IONIC LIQUIDS IN BIOTRANSFORMATIONS AND ORGANOCATALYSIS IONIC LIQUIDS IN BIOTRANSFORMATIONS AND ORGANOCATALYSIS Solvents and Beyond Edited by Pablo Domínguez de María A JOHN WILEY & SONS, INC., PUBLICATION Copyright © 2012 by John Wiley & Sons, Inc. All rights reserved. Published by John Wiley & Sons, Inc., Hoboken, New Jersey. Published simultaneously in Canada. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. 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Dominguez de Maria, Pablo, 1974- TP248.65.P76I59 2012 572.6–dc23 2011038032 Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 CONTENTS Foreword by Prof. Dr. Roger Sheldon xiii Preface xv Contributors xvii PART I FUNDAMENTALS 1 1 IONIC LIQUIDS: DEFINITION, APPLICATIONS, AND CONTEXT FOR BIOTRANSFORMATIONS AND ORGANOCATALYSIS 3 Pablo Domínguez de María 1.1 Ionic Liquids: Defi nition, Development, and Overview of Current Main Applications 3 1.2 On the Greenness of ILs: Toward the Third Generation of ILs and DES 6 1.3 Context of ILs in Biotransformations and Organocatalysis 12 References 13 2 IONIC LIQUIDS AND PROTEINS: ACADEMIC AND SOME PRACTICAL INTERACTIONS 15 Zhen Yang Abbreviations for Ionic Liquid Cations 15 Abbreviations for Ionic Liquid Anions 16 Abbreviations for Ammonium Ionic Liquids 16 Other Abbreviations 17 2.1 Introduction 17 2.2 Ionic Liquids, Water, and Proteins 18 2.2.1 Ionic Nature of Ionic Liquids 18 2.2.2 Protic and Aprotic Ionic Liquids 19 2.2.3 Water Present in the Ionic Liquids 21 2.2.4 Interactions of Water and Ionic Liquids with Proteins 21 2.2.4.1 Effect of Water and Water Activity 22 2.2.4.2 Effect of Ionic Liquids 26 v vi CONTENTS 2.3 Hofmeister Effects on Biocatalysis 26 2.3.1 Hofmeister Effects of Inorganic Salts 27 2.3.1.1 Quantifi cation of Hofmeister Series 28 2.3.1.2 Effect of Ions on Protein Stability 29 2.3.1.3 Effect of Ions on Enzyme Activity 30 2.3.2 Hofmeister Effects of Ionic Liquids 34 2.3.2.1 Effect of Ionic Liquid Ions on Enzyme Performance in Aqueous Solution 34 2.3.2.2 Kinetic Studies of Enzymes in Ionic Liquid-Containing Aqueous Solution 38 2.3.2.3 Enzyme Performance in Ionic Liquid-Dominating Reaction Systems 39 2.4 Impact of Ionic Liquids on Enzymes and Proteins 41 2.4.1 Effect of Ionic Liquids on Enzyme Activity and Stability 41 2.4.1.1 Hydrophobicity and Log P 41 2.4.1.2 Nucleophilicity and H-bond Basicity 44 2.4.1.3 Viscosity 45 2.4.2 Effect of Ionic Liquids on Protein Structure and Dynamics 46 2.4.3 Effect of Ionic Liquids on Protein Refolding and Renaturation 50 2.4.4 Effect of Ionic Liquids on Protein Crystallization and Fibrilization 52 2.5 Protein Extraction by Means of Ionic Liquids 52 2.5.1 Aqueous/Ionic Liquid–Liquid Extraction Systems 52 2.5.2 Ionic Liquid-Based Aqueous Biphasic Systems 53 2.5.3 Water-in-Ionic Liquid Microemulsion Systems 56 2.6 Proper Selection of Ionic Liquids for Biocatalysis 57 2.6.1 Amino Acid Ionic Liquids 57 2.6.2 Ammonium and Phosphonium Ionic Liquids 58 2.6.3 Design of Ionic Liquids for Biocatalysis 59 2.6.4 Proposed Guidelines for Selecting/Designing Biocompatible Ionic Liquids 64 2.7 Concluding Remarks 65 References 66 CONTENTS vii PART II IONIC LIQUIDS IN BIOTRANSFORMATIONS 73 3 IONIC LIQUIDS IN BIOTRANSFORMATIONS: MOTIVATION AND DEVELOPMENT 75 Christina Kohlmann and Lasse Greiner 3.1 First Uses of Ionic Liquids in Biotransformations 75 3.2 Motivation to Use IL in Biotransformations 80 3.3 Challenges for the Use of IL in Biotransformations 91 References 98 4 IONIC LIQUIDS AND OTHER NONCONVENTIONAL SOLVENTS IN BIOTRANSFORMATIONS: MEDIUM ENGINEERING AND PROCESS DEVELOPMENT 103 Pedro Lozano and Eduardo García-Verdugo 4.1 Introduction: Toward Greener Catalytic Processes 103 4.2 The Importance of the Medium Engineering in Biotransformations 106 4.2.1 Enzymes in Nonaqueous Environments 106 4.3 Biocatalysis in Monophasic ILs Systems 110 4.3.1 Medium Engineering in Monophasic ILs System 110 4.3.2 Isolation and Recyclability Issues in Monophasic ILs System 115 4.4 (Bio)catalytic Processes in SCFs 118 4.4.1 Properties of SFCs 118 4.4.2 Medium Engineering in Supercritical Biocatalysis 119 4.4.3 Processes Design for SCF Biocatalysis 122 4.5 Multiphase Biotransformations 124 4.5.1 Biocatalytic Processes in Biphasic Fluorous Solvents 125 4.5.2 Bioprocesses in Water/scCO 2 Systems 126 4.5.3 Bioprocesses in Biphasic ILs System 128 4.5.3.1 Biphasic ILs/Water System 128 4.5.3.2 Phase Behavior of IL/scCO 2 Biphasic Systems 132 4.5.3.3 Bioprocesses in IL/scCO 2 Biphasic Systems 134 4.6 Prospects 140 Acknowledgments 140 References 141 viii CONTENTS 5 IONIC LIQUIDS AS (CO-)SOLVENTS FOR HYDROLYTIC ENZYMES 151 Hua Zhao Nomenclature of ILs 151 Cations 151 Anions 152 5.1 Introduction 152 5.1.1 Type of Hydrolases 152 5.1.2 Properties and Applications of ILs 154 5.2 State-of-the-art: Lipases, Esterases, Proteases in ILs as (co-)Solvents 155 5.2.1 Effect of Physical Properties of ILs on Hydrolase Activity and Stability 156 5.2.1.1 IL Polarity 156 5.2.1.2 Hydrogen-bond (H-bond) Basicity and Nucleophilicity of Anions 157 5.2.1.3 IL Network 160 5.2.1.4 Ion Kosmotropicity 161 5.2.1.5 Viscosity 165 5.2.1.6 Hydrophobicity 165 5.2.1.7 Enzyme Dissolution 170 5.2.2 Other Factors Infl uencing Hydrolase Activity and Stability 171 5.2.2.1 Halide Impurities in ILs 171 5.2.2.2 Water Activity 172 5.2.3 Methods to Improve Hydrolase Activity and Stability 174 5.2.3.1 Enzyme Immobilization 174 5.2.3.2 PEG-Modifi cation 176 5.2.3.3 EPRP 177 5.2.3.4 Water-in-IL Microemulsions. 178 5.2.3.5 Coating Enzymes with ILs 179 5.2.3.6 Designing Hydrolase-Compatible ILs 179 5.3 Use of ILs for (dynamic) Kinetic Resolutions ((D)KRs) 183 5.3.1 Kinetic Resolutions via Hydrolysis in Aqueous Solutions of ILs 183 5.3.1.1 Enantioselective Hydrolysis of Amino Acid Esters 183 5.3.1.2 Enantioselective Hydrolysis of Other Esters 184 5.3.2 Kinetic Resolution via Synthesis in Nonaqueous Solutions of ILs 187 CONTENTS ix 5.3.2.1 Evaluating Hydrolase’s Enantioselectivity via the Kinetic Resolution of 1-phenylethanol 187 5.3.2.2 Kinetic Resolutions of Other Alcohols 188 5.3.2.3 Kinetic Resolutions of Amines 199 5.3.2.4 Kinetic Resolutions Integrated with Supported IL Membranes (SILMs) or Microfl uidic Separation 199 5.3.2.5 Kinetic Resolution Using IL/scCO 2 Biphasic Systems 202 5.4 Hydrolase-Catalyzed Esterifi cations of Saccharides and Cellulose Derivatives in ILs 205 5.5 ILs for Glycosidases 210 5.5.1 Glycosidase-Catalyzed Synthesis in ILs 210 5.5.2 Cellulase-catalyzed Hydrolysis in ILs 211 5.6 Prospects 212 Acknowledgments 213 References 213 6 IONIC LIQUIDS AS (CO-)SOLVENTS FOR NONHYDROLYTIC ENZYMES 229 Daniela Gamenara, Patricia Saenz Méndez, Gustavo Seoane, and Pablo Domínguez de María Nomenclature of ILs 229 6.1 Ionic Liquids and Nonhydrolytic Enzymes 231 6.2 Use of ILs in Oxidoreductase-Catalyzed Enzymatic Reactions 232 6.2.1 Dehydrogenases 232 6.2.2 Laccases, Peroxidases, Oxidases, and Oxygenases 247 6.3 ILs in Lyase-Catalyzed Reactions 253 6.3.1 Aldolases 253 6.3.2 Oxynitrilases 254 6.4 Prospects 256 References 256 7 IONIC LIQUIDS AND WHOLE-CELL–CATALYZED PROCESSES 261 Danielle Dennewald and Dirk Weuster-Botz Abbreviations 261 Abbreviations of Ionic Liquid Cations 261 Abbreviations of Ionic Liquid Anions 262 Abbreviation of Ionic Liquid 262 List of Abbreviations 262 x CONTENTS 7.1 Ionic Liquids Compatible with Whole-Cell Biocatalysis: Fundamentals and Design 263 7.1.1 Biocompatibility 264 7.1.2 Availability and Purity 265 7.1.3 Stability 265 7.1.4 Process Design Criteria 265 7.1.4.1 Viscosity, Density, and Corrosiveness 266 7.1.4.2 Water Miscibility 266 7.1.5 Monophasic versus Biphasic Reaction Mode 266 7.1.6 Hazard Potential 268 7.1.6.1 Ecotoxicity 268 7.1.6.2 Biodegradability 269 7.1.7 Recyclability 271 7.1.8 Availability of Information 271 7.2 Biocompatibility, Tolerance, and Accumulation in the Cell 272 7.2.1 Methods 272 7.2.2 Tolerance 273 7.2.2.1 Composition of the Ionic Liquid and Organism Type 273 7.2.2.2 Other Factors of Infl uence 276 7.2.2.3 Comparison with Organic Solvents 277 7.2.3 Interaction Mechanism 278 7.2.3.1 Effect on the Cell Membrane 279 7.2.3.2 Accumulation inside the Cell 280 7.3 State of the Art 281 7.3.1 Asymmetric Reductions by Whole Cells in Ionic Liquids 282 7.3.2 Other Whole-Cell Biotransformations in Ionic Liquids 304 7.4 Prospects 308 References 310 8 NONSOLVENT APPLICATIONS OF IONIC LIQUIDS IN BIOTRANSFORMATIONS 315 Pablo Domínguez de María and Christina Kohlmann 8.1 Introduction 315 8.2 Ionic Liquids as Additives in Biotransformations 316 8.3 Ionic Liquids for Coating Enzymes: The ILCE Concept 318 CONTENTS xi 8.4 Ionic Liquids Combined with Membranes and Biotransformations 321 8.5 Ionic Liquids Anchoring Substrates 321 8.6 Ionic Liquids and Bioelectrochemistry 324 References 329 PART III IONIC LIQUIDS IN ORGANOCATALYSIS 331 9 IONIC LIQUIDS AS (CO-)SOLVENTS AND CO-CATALYSTS FOR ORGANOCATALYTIC REACTIONS 333 Štefan Toma and Radovan Šebesta 9.1 Nontraditional Media in Organocatalysis 333 9.2 Early Organocatalytic Reactions in Ionic Liquids 334 9.3 Ionic Liquids as Solvents for Organocatalytic Reactions 335 9.3.1 Aldol Reactions 335 9.3.2 Mannich Reactions 341 9.3.3 α-Amination and Aminoxylation of Carbonyl Compounds 342 9.3.4 Michael Additions 343 9.3.5 Miscellaneous Reactions 351 9.4 Ionic Liquids as Co-catalysts for Organocatalytic Reactions: Toward New Reactivities and Selectivities 353 9.5 Key Factors in Choosing Ionic Liquids for Organocatalysis and Prospects 355 References 356 10 “NONSOLVENT” APPLICATIONS OF IONIC LIQUIDS IN ORGANOCATALYSIS 361 Michelangelo Gruttadauria, Francesco Giacalone, Paola Agrigento, and Renato Noto 10.1 Introduction 361 10.2 Immobilizing Ionic Liquids and Organocatalysts 363 10.2.1 Strategy 1a: Covalently Attached “Ionic Liquid” Moieties as Supports 363 10.2.2 Strategy 1b: Covalently Attached “Ionic Liquid” Moieties as Linkers 369 10.2.3 Strategy 1c: Covalently Attached “Ionic Liquid” Moieties as Organocatalysts 372 10.3 Anchoring of Organocatalyst to Ionic Liquids 378 10.3.1 Aldol Reactions 379 10.3.2 Michael Reactions 393 [...]... tris(hydroxymethyl)aminoethane INTRODUCTION Ionic liquids (ILs) are organic salts remaining as liquids under ambient temperatures Since the first reports on performing biotransformations in ILs,1,2 interests in using 18 IONIC LIQUIDS AND PROTEINS: ACADEMIC AND SOME PRACTICAL INTERACTIONS them as a new type of solvents for biocatalysis, either as a solvent or as a co-solvent added to aqueous solution, have been increasing... processing, and catalyst grafting or coating (Chapters 8 and 10) Ionic liquids can also be smartly combined with other nonconventional solvents, such as supercritical fluids, or with innovative process design concepts (Chapter 4) Finally, some ionic liquids can be employed in whole-cell biotransformations, providing novel and promising approaches, including proof-of-principle for deep-eutectic-solvents and. .. guidelines for designing biocompatible ILs for biotransformations 2.2 IONIC LIQUIDS, WATER, AND PROTEINS Biocatalysis in ILs is a complicated system involving ILs, water, and proteins Our discussion of IL–protein interactions should start from the introduction of each of these three major components, their individual existent states, their specific roles in this biocatalytic system, and their interactions... proton in the PIL by using 1H NMR—a larger shift indicates a lower Brønsted acidity and can be adjusted by the choice of Brønsted base and Brønsted acid used in PIL formation.18 20 IONIC LIQUIDS AND PROTEINS: ACADEMIC AND SOME PRACTICAL INTERACTIONS Typical AIL cations R1 + N R2 Pyridinium N+ O R1 N R2 + N R3 Dimethylaminopyridinium R1 N+ R2 R1 R2 Morpholinium Piperidinium R1 R2 N+ R4 R3 + N R Quinolinium... that ionic liquids may bring, for example, leading to the third generation of ionic liquids Likewise, emerging deep-eutectic-solvents represent a promising option, and first uses in biotransformations are briefly discussed herein (Chapters 1, 5, and 7) In addition, an extensive updated state-of-the-art on toxicity and (bio)degradability of commonly used ionic liquids, together with protocols and rules... respectively This includes interesting concepts such as the use of ionic liquid–coated enzymes and the anchoring of organocatalysts to ionic liquids In short, I believe that this book is an important addition to the literature on ionic liquids as reaction media for biocatalytic and organocatalytic processes In addition to its obvious value to practicing organic chemists in both industry and academia, its... acids, and sugar-based structures.25 Herein, natural amino acids have been used extensively26 because of their interesting tunable chemical properties, greater affordability, and high compatibility for living organisms In addition, amino acids incorporate chiral centers into the IL, which may add other interesting properties with promising applications Thus, amino acidbased ILs represent interesting examples... can cover the topic(s) in their widest extent Thanks to the outstanding chapters of many world-class experts in the area, this book is now a reality that I hope will be a useful contribution for researchers in the field, both in academia and industry Since the beginning of my work as editor, I have made it clear in my mind that I do not want a book just covering uses of ionic liquids as solvents, albeit,... to be complimented on bringing this group of knowledgeable authors together to review the state of the art in biocatalysis and organocatalysis in ionic liquids The subjects covered are wide-ranging, from fundamental aspects of interactions between proteins and ionic liquids to their use as reaction media with both hydrolytic and nonhydrolytic enzymes, whole cell bioconversions, and, as a bonus, organocatalytic... trends in environmental processes and green chemistry, it is clear that this will be the most important and sustainable line of development for ILs in the coming years Furthermore, the design of ILs that can be used for certain applications while maintaining acceptable environmental footprints will be crucial Some examples of these combinations have just appeared in the field of biocatalysis, including . IONIC LIQUIDS IN BIOTRANSFORMATIONS AND ORGANOCATALYSIS IONIC LIQUIDS IN BIOTRANSFORMATIONS AND ORGANOCATALYSIS Solvents and Beyond Edited. 18 2.2.1 Ionic Nature of Ionic Liquids 18 2.2.2 Protic and Aprotic Ionic Liquids 19 2.2.3 Water Present in the Ionic Liquids 21 2.2.4 Interactions of Water and