Professional Documents
Culture Documents
Douglas Amato, Thesis
Douglas Amato, Thesis
Douglas Amato
Part I
Latent cysteine residues formed via RAFT
+ R' N 3
Cu(I)
N R'
Limitations
Require an external stimulus (DA & TE/TY) Require additional reagents (TE/TY) Goal - Develop Click chemistry that is biocompatible, nonreversible, and does not require an external stimulus to add new functionality to existing materials
4
Thiazolidine linkages
Reaction is simple
RAFT
Wide range of monomers Terminated with transfer agent Can reduce transfer agent to thiol functionality
Thiazolidine Prepolymer
Prepare a styrene-block-acrylonitrile copolymer
Polymer Synthesis
11
Coupling Experiments
13
14
Conditions : A) TA-1, RAFT; B) AN, RAFT; C) MTS, propyl amine; D) i TBABH4, THF, EtOH ii - DTT, isophthaldehyde
15
Polystyrene
16
PS-PAN
17
PS-PAN-S-S-CH3
18
Coupling
TA-1 and TA-3 showed best coupling, but not near ideal. TA-1 used for optimization due ease of synthesis
19
Potential Issues
Solvent Reaction time Dithiothreitol Basic solution
20
Dithiothreitol
Potassium Carbonate
New goal: synthesis of a single molecule that contains cysteine residue to attach to polymer
24
Part II
Latent small molecule cysteine residues
Goals
1. Design a molecule that contains a latent (i.e. protected) cysteine residue
26
27
Mesylate to thioacetate
29
New Approach
Start with cysteine and add protecting groups
Thia
30
1H
NMR
d
b a c Thia b c a d
31
Next step
Forma-thia
32
1H
NMR
thia
Forma thia
33
Solution
Use acid stable linkage such as amides
35
36
formathia
37
38
Routes
Synthesis of 4-vinylbenzyl amine:
39
a a
a a
40
41
NMR
42
43
NMR
44
45
Alternative synthesis
First attach propargyl amine
46
NMR
47
Evidence of reversibility
48
Conclusion
Latent cysteine residues derived from post-polymerization modification are possible, yet are not fully optimized. A facile, high yielding set of reactions have been found to produce a protected cysteine
Future Work
Attach alkyne protected cysteine to polymers with pendant azides Thiolene/yne chemistry with latent thiol residue in RAFT Creation of new materials with pendent cysteines.
50
Acknowledgements
Advisor: Dr. Philip Costanzo Thesis Committee:
Prof. Chad Immoos
Funding provided by an award from the Research Corporation for Science Advancement
51
Craig Machado
Miles Markmann Leanna Monteleone Chris Pattillo Dimitri Pappademos Alicia Ross Kim Varney Anthony Varni
52
53
54
Thank You
55