radical that is capable of adding monomer and a thiocarbonylthio
radical that is capable of deactivating growing chains via reversible termination [20].
This mechanism is attractive because it produces polymer chains with homogeneous
end groups, unlike externally initiated RAFT polymerization, which produces poly-
mers with heterogeneous end groups due to some initiator-derived chains.
The first instance of a initiator-free aRAFT photopolymerization was reported
in 2015 by McKenzie et al. in which they polymerized N-isopropylacrylamide
(NIPAM) under visible light irradiation at an intensity of 4.8 W in a 4 : 1
water:dioxane mixture, where the dioxane was included only to help the CTA,
2-(((butylthio)carbonothioyl)thio)propanoic acid (BTPA), dissolve [31]. Because
of the low irradiation intensity, the polymerization took ∼20 hours to reach high
monomer conversion (>99%). Lewis et al. experimented with increasing the light
intensity for the polymerization of AM and DMA and reported that increasing the
light-emitting diode (LED) power from 6 to 208 W at 𝜆 = 402 nm led to a decrease in
reaction time to reach >85% conversion from 12 hours to 11 minutes for AM without
a significant loss in the control of the polymerization [32]. A similar conversion
was also shown for DMA. Polymerizations under high irradiation powers, where
the temperatures were not controlled, often led to solution temperatures of up to
80 ∘ C because of both the exothermic nature of the polymerizations and the intense
irradiation. They noted some loss in control of the DMA polymerization at higher
irradiation intensities, probably because of the increased hydrolysis rate of the CTA
100 5 4
80 4
Conversion (%)
ln([M]0/[M])
ln([M]0/[M])
60 3
2
40 2
1
20 1
0 0 0
0 30 60 90 120 150 180 0 20 40 60 80 100 120 140 160 0 2 4 6 8
(a) Time (min) (b) Time (min) (c) Time (min)
Figure 14.4 (a) Polymerization kinetics for V-501-initiated polymerization at 70 ∘ C (squares) and photoinitiated polymerization of HPMA at 25 ∘ C (circles)
in water using a GMA macroCTA, (b) plots of ln([M]0 /[M]) vs. reaction time for V-501 initiated, and (c) for photoinitiated PISA of HPMA in water using a
GMA macroCTA. Source: Reproduced with permission from Tan et al. [26]. © 2004, The Royal Society of Chemistry.
S *
Pn
Z S
S S Pm S S
Pn
S Z Z •
hν •
+ Pn• Pn S • S Pm Pm
Z S
Z
S
Degenerative chain transfer
Pn
Z S
(a) Initiation
* NR3
S
• + NR
Pn 3
Z S
S S Pm S S
Pn
S Z Z •
hν + Pn• Pn S • S Pm Pm
Z S
Z
S • + NR
3 Degenerative chain transfer
Pn
Z S NR3
(b) Initiation
Figure 14.5 (a) Initiator-free photopolymerizations where initiation occurs via

carbon-sulfur bond photolysis and subsequent addition to monomer to achieve a
degenerative chain transfer equilibrium between propagating chains and reversible
termination with the stable sulfur-centred radical. (b) The polymerization rate can be
increased using a tertiary amine (NR3 ) that is proposed to undergo a redox reaction with
the excited-state thiocarbonylthio moiety. Source: Reprinted with permission from Figg
et al. [20]. © 2018, American Chemical Society.
at elevated temperatures [32]. Therefore, taking necessary measures to maintain

moderate temperatures is essential for RAFT photopolymerizations in water.
As noted by Figg and Sumerlin [20] in their review on visible light-mediated
aRAFT polymerization, an alternative way to increase the rate of polymerization for
such a system is via the addition of a tertiary amine [33], which has been hypoth-
esized to undergo a redox reaction with the excited-state thiocarbonylthio to yield
the thiocarbonylthio anion and a carbon-centred radical for initiation/propagation
(Figure 14.5b). The disadvantage to this route is that high stoichiometric amounts
of amine to CTA are often required.
14.3.2.3 PET-RAFT Photopolymerizations

In addition to externally initiated and initiator-free reactions, RAFT polymerization
can also be mediated by PET photocatalysts (PCs). PET catalysts are commonly used
14.3 Initiation 689
S
Pn
Z S
*
PC Oxidation
of PC*
S S Pm S S
Pn
•+ S Z Z
hv PC + + Pn• Pn S • S Pm Pm•
Z S
Z
PC S
Pn Degenerative chain transfer
Z S
(a) Initiation
NR3
* • + NR
PC 3 Reduction
of PC*
•–
hv PC S S Pm S S
Pn
S Z Z
+ Pn• Pn S • S Pm Pm•
Z S
PC Z
S
Degenerative chain transfer
Pn • + NR
Z S 3
NR3
(b) Initiation
Figure 14.6 Photo-induced electron transfer RAFT polymerization using a photocatalyst

(PC) via either (a) an oxidative catalyst pathway or (b) a reductive catalyst pathway (NR3 can
also be ascorbic acid). Source: Reprinted with permission from Figg et al. [20]. © 2018,
American Chemical Society.
in organic syntheses to conduct single-electron redox reactions [34]. PCs can mediate
RAFT polymerization through a redox reaction with the CTA to generate a radical
that can initiate polymerization [35]. Thus in these systems, the CTA acts as both
an initiator and a CTA. As displayed in Figure 14.6, PET-RAFT polymerizations can
occur in two distinct pathways, either an oxidative catalyst pathway (Figure 14.6a)
or a reductive catalyst pathway in the presence of a reducing agent like ascorbic acid
or a tertiary amine (Figure 14.6b).
Boyer and coworkers were the first to report aqueous PET-RAFT polymerization
by employing tris(2,2′ -bipyridyl)ruthenium(II) chloride (Ru[bpy]3 Cl2 ) to polymer-
ize DMA in water at low catalyst loadings relative to CTA (CTA/[Ru(bpy)3 Cl2 ] =
1/0.0002) to form polymers with low dispersities [36]. Utilizing the inexpensive zinc
porphyrin (Zn(II) meso-tetra(4-sulfonatophenyl)porphyrin) as the catalyst, they
reported the aqueous PET-RAFT polymerization of DMA and demonstrated that the
performance of the catalyst could be affected by the pH of the polymerization media
with faster polymerization occurring in near-neutral and basic environments [37].
In addition to metallic compounds, certain water-soluble organic compounds can
act as catalysts for aRAFT photopolymerization. An example of this is the organic
dye eosin Y (EY), which absorbs blue and green light with the absorbance attributed
to the dimer and monomer, respectively [38]. Another example is the water-soluble
version of vitamin B2 (riboflavin)-riboflavin 5′ -mononucleotide (FMN) [39]. FMN
is an intriguing example because it is a naturally occurring biomolecule and opens
the door for potential bioapplications of photo-RAFT polymerization. One of the
first examples of the aRAFT photopolymerization utilizing EY was reported in
2017 by Hawker and coworkers in which they performed a grafting from approach
to graft polymer chains onto yeast and mammalian cells in room temperature
aqueous solution by attaching BTPA to the surface of the cells and then polymerized
PEGA by exposing the solution to visible light irradiation for five minutes [40]. To
provide insights into the use of EY for RAFT polymerization, the Sumerlin group
reported mechanistic studies of EY under blue and green light irradiation using
both oxidative and reductive PET mechanisms [41]. Because thiocarbonylthio
compounds such as CTAs can absorb blue light and undergo photolysis to initiate
polymerization, they found that the best way to prepare precise polymers with
predictable molecular weights utilizing EY as a PET catalyst is under an oxidative
mechanism during green light irradiation. The authors also found that a reduced
solution pH resulted in slower polymerization rates, which they attributed to the
partial protonation/deactivation of the tertiary amine reducing agent or catalyst.
14.4 Deoxygenation Methods

One key limitation of RAFT polymerizations is the sensitivity of the technique to
the presence of oxygen. Unlike conventional radical polymerization where low
concentrations of oxygen can be overcome by increasing the concentration of the
initiating species, RAFT typically requires stringent deoxygenation procedures such
as freeze–pump–thaw cycles or purging with an inert gas before polymerization
because the maintenance of the CTA end group is dependent on the ratio of the
CTA to initiator [3, 10]. In order to synthesize well-defined polymers and block
copolymers, the concentration of the initiating species must be kept low compared
to the CTA concentration, often precluding the ability to add sacrificial initiator to
overcome the presence of oxygen [42].
14.4.1 PET-RAFT
PET-RAFT polymerization can achieve oxygen tolerance in water via a reductive
catalyst pathway if a secondary catalyst (usually a tertiary amine or ascorbic acid)
is included in the system in addition to the PC (Figure 14.6b). In their studies of
EY, the Sumerlin group demonstrated that oxidative catalyst pathways can yield
polymers with molecular weights closer to their predicted molecular weights
[41], although reductive catalyst pathways are commonly reported. Subsequently,
Niu et al. [43] reported the polymerization of DMA using BTPA as the CTA
without prior deoxygenation and Ru(bpy)3 Cl2 in the presence of ascorbic acid
as a reducing agent, which induced a reductive quenching mechanism of the
excited state (Figure 14.6b). They reported monomer conversions of >90% in
30 minutes. Boyer and coworkers [44] showed that like the Ru(bpy)3 Cl2 systems,
systems employing a Zn(II) meso-tetra(4-sulfonatophenyl)porphyrin (ZnTPPS4− )
photocatalyst can achieve oxygen tolerance by the addition of ascorbic acid to
the system and polymerization in the presence of air could be achieved after a
short inhibition period. They also investigated the formation of nanoparticles
with complex morphologies (i.e. spheres, worms, and vesicles) via PET-RAFT
dispersion polymerization of HPMA with water-soluble macroCTAs by utilizing
zinc meso-tetra(N-methyl-4-pyridyl porphine tetrachloride (ZnTMPyP) as a catalyst
and biotin (vitamin B7) as a singlet oxygen quencher and reported that the addition
of a photoresponsive monomer 7-[4-(trifluoromethyl)coumarin] methacrylamide
could be used to crosslink the polymers under UV irradiation, so the nanoparticles
could retain their morphologies in organic solvents [45]. Boyer and coworkers also
reported that EY and FMN in conjunction with ascorbic acid as a reducing agent
can initiate aRAFT polymerization of various monomer families, including AMs,
acrylates, and methacrylates, for the synthesis of homo- and block copolymers
without prior deoxygenation in volumes ranging from 20 to 4400 μl [39].
Zaquen et al. performed oxygen-tolerant PET-RAFT in continuous flow tubular
reactors using EY in the presence of amine-based reducing agents to synthesize var-
ious AM and acrylate diblock and triblock copolymers with high end group fidelity
[46]. They were able to obtain high levels of control over the polymerizations by
manipulating flow rates and light intensity. By coupling multiple flow reactors, they
were able to synthesize triblock copolymers without the need for intermediate purifi-
cation.
14.4.2 Enzyme-Catalyzed Deoxygenation

14.4.2.1 Initiation by Thermal Initiation
Recently, the Stevens group demonstrated the ability to utilize glucose oxidase (GOx)
to deoxygenate the VA-044-initiated RAFT polymerization of HEA, methacrylic
acid (MA), DMA, and HPMA in aqueous phosphate-buffered saline (PBS) solutions
of methanol or dioxane in the presence of CTA 2-(propylthiocarbonothioylthio)-
2-methylpropionoic acid (PMP) in reaction vessels open to the air [47]. GOx
consumes oxygen and produces hydrogen peroxide through the oxidation of glucose
into D-glucono-δ-lactone. Initial kinetic experiments compared the use of GOx
to deoxygenate the thermally initiated polymerization of HEA in both a closed
vessel and an open vessel and compared those polymerizations to one utilizing
a conventional argon degassing procedure (Figure 14.7). The GOx-deoxygenated
polymerization kinetics in both the closed vessel and the open vessel were found
to be similar to those of the polymerization degassed with argon. Although the
GOx-catalyzed oxidation of glucose into D-glucono-δ-lactone produces hydrogen
peroxide, which can generate hydroxyl radicals, no appreciable monomer con-
version was measured in polymerizations without the exogenous initiator VA-044
added (Figure 14.7a, open circles). The polymerizations exhibited linear growth
of molecular weight with increasing conversion, Ð < 1.2, and monotonic shifts in
the chromatograms with no low molecular weight tailing at both target degrees
4×103 2.0
[M]/[CTA] = 25 4 μM GOx
3.0 Argon degass Mn theor
Closed vessel 1.8
3
Mn/Da (GPC)
Ln([M]0/[M])
Open vessel
2.0 No initiator 1.6
Mw/Mn
2
1.4
1.0
1
1.2
0.0
(a) (b) 0 1.0
5 6 7 2 3 4 5 6 7
(e) 103 104
[M]/[CTA] = 100
20×103 2.0
4 μM GOx
3.0 4 μM GOx 10 μM GOx
10 μM GOx 1.8
15 Mn theor
Mn/Da (GPC)
Ln([M]0/[M])
2.0 1.6
Mw/Mn
10
1.4
1.0
5
1.2
0.0
0 1.0
2 4 6 8 2 4 6 8
0 50 100 150 0.0 0.2 0.4 0.6 0.8 1.0
103 104 105
(c) Time (min) (d) Conversion
(f) MW (g mol–1)
Figure 14.7 Kinetics of 2 M HEA polymerizations in 20% methanol/PBS degassed by GOx and stirred at 45 ∘ C. (a, b) Pseudo-first-order kinetic plots with
(closed symbols) and without (open symbols) GOx and VA-044 (a) [M]/[CTA] = 25 and (b) [M]/[CTA] = 100. (c, d) Mn (closed symbols) and Ð (open symbols)
vs. conversion for GOx degassed polymerizations in closed vessels (c) [M]/[CTA] = 25, [GOx] = 4 μM; (d) [M]/[CTA] = 100. (e, f) Corresponding
SEC-normalized refractive index (RI) traces for the kinetics in (c) and (d), respectively, showing a shift in molecular weight with conversion. Source:
Reprinted with permission from Chapman et al. [47]. © 2014, American Chemical Society.
of polymerization (DPs) of 25 (Figure 14.7c,e) and 100 (Figure 14.7d,f). The high
molecular weight shoulders in the chromatograms for the polymerization with a
target DP of 100 that appear at higher conversions were attributed to bimolecular
termination because of increased viscosity and not the presence of GOx because
similar peaks are not seen in the DP 25 chromatograms at high conversion.
The Stevens group later utilized GOx deoxygenation to enable a combinatorial
approach to produce a library of highly controlled homo and block copolymers from
DMA, HPMA, N-acryloylmorpholine (NAM), HEA, 2-hydroxyethyl methacrylate
(HEMA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA) via
open-to-air RAFT polymerizations in 40 μl mixtures of PBS buffer and methanol
or t-butanol using the CTA 4-cyano-4-(propylthiocarbonothioylthio)pentanoic acid
(CPP) [48]. With the use of the GOx, very low concentrations of initiator were able
to be used, allowing high monomer conversion at high target DPs (400 for acrylates
and AMs and 200 for methacrylates and methacrylamides). Additionally, block
copolymers were prepared by the simple addition of a subsequent monomer to the
same well after completion of the previous polymerization.
The Rowan group recently demonstrated the ability of the GOx deoxygenation
system to work for RAFT polymerizations of HEA conducted using PMP as the CTA
and the thermal initiator VA-044 in a variety of complex aqueous solutions including
beer, wine, liquor, and fermentation broth [49]. The RAFT polymerization of HEA
in all the studied mixtures resulted in Ð > 1.2. Interestingly, the pH of the solution
played an important role in the RAFT polymerizations in the complex solutions,
with low pH solutions resulting in lower conversion. The lower conversions at low
pHs were attributed to a decrease in the stability of GOx at lower pH values, thus
impacting its ability to deoxygenate the polymerization mixture.
14.4.2.2 Enzymatic Initiation Systems

Enzymes have also been studied as a means of initiating RAFT polymer-
izations. In 2015, the An group utilized horseradish peroxidase (HRP) to
catalyze the oxidation of acetylacetone (ACAC) by hydrogen peroxide to
generate ACAC radicals to initiate the RAFT polymerization in PBS (pH 7)
of the ‘more activated monomers’ DMA, PEGA, HEA, and PEGMA using
4-cyano-4-(ethylsulfanylthiocarbonyl)sulfanylpentanoic acid (CEP) and the
‘less-activated monomer’ N-vinyl-2-pyrrolidone (NVP) using the xanthate
2-ethoxythiocarbonylsulfanyl-2-methyl-propionic acid 2-hydroxy-ethyl ester
(EMPA) after degassing with nitrogen and injecting hydrogen peroxide to initiate
polymerization [50]. All of the HRP-initiated RAFT polymerizations exhibited
pseudo-first-order kinetics, linear increases in molecular weight with conversion,
and monotonic shifts in size exclusion chromatography (SEC) chromatograms.
Figure 14.8 shows the result of the HRP-initiated RAFT polymerization of DMA in
PBS (pH 7). The An group also investigated coupling GOx deoxygenation to produce
hydrogen peroxide reported by the Stevens group [47] with the HRP initiation
system where they dubbed RAFT polymerization initiated by enzymatic cascade
catalysis. In this novel system, hydrogen peroxide produced by the oxidation of
glucose and consumption of oxygen is used to generate ACAC radicals as the
3.0 25 2.0
120 15 min
2.5 20 1.8 20 min
Ln([M]0/[M])
Mn(kg mol–1)
90 30 min
2.0
DRI (a.u.)
15 1.6 45 min
Mw/Mn
2
R = 0.996 60 min
1.5 60
2
90 min
1.0 R = 0.99 10 1.4 2h
30
0.5 5 1.2
0.0 0
0 1.0
0 10 20 30 40 50 60 0.4 0.5 0.6 0.7 0.8 0.9 1.0 28 30 32 34 36 38
(a) Time (min) (b) Conversion (c) Elution time (min)
Figure 14.8 (a) Pseudo-first-order kinetics, (b) dependence of molecular weight and dispersity on conversion, and (c) evolution of GPC traces over
polymerization time for HRP-initiated aRAFT polymerization of DMA. Source: Reprinted with permission from Zhang et al. [50]. © 2015, American
Chemical Society.
1.0
2.5
0.8
2.0
Ln([M]0/[M])
Conversion
0.6
1.5 2
0.4 R = 0.99
1.0
0.2
0.5
0.0
0 5 10 15 20 25 30 35 5 10 15 20 25 30 35
(a) Time (min) (b) Time (min)
2.0
25 120
1.8 10 min
20 90 15 min
Mn (kg mol–1)
DRI (a.u.)
1.6 25 min
Mw/Mn
15 35 min
2
R = 0.97 60
45 min
10 1.4
30
5 1.2
0
0 1.0
0.5 0.6 0.7 0.8 0.9 26 28 30 32 34 36
(c) Conversion (d) Elution time (min)
Figure 14.9 (a) Plot of monomer conversion over polymerization time, (b)
pseudo-first-order kinetics, (c) dependence of molecular weight and dispersity on
conversion, and (d) evolution of GPC traces over polymerization time for the aRAFT
polymerization of DMA initiated by GOx–HRP cascade catalysis in air. Source: Reprinted
with permission from Zhang et al. [50]. © 2015, American Chemical Society.
initiating species for the RAFT polymerization of DMA in a reaction vessel open
to air. As shown in Figure 14.9, the RAFT polymerization of DMA initiated by
the enzymatic cascade catalysis exhibits all the hallmarks of controlled radical
polymerization, linear pseudo-first-order kinetics, linear increase in molecular
weight with conversion, low Ð, and monotonic shifts in the SEC chromatograms.
Subsequently, An and coworkers investigated utilizing vitamin C (ascorbic acid)
in the GOx deoxygenation-redox initiation cascade to efficiently generate hydroxyl
radicals to initiate the RAFT polymerization of DMA in PBS (pH 7) using CEP as the
CTA in open and sealed reaction vessels exposed to air [51]. In their kinetics study,
the polymerizations conducted in open and sealed vessels have similar polymeriza-
tion rates, but the final conversion in the sealed vessel (70%) was lower than that of
the open vessel (80%). The similar kinetics suggests that the radical concentration
was similar in the two vessels, which is reasonable given that both polymerizations
had the same 10 minutes pre-polymerization incubation in which hydrogen perox-
ide was generated by the GOx before the injection of ascorbic acid. The difference in
the final conversion was suggested to be due to the slightly higher hydrogen peroxide
concentration generated in the open vessel during the later stages of the polymer-
ization because of a higher oxygen diffusion rate due to the vessel being open to
air. Later, Tan, Zhang, et al. reported that photopolymerizations initiated with SPTP
could become oxygen tolerant, and capable of occurring in open vessels, while in the
presence of the oxygen scavenging enzyme GOx and glucose [52].
In an effort to eliminate the restrictions associated with employing natu-
ral enzyme-based catalytic initiation systems, Qiao and coworkers utilized a
glycine-modified metal–organic framework (MOF), MIL-53(FE), composite as a
peroxidase mimic for the generation of hydroxyl radicals to be used to initiate
the RAFT polymerization of DMA, N-hydroxyethyl acrylamide (NHEA), methyl
acrylate (MeA), and 2-(dimethylamino)ethyl methacrylate (DMAEMA) [53]. Qiao
and coworkers utilized both argon purging and the GOx oxidation of glucose
for the deoxygenation of the polymerization solutions. Hydrogen peroxide was
injected in the polymerizations purged with argon while hydrogen peroxide was
formed in situ in the GOx-catalyzed oxidation of glucose. Although both methods
demonstrated characteristic-controlled radical polymerization, it is notable that the
GOx-deoxygenated systems were capable of achieving ultrahigh molecular weight
polymers (M n > 1 MDa) with low Ð. The enzyme mimicking glycine-modified
MIL-53(FE) presents several advantages over natural occurring enzymes for the
initiation of RAFT polymerizations including catalytic activity over a wider range
of experimental conditions (solvent, temperature, and monomer) and simple
post-polymerization catalyst removal.
14.5 Polymerization-Induced Self-assembly

Over the past decade, considerable attention has been devoted to investigating
the formation of nano-objects in solution by PISA via aRAFT polymerization.
In a typical process, a water-soluble macroCTA homopolymer of monomer A is
chain extended in water with a monomer B that gradually becomes insoluble
as the chain grows. This drives the in situ self-assembly to form AB diblock
copolymer nano-objects. The polyA macroCTA serves as a steric stabilizer and
can either be formed in water via solution polymerization or in a suitable organic
solvent, then isolated, and added to water. As Warren and Armes explained in their
review on PISA [54], the B block is usually synthesized via dispersion polymer-
ization of a monomer like HPMA, NIPAM, N,N ′ -diethylacrylamide (DEA), and
2-methoxyethylacrylate (MEA). HPMA is a commonly reported monomer in the
aqueous PISA literature [23–26, 45, 47, 52] and, in its monomeric form, is water
soluble, but forms water-insoluble polymers at high degrees of polymerization.
There are also a few examples of PISA consisting of the emulsion polymerization
of hydrophobic monomers like styrene [55–57]. Aqueous PISA offers a couple of
advantages over typical emulsion polymerization because it can form nanoparticles
below 100 nm and it does not require the use of added surfactants, which could
contaminate the final products. One characteristic of PISA is the acceleration of
polymerization that begins early in the process upon micellar nucleation as shown
in Figure 14.10. This occurs when micelles begin to form and monomer B diffuses
into the micellar core to solvate the growing hydrophobic block, which leads to a
higher local monomer concentration, thus increasing the rate of polymerization.
14.5 Polymerization-Induced Self-assembly 697
BW
M S W V
&J
100 200
2.0
180
1.5
Ln[M0]/Ln[M]
80 Aggregation 160
1.0
140
0.5
Conversion (%)
PHPMA DP
60 120
0.0
0 10 20 30 40 50 60 70 80 90
100
Time (min)
40 80
60
20 40
Onset of aggregation 20
0 0
0 20 40 60 80 100 120
Time (min)
Figure 14.10 HPMA polymerization kinetics obtained for the targeted poly(GMA47 -b-
HPMA200 ) diblock copolymer prepared via aRAFT dispersion polymerization at 70 ∘ C and the
corresponding morphologies found via transmission electron microscopy (TEM):
molecularly dispersed copolymer chains (M), spherical micelles (S), wormlike micelles (W),
branched wormlike micelles, jellyfish (BW & J), and vesicles (V). Source: Reprinted with
permission from Blanazs et al. [58]. © 2011, American Chemical Society.
This effect can also be seen in the inset in Figure 14.10. The first regime corre-
sponds to an induction period, which is common to RAFT polymerization, the
second regime corresponds to the formation of diblock copolymer chains, and the
last regime corresponds to an acceleration of the heterogeneous polymerization
because the HPMA monomers partitioning into the micelle core and solvating the
hydrophobic polyHPMA chains, resulting in a high monomer concentration.
PISA can be conducted with relatively high solid content (≥10% w/w) [24–26].
Various nano-object morphologies have been reported in the literature [25, 59–64],
including spheres, worms, and vesicles. Depending on several factors such as tem-
perature, block molecular weight, composition, concentration, and charge, these
nano-objects can possess kinetically trapped morphologies or can undergo transi-
tions to form different morphologies [65]. An example of the latter was reported by
Ma et al. in which they demonstrated the temperature-induced vesicle-to-lamellae or
vesicle-to-worm morphological transitions of temperature-responsive nano-objects
formed via aRAFT dispersion polymerization [29]. Obtaining consistent morpholo-
gies from a given PISA synthesis often requires the construction of a detailed phase
diagrams [25, 59–64]. An example is from the work of Blanazs et al. who synthe-
sized various nano-objects via RAFT dispersion polymerization of HPMA with GMA
macroCTAs of various lengths [60]. As can be observed from Figures 14.11 and 14.12,
the morphologies of the resulting nano-objects were dependent on three parameters:
10 12 14 16 18 20 22 24 26 Figure 14.11 Phase

diagram for poly(GMA78 -b-
800 800 HPMAX ) copolymers
S+V
synthesized via aqueous
700 700 RAFT dispersion
polymerization at various
PHPMA DP
600 600 concentrations ranging

S between 10 and 25% w/w.
S+W
500 500 S = spherical micelles,
W = worms, and
400 400 V = vesicles. Source:
Reprinted with permission
300 300 from Blanazs et al. [60]. ©
2012, American Chemical
Society.
200 200
10 12 14 16 18 20 22 24 26
Copolymer conc. w/w %
120 Figure 14.12 Phase diagram

summarizing the various mor-
110 phologies observed for the
three series of poly(GMA112 -
100 b-HMPAX ), poly(GMA78 -b-
90 S HMPAX ), and poly(GMA47 -
PGMA DP
b-HMPAX ) diblock copolymers

80 synthesized by aRAFT
dispersion polymerization.
70 S = spherical micelles,
W = worms, BW = branched
60 worms, and V = vesicles.
W BW V Source: Reprinted with
50
permission from Blanazs et al.
40 [60]. © 2012, American
0.65 0.70 0.75 0.80 0.85 Chemical Society.
PHPMA mol fraction
the mean DP of the GMA stabilizing block, the mean DP of the HPMA core forming
block, and the total concentration of copolymer in solution.
PISA-formed nano-objects can be endowed with stimuli responsiveness by
the appropriate choice of macroCTA. Some of the common stimuli include
pH [66, 67] and temperature [24, 25, 61, 64, 68]. Penfold et al. synthesized a
morpholine-functionalized GMA macroCTA and then chain extended it with
HPMA via dispersion polymerization [64]. Lowering the solution pH resulted in
the protonation of the morpholine end groups, which increased the hydrophilic
character of the GMA stabilizing block. Guragain and Perez-Mercader syn-
thesized pH-responsive nano-objects via a one-pot synthesis by utilizing a
PEG-b-polyDMAEMA diblock copolymer macroCTA and chain extending it with
HPMA to form triblock copolymers via PET-RAFT aqueous dispersion polymer-
ization [67]. Because of the pH-sensitive DMAEMA block, the morphologies of
the nano-objects could be manipulated by changing the solution pH. Blanazs
14.6 Grafting from Biomolecules 699
et al. synthesized biocompatible thermoresponsive poly(GMA-b-HPMA) diblock

copolymer nano-objects that form worm-like particles at ambient temperature
and display reversible worm-to-sphere transitions upon cooling to 4 ∘ C [68].
The Tan and Zhang groups synthesized temperature-responsive nano-objects by
utilizing a temperature-responsive stabilizer block and chain extending it with
HPMA in water via dispersion polymerization [24, 25]. They also synthesized
poly(PEGMA-b-HPMA) nanoparticles that demonstrated irreversible morphologi-
cal changes from worms-to-spheres upon cooling from 25 to 4 ∘ C. They attributed
this irreversible nature to the effective steric stabilization effect of the PEGMA
stabilizing block, which may have prevented the sphere-to-worm transition because
of an increase in the interfacial surface energy of the spheres. Penfold et al.
synthesized PEG-b-polyHPMA diblock copolymers that demonstrated irreversible
morphological changes from worms-to-spheres upon cooling from 25 to 4 ∘ C [64].
However, after constructing phase diagrams, they were able to identify a single
diblock copolymer composition, which could undergo reversible worm-to-sphere
changes upon a temperature cycle. Doncom et al. synthesized nanoparticles via
PISA by chain extending a [2-(methacryloyloxy)-ethyl] dimethyl(3-sulfopropyl)
ammonium hydroxide (SBMA)-based macroCTA with HPMA [61]. The SBMA
stabilizer block endowed the particles with temperature responsiveness and also
salt tolerance.
14.6 Grafting from Biomolecules

aRAFT polymerization also offers the unique ability to produce well-defined
protein–polymer conjugates by polymerizing from the surface of a protein under
conditions that will not denature the protein. Two different methods have been
reported in the literature for grafting a polymer from the surface of a protein using
RAFT polymerization, by attaching a CTA to the protein via the Z group or by
attaching the CTA via the R group (Scheme 14.2; [69]). The Z group approach,
while not strictly a ‘grafting from’ polymerization process, offers the benefit of
only dormant ‘living’ chains are attached to the protein because all the terminated
polymer chains remain in solution. Additionally, the polymer can be easily cleaved
from the protein by reducing the thiocarbonylthio moiety. Alternatively, the R
group approach leads to the thiocarbonylthio moiety being distal to the protein,
allowing monomer to be easily added to the growing polymer chain end without
the growing polymer having to diffuse back to the surface of the protein to undergo
chain transfer as is required in the Z group approach. Additionally, the distal
location of the thiocarbonylthio group leads to conjugates that are more stable and
allows for better chain extension to form synthetic block copolymers immobilized
on the protein surface [69].
The Davis and Bulmus groups were the first to report the Z group approach by
attaching a CTA to bovine serum albumin (BSA) using a thiol–disulfide exchange
reaction [70, 71]. In their first report, the BSA macroCTA was utilized to mediate
the γ ray initiated polymerization of oligo(ethylene glycol) acrylate (OEGA) in
S
S RAFT
C
R C R S Z
S Z
CTA immobilization via R-Group
R Monomer
(a) Propagation
from tethered chains
S S
RAFT
C R C
Z S Z S R
Monomer R
CTA immobilization via Z-Group Propagation
from free chains
(b)
Scheme 14.2 R-group (a) and Z-group (b) strategies for preparing polymer–protein
conjugates by reversible addition–fragmentation chain transfer (RAFT) polymerization.
Source: Reprinted with permission from Sumerlin et al. [69]. © 2012, American Chemical
Society.
a 9 : 1 water:DMF (dimethylformamide) mixture at room temperature [70]. The

polymerizations exhibited linear molecular weight increases with monomer con-
version, indicating that the in situ polymerizations were controlled. The authors
published a subsequent study in which they polymerized NIPAM and HEA from
the BSA macroCTA in aqueous media at 25 ∘ C and characterized using SEC, 1 H
nuclear magnetic resonance (NMR) spectroscopy, matrix assisted laser desorption
ionization-time of flight mass spectrometry (MALDI-TOF), and polyacrylamide gel
electrophoresis (PAGE) [71]. Notably, the authors demonstrated that the polymer-
ization process did not prevent the conformation-related esterase activity of BSA.
The Sumerlin group was the first to report the use of the R group approach to
graft polymers from the surface of a protein using aRAFT polymerization [72]. The
authors reacted a maleimide-functionalized CTA, 2-dodecylsulfanylthiocarbonyl-
sulfanyl-2-methylpropionic acid maleimido ethoxyethyl ester, with a free sulfhydryl
cysteine residue of BSA and subsequently utilized the BSA macroCTA to
polymerize NIPAM in phosphate buffer (pH 6). The molecular weight of the
formed poly(NIPAM) was 239 000 g mol−1 (theoretical M n of 234 000 g mol−1 )
with a Ð of 1.38. Additionally, the authors demonstrated the ability of the
temperature-responsive nature of poly(NIPAM) to allow the thermal regulation of
the BSA’s activity without thermally denaturing the protein after multiple heat-
ing/cooling cycles. The Sumerlin group followed their initial work by publishing
References 701
reports on the synthesis of block copolymer protein conjugates using BSA [73] and
lysozyme (LYS) [74] macroCTAs to perform aRAFT polymerization of NIPAM and
DMA. The block copolymer conjugates maintained the thermoresponsive behavior
of the NIPAM block, while the DMA block provided sufficient colloidal stability to
prevent precipitation of the conjugates. Subsequently, the Sumerlin group utilized
metal-free PET-RAFT polymerization using a LYS macroCTA to synthesize a library
of AM, acrylic, and styrenic homo- and block copolymers conjugated to LYS [75].
In addition to the work done to graft synthetic polymers from proteins, there
have also been some reports on using aRAFT polymerization to graft polymers
from nucleic acids. The He group first reported the aRAFT polymerization of
oligo(ethylene glycol) methacrylate (OEGMA) from surface-anchored DNA strands
for biosensing applications [76]. In order to perform the polymerizations, they
attached the CTA CMP to the 5′ end of a single-stranded DNA (ssDNA). The
CMP-functionalized ssDNA was hybridized to the complimentary oligonucleotide
anchored on the surface of a gold nanoparticle. Because CMP is a difunctional,
symmetric trithiocarbonate, the polymerization takes place both on the surface
and on solution. In a later report, the He group reported the surface-initiated
aRAFT polymerization of OEGMA and HEMA using a similar immobilization
scheme as in their previous report [77]. Their results demonstrated an increase in
the polymerization kinetics using the DNA-conjugated CMP compared to CMP
conjugated to the surface using a small-molecule linker. The authors speculated
that the increase in kinetics is a result of the presence of highly charged DNA
backbones and purine/pyrimidine moieties surrounding the reaction sites. Subse-
quently, Lueckerath et al. reported the aqueous solution-based photoRAFT of three
monomer families (methacrylates, acrylates, and AMs) from ssDNA via a grafting
from approach using two conjugated CTAs, BTPA, and CTP and initiated by the
combinations of EY and ascorbic acid [78].
References
1 Chiefari, J., Chong, Y.K., Ercole, F. et al. (1998). Macromolecules 31 (16):

5559–5562. https://doi.org/10.1021/ma9804951.
molecules 34 (7): 2248–2256. https://doi.org/10.1021/ma0018087.
3 Smith, A.E., Xu, X., and McCormick, C.L. (2010). Prog. Polym. Sci. 35 (1–2):
45–93. https://doi.org/10.1016/j.progpolymsci.2009.11.005.
4 Levesque, G., Arsène, P., Fanneau-Bellenger, V., and Pham, T.N. (2000).
Biomacromolecules 1 (3): 400–406. https://doi.org/10.1021/bm000037b.
5 Thomas, D.B., Convertine, A.J., Hester, R.D. et al. (2004). Macromolecules 37 (5):
1735–1741. https://doi.org/10.1021/ma035572t.
6 Levesque, G., Arsène, P., Fanneau-Bellenger, V., and Pham, T.N. (2000).
Biomacromolecules 1 (3): 387–399. https://doi.org/10.1021/bm000288k.
7 Li, Y., Lokitz, B.S., and McCormick, C.L. (2006). Angew. Chem. Int. Ed. 45 (35):
8 Xu, X., Smith, A.E., Kirkland, S.E., and McCormick, C.L. (2008). Macromolecules
41 (22): 8429–8435. https://doi.org/10.1021/ma801725w.
9 Thomas, D.B., Convertine, A.J., Myrick, L.J. et al. (2004). Macromolecules 37
(24): 8941–8950. https://doi.org/10.1021/ma048199d.
10 Moad, G., Rizzardo, E., and Thang, S.H. (2005). Aust. J. Chem. 58 (6): 379–410.
11 Lowe, A.B. and McCormick, C.L. (2008). Handbook of RAFT Polymerization,
235–284. Wiley https://doi.org/10.1002/9783527622757.ch7.
12 Sumerlin, B.S., Donovan, M.S., Mitsukami, Y. et al. (2001). Macromolecules 34
(19): 6561–6564. https://doi.org/10.1021/ma011288v.
13 Donovan, M.S., Sanford, T.A., Lowe, A.B. et al. (2002). Macromolecules 35 (12):
4570–4572. https://doi.org/10.1021/ma020191l.
14 Lai, J.T., Filla, D., and Shea, R. (2002). Macromolecules 35 (18): 6754–6756.
https://doi.org/10.1021/ma020362m.
molecules 36: 1436–1439. https://doi.org/10.1021/ma025960f.
16 Vasilieva, Y.A., Thomas, D.B., Scales, C.W., and McCormick, C.L. (2004). Macro-
molecules 37 (8): 2728–2737. https://doi.org/10.1021/ma035574d.
17 Convertine, A.J., Lokitz, B.S., Lowe, A.B. et al. (2005). Macromol. Rapid Com-
mun. 26 (10): 791–795. https://doi.org/10.1002/marc.200500042.
18 Convertine, A.J., Lokitz, B.S., Vasileva, Y. et al. (2006). Macromolecules 39 (5):
1724–1730. https://doi.org/10.1021/ma0523419.
19 Quinn, J.F., Barner, L., Barner-Kowollik, C. et al. (2002). Macromolecules 35
(20): 7620–7627. https://doi.org/10.1021/ma0204296.
20 Figg, C.A. and Sumerlin, B.S. (2018), ACS Symposium Series, vol. 1285, 43–56.
21 Shi, Y., Gao, H., Lu, L., and Cai, Y. (2009). Chem. Commun. 45 (11): 1368–1370.
https://doi.org/10.1039/b821486g.
22 Shi, Y., Liu, G., Gao, H. et al. (2009). Macromolecules 42 (12): 3917–3926.
https://doi.org/10.1021/ma9000513.
23 Tan, J., Sun, H., Yu, M. et al. (2015). ACS Macro Lett. 4 (11): 1249–1253. https://
24 Tan, J., Bai, Y., Zhang, X. et al. (2016). Macromol. Rapid Commun. 37 (17):
25 Tan, J., Bai, Y., Zhang, X., and Zhang, L. (2016). Polym. Chem. 7 (13):
2372–2380. https://doi.org/10.1039/c6py00022c.
26 Tan, J., Liu, D., Bai, Y. et al. (2017). Polym. Chem. 8 (8): 1315–1327. https://doi
.org/10.1039/c6py02135b.
27 Li, G., Xu, N., Yu, Q. et al. (2014). Macromol. Rapid Commun. 35 (16):
28 Gao, P., Cao, H., Ding, Y. et al. (2016). ACS Macro Lett. 5 (12): 1327–1331.
29 Ma, Y., Gao, P., Ding, Y. et al. (2019). Macromolecules 52 (3): 1033–1041. https://
References 703
30 Otsu, T. (2000). J. Polym. Sci., Part A: Polym. Chem. 38 (12): 2121–2136.

https://doi.org/10.1002/(SICI)1099-0518(20000615)38:12<2121::AID-POLA10>
3.0.CO;2-X.
31 McKenzie, T.G., Fu, Q., Wong, E.H.H. et al. (2015). Macromolecules 48 (12):
32 Lewis, R.W., Evans, R.A., Malic, N. et al. (2018). Polym. Chem. 9 (1): 60–68.
33 Fu, Q., McKenzie, T.G., Tan, S. et al. (2015). Polym. Chem. 6 (30): 5362–5368.
34 Prier, C.K., Rankic, D.A., and MacMillan, D.W.C. (2013). Chem. Rev. 113 (7):
5322–5363. https://doi.org/10.1021/cr300503r.
35 Xu, J., Jung, K., Atme, A. et al. (2014). J. Am. Chem. Soc. 136 (14): 5508–5519.
https://doi.org/10.1021/ja501745g.
36 Xu, J., Jung, K., Corrigan, N.A., and Boyer, C. (2014). Chem. Sci. 5 (9):
3568–3575. https://doi.org/10.1039/c4sc01309c.
37 Shanmugam, S., Xu, J., and Boyer, C. (2016). Polym. Chem. 7 (42): 6437–6449.
38 Chakraborty, M. and Panda, A.K. (2011). Spectrochim. Acta, Part A 81 (1):
458–465. https://doi.org/10.1016/j.saa.2011.06.038.
39 Yeow, J., Chapman, R., Xu, J., and Boyer, C. (2017). Polym. Chem. 8 (34):
40 Niu, J., Lunn, D.J., Pusuluri, A. et al. (2017). Nat. Chem. 9 (6): 537–545. https://
doi.org/10.1038/nchem.2713.
41 Figg, C.A., Hickman, J.D., Scheutz, G.M. et al. (2018). Macromolecules 51 (4):
42 Hill, M.R., Carmean, R.N., and Sumerlin, B.S. (2015). Macromolecules 48 (16):
43 Niu, J., Page, Z.A., Dolinski, N.D. et al. (2017). ACS Macro Lett. 6 (10):
44 Shanmugam, S., Xu, J., and Boyer, C. (2016). Macromolecules 49 (24):
45 Xu, S., Yeow, J., and Boyer, C. (2018). ACS Macro Lett. 7 (11): 1376–1382.
46 Zaquen, N., Kadir, A.M.N.B. et al. (2019). Macromolecules 52 (4): 1609–1619.
47 Chapman, R., Gormley, A.J., Herpoldt, K.L., and Stevens, M.M. (2014). Macro-
molecules 47 (24): 8541–8547. https://doi.org/10.1021/ma5021209.
48 Chapman, R., Gormley, A.J., Stenzel, M.H., and Stevens, M.M. (2016). Angew.
Chem. Int. Ed. 55 (14): 4500–4503. https://doi.org/10.1002/anie.201600112.
49 Schneiderman, D.K., Ting, J.M., Purchel, A.A. et al. (2018). ACS Macro Lett. 7
(4): 406–411. https://doi.org/10.1021/acsmacrolett.8b00069.
50 Zhang, B., Wang, X., Zhu, A. et al. (2015). Macromolecules 48 (21): 7792–7802.
51 Lv, Y., Liu, Z., Zhu, A., and An, Z. (2017). J. Polym. Sci., Part A: Polym. Chem.
55 (1): 164–174. https://doi.org/10.1002/pola.28380.
52 Tan, J., Liu, D., Bai, Y. et al. (2017). Macromolecules 50 (15): 5798–5806. https://
53 Fu, Q., Ranji-Burachaloo, H., Liu, M. et al. (2018). Polym. Chem. 9 (35):
4448–4454. https://doi.org/10.1039/c8py00832a.
54 Warren, N.J. and Armes, S.P. (2014). J. Am. Chem. Soc. 136 (29): 10174–10185.
https://doi.org/10.1021/ja502843f.
55 Zhang, X., Boissé, S., Zhang, W. et al. (2011). Macromolecules 44 (11):
4149–4158. https://doi.org/10.1021/ma2005926.
56 Gurnani, P., Bray, C.P., Richardson, R.A.E. et al. (2019). Macromol. Rapid Com-
mun. 40 (2): 1800314 (1 of 7)–1800314 (7 of 7). https://doi.org/10.1002/marc
.201800314.
57 Ebeling, B., Belal, K., Stoffelbach, F. et al. (2019). Macromol. Rapid Commun. 40
(2): 1800455 (1 of 5)–1800455 (5 of 5). https://doi.org/10.1002/marc.201800455.
58 Blanazs, A., Madsen, J., Battaglia, G. et al. (2011). J. Am. Chem. Soc. 133 (41):
16581–16587. https://doi.org/10.1021/ja206301a.
59 Sugihara, S., Blanazs, A., Armes, S.P. et al. (2011). J. Am. Chem. Soc. 133 (39):
15707–15713. https://doi.org/10.1021/ja205887v.
60 Blanazs, A., Ryan, A.J., and Armes, S.P. (2012). Macromolecules 45 (12):
5099–5107. https://doi.org/10.1021/ma301059r.
61 Doncom, K.E.B., Warren, N.J., and Armes, S.P. (2015). Polym. Chem. 6 (41):
62 Byard, S.J., Williams, M., McKenzie, B.E. et al. (2017). Macromolecules 50 (4):
63 Varlas, S., Georgiou, P.G., Bilalis, P. et al. (2018). Biomacromolecules 19 (11):
64 Penfold, N.J.W., Whatley, J.R., and Armes, S.P. (2019). Macromolecules 52 (4):
65 Williams, M., Penfold, N.J.W., Lovett, J.R. et al. (2016). Polym. Chem. 7 (23):
3864–3873. https://doi.org/10.1039/c6py00696e.
66 Penfold, N.J.W., Lovett, J.R., Warren, N.J. et al. (2016). Polym. Chem. 7 (1):
67 Guragain, S. and Perez-Mercader, J. (2018). Polym. Chem. 9 (29): 4000–4006.
https://doi.org/10.1039/c8py00775f.
68 Blanazs, A., Verber, R., Mykhaylyk, O.O. et al. (2012). J. Am. Chem. Soc. 134
(23): 9741–9748. https://doi.org/10.1021/ja3024059.
69 Sumerlin, B.S. (2012). ACS Macro Lett. 1 (1): 141–145. https://doi.org/10.1021/
mz200176g.
70 Liu, J., Bulmus, V., Herlambang, D.L. et al. (2007). Angew. Chem. Int. Ed. 46
(17): 3099–3103. https://doi.org/10.1002/anie.200604922.
71 Boyer, C., Bulmus, V., Liu, J. et al. (2007). J. Am. Chem. Soc. 129 (22):
7145–7154. https://doi.org/10.1021/ja070956a.
72 De, P., Li, M., Gondi, S.R., and Sumerlin, B.S. (2008). J. Am. Chem. Soc. 130
(34): 11288–11289. https://doi.org/10.1021/ja804495v.
73 Li, M., Li, H., De, P., and Sumerlin, B.S. (2011). Macromol. Rapid Commun. 32
(4): 354–359. https://doi.org/10.1002/marc.201000619.
References 705
74 Li, H., Li, M., Yu, X. et al. (2011). Polym. Chem. 2 (7): 1531–1535. https://doi
.org/10.1039/c1py00031d.
75 Tucker, B.S., Coughlin, M.L., Figg, C.A., and Sumerlin, B.S. (2017). ACS Macro
Lett. 6 (4): 452–457. https://doi.org/10.1021/acsmacrolett.7b00140.
76 He, P., Zheng, W., Tucker, E.Z. et al. (2008). Anal. Chem. 80 (10): 3633–3639.
https://doi.org/10.1021/ac702608k.
77 He, P. and He, L. (2009). Biomacromolecules 10 (7): 1804–1809. https://doi.org/10
.1021/bm9002283.
78 Lueckerath, T., Strauch, T., Koynov, K. et al. (2019). Biomacromolecules 20 (1):
707
15
RAFT-Mediated Polymerization-Induced Self-Assembly

(PISA)†
Franck D’Agosto 1 , Muriel Lansalot 1 , and Jutta Rieger 2
1
Université de Lyon, Université Claude Bernard Lyon 1, CPE Lyon, CNRS, UMR 5128, Catalysis,
Polymerization Processes and Materials (CP2M), 43 Bd du 11 Novembre 1918, Villeurbanne 69616, France
2
Sorbonne Université and CNRS, UMR 8232, Institut Parisien de Chimie Moléculaire (IPCM), Polymer
Chemistry Team (ECP), 4 Place Jussieu, Paris 75005, France
15.1 Introduction
There is no doubt that among the available reversible deactivation radical poly-
merization (RDRP) techniques, reversible addition–fragmentation chain transfer
(RAFT) is the most versatile and powerful way to combine the tolerance of a radical
process with a controlled chain growth for the production of well-defined polymers
[2]. Since the edition of the first handbook on RAFT edited by Wiley in 2008 [3],
RAFT has been confirming its fame and great potential over the existing RDRP
techniques. This is attested by its ever-growing interest since the first report on
RAFT polymerization in the open literature in 1998 [4] and by constantly improving
the control on molar mass while expanding the range of controllable monomers
[5–7]. In addition, the development of RAFT in heterogeneous media has provided
new tools to design macromolecular objects, contributing to the development of
new and original applications [8].
As we will see in this chapter, polymerization-induced self-assembly (PISA) is
probably the best example of this evolution. Indeed, the myriad of macromolecu-
lar architectures that have been obtained through the use of RDRP techniques lies
in the fact that the formed chains can be further extended for the generation of a
second block. Although this feature was extensively used for the production of block
copolymers in solution or bulk polymerizations [9, 10], PISA makes the most of poly-
merizations in dispersed media by chain extending a solvophilic polymer obtained
by RDRP with a solvophobic block and inducing, concomitantly to the growth of
a second solvophobic block, the self-assembly of the resulting block copolymers.
This is made possible by the choice of a dispersing phase that is a selective solvent
of the first block. As a result, PISA is not only an extremely valuable tool to effi-
ciently produce block copolymers, generally including amphiphilic ones, but has
†
D’Agosto et al. [1].

708 15 RAFT-Mediated Polymerization-Induced Self-Assembly (PISA)
Sphere
Core
monomer
Chain p
extension
Self-
Worm
Solvophilic macroRAFT assembly
l
p
v
p Mn, hydrophobic
a.l
Vesicle
v a
Figure 15.1 RAFT-mediated polymerization-induced self-assembly and illustration of the

packing parameter p (by analogy to surfactants, a is the area of the hydrophilic segment and
v and l are the volume and length of the hydrophobic segment, respectively) and the impact
of the solvophobic block molar mass on the packing parameter/morphology [13–15].
also rapidly reached interest as a technique of choice to form nano-objects [11, 12]
that can exhibit various morphologies (Figure 15.1) [13–15].
Theoretically, any RDRP technique or living polymerization technique can
be selected to produce these block copolymer nano-objects by PISA. Indeed,
nitroxide-mediated polymerization (NMP) [13, 16–19], atom transfer radical
polymerization (ATRP) [20–25] or Cu-mediated controlled polymerization [26],
iodine transfer polymerization (ITP) [27], organotellurium-mediated radical poly-
merization (TERP) [28–30], Co-mediated radical polymerization [31], ring-opening
metathesis polymerization (ROMP) [32–35], or reversible complexation-mediated
polymerization (RCMP) [36] have been successfully implemented. However,
RAFT-mediated PISA remains the most employed strategy. In the above-mentioned
first book edition in 2008, the pioneering works of Ferguson et al. [37] on chain
extension of preformed poly(acrylic acid) (PAA) macromolecular RAFT agent
(macroRAFT) in water with a slow feed of n-butyl acrylate (BA) were the only
mention to this strategy, not yet called PISA. Since then, there has been ca. 4000
citations to papers related to PISA (source: Web of Science June 2019; keywords:
PISA – polymer science), among which more than 90% are based on RAFT polymer-
ization, which confirms the general adoption of this fast maturing sub-discipline.
It is worth mentioning that a process that probably strongly inspired RAFT inven-
tors and called addition-fragmentation chain transfer [38–42] (AFCT) exploits
the reactivity of radicals towards vinyl moiety such as methacrylates to form an
adduct radical that is known to proceed mainly via fragmentation, with a minimal
contribution of copolymerization. Although the level of control is not comparable
to RAFT carried out in the presence of thiocarbonylthio compounds, it allows the
production of low dispersity block copolymers if the methacrylate controlling agent
is carried by a macromolecular chain. Early work on so-called macromonomer or
15.2 History/Origin of PISA 709
sulfur-free RAFT polymerization, including its use to form self-stabilized latices by

PISA, is mentioned in Chapter 24 [44–46]. More recent studies have appeared [43]
but will not be the focus of the present review.
To date, more than 20 reviews have already been published on PISA, mainly on
RAFT-mediated PISA, covering the general concepts of the strategy [11, 12, 47–59],
the corresponding design of reactive nano-objects [60], and their biomedical appli-
cations [61–64]. The aim of this chapter is thus not to be an additional contribution
of this type but rather to provide the reader, both incomers to the field and experts,
with a general overview of the topic. For a detailed account of specific features of
RAFT-mediated PISA, the reader should thus be referred to these reviews. After a
brief history that positions PISA in the field of polymer chemistry, this chapter will
cover the fundamentals of the PISA mechanism and review some features and limi-
tations of RAFT-mediated PISA in terms of the choice of the components involved,
the nature of the nano-objects that is achievable, the morphologies that are accessi-
ble and how they can be controlled, and some potential applications.
15.2 History/Origin of PISA

Block copolymers are very attractive materials that have gained attention in
many high-performance applications. These polymers are particularly interesting
when the chemical nature of both blocks is such that the corresponding proper-
ties are not compatible with each other (polar/apolar, attractive/repulsive, and
hydrophilic/hydrophobic). The resulting materials generally exhibit a unique
behaviour originating from hybrid properties. However, the synthesis of A–B
diblock copolymers with such properties is often tricky. In the particular field of
amphiphilic block copolymers, the conditions for the preparation of each block are
sometimes incompatible and the synthesis of the block copolymer then requires two
(or more) steps. The main strategies are (i) the synthesis of one block, followed by
the initiation of the second block, (ii) the selective post-modification of a preformed
diblock copolymer composed of compatible blocks, or (iii) a polymer–polymer
coupling reaction. In any case, the choice of the solvent for an efficient chemistry is
narrowed by the nature of the monomers involved or the targeted polymers.
PISA can find its origin in different fields of polymer science. Polymer chemists
will see in PISA a very original strategy to produce (amphiphilic) block copolymers.
Indeed, PISA that can be in essence defined as the self-assembly of (amphiphilic)
block copolymers during polymerization is a way to alleviate the problems
mentioned above. Works published by polymer chemists almost 25 years ago,
exploiting the livingness of poly(t-butyl styryl)-lithium chains to initiate the anionic
dispersion polymerization of styrene (St) [65] or divinylbenzene (DVB) [66] in
n-hexane, did indeed probably pioneer the concept of what is called today a
PISA process. More recently, Yamauchi et al. [67] observed what they named a
polymerization reaction-induced molecular self-assembling process when simul-
taneously polymerizing isoprene and St in deuterated benzene by living anionic
polymerization initiated by sec-butyllithium. Indeed, the reactivity ratios are such
that a polyisoprene-b-polystyrene block copolymer is formed, and the authors set

up experiments by means of time-resolved small angle neutron scattering (SANS)
measurements to visualize the self-assembly upon the growth of the polystyrene
(PS) block from the polyisoprene first block.
For the emulsion polymer chemists, however, PISA is the result of constant
efforts from researchers in the field of latex synthesis, particularly for coating
applications. These efforts were concentrated on both finding appropriate ways to
get rid of molecular surfactants and transposing all the features of homogeneous
RDRP (solution or bulk) to polymerization in dispersed media [68, 69]. As already
mentioned, the pioneering works on RAFT-mediated PISA from Hawkett, Gilbert,
and coworkers [37] consisted in the starve-feed addition of BA to an aqueous
solution of a PAA macroRAFT. The low solubility of BA in water was sufficient to
induce chain extension of PAA and form a PBA block. The resulting PAA-b-PBA
amphiphilic block copolymers then self-assembled into micellar aggregates that
could swell with BA. The polymerization thus quickly switched from the aqueous
phase to the particle core with a constant feed of radicals coming from water.
These seminal works launched a series of important patents from the Univer-
sity of Sydney related to coating applications [70, 71]. It is worth mentioning
here that, very soon after the discoveries of RAFT by CSIRO/DuPont [72] and
macromolecular interchange of xanthate (MADIX) [73, 74] by Rhodia Chimie,
and two years before the works patented and published by Hawkett, Gilbert, and
coworkers [37], Rhodia Chimie patented the use of hydrophilic macroxanthates
for particle surface functionalization using, however, some molecular surfac-
tants in emulsion polymerization [2, 75]. These last works clearly did not aim
at producing well-defined block copolymers but targeted the formation of latex
particles (formed through conventional emulsion polymerization) stabilized by
the in situ formation of a fraction of block copolymers, which concomitantly
allowed the surface modification of the particles by the hydrophilic macroxanthate
structure.
As mentioned in Section 15.1, these works performed on aqueous emulsion poly-
merization were the first PISA systems based on RAFT and more generally speaking
on a RDRP technique. RAFT-mediated PISA was then quickly transposed to aqueous
[11, 12, 49] and organic dispersion polymerization [47, 51].
15.3 PISA Process

15.3.1 Emulsion, Dispersion, and Precipitation Polymerizations: The
Reference Processes
As already mentioned, PISA proceeds by polymerization in dispersed media, by the
chain extension of a solvophilic polymer obtained by RDRP with a monomer for
which the corresponding polymer is not soluble. Emulsion, dispersion, and pre-
cipitation polymerizations are the three relevant processes to produce polymers in
dispersed media and they are briefly depicted in Sections 15.3.1.1–15.3.1.3.
● Emulsion Polymerization
The main ingredients of an emulsion polymerization are water, a water-soluble
initiator, a surfactant, and a hydrophobic monomer, mostly located in micrometric
droplets and in nanometric surfactant micelles, with however a slight solubility in
water. The decomposition of the initiator in water generates hydrosoluble radicals
that start to add monomer units in the aqueous phase and produce oligoradicals.
Beyond a critical degree of polymerization, the growing oligomeric species become
insoluble and migrate into the monomer-swollen surfactant micelles that then
become nucleated particles, where the polymerization continues. This is called
micellar nucleation. In the absence of micelles, homogeneous nucleation takes
place and consists in the precipitation of these oligomers, generating nuclei that are
stabilized by the surfactant. Regardless of the nucleation, the growing particles are
swollen with monomer diffusing from large monomer droplets through the aqueous
phase, and the polymerization continues until full monomer consumption. The
stability of the final particles is thus achieved by a key component in the process:
the surfactant
● Dispersion Polymerization
In a dispersion polymerization, the situation is different because the monomer is
soluble in the continuous phase, which can be aqueous or organic. However, the cor-
responding polymer is not. The stability of the nuclei formed upon polymerization
is generally ensured by the in situ formation of grafted macromolecular stabilizers
resulting from chain transfer reactions occurring along solvophilic polymer chains
or protective colloids used in the formulation.
● Precipitation Polymerization
Precipitation polymerization is a particular case of dispersion polymerization for
which the monomer does not or poorly swell its polymer. This is, for example, the
case for N-isopropylacrylamide (NIPAM) in water for which the polymerization can
be conducted above the lower critical solubility temperature (LCST) of PNIPAM in
the absence of the surfactant [76, 77].
Replacing the surfactant or stabilizer by a solvophilic chain prepared by RAFT has
led to successful PISA under both emulsion and dispersion polymerization condi-
tions to generate block copolymer particles in a few hours at a similar high solid con-
tent (up to 50 wt% [78]) and under the same undemanding conditions as in emulsion
or dispersion polymerization. This is in striking contrast to the strategies used so far
to obtain the same nano-objects, such as the co-solvent method used to self-assemble
the preformed block copolymers that requires extended periods of time and results
in very low polymer concentrations (<2 wt%) [79].
Regardless of the polymerization process, most of the studies dealing with PISA
employ a preformed, well-defined solvophilic macroRAFT agent. However, several
examples showed that this macroRAFT could be synthesized in the same reactor as
the solvophobic block. This led to the development of the so-called one-pot processes
either starting with a hydrophilic monomer such as acrylic acid (AA) or methacrylic
acid (MAA) in water for emulsion [57, 80, 81], or after hydrolysis of a monomer
such as glycidyl methacrylate (GlyMA), followed by the RAFT polymerization

of the formed glycerol methacrylate (GMA) and dispersion polymerization of
hydroxypropyl methacrylate (HPMA) [82], or using a monomer soluble in mineral
oil, such as lauryl methacrylate (LMA), in dispersion polymerization [78].
In addition, the simultaneous in situ formation and self-assembly in water of
amphiphilic block copolymers should give rise to the formation of morphologies
that have already been observed when self-assembling preformed block copolymers
in a selective solvent of one of the two blocks [79]. The full range of expected
morphologies (spheres, worms, fibres, vesicles, and lamellae) was indeed obtained
by RAFT-PISA by varying the nature and molar mass of the solvophilic macroRAFT
and the solvophobic block and/or the solid content. So far, the vast majority of
the non-spherical morphologies have been obtained in dispersion polymerization.
The monomer-swollen spherical block copolymer particles initially formed during
the process fuse together according to a polymerization-induced reorganization
mechanism [48], as visualized in transmission electron microscopy (TEM) studies
by Armes and coworkers [83]. Although the same process could take place in
emulsion polymerization [84–89], kinetically trapped spheres are obtained most of
the time [90–93] (see Section 15.5).
15.3.2 Main Parameters at Play for a Successful PISA at a Glance

15.3.2.1 MacroRAFT Type
Regardless of the polymerization process (emulsion, dispersion, and precipitation),
the vast majority of the solvophilic macroRAFT employed is based on dithioesters
or trithiocarbonates (TTCs). A slight preference goes to TTCs when water is used as
the dispersing phase because these compounds have been shown to be less sensitive
to hydrolysis. As a result, almost all the papers published on RAFT-mediated PISA
deal with the formation of solvophobic blocks from more activated monomers.
Indeed, as far as we know, only five papers depict the use of solvophilic macro-
RAFT carrying a dithiocarbonate chain end for the formation of block copolymer
particles based on less-activated monomers such as vinyl acetate (VAc) [94–96] or
N-vinylcaprolactam [96–98].
15.3.2.2 Initiation in RAFT-PISA

Contrary to other RDRP techniques such as NMP or ATRP for instance, RAFT
generally requires an external source of radicals usually provided through the
decomposition of organic molecules under thermal-, redox-, or photo-activation.
The initiating step in RAFT is complex and the control partly depends on the
fine-tuning of the relative amounts of the initiator and chain transfer agent. This is
a disadvantage compared to other techniques, particularly when considering block
copolymer syntheses and particularly PISA. Indeed, the formation of the second
block will be unavoidably accompanied by the formation of its homopolymer as
a side product, which may impact the efficiency of the self-assembly. In emulsion
polymerization for example, the desired block copolymer self-assembly may thus
compete with homogeneous nucleation, leading to precipitation of solvophobic

oligomers. This situation is indeed also favoured when the chain transfer efficiency
to the solvophilic macroRAFT is too low [86]. This is however not the case for
the vast majority of RAFT-mediated PISA studies. Regardless of whether PISA
is performed in emulsion or dispersion, the initiator concentration is generally
optimized as in conventional RAFT to minimize the quantity of the homopolymer
produced. As demonstrated by the successful polymerization-induced cooperative
assembly (PICA) process (detailed below) for which the formation of the homopoly-
mer is exacerbated, this low proportion of the homopolymer probably helps in
the nucleation of the block copolymer particles. It is worth mentioning here that
promoting the formation of homopolymer to the detriment of block copolymer is
not without interest as it may boost up the development of surfactant-free emulsion
polymerization based on PISA [57], as discussed in Section 15.3.4.
In conclusion, most of the conventional initiators employed to conduct conven-
tional emulsion or dispersion polymerization such as azo-initiators or photoactive
molecules can be employed to perform RAFT-PISA. When the dispersing phase is
water, ionic azo-initiators or persulfates are preferred.
Photoinitiators can also be used in PISA [56] under appropriate irradiation
conditions using UV [99] or visible light [100]. Original and efficient photoinitiating
systems based on horseradish peroxidase have also been successfully developed in
combination with hydrogen peroxide and ascorbic acid [101]. A way to get around
the additional use of radical initiator can be the recourse to photoinitiated systems
in the absence of molecular photoinitiators. Indeed, the photosensitivity of the
thio-thiocarbonyl chain ends of the solvophilic macroRAFT can also be exploited,
circumventing the undesired formation of homopolymer when targeting block
copolymers. In this case, visible light is preferred over UV to maintain the integrity
of the RAFT end all along the PISA process [102, 103].
15.3.2.3 Chemical Nature of the Blocks

The solvophilic macroRAFT can be obtained by post-modification of a preformed
polymer as observed when poly(ethylene glycol) (PEG) or polydimethylsiloxane is
employed, for example. It is however generally obtained by RAFT polymerization
of the corresponding solvophilic monomer either performed in organic solution,
purified and redissolved in the continuous phase, or directly in water. As mentioned
above, a one-pot strategy, for which the whole PISA process is performed in
the same solvent and reactor, is thus possible [78, 80–82]. The solvophobic core
monomer is selected with respect to the nature of the thiothiocarbonyl chain
end of the solvophilic macroRAFT to ensure a good blocking efficiency [9, 10]
and thus a fast reinitiation (fast consumption of the starting macroRAFT) that
often favours the homogeneity of the resulting block copolymer particle size and
morphology.
The rest of the present chapter will provide the reader with a representative range
of solvophilic monomers and macroRAFT, solvophobic monomers, and solvents to
perform RAFT-PISA.
15.3.3 PITSA, PICA, PIESA, and PIHSA: Different Acronyms However All
Boiling Down to PISA
The vast majority of the RAFT-PISA systems are operating according to the pro-
cess explained above, i.e. chain extension of a preformed solvophilic macroRAFT
with a solvophobic block either by emulsion or dispersion polymerization. However,
considering the tremendous amount of systems and operating conditions used to
conduct RAFT-PISA, the researchers sometimes observed that peculiar behaviours
and different acronyms related to PISA can be found in the literature.
Polymerization-induced thermal self-assembly (PITSA) was coined by Figg
et al. [104] but developed for the first time by An et al. [105] Starting from a
poly(N,N-dimethyl acrylamide) (PDMAAm) macroRAFT, NIPAM was polymerized
under precipitation conditions in the presence of a crosslinker in water at 70 ∘ C. The
chain extension, performed above LCST of PNIPAM, led to the self-assembly of the
resulting PDMAAm-b-PNIPAM triggered both by the growth of the hydrophobic
PNIPAM block and the polymerization temperature. Compared to particles formed
by PISA, PITSA results in amphiphilic block copolymer assemblies that disassemble
by cooling the resulting nano-object dispersion and thus require crosslinking
during the formation of block copolymer particles to maintain their integrity at
room temperature.
PICA was recently coined by Zhu et al. [106] and contemporaneously reported by
Tan et al. [107, 108]. It consists in performing RAFT-PISA in the presence of both a
macroRAFT and a molecular RAFT agent (Figure 15.2). Consequently, amphiphilic
block copolymers form simultaneously to a solvophobic homopolymer, and parti-
cles are generated from homopolymer-based nuclei stabilized by amphiphilic block
copolymers. The additional presence of homopolymer can to some extent help the
transition from the spherical morphology to higher order morphologies as explained
in Section 15.5.3.
PIESA stands for polymerization-induced electrostatic self-assembly. It consists in
synthesizing a double hydrophilic block copolymer by RAFT in water in which the
second block is a polyelectrolyte. The self-assembly is then induced by in situ polyion
complexation either by the presence of a preformed polyelectrolyte homopolymer
(a) (a) (c)
Macro-CTA CTA Monomer Block copolymer Homopolymer
Figure 15.2 Polymerization-induced cooperative assembly (PICA). CTA stands for chain
transfer agent. Source: Reprinted with permission from Zhu et al. [106]. Copyright 2017,
American chemical society.
Figure 15.3 Polymerization-induced electrostatic self-assembly (PIESA). Source: Reprinted

with permission from Cai et al. [111]. Copyright 2018, American chemical society.
during PISA [109, 110] and the growth of a polyelectrolyte block of opposite charge
from the macroRAFT, or by the chain extension of the resulting soluble diblock
copolymer with a monomer of opposite charge [111]. In the last case, this leads to
the formation of a third block strongly interacting upon its growth with the second
block through electrostatic interactions inducing the self-assembly (Figure 15.3).
Eventually, polymerization-induced hierarchical self-assembly (PIHSA) [112]
was performed in ethanol by chain extending a poly(methacrylic acid) (PMAA)
macroRAFT with a monomer containing an azobenzene side group. While the
formed block copolymers self-assemble as a result of solvophobicity of the second
block, the liquid crystalline property of the azobenzene group allows the core block
to self-organize at the same time. This system not only consists in hierarchical
self-assembly, leading to the formation of unconventional morphologies and
their transitions (cuboids, short belts, and ellipsoidal vesicles), but also produces
light-sensitive nano-objects thanks to the configuration switch of the azobenzene
group (see Section 15.3.3).
15.3.4 PISA-Inspired Synthesis of Surfactant-Free Latexes

In the first works reporting the use of macroRAFTs to mediate polymerization
in dispersed media, the main motivation was to introduce a reactive stabilizer,
which was covalently anchored to the final latex particles, or to functionalize
the particle surface (a molecular surfactant being still present) with less empha-
sis placed on their ability to control the polymerization of the core-forming
block. With this in mind, PISA has been used for the synthesis of PS particles
using macroRAFT of polysoaps [113], poly(2-diethylaminoethyl methacrylate)

(PDEAEMA) [114], poly(ethylene glycol) (PEG), poly(2-dimethylaminoethyl
methacrylte) (PDMAEMA) and PEG-b-PDMAEMA [115], or PMAA [116]. PVAc
particles using a dextran-based macroxanthate [94] or PBA particles from a
galactopyranose-functionalized poly(N-acryloylmorpholine) (PNAM) macroRAFT
[117] have also been reported. These latter systems involved low amount of
macroRAFT, high amount of initiator, and/or the use of macroRAFT with a poor
reinitiation efficiency.
The PISA process can thus also provide a valuable pathway for performing
surfactant-free emulsion polymerization, expanding the range of strategies based
on the use of reactive surfactants that have been investigated for many years
[118]. It is worth mentioning here that most of the PISA systems reported in the
literature require important amount of solvophilic species, typically 3–15 wt%
with respect to the core-forming polymer. Considering the restrictions on the use
of low molar mass surfactants, using low amount of macroRAFT consists in an
interesting and economically viable approach to synthesize high solid content
surfactant-free latexes. So far, little attention has been paid to produce such
industrially relevant colloidal formulations. For instance, Lansalot, D’Agosto, and
coworkers recently demonstrated that different kinds of latex particles (40 wt%
solids, based on poly(vinylidene chloride) [119, 120], poly(vinylidene fluoride)
(PVDF) [121], and acrylic latexes [122–125]), incorporating less than 2 wt% of
hydrophilic PEG, PAA, PMAA, or poly(sodium 4-styrene sulfonate) (PSSNa), could
be produced using this strategy. In the latter case, it was also demonstrated that
the strategy was compatible with well-established film crosslinking strategies
(namely, 2-(acetoacetoxy)ethyl methacrylate [AAEM]/hexamethylenediamine, and
diacetone acrylamide [DAAm]/adipic acid dihydrazide [ADH]) and that water
barrier properties of the resulting films could be improved with regard to the use of
low molar mass surfactants. Using a similar low quantity of stabilizer, Rieger and
coworkers had prepared PAA-b-PBA latex nanoparticles [126] to create soft films
[127] possessing a percolating network of PAA, which allowed to combine high
stiffness with extensibility in addition to water and solvent resistance [128].
15.4 Reactive/Functional Nano-objects

As demonstrated in the previous sections, the focus of PISA was initially the control
of the macromolecular architecture via heterogeneous polymerization processes,
progressively associated with the control of particle morphology. The robustness of
the PISA process has now opened up many possibilities to provide the nano-objects
with reactivity and/or functionality, which can be introduced at various stages of the
process: in the initial RAFT agent, in the macroRAFT, and/or in the particle core.
Regardless of the chosen strategy, the aim is either the introduction of a specific
function for a specific goal or a targeted application, or the incorporation of reactive
groups, allowing post-synthesis modification of the particles by further coupling or
crosslinking reactions. Both options can also be combined. In addition, many studies
report the introduction of functional groups able to induce morphological transi-

tions and these examples are discussed in Section 15.5. Moreover, potential applica-
tions of the formed nano-objects are sometimes mentioned in the present section,
even if those developed for very specific applications (e.g. catalysis and bioimaging)
are presented in more detail in Section 15.6.
As mentioned in Section 15.1, PISA is a rapidly expanding field, and the literature
is regularly enriched with new studies. Our aim is not to provide an exhaustive list of
all the functional particles already prepared by PISA but rather to provide the reader
with some specific examples illustrating the different synthetic strategies. A thor-
ough review on the synthesis of reactive and functional nano-objects has recently
been published by Delaittre and coworkers [60].
The examples detailed below rely on either dispersion or emulsion polymeriza-
tion. However, for the sake of simplicity, the process used in each case is not system-
atically indicated.
15.4.1 Via the RAFT Agent: Functionalization of the 𝛂-End of the Shell
Polymer
An easy way to produce particles with a functional shell is to use a RAFT agent with
a functional R reinitiating group, producing solvophilic polymers with functional
α-ends. In most cases, the goal is to functionalize the particle surface. One of
the very first works reporting the synthesis of surface-functional particles relying
on this strategy was made by An et al. [129], who used an azido-functionalized
RAFT agent to prepare PDMAAm polymers, which were then used for the aqueous
microwave-assisted polymerization of NIPAM in the presence of N,N′ -methylene
bisacrylamide as a crosslinker. The surface reactivity of the obtained nanogels
(size < 100 nm) was demonstrated via copper-catalyzed azide–alkyne cycloaddition
with a dansyl probe, leading to the production of fluorescent particles. Later on,
alkoxyamine-functionalized particles were prepared by St Thomas et al. starting
from a symmetrical TTC holding two alkoxyamine moieties [130]. The PAA
macroRAFT prepared from this RAFT agent was used for the synthesis of triblock
copolymer nanoparticles of either PS or PBA in water. The NMP of either St or SSNa
was then triggered from the particle surface, leading to morphological changes
under certain conditions. Aiming at the synthesis of building blocks for larger
supramolecular structures, Ebeling et al. [131] have recently reported the synthesis
of PS particles carrying naphthalene units initially present at the α-chain end of
the macroRAFT agent. They overcame the challenge to localize an intrinsically
hydrophobic moiety at the surface of particles dispersed in water, by using charged
PAA as a stabilizer. Similarly, György et al. [132] aimed at inserting one reactive
epoxy group per chain on average in the shell of poly(benzyl methacrylate) (PBzMA)
nanospheres, either with an epoxy-functional RAFT agent or through a stepwise
copolymerization strategy using GlyMA as a comonomer. They demonstrated
that the epoxy function was much more resistant towards hydrolysis when it was
inserted within the polymer chain than when it was exposed at the α-chain end.
Amine or carboxylic acid functionalities were then introduced via reaction of the
epoxy groups with various thiols.
15.4.2 Via the Solvophilic Block: Functionalization Along the Shell

Polymer
Unlike the previous approach that allows functionalization of the α-end of the
solvophilic block only, the use of functional monomers leads to the introduction
of reactive/functional groups distributed along the solvophilic block, increasing
the density of functional groups on the particle surface. It also broadens the
range of accessible functionalities. Again, the aim is to design shell-functionalized
nano-objects, which are sometimes further crosslinked to freeze their morphology
or to design nano-objects for specific applications.
15.4.2.1 A Variety of Functions

Two strategies were developed by Warren et al. to introduce disulfide groups at
the surface of PGMA-b-PHPMA diblock copolymer worms, thus allowing the
introduction of a latent thiol functionality (Figure 15.4) [133]. In the first route,
a disulfide dimethacrylate (DSDMA) was copolymerized with GMA, while the
second one involved the use of a bifunctional disulfide-based RAFT agent (DSDB).
Each of these macroRAFT was used in varying proportions with a non-functional
PGMA macroRAFT for HPMA dispersion polymerization, leading to different
disulfide-functionalized worm gels. For both kinds of formulation, it was shown
that higher disulfide contents led to stronger gels, presumably as a result of
inter-worm covalent bond formation via disulfide/thiol exchange. The gels pro-
duced by the DSDMA strategy are promising materials to prepare thermoreversible
3D matrix for sheet-based cell cultures [134]. DSDMA was also used to produce
thiol-functionalized vesicles [135]. Indeed, the reductive cleavage of the disulfide
bonds generates thiol groups that readily react with an acrylate containing a
quaternary ammonium to produce cationic vesicles, or with a rhodamine B isoth-
iocyanate reagent to produce fluorescent vesicles. In the former case, drug delivery
applications were targeted because enhanced muco-adhesion was anticipated
for these cationic vesicles. Core-crosslinked thiol-functional vesicles were also
readily prepared by the addition of ethylene glycol dimethacrylate at the end of the
polymerization of HPMA.
Targeting a cheaper and more straightforward synthetic strategy, the Armes group
developed another approach to introduce disulfide groups at the outer surface of
worms. Ratcliffe et al. [136] prepared epoxy-functionalized worm particles of
P(GMA-co-GlyMA)-b-PHPMA that were reacted with cystamine allowing the
introduction of disulfide groups in the worm shell. The simultaneous formation
of secondary amine groups conferred a cationic character to the nano-objects
in water. Depending on the cystamine/epoxy molar ratio, either covalently
crosslinked disulfide-bridged worm gels (stoichiometric amount) or linear primary
amine-functionalized worm gels (large excess of cystamine) were obtained. Again,
such amine-functional hydrogels are expected to offer enhanced mucoadhesive
properties.
P(GMAx-stat-DSDMAy) macro-CTA PGMAx-S-S-PGMAx macro-CTA
S-S
S-S
O
RAFT, O RAFT,
Route 1 Route 2
water PGMAx water
HO
macro-CTA
HPMA
S
S- S-S
S-S
S
S-
S-S
S-S
S
S-S
S-
S-S
S-S
S-S
S-
S
S-S S-S S-S
PHPMAy-PGMAx-PHPMAy
PGMAx-PHPMAy S-S
BAB triblock
AB diblock
Figure 15.4 Incorporation of disulfide functionality into PGMA-b-PHPMA worm gels using
either a disulfide-based methacrylate (DSDMA) or a disulfide-based RAFT agent (DSDB).
Source: Reprinted with permission from Warren et al. [133]. Copyright 2015, American
chemical society.
Yao et al. [137] used a similar approach to form vesicles of P(GMA-co-GlyMA)-b-

PHPMA, however, decorated with β-cyclodextrin (β-CD) via reaction of the epoxy
groups with amine-functionalized β-CD. Taking advantage of the host–guest chem-
istry operating between β-CD and azobenzene groups, azobenzene-functionalized
PEG chains were attached to the vesicle surface, inducing morphological transition
to worms and/or spheres.
Thiol–ene chemistry was also investigated. Oleic acid decorated nano-objects of
various morphologies were first synthesized using a macroRAFT of poly(2-(metha-
cryloyloxy)ethyl oleate) for BzMA dispersion polymerization in n-heptane [138].
Alkyl, carboxyl, hydroxyl, and protected amine functionalities could then be intro-
duced onto the particle surface via reaction of the corresponding thiols with the
pendant double bond of the stabilizer.
Core–shell particles with an organic photosensitizer incorporated in the shell were
recently prepared by Save, Lacombe, and coworkers [139]. Indeed, a photoreactive
monomer, 2-Rose Bengal ethyl acrylate, was successfully incorporated in the PAA
shell of PBA particles, which were then used to produce photoactive films exhibiting
photo-oxidation activity.
Finally, a last example worth mentioning reports the possibility to produce
shell-crosslinked spheres using DAAm as the shell constituting monomer [140].
Polymerization of tert-BA led to the formation of various particle morphologies, the
shell of which could be crosslinked via a ketone–amine reaction.
15.4.2.2 Surface Functionalization by Sugar Moieties and Amino Acids

PISA has also been shown to be a powerful tool to produce particles stabilized by var-
ious polysaccharides or glycopolymers. Ting et al. [141] prepared a macroRAFT from
a glucopyranose-based methacrylamide, which was subsequently used for the syn-

thesis of PS particles prepared with a degradable disulfide crosslinker, thus enabling
eventual degradation to the corresponding linear glycopolymers by a reductant
for drug release applications. Both effective degradation of the particles by a thiol
reagent and successful binding of lectins to the glucose moieties were demonstrated.
Ladmiral et al. [142] later used a similar approach with a galactose-based methacry-
late for the shell and HPMA for the core to form particles of various morphologies.
The availability of the galactose moieties on the particle surface was confirmed by
effective interaction with galectins, and the vesicles proved to be biocompatible
and allowed intracellular delivery of encapsulated rhodamine B. Another vari-
ety of carbohydrate-functional PS nanoparticles was successfully obtained from
glycuronan macromonomers derived from alginates [88]. The synthesis of xyloglu-
can (XG)-functionalized poly(methyl methacrylate) (PMMA) particles, a natural
hemicellulose, was also recently reported [143]. In this case, XG was functionalized
with a dithioester chain end and used for MMA emulsion polymerization. Relying
on the known affinity of XG for cellulose, XG-PMMA particles were adsorbed on
various cellulosic substrates.
Another class of functional particles of interest are the one decorated with amino
acids. In the first system studied by Ladmiral et al. [144], cysteine (Cys) or glu-
tathione (GSH)-based solvophilic macroRAFT were prepared from the correspond-
ing methacrylic monomers. They were then chain extended with a PHPMA block to
produce nano-objects of various morphologies. The obtained worm aqueous disper-
sions formed soft free-standing thermoresponsive gels that underwent degelation
on cooling, resulting from worm to sphere transition. In the second system devel-
oped by Bauri et al. [145], a side-chain L-alanine containing macroRAFT was used
to form PBzMA particles of various morphologies. One of their formulations led
to pure worms, forming a free-standing gel, but in this case, degelation occurred
upon heating. Besides, the molecular chirality coming from the L-alanine groups was
maintained in the polymer, and the hydrogen bonding interactions between these
side-chain chiral amino acids in the fibres led to the formation of one-handed heli-
cal ropes through the hierarchical self-assembly of the block copolymers’ nanofibres.
Finally, films made from such diblock copolymers formed a wrinkle surface where
the fibres were twisted and weaved together. Such nanostructured materials could,
for instance, be applied in adhesive materials or to create platforms for tissue engi-
neering and enhanced cell growth.
15.4.2.3 Fluorinated Shells

A few groups also worked on the introduction of fluorinated moieties in the particle
shell. For instance, Pei et al. prepared particles with pentafluorophenyl (PFP)
shell units [146]. Passerini reaction-derived methacrylates containing PFP groups
were first copolymerized with DMAEMA. The use of the obtained macroRAFT
for dispersion polymerization of 3-phenylpropyl methacrylate resulted in the
formation of different particle morphologies. Reaction of the PFP residues with
various functional thiols allowed the preparation of surface-modified nanoparticles.
The same group also described the synthesis of pentafluorophenyl methacrylate
(PFPMA)-decorated particles and their shell functionalization using various

primary amines [147]. In the study from Shen et al. [148], fluoro moieties were
introduced both in the shell and the core of different particles. In all cases, the core
was composed of poly(heptadecafluorodecyl methacrylate) (PHDFDMA), which is
a semi-fluorinated liquid crystalline (SFLC) polymer. Dispersion polymerization
to form the particles was performed in various solvents using various macroRAFT,
i.e. PEG, PDMAEMA, PMMA, poly(stearyl methacrylate) (PSMA), and finally
poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA). Thus, depending on the molar
mass of the blocks, PTFEMA-b-PHDFDMA ellipsoidal nanoparticles and vesicles
comprising two different semi-fluorinated blocks (respectively amorphous and
crystalline) could be obtained through dispersion polymerizations performed
in DMF. Finally, an interesting study reported the formation of particles with a
fluorinated shell for imaging purposes [149].
15.4.2.4 PISA and CO2

Supercritical carbon dioxide (scCO2 ) is an attractive alternative solvent for disper-
sion polymerization. Fluorinated stabilizers have shown their ability to provide effi-
cient steric stabilization to prevent particle aggregation in scCO2 , and of course, the
use of fluorinated macroRAFT was investigated in PISA. The very first report was
made by Zong et al. [150] who used a poly(1H,1H,2H,2H-perfluorooctyl methacry-
late) (PFOMA) macroRAFT to mediate MMA dispersion polymerization in scCO2 .
Micrometric spherical particles with a broad size distribution and stabilized by a
fluoro-shell were obtained. The presence of fluorine inside the particles was also
shown, indicating that scCO2 acted as a compatibilizer between the PFOMA and
PMMA phases. More recently, Xu et al. also reported MMA dispersion polymer-
ization in scCO2 , but using a poly(dodecafluoroheptyl methacrylate) macroRAFT
[151]. The influence of the molar mass of both blocks as well as the pressure was
studied, and nanoparticles with low size distribution were formed in the best cases,
with particle sizes ranging from 80 to 260 nm depending on the block copolymer
composition.
CO2 has also been used to tune particle morphology. A macroRAFT of
poly(4-vinylpyridine) (P4VP) was used to mediate styrene dispersion polymer-
ization in isopropanol, without CO2 or with a low pressure of CO2 (8.0 MPa, i.e.
80 bar) [152]. The presence of CO2 had a strong effect on the particle morphol-
ogy. Indeed, the properties of the continuous phase are altered by generating a
gas-expanded liquid in the presence of CO2 , and the formation of nano-objects
with a high interfacial core/corona curvature was favoured relative to the corre-
sponding system without CO2 , e.g. rods are formed (with CO2 ) under conditions
where vesicles (no CO2 ) would otherwise form. In a latter work, the same team
used a CO2 -responsive macroRAFT (namely, a statistical copolymer compris-
ing N,N-diethylaminoethyl methacrylate (DEAEMA) and poly(ethylene glycol)
methyl ether methacrylate (M n = 475 g mol−1 ) for dispersion polymerization of
2-hydroxypropyl methacrylate in water and water/MeOH [153]. Pressurization with
CO2 led to protonation of DEAEMA units, thereby offering a means of adjusting
the charge density of the stabilizing layer. The authors demonstrated that a wide
range of tunable particle morphologies were accessible by simply varying the CO2
pressure during polymerization in the range of 10–45 bar.
CO2 use was also valued in a different way by the preparation of CO2 -responsive
particles. Among other approaches, PISA has been used for the synthesis of CO2
switchable latexes. The team of Cunningham [154] used a PDEAEMA macroRAFT
for the synthesis of PS or PMMA particles, with a shell that was both pH and CO2
responsive, which are actually related properties. The tertiary amine groups of the
DEAEMA units can be protonated by introducing CO2 and reversibly deprotonated
by CO2 removal allowing particle coagulation/redispersion cycles.
15.4.3 Via the Solvophobic Block: Core Functionalization

Most of the reported works dealing with core functionalization aim at introducing
specific functional groups inside the particle core and/or provide enhanced particle
stabilization by core-crosslinking. In essence, the thiocarbonylthio chain end of
the polymer chains is buried inside the particles formed by PISA. One of the
most straightforward ways to introduce functionality inside the particle core thus
consists in converting this chain end into a thiol. An et al. used this strategy to
functionalize the PNIPAM-core-crosslinked/PDMAAm-shell particles discussed
in Section 15.4.1 [129]. Before surface functionalization with dansyl probes, the
core was functionalized with fluorescein groups by one-pot aminolysis (with
2-hydroxyethylamine)/Michael addition (with fluorescein o-acrylate). In most cases
though, functionalization comes from the use of a functional comonomer in the
core formation step, allowing access to a broad range of nano-objects.
15.4.3.1 Fluoroparticles
A significant amount of work has been dedicated to the synthesis of fluorine-core
containing particles, one of the main goals being the preparation of (super)hydro-
phobic surfaces (SHS). In the study from Shen et al. described above for shell func-
tionalization [148], fluoro moieties were present in the core of different PHDFDMA
particles prepared from macroRAFT of PEG, PDMAEMA, PMMA, PSMA, and
PTFEMA. Depending on the macroRAFT, particles with different properties
could be obtained. Indeed, the core was in all cases crystalline, whereas the shells
could be either amorphous (PDMAEMA, PMMA, and PTFEMA) or crystalline
(PEG and PSMA). The liquid crystalline nature of the core-forming PHDFDMA
was responsible for the general formation of non-spherical morphologies. The
PHDFDMA containing nanoparticles were demonstrated to be robust Pickering
emulsifiers, leading to the formation of several types of stable oil-in-water or
oil-in-oil emulsions.
PTFEMA can also be used as a core-forming block [92]. The aim of the study
was to design particles with a high core mass density to determine the effective
particle density and the thickness of the PGMA stabilizer layer using both small
angle X-ray scattering (SAXS) and disk centrifuge photosedimentometry. The
same core polymer was used for the formation of PMAA-b-PTEFMA [155] and
PMAA-b-PBzMA-b-PTFEMA [156] particles. PTFEMA was also selected to prepare
SHS [157]. A copolymer of 4-vinyl pyridine (4VP) and vinyl triethoxysilane (VTES)
in which the 4VP units were quaternized was used for the emulsion polymer-
ization of TFEMA. The particles were thus not only core functionalized but also
possessed shell-reactive groups. Indeed, the VTES units allowed further grafting
of silica nanoparticles onto the particles. The film formed from these hybrid
latexes exhibited a nanostructured surface and modification with fluorinated
trichlorosilane led to SHS. Such coatings were also prepared from spin coating of
a mixture of PMAA-b-PBA-b-P(BA-co-FDA) nanoparticles and silica beads (with
FDA: 1H,1H,2H,2H-perfluorodecyl acrylate) [158]. In the study of Qiao et al., a
symmetrical RAFT agent was used to prepare triblock copolymer nanoparticles
of poly(acrylic acid)-b-poly(2,2,3,3,4,4,4-hexafluorobutyl acrylate)-b-poly(acrylic
acid) [159]. Transparent films with elastomer properties were obtained from these
latexes, and further thermal annealing provided hydrophobic coatings.
Another very interesting fluoropolymer is PVDF. The only attempt to perform
PISA starting from VDF was recently reported by Guerre et al. [160] PVAc-b-PVDF
block copolymers were formed in dimethyl carbonate (DMC). The occurrence of
head-to-head additions for both VAc and VDF homopolymerization, combined
with transfer to DMC in the case of VDF, however led to the concomitant formation
of PVAc and PVDF homopolymers. Nevertheless, original micrometric (1–5 μm)
ovoidal flake morphologies, able to stack on each other, were observed, likely driven
by PVDF crystallization.
Finally, two recent studies describe the synthesis of reactive fluorinated
core-crosslinked block copolymer particles. Couturaud et al. [161] proposed the use
of a linear PEG macroRAFT for the polymerization of PFPMA as a core monomer
yielding spherical particles. Similar to the work of Pei et al. discussed above for shell
functionalization [147], the particles could be crosslinked after polymerization by
reaction of the PFP groups with diamines and thus remained stable in water. In
particular, the use of cystamine allowed the formation of redox-responsive particles,
which could be disassembled by the addition of GSH. These core-crosslinked
micelles also demonstrated cytocompatibility. Alternatively, Busatto et al. [162]
reported the dispersion polymerization of 2,3,4,5,6-pentafluorobenzyl methacrylate
mediated by a poly[poly(ethylene glycol) methyl ether methacrylate] (PPEGMA)
macroRAFT. Depending on the respective molar mass of both blocks, the particles
exhibited spherical, worm-like, or vesicular morphologies. Thermoreversible
morphological changes were observed, notably worm-to-sphere transitions.
The morphology could however be locked by crosslinking reaction through
thiol–para-fluoro substitution reactions using dithiols, enabling the morphology to
be maintained across a temperature range and in non-selective solvents.
15.4.3.2 Core-crosslinking
One of the very first examples reporting core-crosslinking, where the aim was to
freeze the particle morphology, was published by Zheng and Pan [163]. A PS macro-
RAFT was used for the dispersion copolymerization of 4VP and DVB in cyclohexane.
Since then, and as mentioned above, crosslinking has been the focus of many studies
dealing with core functionalization. While in the previous section GlyMA was used
in many instances to introduce reactive epoxy groups in the particle shell, GlyMA
can also be used for core functionalization. This was the case in the work of Lovett
et al. [164] who prepared PGMA-shell/P(HPMA-co-GlyMA)-core worms. The
epoxy groups could be ring-opened using 3-aminopropyltriethoxysilane (APTES)
in order to prepare core-crosslinked worms via hydrolysis condensation with
siloxane groups and/or hydroxyl groups on the HPMA residues. The ring-opening
and crosslinking reactions occurred on similar timescales. Crosslinking led to
stiffer worm gels, which remained intact when exposed to methanol or an anionic
surfactant. In addition, the worm aspect ratio could be tuned by the temperature at
which APTES was added, and the cross-linked worms were evaluated as emulsifiers
for the stabilization of n-dodecane-in-water emulsions [165]. A similar study was
conducted with vesicles crosslinked by addition of various diamines [166]. More
recently, the Armes group was able to produce PGMA-b-PGlyMA block copolymer
nanoparticles by emulsion polymerization, preserving most of the epoxy groups
from hydrolysis [93]. A third PBMA block could also be attached to the PGlyMA
one. For PGMA-b-PGlyMA, reaction with NaN3 provided azide-functional nanopar-
ticles, and the possibility to crosslink the particle core by the addition of diamines
was evidenced. Interestingly, using a shorter PGMA block led to the formation of
worms, a morphology that is not very often obtained by emulsion polymerization
[167]. Subsequent reaction with 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl pro-
duced crosslinked worms bearing a high local concentration of stable nitroxide
groups within the worm cores. Such anisotropic nanoparticles could offer potential
applications for charge storage and transport. In all of these studies, some residual
pendent amine groups could be protonated to provide cationic nano-objects. In
the work of Tan et al. [168], particles of pure PGlyMA were also prepared through
photoinitiated dispersion polymerization using a linear PEG macroRAFT. Different
morphologies were obtained, and worms and vesicles were crosslinked by addition
of ethylene diamine. Residual amine groups could be used to complex Ag salts, then
reduced to form vesicles loaded with silver nanoparticles. Their catalytic activity
was demonstrated by reduction of methyl blue.
An and coworkers used AAEM, another interesting monomer employed in
Section 15.3.4, as a comonomer to induce crosslinking with amines, however
employed here as core-forming monomer to form nanospheres and vesicles stabi-
lized by PPEGMA chains [169]. These nano-objects could be further functionalized
or crosslinked via keto-alkoxylamine chemistry. In situ formation of silver nanopar-
ticles by metal complexation and reduction was also demonstrated. The same team
reported the synthesis of ketone-functionalized particles [170]. Using a PDMAAm
macroRAFT, both spheres and vesicles composed of a PDMAAm core were prepared
by dispersion polymerization of DAAm. The nano-objects could be functionalized
using oxime (addition of O-allyl hydroxylamine) or hydrazine (fluorescein-based
semicarbazide) chemistry. They also formed crosslinked vesicles by copolymeriza-
tion of allyl acrylamide and DAAm, crosslinking being delayed to the late stage
of the polymerization (when morphology transition was completed), because
of the different reactivities of the two vinyl groups [171]. Byard et al. prepared
PDMAAm-b-PDAAm particles, but in addition to spheres and vesicles, worms could
also be obtained [172]. Addition of ADH led to crosslinked nano-objects. An interest-

ing class of reactive particles was reported by Jiang et al. who prepared nanospheres
by chain extension of a poly(2-hydroxypropyl methacrylamide) macroRAFT with
DAAm and an ammonium-based N-2-aminoethyl acrylamide hydrochloride [100].
Conjugation with pyridine-2,6-dicarboxaldehyde led to core-crosslinking forming
tridendate ligands able to coordinate Zn(II) species. Using the same copolymer,
the same group also reported the formation of pore-switchable nanotubes (or long
cylindrical vesicles) driven by hydrogen bondings [173].
As mentioned above, PS particles decorated with glucopyranose units could be
crosslinked by copolymerization with a degradable disulfide diacrylate crosslinker
[141]. Addition of 1,4-dithiothreitol as a reductant led to particle degradation into
the corresponding linear chains, demonstrating potential use as drug carriers.
Another way of inducing core-crosslinking is the use of light. This was achieved by
Huang et al. who prepared particles of poly(2-((3-(4-(diethylamino)phenyl)acryloyl)
oxy)ethyl methacrylate) in the presence of PHPMA macroRAFT [174]. Crosslink-
ing occurred upon UV irradiation by photoinduced [2+2] cycloaddition of the
cinnamate groups. The crosslinked nano-objects were used as templates for in situ
formation of gold nanoparticles. An original crosslinking strategy was reported by
the same team [175]. Different particle morphologies were obtained by dispersion
polymerization of 3-formyl-4-hydroxybenzyl methacrylate (FHMA) mediated by a
PHPMA macroRAFT. Reaction of dihydrazine with the salicylaldehyde groups of
PFHMA not only formed salicylaldazine crosslinks but also conferred fluorescence
properties by aggregation-induced emission.
15.4.3.3 Adding a Function Allowing Degradation of the Particle Core

As illustrated in the previous examples, core-crosslinking can provide particles with
additional properties. However, dissolution of the particle core could also be a pow-
erful tool. In that vein, an original work reporting the synthesis of degradable block
copolymer nanoparticles was recently published by Guégain et al. [176]. Radical
ring-opening copolymerization-induced self-assembly (rROPISA) was performed
by copolymerizing BzMA and cyclic ketene acetals (CKA), such as 2-methylene-
4-phenyl-1,3-dioxolane or 5,6-benzo-2-methylene-1,3-dioxepane, in heptane from a
poly(lauryl methacrylate) macroRAFT, leading to spherical particles regardless of
the copolymer compositions investigated. The amount of CKA in the copolymers
ranged from 4 to about 40 mol%, leading to nearly complete degradation for CKA
contents above about 15 mol%. Such degradable vinyl polymer nanoparticles may
find applications in the biomedical field or for environmental protection.
15.4.3.4 CO2 -sensitive Particles

Finally, as mentioned in the previous section, CO2 -responsive particles can present
interesting properties. In the work of Tan et al. [177], the CO2 -sensitive units were
located in the core of P(HPMA-co-DMAEMA) particles prepared from a PPEGMA
macroRAFT. The responsive properties of the particles were illustrated by the
CO2 -triggered release of bovine serum albumin (BSA) used as a model protein.
15.5 Control over the Particle Morphology

The main objective of this section is to establish and explain the fundamental prin-
ciples that control particle morphology in PISA, where the term ‘morphology’ refers
to the particle shape or morphological structure, typically spheres, worms, or vesi-
cles. Again, we will not provide an exhaustive list of all examples reported in the
literature but rather illustrate the different parameters that determine morphology
by citing both pioneering works and most recent studies.
15.5.1 From Spherical to Anisotropic Block Copolymer Particles

As mentioned in Section 15.1, at the start of RAFT-mediated PISA, independently
of the polymerization mechanism, only spherical particles were reported. In some
cases, the size of the particles increased with increasing degree of polymerization
(DPn ) of the solvophobic block [178–180], but in other reports, no correlation was
observed. It rapidly appeared that the particle formation mechanism in PISA was
rather complex and strongly dependent on the studied system. It generally includes
the aggregation of primary particles and their fusion to larger particles [181]. The
first examples of non-spherical particles were described in 2009 by the groups of
Charleux and C.Y. Pan, reporting a NMP polymerization system in water [13] and a
RAFT-mediated dispersion polymerization in methanol [14, 15, 182], respectively.
Shortly after, Armes group reported for the first time the formation of vesicles in
water, also obtained in RAFT dispersion polymerization conditions [183]. These
morphologies were composed of PGMA-b-PHPMA copolymers. Continuous mon-
itoring of the polymerizations by 1 H-NMR, size exclusion chromatography (SEC),
TEM, cryo-TEM, dynamic light scattering (DLS), static light scattering (SLS), and
SAXS provided important insights into the formation mechanism of the different
morphologies [50, 184]. The first nanostructures to form are always spherical
micelles. As the polymerization continues within the particles (increase of DPn ),
non-spherical morphologies can form. It is now well-established that worm-like
particles are formed through fusion of spherical particles following inelastic particle
collisions. In the course of the polymerization, these 1D structures become branched
and the resulting flat octopi-like morphologies reorganize to form vesicles. Such
morphological transitions during polymerization are driven by the increase of the
hydrophobic volume fraction (see Section 15.5.2). Morphological transitions during
polymerization require a reorganization of the macromolecular chains within the
assembly. As such, it has been shown that particles swelling by the monomer plasti-
cizes the core chains increasing their mobility and promoting chain reorganization.
Today, a myriad of solvophilic macroRAFT and solvophobic polymers have
been successfully used to form higher order morphologies under RAFT dispersion
polymerization conditions. In water, however, the number of suitable solvophobic
polymers is very limited. The most frequently studied solvophobic polymers are
PHPMA [54, 184] and PDMAAm [170, 172, 185], but poly(2-methoxyethyl acrylate)
(PMEA) [186], PNIPAM [104], and poly(α-hydroxymethyl acrylates) [187] have also
successfully been used to prepare non-spherical morphologies. Recently, Foster
et al. reported an in silico method based on octanol–water partition coefficients to

predict additional suitable monomers for the use in PISA in aqueous dispersion.
Although the predicted monomers were less common and not all commercially
available, this method might be a valuable tool not only to predict new monomers
but also to predict their self-assembly behaviour, that is, morphologies [188].
Although the choice of monomers for aqueous dispersion polymerizations
remains restricted, all kinds of stabilizer blocks, neutral, ionic, or functionalized pol-
ymers (e.g. PGMA [183], PEG [189], PPEGMA [190], poly(2-(methacryloyloxy)ethyl-
phosphorylcholine) [83], poly(2-(methacryloyloxy)ethyl dimethyl(3-sulfopropyl)
ammonium hydroxide) [191], poly(2-ethyl-2-oxazoline) [192], dextran [193], etc.),
have successfully been used to obtain particles of various morphologies. However,
particle fusion and consequently the formation of higher order morphologies can
be hampered by a too strong particle repulsion [50], typically by using charged
polymers as stabilizers, for instance, using weak polyacids or polybases (e.g. PAA)
[91, 194], cationic stabilizers [195], or high molar mass stabilizing blocks [196].
In emulsion polymerization conditions, the monomer forms a separate reservoir
phase and the formed diblock copolymer particles are swollen by the monomer.
The first description of non-spherical particles dates back to 2010 [194], reporting
the emulsion polymerization of styrene using graft copolymers based on AA and
poly(ethylene glycol) acrylate (PEGA), namely, P(AA-co-PEGA), as macroRAFT.
By adjusting the targeted DPn of the PS block, worm-like micelles and small
vesicles were obtained. Moreover, a transition from spheres to fibres was observed
with increasing monomer conversion, i.e. with an increase in the DPn of the
PS block. Again, these changes in morphologies directly relate to the relative
hydrophilic/hydrophobic block volume fractions. Interestingly, higher order
non-spherical morphologies were only obtained with the graft copolymer, while lin-
ear PAA or PEG homopolymers used as macroRAFT yielded only spherical particles.
In addition, the morphologies were very sensitive to changes in pH or ionic strength
of the polymerization medium. The authors postulated that the particular structure
of the macroRAFT, composed of AA and EO units capable of forming hydrophobic
complexes, was the key element for the formation of non-spherical particles.
Since then, additional systems have been described where non-spherical particles
could be obtained in emulsion polymerization conditions, but the number of
examples remains limited compared to the booming development of higher order
morphologies via dispersion/precipitation polymerization. In terms of hydrophobic
monomers, mainly styrene has been studied [84, 85, 87, 89–91, 178, 179, 194], but
it was shown that MMA [86], t-BA [197], and the more water-soluble monomers
2-hydroxybutyl methacrylate (HBMA) [198] and GlyMA [167] could also provide
non-spherical morphologies. It should be mentioned that – except for the last
two monomers – for all other examples, graft copolymers comprising PEG(M)A
macromonomers were used as stabilizers (copolymers of PEG(M)A with either
(M)AA [84, 85, 179, 194, 199], NAM [87], or hydroxyethyl acrylamide [HEAAm])
[89]. There are a few other reports of higher order morphologies by RAFT aqueous
emulsion polymerization, but these routes typically required small quantities of
either a surfactant and/or a plasticizer [200–203].
15.5.2 Main Parameters that Impact the Particle Morphology

It is nowadays well established that the particle morphology obtained by PISA
depends on various parameters, notably factors that influence the packing param-
eter P, such as the type of polymers used, the solvent, and the molar mass and
architecture of the polymers. These factors have been widely studied for block
copolymer assemblies prepared by traditional post-polymerization assembly
methods [79]. In contrast to these latter methods, in PISA, the assembly forms
while the solvophobic block grows, indicating that not only the properties of the
polymer change during the process but also the solvent properties evolve constantly
during polymerization (as the monomer is consumed). While at the beginning
of the polymerization thermodynamic assemblies might be formed, kinetically
frozen assemblies are often obtained at the end of the polymerization. Morphology
prediction in PISA remains thus difficult. Actually, in addition to intrinsic changes
in the chemical nature of the polymer and the solvent, in PISA, the experimental
polymerization conditions, for instance, stirring, temperature, initiating system,
and monomer concentration and conversion, also play a role. As mentioned
above, particle fusion following inelastic collisions and chain reorganization are
prerequisites for the formation of higher order morphologies. As such, the impact
of stirring speed on morphology has been clearly evidenced in a PISA emulsion
polymerization system [204]. In dispersion polymerization formulations, more and
more authors decrease the volume of the experimental set-ups (<1 ml NMR tubes
[188] or microtitre scales such as in 96-well microtitre plates [205]) and monitor
PISA in situ by NMR or SAXS in unstirred set-ups, but it is questionable whether
such unstirred PISA provides ‘valuable’ results on morphologies.
Another important parameter, which determines the morphology in PISA, is the
monomer concentration. As mentioned above, a higher monomer concentration
promotes the formation of higher order morphologies through plasticizing of the
core chains and an increased number of particles per volume unit in the reaction
medium [186, 189, 206]. The polymerization temperature is another parameter to
be taken into account. Indeed, modification of the polymerization temperature
affects the polymer/polymer and polymer/solvent interaction parameters and may
result in morphological changes through the alteration of the packing parameter
(see also Section 15.5.4). In addition, the temperature also has an effect on the
particle formation mechanism through changes in the propagation rate coefficient
kp or on the polymerization control through alteration in radical flux (in the case
of thermal initiation) [86]. Furthermore, an impact of the initiator concentration
[89, 207] or the type of the initiating system (thermal PISA vs. photo-PISA) has also
been reported [208].
The self-assembly of diblock copolymers has been rationalized by the packing
parameter p (Figure 15.1) [209], a concept which was initially developed for small
amphiphilic molecules (surfactants). p is defined as v/(al), where a is the area of
the surfactant head group, and v and l are the volume and length of the surfactant
tail, respectively. The self-assembly and the resulting morphology are essentially a
balance between the degree of stretching of the core-forming chains, the interfacial
tension between the solvophobic core and its external environment, and repulsive
70
S a
65
60 c
DPn (PDAAm)
55
S+W W+V V
50
45
40 b
W
35
50 70 90 110 130 150 170 190 210
DPn (PDAAm)
Figure 15.5 Phase diagram constructed for a series of PDMAAm-b-PDMAAm diblock

copolymer nano-objects. S = spheres, S + W = mixed spheres and worms, W = worms,
W + V = mixed worms and vesicles, and V = vesicles. Source: Reprinted with permission
from Byard et al. [172]. Copyright 2017, American chemical society.
interactions between shell chains [79]. In essence, the morphology changes with
the increasing volume ratio between the solvophilic and solvophobic segments from
spheres (p ≤ 1/3) to cylinders (1/3 ≤ p ≤ 1/2) to vesicles (1/2 ≤ p ≤ 1) (Figure 15.1).
Strictly speaking, this concept holds only for morphologies at thermodynamic
equilibrium. With the discovery of higher order morphologies by PISA, the concept
was however rapidly applied to PISA-derived assemblies – which are not necessarily
at equilibrium – by varying a certain number of features that are listed below.
15.5.2.1 Varying the Molar Mass

A direct way to control the morphology is thus to tune the volume fraction of
the solvophobic and solvophilic segments through the adjustment of the molar
mass of each block. For a given solvophilic block, by increasing the molar mass
of the solvophobic block, the morphology can thus be transformed from spheres
towards worms to vesicles – provided that a morphological transition is possible
[12, 50, 52, 85, 196]. This has been widely explored in the literature, and many,
rather complete, pseudo-phase diagrams have been constructed. As the packing
parameter is the result of the interplay of polymer/polymer and solvent/polymer
interactions, the absolute molar mass of the block segments depends on the
polymer type and the solvent used for the polymerization. The packing parameter
and thus the morphology are very sensitive to small changes in molar mass [210],
and generally, the pure worms are typically accessible in a very narrow window of
composition (Figure 15.5).
15.5.2.2 Varying the Chemical Nature of the Solvophobic Block

As mentioned above, Mathers, O’Reilly, and coworkers have shown a correlation
between the chemical nature of the monomers to be polymerized and the particle
morphology by comparing the aqueous dispersion polymerization of increasingly
hydrophobic monomers using an in silico method. In identical experimental con-

ditions, the morphologies changed from spherical particles to worms and vesicles
with increasing hydrophobicity of the monomers [188]. An and coworkers synthe-
sized a series of alkyl α-hydroxymethyl acrylates of tunable water solubility to study
systematically the impact of the monomer solubility on morphology [189]. They
have notably observed that the less water-soluble monomers, ethyl- and isopropyl
α-hydroxymethyl acrylate in particular, promoted the formation of higher order mor-
phologies at lower DPn s of the solvophobic block.
The former systems were based on monomers with relatively high water solu-
bility, so that the polymerization mechanism was essentially that of a dispersion
polymerization formulation. As mentioned above, monomers classically used in
aqueous emulsion polymerization formulations often lead to kinetically trapped
spheres – unless stabilizers comprising PEG grafts were used. It should be noted that
the effect of the monomer water solubility on morphology has also been assessed for
monomers that possess a lower solubility in water, which are polymerized at a much
higher concentration. For instance, replacing BzMA (aqueous solubility = 0.4 g l−1
at 70 ∘ C) by HBMA (aqueous solubility = 20 g l−1 at 70 ∘ C) [198] (using a PMAA
macroRAFT at pH 5) allowed to form unusual so-called ‘monkey nut’ morphologies,
whereas spheres were obtained with the less-soluble BzMA. Such an effect of the
monomer solubility had already been reported before comparing the emulsion
polymerization of MMA with that of styrene (aqueous solubility of MMA = 15 g l−1
at 30 ∘ C, of styrene = 0.3 g l−1 at 20 ∘ C) [86]. It seemed that the formation of higher
order morphologies was favoured in the case of more soluble monomer MMA, but
an influence of the differences in rate coefficient was also postulated.
An interesting alternative to selecting suitable monomers or designing new
monomers to tune morphology is the incorporation of solvophilic monomer units
in the solvophobic block. Since 2015, this concept has been reported by several
authors. For instance, 4VP [211] or MMA [212] were added as a comonomer to the
dispersion polymerization of styrene. It was possible to tune the morphology by the
molar ratio of 4VP/styrene in the monomer feed, in addition to adjusting the ratio
of monomer/RAFT ratio (DPn ). Besides, while for styrene alone, only spherical
micelles were generated, the insertion of 25 mol% of MMA into the solvophobic
block enhanced its mobility promoting morphological transitions and the formation
of worms and vesicles. Both examples showed that the incorporation of a more
solvophilic monomer was beneficial for the formation of high-order morphologies.
More recently, the same concept has also been explored by Figg et al. in the aqueous
dispersion polymerization of DAAm with DMAAm demonstrating the general
validity of this concept [213]. Based on SLS analysis, the authors suggested that the
insertion of a hydrophilic monomer alters the thermodynamics of the aggregation,
promoting morphological reorganization.
15.5.2.3 Varying the Topology of the Shell or the Core

As mentioned above, in emulsion polymerization formulations, non-spherical
morphologies are scarce. They had exclusively been observed for formulations
using graft copolymers as macroRAFT obtained by copolymerization of PEG
macromonomers. In 2016, the group of Lansalot and D’Agosto has shown that the
topology of the stabilizer composed of PNAM, to which an average of three PEGA
units as pendant chains were incorporated, had a critical impact on the particle
morphology obtained in the successive emulsion polymerization of styrene [87].
Depending on the presence or absence and the position of the pendant PEG chains
(at the beginning, randomly distributed, or at the end of the chain), different mor-
phologies, notably spheres, nanometric vesicles, or large vesicles, were obtained.
Again, only spherical particles were obtained for the linear, non-branched polymer,
i.e. PNAM homopolymer.
Instead of tuning the topology of the solvophilic macroRAFT agent, Yuan group
inserted bulky and solvophobic comonomers, namely, stearyl acrylate [214] and
2-(perfluorooctyl)ethyl methacrylate [215], in the solvophobic block. They showed
that the vesicle size could be tuned by the molar fraction of the comonomer.
15.5.2.4 Varying the Solvent Quality

Instead of varying the monomer, others have studied the effect of the solvent on
the morphological phase diagram. In one of the first reports, it was shown that the
addition of organic co-solvents (ethanol or dioxane) to the aqueous emulsion poly-
merization of BzMA was beneficial for morphological transitions and the formation
of higher order morphologies. It was also shown that the morphologies strongly
depended on the co-solvent properties: although small amounts of 1,4-dioxane led
to huge morphological changes, much higher amounts of ethanol were necessary
to tune the morphology [199]. More recently, the introduction of non-reactive PEG
in the polymerization medium as a means to alter morphology and to promote
in particular the formation of complex membrane morphologies [216] and the
production of vesicles of uniform size was also described [217]. A particular case
is the combination of specific monomers (styrene/N-phenylmaleimide) with the
mixture of specific solvents (ethanol/methyl ethyl ketone), allowing the forma-
tion of complex morphologies, such as micrometric particles comprising inverse
bicontinuous phases [218].
Instead of co-solvents, additives have also been added to traditional PISA formu-
lations in order to alter the solubility of the monomers. As such, cyclodextrin (CD)
has been added to aid dissolution of a water-immiscible monomer (styrene), allow-
ing for its aqueous dispersion polymerization thanks to host–guest complex for-
mation [219]. Performing PISA of the CD–styrene complexes in the presence of a
PEG macroRAFT gave access to the direct synthesis of various kinetically trapped
PS-based nanostructures in water, in particular hollow nanotubes.
15.5.2.5 PISA in Aqueous Media: Varying pH and/or Ionic Strength

One should not forget the possibility to greatly tune the solvent properties of water
by addition of salts or by changing the pH, which is of greatest importance when-
ever weak polyacids or polybases are used as macroRAFT. For instance, the effect of
pH on morphology had been largely studied for the aqueous emulsion polymeriza-
tion of styrene using P[(M)AA-co-PEG(M)A] macroRAFT as stabilizers [85, 194]. In
addition to being sensitive to changes in pH, a strong impact of the ionic strength
and the salt type was evidenced, both in emulsion [194, 204] and dispersion poly-
merization formulations [220]. The presence of salts may directly alter the pack-
ing parameter through changes in interaction parameters, which may explain the
observed changes in morphology. In addition, salts diminish the electrostatic repul-
sion between individual particles, thereby promoting particle fusion.
Although these former examples demonstrate the pH and salt sensitivity of PISA
when weak polyacids or polybases were used, the surprising effect of a single charged
moiety present in non-ionic macroRAFT agents has also been demonstrated. Several
articles report indeed a great impact of pH on nanoparticles stabilized by a neutral
polymer and terminated by a single weak acid group or a charged unit, but in the
majority of cases, the morphological transitions were induced through pH variation
post-synthesis (cf. Section 15.5.4) [221–223]. To demonstrate the importance of such
an α-end-group during PISA, Khor et al. had compared the aqueous emulsion poly-
merization of styrene using two types of P(HEAm-co-PEGA) macroRAFT agents, the
first one bearing a carboxylic acid α-end-group while the second one was the methyl
ester [89]. Their study revealed a great effect of the end group on the morphologies
over a large range of pH.
15.5.2.6 Varying the Block Copolymer Architecture via the RAFT Agent
Although the impact of the respective molar masses, polymer nature, and solvent
has been extensively studied, much less attention has been paid on the macromolec-
ular architecture. In most of the studies, monofunctional RAFT agents are used,
generating linear copolymers, mostly AB diblock copolymers (A is the solvophilic
block synthesized in the first step and B is the solvophobic block synthesized in the
second step), but ABC triblock copolymers have also been reported. Virtually from
the start of PISA, bifunctional symmetrical RAFT agents producing ABA structures
have also been implemented successfully [224–227], but more recently, trifunctional
[228] or tetrafunctional RAFT agents [229] – leading to the formation of tri-arm or
tetra-arm star polymers – have also been used. These articles show that the structure
of the RAFT agent, i.e. the number of functionality (mono-, bi-, or multifunctional),
the inversion of the Z and R groups leading to BAB [185, 230–232], or (BA)n stars
[229, 233, 234] has a crucial impact not only on the polymerization mechanism and
control but also on the resulting particle morphology. Although it was not always
PEG-CTA PEG-PDAAM linear BCP

PISA
PEG-(CTA)2 PEG-(PDAAM)2 star BCP
Figure 15.6 A(B)2 star architecture promoting the formation of complex morphologies
compared to linear diblock copolymers. Source: Reprinted with permission from Wang et al.
[235]. Copyright 2017, American chemical society.
straightforward to correlate macromolecular architecture and morphology in the

former examples [228, 230], An’s group [235] has proposed an elegant approach to
rationally increase the packing parameter via macromolecular architecture design.
They synthesized a bifunctional asymmetric RAFT agent to which a PEG chain
was coupled through an additional functional group at the symmetry point of the
RAFT agent (Figure 15.6). Compared to linear AB architectures, the resulting A(B)2
tri-arm star copolymers clearly promoted the formation of vesicles as expected for
copolymers with bulky hydrophobic segments, considering the packing parameter
theory (Figure 15.1).
15.5.3 Strategies to Stir Specific Morphologies

Apart from studying systematically different parameters and assessing their impact
on particle morphology, recently, several strategies have been devised to control the
morphology instead of suffering from it. In the previous section, we have reported
that the formation of higher order morphologies can be promoted by increasing the
volume fraction of the hydrophobic block through the rational design of the RAFT
agents [235].
Besides from increasing the hydrophobic volume to increase the packing param-
eter promoting the formation of vesicles/lamellae, other strategies aimed at synthe-
sizing a targeted particle morphology in robust synthesis conditions and to obtain it
as a pure phase, which is not mixed with other morphologies as often observed in
PISA. As an example, the worm morphology is generally obtained in a narrow exper-
imental window [54, 172] (Figure 15.5), and in view of the possible applications,
it would be of great interest to find means to enlarge the experimental window in
which worms can be obtained. In addition, other research projects aim at producing
complex particle morphologies that are not observed in simple PISA formulations,
for instance, cuboids or ellipsoids.
15.5.3.1 Using PICA

As mentioned in Section 15.3.3, Zhu et al. used binary mixtures of macroRAFT and
the parent molecular RAFT agent to promote the formation of higher order mor-
phologies through the concomitant formation of solvophobic homopolymer in a
derived-PISA system called PICA [106]. It should be mentioned that this concept
of mixing a macroRAFT with a molecular RAFT agent has also been explored by
the group of Tan and Zhang using a PEG macroRAFT instead of a PDMAEMA one
[107, 108]. Finally, Zhang group who has worked a lot on inverted RAFT agent struc-
tures, has shown that the mixture of monofunctional PEG TTC macroRAFT with its
bifunctional analogue TTC-PEG-TTC promoted the formation of compartmental-
ized vesicles [231].
15.5.3.2 Using Mesogenic Monomers (PIHSA)

In order to form anisotropic nanoparticles, such as cylinders [236], cuboids [112],
or ellipsoids [148, 237], a known strategy in post-synthesis block copolymer
self-assembly relies on the use of polymers that are able to organize within the
core into (semi)crystalline or liquid crystalline domains [238, 239]. In this respect,
mesogenic monomers, containing cholesteryl [236], azobenzene [112], or long
(semi)fluorinated chains [148, 237], have been used, generally in non-aqueous dis-
persion polymerization formulations. Particles with unusual shapes were obtained
in all examples, which were attributed to the internal liquid crystalline (mostly
smectic phases) organization as determined by SAXS. As discussed in Section
15.3.3, the formation of such anisotropic nanoparticles by PISA containing liquid
crystalline mesogens in their core has also been termed as PIHSA [112].
15.5.3.3 Using Ionic Complexes (PIESA) and Hydrogen-Bonding Units

Other authors have shown that using particular monomers that can undergo
supramolecular interactions, such as H-bonding or the formation of polymeric ionic
complexes (PIC), is also a means to tune morphology in PISA and to produce rather
exotic morphologies (Section 15.3.3). For instance, acrylamides such as DAAm
[173] or nucleobase-based monomers [240, 241] are capable of forming H-bondings
with themselves or with mediator molecules leading to specific structures, while
charged monomers can generate PICs with polyelectrolytes added to PISA [110] or
formed through chain extension of double-hydrophilic AB block copolymers with
a third block of opposite charge [109]. This latter strategy is PIESA, as discussed in
Section 15.3.3.
The previous examples show that there is a current trend to combine supramolecu-
lar chemistry and PISA. Although the latter examples were based on supramolecular
interactions between monomer units of the core chains, Rieger, Stoffelbach, and
coworkers have very recently devised a templating strategy based on interactions
between a single sticker unit placed at the ω-end of each chain. They actually
designed macroRAFTs functionalized by a hydrogen-bonded bisurea sticker [242]
in order to drive PISA towards the nanofibre morphology, via one-dimensional,
directed assembly of the sticker units, which is reinforced by the creation of
hydrophobic domains during PISA (Figure 15.7). This concept was tested in
the synthesis of poly(N,N-dimethylacrylamide)-b-poly(2-methoxyethyl acrylate)
diblock copolymers prepared by dispersion polymerization in water. The results
clearly showed that the developed strategy promotes the formation of nanofibres in
a large experimental window [243].
PDMAc
MEA
PISA
Bis-urea in water
sticker
Water-soluble Self-assembled amphiphilic

functionalized macro-RAFTs diblock copolymers
Figure 15.7 Using bis-urea functional macroRAFT agent for ‘templated PISA’ in water.
Source: Reprinted with permission from Mellot et al. [243]. Copyright 2019, Wiley.
15.5.3.4 Hierarchical Assembly Between Particles

Finally, one should also mention the possibility to construct complex hierarchical
assemblies from primary nanoparticles (obtained by PISA) through supramolecular
interparticle interactions. As an example, raspberry-like nanoparticles have been
produced by controlled heterocoagulation of PEG-stabilized and PAA-stabilized
nanoparticles via hydrogen bonding interactions between PAA and PEG chains
[244]. More recently, the possibility to functionalize the surface of PS particles by
naphthalene units, present at the α-chain end of the PAA macroRAFT, was also
demonstrated [131]. The latter particles should be useful as building blocks to
construct larger supramolecular structures through host–guest interactions.
15.5.4 Post-polymerization Morphological Transitions/Chain

Reorganization
It is well known that amphiphilic block copolymer assemblies prepared by tradi-
tional assembly methods (such as nanoprecipitation or solvent displacement) can
undergo morphological transitions if one of the blocks is responsive to external
stimuli – such as pH or temperature in the simplest case. The result is either the
dissociation of the assembly (also called ‘order-disorder transition’) or a change
in morphology (termed ‘order-order transition’ or ‘morphological transition’).
Although the former case has been largely explored, the latter case was actually
rarely reported for such conventional block copolymer assemblies. In contrast,
post-polymerization morphological order-order transitions play nowadays a major
role in PISA, probably because of the large variety of systems explored and the
possibility to synthesize highly concentrated dispersions, which pave the way to
new properties and applications. Firstly, simply observed, such transitions are now
understood (they are mainly the result of changes in the packing parameter) and
have also found applications. It should be mentioned that they are not always
desired and that chain crosslinking is a means to prevent them by freezing the
assembly (cf. Sections 15.4.2 and 15.4.3). On the other hand, the dynamics of the
assembly must be favourable to the transition. In other words, a kinetically frozen
assembly will not be able to rearrange chains, resulting in a change of morphology
(in reasonable timescales).
Several reviews have summarized and commented order-order transitions (among
other aspects of PISA) [50, 52, 54, 60] or even dedicated the whole review to this
subject [55]. We will thus only briefly summarize the most important stimuli that
have been reported to induce post-polymerization morphological transitions in PISA
and illustrate them by some representative examples. Some of the examples will be
detailed in Section 15.6.
15.5.4.1 Temperature
Temperature-induced morphological transitions (TIMTs) in water have first been
reported for diblock copolymers possessing PHPMA as a core block [245]. It was
shown that such PGMA-b-PHPMA block copolymer worms transformed into spher-
ical micelles, when the solution was cooled from room temperature to 4 ∘ C. The
morphological transition resulted in a change in bulk properties: although entangled

worms form free-standing gels, the corresponding sphere dispersion is a liquid of low
viscosity. A possible application of such thermoresponsive gels is their use as steril-
izable gels. Since then, other types of core polymers (generally rather ‘hydrophilic’
polymers prepared through dispersion polymerization formulations) have also
been reported, for instance, using PDMAAm [172, 246]. These post-polymerization
transitions have been termed temperature-induced morphological transitions
(TIMTs) by Wang et al. [246], and they are usually explained by a change in surface
plasticization, leading to a change in the packing parameter. The transition tem-
perature is generally very sensitive to the molar mass of the polymers and can thus
be tuned by the DPn [210] or by copolymerization. For instance, Warren, Plamper,
and coworkers copolymerized NIPAM with tert-butyl acrylamide (tBuAAm) to
afford PDMAAm-b-P(NIPAM-co-tBuAAm) assemblies for which morphological
transitions could be induced by both temperature and hydrostatic pressure [206].
TIMT have not only been reported in water but also in non-aqueous media, such
as in n-dodecane [247] or in mineral oil [248]. In the latter case, PSMA-b-PBzMA
diblock copolymer assemblies were synthesized through a dispersion polymeriza-
tion formulation. DPn of the polymers was tuned in order to obtain vesicles, which
underwent a vesicle-to-worm transition upon heating above a critical gelation tem-
perature (at 135 ∘ C, as the non-interacting vesicles are converted into weakly inter-
acting worms). This concept provides a new mechanism for the high-temperature
thickening of oils.
15.5.4.2 pH
As mentioned above (Section 15.5.2), morphological transitions can be triggered by a
change of pH, in case the nano-objects are stabilized by a weak polyelectrolyte shell,
or even by a neutral polymer possessing a single ionizable functional group (such
as a carboxylic acid group [221, 222] or a morpholine end group [223]). In the case
of a PGMA-b-PHPMA diblock copolymer synthesized from a carboxylic acid func-
tional RAFT agent, worm-to-sphere [221] or vesicle-to-worm (or sphere) transitions
[222] could be induced by a pH increase. The ionization of the terminal carboxylic
acid group should increase the volume of the hydrophilic segment, triggering the
observed slow morphological transitions. Instead of triggering morphological tran-
sitions, it was also possible to trigger the inversion of the core and shell of spherical
diblock copolymer micelles, possessing two pH-responsive blocks, in the example a
polyamine and a hydrophobic polyacid block, prepared by PISA. Such pH-responsive
spherical micelles are called ‘schizophrenic’ micelles, and they offer the possibility
to incorporate and release a payload on demand [249]. In addition to pH-responsive
diblock copolymer self-assemblies, the concept was also reported for ABC triblock
copolymers, where morphological transitions could be induced by the protonation
of a polyamine middle block [250].
15.5.4.3 ‘Reactive’ Groups

As already mentioned in Section 15.4, ‘reactive groups’ that are able to interact or
react in a larger sense may also induce morphological transitions.
● Degradation. As reported above, morphology is related to the packing parameter

and thus in the simplest case to the DPn of the hydrophilic and hydrophobic blocks.
So finally, a means to alter morphology after polymerization is thus to alter the DPn
of the core block. An elegant while slow strategy to induce order-order morpho-
logical transitions was thus the design of a degradable core block by copolymer-
izing 3-methylidene-1,9-dioxa-5,12,13-trithiacyclopentadecane-2,8-dione (MTC),
a disulfide-based cyclic monomer, yielding copolymers with degradable disulfide
bonds in the main chain. The authors validated their concept and showed that
worm could be transformed into sphere thanks to the chemical degradation of the
hydrophobic P(HPMA-co-MTC) block [251].
● Initiators. A particular type of reactive groups are initiators, i.e. groups that are
capable of initiating the growth of a new polymer chain. As such, in the work
of St Thomas et al., alkoxyamine-functionalized latex nanoparticles were synthe-
sized by RAFT-PISA and depicted in Section 15.4.1. They were used in a sec-
ond polymerization step performed at higher temperature (130 ∘ C) to form of a
double hydrophilic corona (PAA-b-PSSNa), which went along with a switch in
morphology [130].
● Dynamic covalent bonds and supramolecular interactions. A completely different
type of reactive group is the supramolecular interacting group that may bind
to a specific molecule by complexation. The Armes group showed in 2017 how
dynamic covalent chemistry can drive order-order morphological transitions
in aqueous dispersions of PGMA-b-PHPMA diblock copolymer vesicles in
order to release nanoparticle payloads from the vesicles [252, 253]. In the first
example [252], the addition of 3-aminophenylboronic acid (APBA) to such
vesicles at pH ∼ 10 resulted in specific binding of this reagent to some of the
pendent cis-diol groups of the hydrophilic PGMA chains to form phenylboronate
ester bonds. This led to a subtle increase in the effective volume fraction of this
stabilizer block, which in turn caused a reduction in the packing parameter and
hence induced a vesicle-to-worm (or vesicle-to-sphere) morphological transition,
and eventually the release of silica particles. In the same year, the same group
also explored host–guest chemistry, another subclass of supramolecular chem-
istry, to modify the morphological transition of preformed diblock copolymer
assemblies [137]. CD (host)–azobenzene (guest) interactions were exploited
to tune, in particular, the rate of thermally induced morphological transitions
for β-CD-functionalized vesicles constituted of P(GMA-co-GlyMA)-b-PHPMA
diblock copolymers. Addition of azobenzene–methoxypoly(ethylene glycol)
to such vesicles resulted in the formation of an inclusion complex with the
β-CD groups present at the hydrophilic P(GMA-co-GlyMA) chains and led
to a significantly faster change in copolymer morphology compared to the
β-CD-functionalized vesicles alone.
15.5.4.4 Light
In addition to being hydrophobic mesogenic moieties, which can arrange in a liquid
crystalline order (see Sections 15.3.3 and 15.4.2), and their ability to interact with
CD, azobenzenes are also known to be light responsive. Triggered by changes in
wavelength, they can undergo a reversible trans–cis isomerization, which results in

a change in hydrophobicity. Already largely explored for assemblies prepared from
preformed polymers, copolymers possessing pendant azobenzene groups in their
core have also been synthesized by PISA. The UV-light-induced morphological
transformations were again rationalized by the volume change of the hydrophobic
block caused by the isomerization of the azobenzene moieties [112, 254]. Bagheri
et al. proposed another strategy to use light as a trigger to change morphology. They
incorporated 1-pyrenemethyl methacrylate as a comonomer in the solvophobic
block of photoactive nanoparticles, as a means to photochemically trigger particle
dissociation by cleavage of pyrene moieties, leading to a solvophobic–solvophilic
transition of the core polymer [255].
15.5.4.5 Oxygen
To finish with, the same group has also prepared nano-objects possessing core
polymers sensitive to reactive oxygen species, namely, poly(2-(methylthio)ethyl
methacrylate), by a PISA process. In this work, particle disassembly rather than mor-
phological transitions were observed through a hydrophobic–hydrophilic change
in the block copolymer properties because of the oxidation of the thioether groups
[256]. Similarly, Sobotta et al. demonstrate that the cyclic thioether N-acryloyl
thiomorpholine can be used in PISA to afford a hydrophobic block, which can be
transformed upon oxidation into a highly water-soluble sulfoxide, leading again to
the disassembly of the particles [257].
15.6 Applications
As mentioned in previous sections, the possibility to produce nano-objects
of various shapes in high amount and concentration opens the door towards
their application in various fields. Although standard applications of micellar
objects/nanoparticles – such as their use as drug delivery vehicles – have been
explored, original applications related to the possibility to synthesize them at high
solid contents have also been reported. In the latter case, the bulk properties of
these concentrated dispersions have been explored, typically in the case of worm
dispersions that may form free-standing gels and for which the rational design
of the copolymer allowed to make them thermoresponsive. The following part
summarizes the main applications of PISA-derived nanoparticles that have been
explored. For each application, some representative examples are provided.
To date, the most explored field of application for PISA certainly concerns biomed-
ical applications. Indeed, PISA allows the synthesis of core–shell nanoparticles
directly in aqueous media without using co-solvents, combined with the possibil-
ity to encapsulate any kind of payload in situ, i.e. during polymerization. All main
morphologies accessible by PISA have been explored for the encapsulation and deliv-
ery of drugs [64]. Although spherical and worm-like morphologies have been used to
encapsulate hydrophobic drugs, vesicles (also termed polymersomes in the biomedi-
cal field) allow the encapsulation of both hydrophobic (in the bilayer membrane) and
hydrophilic drugs (in the cavity) or other bio-relevant agents (such as enzymes). A
related biomedical application concerns the encapsulation of any type of molecules
or materials useful for imaging purposes. As such, fluorescent dyes, magnetic par-
ticles [258], or alternatively 19 F-containing fluorinated monomers [149, 258] have
been incorporated. Some papers reported the synthesis of model stimuli-responsive
vesicles by PISA able to release various species such as silica nanoparticles [252, 259,
260], BSA [177, 259], rhodamine B [261], Nile red [262], or enzymes [263].
Worm dispersions that form free-standing gels at room temperature (or physiolog-
ical temperature) and that are less viscous at low temperature (because of reversible
morphological worm-sphere transitions, see Section 15.5.4) have also found interest
for biomedical applications as they are sterilizable by filtration at low temperature
[134, 245]. Their potential use as drug delivery systems, for tissue engineering or for
cell storage, has been considered [264]. In contrast, vesicles have also found interest
as mimicking systems for living cells [63, 265]. For instance, enzymes have suc-
cessfully been encapsulated in vesicles and their permeability has been modulated,
for instance, by the incorporation of pores [266]. In addition to mimicking living
cells, another aspect of such bio-hybrids is their use as enzymatic nanoreactors [263,
267]. For more details on biomedical applications of PISA-derived nano-objects, the
reader can refer to recent reviews, which provide an excellent overview on the exist-
ing systems [60, 62, 64].
Another application of particles produced by PISA is catalysis. PISA was
employed to nanostructure the particle cores in order to generate catalytic nanoreac-
tors dispersed in water. This was achieved by the use of hydrophobic monomers car-
rying triphenylphosphine ligands and a crosslinker introduced either at the begin-
ning of the emulsion polymerization or at a later stage. After complexation of Ru, the
resulting catalytic nanoreactors proved to be useful for hydroformylation of octene
[268–271]. Metallic Pd(0) nanoparticles have also been introduced, for instance,
into nanogels obtained by PISA, and showed a remarkable stability in the solid state
and in solution. This feature allowed their successful application as catalysts for the
Mizoroki–Heck reaction between n-BA and a series of bromo- and iodo-arenes [272].
In addition to the examples cited above, a large variety of metal-hybrid nanocatalysts
(most of the incorporating metal particles) have now been synthesized using PISA,
but their detailed description is out of the scope of this review.
An expanding application of PISA-derived particles is their use for the stabiliza-
tion of liquid–liquid interfaces to form the so-called Pickering emulsions [273].
Block copolymer nanoparticles of various morphologies, mainly spheres and worms
[165, 274, 275], but also vesicles [274] have been investigated. Furthermore, the
utility of thermoresponsive particles that undergo worm-to-sphere morphological
transitions in the field of Pickering emulsions has also been demonstrated [276].
The different studies revealed that not only the type of shell and core (crosslinked or
not) polymer but also the particle morphology play a crucial role in their efficiency
to stabilize emulsions. Eventually, one may note that worm-like particles have also
been used successfully to stabilize high internal phase emulsions (HIPEs) [277].
The main particle morphologies have also all been used as templating agents
to produce hollow inorganic nanoparticles, porous materials, or nanocomposites.
One of the first examples was the use of nanoworms as soft templates to produce
hollow silica nanotubes through calcination of the hybrid nanoworms prepared in
a previous synthesis step [278]. More recently, spherical nanoparticles possessing a
soft poly(hydroxyethyl acrylate) core have been used to prepare uniform mesoporous
carbon materials [103]. Another type of inorganic material used in combination with
nanoparticles made by PISA is calcite (CaCO3 ) [279, 280].
Other applications of PISA nanoparticles concern their use as additives in com-
plex formulations. Anisotropic particles or particles that undergo morphological
transitions are of particular interest for these applications. Aqueous dispersions
of long fibres can be used as rheomodifiers to adjust the rheology of complex
formulations [281], whereas thermoresponsive vesicles that exhibit a heat-induced
vesicle-to-worm morphological transition in mineral oil have a potential interest
as lubricants for oils, as heat thickening is an unusual and desired rheological
feature [248]. Another application is in the field of coatings, with the use of hollow
particles (vesicles [282] or bicontinuous microparticles [218]) as opacifiers for paint
films. Besides, the utility of high T g PISA nanofibres as mechanically reinforcing
fillers for soft films has also been demonstrated [283], while highly asymmetric
diblock copolymer nanoparticles composed of a large soft PBA core block and a
short hard PAA shell can be used to prepare nanostructured films with enhanced
properties [127, 128].
Although most of the previous applications concern the individual nanoparticle
itself or the bulk properties of a particle dispersion, other applications concern the
films that can be produced after drying or processing the dispersions. For instance,
thin nanostructured films of PISA nanoparticles (pure polymer particles [284, 285]
or hybrids [286]) have been spin-coated as thin films to construct membranes for
water ultrafiltration purposes.
As mentioned in Section 15.1, PISA was initially developed for emulsion polymer-
ization formulations to produce surfactant-free latexes. The presence of free sur-
factants is still an important issue in the coating industry, and the current expiration
of the RAFT patents is expecting to further boost the industrial demands for develop-
ing PISA for coating applications, hopefully with the aid of academic collaborations.
15.7 Conclusions
As shown in the previous sections, PISA is a very simple and efficient tool to
produce amphiphilic block copolymers in high concentrations and a way to
self-assemble these block copolymers into nano-structured aggregates during their
formation. PISA is attracting a broad range of interests from polymer chemists and
physico-chemists to biologists and, as a direct consequence, PISA is generating a
broad range of hopes for various applications. We believe that the reading of this
overview on RAFT-mediated PISA will easily allow the reader to comprehend the
vast potential of this technique. The transposition of new processes or technolo-
gies to industry is a challenge because it always faces the robustness of, and the
experience gained on, the existing systems. PISA will perform even better in the
near future with the development of process parameters, e.g. continuous processes
[287–289] and will undoubtedly benefit from the well-established industrial field of
polymerization in dispersed media.
Acknowledgements
Drs Bastian Ebeling and Arne Wolpers (C2P2) are gratefully acknowledged for help-
ful discussions.
Abbreviations
(M)AA (meth)acrylic acid
AAEM 2-(acetoacetoxy)ethyl methacrylate
ADH adipic acid dihydrazide
BA n-butyl acrylate
CD cyclodextrin
DAAm diacetone acrylamide
DEAAm N,N-diethyl acrylamide
DEAEMA 2-diethylaminoethyl methacrylate
DLS dynamic light scattering
DMAAm N,N-dimethyl acrylamide
DMAEMA 2-dimethylaminoethyl methacrylate
DPn number-average degree of polymerization
DVB divinylbenzene
GMA glycerol methacrylate
GlyMA glycidyl methacrylate
HBMA 2-hydroxybutyl methacrylate
HDFDMA heptadecafluorodecyl methacrylate
HEAAm hydroxyethyl acrylamide
NMR nuclear magnetic resonance
LCST lower critical solution temperature
macroRAFT macromolecular RAFT agent
NIPAM N-isopropylacrylamide
p packing parameter
PEG(M)A poly(ethylene glycol) methyl ether (meth)acrylate
PFPMA pentafluorophenyl methacrylate
PISA polymerization-induced self-assembly
RAFT reversible addition-fragmentation chain transfer
RDRP reversible-activation radical polymerization
SANS samll angle neutron scattering

SAXS small angle x-ray diffraction
SLS static light scattering
sc CO supercritical carbon dioxide
2
SEC size exclusion chromatography
SMA stearyl methacrylate
St styrene
SSNa sodium 4-styrene sulfonate
(cryo)TEM (cryogenic)transmission electron microscopy
TIMT temperature-induced morphological transitions
VAc vinyl acetate
VDF vinylidene fluoride
4VP 4-vinyl pyridine
References
1 D’Agosto, F., Rieger, J., and Lansalot, M. (2020). RAFT-Mediated

Polymerization-Induced Self-Assemply. Angew. Chem. Int. Ed. 59: 8368. https://
doi.org/10.1002/anie.201911758.
2 Destarac, M. (2018). Polym. Chem. 9: 4947.
3 Barner-Kowollik, C. (ed.) (2008). Handbook of RAFT Polymerization. Weinheim:
Wiley-VCH.
4 Chiefari, J., Chong, B.Y.K., Ercole, F. et al. (1998). Macromolecules 31: 5559.
5 Dommanget, C., D’Agosto, F., and Monteil, V. (2014). Angew. Chem. Int. Ed. 53:
6683.
6 Guerre, M., Rahaman, S.M.W., Améduri, B. et al. (2016). Macromolecules 49:
5386.
7 Abreu, C.M.R., Mendonça, P.V., Serra, A.C. et al. (2012). Macromolecules 45:
2200.
8 Perrier, S. (2017). Macromolecules 50: 7433.
9 Jennings, J., He, G., Howdle, S.M., and Zetterlund, P.B. (2016). Chem. Soc. Rev.
45: 5055.
10 Keddie, D.J. (2014). Chem. Soc. Rev. 43: 496.
11 Charleux, B., D’Agosto, F., and Delaittre, G. (2010). Adv. Polym. Sci. 233: 125.
12 Charleux, B., Delaittre, G., Rieger, J., and D’Agosto, F. (2012). Macromolecules
45: 6753.
13 Delaittre, G., Dire, C., Rieger, J. et al. (2009). Chem. Commun.: 2887.
14 Wan, W.-M., Hong, C.-Y., and Pan, C.-Y. (2009). Chem. Commun.: 5883.
15 Wan, W.-M., Sun, X.-L., and Pan, C.-Y. (2009). Macromolecules 42: 4950.
16 Delaittre, G., Nicolas, J., Lefay, C. et al. (2005). Chem. Commun.: 614.
17 Brusseau, S., D’Agosto, F., Magnet, S. et al. (2011). Macromolecules 44:
5590.
18 Groison, E., Brusseau, S., D’Agosto, F. et al. (2012). ACS Macro Lett. 1: 47.
References 743
19 Qiao, X.G., Lansalot, M., Bourgeat-Lami, E., and Charleux, B. (2013). Macro-
molecules 46: 4285.
20 Wan, W.-M. and Pan, C.-Y. (2007). Macromolecules 40: 8897.
21 Sugihara, S., Sugihara, K., Armes, S.P. et al. (2010). Macromolecules 43: 6321.
22 Wang, G., Schmitt, M., Wang, Z. et al. (2016). Macromolecules 49: 8605.
23 Wang, Y., Han, G., Duan, W., and Zhang, W. (2019). Macromol. Rapid Commun.
40: 1800140.
24 Wang, J., Wu, Z., Wang, G., and Matyjaszewski, K. (2019). Macromol. Rapid
Commun. 40: 1800332.
25 Alzahrani, A., Zhou, D., Kuchel, R.P. et al. (2019). Polym. Chem. 10: 2658–2665.
26 Kapishon, V., Whitney, R.A., Champagne, P. et al. (2015). Biomacromolecules
16: 2040.
27 Sue-eng, S., Boonchuwong, T., Chaiyasat, P. et al. (2017). Polymer 110: 124.
28 Okubo, M., Sugihara, Y., Kitayama, Y. et al. (2009). Macromolecules 42: 1979.
29 Kitayama, Y., Chaiyasat, A., Minami, H., and Okubo, M. (2010). Macromolecules
43: 7465.
30 Kitayama, Y., Moribe, H., Kishida, K., and Okubo, M. (2012). Polym. Chem. 3:
1555.
31 Cordella, D., Debuigne, A., Jérôme, C. et al. (2016). Macromol. Rapid Commun.
37: 1181.
32 Wright, D.B., Touve, M.A., Adamiak, L., and Gianneschi, N.C. (2017). ACS
Macro Lett. 6: 925.
33 Foster, J.C., Varlas, S., Blackman, L.D. et al. (2018). Angew. Chem. Int. Ed. 57:
10672.
34 Torres-Rocha, O.L., Wu, X., Zhu, C. et al. (2019). Macromol. Rapid Commun.
40: 1800326.
35 Le, D., Dilger, M., Pertici, V. et al. (2019). Angew. Chem. Int. Ed. 58: 4725.
36 Sarkar, J., Xiao, L., Jackson, A.W. et al. (2018). Polym. Chem. 9: 4900.
9243.
38 Meijs, G.F. and Rizzardo, E. (1988). Macromol. Chem. Rapid Commun. 9: 547.
39 Yamada, B. and Kobatake, S. (1994). Prog. Polym. Sci. 19: 1089.
40 Rizzardo, E., Meijs, G.F., and Thang, S.H. (1995). Macromol. Symp. 98: 101.
41 Colombani, D. and Chaumont, P. (1996). Prog. Polym. Sci. 21: 439.
42 Moad, G., Rizzardo, E., and Thang, S.H. (2008). Polymer 49: 1079–1131.
43 Moad, G. (2022). An industrial pistory of RAFT Polymerization. In RAFT Poly-
merization: Materials, Synthesis and Applications (eds. Moad, G., Rizzardo, E.),
44 Zhou, D., Kuchel, R.P., and Zetterlund, P.B. (2017). Polym. Chem. 8: 4177.
45 Lotierzo, A., Schofield, R.M., and Bon, S.A.F. (2017). ACS Macro Lett. 6: 1438.
46 Schreur-Piet, Heuts, J.P.A. (2017). Polym. Chem. 8: 6654.
47 Sun, J.-T., Hong, C.-Y., and Pan, C.-Y. (2012). Soft Matter 8: 7753.
48 Sun, J.-T., Hong, C.-Y., and Pan, C.-Y. (2013). Polym. Chem. 4: 873.
49 Warren, N.J. and Armes, S.P. (2014). J. Am. Chem. Soc. 136: 10174.
50 Rieger, J. (2015). Macromol. Rapid Commun. 36: 1458.
51 Derry, M.J., Fielding, L.A., and Armes, S.P. (2016). Prog. Polym. Sci. 52: 1.
52 Lansalot, M., Rieger, J., and D’Agosto, F. (2016). Polymerization-induced
self-assembly: the contribution of controlled radical polymerization to the
formation of self-stabilized polymer particles of various morphologies. In:
Macromolecular Self-assembly (eds. L. Billon and O. Bourisov), 33. Wiley.
53 Lowe, A.B. (2016). Polymer 106: 161.
54 Canning, S.L., Smith, G.N., and Armes, S.P. (2016). Macromolecules 49: 1985.
55 Pei, Y., Lowe, A.B., and Roth, P.J. (2017). Macromol. Rapid Commun. 38:
1600528.
56 Yeow, J. and Boyer, C. (2017). Adv. Sci. 4: 1700137.
57 Zhou, J., Yao, H., and Ma, J. (2018). Polym. Chem. 9: 2532.
58 Six, J.-L. and Ferji, K. (2019). Polym. Chem. 10: 45.
59 Wang, X. and An, Z. (2019). Macromol. Rapid Commun. 40: 1800325.
60 Le, D., Keller, D., and Delaittre, G. (2019). Macromol. Rapid Commun. 40:
1800551.
61 Truong, N.P., Quinn, J.F., Whittaker, M.R., and Davis, T.P. (2016). Polym. Chem.
7: 4295.
62 Khor, S.Y., Quinn, J.F., Whittaker, M.R. et al. (2019). Macromol. Rapid Com-
mun. 40: 1800438.
63 Cheng, G. and Pérez-Mercader, J. (2019). Macromol. Rapid Commun. 40:
1800513.
64 Zhang, W.J., Hong, C.Y., and Pan, C.Y. (2019). Macromol. Rapid Commun. 40:
1800279.
65 Kim, J., Jeong, S.Y., Kim, K.U. et al. (1996). J. Polym. Sci., Part A: Polym. Chem.
34: 3277.
66 Okay, O. and Funke, W. (1990). Macromolecules 23: 2623.
67 Yamauchi, K., Hasegawa, H., Hashimoto, T. et al. (2006). Macromolecules 39:
4531.
68 Monteiro, M.J. and Cunningham, M.F. (2012). Macromolecules 45: 4939.
69 Zetterlund, P.B., Thickett, S.C., Perrier, S. et al. (2015). Chem. Rev. 115: 9745.
70 Such, C.H., Rizzardo, E., Serelis, A.K., et al. (2003). Aqueous dispersions of
polymer particles. WO2003055919A1, filed 20 December 2002 and issued 10
July 2003. University of Sydney, Australia.
71 Hawkett, B.S., Such, C.H., Nguyen, D.N., et al. (2006). Surface polymerisa-
tion process and polymer product using raft agent. WO2006037161A1, filed 04
October 2005 and issued 13 April 2006. The University of Sydney, Australia.
72 Le, T.P., Moad, G., Rizzardo, E., and Thang, S.H. (1998). WO9801478A1, filed
03 July 1997 and issued 15 January 1998. E. I. Du Pont de Nemours & Co.,
USA.
73 Corpart, P., Charmot, D., Biadatti, T., et al. (1998). Method for block polymer
synthesis by controlled radical polymerisation. WO9858974A1, filed 23 June
1998 and issued 30 December 1998. Rhodia Chimie, Fr. invs.
74 Charmot, D., Corpart, P., Adam, H. et al. (2000). Macromol. Symp. 150: 23.
75 Bett, W., Castaing, J.-C., and D’Allest, J.-F. (2001). Surface chemistry
modified latex and resdispersible powders, production and use thereof.
References 745
WO2001042325A1, filed 08 December 2000 and issued 14 June 2001. Rhodia

Chimie, Fr., invs.
76 Meunier, F., Elaïssari, A., and Pichot, C. (1995). Polym. Adv. Technol. 6: 489.
77 Chan, K., Pelton, R., and Zhang, J. (1999). Langmuir 15: 4018.
78 Derry, M.J., Fielding, L.A., and Armes, S.P. (2015). Polym. Chem. 6: 3054.
79 Mai, Y. and Eisenberg, A. (2012). Chem. Soc. Rev. 41: 5969.
80 Ferguson, C.J., Hughes, R.J., Nguyen, D. et al. (2005). Macromolecules 38: 2191.
81 Chaduc, I., Zhang, W., Rieger, J. et al. (2011). Macromol. Rapid Commun. 32:
1270.
82 Ratcliffe, L.P.D., Ryan, A.J., and Armes, S.P. (2013). Macromolecules 46: 769.
83 Sugihara, S., Blanazs, A., Armes, S.P. et al. (2011). J. Am. Chem. Soc. 133:
15707.
84 Zhang, X., Boissé, S., Zhang, W. et al. (2011). Macromolecules 44: 4149.
85 Zhang, W., D’Agosto, F., Boyron, O. et al. (2012). Macromolecules 45: 4075.
86 Zhang, W., D’Agosto, F., Dugas, P.-Y. et al. (2013). Polymer 54: 2011.
87 Lesage de la Haye, J., Zhang, X., Chaduc, I. et al. (2016). Angew. Chem. Int. Ed.
55: 3739.
88 Chaduc, I., Reynaud, E., Dumas, L. et al. (2016). Polymer 106: 218.
89 Khor, S.Y., Truong, N.P., Quinn, J.F. et al. (2017). ACS Macro Lett. 6: 1013.
90 Chaduc, I., Girod, M., Antoine, R. et al. (2012). Macromolecules 45: 5881.
91 Chaduc, I., Crepet, A., Boyron, O. et al. (2013). Macromolecules 46: 6013.
92 Akpinar, B., Fielding, L.A., Cunningham, V.J. et al. (2016). Macromolecules 49:
5160.
93 Hatton, F.L., Lovett, J.R., and Armes, S.P. (2017). Polym. Chem. 8: 4856.
94 Bernard, J., Save, M., Arathoon, B., and Charleux, B. (2008). J. Polym. Sci., Part
95 Binauld, S., Delafresnaye, L., Charleux, B. et al. (2014). Macromolecules 47:
3461.
96 Etchenausia, L., Khoukh, A., Deniau Lejeune, E., and Save, M. (2017). Polym.
Chem. 8: 2244.
97 Etchenausia, L., Deniau, E., Brûlet, A. et al. (2018). Macromolecules 51: 2551.
98 Siirilä, J., Häkkinen, S., and Tenhu, H. (2019). Polym. Chem. 10: 766.
99 Liu, Z., Zhang, G., Lu, W. et al. (2015). Polym. Chem. 6: 6129.
100 Jiang, Y., Xu, N., Han, J. et al. (2015). Polym. Chem. 6: 4955.
101 Tan, J., Xu, Q., Li, X. et al. (2018). Macromol. Rapid Commun. 39: 1700871.
102 Yeow, J., Sugita, O.R., and Boyer, C. (2016). ACS Macro Lett. 5: 558.
103 Tkachenko, V., Matei Ghimbeu, C., Vaulot, C. et al. (2019). Polym. Chem. 10:
2316.
104 Figg, C.A., Simula, A., Gebre, K.A. et al. (2015). Chem. Sci. 6: 1230.
105 An, Z., Shi, Q., Tang, W. et al. (2007). J. Am. Chem. Soc. 129: 14493.
106 Zhu, A., Lv, X., Shen, L. et al. (2017). ACS Macro Lett. 6: 304.
107 Tan, J., Huang, C., Liu, D. et al. (2017). ACS Macro Lett. 6: 298.
108 Tan, J., Xu, Q., Zhang, Y. et al. (2018). Macromolecules 51: 7396.
109 Yu, Q., Ding, Y., Cao, H. et al. (2015). ACS Macro Lett. 4: 1293.
110 Ding, Y., Cai, M., Cui, Z. et al. (2018). Angew. Chem. Int. Ed. 57: 1053.
111 Cai, M., Ding, Y., Wang, L. et al. (2018). ACS Macro Lett. 7: 208.
112 Guan, S., Zhang, C., Wen, W. et al. (2018). ACS Macro Lett. 7: 358.
113 Tichagwa, L., Götz, C., Tonge, M. et al. (2003). Macromol. Symp. 193: 251.
114 Manguian, M., Save, M., and Charleux, B. (2006). Macromol. Rapid Commun.
27: 399.
115 Dos Santos, A.M., Pohn, J., Lansalot, M., and D’Agosto, F. (2007). Macromol.
Rapid Commun. 28: 1325.
116 Wi, Y., Lee, K., Lee, B.H., and Choe, S. (2008). Polymer 49: 5626.
117 Bathfield, M., D’Agosto, F., Spitz, R. et al. (2007). Macromol. Rapid Commun.
28: 1540.
118 Guyot, A. (2004). Adv. Colloid Interface Sci. 108–109: 3.
119 Vinas, J., Velasquez, E., Dufils, P.-E., et al. (2013). Process for the preparation of
a vinylidene chloride polymer. WO2013092587A1, filed 18 December 2012 and
issued 27 June 2013.
120 Velasquez, E., Rieger, J., Stoffelbach, F. et al. (2016). Polymer 106: 275.
121 Devisme, S., Kahn, A., Fuentes-Exposito, M., et al. (2019). Synthesis of
surfactant-free poly(vinylidene fluoride) latexes via raft emulsion polymer-
ization. WO2019063445, filed 21 September 2018 and issued 04 April 2019.
122 Lesage de la Haye, J., Martin-Fabiani, I., Schulz, M. et al. (2017). Macro-
molecules 50: 9315.
123 Martín-Fabiani, I., Lesage de la Haye, J., Schulz, M. et al. (2018). ACS Appl.
Mater. Interfaces 10: 11221.
124 Martín-Fabiani, I., Makepeace, D.K., Richardson, P.G. et al. (2019). Langmuir
35: 3822.
125 Dehan, V., Bourgeat-Lami, E., D’Agosto, F. et al. (2017). Steel Constr. 10: 254.
126 Chenal, M., Bouteiller, L., and Rieger, J. (2013). Polym. Chem. 4: 752.
127 Chenal, M., Rieger, J., Véchambre, C. et al. (2013). Macromol. Rapid Commun.
4: 1524.
128 Chenal, M., Véchambre, C., Chenal, J.-M. et al. (2017). Polymer 109: 187.
129 An, Z., Tang, W., Wu, M. et al. (2008). Chem. Commun.: 6501.
130 St Thomas, C., Guerrero-Santos, R., and D’Agosto, F. (2015). Polym. Chem. 6:
5405.
131 Ebeling, B., Belal, K., Stoffelbach, F. et al. (2019). Macromol. Rapid Commun.
40: 1800455.
132 György, C., Lovett, J.R., Penfold, N.J.W., and Armes, S.P. (2019). Macromol.
Rapid Commun. 40: 1800289.
133 Warren, N.J., Rosselgong, J., Madsen, J., and Armes, S.P. (2015). Biomacro-
molecules 16: 2514.
134 Simon, K.A., Warren, N.J., Mosadegh, B. et al. (2015). Biomacromolecules 16:
3952.
135 Rosselgong, J., Blanazs, A., Chambon, P. et al. (2012). ACS Macro Lett. 1: 1041.
136 Ratcliffe, L., Bentley, K., Wehr, R. et al. (2017). Polym. Chem. 8: 5962.
137 Yao, H., Ning, Y., Jesson, C.P. et al. (2017). ACS Macro Lett. 6: 1379.
138 Maiti, B., Bauri, K., Nandi, M., and De, P. (2017). J. Polym. Sci., Part A: Polym.
Chem. 55: 263.
References 747
139 Boussiron, C., Le Bechec, M., Petrizza, L. et al. (2019). Macromol. Rapid Com-
mun. 40: 1800329.
140 He, J., Xu, Q., Tan, J., and Zhang, L. (2019). Macromol. Rapid Commun. 40:
1800296.
molecules 43: 5211.
142 Ladmiral, V., Semsarilar, M., Canton, I., and Armes, S.P. (2013). J. Am. Chem.
Soc. 135: 13574.
143 Hatton, F.L., Ruda, M., Lansalot, M. et al. (2016). Biomacromolecules 17: 1414.
144 Ladmiral, V., Charlot, A., Semsarilar, M., and Armes, S.P. (2015). Polym. Chem.
6: 1805.
145 Bauri, K., Narayanan, A., Haldar, U., and De, P. (2015). Polym. Chem. 6: 6152.
146 Pei, Y., Noy, J.-M., Roth, P.J., and Lowe, A.B. (2015). Polym. Chem. 6: 1928.
147 Pei, Y., Noy, J.-M., Roth, P.J., and Lowe, A.B. (2015). J. Polym. Sci., Part A:
Polym. Chem. 53: 2326.
148 Shen, L., Guo, H., Zheng, J. et al. (2018). ACS Macro Lett. 7: 287.
149 Zhao, W., Ta, H.T., Zhang, C., and Whittaker, A.K. (2017). Biomacromolecules
18: 1145.
150 Zong, M., Thurecht, K.J., and Howdle, S.M. (2008). Chem. Commun.: 5942.
151 Xu, A., Lu, Q., Huo, Z. et al. (2017). RSC Adv. 7: 51612.
152 Dong, S., Zhao, W., Lucien, F.P. et al. (2015). Polym. Chem. 6: 2249–2254.
153 Zhou, D., Kuchel, R.P., Dong, S. et al. (2019). Macromol. Rapid Commun.
154 Shirin-Abadi, A.R., Jessop, P.G., and Cunningham, M.F. (2017). Macromol.
React. Eng. 11: 1600035.
155 Guo, L., Jiang, Y., Qiu, T. et al. (2014). Polymer 55: 4601.
156 Semsarilar, M., Jones, E.R., and Armes, S.P. (2014). Polym. Chem. 5: 195.
157 Chakrabarty, A., Ponnupandian, S., Kang, N.G. et al. (2018). J. Polym. Sci., Part
158 Ouhib, F., Dirani, A., Aqil, A. et al. (2016). Polym. Chem. 7: 3998.
159 Qiao, Z., Qiu, T., Liu, W. et al. (2016). Polym. Chem. 7: 3993.
160 Guerre, M., Semsarilar, M., Godiard, F. et al. (2017). Polym. Chem. 8: 1477.
161 Couturaud, B., Georgiou, P.G., Varlas, S. et al. (2019). Macromol. Rapid
Commun. 40: 1800460.
162 Busatto, N., Stolojan, V., Shaw, M. et al. (2019). Macromol. Rapid Commun.:
1800346.
163 Zheng, G. and Pan, C. (2006). Macromolecules 39: 95.
164 Lovett, J.R., Ratcliffe, L.P.D., Warren, N.J. et al. (2016). Macromolecules 49: 2928.
165 Hunter, S.J., Thompson, K.L., Lovett, J.R. et al. (2019). Langmuir 35: 254.
166 Chambon, P., Blanazs, A., Battaglia, G., and Armes, S.P. (2012). Langmuir 28:
1196.
167 Hatton, F.L., Park, A.M., Zhang, Y. et al. (2019). Polym. Chem. 10: 194.
168 Tan, J., Liu, D., Huang, C. et al. (2017). Macromol. Rapid Commun. 38:
1700195.
169 Zhou, W., Qu, Q., Yu, W., and An, Z. (2014). ACS Macro Lett. 3: 1220.
170 Zhou, W., Qu, Q., Xu, Y., and An, Z. (2015). ACS Macro Lett. 4: 495.
171 Qu, Q., Liu, G., Lv, X. et al. (2016). ACS Macro Lett. 5: 316.
172 Byard, S.J., Williams, M., McKenzie, B.E. et al. (2017). Macromolecules 50: 1482.
173 Gao, P., Cao, H., Ding, Y. et al. (2016). ACS Macro Lett. 5: 1327.
174 Huang, J., Li, D., Liang, H., and Lu, J. (2017). Macromol. Rapid Commun. 38:
1700202.
175 Huang, J., Zhu, H., Liang, H., and Lu, J. (2016). Polym. Chem. 7: 4761.
176 Guégain, E., Zhu, C., Giovanardi, E., and Nicolas, J. (2019). Macromolecules 52:
3612.
177 Tan, J., Zhang, X., Liu, D. et al. (2017). Macromol. Rapid Commun. 38: 1600508.
178 Rieger, J., Stoffelbach, F., Bui, C. et al. (2008). Macromolecules 41: 4065.
179 Zhang, W., D’Agosto, F., Boyron, O. et al. (2011). Macromolecules 44: 7584.
180 Fielding, L.A., Derry, M.J., Ladmiral, V. et al. (2013). Chem. Sci. 4: 2081.
181 Grazon, C., Rieger, J., Sanson, N., and Charleux, B. (2011). Soft Matter 7: 3482.
182 Wan, W.M., Sun, X.L., and Pan, C.Y. (2010). Macromol. Rapid Commun. 31:
399.
183 Li, Y. and Armes, S.P. (2010). Angew. Chem. Int. Ed. 49: 4042.
184 Blanazs, A., Madsen, J., Battaglia, G. et al. (2011). J. Am. Chem. Soc. 133: 16581.
185 Biais, P., Beaunier, P., Stoffelbach, F., and Rieger, J. (2018). Polym. Chem. 9:
4483.
186 Sugihara, S., Ma’Radzi, A.H., Ida, S. et al. (2015). Polymer 76: 17.
187 Wang, X., Man, S., Zheng, J., and An, Z. (2018). ACS Macro Lett. 7: 1461.
188 Foster, J.C., Varlas, S., Couturaud, B. et al. (2018). Angew. Chem. Int. Ed. 57:
15733.
189 Warren, N.J., Mykhaylyk, O.O., Mahmood, D. et al. (2014). J. Am. Chem. Soc.
136: 1023.
190 Tan, J., Bai, Y., Zhang, X., and Zhang, L. (2016). Polym. Chem. 7: 2372.
191 Doncom, K.E.B., Warren, N.J., and Armes, S.P. (2015). Polym. Chem. 6: 7264.
192 Le, D., Wagner, F., Takamiya, M. et al. (2019). Chem. Commun. 55: 3741.
193 Ferji, K., Venturini, P., Cleymand, F. et al. (2018). Polym. Chem. 9: 2868.
194 Boissé, S., Rieger, J., Belal, K. et al. (2010). Chem. Commun. 46: 1950.
195 Semsarilar, M., Ladmiral, V., Blanazs, A., and Armes, S.P. (2013). Langmuir 29:
7416.
196 Blanazs, A., Ryan, A.J., and Armes, S.P. (2012). Macromolecules 45: 5099.
197 Tan, J., Dai, X., Zhang, Y. et al. (2019). ACS Macro Lett. 8: 205.
198 Cockram, A.A., Neal, T.J., Derry, M.J. et al. (2017). Macromolecules 50: 796.
199 Zhang, X., Rieger, J., and Charleux, B. (2012). Polym. Chem. 3: 1502.
200 Jia, Z., Bobrin, V.A., Truong, N.P. et al. (2014). J. Am. Chem. Soc. 136: 5824.
201 Truong, N.P., Whittaker, M.R., Anastasaki, A. et al. (2016). Polym. Chem. 7: 430.
202 Truong, N.P., Quinn, J.F., Anastasaki, A. et al. (2016). Chem. Commun. 52:
4497.
203 Truong, N.P., Quinn, J.F., Anastasaki, A. et al. (2017). Polym. Chem. 8: 1353.
204 Boissé, S., Rieger, J., Pembouong, G. et al. (2011). J. Polym. Sci., Part A: Polym.
Chem. 49: 3346.
205 Yeow, J., Chapman, R., Xu, J., and Boyer, C. (2017). Polym. Chem. 8: 5012.
206 Steinschulte, A.A., Scotti, A., Rahimi, K. et al. (2017). Adv. Mater. 29: 1703495.
References 749
207 Wan, W.-M. and Pan, C.-Y. (2010). Macromolecules 43: 2672.
208 Blackman, L.D., Doncom, K.E.B., Gibson, M.I., and O’Reilly, R.K. (2017).
Polym. Chem. 8: 2860.
209 Israelachvili, J. (2011). Intermolecular and Surface Forces, 3e. London: Academic
Press.
210 Warren, N.J., Derry, M.J., Mykhaylyk, O.O. et al. (2018). Macromolecules 51:
8357.
211 Shi, P., Zhou, H., Gao, C. et al. (2015). Polym. Chem. 6: 4911.
212 Zhou, J., Zhang, W., Hong, C., and Pan, C. (2016). Polym. Chem. 7: 3259.
213 Figg, C.A., Carmean, R.N., Bentz, K.C. et al. (2017). Macromolecules 50: 935.
214 Huo, M., Xu, Z., Zeng, M. et al. (2017). Macromolecules 50: 9750.
215 Huo, M., Zeng, M., Wu, D. et al. (2018). Polym. Chem. 9: 912.
216 Zhang, Y., Han, G., Cao, M. et al. (2018). Macromolecules 51: 4397.
217 Wu, Y., Tan, M., Su, Z. et al. (2018). New J. Chem. 42: 19353.
218 Yang, P., Ning, Y., Neal, T.J. et al. (2019). Chem. Sci. 10: 4200.
219 Chen, X., Liu, L., Huo, M. et al. (2017). Angew. Chem. Int. Ed. 56: 16541.
220 Zhou, D., Dong, S., Kuchel, R.P. et al. (2017). Polym. Chem. 8: 3082.
221 Lovett, J.R., Warren, N.J., Ratcliffe, L.P.D. et al. (2015). Angew. Chem. Int. Ed.
54: 1279.
222 Lovett, J.R., Warren, N.J., Armes, S.P. et al. (2016). Macromolecules 49: 1016.
223 Penfold, N.J.W., Lovett, J.R., Warren, N.J. et al. (2016). Polym. Chem. 7: 79.
224 Rieger, J., Zhang, W., Stoffelbach, F., and Charleux, B. (2010). Macromolecules
43: 6302.
225 Qiao, Z., Qiu, T., Liu, W. et al. (2017). Polym. Chem. 8: 3013.
226 Chernikova, E.V., Serkhacheva, N.S., Smirnov, O.I. et al. (2016). Polym. Sci. Ser.
B Polym. Chem. 58: 629.
227 Serkhacheva, N.S., Smirnov, O.I., Tolkachev, A.V. et al. (2017). RSC Adv. 7:
24522.
228 Mellot, G., Beaunier, P., Guigner, J.-M. et al. (2019). Macromol. Rapid Commun.
40: 1800315.
229 Cao, M., Nie, H., Hou, Y. et al. (2019). Polym. Chem. 10: 403.
230 Gao, C., Li, S., Li, Q. et al. (2014). Polym. Chem. 5: 6957.
231 Gao, C., Wu, J., Zhou, H. et al. (2016). Macromolecules 49: 4490.
232 Qu, Y., Wang, S., Khan, H. et al. (2016). Polym. Chem. 7: 1953.
233 Zhang, Y., Cao, M., Han, G. et al. (2018). Macromolecules 51: 5440.
234 Zhang, Y., Guan, T., Han, G. et al. (2019). Macromolecules 52: 718.
235 Wang, X., Figg, C.A., Lv, X. et al. (2017). ACS Macro Lett. 6: 337.
236 Zhang, X., Boissé, S., Bui, C. et al. (2012). Soft Matter 8: 1130.
237 Huo, M., Song, G., Zhang, J. et al. (2018). ACS Macro Lett. 7: 956.
238 Tritschler, U., Pearce, S., Gwyther, J. et al. (2017). Macromolecules 50: 3439.
239 Boissé, S., Rieger, J., Di-Cicco, A. et al. (2009). Macromolecules 42: 8688.
240 Kang, Y., Pitto-Barry, A., Maitland, A., and O’Reilly, R.K. (2015). Polym. Chem.
6: 4984.
241 Kang, Y., Pitto-Barry, A., Willcock, H. et al. (2015). Polym. Chem. 6: 106.
242 Mellot, G., Guigner, J.-M., Jestin, J. et al. (2018). Macromolecules 51: 10214.
243 Mellot, G., Guigner, J.-M., Bouteiller, L. et al. (2019). Angew. Chem. Int. Ed. 58:
3173.
244 Chenal, M., Rieger, J., Philippe, A., and Bouteiller, L. (2014). Polymer 55: 3516.
245 Blanazs, A., Verber, R., Mykhaylyk, O.O. et al. (2012). J. Am. Chem. Soc. 134:
9741.
246 Wang, X., Zhou, J., Lv, X. et al. (2017). Macromolecules 50: 7222.
247 Fielding, L.A., Lane, J.A., Derry, M.J. et al. (2014). J. Am. Chem. Soc. 136: 5790.
248 Derry, M.J., Mykhaylyk, O.O., and Armes, S.P. (2017). Angew. Chem. Int. Ed. 56:
1746.
249 Canning, S.L., Neal, T.J., and Armes, S.P. (2017). Macromolecules 50: 6108.
250 Guragain, S. and Perez-Mercader, J. (2018). Polym. Chem. 9: 4000.
251 Ratcliffe, L.P.D., Couchon, C., Armes, S.P., and Paulusse, J.M.J. (2016).
Biomacromolecules 17: 2277.
252 Deng, R., Derry, M.J., Mable, C.J. et al. (2017). J. Am. Chem. Soc. 139: 7616.
253 Deng, R., Ning, Y., Jones, E.R. et al. (2017). Polym. Chem. 8: 5374.
254 Ye, Q., Huo, M., Zeng, M. et al. (2018). Macromolecules 51: 3308.
255 Bagheri, A., Boyer, C., and Lim, M. (2019). Macromol. Rapid Commun. 40:
1800510.
256 Xu, S., Ng, G., Xu, J. et al. (2017). ACS Macro Lett. 6: 1237.
257 Sobotta, F.H., Hausig, F., Harz, D.O. et al. (2018). Polym. Chem. 9: 1593.
258 Karagoz, B., Yeow, J., Esser, L. et al. (2014). Langmuir 30: 10493.
259 Tan, J., Sun, H., Yu, M. et al. (2015). ACS Macro Lett. 4: 1249.
260 Mable, C.J., Gibson, R.R., Prevost, S. et al. (2015). J. Am. Chem. Soc. 137: 16098.
261 Xu, X.-F., Pan, C.-Y., Zhang, W.-J., and Hong, C.-Y. (2019). Macromolecules 52:
1965.
262 Karagoz, B., Boyer, C., and Davis, T.P. (2014). Macromol. Rapid Commun. 35:
417.
263 Blackman, L.D., Varlas, S., Arno, M.C. et al. (2017). ACS Macro Lett. 6: 1263.
264 Canton, I., Warren, N.J., Chahal, A. et al. (2016). ACS Cent. Sci. 2: 65.
265 Garni, M., Wehr, R., Avsar, S.Y. et al. (2019). Eur. Polym. J. 112: 346.
266 Varlas, S., Blackman, L.D., Findlay, H.E. et al. (2018). Macromolecules 51: 6190.
267 Blackman, L.D., Varlas, S., Arno, M.C. et al. (2018). ACS Cent. Sci. 4: 718.
268 Zhang, X., Cardozo, A.F., Chen, S. et al. (2014). Chem. Eur. J. 20: 15505.
269 Cardozo, A.F., Julcour, C., Barthe, L. et al. (2015). J. Catal. 324: 1.
270 Chen, S., Cardozo, A.F., Julcour, C. et al. (2015). Polymer 72: 327.
271 Lobry, E., Cardozo, A.F., Barthe, L. et al. (2016). J. Catal. 342: 164.
272 Pontes da Costa, A., Nunes, D.R., Tharaud, M. et al. (2017). ChemCatChem 9:
2167.
273 Wang, F., Tang, J., Liu, H. et al. (2019). Mater. Chem. Front. 3: 356.
274 Thompson, K.L., Chambon, P., Verber, R., and Armes, S.P. (2012). J. Am. Chem.
Soc. 134: 12450.
275 Thompson, K.L., Mable, C.J., Cockram, A. et al. (2014). Soft Matter 10: 8615.
276 Thompson, K.L., Fielding, L.A., Mykhaylyk, O.O. et al. (2015). Chem. Sci. 6:
4207.
277 Zhang, Q., Wang, C., Fu, M. et al. (2017). Polym. Chem. 8: 5474.
References 751
278 Zhang, W.-J., Hong, C.-Y., and Pan, C.-Y. (2014). J. Mater. Chem. A 2: 7819.
279 Ning, Y., Whitaker, D.J., Mable, C.J. et al. (2018). Chem. Sci. 9: 8396.
280 Ning, Y., Han, L., Derry, M.J. et al. (2019). J. Am. Chem. Soc. 141: 2557.
281 Charleux, B., D’Agosto, F., Inoubli, R., and Magnet, S. (2015). Viscosifiant a
base de particules polymeriques filamenteuses. WO2015011412A1, filed 23 July
2014 and issued 29 January 2015. Universite Claude Bernard Lyon 1, Centre
National de la Recherche Scientifique. Arkema France, Fr.
282 Pham, B.T.T., Nguyen, D., Huynh, V.T. et al. (2018). Langmuir 34: 4255.
283 Albiges, R., Klein, P., Roi, S. et al. (2017). Polym. Chem. 8: 4992.
284 Upadhyaya, L., Semsarilar, M., Fernandez-Pacheco, R. et al. (2016). Polym.
Chem. 7: 1899.
285 Luppi, L., Babut, T., Petit, E. et al. (2019). Polym. Chem. 10: 336.
286 Upadhyaya, L., Egbosimba, C., Qian, X. et al. (2019). Macromol. Rapid
Commun. 40: 1800333.
287 Cockram, A.A., Bradley, R.D., Lynch, S.A. et al. (2018). React. Chem. Eng. 3:
645.
288 Zaquen, N., Azizi, W.A.A.W., Yeow, J. et al. (2019). Polym. Chem. 10: 2406.
289 Zaquen, N., Yeow, J., Junkers, T. et al. (2018). Macromolecules 51: 5165.
753
16
RAFT-Functional End Groups: Installation and

Transformation
Curtin University, School of Molecular and Life Sciences (MLS), Kent Street, Bentley, Perth, Western Australia
6102, Australia
16.1 Introduction
As detailed in previous chapters, reversible addition–fragmentation chain transfer

(RAFT) [1–4] is a robust and versatile example of a reversible deactivation radical
polymerization (RDRP) that operates on the principle of degenerative chain
transfer mediated by certain thiocarbonylthio compounds. Such thiocarbonylthio
compounds are referred to as RAFT agents or more simply as chain transfer
agents (CTAs). The most common examples of such RAFT agent families are
dithioesters (a) (typically dithiobenzoates), trithiocarbonates (b), xanthates (c), and
dithiocarbamates (d) (Figure 16.1).
The relevant structural features of these mediating agents are the so-called R- and
Z-groups. The former is the initiating fragment while the latter controls the bulk
reactivity of a RAFT agent – it essentially determines to which of the above four
general species a particular RAFT agent belongs. We will not discuss the design,
synthesis, and activity of the many reported RAFT agents in this chapter as this is
highlighted in detail elsewhere [5]. However, we note two important features, one
of which is pertinent in the context of this chapter: (i) dithioesters (a) and trithio-
carbonates (b) are the most versatile and widely employed families of RAFT agents,
while in general, the use of xanthates (c) and dithiocarbamates (d) is commonly
limited to particular monomer classes and especially vinyl esters and vinyl amides
and (ii) RAFT agents are often intensely coloured – red, orange, purple, and yellow
are common for dithioesters and trithiocarbonates. This colour, a result of the C=S
bond, is conferred on the resulting (co)polymer as a result of the underlying RAFT
mechanism, vide infra.
From a practical viewpoint, a RAFT (co)polymerization is no more challenging
to conduct than a traditional radical (co)polymerization. In its basic form, a RAFT
(co)polymerization is merely a conventional radical polymerization performed
in the presence of an added thiocarbonylthio compound. As such, the RAFT
mechanism involves the same initiation, propagation, and termination steps as a
754 16 RAFT-Functional End Groups: Installation and Transformation
S S S S
R R R R
S Z S S-Z S OR S NR´R˝
(a) (b) (c) (d)
Figure 16.1 General chemical structure of the four main classes of RAFT agent. (a)
Dithioesters, (b) trithiocarbonates, (c) xanthates, and (d) dithiocarbamates.
conventional radical (co)polymerization but with degenerative chain transfer steps

involving radicals and the RAFT agent superimposed on the underlying chain
mechanism (Scheme 16.1). The finer details associated with the RAFT mechanism
are discussed elsewhere in this book.
Dead chains Dead chains

S S
kt kt X
X
S Z ktr S Z
Pn + Pm Pn + Pm
–ktr
M kp M kp
Kα kβ
–kβ
Pn
S
S Z
Pm
Scheme 16.1 The RAFT process operating in the main equilibrium stage highlighting the
transfer of thiocarbonylthio groups between the propagating chain ends.
The product of a RAFT (co)polymerization, Scheme 16.2 (as with all RDRP
processes), contains very specific α and ω end groups, the exact nature of which is
determined by the choice of RAFT-mediating agent employed in the (co)polymer
synthesis. The produced (co)polymer, in a typical synthesis, will, at the α chain
end, contain initiating groups whose structure is R, assuming that the R-group
of the CTA initiates the majority of polymer chains and not primary radicals
formed from the decomposition of added initiator (I). In the case where the
primary radicals formed from I have the same structure as R, for example, when
2,2′ -azobis(2-methylpropionitrile) (AIBN) is used in conjunction with a CTA
such as 2-cyanopropan-2-yl benzodithioate, then all polymer chains should have
S
Z
S
R S
n + R I, ∆
S Z
α-Chain-end ω-Chain-end
Scheme 16.2 RAFT polymerization highlighting the presence of functionality at the α and
ω termini.
identical initiating groups. For the ω chain end, assuming there are no undesirable
side reactions, each (co)polymer chain will contain a thiocarbonylthio-Z-functional
group. In essence, under ideal conditions, a small-molecule RAFT CTA is converted
to a macromolecular RAFT agent by what amounts to monomer insertion between
the C—S bond.
Several factors motivated the historical development of end group chemistries
on RAFT-prepared (co)polymers. The first open literature report of RAFT came
in late 1998 [6]; the 1990s and early 2000s were an exciting time in synthetic
chemistry and not just polymer chemistry. In 2001, Kolb et al. published their
seminal paper detailing ‘click’ chemistry as a means of preparing new compounds
with a high degree of reliability and selectivity from readily available and cheap
reagents employing a handful of well-developed highly efficient reactions [7].
While arguably aimed, at least initially, at researchers working on the synthesis of
highly complex molecules such as natural products or in the field of drug discovery
and development, the general ‘click’ approach to synthesis was quickly adopted,
and developed, by the polymer chemistry community. It was recognized early in
the history of modern ‘click’ chemistry that the reactions detailed by Kolb et al.
could help address a long-standing problem in polymer science and specifically
the issue of non-quantitative chemical modification of preformed (co)polymers.
Although this may not seem like a particularly important issue on first inspection,
it is worth remembering that all synthetic polymers possess a molecular weight
distribution and, in the case of copolymers, a superimposed compositional distri-
bution. Non-quantitative modification of a pre-prepared (co)polymer superimposes
a second, or third, functionality distribution. In effect, the ‘product’ is highly
heterogeneous.
Before the late 1980s, prior to the development and application of RDRP processes
such as stable radical polymerization (SRP), best exemplified by nitroxide-mediated
polymerization (NMP), and atom transfer radical polymerization (ATRP) in the
early 1990s, the issue of specific functional group incorporation into (co)polymers
could be tackled via the application of protecting group chemistry (especially
in the case of (co)polymers prepared by more traditional ‘living’ processes such
as anionic polymerization or group transfer polymerization [GTP]) or by the
copolymerization of an appropriately functionalized monomer if compatible with
the polymerization process. However, protecting group chemistry still suffers
from limitations in the context of synthetic polymer chemistry, and at that time,
many functional monomers were simply incompatible with controlled polymer-
ization processes of the day and thus were only generally amenable to radical
(co)polymerization. The development of the RDRP processes, first NMP, then
ATRP, and later RAFT, largely eliminated the functional group compatibility issue
while still facilitating the preparation of (co)polymers with well-defined molecular
characteristics. However, while the RDRP processes are highly functional group
tolerant, direct (co)polymerization as a route to instil specific functional groups
commonly still requires the synthesis of a functional monomer. ‘Click’ chemistry,
it seemed, offered the opportunity synthetic polymer chemists had long searched
for – the ability to generate libraries of novel materials from one reactive parent
material, containing a specific functionality, employing highly efficient reactions.

The disclosure of RAFT in late 1998 coupled with the ‘click’ approach to chemical
synthesis in 2001 led to a renaissance in synthetic polymer chemistry. As a result,
the archetypal ‘click’ reaction, the Cu(I)-catalyzed coupling between an alkyne and
an azide [8–10], was quickly applied in synthetic polymer chemistry and especially
in the field of RAFT (co)polymerization, vide infra. The demonstrated utility of
this chemistry subsequently motivated other polymer chemists to examine and
develop additional ‘click’ reactions specifically for the chemical modification of
(co)polymers, and today, there is an impressive, and ever-growing, toolbox of ‘click’,
or ‘click’-like, reactions that have become a near-ubiquitous feature in modern
synthetic (polymer) chemistry.
As noted above, (co)polymers prepared by RAFT can be viewed as polymeric
RAFT agents. From an application perspective, this may be an undesirable struc-
tural feature. This is because (co)polymers prepared by RAFT are inherently
coloured due to the presence of the C=S bond, albeit typically not as intensely
as the corresponding small-molecule RAFT agents. The highly reactive nature of
the terminal thiocarbonylthio group can likewise be perceived to be problematic
because it can result in the undesirable release of sulfur-containing compounds,
which can be highly malodorous. Both these aspects were, in the early days of
RAFT polymerization, viewed by many as clear disadvantages of the technique
and features that would likely limit its large-scale commercial adoption and almost
certainly its use in bio-applications. Not surprisingly, these two features prompted
researchers to explore methods for efficiently removing the thiocarbonylthio group
at the ω chain end in RAFT-prepared polymers and thus the colour and any
potential degradation products. While initially motivated by the perceived disad-
vantages noted above, research in this area of RAFT end group cleavage/removal
unwittingly led to the subsequent development of a range of approaches for not just
removing the end groups but for the further modification and application of RAFT
(co)polymers in novel (bio-)applications.
If we revisit the generic structure of a RAFT-prepared (co)polymer shown in
Scheme 16.2, it is evident that in the context of end group transformations, we
have three options. We can exploit specific functional groups incorporated as
part of the R-group, i.e. the initiating fragment at the α terminus; we can utilize
chemical transformations of the thiocarbonylthio ω end group, or we can use
both. In Sections 16.2 and 16.3, we will highlight how researchers have employed
both α and ω end group chemistries as a means of generating new and interesting
materials, although we state at the outset that transformations/modifications at
the ω chain end are currently the preferred approach given the broader range of
chemistries available. This chapter is not intended to be an exhaustive review of the
field of RAFT end group modification; many excellent reviews are available that
deal with this topic in more detail [11–15]. However, hopefully, this chapter will
aid those new to the field, as well as current practitioners, to gain an appreciation
for the historical development of certain aspects of RAFT (co)polymerization and
the range of chemistries that are available for the introduction of specific terminal
functional groups by pre- and post-polymerization approaches.
16.2 Functionalization and Transformation of RAFT Polymers via the R-group 757
S CN S CN
OH OH
S S
O
(a) (b)
Figure 16.2 Chemical structures of (a) 2-cyano-5-hydroxypentan-2-yl benzodithioate

(CHPB) and (b) 4-cyano-4-((phenylcarbonothioyl)thio)pentanoic acid (CPTP).
16.2 Functionalization and Transformation of RAFT

Polymers via the R-group
The potential to exploit functional groups within the R-group fragment of RAFT
CTAs, and thus at the α chain end of (co)polymers, was evident in the first literature
report concerning RAFT, although not explicitly stated [6]. Of the eight dithioesters
described in this original paper, two (Figure 16.2) contained functional groups with
the potential to serve as reactive handles for further modification.
These two examples were, presumably, included to highlight not only the broader
functional group tolerance of the RAFT process but to demonstrate the impressive
range of conditions under which RAFT polymerization could be performed. For
example, the sodium salt of 4-cyano-4-((phenylcarbonothioyl)thio)pentanoic acid
(CPTP), CPTP-Na, was reported to facilitate the homogeneous aqueous polymer-
ization of sodium styrenesulfonate in a controlled manner. It is fair to state that
from a historical perspective, this single example inspired an extensive research pro-
gram focused around homogeneous aqueous RAFT with significant contributions
coming from the groups of McCormick [16–30] and others [31–39]. It is also likely
the reason that of all the functional groups that can be built into RAFT agents,
those containing –CO2 H groups, have attracted particular attention, especially in
the 2000s [5, 11, 40–48]. The key point here, however, is that one clear, and often
straightforward, approach for the introduction of specific functional groups at the α
terminus is via the application of an R-group-functionalized CTA [49–55]. The only
criteria are that the target functional group be compatible firstly with the CTA, and
more specifically the thiocarbonylthio functional group, and secondly be inert under
RAFT polymerization conditions. This does, of course, preclude certain functional
groups, thiols, and 1∘ and 2∘ amines, for example, but for the most part, desirable
functionality can be built directly into the R-group structure [1–5].
As noted earlier, the interest in RAFT in the late 1990s and early 2000s was
spurred, in part, by the introduction of the concept of the ‘click’ chemistry approach
to synthesis. Many groups globally quickly explored opportunities for combining
RAFT polymerization with the gold standard ‘click’ reaction, the Cu(I)-catalyzed
reaction between an alkyne and an azide [10, 56, 57] (Scheme 16.3).
The main approach adopted by research groups involved the incorporation of
azide or yne functionality into the R-group of RAFT CTAs. Recalling that provided
the desirable functionality is compatible with the overall process of CTA synthesis
and polymerization, then this represents a very powerful, and direct, route for
instilling functionality specifically at the α chain end. The azide functionality is
R1 R1
R1 N N N R1 N N N R1 N N N
N N N Cu(I) N N N ∆
+
+ +
H R2 R2 R2 R2
H R2
1,4-Regioisomer 1,4-Regioisomer 1,5-Regioisomer
Scheme 16.3 The regioselective Cu(I)-catalyzed reaction of an azide with an alkyne and
the non-selective thermal 1,3-dipolar cycloaddition products.
O O
S S S O
N3 O C12H25 N3 O
S S
N3-CTA1 N3-CTA4
O O
N3 S S S
O C12H25 N3 O
S NC S
N3-CTA2 N3-CTA5
NC S
O
O
S S N3 S
N3 O
O
S
N3-CTA3 N3-CTA6
O S CN
S S O
O S
S R O
YNE-CTA1 R = H, TMS YNE-CTA4
S S S
R = CH3, H O
S R S
O
YNE-CTA2
YNE-CTA5
O S
S
S N O N N
S
O
YNE-CTA3 YNE-CTA6
Figure 16.3 Representative examples of RAFT CTAs in which the R-group fragment
contains alkyne or azide functionality.
compatible (note: care should be taken when handling organic azides [58]), the
yne slightly less so given its susceptibility to radical addition but providing care
is taken can be readily incorporated directly via a functional CTA. Figure 16.3
shows examples of R-group-functionalized azide and alkyne RAFT CTAs, including
trithiocarbonates (N3 -CTA1, N3 -CTA2, N3 -CTA3, YNE-CTA1, and YNE-CTA2),
dithioesters (N3 -CTA5, N3 -CTA6, YNE-CTA4, and YNE-CTA5), xanthates
(N3 -CTA4 and YNE-CTA3), and dithiocarbamates (YNE-CTA6) [14]. It is needless
to state, that with such RAFT agents available, the synthetic opportunities are
extensive. For example, each of the compounds shown in Figure 16.3 can be
further modified by pre-polymerization to generate new functional RAFT agents or
exploited post-polymerization to prepare a range of new species.
For example, Akeroyd et al. [59] reported the synthesis and application of
novel triazole-functional trithiocarbonates and xanthates prepared from precur-
sor yne-functional CTAs, including YNE-CTA2 and YNE-CTA3 (Figure 16.3).
All RAFT agents were reported to be effective in mediating the controlled
polymerization of monomers, including styrene, n-butyl acrylate, vinyl acetate,
and N-vinylpyrrolidone. The general synthetic approach adopted is shown in
Figure 16.4 and examples of prepared RAFT agents are given below. A simi-
lar pre-polymerization approach was reported by Puttick et al. [60] in which a
yne-functional trithiocarbonate was reacted with an azido alkyl imidazolium
bromide, yielding a novel room temperature ionic liquid CTA.
Cu(I)-mediated alkyne-azide coupling is not the only ‘click’ process that has been
employed in the post-polymerization modification of RAFT polymer R-groups.
Stamenović et al. [61] reported the synthesis, application, and modification of
norbornenyl-functional xanthate, dithiobenzoate, and trithiocarbonate RAFT
agents (Figure 16.5). The polymerization of styrene, methyl acrylate, 1-ethoxyethyl
R S
R S R S R1–N3
+ S Z
KS Z S Z R1 N
Br
N N
R = H or CH3 + KBr
S CH3 S
Ph N S O Ph N S S
N N N N
S
RO RO
RO
O OR O O S O
O N
RO
OR O O OR N N
RO RO
RO 5 R = Ac or CH3
Figure 16.4 The synthesis of triazole functional RAFT agents from precursor
yne-functional RAFT CTAs and representative examples of CTAs reported.
O O
S O S Ph
Nor-Xan S Nor-Dithio S
O
S S
Nor-Trithio S
Figure 16.5 Chemical structures of norbornenyl-functional RAFT agents.
acrylate, and vinyl acetate proceeded in a controlled manner, provided that

monomer conversions were limited to avoid interference from the norbornenyl
group. The motivation for introducing a norbornenyl reactive species at the α
terminus is based on the well-known, unusually high, reactivity of such groups in
radical thiol–ene reactions [62–64].
For example, polystyrene prepared with Nor-Trithio was reacted with
3-mercaptopropionic acid, benzyl mercaptan, and dodecanethiol (1–5 equiv based
on terminal ene groups) in the presence of 2,2-dimethoxy-2-phenylacetophenone as
a UV-active photoinitiator. In all cases, the terminal groups could be quantitatively
modified within 15 minutes as judged by NMR spectroscopy. Given the large
number of commercially available thiols coupled with the ability to introduce
alternative ene species in the R-group fragment, it is evident that this approach is
highly versatile as a route to α-functional materials. In a complementary approach
employing thiol–yne chemistry, Fontaine and coworkers [65] reported the synthesis
of α,ω-functionalized poly(N-isopropylacrylamide) via the sequential approach
outlined in Scheme 16.4. Homopolymerization of N-isopropylacrylamide with
the yne-functional trithiocarbonate 2-cyano-5-oxo-5-(prop-2-yn-1-ylamino)pentan-
2-yl dodecyltrithiocarbonate yielded a well-defined polymer with unimodal molec-
ular weight distributions provided conversions were limited. Treatment of the
poly(N-isopropylacrylamide) homopolymer with an excess of AIBN [66] resulted
in the removal of the trithiocarbonate end group, with it being replaced by a
O
O O
n N S S
S S
N C12H25 H N C12H25
H H n
NC S NC S
AIBN, DMF O NH
70 °C
O O
PhCH2SH, Me2PPh
AIBN, 80 °C N CN AIBN N CN
PhS
H n H n
Dioxane NC SPh NC
O NH 80 °C, 24 h O NH
Dioxane
Scheme 16.4 The synthesis of α,ω-end-functionalized poly(N-isopropylacrylamide) via

sequential AIBN-mediated trithiocarbonate end group removal, followed by
radical-mediated thiol–yne modification of the α-yne group.
cyanoisopropyl group. In the second step, the ω-modified polymer was treated
with benzyl mercaptan, in the presence of AIBN, under conditions to affect a
radical-mediated double hydrothiolation of the α-yne group yielding the dithioether
product. The authors noted that while the first step was essentially quantitative, the
second, thiol–yne, reaction gave, at best, 40% conversion. Although not discussed,
it seems that a number of yne groups could very well have been lost during the first
step. The same product was also reported to be accessible in a one-pot process.
One particularly powerful and versatile method for the functionalization of the
R-group fragment involves the use of activated ester chemistry and, in particular,
the use of pentafluorophenylesters [67, 68], although N-hydroxysuccinimide
derivatives have also been employed [69, 70]. Such chemistries have been used
to prepare intermediate RAFT agents that are subsequently modified with an
appropriate amine-containing species, including proteins [71], employed directly
as polymerization mediators and modified post-polymerization [72, 73], or used in
conjunction with other facile conjugation chemistries or both [74–78].
Du Prez and coworkers have worked extensively with the thiolactone-functional
species in various applications in monomer/polymer synthesis and modification
[79–82]. Within this body of work, Stamenović et al. [83] reported the synthesis
and application of a thiolactone R-group-functionalized RAFT CTA that was
demonstrated to be useful for the synthesis of cyclic polymers via intramolecular
disulfide formation between the α- and ω-thiol groups (Scheme 16.5).
O
O S S O
H NC
N
S S Ph S Ph
N
O H n
NC S
H
R N O
O
R NH2 Cyclic
SH
N polymer
H n
NC
HS
Scheme 16.5 The synthesis of cyclic polystyrene via intramolecular disulfide formation
via one-pot aminolysis of α-thiolactone groups and ω-thiocarbonylthio species.
Later in the chapter, we will highlight the routes available for end group func-
tionalization employing disulfide chemistry involving thiols derived from cleaved
thiocarbonylthio groups. However, such disulfide chemistry can also be employed
as part of functional R-groups in RAFT CTAs [84–86]. For example, Evgrafova et al.
reported the synthesis of protein/thermoresponsive polymer conjugates employing a
thiol exchange reaction between a pyridyl disulfide group at the α-terminus (derived
from the disulfide-functional R-group) in diethylene glycol acrylate and the parathy-
roid peptide hormone (PTH) (Scheme 16.6) [85].
O
S O
n O
N S O 2
S S S
O RAFT polymerization
O
S S S
N S O
n
S
O O
O
2
PTH SH
O
PTH S S S
S O
n
S
O O
O
2
Scheme 16.6 Conjugation of the parathyroid peptide hormone at the α-terminus of a

RAFT-prepared polymer via a disulfide exchange reaction on a functional RAFT CTA R-group
containing pyridyl disulfide.
16.3 Thiocarbonylthio End Group Removal

and Transformation
As noted in Section 16.1, under certain circumstances, it may be necessary, or

at least desirable, to remove the thiocarbonylthio end group in RAFT-prepared
(co)polymers. The main reasons for this are to remove the colour inherently
associated with the products of a RAFT polymerization, elimination of possible
sulfur-based degradation products, which may be toxic or malodorous, or to negate
the inherent high reactivity of thiocarbonylthio groups for specific applications
and especially those that are bio-based. When we present examples in which the
thiocarbonylthio group is located at the ω chain terminus, we note that these groups
are not necessarily always located at a chain end. However, the chemistries we will
highlight are equally applicable to those materials in which the thiocarbonylthio
groups may be present mid-chain in linear (co)polymers or, for example, in the core
of certain star (co)polymers.
There are many available approaches for the removal or modification of thiocar-
bonylthio groups in RAFT-prepared polymers. All of the known methods have their
roots in small-molecule organic chemistry and as such are, for the most part, well
understood and developed. At the top level, we can classify two general approaches
for modifying RAFT thiocarbonylthio end groups:
1) Complete desulfurization. Such an approach removes the thiocarbonylthio group
in its entirety and is accomplished via one of several radical-based modification
pathways.
2) Chemical modification of the thiocarbonylthio group in which the ‘problematic’
end group is cleaved to yield a macromolecular thiol or converted to a different
S-based species. In the case of end group cleavage, the resulting macromolec-
ular thiol (or thiolate) is commonly captured by one of a variety of available
chemistries. This is arguably the most versatile and widely reported approach
and can yield many different types of new end-functional materials.
16.3.1 Desulfurization of RAFT (Co)Polymers

16.3.1.1 Thermolysis
The total removal of S-containing species from RAFT polymers can be accomplished
by several radical-based routes (Figure 16.6). Executionally, the easiest method
involves thermolysis – simply heating the (co)polymer. This can be performed on
isolated materials or via a flow process [87]. However, the extent, purity of the
product, and mechanism by which end group removal occurs are dependent on
the monomer and the nature of the thiocarbonylthio species. This was evident
∆ X
R n–1 Thermolysis
X Y Y
R´ , [H] H
R n–1 Radical-mediated reduction
X Y X Y
R´ R'
R n–1
X Y X Y
Addition–fragmentation
S Z R´ + O N coupling
R n–1 O
X Y X Y R n–1 N
S X Y X Y
R´ , [H], O2 OOH
R n–1
X Y X Y
R´ , [H], O2 OH Radical-induced
R n–1
X Y X Y oxidation
Co(II), R´ , M X
R n–1
X Y Y
Figure 16.6 General approaches for the desulfurization of RAFT thiocarbonylthio end
groups.
even in the earliest reports from Postma et al. in their studies on trithiocarbonate
and xanthate end group removal in polymers prepared with phthalimidomethyl
R-group-functional CTAs [88, 89]. Researchers from the same group have
also reported on the thermolysis of RAFT-prepared poly(methyl methacrylate)
(PMMA) [90]. The products obtained were highly dependent on the RAFT agent
employed in polymer synthesis. For PMMA prepared with a trithiocarbonate CTA
(2-cyanoprop-2-yl methyl trithiocarbonate), end group removal was proposed to
occur via homolytic cleavage of the PMMA—S bond, followed by depolymerization,
a process that continued until radical annihilation (Scheme 16.7a).
SCH3 S
S ∆
+ CS2 +
S SCH3 CH3S
CO2Me CO2Me S CO2Me CO2Me
_ CO2Me
Depolymerization
R
R–H +
Radical annihilation CO2Me
(a) CO2Me by disproportionation
CO2Me CO2Me ∆ CO2Me CO2Me S
S Ph Chugaev-type + HS Ph
H electrocyclic
S
(b) elimination
Scheme 16.7 Desulfurization pathways in poly(methyl methacrylate) prepared with a

trithiocarbonate CTA (a) and with a dithioester (b).
For PMMA prepared with a dithiobenzoate CTA, elimination was proposed to pro-
ceed by a concerted intramolecular process analogous to the Chugaev reaction [91]
(Scheme 16.7b). In general, thermolysis of dithiobenzoate-prepared (co)polymers is
cleaner and yields macromonomer products whose molecular weight and molec-
ular weight distribution are comparable to the parent polymer, whereas degrada-
tion products are also observed with PMMA prepared with a trithiocarbonate. Sim-
ilar findings were reported by Bressy et al. with silylated methacrylic homopoly-
mers [92]. More recently, Stace et al. [93] examined the effect of the Z-group and
nature of the macro-R-group in ‘switchable’ RAFT agents and thermal desulfuriza-
tion. Although differences were observed between various MAMs (more activated
monomers), the principle finding in this study related to the significantly higher
thermolysis temperatures required for polymers derived from LAMs (less-activated
monomers) such as vinyl acetate vs. those derived from MAMs. Finally, we note
that the thermal stability of a range of small-molecule RAFT agents has also been
examined by Zhou et al. [94].
16.3.1.2 Radical-Mediated Reduction

Complete desulfurization of RAFT polymers can be achieved by radical-mediated
reduction. Inspired by the Barton–McCombie reaction for the deoxygenation of sec-
ondary alcohols [95], such radical-mediated reduction has been applied to other
thiocarbonylthio species including RAFT agents [96]; not surprisingly, the general
approach has also been successfully applied to the complete removal of thiocar-
bonylthio end groups in RAFT-prepared (co)polymers [11, 97].
The general process is based on the fundamental RAFT addition–fragmentation
mechanism (Scheme 16.8). The reaction involves the addition of a radical (X⋅) to the
thiocarbonyl group of the RAFT-prepared (co)polymer (1) generating an intermedi-
ate (2), which fragments to provide a new thiocarbonylthio compound (3) and the
propagating radical (4). Reaction of the propagating radical (4) with a H atom donor
gives the final product, Pn –H, with the thiocarbonylthio group being replaced with
hydrogen.
S S Pn X S S Pn X S S + H X
X + Pn Pn–H + X
Z Z Z
1 2 3 4
Scheme 16.8 General mechanism for the radical-mediated reduction of a RAFT

thiocarbonylthio end group.
Various side reactions can occur, including ‘normal’ termination reactions. The
intermediate (2) and the propagating radical (4) can react with other radical species
such as initiator-derived radicals, transfer agent-derived radicals, and propagating
radicals.
Tributylstannane, Bu3 SnH, has been employed extensively as a H-donor source in
radical-mediated reductions on RAFT-prepared (co)polymers [98–100]. However,
because of the toxicity of stannane and stannane-derived by-products, alternative
H-donors have also been investigated. For example, Chong et al. [97] investigated
the influence of H-donor on polymers with dithiobenzoate and trithiocarbonate
end groups. They reported that the use of toluene and toluene/2-propanol as
H-donors in conjunction with dibenzoyl peroxide or lauroyl peroxide as initiators
resulted in complete end group removal, but bimodal molecular weight distribu-
tions of poly(n-butyl acrylate) and polystyrene were observed. This was attributed
to the coupling of propagating radicals (4) or to termination reactions involving
intermediate (2).
Silanes have also been investigated as H-donors in radical-mediated reduction
reactions [101]. Chong et al. reported that a bimodal molecular weight distribu-
tion was observed when tris(trimethylsilyl)silane was employed as a H-donor in
radical-mediated reduction of polystyrene terminated with dodecyltrithiocarbon-
ate chain ends [97]. They concluded that radical-mediated reduction of RAFT end
groups is more effective with more active H-donor species, with the most effec-
tive being tributylstannane, followed by N-ethylpiperidine hypophosphite (EPHP)
and tris(trimethylsilyl)silanes, followed by 2-propanol, and the least effective being
toluene.
Although not as effective as Bu3 SnH, hypophosphite salts, such as EPHP, do serve
as convenient alternatives to both stannanes and silanes given their reduced tox-
icity and aqueous solubility that can aid significantly in work-up. In fact, EPHP
has been shown to be effective for the removal of dithioester, trithiocarbonate, and
dithiocarbamate end groups on different RAFT-prepared (co)polymers [102–105]. A
further indication of the advantages of using EPHP is the fact that it is commonly
employed to reduce end groups in polymers specifically targeted for bioapplications
[106–108].
More recently, there has been interest in photo-induced RAFT end group
reduction [109–111]. For example, Carmean and coworkers described the
efficient, catalyst-free, UV-mediated removal of thiocarbonylthio groups of
all four major RAFT agent families from a range of polymers including
poly(N,N-dimethylacrylamide), PMMA, poly(N-vinylpyrrolidone), polystyrene, and
poly(methyl acrylate). The general approach, with poly(N,N-dimethylacrylamide)
highlighted, is shown in Scheme 16.9. Simple UV irradiation of the parent RAFT
polymer results in homolytic cleavage of the terminal C—S bond liberating, what is
in essence, a propagating poly(N,N-dimethylacrylamide) radical. This immediately
abstracts H from the donor source, EPHP in this instance, yielding the H-terminated
polymer. The use of EPHP was efficient for all the above noted polymers with the
exception of polystyrene. In this instance, incomplete end group conversion was
observed with EPHP; however, switching the H-donor source to Bu3 SnH did
yield full H-terminated polystyrene without any evidence of undesirable coupled
products.
NH O OH
S Z 365 nm P H
R R R
S H
N O O N 7.0 mW/cm2 N O O N N O O N
(EPHP)
Scheme 16.9 UV-initiated photolysis, followed by H abstraction from EPHP as a facile

route to H-terminated poly(N,N-dimethylacrylamide).
16.3.1.3 Addition–Fragmentation Coupling

In a related process, the reaction of thiocarbonylthio end-terminated (co)polymers
with an excess of an added azo species can be employed to substitute RAFT end
groups with radical fragments originating from the thermal decomposition of the
added azo compound [15]. The general process, highlighting the use of AIBN as the
azo compound, is shown in Scheme 16.10.
AIBN decomposes to form two cyanoisopropyl radicals, which react at the C=S
bond of the thiocarbonylthio group, forming the intermediate carbon-centred
radical, just as expected in a typical RAFT reaction. This intermediate can either
fragment back into the original attacking radical or free the polymeric leaving
group. Assuming that fragmentation occurs in the direction liberating the poly-
meric radical, Pn ⋅, then this species is formed in the absence of monomer but in
+ S S Pn S S Pn Pn + S S
CN CN
CN
Pn
CN
Pn–Pn
Pn
CN
Scheme 16.10 Desulfurization of RAFT-prepared polymer via the reaction with an excess
of AIBN.
the presence of a potentially very high concentration of cyanoisopropyl radicals.

This species can, of course, self-terminate but under the right conditions will react
with a cyanoisopropyl radical, yielding the target end-capped polymer. Perrier et al.
[112] were the first to describe such addition–fragmentation coupling reactions,
highlighting not just the ability to use this chemistry as a means for end group
modification but also as a potential route for recovering CTA. They successfully
applied this approach to a variety of dithiobenzoate/thiocarbonylthio end group
methacrylic, acrylic, acrylamido, and styrenic polymers with various azo initiators.
Chen et al. [113] also examined the removal of thiocarbonylthio end groups in
RAFT-prepared polymers with AIBN. These authors found that while end group
transformation was successful with methacrylic polymers, it was less effective with
acrylic and styrenic polymers. In contrast, the use of lauroyl peroxide did result in
the complete removal of end groups in acrylic and styrenic polymers, but it was
not a clean process and yielded a significant amount of polymer–polymer coupled
products. Interestingly, the amount of polymer–polymer coupled species could be
minimized if a combination of lauroyl peroxide (2 equiv) with AIBN (20 equiv) was
employed.
As with many of the end group transformation chemistries developed during
the preceding two decades, many are now used routinely in many areas of RAFT
chemistry and often feature only as an intermediary step en route to a specific
desired functionality or application. For example, Sarapas et al. [114] employed
such azo coupling chemistry to modify methacrylic and styrenic polymer end
groups in guanidinium-functional species, while Bohec et al. [65] used AIBN
to modify the trithiocarbonate end groups in alkyne-R-group-functionalized
poly(N-isopropylacrylamide). Zhang et al. [66] likewise employed AIBN to
cleave trithiocarbonate end groups in poly(N-isopropylacrylamide) containing a
Boc-protected primary amine in the R fragment before removing the protecting
group and using the polymeric amine to initiate the ring-opening polymerization
of γ-benzyl-L-glutamate N-carboxyanhydride (NCA). Kinoshita et al. [115] success-
fully synthesized telechelic hydroxyl copolymers by using a dithiobenzoate-type
CTA bearing hydroxyl groups, followed by further reaction with VA-086 to cleave
the dithiobenzoate end group and instil a second −OH-functional group. Further
examples of telechelic polymers obtained by such radical addition–fragmentation
coupling have been reported in the literature [74, 116].
An alternative approach to achieve a radical-induced end group modification, to
replace the thiocarbonylthio moiety, is the use of alkoxyamines as a radical source.
Alkoxyamines are, of course, well known in nitroxide-mediated radical polymer-
ization [117]. Although not technically involving RAFT, the potential to exchange
nitroxide end groups with thiocarbonylthio species was demonstrated by Beyou
et al. in the reaction between nitroxide-terminated polymers and thiuram disulfides
(Scheme 16.11), a process that was demonstrated to proceed quantitatively [118].
O ∆ O
N N +
Ph Ph
+
S S N
∆
N S 2 N S
S N Ph S
S S
Scheme 16.11 Conversion of a nitroxide end-terminated polystyrene to a dithiocarbamate

end-functional polymer.
The first reaction between an alkoxyamine and an RAFT agent was carried out
by Ao et al. [119] as part of a study of the kinetics of the RAFT process, while the
exchange of nitroxides with RAFT agents, essentially via an identical route as shown
in Scheme 16.11, was reported by Favier et al. [120]. The efficacy of the process was
reported to be dependent on the nature of both the (macro)alkoxyamine and the
(macro)RAFT agent such that the resulting (macro)alkoxyamine should be more
stable than the starting species.
16.3.1.4 Radical-Induced Oxidation

End group modification of RAFT-synthesized (co)polymers can occur upon reaction
with oxidizing species. Cleavage of the thiocarbonylthio end group and substitu-
tion with a hydroxide group can be achieved through radical-induced oxidation. It
has, for example, been observed that the storage of RAFT CTAs and RAFT-prepared
polymers in cyclic ethers such as tetrahydrofuran (THF) and 1,4-dioxane can lead
to the formation of hydroperoxides end groups through a radical autoxidation pro-
cess with molecular oxygen [121]. It is possible to control the reaction by heating
a RAFT-synthesized (co)polymer at 60 ∘ C with an azo initiator (typically AIBN) in
ambient air. This first step produces hydroperoxide end-terminated (co)polymers,
and subsequent reduction to hydroxyl-functional (co)polymers is achieved by using
triphenylphosphine (Scheme 16.12) [122, 123].
The mechanism involves a radical oxidation cycle with an intermediate chain
transfer step, analogous to the radical autoxidation of ethers [124].
O O O O O O
AIBN, THF PPh3
S Z O OH
R n Air R n OH R n
S
Scheme 16.12 Formation of hydroxy-terminated poly(methyl methacrylate).
Dietrich et al. [122] reported that the radical-induced oxidation of poly(acrylate)s

with trithiocarbonate end groups resulted in the quantitative formation of
hydroperoxyl- and hydroxyl-terminated analogues, whereas dithioester-terminated
polymers gave additional products such as sulfines. In related work, Li et al. [125]
studied the kinetics of radical-induced oxidation of RAFT agents with respect to
the effect of molecular structure. They found that, according to chain transfer
ability, the stability of thiocarbonylthio compounds towards oxidation depends on
both Z and R-groups: electron-deficient Z-groups or bulky R-substituents lead to
a decreased stability, while electron-donating groups in Z-substituents lead to an
increase in stability. As such, trithiocarbonates and xanthates were found to have
higher stability than dithioesters towards oxidation.
Recently, Jesson et al. [126] noted the use of hydrogen peroxide in water as a
convenient route to remove the thiocarbonylthio end groups in methacrylic block
copolymers prepared by polymerization-induced self-assembly.
16.3.2 Heteroatom Diels–Alder Chemistry

One of the ‘click’ chemistries initially noted by Kolb et al. was the Diels–Alder (DA)
reaction [7]. In the classic [4+2] cycloaddition reaction, a hydrocarbon ene (the
dienophile) reacts with a diene via a concerted process to give a cyclohexene prod-
uct. Although the synthetic versatility of the DA reaction is undeniable, traditional
reactions can often require high temperatures (>100 ∘ C) and long reaction times
(>24 hours). Of course, the reactivity of the diene and dienophile can be tuned. The
presence of electron-withdrawing groups on the dienophile, in conjunction with
electron-donating groups on the diene, significantly enhances reactivity (normal
electron demand DA reactions), as does the use of a diene that is locked in the s-cis
conformation such as cyclopentadiene or furan, for example. Similarly, reactivity
can be controlled via inverse electron demand in which electron-donating groups
are attached to the dienophile and electron-withdrawing groups to the diene. Inti-
mately related to the normal DA reactions are those in which the dienophile or diene,
or both, contains heteroatoms (most commonly the heteroatoms are O, N, or S); such
processes are generally referred to as hetero Diels–Alder (HDA) reactions.
Conveniently, the thiocarbonyl-functional group, C=S, serves as an efficient
dienophile in HDA reactions, provided it is ‘activated’ by the presence of an
electron-withdrawing group bonded to C. The general reaction is shown in
Scheme 16.13. Examples of suitable RAFT agents that have been employed
are benzyl (diethoxyphosphoryl)methanedithioate (DEPMD) and benzyl
pyridine-2-carbodithioate (BPCD) (Figure 16.7).
Z
Z S
R
SR
S S
X X
Scheme 16.13 The hetero Diels–Alder reaction between a diene and dithioesters.
S S Figure 16.7 Chemical structures of

EtO benzyl (diethoxyphosphoryl)
N
EtO P S Ph S Ph methanedithioate (DEPMD) and benzyl
O pyridine-2-carbodithioate (BPCD).
DEPMD BPCD
Interestingly, such HDA chemistries have been most commonly employed in

modular approaches to block or star copolymers [127–131] (with the individual
blocks often prepared by two different polymerization processes) or as a means of
surface modification [132, 133]. For example, Sinnwell et al. described the modular
synthesis of AB diblock copolymers of polystyrene with poly(ε-caprolactone)
(Scheme 16.14) [127]. Styrene was homopolymerized under standard RAFT con-
ditions with benzyl (diethoxyphosphoryl)methanedithioate (DEPMA) or BPCD to
give low molecular weight species with M n ∼ 2 and 3 kg mol−1 and corresponding
- of 1.11 and 1.14, respectively. The poly(ε-caprolactone) was prepared with
D
trans,trans-2,4-hexadien-1-ol as the initiator under enzymatic conditions, yielding
a homopolymer with a M n of ∼2.5 kg mol−1 and D - of 1.37. HDA coupling between
the polystyrene homopolymers and poly(ε-caprolactone) were conducted at 50 ∘ C
in CHCl3 . In the presence of ZnCl2 as a catalyst, effective coupling was achieved,
although there was clearly residual polystyrene homopolymer even after 24 hours.
S Z + O H
n O
S m
O
o
CTA: DEPMD or BPCD ZnCl2, 50 C, 24 h or
o
TFA, 50 C, 2h
S Z
n S
O H
O
m
O
Scheme 16.14 A modular approach to AB diblock copolymers of styrene with poly(ε-

caprolactone) prepared via HDA coupling. Source: Modified from Sinnwell et al. [127].
In contrast, when the HDA reaction was catalyzed by trifluoroacetic acid, essentially
complete conversion was realized after only two hours.
Multiarm star polymers are accessible under the same conditions using the
same catalysts (Scheme 16.15) [128]. High yields of the target star polymers
were obtained (although none were quantitatively formed) with those formed
from BPCD-terminated polystyrene being generated faster and in higher yield
(Scheme 16.15). Given the specific usefulness of this particular HDA reaction as
a tool for the modular synthesis of block copolymers and (co)polymers of higher
architecture, it is perhaps not surprising that others have explored HDA chemistry
as a coupling tool for the ‘clicking’ together of homopolymers prepared by RAFT.
Several strategies have been reported including the tetrazine-norbornene inverse
electron demanding DA reaction by Hansell et al. [135]. Although efficient, this is
perhaps limited by the lack of ready availability of the required tetrazine starting
material. However, the application of tetrazines as ligation tools in chemical biology
still attracts significant attention [136–139].
S Z + O
n m
S
CTA: DEPMD or
BPCD
S Z
n S
O
m
Scheme 16.15 Synthesis of 2-, 3-, and 4-arm star polymers via convergent HDA coupling of
polystyrene homopolymers to a multifunctional diene ‘core’ molecule.
Du Prez and coworkers [140–147], and others [148–153], have reported exten-
sively on applications of the 1,2,4-triazoline-3,5-dione (TAD)-based reaction with
examples of normal DA and ene-type reactions known (Scheme 16.16), and readers
are directed to these, and other, references for a more detailed description of vari-
ous TAD-based applications. Indeed, TAD chemistry is extremely well established;
however, in the context of this chapter, we note that there remain few examples in
which it has been applied as a tool for modifying RAFT polymer end groups.
O O
N <20 oC N
R1 N + R1
N N
R2 R2
O O
(a)
O O
H o
N <20 C NH
R1 N + R1 N
N N
R2 R2
O O
(b)
Scheme 16.16 The triazolinedione-diene normal DA reaction (a) and the triazolinedione
Alder-ene reaction (b).
Vandewalle et al. [154] detailed an approach for the introduction of TAD

groups at the α-terminus of RAFT-prepared poly(n-butyl acrylate) via the use of a
pro-TAD-functional trithiocarbonate shown in Figure 16.8. Employing a precursor
urazole derivative is actually common practice, given the well-documented and
extensive chemistry associated with TAD; this approach avoids undesirable side
reactions during initial polymer synthesis. The urazole-functional trithiocarbonate
(URZ-TTC) was readily prepared and isolated on a multigram scale.
URZ-TTC was demonstrated to be an effective CTA and readily mediated the
controlled polymerization of n-butyl acrylate, N,N-dimethylacrylamide, and
styrene under standard RAFT conditions. The authors focused their discussion
on poly(n-butyl acrylate) homopolymers, for which polymerizations were halted
at <70% conversion in order to maximize end group fidelity while also keeping
the molecular weights low. To facilitate conjugation, the urazole functionality was
first converted to the 3H-1,2,4-triazole-3,5(4H)-dione (Scheme 16.17). This was
accomplished via mild oxidation with 1,4-diazabicyclo[2.2.2]octane and bromine
(DABCO-Br). Removal of the dispersed oxidizing agent by simple filtration, fol-
lowed by immediate reaction with hexa-2,4-dien-1-ol, resulted in formation of the
target species within a few seconds.
16.3.3 Generation and Application of Macromolecular Thiols

Perhaps the most common, and certainly the most versatile, approach for modify-
ing thiocarbonylthio groups involves nucleophilic cleavage, followed by trapping
O O Figure 16.8 Chemical structure of a urazole-

functional trithiocarbonate: butyl (1-((6-(3,5-dioxo-1,
HN S S
N 2,4-triazolidin-4-yl)hexyl)amino)-1-oxopropan-2-yl)
HN 6N
H
Bu
carbonotrithioate (URZ-TTC).
S
O
O O
1. oxidation
HN S(C=S)SBu
N 6N n
HN H 2. OH
CO2Bu
O
HO
O O
N S(C=S)SBu
N 6N n
N H
CO2Bu
O
Scheme 16.17 Synthesis of α-end-functionalized poly(n-butyl acrylate) by oxidation of a

terminal urazole-functional group, followed by an HDA reaction with hexa-2,4-dien-1-ol.
of the resulting macromolecular thiol, or thiolate, by one of the numerous avail-

able routes [155] (Figure 16.9). Suitable nucleophiles include 1∘ and 2∘ amines (and
hydrazine hydrate) [54, 134, 156–166], hydroxides [86, 167], azide [168], and hydride
reagents such as NaBH4 [169–173] or LiBEt3 H [174]. In general, all the nucleophilic
cleavage reactions are reasonably rapid and give the corresponding macromolecular
thiol quantitatively. We do, however, note one precaution that is commonly adopted
in such cleavage reactions – it is typical to perform these reactions under oxygen
free conditions and in the presence of a reducing agent such as tributylphosphine
(PBu3 ) or tris(2-carboxyethyl)phosphine (TCEP) [175] in order to negate any appre-
ciable build-up of corresponding macromolecular disulfide (Scheme 16.18). This is
even advisable when using reagents such as hydrazine hydrate, which is able to
serve as a cleavage agent and anti-oxidant because disulfide formation has been
detected in polymers cleaved with this reagent even under deoxygenated conditions
[163]. While we have noted the one-pot approach to clean macromolecular thiol, it
is also possible, if desirable, to conduct a two-step process involving initial cleavage
without taking any precautions against disulfide formation, followed by a second
step in which the product mixture is treated with a reducing agent to obtain pure
macromolecular thiol.
S
Nucleophilic
Pn Pn SH + Pn S S Pn
S Z
cleavage
Scheme 16.18 Nucleophilic cleavage of RAFT thiocarbonylthio end group yielding the
corresponding macromolecular thiol and polymeric disulfide.
Oxidative coupling yielding polymeric disulfides is not the only potential side
reaction that can occur during cleavage of thiocarbonylthio end groups. The nature
of the polymer repeat units, i.e. styrenic vs. methacrylate, can also influence the
outcome of such reactions and must be considered when the goal is to prepare
pristine polymeric thiol. As a representative example, in an early study, Xu et al.
[156] compared the products from the aminolysis, employing cyclohexylamine,
X Pn X Radical thiol-ene
R S
X Pn X
S Radical thiol-yne
R S
Pn
EWG
Pn EWG
Catalyst S
Catalyzed thio-
EWG Michael
Pn EWG
S
Catalyst
S O
Nuc R N C O
Pn Pn R Thiol-isocyanate
S Z Pn SH S N
Base H
O
R Pn R Thiol-epoxy
S
Catalyst OH
R-X
Pn R Thiol-halo
Catalyst S
O
S S OR´
R O Pn S Thio-methanethiosulfonate
S R exchange
S Thio-pyridyl disulfide
R S N Pn S
S R exchange
Figure 16.9 Thiol-X reactions potentially suitable for the modification of macromolecular
thiols derived from RAFT-prepared (co)polymers.
of low molecular weight polystyrene and PMMA-containing dithiobenzoate ω

end groups. In the case of polystyrene, following the reaction for 24 hours, the
major product was the polymeric disulfide formed by oxidative coupling, the
concentration of which increased steadily over the 24 hours reaction time frame. In
the case of PMMA, initially, it appears that disulfide formation did occur; however,
the concentration of this species gradually decreased, ultimately giving a product
with nearly the same molecular weight as the starting material. Using a combina-
tion of size exclusion chromatography (SEC), NMR spectroscopy, matrix-assisted
laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry, and
elemental analysis, the authors established that the main product from the aminol-
ysis of PMMA was a species containing a terminal thiolactone-functional group
formed via a ‘backbiting’ reaction of thiol on the penultimate MMA repeat unit.
Similar results were obtained for poly(2-(dimethylamino)ethyl methacrylate) and
poly(lauryl methacrylate). While the formation of polymers with thiolactone end
groups may be undesirable, it is noted that these early studies on the synthetic
utility of thiolactones in polymer chemistry has been greatly advanced and today
represents one of many functionalities with proven broad utility [79, 176, 177],
including in the general field of RAFT polymerization [178–180].
As a general statement, the occurrence of side reactions during cleavage of
thiocarbonylthio end groups can largely be avoided if the resulting macromolecular
thiol is immediately ‘captured’, often by a reactive species present in situ during
the cleavage process. In fact, and as noted above, while historically end group
cleavage reactions were developed to address the perceived deleterious effect of
the thiocarbonylthio groups in RAFT-prepared (co)polymers, they actually played
a major role in the advancement and application of thiol-based ‘click’ chemistries
in synthetic polymer chemistry [181]. With a macromolecular thiol in hand, it is
possible to access the wide range of the so-called thiol-X chemistries in end group
modification (Figure 16.9), although not all of these reactions are equally applicable
to polymeric thiols.
16.3.3.1 Radical Thiol–Ene Reaction

The radical-mediated hydrothiolation of a C=C bond, with anti-Markovnikov
orientation, the thiol–ene reaction, is perhaps the most studied of all the common
thiol-X chemistries and has an extremely broad synthetic utility [62–64, 182, 183].
However, it is quite rare for an RAFT-derived macromolecular thiol to be employed
directly in a radical thiol–ene reaction. While the synthetic utility of the thiol–ene
reaction is unquestionable, if there is a limitation of the chemistry, then it is the fact
that 2∘ and 3∘ macromolecular thiols derived from RAFT polymer thiocarbonylthio
end groups exhibit very low reactivity in radical thiol–ene processes especially
at stoichiometric ratios of thiol:ene. This low reactivity is typically attributed
to the effective low concentration of thiol groups, especially when attempting
polymer–polymer conjugation reactions [184]. The lower reactivity of 2∘ and 3∘
thiols in small-molecule thiol–ene chemistry has also been noted. However, there
are examples in which the direct reaction of macromolecular thiols with enes,
under radical conditions, has been reported. For example, as part of a broader
report regarding the limitations of radical thiol–ene chemistry for polymer–polymer
conjugation, Koo et al. [185] detailed the reactions of thiol-terminated polystyrene
(prepared by trithiocarbonate-mediated RAFT, followed by aminolysis with
propylamine) with several small-molecule enes such as dodecyl vinyl ether, allyl
ether, and undecanoic acid, under photoinitiated radical conditions. As a general
observation, yields were typically high (c. 90%), except for undecanoic acid (30%),
under a range of conditions and reaction stoichiometries.
However, this is not to say that the radical thiol–ene reaction has not been more
widely employed in the field of RAFT chemistry, indeed in polymer and materials
science in general, vide infra [181]. We have already highlighted the ability to intro-
duce functionality at the α-terminus via this chemistry in RAFT polymers prepared
with norbornenyl-functionalized RAFT agents [61]. In addition, while a detailed
discussion is beyond the scope of this chapter, we note that the radical thiol–ene
reaction has been adopted by numerous groups to modify main chain pendent ene
groups in a range of RAFT-prepared (co)polymers [183].
16.3.3.2 Radical Thiol–Yne Reaction

The radical thiol–yne reaction can be viewed as a sister reaction to the radical
thiol–ene process [186–190]. As such, it possesses similar advantages and lim-
itations. In the radical thiol–yne reaction, we assume that 2 equiv of thiol will
add across the C≡C bond, in a terminal alkyne, which is formally sequential
thiol–yne/thiol–ene processes; the product is the 1,2-dihydrothiolation species, B
in Scheme 16.19. It is beyond the purview of this chapter to discuss the mechanistic
features of the thiol–yne reaction in detail, but we will note that it can be performed
with both activated and non-activated ynes and that the nature of the product can
be tuned based on reaction conditions. In fact, there are six possible products from
the reaction of an yne with thiols, all of which are accessible under appropriate
conditions [190].
SR
RS B
*
RS H
1 4
SR
R S RS
RS
2 3
RS H
RS
Scheme 16.19 General mechanism of the radical-mediated double hydrothiolation of a

C≡C bond, the thiol–yne process.
As with the thiol–ene reaction, the thiol–yne process has been adopted widely in
various areas of synthetic chemistry [190]. In the context of polymer chemistry, the
development of the so-called thiol–yne click copolymerization, characterized by the
single addition of a thiol to an yne (to give poly(vinyl sulfide)s), represents an emerg-
ing but ever-growing field of research [191–194]. By analogy with the thiol–ene reac-
tion, the direct use of polymeric thiols derived from RAFT polymers is uncommon.
However, combining yne-functional RAFT polymers (both as R-groups and as pen-
dent groups) with small-molecule thiols in the radical thiol–yne process is known,
as highlighted earlier in the work of Le Bohec et al. [65]. The thiol–yne reaction has
also been employed in sequential modification reactions. For example, Kumar et al.
[195] reported the combination of RAFT polymer HDA functionalization, followed
by radical thiol–yne double hydrothiolation of ω-terminal groups in poly(tert-butyl
acrylate) polymers (Scheme 16.20).
The synthesis of low molecular weight poly(tert-butyl acrylate) was accom-
plished in toluene with BPCD (Figure 16.7). Subsequent selective reaction of the
diene/yne-functional diester, (2E,4E)-hexa-2,4-dien-1-yl prop-2-yn-1-yl succinate,
with the poly(tert-butyl acrylate) polymers yielded the HDA adducts containing
terminal yne-functional groups. Radical-mediated thiol–yne reaction with thioglyc-
erol, in the presence of a small amount of photoinitiator, gave the four-functional
OH-ω-terminal products. The authors also studies the effect of double hydrothiola-
tion with thioglucose, yielding materials capable of binding lectins. This is not the
only example in which sequential ‘click’ reactions have been adopted as a means of
modifying RAFT polymer end groups and additional examples are given below.
16.3.3.3 Catalyzed Thiol-Michael Additions

The catalyzed addition of a thiol to an activated substrate, the thiol-Michael reac-
tion [196], is, arguably, the most commonly employed reaction in the modification
of thiocarbonylthio end groups, and many examples have been reported in which
the reaction has been utilized to directly instil functional end groups, generate new
materials, or simply as a means of trapping a polymeric thiol to yield an inert end
group [134, 159, 197, 198].
The thiol-Michael reaction can be performed under base- or nucleophile-mediated
conditions; the two different mechanisms are shown in Figure 16.10. A detailed
description of the process is not given here, and readers are directed to several
reviews and papers where it is discussed in more detail [199, 200]. Briefly, and
regardless of the conditions adopted, the thiol, or thiolate, in all instances is derived
from the RAFT-prepared (co)polymer. As such, it is clear that many different types
of macromolecular thiols can be generated simply by varying the (co)monomer and
architecture. The structure of the Michael acceptor can, likewise, be one of many
different species. In fact, it is the wide choice of both donor and acceptor that makes
this chemistry so powerful and popular. In the context of modifying polymeric
thiols prepared by RAFT, suitable families of Michael acceptors that have been uti-
lized include acrylates [201–209], methacrylates [205], acrylamides [49, 210–213],
maleimides [175, 214–223], vinyl sulfones [224], octavinyl-polyhedral oligomeric
silsesquioxane (POSS) [225], vinyl azlactone [226], and multi-functional variants
of these [221, 224, 227, 228]. Typically, such conjugate additions are performed in
one-pot process, i.e. the RAFT polymer thiocarbonylthio end groups are cleaved
in the presence of the Michael acceptor to effectively trap the thiol as soon as it
is formed. Although it is not possible to discuss all of these examples, below we
will highlight several literature reports involving sequential ‘click’ reactions for end
group modification.
Yu et al. [205] reported the synthesis of ω-functionalized poly(N-isopropylacryl-
amide) employing sequential thiol-Michael reactions with radical thiol–ene
O
O
BPCD, AIBN O
Ph S
N O
O O n
Toluene, 65 °C S
O O TFA, CHCl3, 25 °C
HDA Reaction
OH
N O N O S OH OH
OH
Ph S S O HS OH Ph S S O S
O O
n n
O O OH
O O DMPA, DMF O O
UV, 4 h
Thiol-yne reaction
Scheme 16.20 Sequential HDA and thiol–yne reactions as a route to ω-functionalized poly(tert-butyl acrylate).
EWG
RS
Michael addition RS–H
product
NEt3
RS–H RS EWG
RS
EWG
(a)
RS–H Me2PhP
Me2PPh+ EWG Me2PhP
EWG EWG
+ RS
EWG
RS
Michael addition RS–H
product
RS EWG
RS
(b) EWG
Figure 16.10 The general mechanism of the base-catalyzed thiol-Michael reaction (a) and
the nucleophile (phosphine)-catalyzed mechanism (b).
and thiol–yne chemistries. Scheme 16.21 highlights the thiol-Michael/thiol–yne

modification route.
Poly(N-isopropylacrylamide), prepared in the presence of 2-cyanopropan-2-yl
benzodithioate, was treated with octylamine (to cleave the dithioesters to the
corresponding thiols) and propargyl acrylate (the Michael acceptor) in the presence
of dimethylphenylphosphine (a potent catalyst for thiol-Michael addition reactions
[196]) yielding the yne end-functionalized poly(N-isopropylacrylamide). The
ω-yne-functional polymer was subsequently reacted with 6-mercapto-1-hexanol,
1-hexanethiol, and 3-mercaptopropyl polyhedral oligomeric silsesquioxane (100%
excess based on yne-functional groups) in the presence of Irgacure 651 (benzil
dimethyl ketal) as a photoinitiator. This resulted in the quantitative formation, as
judged by 1 H NMR spectroscopy, of the corresponding bis-ω-thioether adducts.
Likewise, if the Michael addition reaction is conducted with allyl methacrylate
rather than propargyl acrylate, it provides access to an allyl-end-functionalized
polymer that can be modified by a radical thiol–ene reaction.
In a related example, also with poly(N-isopropylacrylamide), Li et al. [229]
reported sequential trithiocarbonate end group cleavage with 2-ethanolamine in
the presence of PBu3 , followed by base-mediated thiol-Michael addition to an added
Octylamine, PPhMe2
O o S Ph DCM, RT
AIBN, DMF, 70 C
NC n O
n NH S S
O NH
Ph S CN O
Thiol-Michael
SR
S O S O SR
RS-H
NC n n
O NC O
O NH Photoinitiator O NH
Thiol-yne
Scheme 16.21 Sequential end group cleavage/Michael addition with propargyl acrylate,
followed by radical thiol–yne reaction with the ω-yne-functional group.
O O O O
O O
N N N N
HO2C S 2 HO2C S 2
n O O n O O
SR
O NH O NH
OH
(a) (b)
Figure 16.11 Structures of poly(N-isopropylacrylamide)s formed by sequential

thiol–maleimide/Diels–Alder reactions (a) and thiol–maleimide/thiol–maleimide
reactions (b).
excess of bis-maleimidodiethyleneglycol, yielding the corresponding maleimide

end-functionalized polymer. This was then used to effect further functionalization
via a HDA reaction with anthracen-9-ylmethanol or by reaction with thiols to give
the species shown in Figure 16.11.
In an interesting example of an intra-molecular thiol-Michael reaction, Lu
et al. [230] detailed the synthesis of alkyne-functionalized cyclic polymers
from precursor linear polymers with the key cyclization step being accom-
plished via a thiol-Michael process (Scheme 16.22). For example, polystyrene
was prepared utilizing the yne-OH-functional trithiocarbonate RAFT CTA
3-hydroxy-2-methyl-2-((prop-2-yn-1-yloxy)methyl)propyl 2-(((butylthio)carbonoth-
ioyl)thio)-2-methylpropanoate. The −OH group in the R fragment of the polystyrene
polymer was then acylated with acryloyl chloride, yielding the acrylic-functional
species. The final cyclization step involved a one-pot aminolysis/thiol-Michael
reaction in which hexylamine cleaved the ω-terminal trithiocarbonate and served
as the catalyst for the Michael addition of the resulting macromolecular thiol to
the R-group acrylate functionality giving the cyclic species in ∼80% yield. The
same synthetic procedure was applied to homopolymers of tert-butyl acrylate,
N-isopropylacrylamide, and N,N-dimethylacrylamide.
16.3.3.4 Thiol-Isocyanate Modification

The reaction between thiols and isocyanates is an example of a non-Aldol carbonyl
reaction highlighted by Finn et al. as a member of the general ‘click’ family of
O
S S
O O n nBu
Ph S
OH
Acryloyl chloride
O
S S
O O n nBu
Ph S
O
Hexylamine,
TCEP
O
S
O O n
Ph
O
Scheme 16.22 Synthesis of alkyne-functionalized cyclic polystyrene via an intramolecular

thiol-Michael addition process.
reactions. Intimately related to the more common alcohol–isocyanate reaction,

the thiol-based variant does not suffer from the same side reactions seen in the
alcohol reaction. The product of a thiol–isocyanate reaction, an S-thiocarbamate
(or thiourethane), can generally be obtained quantitatively within a few seconds. In
fact, thiol–isocyanate coupling is one of, if not the, fastest of the thiol-based coupling
chemistries. As with many of these thiol-based chemistries, the thiol-isocyanate
reaction is widely employed in synthetic chemistry and materials science [231–237].
Not surprisingly, this chemistry has been utilized in conjunction with
RAFT-prepared polymers. However, even though the chemistry is facile, quanti-
tative, and generally extremely rapid, there are few reports regarding end group
modification via thiol–isocyanate coupling, and more emphasis has been placed
on side chain modification of RAFT-synthesized (co)polymers with pendent iso-
cyanate groups [238, 239]. The first report detailing RAFT end group modification
via thiol–isocyanate coupling came from Li et al. (Scheme 16.23) [240].
Poly(N,N-diethylacrylamide) with a mean degree of polymerization of 30 (M n ca.
2540 g mol−1 ), prepared via dithiobenzoate-mediated RAFT, was first treated with
CH3 NH2 to cleave the thiocarbonylthio end group. The product was subsequently
treated with TCEP, a mild reducing agent, to convert any polymeric disulfide to
the pristine macromolecular thiol. End group cleavage and disulfide reduction
was confirmed by a combination of SEC and UV–vis spectroscopy. The polymeric
O S Ph
o (1) CH3NH2
AIBN, 70 C R
n N n
S
S N O (2) TCEP
Ph S CN
H
SH S N
R R´–N=C=O R´
n R
n
O
N O RT, THF, N2, NEt3 N O
(a)
O
NCO NCO
NCO O
NCO NCO
NCO
(b)
Scheme 16.23 (a) General scheme for the preparation of thiocarbamate

end-functionalized poly(N,N-diethylacrylamide) and (b) representative examples of
small-molecule isocyanates employed in end group modification.
thiol was subsequently reacted with 14 different small-molecule hydrophobic

isocyanates, examples of which are also shown in Scheme 16.23. As a representative
example, employing real-time FTIR spectroscopy, the authors demonstrated that
the reaction between poly(N,N-diethylacrylamide)-SH and hexyl isocyanate was
rapid, attaining ∼95% conversion within 15 minutes. In all instances, the modified
polymer retained its narrow molecular weight distribution with no evidence of
any coupled disulfide species, attesting to the clean nature of this chemistry.
More recently, Boursier et al. [241] employed the same approach to prepare
methacrylic poly(N-acryloylmorpholine) macromonomers. RAFT-synthesized
poly(N-acryloylmorpholine) was treated with hydrazine hydrate, followed by
NEt3 -mediated coupling with 2-isocyanatoethyl methacrylate. Formation of the
macromonomer was confirmed by a combination of 1 H NMR spectroscopy and
SEC. The authors demonstrated the ability to copolymerize the macromonomer
with methacrylic acid via normal radical polymerization, yielding novel graft
copolymers with potential application as plasticizers in concrete formulations.
16.3.3.5 Thiol-Epoxy Ring Opening

Nucleophilic ring opening of strained heterocycles, such as epoxides, is another
example of a ‘click’ process [7]. The general high reactivity of epoxides has naturally
resulted in their use in a wide range of applications in polymer and materials science
[242–245]. However, as with some of the former chemistries highlighted, the direct
use of a RAFT-derived polymeric thiol in such nucleophilic ring-opening reactions

is rare. Harvison et al. [171] detailed the thiolysis of a series of small-molecule
oxiranes with polystyrene and poly(N,N-diethylacrylamide) under base-mediated
conditions and in the presence of the Lewis acid ZnCl2 . In the case of polystyrene,
the thiocarbonylthio end groups were cleaved with hydrazine hydrate and the
macromolecular thiol isolated and characterized. In reactions with monofunctional
epoxides and ZnCl2 , high conversions were attained, although none were quan-
titative with the highest degree of modification being 88%. Under base-mediated
conditions, the degree of end group modification was similar but suffered from the
formation of macromolecular disulfide as an impurity. In contrast, in a one-pot
approach with poly(N,N-diethylacrylamide) employing NaBH4 as the end group
cleaving agent, and Me2 PPh as a reducing agent in the presence of a small-molecule
epoxide, reactions proceeded smoothly giving essentially quantitative formation of
the ring-opened product as determined by NMR spectroscopy.
16.3.3.6 Thiol-Halo Substitution

Nucleophilic substitution, SN , reactions with alkyl and aryl halides proceed,
under appropriate conditions, with ‘click’ or ‘click’-like characteristics. With
respect to thiol-based reactions, the two most prominent in the literature are the
thiol-bromo/iodo [246, 247] and thiol-para-fluoro [248, 249] reactions.
Nakayama and Okano detailed the one-pot aminolysis/thiol–iodo reaction
between amphiphilic block copolymers prepared by RAFT and 2-iodoethanol [250]
as part of their study on the effect of end groups on the thermoresponsive behaviour
of block copolymers of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-
block-poly(benzyl methacrylate), and Segui et al. [251] likewise adopted the
thiol–iodo reaction in the synthesis of α,ω-dicholesteryl and α,ω-dipyrenyl poly
(N-isopropylacrylamide)s employing a difunctional RAFT agent (Scheme 16.24).
The analogous difunctional cholesteryl derivative was obtained under the same con-
ditions by substituting 1-(4-iodobutyl)pyrene with cholest-5-en-3β-yl 6-iodohexyl
ether.
Xu et al. reported the thiol–bromo reaction as a convenient method for
end group modification of RAFT polymers and also for the preparation of
multiblock and hyperbranched polymers [252]. For example, the one-pot treat-
ment of RAFT-synthesized poly(methyl acrylate) with hexylamine (end group
cleavage agent), triethylamine (base), and 2-bromopropanoate yielded the
ester-end-functionalized polymer quantitatively within 30 minutes.
Reaction with methyl 2-bromo-2-propanoate, a 3∘ halide, was also successful as
was analogous modification on poly(N-isopropylacrylamide). In the same work, it
was demonstrated that use of the R-group bis-bromo-ester-functional RAFT CTA
(Figure 16.12) facilitates the synthesis of polymers which, after aminolysis of the
thiocarbonylthio end groups, are able to undergo inter/intra-molecular thiol–bromo
reactions yielding hyperbranched materials.
In a related work, Chen et al. [253] reported the one-pot synthesis and assembly
of supramolecular dendritic polymers from X-Y2 -type polymeric precursors [254].
Figure 16.13 shows the two precursor building blocks.
O O
S S O S S
n O O n
S S
O NH HN O
n-Butylamine
O O
HS O SH
n O O n
O NH HN O
DMF, TCEP, Na2CO3

I
O O
S O S
n O O n
O NH HN O
Scheme 16.24 The synthesis of α,ω-pyrene difunctionalized poly(N-isopropylacrylamide).
O Figure 16.12 Chemical structure of

({4-cyano-4-[(phenylcarbonothioyl)thio]
O pentanoyl}
Br
azanediyl)bis(ethane-2,1-diyl)bis
O NC S (2-bromo-2-methylpropanoate).
N
O S
Br
O
O NH
S Ph O N
O n
O O NH O
S
HN 11 O O Br
O nBu nBu O O
11
HN O O
S NH O
O 11
O O N
S Ph
n NH
(a) O (b)
Figure 16.13 Barbiturate-linked poly(n-butyl acrylate) (a) and bromo-functional bipyridyl

building blocks (b).
Figure 16.14 Chemical structure of an O

α-yne/bromide-functional polystyrene. S S
O O n nBu
Ph S
O
Br
O
In a one-pot, two-step process, the α,ω-dithiobenzoate terminal groups in

poly(n-butyl acrylate), containing a central pyrimidine-2,4,6(1H,3H,5H)-trione, unit
were cleaved with hexylamine. Performed in the presence of (3,5-bis((6-butyrami-
dopyridin-2-yl)carbamoyl)phenoxy)methyl 2-bromopropanoate (Figure 16.13b),
and following a thiol-bromo reaction, the target X-Y2 species was isolated. The
isolation of the target X-Y2 species was confirmed via a combination of NMR
spectroscopy, MALDI-TOF mass spectrometry (MS), and liquid chromatography at
critical conditions. These wedge-like species were shown to undergo supramolec-
ular self-assembly into disc-like structures as evidenced by NMR and atomic force
microscopies.
In Scheme 16.22, we highlighted the work of Lu et al. and the synthesis of
cyclic polymers from RAFT-prepared linear precursors via an intramolecular
thiol-Michael reaction pathway. In the same report, the authors also described
attempts to obtain the same functional cyclic polymers employing thiol–bromo
chemistry in the cyclization step. With reference to Scheme 16.22, acylation of
the α-located −OH group with 2-bromopropionyl bromide, rather than acry-
loyl chloride, yielded the α-yne/Br-functional species (Figure 16.14). One-pot
aminolysis/thiol–bromo reactions gave cyclic species, although yields were signif-
icantly reduced compared to the thiol-Michael approach with <24% of the cyclic
species formed. Perhaps not surprisingly, the lower yields were due to competing
reaction of the added hexylamine with the 2∘ bromide.
In a recent example of the thiol–bromo reaction, Döhler et al. [255] reported the
chain end functionalization of three-arm star polymers of poly(n-butyl acrylate)
and polystyrene with barbiturate and imidazolium-functional species. Figure 16.15
shows the poly(n-butyl acrylate) derivatives. The poly(n-butyl acrylate) stars
were prepared with a novel trifunctional RAFT agent in which the R-group
fragment was part of the trifunctional core. Star polymer formation was readily
accomplished under standard RAFT conditions yielding materials with M n (as
O O O O O
S S
O O 11 NH O O 11N
n n N
O O O N O O O
H
nBu nBu
3 3
Figure 16.15 Chemical structures of barbiturate and imidazolium end-functionalized

poly(n-butyl acrylate) three-arm star polymers formed by a thiol–bromo ‘click’ reaction.
determined by 1 H NMR spectroscopy) between ∼5500 and 14 300 g mol−1 and

correspond D - of 1.27 and 1.26. Subsequent methylamine-mediated aminoly-
sis, followed by reaction of the resulting thiol-terminated star polymers with
(5-ethyl-2,4,6-trioxohexahydropyrimidin-5-yl)methyl 2-bromopropanoate or
3-(((2-bromopropanoyl)oxy)methyl)-1-methyl-1H-imidazol-3-ium, yielded the
target materials in Figure 16.15 with >95% functionality.
While gaining in popularity, the thiol-para-fluorophenyl reaction is one of the
least examined in the toolbox of thiol-X chemistries. Although it has been employed
in the modification of pendent pentafluorophenyl and pentafluorobenzyl functional
[256, 257] groups, its use in RAFT ω chain end functionalization remains largely
unexplored.
Zhu and coworkers [258, 259] reported the synthesis and application of dise-
lenocarbonyl compounds as mediators for the controlled radical polymerization
of activated and non-activated monomers, the so-called Se-RAFT process. These
Se-analogues of thiol-based RAFT agents have much in common. They can
be prepared via the same general synthetic routes, they are assumed to medi-
ate radical polymerization via the same addition–fragmentation mechanistic
pathway as thiocarbonylthio compounds, and they are able to undergo many
of the same types of chemistries as reported herein, including selenol–Michael
addition, selenol–epoxy, selenol–bromo, and selenol–isocyanate coupling. Inter-
estingly, selenolcarbonylselenol end-functional polystyrenes have been modified
by all of these chemistries as well as by nucleophilic aromatic substitution with
pentafluorostyrene (Scheme 16.25) [259].
OMe
Se Ph Se O
n
Ph Se O Ph Se
OMe
AIBN
F F
F Hexylamine Ph Se F
+ n
PBu3 Ph
F F F
F F
Scheme 16.25 Preparation of polystyrene macromonomers via a combination of Se-RAFT,

aminolysis, and para-fluoro aromatic nucleophilic substitution.
Homopolymerization of styrene in the presence of Se-benzyl O-(4-methoxyphenyl)

carbonodiselenoate and AIBN yielded the expected polymeric species with an
SEC-measured M n of 4300 g mol−1 and D - of 1.22 (at c. 40% monomer conver-
sion). Employing typical conditions for thiocarbonylthio end group removal, the
polystyrene–Se(C=Se)Z analogue was reacted with hexylamine in the presence of
pentafluorostyrene and PBu3 yielding the target styrenic-based macromonomer.
16.3.3.7 Disulfide Reactions

Earlier in this chapter, we noted that in accessing polymeric thiols from
RAFT-prepared (co)polymers, it is common practice to perform the end group
cleavage reaction in the presence of a reducing agent to avoid polymer–polymer
coupling via disulfide formation. However, it is possible to exploit such facile, and
reversible, disulfide formation in the preparation of higher ordered materials as
well as effecting simple end group modification.
Recently, Dao et al. [165] reported the synthesis of ultra-high molecular weight
ABA triblock copolymers employing RAFT. The key to obtaining the target mate-
rials was the aminolysis of trithiocarbonate end groups in precursor AB diblock
copolymers, under oxidizing conditions, to intentionally promote polymer–polymer
disulfide bond formation. Scheme 16.26 shows an example for ABA triblock copoly-
mers of poly(acrylic acid-b-acrylamide-b-acrylic acid). The authors prepared
eight different examples of such triblocks and obtained materials whose final
SEC-measured M n were ≥1 × 106 g mol−1 . The same general approach has been
employed by Whittaker et al. [260] in the reversible formation of linear and cyclic
polymers from α,ω-dithiol-functional polystyrene (HS–polystyrene–SH); by Gho
et al. [261] in the preparation of monocyclic, linear multiblock, bicyclic, and
crosslinked networks based on polystyrene three-arm stars with arms terminated by
SH groups; and by Vogt and Sumerlin [262] and the preparation of redox-responsive
S
O HO2C
S S CO2H HO2C S S
CO2H
OH m
Ammonium persulfate
CO2H S
sodium formaldehyde sulfoxylate
dihydrate
24 h, 20 °C
O
H2N HO2C S S
CO2H
m n
Ammonium persulfate
CO2H CONH2 S
sodium formaldehyde sulfoxylate
dihydrate n-Butylamine, O2
24 h, 20 °C H2O, 50 °C
HO2C S S CO2H
m n n m
CO2H CONH2 CONH2 CO2H
ABA triblock copolymer
Scheme 16.26 Synthesis of ABA triblock copolymers of acrylic acid and acrylamide formed
by disulfide coupling of precursor AB diblock copolymers.
hydrogels based on ABA RAFT-prepared triblocks, with gel formation occurring

after aminolysis/oxidation of the trithiocarbonate groups in self-assembled micelles.
Because disulfides are stable in the absence of a reducing agent or a strong nucle-
ophile, disulfide formation may be employed as a route to incorporate functional, or
reactive, groups into (co)polymers via disulfide exchange reactions. This is readily
achieved in the reaction of RAFT-derived polymeric thiols with reagents contain-
ing an electrophilic sulfur atom [263]. Suitable reagents include pyridyl disulfide
[84, 264–266] or methane thiosulfonates [267–270]. The general reactions are shown
in Scheme 16.27.
N S
X S N
S Z X
R S
n R S N
Y S n
R′–NH2 Y
(a)
O
S SR″
X X
S Z O S R″
R R S
n n
Y S R′–NH2 Y
(b)
Scheme 16.27 The general thiol–pyridyl disulfide (a) and thiol–methanethiosulfonate

exchange reactions (b).
Additionally, and in keeping with many of the other chemistries highlighted

herein, such disulfide exchange reactions are also applicable as a route for modifying
pendent groups in (co)polymers [271–273].
Although it may be desirable to simply isolate and use a pyridyl disulfide
end-terminated polymer, the versatility of this approach lies in the fact that
it is possible to perform thiol exchange reactions on such end-functional
materials. An elegant example of such chemistry was reported by Yu et al. in
the preparation of materials capable of releasing H2 S (Scheme 16.28) [274].
Dithiobenzoate-terminated poly[(oligoethylene glycol methyl ether) methacrylate]
O
NC S Ph NC S NC S
S N O S
n N S n n
S S N
SH
O O O O O O
Ethanolamine
rt, 1 h, CHCl3
O rt, 2 h O O
MeCN Thiol exchange
O O O
Scheme 16.28 The synthesis of an H2 S-releasing polymer via sequential modification of

dithiobenzoate end groups involving cleavage and capture by pyridyl disulfide, followed by
thiol exchange with benzothioic S-acid.
was treated with ethanolamine in the presence of dipyridyl disulfide, yielding the
corresponding pyridyl disulfide end-functional polymer. Subsequent treatment with
benzothioic S-acid gave the acyl-protected perthiol-terminated polymer. Treatment
of the acyl-protected polymer with cysteine, in the presence of a chemoselective
H2 S-responsive fluorescence probe, immediately resulted in a strong fluorescence
at 520 nm indicative of the presence of free H2 S. This proof of concept was extended
to copolymers with advanced architectures, including those capable of pH-induced
self-assembly giving H2 S-releasing micelles.
A real advantage of the thiol–methanethiosulfonate reaction is the ease with
which such reagents are prepared and a broad range of functionalities that can
be introduced, i.e. the nature of R′′ . Two examples based on the introduction of
bio-related functionality should serve to highlight this particular advantage. Roth
et al. [275] detailed a two-step approach to α,ω-functionalized poly(diethylene
glycol monomethyl ether methacrylate) with thyroxin, II in Figure 16.16, at
the α terminus and biotin at the ω-terminus. Key to success was the use of a
pentafluorophenylester-functionalized R-group dithiobenzoate as the RAFT agent,
I and a biotin-functionalized methanethiosulfonate, III Figure 16.16. Following
homopolymerization, the polymer was first reacted with thyroxin in a regioselective
manner at the pentafluorophenylester, instilling thyroxin at the α-terminus. Even
though this reaction involves a primary amine, the dithiobenzoate ω-terminal
groups remain unaffected during this step. Such regioselectivity is one of the
many advantages associated with pentafluorophenylester chemistry. In the second
step, the dithiobenzoate end group is cleaved with propylamine in the presence
of III, resulting in polymeric thiol formation, followed by exchange yielding the
α,ω-functional homopolymer.
α,ω-Modification was confirmed via a combination of 1 H, 13 C, and 19 F NMR;
UV–vis and IR spectroscopies; and SEC. The thyroxin transport protein prealbumin
F
F F I O
O S
I O S
NH2 S N
F F CN S H
O
O HO I CO2H NH
S HN
I
O
I II III O
I
I O
CO2HO S
H
S N NH
HO I N S
H
NC n HN
I O O
O O
Figure 16.16 Chemical structures of a pentafluorophenylester-functional R-group

dithiobenzoate RAFT CTA, I, thyroxin, II, a biotin-functional methanethiosulfonate, III, and a
α,ω-difunctional poly(diethylene glycol monomethyl ether methacrylate) obtained via
sequential nucleophilic substitution and sulfur exchange reactions.
(with two binding sites) and streptavidin (with four biotin binding sites) was
conjugated to the α,ω-functional polymer, resulting in protein–polymer network
formation.
Wang and Ling [276] detailed the synthesis of well-defined block copolymers of
polystyrene with poly(γ-benzyl L-glutamate) via a combination of RAFT and NCA
polymerization. The overall approach is shown in Scheme 16.29.
O H CH2Cl2
NC S S O DMF NC S N
n 11 + S n S t-BOC
O N S TFA
Ph S H n-Butylamine Ph
O
O OBn
DMF
NC S NH2
S O O H H
n NC S N
O S N m
Ph Ph O N n
H
H
Ph O
O
Scheme 16.29 End group modification via aminolysis/sulfur exchange with a protected
amine methanethiolsulfonate, followed by removal of the t-Boc-protecting group and
primary amine-initiated N-carboxyanhydride ring-opening polymerization.
Treatment of trithiocarbonate-terminated polystyrene with n-butylamine in

the presence of S-(2-((tert-butoxycarbonyl)amino)ethyl) methanesulfonothioate
yields the corresponding disulfide end-functional homopolymer; acid-mediated
removal of the t-Boc protecting group gives the primary amine end-functional
polystyrene. The macromolecular primary amine is able to serve as an initiating
species in the ring-opening polymerization of benzyl L-glutamate NCA. Following
block copolymerization, the benzyl group is removed by treatment with NaOH,
yielding the target polystyrene–polypeptide copolymeric material. It should be
noted, however, that while disulfide formation was successful, conversion of the
t-Boc-protected macroinitiator to the free amine analogue was only 50% successful.
Fortunately, polystyrene homopolymer impurity (containing the t-Boc-protected
end group) was readily removed at the end of the ring-opening polymerization by
selective precipitation.
16.3.3.8 Miscellaneous Examples of End Group Transformation

and Applications
As noted earlier in this chapter, researchers continue to develop approaches for the
facile synthesis and modification of (co)polymers; this includes new methods for
modifying end groups in RAFT-prepared (co)polymers, in many cases for very spe-
cific, or targeted, applications. For example, Yu et al. [163] described an approach for
converting dithiobenzoate end groups in RAFT-prepared poly[(oligoethyleneglycol
methyl ether) methacrylate] to the corresponding S-nitrosothiol species, an
important class of nitric oxide donor. Reaction of the parent RAFT polymer with
hydrazine hydrate, followed by purification by dialysis yielded the correspond-
ing macromolecular thiol, as verified by UV–vis spectrophotometry, albeit with
c. 15% polymeric disulfide. Subsequent reaction of the macromolecular thiol,
POEGMA-SH, with nitrous acid (H2 SO4 + NaNO2 , 1 : 2) yielded the polymeric
S-nitrosothiol, POEGMA-SNO, as confirmed by UV–vis spectrophotometry. It is

important to carefully control the stoichiometry in this modification and use a
1 : 1 polymer-SH:nitrous acid ratio. The use of excess nitrous acid results in either
lower yields of the target S-nitrosothiol or in the case of >4 equiv of nitrous acid,
no formation. The authors extended this approach to chain end modification of
pH-responsive copolymer.
Recently, Lee et al. described a process for the conversion of thiocarbonylth-
iol end groups in RAFT polymers to the corresponding Br-terminated species
[160]. Inspired by the facile and quantitative conversion of low molecular thiols
such as 1-dodecanethiol and 1-adamantanethiol to the corresponding bromides
using PPh3 Br2 , the authors examined the same chemistry for the modification of
polystyrene thiocarbonylthio end groups prepared by RAFT. Unfortunately, the
conditions that proved successful for small molecules proved inefficient for the
polystyrene-SH (obtained via aminolysis of the parent homopolymer) yielding
a mixture of polystyrene-SH, polystyrene-Br, and polystyrene-alkene. Following
optimization, the authors did report the successful preparation of polystyrene-Br,
but it required the addition of PPh3 and Br2 separately with careful control of the
stoichiometry. Despite being a promising approach for effecting RAFT-to-ATRP
crossover polymerizations, the general route has not currently been optimized.
The use of hydride reagents such as NaBH4 for the cleavage of RAFT end groups
was first reported in the context of generating polymers capable of stabilizing gold
nanoparticles [169]. In other words, the nanoparticles serve as the ‘capture’ agents
for the in situ-generated polymeric thiolates [277]. This is an extremely facile and
rapid route to polymer–gold conjugates and has also been reported for the modifi-
cation of planar gold surfaces [170] and gold nanorods [278]. The general approach
has been extended to other metallic species including Fe3 O4 [279].
Zhang et al. [280] described the application of the squaric ester 3,4-diethoxycy-
clobut-3-ene-1,2-dione as a hydrolysis-resistant substrate, facilitating polymer–
protein ligation. Several routes were presented in this report, and here, we highlight
the incorporation of the squaric ester species into the R-group of a RAFT CTA and
its subsequent use. Scheme 16.30 outlines the approach adopted.
A two-step process involving substitution, followed by carbodiimide coupling
yielded the squaric ester-functional trithiocarbonate, A (Scheme 16.30). This
was shown to be an effective RAFT agent for the controlled polymerization of
N,N-dimethylacrylamide. Importantly, following polymerization the α-located
squaric ester/amide was demonstrated to be available for a second coupling with
lysozyme. The application of the squaric ester species for protein conjugation was
compared to a similar α-N-hydroxysuccinimide (NHS)-functional polymer with the
squaric ester derivative, exhibiting significantly enhanced hydrolytic stability that
facilitated the formation of the protein–polymer conjugate in a higher yield.
Golf et al. [281] reported an approach for the total removal of RAFT thiocar-
bonylthio end groups based on a Cu(II)-mediated cross-coupling with boronic acids.
The advantages of this particular route are that it allows for the incorporation of
highly functional end groups connected by a C—C bond, and it works quantitatively
with low-to-medium molecular weight polymers. The drawback of this chemistry
O
O
S S H O
O O O O nBu OH S S N
nBu O
OH S
+ H2N S
O N carbodiimide O O
O O H OH A
coupling
O O
AIBN O H NH2
N S S
A + N O nBu
n n
DMAc, 70 °C O S
O N
2h O
O
NH H
N S S
O nBu
n
O S
O N
O
Scheme 16.30 Synthesis of a squaric ester R-group-functional trithiocarbonate, its use as a mediator for the polymerization of N,N-dimethylacrylamide,
and as an amine-reactive site for conjugation post-polymerization.
16.4 Summary 793
is that it requires a benzylic species at the α-carbon. As such, it works well for
polystyrene but is ineffective for acrylates, for example. However, the authors noted
that it was possible to overcome this limitation by a single monomer insertion
strategy (Scheme 16.31).
S Ph AIBN, 0.05 equiv S Ph

Ph 43 Ph
S + 2 43
O O Ph S
Toluene, 80 °C, 2h O O
OMe
(HO)2B Cu(BF4)2.H2O.EtOAc
+ Ph 43
OMe DCE, 80 °C, 16 h Ph
O O
Scheme 16.31 Single styrene monomer insertion in a poly(methyl methacrylate)

homopolymer followed by Cu-mediated coupling with (4-methoxyphenyl)boronic acid as a
route to ω-functional polymers.
Matioszek et al. [282] developed a methodology to quantitatively transform

xanthate groups on acrylic polymers into less-reactive thiocarbonate functions, by
using ozone as the oxidizing agent, transforming the C=S group to a carbonyl [283]
(Scheme 16.32).
O O O
S O3 –SO2
S O
Pn R Pn R
S O Pn S S O
O R
Scheme 16.32 Proposed mechanism for the ozonolysis of xanthates.
In a final example, we note that Soeriyadi et al. detailed the combination of

cobalt-mediated catalytic chain transfer polymerization (CCTP) and RAFT, result-
ing in the removal of the thiocarbonylthtio end groups in PMMA, yielding the
corresponding sulfur-free macromonomers [254].
16.4 Summary
In this chapter, we have highlighted the various chemistries that have been devel-
oped, many now routinely employed, to functionalize RAFT-prepared (co)polymers
at the α-terminus, ω-terminus, or both. We hope that this overview has aided those
new to the field of RAFT end group modification, as well as more experienced
researchers, in the continued development and investigation of novel routes to
ever-more functional materials.
References
45: 5321–5342.
6 Chiefari, J., Chong, Y.K.B., Ercole, F. et al. (1998). Macromolecules 31:
5559–5562.
7 Kolb, H.C., Finn, M.G., and Sharpless, K.B. (2001). Angew. Chem. Int. Ed. 40:
2004–2021.
8 Iha, R.K., Wooley, K.L., Nyström, A.M. et al. (2009). Chem. Rev. 109: 5620–5686.
9 Tasdelen, M.A., Kiskan, B., and Yagci, Y. (2016). Prog. Polym. Sci. 52: 19–78.
10 Binder, W.H. and Sachsenhofer, R. (2007). Macromol. Rapid Commun. 28:
15–54.
11 Moad, G., Chong, Y.K., Postma, A. et al. (2005). Polymer 46: 8458–8468.
12 Willcock, H. and O’Reilly, R.K. (2010). Polym. Chem. 1: 149–157.
13 Moad, G., Rizzardo, E., and Thang, S.H. (2011). Polym. Int. 60: 9–25.
14 Harvison, M.A. and Lowe, A.B. (2011). Macromol. Rapid Commun. 32: 779–800.
15 Harvison, M.A., Roth, P.J., Davis, T.P., and Lowe, A.B. (2011). Aust. J. Chem. 64:
992–1006.
molecules 34: 2248–2256.
17 Sumerlin, B.S., Donovan, M.S., Mitsukami, Y. et al. (2001). Macromolecules 34:
6561–6564.
18 Donovan, M.S., Sanford, T.A., Lowe, A.B. et al. (2002). Macromolecules 35:
4570–4572.
19 Donovan, M.S., Sumerlin, B.S., Lowe, A.B., and McCormick, C.L. (2002).
molecules 36: 1436–1439.
21 Donovan, M.S., Lowe, A.B., Sanford, T.A., and McCormick, C.L. (2003). J.
Polym. Sci., Part A: Polym. Chem. 41: 1262–1281.
22 Sumerlin, B.S., Lowe, A.B., Thomas, D.B., and McCormick, C.L. (2003). Macro-
molecules 36: 5982–5987.
23 Sumerlin, B.S., Lowe, A.B., Thomas, D.B. et al. (2004). J. Polym. Sci., Part A:
Polym. Chem. 42: 1724–1734.
1735–1741.
8941–8950.
26 Convertine, A.J., Lokitz, B.S., Lowe, A.B. et al. (2005). Macromol. Rapid Com-
mun. 26: 791–795.
References 795
27 Vasilieva, Y.A., Scales, C.W., Thomas, D.B. et al. (2005). J. Polym. Sci., Part A:
Polym. Chem. 43: 3141–3152.
28 Scales, C.W., Vasilieva, Y.A., Convertine, A.J. et al. (2005). Biomacromolecules 6:
1846–1850.
29 Convertine, A.J., Lokitz, B.S., Vasilieva, Y. et al. (2006). Macromolecules 39:
1724–1730.
30 Mitsukami, Y., Hashidzume, A., Yusa, S.-i. et al. (2006). Polymer 47: 4330–4340.
31 Lowe, A.B., Sumerlin, B.S., and McCormick, C.L. (2003). Polymer 44:
6761–6765.
32 Wang, R. and Lowe, A.B. (2007). J. Polym. Sci., Part A: Polym. Chem. 45:
2468–2483.
33 Lowe, A.B., Wang, R., Tiriveedhi, V. et al. (2007). Macromol. Chem. Phys. 208:
2339–2347.
35 Obata, M., Kobori, T., Hirohara, S., and Tanihara, M. (2015). Polym. Chem. 6:
1793–1804.
36 Hoff, E.A., Abel, B.A., Tretbar, C.A. et al. (2017). Polym. Chem. 8: 4978–4982.
37 McKenzie, T.G., Colombo, E., Fu, Q. et al. (2017). Angew. Chem. Int. Ed. 56:
12302–12306.
38 Keddie, D.J., Guerrero-Sanche, C., Moad, G. et al. (2011). Macromolecules 44:
6738–6745.
39 Muthukrishnan, S., Pan, E.H., Stenzel, M.H. et al. (2007). Macromolecules 40:
2978–2980.
40 Quek, J.Y., Liu, X., Davis, T.P. et al. (2015). Polym. Chem. 6: 118–127.
41 Wang, R., McCormick, C.L., and Lowe, A.B. (2005). Macromolecules 38:
9518–9525.
9243–9245.
44 Harrisson, S. and Wooley, K.L. (2005). Chem. Commun.: 3259–3261.
45 Skrabania, K., Laschewsky, A., Berlepsch, H.v., and Bottcher, C. (2009). Lang-
muir 25: 7594–7601.
46 Skrabania, K., Miasnikov, A., Bivigou-Koumb, A.M. et al. (2011). Polym. Chem.
2: 2074–2083.
47 Lai, J.T. and Shea, R. (2006). J. Polym. Sci., Part A: Polym. Chem. 44: 4298–4316.
48 Shi, L., Chapman, T.M., and Beckman, E.J. (2003). Macromolecules 36:
2563–2567.
49 Roth, P.J., Davis, T.P., and Lowe, A.B. (2014). Macromol. Rapid Commun. 35:
813–820.
50 Van Herck, S., Hassannia, B., Louage, B. et al. (2019). Eur. Polym. J. 110:
313–318.
51 Tucker, B.S., Coughlin, M.L., Figg, C.A., and Sumerlin, B.S. (2017). ACS Macro
Lett. 6: 452–457.
52 Jiang, D., Zhu, H., Yang, W. et al. (2017). Sens. Actuators, B: Chem. 239:
193–202.
53 Louage, B., van Steenbergen, M.J., Nuhn, L. et al. (2017). ACS Macro Lett. 6:
272–276.
54 Duret, D., Haftek-Terreau, Z., Carretier, M. et al. (2017). Polym. Chem. 8:
1611–1615.
55 Lueckerath, T., Strauch, T., Koynov, K. et al. (2019). Biomacromolecules 20:
212–221.
56 Meldal, M. and Tornøe, C.W. (2008). Chem. Rev. 108: 2952–3015.
57 Hein, J.E. and Fokin, V.V. (2010). Chem. Soc. Rev. 39: 1302–1315.
58 Brase, S., Gil, C., Knepper, K., and Zimmermann, V. (2005). Angew. Chem. Int.
Ed. 44: 5188–5240.
59 Akeroyd, N., Pfukwa, R., and Klumperman, B. (2009). Macromolecules 42:
3014–3018.
19: 2679–2682.
61 Stamenović, M.M., Espeel, P., Camp, W.V., and Du Prez, F.E. (2011). Macro-
molecules 44: 5619–5630.
62 Hoyle, C.E., Lee, T.Y., and Roper, T. (2004). J. Polym. Sci., Part A: Polym. Chem.
42: 5301–5338.
63 Hoyle, C.E. and Bowman, C.N. (2010). Angew. Chem. Int. Ed. 49: 1540–1573.
64 Hoyle, C.E., Lowe, A.B., and Bowman, C.N. (2010). Chem. Soc. Rev. 39:
1355–1387.
65 Bohec, M.e.L., Pioge, S., Pascual, S., and Fontaine, L. (2017). J. Polym. Sci., Part
A: Polym. Chem. 55: 3597–3606.
66 Zhang, X., Li, J., Li, W., and Zhang, A. (2007). Biomacromolecules 8: 3557–3567.
67 Theato, P. (2008). J. Polym. Sci., Part A: Polym. Chem. 46: 6677–6687.
68 Nilles, K. and Theato, P. (2010). J. Polym. Sci., Part A: Polym. Chem. 48:
3683–3692.
5618–5625.
70 Vanparijs, N., Maji, S., Louage, B. et al. (2015). Polym. Chem. 6: 5602–5614.
71 Vanparijs, N., Coen, R.D., Laplace, D. et al. (2015). Chem. Commun. 51:
13972–13975.
72 Wiss, K.T. and Theato, P. (2010). J. Polym. Sci., Part A: Polym. Chem. 48:
4758–4767.
73 Wilkins, L.E., Hasan, M., Fayter, A.E.R. et al. (2019). Polym. Chem. https://doi
.org/10.1039/c1038py01719k.
74 Roth, P.J., Wiss, K.T., Zentel, R., and Theato, P. (2008). Macromolecules 41:
8513–8519.
75 Wiss, K.T., Krishna, O.D., Roth, P.J. et al. (2009). Macromolecules 42: 3860–3863.
76 Roth, P.J., Jochum, F.D., Forst, F.R. et al. (2010). Macromolecules 43: 4638–4645.
77 Roth, P.J., Haase, M., Basché, T. et al. (2010). Macromolecules 43: 895–902.
78 Roth, P.J., Jochum, F.D., and Theato, P. (2011). Soft Matter 7: 2484–2492.
79 Driessen, F., Martens, S., Meyer, B.D. et al. (2016). Macromol. Rapid Commun.
37: 947–951.
References 797
80 Frank, D., Espeel, P., Badi, N., and Du Prez, F.E. (2018). Eur. Polym. J. 98:
246–253.
81 Lysebetten, D.V., Felissati, S., Antonatou, E. et al. (2018). ChemBioChem 19:
641–646.
82 Celasun, S., Remmler, D., Schwaar, T. et al. (2019). Angew. Chem. Int. Ed. 58:
1960–1964.
83 Stamenović, M.M., Espeel, P., Baba, E. et al. (2013). Polym. Chem. 4: 184–193.
84 Liu, J., Bulmus, V., Barner-Kowollik, C. et al. (2007). Macromol. Rapid Com-
mun. 28: 305–314.
85 Evgrafova, Z., Voigt, B., Baumann, M. et al. (2019). ChemPhysChem 20:
236–240.
86 Decker, C.G. and Maynard, H.D. (2015). Eur. Polym. J. 65: 305–312.
87 Hornung, C.H., Postma, A., Saubern, S., and Chiefari, J. (2014). Polymer 55:
1427–1435.
5371–5374.
91 DePuy, C.H. and King, R.W. (1960). Chem. Rev. 60: 431–457.
92 Bressy, C., Ngo, V.G., and Margaillan, A. (2013). Polym. Degrad. Stab. 98:
115–121.
93 Stace, S.J., Fellows, C.M., Moad, G., and Keddie, D.J. (2018). Macromol. Rapid
Commun. 39: 1800228.
94 Zhou, Y., He, J., Li, C. et al. (2011). Macromolecules 44: 8446–8457.
95 Barton, D.H.R. and McCombie, S.W. (1975). J. Chem. Soc., Perkin Trans. 1:
1574–1585.
96 Crich, D. and Quintero, L. (1989). Chem. Rev. 89: 1413–1432.
40: 4446–4455.
98 Chen, M., Ghiggino, K.P., Rizzardo, E. et al. (2008). Chem. Commun.:
1112–1114.
99 Tilley, A.J., Chen, M., Danczak, S.M. et al. (2012). Polym. Chem. 3: 892–899.
100 Hu, N., Ji, W.-X., Tong, Y.-Y. et al. (2010). J. Polym. Sci., Part A: Polym. Chem.
48: 4621–4626.
102 Moughton, A.O., Stubenrauch, K., and O’Reilly, R.K. (2009). Soft Matter 5:
2361–2370.
103 Hasegawa, U., van der Vlies, A.J., Simeoni, E. et al. (2010). J. Am. Chem. Soc.
132: 18273–18280.
104 Hornung, C.H., Postma, A., Saubern, S., and Chiefari, J. (2012). Macromol.
React. Eng. 6: 246–251.
105 Sykes, K.J., Harrisson, S., and Keddie, D.J. (2016). Macromol. Chem. Phys. 217:
2310–2320.
106 Xia, Y., Tang, S., and Olsen, B.D. (2013). Chem. Commun. 49: 2566–2568.
107 Michl, T.D., Locock, K.E.S., Stevens, N.E. et al. (2014). Polym. Chem. 5:
5813–5822.
108 Chong, J.Y.T., Keddie, D.J., Postma, A. et al. (2015). Colloids Surf., A 470: 60–69.
109 Mattson, K.M., Pester, C.W., Gutekunst, W.R. et al. (2016). Macromolecules 49:
8162–8166.
110 Discekici, E.H., Shankel, S.L., Anastasaki, A. et al. (2017). Chem. Commun. 53:
1888–1891.
185–189.
2033–2036.
Chem. 47: 6704–6714.
114 Sarapas, J.M., Backlund, C.M., deRonde, B.M. et al. (2017). Chem. Eur. J. 23:
6858–6863.
115 Kinoshita, K., Takami, T., Mori, Y. et al. (2017). J. Polym. Sci., Part A: Polym.
Chem. 55: 8513–8519.
116 Heredia, K.L., Grover, G.N., Tao, L., and Maynard, H.D. (2009). Macromolecules
42: 2360–2367.
117 Nicolas, J., Guillaneuf, Y., Lefay, C. et al. (2013). Prog. Polym. Sci. 38: 63–235.
118 Beyou, E., Chaumont, P., Chauvin, F. et al. (1998). Macromolecules 31:
6828–6835.
119 Ao, Y., He, J., Han, X. et al. (2007). J. Polym. Sci., Part A: Polym. Chem. 45:
374–387.
121 Gruendling, T., Pickford, R., Guilhaus, M., and Barner-Kowollik, C. (2008). J.
Polym. Sci., Part A: Polym. Chem. 46: 7447–7461.
634–644.
123 Gruendling, T., Dietrich, M., and Barner-Kowollik, C. (2009). Aust. J. Chem. 62:
806–812.
124 Howard, J.A. and Ingold, K.U. (1969). Can. J. Chem. 47: 3809–3815.
125 Li, C., He, J., Zhou, Y. et al. (2011). J. Polym. Sci., Part A: Polym. Chem. 49:
1351–1360.
127 Sinnwell, S., Inglis, A.J., Davis, T.P. et al. (2008). Chem. Commun.: 2052–2054.
128 Inglis, A.J., Sinnwell, S., Davis, T.P. et al. (2008). Macromolecules 41: 4120–4126.
129 Sinnwell, S., Lammens, M., Stenzel, M.H. et al. (2009). J. Polym. Sci., Part A:
Polym. Chem. 47: 2207–2213.
130 Inglis, A.J., Sinnwell, S., Stenzel, M.H., and Barner-Kowollik, C. (2009). Angew.
Chem. Int. Ed. 48: 2411–2414.
131 Langer, M., Mueller, J.O., Goldmann, A.S. et al. (2016). ACS Macro Lett. 5:
597–601.
132 Nebhani, L., Sinnwell, S., Inglis, A.J. et al. (2008). Macromol. Rapid Commun.
29: 1431–1437.
References 799
133 Goldmann, A.S., Tischer, T., Barner, L. et al. (2011). Biomacromolecules 12:
1137–1145.
134 Qiu, X.-P. and Winnik, F.M. (2006). Macromol. Rapid Commun. 27: 1648–1653.
135 Hansell, C.F., Espeel, P., Stamenović, M.M. et al. (2011). J. Am. Chem. Soc. 133:
13828–13831.
136 Oliveira, B.L., Guo, Z., and Bernardes, G.J.L. (2017). Chem. Soc. Rev. 46:
4895–4950.
137 Carthew, J., Frith, J.E., Forsythe, J.S., and Truong, V.X. (2018). J. Mater. Chem.
B. 6: 1394–1401.
138 Koshy, S.T., Zhang, D.K.Y., Grolman, J.M. et al. (2018). Acta Biomaterialia 65:
36–43.
139 Wu, Y., Hu, J., Sun, C. et al. (2018). Bioconjugate Chem. 29: 2287–2295.
140 Houck, H.A., Bruycker, K.D., Billiet, S. et al. (2017). Chem. Sci. 8: 3098–3108.
141 Becker, G., Vlaminck, L., Velencoso, M.M. et al. (2017). Polym. Chem. 8:
4074–4078.
142 Baroni, A., Vlaminck, L., Mespouille, L. et al. (2019). Macromol. Rapid Com-
mun. 40: 1800743.
143 Vonhören, B., Roling, O., Bruycker, K.D. et al. (2015). ACS Macro Lett. 4:
331–334.
144 Houck, H.A., Bruycker, K.D., Barner-Kowollik, C. et al. (2018). Macromolecules
51: 3156–3164.
145 Malgorzata, B., Melania, B., Laetitia, V. et al. (2017). Eur. Polym. J. 89: 230–240.
146 Herck, N.V. and Du Prez, F.E. (2018). Macromolecules 51: 3405–3414.
147 Bruycker, K.D., Billiet, S., Houck, H.A. et al. (2016). Chem. Rev. 116: 3919–3974.
148 Xiao, L., Chen, Y., and Zhang, K. (2016). Macromolecules 49: 4452–4461.
149 Mondal, P., Behera, P.K., and Singha, N.K. (2017). Chem. Commun. 53:
8715–8718.
150 Zhao, Y., Chen, J., Zhu, W., and Zhang, K. (2015). Polymer 74: 16–20.
151 Chen, J., Sun, R., Liao, X. et al. (2018). Macromolecules 51: 10202–10213.
152 Huang, J., Zhang, L., Tang, Z. et al. (2017). Macromol. Rapid Commun. 38:
1600678.
153 Hanay, S.B., Brougham, D.F., Dias, A.A., and Heise, A. (2017). Polym. Chem. 8:
6594–6597.
154 Vandewalle, S., Billiet, S., Driessen, F., and Du Prez, F.E. (2016). ACS Macro
Lett. 5: 766–771.
155 Lowe, A.B. (2013). End-group functionalization of RAFT-prepared polymers
using thiol-X chemistries. In: Thiol-X Chemistries in Polymer and Materials
Science, Chapter 2 (eds. A.B. Lowe and C.N. Bowman), 28–58. RSC Publishing.
156 Xu, J., He, J., Fan, D. et al. (2006). Macromolecules 39: 8616–8624.
243–245.
158 Mayadunne, R.T.A., Jeffery, J., Moad, G., and Rizzardo, E. (2003). Macro-
molecules 36: 1505–1513.
159 Zhang, Q., Voorhaar, L., Geest, B.G.D., and Hoogenboom, R. (2015). Macromol.
Rapid Commun. 36: 1177–1183.
160 Lee, I.-H., Discekici, E.H., Shankel, S.L. et al. (2017). Polym. Chem. 8:
7188–7194.
1444–1448.
162 Lee, C.-U., Roy, D., Sumerlin, B.S., and Dadmun, M.D. (2010). Polymer 51:
1244–1251.
163 Yu, S.H., Hu, J., Ercole, F. et al. (2015). ACS Macro Lett. 4: 1278–1282.
164 Glaria, A., Beija, M., Bordes, R. et al. (2013). Chem. Mater. 25: 1868–1867.
165 Dao, V.H., Cameron, N.R., and Saito, K. (2017). Polym. Chem. 8: 6834–6843.
166 Fan, K.W. and Granville, A.M. (2016). Polymers 8: 81–93.
167 Llauro, M.-F., Loiseau, J., Boisson, F. et al. (2004). J. Polym. Sci., Part A: Polym.
Chem. 42: 5439–5462.
168 Wu, Y., Zhou, Y., Zhu, J. et al. (2014). Polym. Chem. 5: 5546–5550.
169 Lowe, A.B., Sumerlin, B.S., Donovan, M.S., and McCormick, C.L. (2002). J. Am.
Chem. Soc. 124: 11562–11563.
170 Sumerlin, B.S., Lowe, A.B., Stroud, P.A. et al. (2003). Langmuir 19: 5559–5562.
172 Levit, M., Zashikhina, N., Dobrodumov, A. et al. (2018). Eur. Polym. J. 105:
26–37.
173 Litmanovich, E.A., Bekanova, M.Z., Shanddryuk, G.A. et al. (2018). Polymer
142: 1–10.
174 Shan, J., Nuopponen, M., Jiang, H. et al. (2003). Macromolecules 36: 4526–4533.
175 Scales, C.W., Convertine, A.J., and McCormick, C.L. (2006). Biomacromolecules
7: 1389–1392.
176 Espeel, P. and Du Prez, F.E. (2015). Eur. Polym. J. 62: 247–272.
177 Espeel, P., Goethals, F., and Du Prez, F.E. (2011). J. Am. Chem. Soc. 133:
1678–1681.
178 Martens, S., Driessen, F., Wallyn, S. et al. (2016). ACS Macro Lett. 5: 942–945.
179 Langlais, M., Coutelier, O., and Destarac, M. (2018). Macromolecules 51:
4315–4324.
180 Rudolph, T., Espeel, P., Du Prez, F.E., and Schacher, F.H. (2015). Polym. Chem.
6: 4240–4251.
181 Lowe, A.B. and Bowman, C.N. (eds.) (2013). Thiol-X Chemistries in Polymer and
Materials Science. Cambridge: RSC Publishing.
182 Lowe, A.B. (2010). Polym. Chem. 1: 17–36.
183 Lowe, A.B. (2014). Polym. Chem. 5: 4820–4870.
184 Fairbanks, B.D., Love, D.M., and Bowman, C.N. (2017). Macromol. Chem. Phys.
218: 1700073.
185 Koo, S.P.S., Stamenovic, M.M., Prasath, R.A. et al. (2010). J. Polym. Sci., Part A:
Polym. Chem. 48: 1699–1713.
186 Chan, J.W., Zhou, H., Hoyle, C.E., and Lowe, A.B. (2009). Chem. Mater. 21:
1579–1585.
187 Chan, J.W., Hoyle, C.E., and Lowe, A.B. (2009). J. Am. Chem. Soc. 131:
5751–5753.
References 801
188 Lowe, A.B., Hoyle, C.E., and Bowman, C.N. (2010). J. Mater. Chem. 20:
4745–4750.
189 Chan, J.W., Shin, J., Hoyle, C.E. et al. (2010). Macromolecules 43: 4937–4942.
190 Lowe, A.B. (2014). Polymer 55: 5517–5549.
191 Liu, J., Lam, J.W.Y., Jim, C.K.W. et al. (2011). Macromolecules 44: 68–79.
192 Yao, B., Mei, J., Li, J. et al. (2014). Macromolecules 47: 1325–1333.
193 Huang, D., Liu, Y., Guo, S. et al. (2019). Polym. Chem. https://doi.org/10.1039/
c1039py00161a.
194 Alameddine, B., Baig, N., Shetty, S. et al. (2018). Polymer 154: 233–240.
195 Kumar, J., Bousquet, A., and Stenzel, M.H. (2011). Macromol. Rapid Commun.
32: 1620–1626.
196 Chan, J.W., Hoyle, C.E., Lowe, A.B., and Bowman, M. (2010). Macromolecules
43: 6381–6388.
A: Polym. Chem. 47: 3773–3794.
198 Ida, S., Yamawaki, M., Maruta, T., and Hirokawa, Y. (2018). Trans. Mater. Res.
Soc. Jpn. 43: 71–74.
199 Xi, W., Wang, C., Kloxin, C.J., and Bowman, C.N. (2012). ACS Macro Lett. 1:
811–814.
200 Nair, D.P., Podgórski, M., Chatani, S. et al. (2014). Chem. Mater. 26: 724–744.
201 Yin, L., Dalsin, M.C., Sizovs, A. et al. (2012). Macromolecules 45: 4322–4332.
202 Bian, Q., Xiao, Y., and Lang, M. (2012). Polymer 53: 1684–1693.
203 Neindre, M. and Nicolay, R. (2013). Polym. Int. 63: 887–893.
204 Spruell, J.M., Levy, B.A., Sutherland, A. et al. (2009). J. Polym. Sci., Part A:
Polym. Chem. 47: 346–356.
205 Yu, B., Chan, J.W., Hoyle, C.E., and Lowe, A.B. (2009). J. Polym. Sci., Part A:
Polym. Chem. 47: 3544–3557.
206 Zhu, Y., Batchelor, R., Lowe, A.B., and Roth, P.J. (2016). Macromolecules 49:
672–680.
207 Wang, Y., Zheng, Z., Huang, Z., and Ling, J. (2017). Polym. Chem. 8: 2659–2665.
208 Duret, D., Haftek-Terreau, Z., Carretier, M. et al. (2018). Polym. Chem. 9:
1857–1868.
209 Messina, M.S., Graefe, C.T., Chong, P. et al. (2019). Polym. Chem. 10:
1660–1667.
210 Roth, P.J., Davis, T.P., and Lowe, A.B. (2012). Macromolecules 45: 3221–3230.
211 Roth, P.J., Davis, T.P., and Lowe, A.B. (2012). Polym. Chem. 3: 2228–2235.
6475–6484.
213 Zhu, Y., Lowe, A.B., and Roth, P.J. (2014). Polymer 55: 4425–4431.
214 Ho, H.T., Levere, M.E., Pascual, S. et al. (2012). J. Polym. Sci., Part A: Polym.
Chem. 50: 1657–1661.
215 Delaittre, G., Pauloehrl, T., Bastmeyer, M., and Barner-Kowollik, C. (2012).
216 Li, M., De, P., Li, H., and Sumerlin, B.S. (2010). Polym. Chem. 1: 854–859.
217 Huang, X., Boyer, C., Davis, T.P., and Bulmus, V. (2011). Polym. Chem. 2:
1505–1512.
218 Espeel, P., Goethals, F., Stamenović, M.M. et al. (2012). Polym. Chem. 3:
1007–1015.
219 Abel, B.A. and McCormick, C.L. (2016). Macromolecules 49: 6193–6202.
220 Zhao, J., Zhou, Y., Zhou, Y. et al. (2016). Polym. Chem. 7: 1782–1791.
221 Chakma, P., Digby, Z.A., Via, J. et al. (2018). Polym. Chem. 9: 4744–4756.
222 Battistella, C., Yang, Y., Chen, J., and Klok, H.-A. (2018). ACS Omega 3:
9710–9721.
223 Hiruta, Y., Nagumo, Y., Miki, A. et al. (2015). RSC Adv. 5: 73217–73224.
225 Yang, Z., Fu, K., Yu, J., and Liu, X. (2019). J. Inorg. Organomet. Polym. Mater.
29: 59–65.
226 Ho, H.T., Levere, M.E., Soutif, J.-C. et al. (2011). Polym. Chem. 2: 1258–1260.
227 Chan, J.W., Yu, B., Hoyle, C.E., and Lowe, A.B. (2008). Chem. Commun.:
4959–4961.
228 Chan, J.W., Yu, B., Hoyle, C.E., and Lowe, A.B. (2009). Polymer 50: 3158–3168.
229 Li, M., De, P., Gondi, S.R., and Sumerlin, B.S. (2008). J. Polym. Sci., Part A:
Polym. Chem. 46: 5093–5100.
230 Lu, D., Jia, Z., and Monteiro, M.J. (2013). Polym. Chem. 4: 2080–2089.
231 Shin, J., Lee, J., and Jeong, H.M. (2018). J. Appl. Polym. Sci. 135: 46070.
232 Tan, J., Li, C., Dan, S. et al. (2016). Chem. Eng. J. 304: 461–468.
233 Gamardella, F., Ramis, X., De la Flor, S., and Serra, A. (2019). React. Funct.
Polym. 134: 174–182.
234 Shin, J., Matsushima, H., Comer, C.M. et al. (2010). Chem. Mater. 22:
2616–2625.
235 Zou, F., Yue, P., Zheng, X. et al. (2016). J. Mater. Chem. A 4: 10801–10805.
236 Hensarling, R.M., Rahane, S.B., LeBlanc, A.P. et al. (2011). Polym. Chem. 2:
88–90.
237 Hensarling, R.M., Hoff, E.A., LeBlanc, A.P. et al. (2013). J. Polym. Sci., Part A:
Polym. Chem. 51: 1079–1090.
213–220.
239 Hoff, E.A., Abel, B.A., Tretbar, C.A. et al. (2016). Macromolecules 49: 554–563.
240 Li, H., Yu, B., Matsushima, H. et al. (2009). Macromolecules 42: 6537–6542.
241 Boursier, T., Georges, S., Mosquet, M. et al. (2016). Polym. Chem. 7: 917–925.
242 Stuparu, M.C. and Khan, A. (2016). J. Polym. Sci., Part A: Polym. Chem. 54:
3057–3070.
243 De, S. and Khan, A. (2012). Chem. Commun. 48: 3130–3132.
244 Muzammil, E.M., Khan, A., and Stuparu, M.C. (2017). RSC Adv. 7:
55874–55884.
245 McLeod, D.C. and Tsarevsky, N.V. (2016). Macromolecules 49: 1135–1142.
246 Rosen, B.M., Lligadas, G., Hahn, C., and Percec, V. (2009). J. Polym. Sci., Part A:
Polym. Chem. 47: 3931–3939.
References 803
247 Rosen, B.M., Lligadas, G., Hahn, C., and Percec, V. (2009). J. Polym. Sci., Part A:
Polym. Chem. 47: 3940–3948.
248 Agar, S., Baysak, E., Hizal, G. et al. (2018). J. Polym. Sci., Part A: Polym. Chem.
56: 1181–1198.
249 Bhebhe, M.N., De Eulate, E.A., Pei, Y. et al. (2017). Macromol. Rapid Commun.
38: 1600450.
250 Nakayama, M. and Okano, T. (2005). Biomacromolecules 6: 2320–2327.
251 Segui, F., Qiu, X.-P., and Winnik, F.M. (2008). J. Polym. Sci., Part A: Polym.
Chem. 46: 314–326.
252 Xu, J., Tao, L., Boyer, C. et al. (2010). Macromolecules 43: 20–24.
253 Chen, S., Schulz, M., Lechner, B.-D. et al. (2015). Polym. Chem. 6: 7988–7994.
254 Soeriyadi, A.H., Boyer, C., Burns, J. et al. (2010). Chem. Commun. 46:
6338–6340.
255 Döhler, D., Kaiser, J., and Binder, W.H. (2017). Polymer 133: 148–158.
256 Noy, J.-M., Friedrich, A.-K., Batten, K. et al. (2017). Macromolecules 50:
7028–7040.
257 Noy, J.-M., Koldevitz, M., and Roth, P.J. (2015). Polym. Chem. 6: 436–447.
258 Zeng, J., Zhu, J., Pan, X. et al. (2013). Polym. Chem. 4: 3453–3457.
259 Lu, W., An, X., Gao, F. et al. (2017). Macromol. Chem. Phys. 218: 1600485.
260 Whittaker, M.R., Goh, Y.-K., Gemici, H. et al. (2009). Macromolecules 39:
9028–9034.
261 Goh, Y.-K., Whittaker, A.K., and Monteiro, M.J. (2007). J. Polym. Sci., Part A:
Polym. Chem. 45: 4150–4153.
262 Vogt, A.P. and Sumerlin, B.S. (2009). Soft Matter 5: 2347–2351.
263 Schäfer, O. and Barz, M. (2018). Chem. Eur. J. 24: 12131–12142.
264 Boyer, C., Liu, J., Bulmus, V., and Davis, T.P. (2009). Aust. J. Chem. 62: 830–847.
265 Grover, G.N., Lee, J., Matsumoto, N.M., and Maynard, H.D. (2012). Macro-
molecules 45: 4958–4965.
266 Urquhart, M.C., Ercole, F., Whittaker, M.R. et al. (2018). Polym. Chem. 9:
4431–4439.
267 Chua, G.B.H., Roth, P.J., Duong, H.T.T. et al. (2012). Macromolecules 45:
1362–1374.
268 Quek, J.Y., Roth, P.J., Evans, R.A. et al. (2013). J. Polym. Sci., Part A: Polym.
Chem. 51: 394–404.
269 Quek, J.Y., Zhu, Y., Roth, P.J. et al. (2013). Macromolecules 46: 7290–7302.
270 Roth, P.J., Kessler, D., Zentel, R., and Theato, P. (2009). J. Polym. Sci., Part A:
Polym. Chem. 47: 3118–3130.
271 Gevrek, T.N., Cosar, M., Aydin, D. et al. (2018). ACS Appl. Mater. Interfaces 10:
14399–14409.
272 Peng, H., Rübsam, K., Huang, X. et al. (2016). Macromolecules 49: 7141–7154.
273 Ji, X., Liu, J., Liu, L., and Zhao, H. (2016). Colloids Surf., B 148: 41–48.
274 Yu, S.H., Ercole, F., Veldhuis, N.A. et al. (2017). Polym. Chem. 8: 6362–6367.
275 Roth, P.J., Jochum, F.D., Zentel, R., and Theato, P. (2010). Biomacromolecules
11: 238–244.
276 Wang, Y. and Ling, J. (2015). RSC Adv. 5: 18546–18553.
277 Pereira, S.O., Barros-Timmons, A., and Trindade, T. (2018). Polymers 10:
198–215.
279 Wua, Y., Yang, H., Lin, Y. et al. (2016). Mater. Lett. 169: 218–222.
280 Zhang, Z., Vanparijs, N., Vandewalle, S. et al. (2016). Polym. Chem. 7:
7242–7248.
282 Matioszek, D., Dufils, P.-E., Vinas, J., and Destarac, M. (2015). Macromol. Rapid
Commun. 36: 1354–1361.
283 Quiclet-Sire, B. and Zard, S.Z. (2010). Bull. Korean Chem. Soc. 31: 543–544.
805
17
Sequence-Encoded RAFT Oligomers and Polymers

Monash University, School of Chemistry, Polymer Reaction Design Group, 19 Rainforest Walk, Clayton, VIC
3800, Australia
Reversible deactivation radical polymerization (RDRP) techniques such as

reversible addition fragmentation chain transfer (RAFT) polymerization provide
an unprecedented level of control over molecular weight (distributions), com-
positions, and architectures [1–3]. Compared to natural polymers, such as DNA,
proteins, or complex carbohydrates, radical chain growth copolymerization always
results in statistical distributions of chain lengths and monomers (determined by
the monomer reactivity ratios) [4]. Products are inherently of a disperse nature
- ] > 1). Dispersity is typically defined for describing the non-uniformity
(dispersity [D
with respect to molecular weight but can also be used to describe monomer
distributions, or, for example, branches within a chain. Nonetheless, absolute
control over monomer sequence, with precision as achieved by nature in protein
or polynucleotide biosynthesis, was thoroughly explored in the last decennia [5].
These materials have enormous potential for application in, e.g. catalysis (artificial
enzymes), molecular recognition, or data storage [6]. The field has advanced signifi-
cantly, with RAFT polymerization playing an important role as a tool to deliver such
materials. Most research has been devoted to the development of materials with
encoded sequence information. Information is thereby stored in a macromolecule
by the order of comonomers in a multiblock copolymer. The more blocks are added
to a chain, the more information is saved. The advances of RAFT polymerization
in terms of polymerization efficiency and foremost improvements in livingness
of polymerizations have enabled the synthesis of multiblock copolymers with a
significant number of blocks. Although the standard of synthesis was tri- or tetra-
block copolymers just a few years ago [7], materials with more than 20 blocks are
nowadays available with high precision from both RAFT polymerization and cobalt-
or copper-mediated radical polymerizations [5]. If RAFT polymers are sequentially
chain extended in this way, one refers to the so-called sequence-controlled (SC)
polymers. SC polymers generally require a high livingness of polymerizations.
Fast polymerizations are useful to achieve significant sequence lengths in a given
period of time but are not strictly necessary. Still, most SC polymers are built from
806 17 Sequence-Encoded RAFT Oligomers and Polymers
acrylates or acrylamides. High livingness can be achieved by improving process

control [8–10] and by rational choice of initiator concentrations [11, 12]. Perrier and
coworkers had demonstrated that if initiator concentrations are kept significantly
low, full monomer conversions are still achievable for 99% livingness of the process
[11]. In this way, the number of blocks in a polymer becomes virtually infinite. Yet,
the longest reported SC chain for RAFT polymerization consists of 20 blocks [11],
with the overall record being held by Haddleton and coworkers with a polymer
consisting of 24 blocks (made from addition fragmentation radical polymerization
using macromonomers) [13]. Limitations in the number of blocks are given by
several factors. For one, any exogenous production of radicals inevitably creates
new chains during each block extension, diluting the actual multiblock copolymers.
Alongside with some accumulated dead polymer chains, this can lead to significant
amounts of materials already after several block extension steps [14]. Further, the
dispersity of each block increases with each successive extension even if the overall
dispersity remains low [15]. In this way, the sequence information is ‘smeared
out’ and becomes prone to errors. Likewise, the dispersity per block needs to be
taken into account as a lower limit for each block extension, in order to ensure
that every chain in the mixture actually contains all blocks [4]. Yet – despite these
limitations – an impressive realm of materials is opened up by SC polymers, and
the study of the physical properties of these materials is still in its infancy.
In this chapter, the focus will be on the so-called sequence-defined (SD), discrete
polymers (D - = 1) obtained via RAFT or macromolecular design via the interchange
of xanthates (MADIX) polymerization. SD oligomers are a subclass of SC polymers
where single monomers rather than full (higher dispersity) blocks are inserted into
a chain [16]. Various strategies towards the synthesis of SD materials have to date
been proposed, with the majority of them relying on click chemistry-type coupling
reactions [17–25]. These methods are reviewed here [5, 6, 26–29]. RDRP techniques
including RAFT constitute interesting alternatives to these methods. Because RAFT
(or any other RDRP technique) is inherently governed by statistical addition of
monomers to growing chain ends, a stepwise addition of single-monomer units
must rely on either overcoming the statistical nature by selective insertion of single
units into the initiator or control agent or on the separation of mixtures of oligomers
obtained after polymerization.
Zard took a first step towards achieving this via xanthate transfer chemistry [30].
Selective insertion of a single-monomer unit of less-activated monomers (LAMs)
such as vinyl esters, vinyl amides, and allyl monomers was performed in 20–70%
isolated yields [31–35]. In the same study, it was also analysed that single-unit
monomer insertion (SUMI) into xanthates was not possible with more activated
monomers (MAMs). Scheme 17.1 illustrates the radical exchange process of thiocar-
bonylthio derivatives for addition of xanthates to LAMs. Radicals, generated by an
external radical source, can add to the starting xanthate to form a stabilized adduct
radical, which is sterically too hindered to terminate (path A). Therefore, it can
only undergo fragmentation (path B or C). Path B is highly unlikely because of the
generation of a high energy ethyl radical; therefore, favouring path C that simply
leads to the starting xanthate making this reaction path reversible and degenerate.
Sequence-Encoded RAFT Oligomers and Polymers 807
Therefore, the lifetime of a radical increases significantly, making addition to LAMs

(e.g. non-activated alkenes) possible. In the case of addition to a LAM (path D), a
new radical (4) is generated, which in turn can react reversibly with the starting
xanthate (5). Analogous to path C, fragmentation of the intermediate radical (5)
yields the final SUMI product (6) and the initial radical. The presence of xanthate
in the SUMI product, by intermolecular radical addition, was used to introduce
various functional groups, and complex structures could be rapidly assembled. This
novel radical exchange process proved a powerful asset for further modifications
via both radical and non-radical pathways.
S G
R Et
R +
S O 1
Et
O Initiation E
R
R 1 S S G
S A • 3 G
R Et R R •
S•O C D 4
2
S
B R Et
S O
Et • 1
R
+ R
O
R R S G + R•
S S S G
S O Et R •
S O Et
6 5
Scheme 17.1 Reaction scheme for the addition of xanthates to less-activated monomers
(LAMs), in this case olefins. Source: Reproduced with permission from Quiclet-Sire and Zard
SUMI of MAMs was reported for the first time by Chen et al. [36]. They used
such an approach for the synthesis of functionalized RAFT agents for light har-
vesting polymers. A method was proposed to introduce suitable chromophores into
a dithiobenzoate RAFT agent to synthesize light harvesting polymers of acenaph-
thylene, containing a coumarin terminal energy trap (coumarin SUMI, followed by
polymerization of acenaphthylene). Acenaphthyl and coumarin chromophores were
selected as the energy donor and acceptor, respectively, as they fulfil the spectral
overlap requirements for radiationless energy transfer. A conventional RAFT poly-
merization of coumarin was performed; however, an equimolar monomer to RAFT
agent ratio was employed (instead of a large excess of monomer), initiated by a small
amount (1–2% molar equiv) of free radical initiator. As a result, a new dithioben-
zoate macro-RAFT agent was synthesized in 85% isolated yield via a selective SUMI
of a styrene derivative (coumarin) into an initial dithiobenzoate RAFT agent. This
methodology was extended to more complex examples of SUMI via RAFT polymeri-
zation (see example in Scheme 17.2) [38, 39].
Multiple research groups described strategies to synthesize end-functionalized
polymers and junction-functionalized diblock copolymers via SUMI of maleic
NC
S
S
S S
NC
AIBN 70 °C
S
S
CN
Scheme 17.2 Example of a more complex SUMI for the synthesis of dithiobenzoate
macro-RAFT agents. Source: Reproduced with permission from Houshyar et al. [37].
Copyright 2012, Royal Society of Chemistry.
anhydride (MAH) [40, 41] or maleimide [42] into macro-RAFT agents. Both
monomers do not readily homopolymerize; as a consequence, they could be used
in large excess with respect to the macro-RAFT agent to yield the SUMI product.
Klumperman and coworkers investigated the processes that occur during the
early stages (the first few monomer insertion steps) of a RAFT polymerization. Poly-
merization species formed over time were monitored via online (in situ) 1 H nuclear
magnetic resonance spectroscopy (1 H-NMR). In a first report, an AIBN-initiated
RAFT polymerization of styrene, mediated by the RAFT agent cyanoisopropyl
dithiobenzoate at various temperatures and RAFT agent concentrations, and a low
monomer to RAFT agent ratio (first few monomer insertions), was monitored as a
function of time [43]. They found that RAFT polymers with a degree of polymer-
ization (DP) greater than one were formed only after complete conversion of the
initial dithiobenzoate RAFT agent to a dithiobenzoate macro-RAFT agent with one
styrene monomer inserted. This phenomenon was called selective initialization,
with almost no production of RAFT polymers with a DP > 1 until all of the cyanoiso-
propyl dithiobenzoate was converted to a single-monomer insertion macro-RAFT
agent. This selective behaviour was explained by the selective fragmentation in the
RAFT pre-equilibrium towards tertiary radicals and the addition of propagating rad-
icals (of at least DP = 1) to the dithiobenzoate RAFT agent that is much faster than to
the monomer (propagation). Figure 17.1 shows the concentration of dithiobenzoate
species for the RAFT polymerization described above as a function of time, moni-
tored via online 1 H-NMR. Fast depletion of the initial dithiobenzoate RAFT agent
(AD) and rapid formation of the SUMI product (ASD) were observed. After com-
plete depletion of the dithiobenzoate RAFT agent (AD, 50 minutes), the ASD SUMI
product was formed quantitatively, and higher insertion products were identified.
However, no similar behaviour was observed for subsequent monomer additions.
This observed selective initialization behaviour of RAFT-mediated polymeriza-
tion was studied in more depth for a range of different RAFT/MADIX agents and
monomers (including styrene, methyl acrylate, N-vinylpyrrolidone, vinyl acetate,
N
N
S H
H S H H
N H
S S S
N H S
N N S
S
AA AD ASD AS2D AS3D
100
90
Percentage dithiobenzoates
80
70 AD
60 ASD
AS2D
50
Total dithiobenzoates
40
30
20
10
0
0 50 100 150 200 250
Time (min)
Figure 17.1 Online 1 H-NMR monitoring of dithiobenzoate species as a function of time

during the free radical polymerization of styrene at 70 ∘ C mediated by a cyanoisopropyl
dithiobenzoate RAFT agent using AIBN as a thermal initiator. Source: Reprinted with
permission from McLeary et al. [43]. Copyright 2004, American Chemical Society.
and MAH) [43–49]. It was argued by Moad and coworkers that such a selective
initialization process should be observed only if (i) addition of the radical R to
monomer is rapid (efficient reinitiation) with respect to monomer propagation
(kp(0) ≫ kp(1) ) and (ii) the RAFT agent has a high transfer constant so that less
than one monomer unit is inserted per activation cycle (ktr ≫ kp , transfer constant
depends on relative rate of addition to the RAFT agent and fragmentation of the
intermediate radical). Bearing this in mind, the system (choice of RAFT agent
and monomers) can be tuned to obtain high yields (>95%) for the SUMI process
[50, 51]. In general, this means that xanthates and dithiocarbamates are preferred
RAFT agents for SUMI of LAMs (vinyl monomers) and dithiobenzoates and
trithiocarbonates for MAMs (styrenic and acrylic monomers). Switchable RAFT
agents could be suitable for both MAMs and LAMs [52, 53].
The first sequence-defined dimers were synthesized by Quiclet-Sire et al. by xan-
thate transfer chemistry [34]. This was achieved by a SUMI of the electron-poor
vinyl phthalimide, followed by an electron-rich LAM. Moad and coworkers extended
the range of SUMI processes with MAMs into dithiobenzoate and trithiocarbonate
RAFT agents and showed that a wide range of MAMs can be inserted when certain
criteria were met (high transfer constant of RAFT agent and rapid addition of rad-
ical to monomer) [37]. The synthesis of new macro-RAFT agents was explored by
two sequential SUMI of MAMs ‘one at a time’ into an initial trithiocarbonate RAFT
agent [37, 54, 55]. The reaction of the initial RAFT agent, 2-cyanopropan-2-yl decyl
trithiocarbonate, with styrene monomer and AIBN as the thermal initiator, resulted
in the formation of the SUMI product in an isolated yield of 85% (see Scheme 17.3).
Oligomers were not detected, and the main side products were a small amount of ini-
tial RAFT agent and the expected by-products from AIBN decomposition. The same
procedure was applied to a SUMI of N-isopropylacrylamide (NIPAm) with a slightly
higher yield (90%, Scheme 17.3). In a next step, both macro-RAFT SUMI products
were subjected to a similar SUMI process. NIPAm was inserted into the earlier syn-
thesized styrene SUMI (3) and the styrene-NIPAm dimer (4) was obtained in 35%
isolated yield. The reaction rate was relatively slow (because of fragmentation of the
intermediate macro-RAFT radical in favour of the starting materials, for more details
see literature [37]), and the reaction was stopped because of exhaustion of the ther-
mal initiator. Again, no higher oligomers were detected. A SUMI of styrene in the
NIPAm SUMI product for the synthesis of a NIPAm-styrene dimer was unsuccessful.
More in depth analysis of the process was performed via online 1 H-NMR of sim-
ilar SUMI reactions and the kinetics of the system were simulated to consider the
advantages and limitations of the process. In another contribution by Moad et al.
[54], SUMI into a dithioester RAFT agent (2-cyanopropan-2-yl dithiobenzoate) was
explored. AIBN was used as a thermal radical source to avoid initiator-derived inser-
tion products in the first SUMI step. As expected, styrene and NIPAm were success-
fully inserted into the RAFT agent in high yields. Attempts with other monomers
were less successful. SUMI of methyl methacrylate (MMA) formed oligomeric prod-
ucts (because of low transfer constant of dithiobenzoates in MMA polymerization).
Low yields were observed in the SUMI process of MAH (because of the low reactivity
of MAH towards AIBN and reinitiating 2-cyanopropan-2-yl radicals). Also dimers of
styrene –X (with X = MAH, styrene, and NIPAm) were targeted via SUMI of X in the
styrene macro-RAFT agent. SUMI with styrene and NIPAm was slow, which could
be explained by the poor leaving group ability of the propagating species. SUMI of
MAH into the styrene macro-RAFT agent proved to be fast and efficient. Further-
more, RAFT SUMI of various acrylamides was explored in aqueous media [55]. It
seems, however, very crucial to carefully select the RAFT agent, monomer, initiator,
and reaction parameters to optimize the yield of the desired products.
Although SUMI reactions can be carried out with very high efficiency, it is
problematic to use the above strategy to create longer sequences, as monomer
reactivities and RAFT agents must be carefully tuned, thereby limiting the available
choice of monomers. When inserting monomers of the same family, oligomerization
becomes unavoidable after the first SUMI step. Thus, the group of Junkers and
coworkers developed a procedure for the synthesis of SD oligo(acrylate)s with
up to four monomer insertions (consisting of n-butyl acrylate (nBA), tert-butyl
acrylate (tBA), and 2-ethylhexyl acrylate (EHA)) via RAFT polymerization based
on oligomer separation [56]. The RAFT agent 2-cyano-2-propyl dodecyl trithiocar-
bonate (CPD-TTC) was used in very short reactions of only 10 minutes, with NMR
and electrospray ionization mass spectrometry (ESI-MS) analysis showing >99%
RAFT end group retention. This method is independent of the specific acrylate
monomer applied, and as such, a free selection of the preferable sequence order
O NH CN O NH O NH
CN CN Ph CN Ph CN Styrene CN Ph
Styrene NIPAm NIPAm
35% S
S AIBN S AIBN S AIBN S AIBN S
C10H21S S
C10H21S S C10H21S S 85% C10H21S S C10H21S S 90% C10H21S S
2 3 4 2 5 6
Scheme 17.3 Schematic representation of the single-unit monomer insertion (SUMI) process for styrene-NIPAm and NIPAm-styrene macro-RAFT agents
(dimers). Source: Reproduced with permission from Houshyar et al. [37]. Copyright 2012, Royal Society of Chemistry.
Cycle 1 Cycle 2
Figure 17.2 Recycling SEC
1
2.5 Collect fractions trace recorded during
consecutive purification
2.0
cycles of (a) nBA oligo-RAFT
UV signal (mV)
agent and (b) nBA-EHA

macro-RAFT agent. The
1.5 desired oligomer is marked
with an asterisk. Source:
1.0 Vandenbergh et al. [56]. ©
2013, Royal Society of
Chemistry.
0.5
0.0
0 20 40 60 80 100 120
(a) Time (min)
Cycle 1 Cycle 2 Cycle 3 Cycle 4
1.4 Collect fractions
2
1.2
UV signal (mV)
1.0
0.8
0.6
0.4
0.2
0.0
0 20 40 60 80 100 120 140 160 180 200 220
(b) Time (min)
could be synthesized. To cope with the statistical nature of a radical polymerization

reaction, a purification step after each insertion was always performed. Instead of
laborious manual column chromatography, preparative recycling size exclusion
chromatography (SEC) was found to allow facile and automated purification of
mixed samples to obtain uniform SD materials (Figure 17.2). The setup operated
by returning the elution flow of a column bank back to the column entry until
molecules with a different size were separated, monitored via both UV and RI
detection. Separation via recycling SEC gets more difficult the more monomer units
are added to the growing oligomer chain because the hydrodynamic volume, being
the separating factor of SEC, does not scale linearly with chain length. Where the
first monomer insertion still resulted in a respectable yield of 55% (also relatively
low because of the statistical nature of radical polymerization), the final reaction
step and subsequent purification reached a yield of only around 15%.
A further optimization of the SUMI process could be established by continuous
online monitoring and rapid kinetic screening of the reaction via an ESI-MS microre-
actor coupling [57]. In this respect, ESI-MS is unmatched in its ability to determine
specific product patterns, with the possibility for accelerated optimization of SUMI
reactions. In this specific case, the SUMI of EHA into a CPD-TTC macro-RAFT agent
already containing one acrylate monomer insertion was investigated. Insertions of
up to three EHA units were identified and yields for the single-insertion product
were optimized through tuning of reaction temperature, residence time, and reagent
ratios. Only trace amounts of material and minimal time were required because a
single experimental setup affords all experimental data. The so-optimized reaction
conditions of five minutes residence time and a fivefold ratio of EHA to macro-RAFT
agent at 100 ∘ C were easily transferable to the upscaled synthesis (100×) from a
micro- to milliflow reactor process, with a resulting isolated yield of almost 45% for
the EHA-SUMI product.
Subsequently, kinetic modelling was employed to investigate the parameters that
had a positive influence on SUMI reaction efficiencies via RAFT polymerization
[58]. Factors such as radical flux, termination, and RAFT addition rate coefficients
or monomer concentration (at a fixed ratio) were shown to have a negligible effect
on the outcome of the simulations. However, it was the propagation rate that
exhibited a strong chain length dependency with a resulting decrease of individual
reaction yields, especially for the first few insertion steps. From these insights,
several recommendations for reaction optimization could be formulated. Monomer
and RAFT agent concentration can be chosen freely. Reaction temperature and
initiator concentration can be picked according to the desired reaction time unless
extreme conditions are considered that would favour the creation of side products.
To increase the overall polymerization rate, higher monomer equivalents are
advised, while insertion of multiple units does not have a significant effect when
the monomer to RAFT agent ratio is kept below 10 : 1. The observed product
distributions in the simulations are an immediate effect of the individual rate
coefficients rather than the employed control methodology, and thus, similar
results are to be expected from other RDRP techniques [59]. It could further be
shown that after initialization of the RAFT process – once the main equilibrium is
reached – a maximum yield of 50% can be expected per SUMI reaction, thus limiting
the efficiency of the process even for perfect oligomer separation conditions.
These insights enabled the synthesis of a uniform decamer by relying on the
fact that chain growth is not limited to one unit at a time in RDRP reactions [60].
In other words, well-defined structures could be produced directly via multiple
unit monomer insertion (MUMI) resembling the perfectly defined repeating
sequences often found in biological SD materials. Employing this power of RAFT
polymerizations, SUMI and MUMI reactions were combined with four different
acrylic monomers. The targeted discrete oligomers were isolated by automated
flash column chromatography, which was significantly faster than recycling SEC
with isolation of a decamer taking roughly one hour (Figure 17.3). Flash chro-
matography as an oligomer separation method had been introduced by Hawker and
coworkers and provides surprisingly easy access to chain length separations at low
DP [61]. This approach also made it possible to separate longer sequence lengths
than recycling SEC. Isolated yields could be maximized because of the baseline
separation of the various insertion products, hence considerably limiting product
losses. The RAFT end groups were then used to couple two telechelic discrete
S S Figure 17.3 Flash column

N N
chromatography purification
S S 0-8 S S
of the oligomer chain
α-[EHA]1-[nBA]1-[MA]0-8-ω extension with six methyl
acrylate units for the
2 3 synthesis of octamers
4 (8-mers). Source: Reprinted
1 with permission from Haven
5 et al. [60]. Copyright 2017,
0 6
7 8
500 600 700 800 900 1000 1100 1200 1300

m/z
Automated flash separation
Isolated yield
0 = 9%
1 = 16%
2 = 19%
3 = 17%
4 = 11%
5 = 8%
6 = 5%
500 600 700 800 900 1000 1100

m/z
decamers together. Apart from increasing the attainable chain length, this approach
also showcased the plethora of further functionalization possibilities available for
the SUMI and MUMI products by RDRP techniques.
Sawamoto, Ouchi, and coworkers introduced sequence definition via a selective
single-monomer addition process in RDRP via metal-catalyzed living radical
polymerization (LRP) [62, 63]. Although not RAFT polymerization, a brief
overview of this work is highlighted herein because of the high importance in
the field of sequence control via radical polymerization. Also, the strategies used
are in principle transferable to RAFT reactions. Their work was inspired by
nature, which utilizes templates to control the order of propagating monomer
sequence for biopolymers (e.g. DNA and peptides) via an accurately controlled
production process. Radical polymerization would be appropriate for the design
of template chemistry because of the wide range of monomers that could be
used. Metal-catalyzed LRP proved highly suitable for the construction of template
systems towards sequence definition. In a first attempt to design SD oligomers,
two methacrylate monomers were polymerized where control of selectivity in the
radical addition of the monomers was demonstrated via a halide initiator that
carried a recognition site (template) for one of the monomers via ionic interactions
[64]. The competitive radical addition of methacrylic acid (MAA) over MMA by a
factor of 10 (because of the specific interaction between the template amine and
the acid in MAA) permits the predominant synthesis of alternating adducts of both
monomers. In an attempt to optimize the template-assisted system, a crown ether
functionality was introduced, which allowed the recognition of cationic monomers
according to their size [65]. Selective insertion of a sodium methacrylate over a
much more bulky ammonium cation derivative could in this way be achieved. This
concept is illustrated in Scheme 17.4. However, the concept was not appropriate for
iterative processes (oligomers/polymers with full selectivity were still out of reach)
to synthesize SD oligomers unless some recognition sites for different comonomers
could be incorporated. Although both methods showcase selective insertion of a
monomer unit, further development towards longer and more complex structures
still seemed out of reach.
–NH2
RDRP or
or or O O
O O O
HO O O O O O
Na O
N
Cl
Scheme 17.4 Schematic representation of a template-assisted selective monomer

addition. Selective addition of a monomer through recognition of the template moiety via
metal-catalyzed LRP resulting in 1 : 1 adducts. Source: Reproduced with permission from De
Neve et al. [5]. Copyright 2018, Royal Society of Chemistry.
In this template-assisted concept, the monomer addition can be regarded as a

cyclization, controlled via reversible activation under dilute conditions. To gain
more control over the primary oligomer structure (monomer sequence), a new
concept was proposed by Sawamoto and coworkers based on the repetition of
cyclization by introducing two types of orthogonally cleavable and renewable cova-
lent bonds [66]. The initiator-monomer (inimer) molecule in this process carries
both a radical-generating site and an alkene, leading to a repetitive cyclization, bond
cleavage, and regeneration. A schematic representation of this concept is illustrated
in Scheme 17.5. The halide initiator for atom transfer radical polymerization
(ATRP) was connected with a methacrylate-based monomer via two orthogonally
cleavable and renewable bonds, N-hydroxysuccinimide (NHS) ester and 2-pyridyl
disulfide (for detailed reaction schemes of the process, see literature) [66]. The metal
catalyst needed to be carefully selected, and dilute reaction conditions are required
for selective radical formation and cyclization without further chain growth. Fur-
thermore, for every additional ring closure, the reaction solvent, temperature, and
catalyst amount had to be carefully tuned, which makes the application potential of
the process rather limited. However, an iterative method for the template-assisted
synthesis of SD oligomers through radical addition of a single-monomer unit was

designed. High conversion (>90%) was reached for the synthesis of a SD trimer,
thus for a total of two radical additions into the starting inimer molecule.
Forward
Regene
Addition Cleavage -ration
R1 R1
L L L L
Closed Cleaved Opened
Forward
Radical
Regene
Addition Cleavage -ration
R1 R1 R2 R1 R2
L L L
Closed Cleaved Opened
R1 R2 R3 R4 R5 R6
Iterative
Addition L
Cleavage Regene
-ration Sequence-controlled vinyl polymer (oligomer)
Scheme 17.5 Schematic representation of the iterative cyclization and the molecular
structure of inimer carrying two types of cleavable/renewable bonds (NHS-ester and
2-pyridyl disulfide). SUMI was controlled via cyclization. To repeat the cyclization, one of
the cleavable/renewable bonds was cleaved; this was followed by regeneration of the bond
carrying the next vinyl group. Source: Hibi et al. [66]. Licensed under CC by 4.0.
The same group introduced another concept towards the synthesis of SD

oligomers; in this approach, the monomer sequence was controlled by using
methacrylate-based monomers that carry exceptional bulky (adamantyl and
isopropyl-based) and convertible pendant groups [67, 68]. Because of the bulky
pendant group, the monomer is unlikely to homopolymerize because of the steric
hindrance and low ceiling temperature (T c ). The bulky pendant groups could be
easily transformed into any less bulky substituents to reactivate the chain via selec-
tive acidolysis and subsequent esterification reactions (Scheme 17.6). Three iterative
cycles of methacrylate-based monomers were demonstrated to yield a SD trimer. As
mentioned above, the approaches by Sawamoto and Ouchi did not rely on RAFT
reactions per se but are to a large degree transferrable in their concepts to RAFT
SUMI reactions. A fusion of the approaches in the future appears to be promising.
Returning to RAFT reactions, two significant issues come with sequen-
tial RAFT-SUMI using thermal initiating systems being (i) initiator-derived
by-products such as cage products and, in particular, the by-products formed by the
O
O
ATRP
O O
O O
R
R–OH
Esterification Selective
acidolysis
O
HO
Scheme 17.6 Schematic representation of the SUMI process via bulky and convertible
pendant group. Subsequent additions become available via post-modification steps
(acidolysis and subsequent esterification). Source: Reproduced with permission from De
Neve et al. [5]. Copyright 2018, Royal Society of Chemistry.
initiator-derived radicals adding to the monomer (especially when initiator-derived

radicals are different from the initial RAFT leaving or reinitiating group) and (ii)
the low initiator efficiency [14]. These by-products may be avoided by generating
initiating radicals directly from the RAFT agent by photolysis, a process introduced
by Gruendling et al. [69] very similar to the photoiniferter process first described
by Otsu [70]. Recently, these photoinitiating (either directly or with the use of
a photoredox catalyst) processes were investigated in the context of SUMI by a
visible light-mediated radical chain process (photoRAFT) to synthesize discrete
- = 1) oligomers [71]. For the first time, discrete trimers were successfully
(D
synthesized by successive SUMI in high yield under mild reaction conditions.
To avoid oligomerization (multiple monomer units added to an active radical),
it is important that the transfer constant of the RAFT agent is high and addition
of reinitiating radical to the monomer is fast (kp(1) ≫ kp(n) ) as discussed earlier.
Moreover, it is preferred that the product macro-RAFT agent formed by SUMI is
less active as a photoiniferter than the initial RAFT agent. The first styrene-like
monomer was introduced via a direct photoRAFT process with green light in very
high yield. As a second monomer, N-substituted maleimides were selected because
of their high reactivity towards styrene-like propagating radicals (first monomer),
while homopolymerization of maleimides is slow. The SUMI step was performed
via photoinduced electron/energy transfer PET-RAFT polymerization with a
photoredox catalyst under blue light irradiation. Complete conversion was achieved
in 48 hours. As a third monomer, vinyl acetate (VAc) was inserted via PET-RAFT
SUMI using a photocatalyst under red light irradiation. RAFT polymerization of
VAc using trithiocarbonate RAFT agents with thermal initiation is known to be
strongly inhibited (because of slow fragmentation of the intermediate radical) [72].
In the case of SUMI, processes that disfavour propagation following a single-unit
insertion are highly preferable. Figure 17.4 shows gel permeation chromatography
(GPC) and ESI-MS analysis of the corresponding photoRAFT SUMI products

(discrete oligomers).
The proposed mechanism of photoRAFT-SUMI is shown in Scheme 17.7. Photol-
ysis of the RAFT agent causes reversible dissociation of the C—S bond (iniferter
process). The radical (R⋅) formed can add monomer (or RAFT agent, which is a
degenerate process). The radical formed by addition of monomer (R–M⋅) can com-
bine with a thiocarbonylthio radical to form the SUMI product. It can react with
RAFT agent by addition fragmentation, also to form the SUMI product. It may also
add further monomer, which is slow. The relative concentrations of the reacting
species dictate that RAFT should be the dominant process.
S S
hν
R S SZ′ R S SZ′
M
S S
hν
R M S SZ′ R M S SZ′
M Slow
Fast S
R R S SZ′
R M M
R M
S
R S SZ′
Scheme 17.7 Mechanism of photoRAFT-SUMI with a trithiocarbonate RAFT agent. Source:

Reprinted with permission from Haven et al. [55]. Copyright 2018, American Chemical
Society.
In another approach, a new protocol was proposed for incorporating a broad

range of functionalities via available vinyl monomers (acrylates, acrylamides,
and styrene) via catalyst-free photoRAFT-SUMI (green light) [73]. The success of
this strategy relies on successive aminolysis, thiol–ene, and esterification steps to
transform the secondary trithiocarbonate end group photo-SUMI into a more active
tertiary cyanoalkyl trithiocarbonate. Yields were mostly limited by the efficiency of
the isolation step. Discrete oligomers, up to five vinyl monomer repeat units, were
synthesized. In the case of the pentamers, three consecutive SUMI reactions and
two intermediate esterification and thiol–ene steps were performed (Scheme 17.8).
Very recently, Moad and coworkers studied visible light-initiated SUMI of
N,N-dimethylacrylamide (DMAm) into trithiocarbonates in aqueous solution [74].
They concluded that very selective photoSUMI was achieved upon using a high
monomer concentration (up to 1 M solutions) with equimolar RAFT agent/DMAm
ratio and the irradiation wavelength was of high importance for the formation
of SUMI over higher oligomers (or other by-products). For this particular system
(DMAm and 4-((((2-carboxyethyl)thio)carbonothioyl)thio)-4-cyanopentanoic acid
1.2
CDTPA-St-PMI-Lim CDTPA-St-PMI
CDTPA-St-PMI-VAc CDTPA-St
1.0
Normalized RI signal
0.8 CDTPA
0.6
0.4
0.2
0.0
30 31 32 33 34
(A) Retention time (min)
839.39
M + Na+
O N O
CDTPA-St-PMI-Lim O
HO S S
CN S
(a) Calc.: 839.93
M + Na+
789.30
CDTPA-St-PMI-VAc M + Na+
O O N O
767.33 S S
M + H+ HO
CN O O S
(b) Calc.: 789.30
M + Na+
703.27
CDTPA-St-PMI M + Na+ O N O
O
HO S S
CN
S
(c) Calc.: 703.27
M + Na+
508.24
M + H+ CDTPA-St O
525.26 S S
M + NH4+ HO
CN S
Calc.: 508.24
(d)
M + H+
500 600 700 800 900 1000 1100
m/z
(B)
Figure 17.4 GPC traces for the products from sequential PET-RAFT-SUMI into
4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid (CDTPA) (A) and ESI-MS
spectra for the products from sequential PET-RAFT-SUMI (B) into a trithiocarbonate RAFT
agent. Source: Reprinted with permission from Haven et al. [55]. Copyright 2018, American
Chemical Society.
Weak Strong
O R1 R1 O
C12H25S S Fast C12H25S S
OH OH
S CN S R CN
SUMI
R1
O
R2 R2 O S
HO OH
Aminolysis/thiol–ene O R CN
R2 R1
O O
CDTPA C12H25S S O S
O OH
Esterification S CN O R CN
R2 R1
R1 R3
Fast R3 R2 R1 R6 R5 R4 R3 R2 R1
SUMI
Scheme 17.8 Schematic representation for the synthesis of discrete pentamers by SUMI,
aminolysis, thiol-ene, and esterification steps. Source: Reprinted with permission from
Haven et al. [55]. Copyright 2018, American Chemical Society.
RAFT agent), red light (633 nm) provided for selective excitation of the initial
RAFT agent in the presence of DMAm with high-purity SUMI product and high
monomer conversion (>80%). Shorter irradiation wavelengths such as deep blue
(402 nm), blue (451 nm), or green (512 nm) light gave a conversion plateau at
60–70% monomer conversion. Also, a preferred linear pseudo-first-order kinetic
profile to high (>80%) conversion was observed with red light initiation, but
these conditions also showed the slowest reaction rate. The rate of DMAm-RAFT
formation decreased in the series 402 nm (deep blue) > 512 nm (green) > 451 nm
(blue) > 633 nm (red). Furthermore, the use of higher reaction temperatures for the
photoSUMI reaction (65 ∘ C vs. ambient temperature) resulted in a higher reaction
rate and more selective SUMI process (reduction of oligomer formation).
Challenges remaining in the synthesis of SD polymers or oligomers (sequen-
tial SUMI processes) are scalability limitations such as low reaction yields and
long reaction times. Recently, these scalability challenges were addressed by a
PET-RAFT-SUMI protocol through sequential and alternating SUMI of N-phenyl
maleimide (PMI) and indene (Ind) – both non-homopolymerizable monomers – into
a trithiocarbonate RAFT agent under mild reaction conditions in batch and hand-
made flow reactors (Scheme 17.9) [75]. A series of discrete SD polymers up to
pentamers (five sequential SUMI reactions) were synthesized. Purification after
each monomer insertion step was performed by automated flash chromatography
[61]. Pentamers on a gram scale with an overall isolated yield of 56% were obtained
in short production times (<1 week). The authors also studied oxygen tolerance
during the PET-RAFT SUMI process and suggested that the presence of oxygen
had negligible effects on both the activation of the RAFT agent and formation of
S
O N O S
S S S
S O S S
S PMI (M) N O Ind (1)
O N O
BETC
ZnTPP ZnTPP
(Step A) BETC-M (Step B) BETC-M-I
(Yield ~95%) (Yield ~85%)
O N O
S
S S O N O PMI (M)
Ind (1) (Step C)
O N OO N OO N O
PMI (M) (Step D) N
(Step E) N Zn N
BETC-M-I-M-I-M N
(Total yield ~59%, up to 2.3 g in less than ZnTPP

one week using a lab-made flow reactor)
Scheme 17.9 Schematic representation for the PET-RAFT SUMI process for the synthesis of pentamers of N-phenyl maleimide and indenes. Source:
Reproduced with permission from Huang et al. [75]. Copyright 2019, John Wiley & Sons.
the SUMI adduct under the investigated reaction conditions (on product purity and
yield). This facilitated the upscaling process; however, limitations of the process
were running cost and amount of reagents. By implementation of SUMI pro-
cesses in flow, theoretically, kilogram scales could be targeted and the production
time could be reduced by increasing the length of the flow reactor (by keeping
the same dimensions of the tubing), light strip, and the volume capacity of the
syringes.
With such marked advances in the synthesis of SD polymers and oligomers via
RAFT, interest has started shifting towards the application of these materials in,
for example, biomimetics. Functional precision polymers open up a wide array of
opportunities that rely on sequence-specific interactions as observed in biosystems.
Recently, SD N-substituted oligo(acrylamide)s were synthesized that originated
from a direct translation of the side chain functionalities of a well-studied peptide
sequence (Scheme 17.10) [76]. The uniform N-substituted oligo(acrylamide)
pentamers were obtained via RAFT polymerization, following the SUMI protocol
and flash column chromatography separation with isolated yields between 16%
and 37% for individual reaction steps. The parent peptide sequence was known
to solubilize meta-tetra(hydroxyphenyl)-chlorin (m-THPC), a photosensitizer for
photodynamic cancer therapy, by drug structure-specific hosting. Translation
of the active sequence towards synthetic precision polymers showed that the
resulting peptide-mimetic macromolecule retained the drug solubilization and
release kinetics of the parent peptide. Furthermore, these characteristics could be
influenced by varying the side chain on position three with various N-substituted
oligo(acrylamide)s and thereby even allowed for 40% higher payloads and 27 times
faster initial drug release than the natural peptide sequence counterpart.
Peptide-PEG conjugate with parent sequence
PEG
H O
N OH
R O O HO
O
NH2 NH2 R
Direct sequence translation

SUMI oligo(acrylamide)s SAP oligo(ester)s
PEG
PEG
O O
NH2 NH2
Scheme 17.10 Schematic representation of the sequence transfer strategy from a

peptide-PEG conjugate to PEG-conjugated precision sequences. Source: Reproduced with
permission from Maron et al. [76]. Copyright 2019, John Wiley & Sons.
Moving one step closer to biological precision, the concept of stereoregularity

was introduced into synthetic SD SUMI polymers by Xu and coworkers using
alternating radical chain growth via sequential photoRAFT-SUMI [77]. Two
monomer families, being indenes and maleimides, showing little or no tendency
for homopolymerization were inserted. The pool of available monomers could also
be broadened by adjusting the functionalities carried by the selected monomer
families. Insertion of these cyclic monomers into a trithiocarbonate RAFT agent
occurred in a stereospecific manner irrespective of reaction conditions or monomer
functionalities and resulted in trans-linkages along the backbone because of steric
hindrance and the restricted rotation of cyclic monomers during radical addition.
This selectivity was not observed for analogous acyclic monomers, which gave
mixed cis- and trans-insertions. The selection criteria for the monomer and RAFT
agent to ensure successful SUMI reaction were identical to the ones already high-
lighted before. Additionally, indenes are electron donating, whereas maleimides
act as electron acceptors, thereby forming a charge transfer complex and leading to
high reaction rates in an alternating copolymerization.
Recently, Junkers and coworkers studied the physical properties of discrete
oligo(methyl acrylates)s with a degree of polymerization between 1 and 22 (molecu-
lar weight range 432–2261 g mol−1 ) [78]. The aforementioned library was created by
deconstructing an oligomer distribution, obtained via RAFT polymerization, into
its uniform components. Because of the applied synthesis methodology, the discrete
oligomers closely resembled disperse synthetic polymers with a hydrocarbon
backbone as used in the industry. Properties such as diffusivity, glass transition
temperature, and viscosity were systematically examined and compared to the
existing knowledge on disperse higher molecular weight polymers. As could be
expected, marked differences were observed for these discrete oligomers with
glass transition temperatures and intrinsic viscosities well below what is known
for higher dispersity polymers, whereas the inverse was perceived for diffusion
constants. Furthermore, the discrete library offered the opportunity to create new
oligomer distributions on demand (Figure 17.5), hence making it, in principle,
possible to directly target material properties purely by mixing the correct discrete
building blocks together. The artificial oligomer distributions that were established
this way highlighted the limitations associated with molecular weight analysis
via SEC. Understanding the deceptive feature of molecular weight distribution
dispersity is crucial, especially when more and more research aims to create SD
precision polymers.
Within the field of synthesis of sequence-defined materials, RDRP and RAFT
in particular take a special role. Most SD synthesis methods rely on click-like
chemistry in order to build up sequences in a step-wise manner, conceptually not
unlike classical peptide synthesis. In consequence, solid-supported synthesis is
available for these methods. RDRP SUMI does not allow for the same strategy and
appear thus to be more tedious to carry out. Although the maximum chain length
is limited, synthesis can, however, be carried out relatively fast. Purification steps
are required, yet the same is often true for alternative methods. Chain lengths of
up to 10 units are currently possible, and promising results have been obtained
by various research groups, showing that this range can still be extended further.
Overall, RDRP-based SD materials feature the advantage of a stable carbon–carbon
backbone. Also, spacers between two functional R groups on the oligomers are rela-
tively small, allowing for a high information density, and potentially advantageous
0.25
Simulated dn
Experimental dw
Ci (10–3 mmol ml–1)
Experimental dn
Ð = 1.25
0.10 Mn = 1336 g·mol–1
= 671 g·mol–1
0.00
1 22 250 3500 250 3500
Chain length Molar mass (g·mol–1) Molar mass (g·mol–1)
1.7
Simulated dn
Ci (10–3 mmol ml–1)
Experimental dw
Experimental dn
1.0
Ð = 1.39
0.6 Mn = 1265 g·mol–1
= 792 g·mol–1
0.0
1 22 100 3500 100 3500
(a) Chain length (b) Molar mass (g·mol–1) (c) Molar mass (g·mol–1)
Figure 17.5 Schematic representation of the on-demand oligomer distributions with (a) concentrations of each oligomer chain length that were mixed
together, (b) resulting number distributions (simulated and experimental), and (c) resulting double-weighted distributions. Source: Reproduced with
permission from De Neve et al. [78]. Copyright 2019, John Wiley & Sons.
References 825
interaction with biological polymers that feature similarly densely spaced chemical
information. First endeavours into biomedical applications have shown that
RAFT-derived oligo(acrylamide)s are able to fulfil the same function as classical
peptides. This proposes an interesting peptidomimetic route to functional bioactive
materials. The future of these materials is certainly bright, and more application
examples can be expected to be found soon.
References
3 Perrier, S. (2017). Macromolecules 50: 7433–7447.
4 Gody, G., Zetterlund, P.B., Perrier, S., and Harrisson, S. (2016). Nat. Commun. 7:
10514.
5 De Neve, J., Haven, J.J., Maes, L., and Junkers, T. (2018). Polym. Chem. 9:
4692–4705.
6 Lutz, J.-F., Lehn, J.-M., Meijer, E.W., and Matyjaszewski, K. (2016). Nat. Rev.
Mater. 1: 16024.
7 Haven, J.J., Guerrero-Sanchez, C., Keddie, D.J. et al. (2014). Polym. Chem. 5:
5236–5246.
8 Vandenbergh, J., de Moraes Ogawa, T., and Junkers, T. (2013). J. Polym. Sci. A:
Polym. Chem. 51: 2366–2374.
9 Baeten, E., Haven, J.J., and Junkers, T. (2017). Polym. Chem. 8: 3815–3824.
10 Derboven, P., Van Steenberge, P.H.M., Vandenbergh, J. et al. (2015). Macromol.
Rapid Commun. 36: 2149–2155.
11 Gody, G., Maschmeyer, T., Zetterlund, P.B., and Perrier, S. (2013). Nat. Commun.
4: 2505.
12 Gody, G., Maschmeyer, T., Zetterlund, P.B., and Perrier, S. (2014). Macro-
13 Engelis, N.G., Anastasaki, A., Nurumbetov, G. et al. (2017). Nat. Chem. 9:
171–178.
14 Vandenbergh, J. and Junkers, T. (2014). Macromolecules 47: 5051–5059.
15 Harrisson, S. (2018). Polym. Chem. 9: 1366–1370.
16 Lutz, J.-F. (2010). Polym. Chem. 1: 55–62.
17 Hartmann, L. (2011). Macromol. Chem. Phys. 212: 8–13.
18 Martens, S., Landuyt, A., Espeel, P. et al. (2018). Nat. Commun. 9: 4451.
19 Al Ouahabi, A., Kotera, M., Charles, L., and Lutz, J.-F. (2015). ACS Macro Lett. 4:
1077–1080.
20 Gunay, U.S., Petit, B.E., Karamessini, D. et al. (2016). Chem 1: 114–126.
21 Takizawa, K., Tang, C., and Hawker, C.J. (2008). J. Am. Chem. 130: 1718–1726.
22 Solleder, S.C., Zengel, D., Wetzel, K.S., and Meier, M.A.R. (2016). Angew. Chem.
Int. Ed. 55: 1204–1207.
23 Zydziak, N., Konrad, W., Feist, F. et al. (2016). Nat. Commun. 7: 13672.
24 Milnes, P.J., McKee, M.L., Bath, J. et al. (2012). Chem. Commun. 48: 5614–5616.
25 Porel, M., Thornlow, D.N., Phan, N.N., and Alabi, C.A. (2016). Nat. Chem. 8:
590–596.
26 ten Brummelhuis, N. (2015). Polym. Chem. 6: 654–667.
27 Solleder, S.C., Schneider, R.V., Wetzel, K.S. et al. (2017). Macromol. Rapid Com-
28 Badi, N. and Lutz, J.-F. (2009). Chem. Soc. Rev. 38: 3383–3390.
29 Lutz, J.-F., Ouchi, M., Liu, D.R., and Sawamoto, M. (2013). Science 341: 628.
30 Zard, S.Z. (1997). Angew. Chem. Int. Ed. 36: 672–685.
31 Quiclet-Sire, B. and Zard, S.Z. (2006). Chemistry 12: 6002–6016.
32 Quiclet-Sire, B. and Zard, S.Z. (2008). Org. Lett. 10: 3279–3282.
33 Lebreux, F., Quiclet-Sire, B., and Zard, S.Z. (2009). Org. Lett. 11: 2844–2847.
34 Quiclet-Sire, B., Revol, G., and Zard, S.Z. (2010). Tetrahedron 66: 6656–6666.
35 Zard, S. and Quiclet-Sire, B. (2016). Synlett 27: 680–701.
36 Chen, M., Ghiggino, K.P., Mau, A.W.H. et al. (2004). Macromolecules 37:
5479–5481.
37 Houshyar, S., Keddie, D.J., Moad, G. et al. (2012). Polym. Chem. 3: 1879–1889.
38 Chen, M., Ghiggino, K.P., Rizzardo, E. et al. (2008). Chem. Commun.: 1112–1114.
https://doi.org/10.1039/b716471h.
39 Chen, M., Haussler, M., Moad, G., and Rizzardo, E. (2011). Org. Biomol. Chem. 9:
6111–6119.
40 Feng, X.-S. and Pan, C.-Y. (2002). Macromolecules 35: 4888–4893.
41 Sasso, B., Dobinson, M., Hodge, P., and Wear, T. (2010). Macromolecules 43:
7453–7464.
42 Henry, S.M., Convertine, A.J., Benoit, D.S. et al. (2009). Bioconjug. Chem. 20:
1122–1128.
2383–2394.
44 McLeary, J.B., McKenzie, J.M., Tonge, M.P. et al. (2004). Chem. Commun.:
1950–1951. https://doi.org/10.1039/b404857a.
3151–3161.
46 Pound, G., McLeary, J.B., McKenzie, J.M. et al. (2006). Macromolecules 39:
7796–7797.
mun. 27: 1233–1240.
48 van den Dungen, E.T.A., Rinquest, J., Pretorius, N.O. et al. (2006). Aust. J. Chem.
59: 742–748.
49 van den Dungen, E.T.A., Matahwa, H., McLeary, J.B. et al. (2008). J. Polym. Sci.
A: Polym. Chem. 46: 2500–2509.
50 Moad, G., Chiefari, J., Chong, Y.K. et al. (2000). Polym. Int. 49: 993–1001.
2273–2283.
6914–6915.
References 827
34–42.
54 Moad, G., Guerrero-Sanchez, C., Haven, J.J. et al. (2014). RAFT for the control
of monomer sequence distribution – single unit monomer insertion (SUMI)
into dithiobenzoate RAFT agents. In: Sequence-Controlled Polymers: Synthesis,
Self-Assembly, and Properties ACS Symposium Series, vol. 1170, ch. 9 (eds. J.-F.
Lutz, T.Y. Meyer, M. Ouchi and M. Sawamoto), 133–147. American Chemical
Society.
55 Haven, J.J., Hendrikx, M., Junkers, T. et al. (2018). RAFT 20 years later:
RAFT-synthesis of uniform, sequence-defined (Co)polymers. In: Reversible Deac-
tivation Radical Polymerization: Mechanisms and Synthetic Methodologies, ACS
Symposium Series, vol. 1284, ch. 4 (eds. K. Matyjaszewski, H. Gao, B.S. Sumerlin
and N.V. Tsarevsky), 77–103. American Chemical Society.
56 Vandenbergh, J., Reekmans, G., Adriaensens, P., and Junkers, T. (2013). Chem.
Commun. 49: 10358–10360.
57 Haven, J.J., Vandenbergh, J., and Junkers, T. (2015). Chem. Commun. 51:
4611–4614.
58 Haven, J.J., Vandenbergh, J., Kurita, R. et al. (2015). Poly. Chem. 6: 5752–5765.
59 Vandenbergh, J., Reekmans, G., Adriaensens, P., and Junkers, T. (2015). Chem.
Sci. 6: 5753–5761.
60 Haven, J.J., De Neve, J.A., and Junkers, T. (2017). ACS Macro Lett. 6: 743–747.
61 Lawrence, J., Lee, S.H., Abdilla, A. et al. (2016). J. Am. Chem. Soc. 138:
6306–6310.
62 Kato, M., Kamigaito, M., Sawamoto, M., and Higashimura, T. (1995). Macro-
molecules 28: 1721–1723.
63 Ouchi, M. and Sawamoto, M. (2017). Poly. J. 50: 83–94.
64 Ida, S., Terashima, T., Ouchi, M., and Sawamoto, M. (2009). J. Am. Chem. Soc.
131: 10808–10809.
65 Ida, S., Ouchi, M., and Sawamoto, M. (2010). J. Am. Chem. Soc. 132:
14748–14750.
66 Hibi, Y., Ouchi, M., and Sawamoto, M. (2016). Nat. Commun. 7: 11064.
67 Oh, D., Ouchi, M., Nakanishi, T. et al. (2016). ACS Macro Lett. 5: 745–749.
68 Oh, D., Sawamoto, M., and Ouchi, M. (2019). Poly. Chem. 10: 1998–2003.
69 Gruendling, T., Kaupp, M., Blinco, J.P., and Barner-Kowollik, C. (2011). Macro-
70 Otsu, T. (2000). J. Polym. Sci. A: Polym. Chem. 38: 2121–2136.
71 Xu, J., Fu, C., Shanmugam, S. et al. (2016). Angew. Chem. 129 https://doi.org/10
.1002/ange.201610223.
73 Xu, J., Fu, C., Shanmugam, S. et al. (2017). Angew. Chem. Int. Ed. Engl. 56:
8376–8383.
1800240.
75 Huang, Z., Corrigan, N., Lin, S. et al. (2019). J. Polym. Sci. A: Polym. Chem. 57:
1947–1955.
76 Maron, E., Swisher, J.H., Haven, J. et al. Angew. Chem. Int. Ed. Engl. 58:
10747–10751.
13392–13406.
78 De Neve, J., Haven, J.J., Harrisson, S., and Junkers, T. (2019). Angew. Chem. Int.
Ed. 131: 14007–14011.
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Synthesis and Application of Reactive Polymers via RAFT

Polymerization
Martin Gauthier-Jaques 1 , Hatice Mutlu 2 , Heba Gaballa 3 , and Patrick Theato 1,2
1
Institute for Chemical Technology and Polymer Chemistry (ITCP), Karlsruhe Institute of Technology (KIT),
Engesserstraße 18, D-76131 Karlsruhe, Germany
2
Soft Matter Synthesis Laboratory, Institute for Biological Interfaces 3 (IBG-3), Karlsruhe Institute of
Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany
3
Institute of Technical and Macromolecular Chemistry, University of Hamburg, Bundesstr. 45, D-20146
Hamburg, Germany
18.1 Introduction
In this chapter, we will review synthetic methods that will allow for an efficient
chemical functionalization of polymers, which have been synthesized via a
reversible addition fragmentation chain transfer (RAFT) polymerization.
Post-polymerization modifications have undoubtedly contributed enormously
to the synthesis of functional macromolecules. Particularly, the intensive exploita-
tion of polymers bearing reactive side group moieties that are obtained by reversible
deactivation radical polymerization (RDRP) techniques of the respective reactive
monomers have enabled the synthetic access to polymers with highly defined
functionality and architecture. This chemical transformation has become possible
because of the readily available diverse orthogonal organic reactions. Indeed, the
synthetic pool of reactive groups amendable for post-polymerization modifications
has increased considerably in recent years. However, before addressing these
recent advances, it is essential to note and consider some of the pioneering studies,
particularly applicable to the synthesis of these well-defined polymers. For this
purpose, the reader is encouraged to refer to the following recent reviews and
monographs present in the area of post-polymerization modifications [1–6].
In the following, we will first discuss the most common reactive groups
(Scheme 18.1) and the respective monomers thereof, which have been employed
jointly with RAFT polymerization and have been intensively investigated in past
and recent years. They are organized by functional group, which will allow the
reader to easily read only selected paragraphs if desired. Next, we will highlight
selected examples of applications with a biological context, which rely on the
efficient use and interplay of RAFT polymerization and post-polymerization
modification. It shall be noted that the selection of examples was made in order to
830 18 Synthesis and Application of Reactive Polymers via RAFT Polymerization
stimulate the reader in regard to what is synthetically possible and hence makes no
claim to be complete.
F O F
O
O F F F NO2
O O O
N
O O F F F O
O
F F
N-hydroxysuccinimide Pentafluorophenyl Pentafluorobenzyl p-Nitrophenyl
ester (NHS) ester (PFP) ester (PFB) ester (PNP)
O O
S
N O O CF3
O O
O O CF3
O O
Acetone oxime p-dialkylsulfonium phenoxy Hexafluoroisopropanol
Salicylic acid
ester (AO) ester (DASP) ester (HFIP)
ester (SA)
Cl N
O O H H N
N N C
X O O
N(Boc) 2 Cl
N Cl O
di(Boc)amide Acyl chloride Alkyl halide Trichlorotriazine Isocyanate Azlactone
O O
O O S O
O S O N
S
N
H
Maleic anhydride Thiolactone Disulfide Epoxide Aziridine Carbonyl
OH
X
NH2 N3 B
OH
Amine Alkene Alkyne Azide Aryl halide Aryl boronic acid
Scheme 18.1 Overview of the principal reactive groups suitable for post-polymerization
modification that will be discussed thereafter.
18.2 N-Hydroxysuccinimide (NHS)
The N-hydroxysuccinimide (NHS) active ester is a valuable handle to (bio)conjugate

manifold amine-containing compounds onto diverse (co)polymers. Indeed, the
development and utilization of NHS dates back to 1970s when Ringsdorf [7] and
Feré [8] independently reported for the first time the radical polymerization of
a methacrylate derivative of NHS (NHSMA, Scheme 18.2). On the other hand,
initial attempts to polymerize NHSMA through RAFT polymerization using
various dithiocarbamates and dithiobenzoates as chain transfer agent (CTA) in
N,N′ -dimethyl formamide (DMF) have been less successful [9]. The resulting
18.2 N-Hydroxysuccinimide (NHS) 831
polymers had unacceptably broad molecular weight distributions (D - > 1.5), which
was particularly due to its susceptibility to nucleophilic reaction. Also, utilizing
high concentrations of CTA did not improve the limited control over the polymer-
ization rate. Subsequently, random and block copolymers of NHSMA with diverse
vinyl monomers were prepared and thoroughly characterized in order to tackle
the above-mentioned issue. For instance, Kane and coworkers have shown that
RAFT copolymerization of NHSMA with N-(2-hydroxypropyl)methacrylamide
yielded copolymers with M n as high as 50 000 g mol−1 and narrow molecular
weight distributions (1.1 < D
- < 1.3), also disclosing potential applications of these
materials in polymeric therapeutics [10]. In a similar manner, the statistical
copolymerization of NHSA, the acrylate analogue of NHSMA (Scheme 18.2),
with N,N-diethylacrylamide was successful under RAFT conditions with a very
good control of molecular weight (5000 < M n < 130 000 g mol−1 ) for copolymers of
different microstructures.
O O O O
O O O O
N N N N SO3H
O O O O
O O O O
NHSMA NHSA NS4VB sulfoNHSA
Scheme 18.2 Some of the most common NHS monomers.
Although most of the research activities focused on NHS-active ester based

monomers utilize acrylates or methacrylates, the homopolymerization of the
NHS-activated ester of 4-vinyl benzoic acid (NHS4VB) was evaluated by Aamer and
Tew in order to expand the toolbox of polymeric NHS-activated esters synthesized
by RAFT [11]. Interestingly, the polymerization was conducted with a CTA based
on 4-cyano, 4-(thiobenzoylthio)-N-succinimide valerate, i.e. a CTA that contains the
same activated ester as in the monomer. Nonetheless, this CTA was demonstrated
to provide unimodal polymers with control over M n (44 000 < M n < 61 000 g mol−1 )
and dispersity (1.03 < D- < 1.07).
The NHS-active esters of acrylic acid and methacrylic acid provide access to poly-
acrylamides and polymethacrylamides that typically cannot be prepared via direct
polymerization of their corresponding acrylamide monomers. However, the substi-
tution of these activated esters with amine-containing compounds is often restricted
to organic solvents such as DMSO and DMF. Therefore, to overcome this limitation,
Hawker and coworkers [12] have introduced a novel water-soluble NHS-based
monomer, i.e. N-hydroxysulfosuccimidyl acrylate (sulfoNHSA), which was sub-
jected to a rapid photoelectron transfer RAFT polymerization in water at ambient
temperature. The consequent conjugation with amine-containing compounds was
performed in situ because the sulfoNHSA monomer and its respective polymer were
unstable (the half-life of sulfoNHSA is ∼60 minutes), as evidenced by 1 H NMR spec-
troscopy. This instability occurs because the sulfoNHSA functional group is prone
to rapid hydrolysis in water. Inspired by this work, Tanaka and coworkers developed
a novel monomer in which the vinyl group and a sulfoNHS-active ester group were
spaced with an alkyl chain linker in order to tune the hydrolytic stability [13]. The
sulfoNHSA was subsequently subjected to RAFT polymerization in DMSO using a
trithiocarbonate derivative, 2-(benzylsulfanylthiocarbonylsulfanyl)ethanol (BTSE),
at 35 ∘ C to deliver polymers with M n (37 000 < M n < 62 000 g mol−1 ) and acceptable
dispersities (1.34 < D- < 1.52). Eventually, a post-polymerization modification with
an amine-containing saccharide derivative revealed that the hydrolytic stability of
the sulfoNHS ester groups on these polymers was higher than that of the previously
reported sulfoNHS acrylate monomer.
Although a variety of homo- and copolymers based on the above-mentioned
NHS-activated ester derivatives have been successfully prepared in a controlled
fashion by RAFT, two significant side reactions accompany the post-polymerization
reaction of NHS-activated ester-based acrylate and methacrylate (co)polymers:
(i) ring-opening of NHS moieties and (ii) formation of backbone glutarimides by
attack of initially formed methacrylamides on adjacent NHS esters, which limits
their specific implementation as tailor-made polymers.
18.3 Pentafluorophenyl (PFP) Ester and Its Derivatives

The pentafluorophenyl (PFP) ester is a particularly appealing alternative to NHS
esters because of the facts that the PFP functional group is stable during a (radical)
polymerization, not prone to undesired hydrolysis or alcoholysis, and has better
solubility in most common organic solvents. Intriguingly, the first reports on the
activity of the PFP moiety as an active ester functional group date back to the
same time when NHS active ester monomers were recognized [14]. Nevertheless,
it took more than three decades until PFP esters were exploited as a versatile
tool for synthetic polymer functionalization. Subsequently, after the seminal
report on acrylate/methacrylate [15], RAFT polymerization of pentafluorophenyl
methacrylate (PFPMA) was explored in the presence of cumyldithiobenzoate
and 4-cyano-4-((thiobenzoyl)sulfanyl)pentanoic acid, respectively, as CTAs. The
isolated macromolecules exhibited the expected features of well-defined polymers
with M n up to 17 000 g mol−1 (D - < 1.20). The compatibility of these PPFPMAs
as macromolecular RAFT agents was further tested for the copolymerization of
PFPMA with MMA, N-acryloylmorpholine (NAM), and N,N-diethylacrylamide
(DEAM). Based on this work, Klok and coworkers [16] applied RAFT polymer-
ization to synthesize well-defined PPFPMA, which was further reacted with a
manifold functional primary amine to yield water-soluble macromolecules with
identical degrees of polymerization and molecular weight distributions. As a
continuation, Boyer and Davis expanded the horizon of PFP active esters by the
polymerization of an acrylate derivative of PFP, i.e. PFPA [17]. In this pioneering
work, 3-(benzylsulfanylthiocarbonylsulfanyl)propionic acid was selected as a
CTA to synthesize polymers with a well-defined structure (M n in the range of
16 000 g mol−1 and D - of 1.20). A subsequent quantitative post-polymerization
modification of PPFPA with glucosamine and galactosamine opened the possibility
18.3 Pentafluorophenyl (PFP) Ester and Its Derivatives 833
of synthesizing functionalized glycopolymers in one pot. In addition, star-shaped

polymers (5000 < M n < 15 000 g mol−1 , D
- < 1.20) with predesigned chemical func-
tionality were synthesized by employing the copolymerization of PFPAs with
difunctional diamine monomers used as cross-linkers [18]. In order to broaden
the synthetic portfolio, a styrenic derivative of PFP active ester was designed,
namely, pentafluorophenyl 4-vinylbenzoate (PFP4VB, Scheme 18.3) [19]. The
respective polymers (4200 < M n < 28 200 g mol−1 , 1.07 < D
- < 1.41) were synthesized
by employing various dithiobenzoates as the CTAs and AIBN as the radical initiator.
The PFP4VB functional moieties were found to be distinguishably more reactive
than their acrylate and methacrylate counterparts to the extent that they could
be quantitatively modified with even aromatic amines. As a result of the latter,
the variation of the chemical nature of the backbone by combining both PFPMA
and PFP4VB as monomers made it feasible to obtain statistical copolymers that
allow for a sequential conversion of both groups (i.e. with just one specific reactive
group) in an orthogonal-like manner with different amines [20]. In other words,
the PFP4VB repeat units of the copolymers were selectively modified first with
aromatic amines, then modification of PFPMA units with aliphatic amine imparted
fully functionalized statistical copolymers. In addition, block copolymerization
with extreme precision of diverse styrenic derivatives was accomplished by virtue
of a macro-CTA based on the PFP4VB monomer motif [18].
F F F F
F F F F F F F F
O O O O
S
O F O F O F O F
O
F F F F
PFPMA PFPA PFP4VB PFP4VS
F O F O F
F F F F
O O
F F F F F
F F F
PFSty PFBMA PFBA
Scheme 18.3 Most common PFP monomers and some of their derivatives.
Apart from acrylate, methacrylate, and styrenic PFP-activated ester derivatives,

the synthesis of polymers that utilize activated esters of sulfonic acid (e.g. PFP4VS in
Scheme 18.3) as reactive groups has been investigated. Accordingly, the respective
sulfonic acid ester polymers were reacted with an excess amount of amine under
ambient conditions in order to obtain polymeric sulfonamides. Even though the
sulfonic acid ester is significantly slower than the carboxylic acid ester analogue,
it opened the route to a second functionalization using alcohols via a Mitsunobu
reaction.
Another divergent reaction in the realm of PFP active esters is the regiose-
lective nucleophilic aromatic substitution of the labile para-fluoro substituent
of the PFP-group by nucleophiles (such as thiols, amines, etc.). Indeed, quite
recent contributions [21, 22] are comprehensively summarizing and discussing

not only the applications but also the potential of this versatile reaction in the
context of synthesis and modification of polymers and materials made thereof.
Hence, we intend to underpin only some paramount studies in this field of rele-
vance to the RAFT polymerization. In fact, initially, the para-fluoro substitution
reaction (PFTR) had been exploited exclusively for the modification of pentaflu-
orostyrene (PFSty)-based homo- and copolymers, which have been synthesized
under RAFT polymerization conditions, explicitly with AIBN as an initiator and
2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) as a CTA at
70 ∘ C in anisole or DMF [23]. The polymer-analogous reaction was carried out
quantitatively under ambient conditions using a well-defined PPFSy homopoly-
mer as well as block copolymers in the presence of primary thiol derivatives
and commercially available base (i.e. triethylamine (Et3 N)). Although the PFSty
homopolymer represents a suitable precursor for post-polymerization functional-
ization with thiol derivatives, bearing perfluorinated side groups induced limited
solubility in more polar solvents [24]. Furthermore, as a styrene analogue, PFSty is
also not readily suitable for copolymerization with the different methacrylate-based
monomers, hence limiting its versatility. Nonetheless, PFTR studies on a block
copolymer containing PFSty and PFPMA moieties, which was synthesized by
RAFT polymerization with precise control over the molar mass, dispersity, and
functional group incorporation, revealed that PFPMA motif was not inert to PFTR
conditions [25]. Indeed, under optimized reaction conditions (1 equiv base, i.e.
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and 5 equiv thiol) used for the PFTR,
the PFPMA units of the above-mentioned block copolymer were more susceptible
to thiol substitution compared to PFSty units. It was also observed that, in addition
to the para position, both meta positions of PFPMA are also reactive towards thiols.
A highly interesting class of acrylic and methacrylic PFP monomers, which are
synthesized by the virtue of multicomponent Passerini three-component reactions
[26], have been recently reported by Roth and coworkers [27]. Subsequently, a series
of well-defined homopolymers (9700 < M n < 41 800 g mol−1 , 1.12 < D - < 1.19) and
copolymers of the resulting monomers were prepared by RAFT polymerization.
PFTR of the pendent PFP moieties was efficiently performed with a range of
aromatic, glycosidic, and primary, secondary, and tertiary aliphatic thiols within
3–80 minutes, hence resulting in well-defined functional products in the absence
of any observable side reactions. The efficiency of the PFTR was dependent on the
nature of both thiols and base. In other words, in the presence of a weak base such
as Et3 N, acidic thiol derivatives (e.g. thiophenol) are quantitatively undergoing
PFTR in 69 minutes, while utilization of strong base drives the PFTR to completion
within three minutes for less acidic thiol derivates (e.g. 1-octanethiol).
Alternatively, the group of Roth synthesized a novel methacrylic monomer,
namely, pentafluorobenzyl methacrylate (PFBMA, Scheme 18.3), which was for
the first time polymerized via RAFT and further employed in PFTR [28]. In fact,
PPFBMA homopolymers (8600 < M n < 19 800 g mol−1 , 1.14 < D - < 1.29) reacted
quantitatively through para-fluoro substitution with a range of thiols (typically
1.1 equiv of thiol) in the presence of base (DBU or Et3 N) within one hour under
18.4 p-Nitrophenyl Esters and Their Derivatives 835
ambient conditions. Interestingly, no ester cleavage or substitution of ortho- or

meta-fluorides was observed implying a functional group tolerance and the regios-
electivity of the PFTR, respectively. Furthermore, in order to introduce structural
diversity, the PFBMA unit was reacted with arguably the most important class
of nucleophiles for polymer modification, i.e. amines. Contrary to the PFPMA
and PFPA analogues, reactions of PFBMA with various amines did not result in
an ester cleavage via amidation. Indeed, although with less efficiency, a selective
and quantitative substitution of the para-fluoride with amines took place, even if
the reactions were conducted at higher temperatures (i.e. 60 ∘ C) and utilizing an
excess of amines (2.5 equiv). Unfortunately, primary amines delivered products with
di-substitution and slightly increased dispersity (Ð = 1.27), hence indicating that the
efficiency of the post-polymerization functionalization of the polymer-tethered PFB
groups is largely restricted by the availability of functional thiols. Comprehensively,
the group of Roth expanded the toolbox of efficient chemistries that utilize the
para-fluoride of PFBMA and the related Passerini ester–amide methacrylate deriva-
tives, by introducing the quantitative azide–para-fluoro substitution reaction [29].
The above-mentioned monomers were polymerized under RAFT conditions and
reacted with sodium azide in DMF at 80 ∘ C within 60–90 minutes. The respective
azide-modified polymer can undergo three different sequential post-polymerization
modifications, i.e. prototypical click reaction, azide–thioacid reaction, and azide
reduction to amine. Although the prototypical click reaction was the least efficient,
requiring heating overnight and a relatively high amount of Cu(I) catalyst, the
azide–thioacid reaction proceeded under click-like conditions with full conversion
within 15 minutes at ambient temperature. Nevertheless, the poor commercial
availability of the thioacid starting materials may restrict the widespread use of this
chemistry. On the other hand, the azide reduction utilizing DL-dithiothreitol paved
the way towards primary amine-functional polymers, which were successfully
acylated in a third successive post-polymerization modification. Hence, it can be
concluded that the azide-based chemistries could be adopted as a valuable tool
for the (sequential) modification of polymers and the preparation of well-defined
multi-functional materials.
18.4 p-Nitrophenyl Esters and Their Derivatives

In comparison to the growing popularity of the RAFT polymerization of monomers
possessing the NHS and PFP active ester groups, p-nitrophenyl (PNP) active
ester derivatives (Scheme 18.4), which are known for the last 50 years [30], are
considerably less recognized in the field of RAFT polymerization. Although the
advantages of the PNP monomeric derivatives arise from the UV/Vis spectro-
scopically observable p-nitrophenyl phenol via aminolysis, the control over the
polymerization of PNP bearing monomers is slightly challenging because of their
inherent properties as inhibitors/retardators in radical polymerizations and their
susceptibility to produce radicals when heated. Nonetheless, Hu and coworkers
reported for the very first time the synthesis of well-defined PNP-functionalized
polymers based on poly(p-nitrophenyl acrylate) (PPNPA) by RAFT polymerization

[31]. Interestingly, the polymerization was performed in bulk in the presence of
1-(ethoxy carbonyl)prop-1-yl dithiobenzoate (EPDTB) as the CTA and yielded
well-defined PPNPAs (2500 < M n < 11 000 g mol−1 , 1.02 < D- < 1.18). The latter were
further utilized as macro-CTAs for the synthesis of block copolymers with Sty. The
block copolymer PPNPA-b-PS (D - = 1.13) was self-assembled in nitromethane and
subsequently cross-linked with ethylenediamine at ambient temperature to afford
stable nanoparticles. The methacrylate analogue of PNP (i.e. PNPMA, Scheme 18.4)
was polymerized in DMSO using cumyl dithiobenzoate as the RAFT agent by
Maynard et al. [32], and well-defined PPNPMAs (7700 < M n < 19 400 g mol−1 ) with
slightly broader molecular weight distributions (1.15 < D- < 1.29) were obtained in
comparison to PPNPA reported by Hu and coworkers. Nevertheless, the PPNPMA
homopolymer showed considerably high reactivity with amine derivatives (86%
conversion with 10-fold excess) in the presence of Et3 N as a base.
NO2 O O
NO2 O
O
O O
O NO2
PNPA PNPMA PNPC
Scheme 18.4 Some of the most common PNP monomers and their carbonate general
structure derivatives.
Another successful attempt to polymerize a PNP active ester was accomplished

by the virtue of its carbonate analogue (PNPC, Scheme 18.4) [33]. Accordingly,
a monomer with a functionality of PNPC connected to the methacrylate via a
spacer composed of a disulfide linkage and self-immolative linker was copoly-
merized via RAFT. Unfortunately, the conversions of the polymerization were
rather low (18–46%), particularly because of the small release of PNP, which
inhibits the polymerization. Regardless, the active PNP carbonate ester groups
within the copolymer were reacted with an amine derivative of an anticancer
drug to obtain a water-soluble prodrug with a molecular weight in the range of
6000 < M n < 13 000 g mol−1 with D
- < 1.30.
18.5 Miscellaneous Activated Ester Functional Group

Transformations
In the following discussion, we will focus on examples of polymers featuring less
popular activated ester groups, which are considerably limited compared to the vast
literature available on NHS, PFP (PFB), and PNP active ester-based polymers.
18.6 Acetone Oxime (AO)

The acetone oxime (AO) moiety, which exhibits good solubility in various organic
solvents, was introduced as a new class of activated ester derivatives polymerizable
18.8 p-Dialkylsulfonium Phenoxy Ester (DASPE) 837
under conventional and photo-induced RAFT conditions [34]. Polymers of the

acrylate derivative of AO (AOA, Scheme 18.5) were obtained with well-defined
structure with an apparent number-average molecular weights in the range of
4700 < M n < 51 200 g mol−1 (1.19 < D
- < 1.31). The outstanding advantage of these
polyacrylate active esters is their high efficacy to transform themselves into
poly(N-isopropylacrylamides) (PNIPAM) simply by the polymer analogous reaction
with isopropylamine.
O O
S
N O O
O
O O O
AOA MSAA APDMST
O CF3 O CF3 O
O CF3 O CF3
N(Boc)2
HFIPA HFIPMA DBAm
Scheme 18.5 Selection of some less common activated ester monomers.
18.7 Salicylic Acid (SA)

Among the manifold activated ester building blocks, the ones based on salicylic
acid (SA) are of great interest, especially in the field of biological applications,
because of their broad availability, cheap prices, and inherent low cytotoxicity.
Therefore, RAFT polymerization of the methyl ester derivative of SA acrylate
(MSAA, Scheme 18.5) [35] was performed in the presence of DDMAT as a CTA in
dioxane at 65 ∘ C to deliver homopolymers in the range of 4400 < M n < 15 900 g mol−1
(1.19 < D
- < 1.25). Kinetic studies showed that PMSAA has a lower reactivity towards
primary and secondary amines during the post-functionalization reaction when
compared with PPFPMA.
18.8 p-Dialkylsulfonium Phenoxy Ester (DASPE)

In order to induce an external stimuli triggered reactivity switching via polymer
analogous reactions, Kakuchi et al. [36] developed a novel monomer, featuring
para-dialkylsulfonium phenoxy ester moieties, namely, 4-acryloxyphenyldimethyl-
sulfonium triflate (APDMST, Scheme 18.5), which is further readily reactive under
RAFT polymerization conditions in the presence of pentafluorophenyl-(4-phenyl-
thiocarbonylthio-4-cyanovalerate) as a CTA. Although the reactive PAPDMST
reacted selectively with amines, demonstrating typical activated ester behaviour,
PAPDMST was also successfully converted to its deactivated ester state by
thermo-triggered demethylation. As anticipated, the nonreactive polymer did not

afford a conversion with amines, hence featuring a “switched off” reactivity.
18.9 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP)
Although the reactivity of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) derivatives

is considered to be lower than, e.g., their p-nitrophenyl derivatives, HFIP esters
avoid facile side reactions even at elevated temperatures and prevent amino acid
racemization. Attempts to polymerize acrylate- and methacrylate-based HFIP
esters (e.g. HFIPA and HFIPMA, Scheme 18.5) under controlled conditions via
RAFT mediated by 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid were only
successful for HFIPMA and resulted in homopolymers and block copolymers
with adjustable molecular weight (16 400 < M n < 37 900 g mol−1 ) and narrow
molecular weight distributions (1.15 < D- < 1.30) [37]. Indeed, HFIP esters enabled
a quantitative polymer analogous reaction with various water-soluble amines.
The only restriction of the reactions is the formation of the non-acidic volatile
by-product, i.e. HFIP, which on the other hand tolerates manifold functional groups
and promotes the straightforward polymer of the water-soluble methacrylamide
polymers. Nevertheless, because of the toxic nature of the HFIP, the utilization of
these polymers is still controversial.
18.10 Di(Boc)-Acrylamide (DBAm)
Although the field of active ester derivatives is broad, the activation of amide
moieties is less investigated largely because of their inherently lower suscep-
tibility toward nucleophilic substitution. Surprisingly, the activation of amide
derivatives through the introduction of π-electron-withdrawing groups (such as
tosylate or tert-butyloxycarbamate, Boc) on the amide nitrogen rendered more
electrophilic character to the carbonyl and also enhanced the susceptibility of
the amides towards nucleophilic substitution [38]. Accordingly, a new activated
acrylamide monomer, di(Boc)-acrylamide (DBAm, Scheme 18.5), possessing the
above-mentioned properties, was developed [39]. DBAm was subjected to RAFT
polymerization utilizing a trithiocarbonate derivative as CTA. Subsequently, the
obtained well-defined homopolymers with M n up to 11 000 g mol−1 (Ð = 1.27) were
modified via nucleophilic substitution reaction in the presence of both amines and
alcohols to yield the corresponding polyacrylamides and polyacrylates, respectively.
Even though less nucleophilic secondary amines and alcohols required slightly
harsher conditions, the isolated post-modified polymers remained intact during the
modification. However, the final polymers also contained a putative cyclic imide
repeating unit, likely as a result of base-promoted cyclization of adjacent DBAm
units. Despite this, these results expanded the potential of the DBAm active moiety
within the field of advanced macromolecular engineering.
18.12 Alkyl Halide 839
18.11 Acyl Chloride
Another group of activated ester substitutes, the acyl chloride monomers, are an
old class and well-known activated carboxylic acid derivatives that can be subse-
quently modified by a broad range of alcohols and amines in order to quantita-
tively obtain the related esters and amides. Such monomers are the best choice for
post-polymerization modification at preparative/industrial scale, as the acyl chloride
monomers are themselves produced at industrial scale, the produced chloride salt
does not necessitate a heavy work-up, and as the reactions allow fast and quantitative
conversion of the reactant to a large scope of products with a satisfying atom econ-
omy. Acyl chloride monomers also play an important precursor role for the synthesis
of functionalized monomers. Nevertheless, the main drawbacks of such acyl chlo-
ride monomers remain in their incompatibility with nucleophilic functional groups
as well as their high sensitivity to moisture and to nucleophilic impurities. RAFT
copolymerization of acyl chloride monomers (Scheme 18.6) such as acryloyl chlo-
ride (AC), methacryloyl chloride (MAC), or vinylbenzoyl chloride (VBzC) in styrene
were reported to form their respective statistical copolymers [40].
O O
O O
Cl Cl Br
Cl O
AC MAC VBzC BEA
O
O N Cl
Cl N
H
N N
Cl
VBC DCTOEAm
Scheme 18.6 Selection of reactive acyl, alkyl, and aryl halide monomers.
18.12 Alkyl Halide
Alternatively, the halide substitution scope can be extended to the alkyl halide. Such
post-polymerization modifications of alkyl halides preserve the good atom economy
of the acyl chloride but also broaden the range of the nucleophiles, which can be
efficiently used at a price of a reduced reactivity. Because of the undesired reactivity
of alkyl halides with radical species, the polymerization control is usually disadvan-
taged by the use of monomers bearing alkyl halides. However, the polymerization
of monomers such as vinyl benzyl chloride (VBC, Scheme 18.6) was successfully
investigated and even used as a linear precursor for the synthesis of polymer brushes
by modification of the PVBC precursor with the n-alkyl trithiocarbonate anion,
leading to a ‘grafting from’ copolymerization with styrene poly(St-graft-VBC))
[41]. Moreover, the library of monomers bearing a primary halide was broad-
ened in recent years. An example of such a monomer is bromoethyl acrylate
(BEA, Scheme 18.6) which was successfully polymerized to poly(bromoethyl
acrylate) by RAFT polymerization. Such alkyl halide polymers are predisposed to
post-polymerization modification by reaction with a large variety of nucleophiles
such as amines, alcohols, thiols, phosphites, sulfites, or azide anions [42].
18.13 Trichlorotriazine (TCT)

Related to the post-polymerization modification by the substitution of halide,
trichlorotriazine (TCT) chemistry offers interesting outcomes for the generation of
amphiphilic monomers and more generally for the homo- and heterodifunctional-
ization of monomers as amphiphilic monomers are globally difficult to handle or to
obtain by standard post-polymerization modification. Nevertheless, heterodifunc-
tionalization from a single monomer precursor may constitute a good approach
to the synthesis of amphiphilic homopolymers. For this purpose, an acrylamide
monomer bearing one cyanuric chloride ring (2,4,6-trichloro-1,3,5-triazine, TCT)
with two remaining reactive sites (DCTOEAm, Scheme 18.6) was prepared and
polymerized by RAFT polymerization. Subsequent post-polymerization modifica-
tion by nucleophilic aromatic substitution with various amines and thiols led to the
desired homodifunctionalization [43] and heterodifunctionalization [44].
18.14 Isocyanate (NCO)

The isocyanate (NCO)-containing monomers constitute a class of reactive
monomers that exhibit great tolerance for the CTA over the polymerization. Their
reactivity towards thiols, amines, and alcohols allows selective, fast, and quanti-
tative post-polymerization modifications without by-product formation. As the
organic isocyanates are industrially produced by the condensation of primary amine
and phosgene, isocyanates are commercially available in large scales. The versatility
of the post-polymerization modification of isocyanates was recently highlighted by
the RAFT polymerization of 2-(acryloyloxy)ethylisocyanate (AOI, Scheme 18.7) and
its subsequent modification with various amines and thiols, yielding the respective
urea and thiourethane derivatives. Weaker nucleophiles such as alcohols were also
reported to be converted quantitatively into urethane in the presence of a catalytic
amount of dibutyltin dilaurate [45]. A second recent publication investigated
the functionalization of polymers with isocyanate small molecules. For this pur-
pose, poly(N,N-dimethylacrylamide)-block-poly(N-(2-hydroxyethyl)acrylamide)
((PDMAm-block-PHEAm) was first prepared before further modification of the
alcohol groups of the PHEAm block with allylisocyanate or AOI, allowing a second
phase of modification by the Michael addition of a broad range of thiols in the case of
the acrylate or by the thiol-ene reaction in the case of the allyl [46]. A similar strategy
was later applied with the polymerization of N-(2-hydroxypropyl)methacrylamide
18.14 Isocyanate (NCO) 841
(HPMA) by RAFT to poly[N-(2-hydroxypropyl)methacrylamide], which is

promising in biomedical applications. Allylisocyanate was one again used in order
to obtain partial conversion of the alcohol into urethane bearing a terminal allyl for
subsequent thiol-ene chemistry with different dyes, sugars, and biological triggers
[47].
O R = O, NH, S
O
H
NCO N R O = Urethane
O O
NH = Urea
AOI O S = Thiourethane
Scheme 18.7 Overview of the post-polymerization modification available from NCO

bearing monomers.
The use of activated urea as a protected isocyanate was investigated in recent years.
For this purpose, 2-isocyanatoethyl methacrylate was protected with 3,5-dimethyl
pyrazole, imidazole, and 1,2,4-triazole in order to form three respective azole-N-
carboxamide methacrylates as protected isocyanates: (3,5-dimethylpyrazole-N-
carboxamide methacrylate (NCOP), imidazole-N-carboxamide methacrylate
(NCOI), and 1,2,4-triazole-N-carboxamide methacrylate (NCOT) (Scheme 18.8).
The three N-heterocycles showed varying reactivity in the presence of thiols
and amines, i.e. reactivity order: pyrazole < imidazole < triazole), which could
allow for selective post-polymerization modification of NCOT, NCOP, and
NCOI block copolymers. The exact mechanism is not known yet; however,
O O
H H
N R N R′
N O
H
O O
N N
HN HN HN
R= < N < N R′ = S, NH
NH = Urea
NCOP NCOI NCOT S = Thiourethane
Reactivity order
(a)
O
O ∆ O R′H
C N R′
N R N – RH
H H
(b)
O
O ∆ HO R′
N R N R – RH N R′
R′H H
H H
Scheme 18.8 Key aspects of the use of activated urea as protected isocyanate. (a)
Elimination–addition and (b) addition–elimination.
the elimination–addition and the addition–elimination mechanisms are both

acceptable candidates [48].
18.15 Azlactone
The azlactone group within monomers shares many advantages with the isocyanate
chemistry discussed above, as it allows a quantitative and quick conversion of
amines, thiols, and alcohols without by-product formation. In order to illustrate
the azlactone post-polymerization chemistry, poly(2-vinyl-4,4-dimethylazlactone)
was prepared from 2-vinyl-4,4-dimethylazlactone (VDMA, Scheme 18.9) by RAFT
polymerization and subsequently modified by ring opening by a broad range of
amines and alcohols, yielding the functionalized poly(2-acrylamido isobutyrate)s
and poly(2-acrylamido isobutyramide)s [49]. Furthermore, because of the reactivity
gap between the azlactone and the pentafluorophenyl acrylate in the presence of
nucleophiles, block PVDM-b-PPFPA and statistical poly(VDM-stat-PFPA) copoly-
mers were sequentially functionalized by two different nucleophiles, yielding
functionalized polymers bearing two functionalities dispatched with a high degree
of precision [50]. 2-vinyl-4,4-dimethylazlactone (VDMA) was also reported for the
post-polymerization functionalization of PVDMA with amino-pyrene derivative
and “grafted to” PS side chains [51].
O O
O O
O O S
O O S
O N
N
N H
O
VDMA MalA TLaMI TLaAm
H O
O O
N
S S S
O O S N
TLaSt PDSMA
Scheme 18.9 Selection of common azlactone, anhydride, thiolactone, and disulfide

bearing monomers.
18.16 Anhydride
Another example of post-polymerization modification by ring-opening reaction is
illustrated by maleic anhydride (MalA, Scheme 18.9), which can directly be incor-
porated in the polymer backbone by copolymerization with a wide range of styrene
derivative monomers [52]. Moreover, alternative copolymerizations of the electron
poor maleic anhydride with the electron-rich vinyl acetate (VAc) or isopropenyl
acetate (IPAc) were also reported [53]. The key benefit of the introduction of such
18.19 Epoxide 843
anhydride directly in the polymer backbone consist in the post-polymerization

formation of zwitterionic pH-responsive copolymers by the anhydride ring-opening
reaction with various nucleophiles such as ethanolamine derivatives.
18.17 Thiolactone
The key advantage of thiolactones over other cyclic monomers is their capacity to
yield a stoichiometric amount of thiol directly from the initial post-polymerization
ring-opening reaction. The newly formed thiol can be subsequently reacted with
various olefins by Michael addition and thiol–ene chemistries. For example,
RAFT copolymerization of thiolactone-functionalized styrenic monomer (TLaSt,
Scheme 18.9) with styrene yielded poly[St-co-(TLaSt)]. The ring opening of
the thiolactone by several primary amines was reported and subsequent
thiol–ene reactions from the freshly formed thiols were achieved [54]. In a
similar way, RAFT copolymerization of thiolactone-functionalized acrylamide
monomers (TLaAm, Scheme 18.9) and N-isopropylacrylamide (NIPAM) yielded
to poly[(NIPAM)-co-(TLaAm)]. Ring opening was once again achieved with
different primary amines and the formed thiol reacted this time by Michael
addition to the relative acrylate esters [55]. Finally, the RAFT copolymer-
ization of thiolactone-functionalized maleimide (TLaMI, Scheme 18.9) with
N-isopropylacrylamide (NIPAM) or styrene were also reported and yielded the
expected poly[(NIPAM)-co-(TLaMI)] and poly[(St)-co-(TLaMI)] copolymers. The
expected ring-opening of the thiolactone with several primary amines followed by
Michael addition was also reported [56].
18.18 Thiol Exchange (Disulphide)/Michael

Addition/Thiol–Ene
Concerning the thiol–disulfide exchange chemistry, the RAFT copolymerization of
pyridyl disulfide ethyl methacrylate (PDSMA, Scheme 18.9) and poly(ethylene gly-
col) methacrylate (PEG-MA) yielded poly[(PDSMA)-co-(PEG-MA)]. Post-polymeri-
zation modification by thiol–disulfide exchange yielded a random copolymer with
chemically, physically, and biologically responsive properties [57]. A key aspect to
highlight in the thiol–disulfide exchange, the thiol–ene, and the Michael addition
post-polymerization modification is their incompatibility as first modification meth-
ods as the thiol and the alkene are not well tolerated during RAFT polymerization
or more generally during radical polymerization.
18.19 Epoxide
Epoxide (oxirane) chemistry is widely employed at an industrial scale for the
production of cross-linked resins and adhesives. Indeed, in the presence of a
catalytic amount of Lewis acid/base in an aprotic medium, cross-linking by

ring-opening polymerization (CROP/AROP) is favoured. However, by varying the
post-polymerization modification conditions, the ring-opening chemistry of oxi-
ranes can yield new outcomes. By changing the reaction conditions with an excess
of nucleophile in a protic medium, the polymerization can be totally avoided and
a quantitative functionalization of the initial polymer with α-substituted-β-hydroxy
groups can be achieved. For this purpose, RAFT block copolymerization of
glycidyl methacrylate (GMA, Scheme 18.10) with pentafluorostyrene (PFSty),
styrene, methyl acrylate, or butyl acrylate yielded the respective PGMA block
copolymers. Subsequent hydrolysation of the epoxides into diol resulted in an
amphiphilic block copolymer in the case of the PGMA-b-PPFSty copolymer [58].
The post-polymerization modification by a selection of nucleophiles including
amines, thiols, phenol, and azide was also investigated [59]. Furthermore, the
RAFT block copolymerization of 4-vinylphenyloxirane (VPO, Scheme 18.10)
with styrene was also reported and the subsequent CBr4 - and BF3 -catalysed
ring-opening reactions of the epoxides were investigated for a large choice of
alcohols [60]. As the last example, employment of unsaturated fatty acid has been
reported. The RAFT polymerization of a methacrylate-functionalized oleic acid,
2-(methacryloyloxy)ethyl oleate (MAEO, Scheme 18.10) was reported and the
olefinic group of PMAEO was subsequently modified by thiol–ene chemistry or by
mCPBA epoxidation, followed by the ring opening of the epoxide with diamine as
a cross-linker [61]. Unlike the oxirane, the ring-opening reactivity of the aziridine
can be greatly moderated by the third substituent present on the nitrogen as the
presence of electron-withdrawing groups (EWGs) and aromatic substituents will
lead to an increase in reactivity and electron-donating groups (EDG) to a decrease.
Furthermore, the post-polymerization modification of the α-substituted-β-amino
groups also allows great versatility in the functionality of the aziridine poly-
mers. Finally, the RAFT polymerization of a methanesulfonyl-protected aziridine
N-mesyl-2-(4-vinylphenyl)aziridine (NMVPA, Scheme 18.10) yielded PNMVPA in
a controlled fashion [62].
O
O NMs
O O
GMA VPO NMVPA
O
O
O
6 7
O
MAEO
Scheme 18.10 Selection of epoxide, epoxide precursor, and aziridine monomers.

18.21 Triazolinedione 845
18.20 Diels–Alder Cycloaddition

The Diels–Alder [2+4] cycloaddition was widely employed during the last century
in chemistry and in the last decades in the end-functionalization of polymers. Con-
sidering the temperature-driven nature of the equilibrium reaction, thermally trig-
gered self-healing of Diels–Alder cross-linked polymers was investigated. In this
topic, the RAFT polymerization of furfuryl methacrylate (FMA, Scheme 18.11) and
its post-polymerization cross-linking by addition of bismaleimides derivatives was
achieved [63].
Diels–Alder
O
O O N
O N O
O O O
O O
FMA Maleimide
O
O N
O N
O N O O O
O O N
N N
O
TAD
Alder-ene
O
N
O HN O N
N O O
O
O N N
O TAD
N
Scheme 18.11 Similarities between Diels–Alder and Alder–Ene reactions.
18.21 Triazolinedione
In a similar way, the highly electron-deficient double bond of the triazolinedione
(TAD) functional groups allows for an ultrafast Diels–Alder [2+4] cycloaddition
at room temperature. RAFT polymerization of 2-hydroethyl acrylate (HEA)
yielded PHEA. Post-polymerization modification by reaction with hexa-2,4-dienyl
ester succinic anhydride yielded the desired poly(HEA-diene). TAD-terminated
poly(methyl methacrylate) (PMMA), poly(tert-butyl acrylate) (PtBA), or PS
addition yielded in a one minute timescale the expected PHEA-g-PMMA],
PHEA-g-PtBA], and PHEA-gt-PS] [64]. Similarly, to the TAD-diene Diels–Alder
chemistry, the retro Alder–Ene reaction is available at high temperature. Indeed,
the presence of indole with TAD allows an ultrafast Alder–Ene reaction at room
temperature. For example, RAFT copolymerization of 2-hydroxyethyl methacrylate
(HEMA) and methyl methacrylate (MMA) yielded poly[HEMA-co-MMA]. The
post-polymerization incorporation of the indole groups via Steglich esterification
was successfully followed by an ultra-fast Alder–Ene reaction with a bifunctional
1,2,4-triazoline-3,5-dione (TAD) cross-linker [65].
18.22 Carbonyl Groups and their Derivatives

The pH-dependent condensation equilibrium taking place between a primary
amine and a carbonyl to an imine groups is well known, and its use in the
polymer field is well documented. For example, a pH-responsive RAFT triblock
copolymer (mPEO-b-PAPMAm-b-PNIPAM) was synthesized from an initial
mPEO-CTA with N-(3-aminopropyl)methacrylamide (APMAm, Scheme 18.12)
and N-isopropylacrylamide (NIPAm) as second and third block monomers. The
pH-dependent cross-linking of the central PAPMAm block with terephthaldicar-
boxaldehyde (TDA) yielded shell cross-linked (SCL) micelles, which could be
subsequently used as pH-triggered drug release carriers [66]. Nevertheless, the
scope of post-polymerization condensation of carbonyl groups is not restricted
toimine chemistry, as the more stable hydrazone, oxime, and thiooxime by their
respective condensation with hydrazine, hydroxylamine, and thiohydroxylamine
were successfully reported. In order to illustrate the versatility of condensa-
tion products, the RAFT block polymerization of 2-(4-formylbenzoyloxy)ethyl
methacrylate (FBEMA, Scheme 18.12) with MMA yielded (PFBEMA)-b-PMMA.
Post-polymerization modification by the condensation of the aldehyde with
tert-butylhydrazide, O-benzylhydroxylamine, or S-aroylthiohydroxylamine yielded
the related hydrazone, oxime, and thiooxime, respectively. Such thiooximes were
reported to degrade in presence of thiol at neutral pH with the formation of H2 S [67].
Finally, the acid-catalysed dynamic equilibrium of β-ketoesters and enaminones
O O O O
O O
N NH2 O O
H O O O
APMAm AAEMA FBEMA
H
O N S NH
N N N N
Imine Oxime Hydrazone Thiooxime Enaminone
Scheme 18.12 Overview of the carbonyl post-polymerization modifications and some

related examples of monomers.
18.23 Copper-Catalysed Azide–Alkyne Cycloaddition (CuAAC) 847
in the presence of primary amine can also be highlighted. RAFT polymerization

of 2-(acetoacetoxy)ethyl methacrylate (AAEMA, Scheme 18.12) yielded PAAEMA.
Statistical and block copolymerization with poly(ethylene glycol) 500 methacrylate
(PEG-500-MA) or MMA yielded the expected copolymers. Post-polymerization
modification of the β-ketoesters by TsOH-catalysed condensation reactions with
primary amines was achieved [68].
18.23 Copper-Catalysed Azide–Alkyne Cycloaddition

(CuAAC)
In the click chemistry realm, copper-catalysed azide–alkyne cycloaddition (CuAAC)

is known to be one of the most versatile and tolerant orthogonal reactions, and
its application in the polymer field has been widely investigated since its initial
report by Sharpless et al. [69] Nevertheless, both azide and alkyne groups may
suffer from side reactions in the presence of radical species, which can negatively
affect polymerization outcomes. Indeed, side reactions between the RAFT CTA and
the azide may occur when spatially close. Furthermore, any electron-withdrawing
groups should be avoided next to the alkyne group to avoid any incorporation of the
alkyne into the polymer backbone. As an example, a one-pot RAFT polymerization
of a common alkyne monomer, propargyl methacrylate (PgMA, Scheme 18.13),
in tandem with a CuAAC reaction with azide-functionalized galactose, yielded
the desired glycopolymer. Subsequent end-group modification by aminolysis of
the CTA yielded a thiol, which was thereafter employed for the functionalization
of a gold surface [70]. In the case of the presence of azido groups within the
polymer backbone, a RAFT copolymerization of HPMA and N-(3-azidopropyl)
methacrylamide (AzMA, Scheme 18.13) yielded poly[(HPMA)-stat-(AzMA)].
Post-polymerization modification by CuAAC with propargyl dye, propargyl
PEG, and biosensor (prop-2-yn-phosphocholine (PPhCh)) yielded the desired
polyfunctionalized copolymers [71].
O O
N N3 O Cl
O
H
PgMA AzMA VBA VBC
O
N
N3 N O
N
O Azide Nitrone Nitrile oxide
DBCO DIBO
Scheme 18.13 Selection of CuAAC-, SPAAC-, SPANOC-, and SPANC-related structures.

18.24 Strain-Promoted Azide–Alkyne Cycloaddition

(SPAAC)
A related catalyst-free azide–alkyne reaction, the strain-promoted azide–alkyne
cycloaddition (SPAAC), can also be highlighted. In order to favour the [2+3]
cycloaddition, the enthalpy gain during the reaction is highly increased by the high
strain energy contained in the cyclooctyne ring. An example of such chemistry was
investigated with the RAFT polymerization of PFPMA and the post-polymerization
substitution of PFP by dibenzocyclooctyne-amine (DBCO-NH2 , Scheme 18.13) and
ethanolamine, followed by the SPAAC click reaction with azido-modified mannose
and galactose, yielding the desired homogeneous and heterogeneous glycopolymers
[72].
18.25 Nitrone– and Nitrile Oxide–Alkyne

Cycloadditions (SPANOC/SPANC)
Next to the SPAAC chemistry, two similar [2 + 3] dipolar cycloadditions promoted by
the high strain enthalpy of cyclooctyne rings were also published. By substituting the
azido group by a nitrone or a nitrile oxide group, strain-promoted alkyne–nitrone
cycloadditions (SPANC) and strain-promoted alkyne–nitrile oxide cycloaddi-
tions (SPANOC) were successfully reported. RAFT copolymerization of VBC
(Scheme 18.13) and styrene, followed by chain extension with 4-vinylbenzaldehyde
(VBA) and styrene, yielded the expected P(VBC-co-St)-b-P(VBA-co-St). Azide and
oxime functionalities were then introduced at the VBC and VBA units, respectively.
Post-polymerization modification at the azide (SPAAC) and oxime (oxidized with
(diacetoxyiodo)benzene [BAIB] followed by SPANOC) moieties yielded orthogonal
bifunctionalization with a selection of several dibenzocyclooctynol (DIBO) deriva-
tives. A similar route was used to post-functionalize polymers with nitrone groups
for DIBO-functionalization via SPANC [73].
18.26 Cross-coupling Reactions

Among the post-polymerization modification methods, the formation of
C—C bonds is mainly achieved by cross-coupling reaction. As such Suzuki,
Buchwald-Hartwig, and Sonogashira cross-couplings were successfully reported
for the post-polymerization modification of RAFT polymers. RAFT polymeriza-
tion of N-[2-(4-bromophenyl)ethyl]acrylamide (BPEAm, Scheme 18.14) yielded
PBPEAm. Chain extension was achieved by block copolymerization with NIPAM,
yielding the expected PBPEAm-b-PNIPAM], from which Suzuki cross-couplings
with a range of aromatic boronic acid were achieved [74]. RAFT block copoly-
merization of 4-bromophenyl vinyl sulfide (BPVS, Scheme 18.14) and NIPAM
yielded PBPVS-b-PNIPAM. RAFT copolymerization of trimethylsilyl propar-
gyl methacrylate (TMS-PgMA, Scheme 18.14) and MMA yielded the desired
18.28 Multicomponent Reactions (MCR) 849
poly[(TMS-PgMA)-co-MMA]. Post-polymerization deprotection of the terminal

alkyne and subsequent cross-linking by a Sonogashira cross-coupling reaction with
para-diiodo benzene as a cross-linking agent was achieved [75].
O Br Br O
O
O BO
TMS N S
H
TMS-PgMA BPEAm BPVS pBSt
Scheme 18.14 Selection of monomers for cross-coupling and boronic acid/diol

condensation.
18.27 Boronic Acid/Diol Condensation
Aromatic boronic acids present in Suzuki cross-coupling were reported to achieve

quantitative condensation in the appropriate basic pH range with diol-rich
molecules such as sugars. In the recent literature, a pinacol-protected boronic
acid monomer, 4-pinacolatoborylstyrene (pBSt, Scheme 18.14), was reported to be
efficiently block RAFT copolymerized with N,N-dimethylacrylamide (DMA), yield-
ing PpBSt-b-PDMA. Efficient post-polymerization deprotection by trifluoroacetic
acid addition yielded a polymer bearing boronic acid functional groups [76].
Furthermore, the boronic acid polymer was also obtained by an alternative pathway
from PFPA (Scheme 18.3) via post-polymerization substitution. RAFT block copoly-
merization of N-acryloylmorpholine (AcM) and PFPA yielded PAcM-b-PPFPA.
Substitution of the PFP by (3-aminomethyl) phenyl boronic acid and glycine were
achieved to form glucose delivery pH-responsive materials [77].
18.28 Multicomponent Reactions (MCR)
The so-called multicomponent reactions (MCR) consist of a series of efficient

and versatile one-pot reactions involving three or more molecules reacting
to form a single product. For example, post-polymerization modifications by
Biginelli reactions were recently investigated several times. The RAFT polymer-
ization of 2-(acetoacetoxy)ethyl methacrylate (AAEMA, Scheme 18.15) yielded
poly[2-(acetoacetoxy)ethyl methacrylate] (PAEMA). Post-polymerization mod-
ification by Biginelli reaction with urea and benzaldehyde in the presence of
catalysts was achieved [78]. Secondly, the six possible RAFT triblock polymers
consisting of 2-(acetoacetoxy)ethylacrylamide (AAEAm), N,N-dimethylacrylamide
(DMAm), and 4-acryloylmorpholine (AMPL) were synthetized. Five different
benzaldehyde derivatives with urea or thiourea were used in order to form a
6 × 5 × 2 combinational block copolymer library including post-polymerization
modification by Biginelli chemistry [79]. Thirdly, an example of post-polymerization
modification involving the Kabachnik–Fields reaction was also reported in recent

years with the RAFT polymerization of N-(3-aminopropyl)methacrylamide (APMA,
Scheme 18.15). Post-polymerization modification by the Kabachnik–Fields reaction
was achieved with diethylphosphite and a range of aromatic and aliphatic aldehydes
to form the expected poly(aminophosphonate) (polyAPP) polymers. A one-pot
approach was also successfully investigated [80].
O H
N O
O O
O Biginelli reaction
O NH
O O O
O
AAEMA
O
Kabachnik-fields
O NH3Cl O reaction
O
O
O N P
APMA H
O
Scheme 18.15 Overview of the Biginelli and the Kabachnik–Fields reactions from the
corresponding monomer examples.
18.29 Metal–Ligand Coordination
Beside the classical post-polymerization reactions via the modification of a covalent

bond, the creation of ligand–metal bonds results in the incorporation of a metal
complex directly in the polymer structure. Such polymers containing active metal
complexes may play an interesting role in catalysis. In this regard, the RAFT
polymerization of various ligand bearing monomers has been published in the
recent years. Statistical copolymerization of MMA with bipyridine-MA and/or
triphenylphosphine-MA was achieved. Post-polymerization modification by metal
incorporation (Pt, Pd, and Au) was investigated (Scheme 18.16) [81]. In a different
approach, a Zn(II) phthalocyanine cross-linked polymer was obtained from the
RAFT polymerization of 2-methyl-acrylic acid 6-(3,4-dicyano-phenoxy)-hexyl ester
and its post-polymerization modification by the formation of polymeric Zn(II)
phthalocyanine at high temperature [82].
18.30 Bioapplications of Reactive Polymers

In the following paragraphs, selected examples of applications of reactive polymers
in a biological context will be presented. Noteworthy, reactive polymers prepared via
RAFT polymerization also find application in other areas but will be omitted within
the present chapter.
PPh2 O CN
O O
O O N
O 2 O
N 4 O CN
O
Ph2 N N
P N
AuCl O
O
O N Zn N
N
O 4 O
O N MCl2 N N N
M = Pd, Pt
Scheme 18.16 Selection of monomers sharing the capacity to coordinate metal cations.
18.31 Drug Delivery

Amphiphilic block copolymers (ABCs) are widely investigated for biomedical and
pharmaceutical applications owing to their self-assembly into nanostructured
morphologies depending on the solvent properties. Self-assembled amphiphilic
macromolecules, for example, with a hydrophilic shell and a hydrophobic core, have
become some of the most attractive vehicles for insoluble drugs and biomolecules
because of their advantageous stability, biocompatibility, and triggered drug release.
The combination of RDRP techniques and post-polymerization modification has
been extensively employed in engineering functional block copolymers for various
applications. In this regard, the preparation of well-defined amphiphilic block
copolymers was mainly achieved by RAFT polymerization of reactive monomers.
Stenzel et al. reported the synthesis of amphiphilic block copolymers based on
poly(N-(2-hydroxypropyl)methacrylamide (PHPMA) and the reactive PFPMA via
RAFT polymerization, obtaining a macroRAFT stabilizer (Scheme 18.17) [83]. A
successive cross-linking by chain extension of the block copolymer in the presence
of divinyl cross-linkers generated cross-linked nanocapsules. This allowed for
the encapsulation of a hydrophilic cancer drug such as Gemcitabine inside these
polymeric nanocapsules, which was achieved in a one-pot process via the inverse
mini-emulsion periphery RAFT polymerization (IMEPP) approach, stabilized
by the prepared block copolymers. Because of the presence of highly reactive
PFP moieties, a functional biocompatible glucosamine was then introduced via
post-polymerization modification yielding glycopolymer nanocapsules. Exposure to
glutathione led to the degradation of the cross-links of the loaded nanocapsules in
water and hence their disintegration. These biocompatible glycopolymer nanocap-
sules showed potential against pancreatic cancer cells, offering a new drug delivery
carrier of cancer drugs.
Similarly, Zentel et al. proposed a synthetic approach to prepare multi-
functional PHPMA-based copolymers by RAFT polymerization and subsequent
F
F F
F F
O O O O O
CN MeOH, 70 oC CN DMAc, 70 oC CN
S S S S S S
HO HO n
HO
n m
Ph O Ph F Ph
HN O F HN O
N F
HO O HO
H
OH
O F
F
Scheme 18.17 The synthesis of functional block copolymer featuring PFP-active ester via RAFT (macroRAFT stabilizer).
post-polymerization modification of activated ester precursor polymers via

aminolysis [84]. PFPMA and lauryl methacrylate (LMA) precursor polymers
offered a platform to prepare homo-, statistical, and block copolymers of PHPMA
by subsequent polymer-analogous reaction as represented in Figure 18.1. These
libraries of novel amphiphilic HPMA-LMA copolymers that self-assemble into
nano-sized objects have unique properties for in vitro and in vivo applications. The
multi-functional HPMA-LMA copolymers prepared by the reactive ester chemistry
have high potential as drug carriers in the field of tumour immunotherapy.
Further, Theato and coworkers have utilized active ester chemistry to pre-
pare glucose-responsive block copolymers and glycopolymers from a single
reactive prepolymer made by RAFT polymerization containing polyPFPA as a
hydrophobic block [85]. 3-Aminophenylboronic acid, 3-amino-1,2-propanediol, and
D-glucosamine were easily incorporated within the polymer by post-polymerization
modification under mild conditions. Of note, the reactive polyPFPA-based precur-
sor provided a straightforward synthetic approach for the preparation of boronic
acid containing polymers that are otherwise incompatible with direct controlled
polymerization. All polymers obtained showed an identical degree of polymeriza-
tion and low dispersities. The self-assembly behaviour of these polymers could be
adjusted by boronic acid and diol complexation, forming cross-linked micelles with
diameters in the 100 nm range. Upon the addition of glucose, the disintegration of
the polymeric micelles occurred under neutral conditions depending on glucose
concentration. Finally, a controlled release of insulin from the cross-linked micelles
was achieved under diabetic glucose concentrations, offering a very promising
candidate for self-regulated insulin delivery.
The synergy of RAFT polymerization associated with post-polymerization mod-
ification techniques allows the synthesis of a broad range of complex structures
and architectures for drug delivery applications. A similar synthesis involving
the incorporation of multiple functional groups in the polymer structure with-
out post-polymerization modifications is otherwise very limited. For example,
Sanyal et al. reported the synthesis of multi-functional copolymers based on PEG,
a furan-protected maleimide-containing methacrylate (FuMaMA) monomer,
and a hydroxyl group containing methacrylate (HEMA) monomer using RAFT
polymerization (Figure 18.2) [86]. The thermo-responsive self-assembly of these
copolymers and subsequent cross-linking via thiol-maleimide click reaction
between a dithiol-based cross-linker and maleimide reactive groups on the copoly-
mers resulted in multi-functionalized nanogels. The cross-linked nanogels were
successfully conjugated to an amine-containing anti-cancer drug (i.e. doxorubicin)
through acid-labile carbamate linkages. Additionally, the reactive maleimide groups
were modified by thiol-containing peptides and thiol groups from the cross-linker
were utilized to install a maleimide-containing fluorescent dye. The fabrication
strategy offered an interesting platform to allow the multi-functionalization of
polymers for targeted applications in drug delivery.
Dhara and coworkers synthesized a dual-responsive PNIPAM-b-PAA copolymer
by RAFT polymerization and magnetic iron oxide nanoparticles by aqueous copre-
cipitation of 3-aminopropyl-triethoxysilane [87]. PNIPAM-b-PAA copolymers and
NC S
S 1) 2)
HO O O O O O
O O
F F
F F
and F F
F F
O O O O F
F F
F
F F
F
Excess AIBN Excess AIBN Excess AIBN
NC CN NC CN NC CN
n n n m
O O O O O O O O O O
F F F F F F
HO O HO O HO O
F F F F F F
F F F
H2N H2N H 2N
OH OH OH
NC CN NC CN NC CN
n
HO O HO O HO O
Self-assembly in water Self-assembly in water
(a) (b) (c)
Figure 18.1 Synthetic concept of HPMA-based copolymers derived by post-polymerization

modification – RAFT-copolymerized precursor polymers of pentafluorophenyl methacrylate
and LMA can selectively be aminolysed by 2-aminopropanol affording HPMA homo,
statistical, or block copolymers. While (a) HPMA homopolymers are highly water-soluble,
the amphiphilic HPMA-LMA statistical or block copolymers self-assemble into (b)
multicompartment or (c) compound micelles in water. Source: Reprinted with permission
from Nuhn et al. [84]. © 2014, John Wiley & Sons.
R G
C
O S f D
Dye N O
O
N O N Dox
O O
Dox NH2
O O NH
O
O ON O
R
G C SH O
O D f
HS Dye N S
Clickable-Nanogel O
Multi-functional-Nanogel
Figure 18.2 Schematic illustration of nanogels multi-functionalization. Source: Reprinted

with permission from Chambre et al. [86]. © 2018, American Chemical Society.
folic acid were then modified by the aminated iron oxide nanoparticles (NH2 -MNPs)
via EDC/NHS chemistry, yielding modified magnetic nanoparticles (Poly-MNPs)
and folic acid tethered polymer-modified magnetic nanoparticles (FA-MNPs). For
cellular imaging, rhodamine B isothiocyanate was conjugated to FA-MNPs and
doxorubicin (DOX) was loaded into Poly-MNPs and its release in vitro was achieved
under lysosomal conditions. The multi-functional magnetic nanoparticles have
the potential to be used in magnet-guided drug delivery applications and cellular
imaging.
18.32 Bio-conjugation
NHS-based polymers have drawn considerable interest in biomedical sciences

because of their fast bioconjugation with biomolecules featuring amino groups such
as proteins, peptides, or carbohydrates. Pich and coworkers copolymerized cyclic
N-vinylamides (N-vinylcaprolactam, N-vinylpiperidine, and N-vinylpyrrolidone)
with methacrylic acid N-hydroxysuccinimide ester via RAFT polymerization at
varied temperatures and in a range of solvents, obtaining copolymers with variable
chemical composition, controlled molecular weight, and narrow dispersity Ð. The
obtained water-soluble reactive copolymers with NHS-ester groups showed fast
cross-linking with proteins containing lysine linkages, such as enhanced green fluo-
rescent protein (EGFP) and cellulase (CelA2_M2), in water-in-oil (W/O) emulsion,
resulting in fascinating biohybrid nanogels. These conjugated nanogels were proven
to be promising candidates for protein imaging and good colloidal catalysts for
depolymerization of cellulose [88]. Interestingly, the same group later also described
a controlled synthesis of pyridyl disulfide (PDS)-functionalized poly(vinyl lactams),
such as statistical reactive copolymers of poly(N-vinylpyrrolidone-co-pyridyl
disulfide ethyl methacrylate) (PVPD), poly(N-vinylpiperidone-co-pyridyl disulfide
ethyl methacrylate) (PVPID), and poly(N-vinylcaprolactam-co-pyridyl disulfide
ethyl methacrylate) (PVD), via RAFT polymerization at 60 ∘ C in anisole with
methyl 2-(ethoxycarbonothioylthio)-propanoate as a chain transfer agent
(Figure 18.3) [89]. Because of the highly reactive PDS group towards thiol
N S N
N S
O N N S S S
N N S
N N N
O O O O
S S
O S S S N
S
S O N S S N
O S N
VP VPI VCL PDSM
S
S N
PDS-functionalized
copolymers
Spin coating
–SH ligands
EGFP
Functional films with Surface PDS-functionalized Copolymers with

designed architectures engineering films designed architectures
Figure 18.3 Synthesis of reactive copolymers based on N-vinyl lactams with pyridyl disulfide side groups via RAFT polymerization and post-modification
via thiol–disulfide exchange reaction. Source: Reprinted with permission from Peng et al. [89]. © 2016, American Chemical Society.
groups via a specific thiol–disulfide exchange, the PDS-functionalized reactive

polymers were post-modified with a variety of thiol-containing functional groups
including 2-phenylethanethiol (2P), 3-mercaptopropionic acid (3M), methyl
3-mercaptopropionate (M3), 2-mercaptoethanol (2M), 2-aminoethanethiol (2A),
poly(ethylene glycol) methyl ether thiol (PEG-SH), and EGFP under extremely
mild conditions to control cell attachment and growth activity on modified polymer
films. Owing to the high potential cell adhesion and growth, surface engineering
of biocompatible PDS-functionalized copolymers with thiol-containing ligands
offered great potential in tissue engineering, medical implants, and diagnostic
molecular biology.
Li and coworkers synthesized a well-defined protected glycopolymer poly(2-(2,3,4,
6-tetra-O-acetyl-β-D-glucosyloxy)ethyl methacrylate) (PAcGlcEMA) by RAFT poly-
merization with end thiol-reactive PDS group [90]. After deprotection, pendent
glucose units were attached to polymer backbone to yield a hydrophilic gly-
copolymer poly(2-β-D-glucosyloxy)ethyl methacrylate) (PGlcEMA) with high
binding affinity for protein Concanavalin A (Con A). Reduced L-glutathione
(GSH) is an endogenous antioxidant that was conjugated to the reactive thiol
end by thiol–disulfide exchange reaction to generate peptide–glycopolymer bio-
conjugates employed for the delivery of antioxidants. O’Reilly’s group reported
decorated thermo-responsive poly[(oligo ethylene glycol) methyl ether methacry-
late] (PEGMA) polymers with superfolder green fluorescent protein (sfGFP) in
three steps (Figure 18.4) [91]. First, PEGMA with an alkyne-functional end group
was prepared via RAFT polymerization targeting different molecular weights.
Second, the fluorescent protein (sfGFP) was functionalized with non-canonical
azide-functional amino acid residues at different positions. And third, the reactive
azide moieties of sfGFP were conjugated with the alkyne-functional end group
of PEGMA using copper-catalysed alkyne–azide cycloaddition (CuAAC). The
self-assembled structures of these polymer–protein conjugates were found to be
dependent on temperature and on the site of conjugation.
Functionalized CTAs also allow a flexible installation of functional groups, either
prior to or after the polymerization, to the end group of polymers, thus enabling
enhanced delivery characteristics [10]. For example, NHS-folate-functionalized
CTAs were synthesized to prepare a diblock copolymer consisting of a dimethy-
laminoethyl methacrylate block and a dimethylaminoethyl methacrylate, butyl
methacrylate, propylacrylic acid copolymer block (poly(DMAEMA)-b-poly
(DMAEMA-co-BMA-co-PAA)) for targeted siRNA delivery (Figure 18.5). The
folate-functionalized CTA was not only found to be suitable for the synthesis of a
well-defined multi-functional diblock copolymer with narrow dispersities but also
allows for complexation and protection of siRNA and hence demonstrates an effi-
cient, specific cellular folate receptor interaction and in vitro gene knockdown [92].
Narumi and coworkers prepared maltopentaose-conjugated (Mal5 -CTA)-conjugated
chain transfer agent bearing NHS-activated ester moieties for RAFT polymerization
[93]. The use of Mal5 -CTAs enabled the installation of maltopentaose into the
α-chain end of the polymer chain by direct RAFT polymerizations of styrene (S)
and MMA to yield Mal5 -PS and Mal5 -PMMA, respectively, resulting in Maln -hybrid
N
S N N
N3 O
S n Aggregation
sfGFP(T216) O O O N
N N
N3 n = 25, 32, 55 N
N
O N
T
4-5
N3
sfGFP(S2T216) N
N N
N3 N
N
N
sfGFP(S2)
Figure 18.4 Strategy followed for the synthesis of sfGFP-PEGMA bioconjugates via the engineering of three sfGFP analogues with T216, S2T216, and S2
site modification with pAzF before the CuAAc of alkyne-functional PEGMA. Source: Reprinted with permission from Moatsou et al. [91]. © 2015, American
Chemical Society.
18.33 Surface/Particle Modification 859
amphiphilic block copolymers (BCPs) with well-defined structures as materials for

the next generation of sustainable nanostructured bioresource-block copolymer
lithography.
Recently, Sanyal and coworkers synthesized copolymers containing a masked
maleimide group and dopamine via RAFT polymerization featuring surface
anchoring units [94]. Polymeric precursors were coated on a titanium surface
and subjected to a retro-Diels–Alder reaction using a simple thermal treatment.
Antimicrobial peptide E6, successfully conjugated to such polymer coated layers
through a Michael addition, showed antifouling and antimicrobial properties
against both Gram-positive and Gram-negative bacteria.
18.33 Surface/Particle Modification

Char and Li described the synthesis of poly(PFPA) polymer brushes grafted on silica
particle surfaces via surface-initiated (SI)-RAFT polymerization [95]. The reactive
poly(PFPA) polymer brushes were then modified with amine-containing antibodies
followed by amino-terminated PEG yielding silica particles with both PEG and anti-
body immobilized on the surface. This study demonstrates that poly(PFPA)-grafted
SiPs can be an effective alternative for providing clean protein purification and can
also be a suitable material platform for antibody immobilization (Figure 18.6).
Perrier et al. exploited the potential of 4-vinylbenzyl chloride as a functional
halogenated monomer for the introduction of chemical functionalities under
RAFT conditions [96]. They described the synthesis of uniform silica–polymer
core–shell nanoparticles via SI-RAFT utilizing a silica-supported RAFT agent in
DMF and post-polymerization modification of the pVBC-grafted silica particles
with pyren-1-ylmethyl acrylate and TEA-quaternized particles (Figure 18.7). The
incorporation of a charged group and a fluorescent moiety resulted in hybrid
nanoparticles that are sterically stable in biologically relevant conditions with
promising bio-applications. The hybrid nanoparticles are promising for cell
imaging owing to their ability to be endocytosed into human colon cancer cells.
Gopalan et al. synthesized a well-defined block copolymer poly(styrene)-block-
poly(2-vinyl-4,4-dimethylazlactone) (PS-b-PVDMA) by RAFT polymerization in two
steps [97]. The resulting block copolymers not only contain the amine-reactive azlac-
tone functional group but can also self-assemble into thin films with a hexagonally
ordered cylindrical morphology with ∼12 nm scale. Interestingly, the self-assembly
of cylinder-forming PS-b-PVDMA BCP thin films prepared by solvent annealing
with toluene revealed defect-free morphologies over large areas. The resulting
parallel and perpendicularly oriented morphologies containing reactive azlactone
functionality were post-fabricated with infused trimethylaluminium (TMA) vapour
and subsequently yielded arrays of aluminium oxide (ALO) nanowires or nanodots.
The self-assembled PS-b-PVDMA thin films containing azlactone functional groups
provide new platforms for the development of nanometre-sized hard masks for
potential applications in advanced lithography (Figure 18.8).
Gibson and coworkers demonstrated an interesting possibility to combine the
benefits of thiol coating on gold surface with the utility of a glass slide using
N N
S S O
DCC/NHS O
OH
S S S S N
CHCl3, RT
O O
O
1.
O
O
O OH
O OH O N O
O H
N S S O N
N N H O
O H H N
N O S HN N
N N H
HN N
H H2N N
H2N N N
2.
O O
O O
O
HO
N
2:1:1 + siRNA
O OH
O
O N
N H O
HN N
H
H2N N N
Figure 18.5 Synthesis of folate-CTA for polymerization of folate-functionalized diblock copolymers for siRNA delivery. Source: Adapted with permission
from Benoit et al. [92]. © 2011, American Chemical Society.
O
O Si S
O
S
PFPA monomer,
BDB, AIBN
70 °C, 43 h
O
S
O Si
n
O
O O S
F F
F F
(a) F (b)
Antibodies, 1) Amino-terminated PEG,
4 °C, overnight RT, 16 h
2) Antibodies, 4 °C,
overnight
Random copolymer Random copolymer

O O
S S
O Si O Si
m n x y z
O S O O S
O O O
O NH O
O HN F F HN
F F
F F
F
F F O
n
F CH3
Figure 18.6 Schematic for the preparation of poly(PFPA) brush via SI-RAFT polymerization
and (a) subsequent post-modification to immobilize antibody and (b) partial substitution
with amino-PEG, followed by antibody immobilization. Source: Reprinted with permission
from Son et al. [95]. © 2018, American Chemical Society.
thio–ene chemistry in tandem with RAFT polymerization [98]. They prepared two
representative thermo-responsive polymers of poly[oligo(ethylene glycol) methyl
ether methacrylate] (POEGMA) and PNIPAM functionalized with thiol at the
ω-chain ends, providing an anchor points for surface modification by a grafting-to
approach. Polymers prepared by RAFT polymerization with a thiol-end function-
ality were then grafted onto acrylated glass and silicon substrates by a ‘thiol–ene
click’ (Michael addition) (Figure 18.9). The installation of hydrophilic polymers on
surfaces is commonly limited in terms of controlled radical polymerization and the
chemical space for attachment chemistry. This ‘grafting-to’ approach gives an easy
and a straightforward approach to prepare grafted polymers and the characteriza-
tions confirmed that the PNIPAMs resulted in much higher grafting densities than
the POEGMAs. However, both POEGMA and PNIPAM resulted in a significant
decrease in protein binding because of their hydrophilicity. The polymer-coated
glass slides with their nonfouling characteristics will find application in array
applications, particularly for glycomics.
In summary, reactive polymers prepared by RAFT polymerization of various
reactive monomers provide a versatile synthetic platform for numerous applica-
tions. The advantage to not only introduce functionality along the macromolecular
Cl
S S
SiO2 i SiO2
O O
6 S S 6 n
S S
O O
ii
Cl
N
Cl
O O
S O O
SiO2 iii S
O SiO2
6
n m x
S S O
S S 20 μm
6
O n m x
O
(a) (b)
Figure 18.7 (a) Synthetic scheme of silica-supported RAFT polymerization of 4-vinylbenzyl chloride and post-polymerization modification of the
resultant core–shell nanoparticles and (b) confocal microscopy image of human colon cancer cells after two hours of incubation with TEA-quaternized
SiP-p(VBC-co-PyAc) particles. Source: Adapted with permission from Moraes et al. [96]. Copyright 2013, American Chemical Society.
NH2
+
O N HN O
I O
O
NH
(a) I
I-Ar-NH2
Iodoamine
surface coupling
Al2O3
Alumina vapor
infiltration
200 nm
(b)
Figure 18.8 (a) Scheme showing the ring opening of azlactone groups in the PVDMA block
of PS-b-PVDMA by iodobenzylamine. (b) The post-modification of reactive azlactone and
the resultant morphologies. Source: Adapted with permission from Choi et al. [97].
Copyright 2016, American Chemical Society.
RS RS
O O O O
O O O O
3 3
HO Si O Si OH HO Si O Si OH
OH OH
H2SO4 O O O
OH OH 2% Silane O
H2O2 in Toluene R–SH*
SiO2
*R-SH is pOEGMA or pNIPAM,

with or without the RAFT end group
O
HS HS
OH
O X CN O X
O NH
Figure 18.9 Schematic representation of the immobilization of polymers onto acrylate

silane-functionalized glass and silicon surfaces. Source: Reprinted with permission from
Biggs et al. [98]. Copyright 2016, American Chemical Society. Licensed under CCBY 4.0.
chain but also easily at the chain ends provides the synthetic basis for polymers in
numerous applications.
18.34 Conclusion and Outlook
The recent years have witnessed an enormous development of new chemistries suit-
able for efficient post-polymerization modifications, especially of polymers that have
been prepared by RAFT polymerization but also other RDRP techniques. In most
cases, this has led to unprecedented synthetic access to polymers with highly defined
functionality and architecture. Clearly, the development of new efficient chemical
ligation techniques that are compatible with RAFT polymerization will continue. In
this regard, multi-component and sequential reactions will play an important role
as much as externally triggered reactions, such as photo-reactions. In the future, we
will also likely see increased development and application of orthogonal chemistries
within the area of post-polymerization modifications, enabling not only the syn-
thetic access to ever more diversely functionalized polymers, but also digitalization
in polymer synthesis, because of the plethora of applicable orthogonal reactions,
which could be fully automated.
References
1 Theato, P. (2008). Synthesis of well-defined polymeric activated esters. J. Polym.

Sci. A Polym. Chem. 46 (20): 6677–6687.
2 Günay, K.A., Theato, P., and Klok, H.A. (2013). History of post-polymerization
modification. In: Functional Polymers by Post-Polymerization Modification (eds. P.
Theato and H.-A. Klok), 1–44. Weinheim: Wiley-VCH.
3 Günay, K.A., Theato, P., and Klok, H.A. (2013). Standing on the shoulders of
Hermann Staudinger: post-polymerization modification from past to present.
J. Polym. Sci. A Polym. Chem. 51 (1): 1–28.
4 Das, A. and Theato, P. (2015). Activated ester containing polymers: opportunities
and challenges for the design of functional macromolecules. Chem. Rev. 116 (3):
1434–1495.
5 Blasco, E., Sims, M.B., Goldmann, A.S. et al. (2017). 50th anniversary perspec-
tive: polymer functionalization. Macromolecules 50 (14): 5215–5252.
6 Theato, P. and Klok, H.A. (eds.) (2013). Functional Polymers by Post-Polymeri-
zation Modification: Concepts, Guidelines and Applications. Weinheim:
Wiley-VCH.
7 Batz, H.G., Franzmann, G., and Ringsdorf, H. (1972). Model reactions for syn-
thesis of pharmacologically active polymers by way of monomeric and polymeric
reactive esters. Angew. Chem. Int. Ed. Engl. 11 (12): 1103–1104.
8 Ferruti, P., Bettelli, A., and Fere, A. (1972). High polymers of acrylic and
methacrylic esters of N-hydroxysuccinimide as polyacrylamide and poly-
methacrylamide precursors. Polymer 13 (10): 462–464.
References 865
9 Schilli, C., Müller, A.H., Thang, S.H. et al. (2002). Controlled radical poly-
merization of N-isopropylacrylamide and of activated esters for the synthe-
sis of polymer-protein and polymer-drug conjugates. Polym. Prepr. 43 (2):
687–688.
10 Yanjarappa, M.J., Gujraty, K.V., Joshi, A. et al. (2006). Synthesis of copoly-
mers containing an active ester of methacrylic acid by RAFT: controlled
molecular weight scaffolds for biofunctionalization. Biomacromolecules 7 (5):
1665–1670.
11 Aamer, K.A. and Tew, G.N. (2007). RAFT polymerization of a novel activated
ester monomer and conversion to a terpyridine-containing homopolymer. J.
Polym. Sci. A Polym. Chem. 45 (23): 5618–5625.
12 Niu, J., Page, Z.A., Dolinski, N.D. et al. (2017). Rapid visible light-mediated con-
trolled aqueous polymerization with in situ monitoring. ACS Macro Lett. 6 (10):
1109–1113.
13 Tsuji, S., Aso, Y., Ohara, H., and Tanaka, T. (2019). Polymeric water-soluble
activated esters: synthesis of polymer backbones with pendant
N-hydoxysulfosuccinimide esters for post-polymerization modification in water.
Polym. J.
14 Kisfaludy, L., Löw, M., Nyéki, O. et al. (1973). Die Verwendung von Pentafluor-
phenylestern bei Peptidsynthesen. Justus Liebigs Ann. Chem. 1973 (9): 1421–1429.
15 Eberhardt, M., Mruk, R., Zentel, R., and Théato, P. (2005). Synthesis of pentaflu-
orophenyl (meth) acrylate polymers: new precursor polymers for the synthesis of
multifunctional materials. Eur. Polym. J. 41 (7): 1569–1575.
16 Gibson, M.I., Fröhlich, E., and Klok, H.A. (2009). Postpolymerization mod-
ification of poly (pentafluorophenyl methacrylate): synthesis of a diverse
water-soluble polymer library. J. Polym. Sci. A Polym. Chem. 47 (17): 4332–4345.
17 Boyer, C. and Davis, T.P. (2009). One-pot synthesis and biofunctionalization of
glycopolymers via RAFT polymerization and thiol–ene reactions. ChemComm 40:
6029–6031.
18 Boyer, C., Whittaker, M., and Davis, T.P. (2011). Synthesis and postfunctionaliza-
tion of well-defined star polymers via “double” click chemistry. J. Polym. Sci. A
Polym. Chem. 49 (24): 5245–5256.
19 Nilles, K. and Theato, P. (2009). RAFT polymerization of activated
4-vinylbenzoates. J. Polym. Sci. A Polym. Chem. 47 (6): 1696–1705.
20 Nilles, K. and Theato, P. (2010). Sequential conversion of orthogonally function-
alized diblock copolymers based on pentafluorophenyl esters. J. Polym. Sci. A
Polym. Chem. 48 (16): 3683–3692.
21 Agar, S., Baysak, E., Hizal, G. et al. (2018). An emerging post-polymerization
modification technique: the promise of thiol-Para-fluoro click reaction. J. Polym.
Sci. A Polym. Chem. 56 (12): 1181–1198.
22 Delaittre, G. and Barner, L. (2018). The Para-fluoro-thiol reaction as an efficient
tool in polymer chemistry. Polym. Chem. 9 (20): 2679–2684.
23 Riedel, M., Stadermann, J., Komber, H. et al. (2011). Synthesis, post-modification
and self-assembled thin films of pentafluorostyrene containing block copolymers.
Eur. Polym. J. 47 (4): 675–684.
24 Pryor, W.A. and Huang, T.L. (1969). The kinetics of the polymerization of
pentafluorostyrene. Macromolecules 2 (1): 70–77.
25 Varadharajan, D. and Delaittre, G. (2016). Accessing libraries of bifunctional
block copolymers using two distinct pentafluorophenyl moieties. Polym. Chem. 7
(48): 7488–7499.
26 Dömling, A. and Ugi, I. (2000). Multicomponent reactions with isocyanides.
Angew. Chem. Int. Ed. 39 (18): 3168–3210.
27 Noy, J.M., Koldevitz, M., and Roth, P.J. (2015). Thiol-reactive functional poly
(meth) acrylates: multicomponent monomer synthesis, RAFT (co) polymerization
and highly efficient thiol–Para-fluoro postpolymerization modification. Polym.
Chem. 6 (3): 436–447.
28 Noy, J.M., Friedrich, A.K., Batten, K. et al. (2017). Para-fluoro postpolymerization
chemistry of poly (pentafluorobenzyl methacrylate): modification with amines,
thiols, and carbonylthiolates. Macromolecules 50 (18): 7028–7040.
29 Noy, J.M., Li, Y., Smolan, W., and Roth, P.J. (2019). Azide–Para-fluoro substitu-
tion on polymers: multipurpose precursors for efficient sequential postpolymer-
ization modification. Macromolecules 52 (8): 3083–3091.
30 Bodanszky, M. (1955). Synthesis of peptides by aminolysis of nitrophenyl esters.
Nature 175 (4459): 685.
31 Hu, Y.C., Liu, Y., and Pan, C.Y. (2004). Reversible addition–fragmentation trans-
fer polymerization of p-nitrophenyl acrylate and synthesis of diblock copolymers
poly (p-nitrophenyl acrylate)-b-polystyrene. J. Polym. Sci. A Polym. Chem. 42 (19):
4862–4872.
32 Hwang, J., Li, R.C., and Maynard, H.D. (2007). Well-defined polymers with
activated ester and protected aldehyde side chains for bio-functionalization.
J. Control. Release 122 (3): 279–286.
33 Zuwala, K., Smith, A.A., Tolstrup, M., and Zelikin, A.N. (2016). HIV anti-latency
treatment mediated by macromolecular prodrugs of histone deacetylase inhibitor,
panobinostat. Chem. Sci. 7 (3): 2353–2358.
34 Metz, N. and Theato, P. (2007). Controlled synthesis of poly (acetone oxime
acrylate) as a new reactive polymer: stimuli-responsive reactive copolymers. Eur.
Polym. J. 43 (4): 1202–1209.
35 He, L., Shang, J., and Theato, P. (2015). Preparation of dual stimuli-responsive
block copolymers based on different activated esters with distinct reactivities.
Eur. Polym. J. 69: 523–531.
36 Kakuchi, R. and Theato, P. (2012). Changing the reactivity of polymeric
activated esters by temperature: on–off switching of the reactivity of
poly(4-acryloxyphenyldimethylsulfonium triflate). Macromolecules 45 (3):
1331–1338.
37 Nuhn, L., Overhoff, I., Sperner, M. et al. (2014). RAFT-polymerized
poly(hexafluoroisopropyl methacrylate)s as precursors for functional
water-soluble polymers. Polym. Chem. 5 (7): 2484–2495.
38 Szostak, R., Shi, S., Meng, G. et al. (2016). Ground-state distortion in
N-acyl-tert-butyl-carbamates (Boc) and N-acyl-tosylamides (Ts): twisted amides
of relevance to amide N–C cross-coupling. J. Org. Chem. 81 (17): 8091–8094.
References 867
39 Larsen, M.B., Herzog, S.E., Quilter, H.C., and Hillmyer, M.A. (2018). Activated
polyacrylamides as versatile substrates for postpolymerization modification. ACS
Macro Lett. 7 (1): 122–126.
40 Seo, M. and Hillmyer, M.A. (2014). RAFT copolymerization of acid
chloride-containing monomers. Polym. Chem. 5 (1): 213–219.
41 Zheng, Z., Ling, J., and Müller, A.H. (2014). Revival of the R-group approach:
a “CTA-shuttled” grafting from approach for well-defined cylindrical poly-
mer brushes via RAFT polymerization. Macromol. Rapid Commun. 35 (2):
234–241.
42 Barlow, T.R., Brendel, J.C., and Perrier, S. (2016). Poly (bromoethyl acrylate):
a reactive precursor for the synthesis of functional RAFT materials. Macro-
molecules 49 (17): 6203–6212.
43 Kubo, T., Figg, C.A., Swartz, J.L. et al. (2016). Multifunctional homopolymers:
postpolymerization modification via sequential nucleophilic aromatic substitu-
tion. Macromolecules 49 (6): 2077–2084.
44 AdrianáFigg, C. (2017). Modular and rapid access to amphiphilic homopolymers
via successive chemoselective post-polymerization modification. Polym. Chem. 8
(39): 6028–6032.
45 Flores, J.D., Shin, J., Hoyle, C.E., and McCormick, C.L. (2010). Direct RAFT
polymerization of an unprotected isocyanate-containing monomer and sub-
sequent structopendant functionalization using “click”-type reactions. Polym.
Chem. 1 (2): 213–220.
46 Flores, J.D., Treat, N.J., York, A.W., and McCormick, C.L. (2011). Facile, mod-
ular transformations of RAFT block copolymers via sequential isocyanate and
thiol-ene reactions. Polym. Chem. 2 (9): 1976–1985.
47 Francini, N., Purdie, L., Alexander, C. et al. (2015). Multifunctional
poly[N-(2-hydroxypropyl) methacrylamide] copolymers via postpolymeriza-
tion modification and sequential thiol–ene chemistry. Macromolecules 48 (9):
2857–2863.
48 Hoff, E.A., Abel, B.A., Tretbar, C.A. et al. (2016). RAFT polymerization of “split-
ters” and “Cryptos”: exploiting azole-N-carboxamides as blocked isocyanates for
ambient temperature postpolymerization modification. Macromolecules 49 (2):
554–563.
49 Zhu, Y., Quek, J.Y., Lowe, A.B., and Roth, P.J. (2013). Thermoresponsive
(co) polymers through postpolymerization modification of poly(2-vinyl-4,
4-dimethylazlactone). Macromolecules 46 (16): 6475–6484.
50 Li, Y., Duong, H.T., Jones, M.W. et al. (2013). Selective postmodification of
copolymer backbones bearing different activated esters with disparate reactivities.
ACS Macro Lett. 2 (10): 912–917.
51 Kanimozhi, C., Shea, M.J., Ko, J. et al. (2019). Removable nonconjugated poly-
mers to debundle and disperse carbon nanotubes. Macromolecules 52 (11):
4278–4286.
52 Davies, M.C., Dawkins, J.V., and Hourston, D.J. (2005). Radical copoly-
merization of maleic anhydride and substituted styrenes by reversible
addition-fragmentation chain transfer (RAFT) polymerization. Polymer 46 (6):

1739–1753.
53 Stubbs, C., Lipecki, J., and Gibson, M.I. (2016). Regioregular alternating polyam-
pholytes have enhanced biomimetic ice recrystallization activity compared to
random copolymers and the role of side chain versus main chain hydrophobicity.
54 Espeel, P., Goethals, F., Stamenović, M.M. et al. (2012). Double modular mod-
ification of thiolactone-containing polymers: towards polythiols and derived
structures. Polym. Chem. 3 (4): 1007–1015.
55 Reinicke, S., Espeel, P., Stamenović, M.M., and Du Prez, F.E. (2013). One-pot
double modification of p (NIPAAm): a tool for designing tailor-made multire-
sponsive polymers. ACS Macro Lett. 2 (6): 539–543.
56 Rudolph, T., Espeel, P., Du Prez, F.E., and Schacher, F.H. (2015). Poly (thi-
olactone) homo-and copolymers from maleimide thiolactone: synthesis and
functionalization. Polym. Chem. 6 (23): 4240–4251.
57 Liu, X., Hu, D., Jiang, Z. et al. (2016). Multi-stimuli-responsive amphiphilic
assemblies through simple postpolymerization modifications. Macromolecules 49
(17): 6186–6192.
58 Gudipati, C.S., Tan, M.B., Hussain, H. et al. (2008). Synthesis of poly (glycidyl
methacrylate)-block-poly (pentafluorostyrene) by RAFT: precursor to novel
amphiphilic poly(glyceryl methacrylate)-block-poly(pentafluorostyrene). Macro-
mol. Rapid Commun. 29 (23): 1902–1907.
59 Benaglia, M., Alberti, A., Giorgini, L. et al. (2013). Poly (glycidyl methacrylate): a
highly versatile polymeric building block for post-polymerization modifications.
Polym. Chem. 4 (1): 124–132.
60 McLeod, D.C. and Tsarevsky, N.V. (2016). Well-defined epoxide-containing
styrenic polymers and their functionalization with alcohols. J. Polym. Sci. A
Polym. Chem. 54 (8): 1132–1144.
61 Maiti, B., Kumar, S., and De, P. (2014). Controlled RAFT synthesis of side-chain
oleic acid containing polymers and their post-polymerization functionalization.
RSC Adv. 4 (99): 56415–56423.
62 McLeod, D.C. and Tsarevsky, N.V. (2016). Reversible deactivation radical poly-
merization of monomers containing activated aziridine groups. Macromol. Rapid
Commun. 37 (20): 1694–1700.
63 Pramanik, N.B., Bag, D.S., Alam, S. et al. (2013). Thermally amendable
tailor-made functional polymer by RAFT polymerization and “click reaction”.
64 Xiao, L., Chen, Y., and Zhang, K. (2016). Efficient metal-free “grafting onto”
method for bottlebrush polymers by combining RAFT and triazolinedione–diene
click reaction. Macromolecules 49 (12): 4452–4461.
65 Mondal, P., Raut, S.K., and Singha, N.K. (2018). Thermally amendable
tailor-made acrylate copolymers via RAFT polymerization and ultrafast alder-ene
“click” chemistry. J. Polym. Sci. A Polym. Chem. 56 (20): 2310–2318.
References 869
66 Xu, X., Flores, J.D., and McCormick, C.L. (2011). Reversible imine shell
cross-linked micelles from aqueous RAFT-synthesized thermoresponsive tri-
block copolymers as potential nanocarriers for “pH-triggered” drug release.
67 Foster, J.C. and Matson, J.B. (2014). Functionalization of methacrylate poly-
mers with thiooximes: a robust postpolymerization modification reaction and a
method for the preparation of H2 S-releasing polymers. Macromolecules 47 (15):
5089–5095.
68 Sims, M.B., Lessard, J.J., Bai, L., and Sumerlin, B.S. (2018). Functional diversifi-
cation of polymethacrylates by dynamic β-ketoester modification. Macromolecules
51 (16): 6380–6386.
69 Himo, F., Lovell, T., Hilgraf, R. et al. (2005). Copper (I)-catalyzed synthesis of
azoles. DFT study predicts unprecedented reactivity and intermediates. J. Am.
Chem. Soc. 127 (1): 210–216.
70 Lu, J., Zhang, W., Richards, S.J. et al. (2014). Glycopolymer-coated gold nanorods
synthesised by a one pot copper (0) catalyzed tandem RAFT/click reaction.
Polym. Chem. 5 (7): 2326–2332.
71 Ebbesen, M.F., Schaffert, D.H., Crowley, M.L. et al. (2013). Synthesis of
click-reactive HPMA copolymers using RAFT polymerization for drug delivery
applications. J. Polym. Sci. A Polym. Chem. 51 (23): 5091–5099.
72 Martyn, B., Biggs, C.I., and Gibson, M.I. (2019). Comparison of systematically
functionalized heterogeneous and homogenous glycopolymers as toxin inhibitors.
73 Ledin, P.A., Kolishetti, N., and Boons, G.J. (2013). Multifunctionalization of poly-
mers by strain-promoted cycloadditions. Macromolecules 46 (19): 7759–7768.
74 Howe, D.H., McDaniel, R.M., and Magenau, A.J. (2017). From click chemistry to
cross-coupling: designer polymers from one efficient reaction. Macromolecules 50
(20): 8010–8018.
75 Prasher, A., Loynd, C.M., Tuten, B.T. et al. (2016). Efficient fabrication of poly-
mer nanoparticles via sonogashira cross-linking of linear polymers in dilute
solution. J. Polym. Sci. A Polym. Chem. 54 (1): 209–217.
76 Cambre, J.N., Roy, D., Gondi, S.R., and Sumerlin, B.S. (2007). Facile strategy to
well-defined water-soluble boronic acid (co) polymers. J. Am. Chem. Soc. 129
(34): 10348–10349.
77 Gaballa, H., Shang, J., Meier, S., and Theato, P. (2019). The glucose-responsive
behavior of a block copolymer featuring boronic acid and glycine. J. Polym. Sci.
A Polym. Chem. 57 (3): 422–431.
78 Zhu, C., Yang, B., Zhao, Y. et al. (2013). A new insight into the Biginelli reac-
tion: the dawn of multicomponent click chemistry? Polym. Chem. 4 (21):
5395–5400.
79 Wu, H., Yang, L., and Tao, L. (2017). Polymer synthesis by mimicking nature’s
strategy: the combination of ultra-fast RAFT and the Biginelli reaction. Polym.
Chem. 8 (37): 5679–5687.
80 Zhang, Y., Zhao, Y., Yang, B. et al. (2014). One pot’synthesis of well-defined poly
(aminophosphonate) s: time for the Kabachnik–fields reaction on the stage of
polymer chemistry. Polym. Chem. 5 (6): 1857–1862.
81 Müller, R., Feuerstein, T.J., Trouillet, V. et al. (2018). Spatially-resolved multiple

metallopolymer surfaces by photolithography. Chem. Eur. J. 24 (71): 18933–18943.
82 Zhang, J., Wang, L., Li, C. et al. (2014). Preparation and characterization of solu-
tion processable phthalocyanine-containing polymers via a combination of RAFT
polymerization and post-polymerization modification techniques. J. Polym. Sci. A
Polym. Chem. 52 (5): 691–698.
83 Utama, R.H., Jiang, Y., Zetterlund, P.B., and Stenzel, M.H. (2015). Biocompatible
glycopolymer nanocapsules via inverse miniemulsion periphery RAFT polymer-
ization for the delivery of gemcitabine. Biomacromolecules 16 (7): 2144–2156.
84 Nuhn, L., Barz, M., and Zentel, R. (2014). New perspectives of HPMA-based
copolymers derived by post-polymerization modification. Macromol. Biosci. 14
(5): 607–618.
85 Gaballa, H. and Theato, P. (2019). Glucose-responsive polymeric micelles via
Boronic acid–diol complexation for insulin delivery at neutral pH. Biomacro-
molecules 20 (2): 871–881.
86 Chambre, L., Degirmenci, A., Sanyal, R., and Sanyal, A. (2018). Multi-functional
nanogels as theranostic platforms: exploiting reversible and nonreversible
linkages for targeting, imaging, and drug delivery. Bioconjug. Chem. 29 (6):
1885–1896.
87 Sahoo, B., Devi, K.S.P., Banerjee, R. et al. (2013). Thermal and pH responsive
polymer-tethered multifunctional magnetic nanoparticles for targeted delivery of
anticancer drug. ACS Appl. Mater. Inter. 5 (9): 3884–3893.
88 Peng, H., Kather, M., Rübsam, K. et al. (2015). Water-soluble reactive copolymers
based on cyclic N-vinylamides with succinimide side groups for bioconjugation
with proteins. Macromolecules 48 (13): 4256–4268.
89 Peng, H., Rübsam, K., Huang, X. et al. (2016). Reactive copolymers based on
N-vinyl lactams with pyridyl disulfide side groups via RAFT polymerization and
postmodification via thiol–disulfide exchange reaction. Macromolecules 49 (19):
7141–7154.
90 Shi, H., Liu, L., Wang, X., and Li, J. (2012). Glycopolymer–peptide bioconju-
gates with antioxidant activity via RAFT polymerization. Polym. Chem. 3 (5):
1182–1188.
91 Moatsou, D., Li, J., Ranji, A. et al. (2015). Self-assembly of temperature-
responsive protein–polymer bioconjugates. Bioconjug. Chem. 26 (9): 1890–1899.
92 Benoit, D.S., Srinivasan, S., Shubin, A.D., and Stayton, P.S. (2011). Synthesis of
folate-functionalized RAFT polymers for targeted siRNA delivery. Biomacro-
molecules 12 (7): 2708–2714.
93 Togashi, D., Otsuka, I., Borsali, R. et al. (2014). Maltopentaose-conjugated CTA
for RAFT polymerization generating nanostructured bioresource-block copoly-
mer. Biomacromolecules 15 (12): 4509–4519.
94 Gevrek, T.N., Yu, K., Kizhakkedathu, J.N., and Sanyal, A. (2019). Thiol-reactive
polymers for titanium interfaces: fabrication of antimicrobial coatings. ACS Appl.
Polym. Mater. 1 (6): 1308–1316.
References 871
95 Son, H., Ku, J., Kim, Y. et al. (2018). Amine-reactive poly(pentafluorophenyl

acrylate) brush platforms for cleaner protein purification. Biomacromolecules 19
(3): 951–961.
96 Moraes, J., Ohno, K., Maschmeyer, T., and Perrier, S. (2013). Monodis-
perse, charge-stabilized, core–shell particles via silica-supported reversible
addition–fragmentation chain transfer polymerization for cell imaging. Chem.
Mater. 25 (17): 3522–3527.
97 Choi, J.W., Carter, M.C., Wei, W. et al. (2016). Self-assembly and post-fabrication
functionalization of microphase separated thin films of a reactive azlactone-
containing block copolymer. Macromolecules 49 (21): 8177–8186.
98 Biggs, C.I., Walker, M., and Gibson, M.I. (2016). “Grafting to” of RAFTed
responsive polymers to glass substrates by thiol–ene and critical comparison
to thiol–gold coupling. Biomacromolecules 17 (8): 2626–2633.
873
19
RAFT Crosslinking Polymerization

Patricia Pérez-Salinas 1 , Porfirio López-Domínguez 1 , Alberto Rosas-Aburto 1 ,
Julio César Hernández-Ortiz 2 , and Eduardo Vivaldo-Lima 1
1 Universidad Nacional Autónoma de México, Facultad de Química, Departamento de Ingeniería Química,
Ciudad Universitaria, Circuito Exterior S/N, Coyoacán, Ciudad de México 04510, México
2
Amcor Flexibles Gent, Film Extrusion, Ottergemsesteenweg-ZUID 801 B-9000, Ghent, Belgium
19.1 Introduction
Crosslinked polymers are materials of great interest in research and industrial
fields. If synthesized beyond the gelation point, these materials possess a
three-dimensional network structure. Crosslinking in polymer synthesis by
step growth polymerization may result from the polymerization of monomers with
functionality greater than two. Branching promoting functional groups such as
pendent double bonds (PDB) or labile atoms can also promote crosslinking in chain
growth polymerization. Polymer networks can be defined as highly crosslinked
macromolecules in which essentially all the units are connected to each other in
some way, by covalent chemical bonds or physical associations [1, 2].
Polymer networks, gels, and hydrogels are materials designed to swell under the
action of a solvent, which is contained or trapped within the network structure.
Chemical substances can thus be loaded and released, giving rise to a good num-
ber of applications in diverse fields such as catalysis [3]; controlled release of drugs
[4–8], proteins [9], and human cells [10]; synthesis of structured polymers (hierar-
chical porous polymers, HPP) [11]; energy storage [11, 12]; water desalinization [13];
advanced materials [14], such as self-healing polymers [15–18]; and other applica-
tions [19]. One of the most important routes to synthesize polymer networks, rep-
resented in Figure 19.1, is the conventional radical copolymerization (RP) of vinyl
monomers and multivinyl crosslinker comonomers [20–24].
One disadvantage of polymer networks synthesized by conventional RP of divinyl
or multivinyl monomers with vinyl monomers is that their crosslink density distri-
bution is intrinsically very heterogeneous [2]. One way to reduce the heterogeneity of
polymer networks synthesized by RP is to introduce a chemical compound that acts

874 19 RAFT Crosslinking Polymerization
Multiple
connections Porosity,
between two cavities
crosslink Mc3
points
x Mc7
Elastically Homopolymer
y active chains
Hidden
radicals Mc5
Loops
Mc4
Mcn
z Crosslink point
(entanglement)
n
Mci Mc1
Mc2
Mc =
n Dangling double bonds
Dangling
i=1 chains
Crosslinking agent Monomer Radical initiator
Figure 19.1 Schematic representation of synthesis of polymer networks by RP,

representation of the structures within the network structure, and the concept of molecular
weight between entanglements (Mc ). Source: Adapted with permission from Saldívar-Guerra
and Vivaldo-Lima [2]. Copyright 2013, John Wiley & Sons.
as a controller in reversible deactivation radical polymerization (RDRP) techniques

into the reacting formulation [2, 25–28]. As evident from the companion chapters of
this handbook, reversible addition fragmentation chain transfer (RAFT) polymer-
ization is one of the most employed RDRP techniques [29].
Although there is a debate in the literature regarding the effect on polymer net-
work homogeneity of adding a RDRP controller in the recipe, with some authors
claiming that more homogeneous polymer networks are obtained [30, 31], whereas
others claim that no changes are observed [32, 33], the effect in the case of RAFT
synthesis of polymer networks seems to be the production of less heterogeneous
polymer networks [34].
The scope of this chapter includes surveying the plurality of applications found
in the literature related to the synthesis of polymer networks (gels, hydrogels,
and smart polymer networks) by RAFT (co)polymerization with crosslinking
of multi-olefinic monomers. Our starting point is the review by Moad on the
RAFT crosslinking copolymerization of multi-olefinic monomers to form polymer
networks [25]. In that sense, our chapter can be viewed as an update of Moad’s
review. However, our survey of the literature also includes reversible polymer
networks based on ionic bonds, as well as the syntheses of materials described as
nanogels, microgels, core-crosslinked stars, thermo- or pH- responsive materials,
self-healing polymer networks, ‘arm-first’ stars, or hyperbranched polymers that
can be formed by RAFT (co)polymerization of similar components under different
reaction conditions before gelation. Another distinctive characteristic of our chapter
is that it includes a survey on the modelling of polymer network formation by RAFT
(co)polymerization of vinyl/divinyl monomers.
19.2 Structure and Characteristics of Polymer Networks 875
19.2 Structure and Characteristics of Polymer Networks

RP can be carried out in the presence or absence of solvents. When solvents are
used for the synthesis of polymer networks, the growing polymer chains are in a
relaxed state at the early stages of the polymerization. They are therefore able to
move freely during the pre-gelation period. On the other hand, the growing poly-
mer molecules curl, exposing as little as possible of their surface, when the polymer
network synthesis proceeds in the absence of solvents. The final structure, prop-
erties, and characteristics, such as mechanical properties of the produced polymer
network, are therefore influenced by the presence or absence of solvent during the
polymerization [2, 35]. Calculation of polymer network properties such as diffusion
coefficients of loaded chemical compounds [36], molecular weight between entan-
glements [35, 37], swelling [38], and theta temperature [39] depends on the way the
synthesis proceeded.
As stated earlier, the synthesis of polymer networks by RP of vinyl/multi-vinyl
monomers leads to heterogeneous structures. Different substructures within the
polymer network are generated by that process, as observed in Figure 19.1 [2]. From
all these substructures, only elastically active chains can generate porosity and are
responsible for the swelling properties of the polymer network (see Figure 19.1).
The study of swelling is fundamental for the understanding and estimation of
properties and performance of polymer networks. Two theories are available for
the calculation and analysis of swelling. Both are related to large elastic (reversible)
deformation of solids but explained under thermodynamic and mechanical per-
spectives, respectively [35, 40–45]. Molecular weight between entanglements and
average crosslink density are important parameters for the study of polymer net-
works. They can be estimated from swelling measurements. The thermodynamic
description of swelling leads to the Flory–Rehner equation, given by Eqs. (19.1) and
(19.2) for polymer networks synthesized in the absence and presence of solvent,
respectively [40, 41].
( ) ( ( ) )
1 2 𝜌polymer ln 1 − 𝜐2,s + 𝜐2,s + 𝜒1 𝜐2,s
= − ( ) (19.1)
Mc Mn ( ) 1∕ ( 𝜐 )
Vsolvent 𝜐2,s 3 − 22,s
( ) ( ( ) )
1 2 𝜌polymer ln 1 − 𝜐2,s + 𝜐2,s + 𝜒1 𝜐2,s
∘ = M − (( ) 1 ) (19.2)
Mc n 𝜐2,s ∕3 ( 𝜐2,s )
𝜐2,r Vsolvent 𝜐
− 2𝜐
2,r 2,r
0
M c and M c are molecular weights between entanglements for polymer networks
synthesized in the absence and presence of solvent, respectively (g mol−1 ); M n is the
number-average molecular weight of primary molecules, polymer population result-
ing if all crosslinks were broken (g mol−1 ); V solvent is the solvent or swelling agent
molar volume (cm3 g−1 mol−1 ); 𝜌polymer is the polymer-specific volume (cm3 g−1 ); 𝜒 1
is the Flory polymer solvent interaction parameter (dimensionless); 𝜐2,s is the poly-
mer volume fraction in the gel, which can be estimated as inverse experimentally
measured swelling index, Sindex , (dimensionless); and 𝜐2,r is the polymer volume
fraction during the pre-gelation period (dimensionless).
The mechanical description of swelling, in terms of M c , is given by the

Mooney–Rivlin model, given by Eq. (19.3), where 𝜎 is the first normal stress
difference (J); R is the universal gas constant (8.3145 J mol−1 K−1 ); T is the tem-
perature (K); 𝜆 is the solid material deformation (length/characteristic length);
and Q is a material constant (dimensionless) that takes the value of 0.4 for soft
materials (elastomers and gels) and 0.5 for more rigid materials (polyolefin and
polyacrylate rubbers, as well as other networks) [40, 41]. M c should be calculated
using Eqs. (19.1) or (19.2), depending on the absence or presence of solvent,
respectively.
( )[ ]
RT 1 1
𝜎Mooney = 1− + (19.3)
Mc 𝜌polymer Q𝜆 𝜆
Crosslink density distribution, which can be related to the distribution of M c ,
determines the size of chemicals that can be loaded into the polymer network,
its release rate, and its mechanical properties. Nowadays, polymer networks have
extended their fields of application. As a result, some issues related to polymer
network formation, such as the type of monomers, their structures and architec-
tures, their construction sequences and the operating mechanisms of polymer
networks under the action of solvents, chemical compounds, or other stimuli
(e.g. temperature, mechanical deformation, light, pH, and so on), have gained
importance [44, 46–55].

It is possible to control the extent of crosslinking and the occurrence of the gela-
tion point in RP of vinyl/multivinyl monomers in the presence of solvents [56–58]
or chain transfer agents [59]. However, process control strategies in the synthesis
of polymer networks by conventional RP cannot reduce heterogeneity (reduction
of variance of the crosslink density distribution) of the produced materials. That is
why, RDRP methods for synthesis of polymer networks, including RAFT copolymer-
ization of vinyl/multi-divinyl monomers, have been proposed and analysed [26–28].
The idea is that controlled growth of polymer branches from PDBs will result in less
heterogeneous polymer networks.
The most widely used RAFT controllers are those based on thiocarbonylthio com-
pounds. Their general chemical structure is shown in Figure 19.2 [60]. It is observed
in Figure 19.2 that two main groups, Z and R, are attached to the thiocarbonylthio
structure. ‘Z’ modifies both the rate of addition to thiocarbonyl groups of propa-
gating radicals and the rate of fragmentation of intermediate radicals. The kinetic
rate constant for the addition reaction can change by several orders of magnitude
by manipulation of the Z group [60]. The nature of R determines the fragmentation
rate. ‘R’ must be a good homolytic leaving group with respect to the propagating rad-
icals if adequate control is desired. Criteria for adequate selection of RAFT agents,
based on groups R and Z, are available in the literature [25, 29, 60, 61].
Figure 19.2 Chemical structure representation

of a thiocarbonylthio RAFT agent split in two
segments, denoted as A and B.
S S
C R
A B
19.3.1 Synthesis Pathways to Obtain Polymer Networks

The synthesis of polymer networks using RAFT controllers is focused on obtaining
different network architectures, properties, or characteristics. Different synthesis
pathways, sequences, or strategies to assemble the desired material have been pro-
posed. These strategies can be classified in terms of the following categories:
(1) One-step polymerization. In this synthetic route, initiator(s), RAFT agent,

monomer(s), and crosslinking agent are added to the reactor at the same time
at the beginning of the polymerization. Most of these (co)polymerizations
are carried out in batch or semi-batch reactors in the presence of solvents
or dispersing media. As explained earlier, the presence (or absence) of sol-
vent(s) or dispersing media affects the average value of M c obtained, and the
heterogeneity of the polymer network. The literature related to this type of
polymerization is focused on kinetic studies, performance of selected RAFT
controllers, kinetic and molecular weight development simulations studies,
and characterization/performance of the synthesized polymer networks under
different synthesis conditions [8, 62–72].
(2) Multistep polymerization including RAFT block (co)polymerization of linear seg-
ments followed by crosslinking. This route for the synthesis of polymer networks
using RAFT controllers has received significant attention in the literature
[25, 73, 74]. It consists of the RAFT synthesis of one or more linear polymer
segments (blocks), followed by crosslinking using different techniques, as
illustrated in Figure 19.3. Crosslinking routes can be classified according to the
following categories:
(a) Synthesis of linear polymer molecules by RAFT polymerization, followed by
crosslinking. Linear polymer molecules with narrow molecular weight dis-
tributions are synthesized by RAFT polymerization. These linear chains are
then placed into a reactor where crosslinker molecules have been charged
[3, 7, 16, 73–76].
(b) Synthesis of linear precursors by sequential RAFT block copolymerization,
followed by crosslinking. In this category, a first polymer block is built
by RAFT polymerization of one of the monomers. After consumption or
Block formation
n
n
S S
C R S S S S
n n C R C
n R
Z
Z Z
R m R
m
R S S S S R S S
C R
m n m C n m C
n
Z Z Z
Crosslinking
n n
m
n n m
R S S
S S C
C
n Z
m Z
Cyclized chain
Polymer network R
R controlled Mc
R S S
m C R S S
C
Z S S
C Z
Z Linear chain
Crosslinking agent Monomer Radical initiator RAFT controller

S S
C R
Z
Figure 19.3 Schematic representation of multistep polymerizations including a RAFT

block (co)polymerization stage and further crosslinking processes. Source: Adapted with
permission from Moad [25]. Copyright 2014, Society of Chemical Industry.
the first monomer, the second monomer is added, and a second block is
then produced. If multiblock copolymers are desired, sequential blocks
can be added in the same way. At the end, these multi-block polymer
molecules are crosslinked by adding a crosslinker. In some cases, the
crosslinking process takes place at intermediate stages and not at the end
[6, 8, 10, 11, 13, 17–19, 74, 77–84].
(3) Multistep polymerization using a RAFT macro-controller, followed by crosslink-
ing. This type of synthesis has gained importance because of its versatility.
RAFT controllers containing carboxylic acid groups (RAFT-COOH) can be
chemically bonded to almost any type of macromolecule containing hydroxyl
groups (e.g. polymer molecules, ceramics, or fibres). It is based on Steglich
esterification using N,N ′ -dicyclohexylcarbodiimide (DCC). As observed in
Figure 19.4, an anhydride is produced from DCC and the acid group of a
RAFT controller. This anhydride is made to react in situ with the desire
surface. 4-Dimethylaminopyridine (DMAP) is used as a catalyst, although other
procedures can be used. The resulting product is a macro-RAFT controller or
macro-controller [4, 5, 9, 12, 14, 15, 83, 85–89].
(4) Polymer network synthesis using bifunctional RAFT controllers. Symmetric
bifunctional RAFT agents are used in this synthetic route. Under adequate
reaction conditions, these molecules react at both ends, leading to crosslinked
structures. As observed in Figure 19.5, two types of bifunctional RAFT
controllers have been used [25, 90–97].
S
Z
C
H
S
OH C H
O
C
O O
HO O O
HO O
N
OH OH
O H O O Z
S S
HO OH C C C H C S
O
H O N O
S S Z H C C S
C C C + O O O
OH OH H
Z H OH
O O
O
OH N C N OH C
H O O H
C
S S S
OH C C C H
OH O
O O H C
Z O O Z
S
Figure 19.4 Schematic representation of the synthesis of a RAFT macro-controller using

Steglich esterification.
Figure 19.5 Chemical structure S S

representation of different S S S S
C R C R C C R
bifunctional RAFT agents. (a) S Z S
‘R’-connected bis-macro-RAFT Z Z n
agents; (b) ‘Z’-connected bis-RAFT (a) (b)
agents (symmetrical
trithiocarbonates); and (c) diolefinic O S O
RAFT agents.
R C R
O S S O
(c)
(a) Symmetrical structures containing more than one thiocarbonylthio group,

known as ‘R’-connected bis-macro-RAFT agents (see Figure 19.5a).
(b) Symmetrical trithiocarbonates, known as ‘Z’-connected bis-RAFT agents
(see Figure 19.5b). The size of the Z or R groups will determine the size of
pores or cavities within the polymer network structure.
Specific cases of ‘Z’-connected bis-RAFT agents result when the ending groups are
olefinic (double bond), as observed in Figure 19.5c. These diolefinic RAFT agents
work as crosslinking agents with controlled molecular weight between entangle-
ments [98–102].
19.3.2 RAFT Controllers Used in the Synthesis of Polymer Networks

Several issues need to be considered when selecting a RAFT agent for a specific
situation. Not only must the chemical structures of the desired material to be synthe-
sized and polymerization rates be taken into account but also the availability or ease
of synthesis of candidate RAFT agents. As an attempt to gather and straighten the
information related to the state of art on RAFT agents used for synthesis of polymer
networks, we centred our analysis on RAFT agents used for such a purpose. The
information was organized into three tables. In Table 19.1, the acronyms or abbre-
viations used in Tables 19.2 and 19.3 are defined. Table 19.2 summarizes the RAFT
agents used in the synthesis of polymer networks. The case of polymer networks
synthesized using multifunctional RAFT agents is addressed in Table 19.3.
Table 19.1 Abbreviations employed for monomers and chemical compounds.
AIBN Azobis(isobutyronitrile)
Am Acrylamide
AcAc Acrylic acid
AMA Allyl methacrylate
AdAMA 2-(2-[Adenine-9-yl]acetoxyl) ethyl methacrylate
AN Acrylonitrile
BA Butyl acrylate
tBA tert-Butyl acrylate
BAC N,N′ -bis(acryloyl) cystamine
BDDA Butane-1,4-diyl diacrylate
BisEMA Bisphenol A ethoxylate dimethacrylate
BisGMA Bisphenol A glycidyl methacrylate
BMA Butyl methacrylate
BzMA Benzyl methacrylate
CPDTC 2-Cyanopropan-2-yl dodecyl trithiocarbonate
CDMA β-Cyclodextrin methacrylate
DAAM N-(1,1-dimethyl-3-oxobutyl)-acrylamide (diacetone acrylamide)
DAAmEP Diethyl-2-(acrylamido) ethylphosphonate
DEGDMA Diethylene glycol dimethacrylate
DEGMA (Diethylene glycol) monomethyl ether methacrylate
[2-(2-methoxyethoxy)ethyl methacrylate]
DMAEMA Dimethyl aminoethyl methacrylate
DMAPM N-[3-(dimethylamine)-propyl]methacrylamide
DPEHA Dipentaerythritol hexaacrylate
DSDMA Bis(2-methacryloyloxyethyl) disulfide (disulfide dimethacrylate)
DIPMDGP 1,2:3,4-Di-O-isopropylidene-6-O-methacryloyl-a-D-galactopyranose
DVTPhPy 4′ -(4,4′′ -Divinyl-[1,1′ :3′ ,1′′ -terphenyl]-5′ -yl)-2,2′ :6′ ,2′′ -terpyridine
DVB Divinylbenzene
DBVBC 3,6-Dibromo-9-(4-vinylbenzyl)-9H-carbazole
EGDMA Ethylene glycol dimethacrylate
FMA Furfuryl methacrylate
HAD 1,6-Hexanediol diacrylate
HEA Hydroxy ethyl acrylate
HPMAm N-(2-hydroxypropyl) methacrylamide
IBA Isobornyl acrylate
LauMA Lauryl methacrylate
MA Methyl acrylate
(continued)
MAnh Maleic Anhydride

MAA Methacrylic acid
MMA Methyl methacrylate
MEMA 2-N-morpholinoethyl methacrylate
MBAm N,N′ -methylenbisacrylamide
MPh 4-methoxyphenol
MRhB Methacryloxyethyl thiocarbamoyl rhodamine B
MTAC 2-(Methacryloyloxy)ethyltrimethyl ammonium chloride
NAS N-acryloxysuccinimide
NIPAM N-isopropylacrylamide
OEGDMA Oligo(ethylene glycol) dimethacrylate
OEGMEMA Oligo(ethylene glycol) monomethyl ether methacrylate
PDMA Poly(N,N′ -dimethylacrylamide)
PEGDA Poly(ethylene glycol) diacrylate
PEGDMA Poly(ethylene glycol) dimethacrylate
PEGMA Poly(ethylene glycol) methacrylate
PEGMEM Poly(ethylene glycol) methyl ether methacrylate
PDMAEMA Poly (2-[dimethylamino]ethyl methacrylate)
PFPA Perfluorophenyl azide
PPEGMA Poly(poly(ethylene glycol) methyl ether methacrylate)
PDSEMA Pyridyl disulfide ethyl methacrylate
POSS-NH2 Amino isobutyl polyhedral oligomeric silsesquioxane
PVA Polyvinyl alcohol
PDMS Bis(hydroxyethyloxypropyl) polydimethylsiloxane
pSS Sodium 4-vinylbenzenesulfonate
Ph-TAD Phenyl-1,2,4-triazoline-3,5-dione
TEGDMA Triethylene glycol dimethacrylate
STY Styrene
TMSPM 3-(trimethoxysilyl)propyl methacrylate
VPy 4-Vinyl Pyridine
VAc Vinyl acetate
VBA 4-Vinylbenzoic acid
VBzCl 4-Vinylbenzyl chloride
VDM 2-Vinyl-4,4-dimethylazlactone
Table 19.2 RAFT agents used in the synthesis of polymer networks.
Chemical structure References Monomer Crosslinking agent Application
[78] PEGMEM TMSPM Interfacial crosslinking

M n = 300 Nanoparticle dispersions
[103] DEGDMA DEGDMA Hydrogel
copolymers
O [104] DEGMA DEGDMA Hydrogel
[105] DEGMA DEGDMA Hydrogel
OH
N [10] BMA, MAA, MRhB Effective macrophage delivery
PEGMA, NAS nanogels
H3C S S [106] PPEGMA, BAC Core crosslinked star (CCS)
C PDMAEMA,
H2 PDMA
11
S
4-cyano-4-[(dodecylsulfanylthiocarbonyl) [49, 50] HEMA, BMA PEGDMA Structurally tailored and

sulfanyl] pentanoic acid engineered macromolecular
(STEM) gels
CAS 870196–80-8
C19 H33 NO2 S3 [51] FMA 1–3 Propane Phototriggered zwitterionic
−1
DMAPM Sultone hydrogel
403.67 g mol
Ionic crosslinking
Elemental analysis (%):
[48] HEMA, MMA, Ph-TAD Healable thermoreversible
C, 56.53; H, 8.24; N, 3.47; O, 7.93; BMA polymer networks
S, 23.83
[17] FMA, pSS, pSS/MTAC ions Dual responsive self-healable
MTAC acts as crosslinking hydrogels. Ionic crosslink
agents
[8] HEMA, PEGDA Controlled release of drugs
DMAEMA
[77] PDSEMA, Glutathione Controlled release of drugs
DIPMDGP
[107] PEGMA DEGDMA, Thermo-responsive hydrogel
POSS-NH2 with improved mechanical
strength
[108] NIPAM MBAm Hydrogel

OH [109] DMAEMA PVA Surface modification of PVA
S
AcAc
O MPhc
S [55] DBVBC DVTPhPy Responsive fluorescence
N STY (Heck Reaction) chemosensory crosslinked
4-cyano-4-(phenylcarbonothioylthio) Bromobenzene polymer
pentanoic acid [86] MEMA CDMA RAFT Macro-controller of
CAS 201611–92-9 amine-terminated silicon wafer
C13 H13 NO2 S2 Crosslinked-polymer brushes
279.38 g mol−1 Improved diagnostic tools and
Elemental analysis (%): bioseparation
C, 55.89; H, 4.69; N, 5.01; O, [110] PEGMA+Hexyl Gold Nanoparticles Medical application. Gold
11.45; S, 22.95 amine coating enhances X-ray imaging
MTAC microcapsules
[111] MAnh, AN Hydrolysis of Electrospinning polymerization
MAnh leading to
acid. Interactions
with pendent AN
groups
(continued)
[112] STY STY-imidazole Reversible ionically crosslinked

VBA derivates single-chain nanoparticles for
STY-imidazole catalysis
derivates
[6] NIPAM pH and pH- and thermo-responsive
DMAm Temperature crosslinked polymer.
tBA Controlled release of drugs
S [113] DMAEMA EGDMA pH-Responsive dual networks,
LauMA RP and RAFT synthesis
S
N [114] NIPAM pH and pH- and thermo-responsive
tBA temperature crosslinked polymer
2-cyano-2-propyl benzodithioate VPy
CAS 201611–85-0 [115] PEGMA 4-Azidomethyl Stimuli-responsive amphiphilic
C11 H11 NS2 DMAEMA styrene network. Nanogel formation
221.34 g mol−1 STY through core crosslinking and
macrogelation
C, 59.69; H, 5.01; N, 6.33; S, 28.97 [116] DMAEMA 1,2-bis-(2-iodothoxy) Amphiphilic polymer networks
BA ethane with tunable and predictable
mechanical response
[117] HEMA Glass substrate Photoactive substrate based on
PFPA Concanavalin A Steglich esterification
[118] — PEGDMA Photopolymerization kinetics
[13] AcAc, NIPAM MBAm Hydrogel. Water desalinization
[11] VBzCl, STY DVB Hierarchically porous polymer
Porosity control
[18] DAAM Hexanedihydrazide pH-responsive self-healable
Am hydrogel of covalent bonds
O [119] PDMS, DMAm, Pentaerythritol tetra Amphiphilic co-networks
AMA (3-mercaptopropionate) Biomaterial
H3C S S
C OH
H2 [120] PEO 3-aminopropyl Controlled release of antibodies
11 S VDM triethoxysilane-
2-(dodecyl thiocarbonothioylthio)- grafted magnetic
2-methylpropionic acid nanoparticles
CAS 461642–78-4 [121] PEGMEM Graphene oxide Graphene oxide macro-controller
C17 H32 O2 S3 obtained by Stenglich
esterification
364.63 g mol−1
Improved mechanical properties
[122] NIPAM Organoplatinum(II) Thermo-sensitive self-healing
C, 56.00; H, 8.85; O, 8.78; S, 26.38 metallacycles hydrogel
[123] Sulfur chain RAFT agent Electroactive sulfur networks for
with diisopropyl Li ion batteries
benzene
[124] tBA, PEGMEM, 1,2-bis(2-iodoethoxy) Zwitterionic shell-crosslinked
DMAEMA ethane micelles
(continued)
S S DMAm Ethylenediamine Thermal-self-assembly

OH
NIPAM nanocrosslinked particles
S AcAc
2-(([ethylthio]carbonothioyl)thio) [125]
2-methylpropanoic acid
CAS 881037–62-3
C7 H12 O2 S3
224.36 g mol−1
C, 37.47; H, 5.39; O, 14.26; S,
42.87
S [126] STY Sodium Crosslinked core/shell silver
p-Chloromethyl borohydride nanoparticles with improved
S S styrene Silver nanoparticles thermal stability for
nanoelectronics
dibenzyl carbonotrithioate [127, 128] MMA EGDMA Molecular imprinted monolith
[25]a)
CAS 26504–29-0
C15 H14 S3 [129] EHMA EGDMA Chromatographic monolith [25]a)
290.47 g mol−1
C, 62.02; H, 4.86; S, 33.12
O O
[130] MMA RAFT Agent Self-healing polymers based on a

S S
HEA photoactive RAFT
polymerization
S
bis(4-benzoylbenzyl) carbonotrithioate
C29 H22 O2 S3
498.68 g mol−1
Elemental analysis(%):
C, 69.85; H, 4.45; O, 6.42; S, 19.29
S
[131] MMA DSDMA Polymerization kinetics and
quantification of cycle formation
2-phenylpropan-2-yl benzodithioate
CAS 201611–77-0
C16 H16 S2
[132] STY DVB Polymer kinetics
272.43 g mol−1
C, 70.54; H, 5.92; S, 23.54
(continued)
S [133] — OEGDMA Polymerization kinetics [25]a)

S
1-phenylethyl benzodithioate
CAS 37912–25-7
C15 H14 S2
258.40 g mol−1
C, 69.72; H, 5.46; S, 24.82
S [134, 135] OEGMEMA OEGMEMA Polymerization kinetics [25]a)

S
benzyl benzodithioate
CAS 27249–90-7
benzyl benzodithioate
C14 H12 S2
244.38 g mol−1
C, 68.81; H, 4.95; S, 26.24
O
S [65] MMA EGDMA Polymerization kinetics.
OH
Polymerization in supercritical
S CO2 [25]a)
2-([phenylcarbonothioyl]thio)
acetic acid
CAS 942–91-6
C9 H8 O2 S2
212.29 g mol−1
C, 50.92; H, 3.80; O, 15.07; S,
30.21
N
S
[136, 137] BzMA DPEHA Photoembossing application
S
2-cyanobutan-2-yl
benzodithioate
C12 H13 NS2
235.37 g mol−1
C, 61.24; H, 5.57; N, 5.95; S,
27.25
(continued)
[98, 102] MMA Diolefinic RAFT Self-healing polymer

agent
Si S S [138] BA Silica Nanoparticles RAFT agents immobilized on

O
silica nanoparticles via
S monofunctional, bifunctional,
benzyl (3-[methoxydimethyl and trifunctional anchor groups
silyl]propyl) carbonotrithioate
O
Si S S
O
S
benzyl (3-(dimethoxy[methyl]
silyl)propyl) carbonotrithioate
O
O
Si S S
O
S
benzyl (3-(trimethoxysilyl)
propyl) carbonotrithioate
O O [139] — BisEMA Stress relief mechanism
S S
BisGMA
HO OH TEGDMA
S [16] STY Chlorinated with Self-healable ionic crosslinked
2,2′ -(thiocarbonylbis VPy oxalyl chloride and polystyrene and poly(4-vinyl
[sulfanediyl])bis(2-methyl esterification with pyridine)
propanoic acid) 2-bromoethanol
CAS 355120–40-0 [140] STY HDA Nematic liquid crystal composite.
C9 H14 O4 S3 Macro-RAFT agent
282.40 g mol−1 prepared in first
Elemental analysis (%): step
C, 38.28; H, 5.00; O, 22.66; S,
34.06
S [141] (synthesis Macro-controller: EGDMA Core poly(butyl acrylate) and

of STY polystyrene – shell
S macro-controller), MAnh polystyrene-alt-maleic acid
[142] (polymer particles
network Polymer
1-phenylethyl synthesis) Network:
2-phenylethanedithioate
STY
C16 H16 S2
BA
272.43 g mol−1
C, 70.54; H, 5.92; S, 23.54
(continued)
S [143] STY DVB Porous monolith preparation.

Modification post-network
C12H25
S S formation
N
[144] DAAmEP Phosphate groups Synthesis of polymer network
2-cyanopropan-2-yl dodecyl based on phosphorous groups
carbonotrithioate
CAS 870196–83-1 [145] MMA Dangling groups Synthesis of nucleobase-
AdAMA with Nitrogen containing polymers by RAFT
C17 H31 NS3
OEGMA polymerization and RAFT
345.63 g mol−1 dispersion polymerization.
Elemental analysis (%): Self-assembly behaviour of
C, 59.08; H, 9.04; N, 4.05; S, 27.83 nucleobase polymers
S [67] STY DVB Polymerization kinetics
C12H25
S S
N
cyanomethyl dodecyl
carbonotrithioate
CAS 796045–97-1
C15 H27 NS3
317.58 g mol−1
C, 56.73; H, 8.57; N, 4.41; S,
30.29
S O [146] Am MBAm Hydrogel
S S OH
3-(([benzylthio]carbonothioyl)thio)
propanoic acid
[147] BA EGDMA Controlled release
CAS 497931–76-7
C11 H12 O2 S3
272.41 g mol−1
C, 48.50; H, 4.44; O, 11.75; S,
35.31
S [148] BA BDDA Photo-initiated preparation of

C6H13 O
crosslinked film
S S
O
ethyl 2-(([hexylthio]carbono-
C12 H22 O2 S3
294.50 g mol−1
C, 48.94; H, 7.53; O, 10.87; S,
32.66
(continued)
S [149] — BDDA Dilute solution hyperbranched

PEGDA polymer synthesis
N S
benzyl 1H-pyrrole-1-
carbodithioate
CAS 60795–38-2
C12 H11 NS2
233.35 g mol−1
C, 61.76; H, 4.75; N, 6.00; S,
27.48
O [149] — BDDA Dilute solution hyperbranched
polymer synthesis [3]a)
O S
C2H5 O
S
methyl 2-([ethoxycarbonothioyl]
thio)propanoate
C7 H12 O3 S2 [98] STY Di-olefinic RAFT Self-healing polymer
208.30 g mol−1 agent
Elemental analysis (%): [99, 100] BA Di-olefinic RAFT Stress-relief mechanism
C, 40.36; H, 5.81; O, 23.04; S, agent
30.79
a) Poor RAFT control.

Source: Adapted with permission from Moad [25]. Copyright 2014, Society of Chemical Industry.
Table 19.3 Multifunctional RAFT agents used in the synthesis of polymer networks.
Crosslinking
Chemical structure References Monomer agent Application
S [90] BMA EGDMA Model (co)networks. Bis-macro-RAFT agent

S
[91] BA, BMA, EGDMA Model (co)networks. Bis-macro-RAFT agent
S
DMAEMA, prepared in first step
STY
S
1,4-phenylenebis(propane-2,2-diyl) dibenzodithioate [92] TFEMA, EGDMA Model (co)networks. Bis-macro-RAFT agent
C26 H26 S4
[93] DMAEMA, EGDMA Model (co)networks. Bis-macro-RAFT agent
466.74 g mol−1 MAA prepared in first step
C, 66.91; H, 5.61; S, 27.48
[94] MMA EGDMA Model (co)networks. Bis-macro-RAFT agent

O
BA EGDA prepared in first step
S
O STY
n
S
N 2
Core O O
S O
N [150] — — Wavelength-selective polymer network.
S S
N
O N N
(continued)
Crosslinking
Chemical structure References Monomer agent Application
O
S
O O [95] DMAEMA, MMA EGDMA Model(co)networks with hydrolytically
S degradable crosslinks. Bis-macro-RAFT agent
2 prepared in first step.
N
O S
S S O C4H9
C4H9 O
[25, 97] NAM PEGDA Hydrogel with photodegradable crosslinks.
n
S S
Bis-macro-RAFT agent.
S O
O
O S S
[151] Pentaerythritol Tetra(ethylene Light-stimulated reconfiguration crosslinked
O
tetrakis(3-mercap- glycol) diacrylate polymer microparticles.
O topropionate)
S [152] NIPA RAFT agent Thermo-responsive hydrogels.
O Cyclodextrins
S S
O
4
STAR-CTA
S
O
S S [153] NAM Physical Self-healing physically crosslinked hydrogels
O IBA crosslinked
2 hydrogel
N N
S S
H H [154] BA Adenine and Supramolecular blends.
C11H22 N N C11H22
H 3C S S C6H12 S S CH3 Adenine acrylate thymine
O O Thymine acrylate dangling groups
O OH [155] 1-[2-(2-hydroxyethoxy) RAFT Agent Elaboration of well-defined

ethoxy]-5-[2-(2-methoxy telechelic 3-arm star polymer.
ethoxy)
S S
ethoxy]-naphthalene
O S S S S OH
OH S S O
Source: Adapted with permission from Moad [25]. Copyright 2014, Society of Chemical Industry.
The information provided in Tables 19.2 and 19.3 includes basic information
about RAFT agents (structure, name, CAS number if available, molecular weight,
etc.), monomers and crosslinkers used, applications or comments related to each
RAFT agent, and cited references. The main RAFT agents used in the synthesis
of polymer networks, based on literature citations, are 2-cyano-2-propyl ben-
zodithioate, 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid,
and 2-(dodecyl thiocarbonothioylthio)-2-methylpropionic acid. As observed in
Tables 19.2 and 19.3, the application fields for these polymer networks are diverse.
19.4 Synthesis of Polymer Networks by RAFT

Copolymerization of Vinyl/Multivinyl Monomers
in Supercritical Carbon Dioxide as Green Solvent
As explained earlier, RAFT agents and other types of RDRP controllers have been
used in the copolymerization of vinyl/multivinyl monomers, with or without sol-
vent, aiming at producing polymer networks of reduced heterogeneity [156, 157].
When the synthesis proceeds in the presence of solvents [56–58] or chain transfer
agents [59], which help in controlling M c , solvent selection and removal are impor-
tant issues to be considered. Supercritical carbon dioxide (scCO2 ) has been used as a
solvent in polymerization processes, including RDRP [158, 159]. Some of the advan-
tages of using scCO2 as a solvent include its innocuousness, its ease of removal and
recovery, and the fact that it is inexpensive and easy to acquire. On the other hand,
the disadvantages for its use include the initial high cost of investment in equip-
ment because reactors and other process vessels should withstand moderate to high
pressures and moderate to high temperatures [160].
The design and operation of polymerization processes carried out in scCO2
require an understanding of the thermodynamic behaviour of the reacting mixture
(e.g. the vapour–liquid equilibrium, VLE, region in a pressure vs. temperature chart,
as shown Figure 19.6). Solubilities of chemical species in compressed fluids such
as scCO2 are usually not known with precision [161]. Estimation of such values
from thermodynamic equations requires knowing or estimating parameters such
as Hildebrand solubility parameters (𝛿) [162] or Flory interaction parameters. [40]
A novel process for the synthesis of polymer networks of reduced heterogeneity by
RAFT copolymerization of vinyl/divinyl monomers in scCO2 was developed in our
group [163]. Polymerizations in scCO2 usually proceeded in two or more phases as a
dispersion polymerization process. As observed in Figure 19.7, differentiated char-
acteristics of the obtained polymer networks are obtained when the polymerization
proceeds in more than one phase.
Because of severe solubility limitations of many polymers in scCO2 , heteroge-
neous polymerizations are carried out by precipitation, dispersion, or emulsion
processes. The specific type of heterogeneous process will depend on the solu-
bility of the monomers and initiators in scCO2 . Most of the polymeric materials
obtained in scCO2 are produced by heterogeneous processes [164–166]. One way
to envision a dispersion polymerization process is to consider that it starts as a
19.4 Synthesis of Polymer Networks by Raft Copolymerization of Vinyl/Multivinyl Monomers 899
350
Outside the curve
300 supercritical
conditions
250
Pressure (bar)
Inside the curve

200 Vapor-liquid
Equilibrium
150
100
50
0
–100 –50 0 50 100 150 200 250 300
Temperature (°C)
Vapor Liquid
Figure 19.6 Schematic representation of a pressure (P) vs. temperature (T) curve for a
mixture containing monomers and carbon dioxide. Source: Adapted with permission from
Pérez-Salinas et al. [34]. Licensed under CC by 4.0.
Figure 19.7 Image of a poly(HEMA-co-EGDMA) polymer network synthesized in scCO2 .

Two distinguishable materials were obtained because of separation of the reaction mixture
during the synthesis in two phases: (i) a hard and brittle polymer network of hemispherical
shape, which corresponds to the shape of the bottom of the reactor vessel, and (ii) a soft
fluffy powder polymer network polymerized in the upper section of the reactor.
homogeneous process (solution polymerization, stage 1), followed by formation

of a dispersed phase by precipitation of polymer molecules that exceed a critical
size (stage 2) where the polymerization takes place in both phases, and concluding
in stage 3 where monomer is present only in the dispersed phase [166]. Even
though a dispersed phase will be formed in stage 2, it is important for process
operation and reduction of heterogeneity purposes that the reacting mixture is
indeed homogeneous during stage 1. That requires adequate determination of the
Hildebrand solubility parameter
20
for CO2 (J CM–3)0.5
18
16
14
12
10
8
6
206.8
4 179.3
2 151.7
0 124.1
AR re
(B ssu
96.5
)
20
e
30
Pr
40 50 68.9
60 70 80 90 100 41.4
Temperature (°C) 13.8
0–2 2–4 4–6 6–8 8–10 10–12 12–14 14–16 16–18 18–20
Figure 19.8 Hildebrand solubility parameter for CO2 around subcritical and supercritical
conditions.
initial operating conditions, and how they change during polymerization before
the formation of the dispersed phase (Figure 19.6) [166]. Estimation of component
solubilities for the reacting mixture (monomer(s), initiator, RAFT agent, etc.) at ini-
tial conditions can be obtained from Hildebrand solubility parameters (𝛿) or Flory
interaction parameters (𝜒) [40]. Solubility of solute in solvent is expected to occur if
𝛿CO2 (T,P) ≈ 𝛿 solute (T,P) . A polymer solute will be soluble in CO2 at the given T and P
if 𝜒 < 0.84.
Calculation of 𝛿CO2 at temperatures and pressures typical of dispersion polymer-
ization processes using a procedure described in the literature [162] is summarized
in Figure 19.8. Calculated values of the Flory interaction parameter (using the
methods described in Ref. [162]) between a polymer network based on HEMA
(95% weight) and EGDMA (5% weight) and CO2 , system studied experimentally by
our group [34], are shown in Figure 19.9. Finally, the calculated values of 𝜒 for a
2-hydroxyethyl methacrylate (HEMA) and scCO2 system are summarized in a 3-D
plot in Figure 19.10.
It is well known that stabilizers are needed in dispersion polymerization pro-
cesses to obtain particles of small and controlled sizes [164, 165, 167, 168]. One
easily available commercial stabilizer used in the synthesis of polymers by RP
in scCO2 is Krytox, a carboxylic acid end-capped perfluorinated polyether from
DuPont® [34, 169]. Krytox was used as a stabilizer in the pioneering studies on the
synthesis of polymer networks in scCO2 by RAFT copolymerization of STY/DVB
[65], MMA/EGDMA [170], and HEMA/EDGMA, where experimental conditions
are described in Table 19.4 [34].
Flory interaction parameter X (ADIM)

10000
1000
100
6.9
27.6 10
Pressure (BAR)
48.3
68.9
89.6 1
110.3
131.0 0.1
151.7
293.15
303.15
172.4
313.15
323.15
333.15
193.1
343.15
353.15
363.15
373.15
Temperature (K)
0.100 000 001–1 1–10 10–100 100–1000 1000–10 000
Figure 19.9 Calculated values of 𝜒 between a polymer network based on HEMA (95%
weight) and EGDMA (5% weight), and CO2 at operating conditions typical of dispersion
polymerization processes. 𝛿 solute in the calculations was estimated using Fedor’s method.
Flory interaction parameter X (ADIM)
10000
1000
100
6.9
27.6 10
Pressure (BAR)
48.3
68.9
89.6 1
110.3
131.0 0.1
151.7
293.15
303.15
172.4
313.15
323.15
333.15
193.1
343.15
353.15
363.15
373.15
Temperature (K)
0.100 000 001–1 1–10 10–100 100–1000 1000–10 000
Figure 19.10 Calculated values of 𝜒 between HEMA and CO2 .

Table 19.4 Swelling index (SI) and Mc results for conventional RP and RAFT
copolymerization of HEMA and EDGMA in scCO2 .
Krytox
RAFT (Wt% Mc
HEMA EGDMA AIBN agent wrt experimental
Sample (mmol) (mmol) (mmol) (mmol) HEMA) SI (g mol−1 )
G311 25 1.25 0.1 0 5 8.3 7681

G312 25 1.25 0.1 0 0 9.5 10 541
RP
G313 25 1.25 0.1 0 5 6.6 4407
G314 25 1.25 0.1 0 0 7.6 6221
RAFT G315 25 1.25 0.1 0.05 5 5.9 3329
G316 25 1.25 0.1 0.05 0 7.1 5274
G317 25 1.25 0.1 0.05 5 5.1 2289
G318 25 1.25 0.1 0.05 0 5.3 2530
Conditions: T = 65 ∘ C, P = 173 bar, t = 24 hours, 22% w/v CO2 .

Source: Adapted with permission from Pérez-Salinas et al. [34]. Licensed under CC by 4.0.
However, a comparison of scanning electron microscopy (SEM) micropho-

tographs for a case of RAFT copolymerization of HEMA/EDGMA in scCO2 with
no Krytox included in the formulation, and a case where Krytox was present
in the reacting system, resulted in no significant differences being noticed (see
Figure 19.11). As a matter of fact, larger particles were obtained in the case where
Krytox was included in the formulation.
This unexpected result may be explained by the inefficient mixing provided by the
magnetic stirrer bar placed in the interior of the high-pressure cell used as a reactor.
A description of the reacting system used for the experiments with HEMA/EDGMA
[34] is provided in García-Morán et al. [171].
Another possible explanation for this result may be that the appearance of
the dispersed phase may take place from the very beginning of the polymeriza-
tion if the initial operating conditions are contained in the two-phase zone of a
pressure–temperature diagram, as the one shown in Figure 19.6 for the case of
RAFT copolymerization of HEMA/EDGMA in scCO2 [34]. That is why, our operat-
ing procedure for the synthesis of polymer networks by RAFT copolymerization of
vinyl/divinyl monomers in scCO2 starts with creating a pressure (P) vs. temperature
(T) diagram using the software ASPEN for the actual formulation used in the
copolymerization. The P–T diagram for the system studied by Pérez-Salinas et al.
[34] is shown in Figure 19.6. Temperature is set to a value where the initiator works
properly (above 60 ∘ C). Pressure is then set at a value where the reacting mixture is
at supercritical conditions. By following this procedure, it is assured that the initial
conditions are within the supercritical region of the mixture (which can differ from
the supercritical region for pure scCO2 ).
Pressure and RAFT agent content are two important variables for control of poly-
mer network homogeneity, particle size, and morphology. The effects of pressure and
the presence or absence of RAFT agent (4-cyano-4-[(dodecylsulfanylthiocarbonyl)
Figure 19.11 SEM images of

poly(HEMA-co-EGDMA) synthesized
by RAFT copolymerization in scCO2 :
(a) synthesis in the absence of
Krytox and (b) synthesis in the
presence of Krytox. Reaction
conditions summarized in
Table 19.4.
(a)
(b)
sulfanyl] pentanoic acid) on the textural characteristics of poly(HEMA-co-EDGMA)

synthesized in scCO2 is shown are Figure 19.12 [172]. Synthesis conditions are
detailed in Figure 19.12 [172]. In summary, higher pressures seem to improve the
homogeneity of the produced polymer network. The presence of RAFT controller
dramatically improves the texture of the polymer network at higher pressures.
Detailed characterization results and further discussion are offered in Pérez-Salinas
[172].
Characterization by SEM, nitrogen physisorption, differential scanning calorime-
try (DSC), dynamic mechanical analysis (DMA), Fourier transform infrared
spectroscopy (FTIR), as well as performance evaluation in loading and release of
ciprofloxacin and vitamin B12 (see Figure 19.13), of the poly(HEMA-co-EDGMA)
polymer networks synthesized in our group [163], in the presence or absence of
RAFT agent (4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid),
was carried out [63, 163]. Significant structural and morphological differences were
observed. Polymer network particles synthesized by RAFT copolymerization of
HEMA and EDGMA in scCO2 were much more porous than the ones synthesized
in the absence of RAFT agent. They were able to retain higher amounts of vitamin
B12 within their structures. These combined results (including DSC and DMA)
suggest that the polymer network particles synthesized by RAFT copolymerization
are significantly less heterogeneous (nodes more evenly distributed within the
Reaction Pressure Conventional RP RAFT
~1500-1700 psi
Monolith with two different

textures, also implying at least
two phases.
Two different particle size
populations, implying presence
of at least two phases.
~4600-4800 psi
Homogeneous, fine, fluffy

powder.
Two different textures: a hard,
compact hydrogel, and
particulate granules, which
suggest presence of two or
more phases.
Figure 19.12 Comparison of textural characteristics of poly(HEMA-co-EGDMA) synthesized

in scCO2 at different pressures in the presence and absence of RAFT agents.
polymer network structure) than the ones synthesized in the absence of a RAFT
controller [163].
19.5 Modelling of Polymer Network Formation

Our companion chapter in this book entitled ‘Mathematical Modeling of RAFT Poly-
merization’, is focused on the modelling of RAFT polymerization processes where
50
Isotherm type IV
Bottleneck pores
45
40
Amount of vitamin B12 released (%)
35
30
25
20
Isotherm type II
15 Non porous material
10
0
0 200 400 600 800 1000 1200 1400 1600
Time (min)
scCO2 Controlled radial polymeryzation hydrogel scCO2 free radial polymerization hydrogel
Figure 19.13 Vitamin B12 release profiles, morphology, and interpretation of nitrogen
physisorption results for RAFT (blue circles) and conventional RP (red squares) polymer
networks. Source: Adapted with permission from Pérez-Salinas et al. [63]. Copyright 2016,
John Wiley & Sons.
crosslinking and gelation are not an issue. The polymer reaction engineering (PRE)
tools for analysis of polymerization processes, including the use of different mod-
elling techniques for calculation of molecular weight distributions or other polymer
structural characteristics, focused on ‘simple’ polymerization systems using RAFT
chemistry, are described in Chapter 7. This section is focused on the use or extension
of those techniques to the modelling of polymerization kinetics, molecular weight
development, as well as evolution of gel fraction and crosslinking density for systems
where polymer networks are produced.
Two of the pioneering works related to the synthesis of polymer networks by RDRP
are those from Ide and Fukuda [30, 31]. They studied the copolymerization of vinyl
and divinyl monomers in the presence of nitroxide controllers by nitroxide-mediated
radical polymerization (NMP). They concluded that polymer networks synthesized
by NMP are less heterogeneous than those synthesized by conventional RP. Since
then, numerous studies focused on the synthesis of polymer networks using RDRP
methodologies have been conducted, including NMP [173, 174], atom transfer rad-
ical polymerization (ATRP) [175], and RAFT [25, 176] polymerization. This topic
has been reviewed previously [25, 173]. The versatility of RAFT polymerization is
exemplified by its use in the production of polymer networks with unprecedented
capabilities [7, 46, 177]. It is desirable that these techniques allow the synthesis of
homogeneous structures with narrow molar mass distributions (MMDs).
The prediction of polymer network properties, which affect product end-use
performance, including copolymer composition, crosslinking density, and swelling
index, can be achieved by implementation of numerical methods. This section is

focused exclusively on polymer networks synthesized by mechanisms that involve
RAFT chemistry.
19.5.1 Background on Modelling of Crosslinking and RAFT

Polymer molecules synthesized by RAFT copolymerization with crosslinking
of vinyl/divinyl/multivinyl monomers contain several functional groups produced
through conventional and activation/deactivation reactions. The polymerization
scheme includes, as in conventional RP, the following chemical reactions: chemical
initiation, dimerization, thermal self-initiation, first propagation, chain transfer
to small molecules (monomer, solvent, and chain transfer agent), cyclization,
crosslinking, and termination by both combination and disproportionation [173].
Crosslinking occurs when active polymer molecules react with polymer molecules
with available PDB, as shown in Figure 19.14. Crosslinking leads to increasing
or even diverging weight average molecular weight (or weight-average chain
length Pw ).
Divinyl monomers are often used as crosslinkers (e.g., DVB and EGDMA) yielding
‘bridges’ between two polymer molecules. In the case of conventional RP, several
numerical approaches, such as the method of moments [178], Monte Carlo (MC)
[179–184], numerical fractionation technique (NFT) [179, 180, 185–188], generating
functions (GF) method [180, 189], and the software Predici® [181, 183, 187] have
been used to study polymer network formation.
Recently, the copolymerizations of STY and EDGMA, as well as STY
and TEGDMA at 95 ∘ C, in toluene, were studied using NFT [185]. Model predic-
tions and experimental data of monomer conversion, consumed PDBs, copolymer
composition, and gelation time agreed well.
Lazzari et al. [180] compared calculated profiles of weight-average chain
length (Pw ), gel fraction (wg ), and crosslink density obtained from four modeling
approaches: NFT, kinetic MC, a hybrid statistic/kinetic Flory/Tobita model (FT),
and the GF method [180]. It was found that NFT and FT are fast and reliable when
focusing on average properties, while kinetic MC and GF allow calculation of more
detailed properties, such as chain length distribution (CLD), at the expense of larger
computational times. Kinetic MC has also been used to study the copolymerization
of STY and DVB with different amounts of DVB [181]. The model yielded the same
results as the corresponding polymerization scheme implemented in the Predici
software during the pre-gelation period.
On the other hand, if a RAFT agent, whose structure and representation are
shown in Figure 19.2, is added to the reacting mixture, it will react with active
polymer radicals, R•m , to produce one-arm adduct polymer molecules, Rm A• B,
kp* Figure 19.14 Crosslinking reaction,

where kp∗ is the crosslinking kinetic rate
constant.
Table 19.5 Systems properties.
Property Equations
M10 + M20 − M1 − M2
Total monomer conversion x=
M10 + M20
dfi f − Fi dx
Unreacted monomer composition = i
dt 1 − x dt
∑2 ⋅
i=1 kpij 𝜑i fj
Instantaneous copolymer composition Fj =
kp
fi0 − fi (1 − x)
Accumulated copolymer composition Fi =
x
which undergo fragmentation to yield Rm A capped/dormant polymer molecules.

This reaction with the RAFT agent (AB molecule) is known as the pre-equilibrium
step. In the main equilibrium reaction, active polymer radicals and dormant
polymer molecules react to produce two-arm adduct polymer molecules, which
upon fragmentation produce dormant and living polymer molecules of exchanged
sizes. Additionally, Rm A• Rn molecules can undergo termination with active
polymer radicals generating three-arm dead polymer molecules [190]. Polymer-
ization and product properties for the copolymerization of vinyl monomer M 1
and crosslinker M 2 can be calculated using the equations summarized in Table 19.5.
19.5.2 Trifunctional Polymer Molecule Modelling Approach

In this approach, the main equilibrium between active polymer radicals and
dormant polymer molecules is simplified as a direct chain transfer reaction between
the two polymeric species (no polymer adducts produced), as shown in row 4
of Table 19.6. The model is based on the pseudo-kinetic rate constant method
[191]. The elementary reactions of the polymerization scheme considered in
this model, expressed in terms of a single type of polymer molecule denoted as
Rm,r,p , where m, r, and p refer to total number of monomer units, radicals and ‘A’
RAFT capped/dormant units (see Figure 19.15), respectively, are summarized in
Table 19.6. The trifunctional modelling approach has been used to study several
important copolymerizations with crosslinking systems, such as the batch and
semi-batch RAFT copolymerization of AM and N,N’-methylenebis(acrylamide)
(BisAM) using 3-benzyltrithiocarbonyl propionic acid (BCPA) and ammonium
persulfate (APS), at 60 ∘ C [146]. The same total amount of a BisAM solution was
continuously added to the reacting mixture at a constant rate from 0 (batch) to
2, 3, and 4.5 hours to investigate the effect of semi-batch operation on MMD and
branching structure. It was found that higher instantaneous BisAM concentrations
were obtained when shorter feeding periods were used, which resulted in higher
molar masses and branching densities; the model agreed well with the available
experimental data. Gelation took place only when the process was operated in batch
Table 19.6 Polymerization scheme for the trifunctional approach.
Kinetic rate
Reaction Equations constant
Initiation I → 2 R0, 1, 0 f , kd
First propagation R0, 1, 0 + M → R1, 1, 0 ki
Propagation Rm, r, p + M → Rm + 1, r, p (r)kp
Chain transfer to dormant polymer Rm, r, p + Rn, s, q → Rm, r − 1, p + 1 + Rn, s + 1, q − 1 (r)(q)kp
Intermolecular crosslinking Rm, r, p + Rn, s, q → Rm + n, r + s, p + q (r) (n) kp∗
Cyclization Rm, r, p, → Rm, r, p (r)(m)kcyc
Termination by disproportionation Rm, r, p + Rn, s, q → Rm, r − 1, p + Rn, s − 1, q (r)(s)ktd
Termination by combination Rm, r, p + Rn, s, q → Rm + n, r + s − 2, p + q (r)(s)ktc
A Figure 19.15 Schematic representation of the

trifunctional polymer molecule approach.
Mc
mode. Semi-batch operation resulted in molar masses of up to 1.5 × 106 g mol−1

(hyperbranched polymer) without gelation taking place.
The trifunctional model has also been used to study the RAFT miniemulsion
copolymerization of STY and triethylene glycol dimethacrylate (Tri-EGDMA) using
BCPA and sodium dodecyl sulfate (SDS), at 70 ∘ C [192]. It was observed that higher
Tri-EGDMA and lower RAFT agent concentrations resulted in higher values of
polymerization rate, weight-average molar mass (M w ), molar mass dispersity (Ð),
cyclization density (CD), and average number of propagating radicals per particle
(n). Furthermore, two cases conducted in semi-batch mode (continuous addition
of STY) yielded branched polymer molecules with uniform branching density (BD)
distributions.
The RAFT copolymerization of MMA and bis(2-methacryloyl)oxyethyl disulfide
(BMAODS, a cleavable monomer) using 2-cyano-2-propyldodecyl trithiocarbonate
(CPDTTC) and azobis(isobutyronitrile) (AIBN) in toluene, at 70 ∘ C, was investigated
with the purpose of obtaining information on the branching mechanism [193]. After
the formation of branched copolymer molecules, the presence of tributylphosphine
(Bu3 P) promoted the degradation of BMAODS disulfide crosslinkages, resulting
in the production of primary chains. The MMDs before and after disulfide bond
degradation were measured by gel permeation chromatography (GPC). The GPC
traces of the primary chains showed narrow MMDs and M n increased linearly
8 3
Conversions Run 7 Conversions
Mn (kg/mol)
6
PDI
22.8% 22.8% 4 2
46.1% 46.1% 2
0 1
63.6% 63.6% 0 20 40 60 80 100
87.2% 87.2% X (%)
99.6% 99.6% Run 7
102 103 104 105 106 102 103 104 105 106
–1 –1
MW (g mol ) MW (g mol )
(a) (b)
Figure 19.16 GPC traces of samples collected at different conversions for the RAFT
copolymerization of MMA and BMAODS using [MMA]0 /[BMAODS]0 = [MMA]0 /[CPDTTC]0
= 50 and [MMA]0 /[AIBN]0 = 50/0.2 in toluene (55 wt%) at 70 ∘ C: (a) before and (b) after
disulfide bond degradation. Source: Reproduced with permission from Liang et al. [193].
with conversion suggesting living behavior of the copolymerization as observed in

Figure 19.16. The trifunctional molecule approach was used to study the effect of
the amounts of divinyl monomer, RAFT agent, and monomer on the evolution with
conversion of M n , BD, and CD. The weight fraction of the copolymer containing
i-primary chains 𝜔(i), estimated from the GPC traces agreed well with Zhu’s
equation [194] (see Eqs. (19.4), (19.5), and Figure 19.17), where 𝜆p is the average
0.6 0.3
Run 3 Run 5
Run 2 Run 4
0.4 Run 1 0.2 Run 2
ω(i)
ω(i)
0.2 0.1
0.0 0.0
0 5 10 15 20 0 5 10 15 20
(a) i (b) i
0.6
Run 7
Run 2
0.4 Run 6
ω(i)
0.2
0.0
0 5 10 15 20
(c) i
Figure 19.17 Evolution of weight fraction of polymers containing i-primary chains

synthesized by RAFT copolymerization of MMA (1) and BMAODS (2) at (a) various [M1 ]0 /
[M2 ]0 (run 1 = 50/0.5, run 2 = 50/1, and run 3 = 50/1.5); (b) various primary chain lengths by
controlling [AB]0 /[M1 ]0 at 1/50 (run 2), 1/75 (run 4), and 1/100 (run 5); and (c) various initial
monomer concentrations of 15 (run 6), 30 (run 2), and 45 wt% (run 7). Source: Reproduced
with permission from Liang et al. [193]. Copyright 2016, American Chemical Society.
number of branching points per primary molecule and D - p is the molar mass
dispersity of the primary molecule, thus providing support to the random branch-
ing mechanism that takes place in the RAFT copolymerization of vinyl/divinyl
monomers.
[( ) ] ( )𝜎Z i ( )i−1
𝜎Z + 1 i − 1 ! 𝜎Z 𝜆p
𝜔 (i) = ( ) (19.4)
𝜎Z i ! (i − 1)! 𝜎 Z + 𝜆p 𝜎 Z + 𝜆p
𝜎Z + 1
Ðp = (19.5)
𝜎Z
19.5.3 Multifunctional Polymer Molecule Modelling Approach

In the multifunctional polymer molecule modelling approach, a single polymer
population with several functionalities is assumed to be present in the system. This
multifunctional polymer molecule is represented as Rm,r,p,x,f,𝜓 , where m, r, p, x, f , and
𝜓 refer to the number of monomer units, active radicals, ‘A’ capped/dormant units
attached to the polymer molecule, ‘A’ groups attached to two segments of the poly-
mer network, ‘*AB’ groups, and the reacting phase, respectively. The main difference
with the trifunctional model is that in the multifunctional model reactions with
intermediate radicals Rm A• B and Rm A• Rn as well as termination between R•m with
Rm A• Rn are considered in the polymerization scheme and model equations [195].
The polymerization scheme for the RAFT copolymerization with crosslinking of
vinyl and divinyl monomers, represented in terms of multifunctional molecules
(schematic representation shown in Figure 19.18), is summarized in Table 19.7).
A direct solution for Rm,r,p,x,f ,ψ implies the solution of a set of m × r × p × x × f × 𝜓
stiff non-linear ordinary differential equations (ODEs). Because m could reach up to
106 or higher values, this results in prohibitive computational costs. The reduction
of such a set of ODEs can be achieved by using the method of moments, as defined
in Eq. (19.6).
∑
∞
∑
∞
∑
∞
∑
∞
∑
∞
[ ]
Yi,j,u,v,w,𝜓 = mi r j pu xv f w Rm,r,p,x,f ,𝜓 (19.6)
m=1 r=0 p=0 x=0 f =0
The multifunctional modelling approach has been used to analyse the effect
of polymerization conditions on the formation of linear and crosslinked polymer
molecules by RAFT copolymerizations of vinyl/divinyl monomers [195]. The
performance of the multifunctional model has been compared to that of the
AB Figure 19.18 Schematic representation of the

multifunctional polymer molecule approach.
A
Mc
A
Table 19.7 Polymerization scheme for the RAFT copolymerization with crosslinking of
vinyl/divinyl monomers in terms of multifunctional polymer molecules, in phase 𝜓.
Reaction Equations Kinetic rate constant
Initiation I𝜓 → 2 R•in,𝜓 f , kd, 𝜓

Dimerization 2M 𝜓 → D𝜓 kdim, 𝜓
Thermal self-initiation D𝜓 + M𝜓 → D𝜓 + R1,1,0,0,0,𝜓
•
kthi, 𝜓
First propagation: R•in,𝜓 + M𝜓 → R1,1,0,0,0,𝜓 ki, 𝜓
(a) primary radicals
(b) radicals from RAFT B•𝜓 + M𝜓 → R1,1,0,0,0,𝜓 ki, 𝜓
leaving group
(c) dimeric radicals D•𝜓 + M𝜓 → R1,1,0,0,0,𝜓 ki, 𝜓
Propagation Rm, r, p, x, f , 𝜓 + M 𝜓 → (r)kp, 𝜓
Rm + 1, r, p, x, f , 𝜓
Reversible chain transfer Rm,r,p,x,f ,𝜓 + AB𝜓 ↔ (r)kadd, 𝜓 , (f + 1)k_add, 𝜓 ;
to the RAFT agent Rm,r−1,p,x,f +1,𝜓 ↔ (f + 1)kbd, 𝜓 ,
(pre-equilibrium) Rm,r−1,p+1,x,f ,𝜓 + B•𝜓 (p + 1)k_bd, 𝜓
Rm,r,p,x,f ,𝜓 + Rn,s,q,y,g,𝜓
Chain equilibration ↔ Rm+n,r+s−1,p+q−1,x+y+1,f +g,𝜓 (r)(q)ka, 𝜓 ,
(main equilibrium) (x + y + 1)k_a, 𝜓 ;
↔ Rm,r−1,p+1,x,f ,𝜓 + Rn,s+1,q−1,y,g,𝜓
(x + y + 1)kb, 𝜓 ,
(p + 1)(s + 1)k_b, 𝜓
Intermediate radical Rm, r, p, x, f , 𝜓 + Rn, s, q, y, g, 𝜓 → (r)(y)ktir, 𝜓
termination Rm + n, r + s − 1, p + q, x + y − 1, f + g, 𝜓
Intermolecular Rm, r, p, x, f , 𝜓 + Rn, s, q, y, g, 𝜓 → ∗
(r) (n) kp,𝜓
crosslinking (propagation Rm + n, r + s, p + q, x + y, f + g, 𝜓
through pendant double
bonds)
Cyclization Rm, r, p, x, f , 𝜓 → Rm, r, p, x, f , 𝜓 (r)(m)kcyc, 𝜓
Termination by Rm, r, p, x, f , 𝜓 + Rn, s, q, y, g, 𝜓 → (r)(s)ktd, 𝜓
disproportionation Rm, r − 1, p, x, f , 𝜓 + Rn, s − 1, q, y, g, 𝜓
Termination by Rm, r, p, x, f , 𝜓 + Rn, s, q, y, g, 𝜓 → (r)(s)ktc, 𝜓
combination Rm + n, r + s − 2, p + q, x + y, f + g, 𝜓
monofunctional model [196] for the RAFT homopolymerization of styrene using

2-cyano-prop-2-yl 1-dithionaftalate (CPDN) and AIBN at 60 and 72 ∘ C [195]. Both
models generated the same results for monomer conversion vs. time and M n
vs. conversion, as well as concentrations of polymeric species [195]. The RAFT
copolymerization with crosslinking of STY and DVB using benzoyl peroxide (BPO)
and S-thiobenzoyl thioglycolic acid (TBTGA) at 80 ∘ C was also addressed. The
model captured well the effect of RAFT agent concentration on the onset of gelation
and gel content in the polymer.
The multifunctional polymer molecule modelling approach was also used
to study the RAFT homo- and copolymerization (with crosslinking) of HEMA
1
2 3
0.9
0.8
1
0.7 5
Conversion
0.6 4
6
0.5
0.4
0.3
0.2
0.1
0
0 0.5 1 1.5 2 2.5
(a) Time (h)
1010
6 5 4 3
8
10
Mn, Mw (g/mol)
2 1
106
104
102
100
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
(b) Conversion
1
0.9
0.8
0.7
0.6
Wgel
0.5
0.4
0.3
0.2
0.1 6 5 4 3 2 1
0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
(c) Conversion
Figure 19.19 Effect of crosslinker content on (a) conversion vs. time, (b) molecular weight
development, and (c) gel fraction evolution in the RAFT copolymerization of HEMA/EGDMA
in p-dioxane. Simulated profiles: (1) f 20 = 0.001; (2) f 20 = 0.003; (3) f 20 = 0.008; (4)
f 20 = 0.01; (5) f 20 = 0.02; and (6) f 20 = 0.05. Source: Reproduced with permission from
Espinosa-Pérez et al. [64]. Copyright 2014, John Wiley & Sons.
(and a crosslinker). The crosslinkers used were EGDMA and DEGMA [64].
Model predictions and experimental profiles of conversion vs. time agreed well
for the homopolymerization of HEMA using AIBN and cumyl dithiobenzoate
(CDB) in dimethylformamide (DMF) at 60 ∘ C. In the case of copolymerization
of HEMA/DEGMA using CDB and AIBN, it was found that increasing the
amount of crosslinker (5–10 wt%) or decreasing the RAFT/initiator ratio (7 to
5) yielded polymer networks with higher crosslink densities (𝜌). It was also
found that gelation occurred sooner while gel fraction (wg ) increased grad-
ually with conversion. The copolymerization of HEMA and EGDMA using
4-cyano-4-(dodecylsulfanylthiocarbonyl)sulfanyl pentanoic acid in p-dioxane and
in scCO2 was also investigated [64]. It was found for the copolymerization in
p-dioxane that an increase in the amount of crosslinker resulted in lower poly-
merization rates because the propagation rate (kp ) for EGDMA was lower that kp
for HEMA. However, the gelation point occurred sooner for the cases with higher
amounts of divinyl comonomer, as shown in Figure 19.19. The model could also
describe the case in scCO2 where 93% monomer conversion was reached in 16 hours
for a polymerization carried out at 65 ∘ C.
Polymer monoliths are porous solid materials synthesized by RP of vinyl/divinyl
monomers with a high content of the divinyl monomer (crosslinker) in an unstirred
mould or vessel to obtain a single piece of material. RAFT agents can be used to
introduce functional groups into the polymer monolith. The copolymerization of
STY and DVB using AIBN and 2-cyano-2-propyl dodecyl trithiocarbonate (CPDTC)
at 60 ∘ C in dodecanol (45 vol%) and benzene (5 vol%) aimed at producing monolith
structures was investigated by researchers from CSIRO [143] and modelled by our
group [197]. Eight cases were addressed: conventional RP (Case A); RAFT polymer-
ization with [AB]0 /[I]0 =2 (Case B); conventional RP with f 20 = 0.28 (Case C); and
RAFT copolymerization with f 20 = 0.28 and [AB]0 /[I]0 = 0.4, 1, 2, and 10 (Cases
D–G) [143, 197]. As observed in Figure 19.20, typical profiles of ln[M]/[M]0 vs. time
and M n , M w vs. conversion for Cases A and B were obtained. On the other hand,
Figure 19.20 Comparison of 3

conventional homopolymerization of Case A
styrene (Case A) with RAFT Case B
2.5 Case C
homopolymerization of styrene (Case B)
and conventional copolymerization of
styrene-DVB (Case C). Source: 2
Reproduced with permission from
In MO/M
López-Domínguez et al. [197]. Copyright

2014, John Wiley & Sons. 1.5
0.5
0
0 4 8 12 16
Time (h)
3 Figure 19.21 Effect of concentration

Case D of the RAFT agent on polymerization
Case E
rate expressed as lnM0 /M vs. time.
2.5 Case F
Case G D [RAFT]0 =0.0111, 0.0277, 0.0556, and
E 0.277 M for cases D, E, F, and G,
Calculated
2 respectively. Source: Reproduced with
permission from López-Domínguez
In MO/M
et al. [197]. Copyright 2014, John Wiley

1.5 & Sons.
F
1
G
0.5
0
0 4 8 12 16
Time (h)
strong auto-acceleration effects are observed in Figure 19.21 for Cases C–G (bulk
systems). Diffusion-controlled effects (DCE) were accounted for using free volume
theory, as shown in Eq. (19.7). Unusually high values for the 𝛽 i parameters, up to one
order of magnitude higher than those used for systems with low crosslinker content,
were required to fit the experimental data. These unusually high values accounted
for non-isothermal effects during the polymerization, an effect not included in the
model [197]. As expected, it was observed that the increase of RAFT agent delayed
the gelation point, increased compositional drift in the low conversion region, and
increased 𝜌, which suggested that less heterogeneous polymer networks were pro-
duced. Regarding the concentration of polymeric species, living polymer increased
as a consequence of the auto-acceleration effect, while dormant polymer was the
dominant species and remained constant throughout the polymerization.
[ ( )]
0 1 1
ki = ki exp −𝛽i − (19.7)
Vf Vf 0
The multifunctional polymer molecule modelling approach was extended to

two-phase polymerization [62]. The polymerization was assumed to proceed in three
stages. The partition of components between the two phases was calculated using
semi-empirical equations. Formation of polymer network molecules was assumed
to proceed in the dispersed phase only. DCEs were assumed to take place only in this
phase. The system studied was the copolymerization of STY and DVB (crosslinker
constant remained constant at f 20 = 0.01) using BPO and TBTGA at 80 ∘ C and
300 bars. Four cases were analysed. Case 1 corresponded to a conventional RP system
(absence of RAFT agent), which was modelled using a monofunctional approach
reported earlier. As shown in Figure 19.22, RAFT agent content varied in Cases 2–4
([AB]0 /[I]0 = 0.7, 1, and 1.5). As expected, in Case 1, the gelation point occurred
early during the polymerization and it was delayed in Cases 1–4; the more RAFT
agent included in the formulation, the longer it took for gelation to occur. However,
the agreement between experimental data and model predictions was only fair.
0.8
Conversion
0.6
0.4 Case 1
Case 2
Case 3
0.2 Case 4
Calculated
0
0 10 20 30 40 50 60 70
Time (h)
Figure 19.22 Comparison of calculated and experimental profiles of conversion vs. time
for Cases 1–4. Source: Reproduced with permission from López-Domínguez et al. [62].
The multifunctional molecule modelling approach developed in our group has

also been used by Oliveira et al. [198] to model the copolymerization of HEMA
and EGDMA using 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPA), as
well as the copolymerization of MMA and EGDMA using 2-cyano-2-propyl ben-
zodithiobenzoate (CYDB) at 60 ∘ C. The model was contrasted against experimental
data of monomer conversion and gel fraction.
19.5.4 Kinetic Random Branching Theory (KRBT)

The development of the structure properties in solution of branched polymers
synthesized by RDRP methods can be followed by using kinetic random branching
theory (KRBT). [199]. KRBT is based on random branching theory (RBT), which
considers that branched polymers are built up by random assembly of simple units
(oligomeric chains or cluster of linear chains) [200, 201]. If these simple units
are linear chains produced by RDRP methods, their molar masses should follow
a Gaussian-like distribution. Linear chains synthesized by conventional methods
should follow an exponential distribution.
The structure of polymer molecules is determined by five parameters: mean size
of the simple unit (𝜎 (nm)), average number of random steps in the simple unit (𝛾),
persistence number (𝜏), and maximum density of simple units (𝜌0 ).
Several experiments were carried out to test the relationship between
size-mass scaling (radius of gyration (r g (nm)) vs. molar mass (M w ) predicted
( )
[M]
by the theory. It was found that copolymers of MMA/EGDMA [AB]o = 200 ,
( ) o
[M]
MMA/DVB [AB]o = 20 , alternating maleic anhydride (MAnh)/Sty with DVB
( o ) ( )
[DVB]o [DVB]o [DVB]o [DVB]o
= 0.8 and = 1 , DVB = 1 and = 20 , and DVB/MAnh
( [AB]o ) [AB]o [AB]o [AB]o
[DVB]o
[AB]
= 1 agreed well with the theory, suggesting that the polymers can be
o
Table 19.8 List of parameters used in model equations.
Parameter Representation
Branching density BD (Dimensionless)

Cyclization density CD (Dimensionless)
Molar mass dispersity - (Dimensionless)
D
Molar mass dispersity of the primary molecule - p (Dimensionless)
D
Unreacted monomer fraction f i (Dimensionless)
Instantaneous copolymer composition F j (Dimensionless)
Accumulated copolymer composition F i (Dimensionless)
Second-order intrinsic kinetic rate constant for ki0 (l mol−1 s−1 )
reaction i
Kinetic rate constant for propagation of radical type kpij (l mol−1 s−1 )
i with monomer unit j
Pseudo-kinetic rate constant for the forward and ka (l mol−1 s−1 ), k_a (s−1 )
reverse addition step of the chain equilibration
reaction
Pseudo-kinetic rate constant for the forward and kadd (l mol−1 s−1 ), k_add (s−1 )
reverse addition step of the reversible chain transfer
to RAFT agent reaction
Pseudo-kinetic rate constant for the forward and kb (s−1 ), k_b (l mol−1 s−1 )
reverse fragmentation step of the chain equilibration
reaction
Kinetic rate constant for the forward and reverse kbd (s−1 ), k_bd (l mol−1 s−1 )
fragmentation step of the reversible chain transfer to
RAFT agent
Pseudo-kinetic rate constant for effective kcyc (s−1 )
intramolecular propagation through pendant double
bonds
Initiator decomposition kinetic rate constant kd (s−1 )
Initiator decomposition kinetic rate constant kdim (l mol−1 s−1 )
Kinetic rate constant for the first propagation step ki (l mol−1 s−1 )
Pseudo-kinetic rate constant for propagation kp (l mol−1 s−1 )
Termination by combination kinetic rate constant ktc (l mol−1 s−1 )
Termination by disproportionation kinetic rate ktd (l mol−1 s−1 )
constant
Kinetic rate constant for thermal self-initiation kthi (l mol−1 s−1 )
kinetic rate constant for intermediate termination ktir (l mol−1 s−1 )
Monomer j M j (mol)
Molar mass between crosslinking points in absence M c , Mc0 (g mol−1 )
and presence of solvent
Number and weight molar mass M n (g mol−1 )
Average number of propagating radicals per particle n (Dimensionless)
Number- and weight-average chain length Pn , Pw (Dimensionless)
(continued)
Parameter Representation
Material constant Q (Dimensionless)

Radius of gyration r g (nm)
Universal gas constant R (J mol−1 K−1 )
Trifuncional polymer molecule Rm,r,p (mol)
Multifunctional polymer molecule Rm,r,p,x,f (mol)
Polymer radical of size m R•m
One-arm adduct of size m Rm A• B
Dormant polymer of size m Rm A
Two-arm adduct (macro-RAFT radical) of size m + n Rm A• Rn
Polymer volume fraction in the gel 𝜐2, s (Dimensionless)
Polymer volume fraction during the pre-gelation 𝜐2, r (Dimensionless)
period
Free volume V f (l)
Solvent molar volume V solvent (l mol−1 )
Swelling index Sindex (Dimensionless)
Monomer conversion x (Dimensionless)
Gel fraction wg (Dimensionless)
Diffusion-controlled parameter 𝛽 i (Dimensionless)
Hildebrand solubility parameter 𝛿 (Dimensionless)
Polymer density 𝜌polymer (g cm−3 )
Solvent density 𝜌s (g cm−3 )
Crosslinking density 𝜌 (Dimensionless)
Maximum density of simple units 𝜌0 (Dimensionless)
Average number of random steps in the simple unit 𝛾 (Dimensionless)
Flory polymer solvent interaction parameter 𝜒 1 (Dimensionless)
Parameter used in KBT 𝜅 (Dimensionless)
Solid material deformation 𝜆 (Dimensionless)
Average number of branching points per primary 𝜆p (Dimensionless)
molecule
Persistent number 𝜏 (Dimensionless)
Normal stress difference 𝜎 Mooney (J)
Constant used in Zhu’s equation 𝜎 Z (Dimensionless)
Mean size of the simple unit 𝜎 (nm)
Weight fraction of the copolymer containing 𝜔(i) (Dimensionless)
i-primary chains
Phase 𝜓 (Dimensionless)
considered as randomly branched simple units. The evolution of 𝜎 and r g with time
[M]
was also studied for copolymer MMA/DVB ( [AB]o = 20). In addition, by assuming
o
an exponential distribution of monomers in the simple unit, it was shown that
3
increasing dimensionless parameter 𝜅 = 𝜌0 𝜎 or decreasing parameter 𝛾 changes
the relationship between radius of gyration and molar mass from rg ∼ log M w to
rg2 ∼ log M w . The parameters used throughout the text are listed in Table 19.8.
19.6 Closing Remarks

An overview on the use of RAFT chemistry for the synthesis of polymer networks
was presented. Our chapter updates the review on the topic by Moad [25] and
expands it to topics of polymer chemistry not originally covered by him (e.g.
reversible polymer networks based on ionic bonds; syntheses of materials described
as nanogels, microgels, core-crosslinked stars, thermo- or pH- responsive materials,
self-healing polymer networks, and ‘arm-first’ stars or hyperbranched polymers
that can be formed by RAFT (co)polymerization of similar components under
different reaction conditions before gelation).
Two very important topics included in our chapter that were not considered
in Ref. [25] are the synthesis of polymer networks by RAFT copolymerization
of vinyl/divinyl monomers in scCO2 and the mathematical modelling of poly-
mer network formation by copolymerization with crosslinking of vinyl/divinyl
monomers.
Acknowledgements
Financial support from the following sources is gratefully acknowledged: (a)
Consejo Nacional de Ciencia y Tecnología (CONACYT, México), PhD scholarships
granted to P.P.-S. and P.L.-D.; (b) DGAPA-UNAM, Projects PAPIIT IG100718,
IV100119, TA100818, and TA102120, as well as PASPA sabbatical support (U. of
Waterloo, Canada) to E.V.-L.; (c) Facultad de Química-UNAM, research funds
granted to E. V.-L. and A.R.-A. (PAIP 5000-9078 and 5000-9167, respectively); and
(d) University of Waterloo, Department of Chemical Engineering, partial sabbatical
support to E.V.-L.
References
1 Bhattacharya, A. and Ray, P. (2009). Introduction. In: Polymer Grafting and

Crosslinking (eds. A. Bhattacharya, J.W. Rawlins and P. Ray), 1–5. Hoboken, NJ:
Wiley.
2 Hernández-Ortiz, J.C. and Vivaldo-Lima, E. (2013). Crosslinking. In: Handbook
of Polymer Synthesis, Characterization, and Processing (eds. E. Saldívar-Guerra
and E. Vivaldo-Lima), 187–204. Hoboken, NJ: Wiley.
References 919
3 Li, X., Wang, S., Wang, K. et al. (2018). Polymer ionic liquid network: a highly
effective reusable catalyst for one-pot synthesis of heterocyclic compounds. RSC
Adv. 8 (74): 42292–42299.
4 Yang, Z., Kangyu, F., Yu, J. et al. (2018). “pH-triggered” drug release using
shell cross-linked micelles from aqueous RAFT-synthesized PAPMA-b-PNIPAM
copolymers. J. Polym. Res. 25 (8): 164.
5 Yildirim, E. and Caykara, T. (2018). Ibuprofen-imprinted ultrathin poly[N-(2-
hydroxypropyl) methacrylamide] films. J. Appl. Polym. Sci. 135 (4): 45707.
6 Chen, Y., Gao, Y., and Lucília P. Silva, et al. (2018). A thermo-/pH-responsive
hydrogel (PNIPAM-PDMA-PAA) with diverse nanostructures and gel behaviors
as a general drug carrier for drug release. Polym. Chem. 9 (29): 4063–4072.
7 Peng, H., Huang, X., Melle, A. et al. (2019). Redox-responsive degradable
prodrug nanogels for intracellular drug delivery by crosslinking of amine-
functionalized poly(N-vinylpyrrolidone) copolymers. J. Colloid Interface Sci. 540:
612–622.
8 Roointan, A., Farzanfar, J., Mohammadi-Samani, S. et al. (2018). Smart pH
responsive drug delivery system based on poly(HEMA-co-DMAEMA) nanohy-
drogel. Int. J. Pharm. 552 (2): 301–311.
9 Liu, S., Tian, L., Mao, H. et al. (2018). Micellization and sol-gel transition
of novel thermo- and pH-responsive ABC triblock copolymer synthesized by
RAFT. J. Polym. Res. 25 (12): 264.
10 Montgomery, K.S., Davidson, R.W.M., Cao, B. et al. (2018). Effective
macrophage delivery using RAFT copolymer derived nanoparticles. Polym.
Chem. 9 (1): 131–137.
11 Kim, S. and Seo, M. (2018). Control of porosity in hierarchically porous poly-
mers derived from hyper-crosslinked block polymer precursors. J. Polym. Sci. A
Polym. Chem. 56 (8): 900–913.
12 Shin, I., Nam, J., Lee, K. et al. (2018). Poly(ethylene glycol) (PEG)-crosslinked
poly(vinyl pyridine)–PEG–poly(vinyl pyridine)-based triblock copolymers pre-
pared by RAFT polymerization as novel gel polymer electrolytes. Polym. Chem.
9 (42): 5190–5199.
13 Ali, W., Gebert, B., Altinpinar, S. et al. (2018). On the potential of using
dual-function hydrogels for brackish water desalination. Polymers 10 (6): 567.
14 Chen, M., Li, J.-W., Zhang, W.-J. et al. (2019). pH- and reductant-responsive
polymeric vesicles with robust membrane-cross-linked structures: in situ
cross-linking in polymerization-induced self-assembly. Macromolecules 52 (3):
1140–1149.
15 Banerjee, S.L., Hoskins, R., Swift, T. et al. (2018). A self-healable fluorescence
active hydrogel based on ionic block copolymers prepared via ring opening
polymerization and xanthate mediated RAFT polymerization. Polym. Chem. 9:
1190–1205.
16 Dong, P., Cui, K., Xu, F. et al. (2018). Synthesis of new ionic crosslinked
polymer hydrogel combining polystyrene and poly(4-vinyl pyridine) and its
self-healing through a reshuffling reaction of the trithiocarbonate moiety under
irradiation of ultraviolet light. Polym. Int. 67 (7): 868–873.
17 Banerjee, S.L. and Singha, N.K. (2017). A new class of dual responsive
self-healable hydrogels based on a core crosslinked ionic block copolymer
micelle prepared via RAFT polymerization and Diels–Alder “click” chemistry.
Soft Matter 13 (47): 9024–9035.
18 Guo, Z., Ma, W., Hongjian, G. et al. (2017). pH-switchable and self-healable
hydrogels based on ketone type acylhydrazone dynamic covalent bonds. Soft
Matter 13 (40): 7371–7380.
19 Chen, Y., Wang, W., Wu, D. et al. (2018). Injectable self-healing zwitterionic
hydrogels based on dynamic Benzoxaborole–sugar interactions with tunable
mechanical properties. Biomacromolecules 19 (2): 596–605.
20 Flory, P.J. (1953). Molecular weight distributions in nonlinear polymers and
the theory of gelation. In: Principles of Polymer Chemistry, 386–395. Ithaca, NY:
Cornell University Press.
21 Stockmayer, W.H. (1943). Theory of molecular size distribution and gel forma-
tion in branched-chain polymers. J. Chem. Phys. 11 (2): 45–55.
22 Stockmayer, W.H. (1944). Theory of molecular size distribution and gel for-
mation in branched polymers II. General cross linking. J. Chem. Phys. 12 (4):
125–131.
23 Walling, C. (1945). Gel formation in addition polymerization. J. Am. Chem. Soc.
67 (3): 441–447.
24 Storey, B.T. (1965). Copolymerization of styrene and p-divinylbenzene. Initial
rates and gel points. J. Polym. Sci. A: Gen. Papers 3 (1): 265–282.
25 Moad, G. (2015). RAFT (reversible addition–fragmentation chain transfer)
crosslinking (co)polymerization of multi-olefinic monomers to form polymer
networks. Polym. Int. 64 (1): 15–24.
26 Solomon D. H., Qiao G. G. and Abrol S. (1999). Process for microgel prepara-
tion. Patent WO9958588A1.
27 Berge C. T., Fryd M., Johnson J. W., et al. (2000). Microgels and process for
their preparation. Patent WO2000002939A1.
28 Moad, G., Mayadunne, R.T.A., Rizzardo, E. et al. (2003). Synthesis of novel
architectures by radical polymerization with reversible addition fragmentation
chain transfer (RAFT polymerization). Macromol. Symp. 192 (1): 1–12.
29 Moad, G., Rizzardo, E., and Thang, S.H. (2008). Radical addition–fragmentation
chemistry in polymer synthesis. Polymer 49 (5): 1079–1131.
30 Ide, N. and Fukuda, T. (1997). Nitroxide-controlled free-radical copolymer-
ization of vinyl and divinyl monomers. Evaluation of pendant-vinyl reactivity.
31 Ide, N. and Fukuda, T. (1999). Nitroxide-controlled free-radical copolymer-
ization of vinyl and divinyl monomers. 2. Gelation. Macromolecules 32 (1):
95–99.
32 Scott, A.J., Nabifar, A., and Penlidis, A. (2014). Branched and crosslinked
polymers synthesized through NMRP: quantitative indicators for network
homogeneity? Macromol. React. Eng. 8: 639–657.
33 Ward, J.H. and Peppas, N.A. (2000). Kinetic gelation modeling of controlled
radical polymerizations. Macromolecules 33 (14): 5137–5142.
References 921
34 Pérez-Salinas, P., Jaramillo-Soto, G., Rosas-Aburto, A. et al. (2017). Compari-

son of polymer networks synthesized by conventional free radical and RAFT
copolymerization processes in supercritical carbon dioxide. Processes 5 (2): 26.
35 Yui, N., Mrsny, R.J., Park, K. et al. (2004). Reflexive Polymers and Hydrogels.
Understanding and Designing Fast Responsive Polymeric Systems. Boca Raton, FL
(chapter 7): CRC Press LLC.
36 Amsden, B. (1998). Solute diffusion within hydrogels. Mechanisms and models.
37 Bell, C.L. and Peppas, N.A. (1996). Equilibrium and dynamic swelling of poly-
acrylates. Polym. Eng. Sci. 36 (14): 1856–1861.
38 Chuang, W.-Y., Young, T.-H., Wang, D.-M. et al. (2000). Swelling behavior of
hydrophobic polymers in water/ethanol mixtures. Polymer 41 (23): 8339–8347.
39 Lopez, C.G. and Richtering, W. (2017). Does Flory–Rehner theory quantita-
tively describe the swelling of thermoresponsive microgels? Soft Matter 13 (44):
8271–8280.
40 Van Krevelen, D.W. and te Nijenhuis, K. (2009). Mechanical properties of solid
polymers. In: Properties of Polymers. Their Correlation with Chemical Structure;
their Numerical Estimation and Prediction from Additive Group Contributions,
4e, 402–405. Amsterdam, the Netherlands: Elsevier.
41 Hamed, G.R. (2012). Materials and compounds. In: Engineering with Rubber.
How to Desing Rubber Components, 3e (ed. A.N. Gent), 11–36. Cincinnati, OH:
Hanser Publications.
42 Sperling, L.H. (2006). Crosslinked polymers and rubber elasticity. In: Introduc-
tion To Physical Polymer Science, 4e, 427–505. Hoboken, NJ: Wiley.
43 Armando Ortiz Prado, Juan Armando Ortiz Valera, Osvaldo Ruiz Cervantes.
(2013). Introducción a la Mecánica del Medio Contínuo, Universidad Nacional
Autónoma de México, Facultad de Ingeniería, Ciudad Universitaria, México,
pp. 199–324.
44 Chakma, P., Digby, Z.A., Via, J. et al. (2018). Tuning thermoresponsive network
materials through macromolecular architecture and dynamic thiol-Michael
chemistry. Polym. Chem. 9 (38): 4744–4756.
45 Mark, J.E. and Erman, B. (2007). Swelling of networks and volume phase tran-
sitions. In: Rubberlike Elasticity. A Molecular Primer, 2e, 71–77. Cambridge, UK:
Cambridge University Press.
46 Yuan, B., Ding, M., Duan, W. et al. (2018). Thermoresponsive hydrogels with
high elasticity and rapid response synthesized by RAFT polymerization via
special crosslinking. Polymer 159: 1–5.
47 Yang, Z., Abbas, Z.M., Sarkar, A. et al. (2018). Surface-initiated reversible
addition-fragmentation chain transfer polymerization of chloroprene and
mechanical properties of matrix-free polychloroprene nanocomposites. Polymer
135: 193–199.
48 Mondal, P., Raut, S.K., and Singha, N.K. (2018). Thermally amendable
tailor-made acrylate copolymers via RAFT polymerization and ultra-
fast alder-ene “click” chemistry. J. Polym. Sci. A Polym. Chem. 56 (20):
2310–2318.
49 Cuthbert, J., Zhang, T., Biswas, S. et al. (2018). Structurally tailored and engi-
neered macromolecular (STEM) gels as soft elastomers and hard/soft interfaces.
50 Cuthbert, J., Beziau, A., Gottlieb, E. et al. (2018). Transformable materials:
structurally tailored and engineered macromolecular (STEM) gels by controlled
51 Banerjee, S.L., Bhattacharya, K., Samanta, S. et al. (2018). Self-healable antifoul-
ing zwitterionic hydrogel based on synergistic phototriggered dynamic disulfide
metathesis reaction and ionic interaction. ACS Appl. Mater. Interfaces 10 (32):
27391–27406.
52 Li, H., Luo, Y., and Gao, X. (2017). Core–shell nano-latex blending method to
prepare multi-shape memory polymers. Soft Matter 13 (31): 5324–5331.
53 Xu, Q., Sigen, A., Gao, Y. et al. (2018). A hybrid injectable hydrogel from hyper-
branched PEG macromer as a stem cell delivery and retention platform for dia-
betic wound healing. Acta Biomater. 75: 63–74.
54 Li, L., Jiang, R., Chen, J. et al. (2017). In situ synthesis and self-reinforcement
of polymeric composite hydrogel based on particulate macro-RAFT agents. RSC
Adv. 7 (3): 1513–1519.
55 Yang, P.-C., Li, S.-Q., Chien, Y.-H. et al. (2017). Synthesis, chemosensory prop-
erties, and self-assembly of terpyridine-containing conjugated polycarbazole
through RAFT polymerization and heck coupling reaction. Polymers 9 (9):
427.
56 Antonietti, M. and Rosenauer, C. (1991). Properties of fractal divinylbenzene
microgels. Macromolecules 24 (11): 3434–3442.
57 Zhu, S. and Hamielec, A. (1992). Kinetics of polymeric network synthesis via
free-radical mechanisms – polymerization and polymer modification. Macromol.
Symp. 63 (1): 135–182.
58 Tobita, H. and Zhu, S. (1996). Polyradical distribution in free radical crosslink-
ing of polymer chains. J. Polym. Sci. Part B Polym. Phys. 34 (12): 2099–2104.
59 O’Brien, N., McKee, A., Sherrington, D.C. et al. (2000). Facile, versatile and cost
effective route to branched vinyl polymers. Polymer 41 (15): 6027–6031.
60 Keddie, D.J., Moad, G., Rizzardo, E. et al. (2012). RAFT agent design and
synthesis. Macromolecules 45 (13): 5321–5342.
61 Moad, G., Rizzardo, E., and Thang, S.H. (2012). Living radical polymerization
by the RAFT process – a third update. Aust. J. Chem. 65 (8): 985–1076.
62 López-Domínguez, P., Hernández-Ortiz, J.C., and Vivaldo-Lima, E. (2018). Mod-
eling of RAFT copolymerization with crosslinking of styrene/divinylbenzene in
supercritical carbon dioxide. Macromol. Theo. Simul. 27 (1): 1700064.
63 Pérez-Salinas, P., Rosas-Aburto, A., Antonio-Hernández, C.H. et al. (2016). Con-
trolled release of vitamin B-12 using hydrogels synthesized by free radical and
RAFT copolymerization in scCO2 . Macromol. Symp. 360 (1): 69–77.
64 Espinosa-Pérez, L., Hernández-Ortiz, J.C., López-Domínguez, P. et al. (2014).
Modeling of the production of hydrogels from hydroxyethyl methacrylate and
(Di)ethylene glycol dimethacrylate in the presence of RAFT agents. Macromol.
React. Eng. 8 (8): 564–579.
References 923
65 Jaramillo-Soto, G. and Vivaldo-Lima, E. (2012). RAFT copolymerization of

styrene/divinylbenzene in supercritical carbon dioxide. Aust. J. Chem. 65 (8):
1177–1185.
66 Gonçalves, M.A.D., Pinto, V.D., Costa, R.A.S. et al. (2013). Stimuli-responsive
hydrogels synthesis using free radical and RAFT polymerization. Macromol.
Symp. 333 (1): 41–54.
67 Gonçalves, M.A.D., Pinto, V.D., Dias, R.C.S. et al. (2013). Dynamics of network
formation in aqueous suspension RAFT styrene/divinylbenzene copolymeriza-
tion. Macromol. Symp. 333 (1): 273–285.
68 Liu, Q., Wen, X., Xu, S. et al. (2015). Synthesis and properties of the antibacte-
rial hydrogels with enhanced mechanical strengths. Colloid Polym. Sci. 293 (6):
1705–1712.
69 Apostolides, D.E., Hadjicosta, A., and Patrickios, C.S. (2015). Enamine-based
hydrophilic dynamic covalent polymer networks: effects of pH, and copolymer
composition and concentration on the aqueous swelling degrees and the gel
formation times. Macromol. Symp. 358 (1): 21–27.
70 Pal, S., Hill, M.R., and Sumerlin, B.S. (2015). Doubly-responsive hyperbranched
polymers and core-crosslinked star polymers with tunable reversibility. Polym.
Chem. 6 (45): 7871–7880.
71 Zhao, X., Coutelier, O., Nguyen, H.H. et al. (2015). Effect of copolymer com-
position of RAFT/MADIX-derived N-vinylcaprolactam/N-vinylpyrrolidone
statistical copolymers on their thermoresponsive behavior and hydrogel proper-
ties. Polym. Chem. 6 (29): 5233–5243.
72 Hu, W.-t., Yang, H., He, C. et al. (2017). Morphology evolution of
polystyrene-core/poly(N-isopropylacrylamide)-shell microgel synthesized by
one-pot polymerization. Chin. J. Polym. Sci. 35 (9): 1156–1164.
73 Stenzel, M.H. (2008). RAFT polymerization: an avenue to functional polymeric
micelles for drug delivery. Chem. Commun. 30 (30): 3486–3503.
74 Stenzel, M.H. (2009). Hairy core–shell nanoparticles via RAFT: where are the
opportunities and where are the problems and challenges? Macromol. Rapid
Commun. 30 (19): 1603–1624.
75 Wang, J.-Y., Wang, K., Xi, G. et al. (2016). Polymerization of hydrogel net-
work on microfiber surface: synthesis of hybrid water-absorbing matrices for
biomedical applications. ACS Biomater Sci. Eng. 2 (6): 887–892.
76 Sheng, W., Liu, T., Liu, S. et al. (2015). Temperature and pH responsive hydro-
gels based on polyethylene glycol analogues and poly(methacrylic acid) via click
chemistry. Polym. Int. 64 (10): 1415–1424.
77 Zhao, J., Yan, C., Chen, Z. et al. (2018). Synthesis and self-assembly properties
of intracellular redox bioresponsive block copolymers with hepatoma-targeting
groups. Chem. J. Chin. Univ. 39 (7): 1592–1601.
78 Teo, G.H., Zetterlund, P.B., and Thickett, S.C. (2019). Interfacial crosslinking of
self-assembled triblock copolymer nanoparticles via alkoxysilane hydrolysis and
condensation. J. Polym. Sci. A Polym. Chem. 57 (18): 1897–1907.
79 McMahon, S., Kennedy, R., Duffy, P. et al. (2016). Poly(ethylene
glycol)-based Hyperbranched polymer from RAFT and its application as a
silver-sulfadiazine-loaded antibacterial hydrogel in wound care. ACS Appl.

Mater. Interfaces 8 (40): 26648–26656.
80 Tan, V.T.G., Nguyen, D.H.T., Utama, R.H. et al. (2017). Modular photo-induced
RAFT polymerised hydrogels via thiol–ene click chemistry for 3D cell culturing.
Polym. Chem. 8 (39): 6123–6133.
81 Zhao, J., Lu, H., Wong, S. et al. (2017). Influence of nanoparticle shapes on
cellular uptake of paclitaxel loaded nanoparticles in 2D and 3D cancer models.
Polym. Chem. 8 (21): 3317–3326.
82 Sun, X.-L., He, W.-D., Li, J. et al. (2009). RAFT cryopolymerizations of
N,N-dimethylacrylamide and N-isopropylacrylamide in moderately frozen
aqueous solution. J. Polym. Sci. A Polym. Chem. 47 (24): 6863–6872.
83 An, Z., Qiu, Q., and Liu, G. (2011). Synthesis of architecturally well-defined
nanogels viaRAFT polymerization for potential bioapplications. Chem. Com-
mun. 47 (46): 12424–12440.
84 Zhao, T., Sellers, D.L., Cheng, Y. et al. (2017). Tunable, injectable hydrogels
based on peptide-cross-linked, cyclized polymer nanoparticles for neural pro-
genitor cell delivery. Biomacromolecules 18 (9): 2723–2731.
85 Derry, M.J., Fielding, L.A., and Armes, S.P. (2016). Polymerization-induced
self-assembly of block copolymer nanoparticles via RAFT non-aqueous disper-
sion polymerization. Prog. Polym. Sci. 52 (1): 1–18.
86 Demirci, S. (2018). Crosslinked-polymer brushes with switchable capture and
release capabilities. Polymers 10 (9): 956.
87 Zhu, M., Zhang, M., Chen, Q. et al. (2017). Synthesis of midblock-quaternized
triblock copolystyrenes as highly conductive and alkaline-stable anion-exchange
membranes. Polym. Chem. 8 (13): 2074–2086.
88 Namvari, M., Biswas, C.S., Wang, Q. et al. (2017). Crosslinking hydroxylated
reduced graphene oxide with RAFT-CTA: a nano-initiator for preparation of
well-defined amino acid-based polymer nanohybrids. J. Colloid Interface Sci.
504: 731–740.
89 Ribeiro, T., Coutinho, E., Rodrigues, A.S. et al. (2017). Hybrid mesoporous silica
nanocarriers with thermovalve-regulated controlled release. Nanoscale 9 (36):
13485–13494.
90 Krasia, T.C. and Patrickios, C.S. (2006). Amphiphilic polymethacrylate model
co-networks: synthesis by RAFT radical polymerization and characterization of
the swelling behavior. Macromolecules 39 (7): 2467–2473.
91 Achilleos, M., Krasia-Christoforou, T., and Patrickios, C.S. (2007). Amphiphilic
model conetworks based on combinations of methacrylate, acrylate, and
styrenic units: synthesis by RAFT radical polymerization and characterization
of the swelling behavior. Macromolecules 40 (15): 5575–5581.
92 Pafiti, K.S., Loizou, E., Patrickios, C.S. et al. (2010). End-linked semifluori-
nated amphiphilic polymer conetworks: synthesis by sequential reversible
addition−fragmentation chain transfer polymerization and characterization.
93 Pafiti, K.S., Philippou, Z., Loizou, E. et al. (2011). End-linked poly[2-(dimethyl-
amino)ethyl methacrylate]–poly(methacrylic acid) polyampholyte conetworks:
References 925
synthesis by sequential RAFT polymerization and swelling and sans characteri-

zation. Macromolecules 44 (13): 5352–5362.
94 Achilleos, M., Legge, T.M., Perrier, S. et al. (2008). Poly(ethylene glycol)-based
amphiphilic model conetworks: synthesis by RAFT polymerization and charac-
terization. J. Polym. Sci. Part A: Polym. Chem. 46 (22): 7556–7565.
95 Rikkou-Kalourkoti, M. and Patrickios, C.S. (2012). Synthesis and character-
ization of end-linked amphiphilic copolymer conetworks based on a novel
bifunctional cleavable chain transfer agent. Macromolecules 45 (19): 7890–7899.
96 Patrickios, C.S. and Georgiou, T.K. (2003). Covalent amphiphilic polymer
networks. Curr. Opin. Colloid Interface Sci. 8 (1): 76–85.
97 Ercole, F., Thissen, H., Tsang, K. et al. (2012). Photodegradable hydrogels made
via RAFT. Macromolecules 45 (20): 8387–8400.
98 Nicolaÿ, R., Kamada, J., Van Wassen, A. et al. (2010). Responsive gels based
on a dynamic covalent trithiocarbonate cross-linker. Macromolecules 43 (9):
4355–4361.
99 Amamoto, Y., Kamada, J., Otsuka, H. et al. (2011). Repeatable photoinduced
self-healing of covalently cross-linked polymers through reshuffling of trithio-
carbonate units. Angew. Chem. Int. Ed. Engl. 50 (7): 1660–1663.
100 Amamoto, Y., Otsuka, H., Takahara, A. et al. (2012). Changes in network
structure of chemical gels controlled by solvent quality through photoinduced
radical reshuffling reactions of trithiocarbonate units. ACS Macro Lett. 1 (4):
478–481.
101 Fenoli, C.R., Wydra, J.W., and Bowman, C.N. (2014). Controllable reversible
addition–fragmentation termination monomers for advances in photochemically
controlled covalent adaptable networks. Macromolecules 47 (3): 907–915.
102 Yu, L.-X., Zhuo, D., and Ran, R. (2013). Repeatable self-healing of gels based on
a dynamic covalent trithiocarbonate cross-linker under microwave irradiation.
Int. J. Polym. Mater. Polym. Biomater. 62 (14): 749–754.
103 Roy, S.G., Haldar, U., and De, P. (2014). Remarkable swelling capability of
amino acid based cross-linked polymer networks in organic and aqueous
medium. ACS Appl. Mater. Interfaces 6 (6): 4233–4241.
104 Patil, N., Soni, J., Ghosh, N. et al. (2012). Swelling-induced optical anisotropy of
thermoresponsive hydrogels based on poly(2-(2-methoxyethoxy)ethyl methacry-
late): deswelling kinetics probed by quantitative mueller matrix polarimetry.
J. Phys. Chem. B 116 (47): 13913–13921.
105 Patil, N., Roy, S.G., Haldar, U. et al. (2013). CdS quantum dots doped
tuning of deswelling kinetics of thermoresponsive hydrogels based on
poly(2-(2-methoxyethoxy)ethyl methacrylate). J. Phys. Chem. B 117 (50):
16292–16302.
106 Chen, Q., Han, F., Lin, C. et al. (2018). Synthesis of bioreducible core
crosslinked star polymers with N,N ′ -bis(acryloyl)cystamine crosslinker via
aqueous ethanol dispersion RAFT polymerization. Polymer 146: 378–385.
107 Haldar, U., Nandi, M., Maiti, B. et al. (2015). POSS-induced enhancement of
mechanical strength in RAFT-made thermoresponsive hydrogels. Polym. Chem.
6 (28): 5077–5085.
108 Liu, Q.F., Zhang, P., Qing, A.X. et al. (2006). Poly(N-isopropylacrylamide)
hydrogels with improved shrinking kinetics by RAFT polymerization. Polymer
47 (7): 2330–2336.
109 Lin, Y., Wang, L., Zhou, J. et al. (2019). Surface modification of PVA hydrogel
membranes with carboxybetaine methacrylate via PET-RAFT for anti-fouling.
Polymer 162: 80–90.
110 Qie, F., Astolfo, A., Wickramaratna, M. et al. (2015). Self-assembled gold
coating enhances X-ray imaging of alginate microcapsules. Nanoscale 7 (6):
2480–2488.
111 Niu, S., Ding, M., Chen, M. et al. (2013). Synthesis of well-defined copolymer
of acrylonitrile and maleic anhydride via RAFT polymerization. J. Polym. Sci. A
Polym. Chem. 51 (24): 5263–5269.
112 Garmendia, S., Dove, A.P., Taton, D. et al. (2018). Reversible ionically-
crosslinked single chain nanoparticles as bioinspired and recyclable nanoreac-
tors for N-heterocyclic carbene organocatalysis. Polym. Chem. 9 (43): 5286–5294.
113 Kitiri, E.N., Patrickios, C.S., Voutouri, C. et al. (2017). Double-networks based
on pH-responsive, amphiphilic “core-first” star first polymer conetworks pre-
pared by sequential RAFT polymerization. Polym. Chem. 8 (1): 245–259.
114 Yong, P., Yang, Y., Wang, Z. et al. (2016). Diverse nanostructures
and gel behaviours contained in a thermo- and dual-pH-sensitive
ABC(PNIPAM–PAA–P4VP) terpolymer in an aqueous solution. RSC Adv. 6
(91): 88306–88314.
115 Liu, J.C., Uhlir, C., and Parag K. Shah, et al. (2016). Controlled nanogel and
macrogel structures from self-assembly of a stimuli-responsive amphiphilic
block copolymer. RSC Adv. 6 (69): 64791–64798.
116 Achilleos, M., Mpekris, F., Stylianopoulos, T. et al. (2016). Structurally-defined
semi-interpenetrating amphiphilic polymer networks with tunable and pre-
dictable mechanical response. RSC Adv. 6 (49): 43278–43283.
117 Sundhoro, M., Wang, H., Boiko, S.T. et al. (2016). Fabrication of carbohydrate
microarrays on a poly(2-hydroxyethyl methacrylate)-based photoactive substrate.
Org. Biomol. Chem. 14 (3): 1124–1130.
118 Zhuo, D., Ruan, Y., Zhao, X. et al. (2011). Kinetics of UV-initiated RAFT
crosslinking polymerization of dimethacrylates. J. Appl. Polym. Sci. 121 (2):
660–665.
119 Zhang, L., Zhang, C., Peng, X. et al. (2016). A clean synthesis approach to bio-
compatible amphiphilic conetworks via reversible addition–fragmentation chain
transfer polymerization and thiol–ene chemistry. RSC Adv. 6 (21): 17228–17238.
120 Prai-in, Y., Boonthip, C., Rutnakornpituk, B. et al. (2016). Recy-
clable magnetic nanocluster crosslinked with poly(ethylene
oxide)-block-poly(2-vinyl-4,4-dimethylazlactone) copolymer for adsorption
with antibody. Mater. Sci. Eng. C 67: 285–293.
121 Mangadlao, J.D., Huang, R., Foster, E.L. et al. (2016). Graphene
oxide–poly(ethylene glycol) methyl ether methacrylate nanocomposite hydro-
gels. Macromol. Chem. Phys. 217 (1): 101–107.
122 Zheng, W., Chen, L.-J., Yang, G. et al. (2016). Construction of smart supra-
molecular polymeric hydrogels crosslinked by discrete organoplatinum(II)
References 927
metallacycles via post-assembly polymerization. J. Am. Chem. Soc. 138 (14):

4927–4937.
123 Almeida, C., Costa, H., Kadhirvel, P. et al. (2016). Electrochemical activity of
sulfur networks synthesized through RAFT polymerization. J. Appl. Polym. Sci.
133 (39): 43993.
124 Ding, Z.-L., Tao, W.-D.H.J., Jiang, W.-X. et al. (2011). Zwitterionic shell-
crosslinked micelles from block-comb copolymer of PtBA-b-P(PEGMEMA-co-
DMAEMA). J. Polym. Sci. A Polym. Chem. 49 (13): 2783–2789.
125 Adrian Figg, C., Simula, A., Gebre, K.A. et al. (2015). Polymerization-induced
thermal self-assembly (PITSA). Chem. Sci. 6 (2): 1230–1236.
126 Li, A., Zhang, G., Zhu, L. et al. (2015). Facile synthesis of crosslinked core/shell
silver nanoparticles with significantly improved thermal stability. Eur. Polym. J.
68: 379–384.
127 Liu, H., Zhuang, X., Turson, M. et al. (2008). Enrofloxacin-imprinted mono-
lithic columns synthesized using reversible addition-fragmentation chain
transfer polymerization. J. Sep. Sci. 31 (10): 1694–1701.
128 Turson, M., Zhuang, X.L., Liu, H.N. et al. (2009). Evaluation of the clenbuterol
imprinted monolithic column prepared by reversible addition-fragmentation
chain transfer polymerization. Chin. Chem. Lett. 20 (9): 1136–1140.
129 Turson, M., Zhou, M., Jiang, P. et al. (2011). Monolithic poly(ethylhexyl
methacrylate-co-ethylene dimethacrylate) column with restricted access layers
prepared via reversible addition-fragmentation chain transfer polymerization.
J. Sep. Sci. 34 (2): 127–134.
130 Cheng, C., Bai, X., Xu, Z. et al. (2015). Self-healing polymers based on a
photo-active reversible addition-fragmentation chain transfer (RAFT) agent.
J. Polym. Res. 22: 46.
131 Rosselgong, J. and Armes, S.P. (2012). Quantification of intramolecular cycliza-
tion in branched copolymers by 1H NMR spectroscopy. Macromolecules 45 (6):
2731–2737.
132 Norisuye, T., Morinaga, T., Tran-Cong-Miyata, Q. et al. (2005). Comparison of
the gelation dynamics for polystyrenes prepared by conventional and living
radical polymerizations: a time-resolved dynamic light scattering study. Polymer
46 (6): 1982–1994.
133 Yu, Q., Zhu, Y., Ding, Y. et al. (2008). Reaction behavior and network devel-
opment in RAFT radical polymerization of dimethacrylates. Macromol. Chem.
Phys. 209 (5): 551–556.
134 Yu, Q., Xu, S., Zhang, H. et al. (2009). Comparison of reaction kinetics and
gelation behaviors in atom transfer, reversible addition–fragmentation chain
transfer and conventional free radical copolymerization of oligo(ethylene glycol)
methyl ether methacrylate and oligo(ethylene glycol) dimethacrylate. Polymer
50 (15): 3488–3494.
135 Yu, Q., Gan, Q., Zhang, H. et al. (2009). Gelation kinetics of RAFT radical
copolymerization of methacrylate and dimethacrylate. ACS Symp. Ser. 1024:
181–193.
136 Perelaer, J., Hermans, K., Bastiaansen, C.W.M. et al. (2008). Photo-embossed
surface relief structures with an increased aspect ratios by addition of a
reversible addition-fragmentation chain transfer Agent. Adv. Mater. 20 (16):

3117–3121.
137 Perelaer, J., Hermans, K., Bastiaansen, C.W.M. et al. (2009). Photo-embossed
surface relief structures with an increased aspect ratio by addition of kinetic
interfering compounds. J. Photopolym. Sci. Technol. 22 (5): 667–670.
138 Huebner, D., Koch, V., Ebeling, B. et al. (2015). Comparison of monomethoxy-,
dimethoxy-, and trimethoxysilane anchor groups for surface-initiated RAFT
polymerization from silica surfaces. J. Polym. Sci. A Polym. Chem. 53 (1):
103–113.
139 Leung, D. and Bowman, C.N. (2012). Reducing shrinkage stress of dimethacry-
late networks by reversible addition–fragmentation chain transfer. Macromol.
Chem. Phys. 213 (2): 198–204.
140 He, J., Yan, B., Yu, B.Y. et al. (2008). Fine adjustment of network in polymer
network liquid crystal film employing RAFT polymerization. J. Polym. Sci. A
Polym. Chem. 46 (9): 3140–3144.
141 Zhan, X., He, R., Zhang, Q. et al. (2014). Microstructure and mechanical prop-
erties of amphiphilic tetrablock copolymer elastomers via RAFT miniemulsion
polymerization: influence of poly[styrene-alt-(maleic anhydride)] segments. RSC
Adv. 4 (93): 51201–51207.
142 He, R., Zhan, X., Zhang, Q. et al. (2016). Toughening of an epoxy thermoset
with poly [styrene-alt-(maleic acid)]-block-polystyreneblock-poly(n-butyl acry-
late) reactive core–shell particles. RSC Adv. 6 (42): 35621–35627.
143 Barlow, K.J., Hao, X., Hughes, T.C. et al. (2014). Porous, functional,
poly(styrene-co-divinylbenzene) monoliths by RAFT polymerization. Polym.
Chem. 5 (3): 722–732.
144 Graillot, A., Monge, S., Faur, C. et al. (2013). Synthesis by RAFT of innova-
tive well-defined (co)polymers from a novel phosphorus-based acrylamide
monomer. Polym. Chem. 4 (3): 795–803.
145 Yan Kang. (2015). Synthesis and self-assembly of nucleobase-containing poly-
mers by RAFT techniques. PhD Thesis. The University of Warwick.
146 Wang, D., Li, X., Wang, W.-J. et al. (2012). Kinetics and modeling of semi-batch
RAFT copolymerization with hyperbranching. Macromolecules 45 (1): 28–38.
147 Huang, J., Wang, W.J., Li, B.G. et al. (2013). Design and synthesis of poly(butyl
acrylate) networks through RAFT polymerization with crosslinking for
controlled-release applications. Macromol. Mater. Eng. 298 (4): 391–399.
148 Henkel, R. and Vana, P. (2014). The influence of RAFT on the microstruc-
ture and the mechanical properties of photopolymerized poly(butyl acrylate)
networks. Macromol. Chem. Phys. 215 (2): 182–189.
149 Mori, H. and Tsukamoto, M. (2011). RAFT polymerization of diacrylate deriva-
tives having different spacers in dilute conditions. Polymer 52 (3): 635–645.
150 Kaupp, M., Hiltebrandt, K., Trouillet, V. et al. (2016). Wavelength selective poly-
mer network formation of end-functional star polymers. Chem. Commun. 52
(9): 1975–1978.
References 929
151 Cox, L.M., Sun, X., Wang, C. et al. (2017). Light-stimulated permanent shape
reconfiguration in cross-linked polymer microparticles. ACS Appl. Mater. Inter-
faces 9 (16): 14422–14428.
152 Wang, J., Zhu, Z., Jin, X. et al. (2016). Preparation of well-defined
propargyl-terminated tetra-arm poly(N-isopropylacrylamide)s and their click
hydrogels crosslinked with β-cyclodextrin. Polymers 8 (4): 93.
153 Voorhaar, L., De Meyer, B., Du Prez, F. et al. (2016). One-pot automated
synthesis of quasi triblock copolymers for self-healing physically crosslinked
hydrogels. Macromol. Rapid Commun. 37: 1682–1688.
154 Zhang, K., Aiba, M., Fahs, G.B. et al. (2015). Nucleobase-functionalized acrylic
ABA triblock copolymers and supramolecular blends. Polym. Chem. 6 (13):
2434–2444.
155 Belal, K., Poitras-Jolicoeur, S., Lyskawa, J. et al. (2016). A triple carboxylic
acid-functionalized RAFT agent platform for the elaboration of well-defined
telechelic 3-arm star PDMAc. Chem. Commun. 52 (9): 1847–1850.
156 Scherf, R., Müller, L.S., Grosch, D. et al. (2015). Investigation on the homogene-
ity of PMMA gels synthesized via RAFT polymerization. Polymer 58: 36–42.
157 Matyjaszewski, K. (2016). Atom transfer radical polymerization (ATRP): current
status and future perspectives. Macromolecules 45 (10): 4015–4039.
158 Kiran, E. (2016). Supercritical fluids and polymers—the year in review—2014. J.
Supercrit. Fluids 110: 126–153.
159 Boyère, C., Jérôme, C., and Debuigne, A. (2014). Input of supercritical carbon
dioxide to polymer synthesis: an overview. Eur. Polym. J. 61: 45–63.
160 Sadowski, G. (2005). Phase behavior of polymer systems in high-pressure car-
bon dioxide. In: Supercritical Carbon Dioxide in Polymer Reaction Engineering,
1e (eds. M.F. Kemmere and T. Meyer), 15–34. Weinheim, Germany: Wiley-VCH
Verlag GmbH & Co.
161 Gupta, R.B. and Shim, J.J. (2007). Introduction. In: Solubility in Supercritical
Carbon Dioxide, 1e, 1–18. Boca Raton, FL: CRC Press, Taylor & Francis Group.
162 Bush, D. (2005). Equation of State for Windows 95. Software, version 1.0.14.
Atlanta, GA: Georgia Institute of Technology.
163 E. Vivaldo-Lima, M. J. Bernad-Bernad, A. Licea-Claverie, et al. (2013). Polymers
with a low-density network structure and method for producing same by means
of reversible-deactivation radical polymerisation in compressed fluids. Patent
Application MX/a/2013/009053 2013.
164 Kendall, J.L., Canelas, D.A., Young, J.L., and DeSimone, J.M. (1999). Polymer-
izations in supercritical carbon dioxide. Chem. Rev. 99 (2): 543–563.
165 Canelas, D.A. and DeSimone, J.M. (1997). Polymerizations in liquid and super-
critical carbon dioxide. Adv. Polym. Sci. 133: 103–140.
166 Quintero-Ortega, I.A., Vivaldo-Lima, E., Luna-Barcenas, G. et al. (2005).
Modeling of the free-radical copolymerization kinetics with cross linking of
vinyl/divinyl monomers in supercritical carbon dioxide. Ind. Eng. Chem. Res. 44
(8): 2823–2844.
167 Canelas, D.A. and DeSimone, J.M. (1997). Dispersion polymerizations of styrene
in carbon dioxide stabilized with poly(styrene-b-dimethylsiloxane). Macro-
molecules 30 (19): 5673–5682.
168 Jaramillo-Soto, G., Garc𝚤a-Moran, P.R., Enr𝚤quez-Medrano, F.J. et al. (2009).
Effect of stabilizer concentration and controller structure and composi-
tion on polymerization rate and molecular weight development in RAFT
polymerization of styrene in supercritical carbon dioxide. Polymer 50 (21):
5024–5030.
169 Temtem, M., Teresa, C., Gil Santos, A. et al. (2007). Molecular interactions
and CO2 -philicity in supercritical CO2 . A high-pressure NMR and molecular
modeling study of a perfluorinated polymer in scCO2 . J. Phys. Chem. B 111 (6):
1318–1326.
170 Jaramillo-Soto, G., Villa-Ávila, C.M., and Vivaldo-Lima, E. (2013). RAFT copoly-
merization with crosslinking of methyl methacrylate and ethylene glycol
Dimethacrylate in supercritical carbon dioxide. J. Macromol. Sci., A: Pure Appl.
Chem. 50 (3): 281–286.
171 García-Morán, P.R., Jaramillo-Soto, G., Albores-Velasco, M.E., and
Vivaldo-Lima, E. (2009). An experimental study on the free-radical copolymer-
ization kinetics with crosslinking of styrene and divinylbenzene in supercritical
carbon dioxide. Macromol. React. Eng. 3 (1): 58–70.
172 Patricia Pérez-Salinas. (2019). Síntesis y caracterización de redes poliméricas
con heterogeneidad reducida usando copolimerización RAFT de metacrilato de
hidroxietilo (HEMA) y dimetacrilato de etilén glicol (EGDMA) en dióxido de
carbono supercrítico (scCO2 ), Ph.D. Thesis, Materials Science and Engineering
Graduate Program (PCeIM), Instituto de Investigaciones en Materiales (IIM),
Universidad Nacional Autónoma de México (UNAM), Mexico City, México.
173 Vivaldo-Lima, E., Jaramillo-Soto, G., and Penlidis, A. (2016). Nitroxide-mediated
polymerization. In: Encyclopedia of Polymer Science and Technology (ed. H.F.
Mark), 1–48. Wiley.
174 Scott, A.J., Nabifar, A., Hernández-Ortiz, J.C. et al. (2014). Crosslinking
nitroxide-mediated radical copolymerization of styrene with divinylbenzene.
Eur. Polym. J. 51: 87–111.
175 Lyu, J., Gao, Y., Zhang, Z. et al. (2018). Monte Carlo simulations of atom
transfer radical (Homo)polymerization of divinyl monomers: applicability of
Flory–Stockmayer theory. Macromolecules 51 (17): 6673–6681.
176 Poly, J., Wilson, D.J., Destarac, M. et al. (2009). A comprehensive investigation
into “controlled/living” chain growth crosslinking copolymerization includ-
ing a back to basics modeling. J. Polym. Sci., Part A: Polym. Chem. 47 (20):
5313–5327.
177 Satheeshkumar, C. and Seo, M. (2018). Creation of micropores by RAFT
copolymerization of conjugated multi-vinyl cross-linkers. Polym. Chem. 9 (48):
5680–5689.
178 Bachmann, R., Melchiors, M., and Avtomonov, E. (2016). Modelling and opti-
mization of nonlinear polymerization processes. Macromol. Symp. 370 (1):
135–143.
References 931
179 Lattuada, M., Del Gado, E., Abete, T. et al. (2013). Kinetics of free-radical
cross-linking polymerization: comparative experimental and numerical study.
180 Lazzari, S., Hamzehlou, S., Reyes, Y. et al. (2014). Bulk crosslinking copolymer-
ization: comparison of different modeling approaches. Macromol. React. Eng. 8
(10): 678–695.
181 Hamzehlou, S., Reyes, Y., and Leiza, J.R. (2013). A new insight into the forma-
tion of polymer networks: a kinetic Monte Carlo simulation of the cross-linking
polymerization of S/DVB. Macromolecules 46 (22): 9064–9073.
182 Tripathi, A.K., Tsavalas, J.G., and Sundberg, D.C. (2015). Monte Carlo simula-
tions of free radical polymerizations with divinyl cross-linker: pre- and postgel
simulations of reaction kinetics and molecular structure. Macromolecules 48 (1):
184–197.
183 Kryven, I., Berkenbos, A., Melo, P. et al. (2013). Modeling crosslinking polymer-
ization in batch and continuous reactors. Macromol. React. Eng. 7 (5): 205–220.
184 Lyu, J., Gao, Y., Zhang, Z. et al. (2018). Can Flory-Stockmayer theory be applied
to predict conventional free radical polymerization of multivinyl monomers? A
study via Monte Carlo simulations. Sci. China Chem. 61 (3): 319–327.
185 Aguiar, L.G. (2016). Styrene–dimethacrylate copolymerization kinetic modeling.
Polym. Int. 65 (1): 142–151.
186 Lazzari, S. and Storti, G. (2014). Modeling multiradicals in crosslinking
MMA/EGDMA bulk copolymerization. Macromol. Theory Simul. 23 (1): 15–35.
187 Nikitin, A.N., Wulkow, M., and Schütte, C. (2013). Modeling of free radical
styrene/divinylbenzene copolymerization with the numerical fractionation
technique. Macromol. Theory Simul. 22 (9): 475–489.
188 Aguiar, L.G. (2015). A cross-linking copolymerization mathematical model
including phase separation and cyclization kinetics. Macromol. Theory Simul. 24
(3): 176–180.
189 Gonçalves, M.A.D., Pinto, V.D., Dias, R.C.S. et al. (2011). Modeling studies on
the synthesis of superabsorbent hydrogels using population balance equations.
Macromol. Symp. 306–307 (1): 107–125.
190 Monteiro, M.J. and De Brouwer, H. (2001). Intermediate radical termination
as the mechanism for retardation in reversible addition-fragmentation chain
transfer polymerization. Macromolecules 34 (3): 349–352.
191 Wang, R., Luo, Y., Li, B.-G. et al. (2009). Modeling of branching and gelation in
RAFT copolymerization of vinyl/divinyl systems. Macromolecules 42 (1): 85–94.
192 Li, X., Wang, W.-J., Li, B.-G. et al. (2015). Branching in RAFT miniemulsion
copolymerization of styrene/triethylene glycol dimethacrylate and control of
branching density distribution. Macromol. React. Eng. 9 (2): 90–99.
193 Liang, S., Li, X., Wang, W.-J. et al. (2016). Toward understanding of branch-
ing in RAFT copolymerization of methyl methacrylate through a cleavable
dimethacrylate. Macromolecules 49 (3): 752–759.
194 Zhu, S. (1998). Analytical functions for molecular weight and branching dis-
tributions in star-, comb-, and random-branched polymers. Macromolecules 31
(21): 7519–7527.
195 Hernández-Ortiz, J.C., Vivaldo-Lima, E., Dubé, M.A. et al. (2014). Modeling
of network formation in reversible addition-fragmentation transfer (RAFT)
copolymerization of vinyl/divinyl monomers using a multifunctional polymer
molecule approach. Macromol. Theory Simul. 23 (3): 147–169.
196 Pallares, J., Jaramillo-Soto, G., Flores Cataño, C. et al. (2006). A comparison of
reaction mechanisms for reversible addition - fragmentation chain transfer poly-
merization using Modeling tools. J. Macromol. Sci., Part A: Pure Appl. Chem. 43
(9): 1293–1322.
197 López-Domínguez, P., Hernández-Ortiz, J.C., Barlow, K.J. et al. (2014). Model-
ing the kinetics of monolith formation by RAFT copolymerization of styrene
and divinylbenzene. Macromol. React. Eng. 8 (10): 706–722.
198 Oliveira, D., Dias, R.C.S., and Costa, M.R.P.F.N. (2016). Modeling RAFT
gelation and grafting of polymer brushes for the production of molecularly
imprinted functional particles. Macromol. Symp. 370 (1): 52–65.
199 Konkolewicz, D., Gray-Weale, A., and Perrier, S. (2010). The structure of ran-
domly branched polymers synthesized by living radical methods. Polym. Chem.
1 (7): 1067–1077.
200 Konkolewicz, D., Gilbert, R.G., and Gray-Weale, A. (2007). Randomly hyper-
branched polymers. Phys. Rev. Lett. 98 (23): 238301.
201 Konkolewicz, D., Gray-Weale, A., and Perrier, S. (2010). Describing the struc-
ture of a randomly hyperbranched polymer. Macromol. Theory Simul. 19 (5):
219–227.
933
20
Complex Polymeric Architectures Synthesized through

RAFT Polymerization
Thomas G. Floyd 1 , Satu Häkkinen 1 , Matthias Hartlieb 2 , Andrew Kerr 1 , and
Sébastien Perrier 1,3,4
1
University of Warwick, Department of Chemistry, Gibbet Hill Road, Coventry CV4 7AL, UK
2
University of Potsdam, Institute of Chemistry, Karl-Liebknecht-Straße 24-25, Potsdam 14476, Germany
3 University of Warwick, Warwick Medical School, Gibbet Hill Road, Coventry CV4 7AL, UK
4
Monash University, Faculty of Pharmacy and Pharmaceutical Sciences, 381 Royal Parade, Parkville, VIC
3052, Australia
20.1 Introduction
As reversible addition-fragmentation chain transfer (RAFT) polymerization has

grown into a versatile and widely used technique, it has paved the way to the
design of a broad range of polymeric architectures. Chapter 20 describes the various
polymeric structures that can be obtained by RAFT (Figure 20.1), either as unique
materials that can only be obtained by the RAFT process or more traditional
polymeric architectures, whose synthesis is made easily accessible. This chapter
provides an overview of the various architectures obtained by RAFT to date, with a
comment on best practice and general guidelines.
20.2 RAFT Synthesis of Block Copolymers

One of the most advantageous features of RAFT polymerization over radical poly-
merization is the maintenance of chain end fidelity with a ‘living’ chain transfer
agent (CTA) end group, which facilitates the synthesis of block copolymers. Broadly
speaking, there are three main approaches to block copolymer synthesis via RAFT
polymerization – multiple sequential polymerization steps, pre-modification of a
CTA with a polymer to yield a macroCTA followed by chain extension, or the cou-
pling of two polymeric species using the CTA-derived end group (either R or Z)
functionalities (Figure 20.2). There are yet further variations including assembling
blocks through supramolecular interactions or combining multiple polymerization
techniques in various orders.

934 20 Complex Polymeric Architectures Synthesized through RAFT Polymerization
Linear Diblock Multiblock Gradient Cyclic
Star Graft Hyperbranched Miktoarm star
Figure 20.1 Schematic of the various architectures described in this chapter.
RAFT RAFT
(a)
Coupling RAFT
reaction polymerization
(b)
+
Coupling
reaction
= CTA = Monomer A = Monomer B = Reactive groups

(c)
Figure 20.2 (a) Preparation of block copolymers by sequential RAFT polymerizations, (b)
block copolymer synthesis by preparation of a macroCTA and subsequent chain extension,
and (c) block copolymer synthesis by conjugation of two polymeric species.
20.2.1 Block Copolymer by Sequential Polymerization Steps

Of these options, accessing block copolymers through the sequential polymerization
approach is arguably the simplest and most accessible as it can yield diblocks in two
standard polymerization processes starting from the respective monomers and CTA,
in appropriate quantities for the desired molecular weight. For large-scale processes,
this is the most appealing and simplest procedure, similar to standard radical poly-
merization, to access diblock materials. The RAFT process has excellent tolerance
of reaction conditions and functional groups, with the versatility to polymerize a
wide range of monomers among the so-called ‘more activated monomer’ (MAM)
and ‘less activated monomer’ (LAM) groups. As a res1ult of these advantages, there
have been a huge number of publications utilizing RAFT technology to access block
architectures to yield materials for a plethora of applications [1]. There are a num-
ber of considerations for successful block copolymer synthesis though this tech-
nique – the choice of CTA, order of blocks, chain end livingness, polymer solubil-
ity, monomer conversion, and potential side reactions, which will be discussed in
sections 20.2.1.1–20.2.1.6.
20.2.1.1 Choice of CTA

Firstly, as per a standard RAFT homopolymerization, a CTA of suitable reactivity
must be selected to control the monomers of choice in the block polymerization (see
Figure 20.3 for typical examples of CTAs). For the first block, the R and Z groups
play an important role in this; however, for the second block, only the Z group is
pertinent in controlling the polymerization, and therefore, the Z group must provide
control for both monomer species. In the simplest case of block copolymers of two
monomers from the same family (e.g. acrylates), this is trivial; however, if a block
of MAM-LAM were desired, a CTA providing good control of the MAM such as a
trithiocarbonate will retard or entirely inhibit the polymerization rate for the LAM.
The development of switchable RAFT agents has provided a route to controlling this
combination of highly different monomer reactivities.
Dithiobenzoates provide excellent control of meth(acrylates/acrylamides) and
styrene, therefore are highly effective for production of block copolymers from
these monomer families. For block combinations of meth(acrylates/acrylamides)
with acrylates/acrylamides, the use of a trithiocarbonate is generally preferable,
as the dithiobenzoates commonly induce substantial rate retardation for the
polymerization of acrylates/acrylamides because of slow fragmentation of the
highly stabilized intermediate radical with respect to propagation [2, 3]. Narrow
dispersities (∼1.1–1.2) can still be obtained for the use of trithiocarbonate with
methacrylates [4], so they are generally a more versatile choice of RAFT agent
for block copolymer synthesis of MAMs. For LAMs, the use of either xanthates
or dithiocarbamates is recommended [5]; however, these CTAs possess low chain
transfer constants for MAMs, so diblocks with these monomers are not well
S
S S
S
R
S R Z R Z
R Z S N
S S S O
Z
Dithiobenzoates Trithiocarbonates Xanthates Dithiocarbamates
+ H
S N S N
R R
S N S N
Switchable dithiocarbamate
Figure 20.3 General chemical structures of some of the most commonly used RAFT agents.
controlled. For these architectures, the aforementioned switchable RAFT agents

provide uniquely effective control [6–8]. This class of dithiocarbamate compounds
contain a pH-responsive pyridyl functionality on the Z group, while in its unpro-
tonated form, it possesses a low chain transfer constant, suitable for LAMs, but
upon protonation, the intermediate radical is much more effectively stabilized,
thus enabling improved control of MAM polymerizations. One-pot conditions can
therefore be used by the addition of acid to modify the pH and reversibly switch the
CTA from controlling LAMs to MAMs. The use of xanthates for control of ethylene
has also been established by the use of specialized reaction conditions at high
pressures (70 ∘ C, >200 bar) [9]. It is also worth noting the usage of ‘sulphur-free’
RAFT agents, consisting of macromonomers derived from catalytic chain transfer
polymerization, has been reported for the synthesis of multiblock structures of
hydrophobic methacrylate monomers [10]. While such CTAs possess a very low
chain transfer constant and thus perform poorly in solution polymerization [11],
the usage of emulsion conditions with monomer feeding was able to compensate
for this and enable excellent control of block copolymerizations.
Recent advancements in RAFT have also established its use for the control of
cationic polymerizations, enabling the controlled synthesis of poly(vinyl ethers),
which cannot be accessed through radical mechanisms [12, 13]. Trithiocarbonates,
xanthates, and dithiocarbamates with a vinyl ether R group can be used, also allow-
ing for chain extension through a radical process (e.g. vinyl acetate) to yield novel
diblock copolymer structures [14]. This technique therefore allows the direct syn-
thesis of block combinations of radically and cationically polymerizable monomers,
which would otherwise be challenging to access [15, 16].
Difunctional CTAs offer a facile route to higher order block copolymers in fewer
polymerization steps, however are limited to symmetrical structures as a result of
chain extension occurring in both directions (Figure 20.4) [17]. They are particularly
useful for the synthesis of ABA block copolymers in two reactions steps as opposed
to the three required for a mono-functional CTA. Linkage of the CTA groups can
be performed through either the Z or R group of the RAFT agent – in the case of
Z-group, a thiocarbonylthio functionality will be incorporated into the centre of the
polymer, which may be prone to degradation. The polymerization of the exterior
block is performed first and chain extensions will occur within the centre of the
S
R R
S S
R Z R R
Z R R Z R
or
S S
RAFT RAFT
R R
S Z Z S
(a)
S S
Z R R Z Z RR Z
R R Z RR Z
Z S S Z RAFT RAFT
(b) polymerization polymerization
Figure 20.4 (a) Scheme outlining the structure of difunctional CTAs linked by the Z group
and order of monomer incorporation upon polymerization. (b) Scheme of difunctional CTAs
linked by the R groups.
M M
S S
RAFT
Multifunctional CTA Polymerization
(a)
S S
HO OH HO OH O O
S S R S S R
n
O O O O
S
S S
ROP
S S
m n
S
Ph Ph
(b)
Figure 20.5 (A) Scheme showing chain extension of a multifunctional polymeric CTA to
form a mulitblock copolymer. (B) (a) Preparation of the multifunctional CTA by a
condensation reaction. (b) Preparation by ring-opening radical copolymerization of a cyclic
trithiocarbonate with styrene monomer.
polymer to insert the core block. Alternatively by coupling two R groups to make
a difunctional CTA, the composition of central segment will be determined by the
chemical linkage used and thus can be designed for superior stability, while the block
orders must be performed in the opposite order to the Z-group linkage to yield the
same polymeric structure.
Multifunctional CTAs, consisting of a polymer with multiple thiocarbonylthio
moieties placed along the backbone, are another option that allow for the synthesis
of higher order multiblocks in just two reaction steps, although the exact number
of blocks per chain will not be controlled. Polymeric CTAs of this nature can be
prepared by coupling reactions of telechelic RAFT agents [18, 19], or alternatively
by the polymerization of cyclic CTA structures through a ring-opening mechanism
(Figure 20.5) [20, 21]. Because the multifunctional polymer has a distribution
of molecular weights, the number of CTA groups per chain varies significantly;
therefore, upon chain extension, there will also be a broad distribution of the
number of block segments in the resulting structure. Furthermore, the RAFT
mechanism entails fragmentation events across the CTAs of the backbone, leading
to a scrambling of the block orders and the creation of initiator-derived chains of
decreased block quantity. As a result of this, the dispersity of the multiblock copoly-
mer product is often high (PDI > 2) – this technique does not provide precise control
of polymeric architecture. The individual block segments, however, are of narrow
dispersity with molecular weight controlled by the RAFT process, which can be
confirmed by cleavage of the thiocarbonylthio groups and subsequent size exclusion
chromatography (SEC) analysis of the resulting low molecular weight species [20].
20.2.1.2 Block Order

For the synthesis of block copolymers incorporating two different monomer
families, the order of the polymerization steps is a vital consideration for assuring
effective control. After the first step of the polymerization effectively, a ‘macroCTA’
is synthesized, where the R group is now the polymeric unit. The ability of the
macroCTA to efficiently chain extend polymerization of the second block will be
related to the nature of the macro ‘R’ group of the CTA with respect to the propagat-
ing monomer of the second block. It must be an effective leaving group, possessing
a good chain transfer constant, and also be capable of reinitiating polymerization
of the second monomer. According to the RAFT mechanism, an initial propagating
oligomeric radical will add to the CTA to form an intermediate radical situated on
the CTA. This can then fragment either towards the initial propagating species or
towards the macro ‘R-group’, and for successful block copolymer synthesis, the
latter fragmentation must occur. For this to be favourable, the macro R group should
form a more stable radical than the propagating monomer of the second block. As
a general rule, therefore, in RAFT, the MAM should be polymerized first to ensure
efficient chain extension.
As a result of this requirement, monomers that create stabilized tertiary radicals
such as meth(acrylates/acrylamides) must be polymerized as the first block,
followed by chain extension with monomers that produce secondary radicals
(styrenes/acrylamides/acrylates) and then finally by LAMs. Attempting to poly-
merize the blocks in the opposite order will often lead to inefficient reinitiation
from the macroCTA and thus lead to multimodal distributions and increased
dispersities. Combinations of possible blocks are thus restricted by these synthetic
requirements. Early work in RAFT has demonstrated for effective synthesis of a
poly(styrene)-poly(methyl methacrylate) diblock copolymer, that the PMMA block
must be synthesized first as a result of the difference in reactivity. This concept has
been established for a variety of monomer systems, although there will be variations
depending on the exact structure of monomer and thus it is often necessary to try
alternative block orders.
A scheme summarizing these guidelines is shown (Figure 20.6), with the sug-
gested order of polymerization of a monomer going from left to right. The selected
CTAs are merely examples of suitable choices and a large range of many other
RAFT agents have been reported in the literature that may be better suited to a
specific circumstance.
20.2.1.3 Polymer Livingness

During the RAFT process, the use of an external radical initiator source leads to the
formation of initiator-derived chains and ultimately terminated polymers lacking
the CTA end group. In the case of block copolymer synthesis, the presence of
defected chains devoid of the CTA is detrimental to high-fidelity materials and leads
to the formation of ‘dead’ homopolymers of the first block unable to undergo chain
extension, often apparent as a low molecular tail in SEC analysis. Every radical
species introduced into the system will inevitably terminate and those that initiated
polymerization will lead to the formation of a dead polymer product. Therefore,
the livingness (percentage of polymers with the ‘living’ CTA end group) can be
defined as the ratio of moles of CTA to the moles of CTA plus initiated radicals.
A further consideration is the predominant nature of termination – through a
disproportionation mechanism, two separate ‘dead’ chains would be produced,
MAMs LAMs
N O O
O > O O HN O > O
O HN O
R R R R
MAs MAm Sty Ac Am NVP VAc
(a)
S N
S S S
S C12H25 OH C4H9 OH OH
N S S S S O S
O O O
MAc/MAm MAc/MAm Sty
VAc
Sty Sty Ac/Am
NVP
S Ac/Am
S
N S Switchable: HO OH Difunctional:
N S S
MAM + LAM ABA triblocks
O O
(b) N
Figure 20.6 (a) Monomers that fall under the categories of MAMs and LAMs. Blocks should
be prepared starting from left to right. (b) Small selection of suitable CTAs for the
polymerization of the respective monomer families.
whereas recombination would result in one ‘dead’ chain of higher molecular

weight; thus, the ratio of moles of dead to living chains would be affected. Written
as an equation, taking into account the initiator decomposition rate and initiating
efficiency (typically 50% for azoinitiators) gives:
[CTA]
L (%) = ( ) ( f
) (20.1)
[CTA] + 2f × [I]0 × 1 − e−kd ×t × 1 − 2c
where [CTA] is the initial concentration of CTA, f is the initiation efficiency (typi-
cally assumed to be 50%), [I]0 is the initial initiator concentration, kd is the rate coeffi-
cient of decomposition, t is the time, and f c is the coupling factor referring to whether
the terminations occur by combination (f c = 1) or disproportionation (f c = 0).
An implication of this is that there will always be a number of living chains accord-
ing to the moles of CTA, despite the number of terminations that occur. Thus, some
percentage of chains will always be able to undergo chain extension (assuming
effective consumption of macroCTA), unlike in other reversible deactivation radical
polymerizations (RDRPs), such as atom transfer radical polymerization (ATRP) and
nitroxide-mediated polymerization (NMP), in which excessive terminations could
result in complete removal of all active end groups. In these alternative techniques,
an external source of initiator is not required, so the number of termination is not
‘guaranteed’ in the same manner as RAFT, so this is not to say RAFT is necessarily
superior in terms of livingness.
In order to obtain low-dispersity block copolymers, it is paramount to maintain
a high livingness, which in practice is achieved by modifying the polymerization
conditions, in particular, the moles of initiating species ideally to as low a value as
feasible for the polymerization. The CTA/I ratio is a commonly reported parameter
to give a handle on the expected livingness – a CTA/I ratio > 10 is generally rec-
ommended for diblock copolymer synthesis to ensure that at least 90% of chains
can chain extend to successfully create a diblock. In actuality for the purposes of
estimating livingness, the ratio of importance is that of CTA to the initiator con-
sumed and thus will be highly dependent on the reaction time and temperature,
which alters the degree of decomposition of the initiating species. Under equiva-
lent reaction conditions, monomers with slower propagation rates, such as styrene
and methacrylates, will require higher initiator concentrations than monomers with
higher kp values, and therefore, for some systems, there will be greater limitations in
how much the initiator concentration can be lowered. Additionally, targeting larger
degrees of polymerization of each block will decrease chain end livingness – with
equivalent initiator concentrations, a higher molecular weight polymerization will
have a lowered CTA concentration and thus CTA/I ratio, indicating that a larger pro-
portion of chains will be terminated. This reflects the inherent limit of RAFT where
it theoretically will depress the maximal achievable molecular weight with respect to
a comparable radical process. All else being equal targeting lower molecular weights
of each block will therefore be easier to control.
It is also worth noting that, as a result of the RAFT mechanism, a number of
other possible terminated species will occur (Figure 20.7). During the polymeriza-
tion of the first block, initiator-derived chains will introduce an initiator fragment
end group as opposed to the R group from the RAFT agent, and terminations (either
by recombination or by disproportionation) will lead to polymers devoid of the CTA
end group. For the second block chain extension, the possibilities increase further,
as now the initiator-derived chains will lead to the formation of a ‘B’ homopolymer,
which will remain in the final reaction mixture, and additionally, radical termi-
nations could occur between various species, leading to ABA triblock copolymers.
Through these processes, the synthesis of a diblock by sequential polymerization
steps can lead to the formation of homopolymers of both ‘A’ and ‘B’ monomers, in
Living species
Monomer B R Z
R Z
Main population
I Z
Monomer A I Z
I
Initiator derived chain
Initiator I Z
R Z
R T
CTA I Product of termination by R T
disproportionation
Initiator
R T R R T R
Product of termination by
recombination Triblock produced through
termination by recombination
I T
I T
Low population species (also
produces recombination products Plus additional termination products
containing 1 or 2 I groups) of initiator derived species
Figure 20.7 Potential polymeric structures formed during a standard RAFT diblock
polymerization initiated by an external source of radicals from an initiator species.
addition to chain ends differing from that of the R and Z from the CTA – the quan-
tity of these defect chains should again be equivalent to the number of radicals and
thus can be mitigated by the usage of low initiator concentrations. In the case of
a difunctional CTA linked by the R groups, the types of terminations increases yet
further, leading to a complex variety of possibilities including some terminations,
which would not lead to a chain deficient in CTA end groups.
An important consideration when selecting an initiator concentration (and
accordingly the polymer livingness) is the extent of monomer conversion obtained,
which will affect the experimental procedure possible. For quantitative monomer
consumptions, a one-pot procedure can be used where after synthesis of the first
block, a batch of the second monomer can be directly added to the reaction mixture.
If full conversions of the first block are not achievable, however, the reaction
mixture must be purified (often by dialysis or precipitation) before chain extension,
leading to additional experimental steps. Residual quantities of the first monomer
would lead to a gradient-like architecture in the final product if they are not
removed from the reaction mixture before the second step. It is therefore desirable
to use the simpler one-pot procedure, although there can be limitations in terms
of livingness for this approach. RAFT follows standard radical polymerization
kinetics with a first-order relationship to monomer concentrations and accordingly
the reaction rate drops off over the course of the polymerization – this makes the
final period going from 89 to 99% monomer conversion particularly long compared
to a 10% change at lower conversions. Assuming a constant decomposition rate
of initiator for the duration of the polymerization, the longer a reaction time, the
more radical production occurs and thus livingness of the polymer is reduced.
Therefore, to achieve maximal livingness, it would be theoretically preferable to
quench polymerizations at moderate conversions (e.g. 70%) rather than drive the
polymerization to completion as substantially more initiating radicals would be
required to achieve this. In practice, however, one-pot procedures reaching almost
complete conversion with very high chain end fidelity have been established for
block copolymers of a range of monomer families. Despite this, some monomers
may display unusual polymerization behaviour and be difficult to polymerize to
high conversions, necessitating purification steps.
20.2.1.4 Initiation System

In addition to the traditional thermally decomposing initiators (e.g. azo initiators
and peroxide compounds), there are a number of other options, such as redox pair
initiators [22, 23]. These are useful for polymerizations at room temperature; how-
ever, their mechanism of decomposition is less well understood and thus calcula-
tions of livingness through the number of radicals produced may not be accurate.
Initiators that decompose to produce radicals upon exposure to light irradiation can
also be used at varying temperatures and behave in a similar manner to the ther-
mally decomposing systems. There has also been substantial focus in literature on
the use of ‘photo-RAFT’, either through an iniferter mechanism by direct activation
of the CTA compound itself [24–26] or with the usage of a photocatalyst (PET-RAFT)
[27, 28]. Both have been established as effective methods for the synthesis of block
copolymers and complex architectures [29, 30]. In these systems, an external initia-
tor source is not required; therefore, the number of radicals produced is not precisely
known and thus the livingness equations do not apply here, while the potential
defect species arising from initiator-derived chains will also not be present.
20.2.1.5 Further Considerations

Ensuring the solubility of both polymer blocks and monomer throughout the course
of the reaction is an important factor for maintaining control of the polymerization
and accessing the desired molecular weights. It is generally suggested that a good sol-
vent for all components ([macro]RAFT agent, monomer, and resulting block copoly-
mer) should be used, although in the case of amphiphilic diblocks, for example, this
can be particularly challenging. For some syntheses, it may be preferable to carry out
the first block polymerization in one solvent, purify the macroRAFT agent and then
perform chain extended in a different solvent system. In some cases, a difference
in solubility can be exploited for emulsion or polymerization-induced self-assembly
(PISA) processes, where a solvent selective for one block can be utilized to undergo
polymerization in a heterogeneous reaction mixture. Although these approaches can
be advantageous, they often entail additional complications when compared to a
standard solution polymerization.
Finally, the CTA end group could be lost through side reactions of the end group
functionality – in the case of block polymerization, it is particularly pertinent to
prevent this from occurring in order to retain a suitably high chain end fidelity.
Dithiobenzoates and trithiocarbonates are reactive towards nucleophiles, in par-
ticular, amines that will reduce the end group to a thiol and thus prevent further
chain extension – therefore, for the synthesis of amine-containing polymers, they
must be non-nucleophilic (tertiary of quaternized) or utilize monomers with a
protected amine group during polymerization, followed by a deprotection step
post-polymerization. Additionally, CTA groups, particularly dithiobenzaotes,
can be susceptible to hydrolysis in basic aqueous conditions [31] – for aqueous
polymerization at elevated temperatures, such as for the monomer hydroxypropyl-
methacylamide, the use of acidic buffer solutions is recommended to reduce RAFT
agent degradation [32]. Other conditions such as excessive heat (typically >120 ∘ C)
[33], UV irradiation [26], and oxidation [34] are also known to induce degradation
of the CTA end group and therefore should be avoided.
20.2.1.6 Multiblock Copolymers

Increasing the number of blocks in the target polymeric architecture is inherently
challenging because of the accumulation of dead chains throughout each block
extension process. For ease of experimental synthesis, as is important in the case
of multiblocks of high block orders, a one-pot procedure reaching full monomer
conversion is preferred as otherwise time consuming purifications would be
required for each step. The limitation of reaching full monomer conversion is
concomitant with reduction of the polymer livingness as a result of the increased
initiator quantity required. Despite these issues, fairly recent developments in
RAFT synthesis have led to reports of as high as 20 block copolymer structures
with short overall reaction times [35]. These have been most commonly reported
for the acrylamide family of monomers, which have been exploited as a result
of their very high propagation rates, especially in aqueous conditions [36] to
enable polymerization to full monomer conversion with very low concentrations of
initiators and conveniently short reaction times [23, 37]. To achieve fast reactions
rates, the equation for the rate of propagation can be considered, where it is evident
that this can be increased by three parameters – usage of a monomer with high kp ,
(increased by temperature), a high [M], and a high radical flux:
√
[ ∗] f kd [I]0 e−kd t
Rp = kp [M] R = kp [M] (20.2)
kt
where Rp = rate of propagation, kp = rate constant of propagation, [M] = monomer
concentration, [R*] = radical concentration, f = initiation efficiency, kd = rate con-
stant of initiator decomposition, [I]0 = initial initiator concentration, and t = time,
kt = rate constant of termination.
By adopting a rapidly decomposing initiator system, for example, VA-044 at 70 ∘ C
(10 hour half-life temperature = 44 ∘ C), effectively full consumption of initiator can
be reached in under two hours, which facilitates rapid propagation and is convenient
for calculation of the initiator concentration as unreacted reagent is not accumulated
between block extensions. Usage of high monomer concentrations also increases
polymerization rates and is an important factor, although too high concentration
will lead to experimental issues in terms of excessively high viscosities, making the
mixing of subsequent monomer aliquots ineffectual. While a ratio of CTA/I = 10
is typically adequate for control of diblock architectures, this would lead to a very
low livingness (∼38%) for a dodecablock (n = 10) architecture; therefore, the use
of very low initiation concentrations (often CTA/I > 100) and targeting of relatively
short degrees of polymerization are prerequisite for optimal multiblock synthesis.
This approach has also been utilized in continuous flow reactors for the preparation
of acrylate-based multiblock copolymers on scales up to 150 g within 26 hours of
reaction time [38, 39].
20.2.2 Block Copolymers by Chain Extension of a Pre-functionalized

MacroCTA
Alternatively to performing sequential RAFT polymerizations, instead the modifica-
tion of the starting CTA with a polymeric group through a coupling reaction offers
another route to block copolymers (Figure 20.8). One significant advantage is the
ability to incorporate polymers that cannot be polymerized through RAFT, while
also requiring less dependence on developing suitable polymerization conditions
for all blocks. The polymer can be conjugated through either the Z or R group of
the CTA; in either case, this should not significantly impact the activity of the CTA
in terms of its ability to control the polymerization of a second monomer. There-
fore, potential issues with chain extension of the macroCTA due to differences in
monomer reactivity are avoided by this approach, making the synthesis of various
diblocks facile. Performing the initial conjugation through the Z group, however,
R Z
R Z R Z
Coupling RAFT
(a)
Z R
Z R Z R
Coupling RAFT
(b)
Figure 20.8 Scheme showing the preparation of a macroRAFT agent and subsequent chain
extension for (a) connection through the R group and (b) connection through the Z group.
This choice will affect the position of the respective groups in the final block copolymer.
will upon chain extension yield a diblock containing the thiocarboylthio group in
the centre of the polymer, which may be more prone to degradation.
This approach is most conveniently applied with the conjugation of commercial
polymers, although this can be somewhat restrictive in the selection of avail-
able molecular weights. The use of a polymer of high chain end fidelity is also
essential to ensure efficient macroCTA synthesis through the coupling reaction
of the end group – if functionalization is incomplete, residual homopolymer
side products will remain after the chain extension. A common example is the
conjugation of poly(ethylene glycol) containing a terminal alcohol/amine func-
tionality with a carboxylic acid containing CTA [40, 41], which has been used
extensively for the synthesis of amphiphilic block copolymers by chain extension
with a hydrophobic monomer. Other frequently studied macroCTAs include
poly(dimethylsiloxanes) [42, 43] and poly(lactides) [44], among other examples
such as poly(isoprene) [45] and poly(thiophenes) [46]. Click chemistry has also
been used to access a poly(isobutylene) macroCTA, which was then chain extended
with N-isopropylacrylamide to synthesize novel diblocks [47].
20.2.3 Block Copolymers by Conjugation of Two Polymeric Chains

A third method of block polymer synthesis is the coupling of two already formed
polymers, as opposed to the previous example of attaching a polymer to a
small-molecule RAFT agent. In this case, two polymeric materials containing
complementary end group functionalities are reacted together to covalently bind
the two blocks. This approach is particularly appealing as in principle essentially
any two polymer substrates can be reacted to yield a diblock, without the restraints
of sequential polymerizations, thus broadening the possibilities of polymeric
structures. A number of challenges are associated with this technique – the low
concentration of reactive end group when placed on a high molecular weight
polymer and steric hindrance effects reduce the rate of reaction substantially, often
yielding sub-quantitative conversion. For ease of purification, the use of equimolar
quantities of each polymer would be preferable; however, inaccuracies in the
determination of polymer molecular weight (MW) make this difficult to achieve
precisely, and even if done so, the slow reaction rate of the two macromolecules
could lead to incomplete conjugation. Any residual excess of one of the polymer
reactants, either as a result of difference in molarities or incomplete conjugation,
must then be purified to obtain the desired diblock, which depending on the
nature of the substrates may be challenging. For successful implementation of this
approach, it is most commonly combined with Click Chemistries, defined by their
high conversions and lack of side products, facilitating high yield couplings with
minimal purification requirements [48, 49].
20.2.3.1 Block Copolymer Synthesis Through Click Chemistry

As the most established click chemistry reaction, the copper-catalysed azide–alkyne
cycloaddition has been utilized for a range of RAFT-derived polymeric coupling
approaches (Figure 20.9). Through the use of a dithiobenzoate containing
a protected alkyne moiety and an azide functional xanthate, polymers of
6-O-methacryloyl mannose and vinyl acetate could be prepared, respectively,
with the end groups then coupled via ‘click’ to yield a diblock copolymer [50].
This combination of methacrylate and vinyl acetate polymers would otherwise be
quite challenging to access through sequential polymerizations and demonstrates
the increased versatility of the conjugation approach. There are a number of other
examples of this chemistry being utilized with RAFT [51–53]. While usage of a
trimethyl silyl-protected alkyne group appears recommended to ensure that no side
reactions occur during the radical polymerization [54], there have been successful
reports of unprotected alkyne groups being used [55, 56]. One limitation of the
azide–alkyne reaction is the requirement of exogenous copper catalyst, which can
be problematic for the synthesis of polymers intended for biomedical applications
as residual copper contaminant is often present even after purification. As a
result, alternative ‘additive-free’ click chemistries have been explored for diblock
copolymer synthesis. These include the inverse electron demand Diels–Alder
between tetrazine and polymeric norbornene end group [57], and the Diels-alder
of a triazolinedione moiety with a diene [58]. Other click type reactions such as
the sulfur fluoride exchange (SuFEx) chemistry has been identified as orthog-
onal to RAFT radical polymerization and applied to block copolymer synthesis
[59, 60].
Specific to the use of RAFT, the CTA end group itself can also be directly utilized
for coupling reactions such as with hetero-Diels–Alder (HDA) reaction. The C=S
double bond of electron-deficient dithioester compounds is known to undergo
[4+2]-cycloaddition with dienes and therefore by using a CTA with a suitable
Z group functionality, the cycloaddition can be performed post-polymerization
with a diene functional macromolecule. This atom-efficient approach was first
demonstrated by the synthesis of diblocks of poly(styrene)-b-poly(caprolactam)
[61], and since then, further improvements to the reaction were obtained by the
use of a cyclopentadienyl end group in which rapid reaction times (<10 minutes)
for high molecular weight polymers (up to 100 000 g mol−1 ) were observed
[62]. In further combination with photoenol chemistry by the usage of a dual
functional CTA, a triblock copolymer of poly(isoprene-co-styrene)-b-(poly(ethyl
O
P1 P1 S F
P1 O
O
P1 S O
S N N P2
P1 O
Z P2 N N N N
P1
S Z P2 O Si
P1 S S
P2 P2
P2 P1
P2
HN
O
O N
N N
N
P1 N N P1 R R
N P1 N
N N N
O S P2
O S
P2 P1 P1 SH P1 P2
P2 S Z
Figure 20.9 A selection of reported ‘click’ reactions for preparation of RAFT-derived block copolymers.
acrylate)-b-(poly(ethylene oxide) was synthesized by sequential polymer coupling

onto one chain end through thermally induced HDA and secondly to the other
chain end through photo-induced ligation [63].
Additionally, the thiocarbonylthio moiety can be considered a masked thiol func-
tionality, which can then be used for a range of chemistries [64]. Treatment of a
RAFT polymer with nucleophiles such as primary/secondary amines or hydrides
such as NaBH4 can be performed to reveal the reactive thiol polymeric chain end.
Care must be taken, however, to prevent thiol oxidation into disulfides which leads
to formation of high molecular weight species, and therefore, the addition of a phos-
phine reducing agent can be advantageous. This process can also be inefficient for
poly(meth)acrylates where the thiol end group is susceptible to a backbiting side
reaction to yield a thiolactone [65]. Once deprotected, the thiol can then be used for
conjugation to another polymer with a complementary end group, most frequently
via a Michael addition onto an electron-deficient alkene such as a poly(ethylene gly-
col) (PEG) functional acrylate [66], or sequential conjugations to a bismaleimide
linker [67]. Radical thiol-ene additions can also be performed for polymer–polymer
coupling but generally result in poorer yields [68].
In comparison to the other two approaches of block copolymer synthesis, the con-
jugation of two polymeric reagents is arguably the most synthetically challenging
and is generally most effective for relatively low molecular weight polymers in which
chain end fidelity and reaction rates are higher. While the click chemistry techniques
are a very powerful tool, especially for accessing more exotic polymer structures
and block orders, the previous two techniques are often more appropriate for block
copolymer synthesis particularly for large-scale processes or targeting of high molec-
ular weights.
20.2.3.2 Supramolecular Block Copolymers

In a conceptually similar manner, rather than coupling two polymer chains through
a covalent bond, instead supramolecular chemistry can be used to attach the chains
through reversible interactions. There are numerous examples of RAFT-derived
materials using these approaches for block copolymer assembly such as hydrogen
bonding [69], metal complexation [70], or host–guest chemistry [71]. Such an
approach can endow the material with self-healing properties because of the
dynamic nature of supramolecular interactions. The use of a functional CTA
compound containing the supramolecular bonding moiety is a common approach
to synthesize telechelic assembling block copolymers. For example, poly(styrene)
and poly(methyl methacrylate) were synthesized by RAFT using two different
CTAs containing complementary binding units, which then interacted to form a
supramolecular diblock. This could then undergo self-assembly in bulk to yield
highly order phase separated morphologies, which upon exposure to polar sol-
vents, the hydrogen bonding interactions were disrupted allowing one block to be
removed, forming a nanoporous membrane [72]. Through a similar approach with
the use of Hamilton receptor and barbiturate functional CTAs, ABCD tetrablocks
could be created through the selective binding affinity of the two end groups [73],
and in further work with difunctional CTAs of the same chemistry, it was possible
to access higher order multiblock architectures [74].
20.2.4 General Guidelines

Through the outlined approaches, there are often multiple routes to synthesize a
desired block copolymer architecture. In general, the preparation by sequential poly-
merizations is the most recommended as it is suitable for a broad range of monomer
classes, allows for precise control of the molecular weights of each block, and can
be used for a high number of block extensions with appropriate reaction condi-
tions. Alternatively, the usage of a pre-functionalized macroCTA can be a highly
efficient approach, although less versatile in terms of MW control and selection of
monomers. It is particularly useful for synthesis of architectures such as amphiphilic
diblocks involving chain extension from a PEG macroCTA, for example. Finally, the
use of conjugation reactions between polymeric chains, because of their low yield
and limitation in molecular weights, is generally only recommended if the desired
architecture is not accessible through the previously described means.
20.3 Gradient Copolymers

Perhaps the simplest and most easily accessed variation in polymeric architecture
are gradient copolymers, which display an asymmetric distribution of two or more
monomer species across a polymeric chain, offering alternative properties to that of
block or statistical structures [75, 76]. For a radical polymerization of two monomers
of different reactivity ratios, the unequal rate of consumption of each monomer will
lead to a compositional drift of the polymeric product over the course of the reaction
because the lifetime of an individual radical is very short with respect to the total
polymerization time (Figure 20.10). In the case of RAFT, on the other hand, all poly-
mer chains can effectively be considered to grow at the same rate and remain ‘living’
throughout the polymerization, thereby yielding polymer products of approximately
equal composition. Rather than between the separate chains, the compositional drift
will rather be observed across each individual chain, leading to a gradient copolymer
architecture. RAFT, or other RDRP techniques, therefore provides a route to access
alternative gradient copolymer architectures by prevention of compositional drift.
There are two main experimental approaches to synthesize gradient copolymers:
first, the spontaneous approach involving the copolymerization of two monomers
of different reactivity ratios, or secondly, the ‘forced’ approach, whereby one or both
monomers are fed into the reaction mixture at a specific rate. With the latter method-
ology, the composition of the gradient can be much more finely tuned as it is no
longer limited by the reactivity ratios, however, requires experimental optimization
and detailed theoretical understanding to yield the desired composition [77].
The use of xanthate CTAs enables good control of vinyl acetate monomers and
acceptable control of acrylates/acrylamides – because the monomer families pos-
sess significantly different reactivity ratios, they can therefore be copolymerized to
20.4 Cyclic Polymers 949
FRP RAFT
Compositional
drift of
polymers over
course of
reaction
Compositional drift across each chain–

gradient copolymer
Figure 20.10 Copolymerization of two monomers of differing reactivity ratio by

(a) – radical polymerization leads to compositional drift, whereas with (b) – RAFT, gradient
copolymers are formed.
access spontaneous gradient copolymers, as has been demonstrated by copolymerza-

tions of VAc/N-isopropylacrylamide NIPAM [78] and VAc/MA [79]. As an additional
route to gradient copolymers, RAFT was used for radical polymerization with con-
comitant reaction of monomers with an enzyme, thus changing the monomer feed
ratio over the course of the polymerization to yield a gradient copolymer [80]. For
this approach to be successful, the chemical transformation should occur on the
monomer but not on polymeric units and must also be orthogonal to the required
polymerization conditions, which limits the scope in terms of potential substrates.
20.4 Cyclic Polymers
Cyclic polymers represent an interesting class of polymeric architecture because of

their lack of end groups, which can play a significant role in physical properties. Ring
closure reactions of polymeric end groups is the most commonly reported method-
ology to access cyclic RAFT-derived polymers, either using reactions involving the
CTA end group directly such as Diels–Alder [81] and disulfide [82, 83] approaches or
click chemistries such as the azide/alkyne cycloaddition [84] (see section 20.2.3.1 for
more details on these reactions). The usage of a CTA with appropriate functionalities
on the Z and R groups is the simplest approach to realize this. After radical polymer-
ization, the end groups can then be cyclized by a coupling reaction under very dilute
conditions, which is necessary to prevent intermolecular conjugations. As a result of
the low concentrations required, the coupling reactions tend to proceed slowly and
are thus limited to relatively low molecular of polymers (typically <30 000 g mol−1 ).
Cyclic polymers are therefore a synthetically challenging polymeric architecture and

while they have received a fair amount of research focus, they are generally less well
studied than the other architectures outlined in this chapter.
20.5 Star-Shaped Polymers

A further polymer architecture that can be achieved using RAFT polymerization are
star-shaped or star (co)polymers. Here, linear polymers (arms) radiate from a central
unit (core) and the properties of such structures can be, similarly to hyperbranched
or bottlebrush copolymers, quite different to the linear building block. Star polymers
can be classified in two main ways: by their composition or by their synthetic origin.
As the focus of this chapter is on synthetic strategies leading to complex polymer
architectures, the latter approach will be thoroughly examined, whereas compo-
sitional differences in star polymers, such as stars including block copolymers or
miktoarm stars will only be discussed briefly.
20.5.1 Methods to Produce Star-Shaped Copolymers

In general, two major strategies to from star-shaped polymers are known: (i) diver-
gent (also described as core-first method) and (ii) convergent (or arm-first method).
Both are subdivided in different methodologies, which will be discussed here. It
should be mentioned that we restrict the described systems to star polymers that
have been polymerized solely by RAFT polymerization, excluding the use of other
polymerization techniques.
20.5.1.1 Divergent Synthesis of Star (Co)Polymers

Using this principle, the star-shaped polymer is produced by using a multi-functional
core molecule, that is able to initiate a polymerization reaction. In the case of a
RAFT polymerization, CTA molecules are immobilized on the core molecule
and polymeric arms are subsequently grown from this central multifunctional
molecule.
A large variety of structures have been used as core molecules for RAFT-based
star polymers including four-armed stars based on aromatic cores or pentaerythri-
tol as initial structural motifs [85], cyclodextrins [86], porphyrins [87], and other
molecules (Scheme 20.1) with numbers of arms usually ranging between three and
seven [88]. Dendritic or hyperbranched core molecules can be used as well providing
an even higher number of initiation sites per core molecule [89]. A comprehensive
overview can be found in recent review articles [88, 90]. By attachment of different
types of CTA motifs such as trithiocarbonates, dithiobenzoates, or xanthates, and by
utilizing different R-groups, various monomer classes can be controlled and incor-
porated into the shell of the star polymer, ranging from styrenes, (meth)acrylates,
(meth)acrylamides, and vinyl esters.
A general advantage of a divergent process compared to a convergent route is the
improved control over the number of arms of the final structure, as this variable is
CTA
S S O
O O CTA
O O
S S OHO
S S O
HO
O O O HO
O OH OH
O O CTA
O
S S O
S S HO O
O O
HO CTA
S S O
O
(a) OH OH
O
O OH
CTA OH
O O
O OH OH OH
O O CTA
O
CTA
O
O
S O
O S
CTA NH N S
O O S
N HN S
S
(b) CTA
O (c)
Scheme 20.1 Examples of core molecules carrying different CTAs as basis for the
synthesis of star-shaped polymers: (a) pentaerythritol-based CTA [85], (b) porphyrin-based
CTA [87], and (c) cyclodextrin-based CTA [86].
predefined by the substitution of the core molecule. Also, the production of linear
chains that are not coupled to the core and have to be removed after synthesis is a less
drastic problem when using a divergent approach, as linear polymers do not detach
from the core during propagation. However, because of the mechanism of the RAFT
process, a certain amount of initiator-derived linear chains will still be produced.
Disadvantages are that single arms cannot be analysed without detachment from
the star polymer after its synthesis, and, that the synthesis of miktoarm stars using
solely RAFT-polymerization is not possible.
Using the RAFT methodology and a divergent synthesis approach of star-shaped
copolymers, a further variable has to be considered: whether the CTA molecule is
attached to the core via its R-group or via the Z-group. Both scenarios lead to different
mechanisms during the polymerization process and have different advantages and
disadvantages (Figure 20.11).
Using the R-group approach, the leaving group of the CTA, which after fragmenta-
tion carries the active radical, is connected to the core molecule. As a result, polymers
grow directly from the core outwards and radicals are always centred at the growing
polymer star. Using the Z-group approach, the activating group of the CTA is cou-
pled to the core and fragmentation during polymerization will lead to a detachment
of the growing chain from its initial core molecule. The polymer chains will sub-
sequently grow in solution and are immobilized again by reaction with core-bound
Z-group during the RAFT equilibrium.
A major disadvantage of the R-group approach is the localization of the active rad-
ical near the core during chain propagation. This can lead to termination reactions
with other star molecules or linear chains, resulting in the loss of an active arm and
RAFT pre-equilibrium
R-group approach
S
R R
S Z
Z
S
+ +
Z S
S
S R S Z
S I I
R S
R
S Z
S R RAFT main-equilibrium
R S
Z
S S
S S Z
Z M
+ +
Chain tranfer agent
S Z
M S
Termination
Z-group approach RAFT pre-equilibrium

S R S I
S S
Z Z
+ +
R
I R
S
S R
Z S
S Z RAFT main-equilibrium
R S
Z S S
S S S
Z S R Z Z
Z
S S
S + +
R
Chain tranfer agent

M M
Termination
Figure 20.11 Schematic representation of R and Z-group approach in the synthesis of

star-shaped polymers using RAFT polymerization.
deviation from the theoretical molecular weight. In particular, star–star coupling

can lead to bimodal molecular weight distributions, a problem which increases with
concentration and conversion, as well as with the number of arms per core [91]. A
general countermeasure to prevent this type of bimolecular coupling is to keep the
concentration of radicals as low as possible, which can be ensured by a high ratio of
CTA to initiator, or by the use of monomers with a fast propagation rate [91].
Using a Z-group approach, the propagating polymer chains are detached form the
core and termination usually leads to the formation of small linear side products,
which are easier to remove form the final product.
Thus, relatively high molecular weights can be targeted without a significant
broadening of the distribution [92]. A main disadvantage of this method is the
necessity of the diffusion of growing chains to the core molecule. Especially
when polymer arms have a high degree of polymerization, the radical end group
might not be able to access the sterically crowded area near the core molecule,
which is further shielded by already attached polymer arms. This effect leads to
an increased amount of termination as radicals are not able to participate in the
RAFT equilibrium because of steric hindrance of other polymeric arms [93]. In
addition, when core molecules with a low number of attached CTAs are used, the
side product resulting from bimolecular termination of two linear chains is difficult
or even impossible to remove and appears as a shoulder in the molecular weight
distribution, increasing the dispersity.
A further point to consider is the stability of the final star copolymer. Using the
Z-group approach, polymer arms are connected to the core via the thiocarbonylthio
group of the CTA. These molecules are susceptible to degradation by aminolysis,
thermolysis, or mechanical stress [94]. Whether this is considered a feature or a flaw
is strongly dependent on the envisioned application for the produced star-shaped
copolymer.
20.5.1.2 Convergent Synthesis of Star Polymers by RAFT Polymerization

The second major strategy to produce star polymers is the convergent or arm-first
method. As the name suggests, the linear polymer arms are produced first and are
used to from a star architecture in a second reaction step. One obvious advantage
over a divergent approach is the possibility to analyse single arms before incorpo-
ration into the final architecture. However, there is usually a broader distribution
of the number of arms when compared to a divergent strategy, as multiple linear
polymers with non-negligible steric impact have to be coupled to a small-molecule
core. Thus, the reactions used for star formation have to be very efficient and, even
then, the presence of residual linear polymers can usually not be excluded and the
isolation of the final product from the mixture can make this strategy difficult.
In general, one can distinguish between two ways to produce star polymers in a
convergent process based on the connection of arms to the core molecule. (i) A sec-
ond polymerization step can (after initial arm synthesis) be used to connect multiple
polymers to a star-like object and (ii) polymers can be reacted onto a multifunctional
core molecule by a polymer analogue reaction.
R
R
S
R
S Z
R Z
R Z R
R
RAFT RAFT
polymerization polymerization R
R
Figure 20.12 Star polymer synthesis by chain extension using a multifunctional monomer
to form a cross-linked core – example of styrene and divinyl benzene.
When using RAFT polymerization, the first strategy offers an easy access to
star-shaped copolymers as the CTA end groups, located at the chain end of linear
arms, can be utilized for star formation, usually using a bis-functional monomer
(Figure 20.12). Polymerization in the presence of arms will result in the formation of
a highly cross-linked core structure connecting multiple polymers [95]. Compared
to divergent methods, the core compartment will be much bigger and it is much
harder to control the number of arms. While in general the definition is lower using
this convergent strategy, there are many factors influencing the process and careful
optimization can lead to the formation of well-defined star copolymers.
One essential parameter is the ratio of crosslinker to CTA. The size of the
core, as well as the number of arms, scales with the amount of crosslinker. Low
crosslinker/CTA ratios will lead to small star polymer, with a low number of arms
and a low yield of the final structure. With increasing crosslinker amount, the
core will become bigger and the number of arms will consequently increase [96].
However, above a certain ratio, star–star coupling and eventually gelation will occur
[97]. Optimal ratios are often described to be around 10 [96, 98]. The solubility of
the crosslinker molecule seems to play an important role as a low solubility in the
polymerization medium leads to a preformation of the core by phase segregation,
which aids in the synthesis of star polymers and increases the definition of the final
product [96]. This can be improved by the application of heterogeneous reaction
conditions where linear precursors and crosslinkers are part of a dispersion [97].
This is reported to decrease reaction times drastically while also improving the
definition of star copolymers. The core of such systems is however much bigger than
in previous examples, resembling a core cross-linked micelle. Also, the length of the
polymeric arms plays an important role in this context, which is mainly associated
with steric factors. Longer polymer arms are harder to incorporate into a central
core and thus the yield of star polymer, as well as the number of incorporated arms
decreases with increasing molecular weight of the linear precursor [97, 99]. An
interesting example of the arm-first synthetic approach is the AstericTM viscosity
modifier developed by Lubrizol, which is a methacrylate-based star-shaped polymer
[100]. Superior shear stability was observed for these additives as a result of the star
architecture when compared to standard linear polymeric materials. The multi-ton
scale synthesis of this commercial product demonstrates the suitability of the RAFT
process in industrial applications for the preparation of complex architectures.
A second convergent strategy to from star-shaped polymers is the use of functional

end groups to connect linear polymer arms to a central core molecule. The RAFT
methodology is perfectly suited for such an approach as a large variety of functional
groups are tolerated by the polymerization, enabling a range of chemistries to be
used for the connections. Usually, the R-group of the CTA is used for this type of
reaction as it often possesses a functional handle. To ensure a high conversion of core
functionalities, highly efficient reactions have to be used and usually, an excess of
linear precursor is necessary, which has to be removed afterwards. Still the number
of arms is limited as the steric impact of already coupled arms will decrease the
probability of further attachment. A few reactions suitable to synthesize star-shaped
polymers by this method will briefly be described here.
One example is the use of copper-mediated azide alkyne cycloaddition, which was
used to form four-armed star polymers based on an azide functional core and poly-
mers with an alkyne end group, which was introduced by the R-group of the CTA
[101]. Another strategy, particularly suited for polymers made by a RAFT process,
is the direct use of the dithio-ester function in a hetero hetero-Diels–Alder reaction
with a multifunctional diene. As the CTA can be used directly, no further functional
group has to be installed on the polymer or the CTA [102]. A further method making
direct use of the CTA is the reduction of the thiocarbonylthio end group to the thiol
under mild conditions. Thiol end groups can in turn be reached to a multifunctional
core, carrying activated double bonds, in a thiol-ene reaction [103]. A special case
within this frame is the use of a cross-linkable block instead of a single end group
functionality in order to create a star copolymer. This route was for instance followed
by functionalization of one block of a diblock copolymer with furan functionalities,
followed by the addition of bis-functional maleimides, forming a core structure in a
Diels–Alder reaction [104].
20.5.2 Classification by Composition

While so far star polymers have been classified by their origin, a second way to distin-
guish between them is by their architecture. The majority of star-shaped copolymer
discussed so far had only one polymeric component constituting the polymer arm.
However, the use of different homopolymers to form the shell or even the use of
block copolymers offers new perspective for the design of functional nanomaterials.
One main category is miktoarm stars, which have a mixed shell consisting of
different linear polymeric arms. There are only a few ways to produce such struc-
tures entirely using RAFT polymerization and the most straight forward method
is the mixing of different precursors, followed by star formation by formation of a
cross-linked core (Figure 20.13).
Using such a method, the hydrophobicity of different arms plays an important role.
Indeed, the amphiphilic balance of linear precursors has a significant impact on the
definition of the final star polymer [105]. In this context also, the medium used for
the cross-linking reaction and the respective solubilities of the components have to
be considered. It has been shown that combinatorial chemistry can be used to cre-
ate a multitude of different star-shaped copolymers by synthesizing different arms
Cross-linking agent R
R
R Z R
R
R
R Z
RAFT
R
polymerization
(a) R
Cross-linking agent
Z
R Z
R Z Z
Z
R
R Z R
RAFT R
RAFT polymerization
polymerization R
R
(b) Z
Figure 20.13 Methods to produce miktoarm star copolymer using RAFT polymerization
using a convergent approach: (a) mixing of different arms before cross-linking and (b)
‘in-out.’
and mixing them in various ratios before cross-linking [106]. Thus, a large number
of different structures are accessible and can be screened for various applications.
One problem using this method is that different linear precursors might have dif-
ferent probabilities to be incorporated into the star copolymer, based on their steric
hindrance or solubility.
A method to create miktoarm stars with a predefined composition is the so-called
‘in-out’ method. Here, the thiocarbonylthio end groups located in the core of the
star polymer after polymerization of a bis-functional monomer are utilized to grow a
further linear arm from the cross-linked centre. Here also, the hydrophobicity of the
two monomers used can be different without jeopardizing the definition of the final
structure [107]. This approach can also be performed combining core formation and
growth of the second population of arms in one step. Using the alternating copoly-
merization of styrene and maleimide (as crosslinker) in the presence of an excess
of styrene, which will form homopolymeric arms after the maleimide component is
consumed leads to the formation of miktoarm stars [108].
Finally, (multi)block copolymers can be used to create the shell of star-shaped
copolymers using the methods as described before in the section on block copolymer
synthesis by sequential polymerization steps [98].
20.6 Graft Polymers
Graft polymers are macromolecules composed of a long, linear backbone and poly-
meric branches attached to the main chain. When the grafts are of uniform length,
such structures are often referred to as bottlebrush or comb polymers. The topology
of the polymer can range from a comb-like structure to a bottlebrush-like structure
with increasing grafting density, i.e. number of side chains per backbone. High graft-
ing density and long side chains promote extended conformations in both backbone
and side chain directions, whereas low grafting densities and short side chains result
in Gaussian conformations [109] Moreover, if the relative length of the backbone to
the side chain is small, the polymer will appear more star-like [110]. Bottlebrush
polymers typically exhibit high intramolecular and intermolecular steric repulsion,
resulting in unique intrinsic properties. The architecture has gained a fair amount
of attention and has been extensively reviewed in recent literature [111–119]. The
structural complexity of the bottlebrush architecture has also been taken a step fur-
ther by designing bottlebrush polymers into star-like structures [120, 121], networks
[109, 122], and dendronized architectures [123].
Three general synthetic strategies are known for bottlebrush synthesis: grafting
through, grafting from, and grafting onto (Figure 20.14). RAFT polymerization can
be used in all three approaches to yield well-controlled structures. Each approach
offers a good control over some structural parameters while setting limitations to
others; these include the backbone length, side chain length, and grafting density.
For the best results, the aforementioned parameters should be prioritized in order to
select the most appropriate approach. The strategies can also be combined to over-
come challenges associated with a single technique – that is, grafting from can, for
example, be used to complement the grafting through method [124]. The benefits
and limitations of each, as well as some practical and mechanistic considerations,
are discussed in detail below.
Grafting through Grafting to Grafting from
M
M
i i
M
i i
i
M i i i
i
i
M
M
M M
M
Figure 20.14 Three synthetic pathways used for bottlebrush polymer synthesis.
A popular pathway to bottlebrush synthesis is to use two or more living

polymerization techniques to yield the bottlebrush structure. Typically, one is used
for the polymerization of the backbone and another for polymerizing the side
chains; however, complementary techniques can also be used to yield multiblock
and heterograft structures. Various highlighted examples combine RAFT with
other living polymerization techniques, such as ATRP and ring-opening metathesis
polymerization (ROMP). In doing so, the complex architecture can in some cases
be accessed through sequential or even simultaneous monomer addition in one pot
using initiator-functionalized monomers. Other strategies for dual polymerizations
include the use of post-polymerization methods to functionalize a polymer chain
end with a new polymerizable group, and functionalizing polymer side groups
with initiator motifs; such polymers can be used to carry out grafting through and
grafting from polymerizations, respectively [125]. A combination of polymerization
techniques allows the use of a greater variety of monomers than one alone can
cover. Moreover, options for one-pot synthesis are more varied.
20.6.1 Grafting Through

In the grafting through approach, a macromonomer is polymerized to yield a
bottlebrush-like structure where the side chain length is determined by the size
of the macromonomer. Such polymerizations result in bottlebrushes where every
repeating unit along the backbone is guaranteed to have a side chain attached
to it; the method is thus effective for synthesizing high-density bottlebrushes. A
co-monomer can be incorporated in the structure to yield a heterograft bottlebrush
or to act as a spacer between the side chains to reduce the density. In such cases,
the reactivity ratios of the co-monomers should be carefully considered, as different
reactivities may result in gradient polymers. Heterograft block copolymer bottle-
brushes are more easily accessible via the grafting through approach than with the
other two approaches. The use of a RAFT agent in a grafting through polymerization
acts as a means to control the backbone length and yields a bottlebrush with a CTA
terminus, available for further chain extensions [126, 127] or post-modification
[128]. The grafting through strategy can also be advantageous when thorough
characterization of the side chains is required, as this can be carried out before the
polymerization step.
A significant advantage of the grafting through approach is its simplicity: when
commercially available macromonomers can be used, only one step is required
for bottlebrush synthesis. Typical examples of commercial macromonomers
used for the RAFT polymerization of bottlebrush-like polymers include acry-
loyl and methacryloyl-functionalized poly(ethylene glycols) [129, 130] and
poly(dimethylsiloxanes) [129, 131], as well as acrylates and methacrylates car-
rying long aliphatic side groups [132]. Although commercial macromonomers
offer the most effortless route to making bottlebrush polymers, only few suitable
macromonomers are currently commercially available, and thus, macromonomer
synthesis is often required. Macromonomer synthesis can be carried out either
by functionalizing a polymer with a polymerizable end group [133] or by employ-
ing a monomer-functionalized initiator in the macromonomer polymerization
[134–138]. It is important to note that when RAFT is used in the macromonomer

synthesis, a practical upper limit is set for the conversion of the macromonomer
into polymer that can be reached in the grafting through step. This is due to
some polymer chains inevitably lacking the functionality needed for further
polymerization: initiator-derived chains have no R-group functionality at the
α-end and terminated chains lack the thiocarbonylthio functionality at the
𝜔-end [139].
The use of two polymerization techniques for grafting through synthesis has
proven rather popular: typically, one is used to prepare the macromonomer and
another for polymerizing the backbone. A considerable amount of grafting through
literature making use of RAFT combines it with ROMP to give an easy access to
long backbones with narrow dispersities; however, other polymerization techniques
have also been employed [133–138]. By careful consideration of the macromonomer
and backbone polymerizations, the two can in some instances be carried out
sequentially in one pot, yet such reports are rare [136, 140]. The tolerance of RAFT
towards impurities and functional groups makes it a promising candidate for the
second step of a one-pot grafting through synthesis; however, polymerization
of macromonomers with RAFT can be more challenging than with other living
polymerization techniques because of mechanistic reasons.
When the grafting through synthesis of bottlebrush polymers is carried out using
RAFT, the main limitations of the method are typical to any RAFT polymerization
[141]. In order to have a good control over the reaction, the monomer-to-CTA ratio
must remain low enough to limit the time a growing chain spends as a propagating
radical. Thus, the method is best used for preparing bottlebrushes with relatively
short backbones. The use of a macromonomer instead of a low molecular weight
monomer effectively dilutes down the concentration of polymerizable groups in the
reaction mixture; this sets a practical upper limit for the initial monomer concen-
tration and therefore for the rate of polymerization. As a result, the concentration
of polymerizable groups will be extremely low at high conversions, and the reaction
can be difficult to push to completion. Moreover, low initiator concentrations
further complicate the polymerization of a slow propagating macromonomer. For
the synthesis of long brushes, special reaction conditions – such as feeding – may
prove helpful. Overall, RAFT polymerization of macromonomers appears less
popular than with other techniques, and the macromonomers tend to be of mod-
erate size. Some of this could be attributed to unfavourable steric factors, as the
RAFT mechanism requires a propagating bottlebrush to approach the end group of
another. Typical reaction conditions such as low initiator concentration can further
render the synthesis challenging. It is also worth noting that RAFT polymers of
vinyl macromonomers have been shown to exhibit an equilibrium between the rate
of propagation and the rate of depolymerization when heated in the absence of
initiator [129].
20.6.2 Grafting Onto

Grafting onto (also known as grafting to) is a modular approach in which the
backbone and the side chains of the resulting bottlebrush are prepared separately;
side chains are then attached to the backbone by employing complementary

functionalities. The strategy is especially useful for preparing bottlebrush polymers
containing functionalities that are not compatible with the desired polymerization
techniques. The grafting onto method is suitable for preparing bottlebrushes with
long backbones; however, coupling high molecular weight side chains onto the
backbone can prove challenging because of steric effects, especially when targeted
grafting densities are high. RAFT polymerization of the building blocks opens up
possibilities for the preparation of block copolymer and other complex structures, as
well as for end-group modification through functionalities in the R- or the Z-group
of the CTA [128]. The tolerance of RAFT towards a wide range of functionalities
[142] makes it an ideal candidate to be used in the grafting onto strategy. Functional
groups needed for the coupling step can, however, limit the functionalities carried
by the backbone and side chain monomers.
The most significant challenge in the grafting onto approach is the coupling step,
the efficiency of which determines the grafting density of the resulting bottlebrush.
Each attachment of a side chain increases shielding effects near the neighbouring
reacting sites, and the attachment of subsequent side chains becomes sterically
more challenging. The effect is more pronounced with long grafts; thus, side
chain length sets a practical upper limit for the grafting density [143]. Despite
the challenges, high grafting densities have been reported. A typical synthetic
route involves the use of nucleophilic substitution reactions [144, 145] or click
chemistry, such as copper-catalysed azide–alkyne [146–149] or Diels–Alder [150]
cycloadditions. Catalytic reactions can potentially benefit from the proximity of the
subsequent reacting group, as demonstrated by Gan et al. [146]
Steric hindrance near the reacting site can be reduced by employing a backbone
monomer with a relatively long side group; the side group will act as a spacer
between the backbone and the reacting group, and thus neighbouring reactive sites
will be more spread out. Crowdedness near the reacting site can also be reduced
by introducing a comonomer, thus making a bottlebrush with a reduced grafting
density. Similar to the grafting through strategy, an incomplete coupling step can
complicate purification, as the unconjugated side chains must be separated from
the bottlebrush. Typically, an excess of side chains is used to drive the coupling step
to high conversions. Efficient coupling chemistries result in less linear polymer in
the product.
20.6.3 Grafting From

In the grafting from approach, the bottlebrush is synthesized by first preparing a
backbone with pendent initiator functionalities that can then be used to polymer-
ize the side chains. When RAFT polymerization is used for polymerizing the side
chains, these functionalities are CTA moieties that can be tethered to the backbone
either by the R- or Z-group. This strategy can be seen as complementary to the graft-
ing through approach in that it provides an excellent control over the backbone
composition in exchange for reduced control of the side chains. The approach is
useful for making high-density bottlebrush polymers with long backbones and side
chains – a combination that can be difficult to achieve through other strategies. The
backbone composition can be constructed in the same manner as any linear poly-
mer prepared through RAFT polymerization, and the side chains can be further
chain-extended multiple times after the initial bottlebrush has been prepared. This
allows for an immense level of structural complexity to be achieved through sequen-
tial monomer additions. To demonstrate this, Kerr et al. reported the three-step syn-
thesis of a bottlebrush polymer comprising 29 separate domains across the backbone
and side chain regions [151]. Furthermore, heterograft structures can be achieved
by carrying out multiple grafting steps with different polymerization techniques, as
reported by Bolton and Rzayev [152]. The terminal CTA units in the grafts can also
act as reacting sites for further functionalization. Low-density bottlebrushes can be
easily made by incorporating a co-monomer in the backbone from which no side
chains will be grown.
Whether the CTA is attached to the backbone via the Z- or the R-group makes
a considerable difference in the dynamics of the side chain polymerization
(Figure 20.15). When the CTA is attached via the Z-group (Z-group approach; also
known as transfer to [153]), the side chain detaches from the backbone to propagate.
Thus, the approach is mechanistically similar to the grafting onto technique. As side
chains grow longer, shielding effects near the thiocarbonylthio group grow greater,
making the addition of a propagating chain back to the CTA on the main chain more
challenging. This can result in a reduced grafting density, a broad size distribution
of the grafts, and a secondary linear side product – in addition to initiator-derived
chains [137]. In the Z-group approach, intermolecular brush–brush coupling and
Active
Active radical
radical
Looping
Uninitiated
CTA Blocked CTA
Free living chains
Coupled
bottlebrushes Dead polymer
(a) (b)
Figure 20.15 Comparison of the grafting from R- and Z-group approaches. (a) The R-group
grafting from approach. (b) The Z-group grafting from approach.
intramolecular side chain coupling reactions encountered in the R-group approach

are absent for mechanistic reasons.
When the CTA is tethered to the backbone via the R-group (R-group approach),
the propagating chain stays attached to the backbone. The radical can transfer
intramolecularly to an adjacent CTA or intermolecularly to a CTA of another
molecule, allowing for better control over chain growth than in the Z-group
approach. The R-group approach can, however, suffer from bi-radical brush–brush
coupling reactions, manifested as a high molecular weight species or gelation of the
product. The problem is especially pronounced in the preparation of high-density
bottlebrushes and when high backbone concentrations are used, and the effect
typically escalates at high monomer conversions. Furthermore, if the intermolecu-
lar transfer of active radicals is sparse, the bottlebrushes with more active radicals
will grow faster, leading to broad molecular weight distributions. The addition
of a small amount of free CTA, or shuttle-CTA, in the system has been shown
to enhance radical transfer between growing bottlebrushes, as well as suppress
brush–brush coupling [151, 154]. The effect is a result of an increased probability
of radicals getting transferred from a bottlebrush to another with the assistance
of small molecular weight linear chains. In doing so, a linear CTA-derived side
product will be found in the product; however, it can be removed by selective
precipitation methods. Of all the synthetic strategies discussed above, the graft-
ing from R-group approach is superior for making bottlebrushes with long side
chains.
For the preparation of a CTA-decorated bottlebrush backbone, the coupling
of CTA onto the monomer can be carried out either before [155, 156] or after
[151, 154, 157, 158] the backbone polymerization. Coupling onto a polymer chain
can typically be expected to be more challenging than coupling reactions between
two small molecules; the same applies for the characterization and purification of
the resulting product. Here, thorough purification is of high importance as traces
of uncoupled CTA result in a shuttle CTA effect, yielding a linear side product
during the grafting step. In order to achieve a bottlebrush structure by using a
CTA-functionalized monomer, the monomer should not add to the coupled CTA
during the backbone polymerization; addition of functionalized monomer to
itself results in hyperbranched structures (see section 20.7.1). It follows that when
RAFT is used to polymerize both the backbone and the side chains, coupling onto
the backbone is the standard approach; polymerization of a CTA-functionalized
monomer requires a special strategies. Orthogonality can be achieved by combining
RAFT with other polymerization techniques, such as ROMP, ATRP, NMP, or
cationic polymerization [159–163]. RAFT polymerization in both the backbone
and the side chain direction using a CTA-functionalized monomer in one pot was
recently reported using selective photoactivation of the backbone and side chain
CTAs [155, 156].
In the grafting from approach characterization of the side chains is more challeng-
ing than in the other two strategies. The investigation of the initiation efficiency of
the pendant CTAs and a closer look at the side chains requires their cleavage off the
backbone. Moreover, any initiated CTAs cause deviation between the targeted and
resulting side chain degree of polymerizations (DPs). Studies of side chain cleavage
can be found in the literature [137, 151, 164]. The Z-group approach can potentially
provide an easier route for removing the grafts through aminolysis or other degra-
dation of the thiocarbonyl thio-group, whereas for the R-group approach, harsher
reaction conditions are often required. Determination of the final grafting density
can prove difficult, as it arises from an interplay between the initial CTA density on
the backbone, reinitiation efficiency, and termination events – and in the Z-group
approach, steric shielding effects.

RAFT polymerization of graft polymers can yield highly complex structures. The
successful preparation of well-defined polymers requires the selection of an appro-
priate synthetic pathway, as each of the three general approaches has its strengths
and limitations.
The simplest route for making bottlebrush polymers using RAFT polymerization
is to use the grafting through approach with commercial macromonomers. RAFT
polymerization can also be utilized in the macromonomer synthesis. It is the only
approach where every repeating unit along the main chain is guaranteed to have a
side chain attached to it, making it a viable option for the preparation of high-density
bottlebrushes. However, only moderate backbone DPs can be achieved whilst retain-
ing low dispersity of the resulting polymer because of the limited concentration of
reactive groups in the reaction mixture. The problem of low concentration can poten-
tially be overcome by monomer feeding. The side chains of the resulting bottlebrush
are as well defined as the macromonomer and can be characterized separately from
the bottlebrush without the need for their detachment. Low monomer conversions
can lead to tedious purification processes of the product.
For the preparation of bottlebrush polymers with long backbones, the grafting
onto and grafting from approaches are more suitable. Both methods allow for the
backbone to be as long as any linear polymer made by RAFT polymerization. If long
side chains are also required, the grafting from approach is more appropriate than
the grafting onto approach, as the coupling step of the grafting onto approach can
suffer from steric shielding effects near the reacting site. In the grafting onto syn-
thesis, an excess of side chains may be required to achieve high grafting densities,
and any uncoupled side chains require their removal to yield an isolated bottlebrush
product. Using this modular approach, both the backbone and the side chains can
be characterized separately before the coupling step.
While the grafting from the R-group approach is the superior method for making
bottlebrush polymers with long backbones, long side chains, and high grafting densi-
ties, careful consideration of reaction conditions is needed to minimize brush–brush
coupling. The coupling reactions can be suppressed through the addition of a low
molecular weight shuttle-CTA into the side chain polymerization, and by quench-
ing, the reaction before full monomer conversion is reached. The use of a free CTA
in the polymerization results in a linear side product. Characterization of the side
chains requires their cleavage off the backbone. Moreover, the grafting from the syn-
thesis of bottlebrush polymers requires a large amount of CTA to be used and yields
a product with high CTA content, which can potentially be an undesirable property
for certain applications.
20.7 Hyperbranched Polymers

Hyperbranched polymers are an attractive class of polymeric architecture because
of their highly branched and globular, three-dimensional structure. From drug and
gene delivery [165] to oil additives, these materials have found a use in a wide range
of fields. The history of hyperbranched polymers is one as long as synthetic poly-
merization itself, with the first reported hyperbranched structure originating at the
end of the nineteenth century, 20 years before Staudinger’s report ‘Über Polymer-
ization’ [166]. Step growth polymerization of ABn (n ≥ 2) monomers has been the
focus of a significant portion of the studies into the preparation of hyperbranched
polymers. Whilst this is a facile method for the synthesis of this polymer class, rad-
ical polymerization offers a scalable and efficient route towards highly functional
polymers. Combining this with controlled radical polymerization (CRP) techniques
such as RAFT or ATRP, the ability to finely tune the architecture of the resulting
hyperbranched polymers can be realized.
One common challenge in the preparation of hyperbranched polymers is the
avoidance of macroscopic gelation. This can be readily overcome by employing
CRP and in particular RAFT polymerization because of the low concentration of
radicals at a time. Whilst CTAs are generally used to control the polymerization
and reduce dispersity, when applied to hyperbranched systems, their function
is to primarily hinder gelation. Employment of CTAs has the added benefit of
introducing functional handles to the surface of the polymer and allowing for
degradable bonds to be positioned within the polymeric structure.
20.7.1 Self-condensing Vinyl Polymerization

First described by Fréchet et al. [167], SCVP is a method for synthesizing dendritic
polymers by the polymerization of a vinyl monomer containing a pendent group
capable of initiating further polymerization. These inimers can either be homopoly-
merized or copolymerized with other vinyl monomers to form highly branched
polymeric structures. Defined as AB* monomers, upon activation, the B group is
transformed to initiate further polymerization and branching. This is traditionally
achieved by using a monomer containing a vinyl group and an alkyl halide bond.
However, CRP was readily applied to the system by replacement of alkyl halides
with CTAs such as nitroxides (NMP) or thiocarbonylthiols (RAFT/MADIX) [168].
Employing the use of CTAs offers several advantages: reduction of radical concen-
tration – disfavouring macroscopic gel formation, control over the location and
density of branching points, and post-polymerization modification by end group
removal [128].
(a) R-group (b) Z-group
Figure 20.16 Positioning of the thiocarbonylthio group in a polymeric architecture

obtained by SCVP depending on the polymer being prepared via (a) the R- or (b) the
Z-group approach.
For RAFT-SCVP, an inimer is formed by modification of a RAFT agent to include

a vinyl group capable of polymerization. The vinyl group can be attached via the R-
or Z-group of the RAFT agent, with the site of attachment leading to structural dif-
ferences (Figure 20.16). As with traditional RAFT polymerization, the choice of R-
and Z-groups dictates the monomer families able to be polymerized in a controlled
fashion. Trithiocarbonates, xanthates, and even selenium-based RAFT agents have
all been transformed to inimers for RAFT-SCVP and copolymerized with an exhaus-
tive list of monomers [168]. The vast majority of inimers reported in the literature
focused on the modification of the R-group, with only a few reporting Z-group mod-
ification. One could postulate that this is due to the ease of R-group modification,
especially for carboxylic acid containing RAFT agents, with esterification being a
common and facile route. However, this disparity could be due to the structural dif-
ferences between the resulting polymers. Modification of the R-group results in the
thiocarbonylthio positioned at the polymer chain end, whereas Z-group modifica-
tion leads to positioning of this functionality at the branching points within the
polymer. Because of the susceptibility of this motif to degradation (i.e. aminolysis
or reduction), this could be seen as an advantage or disadvantage, depending on the
required properties.
Polymer growth is mediated by two pathways in RAFT-SCVP: propagation of the
vinyl group and chain transfer to the thiocarbonylthio moiety. Backbone formation
is governed by vinyl group propagation of the inimer and, if present, comonomer,
whereas branching is introduced by chain transfer to the thiocarbonylthio groups
incorporated into the backbone, followed by re-initiation and further propagation.
Copolymerization of inimers with monovinyl monomers allows for control over the
branching density and is also used for the introduction of functionality into the poly-
mer. The relative reactivity of the inimer and monomer requires consideration as
differences in reactivity can heavily influence the distribution and location of the
branching points.
Because of the versatility of the RAFT process, a wide range of comonomers have
been applied to RAFT-SCVP. Monomers such as NIPAM have been commonly
incorporated to introduce temperature responsiveness to the polymer [169, 170].
pH [171, 172], redox [173], and enzyme [172] responsive systems have all been
applied to RAFT-SCVP by copolymerization of appropriate monomers.
Functionality can also be introduced into the inimer structure. Wei et al. reported
the synthesis and use of an enzyme-responsive inimer for mediating the polymer-
ization of N-(2-hydroxypropyl)methacrylamide [172]. In the presence of the enzyme
papain, these hyperbranched polymers were degraded into smaller polymeric units.
For a detailed overview of RAFT-SCVP and the applications of the resulting poly-
mers, please refer to the following reviews [168, 174].
20.7.2 Copolymerization of Multifunctional Monomers

The synthesis of hyperbranched polymers can also be achieved by copolymerization
of a monovinyl monomer with a multivinyl monomer. In a radical copolymeriza-
tion, macroscopic gel formation will occur when the number of divinyl monomers
per chain exceeds one.[165] Use of a CTA allows for an increase in divinyl monomer
incorporation whilst avoiding macroscopic gel formation. This was first reported by
Sherrington in what is now known as the ‘Strathclyde route’. [175] It was demon-
strated that by addition of 1-dodecanthiol (DDT) to the polymerization mixture,
macroscopic gel formation could be avoided, whereas in the absence of DDT, gel
formation was observed.
Because of the high availability of multifunctional monomers and the avoidance
of inimer synthesis, the preparation of hyperbranched polymers via this method
is straightforward and accessible. It also readily allows for the introduction of
stimuli-responsive crosslinkers, allowing for the preparation of a wide range of
responsive materials.
With the Strathclyde route using irreversible chain transfer, Perrier and coworkers
were the first to employ the use of a RAFT agent to control the copolymerization
of multifunctional monomers [176]. Initially focusing on the copolymerization
of methyl methacrylate (MMA) and ethylene glycol dimethacrylate (EGDMA),
variation of the CTA/EGDMA ratio was studied. Because of the lower radical
concentration in RAFT polymerization, an increase in cross-linking density is able
to be achieved without macroscopic gelation. A CTA/EGDMA ratio of 1 exhibited
no macroscopic gel formation, even at 100% monomer conversion. However, by
increasing the CTA/EGDMA ratio to 2, beyond the theoretical limit determined
by Flory, gel formation was observed, although only at high monomer conversion
(>95%).
Following on from their initial study, Perrier and coworkers conducted a series
of reactions to investigate the influence of reaction parameters on the obtained
hyperbranched polymers [177]. By increasing the ratio of crosslinker to CTA, higher
MW polymers were obtained; however, one has to be careful when increasing
the crosslinker concentration as to avoid gelation. If the ratio of crosslinker to
CTA is kept constant, but the comonomer concentration is increased, then the
observed MW also increases. This parallels traditional RAFT as the [M]0 : [CTA]0
determines the chain length, and subsequently, the MW. Kinetic studies reveal that
whilst the crosslinker is statistically incorporated into the polymer throughout the
polymerization, the physical cross-linking tends to take place at high monomer

conversion. This is evidenced by an initial linear evolution in MW, followed by
a rapid increase towards high conversions, and can be explained by the relative
concentrations of vinyl bonds. The concentration of pendent vinyl bonds capable
of cross-linking the polymer chains is low compared to that of the comonomer,
which will therefore preferentially react first. As the reaction proceeds, the relative
concentration increases, thereby increasing the likelihood of cross-linking. By
increasing the ratio of a crosslinker relative to comonomer, the cross-linking will
take place at lower concentrations.
The solubility of the crosslinker can also affect the resulting hyperbranched struc-
ture. Use of a hydrophobic crosslinker and hydrophilic monomer in an aqueous
system results in ‘star-like’ polymers with a cross-linked core (See section 20.5.1.2).
Copolymerization of a degradable crosslinker by Pal et al. gave useful insights into
the controlled nature of the RAFT-mediated copolymerization of multifunctional
monomers [178]. Basic degradation of a dilactone crosslinker and subsequent analy-
sis of the resulting chains revealed that the hyperbranched polymers were composed
of linear chains with narrow dispersities. This was further confirmed by Rosselgong
et al. who carried out a similar study with a disulfide cross-linked polymer [179].
Reduction of the disulfides and subsequent analysis of the polymer chains revealed
well-controlled linear chains, analogous to those synthesized in the absence of a
crosslinker.
From these studies, one can assume that hyperbranched polymers consist of
primary chains with dispersity and molecular weight equal to those obtained
from the polymerization in the absence of a crosslinker. Therefore, it is possible to
calculate the number of branching units incorporated, nb , using Eq. (20.3) [180].
Mn,b
nb = −1 (20.3)
Mn,l
M n,b is the number-average molecular weight of the branched polymer and M n,l is
the number-average molecular weight of the primary linear chain.
RAFT polymerization has also been applied to the homopolymerization of multi-
functional monomers such as divinylbenzene (DVB) [181]. In conventional radical
polymerization of DVB, gelation is observed at 15% monomer conversion; however,
by addition of a RAFT agent, this can be delayed to 68%. Linear chains consisting
of pendent vinyl bonds are initially formed, before cross-linking to form a highly
branched network. The same phenomenon was observed when using a poly(methyl
acrylate) macroRAFT agent; however, the point of gelation occurred earlier, at 37%
monomer conversion.
20.7.3 Alternative Methods of Hyperbranched Synthesis

As discussed above, classically hyperbranched polymers were synthesized via the
step growth polymerization of ABn -type (n ≥ 2) monomers. Thiocarbonylthios
can be considered to be masked thiols; therefore, with simple deprotection (i.e.
aminolysis), a polymer prepared by RAFT polymerization can be transformed into
an AB2 -type monomer. Introduction of a B2 functionality to the R-group is straight-

forward, with the introduction of di-bromide [182], 2,2′ -dipyridyl disulfide [183],
or alkynes [184] being reported in the literature. Preparation of hyperbranched
polymers via this convergent method allows for greater control over the linear
polymer between the branching points, with the chain length determined before
cross-linking. It would also enable the introduction of greater structural variation
into the hyperbranched polymer, for example, by use of multiblock copolymers.

If one is attempting to synthesize hyperbranched polymers, the best method devel-
oped so far is that of multifunctional monomer copolymerization. Hyperbranched
polymers can be readily achieved through the copolymerization of commercially
available monomers, removing the synthetic steps required in the other methods
described, e.g. inimer synthesis. However, this method does not offer the best con-
trol over the backbone of the hyperbranched polymer. If fine structural control is
required, then modification of a RAFT agent to include ABn -functionality is pre-
ferred. Ultimately, the choice of synthetic route comes down to the required proper-
ties of the resulting hyperbranched polymer.
20.8 Conclusion
RAFT polymerization has developed as one of the most versatile techniques to gen-
erate polymeric architectures, whose complexity spans from diblock copolymers to
multifunctional macromolecules such as graft, star, and hyperbranched copolymers.
Its popularity among chemists not only comes from its versatility in the materials it
generates but also from the simplicity of the process, which can be relatively easily
scaled up, as illustrated by the few examples of large-scale industrial productions.
The field continues to expand, through contribution on the one hand from poly-
mer chemists aiming at developing new synthetic methodologies, complex archi-
tectures, and simpler process for product scale up and on the other hand from sci-
entists seeking specific architecture for a given application, being in the medical
field, materials science, and so on. Its simple setup and the commercial availability
of all reactants that make RAFT the technique of choice for scientists of any back-
ground to obtain complex architectures that until now were only reachable by skilled
chemists.
Acknowledgements
The Royal Society Wolfson Merit Award (WM130055; S.P.), Monash-Warwick

Alliance (S.P.), the German Research Foundation (DFG, GZ: HA 7725/1-1; M.H.),
and Lubrizol (S.H., A.K.) are acknowledged for financial support.
References 969
References
1 Moad, G., Rizzardo, E., and Thang, S.H. (2013). RAFT polymerization and
some of its applications. Chem–An Asian J. 8 (8): 1634–1644.
2 Perrier, S., Barner-Kowollik, C., Quinn, J.F. et al. (2002). Origin of inhibi-
tion effects in the reversible addition fragmentation chain transfer (RAFT)
polymerization of methyl acrylate. Macromolecules 35 (22): 8300–8306.
3 McLeary, J., McKenzie, J., Tonge, M. et al. (2004). Initialisation in
RAFT-mediated polymerisation of methyl acrylate. Chem. Commun. 17:
1950–1951.
4 Moad, G., Chong, Y., Postma, A. et al. (2005). Advances in RAFT polymer-
ization: the synthesis of polymers with defined end-groups. Polymer 46 (19):
8458–8468.
5 Destarac, M., Charmot, D., Franck, X., and Zard, S. (2000). Dithiocarbamates
as universal reversible addition-fragmentation chain transfer agents. Macromol.
Rapid Commun. 21 (15): 1035–1039.
6 Benaglia, M., Chiefari, J., Chong, Y.K. et al. (2009). Universal (switchable)
RAFT agents. J. Am. Chem. Soc. 131 (20): 6914–6915.
7 Keddie, D.J., Guerrero-Sanchez, C., Moad, G. et al. (2011). Switchable reversible
addition–fragmentation chain transfer (RAFT) polymerization in aqueous
solution, N,N-dimethylacrylamide. Macromolecules 44 (17): 6738–6745.
8 Keddie, D.J., Guerrero-Sanchez, C., Moad, G. et al. (2012). Chain transfer kinet-
ics of acid/base switchable N-aryl-N-pyridyl dithiocarbamate RAFT agents in
methyl acrylate, N-vinylcarbazole and vinyl acetate polymerization. Macro-
molecules 45 (10): 4205–4215.
9 Dommanget, C., D’Agosto, F., and Monteil, V. (2014). Polymerization of ethy-
lene through reversible addition–fragmentation chain transfer (RAFT). Angew.
Chem. Int. Ed. 53 (26): 6683–6686.
tion. Nat. Chem. 9 (2): 171.
ization using ppm concentrations of organic acid. Angew. Chem. Int. Ed. 54 (6):
1924–1928.
13 Sugihara, S., Konegawa, N., and Maeda, Y. (2015). HCl⋅ Et2 O-catalyzed
metal-free RAFT cationic polymerization: one-pot transformation from
metal-free living cationic polymerization to RAFT radical polymerization.
and radical RAFT polymerizations: a versatile route to well-defined poly (ethyl
vinyl ether)-block-poly (vinylidene fluoride) block copolymers. ACS Macro Lett.
6 (4): 393–398.
15 Kottisch, V., Michaudel, Q., and Fors, B.P. (2016). Cationic polymerization of
vinyl ethers controlled by visible light. J. Am. Chem. Soc. 138 (48): 15535–15538.
16 Peterson, B.M., Kottisch, V., Supej, M.J., and Fors, B.P. (2018). On demand
switching of polymerization mechanism and monomer selectivity with orthogo-
nal stimuli. ACS Central Sci. 4 (9): 1228–1234.
17 Mayadunne, R.T., Rizzardo, E., Chiefari, J. et al. (2000). Living polymers by
the use of trithiocarbonates as reversible addition−fragmentation chain trans-
fer (RAFT) agents: ABA triblock copolymers by radical polymerization in two
steps. Macromolecules 33 (2): 243–245.
18 Liu, Y. and Cavicchi, K.A. (2009). Reversible addition fragmentation chain
transfer (RAFT) polymerization with a polymeric RAFT agent containing
multiple trithiocarbonate groups. Macromol. Chem. Phys. 210 (19): 1647–1653.
19 Ebeling, B. and Vana, P. (2011). Multiblock copolymers of styrene and butyl
acrylate via polytrithiocarbonate-mediated RAFT polymerization. Polymers 3
(2): 719–739.
20 Hong, J., Wang, Q., and Fan, Z. (2006). Synthesis of multiblock polymer con-
taining narrow polydispersity blocks. Macromol. Rapid Commun. 27 (1): 57–62.
21 Wu, Y. and Wang, Q. (2010). One-pot synthesis of well-defined multiblock
polymer: combination of ATRP and RAFT polymerization involving cyclic
trithiocarbonate. J. Polym. Sci., Part A: Polym. Chem. 48 (11): 2425–2429.
22 Bai, W., Zhang, L., Bai, R., and Zhang, G. (2008). A very useful redox initiator
for aqueous RAFT polymerization of N-isopropylacrylamide and acrylamide at
room temperature. Macromol. Rapid Commun. 29 (7): 562–566.
23 Martin, L., Gody, G., and Perrier, S. (2015). Preparation of complex multiblock
copolymers via aqueous RAFT polymerization at room temperature. Polym.
Chem. 6 (27): 4875–4886.
24 Ran, R., Yu, Y., and Wan, T. (2007). Photoinitiated RAFT polymerization in the
presence of trithiocarbonate. J. Appl. Polym. Sci. 105 (2): 398–404.
25 Otsu, T., Matsunaga, T., Kuriyama, A., and Yoshioka, M. (1989). Living radical
polymerization through the use of iniferters: controlled synthesis of polymers.
Eur. Polym. J. 25 (7-8): 643–650.
26 Wang, H., Li, Q., Dai, J. et al. (2013). Real-time and in situ investigation of
“living”/controlled photopolymerization in the presence of a trithiocarbonate.
Chem. 6 (31): 5615–5624.
29 McKenzie, T.G., Fu, Q., Wong, E.H. et al. (2015). Visible light mediated con-
References 971
30 Fu, C., Xu, J., Tao, L., and Boyer, C. (2014). Combining enzymatic
monomer transformation with photoinduced electron transfer – reversible
addition-fragmentation chain transfer for the synthesis of complex multiblock
copolymers. ACS Macro Lett. 3 (7): 633–638.
31 Thomas, D.B., Convertine, A.J., Hester, R.D. et al. (2004). Hydrolytic susceptibil-
ity of dithioester chain transfer agents and implications in aqueous RAFT poly-
merizations. Macromolecules 37 (5): 1735–1741.
32 Scales, C.W., Vasilieva, Y.A., Convertine, A.J. et al. (2005). Direct,
controlled synthesis of the nonimmunogenic, hydrophilic polymer,
poly(N-(2-hydroxypropyl) methacrylamide) via RAFT in aqueous media.
33 Chong, B., Moad, G., Rizzardo, E. et al. (2006). Thermolysis of
RAFT-synthesized poly(methyl methacrylate). Aust. J. Chem. 59 (10): 755–762.
34 Vana, P., Albertin, L., Barner, L. et al. (2002). Reversible addition–fragmentation
chain-transfer polymerization: unambiguous end-group assignment via electro-
spray ionization mass spectrometry. J. Polym. Sci., Part A: Polym. Chem. 40 (22):
4032–4037.
35 Gody, G., Maschmeyer, T., Zetterlund, P.B., and Perrier, S. (2013). Rapid and
quantitative one-pot synthesis of sequence-controlled polymers by radical
polymerization. Nat. Commun. 4: 2505.
36 Valdebenito, A. and Encinas, M.V. (2010). Effect of solvent on the free radical
polymerization of N,N-dimethylacrylamide. Polym. Int. 59 (9): 1246–1251.
37 Gody, G., Maschmeyer, T., Zetterlund, P.B., and Perrier, S. (2014). Pushing
the limit of the RAFT process: multiblock copolymers by one-pot rapid mul-
tiple chain extensions at full monomer conversion. Macromolecules 47 (10):
3451–3460.
38 Vandenbergh, J., de Moraes Ogawa, T., and Junkers, T. (2013). Precision syn-
thesis of acrylate multiblock copolymers from consecutive microreactor RAFT
polymerizations. J. Polym. Sci., Part A: Polym. Chem. 51 (11): 2366–2374.
39 Baeten, E., Haven, J.J., and Junkers, T. (2017). RAFT multiblock reactor tele-
scoping: from monomers to tetrablock copolymers in a continuous multistage
reactor cascade. Polym. Chem. 8 (25): 3815–3824.
40 Bartels, J.W., Cauët, S.I., Billings, P.L. et al. (2010). Evaluation of isoprene chain
extension from PEO macromolecular chain transfer agents for the preparation
of dual, invertible block copolymer nanoassemblies. Macromolecules 43 (17):
7128–7138.
41 Warren, N.J., Mykhaylyk, O.O., Mahmood, D. et al. (2014). RAFT aqueous dis-
persion polymerization yields poly (ethylene glycol)-based diblock copolymer
nano-objects with predictable single phase morphologies. J. Am. Chem. Soc. 136
(3): 1023–1033.
42 Pai, T.S., Barner-Kowollik, C., Davis, T.P., and Stenzel, M.H. (2004). Synthesis of
amphiphilic block copolymers based on poly (dimethylsiloxane) via fragmenta-
tion chain transfer (RAFT) polymerization. Polymer 45 (13): 4383–4389.
43 Duong, T.H., Bressy, C., and Margaillan, A. (2014). Well-defined diblock copoly-
mers of poly(tert-butyldimethylsilyl methacrylate) and poly(dimethylsiloxane)
synthesized by RAFT polymerization. Polymer 55 (1): 39–47.
44 Crossland, E.J., Cunha, P., Scroggins, S. et al. (2010). Soft-etch mesoporous
hole-conducting block copolymer templates. ACS Nano 4 (2): 962–966.
45 Saetung, N., Campistron, I., Pascual, S. et al. (2011). Synthesis of natural
rubber-based telechelic cis-1,4-polyisoprenes and their use to prepare block
copolymers via RAFT polymerization. Eur. Polym. J. 47 (5): 1151–1159.
46 Chen, M., Häussler, M., Moad, G., and Rizzardo, E. (2011). Block copolymers
containing organic semiconductor segments by RAFT polymerization. Org.
Biomol. Chem. 9 (17): 6111–6119.
47 Magenau, A.J., Martinez-Castro, N., Savin, D.A., and Storey, R.F. (2009). Poly-
isobutylene RAFT CTA by a click chemistry site transformation approach:
synthesis of poly (isobutylene-b-N-isopropylacrylamide). Macromolecules 42
(21): 8044–8051.
48 Espeel, P. and Du Prez, F.E. (2014). “Click”-inspired chemistry in macromolecu-
lar science: matching recent progress and user expectations. Macromolecules 48
(1): 2–14.
49 Harvison, M.A. and Lowe, A.B. (2011). Combining RAFT radical polymeriza-
tion and click/highly efficient coupling chemistries: a powerful strategy for the
preparation of novel materials. Macromol. Rapid Commun. 32 (11): 779–800.
50 Ting, S.S., Granville, A.M., Quémener, D. et al. (2007). RAFT chemistry and
Huisgen 1,3-dipolar cycloaddition: a route to block copolymers of vinyl acetate
and 6-O-methacryloyl mannose? Aust. J. Chem. 60 (6): 405–409.
51 Huang, Y., Hou, T., Cao, X. et al. (2010). Synthesis of silica-polymer hybrids
by combination of RAFT polymerization and azide-alkyne cycloaddition ‘click’
52 Xue, X., Zhu, J., Zhang, Z. et al. (2010). Synthesis and characterization of
azobenzene-functionalized poly (styrene)-b-poly (vinyl acetate) via the combina-
tion of RAFT and “click” chemistry. Polymer 51 (14): 3083–3090.
53 Zhao, G., Zhang, P., Zhang, C., and Zhao, Y. (2012). Facile synthesis of highly
pure block copolymers by combination of RAFT polymerization, click reaction
and de-grafting process. Polym. Chem. 3 (7): 1803–1812.
54 Quémener, D., Davis, T.P., Barner-Kowollik, C., and Stenzel, M.H. (2006). RAFT
and click chemistry: a versatile approach to well-defined block copolymers.
Chem. Commun. 48: 5051–5053.
55 O’Reilly, R.K., Joralemon, M.J., Hawker, C.J., and Wooley, K.L. (2006). Facile
syntheses of surface-functionalized micelles and shell cross-linked nanoparti-
cles. J. Polym. Sci., Part A: Polym. Chem. 44 (17): 5203–5217.
56 Zhang, T., Zheng, Z., Ding, X., and Peng, Y. (2008). Smart surface of gold
nanoparticles fabricated by combination of RAFT and click chemistry. Macro-
mol. Rapid Commun. 29 (21): 1716–1720.
57 Hansell, C.F., Espeel, P., Stamenovic, M.M. et al. (2011). Additive-free clicking
for polymer functionalization and coupling by tetrazine–norbornene chemistry.
J. Am. Chem. Soc. 133 (35): 13828–13831.
References 973
58 Vandewalle, S., Billiet, S., Driessen, F., and Du Prez, F.E. (2016). Macromolecu-
lar coupling in seconds of triazolinedione end-functionalized polymers prepared
by RAFT polymerization. ACS Macro Lett. 5 (6): 766–771.
59 Brendel, J.C., Martin, L., Zhang, J., and Perrier, S. (2017). SuFEx–a selectively
triggered chemistry for fast, efficient and equimolar polymer–polymer coupling
60 Wang, P., Dong, Y., Lu, X. et al. (2018). Combining click sulfur (VI)-fluoride
exchange with photoiniferters: a facile, fast, and efficient strategy for postpoly-
merization modification. Macromol. Rapid Commun. 39 (3): 1700523.
61 Sinnwell, S., Inglis, A.J., Davis, T.P. et al. (2008). An atom-efficient conjugation
approach to well-defined block copolymers using RAFT chemistry and hetero
Diels–Alder cycloaddition. Chem. Commun. 17: 2052–2054.
62 Inglis, A.J., Stenzel, M.H., and Barner-Kowollik, C. (2009). Ultra-fast
RAFT-HDA click conjugation: an efficient route to high molecular weight
block copolymers. Macromol. Rapid Commun. 30 (21): 1792–1798.
63 Langer, M., Mueller, J.O., Goldmann, A.S. et al. (2016). α,ω-reactive building
blocks based on a dual functional RAFT agent for thermal and light-induced
ligation. ACS Macro Lett. 5 (5): 597–601.
64 Roth, P.J., Boyer, C., Lowe, A.B., and Davis, T.P. (2011). RAFT polymeriza-
tion and thiol chemistry: a complementary pairing for implementing modern
macromolecular design. Macromol. Rapid Commun. 32 (15): 1123–1143.
65 Roth, P.J., Kessler, D., Zentel, R., and Theato, P. (2008). A method for obtaining
defined end groups of polymethacrylates prepared by the RAFT process during
aminolysis. Macromolecules 41 (22): 8316–8319.
66 Spruell, J.M., Levy, B.A., Sutherland, A. et al. (2009). Facile postpolymerization
end-modification of RAFT polymers. J. Polym. Sci., Part A: Polym. Chem. 47 (2):
346–356.
67 Li, M., De, P., Gondi, S.R., and Sumerlin, B.S. (2008). End group transforma-
tions of RAFT-generated polymers with bismaleimides: functional telechelics
and modular block copolymers. J. Polym. Sci., Part A: Polym. Chem. 46 (15):
5093–5100.
68 Koo, S.P., Stamenović, M.M., Prasath, R.A. et al. (2010). Limitations of radical
thiol-ene reactions for polymer–polymer conjugation. J. Polym. Sci., Part A:
Polym. Chem. 48 (8): 1699–1713.
69 Bertrand, A., Chen, S., Souharce, G. et al. (2011). Straightforward prepara-
tion of telechelic H-bonding polymers from difunctional trithiocarbonates and
supramolecular block copolymers thereof. Macromolecules 44 (10): 3694–3704.
70 Moughton, A.O., Stubenrauch, K., and O’Reilly, R.K. (2009). Hollow nanos-
tructures from self-assembled supramolecular metallo-triblock copolymers. Soft
Matter. 5 (12): 2361–2370.
71 Schmidt, B.V. and Barner-Kowollik, C. (2014). Supramolecular X-and H-shaped
star block copolymers via cyclodextrin-driven supramolecular self-assembly.
Polym. Chem. 5 (7): 2461–2472.
72 Montarnal, D., Delbosc, N., Chamignon, C. et al. (2015). Highly ordered

nanoporous films from supramolecular diblock copolymers with
hydrogen-bonding junctions. Angew. Chem. Int. Ed. 54 (38): 11117–11121.
73 Chen, S., Rocher, M., Ladaviere, C. et al. (2012). AB/ABC/ABCD supramolec-
ular block copolymers from Hamilton wedge and barbiturate-functionalized
RAFT agents. Polym. Chem. 3 (11): 3157–3165.
74 Chen, S., Deng, Y., Chang, X. et al. (2014). Facile preparation of supramolec-
ular (ABAC) n multiblock copolymers from Hamilton wedge and
barbiturate-functionalized RAFT agents. Polym. Chem. 5 (8): 2891–2900.
75 Beginn, U. (2008). Gradient copolymers. Colloid. Polym. Sci. 286 (13):
1465–1474.
76 Zhang, J., Farias-Mancilla, B., Destarac, M. et al. (2018). Asymmetric copoly-
mers: synthesis, properties, and applications of gradient and other partially
segregated copolymers. Macromol. Rapid Commun. 39 (19): 1800357.
77 Sun, X., Luo, Y., Wang, R. et al. (2008). Semibatch RAFT polymerization for
producing ST/BA copolymers with controlled gradient composition profiles.
AlChE J. 54 (4): 1073–1087.
neous gradient copolymers with block-and gradient-like features. Polym. Chem.
8 (34): 5023–5032.
copolymerization systems. Macromol. Symp. 325 (1): 38–46.
80 Fu, C., Yang, B., Zhu, C. et al. (2013). Synthesis of gradient copolymers by con-
current enzymatic monomer transformation and RAFT polymerization. Polym.
Chem. 4 (24): 5720–5725.
81 Tang, Q., Wu, Y., Sun, P. et al. (2014). Powerful ring-closure method for prepar-
ing varied cyclic polymers. Macromolecules 47 (12): 3775–3781.
82 Stamenović, M.M., Espeel, P., Baba, E. et al. (2013). Straightforward synthesis of
functionalized cyclic polymers in high yield via RAFT and thiolactone–disulfide
chemistry. Polym. Chem. 4 (1): 184–193.
83 Whittaker, M.R., Goh, Y.-K., Gemici, H. et al. (2006). Synthesis of monocyclic
and linear polystyrene using the reversible coupling/cleavage of thiol/disulfide
groups. Macromolecules 39 (26): 9028–9034.
84 Goldmann, A.S., Quémener, D., Millard, P.-E. et al. (2008). Access to
cyclic polystyrenes via a combination of reversible addition fragmentation
chain transfer (RAFT) polymerization and click chemistry. Polymer 49 (9):
2274–2281.
85 Skey, J., Willcock, H., Lammens, M. et al. (2010). Synthesis and self-assembly
of amphiphilic chiral poly(amino acid) star polymers. Macromolecules 43 (14):
5949–5955.
86 Zhang, L. and Stenzel, M.H. (2009). Spherical glycopolymer architectures using
RAFT: from stars with a – cyclodextrin Core to thermoresponsive CoreShell
particles. Aust. J. Chem. 62 (8): 813–822.
References 975
87 Yusa, S.-I., Endo, T., and Ito, M. (2009). Synthesis of thermo-responsive 4-arm
star-shaped porphyrin-centered poly(N,N-diethylacrylamide) via reversible
addition-fragmentation chain transfer radical polymerization. J. Polym. Sci., Part
A: Polym. Chem. 47 (24): 6827–6838.
88 Ren, J.M., McKenzie, T.G., Fu, Q. et al. (2016). Star polymers. Chem. Rev. 116
(12): 6743–6836.
89 Zhang, C., Zhou, Y., Liu, Q. et al. (2011). Facile synthesis of hyperbranched
and star-shaped polymers by RAFT polymerization based on a polymerizable
trithiocarbonate. Macromolecules 44 (7): 2034–2049.
90 Hu, J., Qiao, R., Whittaker, M.R. et al. (2017). Synthesis of star polymers by
RAFT polymerization as versatile nanoparticles for biomedical applications.
Aust. J. Chem. 70 (11): 1161–1170.
91 Chaffey-Millar, H., Stenzel, M.H., Davis, T.P. et al. (2006). Design criteria for
star polymer formation processes via living free radical polymerization. Macro-
molecules 39 (19): 6406–6419.
92 Boschmann, D. and Vana, P. (2007). Z-RAFT star polymerizations of acrylates:
star coupling via intermolecular chain transfer to polymer. Macromolecules 40
(8): 2683–2693.
93 Stenzel, M.H. and Davis, T.P. (2002). Star polymer synthesis using trithio-
carbonate functional β-cyclodextrin cores (reversible addition–fragmentation
chain-transfer polymerization). J. Polym. Sci., Part A: Polym. Chem. 40 (24):
4498–4512.
94 Altintas, O., Abbasi, M., Riazi, K. et al. (2014). Stability of star-shaped RAFT
polystyrenes under mechanical and thermal stress. Polym. Chem. 5 (17):
5009–5019.
95 Zhang, L. and Chen, Y. (2006). Allyl functionalized telechelic linear polymer
and star polymer via RAFT polymerization. Polymer 47 (15): 5259–5266.
96 Ferreira, J., Syrett, J., Whittaker, M. et al. (2011). Optimizing the generation of
narrow polydispersity ‘arm-first’ star polymers made using RAFT polymeriza-
tion. Polym. Chem. 2 (8): 1671–1677.
97 Tucker, B.S., Getchell, S.G., Hill, M.R., and Sumerlin, B.S. (2015). Facile synthe-
sis of drug-conjugated PHPMA core-cross-linked star polymers. Polym. Chem. 6
(23): 4258–4263.
98 Bray, C., Peltier, R., Kim, H. et al. (2017). Anionic multiblock core cross-linked
star copolymers via RAFT polymerization. Polym. Chem. 8 (36): 5513–5524.
99 Dong, Z.-M., Liu, X.-H., Liu, H.-W., and Li, Y.-S. (2010). Synthesis of novel star
polymers with vinyl-functionalized hyperbranched core via “arm-first” strategy.
100 Brzytwa, A.J. and Johnston, J. (2011). Scaled production of RAFT CTA – a star
performer. Polym. Prepr. 52: 533–534.
101 Roberts, D.A., Crossley, M.J., and Perrier, S. (2014). Fluorescent bowl-shaped
nanoparticles from ‘clicked’ porphyrin–polymer conjugates. Polym. Chem. 5
(13): 4016–4021.
102 Inglis, A.J., Sinnwell, S., Davis, T.P. et al. (2008). Reversible addition fragmenta-
tion chain transfer (RAFT) and hetero-Diels−Alder chemistry as a convenient
conjugation tool for access to complex macromolecular designs. Macromolecules

41 (12): 4120–4126.
103 Chan, J.W., Yu, B., Hoyle, C.E., and Lowe, A.B. (2008). Convergent synthesis
of 3-arm star polymers from RAFT-prepared poly(N,N-diethylacrylamide) via a
thiol–ene click reaction. Chem. Commun. 40: 4959–4961.
104 Bapat, A.P., Ray, J.G., Savin, D.A. et al. (2012). Dynamic-covalent nanostruc-
tures prepared by Diels–Alder reactions of styrene-maleic anhydride-derived
copolymers obtained by one-step cascade block copolymerization. Polym. Chem.
3 (11): 3112–3120.
105 Wei, X., Moad, G., Muir, B.W. et al. (2014). An arm-first approach to cleavable
Mikto-arm star polymers by RAFT polymerization. Macromol. Rapid Commun.
35 (8): 840–845.
106 Cosson, S., Danial, M., Saint-Amans, J.R., and Cooper-White, J.J. (2017).
Accelerated combinatorial high throughput star polymer synthesis via a rapid
one-pot sequential aqueous RAFT (rosa-RAFT) polymerization scheme. Macro-
mol. Rapid Commun. 38 (8): 1600780.
107 Kitiri, E.N., Varnava, C.K., Patrickios, C.S. et al. (2018). Double-networks based
on interconnected amphiphilic “in–out” star first polymer conetworks pre-
pared by RAFT polymerization. J. Polym. Sci., Part A: Polym. Chem. 56 (19):
2161–2174.
108 Ahn, N.Y. and Seo, M. (2016). Heteroarm core cross-linked star polymers
via RAFT copolymerization of styrene and bismaleimide. RSC Adv. 6 (53):
47715–47722.
109 Daniel, W.F.M., Burdyńska, J., Vatankhah-Varnoosfaderani, M. et al. (2015).
Solvent-free, supersoft and superelastic bottlebrush melts and networks. Nat.
Mater. 15: 183.
110 Levi, A.E., Lequieu, J., Horne, J.D. et al. (2019). Miktoarm stars via
grafting-through copolymerization: self-assembly and the star-to-bottlebrush
transition. Macromolecules 52 (4): 1794–1802.
111 Sheiko, S.S., Sumerlin, B.S., and Matyjaszewski, K. (2008). Cylindrical molecu-
lar brushes: synthesis, characterization, and properties. Prog. Polym. Sci. 33 (7):
759–785.
112 Lee, H.-I., Pietrasik, J., Sheiko, S.S., and Matyjaszewski, K. (2010).
Stimuli-responsive molecular brushes. Prog. Polym. Sci. 35 (1): 24–44.
113 Feng, C., Li, Y., Yang, D. et al. (2011). Well-defined graft copolymers: from
controlled synthesis to multipurpose applications. Chem. Soc. Rev. 40 (3):
1282–1295.
114 Rzayev, J. (2012). Molecular bottlebrushes: new opportunities in nanomaterials
fabrication. ACS Macro Lett. 1 (9): 1146–1149.
115 Verduzco, R., Li, X., Pesek, S.L., and Stein, G.E. (2015). Structure, function,
self-assembly, and applications of bottlebrush copolymers. Chem. Soc. Rev. 44
(8): 2405–2420.
116 Müllner, M. and Müller, A.H.E. (2016). Cylindrical polymer
brushes – anisotropic building blocks, unimolecular templates and particulate
nanocarriers. Polymer 98: 389–401.
References 977
117 Foster, J.C., Varlas, S., Couturaud, B. et al. (2019). Getting into shape: reflec-
tions on a new generation of cylindrical nanostructures’ self-assembly using
polymer building blocks. J. Am. Chem. Soc. 141 (7): 2742–2753.
118 Xie, G., Martinez, M.R., Olszewski, M. et al. (2019). Molecular bottlebrushes as
novel materials. Biomacromolecules 20 (1): 27–54.
119 Abbasi, M., Faust, L., and Wilhelm, M. (2019). Comb and bottlebrush poly-
mers with superior rheological and mechanical properties. Adv. Mater. 31 (26):
1806484.
120 Altay, E. and Rzayev, J. (2016). Synthesis of star-brush polymer architectures
from end-reactive molecular bottlebrushes. Polymer 98: 487–494.
121 Cao, X., Zhang, C., Wu, S., and An, Z. (2014). A highly efficient
macromonomer approach to core cross-linked star (CCS) polymers via one-step
RAFT emulsion polymerization. Polym. Chem. 5 (14): 4277–4284.
122 Vatankhah-Varnosfaderani, M., Keith, A.N., Cong, Y. et al. (2018).
Chameleon-like elastomers with molecularly encoded strain-adaptive stiffening
and coloration. Science 359 (6383): 1509–1513.
123 Schlüter, A.D., Halperin, A., Kröger, M. et al. (2014). Dendronized polymers:
molecular objects between conventional linear polymers and colloidal particles.
ACS Macro Lett. 3 (10): 991–998.
124 Shen, D., Xu, B., Huang, X. et al. (2018). (PtBA-co-PPEGMEMA-co-PDOMA)-
g-PPFA polymer brushes synthesized by sequential RAFT polymerization and
ATRP. Polym. Chem. 9 (20): 2821–2829.
125 Lee, D.C., Lamm, R.J., Prossnitz, A.N. et al. (2019). Dual polymerizations:
untapped potential for biomaterials. Adv. Healthc. Mater. 8 (6): 1800861.
126 Minoda, M., Shimizu, T., Miki, S., and Motoyanagi, J. (2013). Thermoresponsive
NIPAM block copolymers containing densely grafted poly(vinyl ether) brushes
synthesized by a combination of living cationic polymerization and RAFT
polymerization. J. Polym. Sci., Part A: Polym. Chem. 51 (4): 786–792.
127 Tanaka, J., Moriceau, G., Cook, A. et al. (2019). Tuning the structure, sta-
bility, and responsivity of polymeric arsenical nanoparticles using polythiol
cross-linkers. Macromolecules 52 (3): 992–1003.
128 Willcock, H. and O’Reilly, R.K. (2010). End group removal and modification of
RAFT polymers. Polym. Chem. 1 (2): 149–157.
129 Flanders, M.J. and Gramlich, W.M. (2018). Reversible-addition fragmentation
chain transfer (RAFT) mediated depolymerization of brush polymers. Polym.
Chem. 9 (17): 2328–2335.
130 Rossi, N.A.A., Zou, Y., Scott, M.D., and Kizhakkedathu, J.N. (2008). RAFT syn-
thesis of acrylic copolymers containing poly(ethylene glycol) and dioxolane
functional groups: toward well-defined aldehyde containing copolymers for
bioconjugation. Macromolecules 41 (14): 5272–5282.
131 Lejars, M., Margaillan, A., and Bressy, C. (2013). Well-defined graft copoly-
mers of tert-butyldimethylsilyl methacrylate and poly(dimethylsiloxane)
macromonomers synthesized by RAFT polymerization. Polym. Chem. 4 (11):
3282–3292.
132 Chong, J.Y.T., Keddie, D.J., Postma, A. et al. (2015). RAFT prepara-
tion and the aqueous self-assembly of amphiphilic poly(octadecyl
acrylate)-block-poly(polyethylene glycol methyl ether acrylate) copolymers.
Colloids Surf., A 470: 60–69.
133 Boursier, T., Georges, S., Mosquet, M. et al. (2016). Synthesis of
poly(N-acryloylmorpholine) macromonomers using RAFT and their copoly-
merization with methacrylic acid for the design of graft copolymer additives for
concrete. Polym. Chem. 7 (4): 917–925.
134 Maher, M.J., Schibur, H.J., and Bates, F.S. (2017). When convergent syntheses
of graft block copolymers diverge: the treachery of chemical images. J. Polym.
135 Patton, D.L. and Advincula, R.C. (2006). A versatile synthetic route to
macromonomers via RAFT polymerization. Macromolecules 39 (25): 8674–8683.
136 Li, A., Ma, J., Sun, G. et al. (2012). One-pot, facile synthesis of well-defined
molecular brush copolymers by a tandem RAFT and ROMP, “grafting-through”
strategy. J. Polym. Sci., Part A: Polym. Chem. 50 (9): 1681–1688.
137 Radzinski, S.C., Foster, J.C., and Matson, J.B. (2015). Synthesis of bottlebrush
polymers via transfer-to and grafting-through approaches using a RAFT chain
transfer agent with a ROMP-active Z-group. Polym. Chem. 6 (31): 5643–5652.
138 Pesek, S.L., Li, X., Hammouda, B. et al. (2013). Small-angle neutron scattering
analysis of bottlebrush polymers prepared via grafting-through polymerization.
139 Vandenbergh, J. and Junkers, T. (2014). Alpha and omega: importance of the
nonliving chain end in RAFT multiblock copolymerization. Macromolecules 47
(15): 5051–5059.
140 Radzinski, S.C., Foster, J.C., and Matson, J.B. (2016). Preparation of bottlebrush
polymers via a one-pot ring-opening polymerization (ROP) and ring-opening
metathesis polymerization (ROMP) grafting-through strategy. Macromol. Rapid
Commun. 37 (7): 616–621.
141 Perrier, S. (2017). 50th anniversary perspective: RAFT polymerization—a user
guide. Macromolecules 50 (19): 7433–7447.
142 Moad, G. (2017). RAFT polymerization to form stimuli-responsive polymers.
Polym. Chem. 8 (1): 177–219.
143 Michalek, L., Mundsinger, K., Barner-Kowollik, C., and Barner, L. (2019). The
long and the short of polymer grafting. Polym. Chem. 10 (1): 54–59.
144 Lanson, D., Schappacher, M., Borsali, R., and Deffieux, A. (2007). Synthesis of
(poly[chloroethyl vinyl ether]-g-polystyrene)comb-b-(poly[chloropyran ethoxy
vinyl ether]-g-polyisoprene)comb copolymers and study of hyper-branched
micelle formation in dilute solutions. Macromolecules 40 (15): 5559–5565.
145 Moriceau, G., Tanaka, J., Lester, D. et al. (2019). Influence of grafting density
and distribution on material properties using well-defined alkyl functional
poly(styrene-co-maleic anhydride) architectures synthesized by RAFT. Macro-
molecules 52 (4): 1469–1478.
References 979
146 Gan, W., Shi, Y., Jing, B. et al. (2017). Produce molecular brushes with
ultrahigh grafting density using accelerated CuAAC grafting-onto strategy.
147 Chu, Y., Li, H., Huang, H. et al. (2018). Uni-molecular nanoparticles of
poly(2-oxazoline) showing tunable thermoresponsive behaviors. J. Polym. Sci.,
Part A: Polym. Chem. 56 (2): 174–183.
148 Wu, Y., Tang, Q., Zhang, M. et al. (2018). Synthesis of bottlebrush polymers
with v-shaped side chains. Polymer 143: 190–199.
149 Quémener, D., Hellaye, M.L., Bissett, C. et al. (2008). Graft block copolymers of
propargyl methacrylate and vinyl acetate via a combination of RAFT/MADIX
and click chemistry: reaction analysis. J. Polym. Sci., Part A: Polym. Chem. 46
(1): 155–173.
150 Xiao, L., Chen, Y., and Zhang, K. (2016). Efficient metal-free “graft-
ing onto” method for bottlebrush polymers by combining RAFT and
triazolinedione–diene click reaction. Macromolecules 49 (12): 4452–4461.
151 Kerr, A., Hartlieb, M., Sanchis, J. et al. (2017). Complex multiblock bottle-brush
architectures by RAFT polymerization. Chem. Commun. 53 (87): 11901–11904.
152 Bolton, J. and Rzayev, J. (2014). Synthesis and melt self-assembly of
PS–PMMA–PLA triblock bottlebrush copolymers. Macromolecules 47 (9):
2864–2874.
153 Foster, J.C., Radzinski, S.C., and Matson, J.B. (2017). Graft polymer synthesis by
RAFT transfer-to. J. Polym. Sci., Part A: Polym. Chem. 55 (18): 2865–2876.
154 Zheng, Z., Ling, J., and Müller, A.H.E. (2014). Revival of the R-group approach:
a “CTA-shuttled” grafting from approach for well-defined cylindrical polymer
brushes via RAFT polymerization. Macromol. Rapid Commun. 35 (2): 234–241.
155 Xu, J., Shanmugam, S., Fu, C. et al. (2016). Selective photoactivation: from a
single unit monomer insertion reaction to controlled polymer architectures. J.
Am. Chem. Soc. 138 (9): 3094–3106.
156 Shanmugam, S., Cuthbert, J., Kowalewski, T. et al. (2018). Catalyst-free selective
photoactivation of RAFT polymerization: a facile route for preparation of comb-
like and bottlebrush polymers. Macromolecules 51 (19): 7776–7784.
157 Xiong, L., Zhang, H., Zhong, A. et al. (2014). Acid- and base-functionalized
core-confined bottlebrush copolymer catalysts for one-pot cascade reactions.
Chem. Commun. 50 (94): 14778–14781.
158 Wang, Y., Ren, R., Ling, J. et al. (2018). One-pot “grafting-from” synthesis of
amphiphilic bottlebrush block copolymers containing PLA and PVP side chains
via tandem ROP and RAFT polymerization. Polymer 138: 378–386.
159 Wu, W., Dai, W., Zhao, X. et al. (2018). Synthesis, self-assembly and drug
release behaviors of reduction-labile multi-responsive block miktobrush quater-
polymers with linear and V-shaped grafts. Polym. Chem. 9 (15): 1947–1960.
160 Nese, A., Li, Y., Averick, S. et al. (2012). Synthesis of amphiphilic
poly(N-vinylpyrrolidone)-b-poly(vinyl acetate) molecular bottlebrushes. ACS
Macro Lett. 1 (1): 227–231.
161 Zehm, D., Laschewsky, A., Liang, H., and Rabe, J.P. (2011). Straightforward
access to amphiphilic dual bottle brushes by combining RAFT, ATRP, and NMP
polymerization in one sequence. Macromolecules 44 (24): 9635–9641.
162 Fenyves, R., Schmutz, M., Horner, I.J. et al. (2014). Aqueous self-assembly of
Giant bottlebrush block copolymer surfactants as shape-tunable building blocks.
J. Am. Chem. Soc. 136 (21): 7762–7770.
163 Ma’Radzi, A.H., Sugihara, S., Miura, S. et al. (2014). Synthesis of thermorespon-
sive block and graft copolymers via the combination of living cationic polymer-
ization and RAFT polymerization using a vinyl ether-type RAFT agent. Polymer
55 (8): 1920–1930.
164 Sumerlin, B.S., Neugebauer, D., and Matyjaszewski, K. (2005). Initiation effi-
ciency in the synthesis of molecular brushes by grafting from via atom transfer
165 Cook, A.B. and Perrier, S. (2019). Branched and dendritic polymer architec-
tures: functional nanomaterials for therapeutic delivery. Adv. Funct. Mater. 30
(2): 1901001. https://doi.org/10.1002/adfm.201901001.
166 Kienle, R.H. and Hovey, A.G. (1929). The polyhydric alcohol-polybasic acid
reaction. I. Glycerol-phthalic anhydride. J. Am. Chem. Soc. 51 (2): 509–519.
167 Fréchet, J.M.J., Henmi, M., Gitsov, I. et al. (1995). Self-condensing vinyl poly-
merization: an approach to dendritic materials. Science 269 (5227): 1080–1083.
168 Alfurhood, J.A., Bachler, P.R., and Sumerlin, B.S. (2016). Hyperbranched poly-
mers via RAFT self-condensing vinyl polymerization. Polym. Chem. 7 (20):
3361–3369.
169 Vogt, A.P., Gondi, S.R., and Sumerlin, B.S. (2007). Hyperbranched polymers via
RAFT copolymerization of an acryloyl trithiocarbonate. Aust. J. Chem. 60 (6):
396–399.
170 Carter, S., Rimmer, S., Sturdy, A., and Webb, M. (2005). Highly branched
stimuli responsive poly[(N-isopropyl acrylamide)-co-(1,2-propandiol-3-
methacrylate)]s with protein binding functionality. Macromol. Biosci. 5 (5):
373–378.
171 Ghosh Roy, S. and De, P. (2014). Facile RAFT synthesis of side-chain amino
acids containing pH-responsive hyperbranched and star architectures. Polym.
Chem. 5 (21): 6365–6378.
172 Wei, X., Luo, Q., Sun, L. et al. (2016). Enzyme- and pH-sensitive branched
polymer–doxorubicin conjugate-based nanoscale drug delivery system for cancer
therapy. ACS Appl. Mater. Interfaces 8 (18): 11765–11778.
173 Zheng, L., Wang, Y., Zhang, X. et al. (2018). Fabrication of hyperbranched
block-statistical copolymer-based prodrug with dual sensitivities for controlled
release. Bioconjugate Chem. 29 (1): 190–202.
174 Wang, X. and Gao, H. (2017). Recent Progress on Hyperbranched Polymers
Synthesized via Radical-Based Self-Condensing Vinyl Polymerization. Polymers
9 (6): 188. https://doi.org/10.3390/polym9060188.
175 O’Brien, N., McKee, A., Sherrington, D.C. et al. (2000). Facile, versatile and cost
effective route to branched vinyl polymers. Polymer 41 (15): 6027–6031.
References 981
176 Liu, B., Kazlauciunas, A., Guthrie, J.T., and Perrier, S. (2005). One-pot hyper-
branched polymer synthesis mediated by reversible addition fragmentation
chain transfer (RAFT) polymerization. Macromolecules 38 (6): 2131–2136.
177 Liu, B., Kazlauciunas, A., Guthrie, J.T., and Perrier, S. (2005). Influence of
reaction parameters on the synthesis of hyperbranched polymers via reversible
addition fragmentation chain transfer (RAFT) polymerization. Polymer 46 (17):
6293–6299.
178 Pal, S., Brooks, W.L.A., Dobbins, D.J., and Sumerlin, B.S. (2016). Employing a
sugar-derived dimethacrylate to evaluate controlled branch growth during poly-
merization with multiolefinic compounds. Macromolecules 49 (24): 9396–9405.
179 Rosselgong, J., Armes, S.P., Barton, W.R.S., and Price, D. (2010). Synthesis
of branched methacrylic copolymers: comparison between RAFT and ATRP
and effect of varying the monomer concentration. Macromolecules 43 (5):
2145–2156.
180 Bannister, I., Billingham, N.C., Armes, S.P. et al. (2006). Development of
branching in living radical copolymerization of vinyl and divinyl monomers.
181 Koh, M.L., Konkolewicz, D., and Perrier, S. (2011). A simple route to functional
highly branched structures: RAFT homopolymerization of divinylbenzene.
182 Xu, J., Tao, L., Boyer, C. et al. (2010). Combining thio−bromo “click” chemistry
and RAFT polymerization: a powerful tool for preparing functionalized multi-
block and hyperbranched polymers. Macromolecules 43 (1): 20–24.
183 Xu, J., Tao, L., Liu, J. et al. (2009). Synthesis of functionalized and biodegrad-
able hyperbranched polymers from novel AB2 macromonomers prepared by
RAFT polymerization. Macromolecules 42 (18): 6893–6901.
184 Konkolewicz, D., Poon, C.K., Gray-Weale, A., and Perrier, S. (2011). Hyper-
branched alternating block copolymers using thiol–yne chemistry: materials
with tuneable properties. Chem. Commun. 47 (1): 239–241.
983
21
Star Polymers by RAFT Polymerization

Stephanie Allison-Logan, Fatemeh Karimi, Mitchell D. Nothling, and
Greg G. Qiao
University of Melbourne, Department of Chemical Engineering, Polymer Science Group, Parkville,
Victoria 3010, Australia
21.1 Star Polymers

Star polymers are a class of branched polymers in which three or more linear arms
extend outwards from a central core. The dense, compact nature of star polymers can
result in unique chemical, thermal, and rheological properties compared with their
linear counterparts. In addition, the unique architecture of star polymers results in
distinct core, arm, and peripheral regions that offer great versatility for customized
structures [1]. As shown in Figure 21.1, each region of the star can be altered and
optimized, enabling endless possibilities.
Star polymers can be synthesized using numerous polymerization techniques
with the most common being ring-opening polymerization (ROP), ring-opening
metathesis polymerization (ROMP), and the controlled radical polymerization
(CRP) methods atom transfer radical polymerization (ATRP), single electron
transfer living radical polymerization (SET-LRP), nitroxide-mediated living radical
polymerization (NMP), and reversible addition fragmentation deactivation chain
transfer (RAFT) polymerization.
ROP involves the ring opening of cyclic monomers such as cyclic esters and
O- and N-carboxyanhydrides (OCA and NCA, respectively) resulting in poly(esters)
from cyclic ester and OCA monomers and poly(amides) from NCA monomers.
Because of the biodegradable nature of the resulting polymers, ROP techniques are
frequently used to synthesize polymers for biomedical applications. ROP typically
requires the use of organic acids/bases or organometallic complexes to achieve fast
reaction times and/or low dispersities. Unlike CRP, ROP is not sensitive to oxygen
scavengers; however, protic contaminants such as water can initiate polymerization
and induce side reactions and even terminate reactions during NCA and OCA
ROP. In addition, incorporation of compatible side chain functionality is more
difficult and the number of commercially available monomers more limited than
for CRP. ROMP also proceeds via ring opening of cyclic monomers and results in
well-defined polymers with readily modified end groups. The development of novel
984 21 Star Polymers by RAFT Polymerization
Homopolymer Statistical Block copolymer

star copolymer star star
Compositional MW miktoarm End-functional

miktoarm star star miktoarm star
Small-compound Macromolecule core- Network core-

core-structured star structured star structured star
Core-functionalised Arm-functionalised End-functionalized

star star star
Figure 21.1 An illustration of potential star polymer structures including stars with varied
composition and sequence of arm polymer, possible miktoarm and core structures, and
different regions of functionalization.
ruthenium and molybdenum catalysts has led to a wider pool of monomers with a
greater range of functionalities; however, the presence of transition metals is often
undesirable.
CRP techniques maintain high chain-end fidelity, which ensures high conversions
and low dispersities; however, stringent oxygen-free environments are generally
required. NMP was the first type of CRP developed, however is less frequently used
because of the developments of ATRP and RAFT due to high reaction temperatures,
poor control over methacrylate and methacrylamide monomers, and comparatively
lower chain-end fidelity. Transition metal-mediated CRP including ATRP and
SET-LRP has been widely used for the synthesis of star polymers using both the
arm-first and core-first approaches. Although compatible of with a large array
of vinylic monomers and capable of conversions greater than 95%, the use of a
transition metal is required and not ideal for certain applications.
RAFT polymerization readily lends itself to the synthesis of star polymers.
Compatible with an enormous range of monomers and multiple possible synthetic
approaches, RAFT is a leading approach for star polymer synthesis. In addition, the
development of photo-mediated RAFT has eradicated the necessity of additional
initiators or catalysts. Although requiring further optimization, recent investi-
gations into the use of xanthates to control radical ROP demonstrate that RAFT
polymerization may also be used to synthesize degradable polymers.
21.2 Synthesis of Star Polymers via RAFT

Polymerization
RAFT polymerization offers exceptional control over polymer molecular weights,
dispersities, and is compatible with a wide range of monomers, making it an
efficient and widely used method for the synthesis of star polymers. The two
approaches to star polymer synthesis via RAFT polymerization are known as
the core-first and arm-first approach. The advantages, disadvantages, and major
developments for both approaches will be thoroughly discussed.
21.2.1 Core-first Approach

The core-first approach requires a multifunctional initiator from which arms can
be polymerized. Any molecule that can be functionalized with three or more RAFT
agents can serve as a core, enabling the use of a wide array of compounds and a
great amount of freedom. Cores as varied as cyclodextrins, [3] porphyrins, [4] hyper-
branched polymers, [5] metal–organic polyhedrons (MOPs), [6] metal–organic
macrocycles (MOMs), [7], and quantum dots [8] have been used for the synthesis
of star polymers, with benzene- and pentaerythritol-based cores among the most
commonly used.
When using the core-first approach, the number of arms is equal to the number
of initiating sites and is therefore known before polymerization (assuming 100% ini-
tiation). This varies greatly from the arm-first approach, where the number of arms
cannot be known until after polymerization and is not easily controlled. To achieve
star polymers with low molecular weight dispersities, all initiating sites must have
equal reactivity and 100% initiation efficiency. It is also important that the rate of
initiation is greater than the rate of propagation and that either no or minimal chain
termination occurs, both of which result in arms that contain different numbers of
repeat units. The primary advantages of the core-first approach are high yields and
facile purification, as low molecular weight monomers are easily separated from the
resulting star polymers [1].
The core-first approach does suffer from some limitations. Star arms cannot
be directly analyzed unless cleaved from the core. The synthesis of star polymers
containing more than one type of arm, known as miktoarm stars, is difficult as
different initiating groups are required, although it has been demonstrated [9, 10].
Star polymers synthesized via the core-first approach generally have a smaller
core domain and lower number of arms than star polymers synthesized using the
arm-first approach; however, the use of hyperbranched cores such as dendrimers
has somewhat alleviated these limitations.
Perhaps the most challenging aspect of the core-first approach is the synthesis
of the multifunctional core. Cores should have the same number of initiating
sites to ensure that the resulting star polymers have the same number of arms,
arm molecular weight, and total molecular weight, any of which could impact
the star properties. Purification is generally required after synthesis of the core,
inhibiting one-pot star polymer synthesis. Although the synthesis of cores is more
commonly performed through conjugation chemistries, RAFT polymerization has
been employed as a facile method of core synthesis.
Zhang et al. reported the use of self-condensing vinyl polymerization
(SCVP)-RAFT to synthesize a core using a polymerizable RAFT agent, followed by
polymerization from these RAFT agents to synthesize the star arms (Figure 21.2)
[2]. To form the hyperbranched macro-chain transfer agent (CTA) core, a RAFT
agent containing a styryl group was copolymerized with methyl acrylate or styrene.
Branching points occurred when both the styryl and trithiocarbonate groups in
one molecule participated in RAFT polymerization. A wide range of conditions
were investigated and the authors concluded that the degree of branching, end
group composition, and CTA functionality could be adjusted by altering the RAFT
monomer and comonomer ratios and reaction time. Although initial macroCTA
cores had dispersities greater than two, the authors were able to adjust conditions
to achieve cores with dispersities as low as 1.16.
Hyperbranched macroCTA cores with approximately 7, 13, or 56 functional RAFT
agents were subsequently used to polymerize styrene or tert-butyl acrylate to form
star polymers. Theoretical and observed molecular weights were similar and dis-
persities ranged from 1.21 to 1.88, indicating that controlled star polymers could be
achieved using this approach. Subsequent works using RAFT to synthesize hyper-
branched cores and subsequent polymerization of arms has further shown the ver-
satility and ease of core-first star polymerization performed using RAFT [11–13].
Although the core-first approach to star polymer synthesis is compatible with
a wide range of polymerization techniques, star polymer synthesis via RAFT
T T
S
b b T
S S
b
S b T
RAFT T
(M1)
b b T
+ [M2]0:[M1]0 > 20
R b
b
(M2)
T T
b T
(i) RAFT T
Hyperbranched poly(VBPT-co-M2) (A)

[M2]0:[M1]0 < 20
T T T
T
T T T
T
T
T T T
b b T
T T T
T (ii) RAFT
b T T
S b T
T St or tBA
T
T T T
b T
T T T
T T
T T
T
Branched poly(VBPT-co-M2) (B)
Star PSt or PtBA with a branched core
Where M2 = MMA, MA, tBA, St; S = Styryl group; b = Polymerized S group; T- = Remaining
unreacted CTA functionality in VBPT unit; T = Terminal propyltrithiocarbonate group.
Figure 21.2 Synthesis of hyperbranched cores using a styryl-RAFT monomer (M1 ) and
styrene or methyl acrylate (M2 ). Once the core synthesis was optimized, subsequent
polymerization from the core via RAFT resulted in well-defined star polymers. Source:
Reprinted with permission from Zhang et al. [2]. Copyright 2011, American Chemical
Society.
polymerization is unique because of the asymmetrical nature of RAFT agents,

which contain a Z- and R-group (Figure 21.3). Which group is conjugated to the
core has important implications for the synthesis and functionality of the star
polymer and should be considered before synthesis of the multifunctional core.
Both approaches have advantages and disadvantages, which have been extensively
studied and will be discussed [1, 14, 15].
21.2.1.1 Z-group Approach

The Z-group approach is used when the Z-group of the RAFT agent is conjugated to
the core. The R-group remains at the periphery of the star polymer while the thiocar-
bonylthio moiety remains at the core. As polymerization proceeds, a linear macro-
radical is formed away from the star polymer core. Because the propagating radical
is not attached to the star core, star–star coupling is prevented. This avoidance of
Fragmenting group Stabilizing group
S R S S
R
S Z
S S
Z S S
S S
S S
S S Z S S
R
R
Z
R
R
S
Z S S
S Z
S S S
S S
S
S S
S
Z S S
S Z
R
R
R-group approach Z-group approach
Figure 21.3 RAFT polymerization of star polymers using the core-first R- and Z-group
approaches.
star–star coupling initially made the Z-group approach the preferred method of star
polymer synthesis via the core-first approach. Termination events can still occur
when two macroradicals react, producing a low molecular weight linear byproduct
and resulting in the loss of at least one living arm from a star. However, this lin-
ear byproduct is much easier to purify from the desired star polymer than the high
molecular weight byproducts resulting from star–star coupling. The mechanism of
polymerization via the Z-group core-first approach is illustrated in Figure 21.4.
The mechanism of polymerization does lead to certain limitations. Macroradi-
cal arms must reattach to the core, which becomes more difficult as the molecular
weight of the arms and the number of arms is increased [3, 5]. The location of the
thiocarbonylthio group in the star core must also be carefully considered. The thio-
carbonylthio group is sensitive to nucleophiles and radicals, both of which can cause
destruction of the RAFT agent. With the RAFT agent located at the core, this means
that the destruction of a RAFT agent will lead to the loss of an arm. This could be
intentionally exploited if a degradable star is desired or to analyse the arms following
star polymer synthesis [16, 17]. It is important to consider before synthesis if expo-
sure to nucleophiles and radicals is likely during the intended application of the star
polymer.
21.2.1.2 R-group Approach

The R-group approach is used when the R-group of the RAFT agent is conjugated to
the core. Because of the orientation of the RAFT agent, the thiocarbonylthio group is
I S I R
S R
S S
R R m
(A)
R m S I S R Pn
m
S S
R m S R S R R
m
S S
(B)
R
R
S S
S S
S S
S S
S R
m
S
R
R
(a)
S S
I R m m R R m m R
S S
R
R
S S
S S
S S
S S
R
(b) R
R
(C)
Figure 21.4 RAFT polymerization of star polymers using the Z-group core-first approach.
Using this approach, the thiocarbonylthio moiety remains attached to the core while the
macroradical arms propagate away from the core, then reattach. The polymerization
proceeds in three phases: (A) initiation, (B) propagation, and (C) termination, and can result
in both (a) desired product and (b) products of undesired termination. Unwanted
termination can occur when macroradical arms react with each other, resulting in a linear
byproduct and stars that have dead chain ends (black circle).
S
S I S S I
Z
Z
m
(A)
S S I S S Pn
m m
Z Z
S
S S
m S Z m
Z
(B)
S
Z
S S
Z S S
S Z
S S
Z
S S Z S S
n
Z
S
Z S S
S Z
S
S
Z
(a)
m n m n m Pn m n–1
S Z S Z
S Z S S
Z S S
S S S S Z S
S S
Z S
Z
S Z
S S
Z Z
S S S
Z S
S S
S Z S S Z S S
Z S S Z S Z
S S
(b) S S S
S Z Z
Z
(C)
Figure 21.5 RAFT polymerization of star polymers using the R-group core-first approach.
In this approach, the propagating radical remains at the star periphery. The polymerization
proceeds in three phases: (A) initiation, (B) propagation, and (C) termination, and can result
in both (a) desired product and (b) products of undesired termination. Unwanted
termination reactions can result in star–star coupling and dead polymer arms that no
longer contain the thiocarbonylthio moiety.
situated at the periphery of the star and the propagating radical moves outwards as
polymerization progresses (Figure 21.5). This has important implications for pos-
sible side and termination reactions throughout the polymerization. Because the
propagating radical is at the star periphery, termination reactions between the grow-
ing arms can result in intra-star termination causing two dead arms, or inter-star
termination, also known as star–star coupling. Both inter- and intra-star termina-
tion reactions will lead to high dispersities; however, inter-star termination results
in a high molecular weight product up to twice the intended molecular weight that
can be difficult to remove.
The primary advantage of the R-group approach is that the thiocarbonylthio group
remains at the periphery of the star. RAFT agents are often coloured, resulting in
coloured products, which is often undesired. The location of the RAFT agent at the
exterior enables destruction of the RAFT agent to remove colour or to introduce
additional functionality. The conversion of RAFT agents to functional groups has
been extensively reviewed, with conversion to groups that can participate in click
reactions being the most appealing [18–20].
The Maynard group exploited the terminal RAFT groups resulting from the
R-group core-first approach to synthesize star poly(N-isopropylacrylamide)
(PNIPAAm)-lysozyme conjugates [21]. The polymerization of four-arm PNIPAAm
stars was stopped at 52% conversion to limit star–star coupling and ensure retention
of the RAFT end group. Using a mechanism previously reported by Perrier et al.
[22], the RAFT agents were reacted with a symmetrical azo-initiator containing
furan-protected maleimide groups to achieve star polymers with terminal protected
maleimide groups. Once deprotected, the enzyme lysozyme was conjugated to
the star polymer via thiol-maleimide click chemistry [21]. More recently, Wang
et al. synthesized four-arm PNIPAAm stars and converted the RAFT group to
an alkyne via one-pot aminolysis and subsequent Michael addition of propargyl
acrylate (Figure 21.6) [23]. The four-arm PNIPAAm star was then reacted with
azide-functionalized β-cyclodextrin, forming a temperature-responsive PNIPAAm
hydrogel. These examples highlight the ease with which star polymers synthesized
using the R-group approach can undergo end-group functionalization.
21.2.1.3 Developments in Synthesis

Although the R- and Z-group approaches for core-first star polymers have been well
studied, there have been few developments that have altered the way the RAFT
core-first approach is conducted since its inception. Most reactions are still carried
out using thermal initiators such as 2,2′ -azobis(2-methylpropionitrile) (AIBN) and
2,2′ -azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (VA-044). Therefore,
the recent usage of photo-mediated RAFT polymerization for the synthesis of star
polymers using the core-first approach has been a welcome and exciting develop-
ment. One mechanism for photoinduced electron or energy transfer (PET)-RAFT
polymerization involves a photoredox reaction between the thiocarbonylthio
group and a photoredox catalyst [24]. The use of a photoredox catalyst provides
temporal control over the polymerization, meaning that reactions can be stopped
and restarted at will. In addition, PET-RAFT can proceed in the presence of air,
thereby eliminating the need for degassing and stringent oxygen-free conditions
typically required for RAFT polymerizations.
The Boyer group reported the use of PET-RAFT to synthesize three- and
four-armed stars with photocatalyst zinc tetraphenylporphyrin (ZnTPP) [25]. The
star polymers were reasonably well controlled with dispersities ranging from 1.1
to 1.5 and used for screening structure–activity relationships. More recently, the
OH Cl N3
O O O
O MsCl O NaN3 O
7 DMF 7 DMSO 7
HO OH HO OH HO OH
β-CD β-CD-CI7 β-CD-(N3)7
S
OH O O
Br S S
4 O 4 O 4
PTB Star-CTA
S O
O O
S S
n nS O
O 4 O 4
O NH O NH
T-PNIPA TP-PNIPA
Figure 21.6 Synthesis of star polymers via R-group core-first approach using RAFT
polymerization. Terminal thiocarbonylthio groups were converted to alkynes, facilitating
hydrogel synthesis through click chemistry. Source: Reprinted with permission from Wang
et al. [23]. Licensed under CC by 4.0.
Boyer and Lim groups used PET-RAFT to modify lanthanide-doped upconversion

nanoparticles (UCNPs), which have unique photoluminescent properties with
potential biomedical applications [26]. UCNPs were coated with silica and func-
tionalized with RAFT agent, from which poly(oligoethylene glycol methyl ether
methacrylate) (POEGMA) was polymerized. The addition of the POEGMA shell
rendered the UNCPs water soluble without affecting the upconversion emission
spectrum of the particles.
Photo-mediated RAFT polymerization can also be performed via direct photolysis
of the RAFT agent, a method known as photoiniferter RAFT polymerization. Linear
polymers synthesized via photoiniferter RAFT polymerization have been shown
to exhibit exceptional chain-end fidelity, leading to monomer conversions greater
than 95% as well as multiblock and ultra-high molecular weight (UHMW) polymers
[27, 28]. Exploiting the high chain-end fidelity resulting from photoinferter RAFT
polymerization, the Qiao group synthesized UHMW star polymers with molecular
weights in excess of 20 MDa using the R-group core-first approach [29]. The authors
first demonstrated the controlled synthesis of poly(dimethylacrylamide) (PDMA)
star polymers from tetrafunctional trithiocarbonate (4-TTC) and xanthate (4-XAN)
cores under blue and purple light, respectively. Further experiments with the 4-XAN
core resulted in star polymers with molecular weights of 3.8 MDa, equivalent to
0.96 MDa per arm, using both purple and UV light. Finally, a modified β-cyclodextrin
core containing 21 RAFT agents was synthesized. A molecular weight of 23 MDa
was targeted, with 96% conversion achieved after 18 hours of UV irradiation for a
theoretical molecular weight of 21.9 MDa. This finding was corroborated by static
light scattering as well as gel-permeation chromatography (GPC) analysis of the
star polymer arms following their cleavage from the core. The authors reported
difficulties synthesizing star polymers when molecular weights greater than 1 MDa
per arm were targeted and attributed these difficulties to the extreme dilution of
the CTA. A summary of the UHMW PDMA star polymers synthesized is shown
in Table 21.1.
The synthesis of UHMW diblock star polymers was reported in 2019 by Dao et al.
[30]. Using a tetrafunctional CTA, the authors synthesized star polymers containing
a neutral poly(acrylamide) inner block and a negatively charged poly(acrylic acid)
outer block via the Z-group core-first approach. Size exclusion chromatograms of
the star polymers showed bimodal distributions following polymerization of the
first block and multimodal distributions following polymerization of the second
block, indicating a loss of control and termination events. Despite the large disper-
sities and multimodal distributions observed, the synthesis of UHMW block star
Table 21.1 Summary of UHMW PDMA star polymers synthesized via photoiniferter RAFT
polymerization using the R-group, core-first approach.
Number DP per Target MW [M]0 Time Conversion M n(theo) M W (SLS) RG

of arms arm (MDa) (M) (h) (%)a) (MDa)b) (MDa)c) (nm)c)
4 10 100 4 1 6 96 3.8 2.5 71.1

4d) 10 100 4 1 102 96 3.8 3.8 74.7
4 20 200 8 3 6 94 7.5 6.3 124.1
21 1 900 4 1 3.5 95 3.8 5.3 105.7
21 11 000 23 0.5 18 96 21.9 20.4 205.1
21 22 000 46 0.5 18 94 43.3 3.2 79.6
a) Conversion was determined using 1 H NMR spectroscopy.

b) Theoretical molecular weights (M n,(theo) ) were determined via monomer conversion values.
c) M W (SLS) and RG were determined by static light scattering.
d) This polymerization was performed using purple light irradiation, while all others were
irradiated with ultraviolet light. The largest reported RDRP star polymer, with M W (SLS) of
20.4 MDa, is highlighted in bold text.
Source: Adapted with permission from Allison-Logan et al. [29]. Copyright 2019, American
Chemical Society.
polymers is an exciting development in the field of polymer chemistry. In addition,

the block star polymers showed promise as polymeric flocculants, highlighting
potential applications of UHMW star polymers.
21.2.2 Arm-first Approach

The arm-first approach to star polymer synthesis requires the crosslinking of linear
arms using di- or multi-functional crosslinking or coupling agents. Unlike the
core-first approach, where the molecular weight of the core is often negligible,
the arm-first approach results in a core that is a crosslinked network and typically
represents approximately 30% of the star polymer’s total molecular weight. Stars
synthesized using the arm-first approach are often referred to as core-crosslinked
stars (CCS), distinguishing them from stars synthesized using the core-first or
grafting-onto approaches [1].
The arm-first approach offers several advantages over the core-first approach.
Most importantly, the arm-first approach does not require synthesis of a multi-
functional core, enabling one-pot synthesis. Unlike the core-first approach, the
polymer arms are easily characterized before crosslinking. The unique nature of the
core resulting from the arm-first approach lends itself to further functionalization,
including the loading of functional compounds. In addition, miktoarm star poly-
mers are more easily synthesized using the arm-first approach. There are however
some disadvantages. Although a greater number of arms can be achieved with the
arm-first approach, the number of arms can only be determined after synthesis and
controlling the number of arms and star molecular weight is difficult. Star polymers
can also be difficult to purify if not all arms are incorporated into the star polymer
because the arms are of a high molecular weight and have similar properties to the
star. Star–star coupling can also occur if the growing cores of separate stars come
into contact.
The arm-first approach via RAFT polymerization can be further divided into the
macroRAFT and macromonomer routes (Figure 21.7). The macroRAFT method,
also referred to as the macro-chain transfer agent (macroCTA) method, is most com-
mon. Following RAFT polymerization of the arm, the incorporated RAFT agent
then acts as the CTA during the crosslinking polymerization step. This method is
dependent on the presence of living RAFT agents in the polymer and achieving near
complete monomer conversion. Any dead chains will not be crosslinked and there-
fore not incorporated into the star polymer, so maintaining livingness of the RAFT
end group is essential. Following arm synthesis, crosslinker can be added directly
to the reaction mixture enabling a facile, one-pot approach to obtain well-defined
star polymers. The macroRAFT approach can also be used with arms synthesized
through alternative polymerization techniques provided a RAFT agent is incorpo-
rated into the arms before crosslinking, allowing RAFT star polymerization of arms
synthesized using other polymerization techniques.
The macromonomer route was first demonstrated by the Matyjaszewski group
using ATRP and requires an arm with a polymerizable vinyl end group [31]. A
small-molecule RAFT agent is used and the arm is incorporated into the star as
S
S Polymerization S Z + Crosslinking
+ R S Z R
MacroRAFT
(a)
S Copolymerization
+ R S Z +
Macromonomer
(b)
Figure 21.7 Synthesis of star polymers using the arm-first approach via RAFT
polymerization can be performed using the (a) macroRAFT and (b) macromonomer
approaches.
a macromonomer during polymerization. The macromonomer route allows for a

lower number of initiating sites than the macroinitiator approach, reducing the
likelihood of star–star coupling [31].
The An group used commercially available 2 kDa poly(ethylene glycol) methacry-
late (PEGMA), highlighting that synthesis of a macroRAFT agent either through
RAFT polymerization of the arm or conjugation of RAFT agent to the arm was not
required for this approach [32]. The PEGMA arm, RAFT agent, and radical ini-
tiator were soluble in phosphate buffer pH 7, while the crosslinker and optional
comonomer formed oil droplets. As polymerization proceeded, a random copolymer
of the macromonomer arm, crosslinker, and spacer comonomer (if used) was pro-
duced. This is in contrast to the macroRAFT approach where polymerization results
in a block copolymer. The resulting amphiphilic copolymers then self-assembled
with the hydrophobic portions forming the core while the PEGMA chains radiated
outwards. The authors investigated each component of the system, varying the con-
centration of phosphate buffer and macromonomer, ratio of crosslinker, presence
of comonomer, and molecular weight of the macromonomer. Most star polymers
formed showed greater than 90% arm incorporation, narrow size distributions, and
dispersities below 1.2. However, poor star formation was observed when the molec-
ular weight of the arm was increased to 4 kDa [32].
This method is ideally suited for the crosslinking of arms that were synthesized
using polymerization techniques other than RAFT. The Heise group synthesized
poly(glutamic acid) (PGA) via NCA ROP initiated by 4-vinylbenzylamine, ensur-
ing that all polymer chains contained a vinyl end group [33]. Initial star polymers
formed via RAFT polymerization were well defined with a dispersity of 1.2, although
arm incorporation was only 14%. The authors found that arm incorporation could
be increased by periodically adding more crosslinker to the reaction, although this
also led to an increase in dispersity. Despite the low arm incorporation, this work
demonstrated the versatility of RAFT polymerization for the crosslinking of star

polymers, even when the arms were prepared using other techniques.
21.2.2.1 Developments in Synthesis

The synthesis of star polymers via the arm-first approach has undergone a number
of developments in the past decade that have led to improved polymers. During the
early days of RAFT polymerization, the arm-first approach was plagued by low arm
incorporation into the star, resulting in high dispersities. Low incorporation of arms
was thought to be due to ‘dead’ chain ends that could not participate in further poly-
merization. However, major developments by the Boyer, Davis, An, and Qiao groups
have made the arm-first approach the new method of choice.
In a seminal paper by Boyer and Davis, the synthesis of well-defined star polymers
with low molecular weight dispersities and high arm incorporation were reported
using the arm-first approach by selecting poorly soluble crosslinkers [34]. Star
polymers with POEGA arms and N,N ′ -bis(acryloyl)cystamine or 1,6-hexanediol
diacrylate as a crosslinker were synthesized using N,N-dimethylformamide (DMF),
acetonitrile, and toluene as a solvent to investigate the effect of crosslinker sol-
ubility on star formation (Figure 21.8a). 1,6-Hexanediol diacrylate is soluble
in all three solvents, while N,N ′ -bis(acryloyl)cystamine is soluble in DMF and
acetonitrile but only partially soluble in toluene. POEGA arms crosslinked with
N,N ′ -bis(acryloyl)cystamine in toluene resulted in well-defined star polymers
with a dispersity of 1.12 and greater than 90% arm incorporation, a dramatic
improvement over previously reported star polymers. All other reactions resulted
in dispersities greater than 1.5, demonstrating the importance of crosslinker and
solvent choice (Figure 21.8b–e). The authors hypothesized that the improved star
formation using N,N ′ -bis(acryloyl)cystamine in toluene was a result of nanophase
separation that induced compartmentalization of the crosslinking. Further exper-
iments demonstrated that high arm incorporation and low dispersity could be
achieved using arms of varying composition and molecular weight as well as other
poorly soluble crosslinkers [34].
Applying a similar concept, the An group has developed and thoroughly
investigated the use of heterogeneous RAFT polymerization systems to develop
well-defined star polymers by emulsion and dispersion RAFT [32, 35–42]. First
reported in 2011, the An group demonstrated the synthesis of CCS polymers in
water with a solid content of 10% w/v via emulsion and dispersion polymerization
and that these star polymers stabilized emulsions during particle synthesis [35].
The versatility of the method was shown using poly(N,N ′ -dimethylacrylamide)
(PDMA), poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA), and
poly(2-methoxyethyl acrylate-co-poly(ethylene glycol) methyl ether acrylate)
(P(MEA-co-PEGA) arms. The emulsion system was conducted with spacing
monomer butyl acrylate and crosslinker poly(ethylene glycol) diacrylate (PEGDA),
while the dispersion system contained N-isopropylacrylamide (NIPAAm) and
methylene bisacrylamide (MBA) as the spacing monomer and the cross-linker,
respectively (Figure 21.9a). In all cases, a high degree of arm incorporation and
dispersities of 1.12 and below were observed from GPC analysis. Interestingly,
S O
AIBN HO S S
S S OH +
O R S n
O
(1) (2–4) R O
P1-9
O O O NH O O
n
O
AIBN
P1-9 + + Z
O OO Z
O R S1-S63
RO
H O OH O
H
N S N
S N N
H
O (C1) O OH H
Z
= (C3)
H H O O
N N
6
O (C2) O O (C4) O
(a)
(b) 10 20 30 40
(c) 10 20 30 40
10 20 30 40
(d)
10 20 30 40
(e)
Retention time (min)
Figure 21.8 (a) Synthesis of star polymers with varying arm compositions and crosslinkers
in a range of solvents to investigate the impact of crosslinker solubility on star formation.
GPC traces of star polymers obtained by RAFT, using N,N′ -bis(acryloyl)cystamine (BAC) as
the crosslinker, in (b) toluene, (c) DMF, (d) acetonitrile, and (e) arm polymer used in this
study before crosslinking. BAC is poorly soluble in toluene, leading to well-defined stars
and is soluble in DMF and acetonitrile where limited star formation was observed [34].
Source: Adapted with permission from Ferreira et al. [34]. Copyright 2011, Royal Society of
Chemistry.
O
S S O
O
S O
O N +
PDMA 3
O
O
S S COOH
S CN
O O Emulsion polymerization
CCS Polymers
PPEGMA O O
8-9
O 1–2 h, 84–94% star yield
S S NH
x + 1.06–1.12 dispersity
y NH
S NH
O O O O
O
P(MEA-co-PEGA)
O O Dispersion polymerization
x:y = 8:2 9
(a)
PDMA arm polymer PPEGMA arm polymer

PDMA CCS, dispersion PPEGMA CCS, dispersion
PDMA CCS, emulsion PPEGMA CCS, emulsion
1.0 1.0
0.8 0.8
0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0
22 24 26 28 30 32 34 36 38 20 22 24 26 28 30 32 34 36 38
Elution time (min) Elution time (min)
(b) (c)
PDMA, emulsion PDMA, dispersion
P(MEA-co-PEGA) arm polymer
PEGMA, emulsion PEGMA, dispersion
P(MEA-co-PEGA) CCS, emulsion
P(MEA-co-PEGA), emulsion
1.0 1.0
0.8 0.8
0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0
22 24 26 28 30 32 34 36 38 0 10 100
(d) Elution time (min) (e) Dh (nm)
Figure 21.9 Core-crosslinked stars synthesized using emulsion and dispersion RAFT
polymerization. (a) Monomers and crosslinkers used for emulsion and dispersion
polymerization. GPC chromatograms of (b) PDMA, (c) PPEGMA, and (d) P(MEA-co-PEGA) arm
and star polymers. (e) Dynamic light scattering chromatogram showing the hydrodynamic
radius of star polymers synthesized used emulsion and dispersion polymerization [35].
Source: Adapted with permission from Qiu et al. [35]. Copyright 2011, Royal Society of
Chemistry.
emulsion polymerization led to greater arm incorporation, higher molecular

weight, and lower dispersity than dispersion polymerization (Figure 21.9b–e).
The next major development was reported by the Qiao group when they used
photoiniferter RAFT polymerization in the synthesis of star polymers via the
arm-first approach [43]. The synthesis of linear polymers via visible light-mediated
RAFT without the use of exogenous radical sources or catalysts was first reported
in 2015 and resulted in improved livingness at monomer conversions greater than
90%, demonstrated using matrix-assisted laser desorption/ionization (MALDI)-ToF
and the one-pot synthesis of a pseudohexablock copolymer [27]. Irradiation with
blue light was shown to directly activate trithiocarbonates, eliminating the need for
additional radical sources. The improved livingness is likely due to the significantly
lower concentration of radicals present in the reaction mixture, resulting in less
termination reactions.
The highly living nature of polymers synthesized via photoiniferter RAFT made
them excellent candidates for the synthesis of star polymers. Using a two-step,
one-pot approach, McKenzie et al. synthesized linear poly(methyl acrylate)
(PMA), which was then crosslinked using ethylene glycol diacrylate (EGDA)
(Figure 21.10a). The ratio of crosslinker to arm was investigated with a ratio of
10 : 1 resulting in the best star formation. A ratio of 5 : 1 resulted in incomplete star
formation while a ratio of 15 : 1 led to a broader size distribution. The degree of
polymerization (DP) of the arm was also important in the synthesis of star polymers.
The crosslinker to arm ratio was held at 10 : 1 while PMA arms with DPs of 60, 80,
and 120 were crosslinked. GPC analysis of the stars formed from PMA DP 60 was
bimodal, with the higher molecular weight product likely the result of coupling
between two star cores because of the small arm length. A DP of 80 resulted in
well-defined star polymers with a dispersity of 1.41 and arm incorporation of 94%.
The largest arms, with DP 120, also result in well-defined stars, albeit with a slightly
higher dispersity and only 89% arm conversion. The lower conversion of DP 120
arms into the star is thought to be caused by reduced access to the core due to the
greater arm length [43].
Importantly, the RAFT chain ends were shown to be still living following star poly-
merization. An in/out star was synthesized, with monomer added to the already
formed stars. Further irradiation with blue light resulted in the polymerization of
new arms from the star core (Figure 21.10b). The number of arms in the initial star
was calculated to be 31 and the number of arms following the in/out polymerization
was found to be 60. The kinetics of monomer conversion during the in/out chain
extension were compared to a control synthesis of linear PMA, with the apparent
rate constant, indicating that the efficiency of polymerization from the core was 95%
and that the functionality of most RAFT agents was maintained [43].
In 2017, the Qiao and Kamigaito groups demonstrated the synthesis of novel
star polymers using a mechanistic transformation from cationic RAFT polymer-
ization to radical RAFT polymerization [44]. Cationic RAFT was first reported
by Kamigaito and coworkers, who demonstrated polymerization of electron-rich
vinyl ether monomers that are not readily polymerized via radical RAFT poly-
merization to obtain linear polymers with dispersities below 1.1 [45]. Synthesis of
S Monomer S Cross-linker
R
S S
Z S S Z
λ ~ 460 nm λ ~ 460 nm
S
OH O O
3S S O O
O
O
O
(a)
S
Z
S S
Monomer
λ ~ 460 nm
1.0 1.2
2nd monomer
1.0
0.8 kap = 1.76 × 10–3 min–1
DRI (GPC)
In[M]0/[M]t
0.8
0.6
0.6
0.4
0.4 Linear control
0.2 kap = 1.86 × 10–3 min–1
0.2
0.0 0.0
18 20 22 24 26 28 30 0 2 4 6 8 10 12
(b) Retention time (min) Irradiation time (hours)
Figure 21.10 Photo-mediated RAFT polymerization for the synthesis of star polymers via
the (a) arm-first approach and (b) from the resulting star core using the in/out technique.
GPC chromatograms show the RI trace of the arm, CCS polymer, and star polymer following
the in/out reaction. The apparent rate of polymerization of the second monomer compared
to the linear control indicated the efficiency of polymerization from the core was 95%.
Source: Adapted with permission from McKenzie et al. [43]. Copyright 2015, American
Chemical Society.
star polymers via cationic RAFT was demonstrated in a one-pot approach, with
linear poly(isobutyl vinyl ether) (PIBVE) prepared and then crosslinked using a
divinyl ether crosslinker. A mechanistic transformation to radical RAFT was also
possible with PIBVE arms being crosslinked using a diacrylate crosslinker. Finally,
the authors showed that a block copolymer of PIBVE and a heterobifunctional
monomer with structure vinyl ether-R-acrylate (e.g. 2-(vinyloxy)ethyl acrylate)
could be synthesized via cationic polymerization of the vinyl ether groups and
then crosslinked to form a star polymer through radical RAFT polymerization of
the pendant acrylate groups. This mechanistic switch enables the synthesis of star
polymers containing monomers not easily synthesized by cationic or radical RAFT
polymerization alone and resulted in the synthesis of well-defined star polymers
with high arm incorporation and dispersities as low as 1.18 [45].
The development of simple, rapid, high-throughput techniques to synthesize
well-defined polymers of all architectures has been an important area in recent
years. In 2017, the Cooper-White group reported the development of rapid one-pot
sequential aqueous RAFT (rosa-RAFT) for the high-throughput synthesis of star
polymers (Figure 21.11) [46]. Polymerizations of acrylate and acrylamide monomers
were performed in a water/dioxane mixture (80/20 v/v) using water-soluble thermal
CTA [monomer]:[CTA]
Monomer
DP
3 min.
100 °C
Cross-linker mCTA mixing

variation
DP
mCTA
[cross-linker]:[mCTA] mixing
3 min.
100 °C
DP
mikto- (b) (c)
[cross-linker]:[mCTA] arm star
(a)
Figure 21.11 (a) Synthesis of homopolymer and mikto-arm star polymers via high-
throughput rosa-RAFT. (b) Reactions were performed in air in 50 μL volumes (c) utilizing a
thermocycler to control each reaction step. Source: Reprinted with permission from Cosson
+ Conjugation
Arm with Multifunctional

functional end group core
Figure 21.12 The grafting-to approach requires the conjugation of arms with a functional
end group to a multifunctional core.
radical initiator VA-044. Crucially, these polymerizations did not require degassing.
Arm polymerization and crosslinking steps only required three minutes each at
100 ∘ C in a thermocycler. The high-throughput technique enabled the rapid syn-
thesis of a library of star polymers using different crosslinkers, crosslinking ratios,
and mixing of macroRAFT arms to synthesis miktoarm star polymers, marking an
important development in the synthesis of star polymers.
21.2.3 Grafting-to Approach

A third method of star polymer synthesis is known as the grafting-to approach and
involves the conjugation of arms onto a functional core (Figure 21.12). This approach
allows for excellent characterization as both the core and arm can be analyzed before
conjugation. It is important to note that although the linear arms can be synthesized
via RAFT polymerization, the actual formation of the star is a result of chemical
conjugation. Similar to end group functionalization of star polymers synthesized by
the R-group core-first approach, RAFT agents can be readily modified to functional
groups that can participate in coupling reactions.
Like the core-first approach, the number of possible arms is pre-determined. How-
ever, ensuring 100% conjugation can be difficult. Achieving quantitative conjugation
becomes more difficult as the number of arms and the molecular weight of arms
increases due to congestion at the core.
21.3 Application of Star polymers

The ease with which RAFT polymerization affords the preparation of various
star sizes, compositions, and functionalities has seen the development of a broad
array of RAFT-mediated star polymers for targeted applications. The unimolecular
structure of star polymers ensures that they maintain their structure and are
not susceptible to shear or disassembly under fluctuating or extreme conditions.
The combined tolerance of RAFT polymerization to many functional groups and
the distinct regions of star polymers facilitates the generation of core-, arm-, or
end-functionalized star polymers [1, 47]. By leveraging the unique property of star
architectures, star polymers prepared via RAFT have found application in diverse
fields, including as drug delivery and imaging contrast agents, viscosity modifiers,
emulsion stabilization, and in advanced material synthesis.
21.3.1 Star Polymers in Biomedical Applications

Controlled delivery of therapeutics is one of the most common applications for star
polymers synthesized by RAFT polymerization. Star polymers have several advan-
tages that enable them to safely transport therapeutic agents to the appropriate site
and control the rate of release. Star polymers are generally between 10 and 100 nm in
diameter, which is often considered the ideal size of nanoparticles for cancer ther-
apy. Particles greater than 10 nm avoid the removal from circulation by the renal
system experienced by smaller particles, while nanoparticles smaller than 100 nm
are thought to passively accumulate in tumours because of the irregular blood vessel
structure in tumours that results from abnormal gene expression and rapid growth.
The core–shell structure of star polymers can shield loaded therapeutics or imag-
ing agents from unwanted degradation and uptake by the body’s immune system,
resulting in increased delivery efficiency while also facilitating functionalization of
the star surface with specific targeting moieties such as peptides, antibodies, and sug-
ars, thus improving delivery to the target site or tissue. In addition, intelligent design
of star polymers can result in therapeutic release over a desired timescale or upon
exposure to a particular stimulus. Because of their advantages and versatility, star
polymers synthesized by RAFT polymerization are promising candidates for deliv-
ery of drug, gene, biomolecule, protein, and imaging agents. As with all materials
designed for biomedical applications, it is essential to ensure the star polymers and
their possible degradation products do not induce inflammatory response or toxicity
before, during, or after delivery [1, 48–50].
The Whittaker and Davis groups designed and synthesized star polymers
by RAFT polymerization for biomedical applications including the delivery of
chemotherapeutic agents, genes, imaging agents, protein inhibitors, and signalling
molecules [50]. In order to prepare star polymers which are soluble in water and the
biological environment, hydrophilic monomers such as poly(oligo(ethylene glycol)
methyl ether acrylate/methacrylate) (POEGA/MA) are most commonly used to
form the star polymer arms. Star polymers comprising POEGA/MA arms have
demonstrated reduced protein adsorption and also provide stability to star polymers
during circulation as they are not susceptible to dissociation in the same way as
self-assembled structures [51–53]. In vivo and in vitro studies have shown that the
POEGA star polymers with different molecular weights (49, 64, and 94 kDa), and
therefore hydrodynamic volumes, exhibit different pharmacokinetics and tumour
disposition behaviours, with the largest star polymers (94 kDa) displaying longer
plasma exposure and improved uptake into solid tumours [52]. The star polymers
may include stimuli-responsive functionalities such as thermoresponsive monomer
NIPAAm [54] and pH-responsive monomer 2-(dimethylamino)ethyl methacrylate
(DMAEMA) [53, 55], which were used in the arm or as a secondary monomer in the
core. These star polymers change their size when exposed to changing temperature
or pH and stimulate the release of the drug at the target site.
Star polymers for biomedical applications should be large enough to avoid removal
by the renal system, leading to improved circulation half-lives. However, star degra-
dation is desirable after cell internalization to improve therapeutic delivery or after
delivery to prevent bioaccumulation. To achieve this end, degradable crosslinkers
such as acid-labile crosslinkers [56, 57] and reduction-sensitive disulfide crosslinkers
are utilized in core structure [53, 58, 59]. These crosslinkers are readily hydrolyzed in
the acidic environment of tumour tissue or reduced by glutathione upon exposure to
the glutathione-rich intracellular environment, resulting in degradation of the core
and therefore the star polymer.
The unique structure of star polymers facilitates the functionalization of the
core, arm, or peripheral regions and can be accomplished by incorporating
functional groups into the crosslinkers, monomers, and RAFT agents used. Com-
mon functionalities include therapeutic molecules, imaging agents, and dyes.
N-hydroxysuccinimide (NHS)-functionalized RAFT agents have been used to
prepare end-functionalized star polymers [60]. Arm-functionalized star poly-
mers were synthesized by incorporating activated ester-based monomers such as
pentafluorophenyl acrylate (PFPA) [60, 61] and 4-vinylbenzyl chloride (VBC) [62]
into the arms. PFPA [60, 63] and vinyl benzaldehyde (VBA) [51, 64] have been
incorporated into cores as secondary monomers during crosslinking to generate
core-functionalized star polymers. It has also been shown that two types of func-
tional groups could be incorporated into star polymers to functionalize them with
both chemotherapeutic drug and magnetic resonance imaging (MRI) contrast agent.
Star polymers were synthesized by incorporating aldehyde-functional monomer
VBA into the core and activated-ester monomer PFPA in the arm (Figure 21.13).
The VBA and PFPA monomers were subsequently modified with chemotherapeutic
drug doxorubicin and an MRI contrast agent based on disparate reactivities of VBA
and PFPA [61].
For gene delivery applications, cationic monomers or cationizable monomers such
as 2-(dimethylamino)ethyl acrylate/methacrylate (DMAEA/MA) were incorporated
into star polymers [65–68]. These monomers form electrostatic interactions with
negatively charged genetic molecules such as DNA or RNA, resulting in complexes
called polyplexes. This electrostatic complexation protects genes from enzymatic
degradation during circulation and ensures the necessary compaction to enter to
the target cells. In addition, star polymers synthesized by RAFT polymerization have
been used for micelle and vesicle formation for drug delivery and imaging [69, 70],
bone regeneration, [71] cell sheet engineering, [72] lectin binding [72], delivery of
nitric oxide to prevent biofilm formation [72], and targeting primary human immune
cell subsets [73], demonstrating their versatility in biomedical applications.
21.3.2 Star Polymers in Other Applications

The unique properties of star polymers allow tunable interactions with other species
in solution. The compact nature of star polymers leads to significantly different
RAFT “Arm-first” First step Second step
polymerization method post-modification post-modification
O x x
NH HN O
O O O O
F F
S O NH N
O
O S O OH
F F
6-8
F N N O O O OH O O CH3
HN Gd H
O O N N
OH
OH
O O O O OH O
Figure 21.13 Schematic illustration of the synthesis of multifunctional core cross-linked star polymers functionalized with MRI contrast agent and
chemotherapeutic drug [61]. Source: Reprinted with permission from Li et al. [61]. Copyright 2015, John Wiley & Sons.
properties than linear polymers of the same molecular weight, while their flexible
arms lead to different behaviours than particles of the same size. Such interactions
can be leveraged for controlling the reactivity of these other species, leading to
altered chemical pathways and affording the preparation of advanced materials.
This section will present a selection of applications in which star polymers were
essential for improved performance.
21.3.2.1 Emulsion Stabilization

Since reporting the synthesis of core-crosslinked star (CCS) polymers via emulsion
and dispersion polymerization in 2011 [35], An and coworkers have pioneered the
use of CCS polymers as emulsion stabilizers [39, 40, 42, 74, 75]. Emulsion systems
have wide industrial relevance, including in food, cosmetics, pharmaceuticals,
coatings, oil recovery, and chemical processing. Qiu et al. demonstrated the use of
a fluorescein-tagged PDMA CCS that adsorbed to the interface of a toluene/water
emulsion with excess PDMA stars remaining the aqueous phase, shown in
Figure 21.14a, and Nile red-stained toluene droplets shown in Figure 21.14b. Stabi-
lized emulsions were used as templates for the synthesis of spherical polystyrene
particles inside the oil droplets. Following solvent evaporation, aggregation of
PDMA stars around the particles (Figure 21.14c) and Nile red-stained poly(styrene)
particles were observed (Figure 21.14d).
Exploiting the versatility of RAFT polymerization, the An group developed
reversible emulsification/demulsification systems readily triggered by external
stimuli, including heat/salt/pH through targeted interactions between stars and
between star arms and solvents (Figure 21.15) [39, 40, 42, 74]. While previous work
had been carried out using amphiphilic star polymers to stabilize emulsions by
having them act as surfactants, An and coworkers focused on CCS polymers with
entirely hydrophilic arms and the structural properties of star polymers that may
cause this stabilizing behaviour. Star polymers are similar in size to particulate
(a) (b) Figure 21.14 Confocal images of

water/toluene (60/40 v/v%) emulsions
containing (a) 0.2 wt% fluorescein-
tagged PDMA stars and (b) Nile red
stained toluene demonstrating the
emulsion stabilizing activity of the
PDMA stars. Following solvent
evaporation, (c) PDMA stars at particle
surface and (d) particles synthesized
using emulsion templating. Scale bar
(c) (d)
is 20 μm [35]. Source: Adapted with
permission from Qiu et al. [35].
Copyright 2011, the Royal Society of
Chemistry.
Temperature
(salt)
Dodecane
Re-emulsify
Aqueous
x y
O O O O
O O 9
Figure 21.15 High internal phase emulsion (HIPE) stabilized by poly(MEAx -co-PEGAy ) star
co-polymers exhibit on-demand demulsification triggered by salt and temperature [42].
Source: Adapted with permission from Chen et al. [42]. Copyright 2014, Royal Society of
Chemistry.
emulsifiers but display greater flexibility, which Chen et al. hypothesized would
allow the CCS polymers to adopt favourable configurations once adsorbed onto the
surface and aid their residence at the surface [39].
Star polymers have also been recently used as dispersants of multiwalled
carbon nanotubes (MWNTs) in aqueous and acetone solutions [76]. Gao et al.
reported the synthesis of an amphiphilic ‘octopus’ star polymer with a RAFT
agent-functionalized silsesquioxane cage using the core-first approach. Star
polymers were shown to produce more stable MWNT dispersions than linear
polymers, which the authors suggested was due to hydrophobic core anchoring to
the nanotube surface while the hydrophilic arms extended outwards and reduced
the hydrophobic area of the MWNT surface (Figure 21.16) [76].
21.3.2.2 Advanced Materials

Numerous applications have been reported in which use of star polymers resulted
in improved properties in comparison to linear polymers. Hendrich and Vana
synthesized linear and star-shaped polymers that underwent redistribution of
copolymer blocks because of the incorporation of bifunctional RAFT agents [77].
Tensile testing demonstrated that inclusion of as little as 5 mol% star polymer led to
higher ultimate strength and material toughness compared to films of pure linear
multiblock polymers. Zheng et al. reported improved resolution using a novel
star polymer photoresist for krypton fluoride (KrF) photolithography [78]. Star
copolymers were synthesized from a tetra-RAFT functionalized pentaerythritol core
S O
S S NH
m
O O O R1
O Si Si
O
R1 Si O O Si R1 O
N
O R1 O
O Si O Si R1
O
R1 Si O Si
R1 Sonication
(SQ-DMAEMA)
S O
R1: mS S N
H
O O
Figure 21.16 Star polymers with POSS core and hydrophilic arms stabilized MWNTs in aqueous solvent [76]. Source: Adapted with permission from Gao
et al. [76]. Copyright 2016, Royal Society of Chemistry.
using tert-butyl acrylate and p-acetoxystyrene as monomers. Use of star copolymers

results in a pattern resolution of 200 nm, demonstrating greater resolution than
analogous linear photoresists.
Star polymers have also shown superior properties as single-ion conduction
polymer electrolytes (SCPE), which are valued for their potential use in energy
storage applications [10]. Miktoarm star polymers were composed of a polyhedral
oligomeric silsesquioxane (POSS) core and poly(ethylene glycol) (PEG) and lithium
poly([styrene-4-sulfonyltrifluoromethyl-sulfonyl] imide) (PSTF-Li) arms. The
lithium-ion conducting stars demonstrated high thermal stability and tunable
dc-conductivity. The improved thermal stability of the star polymer in comparison
to a linear analogue was thought to be a result of the restricted motion of the star
polymer, which is less sensitive to heat. PEG-b-PSTF linear copolymers were found
to have greater dc-conductivity than the star polymer because of the star’s higher T g
value; however, the addition of more PEG arms led to significantly increased conduc-
tivity, highlighting the tunability of star polymer composition and performance [10].
Star polymers can also be used in situations where the use of linear polymers is not
possible. Lin and coworkers synthesized degradable star polymers through a combi-
nation of ROP and RAFT polymerization [79]. ROP of ε-caprolactone was performed
from a β-cyclodextrin core and R-group of RAFT agents were conjugated to the
resulting terminal alcohol groups. RAFT polymerization of 4-chloromethylstyrene
was performed, followed by azide-functionalization by reacting sodium azide
with the chlorine groups. The star polymers were irradiated with UV under dilute
conditions to crosslink the azide groups, resulting in uniform nanoparticles with a
crosslinked shell (Figure 21.17). The authors were able to tailor the nanoparticle size
PCL
P(S-N3)
UV crosslink
Polymer template Core-shell nanoparticles
Figure 21.17 Star polymers with degradable inner block and crosslinkable shell were
synthesized using ROP and subsequent RAFT polymerization. Crosslinking of outer block
and degradation of polyester block resulted in the formation of hollow nanoparticles.
Source: Reprinted with permission from Feng et al. [76]. Copyright 2014, American
Chemical Society.
and shell thickness by altering the size of each block and could control the density
of shell crosslinking by varying the duration of UV irradiation. Finally, degradation
of the poly(caprolactone) core was possible under acidic conditions [79].
21.4 Conclusion
Star polymers are highly valued because of their unique architecture and physical
properties. Although star polymers can be synthesized using a variety of poly-
merization techniques, RAFT polymerization provides excellent control and a
greater degree of tunability and functionalization than most. The multiple synthetic
approaches available facilitate the facile synthesis of star polymers, with varied arm
and core compositions readily produced.
Continued development of RAFT polymerization, in particular novel mecha-
nisms of initiation and RAFT agents offering improved control over a wider range of
monomers, will result in more controlled and more complex star polymers opening
up new materials and applications. As greater spatial and temporal control develops
along with reduced dependence on oxygen-free environments, the application of
star polymers synthesized via RAFT polymerization will continue to expand and
transition towards industrial use.
References
1 Ren, J.M., McKenzie, T.G., Fu, Q. et al. (2016). Star polymers. Chem. Rev. 116
(12): 6743–6836.
2 Zhang, C., Zhou, Y., Liu, Q. et al. (2011). Facile synthesis of hyperbranched
and star-shaped polymers by RAFT polymerization based on a polymerizable
trithiocarbonate. Macromolecules 44 (7): 2034–2049.
3 Stenzel, M.H. and Davis, T.P. (2002). Star polymer synthesis using trithio-
carbonate functional ?-cyclodextrin cores (reversible addition-fragmentation
chain-transfer polymerization). J. Polym. Sci. A Polym. Chem. 40 (24):
4498–4512.
4 Rodriguez, K.J., Hanlon, A.M., Lyon, C.K. et al. (2016). Porphyrin-cored polymer
nanoparticles: macromolecular models for Heme iron coordination. Inorg. Chem.
55 (19): 9493–9496.
5 Huang, J., Wan, D., and Huang, J. (2006). Polymerization of ethyl acrylate using
hyperbranched polyglycerol with multi-RAFT groups as chain transfer agent.
J. Appl. Polym. Sci. 100 (3): 2203–2209.
6 Hosono, N., Gochomori, M., Matsuda, R. et al. (2016). Metal–organic polyhedral
core as a versatile scaffold for divergent and convergent star polymer synthesis.
J. Am. Chem. Soc. 138 (20): 6525–6531.
7 Ji, T., Xia, L., Zheng, W. et al. (2019). Porphyrin-functionalized coordination star
polymers and their potential applications in photodynamic therapy. Polym. Chem.
10 (45): 6116–6121.
References 1011
8 Dilag, J., Kobus, H., and Ellis, A.V. (2013). CdS/polymer nanocomposites
synthesized via surface initiated RAFT polymerization for the fluorescent detec-
tion of latent fingermarks. Forensic Sci. Int. 228 (1–3): 105–114.
9 Ranganathan, K., Deng, R., Kainthan, R.K. et al. (2008). Synthesis of thermore-
sponsive mixed arm star polymers by combination of RAFT and ATRP from
a multifunctional core and its self-assembly in water. Macromolecules 41 (12):
4226–4234.
10 Cao, P.-F., Wojnarowska, Z., Hong, T. et al. (2017). A star-shaped single
lithium-ion conducting copolymer by grafting a POSS nanoparticle. Polymer
124: 117–127.
11 Kitiri, E.N., Patrickios, C.S., Voutouri, C. et al. (2017). Double-networks based on
pH-responsive, amphiphilic “core-first” star first polymer conetworks prepared by
sequential RAFT polymerization. Polym. Chem. 8 (1): 245–259.
12 Haldar, U., Roy, S.G., and De, P. (2016). POSS tethered hybrid “inimer” derived
hyperbranched and star-shaped polymers via SCVP-RAFT technique. Polymer
97: 113–121.
13 Roy, S.G. and De, P. (2014). Facile RAFT synthesis of side-chain amino acids
containing pH-responsive hyperbranched and star architectures. Polym. Chem.
5 (21): 6365–6378.
14 Barner-Kowollik, C., Davis, T.P., and Stenzel, M.H. (2006). Synthesis of star
polymers using RAFT polymerization: what is possible? Aust. J. Chem. 59 (10):
719–727.
15 Mayadunne, R.T., Jeffery, J., Moad, G., and Rizzardo, E. (2003). Living free radi-
cal polymerization with reversible addition−fragmentation chain transfer (RAFT
polymerization): approaches to star polymers. Macromolecules 36 (5): 1505–1513.
16 Boschmann, D., Edam, R., Schoenmakers, P.J., and Vana, P. (2009). Charac-
terization of Z-RAFT star polymerization of butyl acrylate by size-exclusion
chromatography. Macromol. Symp. 275-276 (1): 184–196.
17 Wan, D., Yang, Z., Pu, H. et al. (2009). Xanthate-mediated polymerization of
styrene on hyperbranched polyethylenimine: synthesis, characterization, and
guest-encapsulating property. J. Appl. Polym. Sci. 113 (6): 3702–3709.
18 Moad, G., Rizzardo, E., and Thang, S.H. (2011). End-functional polymers, thio-
carbonylthio group removal/transformation and reversible addition–fragmen-
tation–chain transfer (RAFT) polymerization. Polym. Int. 60 (1): 9–25.
19 Harvison, M.A. and Lowe, A.B. (2011). Combining RAFT radical polymeriza-
tion and click/highly efficient coupling chemistries: a powerful strategy for the
preparation of novel materials. Macromol. Rapid Commun. 32 (11): 779–800.
20 Roth, P.J., Boyer, C., Lowe, A.B., and Davis, T.P. (2011). RAFT polymeriza-
tion and thiol chemistry: a complementary pairing for implementing modern
macromolecular design. Macromol. Rapid Commun. 32 (15): 1123–1143.
21 Tao, L., Kaddis, C.S., Loo, R.R. et al. (2009). Synthesis of Maleimide-end
functionalized star polymers and multimeric protein-polymer conjugates. Macro-
molecules 42 (21): 8028–8033.
22 Perrier, S., Takolpuckdee, P., and Mars, C.A. (2005). Reversible addition–
fragmentation chain transfer polymerization: end group modification for
functionalized polymers and chain transfer agent recovery. Macromolecules 38

(6): 2033–2036.
23 Wang, J., Zhu, Z., Jin, X. et al. (2016). Preparation of well-defined
propargyl-terminated tetra-arm poly(N-isopropylacrylamide)s and their click
hydrogels crosslinked with β-cyclodextrin. Polymers 8 (4): 93.
25 Gormley, A.J., Yeow, J., Ng, G. et al. (2018). An oxygen-tolerant PET-RAFT poly-
merization for screening structure-activity relationships. Angew. Chem. Int. Ed.
57 (6): 1557–1562.
26 Bagheri, A., Arandiyan, H., Adnan, N.N.M. et al. (2017). Controlled direct
growth of polymer shell on upconversion nanoparticle surface via visible light
regulated polymerization. Macromolecules 50 (18): 7137–7147.
27 McKenzie, T.G., Fu, Q., Wong, E.H. et al. (2015). Visible light mediated con-
Chem 2 (1): 93–101.
29 Allison-Logan, S., Karimi, F., Sun, Y. et al. (2019). Highly living stars via
Core-first photo-RAFT polymerization: exploitation for ultra-high molecular
weight star synthesis. ACS Macro Lett. 8 (10): 1291–1295.
30 Dao, V.H., Cameron, N.R., and Saito, K. (2019). Synthesis of UHMW star-shaped
AB block copolymers and their flocculation efficiency in high-ionic-strength
environments. Macromolecules 52 (20): 7613–7624.
31 Gao, H., Ohno, S., and Matyjaszewski, K. (2006). Low polydispersity star poly-
mers via cross-linking macromonomers by ATRP. J. Am. Chem. Soc. 128 (47):
15111–15113.
32 Cao, X., Zhang, C., Wu, S., and An, Z. (2014). A highly efficient macromonomer
approach to core cross-linked star (CCS) polymers via one-step RAFT emulsion
polymerization. Polym. Chem. 5 (14).
33 Audouin, F., Knoop, R.J.I., Huang, J., and Heise, A. (2010). Star polymers by
cross-linking of linear poly(benzyl-L-glutamate) macromonomers via free-radical
and RAFT polymerization. A simple route toward peptide-stabilized nanoparti-
cles. J. Polym. Sci. A Polym. Chem. 48 (20): 4602–4610.
34 Ferreira, J., Syrett, J., Whittaker, M. et al. (2011). Optimizing the generation of
narrow polydispersity ‘arm-first’ star polymers made using RAFT polymerization.
Polym. Chem. 2 (8).
35 Qiu, Q., Liu, G., and An, Z. (2011). Efficient and versatile synthesis of star poly-
mers in water and their use as emulsifiers. ChemComm 47 (47): 12685–12687.
36 Shen, W., Chang, Y., Liu, G. et al. (2011). Biocompatible, antifouling, and Ther-
mosensitive Core−Shell Nanogels synthesized by RAFT aqueous dispersion
References 1013
37 Shi, X., Zhou, W., Qiu, Q., and An, Z. (2012). Amphiphilic heteroarm star poly-
mer synthesized by RAFT dispersion polymerization in water/ethanol solution.
ChemComm 48 (59).
38 Zhang, C., Miao, M., Cao, X., and An, Z. (2012). One-pot RAFT synthesis of core
cross-linked star polymers of polyPEGMA in water by sequential homogeneous
and heterogeneous polymerizations. Polym. Chem. 3 (9).
39 Chen, Q., Cao, X., Liu, H. et al. (2013). pH-responsive high internal phase emul-
sions stabilized by core cross-linked star (CCS) polymers. Polym. Chem. 4 (15).
40 Shi, X., Miao, M., and An, Z. (2013). Core cross-linked star (CCS) polymers with
tunable polarity: synthesis by RAFT dispersion polymerization, self-assembly and
emulsification. Polym. Chem. 4 (6).
41 Zhou, W., Yu, W., and An, Z. (2013). RAFT emulsion polymerization of styrene
mediated by core cross-linked star (CCS) polymers. Polym. Chem. 4 (6).
42 Chen, Q., Xu, Y., Cao, X. et al. (2014). Core cross-linked star (CCS) polymers
with temperature and salt dual responsiveness: synthesis, formation of high
internal phase emulsions (HIPEs) and triggered demulsification. Polym. Chem.
5 (1): 175–185.
43 McKenzie, T.G., Wong, E.H.H., Fu, Q. et al. (2015). Controlled formation of star
polymer nanoparticles via visible light photopolymerization. ACS Macro Lett.
4 (9): 1012–1016.
44 Uchiyama, M., Satoh, K., McKenzie, T.G. et al. (2017). Diverse approaches to star
polymers via cationic and radical RAFT cross-linking reactions using mechanis-
tic transformation. Polym. Chem. 8 (38): 5972–5981.
ization using ppm concentrations of organic acid. Angew. Chem. Int. Ed. 54 (6):
1924–1928.
46 Cosson, S., Danial, M., Saint-Amans, J.R., and Cooper-White, J.J. (2017). Accel-
erated combinatorial high throughput star polymer synthesis via a rapid one-pot
sequential aqueous RAFT (rosa-RAFT) polymerization scheme. Macromol. Rapid
Commun. 38 (8).
47 Förster, N., Schmidt, S., and Vana, P. (2015). Tailoring confinement: nano-carrier
synthesis via Z-RAFT star polymerization. Polymers 7 (4): 695–716.
48 Uhrich, K.E., Cannizzaro, S.M., Langer, R.S., and Shakesheff, K.M. (1999). Poly-
meric systems for controlled drug release. Chem. Rev. 99 (11): 3181–3198.
49 Moad, G., Rizzardo, E., and Thang, S.H. (2013). RAFT polymerization and some
of its applications. Chem. Asian J. 8 (8): 1634–1644.
50 Chung, J.J., Fujita, Y., Li, S. et al. (2017). Biodegradable inorganic-organic
hybrids of methacrylate star polymers for bone regeneration. Acta Biomater.
54: 411–418.
51 Liu, J., Duong, H., Whittaker, M.R. et al. (2012). Synthesis of functional core,
star polymers via RAFT polymerization for drug delivery applications. Macromol.
Rapid Commun. 33 (9): 760–766.
52 Khor, S.Y., Hu, J., McLeod, V.M. et al. (2015). Molecular weight (hydrodynamic
volume) dictates the systemic pharmacokinetics and tumour disposition of
PolyPEG star polymers. Nanomedicine 11 (8): 2099–2108.
53 Wang, K., Peng, H., Thurecht, K.J. et al. (2014). Biodegradable core crosslinked
star polymer nanoparticles as 19 F MRI contrast agents for selective imaging.
Polym. Chem. 5 (5): 1760–1771.
54 Ghamkhari, A., Sarvari, R., Ghorbani, M., and Hamishehkar, H. (2018). Novel
thermoresponsive star-liked nanomicelles for targeting of anticancer agent. Eur.
Polym. J. 107: 143–154.
55 Wang, K., Peng, H., Thurecht, K.J. et al. (2013). pH-responsive star polymer
nanoparticles: potential 19 F MRI contrast agents for tumour-selective imaging.
Polym. Chem. 4 (16): 4480–4489.
56 Wiltshire, J.T. and Qiao, G.G. (2007). Recent advances in star polymer design:
degradability and the potential for drug delivery. Aust. J. Chem. 60 (10): 699–705.
57 Gibson, T.J., Smyth, P., Semsarilar, M. et al. (2020). Star polymers with
acid-labile diacetal-based cores synthesized by aqueous RAFT polymerization
for intracellular DNA delivery. Polym. Chem. 11 (2): 344–357.
58 Wei, X., Gunatillake, P.A., Moad, G. et al. (2014). Synthesis of cleavable
multi-functional mikto-arm star polymer by RAFT polymerization: example
of an anti-cancer drug 7-ethyl-10-hydroxycamptothecin (SN-38) as functional
moiety. Sci. China Chem. 57 (7): 995–1001.
59 Chen, C., Guo, X., Du, J. et al. (2019). Synthesis of multifunctional miktoarm
star polymers via an RGD peptide-based RAFT agent. Polym. Chem. 10 (2):
228–234.
60 Li, Y., Laurent, S., Esser, L. et al. (2014). The precise molecular location of
gadolinium atoms has a significant influence on the efficacy of nanoparticulate
MRI positive contrast agents. Polym. Chem. 5 (7): 2592–2601.
61 Li, Y., Duong, H.T., Laurent, S. et al. (2015). Nanoparticles based on star poly-
mers as theranostic vectors: endosomal-triggered drug release combined with
MRI sensitivity. Adv. Healthc. Mater. 4 (1): 148–156.
62 Esser, L., Lengkeek, N.A., Moffat, B.A. et al. (2018). A tunable one-pot three-
component synthesis of an 125 I and Gd-labelled star polymer nanoparticle for
hybrid imaging with MRI and nuclear medicine. Polym. Chem. 9 (25): 3528–3535.
63 Li, Y., Beija, M., Laurent, S. et al. (2012). Macromolecular ligands for gadolinium
MRI contrast agents. Macromolecules 45 (10): 4196–4204.
64 Kim, S.J., Ramsey, D.M., Boyer, C. et al. (2013). Effectively delivering a unique
Hsp90 inhibitor using star polymers. ACS Med. Chem. Lett. 4 (10): 915–920.
65 Boyer, C., Teo, J., Phillips, P. et al. (2013). Effective delivery of siRNA into cancer
cells and tumors using well-defined biodegradable cationic star polymers. Mol.
Pharm. 10 (6): 2435–2444.
66 Dearnley, M., Reynolds, N.P., Cass, P. et al. (2016). Comparing gene silencing
and physiochemical properties in siRNA bound cationic star-polymer complexes.
67 Teo, J., McCarroll, J.A., Boyer, C. et al. (2016). A rationally optimized nanopar-
ticle system for the delivery of RNA interference therapeutics into pancreatic
tumors in vivo. Biomacromolecules 17 (7): 2337–2351.
References 1015
68 Liao, X., Walden, G., Falcon, N.D. et al. (2017). A direct comparison of linear
and star-shaped poly(dimethylaminoethyl acrylate) polymers for polyplexation
with DNA and cytotoxicity in cultured cell lines. Eur. Polym. J. 87: 458–467.
69 Hira, S.K., Ramesh, K., Gupta, U. et al. (2015). Methotrexate-loaded four-arm
star amphiphilic block copolymer elicits CD8+ T cell response against a highly
aggressive and metastatic experimental lymphoma. ACS Appl. Mater. Interfaces
7 (36): 20021–20033.
70 Pei, D., Li, Y., Huang, Q. et al. (2015). Quantum dots encapsulated glycopolymer
vesicles: synthesis, lectin recognition and photoluminescent properties. Colloid.
Surface. B 127: 130–136.
71 Chung, J.J., Li, S., Stevens, M.M. et al. (2016). Tailoring mechanical properties of
sol–gel hybrids for bone regeneration through polymer structure. Chem. Mater.
28 (17): 6127–6135.
72 Sudo, Y., Kawai, R., Sakai, H. et al. (2018). Star-shaped thermoresponsive poly-
mers with various functional groups for cell sheet engineering. Langmuir 34 (2):
653–662.
73 Glass, J.J., Li, Y., De Rose, R. et al. (2017). Thiol-reactive star polymers display
enhanced association with distinct human blood components. ACS Appl. Mater.
Interfaces 9 (14): 12182–12194.
74 Chen, Q., Deng, X., and An, Z. (2014). pH-induced inversion of water-in-oil
emulsions to oil-in-water high internal phase emulsions (HIPEs) using Core
cross-linked star (CCS) polymer as interfacial stabilizer. Macromol. Rapid Com-
mun. 35 (12): 1148–1152.
75 Ma, K. and An, Z. (2016). Enzymatically crosslinked emulsion gels using
star-polymer stabilizers. Macromol. Rapid Commun. 37 (19): 1593–1597.
76 Gao, S., Yu, Z., Xu, K. et al. (2016). Silsesquioxane-cored star amphiphilic poly-
mer as an efficient dispersant for multi-walled carbon nanotubes. RSC Adv.
6 (36): 30401–30404.
77 Hendrich, M. and Vana, P. (2017). Tuning the mechanical properties of multi-
block copolymers generated by Polyfunctional RAFT agents. Macromol. Mater.
Eng. 302 (6): 1700018.
78 Zheng, X., Ji, C., Liu, J. et al. (2018). Novel star polymers as chemically ampli-
fied positive-tone photoresists for KrF lithography applications. Ind. Eng. Chem.
57 (19): 6790–6796.
79 Feng, C., Pang, X., He, Y. et al. (2014). Robust route to unimolecular core–shell
and hollow polymer nanoparticles. Chem. Mater. 26 (20): 6058–6067.
1017
22
Surface and Particle Modification via RAFT Polymerization:

An Update
Julia Pribyl 1,2 and Brian C. Benicewicz 1
1
University of South Carolina, Department of Chemistry and Biochemistry, Columbia, SC, 29201, USA
2
United States Naval Academy, Chemistry Department, Annapolis, MD 21402, USA
22.1 Introduction
The past decade has seen tremendous utility of reversible addition-fragmentation

chain transfer (RAFT) polymerization to synthesize populations of polymers
attached to surfaces (informally termed ‘brushes’). To date, many common RAFT
agents are commercially available or easily synthesized, leading to their ubiquity in
the synthesis of polymer brushes. The resulting polymer-grafted hybrid materials
exhibit unique properties and are often prepared with exquisite molecular-scale
control. Conveniently, RAFT agents often absorb strongly in the UV-visible region,
making spectroscopic characterization of RAFT agent content simple in many
cases. Ease of characterization and the versatility of RAFT as a polymerization
technique have led to rich development of polymer-grafted surfaces made using
RAFT chemistry.
The physical properties of polymer-grafted surfaces are fundamentally dictated by
the surface density of grafted chains (graft density, σ). On flat surfaces, brush regimes
range from ‘pancake’ conformation at low graft densities to a dense ‘brush’ at high
graft densities (Figure 22.1) [2]. Early simulation work done by Alexander [3] and
de Gennes [4] predicted that low to intermediate brush densities on a flat surface
adhered to a linear dependence of brush height as a function of degree of polymer-
ization (N) for low to intermediate brush densities. Somewhat richer behaviour was
predicted and experimentally measured for brushes grafted from a curved surface
[1]. In short, dilute and semi-dilute polymer brushes (SDPBs) adopt a coiled ‘mush-
room’ conformation, but as the graft density increases, steric repulsions between
chains force chain stretching at the surface. For polymers of sufficient N, a transition
to a more coiled SDPB occurs because of the increased volume at a farther radial dis-
tance from the particle surface. The ability to control these brush parameters (𝜎,N)
is crucial for obtaining the desired properties of polymer-grafted materials. RAFT
chemistry offers the control needed to obtain predictable N, and various grafting
strategies discussed below allow for control of graft density.
1018 22 Surface and Particle Modification via RAFT Polymerization: An Update
(a)
SDPB
SDPB
Mushroom
CPB rc
(b) Increasing graft density (σ)
Figure 22.1 Brush regimes on flat surfaces (a); Brush conformations on curved surfaces
(b) (SDPD = semi-dilute polymer brush, CPB = concentrated polymer brush). Source:
Reprinted with permission from Dukes et al. [1]. Copyright 2010, American Chemical Society.
(a)
(b)
(c)
(d)
Scheme 22.1 Common polymer grafting strategies: (a) physisorption, (b) grafting-to, (c)
grafting-from, and (d) grafting-through.
The method of polymer attachment largely dictates the resulting brush density.
Scheme 22.1 illustrates the four most commonly used polymer attachment meth-
ods, each having its own benefits and drawbacks. Physisorption is achieved through
an attractive (non-covalent) physical association between a portion of a polymer
chain and a surface (Scheme 22.1a). Grafting-to is similar in that a polymer chain
must diffuse to a surface, but it is then attached through a covalent chemical linkage
(Scheme 22.1a). Both these grafting strategies have the advantage of achieving a poly-
mer brush in as little as one synthetic step, but physisorbed chains easily desorb from
the surface. Only low graft densities can be achieved with these methods because
surface-associated chains sterically limit additional polymer chains from diffusing
to the surface. Higher graft densities can be achieved using a grafting-from approach
(Scheme 22.1c), where polymer chains are grown from a tethered initiating group. In
grafting-through approach (Scheme 22.1d), the polymerization is not initiated at the
surface, but polymerizable functional groups on the surface are quickly incorporated
into the growing polymer, resulting in a tethered chain (although not always at the
chain end). In surface-initiated RAFT (SI-RAFT) systems, grafting-from is the dom-
inant approach because of the degree of control and broader range of graft densities
that can be obtained.
In ‘grafting-from’ SI-RAFT syntheses, three specific attachment chemistries exist,
of which generalized structures are shown in Figure 22.2. By simply attaching a rad-
ical initiator to the surface (Figure 22.2a) [5], polymer chains are initiated from the
surface and mediated by a RAFT agent (also termed chain transfer agent, CTA) in
solution. Although it is simple to control the molecular weight (MW) of the grafted
chains by varying the [monomer] : [RAFT] ratio, this approach results in a rela-
tively high fraction of ungrafted chains. More commonly, the RAFT agent is attached
to the surface from either the R-group (Figure 22.2b) [6] or the radical-stabilizing
Z-group (Figure 22.2c) [7]. In these instances, a small amount of free initiator in
solution starts the polymerization, and the surface-tethered RAFT agent mediates
the growing chains from the surface. In general, the majority of polymer chains
end up grafted to the surface using an R- or Z-RAFT attachment, often the desired
result when preparing polymer-grafted surfaces. R-attachment is the most popular
technique because it is more convenient to perform post-polymerization modifica-
tions with the chain transfer functionality at the chain end rather than near the
surface.
The general synthetic strategies to prepare polymer-grafted surfaces using RAFT
polymerization have been laid out here in a general form to to facilitate the dis-
cussion in this chapter. Excellent and comprehensive reviews of specific synthetic
SI-RAFT methods have been discussed by authors of previous reviews [2, 8–10], so
they will not be discussed in-depth here. Rather, the focus of this chapter will be to
highlight unique and advanced polymer-grafted materials developed over approxi-
mately the past decade made possible by the versatility and macromolecular control
exhibited by RAFT chemistry.
Figure 22.2 RAFT attachment S

strategies: (a) surface-tethered radical S Z
I R C C R
initiator, (b) R-group attachment, and (c) I Z S
S
Z-group attachment.
(a) (b) (c)
22.2 Complex Brush Architectures

Almost immediately after the first examples of well-controlled functionalization of
surfaces with polymer brushes via RAFT polymerization and other methods were
published, attempts to model and experimentally create complex brush architectures
and spatially patterned surfaces were commenced. Glotzer and coworkers devel-
oped some of the first theoretical models of shaped particles with attractive polymer
patches assembling to form colloidal crystals, and many other interestingly shaped
particles with patches of grafted polymer were proposed [11, 12]. Many of the pro-
posed structures are still inaccessible with ‘bottom-up’ synthetic techniques either
because of the challenge of creating the shaped nanoparticles or designing robust
attachment chemistry that is spatially controlled. Many advances in preparing com-
plex brushes on flat or particle surfaces are owed to the control and versatility offered
by RAFT chemistry.
Figure 22.3 summarizes some of the advanced brush architectures that have been
synthesized using SI-RAFT. Bimodal brush particles (Figure 22.3a,b) were born from
the discovery that thermodynamically stable dispersion of nanoparticles in a high
MW polymer matrix was not generally achievable with small-molecule ligands nor
a monomodal brush of polymer. In a monomodal system, a large volume fraction of
the grafted polymer is in a stretched conformation, and only the polymer chain ends,
which exist in the semi-dilute polymer regime, have the conformational freedom to
entangle with the free chains in a surrounding polymer matrix. Generally, this leads
to a phenomenon known as autophobic dewetting, which is discussed in further
detail in Section 22.4.
Alternatively, a sparsely grafted brush gives the grafted chains the necessary
conformational freedom. However, at low densities, enough of the particle surface
(which is presumably immiscible with the matrix) is exposed to be a driving force
(a) (b) (c)
(d) (e) (f)
Figure 22.3 Some complex brush architectures prepared via SI-RAFT: (a) bimodal (mixed
MW), (b) mixed bimodal (mixed chemistry), (c) surface-anchored block copolymer, (d) looped
polymer brush, (e) Janus particle, and (f) ‘patchy’ particle.
S
S S
H2N NH2
N
O Si NH2 S
H 2N NH2 CN
O
H2N NH2
RAFT RAFT RAFT

H S
Si N 1st polymerization RAFT RAFT
Silica O S
NC
O Short dense brush
RAFT RAFT
RAFT
RAFT
RAFT cleavage using AIBN 1. Amine functionalization of silica
2. 2nd RAFT attachment of silica RAFT RAFT
2nd RAFT polymerization

Long brush
Scheme 22.2 Synthetic strategy to prepare bimodal brush-grafted silica nanoparticles via
SI-RAFT. Source: Reprinted with permission from Rungta et al. [13]. Copyright 2012,
for phase separation. The idea of grafting a dense and low MW short brush to
screen the attractive van der Waals forces between nanoparticles and then adding
a sparsely grafted high MW brush with the conformational freedom to entangle
with the polymer matrix was achieved using an iterative ‘grafting-from’ SI-RAFT
strategy (Scheme 22.2) first employed by Rungta et al. [13] Two discrete populations
of polymers could be attached with elegant control of graft density and graft
MW of each population. Graft density of a mercaptothiazoline-activated RAFT
agent on spherical silica nanoparticles was controlled by varying the feed ratio of
aminopropyldimethylethoxy silane to silica particles, and excellent control of either
grafted polystyrene (PS) or poly(methyl methacrylate) was demonstrated. Treating
the polymer-grafted particles with a large excess of azobis(isobutyronitrile) (AIBN,
2,2′ -azobis(2-methylpropionitrile)) cleaved the RAFT agent from the chain ends,
and a second (generally less dense) population of RAFT agent was attached using
the same procedure. This second population of tethered RAFT agent was used
to grow a second population of grafted chains. Notably, the second population of
polymer could differ from the first brush based on MW (bimodal, Figure 22.3a), or it
could consist of a different polymer, even a polymer that is immiscible with the first
brush to form a mixed-bimodal brush (Figure 22.3b). The ability to decouple the
entropic and enthalpic aspects of particle dispersion led to enhanced mechanical

and thermal properties in the resulting nanocomposites compared to monomodal
nanocomposites in a similar dispersion state. These enhanced thermomechanical
properties were attributed to the increased interfacial binding between graft and
matrix polymer chains [14].
Grafted block copolymers (Figure 22.3c) are generally prepared by first attaching
the RAFT agent, then growing the first block, isolating the grafted particles, and then
chain-extending with a second monomer to form a grafted block copolymer [15].
Looped graft polymers (Figure 22.3d) have been prepared according to Scheme 22.3
through the use of a RAFT agent, which is bound to the particle on both ends [16].
RAFT attachment via the R-group is shown, but double attachment via the Z-groups
was also demonstrated.
R-group approach: Pm
Pm S
Pm S
S S S S S S S
Z S Z
S Z S S Z S S S
R R R R R R• R R
Pm• Monomer
S S
S S S S
Z Z
S S
R R
R R
R R
Scheme 22.3 Proposed mechanism for the formation of polymer loops via doubly
R-anchored RAFT agents. Source: Reprinted with permission from Rotzoll et al. [16].
The complex brush architectures described so far have largely been applied
homogeneously to the surfaces of interest. There is great interest in building
anisotropically functionalized particles known as patchy particles [17]. The sim-
plest of these patchy particles are those which contain only two regions, which are
chemically or physically disparate, Janus particles (Figure 22.3e). These anisotropic
particles have the potential to assemble into complex supracolloidal structures [18],
act as single-particle surfactants [19], or lock and key colloids, which mimic nature’s
enzyme/receptor system [20, 21], etc. Generally, the chemically disparate sides
are prepared by controlling the surface distribution of small ligands; modifying
the particles with a polymer brush is more challenging. Early work creating Janus
nanoparticles focused on physically limiting access to one side of isotropic colloids
by either masking, deposition, or modification at the surface of an emulsion [22, 23].
Most of these techniques were limited to modification of large particles.
In an attempt to create small Janus nanoparticles, the Huisgen 1,3-dipolar cycload-

dition, commonly known as the copper ‘click’ reaction, was used to attach small
(15 nm diameter) alkyne-functionalized silica nanoparticles to the surface of 100 nm
silica nanoparticles (Figure 22.4a) [24]. Azido-terminated poly(methyl methacry-
late) prepared via RAFT polymerization was then grafted to the exposed side of the
alkyne-functionalized small silica nanoparticles. The small nanoparticles were then
successfully released by ultrasonication, which cleaved the mechanically labile tri-
azole ring that tethered them to the larger nanoparticle. Micelles comprising the
freed Janus particles in THF were observed, indicating that these might make good
particle-based surfactants.
An approach to prepare polymeric Janus nanosheets (PJS) using a clever particle
templating technique was published by Liu et al. [25] A self-assembled monolayer
of RAFT agent was formed on the surface of CaCO3 template particles, then a
bilayer of poly(N-isopropylacrylamide) (PNIPAM), followed by PS was grown
from the surface of the particle (outline of this scheme shown in Figure 22.4d).
By virtue of the RAFT process, the ratios of PS/PNIPAM were highly tunable.
The CaCO3 template particle could then be digested with acid, and the Janus
nanosheets comprising the polymer bilayer were separated using ultrasonication.
The PNIPAM/PS nanosheets were shown to be flexible and thermoresponsive
(Figure 22.4e). Dually responsive PJS were prepared from a similarly constructed
poly(acrylic acid) (PAA)/PNIPAM system.
Recently, syntheses to create patchy particles have transitioned to more scalable
routes. Using template particles, particle deposition, other means of ‘masking’,
or other bottom-up approaches generally yield very little material to study.
Top-down approaches generally offer better scalability. An excellent top-down
approach to prepare particles with tunable size and number of ‘patches’ was
recently published by Lotierzo and coworkers [26]. Nanogels of ω-end unsaturated
poly(methyl methacrylate-co-methacrylic acid)-block-poly(butyl methacrylate)
(P(MMA/MAA)-b-PBMA) were prepared via sulfur-free RAFT polymerization.
Upon addition of base, micelles formed and were core-crosslinked using a tri-
functional methacrylate. The prepared nanogels were then used as a stabilizer in
the emulsion polymerization of styrene. By controlling the pH of the emulsion
polymerization before initiation, the number of nanogel lobes, which decorated
the PS latex particles, was elegantly controlled, ranging from a single lobe per latex
particle at high pH, to many lobes per particle at lower pH values (Figure 22.5a–d).
Preparing flat surfaces that are functionalized with a spatially or chemically
patterned polymer brush is ostensibly more straightforward than doing the same
on small particle surfaces. There are two general approaches to preparing pat-
terned surfaces, bottom-up in which the CTA is patterned onto the surface, then
SI-RAFT results in a spatially patterned brush. Top-down approaches tend to be
simpler and more scalable; an unpatterned brush is grown from the surface and
is then patterned post-polymerization. A simple way to create a complex brush
pattern that leveraged the UV sensitivity of dithiobenzoate-type RAFT agents was
investigated by Choi et al. [27] First, an unpatterned layer of dithiobenzoic acid
benzyl-(4-ethyltrimethoxysilyl) ester was condensed onto the surface of a silicon
N N 3 N3
Polymers N3 3 N3
N3 N3
1 2 3
N3 N3
N3 N3
N3 N3
N3 N3 (d) PJS
N3 N
N3 N3 N3 3
Ultrasonication CuBr
PMDETA (b)
CuBr
PMDETA
Azido-capped polymers
(a) (c) (e)
Figure 22.4 (a) Synthetic route to prepare small (15 nm diameter) Janus nanoparticles, (b) transmission electron microscopy (TEM) image of 15 nm silica
particles attached to larger silica nanoparticles via the copper ‘click’ reaction, (c) Janus particle micelle observed after ultrasonication cleavage of
triazole-linked nanoparticles (scale bars in (b) and (c) = 200 nm). Source: (a) Adapted with permission from Li et al. [24]. Copyright 2013, American
Chemical Society, (b, c) Adapted with permission from Li et al. [24]. Copyright 2011, American Chemical Society (d) synthetic scheme of Janus nanosheet
formation: 1 = RAFT monolayer formation, 2 = growth of polymer bilayer, and 3 = particle digestion/sonication to form discrete PJS; and (e) TEM image of
‘scrolled’ PJS (Scale bar = 200 nm). Source: (d) Adapted with permission from Liu et al. [25]. Copyright 2017, American Chemical Society, (e) Adapted with
permission from Liu et al. [25]. Copyright 2017, American Chemical Society.
Figure 22.5 Scanning electron

microscopy (SEM) images of pH 8.8 pH 5.5
styrene latex particles prepared
via emulsion polymerization
using a nanogel stabilizer at
2.8 wt% with respect to
monomer in which the pH was
adjusted to 8.8 (a), 5.5 (b), 5.0 (c),
and 4.5 (d) before polymeri-
zation. Scale bars = 100 nm. (a) (b)
Source: Adapted with permission
from Lotierzo et al. [26] 2019, pH 5.0 pH 4.5
(c) (d)
wafer. A TEM grid was used as a photomask as the CTA-functionalized wafer

was exposed to UV light, degrading the CTA in regions where the wafer surface
was exposed. Subsequent SI-RAFT polymerization yielded patterned brushes of
poly(pentafluorophenyl acrylate) (PFPA). The PFPA brush was then post-modified
with a fluorescent dye, 5((2-aminoethyl) amino) naphthalene-1-sulfonic acid
(EDANS). Imaging of the dye-functionalized patterned brush with confocal laser
scanning microscopy (CLSM) showed confinement of the dye molecules to the
regions in which the CTA was not photodegraded, and the static water contact
angle for the patterned brushes decreased from 96∘ in PFPA brush to 23∘ for the
EDANS-modified brush. It is important to note that UV exposure with a TEM grid
as the photomask does not represent the lower limit of pattern feature sizes that
can be achieved.
Photopatterned attachment of RAFT agents was also investigated by Barner-
Kowollik and coworkers, which is illustrated in Figure 22.6 [28]. Silicon wafers
were coated with (3-aminopropyl)triethoxysilane and were subsequently reacted
with 4-amidobutyroyl chloride to create a maleimide-coated surface. A photomask
was applied to the surface, and a photoenol-tagged CTA was reacted with the
surface-tethered maleimide groups upon irradiation with 320 nm light. SI-RAFT
from the patterned regions of styrenic imidazolium monomers resulted in highly
patterned ionic polymer brushes. Salt metathesis of the ionic polymer brush with
KMnO4 immediately resulted in a bright purple indication of where the brush was
successfully patterned.
The flexibility of RAFT as a polymer synthesis strategy has enabled the elegant
syntheses of materials with excellent control of grafted polymer architecture on
the molecular scale. Clever combination of RAFT polymerization with other
chemistries has also enabled the development of materials with polymer brushes
that are spatially resolved on particle or flat surfaces and can have a high degree
O
Si O
Si O Si Si O OH O
N O O O
Si O Si O Si O
+ O O S
Si O Si O S Si N
O O Si O O
Si O N O O Si S S
Si H O S S O 10
Si O 10 Si O Si HN O O
Si O Si O O
6 7′ Si 7
Photomask
1: R = Bu, R′ = H, X = Cl–
VAZO-88 5: R = R′ = Me, X = Tf2N–
N X
N
R R R
Bu R N
N X N
MnO4 N
Si O OH O
Si O OH O Si O Si O
O KMnO4 O
Si O Si O Si O S
Si O S O Si N
N Si O O
Si O Si O O O n S S 10
O nS S 10 Si O Si HN O O
Si O Si HN O O Si O O
Si O O Si
Si
9
8a: R = Bu, R′ = H, X = Cl–
8b: R = R′ = Me, X = Tf2N–
Figure 22.6 Illustration of CTA photopatterning via a light-activated photoenol reaction and SI-RAFT polymerization of styrenic imidazolium monomers.
Visualization of the patterned ionic polymer brush was achieved by salt metathesis with KMnO4 . Source: Reproduced with permission from Steinkoenig
et al. [28]. Licensed under CCBY 3.0 unported.
of incorporated functionality. These combinatorial strategies were first adopted

primarily for the synthesis of materials in this section but were quickly adopted for
biomaterials and advanced composites, which are discussed in Sections 22.3–22.5.
22.3 Bioconjugation and Stimuli-responsive Polymer

Brushes
Grafting polymers from proteins is important for improving their solubility and
processability, but the chemical transformations necessary to attach the polymer
are at risk of harming the native folded conformation of the protein [29]. In
addition to these challenges, much of the work done on protein conjugation has
employed a grafting-to method, which results in many complications including
low reaction conversion (especially when the polymer or protein has high MW)
and the challenge of separating ungrafted proteins [30]. RAFT polymerization
is well suited for grafting polymers from proteins because it can adhere to the
mild conditions needed to preserve protein structure and functionality. Recently,
Tucker and co-workers employed photoinduced electron/energy transfer–reversible
addition–fragmentation chain transfer (PET–RAFT) to graft a variety of monomers
from a lysozyme-conjugated CTA [31]. The authors chose to use this light-initiated
RAFT variant to allow for fast polymerization even under dilute monomer condi-
tions. Efficient polymerization of N,N-dimethylacrylamide (DMAM) was observed
using 2 mol% of eosin Y as an organo-photocatalyst. As anticipated, the MWs of the
conjugate increased linearly with conversion, and polymerization could be cycled
on or off with light irradiation (Figure 22.7). Importantly, it was demonstrated that
chain extending from the conjugated CTA with NIPAM was done with high blocking
efficiency, indicating that the trithiocarbonate end groups did not undergo signifi-
cant degradation. The authors noted that there was a distribution of the number of
CTAs attached to the proteins as this conjugation approach was not site specific.
A site-specific conjugation strategy was employed by Li and coworkers [32]. To
prepare proteins with just one CTA per protein, site-directed mutagenesis was used
to substitute a cysteine residue for the Lys148 site present in Escherichia coli inor-
ganic pyrophosphatase (PPase). Although the Cys-substituted PPase contains two
other Cys residues, they are buried within the folded protein structure and are not
thought to be accessible for modification. The exposed Cys residue was reacted with
a maleimide-bearing trithiocarbonate CTA, and light-induced RAFT polymerization
of PNIPAM proceeded with good control. The resulting conjugates had a lower crit-
ical solution temperature (LCST) of 35 ∘ C (slightly higher than the LCST of pure
PNIPAM), and the LCST behaviour was used to tune the activity of PPase. Natively,
PPase catalyzes the hydrolysis of inorganic pyrophosphase to inorganic phosphate.
Below the LCST, the PPase activity was significantly decreased compared to that of
the unmodified protein. Above the LCST of the conjugate, the activity increased,
thus demonstrating the ability of the conjugated PNIPAM to ‘switch’ the function of
the protein on or off depending on temperature.
Total reaction time (min)
1.2 1.2
on off on off on off on off on 0 15 30 45 60 75 90 105 120 135
1 1
0.8 0.8
In([M]0/[M])
In([M]0/[M])
0.6 0.6
0.4 0.4
0.2 0.2
0 0 on off on off on off on off on

0 20 40 60 80 100 120 140 0 20 40 60 80
(a) Time (min) (b) Exposure time (min) (c)
Figure 22.7 (a) Pseudo-first-order kinetics plot showing each on-and-off cycle vs. total reaction time, (b) pseudo-first-order kinetics plot of total light
exposure time, and (c) sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS–PAGE) results showing MW growth only in the presence of light
for each cycle. Source: (a, b) Reprinted with permission from Tucker et al. [31]. Copyright 2017, American Chemical Society, (c) Reprinted with permission
Tucker et al. [31]. Copyright 2017, American Chemical Society.
Long Chain length Short

Initiator
[CTA] (mmol/L)a surface
(no PIPAAm)
0.25 0.5 1.0
Good (<0.5 h) Good (<1 h) Good (<24 h) N.D.
High
PIPAAm density (chains/nm2)
0.04
Good (<1 h) Poor Poor N.D.
Graft
0.03
density
Poor N.D. N.D. N.D.
0.02
Low
Figure 22.8 Cell sheets recovered from grafted PNIPAM brush surfaces by reducing the
temperature to 20 ∘ C. Results are described either as ‘Good’, ‘Poor’, or ‘N.D.’ (not detached).
Scale bars = 100 μm; here, PIPAAm refers to poly(N-isopropylacrylamide). Source: Reprinted
with permission from Takahashi et al. [33]. © 2010, American Chemical Society.
Brushes of PNIPAM as a thermoresponsive polymer are also useful for modulating

cell adhesion. Takahashi et al. used a tethered azo-initiator to graft PNIPAM via
RAFT polymerization from glass slides [33]. By simply changing the temperature,
adhesion or detachment behaviour of a sheet of bovine carotid artery endothelial
cells was manipulated (Figure 22.8). In general, the best detachment of a single sheet
of cells was achieved with the highest tested graft density and graft MW below the
LCST of the PNIPAM brush. The proposed mechanism for good cell sheet detach-
ment was that the interaction between the PNIPAM brush and adsorbed cells was
decreased below the LCST, facilitating easy release of the cell sheets from the surface.
A dually responsive drug nanocarrier was synthesized and tested by Zhang
and coworkers [34]. SI-RAFT was used to grow a block copolymer composed of
poly(methacrylic acid)-block-poly(N-isopropylacrylamide) from silica nanoparticles
(PMAA-b-PNIPAM-g-SiO2 ). At neutral pH and ambient temperature, doxorubicin
(DOX, pK a = 8.6) is protonated and thus strongly interacts with the negatively
charged PMAA block and the drug-loaded nanoparticles are individually dispersed
in an aqueous medium (Figure 22.9, bottom left). In principle, when the pH is
decreased from seven to five, PMAA becomes protonated and the DOX is released
from the inner block. When the DOX release was tested at 25 ∘ C at pH = 5,
approximately 50% of the drug was released after 50 hours. The release of DOX was
amplified by leveraging the thermoresponsiveness of the PNIPAM block above the
LCST temperature. At pH = 5 and 40 ∘ C, the interaction between PMAA and DOX
is weakened and the PNIPAM blocks collapses, causing the particles to aggregate
in solution. The authors asserted that this combination of responses improved the
DOX release by ‘squeezing’ the drug out of the assembly (Figure 22.9, top right).
40°C
e
as
ele
dr
Limited ce
han
release En
Moderate release
25°C
pH 7 pH 5
Figure 22.9 Proposed mechanism for dually responsive DOX release from PMAA-b-
PNIPAM-g-SiO2 nanocarriers. Source: Reprinted with permission from Zheng et al. [34].
After 30 hours, approximately 80% of the loaded DOX was released. These DOX
nanocarriers were found to be highly effective against Hela cells and exceeded
the efficacy of free DOX in an equivalent dose. The synergistic effect of increasing
the local concentration by loading drugs or other antibacterial properties within
nanocarriers has been noted in other work [35, 36].
22.4 Advanced Composites
Perhaps the most mature area of materials prepared by SI-RAFT lies in the field
of composites and polymer-grafted nanoparticles. In this discovery space, much
fundamental work has been conducted on understanding the relationship between
graft density/MW and composite microstructure and properties but also the attach-
ment chemistry to achieve robust polymer attachment to a large variety of particle
substrates. To date, SI-RAFT has been applied to a diverse array of substrates
including silica [37–41], gold [42, 43], TiO2 [44, 45], BaTiO3 [46–48], iron oxide
[49–51], silica-coated iron oxide [52], quantum dots [53, 54], montmorillonite [55],
halloysite nanotubes [56], cellulose [57], indium tin oxide [58], carbon substrates
including graphene oxide [59] and carbon nanotubes [60], polymeric foams [61, 62],
and other polymer substrates [63, 64]. Often, when the substrate is a small particle
(micro- or nano-sized), the intent is to incorporate the particles into a homopolymer
to form a composite material with properties greater than the sum of its parts.
When homogeneously incorporated into the polymer matrix, sub-micron-sized
fillers generate a large interfacial volume with the surrounding polymer matrix
where load transfer (thermal, mechanical, etc.) from the matrix to the filler occurs.
This large interfacial volume between matrix and filler amplifies the property
enhancement bestowed by the filler much beyond what can be achieved using an
identical filler of larger dimension [65]. Sometimes, the nano-sized filler also has
innately superior properties than a chemically similar filler of a larger dimension.
A classic example of this dimension-based property disparity is the comparison
between graphite and carbon nanotubes. Although chemically identical, Young’s
modulus of the nanotubes is nearly an order of magnitude greater than graphitic
carbon fibres [66]. In this section, the use of SI-RAFT polymerization to understand
nanofiller behaviour and to prepare advanced composites and hybrid materials will
be discussed.
Predictable and controlled dispersion of nanofiller within a polymer matrix in
which the bare filler is presumably immiscible is dependent on precise control of
the MW and graft density of the polymer brush that compatibilizes the filler with
the matrix. Intuitively, it seems that simply coating a nanofiller with a brush of poly-
mer with matching chemistry and similar MW to the desired matrix polymer should
lead to thermodynamically favourable homogeneous mixing of the nanofiller and
matrix. However, the story is much more complicated. Early nanocomposite work
showed that when N graft ≫ N matrix and 𝜎 2 N matrix ≫ 1 (where N is the chain length
and 𝜎 is the brush graft density), the matrix polymer chains cannot wet the brush
interface [67]. The consequence is macroscopic phase separation of two phases con-
taining chemically identical polymer. This phenomenon (autophobic dewetting) is
caused by a high osmotic pressure penalty for high MW polymers to penetrate into a
dense polymer brush. SI-RAFT offers the flexibility to independently tailor the graft
density and MW so that this effect is overcome. Not only can wetting behaviour be
tuned but the parameters can be systematically tuned to achieve a variety of isotropic
and anisotropic filler morphologies.
Systematic manipulation of graft density and grafted chain MW with respect to
matrix MW was studied, and a morphology diagram from these experiments was
constructed (Figure 22.10) [68]. PS-grafted nanoparticles (PS-g-SiO2 ) prepared via
SI-RAFT at a series of carefully controlled graft densities and MWs and were each
mixed with a PS matrix (MW = 142 kg mol−1 ). At low graft density and low MW with
respect to the matrix polymer (0.01 ch nm−2 , 25 kg mol−1 ), small spherical aggregates
were observed. As graft density and graft MW were independently increased, a num-
ber of morphologies were observed, both isotropic and anisotropic in nature. The
ability to predict and reproducibly achieve a variety of thermodynamically stable
nanoparticle arrangements represented an exciting advance in the understanding of
how to control nanofiller dispersion. The anisotropic structures (strings or elongated
sheets) are fundamentally interesting, and the ability to predict and target nanofiller
dispersion states had important implications for nanocomposite processing and ulti-
mately the nanocomposite properties.
σ = 0.01 chains nm–2
Mg = 25 kg mol–1 Mg = 51 kg mol–1 Mg = 158 kg mol–1
Grafting density (chains nm–2)
0.10 Dispersed
0.5 μm
σ = 0.05 chains nm–2

0.05
Connected/sheet String
spherical
σ = 0.1 chains nm–2 aggregates
0
0 1 2 3 4 5 6 7
(a) (b) Grafted chain length/matrix chain length
Figure 22.10 Experimentally determined morphology diagram of PS-g-SiO2 in the PS matrix (b) and transmission electron micrographs (a) of PS-g-SiO2
of varying MW and 𝜎 in the PS matrix (MW = 142 kg mol−1 ). Source: Reprinted with permission from Akcora et al. [68]. Copyright 2009, Springer Nature.
Precise control of the nanofiller dispersion state led to significant investigation

into the effect of different dispersion states on nanocomposite properties. There used
to be some debate about the mechanism by which nanofillers improved proper-
ties compared to bulk polymers. On one end of the spectrum, it was thought that
large aggregates of particles in the matrix were the source of reinforcement by act-
ing as a pathway through the polymer on which stress could propagate [69, 70]. On
the other end of the spectrum, other proposed mechanisms included chain immo-
bilization around a polymer-grafted nanoparticle and reinforcement is a result of
the percolation of particle-bound glassy layers [71] or that the matrix chains and
polymer-grafted particles form a network with polymer bridges connecting them
[72–74]. These arguments were settled after SI-RAFT allowed for the control of graft
density and MW needed to systematically prepare nanocomposites with either large
agglomerates or smaller dispersed particles. It was unequivocally shown that the
grafted chains on adjacent particles could entangle forming a percolating network
throughout the material [75]. This work supported the hypothesis that a network
mechanism was the source of polymer reinforcement. This knowledge also allowed
for the development of high-performance materials where the maximum material
reinforcement could be targeted, and the interfacial volume where load transfer and
property enhancement occurs is maximized.
The concept of using the nanofiller interface to incorporate properties other than
mechanical reinforcement is pronounced in dielectric nanocomposites. Bell and
coworkers independently investigated the effect of filler dispersion as well as the
effect of several π-conjugated electroactive surface ligands [76]. Briefly, 15 nm silica
nanoparticles were first functionalized with a dense coating (between 0.22 and
0.44 ch nm−2 ) of either anthracene, thiophene, or terthiophene. A relatively sparse
brush of poly(glycidyl methacrylate) (PGMA) (between 0.04 and 0.15 ch nm−2 )
was grafted via SI-RAFT to selected samples as a matrix-compatibilizing brush. As
expected, the best improvements in dielectric breakdown strength were observed
for nanocomposites with good (homogeneous) particle dispersion. Good dispersion
of nanoparticles, in this case, where the average interparticle distance was 200 nm
or less, creates the largest interfacial area between the nanoparticles. The greatest
dielectric breakdown enhancement was observed for well-dispersed PGMA-g-SiO2
(𝜎 = 0.1 ch nm−2 ) with 0.22 ch nm−2 terthiophene as the surface-tethered elec-
tron trapping ligand. This study is an excellent demonstration of using two
surface-tethered functionalities not only to allow for particle dispersion but also to
enhance a property somewhat decoupled from matrix compatibilization – in this
case, improved dielectric breakdown strength.
Early work on polymer nanocomposites prepared via SI-RAFT focused on
materials that were obviously compatible with the classes of monomers typically
polymerized by RAFT polymerization (styrenics, acrylates, methacrylates, etc.).
Processing and studying nanocomposites made from these materials are generally
straightforward as they are generally highly amorphous, have high glass transi-
tion temperatures, etc. However, many commodity plastics of interest including
polyolefins (polyethylene, polypropylene, etc.) and rubbery polymers are not con-
ventionally compatible with these classes of monomers. However, there are a few
recent examples of nanoparticles modified via SI-RAFT polymerization to prepare

nanomaterials compatible with some of these popular commodity materials.
In principle, reinforcing rubbery materials with nanofillers is straightfor-
ward – tires have been filled with various fillers, chiefly carbon black and silica, for
decades. However, incorporating nano-sized fillers into rubbery materials is not as
deeply explored. Employing an SI-RAFT strategy to prepare small silica particles,
for example, would provide the ability to tune the compatibility of the nanofiller
with a rubbery matrix. Khani and coworkers investigated a high-temperature
SI-RAFT polymerization of isoprene from the surface of silica nanoparticles
[77]. A high-temperature stable trithiocarbonate RAFT agent was chosen, (dode-
cylthio)carbonothioyl)thio)propanoic acid (DoPAT), based on the reports of
high-temperature bulk polymerization of isoprene [78, 79]. The surface-initiated
polymerization was shown to be well-controlled, having predictable MW with
monomer conversion although done in solvent conditions to maintain dispersion of
the silica nanoparticles (Figure 22.11b). Interestingly, the SI-RAFT polymerization
was faster than the free isoprene polymerization in solution, and there was also
a dependence of the polymerization rate on graft density (Figure 22.11a). The
higher graft density was notably faster than the lower graft density. This is similar
to the trend observed for SI-RAFT of PS but the opposite of the trend observed for
SI-RAFT of poly(methyl methacrylate) [80]. To date, no concrete theory exists in the
literature explaining the phenomenon of why the SI-RAFT polymerization of some
monomers is faster than the free polymerization, and sometimes, the SI-RAFT sys-
tem is slower. The polyisoprene (PI)-grafted silica nanoparticles showed reasonably
good dispersion in a PI matrix, demonstrating one of the first examples of a rubbery
nanocomposite prepared via SI-RAFT.
Matrix-free polychloroprene-grafted silica nanocomposites (PCP-g-SiO2 ) were
prepared using a similar trithiocarbonate SI-RAFT system to the PI work
described above [81]. In this case, 2-methyl-2-[(dodecylsulfanylthiocarbonyl)
sulfanyl]propanoic acid (MDSS) was the RAFT agent used. The as-synthesized
PCP-g-SiO2 was crosslinked with MgO and ZnO forming vulcanized rubber sheets
with excellent nanoparticle dispersion. The vulcanized nanocomposites exhibited
tensile strengths up to ∼13 MPa attributed to the good nanoparticle dispersion in the
matrix-free composite. The authors noted that normally silica-reinforced rubbery
composites exhibit decreased tensile strain because of the defects introduced by
particle aggregate defects [82], but that effect was avoided here.
The most abundantly produced class of polymers, polyolefins, represents a signif-
icant challenge for obtaining homogeneous dispersion of nano-sized fillers because
of the high degree of crystallinity, which makes it difficult for polymers of a lesser
degree of crystallinity to mix, even if they are chemically identical. For example,
low-density polyethylene (highly branched) is not miscible with high-density
polyethylene (HDPE, completely linear). This challenge was addressed using
SI-RAFT of poly(alkyl methacrylates) [83]. Silica nanoparticles were grafted
with poly(hexyl methacrylate) (PHMA), poly(lauryl methacrylate) (PLMA), or
poly(stearyl methacrylate) (PSMA). The prepared grafted nanoparticles were
processed into nanocomposites with linear low-density polyethylene as the matrix.
0.5 12 3
free free 2.8
0.45
10 0.14 graft density
0.4 0.14 graft density 2.6
0.42 graft density 0.42 graft density 2.4
0.35
Mn (Kg mol−1)
8
ln ([M0]/[Mt])
0.3 2.2
6 2
Ð
0.25
0.2 1.8
4
0.15 1.6
0.1 1.4
2
0.05 1.2
0 0 1
0 5 10 15 20 0 10 20 30 40
(a) Time (h) (b) Conversion (%)
Figure 22.11 (a) First-order kinetic plots and (b) dependence of molecular weight (solid line, Mn , theory) on the conversion for the SI-RAFT
polymerization of PI-g-SiO2 high surface density (triangle, 100 mmol g−1 , 0.42 ch nm−2 ), low surface density (diamond, 32 mmol g−1 , 0.14 ch nm−2 ), free
DoPAT (circle). All polymerizations were conducted under identical conditions with the ratio of [monomer]:[CTA]:[initiator] 5300 :1: 0.1. Source:
Reproduced with permission from Khani et al. [77]. Copyright 2017, John Wiley & Sons.
PHMA PLMA PSMA
O O
O
O O
O
(a) (b)
(c) (d)
Figure 22.12 TEM images of LLDPE nanocomposites each filled with 4 wt% silica loading of (a) bare silica, (b) PHMA-g-SiO2 , (c) PLMA-g-SiO2 , and (d)
PSMA-g-SiO2 . Grafted samples all had a graft density of 0.16 ch nm−2 . Scale bars = 200 nm. PHMA, poly(hexyl methacrylate); PLMA, poly(lauryl
methacrylate); PSMA, poly(stearyl methacrylate). Chemical structures of grafted polymers (right). Source: Reproduced with permission from Khani et al.
[83]. Copyright 2017, Elsevier.
The dispersion states of the prepared nanocomposites and polymer chemical

structures are shown in Figure 22.12. As the length of the alkyl pendant group
increased, the nanoparticle dispersion in linear low density polyethylene (LLDPE)
improved, with the best dispersion exhibited by PSMA-g-SiO2 . Notably, just the
alkyl pendant groups both allow for matrix-compatibility and shield the polar
methacrylic backbone from the non-polar matrix.
The narrow dispersity of grafted polymer chains afforded by SI-RAFT poly-
merization was leveraged to tune the free volume in matrix-free nanocomposites
which were then evaluated for gas separations [84]. In this work, thin films of
nanoparticles grafted with poly(methyl acrylate) or poly(methyl methacrylate) were
prepared via SI-RAFT at varying graft densities and chain lengths. Specifically, for
the PMA-g-SiO2 system with 𝜎 = 0.43 ch nm−2 , as the chain length increased, the
permeability of CO2 , N2 , and CH4 through the film increased gradually, all reaching
a maximum ‘volcano’ point at the same graft length, followed by a sharp decrease
in permeability. Computer simulations of these systems suggest that at certain
chain lengths, the polymer layer must deform to accommodate ideal nanoparticle
packing, and this deformation results in lower polymer density in periodic regions
of the film (Figure 22.13a). As a result, improved separation of a gaseous mixture of
CH4 and CO2 which approached the Robeson upper bound (an empirical model of
the best possible membranes for this gas separation), is shown in Figure 22.13b. This
promising membrane performance enhancement was attributed to this tunable free
volume.
An exciting advance that used the miscibility of PMMA-g-SiO2 nanoparticles
prepared by SI-RAFT with poly(ethylene oxide) (PEO, a semi-crystalline polymer)
to study the effects of matrix crystallization on the nanofiller was recently pub-
lished [85]. As the authors mention, approximately 75% of commodity plastics are
semi-crystalline but are generally of little use as engineering materials because
0.74
40
0.72
100
0.70
Monomer density
30
PCO2/PCH4
y 0.68
20 0.66
10
0.64 PMA
10
0.62 2008 Upper bound
1991 Upper bound
0.60
10 20 30 40 10 100
(a) x (b)
Figure 22.13 (a) Computer-simulated ‘heatmap’ of monomer density in NPs

(diameter = 10) grafted with polymer chains (monomer diameter = 1, chain length = 10 200
chains per particle, averaged over 500 simulations). (b) Robeson plots comparing the
permeabilities of CO2 and CH4 PMA composites with graft lengths of (•) 27 kDa, (▾) 38 kDa,
(◽) 52 kDa, (⬧) 62 kDa, (★) 92 kDa, and (▴) 132 kDa compared with (⬧) neat PMA. Source:
Reproduced with permission Bilchak et al. [84]. © 2017, American Chemical Society.
(a) (b)
1010
E′ (Pa)
109
20wt% 58°C-7d
20wt% RT quench
neat PEO 58°C-7d
neat PEO RT quench
108
10–3 10–2 10–1 100 101 102
Frequency (Hz)
(c) (d)
Figure 22.14 (a) 20 wt% PMMA-g-SiO2 in 100 kg mol−1 PEO quenched at room
temperature, (b) 20 wt% PMMA-g-SiO2 in 100 kg mol−1 PEO isothermally crystallized at
58 ∘ C for seven days, and (c) high-magnification TEM image for 40 wt% PMA-g-SiO2 in
100 kg mol−1 PEO isothermally crystallized at 58 ∘ C for seven days. (d) Storage modulus (E ′ )
at room temperature for samples either quenched at room temperature (RT quench) or
crystallized at 58 ∘ C for seven days. Source: Reprinted with permission from Zhao et al. [85].
of low mechanical moduli and low glass transition temperatures. These property
deficiencies were addressed by leveraging the crystallization behaviour of PEO
to template the multi-scale assembly of nanoparticles within the composite.
Figure 22.14a shows the TEM micrograph of the PMMA-g-SiO2 /PEO nanocom-
posite simply quenched at room temperature with no particle organization.
Figure 22.14c shows the same composite (same silica loading) after isothermal
crystallization at 58 ∘ C for seven days. The long-range ordering after crystallization
is clearly seen and agrees with molecular dynamics simulations that the particles
can be driven into one of three hierarchical domains during crystallization. From
smallest to largest domain, the regions are (i) engulfed within the PEO crystals
(ii) in the interlamellar regions, or (iii) in the interfibrillar regions. There was an
appreciable increase (nearly an order of magnitude) in the storage modulus (E′ )
between the quenched composite and the hierarchically assembled composite with
the same silica loading (Figure 22.14d). This improvement in E′ was attributed to
the nanoscale ‘brick and mortar’ structure templated by the PEO crystallization.
Importantly, this work begins to fill out some untouched discovery space in the
nanomaterials community by using an influence other than control of nanofiller
molecular parameters (𝜎 and MW) to direct the assembly of nanofiller in a way that
improves the nanocomposite properties.
The past decade has seen tremendous growth in the field of advanced compos-
ites owed to the molecular-scale control afforded by SI-RAFT. A staggering array of
substrates been used as fillers in composites for a variety of applications. Perhaps
the most significant new direction of nanocomposites stems from the discovery of
self-assembled anisotropic structures made possible by tuning graft density and MW
of grafted chains. This line of thinking has led to using top-down strategies to assem-
ble nanofillers, leading to once innocuous materials having new-found potential.
22.5 Shaped Polymer-Grafted Particles

As mentioned at the beginning of Section 22.2, shaped polymer-grafted nanoma-
terials (PGNMs) are interesting because of their theorized properties. However,
in-depth study of such materials remains quite underexplored because of the syn-
thetic challenge of making shaped PGNMs with a high degree of control. Early work
in this field relied on the self-assembly of block copolymers containing a reactive
group, which would be self-assembled in bulk and the discontinuous phase would
then be stabilized by various chemistries including gelation of silicates [86–88], 1–3
ring-opening of epoxy groups [89], UV initiation of vinyl groups [90], etc. Generally,
after crosslinking, the block copolymer assembly may be exposed to a solvent good
for the continuous phase to disperse the stabilized nanoobjects. This dispersion
step is conducted with varying degrees of success. For example, lamellae that form
polymer-grafted plates after solubilization can be particularly difficult to separate
into single sheets, for example. However, this type of approach is robust in that the
domain sizes and desired morphology is easily tuned by simply manipulating the
length of each block within the copolymer – whose RAFT chemistry easily enables.
A simpler method of generating shaped nanoobjects with tunable domain sizes
and orthogonally tunable morphology shape was investigated by Ruan and cowork-
ers [91]. RAFT polymerization was used to prepare poly(3-(triethoxysilyl)propyl)
methacrylate-block-polystyrene (PTEPM-b-PS). Once assembled in the bulk, the
triethoxysilyl groups can be crosslinked upon exposure to acid, forming a silicate.
The authors demonstrated that by starting with only a few different versions of
the PTEPM-b-PS block copolymer and small homopolymers of each PTEPM and
PS, the core shape, core size, and brush length could be independently tuned.
Their elegant approach is summarized in Figure 22.15. For example, if starting
with a PTEPM-b-PS with block lengths such that the bulk morphology is lamellar,
adding sufficient PS homopolymer to the assembly changes the bulk morphology to
PTEPM spheres in a PS continuous phase. Excitingly, it was also demonstrated that
the brush length and core domain size were independently tunable. If simply using
a block copolymer to change morphology or domain size, and a larger core domain
is desired, there is the risk that changing the volume fraction of the PTEPM block
would result in morphological change. By adding small homopolymers to the block
copolymer system, the morphology can remain unchanged and core or brush length
Core shape control

Assemble Cross-link.
Disperse
n m
O O
Si
O O
O Disperse
Disperse
(a)
Core shape control Core size control (lamella) Core size control (cylinder)
A, C, D A, C, D
A, C, D
A, C, D A, C, D A, C, D
A, C, D A, C, D A, C, D
(b) (c) (d)
Brush length control (cylinder) Brush length control (sphere)

A, C, D A, C, D
A, C, D A, C, D
A, C, D A, C, D
(e) (f)
Block copolymer PTEPM-b-PS Oligomer oT Oligomer oS
Figure 22.15 Illustrations of PGNP preparation of various structures by ‘assembly–

crosslink–dispersion method’. (a), (b) PGNPs with different core shapes; (c) lamellar PGNPs
with different core thicknesses; (d) cylindrical PGNPs with different core diameters; (e)
cylindrical PGNPs with different polymer brush lengths; and (f) spherical PGNPs with
different polymer brush lengths. A: Assembly of block copolymer and oligomers. C:
Crosslinking of PTEPM domains. D: Dispersion of bulk materials. Source: Reprinted with
permission from Ruan et al. [91]. © 2015, American Chemical Society.
can be independently tuned. After crosslinking the core, the nanoobjects could then
be dispersed in a good solvent for the PS block. This work represents a significant
advance in top-down preparation of tunable polymer-grafted nanoobjects.
Perhaps more pervasive in the past half-decade of literature is the concept of
polymerization-induced self-assembly (PISA) to prepare tunable nanostructures. In
essence, PISA is the result of chain extending from a macro-CTA with a monomer
that becomes insoluble in the reaction medium as a polymer [92]. As a result of
chain extension, the insoluble polymer aggregates in solution, forming nanostruc-
tures whose shape is a function of the ratio between solvophilic and solvophobic
regions of the block copolymer. RAFT is a flexible platform for this technique,
which is generally performed in water or highly polar media. The most common
nano-shapes accessible by PISA are spherical micelles, worms, and vesicles. In
principle, the nanoobjects can then be stabilized by crosslinking the continuous
domain. Karagoz et al. explored this idea of preparing stabilized structures via
PISA by chain extending from a dithiobenzoate-functionalized poly(oligo(ethylene
glycol)methacrylate with a mixture of styrene and 4-vinylbenzaldehyde [93]. The
incorporated aldehyde groups in the assembled structure were sites for crosslinking
with 1,3-diaminopropane or conjugation with doxorubicin. When release of the
doxorubicin was studied, the shape of the drug-loaded assemblies had a pronounced
effect on cellular uptake. Worm and rod-like assemblies had much lower IC50 values
compared to micelles and vesicles, although no significant difference in the drug
release rate between the different assemblies was observed.
Further fine-tuning of PISA as a technique to prepare well-defined polymeric par-
ticles was explored by Zhou and coworkers [94]. Often, the goal of preparing highly
functional nanostructures is to approximate nature’s elegant structural control of
macromolecules and their assemblies. In this work, low-dispersity nanospheres
and vesicles were prepared via PISA formation of poly(N,N-dimethylacryl-
amide)-block-poly(diacetone acrylamide) (PDMAM-b-PDAAM) (diacetone acry-
lamide (DAAM) is N-(2-methyl-4-oxopentan-2-yl)acrylamide). By lowering the
polymerization temperature and concentration of radical initiator compared to con-
ventional PISA systems, the dispersity of the assembled structures was significantly
decreased. Likely, both measures reduced the rate of polymerization, allowing the
assembling structure time to reorganize and resulting in improved uniformity. The
highly keto-rich core block was then available for post-modification. Although not
used for crosslinking in this work, a highly functional core domain presents oppor-
tunities for incorporating multi-functionality – approaching the molecular-scale
control necessary to mimic and manipulate biological systems.
Dynamic polymeric nanoobjects were prepared via RAFT-mediated PISA,
representing a further enhancement of nanoscale structural control [95]. PISA
of poly(glycerol monomethacrylate)-block-poly(2-hydroxypropyl methacrylate)
(PGlyMA-b-PHPMA) (glycerol monomethacrylate (GlyMA) is 2,3-dihydroxypropyl
methacrylate) was conducted starting with a PGlyMA56 macro-CTA. At room
temperature, the dominant morphology was worms, but upon cooling to 5 ∘ C,
a worm-to-sphere transition was observed (Figure 22.16). In this work, this
temperature-induced morphology transition was used as a wholly synthetic
biomimetic alternative to hydroxyethyl starch (HES), commonly used as a cry-
oprotectant in blood preservation. The addition of a small amount of poly(vinyl
alcohol) to the PGlyMA-b-PHPMA worms resulted in a red blood cell recovery level
indistinguishable from the system currently employed for cellular cryopreservation.
To summarize, at the beginning of this decade, there were a few scarce and
rudimentary methods for creating shaped PGNMs, some with fair control of the
particle shape but fewer with control of particle size or grafted polymer length.
Now, bulk assembly of block copolymers or PISA have evolved as the dominant
routes to preparing nanoobjects with excellent control of shape and dispersity of
size in some cases.
O O
NC S NC S
56 56 155
S OH S
O O O O O O
OH 2-hydroxypropyl OH
methacrylate
ACVA, H2O, OH
OH OH
70 °C, N2
Poly(glycerol
monomethacrylate)
Cool
Heat
Figure 22.16 PISA synthesis of PGlyMA-b-PHPMA diblock copolymer worms and

illustration of reversible worm-to-sphere transition upon cooling below 12 ∘ C. Source:
Reproduced with permission from Mitchell et al. [95]. © 2016, John Wiley & Sons. ACVA is
4,4′ -azobis(4-cyanopentanoic acid) (ACPA).
22.6 Conclusion
The past decade has seen incredible growth in the field of polymer-grafted surfaces
and nanomaterials. Much of the progress and success is owed to RAFT chemistry.
Unparalleled in its chemical compatibility, mild conditions, and general versatil-
ity, RAFT polymerization has been applied liberally in every area of nanoscience.
The result is materials that are stronger, more durable, biomimetic, smarter, and
advanced in every sense. When SI-RAFT is combined with materials made already
great by nature, the result is greater than the sum of its parts.
Happily, the last few years are rich with development in RAFT methodology.
The work conducted on polymer-grafted surfaces described in this chapter focused
solely on RAFT as a controlled radical polymerization, largely in conventional
organic solvent as a polymerization medium. Advances such as aqueous RAFT [96],
light-activated RAFT [97], temperature-programmed RAFT [98], cationic RAFT
[99, 100], switchable RAFT [101, 102], etc., are sure to begin infiltrating the topics
mentioned here. With these new methodologies, the outlook is bright for the next
decade of advanced materials made possible by the ever-increasing versatility of
RAFT as a polymerization technique.
Acknowledgements
This work was supported by the U.S. Department of Energy, Office of Science, Basic
Energy Sciences (BES) under award no. DE-SC0018135.
References 1043
References
1 Dukes, D., Li, Y., Lewis, S. et al. (2010). Conformational transitions of spherical
polymer brushes: synthesis, characterization, and theory. Macromolecules 43:
1564–1570.
2 Zoppe, J.O., Ataman, N.C., Mocny, P. et al. (2017). Surface-initiated controlled
radical polymerization: state-of-the-art, opportunities, and challenges in surface
and interface engineering with polymer brushes. Chem. Rev. 117: 1185–1318.
3 Alexander, S. (1977). Adsorption of chain molecules with a polar head a scaling
description. J. Phys. (Paris) 38: 983–987.
4 de Gennes, P. (1980). Conformations of polymers attached to an interface.
5 Pirri, G., Chiari, M., Damin, F., and Meo, A. (2006). Microarray glass
slides coated with block copolymer brushes obtained by reversible addition
chain-transfer polymerization. Anal. Chem. 78: 3118–3124.
6 Li, C. and Benicewicz, B.C. (2005). Synthesis of well-defined polymer brushes
grafted onto silica nanoparticles via surface reversible addition fragmentation
chain transfer polymerization. Macromolecules 38: 5929–5936.
7 Stenzel, M.H., Zhang, L., and Huck, W.T.S. (2006). Temperature-responsive
glycopolymer brushes synthesized via RAFT polymerization using the Z-group
approach. Macromol. Rapid Commun. 27: 1121–1126.
8 Barbey, R., Lavanant, L., Paripovic, D. et al. (2009). Polymer brushes via
surface-initiated controlled radical polymerization: synthesis, characterization,
properties, and applications. Chem. Rev. 109: 5437–5527.
9 Kumar, S.K., Jouault, N., Benicewicz, B.C., and Neely, T. (2013). Nanocompos-
ites with grafted nanoparticles. Macromolecules 46: 3199–3214.
10 Perrier, S. (2017). 50th Anniversary perspective: RAFT polymerization – a user
guide. Macromolecules 50: 7433–7447.
11 Zhang, Z., Keys, A.S., Chen, T., and Glotzer, S.C. (2005). Self-assembly of
patchy particles into diamond structures through molecular mimicry. Langmuir
21: 11547–11551.
12 Glotzer, S.C. and Solomon, M.J. (2007). Anisotropy of building blocks and their
assembly into complex structures. Nat. Mater. 6: 557–562.
13 Rungta, A., Natarajan, B., Neely, T. et al. (2012). Grafting bimodal polymer
brushes on nanoparticles using controlled radical polymerization. Macro-
molecules 45: 9303–9311.
14 Natarajan, B., Neely, T., Rungta, A. et al. (2013). Thermomechanical proper-
ties of bimodal brush modified nanoparticle composites. Macromolecules 46:
4909–4918.
15 Huang, Y., Zheng, Y., Sarkar, A. et al. (2017). Matrix-free polymer nanocompos-
ite thermoplastic elastomers. Macromolecules 50: 4742–4753.
16 Rotzoll, R. and Vana, P. (2008). Synthesis of poly(methyl acrylate) loops grafted
onto silica nanoparticles via reversible addition-fragmentation chain transfer
polymerization. J. Polym. Sci. A. Polym. Chem. 46: 7656–7666.
17 Zhang, J., Grzybowski, B.A., and Granick, S. (2017). Janus particle synthesis,
assembly, and application. Langmuir 33: 6964–6977.
18 Kraft, D.J., Ni, R., Smallenburg, F. et al. (2012). Surface roughness directed
self-assembly of patchy particles into colloidal Micelles. Proc. Natl. Acad. Sci. U.
S. A. 109: 10787–10792.
19 Chen, Q., Whitmer, J.K., Jiang, S. et al. (2011). Supracolloidal reaction kinetics
of Janus spheres. Science 331: 199–202.
20 Sacanna, S., Irvine, W.T.M., Chaikin, P.M., and Pine, D.J. (2010). Lock and key
colloids. Nature 464: 575–578.
21 Wang, Y., Wang, Y., Zheng, X. et al. (2014). Three-dimensional lock and key
colloids. J. Am. Chem. Soc. 136: 6866–6869.
22 Jiang, S., Schultz, M.J., Chen, Q. et al. (2008). Solvent-free synthesis of Janus
colloidal particles. Langmuir 24: 10073–10077.
23 Zhang, G., Wang, D.Y., and Mohwald, H. (2005). Patterning microsphere sur-
faces by templating colloidal crystals. Nano Lett. 5: 143–146.
24 Li, J., Wang, L., and Benicewicz, B.C. (2013). Synthesis of Janus nanoparti-
cles via combination of reversible click reaction and “Grafting-to” strategies.
Langmuir 29: 11547–11553.
25 Liu, Y., Xu, X., Liang, F., and Yang, Z. (2017). Polymeric Janus nanosheets by
template RAFT polymerization. Macromolecules 50: 9042–9047.
26 Lotierzo, A., Longbottom, B.W., Lee, W.H., and Bon, S.A.F. (2019). Synthe-
sis of Janus and patchy particles using nanogels as stabilizers in emulsion
polymerization. ACS Nano 13: 399–407.
27 Choi, J., Schattling, P., Jochum, F.D. et al. (2012). Functionalization and pat-
terning of reactive polymer brushes based on surface reversible addition and
fragmentation chain transfer polymerization. J. Polym. Sci. A Polym. Chem. 50:
4010–4018.
28 Steinkoenig, J., Bloesser, F.R., Huber, B. et al. (2016). Controlled radical poly-
merization and in-depth mass-spectrometric characterization of poly(ionic
liquid)s and their photopatterning on surfaces. Polym. Chem. 7: 451–461.
29 Alconcel, S.N.S., Baas, A.S., and Maynard, H.D. (2011). FDA-approved
poly(ethylene glycol) − protein conjugate drugs. Polym. Chem. 2:
1442–1448.
30 Wallat, J.D., Rose, K.A., and Pokorski, J.K. (2014). Proteins as substrates for
controlled radical polymerization. Polym. Chem. 5: 1545–1558.
31 Tucker, B.S., Coughlin, M.L., Figg, C.A., and Sumerlin, B.S. (2017).
Grafting-from proteins using metal-free PET−RAFT polymerizations under
mild visible-light irradiation. ACS Macro Lett. 6: 452–457.
32 Li, X., Wang, L., Chen, G. et al. (2014). Visible light induced fast synthesis of
protein-polymer conjugates: controllable polymerization and protein activity.
Chem. Commun. 50: 6506–6508.
33 Takahashi, H., Nakayama, M., Yamato, M., and Okano, T. (2010). Controlled
chain length and graft density of thermoresponsive polymer brushes for opti-
mizing cell sheet harvest. Biomacromolecules 11: 1991–1999.
34 Zheng, Y., Wang, L., Lu, L. et al. (2017). pH and thermal dual-responsive
nanoparticles for controlled drug delivery with high loading content. ACS
Omega 2: 3399–3405.
References 1045
35 Wang, L., Chen, Y.P., Miller, K.P. et al. (2014). Functionalized nanoparticles
complexed with antibiotic efficiently kill MRSA and other bacteria. Chem.
Commun. 50: 12030–12033.
36 Inam, M., Foster, J.C., Gao, J. et al. (2019). Size and shape affects the antimi-
crobial activity of quaternized nanoparticles. J. Polym. Sci. Part A: Polym. Chem.
57: 255–259.
37 Giovino, M., Pribyl, J., Benicewicz, B.C. et al. (2017). Linear rheology of poly-
mer nanocomposites with polymer-grafted nanoparticles. Polymer 131: 104–110.
38 Guenay, K.A., Schuewer, N., and Klok, H.-A. (2012). Synthesis and postpoly-
merization modification of poly(pentafluorophenyl methacrylate) brushes.
Polym. Chem. 3: 2186–2192.
39 Liu, J., Zhang, L., Shi, S. et al. (2010). A novel and universal route to
SiO2 -supported organic/inorganic hybrid noble metal nanomaterials via surface
RAFT polymerization. Langmuir 26: 14806–14813.
40 Moraes, J., Ohno, K., Maschmeyer, T., and Perrier, S. (2013). Monodis-
perse, charge-stabilized, core-shell particles via silica supported reversible
addition-fragmentation chain transfer polymerization for cell imaging. Chem.
Mater. 25: 3522–3527.
41 Li, Q., Zhang, L., Bai, L. et al. (2011). Multistimuli-responsive hybrid nanopar-
ticles with magnetic core and thermoresponsive fluorescence-labeled shell via
surface-initiated RAFT polymerization. Soft Matter 7: 6958–6966.
42 Grande, C.D., Tria, M.C., Jiang, G. et al. (2011). Grafting of polymers from
electrodeposited macro-RAFT initiators on conducting surfaces. React. Funct.
Polym. 71: 938–942.
43 Zengin, A. and Caykara, T. (2012). RAFT-mediated synthesis of
poly(oligoethylene glycol) methyl ether acrylate brushes for biological functions.
J. Polym. Sci., Part A: Polym. Chem. 50: 4443–4450.
44 Hojjati, B. and Charpentier, P.A. (2010). Synthesis of TiO2 -polymer nanocom-
posite in supercritical CO2 via RAFT polymerization. Polymer 51: 5345–5351.
45 Tao, P., Li, Y., Rungta, A. et al. (2011). TiO2 nanocomposites with high refrac-
tive index and transparency. Journal of Materials Chemistry 21: 18623–18629.
46 Yang, K., Huang, X., Huang, Y. et al. (2013). FluoroPolymer@BaTiO3 hybrid
nanoparticles prepared via RAFT polymerization: toward ferroelectric polymer
nanocomposites with high dielectric constant and low dielectric loss for energy
storage application. Chem. Mater. 25: 2327–2338.
47 Qiao, Y., Islam, M.S., Wang, L. et al. (2014). Thiophene polymer-grafted bar-
ium titanate nanoparticles toward nanodielectric composites. Chem. Mater. 26:
5319–5326.
48 Qiao, Y., Yin, X., Wang, L. et al. (2015). Bimodal polymer brush core–shell bar-
ium titanate nanoparticles: a strategy for high-permittivity polymer nanocom-
posites. Macromolecules 48: 8998–9006.
49 Xiao, Z.-P., Yang, K.-M., Liang, H., and Lu, J. (2010). Synthesis of magnetic,
reactive, and thermoresponsive Fe3 O4 nanoparticles via surface-initiated RAFT
copolymerization of N-isopropylacrylamide and acrolein. J. Polym. Sci., Part A:
Polym. Chem. 48: 542–550.
50 Niu, S., Zhang, L., Wang, N. et al. (2013). Fabrication of magnetic nanofibers
via surface-initiated RAFT polymerization and coaxial electrospinning. React.
Funct. Polym. 73: 1447–1454.
51 Wang, H., Luo, W., and Chen, J. (2012). Fabrication and characterization of
thermoresponsive Fe3 O4 @PNIPAM hybrid nanomaterials by surface-initiated
RAFT polymerization. J. Mater. Sci. 47: 5918–5925.
52 Wang, L., Cole, M., Li, J. et al. (2015). Polymer grafted recyclable magnetic
nanoparticles. Polym. Chem. 6: 248–255.
53 Dilag, J., Kobus, H., and Ellis, A.V. (2013). CdS/polymer nanocomposites syn-
thesized via surface initiated RAFT polymerization for the fluorescent detection
of latent fingermarks. Forensic Sci. Int. 228: 105–114.
54 Matsuno, R., Goto, Y., Konno, T. et al. (2009). Controllable nanostructured
surface modification on quantum dot for biomedical application in aqueous
medium. J. Nanosci. Nanotechnol. 9: 358–365.
55 Rzayev, Z.M.O. and Soylemez, A.E. (2011). Functional copolymer/organo-MMT
nanoarchitectures. VI. Synthesis and characterization of novel nanocompos-
ites by Interlamellar controlled/living radical copolymerization via prein-
tercalated RAFT-agent/organoclay complexes. J. Nanosci. Nanotechnol. 11:
3523–3532.
56 Hou, Y., Jiang, J., Li, K. et al. (2014). Grafting amphiphilic brushes onto
halloysite nanotubes via a living RAFT polymerization and their pickering
emulsification behavior. J. Phys. Chem. B 118: 1962–1967.
57 Boujemaoui, A., Mazieres, S., Malmstrom, E. et al. (2016). SI-RAFT/MADIX
polymerization of vinyl acetate on cellulose nanocrystals for nanocomposite
applications. Polymer 99: 240–249.
58 Grande, C.D., Tria, M.C., Jiang, G.Q. et al. (2011). Surface-grafted polymers
from electropolymerized polythiophene RAFT agent. Macromolecules 44:
966–975.
59 Yeole, N., Kutcherlapati, S.N.R., and Jana, T. (2015). Polystyrene–graphene
oxide (GO) nanocomposite synthesized by interfacial interactions between
RAFT modified GO and core–shell polymeric nanoparticles. J. Colloid Interface
Sci. 443: 137–142.
60 Macdonald, T., Gibson, C.T., Constantopoulos, K. et al. (2012). Functional-
ization of vertically aligned carbon nanotubes with polystyrene via surface
initiated reversible addition fragmentation chain transfer polymerization. Appl.
Surf. Sci. 258: 2836–2843.
61 Audouin, F. and Heise, A. (2013). Surface-initiated RAFT polymerization of
NIPAM from monolithic macroporous polyHIPE. Eur. Polym. J. 49: 1073–1079.
62 Barlow, K.J., Hao, X., Hughes, T.C. et al. (2014). Porous, functional,
poly(styrene-co-divinylbenzene) monoliths by RAFT polymerization. Polym.
Chem. 5: 722–732.
63 Pan, G., Ma, Y., Zhang, Y. et al. (2011). Controlled synthesis of water-
compatible molecularly imprinted polymer microspheres with ultrathin
hydrophilic polymer shells via surface-initiated reversible addition-
fragmentation chain transfer polymerization. Soft Matter 7: 8428–8439.
References 1047
64 Yu, H.-Y., Li, W., Zhou, J. et al. (2009). Thermo- and pH-responsive polypropy-
lene microporous membrane prepared by the photoinduced RAFT-mediated
graft copolymerization. J. Membr. Sci. 343: 82–89.
65 Schadler, L.S., Kumar, S.K., Benicewicz, B.C. et al. (2007). Designed interfaces
in polymer nanocomposites: a fundamental viewpoint. MRS Bull. 32: 335–340.
66 Treacy, M.M.J., Ebbesen, T.W., and Gibson, J.M. (1996). Exceptionally high
Young’s modulus observed for individual carbon nanotubes. Nature 381:
678–680.
67 Bansal, A., Yang, H., Li, C. et al. (2006). Controlling the thermomechani-
cal properties of polymer nanocomposites by tailoring the polymer-particle
interface. J. Polym. Sci. B Polym. Phys. 44: 2944–2950.
68 Akcora, P., Liu, H., Kumar, S.K. et al. (2009). Anisotropic self-assembly of
spherical polymer-grafted nanoparticles. Nature Mater. 8: 354–359.
69 Heinrich, G. and Kluppel, M. (2002). Recent advances in the theory of filler
networking in elastomers. Adv. Polym. Sci. 160: 1–44.
70 Gusev, A.A. (2006). Micromechanical mechanism of reinforcement and losses
in filled rubbers. Macromolecules 39: 5960–5962.
71 Long, D. and Sotta, P. (2007). Stress relaxation of large amplitudes and
long timescales in soft thermoplastic and filled elastomers. Rheol. Acta 46:
1029–1044.
72 Maier, P.G. and Goritz, D. (1996). Molecular interpretation of the Payne effect.
Kautsch. Gummi Kunstst. 49: 18–21.
73 Zhu, Z.Y., Thompson, T., Wang, S.Q. et al. (2005). Investigating linear and non-
linear viscoelastic behavior using model silica-particle-filled polybutadiene.
74 Zhu, A.J. and Sternstein, S.S. (2003). Nonlinear viscoelasticity of nanofilled
polymers: interfaces, chain statistics and properties recovery kinetics. Compos.
Sci. Technol. 63: 1113–1126.
75 Moll, J.F., Akcora, P., Rungta, A. et al. (2011). Mechanical reinforcement in
polymer melts filled with polymer grafted nanoparticles. Macromolecules 44:
7473–7477.
76 Bell, M., Krentz, T., Nelson, J.K. et al. (2017). Investigation of dielectric break-
down in silica-epoxy nanocomposites using designed interfaces. J. Colloid
Interface Sci. 495: 130–139.
77 Khani, M.M., Abbas, Z.M., and Benicewicz, B.C. (2017). Well-defined
polyisoprene-grafted silica nanoparticles via the RAFT process. J. Polym. Sci.
Part A: Polym. Chem. 55: 1493–1501.
78 Jitchum, V. and Perrier, S. (2007). Living radical polymerization of isoprene via
the RAFT process. Macromolecules 40: 1408–1412.
79 Germack, D.S. and Wooley, K.L. (2007). Isoprene polymerization via reversible
addition fragmentation chain transfer polymerization. Polym. Sci. Part A: Polym.
Chem. 45: 4100–4108.
80 Li, C., Han, J., Ryu, C.Y., and Benicewicz, B.C. (2006). A versatile method to
prepare RAFT agent anchored substrates and the preparation of PMMA grafted
nanoparticles. Macromolecules 39: 3175–3183.
81 Zheng, Y., Abbas, Z.M., Sarkar, A. et al. (2018). Surface-initiated reversible

addition-fragmentation chain transfer polymerization of chloroprene and
mechanical properties of matrix-free polychloroprene nanocomposites. Polymer
135: 193–199.
82 Qu, L., Wang, L., Xie, X. et al. (2014). Contribution of silica-rubber inter-
actions on the viscoelastic behaviors of modified solution polymerized
styrene butadiene rubbers (M–S–SBRs) filled with silica. RSC Advances 4:
64354–64363.
83 Khani, M.M., Woo, D., Mumpower, E.L., and Benicewicz, B.C. (2017).
Poly(alkyl methacrylate)-grafted silica nanoparticles in polyethylene nanocom-
posites. Polymer 109: 339–348.
84 Bilchak, C.R., Buenning, E., Asai, M. et al. (2017). Polymer-grafted nanoparticle
membranes with controllable free volume. Macromolecules 50: 7111–7120.
85 Zhao, D., Gimenez-Pinto, V., Jimenez, A.M. et al. (2017). Tunable multiscale
nanoparticle ordering by polymer crystallization. ACS Cent. Sci. 3: 751–758.
86 Zhang, K., Gao, L., and Chen, Y. (2007). Organic-inorganic hybrid materials
by self-gelation of block copolymer assembly and nanoobjects with controlled
shapes therof. Macromolecules 40: 5916–5922.
87 Zhang, K., Gao, L., and Chen, Y. (2008). Smart organic/inorganic hybrid
nanoobjects with controlled shapes by self-assembly of gelable block copoly-
mers. Macromolecules 41: 1800–1807.
88 Gao, L., Zhang, K., and Chen, Y. (2011). Functionalization of shaped polymeric
nanoobjects via bulk co-self assembling gelable block copolymers with silane
coupling agents. Polymer 52: 3681–3686.
89 Qin, J., Jiang, X., Gao, L., and Chen, Y. (2010). Functional polymeric
nanoobjects by cross-linking bulk self-assemblies of poly(tert-butyl
acrylate)-block-poly(glycidyl methacrylate). Macromolecules 43: 8094–8100.
90 Hoppenbrouwers, E., Li, Z., and Liu, G. (2003). Triblock nanospheres with
amphiphilic coronal chains. Macromolecules 36: 876–881.
91 Ruan, Y., Gao, L., Yao, D. et al. (2015). Polymer-grafted nanoparticles with
precisely controlled structures. ACS Macro Lett. 4: 1067–1071.
92 Charleux, B., Delaittre, G., Rieger, J., and D’Agosto, F. (2012).
Polymerization-induced self-assembly: from soluble macromolecules to block
copolymer nano-objects in one step. Macromolecules 45: 6753–6765.
93 Karagoz, B., Esser, L., Duong, H.T. et al. (2014). Polymerization-induced
self-assembly (PISA) – control over the morphology of nanoparticles for drug
delivery applications. Polym. Chem. 5: 350–355.
94 Zhou, W., Qu, Q., Xu, Y., and An, Z. (2015). Aqueous polymerization-induced
selfassembly for the synthesis of ketone-functionalized nano-objects with low
polydispersity. ACS Macro. Lett. 4: 495–499.
95 Mitchell, D.E., Lovett, J.R., Armes, S.P., and Gibson, M.I. (2016). Combining
biomimetic block copolymer worms with an ice-inhibiting polymer for the
solvent-free cryopreservation of red blood cells. Angew. Chem. Int. Ed. Engl. 55:
2801–2804.
References 1049
Chem 2: 93–101.
97 Figg, C.A., Hickman, J.D., Scheutz, G.M. et al. (2018). Color-coding visible light
polymerizations to elucidate the activation of trithiocarbonates using Eosin Y.
98 Li, N., Ding, D., Pan, X. et al. (2017). Temperature programed photo-induced
RAFT polymerization of stereo-block copolymers of poly(vinyl acetate). Polym.
Chem. 8: 6024–6027.
99 Uchiyama, M., Satoh, K., and Kamigaito, M. (2016). A phosphonium intermedi-
ate for cationic RAFT polymerization. Polym. Chem. 7: 1387–1396.
100 Michaudel, Q., Chauvire, T., Kottisch, V. et al. (2017). Mechanistic insight into
the photocontrolled cationic polymerization of vinyl ethers. J. Am. Chem. Soc.
139: 15530–15538.
vinyl ether)-block-poly(vinyl fluoride) block copolymers. ACS Macro Lett. 6:
393–398.
102 Kottisch, V., Michaudel, Q., and Fors, B.P. (2017). Photocontrolled inter-
conversion of cationic and radical polymerizations. J. Am. Chem. Soc. 139:
10665–10668.
1051
23
High-Throughput/High-Output Experimentation in RAFT

Polymer Synthesis
Carlos Guerrero-Sanchez 1,2 , Roberto Yañez-Macias 3 , Miguel Rosales-Guzmán 4 ,
Marco A. De Jesus-Tellez 5 , Claudia Piñon-Balderrama 6 , Joris J. Haven 7 , Graeme
Moad 8 , Tanja Junkers 7 , and Ulrich S. Schubert 1,2
1
Friedrich Schiller University Jena, Laboratory of Organic and Macromolecular Chemistry (IOMC),
Humboldtstrasse 10, Jena 07743, Germany
2
Friedrich Schiller University Jena, Jena Center for Soft Matter (JCSM), Philosophenweg 7, Jena 07743,
Germany
3
Centro de Investigación en Química Aplicada (CIQA), Blvd. Enrique Reyna H. 140, Saltillo, Coahuila 25100,
México
4
Universidad Tecnológica de Saltillo, Calle Nogal s/n, Ejido la Providencia, Saltillo, Coahuila 25300, México
5
Centro de Investigación y de Estudios Avanzados (CINVESTAV) Unidad Mérida, A.P. 73, Cordemex, Mérida,
Yucatán 97310, México
6
Centro de Investigación en Materiales Avanzados S. C. (CIMAV-Unidad Monterrey), Advanced Functional
Materials & Nanotechnology Group, Polymer Science & Nanotechnology Lab., Av. Alianza Norte 202,
Autopista Monterrey-Aeropuerto Km 10, PIIT, Apodaca, Nuevo León C.P.66628, México
7 Monash University, School of Chemistry, Polymer Reaction Design Group, 19 Rainforest, Walk Clayton, VIC
3800, Australia
8
23.1 Introduction
High-throughput/high-output experimentation (HT/HO-E), introduced in polymer

research laboratories around the globe over the past two decades, has proven to be a
powerful technique for synthesis, characterization, and screening of polymers. The
main goal has been to expedite the discovery process for new materials by mak-
ing it both more efficient and cost-effective [1–12]. The versatility of HT/HO-E has
allowed the study of a diverse range of reversible addition fragmentation chain trans-
fer (RAFT) polymerization processes, for instance, in homogeneous or heteroge-
neous media, [13–17] or at ambient or high pressure (e.g. suitable techniques for
polymerizing low boiling point monomers) [18]. In addition, both on- and off-line
techniques have also been developed for monitoring the progress of polymeriza-
tion reactions [19–24] as well as HT/HO-E techniques for measuring properties of
generated polymer libraries [1, 2, 5–12]. Thus, HT/HO-E has led to the efficient iden-
tification of suitable polymers for applications such as industrial coatings, sensors,
and biomaterials [6, 7, 9, 11, 25–28].
This contribution analyses the state of the art and utility of HT/HO-E applied in
RAFT synthesis, characterization, and screening of polymer materials. Emphasis is
1052 23 High-Throughput/High-Output Experimentation in RAFT Polymer Synthesis
placed on fundamental aspects and experimental ‘bottlenecks’, which are normally

not addressed in detail in the existing literature. Some of these bottlenecks include
achieving precision and reproducibility in synthetic and product purification
methods. The utilization of HT/HO-E in the field of RAFT polymerization to screen
reagents, evaluate reaction conditions (i.e. the so-called kinetic investigations), and
generate comprehensive and systematic polymer libraries is also discussed. Next,
the importance of screening RAFT polymer libraries generated by HT/HO-E is
illustrated with selected applications in the biomedicine field. Finally, some recom-
mendations and future perspectives for HT/HO-E for RAFT polymer research are
provided.
23.2 Fundamental Experimentation and Limitations

of HT/HO-E in RAFT Polymer Synthesis
Perhaps the most crucial aspect of utilizing HT/HO-E relates to the generation of
reliable experimental data and, therefore, meaningful conclusions derived thereof.
Often, this aspect is partly overlooked. The sometimes over-enthusiastic descrip-
tions of the technological features incorporated in available HT/HO-E platforms can
give rise to the perception that they are all-purpose machines. However, while they
have been validated for several experimental protocols, HT/HO-E platforms must
not be regarded as ‘black boxes’ where all generated data and results are necessarily
precise and reliable. Thus, it is ‘a must’ for any experimentalist to, first of all, ver-
ify the reproducibility and accuracy of the HT/HO-E methods for specific research
tasks.
A particular example of this situation relates to air-sensitive polymerizations (i.e.
moisture and/or oxygen intolerant systems), where suitable pre-conditioning pro-
cedures for reaction vessels and the various components involved in these reac-
tions must be developed and applied before synthesis (e.g. ionic polymerizations).
This is also true for RAFT synthesis as propagating polymer chains are prone to
react with oxygen at diffusion-controlled rates. In this regard, suitable degassing pro-
cesses to eliminate oxygen from reaction media in conventional lab-scale reactors
have been reported, including refluxing of reaction media, inert gas sparging, ultra-
sonic agitation, and freeze–evacuate–thaw protocols [29]. Implementation of these
pre-conditioning processes might negatively impact on the number of reactions that
can be performed in a determined period of time and, therefore, on the productiv-
ity and cost of a project. To minimize this drawback, different degassing methods
have been successfully adapted to HT/HO-E platforms. For instance, many HO-E
platforms designed for automated parallel synthesis can maintain an inert atmo-
sphere within parallel reactors to avoid the exposure of polymerization media to
atmospheric oxygen [30]. Furthermore, parallel reactors can also be placed inside
of a hood or glove box containing an inert atmosphere to allow handling reagents
under these conditions throughout the course of the synthesis [30]. Under these
set-ups, the parallel reactors of a given automated parallel synthesizer would first
be heated and subjected to several evacuate – ‘fill with inert gas’ cycles to eliminate
oxygen and create an appropriate inert atmosphere for the polymerizations [31–33].
Other alternative oxygen-tolerant synthetic techniques and degassing methods have
also been successfully implemented to perform RAFT polymerizations, for instance,
in microwell plates open to air using simple robotics [34] or manual preparation of
the reaction mixtures, [23, 35–39] and an automated parallel freeze–evacuate pro-
cedure [40]. This latter example demonstrated that RAFT polymerizations carried
out in a commercially available automated parallel synthesizer can be very simi-
lar to those performed utilizing a high vacuum freeze–evacuate–thaw protocol in
individual flame-sealed glass ampoules. Other degassing experimental procedures
to eliminate oxygen from polymerization reactions have also been discussed in the
literature [41–43].
23.3 HT/HO-E Kinetic Investigations
Fundamental understanding of reaction mechanisms and kinetics is essential for

designing polymer materials and optimizing chemical processes [13, 20, 44–50]
For instance, the estimation of reactivity ratios for a comonomer pair is a crucial
quantitative aspect in efficiently designing copolymer materials. In this regard,
experimental data obtained through HT/HO-E, available kinetic models, and
computer programs [51] are valuable tools for the estimation of such parameters.
For example, Rosales-Guzmán et al. reported a HO-E protocol (suitable for low
boiling point monomers) to perform RAFT parallel copolymerizations of glycidyl
methacrylate (GMA) and isoprene (IP) at different reaction conditions (i.e. rela-
tively high pressure and high temperature) and used the obtained kinetic data to
estimate the reactivity ratios of this comonomer system [18]. Guerrero-Sanchez
et al. reported a detailed kinetic study on the RAFT copolymerization of methyl
acrylate (MA) and vinyl acetate (VAc) over a broad interval of comonomer feed
compositions, where the obtained comprehensive experimental data allowed for
reliable estimation of the reactivity ratios for this copolymerization system [20].
Other kinetic investigations are the contributions reported by Keddie et al.
[13, 47, 50] on the use of acid/base switchable RAFT agents for the copolymer-
ization of more- and less-activated monomers. For example, the effect of acids of
different strengths and stoichiometries with respect to RAFT agent on the polymer-
ization of N,N-dimethylacrylamide (DMAm) was investigated taking advantage of
automated pH measurements and nuclear magnetic resonance (NMR) sampling
incorporated in a commercially available parallel synthesizer (Figure 23.1) [13]. The
results showed the effect of pK a and acid concentration on the dispersity (Ð), molar
mass, and end groups of the synthesized polymers and demonstrated that switch-
able RAFT polymerization is most effectively carried out in the presence of strong
acids in equimolar amounts (i.e. not exceeding the RAFT agent concentration).
On neutralizing the RAFT end group, it was also possible to form a second block
with the less-activated monomers, VAc and N-vinylpyrrolidone (NVP), and the
intermediate-activated monomer N-vinylcarbazole (NVC), thereby demonstrating
1.50
1 equiv. 8.70 0.3
1.45 0.5 equiv.
0.2 equiv. 8.68 0.2
1.40
8.66 0.1
2nd Derivative
1.35 8.64 0.0
Mw/Mn
δ ppm
1.30 8.62 –0.1
1.25 8.60 –0.2
1.20 8.58 –0.4
1.15 8.56 –0.4
1.10 8.54 –0.5

H H H H 1 2 3 4 5 6
O 2 2 O
Ts CO CO Ac pH
CF3 H2
C
CI
(a) (b)
Figure 23.1 (a) Relationship between acid strength or concentration on the polymer
dispersity (Ð) and (b) a proton nuclear magnetic resonance (1 H NMR) titration curve of a
switchable RAFT agent with an acid; experiments were performed in an automated parallel
synthesizer. Source: Keddie et al. [13]. © 2011, American Chemical Society.
S S Figure 23.2 Schematic

R' “switch” representation of acid/base
N S CN R'
N S CN switchable RAFT agents for
Base
the polymerization of MA,
Acid VAc, and NVC screened with
Controls Controls the aid HO–E techniques.
N MA N NVC,VAc Source: Reproduced with
H
permission from Keddie
H3CO F NC et al. [47]. © 2012, American
R' N
H3C Chemical Society.
Increasing activity
the utility of the switchable RAFT procedure for the synthesis of block copolymers
comprising segments of more- and less-active monomers.
In a second contribution, the RAFT polymerization of MA, NVC, and VAc was
investigated by screening a series of acid/base switchable RAFT agents with N-aryl
substituents (Figure 23.2) [47]. The outcome of these HO-E investigations [13, 47,
50] allowed optimal conditions for the preparation of low Ð NVC-containing block
copolymers to be established and provided a better understanding of the kinetics
of acid/base switchable RAFT polymerization reactions of MA, VAc, and NVC. The
status of NVC as an intermediate-activated monomer was also established.
In another approach, Voorhaar et al. [46] discussed the preparation of ABA
amphiphilic quasi-triblock copolymers with self-healing properties, where the
middle hydrophilic block contained N-acryloylmorpholine (NAM) units, while the
outer hydrophobic quasi-blocks were formed with isobornyl acrylate (IBA). Firstly,
a HO-E kinetic study was performed to determine conditions for an acceptable rate
Autonomous platform for polymer synthesis
Monomer Mn, Mw, D
Control agent
Initiator
Flow reactor Online SEC
Solvent
Figure 23.3 Schematic representation of the system for the self-optimization of RAFT
polymerizations described by Rubens et al. The product stream is injected into an on-line
SEC system, subsequently analyzed and processed by an optimization algorithm. Source:
Rubens et al. [48]. © 2019, John Wiley & Sons.
of the RAFT polymerization of NAM. The use of an appropriate bifunctional RAFT

agent ensured that IBA was incorporated on both sides of the NAM segment to
provide ABA triblock copolymers.
A relatively new RAFT polymerization technique known as photoinduced
energy or electron transfer polymerization (PET-RAFT) has also been reported,
which under certain conditions can be performed under the presence of oxygen
[52, 53]. Kinetic investigations of this technique have been carried out using parallel
polymerizations in micro-well plates [23, 38, 54]. For example, Yeow et al. [23]
carried out the HT/HO-E PET-RAFT synthesis of poly(N,N-dimethylacrylamide)
(PDMAm) using 5,10,15,20-tetraphenylporphine zinc (ZnTPP) as a photocatalyst,
where a spectroscopic technique was utilized to estimate monomer conversion. Ng
et al. [38] also utilized PET-RAFT to study polymerization kinetics of acrylamides,
(meth-)acrylates, and styrenics utilizing ZnTPP as a photocatalyst activated under
yellow light; these systems exhibited an oxygen tolerance as well as a good control
over architecture and molar mass of the obtained polymers.
Continuous flow systems can also be used as HT/HO-E tools for the optimiza-
tion of reaction conditions [48, 55–57]. Rubens et al. introduced an autonomous
platform system for polymer reactions that comprises a continuous flow reactor
coupled with a size exclusion chromatography (SEC) equipment for online mea-
surements (Figure 23.3) [48]. The system is controlled by a self-learning algorithm
able to self-optimize reaction conditions by modifying reaction time, monomer con-
centration, and RAFT agent/initiator ratio to produce polymers of targeted molar
mass with high precision and reproducibility (<2.5% deviation from pre-selected
goal). As model reactions, the thermal and photo-induced RAFT polymerization of
(meth-)acrylates was reported.
23.4 Utilization of HT/HO-E for the RAFT Synthesis

of Polymer Libraries
The synthesis and accessibility of polymer libraries have opened straightforward
opportunities for the elucidation of structure–property–function relationships of
polymers, a better understanding of any potential impediments to research and/or
the development of new applications. Several HT/HO-E approaches to access such
libraries have been reviewed in the literature [12]. These polymer libraries, in com-
bination with different robotic platforms, allow for a fast and efficient optimization
of material properties and materials design [6, 7, 9, 23, 38, 45, 50, 58–60].
A relatively recent trend has revolved around the development of ‘one-pot’ syn-
thetic strategies that produce the so-called quasi-block copolymers [45, 46, 61–63].
The strategy can be considered as a variant of spontaneous gradient copolymers
[20, 64]. These ‘one-pot’ RAFT syntheses have driven efficient HT/HO-E workflows
by eliminating time-consuming intermediate purification steps from complex
multi-step reaction protocols and thereby increased research productivity. Addi-
tionally, premature hydrolytic cleavage was achieved in copolymerization reactions
employing monomers that possess esters and amides as a side group; the prepared
polymer libraries could be used in applications such as surface modification or drug
delivery systems [65].
Guerrero-Sanchez et al. [61] prepared a 15-member quasi-diblock copoly-
mer library of poly(butyl methacrylate-quasi-block-methyl methacrylate)
(P(BMA-qb-MMA)). Three poly(butyl methacrylate) (PBMA) macroRAFT agents
were prepared and aliquots distributed into three sets of five reactors each with the
aid of a liquid handling system of an automated parallel synthesizer. Next, different
amounts of methyl methacrylate (MMA) monomer were added into each reactor of
each series, respectively, and allowed polymerizations continued. Figure 23.4 shows
a schematic representation of one of these series (i.e. 5 quasi-diblock copolymers).
This synthetic approach yields quasi-diblock copolymers rather than pure diblock
copolymers. Nonetheless, it was demonstrated by differential scanning calorimetry
(DSC) that the properties of these materials strongly resemble those expected for
the pure diblock copolymers in that two well-defined glass transition temperatures
characteristic of PBMA and poly(methyl methacrylate) (PMMA) were observed.
In a similar fashion, Haven et al. [45] reported the synthesis of a comprehensive
quasi-diblock copolymer library of butyl methacrylate (BMA) with MMA. In this
approach, PBMA was first synthesized as a macroRAFT agent in high, but not
complete, monomer conversion. Thereafter, without any intermediate purifica-
tion procedure, predetermined amounts of MMA (second monomer), additional
initiator, and solvent were sequentially added into the same reaction pot for
proceeding with the synthesis of a series of the quasi-block copolymer materials or,
more accurately, PBMA-block-P(BMA-stat-MMA). Different temperature profiles
were also tested in optimizing the reaction parameters. In a single experiment,
23 quasi-diblock copolymers (corresponding to time intervals for sampling of one
hour) were obtained by simply taking aliquots from the reactor with the automated
liquid handling system of the parallel synthesizer. This procedure provided valuable
23.4 Utilization of HT/HO-E for the RAFT Synthesis of Polymer Libraries 1057
BMA / RAFT /
VA ZO 88 / DMF MMA / DMF
1
1A
1B
1C
1D
1E
1000 10000 100000
Molar mass
(a) (b) (c)
O
BuO O
NC S OBu S
NC
C12H25 C12H25
HO2C S S VAZO 88 HO2C S S
n
DMF, 85 °C, 9 h
O
OMe BuO O BuO O MeO O
NC S
C12H25
DMF, 85 °C, 9 h HO2C m n q
S S
Figure 23.4 Schematic representation of the automated parallel synthesis of a

quasi-diblock copolymer library via sequential RAFT polymerization (a). SEC traces of some
of the obtained quasi-diblock copolymers illustrating a successful chain extension process
or block formation (b). Reaction scheme of the utilized sequential RAFT polymerization
process (c). Source: Adapted with permission from Guerrero-Sanchez et al. [61]. © 2013,
Royal Society of Chemistry.
and detailed information about the evolution of the molar mass distribution and
the rate of incorporation of MMA and the BMA ‘impurity’ into the quasi-block and,
thus, the monomer sequence distribution. From the kinetic plots, it was concluded
that the sequential RAFT polymerization reaction was well controlled throughout
the entire process. Haven et al. [62] also applied these sequential RAFT polymeriza-
tion techniques to prepare a higher order quasi-block copolymer library comprising
71 different quasi-diblock, -triblock, -tetrablock, and -pentablock copolymers in
an automated parallel synthesizer. A mono-functional RAFT agent was utilized
for the synthesis of ABC and ABCD copolymers while a bi-functional RAFT agent
allowed preparation of BAB and CBABC sequences. In these examples A, B, C, and
D represent BMA, MMA, di(ethylene glycol) methyl ether methacrylate (DEGMA),
and benzyl methacrylate (BzMA), respectively.
While conventional RAFT polymerizations require an inert atmosphere and
the elimination or minimization of oxygen in the reaction media, the implemen-
tation of RAFT polymerization in the presence of oxygen has also been reported
with the subsequent synthesis of polymer libraries [23, 34, 36–38, 60, 63, 66].
For example, Chapman et al. [37] reported a manual combinatorial approach
for the low-temperature (up to 50 ∘ C) RAFT synthesis of homo and copolymers
based on DMAm, NAM, 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl
acrylate (HEA), poly(ethylene glycol) methyl ether methacrylate (PEGMA), and
N-(2-hydroxypropyl)methacrylamide (HPMAm) using glucose oxidase (GOx) as the
deoxygenating agent. Later, Wang et al. [67] also reported the use of GOx to deplete
oxygen in the RAFT polymerization of HEA in an automated and unattended
parallel synthesizer. The reactions were performed in open vessel systems to probe
the effectiveness GOx. The results of the enzyme-degassed reactions were compared
to those observed in reactions using a conventional degassing technique (i.e.
sparging nitrogen gas followed by a closed vessel to maintain an inert atmosphere).
At the investigated conditions, the results revealed that GOx retains sufficient
activity towards oxygen to carry out RAFT polymerizations in different aqueous
media offering a good control on the molar mass of the synthesized polymers and
low Ð (< 1.10). Cosson et al. [63] also reported the RAFT synthesis of star polymers
in PCR tubes in a conventional heating block, leading to a library of 60 polymers
based on N,N-diethylacrylamide (DEAm), N-hydroxyethylacrylamide (HEAm),
N-(3-methoxypropyl)acrylamide (MPAm), NAM, and N-ethylacrylamide (NEAm).
Nanoparticle libraries derived from block copolymer libraries with predictable
highly ordered morphologies (i.e. spherical and worm-like micelles, vesicles, etc.)
can also be produced by a simultaneous RAFT copolymerization/self-assembly
using the technique known as polymerization-induced self-assembly (PISA)
[68–71] in combination with HT/HO-E methods [59, 72, 73]. For example,
Tan et al. [73] developed a photoinitiated oxygen-tolerant method to prepare
well-defined nano-objects from the self-assembly of diblock and triblock copoly-
mers in multi-well plates open to air and at room temperature. A wide range of
morphologies such as sphere, worms, jellyfish, and vesicles were obtained by this
one-pot approach (Figure 23.5).
Piñón-Balderrama et al. [74] also used a HT/HO-E approach for the sulfonation of
the styrenic segment in a PMMA-PS library in order to introduce the functionality
of proton conductivity in this diblock copolymer system. Sulfonated polymers
were deposited on silicon wafers in the form of thin films to evaluate different
self-assembled morphologies. Block copolymers at moderate sulfonation level
(<50%) revealed the formation of lamellar and cylindric morphologies, while
highly sulfonated thin films (∼90%) showed a variety of morphologies such as a
bicontinuous structure, micelles, worm-like, and a combination of worm-like and
micelles structures after being exposed to different solvent vapours or to thermal
annealing procedures.
(Spheres)
Low volume (250 μl) (GOx) (405 nm) (Vesicles)
O2 H2O2
(Worms)
Glucose Gluconolactone
15 min 25 °C, < 15 min
(96-well plates) (96-well plates)
Figure 23.5 Schematic representation of enzymatically degassed photo-PISA-RAFT

polymerizations in 96-well plates. Source: Reproduced with permission from Tan et al. [73].
© 2017, American Chemical Society.
23.5 Applications of RAFT Polymer Libraries in Nanomedicine and Drug Delivery Systems 1059
A different strategy for modifying solvophobic behaviour and introducing

amphiphilic features in different substances was proposed by Estrada et al.
[75]. They used a series of poly(alkylmethacrylates) (i.e. poly(hexyl methacry-
late), poly(lauryl methacrylate), and poly(stearyl methacrylate)) to encapsulate
methylaluminoxane (MAO). The proposed encapsulation procedure induces
the formation of self-assembled nanostructures (inverse micellar like) in the
presence of organic solvents such as n-hexane and/or n-heptane. Subsequently,
the inverse micellar solution containing encapsulated MAO was treated with a
metallocene ((n-Bu-Cp)2 ZrCl2 ) to produce different catalytic systems of PnA-
MAs/MAO/(n-Bu-Cp)2 ZrCl2 that were tested in the polymerization of ethylene.
The results revealed that these micellar-like systems are able to function as ‘nanore-
actors’ to favour the coordination polymerization of ethylene by improving the
stabilization of the metallocene system.
23.5 Applications of RAFT Polymer Libraries

in Nanomedicine and Drug Delivery Systems
Research in drug delivery systems is a very active field whose main purpose is to
reach the precise control over the release process and the amount of drugs delivered
in a specific location for any particular disease in order to increase drug efficacy and
the safety of the patient. In this regard, bioactives, including small organic bioactive
molecules and biomacromolecules (i.e. (ribonucleic acid) RNA, deoxyribonucleic
acid (DNA), proteins, and peptides), and materials with amphiphilic, biodegrad-
able, or stimuli-responsive (pH and temperature) properties, are intensively stud-
ied compounds for this purpose [76–79]. RAFT copolymers represent a promising
alternative for drug delivery systems because they can be readily synthesized con-
taining important properties for fulfilling the requirements of these applications. In
this regard, molar mass, macromolecular architecture, functionality, and composi-
tion of (co-)polymers all play an important role in determining the effectiveness of
a certain drug delivery vehicle. Because structure–property–function relationships
cannot be easily predicted, it is often necessary to synthesize polymer libraries cover-
ing a broad range of properties in order to identify suitable candidates that show an
optimal performance in a particular application. HT/HO-E approaches offer advan-
tages over conventional experimental methods by allowing the accelerated synthesis
of comprehensive and systematic polymer libraries with improved accuracy and
reproducibility.
In this context, researchers have efficiently utilized HT/HO-E approaches for the
preparation of RAFT polymer libraries to screen different materials for applications
in nanomedicine. Selected examples in this direction are briefly discussed below.
Hinton et al. [27], synthesized a set of ABA quasi-triblock copolymers by sequen-
tial RAFT polymerization using an automated parallel synthesizer to investigate
the effect of polymer composition on cell viability, siRNA uptake, serum stability,
and gene silencing. These copolymers were based on oligo(ethylene glycol) methyl
ether methacrylate (OEGMA) and quaternized N,N-dimethylaminoethyl methacry-

late (DMAEMA) (cationic block). The ABA quasi-triblock copolymer series was syn-
thesized with different chain lengths of DMAEMA (38–192 monomer units) and
OEGMA (7–37 monomer units) blocks to determine ‘optimal’ values for copolymer
composition and molar mass to deliver active siRNA while retaining serum stability
and minimal toxicity. The copolymers were prepared in a one-pot synthesis without
removing unreacted DMAEMA from the reaction mixture after the first polymeriza-
tion step. The results of this screening suggested that cell viability and gene silencing
efficiency were strongly correlated with the chain length of the cationic block with
110–120 monomer units being ‘optimal’. The ABA block copolymer architecture also
proved to be a critical aspect because the outer hydrophilic blocks inhibit particle
aggregation and contribute to serum stability and overall efficiency.
Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) is the basis of a
promising system for designing advanced biomaterials for gene transfection
[80]. In this regard, HT/HO-E has been a very useful approach to systemati-
cally modify and optimize copolymers containing this monomer. Adjustment
of parameters, such as molar mass, comonomer composition, degree of quat-
ernization, allow fine tuning properties such as solubility and cloud point of
derived aqueous solutions [81]. In this context, Perevyazko et al. [82] investi-
gated a PDMAEMA library and their corresponding quaternized versions (i.e.
poly[2-(methacryloyloxy) ethyl] trimethyl-ammonium iodide]s (PQDMAEMAs))
to evaluate fundamental macromolecular characteristics of these polymers in
solution such as the molecular hydrodynamics – size, molar mass, shape, and
conformation of the polymer chains. The effect of electrostatic interactions between
and within the quaternized polymer chains and the solvents was studied by
evaluating different properties such as viscosity, sedimentation velocity, density,
diffusivity, and absolute molar mass. The obtained results allowed establishing
structure–property relationships of the quaternized polymers in solution. For
example, it was observed that, even at low concentrations of heavy iodine ions in
the quaternized polymer chains, their rigidity and molecular volume in solution
was increased. In contrast, the partial specific volume showed lower values as
compared to the non-quaternized PDMAEMA precursors, which arose the discus-
sion whether iodine ions may be bound to the macromolecules or fully dissociated
in the solution. Lechuga et al. [83] have also employed a HT/HO-E strategy to
access a library of quasi-block copolymers based on PDMAEMA and quaternized
PDMAEMA (PDMAEMA-qb-P(DMAEMA-co-QDMAEMA)), which have a mod-
ified hydrophilic nature and thermo-induced self-assembly properties in aqueous
solution. The one-pot synthetic strategy in combination with the proposed chemical
modification yielded a variety of nanostructures as a function of temperature.
Morphological transitions of the PDMAEMA-qb-P(DMAEMA-co-QDMAEMA)
were assessed by atomic force microscopy (AFM), revealing the formation of
metastable nanostructures in aqueous solution, where the associative and cationic
interactions of the quaternized moieties present in the polymer chains allows the
stabilization of the formed nanostructures.
A promising approach to improve drug delivery processes is to covalently attach

bioactive moieties into the backbone of polymer chains to yield the so-called
macromolecular prodrugs (MPs) [84]. Zelikin’s group has explored HT/HO-E
polymer synthesis to obtain antiviral RAFT polymer libraries. This effort has
resulted in several valuable contributions focused on the synthesis of MPs [85–87].
One of these contributions described two different ribavirin (RBV)-containing
polymer libraries and demonstrated the therapeutic benefit of these compounds
as broad-spectrum antiviral agents [87]. RBV is a nucleoside analogue that acts
as an antiviral, but it has a limited efficacy because it can produce side effects
(i.e. accumulation in the red blood cells) linked to the development of anaemia
[88]. To address this dose limiting side effect and facilitate an efficient delivery
of RBV, the synthesis and screening of MP libraries with systematic variations in
molar mass and RBV content was performed [87]. These polymer libraries were
based on RBV (meth-)acrylate derivatives that were copolymerized with either
acrylic or methacrylic acid (MAA) using the RAFT technique to achieve a good
control over the RBV loading onto the polymer chains as well as of the molar
mass. The materials were prepared in a commercially available automated parallel
synthesizer and consisted of a total of 48 copolymers divided in one library of 23
poly(acrylate)s and another one of 25 poly(methacrylate)s. Figure 23.6 graphi-
cally shows the obtained experimental values of the number-average molar mass
- , and RBV content. The therapeutic effect of these two MP libraries was
(M n ), D
assessed by measuring the inhibition of production of nitric oxide (NO) in cultured
macrophages. The results showed that copolymers with M n greater than 20 kDa
were ineffective in delivering RBV, whereas acrylate-based polymers within the
range of M n ≈ 5–10 kDa showed the most effectiveness to suppress the production
1.2 1.2
D
1.1 1.1
1.0 1.0
40 40
RBV (%) Mn (kDa)
RBV (%) Mn (kDa)
20 20
0 0
20 20
10 10
0 0
Viability (%)
Viability (%)
100 100
50 50
0 0
100 100
Nitric oxide (%)
Nitric oxide (%)
80 80
60 60
40 40
20 20
0
Poly(acrylic acid) Poly(methacrylic acid)
Reference ribavirin:.... 10 μM ........ 100 μM
Figure 23.6 Graphic representation of the macromolecular characteristics of an MP library

synthesized by RAFT (from top to bottom: D - , Mn , and drug loading (mol% of RBV
(meth-)acrylate)), as well as viability of cultured macrophages and levels of NO produced.
Source: Reproduced with permission from Smith et al. [87]. © 2014, John Wiley & Sons.
of NO and matched the effect achieved by pristine RBV. In each series, an increase
in RBV content resulted in an enhancement of the therapeutic activity. Another
important observation was that poly(acrylic acid)-based polymers without a RBV
load (especially in the low molar mass range) exhibited low production levels of NO,
suggesting that RBV and polymer carrier both contributed to the overall therapeutic
effect. It is important to highlight that this was the first contribution that used
HT/HO-E for the accelerated synthesis, screening, optimization, and establishment
of structure–property–function relationships of antiviral MPs.
In another contribution, the same research group further exploited the bioactivity
of RBV and the advantages of HT/HO-E by designing, synthesizing, and evaluat-
ing a MP library with a dual activity for fighting human immunodeficiency virus
(HIV) and alleviating hepatitis (liver inflammation) [89]. For this, a RBV methacry-
late derivative was copolymerized with HPMAm, a monomer that has been widely
used in the synthesis of biocompatible polymers that act as carriers of drugs [86].
HT/HO-E was used to perform RAFT polymerizations to obtain a MP library com-
prising 17 unique compositions. The RAFT technique allowed the synthesis of mate-
rials with well-defined macromolecular characteristics including low D - , which is an
important property for establishing reliable structure–property–function relation-
ships. The dual bioactivity of this MP library was evaluated using cell culture mod-
els of relevance to the viral hepatitis and anti-HIV research. Because of toxic side
effects of RBV, the hemocompatibility of the polymers was also evaluated in parallel
through a quantitative analysis of their association with red blood cells, hemoly-
sis, and agglutination. The results were very promising because these MPs resulted
in being blood-safe, equally active, as compared to the pristine drug, in prevent-
ing infectivity of HIV and as efficacious as the pristine drug in the inflammation
read-out.
A third example in this field described effective and non-toxic MPs with ther-
apeutic effect against the HIV [85]. To accomplish this, Zelikin and coworkers
synthesized a methacrylate derivative of a well-established anti-HIV drug, azi-
dothymidine (AZT), and obtained copolymer libraries with systematic variation of
molar mass and AZT content. These polymer libraries were based on MAA and
HPMAm monomers and were synthesized with different degrees of polymerization
(50, 25, 250) and AZT load (from 0 up to 15 mol%) using RAFT polymerization
and HT/HO-E techniques. The polymers had low D - and molar mass in good
agreement with theoretical values consistent with a good control over the poly-
merization reaction. After analysing the antiviral activity of these polymer libraries
by various quantitative and qualitative methods, it was concluded that pristine
HPMAm polymers showed no intrinsic antiviral activity. In contrast, treatments
with AZT/HPMAm-containing copolymers showed an improved degree of inhi-
bition of viral infection as the AZT content increased regardless of molar mass.
For MAA-based MPs, remarkable results were achieved with pristine polymers,
which were highly efficient in preventing viral replication, for example, a 20 kDa
poly(methacrylic acid) (PMAA) homopolymer afforded an inhibition of the viral
replication to a non-detectable level, whereas a 10 kDa polymer decreased viral
replication by ca. 70%. This antiviral activity was improved by incorporating AZT
Drug Excipient Spray drying In vitro, Tabletization,

discovery discovery formulation in vivo tests clinical trials
Drugs Precipitation inhibitor Hydrophilic partner Lead excipient: poly(NIPAm-co-DMA)

O O HOOC S S
O NC a bn C12H25
HN NIPAm N DMA N HN S
H O N O
O NH O O
N Am NH2
DEA
O O OH
Phenytoin N O
OH HN
O O O
IPMA HEMA NH
O
N
O O
F
N
F
HN F
O High drug supersaturation
Nilutamide enhanced oral bioavailability
(a) (b) (c) (d)
Figure 23.7 Design of polymer carriers to tailor solubilization for highly hydrophobic
drugs of interest. (a) High-throughput controlled polymer synthesis and screening tools. In
this scheme, (b) the cyclic imide groups of phenytoin and nilutamide motivated the (c)
synthon approach to construct excipients combinatorially with precipitation inhibitor and
hydrophilic units. (d) For spray-dried dispersions with the leading excipient, the NIPAm
inhibitor units adsorbed onto amorphized phenytoin to increase the apparent drug
solubility by over an order of magnitude. Source: Reproduced with permission from Ting
et al. [91]. © 2016, American Chemical Society.
even at low levels. This information suggested that PMAA and AZT might act
synergistically against HIV.
Because many active pharmaceutical ingredients used in drug formulations are
highly hydrophobic, external inactive agents, known as excipients, are often used in
order to improve stability and bioavailability [90]. These compounds are frequently
polymer biomaterials that act as solubilizers of amorphous drug molecules by
suppressing their re-crystallization and by maintaining supersaturation in corre-
sponding dissolutions. This overcomes poor water solubility in gastrointestinal
tract and thereby increasing the therapeutic efficacy and safety. In this regard,
Reineke’s group developed valuable HT/HO-E methods to perform controlled
polymerizations and screenings for the systematic design of tailored polymer
carriers in terms of solubilization of highly hydrophobic drugs (i.e. phenytoin
and nilutamide) (Figure 23.7) [91]. RAFT polymerizations were carried out in a
semi-continuous parallel pressure reactor (ScPPR) to generate over 60 well-defined
polymers with molar masses ranging from 20 to 60 kDa. As depicted in Figure 23.7c,
N-isopropylacrylamide (NIPAm), DEAm, and isopropyl methacrylate (IPMAm)
monomers acted as precipitation inhibitors, while DMAm, acrylamide (Am), and
HEMA increased hydrophilicity of the system. With this HT/HO-E approach, it
was possible to determine an optimal balance between inhibitory and hydrophilic
co-monomers for maximizing drug solubility. In the case of phenytoin, the highest
solubilization was obtained with a poly(NIPAm-co-DMAm) containing 70 mol%
NIPAm.
The use of polymer nanoparticles for cellular delivery of bioactive agents has also
gained great research interest, with targets ranging from tumour cells to inflamed
tissues. These vehicles enable the delivery of pharmaceutical compounds in a
specific and controlled manner. HT/HO-E approaches have allowed the preparation
of block copolymer libraries, which can subsequently be utilized for self-assembling
nanoparticles. The potential benefit of using HT/HO-E approaches in the field
of RAFT copolymer-derived nanoparticles for cellular delivery was demonstrated
by Montgomery et al. [72], who reported the formation of polymer nanoparticles
(from 16 to 143 nm) from a library of RAFT quasi-block copolymers of poly(butyl
methacrylate-co-methacrylic acid) (P(BMA-co-MAA)) hydrophobic block and a
poly[poly(ethylene glycol) methyl ether methacrylate (475)] (P(PEGMA-475))
hydrophilic block, and their ability to act as delivery vehicles into macrophages.
Yildirim et al. [77] reported a dual responsiveness (pH and ultrasound) of polymer
nanoparticles based on a series of statistical RAFT copolymers derived from
3,4-dihydro-2H-pyran-protected HEMA 2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl
methacrylate as hydrophobic moiety and DMAEMA as hydrophilic moiety with
varying content of DMAEMA. In further evaluations of this copolymer system, Nile
red was encapsulated into the nanoparticles and its release profile was investigated
under ultrasound and acidic media exposures.
All in all, the contributions summarized above are clear examples of the bene-
fits and potential of HT/HO-E for the rapid development of efficient drug delivery
systems based on RAFT polymers.
23.5.1 Applications of RAFT Polymer Libraries as Antimicrobial Agents

HT/HO-E platforms have also been utilized for the RAFT synthesis of polymer
materials with antimicrobial properties. This has facilitated the understanding of
the interactions of different polymer materials with bacteria as different variables,
such as monomer nature, molar mass, macromolecular architecture, among
others, can be more systematically investigated. In the past decade, several groups
have developed antimicrobial materials based on cationic polymers prepared via
RAFT polymerization with conventional synthetic approaches [92–95]. Further
understanding of the antimicrobial mechanisms of action and optimization of
these drug-like polymers has also been achieved by combining HT/HO-E and
the PET-RAFT polymerization synthetic technique. For example, Richards et al.
studied a set of 108 antimicrobial copolymers based on DMAEMA (Figure 23.8)
[34]. In this contribution, copolymers with propylene glycol units with outstanding
antimicrobial activity were investigated and mechanistic studies demonstrated the
ability of these materials to inhibit growth of bacteria while minimizing the pertur-
bation of the cell membranes, suggesting an alternative antimicrobial mechanism
of action. Likewise, Boyer group studied the sequence effect of blocks of linear block
copolymers on antimicrobial and hemolytic activity [96]. Specifically, a library of 32
S NC S S
O O O O n m
R NC S S m N Antimicrobial
N OH S
O OO O
N HO N R
OH N
Variable unit
Liquid handling Haemotoxicity

robot
Parallel library synthesis
Figure 23.8 Schematic representation of a HT/HO-E workflow for the discovery of

antimicrobial polymers prepared by PET-RAFT. Source: Reproduced with permission from
Richards et al. [34]. © 2018, John Wiley & Sons.
well-defined multiblock copolymers with the same global composition comprising

hydrophobic, hydrophilic, and cationic monomeric units was synthesized in order
to mimic the structural features and function of phenylalanine, serine, and lysine,
respectively. With the rapid spread of antibiotic-resistant bacterial infections next
to a decline in the availability of new antibiotic drugs, the utilization of RAFT
polymerization in combination with HT/HO-E methods will be powerful tools
in the near future to produce optimized and effective antimicrobial polymers
by allowing fine-tuning different macromolecular parameters. Similarly, this
research approach might provide the required experimental evidence for a deeper
understanding of antimicrobial mechanisms as well as for establishing better
structure–property–function relationships.
23.6 Conclusions
The application of HT/HO-E methods has already provided significant progress in
the study of diverse RAFT polymers. While a substantial outlay of infrastructure is
required to implement HT/HO-E, traditional one-at-a-time methodologies are very
time consuming and therefore ultimately are of high cost with respect to HT/HO-E
in a long-term approach. Automated parallel synthesizers are now recognized to
be of high value for providing fundamental understanding of reaction mechanisms
and kinetics, essential for the design and optimization of RAFT polymerization
processes (Figure 23.9). HT/HO-E has made the synthesis of systematic polymer
libraries more accessible, which, in turn, offer more straightforward opportunities
for the elucidation of structure–property–function relationships. For example,
HT/HO-E synthesis and screening of polymer libraries has led to several advances
in nanomedicine. Although, the use of HT/HO-E has allowed continuous progress
in different areas of polymer chemistry, it has still limitations and various challenges
(a)
(b)
(c)
Figure 23.9 Images of commercially available HO-E tools for photo-assisted parallel RAFT
polymerizations (a), for process research and development with multiple feeding pumps
and automated gravimetric solid dispensing for PISA-RAFT polymerizations, (b) and
high-pressure parallel MTP/well-plate screening reactor blocks for small-scale RAFT
synthesis (c). Source: Images were kindly provided by Chemspeed Technologies AG
(Switzerland).
that have to be addressed to further increase its efficiency and output. First of all,
researchers must verify the reproducibility and accuracy of utilized HT/HO-E
methodologies to draw reliable research conclusions. An important example, in this
regard, relates to air-sensitive polymerizations, such as RAFT, where the utilization
of suitable degassing protocols or methods for eliminating oxygen is a mandatory
aspect for trustworthy HT/HO-E workflows. Furthermore, the development of
reliable and more efficient automated and parallel purification procedures as well
as the integration of on-line characterization methods is still largely unsolved
issues preventing the widespread exploitation and potential of HT/HO-E in the
polymer field. In relation to this, the HT/HO-E methods for the development
of novel synthetic approaches, such as the synthesis of quasi-block copolymers
summarized herein, offer ingenious but still perfectible solutions for the genera-
tion of systematic and comprehensive advanced polymer libraries. Nevertheless,
HT/HO-E approaches to obtain strictly ‘pure’ block copolymer libraries must be still
established for some polymerization methods such as RAFT, which need to include
automated, fast, and/or parallel polymer purification methods. Furthermore,
one-pot approaches may not always be fully suitable for the preparation of block
copolymers because of the intrinsic limitations of different reaction systems such
as solubility of the reagents, monomer reactivity ratios, tolerance to impurities,
etc. All in all, and even with these mentioned limitations, it can be concluded that
HT/HO-E is a facile, versatile, and cost-efficient method for the RAFT synthesis and
screening of polymer materials, as well as for the development and optimization of
RAFT polymerization processes. In the years to come, HT/HO-E is an experimental
methodology that will continue evolving and improving, in particular with the
advent of machine learning and artificial intelligence era, [21, 23, 24] to deliver
new and advanced polymer materials for the development of novel applications in
diverse areas of science and technology.
Abbreviations
Am acrylamide
AMA alkyl methacrylates
APMAm N-(3-aminopropyl)methacrylamide
AZT azidothymidine
BMA n-butyl methacrylate
DEGMA di(ethylene glycol) methyl ether methacrylate
DMAEMA N,N-dimethylaminoethyl methacrylate
DMAPMAm N-[3-(dimethylamino)propyl]methacrylamide
DNA deoxyribonucleic acid
DSC differential scanning calorimetry
-
D dispersity

GOx glucose oxidase
HO-E high-output experimentation
HT/HO-E high-throughput and high-output experimentation
HIV human immunodeficiency virus
HEA hydroxyethyl acrylate
HEAm N-(2-hydroxyethyl)acrylamide
HPMAm N-(2-hydroxypropyl)methacrylamide
IBA isobornyl acrylate
IP Isoprene
IPMA isopropyl methacrylate
MA methyl acrylate
MAO methylaluminoxane
Mn number average molar mass
MPs macromolecular prodrugs
MPAm N-(3-methoxypropyl)acrylamide
NEAm N-ethylacrylamide
NMR nuclear magnetic resonance
NO nitric oxide
OEGMA oligo(ethylene glycol) methyl ether methacrylate
PET-RAFT photo-induced electron/energy transfer-reversible
addition fragmentation chain transfer
PBMA poly(butyl methacrylate)
P(BMA-co-MAA) poly(butyl methacrylate-co-methacrylic acid)
P(BMA-qb-MMA) poly(butyl methacrylate-quasi-block-methyl
methacrylate)
PDMAm poly(N,N-dimethylacrylamide)
P(PEGMA-475) Poly[poly(ethylene glycol) methyl ether methacrylate
(475)]
PDMAEMA poly(N,N-dimethylaminoethyl methacrylate)
PEGMA poly(ethylene glycol) methyl ether methacrylate
PMAA poly(methacrylic acid)
PMMA poly(methyl methacrylate)
1 H NMR proton nuclear magnetic resonance
-qb- -quasi-block-
RAFT reversible addition fragmentation chain transfer
RBV Ribavirin
RDRP reversible deactivation radical polymerizations
RNA ribonucleic acid
ScPPR semi-continuous parallel pressure reactor
References 1069
SEC size exclusion chromatography

VAc vinyl acetate
ZnTPP 5,10,15,20-tetraphenylporphine zinc
Acknowledgements
R.Y.M thanks the support from CONACYT (Consejo Nacional de Ciencia y Tecnolo-
gia, Mexico) through the research grant 299092 (LANIAUTO). M.R.G. acknowledges
the support provided by Universidad Autónoma de Saltillo. M.A.J.T acknowledges
the financial support from CONACyT through project CB-2015/253303.
C.G.S and U.S.S. thank the Center for Excellence “PolyTarget” (SFB 1278, projects
B02 and Z01) of the Deutsche Forschungsgemeinschaft (DFG, Germany) for finan-
cial support.
J.J.H. kindly acknowledges funding from Monash University.
References
1 Davies, M.C., Alexander, M.R., Hook, A.L. et al. (2010). High throughput
surface characterization: a review of a new tool for screening prospective
biomedical material arrays. J. Drug Targeting 18: 741–751. https://doi.org/10
.3109/1061186X.2010.521941.
2 Kranenburg, J.M., Tweedie, C.A., van Vliet, K.J., and Schubert, U.S. (2009).
Challenges and progress in high-throughput screening of polymer mechanical
properties by indentation. Adv. Mater. 21: 3551–3561. https://doi.org/10.1002/
adma.200803538.
3 Guerrero-Sanchez, C., Zhang, J., Vitz, J., and Schubert, U.S. (2018).
High-throughput synthesis of polymers. Encycl. Polym. Sci. Technol. 6: 1–21.
https://doi.org/10.1002/0471440264.pst668.
4 Oliver, S., Zhao, L., Gormley, A.J. et al. (2019). Living in the fast lane – high
throughput controlled/living radical polymerization. Macromolecules 52: 3–23.
5 Hook, A.L., Anderson, D.G., Langer, R. et al. (2010). High throughput methods
applied in biomaterial development and discovery. Biomaterials 31: 187–198.
http://dx.doi.org/10.1016/j.biomaterials.2009.09.037.
6 Potyrailo, R., Rajan, K., Stoewe, K. et al. (2011). Combinatorial and
high-throughput screening of materials libraries: review of state of the art.
ACS Comb. Sci. 13: 579–633. https://doi.org/10.1021/co200007w.
7 De Boer, J. and Van Blitterswijk, C.A. (2013). Materiomics: High-Throughput
Screening of Biomaterial Properties. Cambridge University Press.
8 Schubert, U.S. and Kniep, C.S. (2003). High-throughput and combinatorial meth-
ods in polymer research: their time has come. Macromol. Rapid Commun. 24:
9 Algahtani, M.S., Scurr, D.J., Hook, A.L. et al. (2014). High throughput screening
for biomaterials discovery. J. Controlled Release 190: 115–126. http://dx.doi.org/
10.1016/j.jconrel.2014.06.045.
10 Schubert, U.S. and Amis, E.J. (2004). Combinatorial and high-throughput
approaches in polymer and materials science: hype or real paradigm shift?
Macromol. Rapid Commun. 25: 19. https://doi.org/10.1002/marc.200390106.
11 Grunlan, J.C. and Mehrabi, A.R. (2005). Introduction: combinatorial instruments
and techniques. Rev. Sci. Instrum. 76: 62101. https://doi.org/10.1063/1.1921587.
12 Webster, D.C. and Meier, M.A.R. (2010). Polymer Libraries: Preparation and
Applications BT – Polymer Libraries, 1–15. Berlin, Heidelberg: Springer Berlin
Heidelberg https://doi.org/10.1007/12_2009_15.
13 Keddie, D.J., Guerrero-Sanchez, C., Moad, G. et al. (2011). Switchable reversible
addition–fragmentation chain transfer (RAFT) polymerization in aqueous solu-
tion, N,N-dimethylacrylamide. Macromolecules 44: 6738–6745. https://doi.org/10
.1021/ma200760q.
14 Vandenbergh, J., de Moraes Ogawa, T., and Junkers, T. (2013). Precision synthe-
sis of acrylate multiblock copolymers from consecutive microreactor RAFT poly-
merizations. J. Polym. Sci. Part A Polym. Chem. 51: 2366–2374. https://doi.org/10
.1002/pola.26593.
15 Guerrero-Sanchez, C., Paulus, R.M., Fijten, M.W.M. et al. (2006).
High-throughput experimentation in synthetic polymer chemistry: from RAFT
and anionic polymerizations to process development. Appl. Surf. Sci. 252:
2555–2561. https://doi.org/10.1016/j.apsusc.2005.05.088.
16 Fijten, M.W.M., Meier, M.A.R., Hoogenboom, R., and Schubert, U.S.
(2004). Automated parallel investigations/optimizations of the reversible
addition-fragmentation chain transfer polymerization of methyl methacrylate.
J. Polym. Sci. Part A Polym. Chem. 42: 5775–5783. https://doi.org/10.1002/pola
.20346.
18 Rosales-Guzmán, M., Pérez-Camacho, O., Guerrero-Sánchez, C. et al. (2019).
Semiautomated parallel RAFT copolymerization of isoprene with glycidyl
methacrylate. ACS Comb. Sci. 21: 771–781. https://doi.org/10.1021/acscombsci
.9b00110.
19 Meier, M.A.R. and Schubert, U.S. (2005). Integration of MALDI-TOFMS as
high-throughput screening tool into the workflow of combinatorial polymer
research. Rev. Sci. Instrum. 76: 62211. https://doi.org/10.1063/1.1906123.
copolymerization systems. Macromol. Symp. 325–326: 38–46. https://doi.org/10
.1002/masy.201200038.
References 1071
21 Haven, J.J., Vandenbergh, J., and Junkers, T. (2015). Watching polymers grow:
real time monitoring of polymerizations via an on-line ESI-MS/microreactor
coupling. Chem. Commun. 51: 4611–4614. https://doi.org/10.1039/C4CC10426A.
22 Potyrailo, R.A., Wroczynski, R.J., Lemmon, J.P. et al. (2003). Fluorescence spec-
troscopy and multivariate spectral descriptor analysis for high-throughput
multiparameter optimization of polymerization conditions of combinato-
rial 96-microreactor arrays. J. Comb. Chem. 5: 8–17. https://doi.org/10.1021/
cc020062g.
23 Yeow, J., Joshi, S., Chapman, R., and Boyer, C. (2018). A self-reporting photo-
catalyst for online fluorescence monitoring of high throughput RAFT polymer-
ization. Angew. Chem. Int. Ed. 57: 10102–10106. https://doi.org/10.1002/anie
.201802992.
24 Liu, S., Cheng, Y., Zhang, H. et al. (2018). In Situ monitoring of RAFT poly-
merization by tetraphenylethylene-containing agents with aggregation-induced
emission characteristics. Angew. Chem. Int. Ed. 57: 6274–6278. https://doi.org/10
.1002/anie.201803268.
25 Schubert, U.S. and Kniep, C.S. (2003). No title. Macromol. Rapid Commun. (Spe-
cial Issue Guest Eds.). 24: 3–142.
26 Schubert, U.S. and Amis, E.J. (2004). Combinatorial material research and
high-throughput experimentation in polymer and material research. Macromol.
Rapid Commun. (Special Issue Guest Eds.). 25: 3–386.
27 Hinton, T.M., Guerrero-Sanchez, C., Graham, J.E. et al. (2012). The effect of
RAFT-derived cationic block copolymer structure on gene silencing efficiency.
Biomaterials 33: 7631–7642. http://dx.doi.org/10.1016/j.biomaterials.2012.06.090.
28 Russell, A.J., Baker, S.L., Colina, C.M. et al. (2018). Next generation
protein-polymer conjugates. AlChE J. 64: 3230–3245. https://doi.org/10.1002/
aic.16338.
29 Brown, J.N., Hewins, M., Van Der Linden, J.H.M., and Lynch, R.J. (1981).
Solvent degassing and other factors affecting liquid chromatographic detec-
tor stability. J. Chromatogr. A. 204: 115–122. http://dx.doi.org/10.1016/S0021-
9673(00)81646-5.
30 Schmatloch, S., Meier, M.A.R., and Schubert, U.S. (2003). Instrumentation
for combinatorial and high-throughput polymer research: a short overview.
Macromol. Rapid Commun. 24: 33–46. https://doi.org/10.1002/marc.200390018.
31 Hoogenboom, R., Fijten, M.W.M., Paulus, R.M., and Schubert, U.S. (2006).
Tailor-made copolymers via reversible addition fragmentation chain transfer the
fast way. In: Controlled Radical Polymerization (ed. K. Matyjaszewski), 32–473.
American Chemical Society https://doi.org/10.1021/bk-2006-0944.ch032.
32 Paulus, R.M., Fijten, M.W.M., de la Mar, M.J. et al. (2005). Reversible
addition-fragmentation chain transfer polymerization on different synthesizer
platforms. QSAR Comb. Sci. 24: 863–867. https://doi.org/10.1002/qsar.200520122.
33 Hoogenboom, R. and Schubert, U.S. (2003). The fast and the curious:
High-throughput experimentation in synthetic polymer chemistry. J. Polym.
Sci. Part A Polym. Chem. 41: 2425–2434. https://doi.org/10.1002/pola.10788.
34 Richards, S.-J., Jones, A., Tomás, R.M.F., and Gibson, M.I. (2018). Photochemical
“In-Air” combinatorial discovery of antimicrobial co-polymers. Chem. A Eur. J.
35 Yeow, J., Chapman, R., Xu, J., and Boyer, C. (2017). Oxygen tolerant photopoly-
merization for ultralow volumes. Polym. Chem. 8: 5012–5022. https://doi.org/10
.1039/C7PY00007C.
36 Lv, C., He, C., and Pan, X. (2018). Oxygen-initiated and regulated controlled
radical polymerization under ambient conditions. Angew. Chem. Int. Ed. 57:
37 Chapman, R., Gormley, A.J., Stenzel, M.H., and Stevens, M.M. (2016). Combi-
natorial low-volume synthesis of well-defined polymers by enzyme degassing.
Angew. Chemie. 128: 4576–4579. https://doi.org/10.1002/ange.201600112.
38 Ng, G., Yeow, J., Chapman, R. et al. (2018). Pushing the limits of high through-
put PET-RAFT polymerization. Macromolecules 51: 7600–7607. https://doi.org/10
39 Fu, Q., Xie, K., McKenzie, T.G., and Qiao, G.G. (2017). Trithiocarbonates as
intrinsic photoredox catalysts and RAFT agents for oxygen tolerant controlled
radical polymerization. Polym. Chem. 8: 1519–1526. https://doi.org/10.1039/
C6PY01994C.
40 Guerrero-Sanchez, C., Keddie, D.J., Saubern, S., and Chiefari, J. (2012). Auto-
mated parallel freeze–evacuate–thaw degassing method for oxygen-sensitive
reactions: RAFT polymerization. ACS Comb. Sci. 14: 389–394. https://doi.org/10
.1021/co300044w.
41 Becer, C.R., Groth, A.M., Hoogenboom, R. et al. (2008). Protocol for auto-
mated kinetic investigation/optimization of the RAFT polymerization of
various monomers. QSAR Comb. Sci. 27: 977–983. https://doi.org/10.1002/qsar
.200720159.
42 Rojas, R., Harris, N.K., Piotrowska, K., and Kohn, J. (2009). Evaluation of auto-
mated synthesis for chain and step-growth polymerizations: can robots replace
the chemists? J. Polym. Sci. Part A Polym. Chem. 47: 49–58. https://doi.org/10
.1002/pola.23119.
43 Chapon, P., Mignaud, C., Lizarraga, G., and Destarac, M. (2003). Automated par-
allel synthesis of MADIX (co)polymers. Macromol. Rapid Commun. 24: 87–91.
44 Zheng, Y., Luo, Y., Feng, K. et al. (2019). High throughput screening of gly-
copolymers: balance between cytotoxicity and antibacterial property. ACS Macro
45 Haven, J.J., Guerrero-Sanchez, C., Keddie, D.J., and Moad, G. (2014). Rapid and
systematic access to quasi-diblock copolymer libraries covering a comprehensive
composition range by sequential RAFT polymerization in an automated syn-
thesizer. Macromol. Rapid Commun. 35: 492–497. https://doi.org/10.1002/marc
.201300459.
46 Voorhaar, L., De Meyer, B., Du Prez, F., and Hoogenboom, R. (2016). One-Pot
automated synthesis of quasi triblock copolymers for self-healing physically
References 1073
crosslinked hydrogels. Macromol. Rapid Commun. 37: 1682–1688. https://doi.org/

10.1002/marc.201600380.
47 Keddie, D.J., Guerrero-Sanchez, C., Moad, G. et al. (2012). Chain transfer kinet-
ics of acid/base switchable N-Aryl-N-Pyridyl dithiocarbamate RAFT agents
in methyl acrylate, N-vinylcarbazole and vinyl acetate polymerization. Macro-
molecules 45: 4205–4215. https://doi.org/10.1021/ma300616g.
48 Rubens, M., Vrijsen, J.H., Laun, J., and Junkers, T. (2019). Precise polymer syn-
thesis by autonomous self-optimizing flow reactors. Angew. Chem. Int. Ed. 58:
49 Ting, J.M., Wu, H., Herzog-Arbeitman, A. et al. (2018). Synthesis and assembly
of designer styrenic diblock polyelectrolytes. ACS Macro Lett. 7: 726–733. https://
50 Tselepy, A., Schiller, T.L., Harrisson, S. et al. (2018). Effect of scandium triflate
on the RAFT copolymerization of methyl acrylate and vinyl acetate controlled
by an acid/base “Switchable” chain transfer agent. Macromolecules 51: 410–418.
51 Van Den Brink, M., Van Herk, A.M., and German, A.L. (1999). Nonlinear
regression by visualization of the sum of residual space applied to the inte-
grated copolymerization equation with errors in all variables. I. Introduction of
the model, simulations and design of experiments. J. Polym. Sci. Part A Polym.
Chem. 37: 3793–3803. https://doi.org/10.1002/(sici)1099-0518(19991015)37:
20<3793::aid-pola8>3.0.co;2-q.
52 Xu, J., Jung, K., Atme, A. et al. (2014). A robust and versatile photoinduced
living polymerization of conjugated and unconjugated monomers and its oxygen
tolerance. J. Am. Chem. Soc. 136: 5508–5519. https://doi.org/10.1021/ja501745g.
Chem. 6: 5615–5624. https://doi.org/10.1039/C4PY01317D.
54 Gormley, A.J., Yeow, J., Ng, G. et al. (2018). An oxygen-tolerant PET-RAFT poly-
merization for screening structure-activity relationships. Angew. Chem. Int. Ed.
55 Corrigan, N., Rosli, D., Jones, J.W.J. et al. (2016). Oxygen tolerance in living rad-
ical polymerization: investigation of mechanism and implementation in continu-
ous flow polymerization. Macromolecules 49: 6779–6789. https://doi.org/10.1021/
acs.macromol.6b01306.
56 Hornung, C.H., Guerrero-Sanchez, C., Brasholz, M. et al. (2011). Controlled
RAFT polymerization in a continuous flow microreactor. Org. Process Res. Dev.
15: 593–601. https://doi.org/10.1021/op1003314.
57 Hornung, C.H., von Känel, K., Martinez-Botella, I. et al. (2014). Continuous flow
aminolysis of RAFT polymers using multistep processing and inline analysis.
Macromolecules 47: 8203–8213. https://doi.org/10.1021/ma501628f.
58 Becer, C.R., Hahn, S., Fijten, M.W.M. et al. (2008). Libraries of methacrylic
acid and oligo(ethylene glycol) methacrylate copolymers with LCST behavior.
J. Polym. Sci. Part A Polym. Chem. 46: 7138–7147. https://doi.org/10.1002/pola

.23018.
59 Cockram, A.A., Bradley, R.D., Lynch, S.A. et al. (2018). Optimization of the
high-throughput synthesis of multiblock copolymer nanoparticles in aqueous
media via polymerization-induced self-assembly. React. Chem. Eng. 3: 645–657.
https://doi.org/10.1039/C8RE00066B.
60 Judzewitsch, P.R., Zhao, L., Wong, E.H.H., and Boyer, C. (2019).
High-throughput synthesis of antimicrobial copolymers and rapid evaluation
of their bioactivity. Macromolecules 52: 3975–3986. https://doi.org/10.1021/acs
.macromol.9b00290.
61 Guerrero-Sanchez, C., O’Brien, L., Brackley, C. et al. (2013). Quasi-block
copolymer libraries on demand via sequential RAFT polymerization in an
automated parallel synthesizer. Polym. Chem. 4: 1857–1862. https://doi.org/10
.1039/C3PY21135E.
62 Haven, J.J., Guerrero-Sanchez, C., Keddie, D.J. et al. (2014). One pot synthesis of
higher order quasi-block copolymer libraries via sequential RAFT polymeriza-
tion in an automated synthesizer. Polym. Chem. 5: 5236–5246. https://doi.org/10
.1039/C4PY00496E.
63 Cosson, S., Danial, M., Saint-Amans, J.R., and Cooper-White, J.J. (2017). Accel-
erated combinatorial high throughput star polymer synthesis via a rapid one-pot
sequential aqueous RAFT (rosa-RAFT) polymerization scheme, macromol. Rapid
Commun. 38 (8): 1600780. https://doi.org/10.1002/marc.201600780.
neous gradient copolymers with block- and gradient-like features. Polym. Chem.
8 (34): 5023–5032. https://doi.org/10.1039/C7PY00495H.
65 Heraud, C., Basuki, J., Hughes, T.C., and Mueller, M. (2019). Copolymerization
of pentafluorophenylmethacrylate with hydrophilic methacrylamide monomers
induces premature hydrolytic cleavage. Macromol. Rapid Commun. 40: 1900278.
66 Chapman, R., Gormley, A.J., Herpoldt, K.-L., and Stevens, M.M. (2014). Highly
controlled open vessel RAFT polymerizations by enzyme degassing. Macro-
67 Wang, M., Zhang, J., Guerrero-Sanchez, C. et al. (2019). Enzyme degassing for
oxygen-sensitive reactions in open vessels of an automated parallel synthesizer:
RAFT polymerizations. ACS Comb. Sci. 21: 643–649. https://doi.org/10.1021/
acscombsci.9b00082.
68 Karagoz, B., Boyer, C., and Davis, T.P. (2014). Simultaneous
polymerization-induced self-assembly (PISA) and guest molecule encapsulation.
Macromol. Rapid Commun. 35: 417–421. https://doi.org/10.1002/marc.201300730.
69 Warren, N.J. and Armes, S.P. (2014). Polymerization-induced self-assembly of
block copolymer nano-objects via RAFT aqueous dispersion polymerization. J.
Am. Chem. Soc. 136: 10174–10185. https://doi.org/10.1021/ja502843f.
70 Pei, Y. and Lowe, A.B. (2014). Polymerization-induced self-assembly: ethanolic
RAFT dispersion polymerization of 2-phenylethyl methacrylate. Polym. Chem. 5:
References 1075
71 Ng, G., Yeow, J., Xu, J., and Boyer, C. (2017). Application of oxygen tolerant
PET-RAFT to polymerization-induced self-assembly. Polym. Chem. 8: 2841–2851.
72 Montgomery, K.S., Davidson, R.W.M., Cao, B. et al. (2018). Effective macrophage
delivery using RAFT copolymer derived nanoparticles. Polym. Chem. 9: 131–137.
73 Tan, J., Liu, D., Bai, Y. et al. (2017). Enzyme-assisted photoinitiated
polymerization-induced self-assembly: an oxygen-tolerant method for preparing
block copolymer nano-objects in open vessels and multiwell plates. Macro-
74 Piñón-Balderrama, C., Leyva-Porras, C., Olayo-Valles, R. et al.
(2019). Self-assembly investigations of sulfonated poly(methyl
methacrylate-block-styrene) diblock copolymer thin films. Adv. Polym. Tech.
2019: 4375838. https://doi.org/10.1155/2019/4375838.
75 Estrada-Ramirez, A.N., Ventura-Hunter, C., Vitz, J. et al. (2019). Poly(n-alkyl
methacrylate)s as metallocene catalyst supports in nonpolar media. Macromol.
Chem. Phys. 220: 1970037. https://doi.org/10.1002/macp.201970037.
76 Stenzel, M.H. (2008). RAFT polymerization: an avenue to functional polymeric
micelles for drug delivery. Chem. Commun. 2008 (30): 3486–3503. https://doi
.org/10.1039/B805464A.
77 Yildirim, T., Yildirim, I., Yañez-Macias, R. et al. (2017). Dual pH and ultra-
sound responsive nanoparticles with pH triggered surface charge-conversional
properties. Polym. Chem. 8: 1328–1340. https://doi.org/10.1039/C6PY01927G.
78 York, A.W., Kirkland, S.E., and McCormick, C.L. (2008). Advances in
the synthesis of amphiphilic block copolymers via RAFT polymerization:
Stimuli-responsive drug and gene delivery. Adv. Drug Delivery Rev. 60:
1018–1036. http://dx.doi.org/10.1016/j.addr.2008.02.006.
79 Fairbanks, B.D., Gunatillake, P.A., and Meagher, L. (2015). Biomedical applica-
tions of polymers derived by reversible addition – fragmentation chain-transfer
(RAFT). Adv. Drug Delivery Rev. 91: 141–152. http://dx.doi.org/10.1016/j.addr
.2015.05.016.
80 Agarwal, S., Zhang, Y., Maji, S., and Greiner, A. (2012). PDMAEMA based gene
delivery materials. Mater. Today 15: 388–393. https://doi.org/10.1016/S1369-
7021(12)70165-7.
81 Yañez-Macias, R., Alvarez-Moises, I., Perevyazko, I. et al. (2017). Effect
of the degree of quaternization and molar mass on the cloud point of
poly[2-(dimethylamino)ethyl methacrylate] aqueous solutions: a systematic
investigation. Macromol. Chem. Phys. 218: 1700065. https://doi.org/10.1002/macp
.201700065.
82 Perevyazko, I., Lezov, A., Gubarev, A.S. et al. (2019). Structure-property
relationships via complementary hydrodynamic approaches:
poly(2-(dimethylamino)ethyl methacrylate)s. Polymer (Guildf). 182: 121828.
https://doi.org/10.1016/j.polymer.2019.121828.
83 Lechuga-Islas, V.D., Festag, G., Rosales-Guzmán, M. et al. (2020). Quasi-block
copolymer design of quaternized derivatives of poly(2-(dimethylamino)ethyl
methacrylate): investigations on thermo-induced self-assembly. Eur. Polym. J.

124: 109457. https://doi.org/10.1016/j.eurpolymj.2019.109457.
84 Zovko, M., Zorc, B., Novak, P. et al. (2004). Macromolecular prodrugs: XI. Syn-
thesis and characterization of polymer–estradiol conjugate. Int. J. Pharm. 285:
35–41. http://dx.doi.org/10.1016/j.ijpharm.2004.07.013.
85 Zuwala, K., Smith, A.A.A., Postma, A. et al. (2015). Polymers fight HIV: potent
(pro)drugs identified through parallel automated synthesis. Adv. Healthc. Mater.
4: 46–50. https://doi.org/10.1002/adhm.201400148.
86 Smith, A.A.A., Zuwala, K., Kryger, M.B.L. et al. (2015). Macromolecular pro-
drugs of ribavirin: towards a treatment for co-infection with HIV and HCV.
Chem. Sci. 6: 264–269. https://doi.org/10.1039/C4SC02754J.
87 Smith, A.A.A., Wohl, B.M., Kryger, M.B.L. et al. (2014). Macromolecular pro-
drugs of ribavirin: concerted efforts of the carrier and the drug. Adv. Healthc.
Mater. 3: 1404–1407. https://doi.org/10.1002/adhm.201300637.
88 Soota, K. and Maliakkal, B. (2014). Ribavirin induced hemolysis: a novel mecha-
nism of action against chronic hepatitis C virus infection. World J. Gastroenterol.
20: 16184–16190.
89 Kryger, M.B.L., Smith, A.A.A., Wohl, B.M., and Zelikin, A.N. (2014). Macro-
molecular prodrugs for controlled delivery of ribavirin. Macromol. Biosci. 14:
90 Ting, J.M., Navale, T.S., Jones, S.D. et al. (2015). Deconstructing HPMCAS:
excipient design to Tailor polymer–drug interactions for oral drug delivery. ACS
Biomater. Sci. Eng. 1: 978–990. https://doi.org/10.1021/acsbiomaterials.5b00234.
91 Ting, J.M., Tale, S., Purchel, A.A. et al. (2016). High-throughput excipient dis-
covery enables oral delivery of poorly soluble pharmaceuticals. ACS Cent. Sci. 2:
748–755. https://doi.org/10.1021/acscentsci.6b00268.
92 Paslay, L.C., Abel, B.A., Brown, T.D. et al. (2012). Antimicrobial
poly(methacrylamide) derivatives prepared via aqueous RAFT polymerization
exhibit biocidal efficiency dependent upon cation structure. Biomacromolecules
13: 2472–2482. https://doi.org/10.1021/bm3007083.
93 Chen, Y., Wilbon, P.A., Chen, Y.P. et al. (2012). Amphipathic antibacterial agents
using cationic methacrylic polymers with natural rosin as pendant group. RSC
Adv. 2: 10275–10282. https://doi.org/10.1039/c2ra21675b.
94 Treat, N.J., Smith, D., Teng, C. et al. (2012). Guanidine-containing methacry-
lamide (co)polymers via aRAFT: toward a cell-penetrating peptide mimic. ACS
Macro Lett. 1: 100–104. https://doi.org/10.1021/mz200012p.
95 Michl, T.D., Locock, K.E.S., Stevens, N.E. et al. (2014). RAFT-derived antimi-
crobial polymethacrylates: elucidating the impact of end-groups on activity and
cytotoxicity. Polym. Chem. 5: 5813–5822. https://doi.org/10.1039/C4PY00652F.
96 Judzewitsch, P.R., Nguyen, T.-K., Shanmugam, S. et al. (2018). Towards
sequence-controlled antimicrobial polymers: effect of polymer block order on
antimicrobial activity. Angew. Chem. Int. Ed. 57: 4559–4564. https://doi.org/10
.1002/anie.201713036.
1077
24
An Industrial History of RAFT Polymerization

Graeme Moad
CSIRO Manufacturing, Research Way, Clayton VIC 3168, Australia
24.1 Introduction
This chapter describes the history of radical polymerization with reversible
addition–fragmentation chain transfer (RAFT) and the rapid evolution in applica-
tions of that technique mainly through reference to the patent literature. To limit
the scope of this document, the tables are populated mainly by examples that have
proceeded to granted US patents.
In their 2008 Handbook of RAFT Polymerization chapter ‘Toward New Materials
Prepared via the RAFT Process: From Drug Delivery to Optoelectronics?’ (note the
question mark), Favier et al. [1] surveyed the potential for RAFT polymerization in
various areas and commented that the industrial impact would depend on the versa-
tility and applicability, and on the extra cost for the final product. In 2010, Destarac
came to a similar conclusion [2].
Ten years later, in 2018, the industrial uptake of RAFT and commercial successes
of the various processes for reversible deactivation radical polymerization (RDRP),
including RAFT with thiocarbonylthio compounds, were again considered by
Destarac [3], who asked whether the induction period was over. He comments that,
while the RDRP methods are firmly established as a powerful means for the devel-
opment of next-generation polymer products, there must still be improvements in
their cost/benefit ratio to bring about a broader adoption by industry. Despite this
challenge, the literature, including the patent literature, has seen extremely rapid
growth over the last 20 years.
24.2 Macromonomer RAFT Polymerization

The development of RAFT polymerization using thiocarbonylthio compounds
within the CSIRO–DuPont Engineered Resins Strategic Alliance has its origins
in the earlier developments of macromonomer RAFT polymerization and with
the earlier developments of catalytic chain transfer (CCT) and (not necessarily
reversible) addition–fragmentation chain transfer.

1078 24 An Industrial History of RAFT Polymerization
Reactive
double bond
Intermediate
Addition Fragmentation
kaddR kaddR
R' + H2C CH R R' CH2 CH2 R H2C CH2 R + R'
2 kaddR kaddR
Z Fragmentation Z Addition Z
Macromonomer Weak single bond Macromonomer
RAFT agent RAFT agent
Figure 24.1 Structural features of macromonomer RAFT agents and the intermediate
formed by addition of a radical R′⋅ . R, R′ are homolytic leaving groups (R⋅ must also be able
to efficiently reinitiate polymerization). The activating group Z modifies addition and
fragmentation rates and is typically ester (1), nitrile (2), or aryl (3). Compare with Scheme
2.1 in Chapter 2 (Terminology) [4].
Table 24.1 Macromonomer RAFT agent α-methylvinyl end groups, ZC(=CH2 )CH2 − .
Methacrylate Methacrylonitrile CH α-Methylstyrene CH

CH2 2 2
RO2C NC Ph
H2C H2C H2C
1 R=H, alkyl, substituted alkyl 2 3
The use of the macromonomers (1-3, Figure 24.1, Table 24.1) as addition–
fragmentation transfer agents dates from the 1980s [5]. However, the first pub-
lication relating explicitly to block copolymer synthesis using macromonomers
was published in 1994 (Table 24.2, entry 2). There are earlier patents on the use
of macromonomers in copolymerization of acrylates and methacrylates for the
production of graft copolymers (e.g. Table 24.2, entry 1). Based on the polymeriza-
tion conditions used, it is likely that RAFT complicated these polymer syntheses.
The first patent on the use of the macromonomer RAFT process to impart the
characteristics of living polymerization (low molar mass dispersity, ability to chain
extend, retained end-group functionality) to radical polymerization appeared
in 1996 (Table 24.2, entry 4). The patent was filed only shortly before the first
papers on the topic [27, 28]. Other patents covering the use of RAFT-crosslinking
polymerization to synthesize arm-first stars (Table 24.2; entry 9) and the synthesis
of core- or shell-crosslinked micelles based on RAFT-synthesized amphiphilic block
copolymers followed sometime later (Table 24.2; entry 12).
Patents relating to the synthesis of macromonomers with an α-methylvinyl
end group published subsequent to 1995 are likely to indicate block copolymer
synthesis as a potential application. Very recently, there has been a resurgence of
interest in macromonomer RAFT with various groups examining the properties of
macromonomer-based non-aqueous dispersions (NADs) [29, 30] and what is now
called ‘sulfur-free’ RAFT polymerization [31–33]. This has not yet been reflected in
new patent activity.
Table 24.2 Patents relating to macromonomer RAFT polymerization.
Number Prioritya) Dateb) Assignee Title Brief description ZC(=CH2 )CH2 –c)
1. US5010140A [6] 1989 1991 DuPont Process for preparing CCT used to prepare 1
stabilized polymer stabilized non-aqueous
dispersion dispersions
2. US5362826A 1992 1994 DuPont Method of preparing CCT used to prepare 1
US5371151A 1994 macromonomer macromonomers, which can
WO1993022351A1 [7] 1993 compositions be used to make blocks, etc.
3. US5310807A [8] 1992 1994 DuPont Star polymers made CCT used to prepare
WO1995021205A1 from macromonomers macromonomers, which can
made by cobalt chain be used to make stars
transfer process
4. WO199615157A1 [9] 1994 1996 DuPont– Polymer synthesis Low-dispersity polymers and 13
US6291620B1 2001 CSIRO block polymers by
macromonomer RAFT
polymerization
5. US5955532A 1997 1999 DuPont Aqueous coating Coatings based on use of
WO199903937A1 [10] 1999 composition of a macromonomers to form
self-stabilized self-stabilized latex by
crosslinked latex RAFT-crosslinking
polymerization
6. US5587431A 1995 1996 DuPont Synthesis of terminally Block synthesis in the
WO1996033224A1 [11] 1996 unsaturated oligomers presence of cobalt catalyst
(continued)
7. US6117921A 1996 2000 DuPont Process for making Blocks/grafts as

EP826751A2 [12] 1998 printed images using dispersants in ink-jet ink
pigmented ink jet
compositions
8. WO199731030A1 [13] 1997 1997 DuPont– Catalytic Hyperbranched polymer
US6624261B1 2003 CSIRO polymerization process synthesis
US7148297B2 2006
US7109282B2 2006
US7144963B2 2006
9. WO2000002939 1998 2000 DuPont– Microgels and process Star microgels by arm-first 1
US6653407B2 [14]d) 2003 CSIRO for their preparation method
10. US6262152B1 1998 2001 DuPont Particles dispersed Blocks/grafts as 1
WO2000020520A1 [15] 2000 w/polymer dispersant dispersants in ink-jet ink
having liquid soluble
and cross-linkable
insoluble segments
11. US6306994B1 [16] 1999 2001 DuPont Inks with enhanced Block copolymer pigment 1
substrate binding dispersants
characteristics
12. WO2001077198A1 [17]e) 2000 2001 DuPont– Process of microgel Microgels from 1
US7064151B1 2006 CSIRO synthesis and products self-assembly of
produced therefrom RAFT-made block
copolymers followed by
crosslinking
13. US6503975B1 2000 2003 DuPont Surfactant free Emulsion polymerization 1
EP1138730A2 [18] Axalta aqueous emulsions with macromonomers as
Coating polymerizable surfactants
Systems
14. WO2006138312A1 2005 2006 DuPont Rapid drying lacquers Rheology control agents 1
US20060287437A1 [19] 2015 Axalta containing triblock for coatings
US8937129B2 Coating copolymer for rheology
Systems control
15. WO2008080579A1 [20] 2006 2008 Byk Chemie Comb (block) Comb polymers based on 3
US8153731B2 2012 copolymers poly(styrene-co-maleic
anhydride)
AMS dimer RAFT agent
16. WO2009098025A1 [21] 2008 2009 Byk Chemie Wetting and dispersing Dispersing agents for 3
US8097076B2 2012 agent paints. AMS dimer RAFT
agent
17. US20100081769A1 [22] 2008 2010 DuPont Process for producing Block copolymer pigment 1
Axalta block copolymer dispersants
Coating pigment dispersants
Systems
18. WO2010036867A1 [23] 2008 2010 DuPont Block copolymer Block copolymer pigment 1
US20110144263A1 [24] 2011 Axalta pigment dispersants dispersants
Coating
Systems
19. WO2014074427A1 [25] 2012 2014 3M Addition-fragmentation Allyl sulfide and 1
US9410030B2 2016 agents macromonomer transfer
agents described
20. WO2016133668A1 [26] 2015 2019 3M Addition-fragmentation Stress-reducing 1
US10479848B2 oligomers crosslinking oligomers
a) Priority date.
b) Date published.
c) ZC(=CH2 )CH2 – groups exemplified (Table 24.1).
d) Other US divisionals cover other forms of RDRP.
e) Also covers thiocarbonylthio-RAFT.
Abbreviations: AMS, α-methylstyrene; AMS dimer, 2,4-dimethylpentene; CCT, catalytic chain transfer.
The CSIRO invention of macromonomer RAFT polymerization as a process for

RDRP can be traced to experiments making use of CCT in semi-batch (starved
monomer feed) emulsion polymerization that often provided polymers, which
were thought to have unusually low molar mass dispersity (Ð < 1.4). The use of
CCT for macromonomer synthesis with some reference to the patent literature and
applications of macromonomers has been reviewed by Gridnev and Ittel [34], Heuts
and Smeets [35], and more recently by Slavin et al. [36] and Demarteau et al. [37]
Relevant patents on CCT are summarized in Table 24.3.
There is indication of commercial exploitation of the technology in the literature
[32, 33], although the scale of this effort is difficult to establish. Various application
patents (Table 24.2) were filed by DuPont Performance Coatings, and later DuPont
Electronics or Axalta Coatings Systems, covering products such as coatings composi-
tions, dye or pigment dispersants for inks and coatings, and rheology control agents
(Table 24.2).
Several other methods for forming macromonomers with an α-methylvinyl end
group make use of addition–fragmentation chain transfer. This chemistry has been
reviewed by Rizzardo et al. [51], Moad et al. [52, 53], and Colombani et al. [54, 55].
Some of the patents filed in this area are summarized in Table 24.4. Another
method for producing macromonomers involves polymerization of monosubsti-
tuted monomers under high-temperature/high-dilution conditions, where the
α-methylvinyl end group is formed by backbiting β-scission – see Table 24.5.
24.3 Thiocarbonylthio-RAFT Polymerization

If the term RAFT agent is used unqualified, it can usually be understood to refer to a
thiocarbonylthio-RAFT agent, most often a dithioester, trithiocarbonate, xanthate,
or dithiocarbamate. In this section, we mainly consider thiocarbonylthio-RAFT
agents.
The number of patents or patent applications issued per year on thiocarbonylthio-
RAFT polymerization using the main classes of RAFT agent for the period
1998–2019 is shown in Figure 24.2a. The analysis is based on a ScifinderTM sub-
structure search carried out in April 2020 on the RAFT agent structures combined
with the terms (‘RAFT polymerization’ or ‘radical polymerization’) then refined
by document type = patent. Some patents may refer to more than one class of
RAFT agent. In this case, it will only contribute once to the total number. Scifinder
groups patents and patent applications that share a priority document. These patent
families will only contribute once to the total.
The substructure search is used to generate Figure 24.2, rather than simply
a search for RAFT polymerization, as there are a large number of patents that
mention RAFT polymerization in passing without any actual use of the technique.
In Figure 24.2b, the breakdown of patents or patent applications according to lan-
guage is shown. The number of Chinese language patents or patent applications is
approximately half the total. However, most Chinese applications do not proceed to
grant or to applications in other countries. In the tabulations that follow we have,
Table 24.3 Patents relating to forming macromonomers by catalytic chain transfer polymerization (CCT).
21. SU664434A1 [38] 1977 1980 USSR Method of preparing CCT using Co porphyrin 1
polymers, iminomers and catalysts
oligomers (Molecular
weight control of
methacrylic polymers)
22. US4526945A [39] 1984 1985 SCM Corp Low molecular weight CCT using Co(II) 1
polymers and copolymers glyoxime complexes
23. US4680354A [40] 1986 1987 Glidden Low molecular weight CCT using Co(II) 1
polymers and copolymers complexes
24. US4694054A [41] 1985 1987 DuPont Cobalt(II) chelates as CCT using Co(II) 12
chain transfer agents in complexes
free radical
polymerizations
25. US4722984A 1985 1988 DuPont Pentacyanocobaltate(II) CCT using Co(II) 1
EP229481A2 [42] 1987 catalytic chain transfer complexes
agents for molecular
weight control in free
radical polymerization
26. US4886861A [43] 1985 1989 DuPont Molecular weight control CCT using Co(II) 1
in free radical complexes with
polymerizations coordinated Lewis base
27. US4746713A [44] 1985 1988 DuPont Bimetallic catalytic chain CCT using bimetallic
transfer agents for complexes of W, Cr, Ru,
molecular weight control Mo, Fe, Os
in free radical
polymerization
(continued)
28. US5028677A [45] 1986 1991 DuPont Novel macromonomer Macromonomers formed
compositions by CCT
29. WO1987003605A1 [46] 1985 1987 CSIRO Oligomerization process CCT using Co(III) 1
US5324879A 1994 complexes
30. WO199517435A1 [47] 1993 1995 Zeneca Free radical CCT using Co(II) or
US5770665A 1998 polymerization process Co(III) diarylglyoxime
complexes
31. WO1996013527A1 [48] 1994 1996 Zeneca Free radical CCT using Co(II) or
US5962609A 1999 polymerization process Co(III) diarylglyoxime
complexes
32. WO9941218A1 [49] 1999 1999 DuPont Alpha-methylstyrene AMS dimer synthesis by 3
US6294708B1 2001 dimer derivatives CCT
US6388153B2 2002
33. US20020087006A1 [50] 2001 2002 DuPont Alkyl cobalt (III) CCT using Co(III) —
US6559327B2 2003 Axalta dioximates and process for complexes
US6713427B2 2004 Coating forming the same
US6740618B2 2004 Systems
US6858745B2 2005
a) Priority date.
b) Date published.
Abbreviations: CCT, catalytic chain transfer.
Table 24.4 Patents relating to forming macromonomers by addition–fragmentation chain transfer polymerization.
34. WO1988004304A1 [56] 1986 1988 CSIRO Control of molecular Allyl transfer agents
US5385996A 1995 weight and end-group
US5874511A 1999 functionality of polymers
US5932675A [57]
35. WO9512568A1 [58] 1993 1995 CSIRO/DuPont Polymers formed from Allyl malonate
US5773543A 1998 allylic chain transfer Transfer agents
US5977278A 1999 agents
36. WO1997013792A1 [59] 1995 1997 CSIRO/DuPont Control of molecular Allyl (Cl, Br, alkyl-, or
US6235857B1 2001 weight and end-group arylsulfonyl) transfer
functionality in polymers agents
37. WO2000011041A1 [60] 1998 2003 BASF Thermal- and Allyl (ammonium,
US6576684B1 Ciba Spec Chem photoinitiated radical sulfonium, phosphonium)
polymerization in the transfer agents
presence of an addition
fragmentation agent
38. WO 2007110882A1 [61] 2006 2007 Council of Water-soluble AMS dimer inclusion 3
US7875659B2 2009 Scientific and macromonomers complex with methylated
Industrial containing terminal cyclodextrin
Research, India unsaturation and a process
for the preparation thereof
a) Priority date.
b) Date published.
Abbreviations: AMS, α-methylstyrene; AMS dimer, 2,4-dimethylpentene.
Table 24.5 Patents relating to forming macromonomers 1-3 by other methods.
ZC(=CH2 )
Number Prioritya) Dateb) Assignee Title Brief description CH2 –c)
39. WO9847927A1 1997 1998 DuPont/ Method of Macromonomer 1 2 3

[62] 2002 CSIRO macro- synthesis by
US6376626B1 monomer polymerization
synthesis of monosubsti-
tuted monomers
with backbiting
β-scission
a) Priority date.
b) Date published.
150 150
Dithiobenzoate English
Trithiocarbonate French
Japanese
Xanthate Chinese
100 Other
Dithiocarbamate 100
Publications
Language
Total
50 50
0 0
2000 2005 2010 2015 2000 2005 2010 2015
Year Year
(a) (b)
Figure 24.2 Number of patents or patent applications issued per year on

thiocarbonylthio-RAFT polymerization, (a) using different classes of RAFT agent and (b) for
different languages, for the period 1998–2019. Based on a ScifinderTM substructure search
carried out in April 2020 on the RAFT agent structures and the terms ‘RAFT polymerization’
or ‘radical polymerization’. Some patents may refer to more than one class of RAFT agent. In
this case, it will only contribute one to the total. Patents that do not specify a RAFT agent
structure will not contribute. Patent families will only contribute once to the total.
with a few exceptions, limited the scope to patents, which have progressed to being
granted in the US and which have a working example making use of RAFT.
24.3.1 Development of RAFT Polymerization

In this section, we describe that part of the history of RAFT polymerization that
relates to design and synthesis of thiocarbonylthio-RAFT agents (Table 24.6) and
to the development of the method for the synthesis of low-dispersity, block and
end-functional polymers.
Table 24.6 Thiocarbonylthio-RAFT agent ZC(=S)S– groups described in the patent

literature.
Dithioester
Dithiobenzoate Aryl dithioester S S S
S S
H3CO F
Cl
S S S
S S
4 5 6 7
8
Trifluorodithioacetate Phenyldithioacetate Dithioacetate
S S S S S
S
CF3 H3C
N S S S S S
S
9 10 11 13
12
Alkenyldithioacetate Vinylogous dithoester S
S S S
S S
S
S
14 15 16
Trithiocarbonates
Symmetrical Methanesulfanyl Ethanesulfanyl Propanesulfanyl
S S S S
S H3C S C2H5 S C3H7 S
S S S S
17 18 19 20
Butanesulfanyl Hexanesulfanyl Dodecanesulfanyl
S
S S S
S
C4H9 S C6H13 S C12H25 S
(H3CO)3Si S
S S S 3
21 22 23 24
S S S S
S S HO S S
S S S HO2C S
10
HO2C ClOC C8H17
25 26 27 28
Xanthate
O-alkyl S S S S
C2H5 O
S O S O S
O O S
29 30 31 32
O-fluoroalkyl F F S S
S
F C6F13
F O S O S
O S F
F F F F
F 33 34 35
O-perfluorophenyl O-phenyl xanthate O-(1-(diethoxyphosphaneyl)ethyl O-(1-(diethoxyphosphaneyl)ethyl

F CF3 S S
S
F F C2H5O C2H5O
S P O S P O S
O S
OC2H5 OC2H5
F O S
F 37 38 39
36
(continued)

Dithiocarbamate
Pyrole S Carbazole Imidazole S Triazole S
N S N N N
S N N S N S
S
40 42 43
41
Hydrazinyl F S
F H S
S S N O
N N N
N N N S
H S
S F S
F O
F
45 46 47
44
Pyrazole N S N S N S N S
N N N N
S S S S
Cl Br
48 49 50 51
N-alkyl-N-pyridyl N-alkyl-N-pyridinium
S S
N N
S S
N N
52 H
+
52-H
α-carbonyl O O O O O
S S S S S
N N N O N O N
S S S S
S
O 54 57
55 56
53
O O O C4H9O2C S C2H5O2C S
S S S N N
N N O N O N S S
S S S
CO2CH3
60 61 62
58 59
N,N-diaryl
NH
S S
N N
S S
N S
63 S
64
65
S S
N-aryl-N-alkyl N N S
S S N
S
68
66 67
S S S S S S
N,N-dialkyl N N O N N N N
S S S S S S
69 70 71 72 73
(continued)

Phosphorous-containing RAFT agents
Diethoxyphosphanecarbodithioate Tertrathiophosphate S S S
P P
S S S S S
C2H5O
P S P
S S
S
OC2H5
76
74
75
Others
Sulfine Bis(allyl sulfide)
O
O S
O
S S
S P S S P S S S
79
78
OCH3 OCH3
77
The first patents on RAFT polymerization making use of thiocarbonylthio-RAFT

agents were published in 1998 (Table 24.7, entry 1). The CSIRO/DuPont provisional
on thiocarbonylthio-RAFT polymerization filed in 1996 embraced all major classes
of RAFT agents, namely, dithiocarbamates, xanthates, trithiocarbonates, and
dithioesters. However, in filing the first patent (Table 24.7, entry 1) [63] based on
this provisional, only material relating to dithioesters and trithiocarbonates was
included to avoid potential confusion with the earlier iniferter chemistry [144].
The first Rhodia patent application related to RAFT polymerization (Table 24.7,
entry 3) [75] was also published in 1998 and had claims that pertained to the use of
xanthate and trithiocarbonate RAFT agents, though only xanthates were exempli-
fied. The Rhodia patent was based on a French provisional that broadly described a
wider range of RAFT agents.
A subsequent CSIRO/DuPont filing in 1997 (Table 24.7, entry 6) [83], (published
in 1999), still largely based on the 1996 provisional, broadly claimed xanthate, dithio-
carbamate, and vinylogous dithioester RAFT agents. Rhodia filings based on their
original 1997 French provisional claimed dithiocarbamates (Table 24.7, entry 5) [80]
and vinylogous dithioesters (Table 24.7, entry 4).
The overlap in scope of the various CSIRO/DuPont and Rhodia patent fil-
ings ultimately led to an arrangement whereby going forward the exploitation
of RAFT at Rhodia focused largely on xanthates (in a process they termed
MADIX – macromolecular design by interchange of xanthate), while CSIRO/
DuPont concentrated on dithioesters, trithiocarbonates, and dithiocarbamates. This
division was in line with the commercial interests of both groups at the time.
Other early patents related to the synthesis of specific RAFT agents. The second
CSIRO patent on thiocarbonylthio-RAFT disclosed the synthesis of RAFT agents,
where R is a tertiary radical by radical-induced decomposition of bis(thioacyl)
disulfides (Table 24.7, entry 2). This process allowed the synthesis of RAFT agents
most suited to mediating the polymerization of methacrylates. This patent also
claimed the in situ generation of RAFT agents during radical polymerization by
Table 24.7 Patents relating to the development of thiocarbonylthio-RAFT polymerization
Number Prioritya) Dateb) Assignee Titlec) Brief description ZC(=S)S–d)
1. WO9801478A1 [63] 1996 1998 DuPont/CSIRO Polymerization with living Original CSIRO/DuPont 4 5 10 8 13 17 74
US7250479B2 [64] 2007 characteristics RAFT patent. Focus on RAFT
2010 process with dithioesters,
US7662986B2 [65]
2010 trithiocarbonates. Low Ð
US7666962B2 [66] polymers. Block and star
2010
US7714075B1 [67] polymers
pub [68–71]
2. WO199905099A1 [72] 1997 1999 DuPont/CSIRO Synthesis of dithioester Functional RAFT agent 4
US6512081B1 [73] 2003 chain transfer agents and synthesis. In situ generation
use of bis(thioacyl) of RAFT agents or
pub [74]
disulfides or dithioesters macroRAFT agents
as chain transfer agents
3. WO1998058974A1 [75] 1997 2000 Rhodia Chimie Method for block polymer Block copolymers syntheses 29 30
US6153705A [76] synthesis by controlled with xanthate RAFT agents
pub [77, 78] radical polymerisation
4. WO1999035178A1 1997 1999 Rhodia Chimie Synthesis method for Block copolymers with 14 + others not
US6545098B1 [79] 2003 block polymers by dithioester RAFT agents. listed
controlled radical Dithioesters Z–C(=S)S–R
polymerization from with Z = alkene. Examples
dithioester compounds are the narrow polydispersity
ethyl acrylate (EA) and
styrene homopolymers, and
block copolymer of EA and
styrene
5. WO1999035177A1 [80] 1997 1999 Rhodia Chimie Method for block polymer Polymers formed by RAFT 41 43 66 54 53
US6812291B1 [81] 2004 synthesis by controlled polymerization with (69) (70)
radical polymerization dithiocarbamates
pub [82]
from dithiocarbamate
compounds
6. WO9931144A1 [83] 1997 1999 DuPont/CSIRO Polymerization process RAFT process with xanthates, 15 16 37 38 29 41
US6642318B1 [84] 2003 with living characteristics dithiocarbamates, and 43 54 53 66 (69)
2004 and polymers made vinylogous dithioesters. (70)
US6747111B2 [85]
therefrom Polymers with low dispersity
pub [86]
7. WO2000002939 1998 2000 DuPont/CSIRO Microgels and process for Microgels by arm-first 4
US6355718B1 [87] 2002 their preparation method
US6462114B2 [88] 2002
US6646055B2 [89] 2003
2003
US6653407B2 [14]
2004
US6822056B2 [90]
8. US7049373B2 [91] 1997 2006 Carnegie Process for preparation of Synthesis of graft copolymers 4
Mellon graft polymers by copolymerization of
University macromonomers
9. WO2000075207A1 1999 2000 Rhodia Synthesis method for Polymers made with 33 34 35
US6777513B1 [92] 2004 Chimie polymers by controlled halogenated xanthates RAFT
radical polymerisation
using halogenated
xanthates
10. WO2001042312A1 1999 2000 Rhodia Synthesis method for Use of phosphorylated 39 40
US6809164B2 [93] 2004 Chimie polymers by controlled xanthate esters as RAFT
US7285610B2 [94] 2007 radical polymerisation agents
with xanthates
11. WO 2001042325A1 1999 2001 Rhodia Chimie Surface chemistry RAFT emulsion 29
[95] 2006 modified latex and polymerization for block
US7012114B2 redispersible powders, copolymers
production and use
thereof
12. WO2001077198A1 2000 2001 DuPont/CSIRO Process of microgel Microgels from self-assembly 4
[17] 2006 synthesis and products of RAFT-made block
US7064151B1 [96] produced therefrom copolymers followed by
crosslinking
(continued)
13. WO2002094887A1 2000 2002 Symyx Heterocycle containing Hydrazine-based 48

US6395850B1 [97] 2002 control agents for dithiocarbamate RAFT
living-type free radical agents. Hydrazine part of
polymerization heterocycle (1,2 imidazoline).
Polymerization process
14. WO2002026836A2 2000 2002 Symyx Control agents for Hydrazine-based 45 48 46 47
US6380335B1 [98] 2002 living-type free radical dithiocarbamate RAFT
US6482909B2 [99] 2002 polymerization, methods agents. Polymerization
2003 of polymerizing and process in forming block
US6518448B2 [100]
2003 polymers with same copolymer, or star or
US6569969B2 [101] hyper-branched polymer
2005
US6841624B2 [102]
2005
US6844407B2 [103]
15. WO2002022688A2 2000 2002 Rhodia Chimie Method for block polymer Polymerization in the 29 33
US6916884B2 [104] 2005 synthesis by controlled presence of a RAFT agent or a
radical polymerization in disulfide RAFT agent. Very
the presence of a broad RAFT agent definition.
disulphide compound Examples are xanthates and
xanthogen disulfides
16. WO2002036640A1 2000 2002 Rhodia Chimie Synthesis of block Use of tetrathiophosphate 76
[105] US6890980B2 2005 polymers obtained by RAFT agents
controlled free radical
polymerization
17. WO2002010223A2 2000 2002 Rhodia Chimie Method for synthesis of Dithiophosphoroester 75
US7247688B2 [106] 2007 block polymers by Z1 Z2 P(=S)S–R compound as
controlled free radical RAFT agent
polymerization
18. WO2001060792A1 2000 2001 Noveon S,S′ -bis-(α,α′ -disubstituted- Synthesis and use of 17 23
US6596899B1 [107] 2003 α′′ -acetic acid)- trithiocarbonate RAFT agents
US6962961B2 [108] 2005 trithiocarbonates and prepared by the ketoform
2007 Lubrizol derivatives as reaction
US7279591B2 [109]
2009 initiator-chain transfer
US7495128B2 [110] agent-terminator for
US7659345B2 [111] controlled radical
pub [112] polymerizations and the
process for making the
same
19. WO2004037780A1 2002 2004 Lubrizol S-(α,α′ -disubstituted-α′′ - Synthesis and use of 63 61 62 72 71 73
US7335788B2 [113] 2008 acetic acid) substituted dithiocarbamate RAFT 64 65
US7851582B2 [114] dithiocarbonate agents prepared by the
pub [115] derivatives for controlled ketoform reaction
radical polymerizations,
process and polymers
made therefrom
20. US7205368B2 [116] 2000 2007 Lubrizol S-(α,α′ -disubstituted-α′′ - Synthesis and use of xanthate 29
US7498456B2 [117] 2009 acetic acid) substituted RAFT agents prepared by the
2010 dithiocarbonate ketoform reaction
derivatives for controlled
radical polymerization,
process and polymers
made therefrom
21. US6518364B2 [118] 2001 2003 Symyx Emulsion living-type free Hydrazine-based 45
radical polymerization, dithiocarbamate RAFT
methods and products of agents. Emulsion
same polymerization
22. US7214751B2 [119] 2001 2007 Rhodia Radical polymerization Radical polymerization in 29
Chimie method performed in the presence of Z1 -C(=S)–S–S–C
presence of disulfide (=S)–Z2 . In situ formation of
compounds RAFT agents. The method is
used in the preparation of
block copolymers containing
especially a methacrylic block
(continued)
23. US7317050B2 [120] 2001 2008 Rhodia Chimie Controlled mini-emulsion Controlled mini-emulsion 21 29
free radical radical polymerization in
polymerization presence of a RAFT agent
24. WO2003055919A1 2001 2003 University of Aqueous dispersions of RAFT in emulsion. 12 17 21
US7745553B2 [121] 2010 Sydney polymer particles Amphiphilic macroRAFT 23 25
agents
25. WO2003031480A2 2001 2003 Carnegie Mellon Process for monomer RAFT (and other RDRP) in 4
US7064166B2 [122] 2006 University sequence control in presence of Lewis acids. An
polymerizations example is cumyl
dithiobenzoate
26. WO2003066685A2 2002 2003 University of Chain transfer agents for Dithioesters for use in 4 12 29
US6855840B2 [123] 2005 Southern RAFT polymerization in aqueous polymerization.
US7179872B2 [124] 2007 Mississippi aqueous media Examples are dithiobenzoates
US7186786B2 [125] 2007 with hydrophilic R
2008
US7402690B2 [126]
27. WO2004108770A1 2003 2004 Rensselaer Low odor chain transfer RAFT agents 4 6 7 29 66
US7332552B2 [127] 2008 Polytechnic agents for controlled ZC(=S)S–CH(CN)R.
Institute radical polymerization with R aryl
28. WO2005116097A1 2004 2005 Rhodia Chimie Synthesis of Copolymers Arm-first stars and mikto-arm 29
US20080114128A1 2008 in the Form of a Mikto stars
[128] Star by Controlled Radical
Polymerization
29. US7632966B2 [129] 2004 2009 DuPont Synthesis of Improved trithiocarbonate 23
trithiocarbonate RAFT synthesis from disulfide
agents and intermediates
thereof
30. WO2007071591A1 2005 2007 Rhodia Chimie Synthetic microgel Core-first and arm-first stars 29
[130] 2012 polymer compositions for
US8163100B2 treating and/or modifying
hard surfaces
31. WO2008078055A2 2006 2008 Arkema Copolymers based on Use of comonomer (styrene 17
US8389643B2 [131] 2013 methacrylate units, acrylate) to facilitate control
preparation method over RAFT polymerization of
thereof and use of same methacrylates
32. WO2009153162A1 2008 2009 BASF SE Process for the preparation Hydrophilic macroRAFT 17 21 25
US8912273B2 [132] 2014 of an aqueous polymer agent prepared and used
dispersion for styrene polymerization
in aqueous emulsion
33. WO2009111725A1 2008 2009 Carnegie Mellon Controlled radical RAFT agents used for ATRP 4 17 29 70
US8445610B2 [133] 2013 University polymerization processes initiation. RAFT used to
control ATRP. Dual ATRP
initiator/RAFT agents. Macro
34. WO2011075156A1 2008 2011 ATRP Solutions Control over controlled Feed addition of initiator or —
US8815971B2 [134] 2014 radical polymerization reducing agent during
US9012528B2 [135] 2015 processes polymerization.
US9518136B2 2016 Pilot Polymer No RAFT example.
Technologies US9518136B2 relates
specifically to RAFT
35. WO2012078716A1 2008 2012 ATRP Solutions Control over controlled Feed addition of initiator or —
US8822610B2 [136] 2014 radical polymerization reducing agent during
US9856331B2 2018 processes polymerization.
No RAFT example
36. WO2010083569A1 2009 2010 CSIRO RAFT polymerisation Switchable RAFT agents 52
US9340498B2 [137] 2016
(continued)
37. WO2010019563A1 2008 2009 University of Synthesis of arborescent RAFT self-condensing vinyl 4
[138] 2011 Akron polymers via controlled polymerization
US8883912B2 inimer-type reversible
chain transfer (RAFT)
polymerization
38. WO2012037596A1 2010 2012 CSIRO Continuous flow RAFT solution 23 66
US8946360B2 [139] 2015 polymerisation process polymerization in tubular
reactor
39. WO2016054689A1 2014 2016 CSIRO All-purpose RAFT agent 3,5-Dimethylpyrazole RAFT 49
[140] for polymerization agent. R = cyanomethyl
40. US9156921B2 [141] 2013 2015 California Organocatalyzed PET-RAFT making use of —
Institute of photoredox mediated organic catalysts claimed. No
Technology polymerization using RAFT examples
visible light
41. WO2015113114A1 2014 2015 NewSouth Process for preparing a PET-RAFT process using 4 21 23 25 29
[142] 2016 Innovations polymer either organic or
US20160340463A1 organometallic photoredox
catalysts
42. WO2016197187A1 2016 2016 CSIRO Versatile RAFT agent 4-Subsituted-3,5-dimethyl- 49 50 51
[143] pyrazole RAFT agents.
R = cyanoisobutyl
a) Priority date.
b) Date published.
c) Title of the patent as published.
d) ZC(=S)S– groups exemplified (Table 24.6).
Abbreviations: RDRP, reversible deactivation radical polymerization; PET-RAFT, photo energy or electron transfer-RAFT.
radical-induced decomposition of a bis(thioacyl) disulfide. Similar chemistry with

reference to the use of xanthates was also claimed in two Rhodia patents (Table 24.7,
entries 15, 22). The CSIRO patent also covered other processes that generate a
RAFT agent in situ such as radical addition to a ketene dithioacetal.
Rhodia also filed on more active xanthates with electron-withdrawing groups on
oxygen as RAFT agents. Symyx filed on dithiocarbamate RAFT agents where the
dithiocarbamate nitrogen was contained in a hydrazinyl group (Table 24.7, entries
13, 14, and 21). This class includes the 1H-pyrazole-1-carbodithioates 48 and 49.
Examples of 49 with R = cyanoalkyl were more recently the subject of a CSIRO patent
(Table 24.7, entry 39).
A series of patents filed by Noveon (now Lubrizol) relate to the synthesis of trithio-
carbonate, xanthate, and dithiocarbamate RAFT agents using the ketoform process
(Table 24.7, entries 18–20). The trithiocarbonates prepared by this process are cur-
rently amongst the most used RAFT agents for mediating the polymerization of
more activated monomers (MAMs, see chapter on trithiocarbonates) [145]. The syn-
thesis of RAFT agents by this process has been successfully produced on industrial
scale and exploited in the production of rheology modifiers for oil [146].
Switchable RAFT agents can be ‘switched’, typically by protonation, to be highly
effective with either MAMs and less activated monomers (LAMs) (e.g. 52, 52-H+ ,
Table 24.7, entry 36). RAFT agents with balanced activity are those that show
effectiveness with both LAMs and MAMs even though the quality of control may
be to some extent compromised. This class includes various dithiocarbamates and
xanthates described in the Rhodia and Symyx patents (Table 24.7). CSIRO patented
specific 3,5-dimethyl-1H-pyrazole-1-carbodithioates (49 and 50) in this context
(Table 24.7, entries 39 and 42).
24.3.2 RAFT Emulsion Polymerization

Successful semi-batch RAFT emulsion polymerizations to form low-dispersity
polymers and block copolymers were described in the earliest CSIRO/DuPont
patents (Table 24.7, entries 1 and 6). The starved feed strategy that had been
found successful in improving living characteristics in macromonomer RAFT
polymerization in emulsion was also successful in minimizing retardation and
achieving colloidal stability in thiocarbonylthio-RAFT emulsion polymerization
with the more active thiocarbonylthio-RAFT agents. Examples of RAFT emulsion
polymerization with xanthates appear in the first Rhodia patents (Table 24.7, entry
2, see also entries 12 and 25).
The use of amphiphilic macroRAFT agents in thiocarbonylthio-RAFT poly-
merization was pioneered by University of Sydney (Table 24.7, entry 25, see also
Table 24.8, entries 240–244). This form of RAFT emulsion polymerization was
exploited on a commercial scale by Dulux in Australia in acrylic surface–coatings
applications and for pigment encapsulation/dispersion. There was also a substantial
effort at Goodyear focused on diene-based polymers (Table 24.9, entries 74–85).
Later patents that deal specifically with emulsion or miniemulsion polymerization
are shaded blue in Tables 24.7 and 24.9.
Table 24.8 RAFT agents that have been produced/used on a large scale by industry.
Trade name(s) IUPAC name/structure CAS no EC noa) PubChem CID no
Rhodixan A1TM Methyl 2-((ethoxycarbonothioyl)thio)propanoate 351491-23-1 435-410-2 16720359

S
C2H5
O S CO2CH3
80
BlocBuilder Dibenzyl carbonotrithioate 26504-29-0 460-390-7 233929
DBTM S
DBTTC S S
BM1361
81
DOPAT 2-(((dodecylthio)carbonothioyl)thio)propanoic acid 558484-21-2 695-614-4 59347140
BM1430 S
C12H25
S S COOH
82
DDMAT 2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoic acid 461642-78-4 663-505-0 11473994
CTA-acid S
C12H25
S S COOH
83
CTA1 Butyl 2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoate 1034630-38-0 924-887-7 —
CTA-ester S
C12H25
S S CO2C4H9
84
CPDTTC 2-Cyanopropan-2-yl dodecyl carbonotrithioate 870196-83-1 — 71310910
S
C12H25
S S CN
85
CDTPA 4-Cyano-4-(((dodecylthio)carbonothioyl)thio)pentanoic acid 870196-80-8 687-390-1 57354956
BM1432 S CN
C12H25
S S CO2H
86
CPDB 2-Cyanopropan-2-yl benzodithioate 201611-85-0 687-395-9 9964525
S CN
87
4-Cyano-4-((phenylcarbonothioyl)thio)pentanoic acid 201611-92-9 687-398-5 9921763
S CN
S CO2H
88
2-((phenylcarbonothioyl)thio)acetic acid
942-91-6 213-393-0 70336
S
S CO2H
89
a) European Chemical Agency.

Table 24.9 Patents relating to applications of thiocarbonylthio-RAFT polymerization.
1. WO2004099275A1 2003 2004 3M Azlactone chain transfer agents Chain transfer agents for 29
US6762257B1 [147] 2004 for radical polymerization controlled radical polymerization
(RAFT) are described. The chain
transfer agents have an azlactone
or ring-opened azlactone to
provide telechelic (co)polymers
2. US6747104B1 [148] 2003 2004 3M Azlactone photoiniferters for Dithiocarbamate photoinitiators 70
US6818716B2 radical polymerization
3. WO2007050532A1 2005 2007 3M High clarity cholesteric liquid Polymers made by RAFT 23
US7439000B2 [149] 2008 crystal films polymerization.
4-Cyanobiphenyl benzoate ethyl
acrylate.
Conventional chain transfer
also used
4. WO2007050433A1 2005 2007 3M Infrared light reflecting film Acrylate polymer with liquid 23
US7652736B2 [150] 2010 crystalline pendants made by
RAFT polymerization with
trithiocarbonate
5. WO2013028397A2 [151] 2012 2013 3M Dental compositions Graft to silica particles. 24
US9907733B2 2018 comprising Also relates to
addition-fragmentation macromonomer RAFT
agents
6. WO2015057413A1 [152] 2013 2015 3M Allyl disulfide-containing Dynamic covalent 79
US9758478B2 2017 addition-fragmentation polymers
oligomers
7. WO2010131628A1 [153] 2009 2010 AGC Seimi Monodisperse Higher M n 4
US20120059137A1 2012 Chemical Ltd chloromethylstyrene polymer poly(chloromethylstyrene) made
and producing method thereof by RAFT
8. US7674843B2 [154] 2005 2010 Agfa Graphics Stable pigment dispersions Dispersions containing 4
US7678845 [155] 2010 RAFT-synthesized block
copolymer dispersants
9. WO2006111637A1 [156] 2005 2006 Arkema Method for preparing Alkoxyamines prepared by 70
US20090221850A1 2009 alkoxyamines by photolysis of photolysis of a dithiocarbamate
dithiocarbamates in the presence of a nitroxide
10. WO2012004480A1 [157] 2010 2012 Arkema Compositions with improved Masking odour of RAFT agents, 17
odour comprising a raft agent or including BlocBuilder DB
a polymer obtained using one of
these agents
11. US7713508B2 [158] 2005 2010 Arrowhead Thiation of carbon nanotubes RAFT agent functionality formed —
Center and composite formation on carbon nanotubes
12. WO2012089352A1 2010 2012 Arrowhead In vivo polynucleotide SiRNA delivery. Example 4
WO2012089602A1 2012 Madison delivery conjugates having 16 of US8426554B2 is
US8426554B2 [159] 2013 enzyme sensitive linkages made by RAFT
US8802773B2 [160] 2014
US9198947B2 2015 Hoffmann
US9301990B2 2016 La Roche
US9968647B2 2017
13. WO2013032829A1 2011 2013 Arrowhead Poly(vinyl ester) polymers RAFT-synthesized vinyl 63
US8932572B2 [161] 2015 Madison for in vivo nucleic acid ester copolymers
US9089611B2 [162] delivery
14. WO2013158141A1 2012 2013 Arrowhead Poly(acrylate) polymers Poly(meth)acrylate. 4
US8933047B2 [163] 2015 Madison for in vivo nucleic acid Amine functional
delivery polymers made via tBOC
protected monomers
15. WO2016149313A1 2015 2016 Arrowhead Disulfide-containing Cyclooctyne-alkyl 4
US10047361B2 2018 Pharma- alkyne linking agents disulfide compound as
ceuticals reagent for making
Corp conjugates
(continued)
18. WO2010147876A2 2009 2011 Bausch & Biomedical devices Contact lenses 23 29
US8083348B2 [167] 2011 Lomb
19. WO2010147875A2 2009 2010 Bausch & Biomedical devices Biomedical devices 23 29
US8133960B2 [168] 2012 Lomb
20. WO2010147874A1 2009 2012 Bausch & Biomedical devices, Silicone diblock 17 23 29
US8337551B2 [169] Lomb polymeric materials and copolymer hydrogels
contact lenses comprising
same
21. US7169937B2 [170] 2002 2007 Bayer Dithiocarbamic esters Dithiocarbamate RAFT 30 41 43
US7825193B2 [171] 2002 2010 Lanxess agents with (67)
US7977431B2 [172] 2002 2011 Lanxess R = haloalkenyl. Main
application is RAFT
emulsion polymerization
of chloroprene
22. WO2011032832A1 [173] 2009 2011 Lanxess Nitrile rubbers and production NBR by RAFT in solution 4 17 23
US9023914B2 2015 thereof in organic solvents
23. WO2004055060A1 2002 2007 BioMérieux Method for controlled radical RAFT process to form high M n 4
US7205362B2 [174] polymerization polymer in relatively short
reaction time with control of
radical flux
24. WO2007003781A1 2005 2007 Biomerieux, Fluorescent polymers soluble in Fluorescent RAFT-synthesized 4
US8133411B2 [175] 2012 CNRS an aqueous solution and a polymer for medical diagnostics
method for the production or therapeutics
thereof
25. WO2014165530A1 [176] 2013 2014 Brewer Highly etch-resistant RAFT used for resists to be 25
US9123541B2 2015 Science polymer block for use in used in block copolymer
Inc. block copolymers for self-assembly
directed self-assembly
26. US7230051B2 [177] 2002 2007 BYK-Chemie Use of polyacrylate-modified Block copolymers (polysiloxane 29
GmbH polysiloxanes as levelling agents pre-polymer) as levelling agents
in coating compositions (examples made by RAFT) for
surface-coating compositions
27. WO2004014963A2 [178] 2002 2004 Carnegie Polymers, supersoft elastomers Crosslinked brush polymer as 4
US7019082B2 2004 Mellon and methods for preparing the elastomer
University same
28. WO2005087818A1 [179] 2005 2010 Carnegie Preparation of functional RAFT in combination with ‘click’ 4
US7795355B2 Mellon polymers chemistry
University
29. WO2002070571A1 2001 2002 Coatex SAS Method of controlled free radical Poly(acrylic acid) synthesis by 4 17 29 32
US7345121B2 [180] 2008 polymerisation of acrylic acid RAFT 38 43
and its salts thereof, resulting
low-polydispersity polymers, and
their uses
30. WO2004014967A2 2002 2004 Coatex SAS Method for the controlled radical Poly(acrylic acid) synthesis by 29
US7462676B2 [181] 2008 polymerisation of acrylic acid RAFT
and the salts thereof, polymers
thus obtained and applications
thereof
31. WO2005095466A1 2004 2005 Coatex SAS Trithiocarbonate derivatives and Trithiocarbonates used for RAFT 17
US7956211B2 [182] 2011 the use thereof in the form of AA polymerization in water
US8227633B2 [183] 2012 transfer agents for acrylic acid
US8470750B2 [184] 2002 2013 controlled radical polymerisation
32. WO2006024706A1 2004 2006 Coatex SAS. Polymers produced by using Poly(AA) by RAFT 17 29
US8053497B2 [185] 2011 sulphur compounds in the form polymerization in water
of transfer agents for controlled
radical polymerisation of acrylic
acid and the use thereof
(continued)
33. WO2008084298A1 2007 2012 Coatex SAS Use of a rheological additive in Additive can be made by RAFT. —
US8110130B2 [186] the manufacture of concrete by No RAFT examples
vibrocompaction
34. US7851572B2 [187] 2004 2010 Coatex SAS Polymers produced by using Low-dispersity AA copolymers 17 29
sulphur compounds in the form by RAFT polymerization
of transfer agents for controlled
radical polymerisation of acrylic
acid and the use thereof
35. WO2014022365A1 [188] 2012 2014 Columbia Cyclopropenium polymers Monomers containing 4
US9758606B2 2017 Univer- and methods for making cyclopropenium ions
US10385150B2 2019 sity of the same polymerized by RAFT
New York
36. WO2010096464A1 2008 2010 Colorado Gold/lanthanide Nanoparticle-bound 23
US8968705B2 [189] 2015 School of nanoparticle conjugates RAFT polymers.
Mines and uses thereof Biomedical imaging
applications
37. WO2008064972A1 2006 2008 Unilever Brush copolymers Brush copolymers made by 23
US7960479B2 [190] 2011 Conopco, Inc ROMP/RAFT
38. WO2012069403A2 2010 2012 Continental Process for producing Surface-initiated RAFT 17 20
US8912267B2 [191] 2014 Reifen polymer-functionalized filler polymerization from silica
particles particles or carbon black
39. WO2016180805A1 [192] 2015 2015 Continental Raft agent, polymerization Tyre compositions 23
US10442877B2 2018 Reifen method, polymer, rubber
mixture, and use thereof
40. EP3109064B1 [193] 2016 2018 Continental Method for co-polymerization, Preparation of butadiene-b-VAc 52
Reifen co-polymer and rubber and related copolymers
composition and their use
41. US7811555B2 [194] 2005 2010 Cordis Tri-branched biologically active Tri-branched copolymers. 4
Corporation copolymer Biomedical applications.
No actual examples
42. US7411053B2 [195] 2006 2008 (Clark Ligand-functionalized/azo Metallopolymers. Ligand 4
University, compounds and methods of use functional chain ends
Atlanta)
43. WO2017029412A1 2015 2017 CNRS, Ecole Boronic polymer crosslinking Dynamic covalent polymers. 4
US10005900B2 2018 Superieure de MMA copolymer with pendant
US10329414B2 [196] 2020 Physique et boronic ester functionality
Chimie prepared
Industrielles
de Ville Paris
44. WO2017029311A1 2015 2017 Ecole Composition comprising a Dynamic covalent polymers. 4
WO2017029315A1 2015 2017 Superieure de cross-linked polymer network, MMA copolymer with pendant
US9994651B2 2018 Physique et prepared by radical aldehyde functionality prepared
US10584190B2 [197] 2020 Chimie copolymerisation, comprising
Industrielles pending links and cross-links
de Ville Paris exchangeable by aldehyde-imine
exchange reactions and/or by
imine-imine exchange reactions,
preparation process and use
45. WO2015099913A1 [198] 2013 2019 Cytec Polyacrylonitrile (PAN) polymers Acrylonitrile copolymer for 4 17 23
US10189985B2 Industries Inc with low polydispersity index carbon fibre
US10647844B2 (PDI) and carbon fibres made
therefrom
46. WO2010147011A1 [199] 2009 2010 Denka Polychloroprene, process RAFT emulsion 4 41 42
for production of same, polymerization of
and adhesives containing chloroprene
same
47. WO2005031461A1 2003 2005 DuPont Low-polydispersity Resist polymers made by 25
US7696292B2 [200] 2010 photoimageable acrylic RAFT
polymers, photoresists and
processes for
microlithography
(continued)
48. WO2005031462A1 2004 2005 DuPont Low-polydispersity Photoresist polymers by 25

US7408013B2 [201] 2008 CSIRO photoimageable polymers RAFT
and photoresists and
processes for
microlithography
49. US8034534B2 [202] 2006 2011 DuPont Fluorinated polymers for Resist polymers made by 25
use in immersion RAFT
lithography
50. WO2008019450A1 2006 2008 CSIRO Polymeric coatings and Surface-initiated 19 70
US8124188B2 [203] 2012 methods for forming them polymerization to form
US8795782B2 [204] 2014 biocompatible surfaces
51. WO2009155657A1 2009 2013 CSIRO Conducting and Synthesis of block 4 18 21
US8501889B2 [205] 2008 2015 semiconducting organic copolymers comprising a
US8993697B2 [206] 2008 materials semiconductor segment by
RAFT. Divisional covers
macroRAFT agents
52. WO2014138807A1 2013 2014 CSIRO Polymer derived from High-molecular-weight 4
US9458263B2 2016 acrylonitrile polyacrylonitrile and copolymers
US9777081B2 [207] 2017 for carbon fibre
53. US7468415B2 [208] 2007 2008 DuPont Method for preparing Monomer is polymerized by 25
glycidyloxystyrene monomers RAFT in the examples
and polymers thereof
54. US8304572B2 [209] 2007 2012 DuPont Synthesis of Monomer synthesis based on 25
fluoroalcohol-substituted fluorinated epoxide.
(meth)acrylate esters and Tetrapolymer example made by
polymers derived therefrom RAFT
55. US8734898B2 [210] 2012 2014 DuPont Method for producing Styrene/acrylic acid/butyl —
encapsulated nanoparticles acrylate copolymer made by
RAFT
56. US9815947B2 [211] 2015 2017 DuPont Substantially symmetrical 3-arm Star comprising central core and 25
star block copolymers outer blocks RAFT agent
prepared from acid functional
trithiocarbonate and
tris(4-hydroxy-phenyl)ethane
57. WO2010096422A1 2009 2010 Duke Biomolecule polymer RAFT polymerization 4
US8497356B2 [212] 2013 Univer- conjugates and methods from protein-bound RAFT
sity for making the same agents
58. WO2009090252A1 [213] 2008 2009 DSM Water-borne crosslinkable Crosslinkable copolymer 29
US9567476B2 2017 block copolymers coatings. Block copolymer
obtained using RAFT dispersant made by RAFT
59. WO2008122576A1 [214] 2007 2008 DSM Aqueous Anti-microbial coatings. 29
US9340699B2 2016 oligomer/polymer Quaternary amine
emulsion with cationic functional polymers
functionality
60. WO2010000725A1 [215] 2008 2010 DSM Adhesion to metal Anti-corrosive coatings 29
surfaces with block
copolymers obtained
using RAFT
61. WO2009121911A1 [216] 2008 2009 DSM Adhesion to plastic with Coatings for plastics. 29
US9255211B2 2016 block copolymers Block copolymer
obtained using RAFT dispersant made by RAFT
62. WO2009138493A1 [217] 2008 2009 DSM Block copolymers Blocks made by RAFT 29
obtained using raft emulsion polymerization
63. WO2019121782A1 [218] 2018 2019 DSM Waterborne crosslinkable Blocks made by RAFT 13 18 22
dispersions emulsion polymerization
for coatings applications
(continued)
64. US6756457B2 [219] 2002 2004 Eastman Kodak Polymerization process Onium salt plus an organic sulfur 70
compound (e.g. sulfide, disulfide,
RAFT agents) gives living
polymerization initiator
65. US9428649B2 [220] 2010 2016 E Ink California Electrophoretic dispersion Polymer-grafted pigment 4
US9732231B2 [221] 2010 2017 Method of making particles made by
electrophoretic dispersion surface-initiated RAFT
66. WO2017046652A1 [222] 2014 2018 Ecole Glycotargeting Glycopolymer–antigen 4

US10046056B2 Polytech- therapeutics conjugates
nique
Federale
de
Lausanne
67. WO2004083169A1 [223] 2003 2004 Rohmax Process for preparing dithioesters Dithiobenzoate synthesis 4
US6841695B2 2005 Evonik
68. WO2004087850A1 [224] 2003 2004 Rohmax Lubricating oil composition with Lubricating oil composition 4
US8288327B2 2012 Evonik good frictional properties
69. WO2011101176A1 [225] 2010 2011 Evonik Functional materials with Hetero-Diels–Alder process for 9
US8916635B2 2014 reversible crosslinking chain linking to thiocarbonylthio
compound
70. WO2013013873A1 [226] 2011 2013 Evonik Polymer powder for producing Hetero-Diels–Alder process. No —
US8981010B2 2015 three-dimensional objects RAFT examples
71. WO2013017349A1 [227] 2011 2013 Evonik Low molecular weight products Hetero-Diels–Alder process for 74
US10030105B2 2018 and use thereof as reversible or chain linking to thiocarbonylthio
permanent low-temperature compound
crosslinking agent in Diels-Alder
reactions
72. US10308748B2 [228] 2015 2019 Florida State Lignin-containing polymers RAFT-click chemistry used 23
University
73. WO2007137418A1 [229] 2006 2007 Fluidigm Polymer backbone DMAm/NAS copolymer, 4
US9012239B2 2015 Canada element tags NAS converted to
US9296838B2 2016 Inc metal-ligating pendant
US10072104B2 2018 group
74. US6369158B1 [230] 1999 2002 Goodyear Dibenzyltrithio-carbonate RAFT copolymerization in (17)
molecular weight emulsion. Dibenzyl
regulator for emulsion trithiocarbonate used for
polymerization SBR. Poor control
75. WO2004060928A1 2002 2004 Goodyear Styrene acrylonitrile Triblock made by RAFT 17
US7592409B2 [231] 2009 isoprene triblock emulsion polymerization
copolymer
76. WO2004060928A1 2002 2004 Goodyear Controlled Polymerization Preparation of 17
US7767775B2 [232] 2010 poly(St)-b-(diene-co-MAN)
and other MAN blocks by
RAFT emulsion
polymerization
77. US6992156B2 [233] 2003 2006 Goodyear Controlled polymerization RAFT emulsion 17
US7098280B2 [234] 2006 polymerization.
Emulsifier prepared in situ
78. US7528204B2 [235] 2004 2009 Goodyear Hydrogenation and RAFT emulsion 17
epoxidation of polymers polymerization followed
made by controlled by other processes
polymerization
79. US7462674B2 [236] 2005 2008 Goodyear Oxathiazaphospholidine free Potential RAFT agent 77
US7345186B2 [237] 2008 radical control agent
US7488786B2 [238] 2009
80. US7625985B1 [239] 2005 2009 Goodyear Water-based process for Poly(4-vinylpyridine) 17 23 27
the preparation of block copolymers used in
polymer-clay water as
nanocomposites dispersants/exfoliants for
clay nanocomposites
(continued)
81. US7230063B1 [240] 2006 2007 Goodyear Functional Trithiocarbonates of 17 23 27

trithiocarbonate RAFT general structure for 28
agents emulsion polymerization
ZS–C(=S)S–Y, where Z
group is a functional alkyl
(contains COOH, OH); Y
group is capable of
activating a vinylic carbon
towards free-radical
addition
82. US7671152B2 [241] 2006 2010 Goodyear Surfactantless synthesis of Poly(4-vinylpyridine) 17 23 27
amphiphilic cationic block macro-RAFT
copolymers agent-derived block
copolymers. RAFT
emulsion
83. US7335714B1 [242] 2007 2008 Goodyear Sulfine control agents for Sulfines claimed to give RDRP 78
synthesizing polymers possibly by RAFT
84. US7812108B2 [243] 2007 2010 Goodyear Hydrogenation and Hydrogenation of 17
epoxidation of polymers RAFT-synthesized
made by controlled polymers with hydrazine
polymerization
85. US8178637B2 [244] 2007 2012 Goodyear Controlled Polymerization Preparation of 17
poly(St)-b-(diene-co-AN)
by RAFT and other RDRP
in emulsion
86. US8415432B1 [245] 2011 2013 Goodyear Rubber composition and PNIPAm-bisthiol (made by 23
pneumatic tire RAFT) used in vulcanization of
poly styrene-butadiene rubber
87. US8759451B2 [246] 2011 2013 Goodyear Method of making a graft Graft copolymers to diene 23
copolymer polymers by RAFT
88. US8563656B1 [247] 2012 2013 Goodyear Method to improve green Thiol functional poly(NIPAm) 23
strength in elastomers made by RAFT use as blend
component
89. US8883884B2 [248] 2012 2014 Goodyear Pneumatic tire Thiol functional poly(NIPAm) 23
made by RAFT use as blend
component
90. US8309630B2 [249] 2010 2012 Hewlett-Packard Polymer-encapsulated pigment Example use RAFT. RAFT 4
pigment dispersants
91. US7521090B1 [250] 2008 2009 IBM Method of use of Block copolymer 4
US7989026B2 [251] 2008 2011 epoxy-containing lithography.
cycloaliphatic acrylic poly(St)-b-poly(MMA)
polymers as orientation used in process was made
control layers for block by RAFT
copolymer thin films
92. WO2016066586A1 [252] 2014 2016 Illumina Polymers and DNA Coatings with grafted 4 23
US9815916B2 2017 Cam- copolymer coatings DNA
US10208142B2 2019 bridge
US10577439B2 2019 Ltd
93. US10093758B2 [253] 2013 2018 Iowa State Thermoplastic elastomers via Block copolymers based on 4 17
University reversible monomers derived from
Research addition-fragmentation chain triglycerides
Foundation transfer polymerization of
triglycerides
94. US6720429B2 [254] 2002 2004 ITRI Thiocarbonylthio compound and RAFT agents Z–C(=S)S–R with 46
living free radical polymerization R = imidomethyl
using the same
95. US7632959B2 2003 2011 ITRI Thiocarbonylthio compound and RAFT agents with Z = CF3 or 6 11
US7968743B2 [255] free radical polymerization 4-methoxyphenyl
employing the same
(continued)
96. WO2005038734A2 2003 2005 Johns Hopkins Authentication of products using Molecularly imprinted polymers 4
US7799568B2 [256] 2010 University molecularly imprinted polymers
97. WO2005103655A1 2004 2005 Johns Hopkins Processable molecularly Molecularly imprinted polymers 4
US7678870B2 [257] 2010 University imprinted polymers
98. US8241575B2 [258] 2008 2012 Johns Molecularly imprinted RAFT-made polymers 4
Hopkins polymer sensor device used to make sensor
Univer-
sity
99. WO2005003198A1 2003 2005 JSR Photoresist polymer Photoresists based on 48 49
US7510817B2 [259] 2009 compositions bulky methacrylates
100. WO2005000924A1 2003 2005 JSR Photoresist polymers Photoresists based on 48 49
US7517634B2 [260] 2009 bulky methacrylates
101. WO2002098944A1 2001 2002 Kaneka Polyurethane polymer Polyurethanes prepared from 4
US6992138B2 [261] 2006 bis-thiols made by RAFT
end-group aminolysis
102. WO2002098929A1 2001 2002 Kaneka Process for producing polymer Silyl-functional isocyanate used 4
US6914110B2 2005 having crosslinkable silyl group
and curable composition
103. WO2003008474A1 2001 2003 Kaneka Block copolymer Acrylonitrile or 4
US7094833B2 [262] 2006 methacrylonitrile containing
block copolymers made by RAFT
104. WO2002081561A1 2001 2002 Kaneka Thermoplastic resin composition Thermoplastic elastomers 4
US7211625B2 [263] 2007 and elastomer composition (acrylic block copolymers) made
by RAFT
105. WO2016112883A2 [264] 2015 2019 Karlova Macromolecular Protein bioconjugates 4
US10302632B2 Univer- conjugates for comprising an imaging
sity visualization and probe
separation of proteins and
cells
106. WO2009012202A1 2007 2009 Kemira Oyj Mineral dispersants and RAFT-made acrylic 17
US7875213B2 [265] 2011 methods for preparing mineral polyelectrolyte dispersants for
slurries using the same processing mineral slurries
107. US8518497B2 [266] 2009 2013 Korea Advanced Methods for the preparation of Concurrent RAFT and ATRP 4
Institute of coil-comb block copolymers
Science and and their nanostructures
Technology
108. WO2009107987A2 2008 2009 Kyung pH-sensitive polyethylene PEO macro-RAFT agent 29
US8420771B2 [267] 2013 Hee Uni- oxide co-polymer and used to make
versity synthetic method thereof pH-responsive block
copolymer
109. US20050238594A1 [268] 2003 2005 L’Oreal Block ethylenic Block copolymers made by 29 63
copolymers comprising a RAFT
vinyllactam block,
cosmetic or
pharmaceutical
compositions comprising
them and cosmetic use of
these copolymers
110. US7585922B2 [269] 2005 2009 L’Oreal Polymer particle Block copolymers 4
US7816464B2 [270] dispersion, cosmetic containing a segment
compositions comprising based on methacrylates
it and cosmetic process with silane functionality
using it made by RAFT
111. WO2006097529A1 [271] 2005 2006 L’Oreal Cosmetic Use of a Block copolymers made by 29
US20080233077A1 2008 Particular Copolymer as RAFT
Skin Tensor in a Cosmetic
Composition
112. WO2010046229A1 [272] 2008 2010 L’Oreal Dispersion of soft polymer Block copolymers made by 12
US10745582B2 2020 particles, cosmetic RAFT
composition comprising it
and cosmetic treatment
method
(continued)
113. WO2009101113A2 [273] 2008 2009 L’Oreal Oil-in-water emulsion Block copolymers made by 29
US10925815B2 2011 comprising an RAFT emulsion polymer
amphiphilic polymer
114. WO2012156630A1 [274] 2011 2012 L’Oreal Block polymer including Block copolymers made by 23
US20140105838A1 2014 isobutyl acrylate and RAFT
acrylic acid, cosmetic
composition and
treatment method
115. US7115683B2 [275] 2002 2006 LG Chem Organic-inorganic Nanocomposite prepared from 4
nanocomposite and preparation layered silicate salt made by
thereof adding a cationic initiator and a
cationic RAFT agent to a layered
silicate
116. US6888020B2 [276] 2003 2005 LG Chem Water-soluble dithioesters and RAFT agents with quaternary 4 41
method for polymerization ammonium substituent on R and
thereof use for polymerization in
aqueous media
117. US8911537B2 [277] 2010 2014 LG Chem, ICUF Adsorbent of volatile organic Acrylamide-based macroporous 4
Hanyang compounds and adsorption polymer prepared by RAFT
University method using thereof
118. WO2012057443A2 2010 2012 LG Chem Acrylamide-based mesoporous 4 23
US9109063B2 2015 polymer and preparation method
thereof
119. WO2012144735A2 [278] 2011 2012 LG Chem Diblock copolymer, Polymers for block 4
US9493588B2 2016 preparation method copolymer lithography
thereof, and method of
forming nano pattern
using the same
120. WO2016053014A1 [279] 2014 2016 LG Chem Method of manufacturing Block copolymer 4
US10287430B2 2019 patterned substrate lithography process
121. WO2016053005A1 [280] 2014 2016 LG Chem Block copolymer Block copolymers for 4
US10310378B2 2019 self-assembly. Block
US10532546B2 2020 copolymer lithography
122. WO2001060792A1 2002 2005 Noveon S,S′ -bis-(α,α′ -disubstituted- RAFT-made polymers as 12 23
US6894116B2 [281] α′′ -acetic acid)-trithiocarbonates toughening agents in, e.g.
and polymers thereof for adhesive, composite, coatings,
toughening thermosetting resins sealants, caulks, potting resins,
or laminates
123. WO2006023691A2 2004 2006 Lubrizol Associative thickeners for Rheology modifiers prepared by 12 23 73
US7495050B2 [282] 2009 aqueous systems RAFT
124. US8137754B2 [283] 2004 2012 Lubrizol Hydroxyl-terminated Synthesis of hydroxyl-functional 69 73
thiocarbonate containing telechelics for use in
compounds, polymers, and polyurethanes
copolymers, and polyurethanes
and urethane acrylics made
therefrom
125. WO2006020281A1 2004 2006 Lubrizol Hydroxyl-terminated Polyurethanes prepared from 17 29 69 73
US8709543B2 [284] 2014 thiocarbonate containing RAFT-synthesized
compounds, polymers, and hydroxy-functional polymers
copolymers, and polyurethanes
and urethane acrylics made
therefrom
126. WO2006047393A1 [285] 2005 2006 Lubrizol Process for preparing polymers RAFT polymer synthesis 4 23
US8513172B2 2013 and compositions thereof includes blocks and stars
US9809780B2 2017
(continued)
127. WO2008058108A2 2006 2008 Lubrizol Crosslinked polymer Star microgel oil additives 4
US8012917B2 [286] 2011
128. WO2007127661A1 2006 2007 Lubrizol Star polymer lubricating Star microgel oil additives 23
US9006159B2 [287] 2015 composition
129. WO2007127660A1 [288] 2006 2013 Lubrizol Star polymer lubricating Star polymer additive 4 23
US9359577B2 composition
US9410104B2
130. WO2008145613A1 2007 2008 Lubrizol Graft copolymer and Graft copolymers as pigment -
US8268925B2 [289] 2012 compositions thereof dispersants
131. US8507422B2 [290] 2007 2013 Lubrizol Antiwear polymer and Star microgel anti-wear additives 23
lubricating composition thereof
132. WO2012030616A1 2010 2012 Lubrizol Star polymer and lubricating Microgel star-block copolymers 23
US8937035B2 [291] 2015 composition thereof
133. WO2011031659A1 [292] 2010 2011 Lubrizol Farm tractor lubricating Amphiphilic block copolymer 23
US9528072B2 2012 composition with good water additive
tolerance
134. WO2014031154A1 [293] 2013 2014 Lubrizol Loose core star polymers and Star polymers by crosslinking —
US20150183915A1 2015 lubricating composition thereof polymerization
US20180208696A1 2018
135. WO2016182711A1 [294] 2015 2019 Lubrizol Water soluble chain transfer Salts of carboxyl-functional 23
US10280101B2 agents RAFT agents
136. WO2012048009A2 2010 2012 Massachusetts Nanostructured Example is peptide 19

US8916683B2 [295] 2014 Institute physically-associating conjugate to RAFT
of Tech- hydrogels for injectable, poly(NIPAm) via
nology responsive, and tough maleimide
biomaterials
137. WO2014161031A1 [296] 2013 2014 NewSouth Nanoparticles for drug Drug-delivery vehicle 4
US10251958B2 2019 Innova- delivery comprising based on albumin
tions albumin having a polymer conjugate
chain coupled thereto
138. WO 2010133680A1 2009 2010 Novartis Actinically-crosslinkable Crosslinkable prepolymer 4
US8383744B2 [297] 2013 AG siloxane-containing made by RAFT. Contact
copolymers lens application
139. US6858309B2 [298] 2001 2005 Polymerat Methods of polymerization Living/controlled polymerization 4 12
on polymeric solid supports
140. WO2004078785A1 2003 2004 Polymers Dispersing agents in Copolymer dispersants prepared 23
US7837899B2 [299] 2010 Australia nanocomposites by controlled radical
polymerization (ATRP, RAFT,
NMP) for clay in polymer
nanocomposites
141. WO2004113436A1 2003 2004 Ciba Specialty Acrylic dispersing agents in Copolymer dispersants made by 21 23 37
US7288585B2 [300] 2007 Chemicals, nanocomposites RAFT used in polyolefin
Polymers nanocomposites
Australia,
CSIRO
142. WO2007039435A1 2005 2012 Advanced Dispersing agents in composites Dispersants as in US7837899 for -
US8110626B2 [301] Polymerik talc (and other particles) in
polymers
143. WO2010015599A1 2008 2010 Polymers CRC Functionalized thin film RAFT functional membrane 18 26
US8544658B2 [302] 2013 polyamide membranes used for surface-initiated
polymerization
144. US8658149B2 [303] 2008 2014 Ramot At Conjugates of a polymer, a HPMA-based (amongst 17
US9095618B2 [304] Tel-Aviv bisphosphonate and an other) copolymers
Univer- anti-angiogenesis agent comprising segments with
sity and uses thereof in the attached anti-angiogenesis
treatment and monitoring agent and segments with
of bone related diseases bisphosphonate
bone-targeting agent
(continued)
145. US6765076B2 [305] 2001 2004 Rensselaer Transition metal superoxides The transition metal superoxide 4 12
Polytechnic is effectively used as
Institute heterogeneous initiator for living
or controlled free-radical
polymerization. Dibenzyl
trithiocarbonate used
146. US6458968B2 [306] 2000 2002 Rensselaer Dithiocarboxylic ester synthetic Dithioester synthesis by reacting 4
Polytechnic process a carboxylic acid compound, an
Institute alcohol or a thiol, and
phosphorous pentasulfide
147. US8518473B2 [307] 2010 2013 Rensselaer Nanofilled polymeric TiO2 nanocomposites. 4
Polytechnic nanocomposites with tunable Titania-bound RAFT agent
Institute index of refraction
148. WO2012148631A1 2011 2012 Rensselaer Self-healing electrical insulation 6-Azidohexyl 4
US8796372B2 [308] 2014 Polytechnic methacrylate–grafted
Institute nanoparticles
149. WO2001016187A1 1999 2001 Rhodia Chimie Gelled aqueous composition Viscoelastic gels from 29
US6506837B2 [309] 2003 comprising a block copolymer amphiphilic block copolymers
containing at least one
water-soluble block and one
hydrophobic block
150. WO2001094263A2 2000 2001 Rhodia Chimie Process for preparing colloids of Preparation of mineral colloids of 29
US6500871B1 [310] 2002 particles coming from the defined size in aqueous
hydrolysis of a salt of a metal dispersion using block
cation surfactants
151. WO2002008307A1 2000 2002 Rhodia Chimie Method for synthesis of hybrid Preparation of hybrid 29
US6858696B2 [311] 2005 silicon and organic copolymers silicone–organic block
by controlled free radical copolymers containing siloxane
polymerization segments by RAFT
152. WO2001095034A1 2000 2001 Rhodia Photosensitive Styrenic block copolymer 14 39
US6953649B2 [312] 2005 Chimie composition for photoresists made
photoresist manufacture by RAFT
153. WO2003050195A2 2001 2009 Rhodia Method for depositing a Block copolymer 29
US7473730B2 [313] polymer onto a surface by containing ionic block for
applying a composition cosmetic applications
onto said surface
154. WO2003050185A1 2001 2009 Rhodia Formulation comprising Block copolymer 29
US7531597B2 [314] an ionic compound, a containing ionic block for
polyionic polymer, and a cosmetic applications.
block copolymer Formulation for stable
dispersion
155. WO2002068486A2 2001 2002 Rhodia Chimie Water-soluble block copolymers Water-soluble 29
US6437040B2 [315] 2002 comprising a hydrophilic block hydrophilic–hydrophobic blocks.
and a hydrophobic block Use as adhesion promoter in
paint or as wetting agent
156. WO2003006549A1 2001 2003 Rhodia Chimie Composition comprising a Aqueous gel from block 29
US6559233B2 [316] 2003 copolymer at least two charged copolymer. Charged block
blocks and type of opposite copolymers. The aqueous
charge composition is used as
thickeners, in exploitation of
petroleum or gas deposits; in
detergents and cosmetics; and for
metal treatment
157. WO2002070861A1 2001 2002 Rhodia Chimie Hydraulic fracturing fluid Hydraulic fluids based on block 29
US6579947B2 [317] 2003 comprising a block copolymer copolymers
containing at least one
water-soluble block and one
hydrophobic block
(continued)
158. WO2003050195A2 2001 2003 Rhodia Method for depositing a Water-borne hair/skin 29
US6906128B2 [318] 2005 Chimie polymer onto a surface by coatings
applying a composition
onto said surface
159. WO2003050185A1 2001 2003 Rhodia Formulation comprising Block copolymer 29
US6933340B2 [319] 2005 Chimie an ionic compound, a synthesized by RAFT used
polyionic polymer, and a in cosmetics application
block copolymer
160. WO2003050184A1 2001 2003 Rhodia Cosmetic composition The use of diblock 29
US7235231B2 [320] 2007 Chimie comprising a block copolymer as a modifier of
copolymer properties of cosmetic
compositions, copolymer
comprises two blocks,
block A and block B,
wherein block A is a
polycationic block and
block B is a neutral block
161. WO2002090392A1 2001 2002 Rhodia Process for the preparation Hydrophilic–hydrophobic 29
US6825290B2 [321] 2004 Inc. of latices using block blocks as surfactants in
copolymers as surfactants making latex paints
162. WO2004044114A1 2002 2004 Rhodia Chemie Crease-resistant composition Block copolymer application 29
US7378033B2 [322] 2008 comprising a copolymer of
controlled architecture, for
articles made of textile fibres
163. US7423161B2 [323] 2002 2008 Rhodia Chimie Compounds comprising a LPO-initiated SUMI of functional 29
US7820831B2 [324] 2002 2010 thiocarbonyl-sulfanyl group, xanthates
which can be used for the radical
synthesis
of-α-perfluoroalkylamines
164. WO2003076531A1 2002 2003 Rhodia Chimie Use of block copolymers bearing Block copolymers containing, 29
US7439292B2 [325] 2008 phosphate and/or phosphonate e.g. 2-(methacryloyloxy)ethyl
functions as adhesion promoters phosphate
or as protecting agents against
the corrosion of a metallic
surface
165. WO2005074631A2 2004 2005 Rhodia Inc. Rare earth aggregate formulation Block copolymers are made by —
US7468413B2 [326] 2008 using di-block copolymers RAFT and used in extracting,
dispersing rare-earth metals, and
forming nanoparticles
166. WO2006097641A1 2005 2006 Rhodia Block copolymers useful Styrene-co-MAA acrylate 29
US8207273B2 [327] 2012 Chimie as tensioning agents blocks made with
xanthate RAFT agents
167. WO2010046342A1 2008 2010 Rhodia Composition for household care AM/MBA-based microgels 29
US8791058B2 2014 Operations containing a cationic nanogel
168. WO2013113750A1 [328] 2012 2013 Rhodia Live poly(N-vinyl lactam) NVP-based blocks 29
US9487598B2 2016 Operations reactive stabilizers for dispersed
phase polymerization
169. WO2013113752A1 [329] 2012 2013 Rhodia Dispersed phase polymerization NVP-based blocks used as 29
US9255163B2 2016 Operations of halogenated vinyl monomers stabilizers for dispersion
in the presence of life reactive polymerization
stabilizers
170. WO2014167056A1 [330] 2013 2014 Rhodia Fracturing fluids based on High molar mass 29
US10323175B2 2019 Operations associative polymers and on AM/AMPS/LMA as associative
labile surfactants polymer
(continued)
171. WO2013060741A1 [331] 2011 2013 Rhodia Preparation of RAFT emulsion 29

US9580535B2 2017 Opera- amphiphilic block polymerization. Initial
tions polymers by controlled formation of a hydrophilic
radical micellar block. Rheology control
polymerisation agents. Oil recovery
172. WO2013132108A1 [332] 2012 2013 Rhodia Controlled radical Aqueous dispersion 29
US10160821B2 2018 Opera- polymerization in polymerization
tions water-in-water dispersion
173. WO2015144475A1 [333] 2014 2015 Rhodia Amphiphilic multiblock RAFT emulsion 29
US10450397B2 2019 Opera- polymers polymerization. Initial
tions formation of a hydrophilic
block
174. US8829133B2 [334] 2012 2014 Ricoh, ABA triblock copolymer, Poly(11-acrylamidoundec 17
University of thickener, and aqueous anoic acid)-block-poly
Hyogo composition (DMAm)-block-poly(11-
acrylamidoundecanoic acid) as
thickener
175. US6841695B2 [335] 2003 2005 RohMax Process for preparing dithioesters Preparation of dithioester from 4
dithioacid and olefin or
dithiocarboxylic salt with alkyl
halide by phase- transfer
chemistry
176. WO2006105926A1 2005 2006 Rohmax Polyalkyl (meth)acrylate Anti-friction oil additive 4
US8101559B2 [336] 2012 Additives copolymers having outstanding
US8722601B2 [337] 2014 Evonik properties
177. WO2007108867 2001 2007 SABIC Thermoplastic composition, Polycarbonates, including 17
A1US7498398B2 [338] 2009 Innovative method of making, and articles acrylate blocks
Plastics formed therefrom
178. US8757264B2 [339] 2010 2014 Schlumberger Viscous wellbore fluids Amphiphilic copolymers 23
Technology comprising cucurbituril 8
Corporation
179. WO2004011505A1 [340] 2002 2004 Stichting Dutch Process for the copolymerization RAFT copolymerization of 4 17
Polymer of a-olefins with vinyl monomers α-olefins with acrylates
Institute
180. WO2016005288A1 [341] 2104 2016 Smith & Improvements in and relating to Sensor comprising a 41
WO2016012219A2 [342] Nephew devices hyperbranched PNIPAm
181. WO2017029630A1 [343] 2015 2017 Stellenbosch 3-methylene-2-pyrrolidone RAFT (co)polymerization 4 20

Univer- based polymers of NVP. Also other RDRP
sity
182. WO2016024240A1 [344] 2014 2016 Stellenbosch Conjugate for treating PNVP biopolymer 29
US10479854B2 2019 Univer- malaria conjugate
sity
183. US6716948B1 [345] 1999 2004 Symyx Controlled-architecture polymers Star, branched, grafted, or —
US7259217B2 [346] 2007 and use thereof as separation hyper-branched polymers soluble
media or dispersible in aqueous media,
useful for electrophoresis.
Examples are alkoxyamines.
RAFT agents claimed
184. WO2001002452A1 2000 2001 Symyx Polymer brushes for Biosensors for detecting 70
US6692914B1 [347] 2004 immobilizing molecules to the presence and
US6833276B2 [348] 2004 a surface or substrate, concentration of
where the polymers have bio-molecules in a
water-soluble or biological sample. Silica
water-dispersible surface–bound
segments and probes dithiocarbamates (or
bonded thereto nitroxide)
185. WO2002028932A2 2000 2006 Symyx Methods of making ABA-type Bis-RAFT agents used for 41
US7067586B2 [349] block copolymers having a making ABA triblocks
random block of hydrophobic
and hydrophilic monomers
186. US6667376B2 [350] 2002 2003 Symyx Control agents for living-type RAFT agents Z–C(=S)S–R, 36
free radical polymerization and where Z is –O–N(R1 )(R2 )
methods of polymerizing
(continued)
187. US6803410B2 [351] 2003 2004 Symyx Cellulose copolymers that Grafts to cellulose using RAFT. 29 41
modify fibres and surfaces The cellulosic backbone
polymers allow for the
modification of fibres or surfaces,
preferably in presence of water to
provide a desired effect
188. WO2005003192A1 2003 2005 Symyx Synthesis of photoresist Photoresists based on 48 49
US7250475B2 [352] 2007 polymers bulky methacrylates made
US7399806B2 [353] 2008 by RAFT. Pyrazoline
RAFT agent
189. WO2001098383A1 2000 2001 Tesa AG Method for producing Pressure-sensitive adhesives 4 17
US6765078B2 [354] 2004 polyacrylates made by RAFT. Claim focuses on
reaction conditions. Step claimed
to be novel is late addition of a
peroxide initiator to drive
polymerization to high
conversion and possibly
introduce branching
190. US6703441B2 [355] 2001 2004 Tesa AG Oriented acrylic block Pressure-sensitive adhesives 17
copolymers based on triblock copolymers.
Bis(phenylethyl)
trithiocarbonate) used in
examples
191. US6720399B2 [356] 2001 2004 Tesa AG UV-crosslinkable acrylic hotmelt Acrylic triblocks made by RAFT 17
PSAs with narrow molecular as UV-curable pressure-sensitive
weight distribution adhesives
192. WO2003000794A1 2001 2003 Tesa AG Strippable systems based on Polyacrylate-based block 17
US6723407B2 [357] 2004 acrylic block copolymers copolymers as pressure-sensitive
adhesives with improved
adhesive properties (especially
adhesive strength)
193. US6723786B2 [358] 2001 2004 Tesa AG Pressure sensitive adhesive, Acrylic triblocks made with 17
particularly for apolar surfaces trithiocarbonates as
pressure-sensitive adhesives
194. WO2003046030A1 2001 2003 Tesa AG Crosslinking of A process for increasing the 17
US7271203B2 [359] 2007 photoinitiator-initialized molecular weight of
polyacrylates polyacrylates, where
polyacrylates are functionalized
at least on one part of their chain
ends by photoinitiator groups X
are exposed to UV radiation, so
that a direct linking reaction of
the polyacrylates takes place
195. WO2002010309 2001 2002 Tesa AG Adhesive material based on Block copolymers of 17
A1US7307115B2 [360] 2007 block copolymers having a P(A)–P(B)–P(A) as
p(a)-p(b)-p(a) structure pressure-sensitive adhesives
made with RAFT, where P(A)
has a glass transition temperature
of 0 ∘ C or below, P(B) has a glass
transition temperature of 20 ∘ C
or above, and P(A) and P(B) are
immiscible.
196. WO2003046031A1 2001 2008 Tesa AG 2-Component crosslink of A process for increasing the 17
US7402632B2 [361] end-functionalized polyacrylates molecular weight of
polyacrylates, wherein
polyacrylates functionalized at
least on some of their chain ends
by functional groups X are
prepared by the RAFT process
using thiocarbonates
(continued)
197. WO2003000794A1 2001 2003 Tesa AG Adhesive masses based on block Triblock polymers made by 17
WO2003000819A1 2003 copolymers of structure RAFT in adhesive compositions
US8129470B2 [362] 2012 P(A)-P(B)-P(A) and
P(B)-P(A)-P(B)
198. WO2004018582A1 2002 2004 Tesa AG Method for the production of Pressure-sensitive adhesives. 17
US7514515B2 [363] 2009 acrylate adhesive materials using Contains metal complexes
metal-sulphur compounds
199. WO2004015020A1 2002 2004 Tesa AG Adhesive materials having a high Pressure-sensitive adhesive 17
US7758933B2 [364] 2010 refractive index based on acrylate comprising an acrylate block
block copolymers copolymer with high refractive
index
200. US7459499B2 [365] 2003 2008 Tesa AG Pressure-sensitive adhesive based Pressure-sensitive adhesive 17
on acrylate block copolymers comprising an acrylate block
copolymer having at least two
chemically distinguishable,
covalently interlinked acrylate
polymer blocks P in
microphase-separated regions
and each having a softening
temperature between −125 and
+20 ∘ C.
201. US7432326B2 [366] 2004 2008 Tesa AG Pressure-sensitive adhesive based The invention provides an 17
on acrylate block copolymers acrylate-based pressure-sensitive
adhesive comprising a polymer
blend
202. WO2006027385A1 2004 2006 Tesa AG Method for producing contact Contact adhesives made by 17
WO2006027386A1 2006 adhesive masses containing RAFT. Dibenzyl trithiocarbonate
US7605212B2 [367] 2009 acrylic used
203. US8822130B2 [368] 2012 2014 Texas A&M Self-assembled structures, Photoresists based on 4
University, method of manufacture graft-block copolymers
Rohm and Haas thereof and articles
Electronics comprising the same
Materials
204. WO2003010268A1 2001 2003 Unilever Use of compounds in products Polysaccharide-based graft 29 41
EP1409627B1 [369] 2005 for laundry applications polymers. Isocyanate functional
RAFT agents
205. WO2004056952A1 2002 2004 Unilever Laundry treatment compositions A laundry treatment–based On
US7179777B2 [370] 2007 Henkel comprising a polymer with a PDMS-block-(cationic polymer)
cationic and polydialkylsiloxane that can be made by RAFT
moiety
206. WO2009147338A1 2008 2009 Universite Amphiphilic block Amphiphilic PEO-based 4 23
US8598289B2 [371] 2013 Pierre Et copolymer and method for macroRAFT agents in
Marie preparing same emulsion
Curie,
CNRS,
Univer-
site De
Liege
207. US10023700B2 [372] 2016 2018 University Hydrogel Hydrogel based on 23
of Alberta NIPAm/dopamine
acrylamide copolymer
segment for drug delivery
208. US9158200B2 [373] 2013 2015 University of Compositions for controlled Silicon-containing blocks for 4
California assembly and improved ordering lithographic applications. 4VP
of silicon-containing block blocks by RAFT
copolymers
209. US8211996B2 [374] 2008 2012 University Well-defined RAFT-made block 26
of Cali- donor-acceptor rod-coil copolymer
fornia diblock copolymer based
on P3HT containing C60
210. US8153729B2 [375] 2008 2012 University of Highly efficient agents for RAFT-synthesized 4
California dispersion of nanoparticles in hyperbranched polymers as
Mitsubishi matrix materials dispersants
Chemical
(continued)
211. US9676888B2 [376] 2010 2017 Mitsubishi Chain transfer agent and Amphiphilic RAFT agents Not listed
US9452978B2 [377] 2010 2016 Chemical emulsion polymerization for emulsion
using the same polymerization. Aryl
dithioester or
trithiocarbonate where Z
is hydrophilic group
212. WO 2013082196 [378] 2011 2013 University bFGF-polymer conjugates, Heparin-mimicking 19
US 9925270B2 2018 of Cali- methods for making the polymer and conjugates
US10039807B2 2018 fornia same and applications
thereof
213. WO2016025668A1 [379] 2014 2016 University Substituted polyesters by Conjugates. Formation of 19
US10273333B2 2019 of Cali- thiol-ene modification: trehalose co-polymers.
fornia rapid diversification for Polyesters formed by
therapeutic protein RAFT ROP of BMDO
stabilization
214. WO2013112897A1 [380] 2012 2013 University Stabilization of Glycopolymer conjugates 19
US9901648B2 2018 of Cali- biomolecules using sugar for stabilization of
US10543280B2 2020 fornia polymers biomolecules
215. WO2006086646A2 2005 2006 University Stress relief for crosslinked Use of a RAFT process to 17 79
US7943680B2 [381] 2005 2011 of polymers for dental control stress in
US8404758B2 [382] 2013 Colorado materials crosslinking
polymerization. Dynamic
covalent polymers
216. US8877830B2 [383] 2005 2014 University Stress relief for crosslinked Dental application of 17 79
of polymers polymer containing
Colorado trithiocarbonate
functionality. Dynamic
covalent polymers
217. US9193682B2 [384] 2013 2016 University Synthesis of Dynamic covalent 17 79
of trithiocarbonates and allyl polymers
Colorado sulfides and their
application into advances
in covalent adaptable
networks
218. US9758597B2 [385] 2011 2017 University of Reducing Symmetrical RAFT agents used 17
Colorado polymerization-induced in crosslinking formulations
shrinkage stress by reversible
addition-fragmentation chain
transfer
219. WO2019183140A1 [386] 2018 2019 University Tough, healable Self-healing materials. 79
of composites displaying Dynamic covalent
Colorado stress relaxation at the polymers
resin-filler interface
220. US10512607B2 [387] 2015 2019 University Polymeric particles, Propacrylic acid–based 23
of Florida method for cytosolic polymer used in drug
Vanderbilt delivery of cargo, methods delivery
Univer- of making the particles
sity
221. US8669335B2 [388] 2010 2014 University of Knotty polymers via Macrocyclic structures. Various —
Houston supramolecularly templated dithioesters and
macroinitiators and living trithiocarbonates used
polymerization and methods for
making and using same
222. US8802235B2 [389] 2012 2014 University Drug and imaging agent Star polymers from 29
of Kansas delivery compositions and multi-xanthate RAFT
methods agent
223. US7687600B2 [390] 2004 2010 University Invertible amphiphilic Invertible micelles for 4
of Mas- polymers drug delivery from block
sachusetts copolymers made by
RAFT
(continued)
224. US8198368B2 [391] 2007 2012 University of Cleavable block copolymers, Thiol-terminated polymer 4
US8546488B2 [392] 2007 2013 Massachusetts functionalized nanoporous thin converted to macroRAFT agent
films and related methods of and used to make blocks
preparation
225. WO2009023158A2 2007 2009 University Polymeric reverse micelles Amphiphilic polymeric 4
US8969026B2 [393] 2015 of Mas- as selective extraction micelles
sachusetts agents and related
methods of MALDI-MS
analysis
226. WO2012162307A2 [394] 2011 2013 University Crosslinked polymer Encapsulated therapeutics 4 23
US9592302B2 2017 of Mas- nano-assemblies and uses
US10358531B2 2019 sachusetts thereof
227. US10562901B2 [395] 2017 2020 University Temozolomide Polymer therapeutic 4
of Mas- compounds, polymers containing temozolomide
sachusetts prepared therefrom, and
method of treating a
disease
228. US8496997B2 [396] 2010 2013 University of Process for the preparation of a Layer-by-layer assembly and 4
Melbourne cross-linked multilayer film crosslinking process. RAFT used
amongst other methods
229. US7999020B2 [397] 2007 2011 University Ion gels and electronic An ion gel, including an 23
of Min- devices utilizing ion gels ionic liquid and a block
nesota copolymer
230. US8420704B2 [398] 2007 2013 University of Nano-structured polymer Crosslinked polymer monoliths —
Minnesota composites and process for with degradable block. RAFT
preparing same agent not specified
231. US8840339B2 [399] 2008 2014 University of Soil remediation process Polymers containing groups with 29
Queensland bind metals
232. WO2014152451A2 [400] 2013 2014 University Compositions and Therapeutic delivery to 19
US9949950B2 2018 of methods for controlled bone
US10195284B2 2019 Rochester localized delivery of bone
forming therapeutic
agents
233. US8592539B2 [401] 2010 2013 University of Preparation of No RAFT examples —
South Carolina cobaltocenium-containing
monomers and their polymers
234. US8865796B2 [402] 2011 2014 University of Nanoparticles with multiple Surface-initiated RAFT 4
US9109070B2 [403] South Carolina attached polymer assemblies and polymerization multiple
US9475922B2 use thereof in polymer functionalization–
composites polymerization–deactivation
steps
235. US9725544B2 [404] 2013 2017 University Preparation of conjugated RAFT polymerization of 4
of South aromatic/heteroaromatic macromonomers
Carolina oligomer-containing containing conjugated
dielectric polymers and oligomeric (e.g.
their applications oligothiophene) segments
236. US9732169B2 [405] 2014 2017 University of Raft agents and their use in the Grafting from 41
US10494461B2 South Carolina development of RAFT-functionalized silica
polyvinyl-pyrrolidone grafted nanoparticles
nanoparticles
237. US10556980B2 2014 2020 University of Poly alkyl (meth)acrylates grafted Surface-initiated RAFT 4
South Carolina nanoparticles and their methods polymerization from particles
of manufacture and use
(continued)
238. US7138468B2 [406] 2002 2006 University Preparation of transition Gold and other 4
US7417096B2 [407] 2002 2008 of metal nanoparticles and nanoparticles from
US8084558B2 [408] 2002 2011 Southern surfaces modified with RAFT-made polymers,
Missis- (co)polymers synthesized useful in optics, medicine,
sippi by RAFT electronics, biochips,
high-throughput
screening, and biological
transfer agents
239. US7718432B2 [409] 2006 2010 University Non-immunogenic, HPMAm block copolymer 4
of hydrophilic/cationic block for controlled-release
Southern copolymers and uses applications
Missis- thereof
sippi
240. WO2006037161A1 [410] 2004 2006 University Polymerisation process RAFT in emulsion. 17 21
US9731321B2 2017 of Sydney and polymer product Amphiphilic macroRAFT
agents. TiO2 particle
encapsulation
241. WO2007112503A1 2006 2007 University Polymer product and Polymer-encapsulated 21
US8796359B2 [411] 2014 of Sydney interfacial polymerisation particles made by RAFT
US8779029B2 [411] 2014 process using RAFT agent emulsion polymerization
242. WO2009137889A1 2008 2009 University Polymer microgel beads Polymer-encapsulated 21
US8765183B2 [412] 2014 of Sydney magnetic nanoparticles
made by RAFT emulsion
polymerization
243. WO2009137888A1 2008 2009 University Polymer microgel beads Polymer-encapsulated 21 22
US8852641B2 [413] 2014 of Sydney and preparative method magnetic nanoparticles
thereof made by RAFT emulsion
polymerization
244. WO2009137890A1 2008 2009 University Administrable Drug-delivery particles 21
US8709486B2 [414] 2014 of Sydney compositions made by RAFT emulsion
polymerization
245. WO2011066608A1 [415] 2009 2010 University Water swellable polymer Polymer-encapsulated 17 21
US9255198B2 2016 of Sydney materials comprising particulate material (e.g.
particulate core and water TiO2 ) prepared by RAFT
swellable RAFT polymer emulsionpolymerization
shell
246. WO2012142669A1 [416] 2011 2012 University Method for the treatment Iron oxide nanoparticles 21
US10376589B2 [417] 2019 of Sydney of a solid tumour formed by emulsion
polymerization
247. US7718193B2 [418] 2007 2010 University Temperature- and Block copolymers 23
of Wash- pH-responsive polymer
ington compositions
248. US7981688B2 [419] 2007 2011 University Stimuli-responsive Stimuli-responsive 23
US8507283B2 [420] 2007 2013 of Wash- magnetic nanoparticles magnetic nanoparticles
ington and related methods
249. WO2011159721A2 2009 2013 University System and method for PNIPAm-based magnetic 23
US8426214B2 [421] of Wash- magnetically nanoparticles
ington concentrating and
detecting biomarkers
250. WO2009140427A2 [422] 2008 2009 University Diblock copolymers and Block copolymers for 19
US9476063B2 2016 of Wash- polynucleotide complexes therapeutic delivery of
US9862792B2 2018 ington, thereof for delivery into polynucleotides
Genevant cells
Sciences
(continued)
251. WO2009140421A2 [423] 2008 2009 University Polymeric carrier Block copolymers for 19
US9006193B2 2015 of Wash- therapeutic delivery
ington,
Genevant
Sciences
252. WO2010077678A2 [424] 2008 2010 University ω-functionalized Polymer conjugates with 19
US9593169B2 2017 of Wash- polymers, different architectures
US10066043B2 2018 ington, junction-functionalized
Genevant block copolymers,
Sciences polymer bioconjugates,
and radical chain
extension polymerization
253. WO2011062965A2 [425] 2009 2011 University Targeting monomers and Polymerization of 19
US9415113B2 2016 of Wash- polymers having targeting monomer derivatives of
ington, blocks folate
Genevant
Sciences
254. WO2009140429A2 [426] 2009 2010 University Micellic assemblies Therapeutic delivery 19
US9339558B2 2016 of Wash- comprising a plurality of
US9662403B2 2017 ington, copolymers
US10420790B2 2017 Genevant
Sciences
255. WO2018165194A1 [427] 2017 2018 University Cell-based methods and Therapeutic delivery 19
WO2018165198A1 [428] of Wash- compositions for
ington, therapeutic agent delivery
CSIRO and treatments using same
256. WO2019160983A1 [429] 2018 2019 University Radiant star nanoparticle Stars with hyperbranched 19
of Wash- prodrugs and related core made by RAFT used
ington, methods for therapeutic delivery
CSIRO
257. US9533006B2 [430] 2007 2017 University of Marine coatings based on Anti-fouling coatings based on 4
US10544312B2 2020 Washington cationic polymers copolymers containing betaines
258. US9181432B2 [431] 2012 2013 US Secretary of Branched additives for polymer Thiol-functional polymer grafted 23
US10494485B2 2019 Army toughening to SBS by thiol-ene process.
Other grafting processes also
mentioned
259. WO2017156250A2 [432] 2016 2019 US Acute care cover for severe Wound dressings 23
US10472450B2 Secretary injuries
of Navy
260. WO2014066912 [433] 2012 2014 Vanderbilt Polymeric nanoparticles Library of PEG block 19
US10172956B2 2019 Univer- copolymers synthesized
sity
261. US8197847B2 [434] 2006 2012 Warwick Process for making Polymers with pendant —
Effect polymers and supports azide or alkyne groups.
Polymers comprising pendant sugar Used for glycopolymer
side groups synthesis. No RAFT
examples
262. WO2016138528A1 [435] 2015 2016 Wayne Methods and Block copolymer used in 17
US10596300B2 State Uni- compositions relating to hydrogel coating for
versity biocompatible implants implants
263. WO2011140318A1 [436] 2010 2017 Johnson Non-reactive, hydrophilic Polymers comprising a 22 29
US9815979B2 [437] & polymers having terminal hydrophilic segment and a
US10301465B2 Johnson siloxanes and methods for siloxane segment. Made
Vision making and using the by copolymerization of
Care same hydrophilic monomers
using a siloxane-based
RAFT agent (PNVP with
xanthate, PDMAm with
trithiocarbonate)
264. WO2012151135A1 [438] 2011 2012 Johnson Medical devices having Ionic silicone hydrogels as 22
US9170349B2 2015 & homogeneous charge contact lens material
US9599751B2 2017 Johnson density and methods for
US10386545B2 2019 Vision making same
Care
(continued)
265. WO2013176886A2 2012 2013 Johnson Polymers and nanogel Contact lens material 22
WO2013177506A2 [439] 2013 & materials and methods for
WO2013177523A2 [440] 2013 Johnson making and using the
US9244196B2 2016 Vision same
US9297929B2 2016 Care
US9625617B2 2017
US9726906B2 2017
US10073192B2 2018
US10502978B2 2019
US10502867B2 2019
266. US9428649B2 [220] 2010 2016 E Ink California Electrophoretic dispersion Polymer-grafted pigment 4
US9732231B2 [221] 2010 2017 Method of making particles made by
electrophoretic dispersion surface-initiated RAFT
a) Priority date.
b) Date published.
c) Spelling of Title reflects that used on the patent document.
d) ZC(=S)S– groups exemplified (refer Table 24.6).
24.3.3 Synthesis of Stars and Nano- or Microgels by RAFT

Polymerization
Star synthesis making use of multi-RAFT agents is described in the first RAFT
patents (Table 24.7, entry 1). The arm-first method for synthesis of stars (also
called microgels) involves a RAFT crosslinking copolymerization mediated by a
macroRAFT agent (Table 24.7, entry 7). Use of a mixture of macroRAFT agents,
in principle, provides a mikto-arm polymer (Table 24.7, entry 30). The core-first
approach involves a RAFT crosslinking copolymerization to which arms are grafted
by a subsequent RAFT polymerization step (Table 24.7, entries 30 and 32). These
arm-first and core-first strategies can be combined in the so-called in–out method.
Other processes for star or microgel synthesis by RAFT polymerization involve the
self-assembly of amphiphilic block copolymer followed by core or shell crosslinking
(Table 24.7, entry 12) and self-condensing vinyl polymerization (Table 24.7, entry
36).
24.3.4 RAFT Applications

There are many patents that describe applications of RAFT polymerization. In the
tabulation below we have, for the most part, limited the scope to patents that have
progressed to being granted in the US and that have a working example making use
of RAFT polymerization. We also indicate the type of RAFT agent used in those
examples. Often a larger range of RAFT agents and sometimes RDRP methods is
claimed.
This survey is not comprehensive but does serve to illustrate the potential applica-
tions of RAFT in an industrial/commercial context. Various bioapplications (ther-
apeutic, cosmetic, ophthalmic) are highlighted in green. Patents relating to RAFT
emulsion polymerization are shaded blue. Electronics applications (resists, polymer
semiconductors) are shaded yellow.
Some open literature publications on the industrial application of RAFT polymer-
ization have appeared [441–443]. The development of RAFT applications has been
facilitated by the availability of RAFT agents in quantities suitable for research by
Strem [444], Merck (Sigma Aldrich) [445, 446], and Boron Molecular under license
from CSIRO. Recent years have seen the large-scale (multi-kg or, in a few cases,
multi-ton) production of Rhodixan A1TM (80) by Rhodia (Solvay), Blocbuilder DBTM
(81) by Arkema [447], CTA-1 (84) by Lubrizol [146], DOPAT (82) by Dulux, and
CDTPA (86) by DuPont (Table 24.7, entry 30) [448] mainly for internal use within the
respective companies. Those known to be listed on the European Chemical Agency
C&L inventory are shown in Table 24.8. Only 80, 81, and 89 appear to be registered
for REACH in Europe. RAFT agents 81 and 82 are registered under NICNAS in Aus-
tralia. A wider range of thiocarbonylthio-RAFT agents, including 81, 85, and 86, is
available on scale for industry from Boron Molecular [449].
24.3.5 RAFT Thiocarbonylthio-End-Group Removal/Transformation

A significant amount of patent activity has concerned RAFT end-group removal
(Table 24.10). In these patents, the methods are typically only exemplified for a very
limited selection of RAFT agents and for a narrow range of polymers with those end
groups. However, broad applicability for the various methods is usually claimed.
Table 24.10 Patents disclosing methods for RAFT end-group removal/transformation.
1. WO2002072642A1 2001 2002 Kaneka Process producing Alkene-terminated 4

US7009004B2 [450] 2006 vinyl polymer having polymers made by
US7081503B2 [451] 2006 alkenyl group at end, RAFT end-group
vinyl polymer, and aminolysis and
curable composition reaction thiol end
polymer with
allyl-isocyanate
2. WO2002090397A1 2001 2002 Rhodia Method for free radical A method of removing 29
US7109276B2 [452] 2006 Chimie reduction of thiocarbonylthio and
dithiocarbonylated or dithiophosphoryl
dithiophosphorylated terminal groups by
functions borne by a contacting it with a
polymer source of free radicals
and an organic
compound with a
labile hydrogen atom.
3. WO2002090424A1 2001 2002 Rhodia Method for synthesis of Isobutyl xanthate 31
US7396901B2 [453] 2008 Chimie polymers with thiol end-group thermolysis
functions
4. WO2003070780A1 2002 2003 Rhodia Process for removing a Removal of 29
US6794486B2 [454] 2004 Chimie dithiocarbonyl group thiocarbonylthio group
at the end of a polymer by treatment with
chain amine not
triethanolamine in an
organic solvent. Only
example is aqueous
ammonium hydroxide.
5. WO2004089994A1 [455] 2001 2004 Symyx Cleaving and replacing End-group removal by 49
US7012119B2 2006 thio-control agent heating with peroxide
moieties from polymers (LPO). Optional presence
made by living-type free of addition–fragmentation
radical polymerization transfer agents (AMS
dimer) is mentioned.
6. US20040266953A1 2003 2004 Symyx Removal of the RAFT end-group removal 48 49
US6919409B2 [456] 2005 thiocarbonylthio or by chain transfer with a
thiophosphorylthio end radical source. At least
group of polymers and 50% of the thio-groups are
further functionalization replaced with a group of
thereof interest other than
hydrogen.
7. WO2005061555A1 [457] 2003 2005 University Polymerisation using RAFT end-group removal 4 25
US20070299221A1 2007 of Leeds chain transfer agents by radical-induced
US20090215965A1 2009 coupling. Solid-supported
2010 RAFT polymerization.
US20100160574A1
8. WO2005040233A1 2003 2005 Rhodia Method for partial or total Ozonolysis of RAFT end 29
US7473740B2 [458] 2009 Chimie oxidation of one or several groups.
pub [459] thiocarbonylthio ends of a
polymer obtained by
radical polymerisation
controlled by reversible
9. WO2005113612A1 2004 2005 CSIRO Method for removing End-group removal with 4 23
US7807755B2 [460] 2010 sulfur-containing radical-induced reduction
end-groups with hypophosphite
(continued)
10. WO2013086585A1 [461] 2011 2013 CSIRO RAFT polymers End-group removal in 4 18 23 25
US9650450B2 2017 continuous flow by
thermolysis,
radical-induced reduction,
or aminolysis
11. US8283436B2 [462] 2006 2012 CSIRO Process for synthesizing Use of functional reagent 4 23
thiol terminated polymers in end-group removal
12. WO2013062789A1 [463] 2012 2013 DuPont Processes for removing Improved procedure for 23
sulfur-containing end end-group removal with
groups from polymers hypophosphite
13. WO2017027557A1 [464] 2015 2017 Henkel Thiocarbonylthio-free End-group removal with 23
US20180155463A1 RAFT polymers and the hydrogen peroxide
process of making the
same
14. WO2018017478A1 [465] 2016 2018 University Catalytic functional group End-group removal with 23
of Cali- removal from a polymer use of photoredox catalyst
fornia and H-atom donor
15. WO2020100086A1 [466] 2018 2020 KAUST Removal of End-group removal with 4 23 29 66
thiocarbonylthio end trialkylborane plus
groups from polymers oxygen.
synthesized by reversible
chain transfer
polymerization
a) Priority date.
b) Date published.
c) Spelling of Title reflects that used on the patent document.
d) ZC(=S)S– groups exemplified (refer Table 24.6).
References 1141
Table 24.10 is not a comprehensive list of patents disclosing methods for

end-group removal. It contains most patents where end-group removal is a primary
focus. Detailed discussion on end-group removal/transformation can be found in
the chapter by Lowe and Dallerba [467] and is given some coverage in the chapters
on the individual classes of RAFT agents (i.e. dithioesters [468], trithiocarbonates
[145], xanthates [469], dithiocarbamates [470]).
Abbreviations
AA acrylic acid
BMDO 5,6-benzo-2-methylene-1,3-dioxepane
CCT catalytic chain transfer
HPMAm N-(2-hydroypropyl)methacrylamide
LAM less activated monomer
LPO lauroyl peroxide
MAM more activated monomer
NMP nitroxide-mediated polymerization
NVP N-vinyl pyrrolidone
PDMS poly(dimethylsiloxane)
ROMP ring-opening metathesis polymerization
ROP ring-opening polymerization
SUMI single-unit monomer insertion
VAc vinyl acetate
4VP 4-vinylpyridine
References
1 Favier, A., de Lambert, B., and Charreyre, M.-T. (2008). Toward new materi-
als prepared via the RAFT process: from drug delivery to optoelectronics? In:
Handbook of RAFT Polymerization (ed. C. Barner-Kowollik), 483–535. Wein-
heim: Wiley-VCH. doi: 10.1002/9783527622757.ch13.
2 Destarac, M. (2010). Controlled radical polymerization: industrial stakes, obsta-
cles and achievements. Macromol. React. Eng. 4: 165–179. doi: 10.1002/mren
.200900087.
3 Destarac, M. (2018). Industrial development of reversible-deactivation radical
polymerization: is the induction period over? Polym. Chem. 9: 4947–4967. doi:
10.1039/C8PY00970H.
4 Moad, G. (2022). Terminology in reversible deactivation radical polymerization

(RDRP) and reversible addition-fragmentation chain transfer (RAFT) polymer-
Moad, E. Rizzardo), 15–24. Weinheim: Wiley-VCH.
5 Cacioli, P., Hawthorne, D.G., Laslett, R.L. et al. (1986). Copolymerization of
w-unsaturated oligo(methyl methacrylate): new macromonomers. J. Macromol.
Sci., Chem. A23: 839–852. doi: 10.1080/00222338608069476.
6 Antonelli, J.A., Scopazzi, C., and Doherty, M.M. (1991). Process for preparing
stabilized polymer dispersion. US5010140A. du Pont de Nemours, E. I., and Co.
7 Darmon, M.J., Berge, C.T., and Antonelli, J.A. (1993). Process of polymerization
in an aqueous system. WO9322351A1. du Pont de Nemours, E. I., and Co.
8 Antonelli, J.A. and Scopazzi, C. (1994). Star polymers made from
macromonomers made by cobalt chain transfer process. US5310807A. du Pont
de Nemours, E. I., and Co.
9 Moad, G., Moad, C.L., Krstina, J. et al. (1996). Preparation of block copolymer
with low dispersity by radical polymerization. WO9615157A1. Du Pont/CSIRO.
10 Chang, D.C.K. and Fryd, M. (1999). Water-thinned coatings compositions con-
taining self-stabilized crosslinked latexes. WO9903937A1. E. I. Du Pont de
Nemours & Co.
11 Gridnev, A.A. and Ittel, S.D. (1996). Synthesis of terminally unsaturated
oligomers. WO9633224A1. E. I. Du Pont de Nemours & Co.
12 Ma, S.-H. and Fryd, M. (1998). Aqueous dispersions containing graft copoly-
mers as the dispersants. EP826751A2. E. I. Du Pont de Nemours & Co.
13 Moad, G., Rizzardo, E., Moad, C.L. et al. (1997). Catalytic polymerization pro-
cess and the resulting polymers with terminal unsaturation. WO9731030A1.
E. I. Du Pont de Nemours & Co., USA; Commonwealth Scientific & Industrial
Research Organization; Moad, G., Rizzardo, E., Moad, C.L., Ittel, S.D., Wilczek,
L., Gridnev, A.A.
14 Berge, C.T., Fryd, M., Johnson, J.W. et al. (2003). Process for preparing star
shaped microgels from macromonomers with terminal ethylenic unsaturation.
US6653407B2. duPont/CSIRO/University of Melburne.
15 Fryd, M. and Visscher, K.B. (2000). Dispersions having improved stability using
polymer dispersant for encapsulating pigment. WO2000020520A1. E. I. Du Pont
de Nemours & Co.
16 Donald, D.S., Hertler, W.R., and Ma, S.-H. (2001). Block copolymer dispersing
agents for inks with enhanced substrate binding characteristics. US6306994B1.
E. I. Du Pont de Nemours & Co.
17 Berge, C.T., Chiefari, J., Johnson, J.W. et al. (2001). Microgel synthesis and
products produced therefrom. WO2001077198A1. E. I. Du Pont de Nemours &
Co; Commonwealth Scientific and Industrial Research Organization.
18 Huybrechts, J. (2001). Aqueous polymer emulsions for coatings. EP1138730A2.
E. I. Dupont De Nemours and Co.
19 Ma, S.-H. and Kelly, R.J. (2006). Rapid drying lacquers containing triblock
copolymer for rheology control. US20060287437A1. E. I. du Pont de Nemours
and Co., USA.
References 1143
20 Goebelt, B., Omeis, J., Orth, U. et al. (2008). Graft (block)copolymers for
wetting agents or dispersants for powders. WO2008080579A1. BYK-Chemie
G.M.b.H., Germany.
21 Goebelt, B., Nagel, C., Omeis, J. et al. (2009). Wetting and dispersing agent.
WO2009098025A1. BYK-Chemie GmbH, Germany.
22 Ma, S.-H. (2010). Producing block copolymer pigment dispersants.
US20100081769A1. E. I. Du Pont de Nemours and Company, USA.
23 Ma, S.-H. (2010). Block copolymer pigment dispersants. WO2010036867A1. E. I.
Du Pont de Nemours and Company, USA.
24 Ma, S.-H. (2011). Block copolymer pigment dispersants. US20110144263A1. E. I.
Du Pont De Nemours and Company, USA.
25 Joly, G.D., Abuelyaman, A.S., Fornof, A.R. et al. (2014). Addition-fragmentation
agents used in dental compositions. WO2014074427A1. 3M Innovative Proper-
ties Company, USA.
26 Moser, W.H., Fornof, A.R., Joly, G.D. et al. (2016). Addition-fragmentation
process for preparation of stress-reducing crosslinked oligomers and dental
applications. WO2016133668A1. 3M Innovative Properties Company, USA.
Macromolecules 28: 5381–5385. doi: 10.1021/ma00119a034.
28 Krstina, J., Moad, C.L., Moad, G. et al. (1996). A new form of controlled growth
free radical polymerization. Macromol. Symp. 111: 13–23. doi: 10.1002/masy
.19961110104.
29 Zhang, M. and Hutchinson, R.A. (2018). Synthesis and utilization of low
dispersity acrylic macromonomer as dispersant for nonaqueous dispersion
polymerization. Macromolecules 51: 6267–6275. doi: 10.1021/acs.macromol
.8b01169.
30 Yang, W. and Hutchinson, R.A. (2016). Investigating the effectiveness of reac-
tive dispersants in non-aqueous dispersion polymerization. Macromol. React.
Eng. 10: 71–81. doi: 10.1002/mren.201500028.
31 Shegiwal, A., Wemyss, A.M., Schellekens, M.A.J. et al. (2019). Exploiting cat-
alytic chain transfer polymerization for the synthesis of carboxylated latexes via
sulfur-free RAFT. J. Polym. Sci., Part A: Polym. Chem. 57: E1–E9. doi: 10.1002/
pola.29302.
32 Engelis, N.G., Anastasaki, A., Whitfield, R. et al. (2018). Sequence-controlled
methacrylic multiblock copolymers: expanding the scope of sulfur-free RAFT.
Macromolecules 51: 336–342. doi: 10.1021/acs.macromol.7b01987.
tion. Nat. Chem. 9: 171–178. doi: 10.1038/nchem.2634.
34 Gridnev, A.A. and Ittel, S.D. (2001). Catalytic chain transfer in free-radical poly-
merizations. Chem. Rev. 101: 3611–3660. doi: 10.1021/cr9901236.
35 Heuts, J.P.A. and Smeets, N.M.B. (2011). Catalytic chain transfer and its derived
macromonomers. Polym. Chem. 2: 2407–2423. doi: 10.1039/C1PY00224D.
36 Slavin, S., McEwan, K., and Haddleton, D.M. (2012). Cobalt-catalyzed chain
transfer polymerization: a review. Polymer Science: A Comprehensive Reference
(eds. K. Matyjaszewski and M. Möller), 249–275. Amsterdam: Elsevier. doi: 10
.1016/B978-0-444-53349-4.00068-6.
37 Demarteau, J., Debuigne, A., and Detrembleur, C. (2019). Organocobalt
complexes as sources of carbon-centered radicals for organic and polymer
chemistries. Chem. Rev. 119: 6906–6955. doi: 10.1021/acs.chemrev.8b00715.
38 Enikolopov, N.S., Korolev, G.V., Marchenko, A.P. et al. (1980). Molecular weight
control of methacrylic polymers. SU664434A1. Institute of Chemical Physics,
Chernogolovka, USSR; Siberian Institute of Petroleum Chemistry.
39 Carlson, G.M. and Abbey, K.J. (1985). Low-molecular-weight polymers and
copolymers. US4526945A. SCM Corp.
40 Lin, J.C. and Abbey, K.J. (1987). Low molecular weight polymers and copoly-
mers. US4680354A. Glidden Co., USA.
41 Melby, L.R., Janowicz, A.H., and Ittel, S.D. (1986). Cobalt(II) chelates as
chain-transfer agents in free-radical polymerizations. EP199436A1. du Pont
de Nemours, E. I., and Co.
42 Janowicz, A.H. (1987). Pentacyanocobaltate (II) catalytic chain transfer agents
for molecular weight control in free radical polymerization. EP229481A2. du
Pont de Nemours, E. I., and Co.
43 Janowicz, A.H. (1989). Process and agents for molecular weight control in
free-radical polymerization reactions of acrylic and/or styrene monomers.
US4886861A. du Pont de Nemours, E. I., and Co.
44 Janowicz, A.H. (1988). Bimetallic catalytic chain transfer agents for molec-
ular weight control in free radical polymerization. US4746713A. du Pont de
Nemours, E. I., and Co.
45 Janowicz, A.H. (1991). Catalytic chain-transfer agents for macromer prepara-
tion. US5028677A. du Pont de Nemours, E. I., and Co.
46 Hawthorne, D.G. (1987). Oligomerization process. WO8703605A1. Common-
wealth Scientific and Industrial Research Organization, Australia.
47 Haddleton, D.M., Muir, A.V.G., and Leeming, S.W. (1995). Free radical polymer-
ization process. WO9517435A1. Zeneca Ltd.
48 Haddleton, D.M., Muir, A.V.G., Leeming, S.W. et al. (1996). Cobalt com-
plex preparation and use for molecular weight control in oligomerization.
WO199613527A1. Zeneca Limited.
49 Gridnev, A.A. (1999). Process and cobalt coordination complex catalysts for the
preparation of dimers from α-methylstyrenes. WO9941218A1. E. I. Du Pont de
Nemours & Co.
50 Gridnev, A.A. and Nikiforov, G.A. (2002). Preparation of alkylcobalt(III)
dioximates as polymerization catalysts. US20020087006A1. E. I. Du Pont de
Nemours and Company.
51 Rizzardo, E., Meijs, G.F., and Thang, S.H. (1995). Chain transfer by radi-
cal addition-fragmentation mechanisms: synthesis of macromonomers and
end functional oligomers. Macromol. Symp. 98: 101–123. doi: 10.1002/masy
.19950980109.
References 1145
52 Moad, G., Rizzardo, E., and Thang, S.H. (2008). Radical addition-fragmentation
chemistry in polymer synthesis. Polymer 49: 1079–1131. doi: 10.1016/j.polymer
.2007.11.020.
53 Moad, G., Rizzardo, E., and Thang, S.H. (2012). Radical addition-fragmentation
chemistry and RAFT polymerization. Polymer Science: A Comprehensive Ref-
erence, vol. 3 (eds. K. Matyjaszewski and M. Möller), 181–226. Amsterdam:
Elsevier. doi: 10.1016/B978-0-444-53349-4.00066-2.
54 Colombani, D. and Chaumont, P. (1996). Addition-fragmentation processes in
free radical polymerization. Prog. Polym. Sci. 21: 439–503. doi: 10.1016/0079-
6700(95)00024-0.
55 Colombani, D. (1999). Driving forces in free radical addition-fragmentation pro-
cesses. Prog. Polym. Sci. 24: 425–480.
56 Rizzardo, E., Meijs, G.F., and Thang, S.H. (1988). Control of molecular weight
and end group functionality of polymers. WO8804304A1. Commonwealth
Scientific and Industrial Research Organization, Australia.
57 Rizzardo, E., Meijs, G.F., and Thang, S.H. (1999). Free-radical chain transfer
polymerization process. US5932675A. Commonwealth Scientific and Industrial
Research Organisation, Australia.
58 Rizzardo, E., Thang, S.H., Moad, G., and Berge, C.T. (1995). Allylic chain trans-
fer agents. WO9512568A1. Commonwealth Scientific and Industrial Research
Organisation, Australia.
59 Rizzardo, E., Thang, S.H., Moad, G., and Chong, Y.K. (1997). Control of molec-
ular weight and end-group functionality in addition polymers. WO9713792A1.
Commonwealth Scientific and Industrial Research Organisation, Australia; E. I.
Du Pont de Nemours & Co.; Rizzardo, E., Thang, S.H., Moad, G., Chong, Y.K.
60 Desobry, V., Murer, P., and Schuwey, A. (2000). Thermal- and photoinitiated
radical polymerization in the presence of an addition fragmentation agent.
WO2000011041A1. Ciba Specialty Chemicals Holding.
61 Kulkarni, M.G. and Patil, P.M. (2007). Water-soluble macromonomers contain-
ing terminal unsaturation and their preparation. WO2007110882A1. Council of
Scientific & Industrial Research, India.
62 Chiefari, J., Moad, G., Rizzardo, E., and Gridnev, A.A. (1998). Method of
macromonomer synthesis. WO9847927A1. DuPont/CSIRO.
living characteristics. WO9801478A1. DuPont/CSIRO.
living characteristics. US7250479B2. CSIRO.
68 Chiefari, J., Chong, Y.K., Ercole, F. et al. (1998). Living free-radical polymeriza-
tion by reversible addition-fragmentation chain transfer – the RAFT process.
Macromolecules 31: 5559–5562. doi: 10.1021/ma9804951.
69 Chong, Y.K., Le, T.P.T., Moad, G. et al. (1999). A more versatile route to block
copolymers and other polymers of complex architecture by living radical poly-
merization – the RAFT process. Macromolecules 32: 2071–2074. doi: 10.1021/
ma981472p.
70 Moad, G., Chiefari, J., Krstina, J. et al. (2000). Living free rad-
ical polymerization with reversible addition fragmentation
chain transfer (the life of RAFT). Polym. Int. 49: 993–1001. doi:
10.1002/1097-0126(200009)49:9<993::AID-PI506>3.0.CO;2-6.
defined polymers by reversible addition fragmentation chain transfer. In
Controlled/Living Radical Polymerization, ACS Symposium Series 768 (ed. K.
Matyjaszewski), 278–296. Washington, DC: American Chemical Society. doi: 10
.1021/bk-2000-0768.ch020.
72 Rizzardo, E., Thang, S.H., and Moad, G. (2003). Synthesis of dithioester chain
transfer agents and use of bis(thioacyl) disulfides or dithioesters as chain trans-
fer agents. WO1999005099A1. CSIRO/DuPont.
73 Rizzardo, E., Thang, S.H., and Moad, G. (2003). Synthesis of dithioester chain
transfer agents and use of bis(thioacyl) disulfides or dithioesters as chain trans-
fer agents. US6512081B1. CSIRO/DuPont.
74 Thang, S.H., Chong, Y.K., Mayadunne, R.T.A. et al. (1999). A novel synthesis
of functional dithioesters, dithiocarbamates, xanthates and trthicarbonates.
Tetrahedron Lett. 40: 2435–2438. doi: 10.1016/S0040-4039(99)00177-X.
75 Corpart, P., Charmot, D., Zard, S.Z. et al. (1998). Method for block polymer syn-
thesis by controlled radical polymerisation. WO1998058974A1. Rhodia Chimie.
76 Corpart, P., Charmot, D., Zard, S.Z. et al. (2000). Method for block polymer syn-
thesis by controlled radical polymerisation. US6153705A. Rhodia Chimie.
77 Charmot, D., Corpart, P., Adam, H. et al. (2000). Controlled radical
polymerization in dispersed media. Macromol. Symp. 150: 23–32. doi:
10.1002/1521-3900(200002)150:1<23::AID-MASY23>3.0.CO;2-E.
78 Taton, D., Wilczewska, A.Z., and Destarac, M. (2001). Direct synthesis of
double hydrophilic statistical di- and triblock copolymers comprised of acry-
lamide and acrylic acid units via the MADIX process. Macromol. Rapid
Commun. 22: 1497–1503. doi: 10.1002/1521-3927(20011201)22:18<1497:
:AID-MARC1497>3.0.CO;2-M.
79 Bouhadir, G., Charmot, D., Corpart, P., and Zard, S. (2003). Synthesis method
for block polymers by controlled radical polymerization from dithioester com-
pounds. US6545098B1. Rhodia Chimie.
80 Corpart, P., Charmot, D., Zard, S. et al. (1999). Method for block polymer syn-
thesis by controlled radical polymerization from dithiocarbamate compounds.
WO1999035177A1. Rhodia Chimie.
81 Corpart, P., Charmot, D., Zard, S. et al. (2004). Method for block polymer syn-
thesis by controlled radical polymerization from dithiocarbamate compounds.
US6812291B1. Rhodia Chimie.
82 Destarac, M., Charmot, D., Franck, X., and Zard, S.Z. (2000). Dithiocar-
bamates as universal reversible addition-fragmentation chain transfer
References 1147
agents. Macromol. Rapid Commun. 21: 1035–1039. doi: 10.1002/1521-3927

(20001001)21:15<1035::AID-MARC1035>3.0.CO;2-5.
83 Chiefari, J., Mayadunne, R.T., Moad, G. et al. (1999). Polymerization with
living characteristics with controlled dispersity using chain transfer agents.
WO9931144A1. E. I. Du Pont De Nemours and Company, USA; Commonwealth
Scientific and Industrial Research Organization.
84 Chiefari, J., Mayadunne, R.T., Moad, G. et al. (2003). Polymerization process
with living characteristics and polymers made therefrom. US6642318B1. du
Pont/CSIRO.
85 Chiefari, J., Mayadunne, R.T., Moad, G. et al. (2004). Polymerization process
with living characteristics and polymers made therefrom. US6747111B2. du
Pont/CSIRO.
86 Mayadunne, R.T.A., Rizzardo, E., Chiefari, J. et al. (1999). Living radical poly-
merization with reversible addition-fragmentation chain transfer (RAFT poly-
merization) using dithiocarbamates as chain transfer agents. Macromolecules 32:
6977–6980. doi: 10.1021/ma9906837.
87 Berge, C.T., Fryd, M., Johnson, J.W. et al. (2002). Microgels and process for
their preparation. US6355718B1. duPont/CSIRO.
their preparation. US6462114B2. duPont.
91 Matyjaszewski, K., Lutz, J.-f., and Shinoda, H. (2006). Process for preparation of
graft polymers. US7049373B2. Carnegie Mellon University, USA.
92 Destarac, M., Charmot, D., Zard, S., and Franck, X. (2004). Synthesis method
for polymers by controlled radical polymerisation using halogenated xanthates.
93 Destarac, M., Charmot, D., Zard, S., and Gauthier-Gillaizeau, I. (2004). Synthe-
sis method for polymers by controlled radical polymerisation with xanthates.
94 Destarac, M., Charmot, D., Zard, S., and Gauthier-Gillaizeau, I. (2007). Synthe-
sis method for polymers by controlled radical polymerisation with xanthates.
95 Bett, W., Castaing, J.-c., and D’Allest, J.-f. (2001). Surface chemistry modified
latex and redispersible powders, production and use thereof. WO2001042325A1.
Rhodia Chimie.
96 Berge, C.T., Chiefari, J., Johnson, J.W. et al. (2006). Process of microgel synthe-
sis and products produced therefrom. US7064151B1. duPont/CSIRO.
97 Charmot, D. and Chang, H.T. (2002). Heterocycle containing control agents for
living-type free radical polymerization. US6395850B1. Symyx Technologies, Inc.
98 Charmot, D., Chang, H.T., and Huefner, P. (2002). Control agents for living-type
free radical polymerization, methods of polymerizing and polymers with same.
US6380335B1. Symyx Technologies, Inc.
99 Charmot, D., Chang, H.T., and Li, Y. (2002). Compounds useful for control
agents for living-type free radical polymerization. US6482909B2. Symyx Tech-
nologies, Inc.
100 Chang, H.T., Charmot, D., and Li, Y. (2003). Compounds useful for control
agents for living-type free radical polymerization. US6518448B2. Symyx Tech-
nologies, Inc.
101 Charmot, D. and Chang, H.T. (2003). Control agents for living-type free
radical polymerization, methods of polymerizing and polymers with same.
102 Charmot, D., Chang, H.T., Li, Y., and Huefner, P. (2005). Control agents for
living-type free radical polymerization, methods of polymerizing and polymers
with same. US6841624B2. Symyx Technologies, Inc.
103 Charmot, D., Chang, H.T., and Wang, W. (2005). Control agents for living-type
free radical polymerization, methods of polymerizing and polymers with same.
104 Destarac, M. (2005). Method for block polymer synthesis by controlled radi-
cal polymerization in the presence of a disulphide compound. US6916884B2.
Rhodia Chimie.
105 Destarac, M., Leising, F., Dureault, A. et al. (2002). Synthesis of block polymers
obtained by controlled free radical polymerization. WO2002036640A1. Rhodia
Chimie.
106 Destarac, M., Leising, F., Gnanou, Y. et al. (2007). Method for synthesis of
block polymers by controlled free radical polymerization. US7247688B2. Rhodia
Chimie.
107 Lai, J.T. (2003). S,S′ -bis-(α,α-disubstituted-α′′ -acetic acid)-trithiocarbonates and
derivatives as initiator-chain transfer agent-terminator for controlled radical
polymerizations and the process for making the same. 6596899. Noveon.
polymerizations and the process for making the same. US6962961B2. Noveon.
polymerizations and the process for making the same. US7279591B2. Noveon.
110 Lai, J.T.-Y. (2009). S-S′ -bis-(α,α′ -Disubstituted-α′′ -acetic acid) – trithiocarbonates
and derivatives as initiator-chain transfer agent-terminator for controlled radical
polymerizations and the process for making the same. US7495128. Lubrizol.
111 Lai, J.T.-Y. (2010). S,S′ -bis-(α,α′ -Disubstituted-α′′ -acetic acid) – trithiocarbonates
and derivatives as initiator-chain transfer agent-terminator for controlled radical
polymerizations and the process for making the same. US7659345B2. Lubrizol.
112 Lai, J.T., Filla, D., and Shea, R. (2002). Functional polymers from novel
carboxyl-terminated trithiocarbonates as highly efficient RAFT agents. Macro-
molecules 35: 6754–6756. doi: 10.1021/ma020362m.
113 Lai, J.T.-Y. (2008). S-(α,α′ -disubstituted-α′′ -acetic acid) substituted dithiocar-
bonate derivatives for controlled radical polymerizations, process and polymers
made therefrom. US7335788B2. Lubrizol Advanced Materials, Inc.
References 1149
114 Lai, J.T.-Y. (2010). S-(α,α′ -disubstituted-α′′ -acetic acid) – substituted dithiocar-
bonate derivatives for controlled radical polymerizations, process and polymers
made therefrom. US7851582. Lubrizol.
115 Lai, J.T. and Shea, R. (2006). Controlled radical polymerization by carboxyl-
and hydroxyl-terminated dithiocarbamates and xanthates. J. Polym. Sci., Part A:
Polym. Chem. 44: 4298–4316. doi: 10.1002/pola.21532.
116 Lai, J.T.-Y. (2007). S,S′ -bis-(α,α-disubstituted-α′′ -acetic acid)-substituted dithio-
carbonate derivatives for controlled radical polymerizations, process and
polymers made therefrom. US7205368B2. Noveon, Inc.
117 Lai, J.T.-Y. (2009). S-(α,α′ -disubstituted-α′′ -acetic acid) substituted dithiocar-
bonate derivatives for controlled radical polymerization, process and polymers
made therefrom. US7498456. Lubrizol
118 Charmot, D., Chang, H.T., Huefner, P., and Li, Y. (2003). Emulsion living-type
free radical polymerization, methods and products of same. US6518364B2.
Symyx Technologies, Inc.
119 Catala, J.-M. (2007). Radical polymerization method performed in the presence
of disulfide compounds. US7214751B2. Rhodia Chimie.
120 Destarac, M. and Bzducha, W. (2008). Controlled mini-emulsion free radical
polymerization. US7317050B2. Rhodia Chimie.
121 Such, C.H., Rizzardo, E., Serelis, A.K. et al. (2010). Aqueous dispersions of
polymer particles. US7745553B2. University of Sydney.
122 Matyjaszewski, K., Kirci, B., Lutz, J.F., and Pintauer, T. (2006). Process for
monomer sequence control in polymerizations. US7064166B2. Carnegie Mellon
University.
123 McCormick, C.L., Donovan, M.S., Lowe, A.B. et al. (2005). Chain transfer
agents for raft polymerization in aqueous media. US6855840B2. University of
Southern Mississippi.
agents for RAFT polymerization in aqueous media. US7179872B2. University of
127 Benicewicz, B. and Li, C. (2008). Low odor chain transfer agents for controlled
radical polymerization. US7332552B2. Rensselaer Polytechnic Institute.
128 Pitois, C., Destarac, M., and Taton, D. (2008). Synthesis of mikto-star copoly-
mers by controlled radical polymerization. US20080114128A1. Rhodia Chimie.
129 Farnham, W.B. (2009). Synthesis of trithiocarbonate raft agents and intermedi-
ates thereof. US7632966B2. du Pont.
130 Pitois, C. and Karagianni, K. (2007). Composition for treating and/or modifying
hard surfaces, containing a synthetic polymer. WO2007071591A1. Rhodia Oper-
ations.
131 Couvreur, L. and Magnet, S. (2013). Copolymers based on methacrylate units,

preparation method thereof and use of same. US8389643B2. Arkema.
132 Venkatesh, R. and Raman, V.I. (2014). Process for the preparation of an aque-
ous polymer dispersion. US8912273B2. BASF SE.
133 Kwak, Y., Nicolay, R., and Matyjaszewski, K. (2013). Controlled radical poly-
merization processes. US8445610B2. Carnegie Mellon University.
134 Jakubowski, W. and Spanswick, J. (2014). Control over controlled radical poly-
merization processes. US8815971B2. ATRP Solutions.
137 Rizzardo, E., Chiefari, J., Benaglia, M. et al. (2016). RAFT polymerisation.
US9340498B2. CSIRO.
138 Puskas, J.E. and Heidenreich, A.J. (2010). Synthesis of arborescent polymers via
controlled inimer-type reversible addition-fragmentation chain transfer (RAFT)
polymerization. WO2010019563A1. The University of Akron, USA.
139 Chiefari, J., Hornung, C., and Saubern, S. (2015). Continuous flow polymerisa-
tion process. US8946360B2. CSIRO.
140 Tsanaktsidis, J. and Gardiner, J. (2016). All purpose RAFT agent for polymer-
ization. WO2016054689A1. CSIRO.
141 Miyake, G.M. (2015). Organocatalyzed photoredox mediated polymerization
using visible light. US9156921B2. California Institute Of Technology.
142 Xu, J. and Boyer, C.A.J.-M. (2015). Manufacture of polymers by photopolymer-
ization. WO2015113114A1. NewSouth Innovations Pty. Limited, Australia.
143 Gardiner, J. and Tsanaktsidis, J. (2016). Versatile RAFT agent, polymers pre-
pared using the RAFT agent, and method of preparing polymer using the
RAFT agent. WO2016197187A1. Commonwealth Scientific and Industrial
Research Organisation, Australia.
144 Otsu, T. (2000). Iniferter concept and living radical polymer-
ization. J. Polym. Sci., Part A: Polym. Chem. 38: 2121–2136. doi:
10.1002/(SICI)1099-0518(20000615)38:12<2121::AID-POLA10>3.0.CO;2-X.
146 Brzytwa, A.J. and Johnson, J. (2011). Polym. Prepr. (Am. Chem. Soc., Div. Polym.
Chem.) 52: 533–534.
147 Lewandowski, K.M., Fansler, D.D., Wendland, M.S. et al. (2004). Azlactone
chain transfer agents for radical polymerization. US6762257B1. 3M Innovative
Properties Company.
148 Wendland, M.S., Lewandowski, K.M., Fansler, D.D. et al. (2004). Azlactone pho-
toiniferters for radical polymerization. US6747104B1. 3M Innovative Properties.
149 Bai, F., Radcliffe, M.D., Montello, A.D. et al. (2008). High clarity cholesteric liq-
uid crystal films. US7439000B2. 3M.
References 1151
150 Padiyath, R., Radcliffe, M.D., Thomas, C.U. et al. (2010). Infrared light reflect-
ing film. US7652736. 3M.
151 Joly, G.D., Abuelyaman, A.S., Craig, B.D. et al. (2013). Dental compositions
comprising addition-fragmentation agents. WO2013028397A2. 3M Innovative
Properties Company.
152 Fornof, A.R., Moser, W.H., Abuelyaman, A.S. et al. (2015). Allyl
disulfide-containing addition-fragmentation oligomers. WO2015057413A1.
3M Innovative Properties Company.
153 Kambara, R., Mori, H., Endo, T., and Yonemori, S. (2010). Monodisperse
chloromethylstyrene polymers and their manufacture. WO2010131628A1. AGC
Seimi Chemical, Japan.
154 Louwet, F., Deroover, G., Groenendaal, B. et al. (2010). Stable pigment disper-
sions. US7674843. Agfa Graphics.
155 Louwet, F., Deroover, G., Groenendaal, B. et al. (2006). Stable pigment disper-
sions comprising a block copolymer consisting of ionic aromatic monomers.
US7678845B2. Agfa-Gevaert, Belg.
156 Bertin, D., Couturier, J.L., Gigmes, D. et al. (2009). Method for preparing
alkoxyamines by photolysis of dithiocarbamates. WO2006111637A1. Arkema
France.
157 Couvreur, L. (2012). Compositions with improved odor comprising a RAFT
agent or a polymer obtained using one of these agents. WO2012004480A1.
Arkema France.
158 Curran, S.A. and Ellis, A.V. (2010). Thiation of carbon nanotubes and compos-
ite formation. US7713508B2. Arrowhead Center.
159 Rozema, D.B., Wakefield, D.H., Lewis, D.L. et al. (2013). In vivo polynucleotide
delivery conjugates having enzyme sensitive linkages. US8426554B2. Arrowhead
Madison.
160 Rozema, D.B., Lewis, D.L., Wakefield, D.H. et al. (2014). In vivo polynucleotide
delivery conjugates having enzyme sensitive linkages. US8802773B2. Arrowhead
Madison.
161 Wakefield, D.H., Rossi, N., and Sheik, D. (2015). Poly(vinyl ester) polymers for
in vivo nucleic acid delivery. US8932572B2. Arrowhead Madison.
162 Wakefield, D.H., Rossi, N.A., and Sheik, D. (2015). Poly(vinyl ester) polymers
for in vivo nucleic acid delivery. US9089611B2. Arrowhead Madison Inc.
163 Wakefield, D.H., Rozema, D.B., Rossi, N. et al. (2015). Poly(acrylate) polymers
for in vivo nucleic acid delivery. US8933047B2. Arrowhead Madison.
164 Linhardt, J.G., Shipp, D.A., and Kunzler, J.F. (2011). Coating solutions compris-
ing segmented reactive block copolymers. US7942929B2. Bausch & Lomb.
165 Linhardt, J.G., Shipp, D.A., Kunzler, J.F., and Vanderbilt, D.P. (2012). Coating
solutions comprising segmented interactive block copolymers. US8100528B2.
Bausch & Lomb.
166 Linhardt, J.G., Nunez, I.M., McGee, J.A. et al. (2011). Biomedical devices.
US8043369B2. Bausch & Lomb.
167 Linhardt, J.G., Kunzler, J.F., and Shipp, D.A. (2011). Biomedical devices.
168 Linhardt, J.G., McGee, J.A., and Nunez, I.M. (2012). Biomedical devices.
169 Linhardt, J.G., Nunez, I.M., McGee, J.A. et al. (2012). Biomedical devices.
170 Achten, D., Klimpel, M., Barriau, E. et al. (2007). Dithiocarbamic esters.
US7169937B2. Bayer Aktiengesellschaft.
US7825193B2. Lanxess.
US7977431B2. Lanxess.
173 Klimpel, M., Brandau, S., Westeppe, U. et al. (2011). Nitrile rubbers and pro-
duction of same in organic solvents. WO2011032832A1. LANXESS Deutschland.
174 Favier, A. and Charreyre, M.-T. (2007). Method for controlled radical polymer-
ization. US7205362B2. bioMérieux.
175 Charreyre, M.-T., Mandrand, B., Martinho, J.M.G. et al. (2012). Fluorescent
polymers soluble in an aqueous solution and a method for the production
thereof. US8133411B2. Biomerieux, CNRS.
176 Xu, K., Hockey, M.A., and Guerrero, D. (2014). Highly etch-resistant polymer
block for use in block copolymers for directed self-assembly. WO2014165530A1.
Brewer Science Inc., USA.
177 Gobelt, B., Bubat, A., Frank, A., and Haubennestel, K. (2007). Use of
polyacrylate-modified polysiloxanes as levelling agents in coating compositions.
US7230051B2. BYK-Chemie GmbH.
178 Pakula, T. and Matyjaszewski, K. (2004). Polymers, supersoft elastomers and
methods for preparing the same. WO2004014963A2. Carnegie Mellon Univer-
sity, USA.
179 Matyjaszewski, K., Sumerlin, B.S., Tsarevsky, N., and Spanswick, J. (2005).
Preparation of tetrazole polymers with controlled functionality for pharmaceuti-
cal use. WO2005087818A1. Carnegie Mellon University.
180 Suau, J.M., Egraz, J.B., Claverie, J., and Ladaviere, C. (2008). Method of con-
trolled free radical polymerisation of acrylic acid and its salts thereof, resulting
low-polydispersity polymers, and their uses. US7345121B2. Coatex S.A.S.
181 Suau, J.M. and Egraz, J.B. (2008). Method for the controlled radical poly-
merisation of acrylic acid and the salts thereof, polymers thus obtained and
applications thereof. US7462676B2. Coatex S.A.S.
182 Suau, J.-M. and Jacquemet, C. (2011). Trithiocarbonate derivatives and the
use thereof in the form of transfer agents for acrylic acid controlled radical
polymerisation. US7956211B2. Coatex.
183 Suau, J.M. and Jacquemet, C. (2012). Trithiocarbonate derivatives and the
polymerisation. US8227633B2. Coatex S.A.S.
184 Suau, J.M. and Jacquemet, C. (2013). Trithiocarbonate derivatives and the
polymerisation. US8470750B2. Coatex S.A.S.
References 1153
185 Suau, J.-M. and Jacquemet, C. (2011). Polymers produced by using sulphur
compounds in the form of transfer agents for controlled radical polymerisation
of acrylic acid and the use thereof. US8053497B2. Coatex.
186 Kensicher, Y. and Platel, D. (2012). Use of a rheological additive in the manu-
facture by vibrocompaction of a water and hydraulic binder based formulation,
formulation obtained. US8110130B2. Coatex.
187 Suau, J.-M. and Jacquemet, C. (2010). Polymers produced by using sulphur
compounds in the form of transfer agents for controlled radical polymerisation
of acrylic acid and the use thereof. US7851572B2. Coatex.
188 Lambert, T.H., Campos, L.M., and Bandar, J. (2014). Manufacturing of stable
cyclopropenium cation-containing branched, dendritic, cross-linked and block
polymeric systems. WO2014022365A1. Columbia University New York, USA.
189 Boyes, S.G. and Rowe, M.D. (2015). Gold/lanthanide nanoparticle conjugates
and uses thereof. US8968705B2. Colorado School Of Mines.
190 Cheng, C., Khoshdel, E., and Wooley, K.L. (2011). Brush copolymers.
US7960479B2. Conopco.
191 Herzog, K., Vana, P., Mueller, L. et al. (2014). Process for producing
polymer-functionalized filler particles. US8912267B2. Continental Reifen
Deutschland.
192 Herzog, K., Mueller, L., Recker, C. et al. (2016). RAFT agent, polymeriza-
tion method, polymer, rubber mixture, and use thereof. WO2016180805A1.
Continental Reifen Deutschland.
193 Herzog, K., Mueller, L., Recker, C. et al. (2016). Method for co-polymerization,
co-polymer and rubber composition and their use. EP3109064A1. Continental
Reifen.
194 Zhao, J.Z. (2010). Tri-branched biologically active copolymer. US7811555B2.
Cordis.
195 Harruna, I.I. and Zhou, G. (2008). Ligand-functionalized/azo compounds and
methods of use thereof. US7411053B2 (inventors).
196 Leibler, L., Nicolay, R., and Rottger, M. (2020). Boronic polymer crosslinking.
US10329414B2. CNRS, Ecole Superieure de Physique de Chimie Industrielles de
la Ville de Paris.
197 Leibler, L., Nicolay, R., and Rottger, M. (2020). Crosslinked polymers compris-
ing exchangeable bonds and crosslinks via aldehyde-imine and imine-imine
exchange reactions. WO2017029311A1. Ecole Superieure de Physique et de
Chimie Industrielles de la Ville de Paris, Fr.
198 Tang, L., Thomas, A.D., and Harmon, B.D. (2015). Polyacrylonitrile with low
polydispersity index for carbon fibers. WO2015099913A1. Cytec Industries.
199 Tamai, H., Otsu, T., and Mori, H. (2010). Polychloroprenes with narrow poly-
dispersibility, their manufacture and their adhesives. WO2010147011A1. Denki
Kagaku Kogyo Kabushiki Kaisha.
200 Farnham, W.B., Fryd, M., and Schadt, F.L. III (2010). Low-polydispersity pho-
toimageable acrylic polymers, photoresists and processes for microlithography.
US7696292B2. CSIRO.
201 Feiring, A.E., Fryd, M., and Schadt, F.L. (2008). Low-polydispersity pho-
toimageable polymers and photoresists and processes for microlithography.
US7408013B2. CSIRO.
202 Farnham, W.B. and Moudgil, S. (2011). Fluorinated polymers for use in immer-
sion lithography. US8034534B2. du Pont.
203 Meagher, L., Thissen, H., Pasic, P. et al. (2012). Polymeric coatings and meth-
ods for forming them. US8124188B2. CSIRO.
204 Meagher, L., Thissen, H., Pasic, P. et al. (2014). Polymeric coatings and meth-
ods for forming them. US8795782B2. CSIRO.
205 Chen, M., Moad, G., Rizzardo, E. et al. (2013). Conducting and semiconducting
organic materials. US8501889B2. CSIRO.
206 Chen, M., Moad, G., Rizzardo, E. et al. (2015). Conducting and semiconducting
organic materials. US8993697B2. CSIRO.
207 Cai, J.Y. (2017). Polymer derived from acrylonitrile. US9777081B2. CSIRO.
208 Kunitsky, K., Shah, M.C., Shuey, S.W., and Wagman, M.E. (2008). Method for
preparing glycidyloxystyrene monomers and polymers thereof. US7468415B2.
duPont.
209 Farnham, W.B. (2012). Synthesis of fluoroalcohol-substituted (meth)acrylate
esters and polymers derived therefrom. US8304572B2. duPont.
210 Meth, J.S. (2014). Method for producing encapsulated nanoparticles.
US8734898B2. duPont.
211 Farnham, W.B., Sheehan, M.T., Tran, H.V., and Zhang, D. (2017). Substantially
symmetrical 3-arm star block copolymers. US9815947B2. duPont.
212 Chilkoti, A. and Gao, W. (2013). Biomolecule polymer conjugates and methods
for making the same. US8497356B2. Duke University.
213 Schellekens, M.A.J., Nabuurs, T., Geurts, J., and Overbeek, G.C. (2009).
Water borne crosslinkable block copolymers obtained using RAFT polymn.
WO2009090252A1. DSM IP Assets.
214 Schellekens, M.A.J., Geurts, J., Nabuurs, T., and Overbeek, G.C. (2008). Aque-
ous oligomer/polymer emulsion with cationic functionality. WO2008122576A1.
DSM IP Assets B.V., Neth.
215 Schellekens, M.A.J., Nabuurs, T., Geurts, J., and Overbeek, G.C. (2010). RAFT
block copolymer-containing coating compositions with improved adhesion to
metal surfaces. WO2010000725A1. DSM IP Assets.
216 Schellekens, M.A.J., Overbeek, G.C., Nabuurs, T., and Geurts, J. (2009). Adhe-
sion to plastic with block copolymers obtained using RAFT. WO2009121911A1.
DSM IP Assets.
217 Schellekens, M.A.J., Nabuurs, T., Geurts, J., and Overbeek, G.C. (2009). Block
copolymers obtained using raft. WO2009138493A1. DSM IP Assets.
218 Schellekens, M.A.J., De Bont, J.H., Barbosa, J. et al. (2019). Waterborne
crosslinkable dispersions. WO2019121782A1. DSM IP Assets.
219 Wang, J.-S. (2004). Polymerization process. US6756457B2. Eastman Kodak Com-
pany.
220 Li, Y., Du, H., Liu, Y. et al. (2016). Electrophoretic dispersion. US9428649B2. E
Ink California.
References 1155
221 Li, Y., Du, H., Liu, Y. et al. (2017). Method of making electrophoretic disper-
sion. US9732231B2. E Ink California.
222 Hubbell, J.A. and Wilson, D.S. (2017). Glycotargeting therapeutics.
WO2017046652A1. Ecole Polytechnique Federale de Lausanne.
223 Bollinger, J.M. and Wang, J.-L. (2004). Process for preparing dithioesters in a
biphasic system. WO2004083169A1. Rohmax Additives.
224 Dardin, A., Mueller, M., and Eisenberg, B. (2004). Lubricating oil composition
with good friction characteristics. WO2004087850A1. Rohmax Additives.
225 Schmidt, F.G., Krause, S., Hennig, A. et al. (2011). Function materials with
reversible crosslinking. WO2011101176A1. Evonik Roehm.
226 Schmidt, F.G., Hilf, S., Zhou, J. et al. (2013). Polymer powder for producing
three-dimensional objects. WO2013013873A1. Evonik Roehm.
227 Schmidt, F.G., Hilf, S., Spyrou, E. et al. (2013). Low molecular products, and
their use as reversible or permanent low-temperature crosslinking agents by
Diels–Alder reactions. WO2013017349A1. Evonik Degussa.
228 Chung, H. (2016). Lignin-containing polymers and their preparation and
self-healing polymers. US20160222151A1. Florida State University Research
Foundation, Inc., USA.
229 Winnik, M.A., Nitz, M., Baranov, V., and Lou, X. (2007). Polymer back-
bone element tags in form of metal-polymer conjugates for ICP-MS linked
immunoassays. WO2007137418A1. Can.
230 Senyek, M.L., Kulig, J.J., and Parker, D.K. (2002). Dibenzyltrithiocarbonate
molecular weight regulator for emulsion polymerization. US6369158B1. The
Goodyear Tire & Rubber Company.
231 Parker, D.K., Feher, F.J., and Mahadevan, V. (2009). Styrene acrylonitrile iso-
prene triblock copolymer. US7592409. Goodyear.
232 Parker, D.K., Feher, F.J., and Mahadevan, V. (2010). Controlled polymerization.
US7767775. Goodyear.
US6992156B2. The Goodyear Tire & Rubber Company.
US7098280B2. The Goodyear Tire & Rubber Company.
235 Parker, D.K., Feher, F.J., and Mahadevan, V. (2009). Hydrogenation and
epoxidation of polymers made by controlled polymerization. US7528204B2.
Goodyear.
236 Parker, D.K. (2008). Oxathiazaphospholidine free radical control agent.
US7462674B2. Goodyear.
239 Parker, D.K. and Yang, X. (2009). Water-based process for the preparation of
polymer-clay nanocomposites. US7625985B1. Goodyear.
240 Parker, D.K. (2007). Functional trithiocarbonate RAFT agents. US7230063B1.
The Goodyear Tire & Rubber Company.
241 Parker, D.K. and Kulig, J.J. (2010). Surfactantless synthesis of amphiphilic
cationic block copolymers. US7671152B2. Goodyear.
242 Feher, F.J., Mahadevan, V., and Parker, D.K. (2008). Sulfine control agents for
synthesizing polymers. US7335714B1. The Goodyear Tire & Rubber Company.
243 Parker, D.K., Feher, F.J., and Mahadevan, V. (2010). Hydrogenation and
epoxidation of polymers made by controlled polymerization. US7812108B2.
Goodyear.
US8178637. Goodyear.
245 Mruk, R., Schmitz, F., Roskamp, R.F. et al. (2013). Rubber composition and
pneumatic tire. US8415432B1. Goodyear.
246 Mruk, R., Schmitz, F., Roskamp, R.F. et al. (2014). Method of making a graft
copolymer. US8759451B2. Goodyear.
247 Ma, L., Mruk, R., and Hahn, B.R. (2013). Method to improve green strength in
elastomers. US8563656B1. Goodyear.
248 Ma, L., Roskamp, R.F., Mruk, R. et al. (2014). Pneumatic tire. US8883884B2.
Goodyear.
249 Chun, D.P.Y. and Ng, H.T. (2012). Polymer-encapsulated pigment.
US8309630B2. Hewlett-Packard.
250 Cheng, J., Kim, H., Rettner, C.T. et al. (2009). Method of use of
epoxy-containing cycloaliphatic acrylic polymers as orientation control layers
for block copolymer thin films. US7521090B1. IBM.
251 Cheng, J., Kim, H.-C., Rettner, C.T. et al. (2011). Method of use of
epoxy-containing cycloaliphatic acrylic polymers as orientation control layers
for block copolymer thin films. US7989026B2. IBM.
252 Brown, A.A., George, W.N., Richez, A. et al. (2016). Novel polymers for sur-
face functionalization and immobilization of DNA for high-throughput DNA
sequencing by synthesis. US20160122816A1. Illumina Cambridge Limited, UK.
253 Cochran, E.W., Williams, R.C., Hernandez, N., and Cascione, A. (2014).
Thermoplastic elastomers via reversible addition-fragmentation chain trans-
fer polymerization of triglycerides. US20140343192A1. Iowa State University
Research Foundation, Inc., USA.
254 Mathew, L. and Shih, K.-C. (2004). Thiocarbonylthio compound and living free
radical polymerization using the same. US6720429B2. Industrial Technology
Research Institute.
255 Shih, K.C., Chung, P.W., and Wang, M.H. (2011). Thiocarbonylthio compound
and free radical polymerization employing the same. US7968743B2. ITRI.
256 Charles, J.H.K. and Murray, G.M. (2010). Authentication of products using
molecularly imprinted polymers. US7799568B2. Johns Hopkins University.
257 Southard, G.E. and Murray, G.M. (2010). Processable molecularly imprinted
polymers. US7678870B2. Johns Hopkins University.
258 Murray, G.M., Mason, A.F., and Ott, E.W. (2012). Molecularly imprinted poly-
mer sensor device. US8241575B2. Johns Hopkins University.
259 Benoit, D., Safir, A., Chang, H.-T. et al. (2009). Photoresist polymer composi-
tions. US7510817B2. JSR.
References 1157
260 Benoit, D., Safir, A., Chang, H.-T. et al. (2009). Photoresist polymers.
US7517634B2. JSR.
261 Tsuji, R. and Hiiro, T. (2006). Polyurethane polymer. US6992138B2. Kaneka
Corporation.
262 Tsuji, R. and Hiiro, T. (2006). Block copolymer. US7094833B2. Kaneka Corpora-
tion.
263 Tsuji, R. and Hiiro, T. (2007). Thermoplastic resin composition and elastomer
composition. US7211625B2. Kaneka Corporation.
264 Sacha, P., Konvalinka, J., Schimer, J. et al. (2016). Macromolecular conju-
gates for visualization and separation of proteins and cells. WO2016112883A2.
Ustav Organicke Chemie a Biochemie Av Cr, V.V.I., Czech Rep.; Ustav Makro-
molekularni Chemie Av Cr, V.V.I.; Univerzita Karlova v Praze, Prirodovedecka
Fakulta.
265 Lynch, T.J. (2011). Mineral dispersants and methods for preparing mineral slur-
ries using the same. US7875213B2. Kemira.
266 Kim, S.Y. and Seo, M. (2013). Methods for the preparation of coil-comb block
copolymers and their nanostructures. US8518497B2. Korea Advanced Institute
Of Science And Technology.
267 Kim, J.A. and Yoo, H. (2013). PH-sensitive polyethylene oxide co-polymer and
synthetic method thereof. US8420771B2 (inventors).
268 Mougin, N. (2005). Block copolymer comprising a vinyllactam block for cosmet-
ics and pharmaceuticals. EP1514884A1. L’Oreal.
269 Farcet, C. (2009). Polymer particle dispersion, cosmetic compositions compris-
ing it and cosmetic process using it. US7585922B2. L’Oreal.
270 Farcet, C. (2010). Polymer particle dispersion, cosmetic composition comprising
it and cosmetic process using it. US7816464B2. L’Oreal.
271 Cassin, G. (2006). Cosmetic use of a particular copolymer as skin tensor in a
cosmetic composition. WO2006097529A1. L’Oreal.
272 Farcet, C., Houillot, L., Save, M., and Charleux, B. (2010). Cosmetic compo-
sition comprising a dispersion of soft polymer particles. WO2010046229A1.
L’Oreal.
273 Simonnet, J.-T., L’Alloret, F., Bressy, L., and Moujahed, Z. (2009). Oil-in-water
emulsion comprising an amphiphilic polymer. WO2009101113A2. L’Oreal.
274 Farcet, C. and Lion, B. (2012). Cosmetic compositions comprising isobutyl acry-
late and acrylic acid diblock copolymers. WO2012156630A1. L’Oreal.
275 Kim, H.-J. and Kim, D.-R. (2006). Organic-inorganic nanocomposite and prepa-
ration thereof. US7115683B2. LG Chem, Ltd.
276 Kim, H.-J. and Kim, D.-R. (2005). Water-soluble dithioesters and method for
polymerization thereof. US6888020B2. LG Chem, Ltd.
277 Han, Y.K., Lee, J.G., and Kim, S.H. (2014). Adsorbent of volatile organic
compounds and adsorption method using thereof. US8911537B2. LG Chem,
Industry-University Cooperation Foundation Hanyang University.
278 Han, Y.-K., Lee, J.-G., and Kim, S.-H. (2012). Acrylate-acrylamide diblock
copolymers and methods of producing diblock copolymers and forming
nanopatterns. WO2012144735A2. LG Chem.
279 Ku, S.J., Lee, M.S., Ryu, H.J. et al. (2016). Method for producing patterned sub-
strate using self-assembly of block copolymers. WO2016053014A1. LG Chem.
280 Choi, E.Y., Park, N.J., Kim, J.K. et al. (2016). Production of diblock
copolymer with self-assembly characteristic using RAFT polymerization.
WO2016053005A1. LG Chem.
281 Lai, J.T.-Y., Lepilleur, C.A., Weber, C.D. et al. (2005). S,S′ -bis-(α,α-disubstituted-
α′′ -acetic acid) – trithiocarbonates and polymers thereof for toughening ther-
mosetting resins. US6894116B2. Noveon.
282 Lai, J.T.-Y. and Hsu, S.-J.R. (2009). Associative thickeners for aqueous systems.
US7495050B2. Lubrizol.
283 Lai, J.T.-Y., Pajerski, A.D., and Shea, R.P. (2012). Hydroxyl-terminated thiocar-
bonate containing compounds, polymers, and copolymers, and polyurethanes
and urethane acrylics made therefrom. US8137754B2. Lubrizol.
284 Lai, J.T.Y., Pajerski, A.D., and Shea, R.P. (2014). Hydroxyl-terminated thiocar-
bonate containing compounds, polymers, and copolymers, and polyurethanes
and urethane acrylics made therefrom. US8709543B2. Lubrizol Advanced
Materials.
285 Baum, M., Schober, B., Davies, M., and Visger, D. (2006). Process for preparing
star polymers by controlled radical polymerization and compositions thereof.
WO2006047393A1. The Lubrizol Corporation.
286 Johnson, J.R., Visger, D.C., Baum, M. et al. (2011). Crosslinked polymer.
US8012917B2. Lubrizol.
287 Schober, B.J., Davies, M.C., Sutton, M.R. et al. (2015). Star polymer lubricating
composition. US9006159B2. Lubrizol.
288 Baker, M.R., Baum, M., and Schober, B.J. (2007). Star polymer lubricating com-
position. WO2007127660A1. The Lubrizol Corporation.
289 Richards, S.N. and Shooter, A.J. (2012). Graft copolymer and compositions
thereof. US8268925B2. Lubrizol.
290 Price, D., Mosier, P.E., Vilardo, J.S., and Baum, M. (2013). Antiwear polymer
and lubricating composition thereof. US8507422B2. Lubrizol.
291 Qin, H., Baum, M., and Johnson, J.R. (2015). Star polymer and lubricating com-
position thereof. US8937035B2. Lubrizol.
292 Abraham, W.D., Baum, M., Qin, H., and Wang, Y. (2011). Farm tractor lubricat-
ing oil composition with good water tolerance. WO2011031659A1. The Lubrizol
Corporation.
293 Johnson, J.R. and Schober, B.J. (2014). Loose core star polymers and lubricating
composition thereof. WO2014031154A1. The Lubrizol Corporation.
294 Miller, C.G. and Kim, H. (2016). Water-soluble chain transfer agents for prepar-
ing water-soluble polymers by Reversible Addition Fragmentation Chain Trans-
fer polymerization. WO2016182711A1. The Lubrizol Corporation.
295 Olsen, B.D., Glassman, M.J., and Chan, J. (2014). Nanostructured
physically-associating hydrogels for injectable, responsive, and tough bioma-
terials. US8916683B2. Massachusetts Institute Of Technology.
296 Stenzel, M.H., Scarano, W., Svejkar, D., and Liang, M. (2014). Nanoparticles for
drug delivery comprising albumin and antisense DNA having a polymer chain
References 1159
of acrylic polymers, polyesters and polyethers. WO2014161031A1. NewSouth

Innovations.
297 Justynska, J. and Seiferling, B. (2013). Actinically-crosslinkable
siloxane-containing copolymers. US8383744B2. Novartis AG.
298 Kambouris, P., Whittaker, M., Davis, T. et al. (2005). Methods of polymeriza-
tion. US6858309B2. Polymerat Pty. Ltd.
299 Moad, G., Simon, G.P., Dean, K.M. et al. (2010). Dispersing agents in nanocom-
posites. US7837899B2. Polymers Australia.
300 Moad, G., Simon, G.P., Dean, K.M. et al. (2007). Acrylic dispersing agents in
nanocomposites. US7288585B2. Ciba Specialty Chemicals Corp.
301 Moad, G., Li, G., Campbell, J.A. et al. (2012). Dispersing agents in composites.
US8110626B2. Advanced Polymerik.
302 Stenzel, M.H., Godoy-Lopez, R., Harrisson, S., and Rizzardo, E. (2013). Func-
tionalized thin film polyamide membranes. US8544658B2. Polymers CRC.
303 Satchi-Fainaro, R., Miller, K., Shabat, D., and Erez, R. (2014). Conjugates of
a polymer, a bisphosphonate and an anti-angiogenesis agent and uses thereof
in the treatment and monitoring of bone related diseases. Ramot At Tel-Aviv
University.
304 Satchi-Fainaro, R., Miller, K., Shabat, D., and Erez, R. (2015). Conjugates of a
polymer, a bisphosphonate and an anti-angiogenesis agent and uses thereof in
the treatment and monitoring of bone related diseases. US9095618B2. Ramot At
Tel-Aviv University.
305 Benicewicz, B.C., Kanagasabapathy, S., and Sudalai, A. (2004). Transition metal
superoxides. US6765076B2. Rensselaer Polytechnic Institute.
306 Benicewicz, B.C., Kanagasabapathy, S., and Sudalai, A. (2002). Dithiocarboxylic
ester synthetic process. US6458968B2. Rensselaer Polytechnic Institute.
307 Tao, P., Li, Y., Benicewicz, B. et al. (2013). Nanofilled polymeric nanocompos-
ites with tunable index of refraction. US8518473B2. Rensselaer Polytechnic
Institute.
308 Nelson, J.K., Benicewicz, B., Rungta, A., and Schadler, L.S. (2014). Self-healing
electrical insulation. US8796372B2. Rensselaer Polytechnic Institute.
309 Destarac, M., Joanicot, M., and Reeb, R. (2003). Gelled aqueous composition
comprising a block copolymer containing at least one water-soluble block and
one hydrophobic block. US6506837B2. Rhodia Chimie.
310 Gerardin, C., Anthony, O., Chane-Ching, J.-Y., and Destarac, M. (2002). Pro-
cess for preparing colloids of particles coming from the hydrolysis of a salt of a
metal cation. US6500871B1. Rhodia Chimie.
311 Destarac, M., Mignani, G., Zard, S. et al. (2005). Method for synthesis of hybrid
silicon and organic copolymers by controlled free radical polymerization.
312 Prat, E. and Destarac, M. (2005). Photosensitive composition for photoresist
manufacture. US6953649B2. Rhodia Chimie.
313 Cadena, N., Destarac, M., Herve, P., and Wilczewska, A.Z. (2009). Method
for depositing a polymer onto a surface by applying a composition onto said
surface. US7473730B2. Rhodia.
314 Herve, P., Destarac, M., Anthony, O. et al. (2009). Formulation comprising an
ionic compound, a polyionic polymer, and a block copolymer. US7531597B2.
Rhodia.
315 Anthony, O., Bonnet-Gonnet, C., Destarac, M. et al. (2002). Water-soluble
block copolymers comprising a hydrophilic block and a hydrophobic block.
316 Bavouzet, B., Destarac, M., Herve, P., and Taton, D. (2003). Composition com-
prising a copolymer at least two charged blocks and type of opposite charge.
317 Heitz, C., Joanicot, M., and Tillotson, R.J. (2003). Hydraulic fracturing fluid
comprising a block copolymer containing at least one water-soluble block and
one hydrophobic block. US6579947B2. Rhodia Chimie.
318 Cadena, N., Destarac, M., Herve, P., and Wilczewska, A.Z. (2005). Method
for depositing a polymer onto a surface by applying a composition onto said
surface. US6906128B2. Rhodia Chimie.
319 Herve, P., Destarac, M., Anthony, O. et al. (2005). Formulation comprising an
ionic compound, a polyionic polymer, and a block copolymer. US6933340B2.
Rhodia Chimie.
320 Bavouzet, B., Destarac, M., Herve, P., and Wilczewska, A.Z. (2007). Cosmetic
composition comprising a block copolymer. US7235231B2. Rhodia Chimie.
321 Adam, H. and Liu, W.-L. (2004). Process for the preparation of latices using
block copolymers as surfactants. US6825290B2. Rhodia Inc.
322 Harrison, I., Destarac, M., and Geffroy, C. (2008). Crease-resistant composition
comprising a copolymer of controlled architecture, for articles made of textile
fibers. US7378033B2. Rhodia.
323 Zard, S., Gagosz, F., and Tournier, L. (2008). Compounds comprising a
thiocarbonyl-sulfanyl group, which can be used for the radical synthesis
of-α-perfluoroalkylamines. US7423161B2. Rhodia.
324 Zard, S., Gagosz, F., and Tournier, L. (2010). Compounds comprising a
thiocarbonyl-sulfanyl group which can be used for the radical synthesis of
α-perfluoroalkylamine compounds. US7820831B2. Rhodia.
325 Destarac, M., Bonnet-Gonnet, C., and Cadix, A. (2008). Use of block copoly-
mers bearing phosphate and/or phosphonate functions as adhesion pro-
moters or as protecting agents against the corrosion of a metallic surface.
US7439292B2. Rhodia.
326 Yokota, K., Berret, J.F., Tolla, B., and Morvan, M. (2008). Rare earth aggregate
formulation using di-block copolmers. US7468413B2. Rhodia.
327 Bzducha, W. (2012). Block copolymers useful as tensioning agents.
US8207273B2. Rhodia.
328 Destarac, M. and Wilson, J. (2013). Living poly(N-vinyllactam) reactive stabiliz-
ers for dispersed phase polymerization. WO2013113750A1. Rhodia Operations.
329 Destarac, M. and Wilson, J. (2013). Dispersed phase polymerization of
halogenated vinyl monomers in the presence of life reactive stabilizers.
WO2013113752A1. Rhodia Operations.
References 1161
330 Cadix, A. and Wilson, J. (2014). Fracturing fluids based on associative polymers
and displaceable surfactants. WO2014167056A1. Rhodia Operations.
331 Wilson, J., Destarac, M., and Cadix, A. (2013). Preparation of amphiphilic block
polymers by controlled radical micellar polymerization. WO2013060741A1. Rho-
dia Operations.
332 Destarac, M. and Wilson, J.D. (2013). Controlled radical polymerization in a
water-in-water dispersion. WO2013132108A1. Rhodia Operations.
333 Harrisson, S. and Wilson, J. (2015). Amphiphilic multiblock polymers.
WO2015144475A1. Rhodia Operations.
334 Usui, Y. and Yusa, S. (2014). ABA triblock copolymer, thickener, and aqueous
composition. US8829133B2. Ricoh, University Of Hyogo.
335 Bollinger, J.M. and Wang, J.-L. (2005). Process for preparing dithioesters.
US6841695B2. Rohmax Additives GmbH.
336 Mueller, M., Stoehr, T., and Eisenberg, B. (2012). Polyalkyl (meth)acrylate
copolymers having outstanding properties. US8101559B2. Rohmax Additives.
337 Mueller, M., Stoehr, T., and Eisenberg, B. (2014). Polyalkyl (meth)acrylate
copolymers having outstanding properties. US8722601B2. Rohmax Additives.
338 Di, J., Mullen, B., and Sybert, P.D. (2009). Thermoplastic composition, method
of making, and articles formed therefrom. US7498398B2. Sabic Innovative
Plastics.
339 Scherman, O.A., Appel, E., and Hughes, T. (2014). Viscous wellbore fluids.
US8757264B2. Schlumberger Technology Corporation.
340 Venkatesh, R. and Klumperman, L. (2004). Process for copolymerization of
α-olefins with vinyl monomers using thiocarbonylthio compounds as chain
transfer agents. EP1384729A1. Dutch Polymer Institute, Neth.
341 Hicks, J.K., Rimmer, S., McCulloch, D., and Hoskins, R. (2016). Improvements
in and relating to polymer materials. WO2016005288A1. Smith & Nephew.
342 Hicks, J.K., Rimmer, S., Hoskins, R., and McCulloch, D. (2016). Improvements
in and relating to devices. WO2016012219A2. Smith & Nephew.
343 Klumperman, L., Pfukwa, R., and Heyns, I.M. (2017). Synthesis of
3-methylene-2-pyrrolidone based polymers. WO2017029630A1. Stellenbosch
University, S. Afr.
344 Klumperman, L., Reader, P.W., and Rautenbach, M. (2016). Conjugate for treat-
ing malaria. WO2016024240A1. Stellenbosch University, S. Afr.
345 Klaerner, G., Petro, M., Charmot, D., and Benoit, D. (2004).
Controlled-architecture polymers and use thereof as separation media.
346 Klaerner, G., Petro, M., Charmot, D., and Benoit, D. (2007).
Controlled-architecture polymers and use thereof as separation media.
347 Klaerner, G., Nielsen, R.B., Mansky, P. et al. (2004). Polymer brushes for
immobilizing molecules to a surface or substrate, where the polymers have
water-soluble or water-dispersible segments and probes bonded thereto.
348 Klaerner, G., Nielsen, R.B., Mansky, P. et al. (2004). Polymer brushes for immo-
bilizing molecules to a surface and having water-soluble or water-dispersible
segments therein and probes bonded thereto. US6833276B2. Symyx Technolo-
gies, Inc.
349 Liu, M., Hajduk, D., Frechet, J.M.J. et al. (2006). Methods of making ABA-type
block copolymers having a random block of hydrophobic and hydrophilic
monomers. US7067586B2. Symyx Technologies, Inc.
350 Charmot, D., Chang, H.-T., Jayaraman, M., and Nava-Salgado, V. (2003). Control
agents for living-type free radical polymerization and methods of polymerizing.
US6667376B2B2. Symyx Technologies, Inc.
351 Charmot, D., Jayaraman, M., Chang, H.T. et al. (2004). Cellulose copolymers
that modify fibers and surfaces. 6803410. Symyx Technologies, Inc.
352 Benoit, D., Safir, A., Chang, H.-T. et al. (2007). Synthesis of photoresist poly-
mers. US7250475B2. Symyx Technologies, Inc.
mers. US7399806B2B2. Symyx.
354 Husemann, M., Zollner, S., and Losch, M. (2004). Method for producing poly-
acrylates. US6765078B2. Tesa AG.
355 Husemann, M. and Dollase, T. (2004). Oriented acrylic block copolymers.
US6703441B2. Tesa Aktiengesellschaft.
356 Husemann, M. and Zollner, S. (2004). UV-crosslinkable acrylic hotmelt PSAs
with narrow molecular weight distribution. US6720399B2. Tesa AG.
357 Dollase, T., Husemann, M., and Luhmann, B. (2004). Strippable systems based
on acrylic block copolymers. US6723407B2. Tesa AG.
358 Husemann, M. and Zollner, S. (2004). Pressure sensitive adhesive, particularly
for apolar surfaces. US6723786B2. Tesa AG.
359 Husemann, M. and Zöllner, S. (2007). Crosslinking of photoiniator-initialized
polyacrylates. US7271203B2. tesa Aktiengesellschaft.
360 Husemann, M. and Zöllner, S. (2007). Adhesive material based on block copoly-
mers having a P(A)-P(B)-P(A) structure. US7307115B2. tesa AG.
361 Husemann, M. and Zöllner, S. (2008). 2-Component crosslink of
end-functionalized polyacrylates. US7402632B2. Tesa AG.
362 Dollase, T., Husemann, M., and Luhmann, B. (2012). Adhesive masses
based on block copolymers of structure P(A)-P(B)-P(A) and P(B)-P(A)-P(B).
US8129470B2. Tesa.
363 Husemann, M. and Zollner, S. (2009). Method for the production of acrylate
adhesive materials using metal-sulphur compounds. US7514515B2. Tesa.
364 Dollase, T. and Husemann, M. (2010). Adhesive materials having a high refrac-
tive index based on acrylate block copolymers. US7758933B2. Tesa.
365 Husemann, M., Dollase, T., and Luhmann, B. (2008). Pressure-sensitive adhe-
sive based on acrylate block copolymers. US7459499B2. Tesa AG.
366 Husemann, M., Dollase, T., and Lühmann, B. (2008). Pressure-sensitive adhe-
sive based on acrylate block copolymers. US7432326B2. Tesa AG.
367 Dollase, T. and Koop, M. (2009). Method for producing contact adhesive masses
containing acrylic. US7605212B2. Tesa.
References 1163
368 Cho, S., Sun, G., Wooley, K.L. et al. (2014). Self-assembled structures, method
of manufacture thereof and articles comprising the same. US8822130B2. Texas
A&M University, Rohm And Haas Electronics Materials.
369 Charmot, D., Jayaraman, M., Chang, H. et al. (2005). Use of compounds in
products for laundry applications. EP1409627B1. Unilever Research.
370 Blokzijl, W., Carswell, R.J., Charmot, D. et al. (2007). Laundry treatment com-
positions comprising a polymer with a cationic and polydialkylsiloxane moiety.
US7179777B2. Unilever Home & Personal Care USA Division of Conopco, Inc.
371 Charleux, B., Rieger, J., and Stoffelbach, F. (2013). Amphiphilic block copoly-
mer and method for preparing same. US8598289B2. Universite Pierre Et Marie
Curie, CNRS, Universite De Liege.
372 Zeng, H., Li, L., and Yan, B. (2018). A mussel-inspired injectable hydrogel with
self-healing and anti-biofouling capabilities. US10023700B2. The Governors of
the University of Alberta, Can.
373 Montarnal, D., Hawker, C.J., Kramer, E.J., and Fredrickson, G.H. (2015). Com-
positions for controlled assembly and improved ordering of silicon-containing
block copolymers. US9158200B2. University of California.
374 Yang, C. and Wudl, F. (2012). Well-defined donor-acceptor rod-coil diblock
copolymer based on P3HT containing C60 . US8211996B2. University of Califor-
nia.
375 Hawker, C.J., Vestberg, R., and Ueno, N. (2012). Highly efficient agents for
dispersion of nanoparticles in matrix materials. US8153729B2. University of
California, Mitsubishi Chemical.
376 Noda, T., Nakaya, F., Sakashita, K. et al. (2012). Novel chain transfer agent and
emulsion polymerization using the same. US9676888B2. Mitsubishi Chemical.
377 Noda, T., Nakaya, F., Sakashita, K. et al. (2016). Chain transfer agent and emul-
sion polymerization using the same. US9452978B2. Mitsubishi Rayon.
378 Maynard, H.D. and Nguyen, T. (2013). Basic fibroblast growth factor
(bFGF)-polymer conjugates as heparin mimicking polymers. WO2013082196A1.
University of California, USA.
379 Maynard, H.D. (2016). Biodegradable trehalose glycopolymers, structures and
methods of making biodegradable trehalose co-polymers. WO2016025668A1.
University of California, USA.
380 Maynard, H.D., Mancini, R.J., Lee, J., and Lin, E.-W. (2013). Stabilization of
biomolecules using sugar polymers. WO2013112897A1. University of California,
USA.
381 Bowman, C.N. and Scott, T.F. (2011). Stress relaxation in crosslinked polymers.
US7943680B2. University of Colorado.
382 Bowman, C.N. and Scott, T.F. (2013). Stress relaxation in crosslinked polymers.
US8404758B2. University Of Colorado.
383 Bowman, C.N., Kloxin, C., Park, H.Y., and Leung, D. (2014). Stress relief for
crosslinked polymers. US8877830B2. University Of Colorado.
384 Fenoli, C.R. and Bowman, C.N. (2015). Synthesis of trithiocarbonates and allyl
sulfides and their application into advances in covalent adaptable networks.
US9193682B2, USA.
385 Bowman, C. and Leung, D. (2017). Reducing polymerization-induced shrink-

age stress by reversible addition-fragmentation chain transfer. US9758597B2.
University of Colorado, USA.
386 Bowman, C.N., Sowan, N., and Cox, L.M. (2019). Tough, healable composites
displaying stress relaxation at the resin-filler interface. WO2019183140A1. The
Regents of the University of Colorado, USA.
387 Keselowsky, B.G., Lewis, J., Fernando, L.P. et al. (2017). Polymeric particles,
method for cytosolic delivery of cargo, methods of making the particles.
US10512607B2. Vanderbilt University, USA; University of Florida Research
Foundation, Inc.
388 Advincula, R (2011). Knotty polymers via supramolecularly templated macroini-
tiators and living polymerization and methods for making and using same.
US8669335B2. University Of Houston.
389 Forrest, M.L., Duan, S., Cai, S. et al. (2014). Drug and imaging agent delivery
compositions and methods. US8802235B2. University Of Kansas.
390 Thayumanavan, S. (2010). Invertible amphiphilic polymers. US7687600B2.
University of Massachusetts.
391 Thayumanavan, S., Klaikherd, A., and Ghosh, S. (2012). Cleavable block copoly-
mers, functionalized nanoporous thin films and related methods of preparation.
US8198368B2. University of Massachusetts.
392 Thayumanavan, S., Klaikherd, A., and Ghosh, S. (2013). Cleavable block copoly-
mers, functionalized nanoporous thin films and related methods of preparation.
US8546488B2. University Of Massachusetts.
393 Thayumanavan, S., Vachet, R., Savariar, E.N., and Combariza, M.Y. (2015).
Polymeric reverse micelles as selective extraction agents and related methods of
MALDI-MS analysis. US8969026B2. University Of Massachusetts.
394 Thayumanavan, S. (2012). Crosslinked polymer nanoassemblies for drug deliv-
ery and diagnostic agents. WO2012162307A2. University of Massachusetts,
USA.
395 Emrick, T., Skinner, M., Ward, S.M., and Saha, B. (2018). Temozolomide
compounds, polymers prepared therefrom, and method of treating a disease.
US10562901B2. The University of Massachusetts, USA.
396 Caruso, F., Qiao, G.G., Blencowe, A.R. et al. (2013). Process for the preparation
of a cross-linked multilayer film. US8496997B2. University Of Melbourne.
397 Frisbie, C.D. and Lodge, T.P. (2011). Ion gels and electronic devices utilizing ion
gels. US7999020B2. University of Minnesota.
398 Hillmyer, M. and Chen, L. (2013). Nano-structured polymer composites and
process for preparing same. US8420704B2. University Of Minnesota.
399 Rossato, L.S.R., Monteiro, M., Whittaker, M. et al. (2014). Soil remediation pro-
cess. US8840339B2. University Of Queensland.
400 Benoit, D. and Puzas, J.E. (2014). Compositions and methods for controlled
localized delivery of bone forming therapeutic agents. WO2014152451A2. Uni-
versity of Rochester, USA.
401 Tang, C. and Ren, L. (2013). Preparation of cobaltocenium-containing
monomers and their polymers. US8592539B2. University Of South Carolina.
References 1165
402 Benicewicz, B.C., Rungta, A., Viswanath, A. et al. (2014). Nanoparticles with
multiple attached polymer assemblies and use thereof in polymer composites.
US8865796B2. University Of South Carolina.
403 Benicewicz, B.C., Rungta, A., Viswanath, A. et al. (2015). Nanoparticles with
multiple attached polymer assemblies and use thereof in polymer composites.
US9109070B2. University of South Carolina.
404 Tang, C., Qiao, Y., Ploehn, H.J., and Islam, M.D.S. (2017). Preparation of con-
jugated aromatic/heteroaromatic oligomer-containing dielectric polymers and
their applications. US9725544B2. University of South Carolina.
405 Wang, L. and Benicewicz, B.C. (2017). Raft agents and their use in the develop-
ment of polyvinylpyrrolidone grafted nanoparticles. US9732169B2. University Of
South Carolina.
406 McCormick, C.L. III Lowe, A.B., and Sumerlin, B.S. (2006). Preparation of
transition metal nanoparticles and surfaces modified with (CO)polymers syn-
thesized by RAFT. US7138468B2. University of Southern Mississippi.
407 McCormick, C.L., Lowe, A.B., and Sumerlin, B.S. (2008). Preparation of transi-
tion metal nanoparticles and surfaces modified with (CO) polymers synthesized
by RAFT. US7417096B2. University Of Southern Mississippi.
408 McCormick, C.L. III Lowe, A.B., and Sumerlin, B.S. (2011). Preparation of tran-
sition metal nanoparticles and surfaces modified with (co)polymers synthesized
by RAFT. US8084558B2. University of Southern Mississippi.
409 Scales, C.W., Huang, F., and McCormick, C.L. (2010). Non-immunogenic,
hydrophilic/cationic block copolymers and uses thereof. US7718432B2. Univer-
sity of Southern Mississippi.
410 Hawkett, B.S., Such, C.H., Nguyen, D.N. et al. (2006). Surface polymeriza-
tion process using RAFT agents for manufacture of polymer-encapsulated
particulates. WO2006037161A1. The University of Sydney, Australia.
411 Hawkett, B.S., Such, C.H., and Nguyen, N. (2014). Polymer product and interfa-
cial polymerisation process using RAFT agent. US8796359B2. University of Syd-
ney.
412 Hawkett, B.S. and Jain, N. (2014). Polymer microgel beads. US8765183B2.
University of Sydney.
413 Hawkett, B.S. and Jain, N. (2014). Polymer microgel beads and preparative
method thereof. US8852641B2. University of Sydney.
414 Hawkett, B.S., Jain, N., Pham, T.T.B. et al. (2014). Administrable compositions.
US8709486B2. University of Sydney.
415 Baker, M.P., Davey, T.W., Hawkett, B.S. et al. (2011). Water-swellable
polymer-encapsulated materials. WO2011066608A1. The University of Sydney,
Australia.
416 Hawkett, B.S., Hambley, T.W., Bryce, N.S. et al. (2012). Treatment of a solid
tumour comprising co-administration of polymeric steric stabilized particu-
late material and cellular toxin. WO2012142669A1. The University of Sydney,
Australia.
417 Hawkett, B.S., Hambley, T.W., Bryce, N.S. et al. (2015). Method for the treat-
ment of a solid tumour. US10376589B2. The University of Sydney, Australia.
418 Stayton, P.S., Hoffman, A.S., Yin, X. et al. (2010). Temperature- and
pH-responsive polymer compositions. US7718193B2. University of Washington.
419 Stayton, P.S., Hoffman, A.S., Lai, J.-i. et al. (2011). Stimuli-responsive magnetic
nanoparticles and related methods. US7981688B2. University of Washington.
420 Stayton, P.S., Hoffman, A.S., Lai, J. et al. (2013). Stimuli-responsive magnetic
nanoparticles and related methods. US8507283B2. University of Washington.
421 Stayton, P.S., Nash, M., and Lai, J. (2013). System and method for magnet-
ically concentrating and detecting biomarkers. US8426214B2. University of
Washington.
422 Stayton, P.S., Hoffman, A.S., Convertine, A.J. et al. (2009). Diblock copolymers
and polynucleotide complexes thereof for delivery into cells. WO2009140427A2.
University of Washington, USA; PhaseRx.
423 Stayton, P.S., Hoffman, A.S., Convertine, A.J. et al. (2009). Polymeric carrier for
the delivery of polynucleotides into a living cell. WO2009140421A2. University
of Washington, USA; PhaseRx, Inc.
424 Stayton, P.S., Hoffman, A.S., Convertine, A.J. et al. (2010).
Omega-functionalized polymers, junction-functionalized block copoly-
mers, polymer bioconjugates, and radical chain extension polymerization.
WO2010077678A2. University of Washington, USA; PhaseRx, Inc.
425 Monahan, S.D., Johnson, P.H., Declue, M.S. et al. (2011). Targeting monomers
and polymers having targeting blocks. WO2011062965A2. University of Wash-
ington, USA; Phaserx, Inc.
426 Stayton, P.S., Hoffman, A.S., Convertine, A.J. et al. (2009). Micellic assem-
blies comprising a plurality of copolymers. WO2009140429A2. University of
Washington, USA; PhaseRx.
427 Stayton, P.S., Montgomery, K., Crane, C. et al. (2018). Engineered cells and
agent compositions for therapeutic agent delivery and treatments using same.
WO2018165194A1. University of Washington, USA; Seattle Children’s Research
Institute; Commonwealth Scientific and Industrial Research Organisation.
428 Stayton, P.S., Convertine, A., Das, D. et al. (2018). Cell-based methods and
compositions for therapeutic agent delivery and treatments using same.
WO2018165198A1. University of Washington, USA; Seattle Children’s Research
Institute; Commonwealth Scientific and Industrial Research Organisation.
429 Convertine, A.J., Postma, A., Ratner, D.M. et al. (2019). Radiant star nanoparti-
cle prodrugs and related methods. WO2019160983A1. University of Washington,
USA; Commonwealth Scientific and Industrial Research Organisation.
430 Jiang, S., Xu, X., Li, Y. et al. (2009). Marine coatings. US9533006B2. University
of Washington, USA.
431 Mrozek, R.A., Lenhart, J.L., Lambeth, R.H., and Andzelm, J.W. (2013).
Branched additives for polymer toughening. US20130303712A1. United States
Dept. of the Army, USA.
432 Wynne, J.H., Lundin, J.G., McGann, C.L. et al. (2017). Acute care cover for
severe injuries. WO2017156250A2. United States Dept. of the Navy, USA.
433 Duvall, C.L., Nelson, C.E., Kintzing, J. et al. (2014). Polymeric nanoparticles
comprising PEG-methacrylate block copolymers. WO2014066912A1. Vanderbilt
University, USA.
References 1167
434 Haddleton, D.M., Mantovani, G., and Ladmiral, V. (2012). Process for making
polymers and supports comprising pendant sugar side groups. US8197847B2.
Warwick Effect Polymers.
435 Cao, Z., Wang, W., and Yue, Z. (2016). Methods and compositions relating to
biocompatible implants and a biocompatible hydrogel-encapsulated therapeutic
agent. WO2016138528A1. Wayne State University, USA.
436 Scales, C., Venkatasubban, K., Mahadevan, S. et al. (2011). Non-reactive,
hydrophilic polymers having terminal siloxanes and uses of the same.
WO2011140318A1. Johnson & Johnson Vision Care, Inc., USA.
437 Scales, C., Venkatasubban, K., Mahadevan, S. et al. (2017). Non-reactive,
hydrophilic polymers having terminal siloxanes and methods for making and
using the same. US9815979B2. Johnson & Johnson Vision Care.
438 George, E., Mahadevan, S., Venkatasubban, K. et al. (2012). Medical devices
having homogeneous charge density and methods for making same.
WO2012151135A1. Johnson & Johnson Vision Care, Inc., USA.
439 Scales, C.W., McCabe, K.P., and Healy, B.M. (2013). Polymers and nanogel
materials and methods for making and using the same. WO2013177506A2.
Johnson & Johnson Vision Care, Inc., USA.
440 Scales, C.W., McCabe, K.P., and Healy, B.M. (2013). Polymers and nanogel
materials and methods for making and using the same. WO2013177523A2.
Johnson & Johnson Vision Care, Inc., USA.
441 Lai, J., Egan, D., Hsu, R. et al. (2006). Applications of telechelic reversible addi-
tion fragmentation chain transfer polymers. In: ACS Symposium Series. 944 (ed.
K. Matyjaszewski), 547–563. https://doi.org/10.1021/bk-2006-0944.ch037.
442 Lubnin, A., Lenhard, S., and Lai, J. (2006). RAFT emulsions, microemulsions
and dispersions. Surf. Coat. Int., Part B: Coat. Trans. 89: 293–304. doi: 10.1007/
BF02765581.
443 Lubnin, A., O’Malley, K., Hanshumaker, D., and Lai, J. (2010). Waterborne
RAFT polymers. Eur. Polym. J. 46: 1563–1575. doi: 10.1016/j.eurpolymj.2010.04
.005.
444 Moad, G., Rizzardo, E., and Thang, S.H. (2011). A RAFT tutorial. Strem Chem.
25: 2–10.
445 Grajales, S. (ed.) (2012). Controlled Radical Polymerization Guide. St. Louis, MO:
Sigma-Aldrich.
446 Moad, G., Rizzardo, E., and Thang, S.H. (2010). Reversible addition fragmenta-
tion chain transfer (RAFT) polymerization. Mater. Matters 5: 2–5.
447 Couvreur, L., Guerret, O., Laffitte, J.-A., and Magnet, S. (2005). Polym. Prepr.
(Am. Chem. Soc., Div. Polym. Chem.) 46: 219–220.
448 Sheehan, M.T., Farnham, W.B., Okazaki, H. et al. (2008). RAFT technol-
ogy for the production of advanced photoresist polymers. Proc. SPIE 6923:
69232E/69231–69232E/69239. doi: 10.1117/12.772115.
449 Postma, A. and Skidmore, M. (2022). How to do a RAFT polymerisation. In:
450 Tsuji, R. and Hiiro, T. (2006). Process producing vinyl polymer having alkenyl
group at end, vinyl polymer, and curable composition. US7009004B2. Kaneka
Corporation.
451 Tsuji, R. and Hiiro, T. (2006). Process producing vinyl polymer having alkenyl
group at end, vinyl polymer, and curable composition. US7081503B2. Kaneka
Corporation.
452 Wilczewska, Z.A., Destarac, M., Zard, S. et al. (2006). Method for free radical
reduction of dithiocarbonylated or dithiophosphorylated functions borne by a
polymer. US7109276B2. Rhodia Chimie.
453 Wilczewska, Z.A., Destarac, M., Adam, H. et al. (2008). Method for synthesis of
polymers with thiol functions. US7396901B2. Rhodia Chimie.
454 Adam, H. and Liu, W.-L. (2004). Process for removing a dithiocarbonyl group at
the end of a polymer chain. US6794486B2. Chimie, Rhodia.
455 Charmot, D., Chang, H.-t., Wang, W., and Piotti, M. (2004). Removal of thio-
carbonyl end groups of polymers. WO2004089994A1. Symyx Technologies, Inc.,
USA.
456 Charmot, D. and Piotti, M. (2005). Removal of the thiocarbonylthio or thio-
phosphorylthio end group of polymers and further functionalization thereof.
457 Perrier, S. (2005). Polymerisation using chain transfer agents.
WO2005061555A1. The University of Leeds, UK.
458 Zard, S., Sire, B., and Jost, P. (2005). Process for partial or total oxidizing one or
several thiocarbonylthio ends of a polymer arising from radical polymerization
controlled by reversible addition-fragmentation. US7473740B2. Rhodia Chimie,
Fr.
459 Matioszek, D., Dufils, P.-E., Vinas, J., and Destarac, M. (2015). Selective and
quantitative oxidation of xanthate end-groups of RAFT poly(n-butyl acrylate)
latexes by ozonolysis. Macromol. Rapid Commun. 36: 1354–1361. doi: 10.1002/
marc.201500115.
460 Farnham, W.B., Moad, G., Thang, S.H. et al. (2010). Method for removing
sulfur-containing end groups. US7807755B2. CSIRO.
461 Chiefari, J., Hornung, C., Postma, A., and Saubern, S. (2013). Removal of thio-
carbonylthio groups from RAFT polymers. WO2013086585A1. Commonwealth
Scientific and Industrial Research Organisation, Australia.
462 Moad, G., Rizzardo, E., and Thang, S.H. (2012). Process for synthesizing thiol
terminated polymers. US8283436B2. CSIRO.
463 Farnham, W.B., Fryd, M., and Sheehan, M.T. (2013). Methods for removing
sulfur-containing end groups from polymers. WO2013062789A1. E. I. du Pont
de Nemours and Company, USA.
the process of making the same. WO2017027557A1. Henkel.
465 Mattson, K.M., Hawker, C.J., Pester, C.W. et al. (2018). Catalytic functional
group removal from a polymer. WO2018017478A1. The Regents of University of
California, USA.
References 1169
466 Feng, X., Alagi, P., Gnanou, Y., and Hadjichristidis, N. (2020). Removal
of thiocarbonylthio end groups from polymers synthesized by reversible
addition-fragmentation chain transfer polymerization. WO2020100086A1. King
Abdullah University of Science and Technology, Saudi Arabia.
tion: Materials, Synthesis and Applications (G. Moad and E. Rizzardo), 223–270.
ization. In: RAFT Polymerization: Materials, Synthesis and Applications (eds.
G. Moad and E. Rizzardo), 495–550. Weinheim: Wiley-VCH.
1171
25
Cationic RAFT Polymerization

Nagoya University, Graduate School of Engineering, Department of Molecular and Macromolecular
Chemistry, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
25.1 Introduction
Reversible addition fragmentation chain transfer (RAFT) polymerizations

refer to radical polymerizations involving a RAFT process mainly using a
thiocarbonylthio compound, and the term was coined to describe such poly-
merizations by Rizzardo et al. in 1998 [1]. As described in this book, radical
RAFT polymerizations based on sulfur compounds are among the most
widely used living/controlled or reversible deactivation radical polymeriza-
tions for precision polymer synthesis [2]. However, the term RAFT, which is
an acronym for reversible addition fragmentation chain transfer, is not lim-
ited to polymerizations proceeding via radical processes using thiocarbonylthio
compounds and can be used more generally for describing any reaction pro-
ceeding via a similar RAFT chain transfer mechanism. Furthermore, RAFT
polymerizations are categorized as degenerative chain transfer (DT) polymeri-
zations, proceeding via similar reversible chain transfers between propagating and
dormant polymer chain ends, which allows the effective control of not only radical
polymerizations but also other chain growth polymerizations using appropriate
chain transfer agents [3, 4].
This chapter focuses on RAFT or DT polymerizations that specifically proceed
via a cationic intermediate, namely, cationic RAFT or DT polymerizations, in con-
trast to many chapters, which mainly address radical RAFT polymerizations. There-
fore, this chapter first presents the background and provides an overview of cationic
RAFT polymerizations and then presents details in terms of effective RAFT or DT
agents; cationic initiators, cationogens, or catalysts; monomers; and the design of
well-defined polymers such as end-functionalized, block, and star polymers.

1172 25 Cationic RAFT Polymerization
25.2 Background and Overview of Cationic RAFT

Polymerizations
25.2.1 Living Cationic Polymerization and Mechanism

Living cationic polymerization was achieved with isobutyl vinyl ether (IBVE) using
hydrogen iodide (HI) as an initiator and iodine (I2 ) as an activator by Higashimura,
Sawamoto, and Miyamoto in 1984 [5] and with isobutylene (IB) using cumyl acetate
and BCl3 by Faust and Kennedy in 1986 [6]. Since then, many living cationic poly-
merizations have been developed with various monomers using a broad range of
compounds; however, except for a few examples, they are mostly based on the Lewis
acid-catalyzed processes [7–11].
The Lewis acid-catalyzed living cationic polymerizations proceed via car-
bocationic species generated through the reversible activation of a covalent
carbon–halogen or carbon–oxygen ester bond by a metal halide, where the prop-
agating cationic species can be stabilized by nucleophilic counter-anions derived
from the halide or carboxylate and Lewis acid catalyst (Figure 25.1a). In view of
kinetic treatments [12], this type of living cationic polymerization can be catego-
rized into the same family as that of metal-catalysed living radial polymerizations
[13] or atom transfer radical polymerizations [14] because the reversible generation
of the propagating species relies on the catalyst-induced activation of the dormant
species.
In addition to the Lewis acid-catalyzed mechanisms, another type of living
cationic polymerization without using Lewis acid catalysts was reported by
Webster et al. in 1990 [15]. Living cationic polymerization is achieved using
MtXn + –
CH2 CH X CH2 CH X MtXn
R R
Dormant Active
(a)
+ R – + –
CH2 CH S OTf CH2 CH OTf SR2
R R R
Dormant Active
(b)
+ –
C A + –
CH2 CH S C Z CH2 CH A S C Z
R S R S C
Dormant Active
(c)
Figure 25.1 Three general mechanisms for living cationic polymerization. (a) Lewis
acid-catalyzed living cationic polymerization, (b) sulfide-mediated living cationic
polymerization, and (c) cationic RAFT polymerization.
25.2 Background and Overview of Cationic RAFT Polymerizations 1173
trifluoromethanesulfonic or triflic acid (TfOH) as the initiator in the presence of a

large amount of dialkyl sulfide, such as Me2 S or tetrahydrothiophene, which forms
a stable sulfonium polymer chain end via interactions with the propagating carbo-
cationic species derived from TfOH and vinyl ether (Figure 25.1b). The sulfonium
terminal serves as the dormant species and automatically and reversibly generates
the propagating cationic species to induce living cationic polymerization. This living
cationic polymerization can be grouped in the same category as nitroxide-mediated
radial polymerizations [16] because the propagating species reversibly forms
without a catalyst based on a dissociation–combination mechanism.
Despite such similarities in the mechanisms of living cationic and radical polymer-
izations, no distinct RAFT or DT processes were reported until 2015 [17]. In 1996, a
DT process for a living cationic polymerization was suggested by Müller et al. [18],
who kinetically analysed the cationic polymerization of isobutylene with dicumyl
dichloride (DiCumCl) and BCl3 originally developed by Kennedy, Smith, and Ivan
in the 1980s [19, 20]. Although Kennedy and coworkers only mentioned the con-
tribution of the irreversible chain transfer of the polyisobutylene cation to DiCumCl
in the polymerization, in which DiCumCl was named inifer, other researchers eval-
uated and discussed the possibility of a reversible chain transfer process between
the carbocationic species and the dormant C–Cl terminal later on [18, 21, 22]. A
reversible chain transfer process has also been suggested by Cramail, Deffieux, and
Nuyken in the living cationic polymerization of vinyl ethers using the HI adduct
of IBVE (HI–IBVE) as an initiator without Lewis acid catalysts but in the presence
of an ammonium salt [23, 24]. The contribution of the DT process is indirectly sup-
ported by the result that the HCl adduct of IBVE (HCl–IBVE), which does not initiate
the polymerization of IBVE in the presence of nBu4 NClO4 , can participate in the
initiation in the presence of HI–IBVE and nBu4 NClO4 . This result suggests that
the carbocationic species, which is generated from the C—I bond of HI–IBVE and
nBu4 NClO4 , abstracts a chloride anion from the C—Cl bond of HCl–IBVE to gen-
erate an additional initiating carbocationic species and that similar activations of
the C—I and C—Cl bonds by the carbocationic species also occur even during the
cationic polymerization. Then, in 2015, a distinct cationic RAFT polymerization of
vinyl ether was reported using a similar thiocarbonylthio compound in the presence
of a cationic initiator such as TfOH (Figure 25.1c) [17].
25.2.2 Overview of Cationic RAFT Polymerizations and Comparison

to Radical RAFT Polymerizations
As in radical RAFT polymerizations, the cationic RAFT polymerizations proceed via
a similar RAFT mechanism but via a cationic intermediate. In the first example of
a cationic RAFT polymerization (Figure 25.2), the carbocationic species, which is
generated from a cationic initiator such as TfOH, adds to the C=S bond of a thiocar-
bonylthio compound as a chain transfer agent to generate the cationic intermediate
stabilized by the sulfur atoms, which is quite typical of such reactions. The cationic
intermediate then undergoes fragmentation to generate the carbocationic species
that originates from the chain transfer agent along with a dormant species with a
Initiation from protonic acid follwed by propagation

(M) (Pn+ )
+ – R1 + – M + –
H OTf H OTf H n–1 OTf
R1 R1 R1
Reversible chain transfer to RAFT agent
– –
+
OTf OTf
Pn S S S + S S S + –
M R Pn R Pn R OTf
Z Z Z
(Re)initiation from carbocation of RAFT agent followed by propagation

+
( Pm )
+ – M + – M + –
R OTf R OTf R m–1 OTf
R1 R1 R1
Reversible (degenerative) chain transfer to RAFT terminal

– – –
+
OTf OTf +
OTf
Pm S S S + S S S Pn
M Pn Pm Pn Pm M
Z Z Z
Figure 25.2 General scheme for cationic RAFT polymerization using RSC(S)Z and TfOH.
thiocarbonylthio terminal. The resulting carbocationic species originating from the

RAFT agent adds to the monomer to form the cationic propagating species, and
the resulting thiocarbonylthio chain end undergoes a similar addition fragmenta-
tion process with another propagating carbocationic chain end to generate a new
carbocationic propagating species via the RAFT mechanism.
As expected from the cationic RAFT mechanism, compared with its radical RAFT
counterpart, it offers some similar and some different features. (i) The molecular
weight distribution (MWD) should become narrower as the RAFT process becomes
faster than the propagation. (ii) The R and Z groups of the thiocarbonylthio com-
pound (R–SC(S)Z) should be selected such that the RAFT process is faster. (iii) The
R group should promptly form the cationic species via fragmentation once the addi-
tion to the C=S group occurs. (iv) The Z group should be more or less electron
donating such that it can stabilize the intermediate to facilitate the RAFT process.
(v) The RAFT or DT agents may not be limited to thiocarbonylthio compounds and
can be varied as long as they mediate a fast and reversible chain transfer process
(Figure 25.3). (vi) The cationic RAFT process requires a cationic initiator, cationo-
gen, or catalyst that can generate the propagating carbocationic species. (vii) The
molecular weight can be generally controlled by the feed ratio of monomer to RAFT
agent when the amount of initiator is very low compared with the RAFT agent.
(viii) The counter-anion, which typically originates from the initiator, should affect
the cationic propagation in terms of the rate and stereochemistry, unlike in radical
RAFT polymerizations, where no such counterpart exists. (ix) Cationic RAFT poly-
merizations using a thiocarbonylthio RAFT agent may be compatible with radical
+ +
Pn S S S + S S S Pm
M Pm Pn Pm Pn M
Z Z Z
+ + +
Pn Pm Pn Pm Pn Pm
M S S S M
R R R
+ +
Pn O O Pm Pn O + O Pm Pn O O Pm
M P P P M
R R R R R R
+ + +
Pn Pm Pn Pm Pn Pm
M O O O M
R R R
+ +
Pn O O O + O O O Pm
M Pm Pn Pm Pn M
NR2 NR2 NR2
+ +
Pn O O Pm Pn O + O Pm Pn O O Pm
M S S S M
R O R O R O
Figure 25.3 Intermediates in cationic RAFT or DT polymerization.
RAFT polymerizations and can be utilized for the synthesis of novel well-defined
copolymers consisting of cationically and radically polymerizable monomers.
These features are important not only for designing cationic RAFT or DT polymer-
izations but also for creating novel well-defined polymers with unique properties
and functions, as described below.
25.3 Design of Cationic RAFT or DT Polymerizations

The components of cationic RAFT or DT polymerizations are (i) the chain transfer
agents, which efficiently induce fast and reversible chain transfer reactions via
a cationic intermediate; (ii) initiators, cationogens, or catalysts, which generate
cationic initiating species; and (iii) cationically polymerizable monomers. This
section summarizes the design of cationic RAFT or DT polymerizations in terms of
these components.
25.3.1 RAFT or DT Agents for Cationic Polymerizations

Various compounds, which are formally adducts of a protonic acid and a cationi-
cally polymerizable monomer such as vinyl ethers and p-methoxystyrene (pMOS),
Thiocarbonylthio compounds
S NEt2 S NPh2 S SEt S OEt S OEt S NEt2
Oi-Bu S Oi-Bu S Oi-Bu S Oi-BuS OEt S S
1 2 3 4 10
OMe
S S S S OMe 8
N
Oi-Bu S O Oi-Bu S Oi-Bu S Oi-Bu S
5 6 7 9
Thioethers
Sn-Bu Ss-Bu St-Bu Sn-Bu S S
4
Oi-Bu Oi-Bu Oi-Bu Oi-Pr O O
11 12 13 24
tBuMe2SiO 20 OSiMe2tBu
S S S S S S
Oi-Bu Oi-Bu Oi-Bu
OMe CI OMe CI
14 15 16
17 18 19
OMe OMe OMe
Oxoacid esters
On-Bu OPh Ph Others
O O O
P On-Bu P OPh PH OMe
Oi-Bu O Oi-BuO Oi-Bu O
Oi-Bu
21 22 23 OMe NO2 30
O NMe2 O O CF3 O O CI
Oi-Bu O Oi-Bu O Oi-Bu O Oi-Bu O Oi-Bu O Oi-Bu
25 26 27 28 29 31
Figure 25.4 Various cationic RAFT or DT agents.
have been employed as possible chain transfer agents in cationic polymerizations

(Figure 25.4). Cationic RAFT polymerizations were first reported for IBVE using a
series of thiocarbonylthio compounds (R–SC(S)Z) (1–5), which may generate car-
bocations (R+ ) with the same structure as those derived from IBVE, with various
Z groups, such as dithiocarbamates, trithiocarbonates, and xanthates, in the pres-
ence of a small amount of TfOH as the initiator or cationogen [17]. The MWDs of
the resulting polymers are highly dependent on the Z group. Dithiocarbamates with
alkyl and phenyl groups (1 and 2) give the narrowest MWDs (M w /M n < 1.1), whereas
pyrrolidinone dithiocarbamate (5) with an adjacent electron-withdrawing carbonyl
moiety results in a broader MWD (M w /M n = 1.8). Furthermore, trithiocarbonate (3)
also effectively provides polymers with narrow MWDs (M w /M n = 1.1–1.2) with high
molecular weights (M n ∼ 105 ), while xanthate (4) results in slightly broader MWDs
(M w /M n = 1.5–1.6). An electron-donating substituent thus stabilizes the cationic
intermediate, enhancing the reversible chain transfer process and enabling good
molecular weight control.
Some of these thiocarbonylthio compounds (1 and 3–5) and additional com-
pounds (6 and 7) have been used for the cationic polymerizations of various alkyl
vinyl ethers, including IBVE, using photoredox catalysts (see Section 25.3.2), which
produces cationic propagating species directly from the RAFT agents [25–27]. Sim-
ilarly, dithiocarbamate (1) and trithiocarbonate (3) can serve as efficient cationic
RAFT agents to provide polymers with narrow MWDs (M w /M n = 1.1–1.2) [26].

In addition, xanthate (4), pyrrolidinone dithiocarbamate (5), and dithiobenzoate
(6) give polymers with M n s close to the calculated values but with broader MWDs
(M w /M n = 1.9–2.2) because of the slower RAFT process [27]. A similar electronic
effect through resonance, which narrows the MWD (M w /M n = 1.5), is observed
with an electron-donating p-methoxy substituent on dithiobenzoate (7). The
dithiocarbamate that can generate the carbocation of pMOS (8) is not efficient as
a RAFT agent for vinyl ethers because fragmentation into the pMOS carbocation
hardly occurs in comparison to the formation of the more stable vinyl ether cation.
Other thiocarbonylthio compounds (dithioacetate [9] and xanthate [10]) and
trithiocarbonate (3), which can generate vinyl ether carbocations, have been
employed for the cationic polymerization of vinyl ethers and pMOS in the presence
of HCl with Et2 O to produce polymers with controlled molecular weights and
narrow MWDs [28–30].
In contrast to radical RAFT polymerizations, compounds other than thiocar-
bonylthio can be used as cationic RAFT or DT agents, as they can react with
the propagating carbocationic species and induce fast, reversible chain transfer
reactions via a stable cationic intermediate. Another series of efficient cationic
chain transfer agents is thioether. In particular, thioacetal (11), which can be easily
prepared from IBVE and n-butanethiol in the presence of a catalytic amount of
methanesulfonic acid (CH3 SO3 H), is effective for controlling the cationic poly-
merization of IBVE in the presence of a small amount of TfOH to give polymers
with controlled molecular weights and narrow MWDs (M w /M n = 1.1–1.2) [31].
The polymerization is supposed to proceed via a cationic DT mechanism, in which
the sulfonium intermediate forms via the attack of the dormant thioether terminal
by the propagating cationic species. In addition to the similar electronic effects
of thioethers, steric effects are observed. By increasing the bulkiness around the
thioether using secondary (12) and tertiary butanethiol (13) derivatives, the MWDs
become broader (M w /M n = 1.6 and 1.8) because of the slower DT process, which is
significantly affected by the adjacent substituents. Electronic effects are observed
when using thioethers derived from substituted thiophenols (14–16), and the
MWDs gradually become broader (M w /M n = 1.52, 1.90, and 1.93). While thioacetal
such as 11 completely inhibit the cationic polymerization of pMOS, thioethers,
such as adducts of pMOS and thiophenols (17–19), are more efficient cationic DT
agents. A slight electronic effect is observed on the MWDs. A notable feature of
the thioether-based system is the high stability of not only the adduct but also the
dormant polymer terminal, even during the work-up process under air. Based on
these characteristics, a thioether derived from a functionalized vinyl ether and
butanedithiol (20) can serve as a bifunctional reversible chain transfer agent to give
α,ω-functionalized telechelic polymers linked by stable thioacetal linkages in the
middle of the polymer chains [31].
Oxoacid esters can also serve as RAFT agents in cationic polymerizations.
Especially, adducts of IBVE and phosphorous-based acids, such as phosphoric
and phosphinic acids (21–23), are efficient reversible chain transfer agents for
producing poly(IBVE) with controlled molecular weights up to 105 and narrow
MWDs (M w /M n = 1.1–1.2), where the phosphonium intermediate contributes to

the RAFT process, as suggested by 31 P NMR analysis [32]. The phosphorous-based
RAFT agents and the obtained polymers are colourless and odourless, although
the quenching of the polymerization with methanol results in complete removal
of the phosphorous group from the dormant terminal. Interestingly, mixtures of
phosphoric acid- (21) and thiol-based (24) chain transfer agents give polymers not
only with controlled molecular weights and narrow MWDs but also with mixtures
of α- and ω-termini, indicating nearly equivalent crossover reactions between the
two reversible chain transfer agents during propagation.
Carboxylic acid esters (25–29) are less efficient as reversible chain transfer agents
for the cationic polymerization of IBVE. However, some electronic effects are
observed. Among them, a carbamic acid ester with an electron-donating nitrogen
atom (25) results in polymers with M n s close to the calculated values but with a
slightly broadened MWD (M w /M n = 1.6). In contrast, carboxylic acid esters with
electron-withdrawing substituents such as CF3 – and NO2 – moieties, as in 27 and
29, are much less effective, resulting in much higher molecular weights than those
achieved with CH3 - and MeO-moieties, as in 26 and 28, respectively.
Table 25.1 summarizes the M n and M w /M n values of polymers obtained via
cationic polymerizations of IBVE under similar conditions [31, 32] and chain
transfer constants (Ctr ) calculated using M n , M w , monomer conversions, and
concentrations of each component according to the equations describing their
relationships [33]. The effective chain transfer agents with high Ctr values for
vinyl ethers thus include dithiocarbamates, phosphoric or phosphinic acid esters,
trithiocarbonates, and thioethers. An acetal (30) was less efficient than thioacetal. In
addition, HCl–IBVE (31), which is one of the best initiators for Lewis acid-catalyzed
living cationic polymerizations of vinyl ethers, is not suitable as a reversible chain
transfer agent.
Although RAFT or DT agents can generally be synthesized before the polymer-
ization, preparation and isolation are not necessary for producing polymers with
controlled molecular weights and narrow MWDs [32, 34]. The addition of mixtures
of phosphoric acid dibutyl ester ((n-BuO)2 PO2 H) and a trace amount of TfOH to a
solution of IBVE provides polymers with a level of control similar to that obtained
using the isolated adducts. 1-Octanethiol (n-C8 H17 SH) can be used in place of
(n-BuO)2 PO2 H. In these polymerizations, the corresponding adduct, which works
as a chain transfer agent, is formed in situ before the cationic polymerization. This
method is very simple and easy to handle and does not require the preparation
of a chain transfer agent. In addition, methanesulfonic acid (CH3 SO3 H), whose
adduct is difficult to isolate because of its instability, is also effective in the presence
of a small amount of TfOH, indicating that sulfoxonium ions can also work as
intermediates for cationic RAFT polymerizations [34].
Simple alcohols, such as methanol, ethanol, and isopropanol, have been used
as precursors of chain transfer agents for the cationic polymerization of pMOS in
the presence of photoredox catalysts to afford polymers with controlled molecular
weights and narrow MWDs (M w /M n = 1.1–1.2) (see Section 25.3.2) [35]. The con-
tribution of the oxonium intermediate via the DT mechanism has been suggested.
Table 25.1 Mn , Mw /Mn , chain transfer constants (C tr ) obtained in cationic RAFT or DT

polymerization of IBVE under similar conditions.a)
Conv. Mn
Entry Compound –X (%)b) M n c) (Calcd)d) M w /M n c) C tr e)
1 1 –SC(S)NEt2 96 5100 5000 1.08 150

2 2 –SC(S)NPh2 95 5900 5100 1.08 150
3 20 –OP(O)(OnBu)2 97 4900 5000 1.09 60
4 22 –OP(O)PhH 94 5100 4800 1.08 37
5 21 –OP(O)(OPh)2 93 4900 4800 1.16 18
6 3 –SC(S)SEt 90 5000 4700 1.18 12
7 11 –Sn-Bu 92 5600 4900 1.19 8.5
8 4 –SC(S)OEt 94 4700 4900 1.59 2.0
9f) 24 –OC(O)NMe2 96 4900 5000 1.62 1.7
10 29 –OCH3 89 5800 4800 1.82 1.6
11 5 –SC(S)pyrrolidone 92 4900 4900 1.88 1.3
12 25 –OC(O)CH3 92 8700 4900 3.41 0.22
13 27 –OC(O)C6 H4 OCH3 97 8000 5000 5.33 0.20
14 30 –Cl 94 27700 4800 2.72 0.07
15 28 –OC(O)C6 H4 NO2 96 29500 5000 3.23 0.05
16 26 –OC(O)CF3 91 37200 4700 2.84 0.05
a) Polymerization condition: [M]0 /[chain transfer agent]0 /[TfOH]0 = 500/10/0.05 mM in

n-hexane/CH2 Cl2 /Et2 O (80/10/10) at –40 ∘ C.
b) Determined by 1 H NMR.
c) The M n and M w /M n were determined by SEC.
d) M n (Calcd) = MW(IBVE) × [M]0 /[chain transfer agent] × Conv. + MW (chain transfer agent).
e) Chain transfer constant.
f) [TfOH]0 = 0.50 mM.
Modified from tables in [31, 32].
25.3.2 Initiators, Cationogens, or Catalysts for Cationic RAFT or DT

Polymerizations
For cationic RAFT or DT polymerization, initiators, cationogens, cation sources,
or catalysts that can generate propagating carbocationic species must be used
(Figure 25.5) in addition to chain transfer agents.
As conventional radical initiators are employed in radical RAFT polymer-
ization, as typical cationic initiators, strong protonic acids such as TfOH have
been employed for cationic RAFT polymerizations [17]. In contrast to radical
initiators, such as 4,4′ -azobisisobutyronitrile (AIBN) that gradually decomposes
to generate radical species, all TfOH molecules can immediately initiate cationic
polymerizations. Therefore, the molecular weights are influenced not only by
the concentration of RAFT agent but also by that of TfOH, where the M n value
Protonic acids Organic halides + metal salts

CF3SO3H + – CF3
CI Ag CF3SO3
(CF3SO2)2NH + –
Ag SbF6 + –
HCI. Et2O Oi-Bu Na B
+ –
Ag PF6
31
CF3
4
Photo-catalysts Electro-catalysts
X +
O• O
Y, X
N N
32a: O, Me
32b: O, OMe
– e–
32c: O, H
32d: O, Br + –
32e: S, H TEMPO (n-Bu4N CIO4 )
+ H + O–
Y O
– CI CN CI
BF4 CN
X X
– 2e–
+ – CI CN CI CN
F F PF6
H + O– O
X + –
DDQ2– (n-Bu4N PF6 )
N N
F3C Chemical catalysts
F3C + – BF
N N 4
X
33a: CF3 at 5/5’ Fe
X
33b: CF3 at 4/4’
F F 34
33c: F at 5/5’
Figure 25.5 Initiators, cationogens, and catalysts for cationic RAFT or DT polymerization.
is theoretically determined by the feed ratio of the monomer to the sum of the
RAFT agent and TfOH (M n ∝ [M]0 /([RAFT agent]0 + [TfOH]0 )). This relationship
has been confirmed in cationic RAFT polymerizations of IBVE using 3 and TfOH
[17]. However, the effects of TfOH on the molecular weight of the resulting
polymers can be negligible when the concentration of TfOH is sufficiently low.
Indeed, a trace amount of TfOH ([TfOH]0 = 0.05 mM or 8 ppm in the solution;
[TfOH]0 /[M]0 = 10–4 ; [TfOH]0 /[3]0 = 5 × 10–3 ) is enough to induce the cationic
RAFT polymerization of IBVE, while the molecular weight of the polymer is
substantially determined by the feed ratio of IBVE to 3.
Other strong protonic acids, such as trifluoromethanesulfonic imide or triflimide
((CF3 SO2 )2 NH : Tf2 NH), can be used to induce very fast polymerization [17].
However, weaker protonic acids, such as CH3 SO3 H and CF3 CO2 H, do not produce
polymers, most likely because they form an adduct of IBVE with its more nucle-
ophilic counter-anion. An interesting but curious result has been obtained using
an HCl solution of Et2 O as an initiator in conjunction with 9 or an acetic acid
adduct of 2-methoxyethyl vinyl ether as a chain transfer agent [28]. The cationic
polymerization of IBVE gives polymers with narrow MWDs. Because acetate is
not a good chain transfer agent for cationic RAFT polymerizations of vinyl ethers
(Table 25.1) but is a good initiator for Lewis acid-catalyzed cationic polymerizations
[11], a small amount of HCl, which may remain due to the slow initiation in the
presence of Lewis basic Et2 O, can act as a Lewis acid catalyst for the activation of
the thioester and oxygen ester terminals.
Another method to form cationic species is to use mixtures of an organic halide
and a metal salt with a counter-anion with low nucleophilicity. In particular,
equimolar mixtures of HCl–IBVE (31) and silver salts (Ag+ ) of triflate (TfO– ), hex-
afluoroantimonate (SbF6 – ), or hexaflurophosphate (PF6 – ) result in cationic species
with various counter-anions and insoluble silver chloride to induce the cationic
RAFT polymerization of IBVE in the presence of 1 as a RAFT agent, affording
polymers with controlled molecular weights and narrow MWDs (M w /M n ≤ 1.1)
[36]. A sodium salt with a non-nucleophilic counter-anion (Na+ B[3,5-(CF3 )2 Ph]4 –
or Na+ BArF– ) can also be used upon mixing with 31 in the presence of 3 at
–78 ∘ C to achieve almost atactic poly(IBVE) (r : m = 48 : 52) with narrow MWDs
(M w /M n ≤ 1.1) because the tacticity is determined by the non-nucleophilic
counter-anion and the molecular weight is controlled by the RAFT process. This
result suggests the possibility of simultaneously controlling the molecular weight
and tacticity with the RAFT agent and counter-anion, respectively; simultaneously
controlling these parameters in Lewis acid-catalyzed living cationic polymerizations
is quite difficult because the counter-anion plays both roles.
As in the case of photoredox radical RAFT polymerizations [4], photoredox
catalysts are similarly effective for generating cationic species directly from chain
transfer agents to induce cationic RAFT polymerizations. However, in cationic
RAFT polymerizations, photoredox catalysts should oxidize the RAFT agent to pro-
duce the carbocationic species and a radical fragment, in contrast to the photoredox
radical RAFT polymerization in which the photoredox catalysts reduce the RAFT
agent to produce the radical and an anionic fragment. The first process has been
reported in the cationic polymerization of pMOS using 2,4,6-tri(p-tolyl)pyrylium
tetrafluoroborate (32a) under blue LED irradiation (450 nm) in the presence of
MeOH as a precursor of the chain transfer agent, where an initiation mechanism
involving the single-electron oxidation of pMOS is proposed [35]. Furthermore, a
series of 2,4,6-triarylpyrylium salts (32a–32e) have been employed in conjunction
with various thiocarbonylthio compounds for the cationic polymerization of various
vinyl ethers under blue LED irradiation (450 nm) [26, 27]. All these photoredox
catalysts afford poly(IBVE) with controlled molecular weights and narrow MWDs
(M w /M n = 1.1–1.2), although the polymerization rates depend on the substituents of
the pyrylium salts, which affect the activities and redox potentials of the photoredox
catalysts. The temporal control of the polymerization was achieved by switching the
irradiation on and off, and the controllability is also dependent on the photoredox
catalysts. The temporal control can be improved by using more stable polypyridyl
iridium complexes (33a–33c), as both the excited- and ground-state redox potentials
of the catalysts are important [37].
Electroredox catalysts can also be used to generate cationic propagating

species from vinyl ethers and the thiocarbonylthio moiety of the RAFT agents
upon exposure to an electric current. As a precursor of the oxidizing agent,
(2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) has been used in the presence of 1
and n-Bu4 NClO4 , which serves as an electrolyte as well as a counter-anion, for the
cationic polymerization of IBVE [38]. When an oxidizing current is applied, TEMPO
is oxidized at the anode to generate the TEMPO cation, which oxidizes 1 to generate
the carbocation and a thiyl radical via the mesolytic cleavage of the C—S bond.
This electrochemical system is effective not only for vinyl ethers but also for pMOS,
which cannot be polymerized by photochemical processes with thiocarbonylthio
compounds, and provides polymers with controlled molecular weights. Temporal
control is achieved by switching the electrical stimulus between oxidizing and
reducing currents. Alternatively, 2,3-dichloro-5,6-dicyanodipehnol (DDHQ) has
been employed in conjunction with 3 and n-Bu4 NPF6 in the polymerization of IBVE
to afford polymers with controlled molecular weights under an oxidizing potential,
which oxidized DDQ2– to DDQ [39]. The system is also effective for other vinyl
ethers, pMOS, and p-hydroxystyrene (pHS). Temporal control can also be achieved
by switching the applied potential on and off.
As a chemical single-electron oxidizing catalyst, ferrocenium tetrafluoroborate
(FcBF4 ) effectively provides well-controlled polymers with narrow MWDs from
vinyl ethers and pMOS in conjunction with 1, which is oxidized by FcBF4 [40, 41].
The temporal control of the polymerization can be achieved through the addition
of a dithiocarbamate anion with sodium salt as the reducing agent.
25.3.3 Monomers for Cationic RAFT or DT Polymerizations

Monomers that can be polymerized in a controlled manner using cationic RAFT or
DT polymerizations include vinyl ethers and relatively highly cationically polymer-
izable styrenes with electron-donating substituents, such as p-alkoxystyrenes, pHS,
and α-methylstyrene (αMS) (Figure 25.6).
Vinyl ethers Styrenes
O O O O O
EVE NPVE IPVE CHVE

OMe OH
pMOS pHS αMS
O O O O O O
O
CI OEt
NBVE IBVE TBVE CEVE EOEVE 35
Figure 25.6 Monomers for cationic RAFT or DT polymerization.

The cationic RAFT or DT polymerizations based on not only thiocar-

bonylthio compounds but also thioethers and phosphoric acid esters are
generally effective for polymerizing various alkyl vinyl ethers, including IBVE
[17, 26–28, 30–32, 34, 36–42], ethyl vinyl ether (EVE) [24, 26, 27, 31, 36, 38, 40, 43, 44],
n-propyl vinyl ether (NPVE) [26, 28, 39, 40], isopropyl vinyl ether (IPVE) [30],
n-butyl vinyl ether (NBVE) [26, 27, 30, 38–40], tert-butyl vinyl ether (TBVE)
[30], and cyclohexyl vinyl ether (CHVE) [31, 40], as are the Lewis acid-catalyzed
living cationic polymerizations [7–11]. The RAFT or DT agents should be designed
to generate a vinyl ether-type cation, which is similar to the propagating species in
cationic polymerizations of vinyl ethers to induce smooth chain transfer reactions.
For vinyl ethers, all the cationogens (protonic acids and organic halides with metal
salts) and catalysts (oxidizing photo-, electro-, and chemical redox catalysts) already
shown in Figure 25.5 are available. Interestingly, alkyl vinyl ethers, such as IPVE,
TBVE, and CHVE, which have a branch on the carbon adjacent to the ether oxygen,
are the most reactive monomers in cationic polymerizations and can be polymerized
in a controlled manner using the same RAFT cationic systems; however, slightly
broader MWDs are observed in some cases [31, 40]. Cationic RAFT polymerizations
are thus more universal than Lewis acid-catalyzed polymerizations, in which an
initiator, a Lewis acid catalyst, and/or an additive are more judiciously selected
depending on the reactivity of the monomer.
Functionalized vinyl ethers, such as 2-chloroethyl vinyl ether (CEVE) [17, 26, 38–
40] and 2-ethoxyethyl vinyl ether (EOEVE) [28], are also polymerized in a controlled
fashion via a cationic RAFT mechanism, in which the polar groups in the side chains
are not involved in the polymerization. In addition, a vinyl ether (35) with an acry-
late unit in the side chain can be polymerized in a controlled manner to give linear
polymers with the acrylate moiety in the side chains, which can be subsequently
used for crosslinking reactions to generate star polymers as described in Section 25.4
[41].
As for styrenic monomers, pMOS, one of the most cationically reactive styrenic
monomers due to the electron-donating methoxy substituent at the four position
of the phenyl group, has been successfully polymerized using thiocarbonylthio
compounds, thioethers, and methanol as chain transfer agents in the presence of
TfOH, organic halides with metal salts, and photo-, electro-, and chemical redox
catalysts [17, 29, 31, 35, 36, 38–40]. Effective chain transfer agents for styrenic
monomers include not only 3, which generates a more stable vinyl ether-type cation
and can induce efficient chain transfer, but also 17, which results in pMOS-type
carbocationic species similar to the propagating carbocation in the cationic poly-
merization of pMOS. Although photoredox catalysts are not effective for inducing
the cationic polymerization of pMOS when combined with thiocarbonylthio
compounds, combinations with electro- and chemical redox catalysts are more
efficient due to their stronger oxidizing potentials [38–40].
A phenolic monomer, pHS, can also be polymerized in a controlled manner with-
out using any protecting groups, which are usually used for cationic polymeriza-
tions of pHS because phenols can react with Lewis acids to deactivate the catalyst.
Cationic RAFT polymerizations can be metal-catalyst free and thus effective for
direct polymerizations resulting in polymers with controlled molecular weights and

narrow MWDs [17, 39].
Another cationically reactive styrenic monomer, αMS, can be polymerized in a
controlled manner in the presence of thioether 18 using a mixture of 30 and metal
salts with PF6 – , SbF6 – , or BArF– as a cationogen, although the MWDs are relatively
broad (M w /M n = 1.3–1.6) in comparison to those of vinyl ethers and pMOS [36].
The selection of the counter-anion is also important as triflate anion results in only
low molecular weight oligomers because of irreversible chain transfer via β-proton
elimination from the α-methyl group induced by triflate anion.
Although cationic RAFT or DT polymerizations are thus effective for vinyl ethers
and highly cationically polymerizable styrenes such as pMOS, there have been no
successful results for less-activated monomers such as styrene and isobutylene,
which result in less stable carbocations. These could be more challenging targets
in terms of metal-free controlled/living cationic polymerizations of common vinyl
monomers.
25.4 Design of Well-Defined Polymers by Cationic RAFT

or DT Polymerizations
Cationic RAFT or DT polymerizations are effective for the synthesis of various

well-defined polymers with controlled structures including (i) end-functionalized,
(ii) block, and (iii) star polymers. These polymers may be obtained not only
via a cationic mechanism but also by combining the cationic and radical RAFT
processes based on the similarity between the two systems. This section describes
the design and synthesis of well-defined polymers using cationic RAFT and DT
polymerizations.
25.4.1 End-Functionalized Polymers

As there are generally two methods, i.e. functionalized initiator and end-capping
methods, for the synthesis of end-functionalized polymers in controlled/living poly-
merizations, both methods are also effective in cationic RAFT or DT polymerizations
(Figure 25.7).
As for the functionalized initiator method, a bifunctional DT agent (20) has
been prepared from tert-butyldimethylsilyl-protected 2-hydroxyethyl vinyl ether
and 1,4-butanedithiol and used for the cationic DT polymerization of IBVE in
the presence of trance TfOH [31]. Even after quenching the polymerization with
methanol followed by deprotection of the silyl group, the thioacetal linkage in the
middle of the polymer chains is intact and retains the telechelic structure because
of the presence of hydroxyl groups at both chain ends. This telechelic polymer
can undergo chain extension with diisocyanate via the formation of urethane
linkages to afford higher molecular weight polymers with multiblock polyurethane
structures.
25.4 Design of Well-Defined Polymers by Cationic RAFT or DT Polymerizations 1185
Functionalized initiator method
S S
n 4 n
O O O O
HO OH
End-capping method
O O O Ph
n 4 n 4 n
O O O O O O
Figure 25.7 End-functionalized polymers via cationic RAFT or DT polymerization.
An efficient one-pot end-capping reaction of poly(IBVE), which is prepared from

3 in the presence of an Ir-based photoredox catalyst (33a) under blue LED irradi-
ation, is attained by using a series of functionalized alcohols upon further addi-
tion of the photocatalyst and 2,6-di-tert-butylpyridine as a proton trap to yield the
end-functionalized polymers with alkene, alkyne, and benzene units via the forma-
tion of acetal linkages [37]. In contrast, no acetal formation is observed when using
other photoredox pyrylium catalysts, such as 32b.
25.4.2 Block Copolymers

Because cationic RAFT or DT polymerizations yield well-controlled polymers of
vinyl ethers and pMOS with high chain end fidelity, their block copolymers have
been prepared by the addition of a second monomer to the polymerization mixture
upon nearly complete consumption of the first monomer; this process is similar to
what is used in Lewis acid-catalyzed living cationic polymerizations.
In addition to successful results in monomer addition experiments for the cationic
RAFT or DT polymerizations of vinyl ethers using thiocarbonylthio compounds,
thioethers, and phosphoric acid esters in the presence of trace TfOH [17, 31, 32],
block copolymers of IBVE and EVE can be synthesized via cationic RAFT polymer-
izations using 1 and 3 in the presence of photoredox (32b), electroredox (TEMPO),
and chemical redox (34) catalysts [26, 38, 40] (Figure 25.8). The formation of unde-
sired homopolymers of the second monomer can be suppressed in cationic RAFT
polymerization because all the TfOH molecules initiate the polymerization instan-
taneously. This is in sharp contrast to what is observed in radical RAFT polymeriza-
tions, in which radical initiators such as AIBN gradually decompose and constantly
generate new chains even during block copolymerizations.
The sequential addition of a vinyl ether with an acryloyl group (35) to a cationic
RAFT polymerization of IBVE with 3 in the presence of trace TfOH results in
block copolymers possessing acryloyl moieties in the side chains of the second
Cationic-cationic
EVE-b-IBVE
IBVE-b-pMOS
IBVE-b-EVE IBVE-b-35
pMOS-b-IBVE
Cationic-radical
IBVE-b-MA IBVE-b-EA
NPVE-b-PEGA
EOEVE-b-PEGA
IBVE-b-VAc IPVE-b-VAc IBVE-b-MMA

NBVE-b-VAc
IBVE-b-S
IBVE-b-tBOS pMOS-b-VAc
EVE-b-VDF EVE-b-(CTFE-alt-EVE)
Figure 25.8 Block copolymers via cationic RAFT or DT polymerization.

block, which can be used for the synthesis of star polymers by subsequent radical
crosslinking reaction as described below [45].
Block copolymers of IBVE and pMOS have also been prepared by adding pMOS
to poly(IBVE) prepared from 3 in the presence of an electroredox catalyst (DDQ)
[39]. The block copolymer with the opposite order of pMOS and IBVE has also been
reported using a sequential addition method, where IBVE is added to poly(pMOS)
obtained from 4 in the presence of HCl and Et2 O, although this order may not be
appropriate for block copolymer synthesis as the RAFT terminus of the second
monomer is more likely to undergo fragmentation rather than the first block [29].
One of the most notable features of cationic RAFT polymerizations using thiocar-
bonylthio compounds is in the terminal structure, which can be directly utilized for
subsequent radical RAFT polymerizations without any modification reactions for
the synthesis of block copolymers consisting of cationically and radically polymeriz-
able monomers. Vinyl ethers and pMOS are used as the cationically polymerizable
monomers, whereas the radically polymerizable monomers are various conjugated
and unconjugated vinyl monomers, including acrylates, methacrylates, vinyl
acetate (VAc), styrenes, vinylidene fluoride (VDF), and chlorotrifluoroethylene
(CTFE). In most of these syntheses, the first block is prepared by a cationic RAFT
polymerization followed by precipitation, and this block is used as a macroRAFT
agent for the radical RAFT polymerization of the second monomer to result in
the block copolymers, in which the block segments are directly linked via stable
carbon–carbon single bonds originating from the vinyl groups through a mecha-
nistic switch from cationic to radical RAFT polymerizations. The thiocarbonylthio
compounds should be selected primarily based on the second monomer because
the structures of the RAFT agents that are suitable for conjugated monomers are
different from those suitable for unconjugated monomers.
Block copolymers of EVE and methyl acrylate (MA) have been prepared using
trithiocarbonate (3) as the RAFT agent for the cationic polymerization of EVE in
the presence of TfOH, followed by the radical polymerization of MA using isolated
poly(EVE) as the macroRAFT agent in the presence of AIBN [17]. The synthesis
of a series of block copolymers of various vinyl ethers (IBVE, NPVE, and EOEVE)
and acrylates with ethyl (EA) and poly(ethylene glycol) methyl ether (PEGA)
substituents has been achieved using dithioacetate (9) in the presence of HCl and
Et2 O for the first block and AIBN for the second block [28]. One-pot direct block
copolymerization is possible without isolation of the first block for the synthesis
of the IBVE-b-EA block copolymer. For block copolymers containing other conju-
gated vinyl monomers in the second block, methyl methacrylate (MMA), styrene,
and tert-butoxystyrene (tBOS) have been employed as radically polymerizable
monomers for the radical RAFT polymerization using poly(IBVE) prepared from 9
as the macroRAFT agent [28].
Xanthate or dithiocarbamate should be used for the synthesis of diblock copoly-
mers of unconjugated monomers such as VAc because they are more suitable for
the second RAFT radical polymerization. Block copolymers of IBVE and VAc have
thus been prepared using xanthate (4) for the cationic polymerization of IBVE in
the presence of TfOH, followed by the radical polymerization of VAc using isolated
poly(IBVE) with the xanthate terminal as the macroRAFT agent in the presence of
AIBN [17]. The acetyl groups of the VAc units are removed by saponification to afford
the amphiphilic block copolymers of alkyl vinyl ether and vinyl alcohol. Similarly,
a series of block copolymers of other alkyl vinyl ethers (NBVE and IPVE) or pMOS
with VAc have been prepared using another xanthate (10) in the presence of HCl
and Et2 O for the first block and AIBN for the second block [30]. The saponification
also results in amphiphilic block copolymers, which form micelles in water.
Fluoroalkenes such as VDF and CTFE have been used as the second monomer for
the preparation of block copolymers containing vinyl ether as the first block [43, 44].
Since these fluoroalkenes are unconjugated monomers, xanthate (4) and dithiocar-
bamate (1, 2) were selected for the synthesis of the first block (the poly(EVE) seg-
ment) in the presence of TfOH. The isolated poly(EVE) was then employed as the
macroRAFT agent for the radical polymerization of VDF in the presence of tert-amyl
peroxy-2ethylhexanoate (Trigonox 121) as a radical initiator to afford block copoly-
mers having incompatible block segments with a low glass transition temperature
(T g = –35 ∘ C) of poly(EVE) and a high melting temperature (T m = 160–170 ∘ C) of
poly(VDF). Similarly, the same isolated poly(EVE) has been used as a macroRAFT
agent for the alternating radical copolymerization of CTFE and EVE in the pres-
ence of Trigonox 121 to afford an EVE-b-(CTFE-alt-EVE) block copolymer. Another
approach with the block order reversed using poly(CTFE-alt-EVE) as the macro-
RAFT agent for the second cationic RAFT polymerization of EVE was not successful
because the electron-withdrawing CTFE unit adversely affects the RAFT process in
cationic RAFT polymerizations.
The thiocarbonylthio terminal resulting from vinyl ether can also be cleaved
to afford the cationic species using a metal halide as a Lewis acid catalyst for the
living cationic polymerization of vinyl ethers [46]. However, the contribution of the
cationic RAFT mechanism is negligible under these conditions. The block copoly-
mers of MA and IBVE have thus been prepared by radical RAFT polymerizations
of MA followed by a Lewis acid-catalyzed living cationic polymerization of IBVE.
The combination of radical RAFT polymerization and Lewis acid-catalyzed living
cationic polymerization for mixtures of vinyl ethers and radically polymerizable
monomers, such as MA and VAc, enables the synthesis of multiblock copolymers
via in situ reversible switching between radical and cationic polymerization
[47–49].
Such interconvertible cationic and radical polymerizations via concurrent acti-
vation of the dormant thioester bond also proceed via both cationic and radical
RAFT mechanisms. Photocontrolled interconvertible polymerizations have been
reported for IBVE and MA using 3 as a common RAFT agent in the presence
of photo-oxidizing (32b) and photo-reducing (Ir(ppy)3 ; ppy = 2-phenylpyridine)
catalysts, which generate the cationic and radical propagating species, respectively,
to result in multiblock copolymers under blue LED irradiation [42]. Alternatively,
the combination of two orthogonal stimuli, such as the photo-reducing catalyst
(Ir(ppy)3 ) and a chemical oxidizing catalyst (34), enables the production of similar
multiblock copolymers in which the block segment lengths can be tuned by the two
stimuli [40].
25.4.3 Star Polymers

Among the various methods for synthesizing star or star-shaped polymers using
controlled/living polymerizations, the linking reactions of linear polymers with
divinyl compounds are the most efficient for the large-scale synthesis of star
polymers with a relatively large number of arms (>10) and a statistical distribution
of the numbers of arms.
This method has been used in the cationic RAFT polymerization of IBVE with
3 and TfOH in conjunction with divinyl ethers, such as 36 and 37, which forms a
microgel core via simultaneous block polymerization and crosslinking reactions
(Figure 25.9) [45]. In particular, 37, which has a relatively rigid cyclohexane-based
linker, results in star polymers with controlled molecular weights (M w = 3–7 × 105 ),
narrow MWDs (M w /M n = 1.1–1.2), and controlled arm numbers (N arm = 20–50)
and sizes (Dn = 20–28 nm, Dw /Dn = 1.03–1.05) in high yields (>90%). Although
another approach using diacrylates, such as 38 and 39, for simultaneous block
S SEt TfOH IBVE S SEt

n S SEt
Oi-Bu S Cationic RAFT Oi-Bu Oi-Bu S Arm polymers S
3 polymerization
(i) R S SEt
RRR S
Cationic RAFT RR S
R EtS RRR
block & cross linking S
Star polymer
(ii) S SEt
R
RRR S
Radical RAFT RR S
R EtS RRR
block & cross linking S
Star polymer
(iii) R
S SEt
Cationic RAFT RRR S Radical RAFT
block polymerization cross linking
Star polymer
One-Pot, No Mechanistic Transformation
Isolation, Mechanistic Transformation
Divinyl monomers
Vinyl Ether–R–Vinyl Ether Acylate–R–Acrylate O Vinyl Ether–R–Acrylate
O O O
O O O
36 O 38 O
O 40
O O O
O O O
37 39 35
O O
Figure 25.9 Star polymers via cationic RAFT or DT polymerization.

polymerization and crosslinking reactions of isolated poly(IBVE) with a trithio-

carbonate terminal via a radical RAFT mechanism is less efficient in terms of the
yield of star polymer, and hetero divinyl monomers (35, 40) with a vinyl ether and
acrylate unit are more efficient for the radical crosslinking reaction. Furthermore,
a block copolymer of IBVE and 35 prepared by a cationic RAFT polymerization
via the sequential addition of 35 has been isolated, and the pendent acrylate units
of the polymer were subjected to radical crosslinking in the presence of V-70
(2,2′ -azobis(4-methoxy-2,4-dimethylvaleronitrile)) to afford star polymers with
controlled molecular weights (M w = 2.7 × 105 ), narrow MWDs (M w /M n = 1.18), and
controlled arm numbers (N arm = 16) and sizes (Dn = 19 nm, Dw /Dn = 1.04) in high
yields (89%). The combination of cationic and radical RAFT processes thus allows
access to diverse star polymers and their synthetic methods.
25.5 Summary and Outlook for Cationic RAFT or DT

Polymerizations
The field of cationic RAFT polymerizations, which began with the use of thiocar-
bonylthio compounds by analogy to radical RAFT polymerizations, has grown in
terms of the available chain transfer agents, initiators or catalysts, monomers, and
controlled polymer structures. The RAFT and DT mechanisms have thus created
a new branch of controlled/living cationic polymerizations. The cationic RAFT
and DT polymerizations can be metal-free and operationally simpler than Lewis
acid-catalyzed living cationic polymerizations. The similarity and good compati-
bility with radical RAFT polymerizations not only enables the direct synthesis of
block copolymers of cationically and radically polymerizable monomers but also
allows the preparation of copolymers with novel sequences via interconvertible
radical and cationic polymerizations.
Because cationic RAFT or DT polymerizations are still developing, a few chal-
lenges remain. Styrene and isobutylene are important targets because they are more
common but less reactive in cationic polymerizations. A system that works at higher
temperatures may also be another challenge. The development and combination of
stereocontrolled cationic polymerizations, which enable the simultaneous control
of the molecular weight and structure of the resulting polymers, are attractive in
view of the new polymeric materials developed based on cationic polymerizations.
Further combinations of other controlled/living polymerizations, including radical
RAFT polymerizations, widen the scope of accessible, novel, and well-defined
polymer structures. In addition, products obtained via metal-free cationic RAFT or
DT polymerizations will contribute to the development of novel materials, such as
biomaterials and electronic materials.
Abbreviations
αMS α-methylstyrene
AIBN 4,4′ -azobisisobutyronitile
References 1191
CEVE 2-chloroethyl vinyl ether

CHVE cyclohexyl vinyl ether.
CTFE chlorotrifluoroethylene
DDHQ 2,3-dichloro-5,6-dicyanodipehnol
DDQ 2,3-dichloro-5,6-dicyano-p-benzoquinone
DiCumCl dicumyl dichloride
DT degenerative chain transfer
EOEVE 2-ethoxyethyl vinyl ether
IB isobutene
IBVE isobutyl vinyl ether
MA methyl acrylate
MWD molecular weight distribution
NBVE n-butyl vinyl ether
NPVE n-propyl vinyl ether
PEGA poly(ethylene glycol) methyl ether acrylate
pHS p-hydroxystyrene
pMOS p-methoxystyrene
RAFT reversible addition fragmentation chain transfer
tBOS tert-butoxystyrene
TBVE tert-butyl vinyl ether
TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl
Tf2 NH trifluoromethanesulfonic imide
TfOH trifluoromethanesulfonic acid
VAc vinyl acetate
VDF vinylidene fluoride
V-70 2,2′ -azobis(4-methoxy-2,4-dimethylvaleronitrile)
References
1 Chiefari, J., Chong, Y.K., Ercole, F. et al. (1998). Living free-radical polymer-
ization by reversible addition–fragmentation chain transfer: the RAFT process.
2 Moad, G. and Solomon, D.H. (2006). The Chemistry of Radical Polymerization:
Second Fully Revised Edition. Oxford: Elsevier.
3 Kamigaito, M., Satoh, K., and Uchiyama, M. (2019). Degenerative chain-transfer
process: controlling all chain-growth polymerizations and enabling novel
monomer sequences. J. Polym. Sci., Part A: Polym. Chem. 57: 243–254.
4 McKenzie, T.G., Fu, Q., Uchiyama, M. et al. (2016). Beyond traditional RAFT:
alternative activation of thiocarbonylthio compounds for controlled polymeriza-
tion. Adv. Sci. 3: 1500394.
5 Miyamoto, M., Sawamoto, M., and Higashimura, T. (1984). Living polymeriza-

tion of isobutyl vinyl ether with the hydrogen iodide/iodine initiating system.
6 Faust, R. and Kennedy, J.P. (1986). Living carbocationic polymerization. Polym.
Bull. 15: 317–323.
7 Sawamoto, M. (1991). Modern cationic vinyl polymerization. Prog. Polym. Sci. 16:
111–172.
8 Matyjaszewski, K. (ed.) (1996). Cationic Polymerizations. New York: Marcel
Dekker.
9 Puskas, J.E. and Kaszas, G. (2000). Living cationic polymerization of
resonance-stabilized monomers. Prog. Polym. Sci. 25: 403–452.
10 Goethals, E.J. and Du Prez, F. (2007). Carbocationic polymerizations. Prog.
Polym. Sci. 32: 220–246.
11 Aoshima, S. and Kanaoka, S. (2009). A renaissance in living cationic polymeriza-
tion. Chem. Rev. 109: 5245–5287.
12 Goto, A. and Fukuda, T. (2004). Kinetics in living radical polymerization. Prog.
Polym. Sci. 29: 329–385.
13 Kamigaito, M., Ando, T., and Sawamoto, M. (2001). Metal-catalyzed living radical
polymerization. Chem. Rev. 101: 3689–3745.
14 Matyjazsewski, K. and Xia, J. (2001). Atom transfer radical polymerization.
Chem. Rev. 101: 2921–2990.
15 Cho, C.G., Feit, B.A., and Webster, O.W. (1990). Cationic polymerization of
isobutyl vinyl ether: livingness enhancement by dialkyl sufides. Macromolecules
23: 1918–1923.
16 Hawker, C.J., Bosman, A.W., and Harth, E. (2001). New polymer synthesis by
nitroxide mediated living radical polymerizations. Chem. Rev. 101: 3661–3688.
ization using ppm concentrations of organic acid. Angew. Chem. Int. Ed. 54:
1924–1928.
18 Müller, A.H.E., Yan, D., and Litvinenko, G. (1996). Kinetic analysis of “living”
polymerization systems exhibiting slow equilibria. 4. “Degenerative” mecha-
nism of group transfer polymerization and generation of free ions in cationic
polymerization. Macromolecules 29: 2346–2353.
19 Kennedy, J.P. and Smith, R.M. (1980). New telechelic polymers and sequential
copolymers by polyfunctional initiator-transfer agents (inifers). II. Synthesis
and characterization of α,ω-di(tert-chloro)polyisobutylenes. J. Polym. Sci., Polym.
Chem. Ed. 18: 1523–1537.
20 Iván, B. and Kennedy, J.P. (1990). Living carbocationic polymerization. 31. A
comprehensive view of the inifer and living mechanisms in isobutylene polymer-
ization. Macromolecules 23: 2880–2885.
21 Mayr, H. and Shade, C. (1988). The role of chain transfer process in inifer/boron
trichloride initiated polymerizations of isobutene. Makromol. Chem., Rapid Com-
mun. 9: 483–488.
22 Matyjaszewski, K. (1997). Comparison of controlled living carbocationic and rad-
ical polymerizations. ACS Symp. Ser. 665: 12–24.
References 1193
23 Cramail, H., Deffieux, A., and Nuyken, O. (1993). Polymerization of isobutyl

vinyl ether in the presence of mixed α-chloro- and α-iodo ethers with tetrabuty-
lammonium perchlorate. Makromol. Chem., Rapid Commun. 14: 17–27.
24 Cramail, H. and Deffieux, A. (1994). Kinetic study of the “living” cationic poly-
merization of cyclohexyl vinyl ether initiated by hydrogen iodide in the presence
of ammonium salts. Macromolecules 27: 1401–1406.
25 Michaudel, Q., Kottisch, V., and Fors, B.P. (2017). Cationic polymerization: from
photoinitiation to photocontrol. Angew. Chem. Int. Ed. 56: 9670–9679.
26 Kottisch, V., Michaudel, Q., and Fors, B.P. (2016). Cationic polymerization of
vinyl ethers controlled by visible light. J. Am. Chem. Soc. 138: 15535–15538.
27 Michaudel, Q., Chauviré, T., Kottisch, V. et al. (2017). Mechanistic insight into
the photocontrolled cationic polymerization of vinyl ethers. J. Am. Chem. Soc.
139: 15530–15538.
28 Sugihara, S., Konegawa, N., and Maeda, Y. (2015). HCl⋅Et2 O-catalyzed metal-free
RAFT cationic polymerization: one-pot transformation from metal-free living
cationic polymerization to RAFT radical polymerization. Macromolecules 48:
5120–5131.
29 Sugihara, S., Okubo, S., and Maeda, Y. (2016). Metal-free RAFT cationic poly-
merization of p-methoxystyrene with HCl⋅Et2 O using a xanthate-type RAFT
cationogen. Polym. Chem. 7: 6854–6863.
30 Sugihara, S., Sakamoto, Y., Nakayama, M. et al. (2018). Transformation from
xanthate-type cationogen mediated metal-free RAFT cationic polymerization
with “HCl⋅Et2 O” into RAFT radical polymerization to form poly(alkyl vinyl
ether)-b-polyvinyl alcohol amphiphiles. Polymer 154: 153–163.
31 Uchiyama, M., Satoh, K., and Kamigaito, M. (2015). Thioether-mediated degener-
ative chain-transfer cationic polymerization: a simple metal-free system for living
cationic polymerization. Macromolecules 48: 5533–5542.
32 Uchiyama, M., Satoh, K., and Kamigaito, M. (2016). A phosphonium intermedi-
ate for cationic RAFT polymerization. Polym. Chem. 7: 1387–1396.
33 Müller, A.H.E., Yan, D., Litvinenko, G. et al. (1995). Kinetic analysis of “living”
polymerization systems exhibiting slow equilibria. 2. Molecular weight distri-
bution for degenerative chain transfer (direct actively exchange between active
and “dormant” species) at constant monomer concentration. Macromolecules 28:
7335–7338.
34 Uchiyama, M., Sakaguchi, M., Satoh, K., and Kamigaito, M. (2019). A
user-friendly living cationic polymerization: degenerative chain-transfer poly-
merization of vinyl ethers by simply using mixtures of weak and superstrong
protonic acids. Chinese J. Polym. Sci. 37: 851–857.
35 Perkowski, A.J., You, W., and Nicewicz, D.A. (2015). Visible light photoinitiated
metal-free living cationic polymerization of 4-methoxytstyrene. J. Am. Chem. Soc.
137: 7580–7583.
36 Uchiyama, M., Satoh, K., and Kamigaito, M. (2016). Diversifying cationic RAFT
polymerization with various counteranions: Generation of cationic species from
organic halides and various metal salts. ACS Macro Lett. 5: 1157–1161.
37 Kottisch, V., Supej, M.J., and Fors, B.P. (2018). Enhancing temporal control and
enabling chain-end modification in photoregulated cationic polymerizations by
using iridium-based catalysts. Angew. Chem. Int. Ed. 57: 8260–8264.
38 Peterson, B.M., Lin, S., and Fors, B.P. (2018). Electrochemically controlled
cationic polymerization of vinyl ethers. J. Am. Chem. Soc. 140: 2076–2079.
39 Sang, W. and Yan, Q. (2018). Electro-controlled living cationic polymerization.
Angew. Chem. Int. Ed. 57: 4907–4911.
40 Peterson, B.M., Kottisch, V., Supej, M.J., and Fors, B.P. (2018). On demand
switching of polymerization mechanism and monomer selectivity with orthogo-
nal stimuli. ACS Cent. Sci. 4: 1228–1234.
41 Discekici, E.H. and de Alaniz, J.R. (2018). Next-generation materials via orthogo-
nal stimuli. ACS Cent. Sci. 4: 1087–1088.
42 Kottisch, V., Michaudel, Q., and Fors, B.P. (2017). Photocontrolled interconver-
sion of cationic and radical polymerizations. J. Am. Chem. Soc. 139: 10665–10668.
vinyl ether)-block-poly(vinyliene fluoride) block copolymers. ACS Macro Lett. 6:
393–398.
44 Guerre, M., Uchiyama, M., Lopez, G. et al. (2018). Synthesis of
PEVE-b-P(CTFE-alt-EVE) block copolymers by sequential cationic and radical
RAFT polymerization. Polym. Chem. 9: 352–361.
45 Uchiyama, M., Satoh, K., McKenzie, T.G. et al. (2017). Diverse approaches to star
polymers via cationic and radical RAFT cross-linking reactions using mechanistic
transformation. Polym. Chem. 8: 5972–5981.
46 Kumagai, S., Nagai, K., Satoh, K., and Kamigaito, M. (2010). In-situ direct
mechanistic transformation form RAFT to living cationic polymerization for
(meth)acrylate–vinyl ether block copolymers. Macromolecules 43: 7523–7531.
47 Aoshima, H., Uchiyama, M., Satoh, K., and Kamigaito, M. (2014). Interconvert-
ible living radical and cationic polymerization through reversible activation of
dormant species with dual activity. Angew. Chem. Int. Ed. 53: 10932–10936.
48 Satoh, K., Hashimoto, H., Kumagai, S. et al. (2017). One-shot controlled/living
copolymerization for various comonomer sequence distributions via dual radical
and cationic active species from RAFT terminals. Polym. Chem. 8: 5002–5011.
49 Satoh, K., Fujiki, Y., Uchiyama, M., and Kamigaito, M. (2018). Vinyl ether/vinyl
ester copolymerization by cationic and radical interconvertible simultaneous
polymerization. ACS Symp. Ser. 1284: 323–334.
1195
Index
a 376, 380–385, 388–393, 395–406,

ABA triblock copolymers 26 409, 424–425, 501, 508–509, 549,
by disulfide formation 787–788 555–557, 560–564, 572, 585, 615,
by photoinduced energy or electron 624, 635, 650, 652, 654, 734, 777,
transfer (PET)-RAFT 632 806, 810, 818, 935, 938, 948,
quasi-ABC triblock copolymers 1057 1055, see also acrylamide (Am)
quasi-triblock copolymers 1054–1055, 2-acrylamido-2-methylpropane-
1059–1060 sulfonate sodium salt (AMPS),
by radical-radical termination 940 N-acryloylmorpholine (NAM),
by sequential monomer addition N,N-diethylacrylamide,
1059–1060 N,N-dimethylacrylamide
using symmetrical trithiocarbonates (DMAm), N-(2-hydroxyethyl)
382–386, 684, 936, 939, 1055 acrylamide (HEAm),
using Z-connected bis-RAFT agents N-isopropylacrylamide (NIPAm)
235–236, 370, 375 2-(acetoacetoxy)ethylacrylamide
AB diblock copolymers 26, 679, 696, (AAEAm) 849
718, 732, 770, 787, see also aqueous RAFT 684, 686, 701
diblock copolymers di(BOC)-acrylamide 838
acenaphthyl chromophore 807 with dithiocarbamates 572
donor in light-harvesting polymers with dithioesters 241, 244, 249, 257,
807 276–279
acenaphthylene (ACE) 302, 418, 557, experimental procedures 47–48
807 acrylamide in solution 46
2-(acetoacetoxy)ethyl methacrylate N,N-diethylacrylamide is solution
(AAEMA) 847, 849 46
acetone oxime (AO) group 830, 836–837 N,N-dimethylacrylamide is solution
active ester 830, 836–837 46
functional monomer 836 functional acrylamides
reaction with amino groups 836–837 active ester 426
acrylamide(s) 27, 28, 43–46, 107, 112, alkyne 426
118, 130, 226, 233, 235, 239–242, azide 289
245, 247–251, 253, 254, 256–260, betaine 270
273–275, 280, 369, 371, 373, 374, bisphosphonate 44
1196 Index
acrylamide(s) (contd.) copolymers 48

hydroxyl, see N-(2-hydroxyethyl) with dithiocarbamates 556–565, 572
acrylamide (HEAm) with dithioesters 240, 268–270
protected thiol 421 experimental procedures
protected amine 283, 421 acrylic acid in solution 43
with functional trithiocarbonates butyl acrylate in solution 41
394–408 t-butyl acrylate in solution 43
N-isopropylacrylamide is solution 44 butyl acrylate in surfactant-free
photoinduced energy or electron emulsion 42
transfer (PET)-RAFT 1055 3,5-dibromobenzyl acrylate in
photoRAFT 701 solution 42
RAFT agent selection 27–28, 43–45, 2-ethylhexyl acrylate in solution 42
112 methyl acrylate block
redox RAFT 648, 650 N-vinylcarbazole in solution
with thiocarbonates 107, 112, 130, 51
369, 396–406, 409 methyl acrylate in solution 51
with trithiocarbonates 44, 107, 112, octadecyl acrylate in solution 42
130, 226, 369, 376, 380–385, (oligo(ethylene glycol) monomethyl
388–393, 395–406, 409 ether) acrylate in solution 43
with xanthates 44, 112, 508 functional acrylates
2-acrylamido-2-methylpropanesulfonic active ester 282, 420
acid sodium salt (AMPS) 128, alkyne 281, 420
245, 246, 276, 305, 374, 381, 385, ATRP inimer 285, 424
416, 424, 509, 530, 681, 682, 1121 isocyanate 284
acrylates 27, 28, 37–39, 41–44, 48, 50, 60, NMP inimer 285, 424
65, 71, 77–79, 85, 86, 88, 107, protected thiol 283, 421
112, 130, 171, 226, 233, 235, 237, protected amine 283, 284, 421
239–274, 280, 303, 304, 310, 369, with functional trithiocarbonates
371–377, 380–382, 384, 385, 394–407
388–407, 409, 414, 424, 425, 428, RAFT agent selection 27–28, 112
501, 508–509, 555, 557–565, 572, surfactant-free emulsion
573, 578, 585, 587, 591, 615, 624, polymerization 42
627, 629, 649, 652, 654, 658, 667, with trithiocarbonates 38, 41, 48, 107,
685, 691, 693, 701, 777, 779, 780, 112, 130, 226, 369, 371–377,
793, 806, 813, 818, 831–833, 838, 380–382, 384, 385, 388–407, 409,
840, 843, 935, 938, 943, 947, 948, 425, 428, 615, 624, 935
958, 986, 1001, 1033, 1078, 1100, with xanthates 501, 508
1123, 1126, 1183, 1187, 1190, see acrylic acid (AA) 43, 147, 152, 209, 711,
also butyl acrylate, 2-ethylhexyl 787, 1103, 1104, 1106
acrylate, methyl acrylate, experimental procedure 43
octadecyl acrylate NHS ester, see
(oligo(ethylene glycol) N-acryloyloxysuccinimide
monomethyl ether) acrylate, acrylonitrile (AN)
(poly(ethylene glycol) blocks 241, 257
monomethyl ether) acrylate copolymers
Index 1197
acrylonitrile/butadiene 250, 260 pentafluorophenyl (PFP) ester,

acrylonitrile/maleic anhydride 883 salicylic acid ester
acrylonitrile/methacrylic acid 209 acyl chloride 580, 830, 839
acrylonitrile/styrene 241, 242 acryloyl chloride 780–781, 839
with dithiocarbamates 550 functional monomers 288, 290, 425,
with dithioesters 112, 234, 242, 244, 426, 831–836, 1004
245, 247 functional RAFT agents 34, 280, 281,
propagating radicals 666 394, 396, 408, 420, 426, 630, 832,
RAFT agent selection 28, 112 833, 835–838, 852
rate coefficients for radical addition (ki , intermediate in ketoform reaction 580
kp ) 107 methacryloyl chloride 839
with trithiocarbonates 112, 368, vinylbenzoyl chloride 839
371–374 addition–fragmentation coupling
4-acryloxyphenyldimethylsulfonium 766–768
triflate (APDMST) 837 addition rate coefficient, see rate
N-(2-acryloyloxyethyl)pyrrolidone (NAP) coefficients
685 adipic acid dihydrazide (ADH) 716, 725
acryloyl chloride (AC) 780, 785, 839 aliphatic dithioesters 32, 38, 223,
N-acryloylmorpholine (NAM) 275, 425, 236–237, 313, see also
507, 520, 572, 653, 693, 716, 782, 2-phenylpropan-2-yl
832, 849, 1054 2-phenylethanedithioate
with dithiocarbamates 562, 572 alkoxyamines 205, 295–297, 395, 433,
with dithioesters 242, 245, 248, 260, 435, 717, 737, 768
280 addition–fragmentation coupling 768
end-group removal 441 ESARA 297, 435, 768
with trithiocarbonates 373, 380–383, NMP inimer 423
385, 389–391, 396, 401, 404–406, -
RAFT-T-NMP 297, 435
425 alkyl diethyldithiocarbamate (DC)
2-(acryloyloxy)ethylisocyanate, see 656–657
2-isocyanatoethyl acrylate initiators 668
N-acryloyloxysuccinimide (acrylic acid, alkyl halide 295, 296, 408, 433, 500, 579,
NHS ester) 815, 816, 832, 855 656, 659–660, 830, 839–840, 964,
with dithioesters 1141 1122
with trithiocarbonates 1103 alkyl pseudohalides 656–658, 668–669
activators re-generated by electron alkyne group 847, 848, 945, see also yne
transfer (ARGET)-ATRP alkyne-functional monomer 288–289,
concurrent ATRP/RAFT 658–689 426, see also propargyl acrylate,
active ester 830–836, see also acetone propargyl methacrylate
oxime (AO) group, alkyne-functional RAFT agent 235,
p-dialkylsulfonium phenoxy 280, 426, 521, 780, 781, 857, 858,
ester (DASPE), 1023
hexafluoroisopropanol ester, copper-catalyzed azide–alkyne
N-hydroxysuccinimide (NHS) cycloaddition 717
ester, nitrophenyl ester, strain-promoted azide–alkyne
pentafluorobenzyl (PFB) ester, cycloaddition 848
1198 Index
alkyne group (contd.) RAFT mechanism transformation

thiol–yne reactions 776–780 -
(RAFT-T-anionic) 436
allyl ether 775 anthracen-9-ylmethanol 780
O-allyl hydroxylamine 724 anti-Markovnikov orientation 775
allylisocyanate 840–841, 1138 antimicrobial polymers 630–633, 859,
allyl methacrylate (AMA) 38, 409, 779 1064–1065
aluminium napthalocyanine (AlNc) against Acinetobacter baumannii
621–622 631–632
aluminium phthalocyanine (AlPc) 612, against Escherichia coli 631–632
621, 623 against Mycobacterium smegmatis
2-aminoethanethiol 857 631, 632
N-2-aminoethyl acrylamide hydrochloride against Pseudomonas aeruginosa
(AEAm) 725 631–632
N-(2-aminoethyl)methacrylamide against Staphylococcus aureus 631,
(AEMAm) 44, 240, 245, 246, 632
284, 422, 424 aqueous PISA 507, 696
2-aminoethyl methacrylate
aqueous RAFT (aRAFT) polymerization
(hydrochloride) (AEMA) 38,
deoxygenation methods 690–696
129, 240, 241, 244, 245, 253, 284,
grafting from biomolecules
371, 422
699–701
copolymers 846
photoinitiated 685–686
3-amino-1,2-propanediol 853
polymerization induced self-assembly
N-(3-aminopropyl)acrylamide
(PISA) 696–699
hydrochloride (APAm) 422
RAFT agents 679–684
N-(3-aminopropyl)methacrylamide
thermally initiated (azo-compound
hydrochloride (APMAm) 240,
initiators) 684–685
245, 246, 284, 381, 390, 422, 424,
3-arm star polymers 191, 200, 205, 631,
434, 846
785
3-aminopropyltriethoxysilane (APTES)
724 aromatic dithioesters 37, 223, 227, 230,
4-amino-2,2,6,6-tetramethylpiperidin- 233–237, 239, 241, 278, 301, 302,
1-oxyl 724 313, see also benzyl
ammonium persulfate (APS) 506, 650, benzodithioate, benzyl
787, 907 pyridine-2-carbodithioate,
thermal initiation 911 cyanomethyl benzodithioate
redox initiation 505–506, 650, 787 4-cyano-4-((phenylcarbono-
amphiphilic block copolymers (ABCs) thioyl)thio)pentanoic acid
516, 517, 524, 530, 709–710, 712, 2-cyanopropan-2-yl
714, 735, 740, 783, 844, 851, 859, benzodithioate 2-cyanopropan-
944, 1078, 1116, 1118, 1127, 2-yl naphthalene-1-
1137, 1188 carbodithioate, dithioesters
anhydride group 842–843, 878, see also 1-phenylethyl benzodithioate
maleic anhydride, 2-phenylpropan-2-yl
N-carboxyanhydrides benzodithioate
anionic polymerization 435, 709, 755 S-aroylthiohydroxylamine 846
Index 1199
aryl(pyridin-4-yl)carbamodithioates 2,2′ -azobis(N-(2-carboxyethyl)-2-

(N-aryl-N-(pyridin-4-yl) methylpropionamidine) 684
dithiocarbamates 567 4,4′ -azobis(4-cyanopentanoic acid)
ascorbic acid (AsAc) 43, 48, 506, 512, (ACPA) 32, 36, 37, 42, 45, 308,
620–621, 624–625, 652, 689–691, 439, 579, 589, 684, 1042
695, 701, 713 ′
1,1 -azobis(1-cyclohexanenitrile)
atom-transfer radical polymerization (ACHN) 29, 39, 40, 46, 49, 52,
(ATRP) 16, 17, 61, 118, 176, 308, 309, 444
178, 296, 424, 435, 500, 552, 579, 4,4′ -azobis[2-(imidazolin-2-yl)propane]
588, 617, 656, 660, 708, 755, 815, dihydrochloride (VA-044)
905, 939, 983, 1172 684–685
ATRP inimers 296, 423, 426, 436 ′
2,2 -azobis(4-methoxy-2,4-dimethyl-
concurrent ATRP/RAFT 296, pentanenitrile) 684
657–659, 668 2,2′ -azobis(2-methylbutyronitrile)
RAFT mechanism transformation (AMBN) 579
-
(RAFT-T-ATRP) 296, 435
2,2′ -azobis[2-methyl-N-(2-hydroxy-
azide group
ethyl)propionamide] 684
azide-functional monomer 252, 253,
2,2′ -azobis(2-methylpropionitrile)
426, 649, 847, see also N-(3-
(AIBN) 195, 198, 754, 991,
azidopropyl)methacrylamide
1021
azide-functional RAFT agent 402,
dimethyl 2,2′ -azobis(2-methyl-
407, 516, 520, 757–761
propionate) (AIBMe) 88, 89,
bis-azide RAFT agent
298, 589
(bis-N3 -thiocarbonylthio
azole-N-carboxamide methacrylates 841
compound [TTC]) 634
3,5-dimethylpyrazole-N-carboxamide
carbonyl azide-functional RAFT
methacrylate 841
agent 403
imidazole-N-carboxamide methacrylate
azide installation post polymerization
408, 515, 630, 839, 847, 1019 841
azide reduction to amine 835 1,2,4-triazole-N-carboxamide
azide–thioacid reaction 835 methacrylate 841
copper-catalyzed azide–alkyne
cycloaddition 717 b
RAFT agent synthesis 504, 507 BAB triblock copolymers
Star polymers synthesis 991, 1009 using R-connected bis-RAFT agents
strain-promoted azide–alkyne 378
cycloaddition 848 balanced activity RAFT agents 2, 549,
N-(3-azidopropyl)methacrylamide 559, 582–583, 593, 1097, see also
(AzMA) 847 1H-pyrazole-1-carbodithioates
azlactone group 46, 280, 282, 398, 421, barbiturate-linked poly(n-butyl acrylate)
477, 830, 842, 859, 863 784
functional monomer, see Barton–McCombie reaction 765
2-vinyl-4,4-dimethylazlactone base catalyzed thiol-Michael reaction
functional RAFT agent 398 779
azo-compound initiators (dialkyldiazenes) benzil dimethyl ketal (Irgacure 651) 779
1200 Index
benzodithioates, see dithiobenzoates, benzyl pyridine-2-carbodithioate (BPCD)

dithioesters 250, 769, 770
5,6-benzo-2-methylene-1,3-dioxepane benzyl 1H-pyrrole-1-carbodithioate 48,
(BMDO) 287, 289, 428, 429, 557, 894
503, 513, 514, 725, 1128 crosslinking polymerization 894
ring-opening copolymerization- experimental procedure
induced self-assembly N-vinylphthalimide solution
(rROPISA) 725 polymerization 48
benzothioic S-acid 788–789 3-(((benzylthio)carbonothioyl)thio)
benzoyloxy radicals 648–649 propanoic acid (BCPA)
benzoyl peroxide (BPO, dibenzoyl [3-(benzylsulfanylthiocarbonyl-
peroxide) 648, 911 sulfanyl)propionic acid] 392,
benzoyl peroxide/N,N-dimethylaniline 832
redox system 648 bioapplications of RAFT
BPO/amine redox system 648 antimicrobial polymers 630–633, 1065
in eRAFT 671 bioconjugate synthesis 858
in RAFT end-group removal 444, 446, cosmetic applications 1119, 1120,
765 1137
benzyl benzodithioate (benzyl drug delivery 4, 718, 851–855
dithiobenzoate) 249, 888 high throughput library synthesis
application scope 888 629–633, 1059–1064
experimental procedure ophthalmic applications (contact lens)
styrene polymerization in emulsion 1137
36 patents 1, 298, 299, 436, 740, 1090,
benzyl (diethoxyphosphoryl) 1137
methanedithioate (DEPMD) therapeutic applications 1003, 1004
769–770 bioconjugation 525, 855–859, 1027–1030
benzyl dithioacetate, see benzyl 2,2′ -bipyridine (bpy), see copper activators
ethanedithioate biotin 691, 789, 790
benzyl ethanedithioate (benzyl bis(2-acrylamido)ethyl disulfide (disulfide
dithioacetate) 261 diacrylamide, DSDAm) 290,
in emulsion polymerization 104 401, 429
′
O-benzylhydroxylamine 846 N,N -bis(acryloyl)cystamine 429, 996,
benzyl (2-hydroxyethyl) carbonotrithioate 997
[2-(benzylsulfanylthiocarbonyl- bis(2-acryloyloxy)ethyl disulfide (disulfide
sulfanyl)ethanol (BTSE)] 832 diacrylate, DSDA) 290, 383,
-
ROP-T-RAFT initiator 396 401, 429
benzyl mercaptan 760, 761 bis-azide RAFT agent (bis-N3 -thiocarbon-
benzyl methacrylate ylthio compound [TTC]) 634
experimental procedures (3,5-bis((6-butyramidopyridin-2-yl)
benzyl methacrylate in solution 41 carbamoyl)phenoxy)methyl
poly(benzyl methacrylate)-block-poly 2-bromopropanoate 785
(N-(2-hydroxypropyl)methacryl- S,S -bis(α,α′ -dimethyl-α′′ -acetic
′
amide) in solution 53 acid)-trithiocarbonate), see

Index 1201
2,2′ -(thiocarbonylbis(sulfan- xanthates 509–521

ediyl))bis(2-methylpropanoic BOC protecting group, see
acid) t-butyloxycarbonyl protecting
bismaleimide linker 947 group
bis-maleimidodiethyleneglycol 780 bond dissociation energy (BDE) 143, 615
bis(2-methacryloyloxy)ethyl disulfide carbon–halogen in ATRP initiator 656
(disulfide dimethacrylate, carbon–oxygen in alkoxyamine 1172
DSDMA) 287, 290, 718, 719, carbon–sulfur in RAFT agent 550,
887 615, 618, 688
bis-RAFT agents 235, 257, 259, 262, 378, boronic acid/diol condensation 849
879, 1123 bottlebrush polymers 434, 590, 957–961,
bis-aliphatic dithioesters 237 963, 964
bis-aromatic dithioesters 235–236 branched wormlike micelles 697
bis-trithiocarbonates 370–378 4-bromobenzenediazonium
disulfide functional 718 tetrafluoroborate (BrPhN2 + )
R-connected 235–236, 376, 378 670–672
triblock copolymer synthesis, see ABA bromoethyl acrylate (BEA) 840
triblocks, BAB triblocks N-[2-(4-bromophenyl)ethyl]acrylamide
Z-connected 235–236, 370, 375 (BPEAm) 848
bis(thioacyl) disulfides 238, 408, 2-bromopropanoate 783
578–579, 1089, 1090, 1097 brush polymers 1020–1027, see also graft
thiuram disulfides 551, 578–580, 590, polymers
768 bimodal molar mass 311, 443
xanthogen disulfides 500, 1092 block copolymer 1020, 1023
block copolymers, see also ABA triblock Janus 1020, 1022–1024
copolymers, ABC triblock looped 1020, 1022
copolymers, BAB triblock mixed composition (mikto-arm) 1020
copolymers, diblock copolymers, patchy 1020, 1022
multiblock copolymers, buffer
quasi-block copolymers acetate buffer 45
aliphatic dithioesters 236–237 phosphate buffered saline (PBS)
aromatic dithioesters 233–235 691–693, 695
cationic RAFT polymerization butadiene (Bd)
1171–1190 blocks 530
dithiocarbamates 556–572, 582–585 copolymers
DNA conjugates 701 butadiene–styrene 530
experimental procedures 51–53 acrylonitrile/butadiene 209
flow chemistry 636 with dithioesters 313
functional dithioesters 233, 251–257 homopolymer 278, 425
mechanistic considerations 95–132 with trithiocarbonates 374, 382, 383,
protein conjugates 701 390, 391, 425
redox initiation 648–656 S-(2-((t-butoxycarbonyl)amino)ethyl)
switchable RAFT agents 116–118, methanesulfonothioate 790
583–585 thiol–methanethiosulfonate reaction
trithiocarbonates 380–407 789
1202 Index
N-t-butylacrylamide (tBAM) 517 c

butyl acrylate (BA, n-butyl acrylate) 39, carbonotrithioates, see trithiocarbonates
41–43, 51, 62, 63, 68, 85, 90, 193, 4-(((2-carboxyethyl)thio)carbonothioyl)
234, 367, 368, 424, 503, 550, 554, thio)-4-cyanopentanoic acid
572, 589, 616, 657, 666, 672, 759, 818–820
765, 772, 773, 777, 778, 780, 784, application scope 27, 383
785, 810, 844, 845, 986, 996, industrial use 30
1009, 1106 3-((((1-carboxyethyl)thio)carbonothioyl)
t-butyl acrylate (tBA) 39, 43, 424, 589, thio)propanoic acid 27, 389,
615, 672, 777, 778, 780, 810, 845, 423
986, 1009 application scope 27, 389
butyl (1-(((3,5-dioxo-1,2,4-triazolidin-4-yl) 2-(1-carboxyl-1-methylethylsulfanyl-
hexyl)amino)-1-oxopropan-2-yl) thiocarbonylsulfanyl)-2-methyl-
carbonotrithioate (URZ-TTC) propionic acid (CMP), see
772 2,2′ -(thiocarbonylbis(sulfane-
butyl 2-(((dodecylthio)carbonothioyl) diyl))bis(2-methylpropanoic
thio)-2-methylpropanoate (CTA acid)
ester) 387, 1098 2-carboxyprop-2-yl radicals 369
t-butyl hydroperoxide 48, 652 catalytic chain transfer (CCT) 793, 936,
butyl methacrylate (n-butyl methacrylate) 1077–1078, 1082, 1083
38, 409, 555, 668, 727, 857, cationic RAFT polymerization
1056 1173–1175
t-butyloxycarbonyl (BOC) primary amine block copolymers 1185–1188
protecting group design 1175–1184
in monomer 129, 280, 837, 838, see end-functionalized polymers
also di(BOC)-acrylamide 1184–1185
in RAFT agent 280, 1101 initiators 1179–1182
in reagent 280, see also monomers 1182–1184
S-(2-((t-butoxycarbonyl) RAFT agents 1175–1179
amino)ethyl) methanesulfonoth- RAFT mechanism transformation
ioate -
(cationic-T-RAFT) 435,
2-(((butylthio)carbonothioyl)thio) 1187–1190
propanoic acid (BTPA, BuPAT) star polymers 1189–1190
390, 686 chain length distribution (CLD) 66, 98,
aqueous RAFT (aRAFT) 686, 690, 199, 552, 906
701 chain transfer coefficient (Ctr ) 96–103,
functional derivatives 226–230, 362
ATRP initiator 405 apparent chain transfer coefficient
t-butyldimethsilyl 406 (Ctr app )
poly(dimethylsiloxane) dithiocarbamates 552–554, 580
(PDMS) 407 dithioesters 101, 228–229
protected maleimide 435 trithiocarbonates 363–365
photoinduced energy or electron xanthates 507–508
transfer (PET-RAFT) 1055 measurement of 97–103
Index 1203
dispersity method 102, 227, 230, co-mediated radical polymerization 708

363–365 composites 1030–1039
kinetic simulation 103, 228–229, anisotropic structures 1031, 1039
363–365 SI-RAFT 1030–1039
ln(CLD) method 97–98 computational chemistry 139, 152, 153,
Mayo method 97–98, 100, 228–229, 156, 159, 165, 167, 172, 180
363–365, 552–554 Concanavalin A (ConA) 630, 857
M n (0) method 228–229, 363–365 confocal laser scanning microscopy
Walling method 98–100, 228–229, (CLSM) 1025
363–365, 552–554 continuum models 147
reverse chain transfer coefficient (C-tr ) controlled/living polymerization, see
97, 226–230 reversible deactivation
chain transfer rate coefficient (ktr ) 96, polymerization
125, 226–230, 362 controlled radical polymerization (CRP)
apparent chain transfer rate coefficient 15, 60, 176, 614, 625–626, 630,
(ktr app ) 167 695–696, 786, 861, 964, 983,
reverse chain transfer rate coefficient
1042, see also reversible
(k-tr ) 97, 226–230
deactivation radical
measurement of 97–103
polymerization
chain transfer agent (CTA), see RAFT
copolymerization 48, 753–755
agent
branched copolymerization 209
chemoselective H2 S-responsive
of multifunctional monomer 966–967
fluorescence probe 789
copolymers 755, see also block
2-chloroethyl vinyl ether (CEVE) 1183
copolymers, gradient
4-chloromethylstyrene (4-vinylbenzyl
copolymers
chloride) 241, 248, 259, 275,
desulfurization of RAFT (co)polymers
374, 381, 383, 386, 387, 390, 391,
763–769
401, 425, 508, 557, 559, 572, 839,
copper activators, see also ligands
848, 859, 1004, 1009
with dithiocarbamates 557, 559, 572 in alkoxyamine synthesis
with dithioesters 241, 248, 259, 275 CuX/Me6 TREN 515
with trithiocarbonates 374, 381, 383, in alkyne-azide coupling
386, 387, 390, 391, 401, 425 CuX/PMDETA 759, 1024
with xanthates 494, 501, 508 in concurrent RAFT/ATRP
chloroprene 242, 247, 250, 260, 393, 425, CuX/dNbpy 657
1034 CuX/Me6 TREN 657
SI-RAFT 1034 CuX/PMDETA 657
chlorophyll a (Chl a) 619–620 CuX/TPMA 657
cholest-5-en-3β-yl 6-iodohexyl ether 783 in radical generation
classically hyperbranched polymers 967 CuX/Me6 TREN 120, 515
click chemistry approach 515, 520, 523, in redox RAFT
649, 755, 757, 806, 847, 944–947, CuII (DC)2 /bpy 668
949, 960, 991, 992 CuX/Me6 TREN 658
CMP-functionalized ssDNA 701 CuX/PMDETA 300, 656–658, 669
comb polymers 280, 426, 956 CuX/TPMA 658–659, 669–670
1204 Index
copper catalyzed azide-alkyne 2-cyanobutan-2-yl 3,5-dimethyl-1H-

cycloaddition (CuAAC) 521, pyrazole-1-carbodithioate 28,
717, 847, 857, 945, 955, 30, 119, 560, 579, 582–583
1023 application scope 28, 560, 582–583
copper-mediated polymerization 708 chain transfer coefficient 583
core-crosslinked stars (CCS) 292, 430, industrial use 30, 560, 1099
874, 918, 994, 996, 998, synthesis of 579
1006–1007 4-cyano-4-(((dodecylthio)carbonothioyl)
core-crosslinked nanoparticles 718, thio)pentanoic acid 27, 31, 39,
722–725 46, 49, 131, 382, 438–439, 612,
degradable core 725 614–615, 627–628, 819, 898,
thiol-functional vesicles 718 902–903, 913, 1137
coumarin chromophore 277, 613, 629, application scope 27, 382
691, 807 deoxygenation methods 31
acceptor in light-harvesting polymers experimental procedure
242, 277, 807 N-isopropylacrylamide in solution
46
dye 613, 629
methyl methacrylate in solution 39
in photoresponsive methacrylamide
poly[(methacrylic acid)-co-(oleyl
691
methacrylate)] in solution 49
in styrenic monomer 241, 247, 277
industrial use 30, 1097, 1099
cross-coupling reactions 311, 591,
PET-RAFT 131, 614–615, 627–628
848–849
side reactions 438–439
crosslink density distribution 873, 876
4-cyano-4-(((ethylthio)carbonothioyl)
crosslinked polymers 873, 910
thio)pentanoic acid 381,
crosslinking monomers, see divinyl
438–439, 681, 693, 695
monomers
application scope 381
cumene hydroperoxide (CHP) 43, 652
cumene hydroperoxide-ascorbic acid
4-cyano-4-(((propylthio)carbonothioyl)
redox system 648, 652 thio)pentanoic acid 382, 693
cumyl dithiobenzoate (CDB), see application scope 382
2-phenylpropan-2-yl 2-cyano-5-hydroxypentan-2-yl
benzodithioate benzodithioate (CHPB) 251,
cumyl phenyldithioacetate (CPDA), see 757
2-phenylpropan-2-yl cyanoisopropyl decyl trithiocarbonate, see
2-phenylethanedithioate 2-cyanopropan-2-yl decyl
curve-crossing model 167, 169–170 carbonotrithioate
cyanoalkyl RAFT agents 105, 108, 110, cyanoisopropyl dithiobenzoate, see
130, 175, 233–236, 368–369 2-cyanopropan-2-yl
2-cyanobutan-2-yl 4-chloro-3,5-dimethyl- benzodithioate
1H-pyrazole-1-carbodithioate cyanoisopropyl 1-dithionapthalate, see
28, 30, 40 2-cyanopropan-2-yl
application scope 28, 560, 582–583 naphthalene-1-carbodithioate
industrial use 30, 560, 1096 cyanoisopropyl N,N-diethyldithio-
synthesis of 579 carbamate, see
Index 1205
2-cyanopropan-2-yl polymerizations 47, 569–570

diethylcarbamodithioate experimental procedure
cyanoisopropyl dodecyl trithiocarbonate, N-vinylcarbazole in solution 47
see 2-cyanopropan-2-yl dodecyl synthesis 580
carbonotrithioate 4-cyanopentanoic acid dithiobenzoate, see
cyanoisopropyl methyl trithiocarbonate, 4-cyano-4-((phenylcarbono-
see 2-cyanopropan-2-yl methyl thioyl)thio)pentanoic acid
carbonotrithioate 4-cyano-4-((phenylcarbonothioyl)thio)
cyanoisopropyl radicals, see pentanoic acid (4-cyano-
2-cyanopropan-2-yl radicals pentanoic acid dithiobenzoate)
(NIPAM) 35, 45, 228, 244–245, 294, 299,
cyanomethyl benzodithioate 250 309, 614, 627, 628, 662, 671,
polymerizations 250 679–681, 683, 701, 757, 832, 838,
cyanomethyl 3,5-dimethyl-1H-pyrazole- 915, 1099
1-carbodithioate 9, 27, 30, 40, chain transfer coefficient 228
eRAFT 662–664, 667, 672
46, 49, 52, 119, 583
experimental procedures
application scope 27, 582–583
N-(2-hydroxylpropyl)methacrylamide
chain transfer coefficient 583
in pH 5.2 buffer 45
N-[3-aminopropyl] methacrylamide
N,N-dimethylacrylamide in solution
in pH5 buffer 45
46
functional derivatives 251–252
methyl acrylate in solution 40
active ester 252
poly[(methyl acrylate)-co-N,N-dimethy-
azide 252
lacrylamide] in solution 49
dibromomaleimide 254
poly(N,N-dimethylacrylamide)-block-
ene 254
poly(vinyl acetate) in solution
hydroxyl 251
52
NHS ester 251, 831
industrial use 30
norbornene 254
polymerizations 40, 46, 49, 52, 119, protected maleimide 254–255
560 poly(dimethylsiloxane) (PDMS)
cyanomethyl dodecyl carbonotrithioate 255–256
391, 426 poly(ethylene glycol) (PEG) 256
polymerizations 391 thiolactone 254
cyanomethyl methyl(phenyl) carbamodi- yne 253–254
thioate (N-methyl-N-phenyl- industrial use 1097, 1099
dithiocarbamare) 28, 30, 149, PET-RAFT 294, 300
179 polymerizations 45, 244–245
application scope 28 SUMI 294
industrial use 29–30 2-cyanopropan-2-yl radicals
polymerizations 564 (cyanoisopropyl radicals) 107,
cyanomethyl methyl(pyridin-4-yl)car- 440, 766–767, 810
bamodithioate 30, 47, rate coefficient for monomer addition
569–570 107
1206 Index
2-cyanopropan-2-yl benzodithioate (cyanoisopropyl methyl

(cyanoisopropyl dithiobenzoate) trithiocarbonate) 380, 764
2, 27, 30, 33, 40–41, 46, 49, 51, application scope 380
67–69, 108, 109, 111, 122, 124, 2-cyanopropan-2-yl naphthalene-1-
149, 151, 161, 164–166, 211, 242, carbodithioate (cyanoisopropyl
662, 754, 779, 909–910 1-dithionapthalate) 211, 246,
application scope 27, 242 616
chain transfer coefficient 228, 230 application scope 247
eRAFT 662 mathematical modeling 211
experimental procedures 2-cyanopropan-2-yl 1H-pyrrole-1-
butyl acrylate polymerization in carbodithioate 194, 557, 579
solution 41 application scope 557
methyl methacrylate polymerization mathematical modeling 194, 208
in solution 40–41 synthesis of 579
poly(methyl methacrylate-co- cyclic ketene acetals 510, 513–514, 531,
trimethylsilyl methacrylate- 725, see also 5,6-benzo-2-methyl-
co-t-butyl dimethylsilyloxy- ene-1,3-dioxepane (BMDO)
2-methylene-4-phenyl-1,3-
styrene) in solution 49
dioxolane
industrial use 30, 1097, 1099
cyclic polymers 5, 515, 519–520, 761,
initialization 67–69, 151
780, 785, 787, 949–950
RAFT equilibrium coefficient 124,
polystyrene 761, 781
232
cyclic N-vinylamides, see
2-cyanopropan-2-yl diethylcarbamodi-
B-vinylcaprolactam,
thioate (cyanoisopropyl
N-vinyl-2-piperidone,
N,N-diethyldithiocarbamate)
N-vinylpyrrolidone
564, 668
[4+2] cycloaddition reaction 769
application scope 564
β-cyclodextrin (β-CD) 719, 731, 737,
eRAFT 668
950–951, 985, 991, 993, 1009
2-cyanopropan-2-yl decyl
cyclohexylamine 773–774
carbonotrithioate cyclopentadiene 769
(cyanoisopropyl decyl cyclopolymerization 5, 280, 288,
trithiocarbonate) 810 426–428, 514
2-cyanopropan-2-yl dodecyl cysteine (Cys) 303, 306, 700, 720, 789,
carbonotrithioate 1027
(cyanoisopropyl dodecyl
trithiocarbonate) 30, 165, 198, d
201, 364–367, 380–381, 427, 430, degassing, see deoxygenation
810, 813, 908, 913, 1097, 1099 density functional theory (DFT)
application scope 368–369 140–142, 144, 157, 174, 512, 519,
chain transfer coefficient 364–365 660, 664
industrial use 1097, 1099 deoxygenation in RAFT polymerization
RAFT equilibrium coefficient 366 (degassing) 31, 34, 40–42,
2-cyanopropan-2-yl methyl 46–53, 439, 611, 619, 654–656,
carbonotrithioate 691–696, 1052–1053, 1058, 1067
Index 1207
enzyme-catalyzed deoxygenation octadecyl acrylate in solution 42

654–656, 691–696, 1057–1058 industrial use 27, 1098, 1137
with enzyme-mediated initiation Blocbuilder DBTM 1098
654–656, 693–696 RAFT crosslinking polymerization
with thermal initiation 691–693 886
experimental procedures 34–37, RAFT equilibrium coefficients 366
39–43, 46–53 dibenzyl trithiocarbonate, see dibenzyl
in high throughput experiments 630, carbonotrithioate
1052–1053, 1059, 1067 diblock copolymer 510, 513, 516–517,
kinetics of MMA polymerization 31 519, 679, 696–699, 709, 715, 718,
in PET-RAFT 439, 611, 619, 630, 720, 727–729, 732, 734–737, 740,
690–691, 1058 770, 787, 807, 860, 936, 938, 940,
deoxygenation in RAFT end-group 945, 955, 968, 1042, 1056–1058,
removal 773 1187
desulfurization of RAFT polymers mechanistic consideration 103–105
addition-fragmentation coupling di(BOC)-acrylamide (DBAm) 838
766–768 3,5-dibromobenzyl acrylate 42
radical-induced oxidation 768–769 dibromotrithiocarbonate [DiBrTTCm, bis
radical-mediated reduction 765–766 (5-bromo-5-methyl-4-oxohexyl)
thermolysis 763–764 2,2′ -(thiocarbonylbis(sulfane-
DET-RAFT polymerization 660 diyl))bis(2-methylpropanoate)]
diacetone acrylamide (DAAm, ATRP initiator 657
N-(1,1-dimethyl-3-oxobutyl) N,N′ -dicyclohexylcarbodiimide (DCC)
acrylamide) 44, 424, 716, 719, 37, 238, 239, 878
724, 725, 730, 734 Diels-Alder [2+4] cycloaddition 845
dialkyldiazene initiators, see diene monomers, see also butadiene,
azo-compound initiators chloroprene, isoprene
N,N-dialkyldithiocarbamates 114, 116, with dithioesters 278–279
550, 551, 581, 586, 588, 590 with trithiocarbonates 425
p-dialkylsulfonium phenoxy ester (diethoxyphosphoryl)methanedithioates
(DASPE) 837–838 769, 770, 1089, 1090, 1110, see
4-acryloxyphenyldimethylsulfonium also benzyl (diethoxyphospho-
triflate 837 ryl)methanedithioate
dibenzoyl peroxide, see benzoyl peroxide N,N-diethylacrylamide (DEAm) 46, 696,
(BPO) 781–783, 831, 832, 1058
dibenzyl carbonotrithioate (DBTTC, experimental procedures
dibenzyl trithiocarbonate) 27, N,N-diethylacrylamide is solution 46
42, 111, 374, 376–377, 427, 886, with dithioesters 242, 246, 249, 250,
1098, 1126 260, 273, 305
application scope 27, 374 with trithiocarbonates 385, 390–392,
chain transfer coefficients 364–365 403, 424
experimental procedures 4-(diethylamino)salicylaldehyde (DEAS)
3,5-dibromobenzyl acrylate in 649
solution 42 diethylene glycol acrylate (DEGDA) 385,
2-ethylhexyl acrylate in solution 42 392
1208 Index
diethylene glycol dimethacrylate N-(1,1-dimethyl-3-oxobutyl)acrylamide,

(DEGDMA) 288, 382, 383, 430, see diacetone acrylamide
882, 883 4,4′ -dinonyl-2,2′ -bipyridine (dNbpy), see
(diethylene glycol monomethyl ether) copper activators
acrylate (DEGA) 761–762 2,5-dioxopyrrolidin-1-yl 4-vinylbenzoate
(diethylene glycol monomethyl ether) (4-vinylbenzoic acid, NHS ester)
methacrylate (DEGMA) 287, 246, 389, 830–832
761–762, 913, 1057 diphenylacetylene 661
α,ω-difunctional polymer 789 α,ω-dipyrenyl poly(N-isopropyl-
difunctional CTAs, see bis-RAFT agents acrylamide) 783
2,3-dihydroxypropyl methacrylate, see 2,2′ -dipyridyl disulfide 788–789, 968
glycerol monomethacrylate discrete oligomers 813, 818, 823
2-(diisopropylamino)ethyl methacrylate oligo(methyl acrylate) 823
(DPAEMA) 683 diselenocarbonyl compounds 786
N,N-dimethylacrylamide (DMAm) 46, dispersion polymerization 38, 187, 195,
49, 52, 117, 118, 273, 287, 295, 211, 437–439, 650, 686, 691,
305, 509, 516, 519, 520, 572, 583, 696–699, 709–713, 718–721,
723–732, 734, 736, 898, 900–901,
587, 590, 618, 652, 654–656, 684,
996, 998–999, 1006
686, 689–691, 693–696, 701, 772,
dispersity 28, 33, 37–39, 88, 102–105,
780, 791, 792, 818, 820, 849, 903,
123, 124, 206, 227, 230, 363, 427,
1027, 1053, 1057, 1063
511, 513, 530, 626, 654, 805–806,
823, 831, 834–835, 953, 967, 1041
N,N-dimethylacrylamide in solution
dissociative electron transfer (DET)-RAFT
46
179, 300, 437, 660
poly(N,N-dimethylacrylamide)-block-
disulfide group
polystyrene by surfactant-free
bis-RAFT agents
emulsion polymerization
bis-dithiobenzoate (DSDB) 718, 719
36–37
monomers, see bis(2-methacryloyl)
propagating radical 766 oxyethyl disulfide
selective initialization 108 disulfide diacrylamide (DSDAm), see
single unit monomer insertion (SUMI) bis(2-acrylamido)ethyl disulfide
108 disulfide diacrylate (DSDA), see
with dithioesters 234, 241, 243, bis(2-acryloyloxy)ethyl disulfide
245–251, 253, 256, 259, 260, 273, disulfide dimethacrylate (DSDMA),
288, 295, 305 see bis(2-methacryloyloxy)ethyl
with trithiocarbonates 107, 817 disulfide
2-(dimethylamino)ethyl methacrylate RAFT agents 399
(DMAEMA) 240, 409, 555, RAFT inimers 292, 296
615, 632, 696, 698, 716, 720, 857, reactions 787–790
1003, 1060, 1064 reagents, see S-(2-((t-butoxycarbonyl)
block 857 amino)ethyl)
4-dimethylaminopyridine (DMAP) 37, methanesulfonothioate,
878 bis(thioacyl) disulfide
dimethyl(phenyl)phosphine 779 2,2′ -dipyridyl disulfide
Index 1209
dithiobenzoates (benzodithioates) 59, by reaction with nucleophiles

76–89, 187, 223, 659–664, 753, 589–590
759, 764, 767, 781, 808, 830, 935, by thermolysis 590–591
see also dithioesters monomers 555–575
kinetic analysis 85–87 1,1-disubstituted MAMs 557
macroRAFT agent 807, 808 methacrylates 557
MMA model system 88–89 LAMs, IAMs 550, 572, 576
quantum-chemical calculations 87–88 vinyl monomers 552, 576
retardation mechanisms monosubstituted MAMs 572–575
intermediate radical termination acrylamides 572, 573
77, 119–123 acrylates 572, 574
missing step reaction 77–85, 88–90, styrenes 572, 575
121 RAFT mechanism transformation
slow fragmentation 59, 76, 77, 85, 587–588
86, 123–126 -
RAFT-T-ATRP 588
dithiocarbamates 112, 114, 662, 668, -
RAFT-T-ROMP 587–588
753, 759, 830, 936, 1177, see also -
ROP-T-RAFT 587
N,N-dialkyldithiocarbamates, -
ROMP-T-RAFT 587–588
aryl(pyridin-4-yl)carbamodi- selection of 552, 577, 582, 593
thioates 1H-imidazole-1-carbod- R substituent 585
ithioates 1H-pyrazole-1-carbod- switchable dithiocarbamates 30, 47,
ithioates, cyanomethyl methyl 51–52, 116–118, 583–585, see
(phenyl)carbamodithioate, also methyl(pyridin-4-yl)
methyl(pyridin-4-yl)carbamodi- carbamodithioates
thioates 1H-pyrrole-1- synthesis of dithiocarbamates
carbodithioates 575–580
activity of 580–586 dithiocarbonates, see xanthates
application scope 555–575 dithioesters (dithioates) 223–313, 753,
balanced activity 549, 559–563, 759, see also benzyl
582–583, 593, see also benzodithioate, benzyl
1H-pyrazole-1-carbodithioates (diethoxyphosphoryl)
canonical forms 114, 582 methanedithioate, benzyl
cationic polymerization 585 pyridine-2-carbodithioate,
chain transfer coefficients 553–554, cyanomethyl benzodithioate
580–586 4-cyano-4-((phenylcarbono-
emulsion polymerization 587–588 thioyl)thio)pentanoic acid
dithiocarbamate group removal/ 2-cyanopropan-2-yl
transformation 588–591 benzodithioate
by copper-promoted cross-coupling 2-cyanopropan-2-yl
591 naphthalene-1-carbodithioate,
by oxidation 591 dithiobenzoates 2-((phenyl-
by radical-induced coupling 588 carbonothioyl)thio)acetic acid
by radical-induced 1-phenylethyl benzodithioate
disproportionation 588–589 2-phenylpropan-2-yl
by radical-induced reduction 589 benzodithioate
1210 Index
dithioesters (dithioates) (contd.) monosubstituted MAMs

2-phenylpropan-2-yl acrylamides 273, 276
2-phenylethanedithioate acrylates 240, 277, 281
application scope 234 acrylonitrile 112, 234, 242, 244,
aliphatic dithioesters 236–237, 245, 247
260–261 diene 278–279
aromatic dithioesters 235–236, styrenics 277–278, 280
241–259 dithioesters with reactive
bis-aliphatic dithioesters 237, 262 functionality 279–285
atom-transfer radical polymerization publication statistics 224, 233, 236
296 RAFT agent selection 230–237
bis-aromatic dithioesters 235, 257–259 RAFT mechanism transformation 295
crosslinking polymerization 288, -
cationic-T-RAFT 1187–1190
290–291 nitroxide-mediated polymerization
model co-networks 291 (NMP) 297
cyclopolymerization 287, 288 ring-opening polymerization (ROP)
dithioester group removal/ 295–296
transformation 302–313 ring-opening metathesis
boronic acid cross-coupling 311 polymerization (ROMP) 296
electrocyclic reaction 310–311 RAFT-SUMI 292–295
oxidation 306
ring-opening polymerization 287,
radical-induced coupling 303, 306
295–296
radical-induced reactions 303–311
self-condensing vinyl polymerization
radical-induced reduction 306
292–294
reaction with nucleophiles 302–303
side reactions 126–130, 313
thermolysis 309–310
with reactive functionality 279–285
α,ω-dithiol functional polystyrene 787
synthesis of 237–239
emulsion/miniemulsion
1,4-dithiothreitol 304–305, 724
polymerization 301–302
divinyl monomers, (crosslinking
industrial use 1098–1099, 1137
monomers) 288, 290, 428–430,
initiation, see also redox initiation
photoinitiation 299–300 906–907, 910, 911, 966, see also
thermal initiation 298–299 bis(2-acrylamido)ethyl disulfide
inimers 292–294 (DSDAm), N,N ′ -bis(acryloyl)
chain transfer coefficients 226–230 cystamine, bis(2-acryloyloxy)
equilibrium coefficients 230–232 ethyl disulfide (DSDA),
mechanism 224–232 bis-maleimidotriethylene glycol,
monomers bis(2-methacryloyloxy)ethyl
1,1-disubsituted MAMs 239–240 disulfide (DSDMA), ethylene
methacrylamides 240, 272–273 glycol dimethacrylate
methacrylates 239–240, 263–271 (EGDMA), diethylene glycol
1,2-disubsituted MAMs 279 diacrylate (DEGDA), diethylene
macromonomers 280–287 glycol dimethacrylate
monosubstituted LAMs and IAMs (DEGDMA), divinylbenzene,
279 methylene-bis-acrylamide
Index 1211
(MBAm), triethylene glycol drug delivery 4, 718, 738–739, 851–855,

dimethacrylate (TEGDMA) 1003, 1004, 1029, 1056,
crosslinking monomers 288, 290, 1059–1064
428–430 dual concurrent electrochemically
crosslinking polymerization mediated ATRP/RAFT 669
polymer networks 288, 428–430, dual-responsive PNIPAM-b-PAA
873–918 copolymer 853
star microgels 288, 428–430 dynamic polymeric nanoobjects 1041
divinylbenzene (DVB) 241, 250, 256,
258, 288, , 381, 385, 386, 391, e
395–397, 430, 709, 723, 885, 887, electrochemically-initiated RAFT
892, 900, 906, 911, 913–915, 918, polymerization (eRAFT)
967 299–300, 436–437, 660–673
with dithioesters 241, 250, 256, 261, ATRP initiation 668–670
288 direct eRAFT 665–667
initiator reduction 670–673
PISA 709, 723
benzoyl peroxide 670–671
with trithiocarbonates 381, 385, 386,
diazonium salt 671–672
391, 395–397, 430
monomers
1-dodecanthiol (DDT) 760, 791, 966
butyl acrylate 666, 667
2-(dodecylthiocarbonothioylthio)-2-methyl-
butyl methacrylate 666, 668
propionic acid (DDMAT) 37,
ferrocenyl methacrylate 673
385–387, 417, 424, 614–615,
methyl methacrylate 666, 669–671
662–664, 668–672, 834, 837, 898,
styrene 666–668
1098, 1132
organic mediators 667–668
application scope 385–387
RAFT agents 661–665
4-cyano-4-((phenylcarbonothioyl)
acrylic acid in solution 41
thio)pentanoic acid 662–664,
t-butyl acrylate in solution 41 667, 672
styrene surfactant-free in emulsion 2-cyanopropan-2-yl benzodithioate
37 (cyanoisopropyl dithiobenzoate)
industrial use 1098, 1137 662
maleimido ethoxyethyl ester 403, 700 2-cyanopropan-2-yl diethylcarbamo-
photoinitiated RAFT 614–615 dithioate (cyanoisopropyl
redox initiated RAFT 662–664, N,N-diethyldithiocarbamate)
668–672 668
2-(((dodecylthio)carbonothioyl)thio) dithiobenzoates 313, 661–665, 667,
propanoic acid (DoPAT) 27, 672
30, 209, 390, 1034, 1035 reduction potential 661
application scope 27, 390 trithiocarbonates 436–437
industrial use 30, 1098, 1137 surface initiated (SI-eRAFT) 672
SI-RAFT 1034, 1035 electron affinity (EA) 176
dodecyl vinyl ether 775 electron paramagnetic resonance (EPR)
doxorubicin (DOX) 853, 855, 1004, 1029, 59–65, 70–76, 81, 86–87, 89–91,
1041 103, 124, 149, 204, 367
1212 Index
emulsion polymerization 34–37, 42, 195, glucose oxidase (GOx) 654, 696
301, 302, 437–438, 587, 710, horseradish peroxidase (HRP)
1078–1080, 1091, 1093–1095, 693–695
1097, 1101, 1105–1111, 1113, enzyme catalyzed deoxygenation
1122, 1127, 1132–1133, 1137, see enzymatic initiation systems 693–696
also polymerization-induced initiation by thermal initiation
self-assembly (PISA) 691–693
amphiphilic macroRAFT agents enzyme-responsive inimer 966
36–37, 42, 48, 1080, 1094, 1097, Eosin Y (EY) 300, 612, 623, 624, 630,
1109–1110 635, 689, 690, 1027
with dithiocarbamates 587 epoxide group 783, 843–844
with dithioesters 301–302 epoxy-functional monomer, see glycidyl
experimental procedures methacrylate
butyl acrylate 42 eRAFT, see electrochemically-initiated
styrene 36–37 RAFT polymerization
with macromonomer RAFT agents ester-end-functionalized polymer 783
1078–1079 2-ethanolamine 779
mathematical modeling 2-((ethoxycarbonothioyl)thio)acetic acid
deterministic modelling 195, 209 (ethylxanthogenacetic acid)
stochastic modelling 205–206 48, 495, 510, 514
patents 1078–1080, 1091, 1093–1095, application scope 495
1097, 1101, 1105–1111, 1113, experimental procedure
1122, 1127, 1132–1133, 1137 vinyl acetate polymerization in
sulfur-free emulsion polymerization solution 48
1078–1079 1-(ethoxycarbonyl)prop-1-yl
surfactant-free emulsion dithiobenzoate (EPDTB) 836
polymerization 36–37, 42, 48, 1-ethoxyethyl acrylate 759–760
1080, 1097, 1098 2-ethoxyethyl vinyl ether (EOEVE)
with trithiocarbonates 409 1183, 1187
with xanthates 505–507, 510, 513 ethyl α-bromoisobutyrate (EBiB, ethyl
enaminones 846 2-bromo-2-methylpropanoate)
end-functionalized polymers 807, 659, 669, 670
1184–1185 ethylene glycol diacrylate (EGDA) 288,
α-end-functionalized poly(n-butyl 494, 501, 996, 999
acrylate) 772–773 ethylene glycol dimethacrylate (EGDMA)
α,ω-end-functionalized poly(N-isopropy- 198, 241, 243, 288, 291, 381, 386,
lacrylamide) 761 391, 400, 430, 884, 886, 889,
end-group fidelity, see livingness 899–901, 906, 908, 912–913, 915,
end-group removal, see RAFT end-group 966
removal 2-ethylhexyl acrylate (EHA) 39, 42, 424,
Energy-Directed Tree Search 145, 152 810
enhanced green fluorescent protein N-ethylpiperidine hypophosphite (EPHP)
(EGFP) 855, 857 443, 529, 765, 766
enzymatic initiation systems 654–656, S-ethyl-S’-(α,α′ -dimethyl-α′′ -acetic acid)
693–696 trithiocarbonate, see
Index 1213
2-(((ethylthio)carbonothioyl) folic acid tethered polymer-modified

thio)-2-methylpropanoic acid magnetic nanoparticles
O-ethyl-S-(1-methoxycarbonylethyl) (FA-MNPs) 855
dithiocarbonate, see methyl 2-(4-formylbenzoyloxy)ethyl methacrylate
2-((ethoxycarbonothioyl)thio) (FBEMA) 846
propanoate 3-formyl-4-hydroxybenzyl methacrylate
ethyl 2-((phenoxycarbonothioyl) (FHMA) 725
thio)propanoate 616 fragmentation rate coefficient, see rate
ethyl 2-(((propylthio)carbonothioyl)thio) coefficients
propanoate (S’-(1-ethoxycarbon- α,ω-functionalized
ylethyl) S-propyl trithiocarbon- poly(N-isopropylacrylamide)
ate) 72–76, 366, 367, 391 760
RAFT equilibrium coefficients 72–76, ω-functionalized
366 poly(N-isopropylacrylamide)
2-(((ethylthio)carbonothioyl)thio)-2- 760, 777
methylpropanoic acid 384, α,ω-functionalized poly(diethylene glycol
monomethyl ether
681, 685, 886
methacrylate) 789
aqueous RAFT 681, 685
ω-functionalized poly(tert-butyl acrylate)
crosslinking polymerization 886
778
functional derivatives
functional monomers 240, 280, 424, 425,
active ester 394
433, 718, 755, 954, see also
protected thiol 399
reactive groups
protected maleimide 403
functional RAFT agents 775, 807, 1004,
polymerizations 384
see also reactive groups
(5-ethyl-2,4,6-trioxohexahydropyrimidin-
aromatic dithioesters 235
5-yl)methyl 2-bromopropanoate
trithiocarbonates 379–408, 433, 759
786
furan 435, 769, 853, 955, 991
ethylxanthogenacetic acid, see 2-((ethoxy- furan-protected maleimide 435, 853,
carbonothioyl)thio)acetic 991
acid reactive group 955
f g
fast polymerizations 624, 654, 805, 1027, galactopyranose-functionalized
1180 poly(N-acryloylmorpholine)
ferrocenyl methacrylate (FcMMA) 673 macroRAFT 716
flash chromatography 813, 820 galactosamine 832
flat surfaces 1017, 1018, 1023, 1025 gel permeation chromatography (GPC)
Flory interaction parameter 898, 900 35, 36, 41, 49, 50, 52, 53, 649,
Flory polymer solvent interaction 651, 653, 658, 668, 695, 818, 819,
parameter 875 908, 909, 993, 996, 998–1000, see
fluorescein-based semicarbazide 724 also size exclusion
fluoroalkenes 1188 chromatography (SEC)
fluoroparticles 720, 722–723 Gilson Pipetmax 632
fraction of living chains, see livingness liquid handling robot 632
1214 Index
D-glucono-δ-lactone 691 grafting from 960–963

D-glucosamine 832, 851, 853 grafting onto 959–960
glucose oxidase (GOx) 654, 656, grafting through 958–959
691–693, 695, 696, 1057, 1058 graft water-soluble acrylates 624
glutathione (GSH)-based solvophilic grafting from biomolecules 699–701
macroRAFT 720, 723, 857 graphitic carbon nitride (g-C3 N4 ) 622
glycerol methacrylate, see glycerol group transfer polymerization (GTP)
monomethacrylate 755
glycerol monomethacrylate (GMMA
2,3-dihydroxypropyl h
methacrylate, glycerol halo-olefins 512–513, see also vinyl
methacrylate) 242–243, 263, chloride, vinyl halides,
382–383, 406–407, 410, 559–560, vinylidene chloride, vinylidene
572, 686–687, 697–699, 711, fluoride
718–720, 722–724, 726, 735–737, hemoglobin (Hb) 654, 655
844, 1041–1042 hetero Diels-Alder reaction 310,
with dithiocarbamates 559–560, 572 769–773, 777, 778, 945, 947, 955
with dithioesters 242–244, 273–274
heterodienophiles
with trithiocarbonates 382–383,
(diethoxyphosphoryl)methanedithioates
405–406, 410
769, 770
glycidyl methacrylate (GMA) 242–244,
pyridine-2-carbodithioates 769
246–247, 293, 365, 371, 375,
triazolinediones 771–772
380–383, 555, 556, 615, 712, 718,
heterogeneous polymerization, see also
844, 1033, 1053
PISA
glycomonomers 239, 267, 272, 274, 278,
dispersion polymerization 38, 187,
see also 6-O-methacryloyl
194, 195, 211, 437–439, 506, 650,
mannose
686, 691, 696–699, 709–714,
with dithioesters 40, 237–238,
718–721, 723–726, 729–731, 734,
267–268, 272, 274, 276, 278
with trithiocarbonates 413–419 736, 898, 900–901, 996, 998–999,
glycopolymers 832–833, 847, 848, 851, 1006
853, 857 emulsion polymerization 34–37, 42,
poly(2-(2,3,4,6-tetra-O-acetyl-𝛽-D- 187, 195, 205, 209–210, 301–302,
glucosyloxy)ethyl methacrylate) 409, 505–507, 587, 710,
(PAcGlcEMA) 857 1078–1080, 1091, 1093, 1097,
gradient copolymers 26, 207–208, 515, 1102, 1105, 1109, 1110, 1114,
519, 531, 948–949 1122, 1128, 1132, 1137
modelling of 207–208 inverse emulsion polymerization 530
graft copolymers 4, 295, 310, 433–435, miniemulsion polymerization 195,
520, 521, 587, 727, 782, 956–964, 205–206, 505, 507, 513, 908
1027, 1078 precipitation polymerization 710–712
graft-block copolymers 1022 suspension polymerization 195–196
graft density 1017, 1021, 1029–1031, hexa-2,4-dien-1-ol 772, 773
1033, 1034, 1039 (2E,4E)-hexa-2,4-dien-1-yl prop-2-yn-1-yl
general guidelines 963–964 succinate 777
Index 1215
1,1,1,3,3,3-hexafluoroisopropanol (HFIP) hydroxy-functional dithioesters 295

838 hydroxy-functional trithiocarbonates
1-hexanethiol 779 434
hexyl isocyanate 782 N-(2-hydroxyethyl)acrylamide (HEAm)
hierarchical porous polymers (HPP) 873 384, 390, 391, 397, 438, 696, 727,
high throughput (HTP) polymer libraries 840
630, 631, 633 N-(2-hydroxylethyl methacrylate (HEMA)
high throughput and high output 198, 409, 425, 701, 853, 902
experimentation (HT/HO-E) 2-hydroxypropyl)methacrylamide
antimicrobial agents 1064–1065 (HPMAm) 45, 53, 438, 686,
bottlenecks 1052 687, 691, 693, 696–699, 712, 718,
fundamental aspects and limitations 724, 725, 737, 831, 841, 847, 853,
1052–1053 854, 966
kinetic investigations 1053–1055 2-hydroxypropyl methacrylate (HPMA)
nanomedicine and drug delivery 45, 53, 438, 686, 687, 691, 693,
systems 1059–1065 696–699, 712, 718, 719, 724–726,
star polymer synthesis 1000 737, 841, 847, 853, 854
synthesis and accessibility 1056, 1059 4-hydroxystyrene 392, 425, 565–566, 572
versatility 1051 hypophosphite salts 766
Hildebrand solubility parameter 898,
900 i
horseradish peroxidase (HRP) 693–695, imidazole
713 as isocyanate protecting group 841
hydrazine hydrate 525, 773, 782, 783, in trithiocarbonate synthesis 408
790 1H-imidazole-1-carbodithioates 550,
2-hydroethyl acrylate (HEA) 425, 615, 559–560, 572, 577–578
685, 691–693, 700, 845, 1057 1H-imidazole-4-carbodithioates 209,
hydrogels and 3D printing 633–634 210
hydrogen peroxide 306, 446, 526, 591, indene monomers 628, 820–823
624, 691, 693, 695, 696, 713, 769 single unit monomer insertion (SUMI)
hydroperoxide end-terminated 628, 820–823
(co)polymers 768 industrial applications of RAFT
2-hydroxybutyl methacrylate (HBMA) 529–530, 1077–1136
727, 730 biomedical applications 1137
2-hydroxyethyl acrylate (HEA) 615, 653, patents 1100–1104, 1106–1108,
685, 1057 1111–1114, 1116–1117, 1119,
2-hydroxyethylamine 722 1122–1124, 1127–1136
2-hydroxyethyl 2-((ethoxycarbonothioyl) electronic applications 1137
thio)-2-methylpropanoate patents 1102, 1106, 1111, 1112,
(2-ethoxythiocarbonylsulfanyl-2- 1114–1115, 1118, 1123, 1126,
methyl-propionic acid 2-hyd- 1127, 1129–1131
roxyethyl ester) 496, 517, 693 emulsion polymerization 1097
2-hydroxyethyl methacrylate (HEMA) patents 1102, 1106–1111, 1114,
38, 126, 521, 615, 693, 846, 900, 1120–1122, 1127, 1131–1133
1057 end-group removal
1216 Index
industrial applications of RAFT (contd.) intermediate activated monomers (IAMs),

patents 1137–1141 see N-vinylcarbazole
macromonomer RAFT polymerization intermediate radical termination (IRT)
1077–1086 59, 60, 76, 77, 80, 86, 90, 91,
RAFT agents 1087–1088, 1098–1099 119–126, 171, 187, 188, 191–194,
stars and microgels 1137 200–201, 205, 206, 225, 226, 279,
thiocarbonylthio RAFT polymerization 361, 425, 442
1082, 1086–1136 inverse mini-emulsion periphery RAFT
key patents 1086, 1089–1096 polymerization (IMEPP)
iniferter 299–300, 551, 552, 611, 617, approach 851
624, 818, 941, 1089, see also iodine transfer polymerization (ITP) 708
photoiniferter ionization energy (IE) 176
inimer RAFT agents 292–294, 433–436, iridium photocatalyst, see
629, 815–816, 966, 987 tris(2-phenylpyridine)iridium
acrylates 293 (III) (fac-Ir(ppy)3 ), PET-RAFT
methacrylates 293, 431, 628, 629, see isocyanate (NCO) group
also 1-(methacryloyloxy) functional monomer 283–285, 422,
propan-2-yl 4-(((butylthio) 426, 840–842, see also
carbonothioyl)thio)-4-cyan- 2-isocyanatoethyl acrylate
opentanoate 2-isocyanatoethyl methacrylate
methacrylamides 431, see also functional RAFT agent 403
1-methacrylamidopropan-2-yl reagent 782, see also allyl isocyanate,
4-(((butylthio)carbonothioyl) hexyl isocyanate
thio)-4-cyanopentanoate selenol–isocyanate reaction 786
in self-condensing vinyl polymerization thiol-isocyanate reaction 774, 780–782
dithioesters 292–294 2-isocyanatoethyl acrylate 840
enzyme responsive 966 2-isocyanatoethyl methacrylate 782, 841
trithiocarbonates 430–432, 987 protected monomer, see
styrenes 209–210, 293–294, 431–432, azole-N-carboxamide
987, see also 4-vinylbenzyl methacrylates
1H-imidazole-4-carbodithioate isoprene 242–243, 273, 382–383,
in synthesis of sequence-defined 385–387, 390–391, 419, 424–425,
polymers 815–816 431, 944, 945, 1034, 1055
initiators, see also azo-compound high throughput synthesis 1053
initiators, peroxide initiators, mscroRAFT agents 944, 945
photoinitiators SI-RAFT 1034
photo-redox initiators 436 isopropenyl acetate (IPAc) 842–843
photoiniferters (RAFT agents) 109,
130–131, 298–299, 436 j
γ-radiation 109 junction-functionalized diblock
redox initiators 4, 47, 109, 504–505, copolymers 807
591, 648–656, 672–673, 684, 695
Fenton’s reagent 648, 652–654 k
bio-Fenton’s reagent 654 ketoform reaction 418–419, 580, 581
initer 551 ketone functionalized particles 724
Index 1217
kinetic modeling, see mathematical tris[2-(dimethylamino)ethyl]amine

modeling (Me6 TREN), see also copper
kinetic rate coefficients, see rate activators
coefficients CuX/Me6 TREN 120, 515, 657, 658
Krytox 900, 902, 903 tris(2-phenylpyridine)
tris(2-phenylpyridine)iridium(III)
l (fac-Ir(ppy)3 ) 300, 612,
lauroyl peroxide (LPO, dodecanoyl 617–619, 623, 627, 628, 1188
peroxide) 303–304, 308, 309, tris(2-pyridylmethyl)amine (TMPA), see
442–443, 528–529, 589, 765–767, also copper activators
1139 CuX/TMPA 657–659, 669–670
in RAFT end-group removal 306, 308, light-harvesting polymers 294, 807
309, 442–443, 528–529, 589, limonene 369, 620, 628
live cell graft polymerizations 634–635
765–767, 1139
Saccharomyces cerevisiae 635
in SUMI 1120–1121
living cationic polymerization 517,
lauryl methacrylate (LMA, dodecyl
1172–1173
methacrylate) 409, 712, 725,
livingness (L) (fraction of living chains,
774, 853, 1034, 1059
end-group fidelity)
leaving group ability 96–97, 100, 105, living polymerization 15
109–111, 361, 442, 810 PET-RAFT polymerization 618
less activated monomers (LAMs) 46, 47, RAFT polymerization 116, 128, 225,
116–118, 234, 239, 278–279, 287, 298–299, 550, 938–942
359, 368–370, 425, 428, 447, 549, living polymerization
550, 555, 575, 582, 583, 585, 587, RAFT mechanism transformation 295
591, 593, 693, 764, 806, 807, 809, terminology 15–18
934–936, 938, 939, 1097, see also lower critical solution temperature (LCST)
vinyl amides, vinyl esters, vinyl 512, 517, 714, 1027, 1029
lysozyme 524, 526, 624, 701, 791, 991,
imides
1027
Lewis acid-catalyzed mechanisms 1172
ligands
m
2,2′ -bipyridine (bpy), see also copper
(macro)alkoxyamines 205, 295, 297, 395,
activators 435, 717, 737, 768
II
Cu (DC)2 /bpy 668 addition-fragmentation coupling 768
tris(2,2′ -bipyridyl)ruthenium(II) ESARA 297, 435, 768
chloride (Ru(bpy)3 Cl2 ) 310, NMP inimer 423
618–619, 635, 689–691 -
RAFT-T-NMP 296, 435
4,4′ -dinonyl-2,2′ -bipyridine (dNbpy), macro-chain transfer agent (macroCTA),
see also copper activators see macroRAFT agent
CuX/dNbpy 657 macromolecular design by interchange of
N,N,N ′ ,N ′′ ,N ′′ -pentamethyldiethyl- xanthates (MADIX) 1, 493,
enetriamine (PMDETA), see also 530, 551, 710, 806, 1089
copper activators macromolecular thiol
CuX/PMDETA 300, 656–658, 669, catalyzed thiol-michael additions
759, 1024 777–780
1218 Index
macromolecular thiol (contd.) 685–687, 691, 696–701, 768, 933,

disulfide reactions 787–790 934, 937–939, 943–994
oxidative coupling 773 cores 986
pristine polymeric thiol 773 macro-RAFT SUMI products 810
radical thiol-ene reaction 775–776 macroRAFT type PISA 712
thiol-epoxy ring-opening 782–783 MALDI-TOF mass spectrometry 774
thiol-halo substitution 783–786 maleic anhydride (MAH) 241, 242, 245,
thiol-isocyanate modification 780–781 248, 249, 253, 254, 260, 279, 294,
tributylphosphine (PBu3 ) 773 373, 374, 386, 387, 389, 390, 392,
tris(2-carboxyethyl)phosphine (TCEP) 427–428, 433, 557, 807, 809, 810,
773 830, 842–843, 883, 891, 915
macromonomer RAFT agent cyclocopolymerization with divinyl
(macromonomer CTA) 936, ether 427–428
1078 single unit monomer insertion (SUMI)
synthesis of 294, 430, 433, 807, 809, 810
catalytic chain transfer (CCT) 1079 styrene/maleic anhydride copolymer
macromonomer RAFT polymerization 241, 242, 248, 249, 260, 261,
(sulfur-free RAFT 372–373, 387–388, 390–392, 842,
polymerization) 936, 891, 915
1077–1082 maleimide crosslinker 845, 947,
emulsion polymerization 936, 955, 956
1078–1079 in star synthesis 955, 956
industrial use 1077–1082 maleimide end-functional polymer 633,
mechanism 1078 780, 991
nanogel synthesis 1023 thiol-maleimide reaction 947, 991
macromonomers 96, 167, 280, 287, 426, maleimide-functional initiator
427, 433, 434, 720, 727, 731, 782, radical-induced coupling 991
786, 793, 806, 936, 958, 959, 963, maleimide-functional RAFT agent 700,
994, 1077–1083, 1085, 1086 1027
in arm-first star synthesis 994–995 furan-protected 394, 434–435
with dithioesters 287 in SI-RAFT 1025, 1027
in grafting through 958–959 maleimide monomers 279, 424, 588,
methacryloyl 286–287, 427, 958 589, 627–628, 777
peptide 427 furan-protected 282, 853
polycaprolactone (PCL) 263–264 N-methylmaleimide (NMMI)
poly(ethylene glycol) (PEG) 286–287, 246–247, 261, 278–279, 393,
426, 958 557–558
poly(dimethylsiloxane) (PDMS) 1-(2-oxotetrahydrothiophen-3-yl)-1H-
281–282, 958 pyrrole-2,5-dione
polyoxazoline 285 (thiolactone-functional
with trithiocarbonates 426–427 maleimide) 843
macroRAFT agent (macro-chain transfer N-phenylmaleimide (NPMI) 255, 260,
agent, macroCTA) 98, 102, 279, 380, 384, 393, 557, 589, 820,
105, 118, 297, 680, 681, 683, 821
Index 1219
single unit monomer insertion (SUMI) merocyanine 613, 629

369, 393, 430, 433, 627–628, 807, metal free photocatalysts 622–625
817, 820–823 metalloporphyrin 617, 620, 628
mathematical modeling (kinetic meta-tetra(hydroxyphenyl)-chlorin
modeling, numerical (m-THPC) 822
simulation) methacrylamides 43–46, 223, 233, 239,
ab initio kinetic modelling 165–167 240, 272, 313, 325, 368, 409,
deterministic modeling 188–204 438–439, 447, 530, 550, 629, 683,
diffusion coefficients 196–198 686, 691, 693, 724, 831, 838, 840,
full molecular weight distributions 841, 846, 847, 850, 851, 966, 985,
198–204 1057
explicit integration methods amino-functional, see N-(2-aminoethyl)
199–201 methacrylamide hydrochloride,
Predici® software 201–204 N-(3-aminopropyl)methacry-
probability generating function lamide hydrochloride
201, 202 azide functional, see N-(3-azidopropyl)
hybrid methods 206 methacrylamide
matrix-free polychloroprene grafted
with dithioesters 223, 233, 234, 240,
silica nanocomposites 1034
244, 252, 272–273, 293
method of moments 188–190
heterogeneous systems 194–196
N-(3-aminopropyl)methacrylamide
homogeneous systems 190–194
in aqueous solution 45
polymer networks
N-(2-hydroxypropyl)methacrylamide)
kinetic random branching theory
in aqueous solution 45
(KRBT) 915–918
poly(benzyl methacrylate)-block-poly
trifunctional molecule approach
(N-(2-hydroxypropyl)methacry-
907–910
lamide) in solution 53
multifunctional molecule approach
functional methacrylamides
910–915
polymerization processes azide, see N-(3-azidopropyl)
branched copolymerizations methacrylamide
209–210 hydroxyl, see N-(2-hydroxypropyl)
CSTRs/PFR 208–209 methacrylamide
microwave-assisted RAFT glycomonomers 272
polymerization 210–211 protected amine 283, see also N-(2-
semibatch polymerization 206–208 aminoethyl)methacrylamide
Predici® software 64, 65, 73, 103, 124, hydrochloride (AEMAm),
165, 187, 201–204, 906 N-(3-aminopropyl)methacry-
stochastic modeling 204–206 lamide hydrochloride
Monte Carlo 204–205 (APMAm)
2-mercaptoethanol (2M) 857 protected thiol 282
6-mercapto-1-hexanol 779 RAFT agent selection 27–28, 43–45,
3-mercaptopropionic acid (3M) 760, 857 112
3-mercaptopropyl polyhedral oligomeric with trithiocarbonates 368, 380–382,
silsesquioxane 779 388–391, 396–398, 413, 416–417
1220 Index
1-methacrylamidopropan-2-yl epoxy, see glycidyl methacrylate

4-(((butylthio)carbonothioyl) (GMA)
thio)-4-cyanopentanoate 431 hydroxyl, see glycerol
methacrylates 38, 239, 263, 409, 412, monomethacrylate (GMMA)
701, 767, 816, 834, see also butyl 2-hydroxylethyl methacrylate
methacrylate (BMA), methyl (HEMA) 2-hydroxypropyl
methacrylate (MMA), lauryl methacrylate (HPMA)
methacrylate (LMA), octadecyl glycomonomers 267
methacrylate (ODMA) isocyanate-functional, see
crosslinking monomers 202 2-isocyanatoethyl methacrylate
with dithiocarbamates 555–561 284
balanced activity 559–561, 582–583 oleate 844
switchable 568 PEG, see poly(ethylene glycol)
with dithioesters 239–248, 257–259 monomethyl ether methacrylate
aliphatic dithioesters 563–564 (PEGMA)
aromatic dithioesters 241–248 protected amine, see (2-aminoethyl)
methacrylate hydrochloride
bis-dithioesters 260–263
(AEMA)
functional dithioesters 251–257
protected thiol 283
silane 284
benzyl methacrylate in solution 41
tertiary amine 2-(dimethylamino)
6-O-methacryloyl mannose in
ethyl methacrylate) (DMAEMA)
solution 40
283–284
methyl methacrylate in solution
inimers
39–41
ATRP 285
poly(N-(2-hydroxypropyl)metha-
RAFT 283, 293
crylamide)-block-poly(benzyl
RAFT agent selection 27–28, 112
methacrylate) 53
star polymers 954
poly(N-isopropylacrylamide-co-sodium
with trithiocarbonates 320–389, 412,
methacrylate), in solution 50 416–417
poly(methyl methacrylate)-block-poly bis-trithiocarbonates 376–378
(butyl acrylate) 51 non-symmetric trithiocarbonates
poly(methyl methacrylate-co-trime- 380–389
thylsilyl methacrylate-co-t-butyl symmetric trithiocarbonates
(dimethyl)silyloxystyrene), in 371–373
solution 49 functional, trithiocarbonates 367,
poly(methacrylic acid-co-oleyl 401–402
methacrylate) in solution 49 with xanthates 509–510, 530
poly(triphenylmethyl semi-batch emulsion polymerization
methacrylate-co-methacrylic 510
acid), in solution 49 methacrylic acid (MAA) 49–50, 209,
functional methacrylates 311, 691, 711, 715, 782, 815, 831,
alkyne 281, see also propargyl 855, 1023, 1029, 1061, 1062, 1064
methacrylate NHS ester, see N-methacryloyloxy-
azide 281 succinimide (MAS)
Index 1221
methacrylic poly(N-acryloylmorpholine) oxycarbonylethyl)dithiocar-

macromonomers 782 bonate, Rhodixan A1) 47, 494,
methacryloyl chloride 839 508–514, 857
methacryloyl-functionalised application scope 494, 508–514
poly(ethylene glycols) 958 experimental procedure
6-O-methacryloyl mannose 40, 945 vinyl acetate in solution 47
[2-(methacryloyloxy)-ethyl] transfer coefficients 508
dimethyl(3-sulfopropyl) methyl 2-((isopropoxycarbonothioyl)
ammonium hydroxide 699 thio)acetate (methyl (isopropo-
2-(methacryloyloxy)ethylisocyanate, see xycarbonothioyl)sulfanylacetate)
2-isocyanatoethyl methacrylate 33, 52
2-(methacryloyloxy)ethyl oleate (MAEO) methyl 3-mercaptopropionate (M3) 857
719, 844 methyl 2-((methyl(pyridin-4-yl)
1-(methacryloyloxy)propan-2-yl carbamothioyl)thio)propanoate
4-(((butylthio)carbonothioyl) 30, 47, 51, 52
thio)-4-cyanopentanoate application scope 569
[2-(2-(butyltrithiocarbonate)-
experimental procedure
propionate)ethyl methacrylate]
methyl acrylate in solution 51
628, 629
poly(methyl acrylate)-block-poly(N-
N-methacryloyloxysuccinimide (NMS,
vinylcarbazole) in solution 51
methacrylic acid, NHS ester)
styrene in solution 52
243, 281, 420, 830–832, 855
polystyrene-block-poly(vinyl acetate)
method of moments (MM) 188
in solution 52
heterogeneous systems 194–196
methyl methacrylate (MMA) 31, 38, 88,
dispersion polymerization 195
99, 104, 111, 117, 130, 147, 148,
emulsion polymerization 195
154, 172, 193, 234, 368, 369, 503,
suspension polymerization 195–196
510, 549, 550, 554, 648, 666, 810,
homogeneous systems 190–194
846, 966, 1056, 1187
2-methoxyethylacrylate (MEA) 650, 696
methyl acrylate (MA) 39, 40, 51, 75, 76, experimental procedures
117, 130, 164, 172, 205, 234, 368, methyl methacrylate in solution
421, 503, 505, 550, 572, 615, 622, 39–41
648, 666, 696, 759, 808, 814, 844, poly(methyl methacrylate)-block-
986, 987, 1053, 1187 poly(butyl acrylate) 51
rate coefficients for radical addition poly(methyl methacrylate-co-
(ki , kp ) 107 trimethylsilyl methacrylate-co-t-
2-methyl-acrylic acid butyl(dimethyl)silyloxystyrene),
6-(3,4-dicyano-phenoxy)-hexyl in solution 49
ester 850 mathematical modeling 193–194,
Methylene-bis-acrylamide (MBA) 524, 197–198, 208
717, 907, 996 model system with dithiobenzoate
methyl 2-bromo-2-propanoate 783 88–89
2-methylene-4-phenyl-1,3-dioxolane 725 RAFT equilibrium constant 88
methyl 2-((ethoxycarbonothioyl)thio) rate coefficients for radical addition
propanoate (O-ethyl-S-(1-meth- (ki , kp ) 107
1222 Index
methyl methanethiolsulfonate (methyl more activated monomers (MAMs) 2,

methanesulfonothioate) 305 38, 114, 226, 359, 549, 693, 712,
methyl(pyridin-4-yl)carbamodithioates 764, 806, 934, 1097
(N-methyl-N-(4-pyridinyl)dithio- 1,1-disubstituted MAMs 239–240,
carbamates) 51, 116–117, 273, 409, 424, 555, 572, see also
554–555, 567–571, 583–585, see methacrylamides, methacrylates
also cyanomethyl methyl monosubstituted MAMS, see
(pyridin-4-yl)carbamodithioate, acrylamides, acrylates,
methyl 2-((methyl(pyridin-4-yl) acrylonitrile, diene monomers,
carbamothioyl)thio)propanoate styrenic monomers
application scope 116–117, 567–571 multiblock copolymers 105, 519, 530,
canonical forms 583–584 618, 626, 652, 805, 806, 878,
monomers 567–571 942–943, 968, 1065, 1188
polyMAM-block-polyLAM synthesis from multiRAFT agents 937
116, 584 by PET-RAFT 618, 626, 632
transfer coefficients 554 by sequential addition 942–943, 1057,
1065
N-methyl-N-(4-pyridinyl)dithiocarba-
multicomponent reactions (MCR)
mates, see methyl(pyridin-4-yl)
849–850
carbamodithioates
multiolefinic monomers 288, 430, 874,
4-methylstyrene 241, 249, 260, 275, 407,
see also divinyl monomers
425
multiple unit monomer insertion (MUMI)
Me6 TREN, see, copper activators, tris[2-
813, 814
(dimethylamino)ethyl]amine
multiRAFT agents (multifunctional
micellar nucleation 696, 711
RAFT agents) 879, 895, 937
miktoarm stars 523, 950, 951, 955, 956,
multistep polymerization 877, 878
986, 994, 1002, 1009
multiwalled carbon nanotubes (MWNTs)
missing-step reaction 77–86, 88–90
1007, 1008
Mitsunobu reaction 239, 408, 833
Mycobacterium smegmatis 631, 632
molar mass distribution (MMD) 61, 187,
204, 208, 210, 211, 443, 512, 514, n
905, 908 N-carboxyanhydrides (NCA) 434, 767,
molecular orbital calculations, see 790, 983, 995
quantum-chemical calculations γ-benzyl-L-glutamate
molecular weight distribution (MWD) N-carboxyanhydride (NCA)
25, 31, 32, 36, 37, 48, 97, 106, 767, 790
109, 111, 115, 116, 119, 122, 125, -
RAFT-T-ROP 434, 767, 790
126, 129, 187, 303, 509, 511, 513, N-isopropylacrylamide (NIPAM) 44, 46,
517, 520, 521, 620, 625, 636, 755, 50, 210, 234, 368, 503, 506, 550,
760, 764, 765, 782, 823, 831, 832, 615, 616, 634, 650, 686, 711, 780,
836, 838, 877, 905, 953, 962, 1174 783, 810, 843, 846, 944, 949, 965,
monomers, see intermediate activated 991, 996, 1003, 1063
monomers (IAMs), less activated 3-nitrobenzonitrile 667
monomers (LAMs), more o-nitrobenzyl functionalities 629
activated monomers (MAMs) o-nitrobenzyl methacrylate 629
Index 1223
p-nitrophenyl ester 835–836 norbornenyl-functional RAFT agents

S-nitrosothiol species 790 760
2-nitro-m-xylene 667 xanthate 759
nanoclay attapulgite (ATP) 649, 650 nucleophile (phosphine) catalyzed
NHS ester, see N-hydroxysuccinimide mechanism 777, 779
(NHS) ester numerical simulation, see mathematical
N-hydroxysuccinimide (NHS) ester 815, modeling
830–832, 1004
of acrylic acid, see N-acryloyl o
oxysuccinimide (NAS) octadecyl acrylate (ODA) 42
in bioconjugation 857 blocks 372, 374
by copolymerization of multifunctional copolymers 259, 377, 389
monomers 966–967 experimental procedure 42
hyperbranched polymers 515, 524, homopolymer 42, 374, 389
964–968, 986 with trithiocarbonates 42, 373, 389
of methacrylic acid, see N-methacrylo- 1-octanethiol 834, 1178
yloxysuccinimide (NMS)
octanol–water partition coefficient 727
NHS functional monomer 281–282,
octylamine 779
420–421, 830–832
oleic acid decorated nano-objects 719
NHS functional RAFT agent 252,
oligo(ethylene glycol) acrylate (OEGA)
394–398, 498, 857, 860
43, 69, 240, 424–426, 615, 690,
dithioester 251–252
693, 699, 701, 727–728, 730, 943,
trithiocarbonate 394–398
1187
xanthate 498
oligo(ethylene glycol) methacrylate
by self-condensing vinyl polymerization
(OEGMA) 634, 701, 1041,
(SCVP) 964–966, 986
1059, 1060
of 4-vinylbenzoic acid, see
oligomer separation 813
2,5-dioxopyrrolidin-1-yl
4-vinylbenzoate organotellurium-mediated radical
nitroxide-mediated polymerization polymerization (TERP) 708
(NMP) 118, 176–178, 273, 295, oxygen tolerance
297, 424, 426, 433, 435, 523, 550, PET-RAFT 624, 691
552, 708, 712, 717, 726, 755, 905,
939, 962, 964, 983, 985 p
RAFT mechanism transformation para-fluoro substitution reaction (PFTR)
-
(RAFT-T-NMP) 435 194, 723, 834, 835
nitroxide-terminated polymers 768 parathyroid peptide hormone, (PTH)
NMR spectroscopy 36, 41, 49, 52, 53, 81, 612, 622, 634, 761, 762
85, 511, 513, 519, 700, 760, 774, parent hydrogels 634
779, 782, 783, 785, 786, 831 Passerini reaction-derived methacrylates
non-activated alkenes 807 720, 835
non-Aldol carbonyl reaction 780 PEG-dibenzocyclooctyne
non-homopolymerizable monomers 820 (tetra-DBCO-PEG) 634
non-symmetric trithiocarbonates 360, PEG dithiol 633
361, 368, 378–393, 396 pendent double bonds (PDB) 873, 906
1224 Index
pentafluorobenzyl (PFB) ester industrial use 1099

monomers, see pentafluorobenzyl phenothiazine 612, 617, 622
methacrylate (PFBMA) 1-phenylethyl benzodithioate 109, 111,
pentafluorobenzyl methacrylate (PFBMA) 120, 122, 124, 205, 228, 229, 248,
723, 834, 835 292, 888
pentafluorophenyl (PFP) ester 830, application scope 248
832–835 chain transfer coefficient 228, 229
monomers, see pentafluorophenyl crosslinking polymerization 888
methacrylate, N-phenyl maleimide (PMI) 820, 821
pentafluorophenyl 2-phenylpropan-2-yl benzodithioate
4-vinylbenzoate (cumyl dithiobenzoate, CDB)
nanoparticle shell-units 720 33, 34, 40, 41, 49, 67, 108, 126,
RAFT agents 789, 837 149, 164, 228, 233, 241, 292, 301,
pentafluorophenyl ester-functionalized 658, 832, 836, 913
R-group dithiobenzoate 789 application scope 27, 241
pentafluorophenyl methacrylate experimental procedure
(PFPMA) 38, 240, 720–721, benzyl methacrylate in solution
723, 832–835, 848, 851, 854 41–42
decorated particles 720 6-O-methacryloyl mannose in
pentafluorophenyl-(4-phenylthiocarbon- solution 49
ylthio-4-cyanovalerate) 837 styrene in solution 33–35
pentafluorophenyl 4-vinylbenzoate chain transfer coefficient 228
(PFP4VB) 833 industrial use 30
pentafluorostyrene (PFSty) 425, 786, side reactions 126
834, 844 stability 126
based homo-and copolymers 834 2-phenylpropan-2-yl
pentamers 818, 820 2-phenylethanedithioate (cumyl
N,N,N ′ ,N ′′ ,N ′′ -pentamethyldiethylenetri- phenyldithioacetate, CPDA)
amine (PMDETA), see copper 105–106, 260
activators application scope 260
peroxide initiators 32, see also 3-phenylpropyl methacrylate 720
ammonium persulfate (APS), phosphate buffered saline (PBS)
benzoyl peroxide (BPO), t-butyl 691–693, 695
hydroperoxide, cumene photoinduced energy or electron
hydroperoxide (CHP), lauroyl transfer-RAFT (PET-RAFT)
peroxide (LPO) 299–300, 436, 504, 505, 617–625,
‘solvent-initiated’ RAFT 654 628, 629, 635, 688–690, 701, 817,
PET-RAFT, see photoinduced energy or 991, 1055, 1064–1065
electron transfer-RAFT with dithiobenzoates 299–300
pH 736 high throughput experiments
-sensitive DMAEMA block 698 629–633, 1064–1065
zwitterionic pH-responsive copolymers oxygen tolerance 439, 624, 691
843 photocatalysts
phenazine organophotocatalysts 617 eosin Y (EY) 300, 612, 623–625,
2-((phenylcarbonothioyl)thio)acetic acid 630, 635, 689–691, 701, 1027
Index 1225
pheophorbide A 617, 628 2,2-dimethoxy-2-phenylacetophenone

rose bengal 624, 719 760
tris(2,2′ -bipyridyl)ruthenium(II) 2-methyl-1-[4-(methylthio)phenyl]-2-
chloride (Ru(bpy)3Cl2 ) 300, morpholin-4-ylpropan-1-one
618–619, 635, 689–691 63, 70, 73–75, 85, 88
tris(2-phenylpyridine)iridium(III) type II, 612
(fac-Ir(ppy)3) 300, 612, photoRAFT polymerization, see also
617–619, 623, 627, 628, 1188 photoinduced energy or electron
zinc(II) (2,3,7,8,12,13,17,18- transfer (PET)-RAFT
octaethyl-5,10,15,20-tetraphenyl- high throughput (HTP) polymer
porphyrin) (ZnOETPP) libraries 630
621–622 hydrogels and 3D printing 633–634
zinc-iron oxide semiconductor live cell graft polymerization 634–635
(Zn0.64 Fe2.36 O4 ) 616 photoiniferter polymerization
zinc(II) meso-tetra(N-methyl- 613–625
4-pyridyl) porphine photoinitiation 612–613
tetrachloride (ZnTPMPyP)
photoredox catalysis 617–625
629, 691
single unit monomer insertion (SUMI)
zinc(II) meso-tetra(4-sulfonato-
625–628
phenyl)porphyrin) (ZnTPPS4− )
wavelength orthogonal polymerization
621, 689, 691
628–629
zinc(II) 5,10,15,20-tetraphenyl-21H,
photoRAFT-SUMI, see photoinduced
23H-porphine (zinc tetraphenyl
energy or electron transfer
porphyrin, ZnTPP) 300, 617,
(PET)-RAFT SUMI
620, 628–631, 991, 1055
photoredox initiation, see photoinduced
star polymer synthesis 991–994
energy or electron transfer
single unit monomer insertion (SUMI)
(PET)-RAFT
294, 436, 625–628, 817–820
photoresponsive monomer
with trithiocarbonates 436
photoiniferter process 109, 130–131, 7-[4-(trifluoromethyl)coumarin]metha-
299, 436, 551, 613–625, 817 crylamide 691
photoiniters 551 physisorption 903, 905, 1018
photoinitiation 130, 294, 299–300, 370, Pickering emulsions 722, 739
436, 575, 585, 612–613, 685 4-pinacolatoborylstyrene (pBSt) 849
photoinitiators, see also photoinduced PISA, see polymerization-induced
energy or electron transfer self-assembly
(PET)-RAFT, photoiniferter polyacrylamide gel electrophoresis
process (PAGE) 700
in pulsed laser photolysis (PLP) 60–65 polydentate amine ligand 656
type I, 612–613 poly(ethylene glycol) (PEG) 38, 39, 240,
acetophenones 612 287, 555, 649, 650, 685, 693, 713,
acyl-phosphine oxides 612 721, 727, 737, 843, 847, 857, 944,
benzoin ethers 612 995, 996, 1009, 1057, 1064, 1187
benzoin ketals 612 (poly(ethylene glycol) monomethyl
benzophenone 612 ether)acrylamide 635
1226 Index
poly(ethylene glycol) monomethyl ether RAFT crosslinking polymerization

acrylate (PEGA) 286, 685, 996 288, 292, , 429, 876–898
blocks 250, 253 crosslinking monomers (divinyl
copolymers 245 monomers, multivinyl
with dithioesters 248, 249 monomers) 288, 290, 428, 430,
homopolymer 248, 249 879–898
poly(ethylene glycol) monomethyl ether RAFT agents (controllers) 879–898
methacrylate (PEGMA) 409, synthesis pathways 877–879
426, 438, 555, 572, 650, 659, 693, structure and characteristics 875–876
699, 721, 788, 790, 847, 857, 858, supercritical carbon dioxide 898–904
861, 958, 992, 995, 996, 1057, polymer–protein binding affinity 631
1059, 1064 polymeric CTA, see macroRAFT agent
thermo-responsive polymer 857 polymeric disulfides 773–774, 781, 790
poly(ethylene glycol) methyl ether thiol polymeric ionic complexes (PIC) 734
(PEG-SH) 857 polymeric Janus nanosheets (PJS) 1023,
poly(ethylene oxide) (PEO) 37, 516, 683, 1024
1037–1038, see also polymeric S-nitrosothiol 790–791
poly(ethylene glycol) (PEG) polymerization-induced self-assembly
polyhedral oligomeric silsesquioxane (PISA) 507, 629, 679, 696,
(POSS) 5, 777, 779, 1009 707–710, 712, 726, 942, 1040,
poly(lactide) 944 1041
polymer, see under respective monomer applications 738–740
polymer grafted nanoparticles cooperative assembly (PICA) 713,
1022–1027, 1039–1042 714, 733
in composites 1030–1039 dispersion polymerization 711
synthesis electrostatic self-assembly (PIESA)
assemble-crosslink-disperse 1009, 714–715, 734
1039–1040 emulsion polymerization 711
PISA 1040–1042 from spherical to anisotropic block
SI-RAFT 1022–1027 copolymer particles 726–727
polymer grafted surfaces, see hierarchical self-assembly (PIHSA)
surface-initiated RAFT 714–715, 733–734
(SI-RAFT) history/origins of 709–710
polymer monoliths 913 initiation in RAFT-PISA 712–713
polymer networks macroRAFT type 712
background 906–907 parameters that impact the particle
mathematical modeling morphology 728–733
kinetic random branching theory poly(methacrylic acid) (PMAA) 715
(KRBT) 915–918 polymerization-induced cooperative
multifunctional molecule approach assembly (PICA) 714
910–915 polymerization-induced electrostatic
trifunctional molecule approach self-assembly (PIESA) 715
907–910 polymerization-induced hierarchical
model co-networks 288, 291, 895 self-assembly (PIHSA) 715
Index 1227
polymerization-induced thermal protein-polymer conjugates 679, 699,

self-assembly (PITSA) 714 790–791
post-polymerization morphological protein-thermoresponsive polymer
transitions/chain reorganization conjugates 761
735–738 pseudo-kinetic rate constants method
precipitation polymerization 711–712 907
reactive/functional nano-objects pulsed-laser polymerization (PLP) 60,
716–717 61, 65, 151, 201
solvophilic macroRAFT 713 SP-PLP-EPR method 60–61, 64,
strategies to stir specific morphologies 71–72, 88, 90, 367
733–735 1H-pyrazole-1-carbodithioates 28, 559,
surfactant-free latexes 715–716 583, see also 2-cyanobutan-2-yl
polymerization-induced thermal 3,5-dimethyl-1H-pyrazole-1-
self-assembly (PITSA) 506, 714 carbodithioate, cyanomethyl
population balance equations (PBEs) 3,5-dimethyl-1H-pyrazole-
188–189, 199 1-carbodithioate
precipitation polymerization 711–712 application scope 28, 559–563,
Predici® software, see mathematical 582–583
modeling 1-pyrenemethyl methacrylate 738
pristine polymeric thiol 773 pyren-1-ylmethyl acrylate 859
propacrylic acid (PAA pyridine-2,6-dicarboxaldehyde 725
2-methylenebutanoic acid) 2-pyridyl disulfide end-group 398–399,
381, 386, 392, 397, 438, 439 761–762, 788–789, 815–816
propagation rate coefficient, see rate 2-pyridyl disulfide functional monomer
coefficients 283, 421, 842, 843, 855–857
pro-TAD-functional trithiocarbonate acrylamide 385, 421
772 acrylate 282, 381, 421
propargyl acrylate 39, 434, 649, 779–780, copolymer 244, 245, 381, 386,
991 855–857
propargyl methacrylate (PgMA) 521, with vinyl lactam 855–857
847–849 methacrylamide 245, 282, 421
2-(propylthiocarbonothioylthio)-2-methyl- methacrylate 39, 244, 246, 283, 385,
propionoic acid (PMP) 691 421, 843, 856–857
prop-2-yn-phosphocholine (PPhCh) 847 2-pyridyl disulfide functional RAFT agent
protecting group 399
for isocyanate, see imidazole, 1H-pyrrole-1-carbodithioates 550, 577,
azole-N-carboxamide 578, 581, 582, 588, 593, 894, see
methacrylates also benzyl 1H-pyrrole-1-
for primary amine, see carbodithioate
t-butyloxycarbonyl (BOC) 129 2-cyanopropan-2-yl
for thiol, see benzothioic S-acid, 1H-pyrrole-1-carbodithioate
S-(2-((t-butoxycarbonyl)amino) application scope 556–557
ethyl) methanesulfonothioate crosslinking polymerization 894
2,2′ -dipyridyl disulfide synthesis of 577–578
1228 Index
q 2-carboxyprop-2-yl radicals 369

quantum-chemical calculations 60, for 1,1-disubsituted MAMs 368–369
65–66, 72, 79, 87–88, 90, 139–180 for IAMs and LAMs 369
ab initio kinetic modelling 152–167 for monosubstituted MAMs 369
methodology 65–66, 140–152 stability 109
radical stabilization energy (RSE) 176 with trithiocarbonates 367–370
RAFT agent design 176–179 side reactions 109, 114–116, 126–130,
RAFT equilibrium coefficient 65–66, 680–681
87–88, 152–156, 159–164 hydrolysis 109, 680–681
retardation mechanisms 164, 179 Z-substituent (activating group) 109,
slow fragmentation model 167–171 112
side reactions in RAFT 156–159 affect on chain transfer coefficient
structure-reactivity predictions 113
167–179 affect on reactivity 116–118
transition state theory affect on reaction kinetics 118–119
quasi-block copolymers 118, 1054, intermediate radical termination
1056–1060, 1064 119–123
standard 140–147 side reactions, stability 114–116,
variational 140, 146 126–130
quinone 612 slow fragmentation 123–126
r alkylating agent with carbodithioate
radical stabilization energy (RSE) 172 237, 408, 500, 575–577
radical thiol-ene reaction 760, 775–776, 1,3-dipolar cycloaddition 413, 502
779 of dithiocarbamates 575–580
radical thiol-yne reaction 776–777, 780 of dithioesters 237–239
RAFT agent (chain-transfer agent, CTA, esterification or amidation 238, 408
ZC=SSR), see also Markovnikov addition of dithioacid to
dithiocarbamates, dithioesters, olefin 237
macromonomer RAFT agent, ketoform reaction 408, 580, 581
trithiocarbonates, xanthates nucleophile with dithiochloroformate
chain transfer coefficient (Ctr ) or thiocarbonyl-bis-imidazole
96–103, 226–230, 362 408, 577–578
dithiocarbamates 552–554, 580 radical-induced ester exchange 238,
dithioesters 101, 228–229 408
trithiocarbonates 363–365 radicals with a bis(thioacyl)disulfide
xanthates 507–508 238, 408, 418, 500, 578–580
R-substituent (homolytic leaving single unit monomer insertion (SUMI)
group) 109, 112, 367–370 238, 292, 294–295, 408, 430
affect on chain transfer coefficient thionation 238
96–97 thiol exchange 238, 408, 504
affect on re-initiation and of trithiocarbonates 408–409, 430, 433
initialization 105, 107–108 of xanthates 493–500, 504
for block copolymer synthesis RAFT crosslinking polymerization, see
103–106, 369–370 polymer networks
Index 1229
RAFT (end-)group radical-induced disproportionation

removal/transformation 442–443
dithiocarbamates 588–591 radical-induced reduction 443, 444
cross-coupling with aryl boronic reaction with nucleophiles 444, 445
acids 591 thermolysis 444–446
radical-induced coupling 588, 589 xanthates 525–529
radical-induced disproportionation reaction with nucleophiles 525–526
588–589 oxidation 526–527
radical-induced reduction 589, 590 radical-induced reduction 528–529
reaction with nucleophiles 589–590 thermolysis 527–528
oxidation 591 RAFT mechanism transformation
thermolysis 590–591 295–297, 433–436, 587–588
dithioesters 302–313 with dithiocarbamates 587–588
cross-coupling with aryl boronic -
RAFT-T-ATRP 588
acids 311, 312 -
electrocyclic reaction 310–311 -
ROP-T-RAFT 587
oxidation 306, 310 -
radical-induced coupling 303, 306 with dithioesters 295–297
radical-induced disproportionation ESARA process 297
303, 306–308 -
RAFT-T-ROMP 256, 296
radical-induced reduction 303, 306, -
ROMP-T-RAFT 296
307, 309 -
RAFT-T-ROP 256, 295–296
reaction with nucleophiles 302–305 -
ROP-T-RAFT 295–296
thermolysis 309–310 -
RAFT-T-ATRP 296
hetero Diels Alder 769–772 -
RAFT-T-NMP 297
radical-induced coupling 303, with trithiocarbonates 433–436
307–308, 439–442, 556, 589, -
cationic-T-RAFT 435, 1187–1190
766–768 -
RAFT-T-anionic 435
radical-induced oxidation 768–769 -
RAFT-T-ATRP 435–436
radical-induced reduction 306, 309, -
RAFT-T-NMP 435
442–443, 528–529, 589, 590, -
RAFT-T-ROAMP 435
765–766 -
reaction with nucleophiles (reactions of -
RAFT-T-ROP 434
thiol-ends) 302–303, 444–445, -
ROP-T-RAFT 434
525–526, 589–590, 681–684, -
772–790 with xanthates 516–519
aminolysis 681–684, 772–790 -
cationic-T-,RAFT 517–518,
hydrolysis 680–681 1187–1190
thermolysis 309–310, 444–446, -
ROP-T-RAFT 517
527–528, 590–591, 763–764 RAFT PISA, see polymerization-induced
trithiocarbonates 439–446 self-assembly RAFT
oxidation 446, 447 polymerization, see reversible
radical-induced coupling addition-fragmentation chain
439–442 transfer polymerization
1230 Index
RAFT-single-unit monomer-insertion cross coupling with aryl bromide

(RAFT-SUMI) 4, 179, 235, 279, group 848–849
292, 294–295, 311, 361, 367, 408, cross-coupling with RAFT agent
424, 426, 430, 433, 625–628, 311, 591, 791
806–823 (4-vinylphenyl)boronic acid 384,
into dithioesters 292, 294–295 849
sequential SUMI azlactone group 282, 830, 842, 859,
styrene-NIPAm dimer 810 863
of styrene 810 functional monomer, see
into trithiocarbonates 430, 433 2-vinyl-4,4-dimethylazlactone
rate coefficients functional RAFT agent 398
addition to RAFT agent (kadd ) 95, 101, polymers 859, 863
103, 125 azide group, see azide group
addition to monomer (ki ) 105, 107 aziridine group 830
initiator decomposition (kd ) 100 disulfide group 830, 843, see also
fragmentation (k-add , kβ , kfrag ) 95, 103, 2-pyridyl disulfide
126 thiol–disulfide exchange 843
propagation (kp ) 96, 101, 105, 107, 126 epoxide group 843–844
rate constants, see rate coefficients isocyanate group, see isocyanate group
γ-ray irradiation 505 redox initiation 4, 47, 109, 300, 504–506,
reactive groups 716, 723, 736–737, 788, 591, 648–656, 672, 684, 695, see
829–830, 833, 853, 963, 1039, see also eRAFT, photoredox
also alkyne group, azide group, initiation
isocyanate group ammonium persulfate–sodium
active ester 252–253, 281–282, 394, formaldehyde sulfoxylate 506,
396, 426, 830–838, see also acyl 650, 787
chloride, acetone oxime (AO) benzoyl peroxide–amine 505, 648–649
group, p-dialkylsulfonium benzoyl peroxide–N,N-dimethylaniline
phenoxy ester (DASPE), 648–649
anhydride group, t-butyl hydroperoxide–ascorbic acid
N-hydroxysuccinimide (NHS) 648, 652
ester, nitrophenyl ester, cumene hydroperoxide–ascorbic acid
pentafluorobenzyl (PFB) ester, 648, 652
pentafluorophenyl (PFP) ester, iron(II)–hydrogen peroxide (Fenton’s
salicylic acid ester reaction) 648, 652–654
monomer 290–291, 426, 830–838 bio-Fenton’s reaction 648, 654
RAFT agent 251–252, 396–398 potassium persulfate–sodium
acyl chloride 830, 839 thiosulfate 650
acryloyl chloride 780–781, 839 potassium persulfate–sodium ascorbate
methacryloyl chloride 839 650, 652
4-vinylbenzoyl chloride 839 redox-RAFT 179, 300, 656–660
alkyl halide 830, 839–840 copper activator 656–659
alkyne, see alkyne group dissociative electron transfer
aryl boronic acid 311, 384, 591, 791, (DET)-RAFT 179, 660
830, 848–849, 853 sodium dithionite activator 660
Index 1231
redox responsive hydrogels 787–788 ring-opening polymerization (ROP) 5,

retardation in RAFT polymerization 287, 295–296, 428, 434, 435, 517,
32, 37–38, 59–60, 66–69, 76–77, 523–524, 587, 629, 767, 790, 844,
86, 88–91, 107, 116–120, 958, 983, 985, 995, 1009
122–124, 126, 164, 179, 187, RAFT mechanism transformation
190–191, 193–194, 205, 210, 223, -
RAFT-T-ROP 434, 435
225–226, 230, 233, 235, 237, 278, -
ROP-T-RAFT 295–296, 434, 435
279, 301, 313, 359, 367–369, 409, ring-opening copolymerization-
425, 504, 523, 530, 549, 581–583, induced self-assembly
935 (rROPISA) 725
thiolactone groupreactive polymers, see room temperature RAFT polymerization
reactive group 648, 845
reversible addition-fragmentation chain rose bengal 624, 719
transfer (RAFT) polymerization ruthenium photocatalyst, see tris(2,2′ -
overview 1–5 bipyridyl)ruthenium(II)
terminology 18–24 chloride (Ru(bpy)3 Cl2 )
reversible complexation-mediated
polymerization (RCMP) 708
s
salicylic acid (SA) 837
reversible crosslinking copolymerization
Se-benzyl O-(4-methoxyphenyl)
(RCC) 524
carbonodiselenoate 786
reversible deactivation polymerization
selective initialization 108, 292, 808–809
(RDP, controlled
self-assembly of block copolymers 709,
polymerization)
851
RAFT mechanism transformation 295
self-condensing vinyl polymerization
reversible deactivation radical
(SCVP) 4, 524, 964–966, 986,
polymerization (RDRP,
1137
controlled radical
RAFT inimers
polymerization)
dithioesters 292–294
RAFT mechanism transformation 295 enzyme responsive 966
terminology 15–18 trithiocarbonates 430–432
R-group, see RAFT agent semi-batch RAFT polymerization 187,
Rhodixan A1, see methyl 2-((ethoxycarbon 188, 193–195, 206–208, 301,
othioyl)thio)propanoate 437–438, 509, 907, 1077–1078
ring closure reactions 520, 949 copolymerization 187, 188, 193–195,
ring-opening alkyne metathesis 206–208, 907
polymerization (ROAMP) 435 mathematical modeling 206–208, 907
RAFT mechanism transformation starved feed emulsion polymerization
-
(ROAMP-T-RAFT) 435 with dithioesters 301
ring-opening metathesis polymerization with macromonomer RAFT
(ROMP) 296, 434–435, 1077–1078
587–588, 708, 958–959, 962, 983 with trithiocarbonates 437–438
RAFT mechanism transformation with xanthates 437, 510
-
RAFT-T-ROMP 255, 296, 434–435 sequence controlled (SC) polymers 179,
-
ROMP-T-RAFT 296, 434–435 626, 628, 805, 816
1232 Index
sequence-defined (SD) polymers dimethyl carbonate (DMC) 114, 116,

discrete polymers 806 723
oligo(acrylate)s 810 N,N-dimethylformamide (DMF) 48,
oligomers 816 53, 409, 445, 577, 589, 615, 650,
shell-crosslinked (SCL) micelles 846 661–672, 721, 831, 834–835, 859,
shell-crosslinked nanoparticles 1009 913, 992, 996–997
shell-functional nanoparticles 712–723, dimethyl sulfoxide (DMSO) 46, 408,
950, 956 439, 577, 619, 620, 622, 624, 630,
silanes 445, 765–766, 863, 1021 631, 659
silica nanoparticles 723, 739, 1021, 1023, 1,4-dioxane 36, 43, 46, 47, 49, 50, 210,
1029, 1033–1034 295, 615, 652, 654, 686, 691, 731,
single unit monomer insertion (SUMI), 768, 837
see RAFT-single unit monomer ethanol 43, 126, 577, 615
insertion (RAFT-SUMI) ethyl acetate (EtOAc) 578
single-stranded DNA (ssDNA) 701 heptane (n-heptane) 719, 1059
size exclusion chromatography (SEC) methanol 50, 126, 615, 618
98, 101–102, 119, 201, 205, 511, N-methyl-2-pyrrolidone (NMP) 621
514, 590, 693, 695, 700, 726, 774, 2-propanol 443, 765
781–782, 786–787, 812–813, supercritical carbon dioxide (scCO2 )
937–938, 1055, 1057, see also gel 32, 195
permeation chromatography tetrahydrofuran (THF) 42, 43, 306,
(GPC) 445, 649
slow fragmentation 59, 76–77, 85–86, toluene 41, 120, 443, 444, 522, 578,
119–120, 123–126, 164, 167–171, 615, 618, 996–997
187, 203, 649, 670, 817, 935 water 32, 36, 37, 42, 48, 126, 516, see
sodium borohydride (NaBH4 ) 773, 783, also aqueous RAFT
791, 947 acetate buffer 45
sodium styrene-4-sulfonate, see 4-viny- phosphate buffered saline (PBS)
lbenzenesulfonate sodium salt 691–693, 695
sodium dodecyl sulfate (SDS) 36, 908 solvophilic macroRAFT agent 711–713,
sodium phenyl-2,4,6-trimethylbenzoyl 720, 726, 731
phosphinate (SPTP) 685–686, spherical micelles 516, 697–698, 726,
695–696 730, 735–736, 1041
sodium 4-vinylbenzenesulfonate, see squaric ester 3,4-diethoxycyclobut-3-
4-vinylbenzenesulfonate sodium ene-1,2-dione
salt in bioconjugation 791
solvents (for polymerization) stable radical-mediated polymerization
acetic acid 615 (SRMP) 755, see also
acetone 615 nitroxide-mediated radical
acetonitrile (MeCN) 40–41, 46, 51, 52, polymerization (NMP)
615, 996–997 stannanes 765–766
anisole 41 by-products 765
benzene 39, 52 star polymers 523, 950–956
chlorobenzene 52 applications 1002–1010
N,N-dimethylacetamide 40, 46 advanced materials 1007–1010
Index 1233
biomedical 1003–1004 solution polymerization 33–35

emulsion stabilization 1006–1007 RAFT agent selection 112, 113
classification of 955–956 rate coefficients for radical addition
compact nature 983 (ki , kp ) 107
controlled radical polymerization 983 selective initialization 108, 149–151,
core-crosslinked, see arm-first 292, 808, 809
(convergent) synthesis single unit monomer insertion (SUMI)
high throughput synthesis 630–631, 108, 808–810
1000 with dithiobenzoates
in-out stars 956 kinetics 76, 78, 81, 82, 91, 118–126
mikto-arm stars 951, 955, 956 RAFT agent stability 126
polymer libraries 630–631 with switchable RAFT agent 116–118
ring-opening metathesis polystyrene-block-poly(vinyl acetate)
polymerization (ROMP) 983 116
ring-opening polymerization (ROP) styrenic monomers (styrenes, styrenics)
983 34, 237, 239, 275, 277–278, 294,
synthesis 950–956, 985–1002
409, 417–418, 425, 555, 572, 575,
arm-first (convergent) synthesis
627–628, 807, 842, 843,
994–1002
1171–1172, see also
core-first (divergent) synthesis
4-chloromethylstyrene
630–631, 985–987
4-hydroxystyrene, styrene
grafting-to approach 1002
4-methylstyrene 2-vinylpyridine
R-connected core 988–991
4-vinylpyridine
Z-connected core 987–988
with dithiocarbamates 550, 556–566,
star-star coupling 80, 953–954, 987–988,
572, 575
990–991, 994–995
with dithioesters 234, 277–279
starved feed polymerization, see
aromatic dithioesters 241–247
semi-batch polymerization
aliphatic dithioesters 260–261
stimuli-responsive polymer brushes
1027–1030 RAFT agent selection 27–28, 112
stochastic modeling techniques (SMTs) with trithiocarbonates 368, 369,
204–206 417–419, 425
Monte Carlo 204–206 symmetric trithiocarbonates
strain-promoted alkyne cycloadditions 371–374
alkyne-functional RAFT agents non-symmetric trithiocarbonates
400–401 380–393
alkyne-nitrile oxide cycloaddition with xanthates 494, 496, 508, 530
(SPANOC) 848 styrene-4-sulfonate sodium salt, see
alkyne-nitrone cycloaddition (SPANC) 4-vinylbenzenesulfonate sodium
848 salt
azide-alkyne cycloaddition (SPAAC) N-substituted maleimides 817
400, 520, 634, 847, 848 N-substituted oligo(acrylamide)s 822
styrene (St) 33, 112, 648, 709, 759, 808 sugar moieties and amino acids 719–720
experimental procedures sulfur-fluoride exchange (SuFEx)
emulsion polymerization 36–37 chemistry 945
1234 Index
sulfur-free RAFT polymerization, see symmetrical trithiocarbonates 379, 408,

macromonomer RAFT 439, 879
polymerization synthetic metalloporphyrins 620
sulfur-free RAFT agents, see
macromonomer RAFT agents t
SUMI, see single unit monomer insertion t-butyl-, see under ‘B’
supercritical carbon dioxide (scCO2 ) 32, telechelic polymers 519–520, 524, 768,
187, 195, 211, 721, 898–904 1177, 1184
supramolecular block copolymers discrete decamers 813–814
947–948 hydroxyl copolymers 767
supramolecular interactions 734, 737, temperature-induced morphological
933, 947 transitions (TIMT) 735–736
surface-initiated photoiniferter-mediated templating agents 739
polymerization (SI-PIMP) 552 terephthaldicarboxaldehyde (TDA) 846
surface-initiated RAFT (SI-RAFT) 235, tert-butyl-, see t-butyl–indexed under ‘b’
379, 552, 649, 859, 861, tetrafunctional trithiocarbonate (4-TTC)
1019–1021, 1023, 1025, 993
1029–1031, 1033–1034, 1037, 5,10,15,20-tetraphenyl-21H,23H-porphine
1039, 1042, see also brush zinc (ZnTPP) 300, 617, 620,
architecture 628–631, 991, 1055
bioconjugation 1027–1030 tetraphenylporphyrin (TPP) 620–621,
brush architecture 1020–1027 667
bimodal molar mass 1020, 1021 thermal initiators 32, 194, 298–299, 436,
block copolymer 1020, 1022 504, 647, 684–685, 693, 809–810,
Janus 1020, 1022–1024 991
looped 1020, 1022 thermolysis 309–310, 444, 445, 525,
mixed composition (mikto-arm) 527–528, 590–591, 763–764, 953
1020 thiazine 613
patchy 1020, 1022 S-thiocarbamate 781
composites 1030–1039 2,2′ -(thiocarbonylbis(sulfanediyl))bis(2-
stimuli responsive brush 1027–1030 methylpropanoic acid)
surface/particle modification 859–864 (2-(1-carboxyl-1-methylethyl-
surfactant-free latexes 715–716, 740 sulfanylthiocarbonylsulfanyl)-
switchable RAFT agents 2, 30, 47, 51–52, 2-methylpropionic acid,
116–118, 132, 555, 567–571, S,S′ -bis(α,α′ -dimethyl-α′′ -acetic
583–585, 587, 591, 593, 764, 809, acid)-trithiocarbonate) 36–37,
935, 1053–1054, 1097, see also 46, 50, 371, 681, 684–685, 701
aryl(pyridin-4-yl)carbamodithi- aqueous RAFT polymerization 681,
oates, cyanomethyl methyl 684–685, 701
(pyridin-4-yl)carbamodithioate, experimental procedures
methyl(pyridin-4-yl)carbamodi- acrylamide in solution 46
thioates, methyl 2-((methyl N,N-dimethylacrylamide in solution
(pyridin-4-yl)carbamothioyl) 36
thio)propanoate, methyl poly(N,N-dimethylacrylamide)-block-
(pyridin-4-yl) carbamodithioates polystyrene by surfactant-free
Index 1235
emulsion polymerization transfer coefficient, see chain transfer

36–37 coefficient
poly[N-isopropylacrylamide-co- transition state theory
(sodium methacrylate)-co-N- standard 140–147
cyclohexylacrylamide] in variational 140, 146
solution 50 triazole-functional trithiocarbonates 759
functional derivatives 394–395 1,2,4-triazoline-3,5-dione (TAD) 771,
active ester 394 772, 845
protected maleimide 394 triazolinedione Alder-ene reaction
yne 395 772
polymerizations 371 triazolinedione-diene Diels Alder
thiol reaction 772
thiol-disulfide exchange 843 triblock copolymers, see ABA triblock
thiol-ene reaction 719, 775–776, copolymers, ABC triblock
840–841, 843 copolymers, BAB triblock
thiol-epoxy ring-opening 782–783 copolymers
thiol-halo substitution 783–786 tributylphosphine (PBu3 ) 773, 908
tributylstannane (Bu3 SnH) 443–444,
thiol-isocyanate reaction 780–782
529, 590, 765–766
thiol-methanethiosulfonate reaction
2,4,6-trichloro-1,3,5-triazine (TCT) 830,
305, 774, 789
840
thiol-Michael reaction 777, 779–780
triethylamine (Et3 N) 238, 621, 783, 834
thiol-para-fluorophenyl reaction 786
triethylene glycol dimethacrylate
thiol-terminated polystyrene 775
(TEGDMA) 288, 430, 432, 908
thiol-yne click copolymerization 776
trimethylaluminium (TMA) 859
thiolactones 843
(2,4,6-trimethylbenzoyl) diphenyl-
functional species 761
phosphine oxide (TPO)
-functionalized acrylamide monomers
685
(TLaAm) 843
trimethylsilyl propargyl methacrylate
-functionalized maleimide (TLaMI) (TMS-PgMA) 848–849
843 triphenylphosphine 739, 768, 850
-functionalized styrenic monomer 843 tris(2,2′ -bipyridyl)ruthenium(II) chloride
R-group functionalized RAFT agent (Ru(bpy)3 Cl2 ) 300, 618–619,
761 635, 689–691
thiolates 306, 661, 663, 763, 773, 777, 791 tris(2-carboxyethyl)phosphine (TCEP)
thiophenol 834, 1177 773, 781
thiourethane 781, 840–841 tris[2-(dimethylamino)ethyl]amine
thioxanthene 613 (Me6 TREN), see copper
thiuram disulfides 578–580, 590, 768, activators
1089, 1100 tris(2-phenylpyridine)iridium(III)
toluene 41, 49, 63–65, 69–76, 81–82, 85, ( fac-Ir(ppy)3 ) 300, 504, 612,
87–88, 90, 120, 201, 203–204, 617–619, 623, 627, 628, 1188
443, 615, 618, 765, 777, 859, 906, tris(2-pyridylmethyl)amine (TMPA), see
908–909, 996–997, 1006 copper activators
trans, trans-2,4-hexadien-1-ol 770 tris(trimethylsilyl)silanes 443, 765
1236 Index
trithiocarbonates (carbonotrithioates) functional trithiocarbonates 379,

72–77, 86, 130, 194, 226, 237, 394–407, 409
359–447, 614–615, 620, 624, 628, description 379, 407
661, 662, 753, 759, 775, 809, non-symmetric 396–407
817–820, 823, 935, 936, 1034, symmetric 394–395
1089, 1098, 1141, see also butyl group removal/transformation
2-(((dodecylthio)carbonothioyl) 439–446
thio)-2-methylpropanoate by oxidation 446, 447
4-(((2-carboxyethyl)thio)carbon- by radical-induced
othioyl)thio)-4-cyanopentanoic disproportionation 442–443
acid 3-((((1-carboxyethyl)thio) by radical-induced processes
carbonothioyl)thio)propanoic 439–442
acid 2-(((ethylthio)carbonothioyl) by radical-induced reduction
thio)-2-methylpropanoic acid 443–444
2-(((butylthio)carbonothioyl)thio) by reaction with nucleophiles 444,
propanoic acid (BTPA) 445
4-cyano-4-((phenylcarbonothioyl) by thermolysis 444, 445
thio)pentanoic acid homolytic leaving group (R) selection
2-cyanopropan-2-yl dodecyl 367–374, 380–393
carbonotrithioate, dibenzyl for block copolymer synthesis
carbonotrithioate (DBTTC) 369–370
2-(dodecylthiocarbonothioylthio)- for 1,1-disubsituted MAMs
2-methylpropionic acid (DDMAT) 368–369
2-(((dodecylthio)carbonothioyl) for IAMs and LAMs 369
thio)propanoic acid (DoPAT) for monosubstituted MAMs 369
2,2′ -(thiocarbonylbis(sulfane- industrial use 1098–1099, 1137
diyl))bis(2-methylpropanoic monomers, see also polymerizations
acid) acrylamides 415–417, 424–425
activating group (Z) selection 368, 370 acrylates 414–415, 424
ATRP initiator 405, 423, 435–436, 657 diene monomers 425
dibromotrithiocarbonate 657 1,1-disubstituted monomers 414
bis-trithiocarbonates 370, 376–378 methacrylamides 409, 413
R-connected 376–378 methacrylates 410–412
R (or Z)-connected 370, 378 monosubstituted monomers 425
chain transfer coefficients 362–367 macromonomers 426, 427
conjugates 379, 408 with reactive functionality
lysozyme 624 420–423, 426
crosslinking polymerization 428–430 styrenics 417–419, 425
multiolefinic monomers 429 vinyl monomers 419, 425
networks 428, 430 photoinitiation 436
stars, microgels 430 polymerizations
cyclopolymerization 426–428 bis-trithiocarbonates
emulsion/miniemulsion/dispersion R-connected 376–377
polymerization 437–438 Z-connected 375
Index 1237
non-symmetric trithiocarbonates v
380–393 vinyl acetate (VAc) 47, 105, 107, 114,
functional 394–407 117, 156–157, 164, 172, 175–176,
symmetric trithiocarbonates 179, 513, 549, 628, 712, 759, 760,
371–374 764, 808, 817, 842, 936, 945, 948,
functional 394–395 1053
publication statistics 360, 379 experimental procedure 47
ring-opening polymerization 428 rate coefficients for radical addition (ki ,
RAFT equilibrium coefficients 72–76, kp ) 107
366 with dithioesters 234
RAFT mechanism transformation vinyl amides 2, 27–28, 46–48, 359, 572,
-
cationic-T-,RAFT 435, 1187–1190 753, 806, 855, see also
-
RAFT-T-anionic 435 N-vinylcaprolactam, N-vinyl
-
RAFT-T-ATRP 435–436 monomers, N-vinyl-2-piperi-
-
RAFT-T-NMP 435 done, N-vinylpyrrolidone
-
RAFT-T-ROAMP 435 with dithiocarbamates 572
-
RAFT-T-ROMP 434–435 RAFT agent selection 27–28, 112
-
RAFT-T-ROP 434 with xanthates 502, 511–512
-
ROP-T-RAFT 434 vinyl benzoate 48, 242, 496, 510
-
ROMP-T-RAFT 434–435 experimental procedure 48
RAFT single-unit monomer insertion 4-vinylbenzaldehyde 244, 848, 1041
(RAFT SUMI) 430, 433 4-vinylbenzenesulfonate sodium salt,
RAFT mechanism 72–76, 359–362 (styrene-4-sulfonate sodium
symmetric trithiocarbonates 362 salt) 245, 248, 249, 258, 259,
non-symmetric trithiocarbonates 273, 679, 882
361 4-vinylbenzoic acid 389, 391, 884
reaction conditions and side-reactions NHS ester, see 2,5-dioxopyrrolidin-1-yl
438–439 4-vinylbenzoate
redox-initiated RAFT with 436–437 4-vinylbenzyl chloride (VBC), see
self-condensing vinyl polymerization 4-chloromethylstyrene
430–432 4-vinylbenzyl 1H-imidazole-4-
structural features of 360 carbodithioate 209–210, 294
synthesis of 408–409 mathematical modeling 209–210
triblock copolymer synthesis 370, 375, N-vinylcaprolactam 47, 506, 560, 564,
377 572, 712, 855
with dithiocarbamates 561, 564, 572
u with xanthates 494, 502, 506
ultra-high molecular weight (UHMW) N-vinylcarbazole 28, 47, 51, 116, 234,
polymers 509, 654, 992–994 278, 359, 368, 369, 426, 494, 495,
undecanoic acid 775 498, 499, 502, 511, 512, 516, 517,
urazole derivative 772 523, 549, 550, 554, 567, 569, 571,
urazole functional trithiocarbonate 572, 660, 1053–1054
(URZ-TTC) 772 with dithiocarbamates 549, 550, 554,
UV or visible light 504–505, 512, 614, 565, 569, 571, 572
617, 685 with dithioesters 234, 250, 278
1238 Index
N-vinylcarbazole (contd.) with dithiocarbamates 572, 576

experimental procedure 47 with xanthates 502–503, 511–512
with xanthates 494, 495, 498, 499, 502, O-vinyl monomers, see vinyl esters,
511, 512, 516, 517, 523 vinyl ethers
vinyl chloride (VC) 151, 179, 496, 503, P-vinyl monomers, see vinyl
513, 516 phosphonic acid
with dithiocarbamates 179, 564, 572 S-vinyl monomers 502, 510–511
with xanthates 496, 503, 513, 516 Si-vinyl monomers, see vinyl
2-vinyl-4,4-dimethylazlactone 46, 244, triethoxysilane
281, 824, 842 vinyl phosphonic acid (VPA) 508, 511,
copolymer 244, 842 516, 531
vinyl esters 2, 27–28, 46–48, 359, 501, N-vinylphthalimide 48, 249, 400, 503,
504, 508, 510, 531, 549, 572, 585, 512, 557, 572, 809
753, 806, 950, see also vinyl experimental procedure 48
acetate, vinyl benzoate with dithiocarbamates 557, 572
RAFT agent selection 27–28, 112 N-vinyl-2-piperidone 494, 502, 503, 512,
with dithiocarbamates 572 855
with xanthates 501, 508, 510 N-vinylpyrrolidone 28, 46–48, 116, 234,
vinyl ethers 936, 1172–1190 241, 245, 249, 278–280, 368, 504,
2-chloroethyl vinyl ether (CEVE) 506–508, 511–513, 515, 517, 520,
1182, 1183 523, 525, 530, 550, 557, 564,
dodecyl vinyl ether 775 567–569, 571, 572, 575, 583, 587,
ethyl vinyl ether 1182, 1183, 1186 591, 652, 693, 1053
2-ethoxyethyl vinyl ether (EOEVE) experimental procedure 48
1182, 1183, 1187 with dithiocarbamates 550, 557, 565,
isobutyl vinyl ether 1172, 1176, 1182, 567–569, 571, 572, 575, 583, 587,
1183, 1186 591
2-methoxyethyl vinyl ether 1181 with dithioesters 234, 241, 244, 249,
vinyl halides, see halo-olefins, vinyl 287
chloride with xanthates 504, 506–508, 511–513,
vinylidene chloride (VCl2) 245, 249, 250 515, 517, 520, 523, 525, 530
vinylidene fluoride (VF2) 494, 499, 503, vinyl triethoxysilane (VTES) 723
507, 512, 516, 518, 519, 531, 565 vinylbenzoyl chloride (VBzC) 839
with dithiocarbamates 565, 572 2-vinylpyridine 241, 248, 253, 256, 258,
with xanthates 494, 499, 503, 507, 512, 294, 304, 572, 583, 615, 649
516, 518, 519, 531 4-vinylpyridine 241, 247, 248, 250, 253,
vinyl imides 47, see also 294, 572, 722
N-vinylphthalimide vitamin B12 release profiles 905
vinyl monomers vitamin B2 (riboflavin)-riboflavin
N-vinyl monomers, see also vinyl 5′ -mononucleotide (FMN) 690
amides, N-vinylcarbazole, vitamin C, 695, see also ascorbic acid
N-vinylcaprolactam, vinyl
imides, N-vinylphthalimide, w
N-vinyl-2-piperidone, water soluble macroRAFT agent 680,
N-vinylpyrrolidone 686, 691, 696
Index 1239
water soluble RAFT agent 680 cyclic ketene acetals 513–514

water-soluble methacrylamide polymers diallyl monomers 514
838 ethylene 513
water-soluble trithiocarbonate 650, 652, methacrylates 509–510
654 styrenics 508
wavelength orthogonal polymerization vinyl esters 510
628–629 N-vinyl monomers 511–512
wormlike micelles 697 S-vinyl monomers 510–511
vinyl phosphonic acid 511
x polymerization conditions 506–507
xanthates (dithiocarbonates) 48, 69, 72, heterogeneous polymerization
112–114, 194, 198, 493, 507–508, 506–507
517, 520, 524, 650, 662, 753, 759, high pressure polymerization 506
936, 948, 1176–1177, 1187–1188, RAFT mechanism transformation
see also 2-((ethoxycarbonothioyl) -
cationic-T-,RAFT 1187–1190
thio)acetic acid, ethyl 2-((phen-
oxycarbonothioyl)thio)prop-
synthesis of 493, 494, 500
anoate 2-hydroxyethyl
xanthene dyes 623–625, 635
2-((ethoxycarbonothioyl)thio)-2-
xanthogen disulfides 500
methylpropanoate, methyl
xanthone 613
2-((ethoxycarbonothioyl)thio)
xyloglucan (XG) 720
propanoate
canonical forms 114
y
cationic RAFT polymerization
yne, see also alkyne
1176–1177, 1187–1188
ω-yne end-functional polymer 779
end-group removal 525–529
poly(N-isopropylacrylamide) 779
nucleophilic reaction 525–526
yne-functional monomer 279–280,
oxidation 526–527
radical-induced reduction 528–529 420, see also alkyne-functional
thermolysis 527–528 monomer, propargyl acrylate,
industrial applications 529–530 propargyl methacrylate
initiation 504–506 yne-functional trithiocarbonate 759
kinetics 507–508 2-cyano-5-oxo-5-(prop-2-yn-1-
macromolecular architectures ylamino)pentan-2-yl-dodecyl-
514–524 trithiocarbonate 760
block copolymers 516–519 yne-hydroxyl-functional
cyclic polymers 519–520 trithiocarbonate 780
end-functional polymers 515–516 yttrium(III) trifluoromethanesulfonate
gradient copolymers 519 (Y(OTf)3 ) 618
graft copolymers 520–521
hyperbranched polymers 524 z
star polymers 521–524 Z group, see also RAFT agent
mathematical modeling 194, 198 Z-connected bis-RAFT agents 879
monomers 508–514 zinc-iron oxide semiconductor
acrylates and acrylamides 508–509 (Zn0.64 Fe2.36 O4 ) 616
1240 Index
zinc(II) meso-tetra(N-methyl-4-pyridyl) zinc(II) (2,3,7,8,12,13,17,18-octaethyl-

porphine tetrachloride 5,10,15,20-tetraphenylporphyrin)
(ZnTPMPyP) 629, 691 (ZnOETPP) 621–622
zinc(II) tetraphenyl porphyrin (ZnTPP) zwitterionic pH-responsive copolymers
310, 617, 620, 628–630, 991, 1055 843
zinc(II) meso-tetra(4-sulfonatophenyl)
porphyrin) (ZnTPPS4- ) 621,
689, 691

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Methods, Synthesis and Applications

Methods, Synthesis and Applications

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1 Overview of RAFT Polymerization 1

2 Terminology in Reversible Deactivation Radical

3 How to Do a RAFT Polymerization 25

3.5 RAFT Polymerization of Methacrylates and Acrylates 37

4 Kinetics and Mechanism of RAFT Polymerizations 59

5 RAFT Polymerization: Mechanistic Considerations 95

5.2.1 Chain Transfer and Leaving Group Ability 96

6 Quantum Chemical Studies of RAFT Polymerization 139

7 Mathematical Modelling of RAFT Polymerization 187

7.2.1.1 Homogeneous Systems 190

8 Dithioesters in RAFT Polymerization 223

8.5.4 Monosubstituted IAMs and LAMs 279

9 Trithiocarbonates in RAFT Polymerization 359

9.21.4 Trithiocarbonate Group Removal by Reaction with Nucleophiles 444

10 Xanthates in RAFT Polymerization 493

10.3.1.4 Redox Initiation 505

10.7.1 Nucleophilic Reaction (Aminolysis/Hydrolysis/Ionic Reduction) 525

11 Dithiocarbamates in RAFT Polymerization 549

11.9.4 Dithiocarbamate Group Removal by Reaction with

12 Photo RAFT Polymerization 611

13 Redox-Initiated RAFT Polymerization and (Electro)chemical

14 Considerations for and Applications of Aqueous RAFT

15 RAFT-Mediated Polymerization-Induced Self-Assembly

16 RAFT-Functional End Groups: Installation and

17 Sequence-Encoded RAFT Oligomers and Polymers 805

18 Synthesis and Application of Reactive Polymers via RAFT

19 RAFT Crosslinking Polymerization 873

20 Complex Polymeric Architectures Synthesized through RAFT

21 Star Polymers by RAFT Polymerization 983

22 Surface and Particle Modiﬁcation via RAFT Polymerization: An

23 High-Throughput/High-Output Experimentation in RAFT

24 An Industrial History of RAFT Polymerization 1077

25 Cationic RAFT Polymerization 1171

1 Overview of RAFT Polymerization 1

2 Terminology in Reversible Deactivation Radical

3 How to Do a RAFT Polymerization 25

4 Kinetics and Mechanism of RAFT Polymerizations 59

5 RAFT Polymerization: Mechanistic Considerations 95

6 Quantum Chemical Studies of RAFT Polymerization 139

7 Mathematical Modelling of RAFT Polymerization 187

8 Dithioesters in RAFT Polymerization 223

9 Trithiocarbonates in RAFT Polymerization 359

10 Xanthates in RAFT Polymerization 493

11 Dithiocarbamates in RAFT Polymerization 549

12 Photo RAFT Polymerization 611

13 Redox-Initiated RAFT Polymerization and (Electro)chemical

14 Considerations for and Applications of Aqueous RAFT

14.4.2 Enzyme-Catalyzed Deoxygenation 691

15 RAFT-Mediated Polymerization-Induced Self-Assembly