Dynamic Combinatorial Chemistry: In Drug Discovery, Bioorganic Chemistry, and Materials Science

275 Pages·2010·15.577 MB·English

Dynamic Combinatorial

Chemistry
Dynamic Combinatorial
Chemistry
In Drug Discovery, Bioorganic
Chemistry, and Materials Science
Edited by
Benjamin L. Miller
University of Rochester
Rochester, New York
Copyright © 2010 by John Wiley & Sons, Inc.
Published by John Wiley & Sons, Inc., Hoboken, New Jersey. All rights reserved.
Published simultaneously in Canada
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Library of Congress Cataloging-in-Publication Data:
Miller, Benjamin L.
Dynamic combinatorial chemistry : in drug discovery, bioorganic chemistry, and
materials science / Benjamin L. Miller.
p. cm.
Includes index.
ISBN 978-0-470-09603-1 (cloth)
1. Combinatorial chemistry. I. Title.
QD262.M64 2009
615(cid:1).19—dc22
2009019344
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
Contents
Preface vii
Contributors ix
Chapter 1: Dynamic Combinatorial Chemistry:
An Introduction 1
Benjamin L. Miller
Chapter 2: Protein-Directed Dynamic Combinatorial
Chemistry 43
Michael F. Greaney and Venugopal T. Bhat
Chapter 3: Nucleic Acid-Targeted Dynamic
Combinatorial Chemistry 83
Peter C. Gareiss and Benjamin L. Miller
Chapter 4: Complex Self-Sorting Systems 118
Soumyadip Ghosh and Lyle Isaacs
Chapter 5: Chiral Selection in DCC 155
Jennifer J. Becker and Michel R. Gagné
Chapter 6: Dynamic Combinatorial Resolution 169
Marcus Angelin, Rikard Larsson, Pornrapee
Vongvilai, Morakot Sakulsombat, and Olof Ramström
v
vi CONTENTS
Chapter 7: Dynamic Combinatorial Chemistry
and Mass Spectrometry: A Combined
Strategy for High Performance
Lead Discovery 201
Sally-Ann Poulsen and Hoan Vu
Chapter 8: Dynamic Combinatorial Methods in
Materials Science 229
Takeshi Maeda, Hideyuki Otsuka, and
Atsushi Takahara
Index 261
Preface

In a relatively short period, dynamic combinatorial chemistry has grown
from proof - of - concept experiments in a few isolated labs to a broad con-
ceptual framework, finding application to an exceptional range of problems
in molecular recognition, lead compound identification, catalyst design,
nanotechnology, polymer science, and others. This book brings together
experts in many of these areas, as well as in the analytical techniques nec-
essary for the execution of a successful DCC experiment. While there have
been several outstanding general reviews of the field published over the
past few years, the time seemed ripe for an overview in book form.
DCC is useful both because of its ability to rapidly provide access to
libraries of compounds in a resource- conserving fashion (i.e., there are
few things simpler than mixing molecular components and allowing them
to “ evolve ” towards an optimized result), and because it can also yield
completely unexpected structures, or molecules not readily accessible by
traditional synthesis. As the reader will see, this book is full of exam-
ples showcasing both of these strengths. Challenges inherent in the DCC
technique (or suite of techniques) and opportunities for advancement are
highlighted as well, and hopefully will spark the development of new
solutions and strategies. In some cases, particular examples are discussed
in more than one chapter, in order to allow their exploration in different
contexts.
The chapters contained herein cover the literature from the beginning
of what came to be known as dynamic combinatorial chemistry (but was
initially known as a confusing mix of things!) up to late 2008. A brief
vii
viii PREFACE
overview of historical antecedents to DCC is also provided. Of course, it is
inevitable that despite the best of intentions, there may be research groups
active in the field whose work is not covered as comprehensively as one
might wish. We hope that any researchers thus inadvertently neglected will
accept our apologies.
My personal thanks goes to the broad community of scientists working
on DCC and affiliated techniques; I have been continuously pleased by
your openness and helpfulness, and astounded by your creativity. Hope-
fully this book does justice to all of your efforts. Closer to home, the
DCC projects that have unfolded in our group at Rochester occurred only
because of the persistence and intelligence of my coworkers, and therefore
I would like to thank Bryan Klekota, Mark Hammond, Charles Karan,
Brian McNaughton, Peter Gareiss, and Prakash Palde for their efforts and
continuing interest. Finally, thanks are also owed to Jonathan Rose, our
editor at Wiley, for his exceptional patience during the process of assem-
bling this book.
I hope you will find this volume to be a useful guide to the state of the
art in DCC, as well as a source of inspiration for your own efforts in this
field.
BENJAMIN L. MILLER
Rochester, New York
September 2009
Contributors
Marcus Angelin, Department of Chemistry, KTH—Royal Institute of
Technology, Stockholm, Sweden
Jennifer J. Becker, U.S. Army Research Office, Research Triangle Park,
North Carolina
Venugopal T. Bhat, School of Chemistry, University of Edinburgh,
Edinburgh, United Kingdom
Michel R. Gagné, Department of Chemistry, University of North
Carolina, Chapel Hill, North Carolina
Peter C. Gareiss, Department of Dermatology, University of
Rochester, Rochester, New York
Soumyadip Ghosh, Department of Chemistry and Biochemistry,
University of Maryland, College Park, Maryland
Michael F. Greaney, School of Chemistry University of Edinburgh,
Edinburgh, United Kingdom
Lyle Isaacs, Department of Chemistry and Biochemistry, University of
Maryland, College Park, Maryland
Rikard Larsson, Department of Chemistry, KTH—Royal Institute of
Technology, Stockholm, Sweden
Takeshi Maeda, Institute for Materials Chemistry and Engineering
Kyushu University, Fukuoka, Japan
ix
x CONTRIBUTORS
Benjamin L. Miller, Department of Dermatology, University of
Rochester, Rochester, New York
Hideyuki Otsuka, Institute for Materials Chemistry and Engineering,
Kyushu University, Fukuoka, Japan
Sally-Ann Poulsen, Eskitis Institute for Cell and Molecular
Therapies, Griffith University, Queensland, Australia
Olof Ramström, Department of Chemistry, KTH—Royal Institute of
Technology, Stockholm, Sweden
Morakot Sakulsombat, Department of Chemistry, KTH—Royal Insti-
tute of Technology, Stockholm, Sweden
Atsushi Takahara, Institute of Materials Chemistry and Engineering,
Kyushu University, Fukuoka, Japan
Pornrapee Vongvilai, Department of Chemistry, KTH—Royal Institute
of Technology, Stockholm, Sweden
Hoan Vu, Eskitis Institute for Cell and Molecular Therapies, Griffith
University, Queensland, Australia
Figure 4.2 Hydrogen bonding region (8.0 – 14.5 ppm) of the 1 H NMR spectra (H O
2
sat. CDCl , 500 MHz, 298 K) recorded for ( a ) 9 (cid:1) Ba 2 (cid:2) (cid:2) 2Pic – , ( b ) 10 (cid:1) 2Ba 2 (cid:2)
3 10 16
4Pic – , ( c ) 19 , ( d ) 20 (cid:1) 21 , ( e ) 17 , ( f ) 18 , ( g ) 15 , ( h ) ( (cid:2) ) - 16 (cid:1) ( (cid:3) ) - 16, ( i ) a self-
2 3 6 2 2 2
sorted mixture comprising 9 (cid:1) Ba2 (cid:2) (cid:2) 2Pic – , 10 (cid:1) 2Ba 2(cid:2) 4Pic – , 19 , 20 (cid:1) 21 , 17 ,
10 16 2 3 6 2
18 , 15 , and ((cid:2) ) - 16 (cid:1) ( (cid:3) ) - 16. The representations depict the species present in
2 2
solution. The resonances are color coded to aid comparison. See pages 127–128 for
text discussion of this figure.
Scheme 4.10 The sequential addition of various CB[n ] and guests to 41 induces
folding, forced unfolding, and refolding of 41 into four different conformations.
See pages 133–135 for text discussion of this figure.