Host–Guest Chemistry

Supramolecular Inclusion in Solution

Brian D. Wagner

• Publisher: De Gruyter
• Year: 2020
• Print ISBN: 9783110564365
• eBook ISBN: 9783110564396
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Inorganic Chemistry

This textbook addresses the chemical and physicochemical principles of supramolecular host-guest chemistry in solution. It covers the thermodynamics and dynamics of inclusion and highlights several types of organic hosts. Various applications of host-guest chemistry in analytical and environmental chemistry as well as pharmaceutical and chemical industry demonstrate the versatile usability of molecular cages.

Chapter 1 Introduction

Host–guest inclusion in solution occurs when a guest solute molecule becomes fully encapsulated or partially included within the interior cavity of a larger, hollow host solute molecule, to form a host–guest inclusion complex. Host-guest inclusion is an interesting and fundamental example of a supramolecular process. In these processes (described in detail in Section 1.1.) two or more molecular species are bound by intermolecular forces. The solvent plays a fundamental role in this phenomenon, the most important solvent for this process being water, as the vast majority of host–guest inclusion complexation occurs in aqueous solution, for various reasons as will be discussed. This process results in significant changes to the physical and spectroscopic properties of the guest (and, in some cases, the host), including changes to the guest solubility, stability, reactivity, infrared and UV–visible absorption properties, and fluorescence properties.

Supramolecular chemistry, in general, and host–guest inclusion phenomena, in particular, have become an integral part of modern chemistry research, both from a fundamental and an applied perspective. Applications of host–guest inclusion vary, and include drug delivery, separations science, food and cosmetic industries, reaction catalysis, and materials science. From this perspective, it is useful for scientific researchers at all levels to have a good understanding of this key area of supramolecular chemistry, in terms of the self-assembly and driving forces for inclusion involved, the useful effects inclusion can have on specific guests of interest, the variety of organic host molecules (with a wide range of cavity shapes and characteristics) available for use, and the best experimental and theoretical methods for investigating their properties and inclusion complexation.

Host–guest inclusion chemistry is also fairly commonly used in products with which people are familiar in their everyday lives. For example, some fabric refresher sprays contain cyclodextrins (CDs), one of the common families of host molecules used in research and applications (and one which will be extensively discussed in the following chapters). These CD hosts when sprayed onto fabric, such as on furniture, tend to “trap” the odor molecules as guests within their internal cavities, preventing them from traveling through the air, hence, reducing their perceived odor. As a further example, some chewing gum also contain CDs, to trap flavor molecules and allow them to be released slowly, thereby increasing the length of time that the flavor of the gum lasts while being chewed in the aqueous (saliva) environment of the mouth.

This book presents in detail the fundamental aspects of this interesting and highly applicable phenomenon of host–guest inclusion in solution, with the goal of providing the reader with an in-depth, practical working knowledge of the process, its history, how it can be achieved, how it can be understood, how it can be studied and characterized experimentally, the wide range of host molecules available, and how it can be usefully applied.

1.1 Supramolecular chemistry

Supramolecular chemistry deals with the synthesis and properties of chemical systems involving two or more discrete molecular species joined together via noncovalent, intermolecular forces only. By contrast, molecular chemistry deals with the synthesis of new molecules via the breaking of existing covalent bonds and the formation of new covalent bonds, to create new molecules. Supramolecular structures have properties different from the discrete molecular components and have a wide variety of applications. These intermolecular forces of attraction include van der Waals forces, dipole–dipole, ion–dipole, and hydrogen bonding. A key feature resulting from the noncovalent nature of the connections between the molecular components in supramolecular architectures is that the relatively weak “bonding” means that the process is highly reversible, as the connections can easily be broken. Supramolecular structures are therefore equilibrium structures; for example, a molecule that is bound in a supramolecular structure can easily be released. This leads to many of the applications of such systems. A related feature of supramolecular systems is that they are constructed through self-assembly and typically represent the thermodynamically most stable interaction of the components. In this way, supramolecular structures are much easier to prepare than the corresponding covalent molecular products, as the joining of the components does not involve synthetic chemistry (although often the preparation of the components themselves relies heavily on the use of organic or inorganic chemistry synthetic techniques).

Research in the area of supramolecular chemistry has grown significantly in the past few decades. This relatively young field spans across the traditional chemistry disciplines, with aspects of and relevance to organic, inorganic, analytical, biological, and theoretical chemistry. Furthermore, the reversible nature of supramolecular systems, their formation through self-assembly, and the predominant use of aqueous media have all contributed to their significant potential for useful applications, and the widespread interest in their fundamental properties and nature. A discussion of the history of supramolecular chemistry, with the aim of placing this field in a historical context, to establish how it has evolved and where it will lead, is presented in detail in Chapter 2.

The status and importance of supramolecular chemistry as a scientific pursuit was recognized by the awarding of the 1987 Nobel Prize in Chemistry to Professors Donald J. Cram of UCLA, Jean-Marie Lehn of the University of Strasbourg, and Charles J. Pederson of Dupont, “for their development and use of molecules with structure-specific interactions of high selectivity” [1.1]. These three scientists are recognized as pioneers of host–guest chemistry. Charles J. Pederson did extensive work with crown ethers starting in the 1960s and established their utility as hosts for metal ion and other cationic guests [1.2–1.4]. He published a seminal paper on crown ethers in the Journal of the American Chemical Society in 1967 [1.5]. Donald J. Cram [1.6, 1.7] extended the idea of these molecular hosts to three dimensions, developing such 3D hosts as cavitands, carcerands, and hemicarcerands (see Sections 9.2 and 9.5), and exploring their ability to encapsulate molecular guests [1.8, 1.9]. He published a total of over 400 papers, including a series of 67 papers with titles starting with “Host-Guest Complexation. Xx,” for example number 46 on cavitands [1.10] and many other seminal papers, such as on rigid organic hosts [1.11]. Jean-Marie Lehn was an early innovator in the area of supramolecular chemistry, developing a range of organic hosts such as cyptands (see Section 9.3), and developed both the term and concepts of supramolecular chemistry [1.12–1.14]. He has published extensively, with over 900 peer-reviewed papers in the chemical literature.

Professor Lehn, who in fact was the person who coined the term “supramolecular chemistry,” and thus can in many respects be considered to be the “godfather of supramolecular chemistry,” has also published extensively on the definition, philosophy, nature, history, and context of supramolecular chemistry, in a number of thoughtful and illuminating articles and books [1.15–1.20]. In his Nobel Prize acceptance speech [1.15], Professor Lehn stated that:

Supramolecular chemistry may be defined as “chemistry beyond the molecule”, bearing on the organized entities of higher complexity that result from the association of two or more chemical species held together by intermolecular forces.

This is the working definition of supramolecular chemistry that will be used throughout this book; the central concept being that supramolecular structures, such as host–guest inclusion complexes, are held together solely by noncovalent, intermolecular forces of attraction. Supramolecular chemistry is in this way distinguished from molecular synthetic chemistry, the chemistry of the covalent bond. A key feature of supramolecular systems is that they from via self-assembly, such that component molecules simply need to be mixed together, in solution for example, and the resulting supramolecular structures form spontaneously. The thermodynamics of such self-assembly processes are discussed in detail in Chapter 3. In addition, since there must be proper correspondence, or fit, between the molecular components involved, this leads to another central concept in supramolecular chemistry, that of molecular recognition [1.15].

The Nobel Prize in Chemistry for Cram, Lehn, and Pedersen in 1987 was recently followed by further recognition and validation of supramolecular chemistry by the awarding of the 2016 Nobel Prize in Chemistry to Professors Jean-Pierre Suavage of the University of Strasbourg (who was a PhD student of Jean-Marie Lehn), J. Fraser Stoddart of Northwestern University, and Bernard L. Feringa of the University of Groningen “for the design and synth...

Table of contents

• Title Page
• Copyright
• Contents
• Preface
• List of Important Abbreviations and Symbols
• Chapter 1 Introduction
• Chapter 2 Historical aspects
• Chapter 3 Driving forces, thermodynamics, and kinetics of inclusion in aqueous solution
• Chapter 4 Spectroscopic methods for studying host–guest inclusion in solution
• Chapter 5 Other experimental methods for studying host–guest inclusion in solution
• Chapter 6 Extraction of binding constants from experimental data
• Chapter 7 Cyclodextrins as hosts
• Chapter 8 Cucurbit[n]urils as hosts
• Chapter 9 Other molecular hosts in aqueous solution
• Chapter 10 Host–guest inclusion in mixed aqueous and nonaqueous solution
• Chapter 11 Applications of host–guest inclusion in solution
• Chapter 12 Conclusions and summary
• Index