Principles and advances in supramolecular catalysis 9780367111649, 0367111640, 9780429059063

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Content: Introduction. Organic and inorganic Supramolecular catalysts: design and function. Containers and Vessels for Supramolecular catalysis. Interlocked systems in catalysis and switching. Dendrimers in suparmolecular catalysis. Versatility in supramolecular catalysis.

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Principles and Advances in Supramolecular Catalysis

Principles and Advances in Supramolecular Catalysis

Jubaraj Bikash Baruah

CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2019 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed on acid-free paper International Standard Book Number-13: 978-0-367-11164-9 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilised in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Names: Baruah, Jubaraj Bikash, author. Title: Principles and advances in supramolecular catalysis / by Jubaraj Bikash Baruah. Description: Boca Raton : CRC Press, Taylor & Francis Group, 2019. | Includes bibliographical references. Identifiers: LCCN 2019000217| ISBN 9780367111649 (hardback : alk. paper) | ISBN 9780429059063 (ebook) Subjects: LCSH: Supramolecular chemistry. | Catalysis. Classification: LCC QD878 .P75 2019 | DDC 541/.226--dc23 LC record available at https://lccn.loc.gov/2019000217 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com

Contents Preface......................................................................................................................vii Acknowledgments......................................................................................................ix Author........................................................................................................................xi Chapter 1 Introduction...........................................................................................1 1.1 Definition and Approaches......................................................... 1 1.2 What Biology Tells Us about Catalysis: Specific Cases............. 2 1.3 Complementary Weak Interactions and Molecular Recognition������������������������������������������������������������������������������ 12 1.4 Self-Assembly of Multicomponents Suitable for Catalytic Reactions������������������������������������������������������������������ 19 1.5 Energetic Aspects of Supramolecular Catalysis.......................25 1.6 Advantages of Supramolecular Catalysis.................................34 References........................................................................................... 38 Chapter 2 Organic and Inorganic Supramolecular Catalysts: Design and Function........................................................................................ 41 2.1

Salient Features of Supramolecular Catalysis.......................... 41 2.1.1 Fundamental Basis...................................................... 42 2.1.2 Intermediate Characterization..................................... 54 2.1.3 Product Selectivity Including Stereo Specificity......... 62 2.2 Inorganic Supramolecular Catalysis......................................... 69 2.2.1 Design of Mononuclear Inorganic Complexes for Supramolecular Catalysis������������������������������������� 74 2.2.2 Polynuclear Inorganic Complexes as Supramolecular Catalyst�������������������������������������������� 82 2.2.3 Metal Organic Frameworks and Coordination Polymers......................................................................90 2.3 Artificial Enzymes................................................................... 98 2.3.1 Biomimetic Metal Organic Frameworks................... 106 2.4 Applied Organocatalytic Reactions Taking Advantage of Supramolecular Features��������������������������������������������������� 111 References......................................................................................... 115 Chapter 3 Containers and Vessels for Supramolecular Catalysis...................... 121 3.1

Container Molecules............................................................... 121 3.1.1 Cages and Containers for Supramolecular Catalysis.................................................................... 127 3.1.2 Noncovalently Linked Cages for Supramolecular Catalysis.................................................................... 129 v

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Contents

3.1.3 Cavitands for Supramolecular Catalysis................... 130 3.1.4 Foldamers for Supramolecular Catalysis.................. 133 3.2 Inorganic Container Molecules.............................................. 136 3.2.1 Polydentate Ligands and Metal Coordination........... 138 3.2.2 Inorganic Container Molecules from Mono- and Dinuclear Complexes����������������������������������������������� 141 3.2.3 Molecular Flasks....................................................... 144 3.2.4 Inorganic Cages for Supramolecular Catalysis......... 146 3.2.5 Confining Inorganic Active Sites.............................. 153 References......................................................................................... 156 Chapter 4 Interlocked Systems in Catalysis and Switching............................... 159 4.1 Principles of Dynamic Interlocked Systems in Catalysis....... 159 4.1.1 Dynamic Aspects of Concealing and Revealing Catalytic Sites����������������������������������������������������������� 165 4.1.2 Utility of Interlocked Systems in Supramolecular Catalysis������������������������������������������������������������������� 168 4.1.3 Metallacycles in Catalysis......................................... 168 4.2 Control of Catalytic Activity by Switching............................ 171 4.2.1 Chemical Switching.................................................. 175 4.2.2 Electrochemical and Photochemical Switching........ 176 4.2.3 Stimulus-Guided Switching...................................... 177 References......................................................................................... 180 Chapter 5 Dendrimers in Supramolecular Catalysis......................................... 183 5.1 Principles and Definitions...................................................... 183 5.2 Convergent and Divergent Approaches for Dendrimers........ 183 5.3 Modification of Interior and Exterior of Dendrimers............. 184 5.4 Micelles in Supramolecular Catalysis.................................... 195 5.5 Gels and Ionic Liquids as Catalysts....................................... 198 References......................................................................................... 203 Chapter 6 Versatility in Supramolecular Catalysis............................................207 6.1

Material Design and Processes..............................................207 6.1.1 Biomaterials..............................................................207 6.2 Confinement of Nanoparticles as Catalysts............................207 6.3 Supramolecular Catalyst Immobilisation...............................209 6.4 Supramolecular Autocatalysis................................................ 211 6.5 Sensing through Supramolecular Catalysis............................ 216 6.6 Modified Biomolecules as Catalysts....................................... 218 6.7 Conclusion and Outlook......................................................... 219 References......................................................................................... 220 Index....................................................................................................................... 223

Preface In the context of our general life, the word catalyst is related to describe the facilitation of everyday activities. Similarly, the term supramolecular catalyst is like working under an umbrella to do everyday works in a protective and controlled manner to bring about a speedy, desired and specific output. In a chemical sense, supramolecular chemistry has emerged as a subject forecast to improve fuel, energy, healthcare and the environment. Nature performs reactions in self-made enclosures and has its own carrier systems to mix reagents. Supramolecular catalysis utilises complementary weak interactions through molecular recognition to control and increase the efficacy of chemical reactions. The redox and photochemical properties of any reacting components guide the chemical reactivities of many supramolecular catalysts, and thereby provide scopes to tune catalytic reactivities. Self-assemblies, cages, surface modifications, molecular recognition, control of particle sizes and multicomponent catalyst systems have enabled the design of new supramolecular catalysts. Such catalysts have found applications to tune reactivity and, importantly, in many selective syntheses. Many natural processes such as self-replication and self-assembly performed through supramolecular interactions have increased the importance of the subject. Solid-state assemblies are useful in carrying out cycloaddition reactions and mechano-chemical reactions. Metal organic frameworks have provided many artificial metalloenzymes. Foldamers, atropisomers, capsules, bowl-like structures and molecular flasks have provided scopes to stabilise, modify reactive intermediates and increase the efficacy of reactions. This book is an attempt to agglomerate those interdisciplinary topics in a systematic way and to decipher a new subject which will have long-term impact for general concerns. Jubaraj Bikash Baruah

vii

Acknowledgments The desire to systematically present an emerging subject like supramolecular catalysis in the form of a book has been a concern of the author’s for quite some time. The author accepted Renu Upadhyay of Taylor & Francis’s invitation to write this book. I wish to sincerely thank Renu Upadhyay for this opportunity. I also wish to thank Shikha Garg for handling the production tasks. A newly growing subject has much to absorb from very recent as well as past original literature. In this book, an attempt is made to articulate the relevant contributions as a reference section in each chapter. I acknowledge all the scientists who contributed to the subject through acknowledged original works. It is not possible in a textbook to highlight certain literature; I acknowledge the contributors if their work has not appeared in reference sections. Finally, one requires support from family for such a work; the support received from my wife, Helen, and my son, Jnanbikash, is immense. I also thank the Indian Institute of Technology, Guwahati for the use of facilities related to the literature.

ix

Author Jubaraj Bikash Baruah hails from Assam, India. He obtained his PhD from the Indian Institute of Science, Bangalore, from research under the supervision of Prof. A. G. Samuelson. After his PhD, he did postdoctoral study under Prof. Kohtaro Osakada and Prof. Takakazu Yamamoto of the Tokyo Institute of Technology, Japan. He served Gauhati University as a lecturer before moving to the Indian Institute of Technology, Guwahati. He was the founding member of the Department of Chemistry of the Indian Institute of Technology, Guwahati, where he serves as a senior professor. He served as founder Head in-Charge of Chemistry, Head of the Chemistry Department and Dean of Research and Development of the Indian Institute of Technology, Guwahati. His major research interest is in the novel properties associated with supramolecular systems. He has published over 250 research articles in reputed journals and has written two books.

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1

Introduction

1.1  DEFINITION AND APPROACHES A catalyst is a chemical compound that changes the rate of chemical reactions but is not consumed. Jons Berzelius introduced the term catalysis, which originated from the Greek words kata and lyein. In Greek, kata means down and lyein means loosen. Commonly, the word catalysis is extensively used in expressing general matters of discussion in every sphere of life, and it generally refers to difficult tasks done by an object in an easier way, where the object under consideration is not affected after performing the job. The study on the chemical aspects of catalysis started from the latter part of the 1700s. The literature on catalysis started with some of the early works of Sir Humphry Davy, who observed an increase in the rate of certain organic chemical reactions by platinum. At that time, Michael Faraday also observed that the rate of hydrogen and oxygen produced by electrolytic splitting of water was accelerated by platinum. Russian chemist Gottlieb Kirchhof, in the early part of the eighteenth century, noticed that a suspension of starch in boiled water remained suspended without decomposition, but in the presence of concentrated acid, the starch transformed to glucose. This reaction was facilitated by acid, and at the end of the reaction, the acid remained unchanged. Continued research on these systems led to the development of many homogeneous and heterogeneous catalytic reactions. In the later part of the eighteenth century, mercury catalyzing reactions to produce indigo dye was discovered. During this period of the century, nickel catalysed hydrogenation reactions of oil to prepare edible fats was also discovered, which made gateways for several new catalytic reactions. Discovery of these reactions provided a timely impetus to explore catalysis and helped to establish the facts about catalytic reactions in a systematic and formulated manner. Another discovery in the early part of the nineteenth century was on the use of a catalyst to combine nitrogen and hydrogen under pressure to form ammonia, this reaction attracted large industrial interest to catalytic reactions. In the middle part of the nineteenth century, independent discoveries of new catalysts for synthesis of polymers by Ziegler and Natta made a great impact on the industrial production of polymeric materials. Accompanied by progressive growth on the topic of catalysis, the logistical aspects of selective products with stereo- and regio-chemical control of products emerged. In these topics, weak interactions have contributed significantly, and the topic of supramolecular catalysis has taken a stand on its own as a subject area for research and applications.1–4 Generally, a recognition unit or unit with prominent supramolecular features is incorporated into the scaffold of a conventional catalyst to design a supramolecular catalyst. By doing that, a specific molecule gets along with such a catalyst. For example, urea derivatives are useful in molecular recognition. They catalyse or mediate the reactivity of various nucleophiles and activate substrates for catalytic reactions. A catalyst with supramolecular features does not necessarily significantly improve catalytic ability with respect to another 1

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Principles and Advances in Supramolecular Catalysis

catalyst analogue without a supramolecular feature; such compounds are suitable as catalysts but do not function as supramolecular catalysts. It is a concern for all of us to keep the environment clean and safe. To do so, control of the toxic substances generated from automobile engines is of the utmost concern. It is necessary to destroy or convert hazardous substances such as gases like carbon monoxide and sulphur dioxide that come out as exhaust to less harmful substances. Catalytic converters do so to a limited extent. Catalytic converters are composed of regenerable materials accelerating the decomposition of specific hazardous materials. For the safety of future life in the world, there is also a compulsion on us to keep the atmosphere protected from any hazardous matter. The ozone layer protects living beings from exposure to ultraviolet radiation by absorbing it in the atmosphere. Exposure to the ultraviolet radiation of the sun by living beings is dangerous. One threat to the environment immediately is from the depletion of the ozone layer in the atmosphere. The depletion of ozone is caused by the chlorofluoro hydrocarbons produced on the earth, which penetrate to the ozone layer and decompose ozone molecules. The chlorine radicals produced from chlorofluoro hydrocarbons are converted to chlorine. These chlorine molecules act as catalysts to deplete ozone by transforming it to oxygen. The catalytic activity for such a conversion by chlorine is so high that about a million ozone molecules can be destroyed by a single chlorine molecule in a second. Hence, the utilization of chlorofluoro hydrocarbons is banned and replacements have come to be used. These are two examples of simple catalytic reactions that concern our environment, and the examples show the important role of catalytic reactions in day-to-day life.

1.2  WHAT BIOLOGY TELLS US ABOUT CATALYSIS: SPECIFIC CASES Biological conversion of starch to sugar was a stage setter to reveal an independent class of catalyst systems called enzyme catalysts. Enzymes are biological macromolecules composed of numbers of amino acids linked together through amide bonds. The enzymes are uniquely able to enhance or retard the rates of many biological reactions. Some such rate-enhanced reactions do not take place in water and/or at ambient conditions without an enzyme catalyst. Enzyme catalysts find use in industrial processes involving preparation of fermented products, baking, brewing, detergents, pharmaceuticals and textiles. Some common processes encountered in biology are urea conversion to ammonia, which is done by an enzyme called urease; glucose to alcohol done by zymase; inversion of cane sugar is catalysed by invertase; and starch conversion to maltose in the presence of an enzyme called diatase. According to the types of catalytic reactions caused by enzymes, they are classified and categorised into six main enzyme classes, which are listed in Table 1.1. In-depth knowledge of catalytic intermediates, mechanistic paths and catalytic cycles of catalytic reactions provides insights into the sustainability and utility of catalysts. New efficient design of a catalyst requires understanding of the energetics as well as kinetics of the catalytic reactions. The fundamental principles that rule a common catalytic reaction are valid for natural catalytic reactions caused by enzymes. Due to the superior ability of nature in the design aspects to manipulate reactivity and selectivity, an enzyme performs catalytic reactions at an enormously

3

Introduction

TABLE 1.1 Different Enzymes and Their Functions Name of Enzyme Oxidoreductases Transferases Hydrolases Lyases or synthases Isomerases Ligases

Performing Reactions Redox reactions, especially involving C─O, C─C, C─N bonds. Reductive amination of C─O bonds; oxidation of C─H bonds. Reactions that transfer functional groups such as methyl, acyl, amino, phosphoryl, glycosyl, nitro, thiolate groups. Reversible and irreversible hydrolysis of functional groups such as esters, amides, nitriles, strained rings. Addition of small molecules to double bonds. Racemizations, epimerizations and rearrangement reactions involving isomers. Enzymatically active only when combined with another counterpart such as adenosine triphosphate.

accelerated rate as compared to a synthetic catalyst. Nature has evolved through natural processes over a vast period of time and provided a robust system; hence, design of catalysts in a similar manner to nature by artificial means is an uphill task. Despite the complicated structures of enzymes and the reaction of complicated intermediates involved in an enzyme-catalysed reaction, enzyme catalysis is understood to an extent just sufficient to develop biological mimics through synthetic means. Enzyme-catalysed reactions are guided by four principal factors: (a) templates provided by nature through complementary interactions to confine substrates, and the active sites those may be referred to as catalytic pockets; (b) generation of hydrophobic pockets within an enzyme catalyst by noncovalent interactions in water as medium; (c) association of each enzyme with self-replication properties to decide the type and course of a reaction; and, finally, (d) the allosteric properties associated with enzymes due to cofactors. Lowering the free energy of the transition state to provide new path(s) leading to product(s) is the common referral issue in synthetic as well as natural catalysis. Enzymes in general are more effective catalysts due to the specific substrate binding ability and the presence of logical active sites for substratespecific reactions to provide specific products. Broad ranges of organic reactions, such as redox reactions, carbon—carbon bond-forming reactions and hydrolytic reactions, are catalysed by enzymes. Nature provides the required architecture for enzyme catalysis to specifically bind stereo-isomers. It makes way for stereo-selective products. It is interesting to note that enzyme catalysis initially was not a tasty cup of tea for organic chemists. It was due to studies on the reactivities that were restricted within a narrow window of substrates, limiting applicability of the subject. Moreover, the isolation and stability of enzymes were also concerns to scientists. But with the progress of time, economically viable procedures for the preparation of enzymes through high cell density fermentation has helped enzyme catalysis to emerge as one of the prominent catalytic process. The three-dimensional active sites of an enzyme recognise molecules through confinement or complementing weak interactions, hence imbuing selectivity in reactions and products. Besides this, high chemo- and stereoselectivity of products in enzyme catalysis have established the topic at the crest of

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Principles and Advances in Supramolecular Catalysis

the sciences dealing with the catalytic reactions. Many difficult regio-, enantio-, and diastereo-selective reactions are made easy by using enzyme-catalysed reactions.5 Biological chemical reactions are guided by supramolecular interactions and selfassemblies. In a real sense, nature has no reaction vessel to mix components; neither are there hands to mix the components or control the mixing process. Biological reactions conventionally proceed in aerobic conditions in the presence of water and also do not use drastic reaction conditions to synthesise a product. In biology, the rate of mixing and other thermodynamic parameters, including transport of the waste as well as useful products, occur in a controlled manner. The kinetic approach to studying enzyme catalysis banks on the formation of activated species known as an enzyme—substrate complex. The activated species formed between an enzyme and reactant transforms reactants into products. A subsequent stage is required in the case where there is interaction between the product and enzyme; in such a situation, a product is bound to the enzyme. In general, the products are dismantled from the enzyme-product adduct, and thereby the enzyme gets ready to cause the next catalytic cycle by interacting again with a substrate molecule, forming an enzyme—substrate complex (reactive intermediate). Enzymecatalysed reactions are formulated from different intermediate equilibriums to set up equations known as the Michaelis and Menten equations. For the success of an enzyme-catalysed reaction, the hydrogen ion concentration and temperature are prime parameters. Enzyme-catalysed reactions are green by virtue of definition; in biological chemistry, substrates, enzymes and products are in water. Many enzyme-catalysed reactions are also performed in organic solvents that are not environmentally benign. In many cases, the use of solvents other than water helps to overcome the problem of insolubility of many organic compounds in water. This enhances the viability of using enzyme catalysts in organic synthesis as a common practice. Lock-and-key theory is one way to understand the catalytic action of enzymes. This theory uses the analogy of having a relation between a substrate and enzyme as a process of fitting a key into a lock. It also suggests that when a substrate binds to an active site by a lock-and-key process (1.1a) there is no change in the shape of the active site. Such complementary fitting of a substrate to an enzyme (Figure 1.1) guides enzyme-catalysed reactions. There is also another model called the induced-fit model (1.1b) for understanding enzyme activities. According to this model, there exist some amounts of noncomplementarity to bind, but the host has sufficient flexibility and shape to have compatible interactions through reorganizing itself to adopt the appropriate geometry. This model explains the catalysis of certain enzymes that catalyse reactions of multiple substrates. Enzyme-catalysed reactions are keys in light production as well as in certain protective measures. Some living organisms convert chemical energy into light through a process called bioluminescence. There are many living organisms such as bacteria, fungi, crustaceans, molluscs, fishes and insects that glow when light falls on them. In general, emission of light arises from the oxidised product of compound luciferin, caused by the catalytic reaction of an enzyme luciferase. Two insects using catalytic reactions for light generation and protective measures are shown in Figure 1.2.

5

Introduction

1.1a

1.1b

FIGURE 1.1  Lock-and-key and induced-fit mechanism. 1.2a

1.2b

FIGURE 1.2  Firefly (1.2a) and beetles (1.2b). Insects using enzyme catalysis to generate (a) light and (b) defence.

Firefly bioluminescence is fuelled by conversion of adenosine triphosphate to inorganic pyrophosphate to cause conversion of firefly luciferase to the oxidised form adduct of luciferase with oxyluciferin (Figure 1.3). Firefly luciferase specifically forms an adduct with the nucleotide triphosphate. The adenylate formed in this way is the true substrate of the subsequent oxidative chemistry. In the first step, luciferase adds to D-luciferin to form enzyme-bound D-luciferin—adenosine mono-phosphate. Formation of this adduct is facilitated by magnesium ions. The adduct reacts with oxygen to produce an oxidised form in an excited state. These excited luciferinoxyluciferin adducts decay to a ground state through emission of light, with quantum yield ranging from 0.4–0.6. In the course of the reaction, carbon dioxide gas evolves. The reactions are shown in Scheme 1.1. The luciferase enzyme acts as a monooxygenase to cause the catalytic oxidation.6 For protective measures of certain insects, they release gases, and the release of gas is very fast, comparable to an explosion at a micro level caused by such insects. An insect named the bombardier beetle, under a panic situation or in apprehension of danger, sprays an irritating substance through a sudden blast from the prostate part of the body (circled in Figure 1.2), which it uses as a biologically built-in weapon. The spray is as hot as 100°C and spreads to a 10–20 cm distance with a velocity of about

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Principles and Advances in Supramolecular Catalysis

1.3a

1.3b

1.3c 1.3d

1.3e

FIGURE 1.3  Structures of different components involved in biophotoluminescence of firefly.

SCHEME 1.1  The reactions resulting in emission by oxidation of luciferin.

10 m/sec. The entire process happens as a result of the ability of the pygidial glands of the beetles to control the reactants of the process. The gland acts as a reservoir to provide (a) a reaction chamber and also (b) the exit path to discharge the products. The reservoir stores an aqueous solution of hydrogen peroxide, 1,4-dihydroxybenzene and alkanes. The reaction chamber contains peroxidase and catalase enzymes that perform catalysis to cause very fast reactions among the reactants. When beetles spray the hot, irritating gas for their self-defence, there is a biological process that transfers the components of the reactants in the reservoir to the enzyme-containing chamber. By this process, a molecule of 1,4-dihydroxybenzene is oxidised to 1,4-benzoquinone and, as a consequence of this oxidation, oxygen also evolves by the decomposition of hydrogen peroxide. The 1,4-benzoquinone molecule being a component of the spray, it is the root cause of the irritation caused by the dispersed spray by the beetle. Whereas the exothermic nature of the reaction releases hot oxygen and provides

7

Introduction

1.4a

1.4b 1.4c

1.4d 1.4e

1.4f

FIGURE 1.4  Examples of molecules recognised to different extent by thrombin and trypotosin enzymes. (U. Obstl et al. Chem. Bio. 1997, 4, 287–295.7)

the heat to the spraying liquid/gas mixture. During these courses of action, water vaporises, pressure builds up and the spray explodes from the exit channel. The natural blood-clotting process is controlled by certain enzymes; thrombin is an enzyme which facilitates the process of blood clotting. This enzyme is also used as part of drug discovery to find selective binding with inhibitors for the process. The lead compounds 1.4a to 1.4f shown in Figure 1.4 are suitable for such a purpose. They fit into the hydrophobic pockets in which the residual functional groups located at different sites of a protein can interact through complementary hydrogen bonds. The crystal structure of the thrombin binding to 1.4a has the phenolic O ─H group of tyrosine of the enzyme interacts with an oxygen atom of the ether part of the compound. Whereas the glycine residues interact with the N─H and C═O bonds of the compound. The amidinium part has complementarities with carboxylic acid of aspartate residue. The compound 1.4f is enclosed in hydrophobic pockets of thrombin, as shown in Figure 1.5. Each pocket has a characteristic name; for example, the D-pocket of thrombin is named because of its location at a ‘distal’ from the catalytic Ser195. The S1 pocket is a deep hydrophobic pocket of the enzymes like trypsin and thrombin that contain an aspartate moiety, and this pocket dictates the selective cleavage of peptide bonds. The aspartate part of this pocket binds to the amidinium cation. The relative binding abilities of these compounds are determined by the ratios of their binding constants with two enzymes listed in Table 1.2. These results suggest the ability of thrombin to recognise them differs from the closely related enzyme trypsine. Thrombin has high selectivity for the compound 1.4c, whereas trypsin recognises the compound 1.4b in a better way than the others. Certain enzymes require additional nonprotein components called cofactors to perform catalysis.8 Cofactors are either linked to the enzyme through covalent linkage or through noncovalent interactions. The covalently linked ones are known as

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Principles and Advances in Supramolecular Catalysis

FIGURE 1.5  The environment around the molecule 1.4f embedded in the hydrophobic pockets of thrombin. (U. Obstl et al. Chem. Bio. 1997, 4, 287–295.7)

TABLE 1.2 Comparison of the Binding Abilities of Different Compounds with Trypsin and Thrombin Binding Constant (K in µM) Compound No 1.4a 1.4b 1.4c 1.4d

Thrombin

Trypsin

0.5 2.0 9.2 6.2

1.1 64.0 40.0 31.0

Selectivity (Ktrypsin/Kthrombin) 2.2 32.0 4.34 5.0

prosthetic groups, while those noncovalently linked are called coenzymes. Biological catalytic reactions involve weak interactions, and several of them involve changes in the redox properties at intermediate steps. Due to such facts, coenzymes get modified during the course of reactions, making it less suitable to use cofactors in catalytic amounts. To avoid such operational difficulties of coenzymes, a stoichiometric amount of an additional reactant is required to keep the cofactor active for multiple catalytic cycles.

9

Introduction

1.6a

1.6b

1.6c

FIGURE 1.6  Epoxide hydrolase-catalysed conversion of epoxide-converting enzymes through covalently linked intermediate. (K. Drauz et  al. Enzyme Catalysis in Organic Synthesis, 3rd ed. 2012, Wiley-VCH Verlag GmbH & Co. KGaA.8)

In biological systems, hydrolytic ring-opening reactions of epoxides to form the corresponding diol are caused by epoxide hydrolases. The intermediates of such hydrolysis have covalent links between enzyme and substrate. Accordingly, these types of enzyme-catalysed reactions are classified as covalent enzyme catalysis. In this hydrolysis process, the nucleophilic oxygen atom of aspartate attacks the electrophilic carbon atom of the epoxide ring (Figure 1.6). This results in ring opening as well as ester formation, producing a covalent intermediate. Hydrolysis of this intermediate by water is facilitated by a histidine residue. The reaction sequences are shown in Figure 1.6 where, in the first step, an ester bond is formed at Asp107. In the second step, hydrolysis of the covalent intermediate occurs; this hydrolysis process involves an extended hydrogen-bonded intermediate which has a His275 residue anchoring water and the reactant. The enzyme is regenerated after the hydrolysis and eventually a diol is formed. Thus, during formation of the diol, in fact, epoxide takes up an oxygen atom from the enzyme and water compensates for this in the enzyme. On the other hand, leukotriene A4 epoxide hydrolase contains a zinc ion, and hydrolysis by this enzyme involves a noncovalent catalytic mechanism. The zinc ion of the active site is coordinated to two nitrogen atoms of histidine residues, and the other two coordination sites have a water molecule and a glutamate residue (1.7a).

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Principles and Advances in Supramolecular Catalysis

1.7a

1.7b

FIGURE 1.7  A noncovalent enzyme catalysed ring opening reaction. (K. Drauz et al. Enzyme Catalysis in Organic Synthesis, 3rd ed. 2012, Wiley-VCH Verlag GmbH & Co. KGaA.8)

The ring opening of epoxide is facilitated by the water molecule held to the zinc ion. The example of substrate shown in Figure 1.7 has a conjugated olefin part. A water molecule attacks a carbon located at the distal end of the conjugated double bonds. This is due to the Lewis acid property of the zinc ion and to draw electron density towards the coordination site through resonance by opening the epoxide ring. The carboxylic acid group of the substrate forms an ion pair with the enzyme to act as the lock. There are many examples of metal ion-catalysed reactions in biology where modification of intermediates of hydrolytic reactions shifts the respective equilibrium towards the product side. There are also many catalytic electron-transfer biological reactions involving metal ions, so metalla-enzymes are useful in hydrolytic as well as redox reactions of biological interest. Radiobacter halo-alcohol dehalogenase enzymes cause halo-hydroxylation reactions of epoxides. In such enzyme-catalysed reactions, the halide ions are the nucleophiles to open the epoxide ring. The example shown in Figure 1.8 has arginine—tyrosine residues which bind to the epoxide group of the reactant and activate the epoxide. The halide ions held in the selective pockets of the enzymes react with the activated epoxide. Specific pockets of the enzymes provide the required spaces to confine the nucleophiles. They also confer geometry and orientation to the reactant appropriate for the nucleophilic attack of halide ions (in this case, it is chloride). This catalytic reaction belongs to a category of enzyme-catalysed reactions called electrostatic catalysis. The term electrostatic is used for these reactions as the electrostatic interaction is the predominant factor in their transition states.

11

Introduction

1.8c

1.8b

1.8a

FIGURE 1.8  Chlorohydroxylation of epoxide by radiobacter haloalcohol dehalogenase. (K. Drauz et al. Enzyme Catalysis in Organic Synthesis, 3rd Ed. 2012. Wiley-VCH Verlag GmbH & Co. KGaA.8)

1.9b

1.9a

1.9c

1.9e 1.9d

FIGURE 1.9  A reaction undergoing proton transfer to form product.

There are many proton-transfer reactions in biology that are catalysed by enzymes. These reactions provide several interesting useful insights to design new enzymes mimicking supramolecular catalysis. The intermediate 1.9c (Figure 1.9) is not stable without a supramolecular environment. Such intermediates are responsible for the formation of esters in the enzyme-catalysed reactions of alcohol with amide. In those reactions, the intermediate 1.9c remains in equilibrium with 1.9d. The intermediate 1.9d reacts with a hydronium ion to form ester 1.9e. If the exchange between 1.9c and

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Principles and Advances in Supramolecular Catalysis

1.9d is fast, the ester formation rate is not influenced by a functional group. An acid or base counterpart in the enzyme increases the rate of the reaction of the intermediate 1.9c. When the reaction of water with the intermediate 1.9c is slow, then a fraction of the intermediate formed at a particular time is converted to the product. This is prominently caused by the enzyme while performing such catalytic reactions. Many routine catalytic reactions perform at a close capacity to that of a corresponding biological reaction when the characteristic features of noncovalent interactions are improvised. The subject of supramolecular catalysis has emerged from thorough knowledge of host—guest chemistry, complexity of ions, selfassembly and encapsulation together with the fundamental aspects of conventional catalysis. The supramolecular chemistry introduced in design principles of a catalyst or efforts to understand special supramolecular aspects to justify specific features in conventional catalysis has strengthened the subject of supramolecular catalysis. The concepts of molecular recognition on rate enhancement, selective product formation, discrimination between reactants and preference to release a product from a supramolecular system coupled with reactivity study encompass supramolecular catalysis. Chemo-, stereo- and regio-selective products with high turnover and atom economy have demarcated supramolecular catalysis as a pioneering new subject area with future prospects. Thus, this category of catalysis is not different from conventional catalysis but involves supramolecular interactions as extra features. In general, due to the interplay among different noncovalent interactions and the necessity of kinetically controlled assemblies in the catalytic process, it is difficult to forecast the design of a multifunctional assembly as an intermediate in supramolecular catalysis. Thus, it is a difficult task to design a supramolecular catalyst a priori. There are many weak interactions such as cation-π, C–H-π, π–π interactions and steric repulsions responsible for stabilizing intermediates of catalytic reactions, and these interactions also facilitate enantioselective catalysis and control rates. The supramolecular features of many inorganic coordination complexes significantly change the reactivity, and many of those serve as catalysts due to such features associated with them. This provides scope to describe a supramolecular catalytic process from the first principle of catalysts. Alternatively, supramolecular catalysis includes recognition of substrates followed by organization of constructing assemblies as a reaction intermediate or of new molecules. The foregoing general descriptions may be summarised by limiting supramolecular catalysis to those reactions that involve supramolecular interactions where weak interaction schemes are independent of the basic catalytic reaction.

1.3 COMPLEMENTARY WEAK INTERACTIONS AND MOLECULAR RECOGNITION Depending on the nature of the host, there are several ways host molecules retain guest molecules. The spatial relationship between host and guest categorises them based on the process of retaining guests. The processes are entrapping guests in a capsular structure, nesting, perching, polar surface interactions, sandwiching and wrapping. In capsular interaction, the guest molecule gets into the interior void present within a host, whereas nesting involves fitting the guest into a curved space available on the

Introduction

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host molecule, similar to a nest. In the perching process, the guest is held on the edge of a polyhedral host. The sandwiching process involves engulfing the guest between sandwich types of structures, whereas warping is a process in which host molecules form enclosure assemblies or adopt a shape to wrap up a guest. Recognition of a molecule means specific and selective interactions between two or more molecules to form a stable host—guest complex over other similar analogous combinations. The complementary effects of weak interactions or additional weak interactions over normal interactions are of prime concern in molecular recognition. To have molecular recognition in supramolecular chemistry, two or more molecules bind to one another in a specific geometry. This is especially the case when a central molecule under consideration prefers to interact with one among several alternative molecules. To execute molecular recognition, a set of molecules utilise specific noncovalent interactions such as hydrogen bonds, metal coordination, hydrophobic forces, van der Waals forces, π-π interactions, ion-π interactions and electrostatic interactions. Generally, a relatively bigger or comparably sized partner molecule among a set of interacting molecules, which is called a guest molecule, accommodates or binds the other partner molecules called guest molecules. The interactions between such molecules are referred to as host—guest interactions. However, host—guest interactions or molecular recognition require complementing sizes and shapes inside a cavity, vacant spaces in container-like molecules or suitable space on a surface. The lock-and-key interaction between enzyme and substrate is an example of a molecular recognition process. Molecular recognition may be an intermolecular or an intramolecular phenomenon. For example, protein folding takes place through an intramolecular recognition process. Among self-assemblies of biological systems with intermolecular hydrogen bonds, protein—protein interactions, protein—substrate interactions, base—pair interactions in DNA, DNA—substrate interactions and so on are commonly observed. In the biological context, there is always a necessity to explore the role of noncovalent interactions for molecular understanding of biochemical processes. Such processes with biological molecules provide practical applications and pave the way to extrapolate the concepts to artificial synthetic systems. In biological or rather in any noncovalent assembly, a final self-assembled structure is obtained as a consequence of the interplay of weak interactions. Hence, the magnitudes of weak interactions contributing to a self-assembly are very important. Some such common interactions influencing supramolecular catalysis are listed in Table 1.3. Depending on the magnitude of hydrogen bond interactions, there are three different types of hydrogen-bonds: strong, moderate and weak hydrogen bonds. Moderate hydrogen bonds are of energy