Crystal engineering

The area broadly described as crystal engineering is currently expanding at a brisk pace. Imaginative schemes for supramolecular synthesis, and correlations between molecular structure, crystal packing and physical properties are presented in the literature with increasing regularity. In practice, crystal engineering can be many different things; synthesis, statistical analysis of structural data, ab initio calculations etc. Consequently, we have been provided with a new playing field where chemists from traditionally unconnected parts of the spectrum have exchanged ideas, defined goals and made creative contributions to further progress not only in crystal engineering, but also in other disciplines of chemistry. Crystal engineering is delineated by the nature and structural consequences of intermolecular forces, and the way in which such interactions are utilized for controlling the assembly of molecular building blocks into infinite architectures. Although it is important to acknowledge that a crystal structure is the result of a subtle balance between a multitude of non-covalent forces, this article will focus on design strategies based upon the hydrogen bond and will present a range of approaches that have relied on the directionality and selectivity of such Dr Christer B. Aaker6y, although a Norwegian citizen, was educated in Sweden where he obtained an M.Sc. at Uppsala University in 1986. He then embarked on . further studies at the University of Sussex, England, where he acquired a D.Phil. in Chemistry in 1990. He was subsequently awarded a Scholarship from the Royal Swedish Academy o f Sciences that enabled him to spend 8 months as a Research Fellow at the University of Minnesota in the laboratory of the late Professor M. C. Etter. From 1993 to 1996 he held a Lectureship in Chemistry at the Queen's University of Beljast, Northern Ireland. In September 1996 he accepted a position as Assistant Professor in Supramolecular Chemistry at Kansas State University, Manhattan, Kansas, where he continues to develop his research in crystal engineering, intermolecular interactions, molecular modelling and polymorphism. (~.;'~ 1997 International Union o f Crys ta l lography Printed in Great Britain . all rights reserved interactions in the synthesis of predictable one-, twoand three-dimensional motifs. 1. Concept and background Since the early days of structural and solid-state chemistry, many chemists have (sometimes unbeknown to themselves! ) been working in the field of crystal engineering. Although the phrase itself did not appear until 1971 when it was introduced by Schmidt ( 1971 ), we only need to visit a recent definition by Desiraju (1989) to realise that structural chemistry and X-ray crystallography were involved with crystal engineering long before the concept itself had been explicitly verbalized: . crystal engineering . the understanding of intermolecular interactions in the context of crystal packing and in the utilization of such understanding in the design of new solids with desirable physical and chemical properties. It is also becoming clear that this particular topic must hold considerable and widespread appeal and fascination because, all of a sudden, it seems as if everyone is doing crystal engineering! Manuscripts dealing specifically with 'designer-architectures' and with strategies for controlling and predicting structures are published on a regular basis, and several review articles (Lehn, 1988, 1990; Aaker6y & Seddon, 1993; Braga & Grepioni, 1996; Russel & Ward, 1996; Subramanian & Zaworotko, 1994; Desiraju, 1995a; Rebek, 1996) and books (Desiraju, 1989, 1995b; V'6gtle, 1991; Lehn, 1995)have provided valuable overviews of the exciting and inspiring research efforts that have been presented during the last decade. Before examining recent developments, it is useful to remind ourselves of the origins of the term 'crystal engineering'. During a study of photochemical dimerization reactions of cinnamic acid derivatives, Schmidt and co-workers established that the spatial relationship between neighbouring molecules played a dramatic role in determining reactivity (Cohen & Schmidt, 1964). These topochemical reactions were controlled by the structure of the material, i.e. the spatial arrangement of molecules in the solid. The ability to selectively change or optimize such reactions would therefore only come Acta Cr3,stallographica Section B ISSN 0108-7681 ,~, 1997 570 CRYSTAL ENGINEERING about with control over the structure. Unfortunately, it turns out to be very difficult to foresee structural changes as a function of changes in molecular substitution patterns or in molecular geometry. Molecular shape does not necessarily manifest itself in a predictable manner in the crystalline lattice either in terms of space group, unitcell dimensions or packing patterns. Since each crystal structure is the result of a delicate balance between a range of intermolecular forces, many of which are weak and non-directional, even a small change in the molecular structure, or isomerism, may lead to dramatic and unpredictable changes in the extended crystal structure. Hence, an improved understanding of the strength, directional behaviour, structural influence, in short, the very essence of non-covalent forces, becomes the underlying focus for initial research into crystal engineering. Since intermolecular interactions govern molecular recognition at every level, every crystal structure is eventually the result of recognition processes which lead to thermodynamically favourable (albeit sometimes temporary) 3-D (three-dimensional) assemblies of molecules or ions. Bearing in mind that a crystalline material can, in theory, be assembled in an almost infinite number of ways (even within the constraints of crystal symmetry), these recognition mechanisms are extraordinarily selective, since most crystallites in every bulk sample display the same structural arrangement. This situation was recognized by Dunitz (1991) who succinctly described the crystal as the 'supramolecule per excellence'. Indeed, each crystal represents the culmination of highly specific, reliable and reproducible molecular recognition. Consequently, each crystal structure contains important information about the way in which intermolecular forces compete and collaborate and eventually create an energetically balanced system. Therefore, it seems a shame to resort to rather crude phrases like 'packing forces' (which appear far too often in the literature) when attempting to rationalize and describe new structures. Instead, if we try to take a little bit more care in the analysis of structures, packing motifs and differences in molecular conformation, our crystals may release their inherent information to us in a more digestible and understandable format. Nowacki (1942) examined space-group preference of ca 3000 structures and noticed that almost every other organic compound could be found in one of three space groups, P21/c, P2~ and P212121. He related this skewed distribution to the presence of specific symmetry elements within these space groups which, in turn, optimized electrostatic interactions between neighbouring molecules. At the same time, Kitaigorodsky (1961, 1973) began to study crystal systematics and the vast body of his work has arguably made him one of the key figures in developing a better understanding of crystal packing and structure analysis of organic compounds. His principles of close packing provided much needed organization of a rapidly growing pool of structural information and they neatly summarize the structural consequences of the balance between non-covalent forces within a crystalline lattice. Kitaigorodsky pioneered the notion that molecules strive to pack with maximum density (thus minimizing the free, 'empty', volume). In the course of this work, Kitaigorodsky also asked decisive questions about e.g. lattice dynamics, static crystals, imperfect crystals and phase transformations, and his contributions also gave inspiration and momentum to the development of molecular mechanics and force-field calculations. Other notable contributions to the interpretation of observed intermolecular bond distances include Sutor's (1962, 1963) contention that attractive C H . O hydrogen-bond interactions could play a role in determining extended crystal structures. This notion was initially met with considerable skepticism (Donohue, 1968), but was later completely vindicated using neutron diffraction data (Taylor & Kennard, 1982). Hassel & Romming (1967) made incisive observations about distances and preferential geometries for oxygen. • halogen interactions in acyl halides. The question of how we can rationalize and interpret these, and other, unexpectedly short intermolecular distances is still hotly debated and both experimental and theoretical data have been furnished in order to shed more light on these arguments. Systematic analyses of structural data continue to provide invaluable information about packing preferences, space-group bias and conformational partiality, and these studies have become even more powerful thanks to ongoing improvements and developments of the Cambridge Structural Database (Allen, Kennard & Taylor, 1983). Today, it makes perfect sense to expect that every structural paper is accompanied by a comparative study of related structures (if available), in order to place the characteristics of a new crystal structure in the proper context. In this way, unusual intraor intermolecular features can be detected readily and the 'unexpected' can often stimulate new ideas or reinterpretations of 'well known' behaviour. Consequently, crystal engineering is not just about finding quick routes to new materials with improved thermal stabilities, shorter response times or larger nonlinear optical coefficients. Equally important, and equally valid, is the task of searching for a better understanding of how fundamental l