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Chiral Analysis

Advances in Spectroscopy,
Chromatography and
Emerging Methods
Second Edition

Edited by
PRASAD L. POLAVARAPU
Vanderbilt University, Nashville, TN, United States
Elsevier
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Chiral Analysis

Advances in Spectroscopy,
Chromatography and
Emerging Methods
Second Edition

Edited by
PRASAD L. POLAVARAPU
Vanderbilt University, Nashville, TN, United States
CONTENTS

List of Contributors xiii

Prefacexvii

Part One Chirality in Nature 1

1. Chiral Asymmetry in Nature 3

Dilip Kondepudi

1.1 Introduction3
1.2 Chirality: terminology and quantification issues 3
1.3 Chiral asymmetry in nature 10
1.4 Theory of spontaneous chiral symmetry breaking 15
1.5 Sensitivity of chiral symmetry breaking transitions to asymmetric
interactions19
1.6 Examples of spontaneous chiral symmetry breaking 22
1.7 Concluding remarks 25
References25

2. Remote Sensing of Homochirality: A Proxy for the Detection

of Extraterrestrial Life 29
C.H. Lucas Patty, Inge Loes ten Kate, William B. Sparks, Frans Snik

2.1 Introduction29
2.2 Homochirality30
2.3 Chemical and biological mechanisms for creating circular
spectropolarimetric signals 35
2.4 Considerations for the remote sensing of homochirality in our solar
system and beyond 45
2.5 Instrumentation50
2.6 Conclusion and outlook 60
References61

Part Two Spectroscopic Methods and Analyses 71

3. Light Polarization and Signal Processing in Chiroptical

Instrumentation73
Kenneth W. Busch, Marianna A. Busch

3.1 Introduction73
Part A—The polarization of light 73
3.2 Light as a wave 74

v
vi Contents

3.3 Types of polarized light 76

3.4 Production of linearly polarized light 81
3.5 Production of circularly polarized light 98
3.6 Production of elliptically polarized light 101
3.7 Photoelastic modulators 101
Part B—Signal handling 105
3.8 Noise in electrical circuits 105
3.9 Noise reduction strategies 108
3.10 Application of phase-sensitive detection in chiroptical instrumentation 123
Appendix A basic optics 126
Appendix B signal handling 136
References150

4. Chiroptical Spectroscopic Studies on Soft Aggregates

and Their Interactions 153
Vijay Raghavan, Prasad L. Polavarapu

4.1 Introduction153
4.2 OR studies 158
4.3 ECD studies 172
4.4 VCD studies 184
4.5 ROA studies 193
4.6 Summary195
References195

5. Vibrational Optical Activity in Chiral Analysis 201

Laurence A. Nafie, Rina K. Dukor

5.1 Introduction201
5.2 Definitions of VOA 204
5.3 Measurement of VOA 206
5.4 Theoretical basis of VOA 208
5.5 Calculation of VOA 214
5.6 Determination of AC 216
5.7 Determination of ee of multiple chiral species 226
5.8 VOA of solids and formulated products 235
5.9 Summary and conclusions 238
References239

6. Raman Optical Activity 249

Saeideh Ostovar pour, Laurence D. Barron, Shaun T. Mutter, Ewan W. Blanch

6.1 Fundamental principles 250

6.2 Experimental ROA studies 256
Contents vii

6.3 Enhancement of ROA signals 270

6.4 Recent ROA instrumentation developments 273
6.5 Computational modeling of ROA spectra 274
6.6 Concluding remarks: future opportunities 282
References284

7. Chiral Molecular Tools Powerful for the Preparation

of Enantiopure Compounds and Unambiguous Determination
of Their Absolute Configurations by X-Ray crystallography
and/or 1H NMR Diamagnetic Anisotropy 293
Nobuyuki Harada

7.1 Introduction293
7.2 Methodologies for determining AC and their evaluations 294
7.3 Methodologies for chiral synthesis and their evaluations 297
7.4 Camphorsultam dichlorophthalic acid, CSDP acid (−)-1,
and camphorsultam phthalic acid, CPS acid (−)-5, useful
for enantioresolution of alcohols by HPLC and determination
of their ACs by X-ray crystallography 299
7.5 A novel chiral molecular tool, 2-methoxy-2-(1-naphthyl)-propionic
acid {MαNP acid (s)-(+)-2}, useful for enantioresolution of alcohols
and determination of their ACs by the 1H nmr diamagnetic anisotropy
method312
7.6 Complementary use of CSDP acid (−)-1 and MαNP acid (s)-(+)-2
for enantioresolution of alcohols and determination of their ACs
by X-ray crystallographic and 1H nmr diamagnetic anisotropy
methods325
7.7 Conclusions338
References339

8. Chiroptical Probes for Determination of Absolute

Stereochemistry by Circular Dichroism Exciton Chirality
Method345
Kuwahara Shunsuke, Ikeda Mari, Habata Yoichi

8.1 Introduction345
8.2 A chiroptical probe for chiral resolution and determination
of the absolute configuration of aromatic alcohols 346
8.3 A chiroptical probe for determination of the absolute configuration
of primary amines 352
8.4 A chiroptical probe for chirality transcription and amplification
by the forming of [2]pseudorotaxanes 358
8.5 Conclusions363
References363
viii Contents

9. Chiral Analysis by NMR Spectroscopy: Chiral Solvating Agents 367

Federica Balzano, Gloria Uccello-Barretta, Federica Aiello

9.1 Introduction367
9.2 Low-molecular-weight csas 371
9.3 CSAs involving ion pairing processes 383
9.4 Molecular tweezer csas 389
9.5 Synthetic macrocycle csas 391
9.6 Cyclodextrins401
9.7 Natural products 406
9.8 Lyotropic chiral liquid crystals 408
9.9 Chiral sensing 409
9.10 Configurational assignments 409
9.11 Conclusions411
References412

10. Chiroptical Spectroscopy of Biofluids 429

Vladimír Setnička, Lucie Habartová

10.1 Introduction429
10.2 Blood and blood-based derivatives 430
10.3 Hen egg white 446
10.4 Vitreous humor 447
10.5 Urine447
10.6 Chiroclinics—chiroptical methods as diagnostic tools 452
10.7 Concluding remarks 459
References460

Part Three Chromatographic and Electromigration Methods 467

11. Chiral Gas Chromatography 469

Rahul A. Patil, Choyce A. Weatherly, Daniel W. Armstrong

11.1 Introduction469
11.2 Commercial stationary phases 471
11.3 Non-commercial stationary phases 490
11.4 Conclusions500
References500

12. Chiral Liquid Chromatography 507

Muhammad F. Wahab, Choyce A. Weatherly, Rahul A. Patil,
Daniel W. Armstrong

12.1 Introduction507
12.2 Historical background of chiral liquid chromatography 508
Contents ix

12.3 Interactions in chiral liquid chromatography 509

12.4 Chiral separations in liquid chromatography today 512
12.5 Salient features of chiral liquid chromatography 512
12.6 Major classes of modern chiral stationary phases (CSPs)
for liquid chromatography: the “α” of the resolution equation 515
12.7 Packing process of high-efficiency chiral phases (“N” in the resolution
equation)534
12.8 Method development in chiral LC (adjustment of “k” in the resolution
equation)535
12.9 Special detectors in liquid chiral chromatography 536
12.10 Recent developments in enhancing chiral resolution using
ultrahigh efficiency supports 539
12.11 Instrumental considerations for fast chiral LC 544
12.12 Future directions and developments in chiral liquid chromatography 558
References558

13. Enantioseparations by Capillary Electromigration Techniques 565

Bezhan Chankvetadze

13.1 Introduction565
13.2 Separation principle in chiral CE: electrophoretic or chromatographic? 566
13.3 Enantioseparations with charged and uncharged chiral selectors 567
13.4 Enantioselective and nonselective phenomena in chiral CEKC567
13.5 Similarities and differences between enantioseparations
by pressure-driven chromatography and CEKC569
13.6 Modes of enantioseparations in CEKC574
13.7 Chiral selectors 584
13.8 Selector–selectand interaction in chiral CE586
13.9 Mathematical models of CE enantioseparations 589
13.10 Enantioseparations in capillary electrochromatography 593
13.11 Future trends 600
References601

14. Recent Developments in Chiral Separations by Supercritical

Fluid Chromatography 607
Roberta Franzini, Alessia Ciogli, Francesco Gasparrini, Omar H. Ismail,
Claudio Villani

14.1 Introduction607
14.2 Chiral stationary phases for SFC610
14.3 Analytical separations 612
14.4 Ultrafast high-efficient SFC separations 618
14.5 Conclusions626
References626
x Contents

15. Chiral Separation Strategies in Mass Spectrometry: Integration

of Chromatography, Electrophoresis, and Gas-Phase Mobility 631
James N. Dodds, Jody C. May, John A. McLean

15.1 Introduction631
15.2 Chromatography and mass spectrometry 633
15.3 Liquid chromatography 635
15.4 Electrophoresis–mass spectrometry 637
15.5 Isomer separations by IM-MS 640
15.6 Conclusions643
References644

Part Four Emerging Methods 647

16. Cavity-based Chiral Polarimetry 649

Dimitris Sofikitis, George E. Katsoprinakis, Alexandros K. Spiliotis,
T. Peter Rakitzis

16.1 Introduction649
16.2 Optical activity 650
16.3 Single-pass polarimetry 652
16.4 Cavity ring-down polarimetry 654
16.5 Cavity ring-down polarimetry with signal reversals 660
16.6 Continuous-wave cavity-enhanced polarimetry with signal reversals 672
16.7 Future outlook and conclusions 675
References676

17. Quantitative Chiral Analysis by Molecular Rotational

Spectroscopy679
Brooks H. Pate, Luca Evangelisti, Walther Caminati, Yunjie Xu,
Javix Thomas, David Patterson, Cristobal Perez, Melanie Schnell

17.1 Introduction679
17.2 Basic principles of molecular rotational spectroscopy 682
17.3 Chiral tag rotational spectroscopy for enantiomer analysis 698
17.4 Three-wave mixing rotational spectroscopy for enantiomer analysis 714
17.5 Conclusions723
References725

18. Chiral Rotational Spectroscopy 731

Robert P. Cameron, Jörg B. Götte, Stephen M. Barnett

18.1 Introduction731
18.2 Chiral rotational spectroscopy 732
Contents xi

18.3 Chiral rotational spectra 734

18.4 Chiral rotational spectrometer 743
References747

19. Chiral Analysis and Separation Using Molecular Rotation 753

Mirianas Chachisvilis

19.1 Introduction753
19.2 Chiral separations in SFs754
19.3 Chiral separations in REFs762
19.4 Summary776
References776

Index779
LIST OF CONTRIBUTORS

Federica Aiello
University of Pisa, Pisa, Italy
Daniel W. Armstrong
Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington,TX,
United States
Federica Balzano
University of Pisa, Pisa, Italy
Stephen M. Barnett
University of Strathclyde, Glasgow, United Kingdom
Laurence D. Barron
University of Glasgow, Glasgow, United Kingdom
Ewan W. Blanch
RMIT University, Melbourne,Vic., Australia
Kenneth W. Busch
Baylor University, Waco, TX, United States
Marianna A. Busch
Baylor University, Waco, TX, United States
Robert P. Cameron
University of Strathclyde; University of Glasgow, Glasgow, United Kingdom; Max Planck
Institute for the Physics of Complex Systems, Dresden, Germany
Walther Caminati
Department of Chemistry “Giacomo Ciamician”, University of Bologna, Bologna, Italy
Mirianas Chachisvilis
Solvexa LLC, Keswick, CT, San Diego, CA, United States
Bezhan Chankvetadze
Tbilisi State University, Tbilisi, Georgia
Alessia Ciogli
Sapienza University of Rome, Rome, Italy
James N. Dodds
Vanderbilt University, Nashville, TN, United States
Rina K. Dukor
BioTools, Inc., Jupiter, FL, United States
Luca Evangelisti
Department of Chemistry “Giacomo Ciamician”, University of Bologna, Bologna, Italy

xiii
xiv List of Contributors

Roberta Franzini
Sapienza University of Rome, Rome, Italy
Francesco Gasparrini
Sapienza University of Rome, Rome, Italy
Jörg B. Götte
University of Strathclyde; University of Glasgow, Glasgow, United Kingdom; Nanjing
University, Nanjing, China
Lucie Habartová
University of Chemistry and Technology Prague, Prague, Czech Republic
Nobuyuki Harada
Tohoku University, Sendai, Japan
Omar H. Ismail
Sapienza University of Rome, Rome, Italy
Inge Loes ten Kate
Utrecht University, Utrecht, The Netherlands
George E. Katsoprinakis
IESL-FORTH; University of Crete, Heraklion-Crete, Greece
Dilip Kondepudi
Wake Forest University, Winston-Salem, NC, United States
Ikeda Mari
Department of Chemistry, Education Center, Faculty of Engineering, Chiba Institute of
Technology, Chiba, Japan
Jody C. May
Vanderbilt University, Nashville, TN, United States
John A. McLean
Vanderbilt University, Nashville, TN, United States
Shaun T. Mutter
Cardiff University, Cardiff, United Kingdom
Laurence A. Nafie
Syracuse University, Syracuse, New York, NY; BioTools, Inc., Jupiter, FL, United States
Saeideh Ostovar pour
RMIT University, Melbourne,Vic., Australia
Brooks H. Pate
Department of Chemistry, University of Virginia, Charlottesville,VA, United States
Rahul A. Patil
Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington,TX,
United States
List of Contributors xv

David Patterson
Department of Physics, University of California Santa Barbara, Santa Barbara, CA,
United States
C.H. Lucas Patty
Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Cristobal Perez
Max Planck Institute for the Structure and Dynamics of Matter, Hamburg, Germany
Prasad L. Polavarapu
Vanderbilt University, Nashville, TN, United States
Vijay Raghavan
Vanderbilt University, Nashville, TN, United States
T. Peter Rakitzis
IESL-FORTH; University of Crete, Heraklion-Crete, Greece
Melanie Schnell
Max Planck Institute for the Structure and Dynamics of Matter, Hamburg, Germany
Vladimír Setnička
University of Chemistry and Technology Prague, Prague, Czech Republic
Kuwahara Shunsuke
Department of Chemistry, Faculty of Science, Toho University; Research Center for
Materials with Integrated Properties, Toho University, Chiba, Japan
Frans Snik
Leiden University, Leiden, The Netherlands
Dimitris Sofikitis
IESL-FORTH; University of Crete, Heraklion-Crete, Greece
William B. Sparks
Space Telescope Science Institute, Baltimore, MD, United States
Alexandros K. Spiliotis
IESL-FORTH; University of Crete, Heraklion-Crete, Greece
Javix Thomas
Department of Chemistry, University of Alberta, Edmonton, AB, Canada
Gloria Uccello-Barretta
University of Pisa, Pisa, Italy
Claudio Villani
Sapienza University of Rome, Rome, Italy
Muhammad F. Wahab
Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington,TX,
United States
xvi List of Contributors

Choyce A. Weatherly
Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington,TX,
United States
Yunjie Xu
Department of Chemistry, University of Alberta, Edmonton, AB, Canada
Habata Yoichi
Department of Chemistry, Faculty of Science, Toho University; Research Center for
Materials with Integrated Properties, Toho University, Chiba, Japan
PREFACE

The subject of chirality spans different disciplines and has become a focal
point for the discussion on its role in the origin of life.The ubiquitous pres-
ence of chirality that drives the sustenance of life on this planet raises the
specter of the potential for its presence outside of this planet and for the
existence of extraterrestrial life. These fundamental topics render chirality
an important role for scientific curiosity and investigations. Modern drug
development and pharmaceutical research are heavily influenced by the
role of chirality in their respective goals. Separations of the enantiomers
of chiral compounds, distinguishing among diastereomers, determining the
three dimensional structures of chiral molecules are the topics that domi-
nate natural sciences today and are broadly categorized under the banner
of Chiral Analysis.
The first edition of Chiral Analysis, edited by Kenneth Busch and Mari-
anna Busch, appeared in 2006 describing the current-state-of research at
that time. As fundamental science undergoes never-ending development,
one finds 12 years later, that the then existing methods have undergone
major refinements and several new methods have come into practice. For
active researchers, it is important to stay informed of these developments.
Therefore, the purpose of this second edition is to update the then existing
methods as well as to describe the newly developed methods.
This book is divided into four sections. The first section, Chirality in
Nature, contains two chapters. The first chapter has been updated from the
first edition. The second chapter is newly written and presents state of the
art in remote sensing of homo chirality. The second section, Spectroscopic
Methods and Analyses, presents eight chapters on different chiroptical spec-
troscopic methods. Among these, Chapters 3, 5, 6 and 8 are updated ver-
sions from the first edition, while the others, namely, Chapters 4, 7, 9 and
10 are newly written. The third section, Chromatographic and Electromi-
gration Methods, provides state of the art in chromatographic chiral sepa-
rations in five different chapters. All these five chapters are newly written.
The fourth section, Emerging Methods, contains four new chapters that
describe newly emerged methods in recent years, each describing a new
independent method with novel applications.

xvii
xviii Preface

This book is intended to serve as a guide for those interested in chiral

analysis. Graduate students as well as scientific professionals pursuing chiral-
ity in physical chemistry, analytical chemistry, organic chemistry, biology
and pharmaceutical research will find the relevant topics needed to pursue
their independent research. In addition, researchers interested in chirality, as
well as seasoned practitioners in this area, will find the chapters written by
leading experts in their respective areas, a valuable resource.
I would like to thank all of the authors of the chapters in this volume for
their dedication and willingness in deciphering their scientific innovations
to wider scientific community and for their cooperation throughout this
project.Without assistance from these dedicated scientists this volume could
not have been produced. Finally, I thank Kathryn Morrissey, Acquisitions
Editor at Elsevier, for reaching out to me to undertake this book project.

Prasad L. Polavarapu
Vanderbilt University, Nashville, TN, United States
 PART ONE

Chirality in Nature
 CHAPTER 1

Chiral Asymmetry in Nature

Dilip Kondepudi
Wake Forest University, Winston-Salem, NC, United States

1.1 INTRODUCTION
The wide-ranging chiral asymmetry in nature has given rise to a
multidisciplinary interest in chirality. It is remarkable that nature does not
exhibit left–right symmetry at any level: morphological, molecular, and
even at the most fundamental level of elementary particle interactions
[1–3]. At the astronomical level, circularly polarized light has been found in
Orion Nebula [4], indicating the existence of large regions of space with
asymmetry.
Chiral asymmetry in biomolecules—the predominance of l-amino ac-
ids and d-sugars—has profound consequences for pharmaceutical and ag-
ricultural chemistry. It necessitates us to develop a theoretical framework in
which we can quantitatively study chirality and study processes that gener-
ate chiral asymmetry. In this chapter, we will discuss the basic definitions
and nomenclature used to describe chiral systems. This will be followed by
a brief survey of known chiral asymmetries in nature and questions they
raise.We will then present a general theory of spontaneous chiral symmetry
breaking and discuss examples of spontaneous generation of asymmetry.

1.2 CHIRALITY: TERMINOLOGY AND

QUANTIFICATION ISSUES
When an object is not identical to its mirror image, it is said to be
“chiral”. Lord Kelvin, who introduced this terminology, defined it thus:
“I call any geometrical figure, or any group of points, chiral, and say it has
chirality, if its image in a plane mirror, ideally realized, cannot be brought
to coincide with itself ” [5]. A chiral object or a geometrical figure and its
mirror image are thus distinguishable and they could be simply identified
as “left-handed” or “right-handed”, a terminology that can readily be un-
derstood because we are asymmetric in the use of our hands. But there is
a subtle issue here: how do you specify what we mean by a “left-handed

Chiral Analysis. http://dx.doi.org/10.1016/B978-0-444-64027-7.00001-X

Copyright © 2018 Elsevier B.V. All rights reserved. 3
4 Dilip Kondepudi

Figure 1.1 Examples of basic chiral units. All complex objects can be reduced to a set of
basic chiral units. As shown in the lower part, every basic chiral unit can be associated
with a directed circle and a vector which together define a right- or left-handed helix.

object” to the one who does not know what it is, say to a being on a dis-
tant planet? Could we send this information as a radio signal coded as a
sequence of digits (“0” and “1”)? The answer to this question turns out to
be negative; it is not possible to specify what one means by “left” or “right”
in a linear sequence of digits. A three-dimensional object or a chirally asym-
metric phenomenon in nature is needed to specify this information [6–8].
While Kelvin’s definition clearly identifies chiral object, we often have
a need to distinguish between a simple chiral object, such as a tetrahedral
molecule with four different atoms, and a complex chiral object, such as a
protein. To describe chirality of assemblies of simple achiral building blocks,
we may define a basic chiral unit as an object that cannot be divided into two
or more chiral objects; any disassembly of such a unit will result in achiral
subunits. Some examples of basic chiral units are shown in Fig. 1.1. Ac-
cording to this definition, a helix made of a continuous line segment is not
a basic chiral unit; however, a helical assembly of sphere consisting of four
spheres is a basic chiral unit. All basic chiral units can be associated with a
direction of rotation and an arrow that together define a helix as shown
in Fig. 1.1. (In certain situations, one might identify the direction of rota-
tion with an axial vector, while the arrow is a vector. The combination of
Chiral Asymmetry in Nature 5

a vector and an axial vector defines chirality.) Through such association, we

can specify the absolute configuration of all basic chiral units. The chiral-
ity of a large assembly of simple achiral units has to be described in terms
of chirality of such basic chiral units. We will discuss more about this point
later in this chapter.

1.2.1 Cahn–Ingold–Prelog classification of chiral molecules

In the case of chiral molecules, a system of rules that identifies the absolute
structure of the two enantiomers as R (Rectus, Latin word for “right”) and
S (Sinister, Latin word for “left”) was proposed by Cahn et al. [9]. These
rules have been adopted by IUPAC.The two molecular structures are called
enantiomers of a chiral molecule. This designation is particularly suited for
chiral organic molecules in which a carbon is bonded to four different
atoms or groups, R1, R2, R3, and R4 as shown in Fig. 1.2. Each of the
four groups bonded to the carbon are ranked by the atomic number of the
atom directly bonded to the carbon, higher atomic number corresponding
to a higher rank. If two or more atoms have the same atomic number, then
other atoms in each group’s chain are compared until a difference is found.
If all the atomic numbers are the same, then atomic masses are used instead

Figure 1.2 An example of R-enantiomer in accordance with Cahn–Ingold–Prelog rules.

The four groups, R1–R4, attached to the central carbon are ranked, R1 > R2 > R3 > R4.
Pointing the lowest ranked group away from the viewer, the clockwise rotation
R1 → R2 → R3, defines the molecule as R-enantiomer. If the rotation is in the counter-
clockwise direction, then it is a S-enantiomer.
6 Dilip Kondepudi

for ranking the groups. Thus, a CH3 has a lower rank than CH2OH or
CH2CH3; similarly, the isotope D has a higher ranking than H. In Fig. 1.2,
the ranking is assumed to be R1 > R2 > R3 > R4. For such a molecule,
the “arrow” is defined as that pointing from the central carbon to the group
with the lowest rank, R4. The rotation direction is obtained from the three
highest ranking groups by moving from the highest to the lowest ranking
group, that is, R1 → R2 → R3. If this rotation and the arrow define a right-
handed helix, the molecule is classified as R; if the helix is left-handed, the
molecule is classified as S. It is possible that the two of the four groups, say
R1 and R2, are stereoisomers. In that case, the Cahn–Ingold–Prelog rules
specify a precise way of ranking the two groups. These rules may be found
in Ref. [9].
Before the Cahn–Ingold–Prelog rules were formulated, the terminology
for identifying the two enantiomers of a chiral molecule was based on opti-
cal rotation. Linearly polarized light of a particular wavelength undergoes
a rotation as it propagates through a solution or a crystal of a chiral com-
pound. A solution or solid that rotates linearly polarized light is said to be
optically active. In fact, the discovery of optical activity by the physicist Biot
in 1815 and Louis Pasteur’s insight that it was related to molecular asym-
metry gave us a general means to identify enantiomers. Consequently, the
handedness of a molecule was identified by its optical activity. If the light
was rotated clockwise as it approaches the viewer (Fig. 1.3), the solution
was designated “dextro-rotatory” or “+” and the enantiomer causing such a
rotation was called d-enantiomer; if the light rotated counter-clockwise, the
rotation was called “levo-rotatory” or “−” and the corresponding enantiomer
is called l-enantiomer. This designation does not give us the absolute mo-
lecular structure, that is, one cannot say which one of the two mirror-image
structures of the molecule gives rise to the observed optical rotation. In
fact, the optical rotation for a given compound depends on the wavelength
of the light and it can be dextro at one wavelength and levo at another.

Figure 1.3 Optical activity is the rotation of linearly polarized light as it passes through
the sample. As shown in the figure, if the direction of polarization rotates clockwise as
it approaches the viewer, the substance is dextro-rotatory and is designated “d” or “+”. If
the rotation is in counter-clockwise direction, the substance is levo-rotatory or “l”. or “−”.
Optical activity arises when the refractive indices of left- and right-circularly polarized
light are unequal.
Chiral Asymmetry in Nature 7

Figure 1.4 The terminology “l- and d-amino acids” refers to the geometric structure as
shown. Solutions of l-amino acids can be levo- or dextro-rotatory.

In addition, for a given wavelength, the direction of rotation can change

with the solvent. Clearly the designation “R and S” specifies the molecular
structure more precisely and it is preferred over the “l and d” designation.
Since optical activity is readily measured and often used to analyze chiral
products of a reaction, if the optical activity of enantiomer is known, it is
specified by combining the R–S and l–d notation; thus R(–) indicates that
the R-enantiomer is levo-rotatory.
In addition to the R–S designation, another designation that is also used
in the context of amino acids and sugars identifies the enantiomers as l and
d, which in the case of sugars is tied to the designation given to glyceralde-
hyde. This designation refers to the absolute structure as shown in Fig. 1.4.
This designation is independent of the side chain and hence all l-amino
acids have a similar basic structure. However, depending on the side chain,
an l-amino acid may be designated R or S, a point that needs to be noted
when using the R/S designation for the biologically dominant l-amino
acids.

1.2.2 Optical rotation

The angle through which linearly polarized light is rotated, that is, the opti-
cal rotation, is usually denoted by α. Optical rotation is due to the difference
in the refractive indices of right- and left-circularly polarized light. Linearly
polarized light may be considered as a combination of the right- and left-
circularly polarized light, that is, linearly polarized light may be resolved
into right- and left-circularly polarized components. If the two compo-
nents travel at different speeds, the resultant linear polarization undergoes a
rotation. If nR and nL are the refractive indices of right- and left-circularly
8 Dilip Kondepudi

polarized light, respectively, for light of wavelength λ, traversing a path in a

chiral medium of length l, the optical rotation α is given by
πl
α= (n − nR ) (1.1)
λ L
In most practical situations, to a good approximation, optical activity of
a solution is directly proportional to its concentration and the path length
(length of the polarimeter tube). In addition, α also depends on the wave-
length, the solvent, and the temperature. Consequently, specific rotation,
[α], of light of wavelength λ, at a temperature T is defined as
λ
[α ]Tλ = (1.2)
lc
in which c is the concentration in g/mL and l is the path length in decimeters.

1.2.3 Enantiomeric excess

Optical activity of a solution is proportional to the difference in the amounts
of the two enantiomers. This difference, which is a measure of the chiral
asymmetry of the systems, is often quantified in terms of enantiomeric excess
(EE), which is defined as
|[ R ] − [S ]|
Enantiometric Excess= (1.3)
([ R ] + [S ])

in which [R] and [S] are the concentrations of the two enantiomers. It is a
measure of asymmetry relative to the total amount of the substance, not an ab-
solute measure of the difference in the amount of R and S. As we shall see be-
low, in formulating a general theory of spontaneous chiral symmetry breaking,
the difference ([R] − [S]) is mathematically more convenient to use than EE.

1.2.4 Crystal enantiomeric excess

In nucleation of chiral crystals, asymmetries can arise due to chirally auto-
catalytic processes. In this case, the asymmetry is due to the difference in
the number of levo- and dextro-rotatory crystals. For this reason, one might
define a crystal enantiomeric excess (CEE) as
Nl − Nd
CEE = (1.4)
Nl + Nd
Chiral Asymmetry in Nature 9

in which Nl and Nd are the number of levo- and dextro-rotatory crystals.

This quantity measures the asymmetry in nucleation, not in the total num-
ber of molecules.

1.2.5 Chirality measures

When we look at chiral objects, we often have a sense that one is “more
chiral” than another. This notion could be intrinsic to the chiral objects
themselves or in their interaction with other chiral objects. For example,
when we compare two molecules that are in the shape of a twisted H, one
could say the one with the larger twist angle is “more chiral”, which is a
measure intrinsic to the object.The specific rotation for a given wavelength
and other well-specified conditions, a measure not intrinsic to the object,
could be used to compare the chirality of molecules, the molecules with
larger rotation being “more chiral”.
It is desirable to have the measure be such that: (i) the value of the chiral-
ity measure changes continuously with the shape of the object and is equal
in magnitude but opposite in sign for enantiomers, (ii) the chirality measure
is zero if and only if the object is achiral. It turns out that it is impossible to
define a universal measure with these two properties! This is because enan-
tiomers of certain chiral objects can be transformed from one to the other
through a series of states which are all chiral—just as a left-hand glove can
be transformed to a right-hand glove by turning it inside out one finger at
a time. Examples of such transformations were noted by Mislow [10,11].
Molecules in which such a transformation can be realized are called “mo-
lecular gloves”. During such a transformation, the corresponding chirality
measure has to change continuously from positive to negative (or vice ver-
sa) and hence must cross zero.The transformation, however, consists entirely
of chiral states. Hence, there must be a chiral state whose chirality measure is
zero, contrary to the requirement (ii). If an R-enantiomer of a molecule can
be transformed into an S-enantiomer through intermediate states which are
all chiral, it means there is no well-defined achiral state at which the change
from R to S occurs; hence the point at which the change in designation is
made is arbitrary: the notion of “left” and “right” cannot be made absolute.
Avoiding the ambiguity that arises with the sign of a chirality measure,
the intrinsic chirality of an object can be viewed, for example, in terms of
how different the two enantiomers are from each other. In this regard, sev-
eral measures have been proposed [12–17]. Buda et al. [13] define a degree
of chirality as: “the value of a real-valued, continuous function that is zero if
and only if the object is achiral. The degree of chirality is the measure of
10 Dilip Kondepudi

an absolute quantity and its value is therefore the same for both enantio-
morphs of the measure object”. An example of the degree of chirality is the
maximum amount of overlap between a chiral object and its enantiomer.
Clearly, in this measure, the degree of all achiral objects is zero and all chiral
objects is nonzero.
Only chiral objects can distinguish between the enantiomers of a chiral
molecule. Could we not define a measure of chirality on the basis of in-
teraction of reference chiral object with all chiral molecules? For example,
could we take optical rotation (at specified wavelength, temperature, and
other conditions) as a measure of chirality? This approach too has difficul-
ties because there are some chiral molecules [11] whose optical activity
is for all practical purposes immeasurable and there is no simple, reliable,
theoretical way to predict what it would be. Furthermore, a molecule that
is classified as “left-handed” on the basis of optical rotation with one achiral
solvent, may have to be classified as “right-handed” with another achiral
solvent which indicates that this notion of “left” and “right”, derived from
the interaction of the molecule with right- and left-circularly polarized
photons of a particular wavelength, is also dependent on the environment
and somewhat arbitrary.
Though there is no universal measure of chirality, it must be noted that
there are situations in which quantifying chirality could be extremely useful
in organizing and understanding chiral interactions [18–20].

1.3 CHIRAL ASYMMETRY IN NATURE

That nature does not treat “left” and “right” equally is not only re-
markable, but also puzzling because the fundamental laws have a high de-
gree of symmetry in many respects. All basic laws of physics are invariant
under translations in space and time and rotations in space. Electromag-
netic phenomenon is also invariant under mirror reflection, more precisely,
parity (which is equivalent to mirror reflection and a rotation). But other
fundamental interactions, at the nuclear level, are not invariant under par-
ity. In this section, we will briefly survey the chiral asymmetries found at
various levels of scale, from the nuclear level to the level of morphology of
mammals.

1.3.1 Asymmetry in nuclear processes

Chiral asymmetry in nuclear processes responsible for β-radioactivity was
discovered in 1957 by Wu [21]. Some unstable nuclei “decay” to a lower
Chiral Asymmetry in Nature 11

state of energy by emitting electrons or positrons, also called β-particles.

The isotope of cobalt, cobalt-60, for example, emits electrons. The nucleus
of cobalt-60 has spin, but a stationary particle with a spin is not chiral; it
does not possess handedness unless there is a direction associated with spin
that could be used to define chirality. (In identifying the “north pole” using
the right hand, we are imposing the chirality of the hand on the spinning
sphere; a stationary spinning object is not chiral.) If there is an additional
direction associated with a static spinning object, however, one could define
left and right. In the case of radioactivity in cobalt-60, when the nuclei are
placed in a magnetic field, their spin axes line up along the magnetic field.
In cobalt-60, nuclei aligned in a magnetic field, more electrons were emit-
ted from one of the two hemispheres, thus indicating the handedness of this
phenomenon. If the two hemispheres of a spinning sphere are not identical,
then that object is chiral because the lack of identity of the two hemispheres
could be used to define a direction, which along with the rotation defines
a helix.
Further studies of β-radioactivity revealed that the emitted electrons
themselves exhibit asymmetry. Since electrons have spin, one can associate
left- or right-helicity to each electron by projecting its momentum vector
along the spin axis. It was found that the electrons emitted by radioactive
nuclei are predominantly left-helical. Chiral asymmetry in β-radioactivity
appears in other ways as well.The emission of β-particles is accompanied by
the emission of elusive particles called the neutrinos, which also have spin.
All neutrinos generated in β-radioactivity are left-helical and antineutrinos
are right-helical. Neither right-helical neutrinos nor left-helical antineu-
trinos have been detected; they are presumed not to exist. If there were
equal number left-helical neutrinos and right-helical anti-neutrinos then
we might say that left–right symmetry is restored, but this would require a
balance between matter and antimatter. As far as we can tell, there is matter
in the universe but not antimatter.The consequence is that present universe
is filled exclusively with left-helical neutrinos.

1.3.2 Asymmetry in atoms

We now move from the level of the nucleus to the level of the atom.
Before the forces that held the particles in the atomic nucleus were dis-
covered, physicists knew two fundamental forces in nature: gravity and
electromagnetism. With the discovery of the nucleus, in which positively
charged protons and uncharged neutrons were held together, new forces
came to light. Soon after, studies in nuclear physics showed that there were
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moment, listening; everything was quiet. I eased it open and stepped
onto the ramp inside the building. In the gloom, polished mahogany
and chrome-work threw back muted highlights. I circled, slipped the
mooring rope, and was about to step into the cockpit when I heard
the bolt of a rifle snick home. I whirled, threw myself flat. The
deafening bam of a 30 calibre fired at close quarters laid a pattern of
fine ripples on the black water. I rolled, hit with a splash that drowned
a second shot, and dove deep. Three strokes took me under the
door, out into the green gloom of open water. I hugged the yellowish
sand of the bottom, angled off to the right, and kept going.
I had to get out of my jacket, and somehow I managed it, almost
without losing a stroke. And there went all the goodies I'd stashed
away in the pockets, down to the bottom of the drink. I still had the
memory-trace in my slacks. I managed thirty strokes before having to
surface. I got half a gulp of fresh air before the shot slapped spray
into my face and echoed off across the water. I sank like a stone,
kicked off, and made another twenty-five yards before I had to come
up. The rifleman was faster this time. The bullet creased my shoulder
like a hot iron, and I was under water again. My kick-work was weak
now; the strength was draining from my arms fast. I had to have air.
My chest was on fire and there was a whirling blackness all around
me. I felt consciousness fading....
As from a distance I observed the clumsy efforts of the swimmer,
watched the flounderings of the poor, untrained creature.... It was
apparent that an override of the autonomic system was required. With
dispatch I activated cortical area omicron, rerouted the blood supply,
drew an emergency oxygen source from stored fats, diverting the
necessary energy to break the molecular bonds.
Now, with the body drawing on internal sources, ample for six
hundred seconds at maximum demand, I stimulated areas upsilon
and mu. I channeled full survival-level energy to the muscle
complexes involved, increased power output to full skeletal tolerance,
eliminated waste motion.
The body drove through the water with the fluid grace of a sea-
denizen....

I floated on my back, breathing in great surges of cool air and blinking

at the crimson sky. I had been under water, a few yards from shore,
drowning. Then there was an awareness, like a voice, telling me what
to do. From out of the mass of Vallonian knowledge I had acquired, I
had drawn what I needed. And now I was here, half a mile from the
beach, winded but intact. I felt beat and hungry, but I had to keep my
mind on the problem of getting to the mainland. It was a fifteen-mile
swim, but if the boys on shore could keep each other occupied, I
ought to be able to make it. The full moon would make steering easy.
And the first thing I would do when I got out of this would be to order
the biggest, rarest steak in South America.

CHAPTER XI
I sat at the kitchen table in Margareta's Lima apartment and gnawed
the last few shreds off the stripped T-bone, while she poured me
another cup of coffee.
"Now tell me about it," she said. "You say they burned your house,
but why? And how did you get here?"
"They got so interested in the fight, they lost their heads," I said.
"That's the only explanation I can think of. I figured they'd go to some
pains to avoid damaging me. I guessed wrong."
"But your own people...."
"Maybe they were right: they couldn't afford to let the Russkis get
me."
"But how did you get covered with mud? And the blood stains on your
back?"
"I had a nice long swim: five hours' worth. Then another hour getting
through a mangrove swamp. Lucky I had a moon. Then a three-hour
hike...."
"You'd better get some sleep," said Margareta. "What do you want me
to do?"
"Get me some clothes," I said. "A grey suit, white shirt, black tie and
shoes. And go to my bank and draw some money, say five thousand.
Oh yeah, see if there's anything in the papers. If you see anybody
hanging around the lobby when you come back, don't come up; give
me a call and I'll meet you."
She stood up. "This is really awful," she said. "Can't your embassy—"
"Didn't I mention it? A Mr. Pruffy, of the embassy, came along to hold
Smale's hand ... not to mention a Colonel Sanchez. I wouldn't be
surprised if the local cops weren't in the act by now...."
"Where will you go?"
"I'll get to the airport and play it by ear. I don't think they've alerted
everybody. It was a hush-hush deal, until it went sour; now they're still
picking up the pieces."
"The bank won't be open for hours yet," said Margareta. "Go to sleep
and don't worry. I'll take care of everything."
I knew I wasn't alone as soon as I opened my eyes. I hadn't heard
anything, but I could feel someone in the room. I sat up slowly, looked
around.
He was sitting in the embroidered chair by the window: an ordinary-
looking fellow in a tan tropical suit, with an unlighted cigarette in his
mouth and no particular expression on his face.
"Go ahead, light up," I said. "Don't mind me."
"Thanks," he said, in a thin voice. He took a lighter from an inner
pocket, flipped it, held it to the cigarette.
I stood up. There was a blur of motion from my visitor, and the lighter
was gone and a short-nosed revolver was in its place.
"You've got the wrong scoop, mister," I said. "I don't bite."
"I'd rather you wouldn't move suddenly, Mr. Legion."
"Which side are you working for?" I asked. "And can I put my shoes
on?"
He rested the pistol on his knee. "Get completely dressed, Mr.
Legion."
"Sorry," I said. "No can do. No clothes."
He frowned slightly. "My jacket will be a little small for you," he said.
"But I think you can manage."
"How come you didn't figure I was dead?" I asked.
"We checked the house," he said. "No body."
"Why, you incompetent asses. You were supposed to think I
drowned."
"That possibility was considered. But we made the routine checks
anyway."
"Nice of you to let me sleep it out. How long have you been here?"
"Only a few minutes," he said. He glanced at his watch. "We'll have to
be going in another fifteen."
"What do you want with me?" I said. "You blew up everything you
were interested in."
"The Department wants to ask you a few questions."
I looked at the pistol. "I wonder if you'd really shoot me," I mused.
"I'll try to make the position clear," he said. "Just to avoid any
unfortunate misunderstanding. My instructions are to bring you in,
alive—if possible. If it appears that you may evade arrest ... or fall into
the wrong hands, I'll be forced to use the gun."

I pulled my shoes on, thinking it over. My best chance to make a

break was now, while there was only one watch dog. But I had a
feeling he was telling the truth about shooting me. I had already seen
the boys in action at the house.
He got up. "Let's step into the living room, Mr. Legion," he said. I
moved past him through the door. In the living room the clock on the
mantle said eleven. I'd been asleep for five or six hours. Margareta
ought to be getting back any minute....
"Put this on," he said. I took the light jacket and wedged myself into it.
The telephone rang.
I looked at my watchdog. He shook his head. We stood and listened
to it ring. After a while it stopped.
"We'd better be going now," he said. "Walk ahead of me, please. We'll
take the elevator to the basement and leave by the service entrance
—"
He stopped talking, eyes on the door. There was the rattle of a key.
The gun came up.
"Hold it," I snapped. "It's the girl who owns the apartment." I moved to
face him, my back to the door.
"That was foolish of you, Legion," he said. "Don't move again."
I watched the door in the big mirror on the opposite wall. The knob
turned, the door swung in ... and a thin brown man in white shirt and
white pants slipped into the room. As he pushed the door back he
transferred a small automatic to his left hand. My keeper threw a
lever on the revolver that was aimed at my belt buckle.
"Stand absolutely still, Legion," he said. "If you have a chance, that's
it." He moved aside slightly, looked past me to the newcomer. I
watched in the mirror as the man in white behind me swiveled to keep
both of us covered.
"This is a fail-safe weapon," said my first owner to the new man. "I
think you know about them. We leaked the information to you. I'm
holding the trigger back; if my hand relaxes, it fires, so I'd be a little
careful about shooting, if I were you."
The thin man swallowed. He didn't say anything. He was having to
make some tough decisions. His instructions would be the same as
my other friend's: to bring me in alive, if possible.
"Who does this bird represent?" I asked my man.
"He's a Soviet agent."
I looked in the mirror at the man again. "Nuts," I said. "He looks like a
waiter in a chile joint. He probably came up to take our order."
"You talk too much," said my keeper between his teeth. He held the
gun on me steadily. I watched his trigger finger to see if it looked like
relaxing.
"I'd say it's a stalemate," I said. "Let's take it once more from the top.
Both of you go—"
"Shut up, Legion." My man licked his lips, glanced at my face. "I'm
sorry. It looks as though—"
"You don't want to shoot me," I blurted out, loudly. In the mirror I had
seen the door, which was standing ajar, ease open an inch, two
inches. "You'll spoil this nice coat...." I kept on talking: "And anyway it
would be a big mistake, because everybody knows Russian agents
are stubby men with wide cheekbones and tight hats—"
Silently Margareta slipped into the room, took two quick steps, and
slammed a heavy handbag down on the slicked-back pompadour that
went with the Adam's apple. The man in white stumbled and fired a
round into the rug. The automatic dropped from his hand, and my pal
in tan stepped to him and hit him hard on the back of the head with
his pistol. He whirled toward me, hissed "Play it smart" just loud
enough for me to hear, then turned to Margareta. He slipped the gun
in his pocket, but I knew he could get it out again in a hurry.
"Very nicely done, Miss," he said. "I'll have this person removed from
your apartment. Mr. Legion and I were just going."
Margareta looked at me. I didn't want to see her get hurt—or
involved.
"It's okay, honey," I said. "This is Mr. Jones ... of our Embassy. We're
old friends." I stepped past her, headed for the door. My hand was on
the knob when I heard a solid thunk behind me. I whirled in time to
clip the FBI on the jaw as he fell forward. Margareta looked at me,
wide-eyed.
"That handbag packs a wallop," I said. "Nice work, Maggie." I knelt,
pulled off the fellow's belt, and cinched his hands behind his back
with it. Margareta got the idea, did the same for the other man, who
was beginning to groan now.
"Who are these men?" she asked.
"I'll tell you all about it later. Right now, I have to get to some people I
know, get this story on the wires, out in the open. State'll be a little
shy about gunning me down or locking me up without trial, if I give the
show enough publicity." I reached in my pocket, handed her the
black-&-gold-marked cylinder. "Mail this to—Joe Dugan—at Itzenca,
general delivery."
"All right," Margareta said. "And I have your things." She stepped into
the hall, came back with a shopping bag and a suit carton. She took a
wad of bills from her handbag and handed it to me.
I went to her and put my arms around her. "Listen, honey: as soon as
I leave go to the bank and draw fifty grand. Get out of the country.
They haven't got anything on you except that you beaned a couple of
intruders in your apartment, but it'll be better if you disappear. Leave
an address care of Poste Restante, Basle, Switzerland. I'll get in
touch when I can."
Twenty minutes later I was pushing through the big glass doors onto
the sidewalk, clean-shaven, dressed to the teeth, with five grand on
one hip and a .32 on the other. I'd had a good meal and a fair sleep,
and against me the secret services of two or three countries didn't
have a chance.
I got as far as the corner before they nailed me.

CHAPTER XII
"You have a great deal to lose," General Smale was saying, "and
nothing to gain by your stubbornness. You're a young man, vigorous
and, I'm sure, intelligent. You have a fortune of some million and a
quarter dollars, which I assure you you'll be permitted to keep. As
against that prospect, so long as you refuse to co-operate, we must
regard you as no better than a traitorous criminal—and deal with you
accordingly."
"What have you been feeding me?" I said. "My mouth tastes like
somebody's old gym shoes and my arm's purple to the elbow. Don't
you know it's illegal to administer drugs without a license?"
"The nation's security is at stake," snapped Smale.
"The funny thing is, it must not have worked, or you wouldn't be
begging me to tell all. I thought that scopolamine or whatever you're
using was the real goods."
"We've gotten nothing but gibberish," Smale said, "most of it in an
incomprehensible language. Who the devil are you, Legion? Where
do you come from?"
"You know everything," I said. "You told me so yourself. I'm a guy
named Legion, from Mount Sterling, Illinois, population: one thousand
eight hundred and ninety-two."
Smale had gone white. "I'm in a position to inflict agonies on you, you
insolent rotter," he grated. "I've refrained from doing so. I'm a soldier; I
know my duty. I'm prepared to give my life; if need be, my honor, to
obtain for my government the information you're withholding."
"Turn me loose; then ask me in a nice way. As far as I know, I haven't
got anything of military significance to tell you, but if I were treated as
a free citizen I might be inclined to let you be the judge of that."
"Tell us now; then you'll go free."
"Sure," I said. "I invented a combination rocket ship and time
machine. I travelled around the solar system and made a few short
trips back into history. In my spare time I invented other gadgets. I'm
planning to take out patents, so naturally I don't intend to spill any
secrets. Can I go now?"
Smale got to his feet. "Until we can safely move you, you'll remain in
this room. You're on the sixty-third floor of the Yordano Building. The
windows are of unbreakable glass, in case you contemplate a
particularly untidy suicide. Your person has been stripped of all
potentially dangerous items. The door is of heavy construction and
securely locked. The furniture has been removed so you can't
dismantle it for use as a weapon. It's rather a drab room to spend
your future in, but until you decide to co-operate this will be your
world."

I didn't say anything. I sat on the floor and watched him leave. I
caught a glimpse of two uniformed men outside the door. No doubt
they'd take turns looking through the peephole. I'd have solitude
without privacy.
I stretched out on the floor, which was padded with a nice thick rug,
presumably so that I wouldn't beat my brains out against it just to
spite them. I was way behind on my sleep: being interrogated while
unconscious wasn't a very restful procedure. I wasn't too worried. In
spite of what Smale said, they couldn't keep me here forever. Maybe
Margareta had gotten clear and told the story to some newsmen; this
kind of thing couldn't stay hidden forever. Or could it?
I thought about what Smale had said about my talking gibberish
under the narcotics. That was an odd one....
Quite suddenly I got it. By means of the drugs they must have tapped
a level where the Vallonian background briefing was stored: they'd
been firing questions at a set of memories that didn't speak English. I
grinned, then laughed out loud. Luck was still in the saddle with me.

The glass was in double panels, set in aluminum frames and sealed
with a plastic strip. The space between the two panels of glass was
evacuated of air, creating an insulating barrier against the heat of the
sun. I ran a finger over the aluminum. It was dural: good tough stuff. If
I had something to pry with, I might possibly lever the metal away
from the glass far enough to take a crack at the edge, the weak point
of armor-glass ... if I had something to hit it with.
Smale had done a good job of stripping the room—and me. I had my
shirt and pants and shoes, but no tie or belt. I still had my wallet—
empty, a pack of cigarettes with two wilted weeds in it, and a box of
matches. Smale had missed a bet: I might set fire to my hair and burn
to the ground. I might also stuff a sock down my throat and strangle,
or hang myself with a shoe lace—but I wasn't going to.
I looked at the window some more. The door was too tough to tackle,
and the heavies outside were probably hoping for an excuse to work
me over. They wouldn't expect me to go after the glass; after all, I
was still sixty-three stories up. What would I do if I did make it to the
window sill? But we could worry about that later, after I had smelled
the fresh air.
My forefinger found an irregularity in the smooth metal: a short
groove. I looked closer, saw a screw-head set flush with the
aluminum surface. Maybe if the frame was bolted together—
No such luck; the screw I had found was the only one. What was it
for? Maybe if I removed it I'd find out. But I'd wait until dark to try it.
Smale hadn't left a light fixture in the room. After sundown I'd be able
to work unobserved.

A couple of hours went by and no one came to disturb my solitude,

not even to feed me. I had a short scrap of metal I'd worked loose
from my wallet. It was mild steel, flimsy stuff, only about an inch long,
but I was hoping the screw might not be set too tight. Aluminum
threads strip pretty easily, so it probably wasn't cinched up too hard.
There was no point in theorizing. It was dark now; I'd give it a try. I
went to the window, fitted the edge of metal into the slotted screw-
head, and twisted. It turned, just like that. I backed it off ten turns,
twenty; it was a thick bolt with fine threads. It came free and air
whooshed into the hole. The screw apparently sealed the panel after
the air was evacuated.
I thought it over. If I could fill the space between the panels with water
and let it freeze ... quite a trick in the tropics. I might as well plan to fill
it with gin and set it on fire.
I was going in circles. Every idea I got started with "if". I needed
something I could manage with the materials at hand: cloth, a box of
matches, a few bits of paper.
I got out a cigarette, lit up, and while the match was burning
examined the hole from which I'd removed the plug. It was about
three sixteenths of an inch in diameter and an inch deep, and there
was a hole near the bottom communicating with the air space
between the glass panels. It was an old-fashioned method of
manufacture but it seemed to have worked all right: the air was
pumped out and the hole sealed with the screw. It had at any rate the
advantage of being easy to service if the panel leaked. Now with
some way of pumping air in, I could blow out the panels....
There was no pump on the premises but I did have some chemicals:
the match heads. They were old style too, like a lot of things in Peru:
the strike-once-and-throw-away kind.
I sat on the floor and started to work, chipping the heads off the
matchsticks, collecting the dry, purplish material on a scrap of paper.
Thirty-eight matches gave me a respectable sample. I packed it
together, rolled it in the paper, and crimped the ends. Then I tucked
the makeshift firecracker into the hole the screw had come from.
Using the metal scrap I scraped at the threads of the screw, blurring
them. Then I started it in the hole, half a dozen turns, until it came up
against the match-heads.
The shoes Margareta had bought me had built-up leather heels: hell
on the feet, but just the thing to pound with.

I took the shoe by the toe and hefted it: the flexible sole gave it a
good action, like a well-made sap. There were still a couple of "if's" in
the equation, but a healthy crack on the screw ought to drive it
against the packed match-heads hard enough to detonate them, and
the expanding gasses from the explosion ought to exert enough
pressure against the glass panels to break them. I'd know in a
second.
I flattened myself against the wall, brought the shoe up, and laid it on
the screw-head.
There was a deafening boom, a blast of hot air, and a chemical stink,
then a gust of cool night wind—and I was on the sill, my back to the
street six hundred feet below, my fingers groping for a hold on the
ledge above the window. I found a grip, pulled up, reached higher, got
my feet on the muntin strip, paused to rest for three seconds, reached
again....
I pulled my feet above the window level and heard shouts in the room
below:
"—fool killed himself!"
"Get a light in here!"
I clung, breathing deep, and murmured thanks to the architect who
had stressed a strong horizontal element in his facade and arranged
the strip windows in bays set twelve inches from the face of the
structure. Now, if the boys below would keep their eyes on the street
underneath long enough for me to get to the roof—
I looked up, to get an idea how far I'd have to go—and gripped the
ledge convulsively as the whole building leaned out, tilting me back....
Cold sweat ran into my eyes. I squeezed the stone until my knuckles
creaked, and held on. I laid my cheek against the rough plaster,
listened to my heart thump. Adrenalin and high hopes had gotten me
this far ... and now it had all drained out and left me, a frail ground-
loving animal, flattened against the cruel face of a tower like a fly on a
ceiling, with nothing between me and the unyielding concrete below
but the feeble grip of fingers and toes. I started to yell for help, and
the words stuck in my dry throat. I breathed in shallow gasps, feeling
my muscles tightening, until I hung, rigid as a board, afraid even to
roll my eyeballs for fear of dislodging myself. I closed my eyes, felt
my hands going numb, and tried again to yell: only a thin croak.
A minute earlier I had had only one worry: that they'd look up and see
me. Now my worst fear was that they wouldn't.
This was the end. I'd been close before, but not like this. My fingers
could take the strain for maybe another minute, maybe even two;
then I'd let go, and the wind would whip at me for a few timeless
seconds, before I hit.

Down inside of me a small defiance flickered, found a foot-hold,

burned brighter. I would die ... but Hell, that would solve a lot of
problems. And if I had to die, at least I could die trying.
My mind moved in to take over from my body. It was the body that
was wasting my last strength on a precarious illusion of safety,
numbing my senses, paralyzing me. It was a tyranny I wouldn't
accept. I needed a cool head and a steady hand and an unimpaired
sense of balance; and if the imbecile boy wouldn't co-operate the
mind would damn well force it. First: loosen the grip—Yes! if it killed
me: bend those fingers!
I was standing a little looser now, my hands resting flat, my legs
taking the load. I had a good wide ledge to stand on: nearly a foot,
and in a minute I was going to reach up and get a new hold and lift
one foot at a time ... and if I slipped, at least I'd have done it my way.
I let go, and the building leaned out, and to hell with it....
I felt for the next ledge, gripped it, pulled up, found a toe-hold.
Sure, I was dead. It was a long way to the top, and there was a fancy
cornice I'd never get over, but when the moment came and I started
the long ride down I'd thumb my nose at the old hag, Instinct, who
hadn't been as tough as she thought she was....

I was under the cornice now, hanging on for a breather and listening
to the hooting and hollering from the window far below. A couple of
heads had popped out and taken a look, but it was dark up where I
was and all the attention was centered down where the crowd had
gathered and lights were playing, looking for the mess. Pretty soon
now they'd begin to get the drift—so I'd better be going.
I looked up at the overhang ... and felt the old urge to clutch and hang
on. So I leaned outward a little further, just to show me who was
boss. It was a long reach, and I'd have to risk it all on one lunge
because, if I missed, there wasn't any net, and my fingers knew it; I
heard my nails rasp on the plaster. I grated my teeth together and
unhooked one hand: it was like a claw carved from wood. I took a
half-breath, bent my knees slightly; they were as responsive as a
couple of bumper-jacks bolted on at the hip. Tough; but it was now or
never....
I let go with both hands and stretched, leaning back....
My wooden hands bumped the edge, scrabbled, hooked on, as my
legs swung free, and I was hanging like an old-time sailor strung up
by the thumbs. A wind off the roof whipped at my face and now I was
a tissue-paper doll, fluttering in the breeze.

I had to pull now, pull hard, heave myself up and over the edge, but I
was tired, too tired, and a dark curtain was falling over me....
Then from the darkness a voice was speaking in a strange language:
a confusion of strange thought symbols, but through them an ever
more insistent call:
... dilate the secondary vascular complex, shunt full conductivity to
the upsilon neuro-channel. Now, stripping oxygen ions from fatty cell
masses, pour in electro-chemical energy to the sinews....
With a smooth surge of power I pulled myself up, fell forward, rolled
onto my back, and lay on the flat roof, the beautiful flat roof, still warm
from the day's sun.
I was here, looking at the stars, safe, and later on when I had more
time I'd stop to think about it. But now I had to move, before they'd
had time to organize themselves, cordon off the building, and start a
door-to-door search.
Staggering a bit from the exertion of the long climb I got to my feet,
went to the shed housing the entry to the service stair. A short flight of
steps led down to a storeroom. There were dusty boards, dried-up
paint cans, odd tools. I picked up a five-foot length of two-by-four and
a hammer with one claw missing, and stepped out into the hall. The
street was a long way down and I didn't feel like wasting time with
stairs. I found the elevator, got in and pushed the button for the foyer.

In a few seconds it stopped and the doors opened. I glanced out,

tightened my grip on the hammer, and stepped out. I could see the
lights in the street out front and in the distance there was the wail of a
siren, but nobody in the lobby looked my way. I headed across toward
the side exit, dumped the board at the door, tucked the hammer in the
waist band of my pants, and stepped out onto the pavement. There
were a lot of people hurrying past but this was Lima: they didn't waste
a glance on a bare-footed carpenter.
I moved off, not hurrying. There was a lot of rough country between
me and Itzenca, the little town near which the life boat was hidden in
a cañon, but I aimed to cover it in a week. Some time between now
and tomorrow I'd have to figure out a way to equip myself with a few
necessities, but I wasn't worried. A man who had successfully taken
up human-fly work in middle life wouldn't have any trouble stealing a
pair of boots.
Foster had shoved off for home three years ago, local time, although
to him, aboard the ship, only a few weeks might have passed. My
lifeboat was a midge compared to the mother ship he rode, but it had
plenty of speed. Once aboard the lugger ... and maybe I could put a
little space between me and the big boys.
I had used the best camouflage I knew of on the boat. The near-
savage native bearers who had done my unloading and carried my
Vallonian treasures across the desert to the nearest railhead were not
the gossipy type. If General Smale's boys had heard about the boat,
they hadn't mentioned it. And if they had: well, I'd solve that one when
I got to it. There were still quite a few 'if's' in the equation, but my
arithmetic was getting better all the time.

CHAPTER XIII
I took the precaution of sneaking up on the lifeboat in the dead of
night, but I could have saved myself a crawl. Except for the fact that
the camouflage nets had rotted away to shreds, the ship was just as I
had left it, doors sealed. Why Smale's team hadn't found it, I didn't
know; I'd think that one over when I was well away from Earth.
I went into the post office at Itzenca to pick up the parcel Margareta
had mailed me with Foster's memory-trace in it. While I was checking
to see whether Uncle Sam's minions had intercepted the package
and substituted a carrot, I felt something rubbing against my shin. I
glanced down and saw a grey and white cat, reasonably clean and
obviously hungry. I don't know whether I'd ploughed through a field of
wild catnip the night before or if it was my way with a finger behind
the furry ears, but kitty followed me out of Itzenca and right into the
bush. She kept pace with me, leading most of the time, as far as the
space boat, and was the first one aboard.
I didn't waste time with formalities. I had once audited a briefing rod
on the boat's operation—not that I had ever expected to use the
information for a take-off. Once aboard, I hit the controls and cut a
swathe through the atmosphere that must have sent fingers jumping
for panic buttons from Washington to Moscow.
I didn't know how many weeks or months of unsullied leisure
stretched ahead of me now. There would be time to spare for
exploring the boat, working out a daily routine, chewing over the
details of both my memories, and laying plans for my arrival on
Foster's world, Vallon. But first I wanted to catch a show that was
making a one-night stand for me only: the awe-inspiring spectacle of
the retreating Earth.

I dropped into a seat opposite the screen and flipped into a view of
the big luminous ball of wool that was my home planet. I'd been
hoping to get a last look at my island, but I couldn't see it. The whole
sphere was blanketed in cloud: a thin worn blanket in places but still
intact. But the moon was a sight! An undipped Edam cheese with the
markings of Roquefort. For a quarter of an hour I watched it grow until
it filled my screen. It was too close for comfort. I dumped the tabby
out of my lap and adjusted a dial. The dead world swept past, and I
had a brief glimpse of blue burst bubbles of craters that became the
eyes and mouth and pock marks of a face on a head that swung
away from me in disdain and then the sibling planets dwindled and
were gone forever.
The life boat was completely equipped, and I found comfortable
quarters. An ample food supply was available by the touch of a panel
on the table in the screen-room. That was a trick my predecessor with
the dental jewellery hadn't discovered, I guessed. During the course
of my first journey earthward and on my visits to the boat for saleable
playthings while she lay in dry-dock, I had discovered most of the
available amenities aboard. Now I luxuriated in a steaming bath of
recycled water, sponged down with disposable towels packed in
scented alcohol, fed the cat and myself, and lay down to sleep for
about two weeks.
By the third week I was reasonably refreshed and rested. The cat
was a godsend, I began to realize. I named her Itzenca, after the
village where she adopted me, and I talked to her by the hour.
"Say, Itz," said I, "where would you like your sand-box situated? Right
there in front of the TV screen?"
No, said Itzenca by a flirt of her tail. And she walked over behind a
crate that had never been unloaded on earth.
I pulled out a box of junk and slid the sand-box in its place. Itzenca
promptly lost interest and instead jumped up on the junk box which
fell off the bench and scattered small objects of khaff and metal in all
directions.
"Come back here, blast you," I said, "and help me pick up this stuff."
Itz bounded after a dull-gleaming silver object that was still rolling. I
was there almost as quick as she was and grabbed up the cylinder.
Suddenly horsing around was over. This thing was somebody's
memory.

I dropped onto a bench to examine it, my Vallonian-inspired pulse

pounding. Itz jumped up into my lap and nosed the cylinder. I was
trying to hark back to those days three years before when I had
loaded the lifeboat with all the loot it would carry, for the trip back to
Earth.
"Listen, Itz, we've got to do some tall remembering. Let's see: there
was a whole rack of blanks in the memory-recharging section of the
room where we found the three skeletons. Yeah, now I remember: I
pulled this one out of the recorder set. I showed it to Foster when he
was hunting his own trace. He didn't realize I'd pulled it out of the
machine and he thought it was an empty. But I'll bet you somebody
had his mind taped, and then left in a hurry, before the trace could be
color-coded and filed.
"On the other hand, maybe it's a blank that had just been inserted
when somebody broke up the play-house.... But wasn't there
something Foster said ... about when he woke up, way back when,
with a pile of fresh corpses around him? He gave somebody
emergency treatment and to a Vallonian that would include a
complete memory-transcription.... Do you realize what I've got here in
my hand, Itz?"
She looked up at me inquiringly.
"This is what's left of the guy that Foster buried: his pal, Ammaerln, I
think he called him. What's inside his cylinder used to be tucked away
in the skull of the Ancient Sinner. The guy's not so dead after all. I'll
bet his family will pay plenty for this trace, and be grateful besides.
That'll be an ace in the hole in case I get too hungry on Vallon."
I got up, crossed the apartment and dropped the trace in a drawer
beside Foster's own memory.
"Wonder how Foster's making out without his past, Itz? He claimed
the one I've got here could only be a copy of the original stored at
Okk-Hamiloth, but my briefing didn't say anything about copying
memories. He must be somebody pretty important to rate that
service."
Suddenly my eyes were rivetted to the markings on Foster's trace
lying in the drawer. "Zblood! The royal colors!" I sat down on the bed
with a lurch. "Itzenca, old gal, it looks like we'll be entering Vallonian