Dynamic Combinatorial Chemistry

Dynamic Combinatorial ChemistryIn Drug Discovery, Bioorganic Chemistry, and Materials Science

Edited by

Benjamin L. MillerUniversity of RochesterRochester, 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�.19—dc22

2009019344

Printed in the United States of America

10 9 8 7 6 5 4 3 2 1

v

Contents

Preface vii

Contributors ix

Chapter 1: Dynamic Combinatorial Chemistry: An Introduction 1Benjamin L. Miller

Chapter 2: Protein-Directed Dynamic Combinatorial Chemistry 43Michael F. Greaney and Venugopal T. Bhat

Chapter 3: Nucleic Acid-Targeted Dynamic Combinatorial Chemistry 83Peter C. Gareiss and Benjamin L. Miller

Chapter 4: Complex Self-Sorting Systems 118Soumyadip Ghosh and Lyle Isaacs

Chapter 5: Chiral Selection in DCC 155Jennifer J. Becker and Michel R. Gagné

Chapter 6: Dynamic Combinatorial Resolution 169Marcus Angelin, Rikard Larsson, Pornrapee Vongvilai, Morakot Sakulsombat, and Olof Ramström

Chapter 7: Dynamic Combinatorial Chemistry and Mass Spectrometry: A Combined Strategy for High Performance Lead Discovery 201Sally-Ann Poulsen and Hoan Vu

Chapter 8: Dynamic Combinatorial Methods in Materials Science 229Takeshi Maeda, Hideyuki Otsuka, and Atsushi Takahara

Index 261

vi CONTENTS

vii

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

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

viii PREFACE

ix

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

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

x CONTRIBUTORS