How do molecules aggregate in solution, and how do these aggregates consolidate themselves in crystals? What is the relationship between the structure of a molecule and the structure of the crystal ...it forms? Why do some molecules adopt more than one crystal structure? Why do some crystal structures contain solvent? How does one design a crystal structure with a specified topology of molecules, or a specified coordination of molecules and/or ions, or with a specified property? What are the relationships between crystal structures and properties for molecular crystals? These are some of the questions that are being addressed today by the crystal engineering community, a group that draws from the larger communities of organic, inorganic, and physical chemists, crystallographers, and solid state scientists. This Perspective provides a brief historical introduction to crystal engineering itself and an assessment of the importance and utility of the supramolecular synthon, which is one of the most important concepts in the practical use and implementation of crystal design. It also provides a look to the future from the viewpoint of the author, and indicates some directions in which this field might be moving.
A Bond by Any Other Name Desiraju, Gautam R.
Angewandte Chemie (International ed.),
January 3, 2011, Volume:
50, Issue:
1
Journal Article
Peer reviewed
A hydrogen bond is an interaction wherein a hydrogen atom is attracted to two atoms, rather than just one, and acts like a bridge between them. The strength of this attraction increases with the ...increasing electronegativity of either of the atoms, and in the classical view, all hydrogen bonds are highly electrostatic and sometimes even partly covalent. Gradually, the concept of a hydrogen bond has become more relaxed to include weaker and more dispersive interactions, provided some electrostatic character remains. A great variety of very strong, strong, moderately strong, weak, and very weak hydrogen bonds are observed in practice. Weak hydrogen bonds are now invoked in several matters in structural chemistry and biology. While strong hydrogen bonds are easily covered by all existing definitions of the phenomenon, the weaker ones may pose a challenge with regard to nomenclature and definitions. Recently, a recommendation has been made to the International Union of Pure and Applied Chemistry (IUPAC) suggesting an updated definition of the term hydrogen bond. This definition will be discussed in greater detail.
Speak not against my bond: Another definition of the hydrogen bond? Strong hydrogen bonds satisfy all current definitions of this phenomenon, but as weaker interactions XH⋅⋅⋅YZ have been brought into the scope of hydrogen bonding, the definitions have had to change.
Crystal engineering, the design of molecular solids, is the synthesis of functional solid-state structures from neutral or ionic building blocks, using intermolecular interactions in the design ...strategy. Hydrogen bonds, coordination bonds, and other less directed interactions define substructural patterns, referred to in the literature as supramolecular synthons and secondary building units. Crystal engineering has considerable overlap with supramolecular chemistry, X-ray crystallography, materials science, and solid-state chemistry and yet it is a distinct discipline in itself. The subject goes beyond the traditional divisions of organic, inorganic, and physical chemistry, and this makes for a very eclectic blend of ideas and techniques. The purpose of this Review is to highlight some current challenges in this rapidly evolving subject. Among the topics discussed are the nature of intermolecular interactions and their role in crystal design, the sometimes diverging perceptions of the geometrical and chemical models for a molecular crystal, the relationship of these models to polymorphism, knowledge-based computational prediction of crystal structures, and efforts at mapping the pathway of the crystallization reaction.
Conspectus The halogen bond is an attractive interaction in which an electrophilic halogen atom approaches a negatively polarized species. Short halogen atom contacts in crystals have been known for ...around 50 years. Such contacts are found in two varieties: type I, which is symmetrical, and type II, which is bent. Both are influenced by geometric and chemical considerations. Our research group has been using halogen atom interactions as design elements in crystal engineering, for nearly 30 years. These interactions include halogen···halogen interactions (X···X) and halogen···heteroatom interactions (X···B). Many X···X and almost all X···B contacts can be classified as halogen bonds. In this Account, we illustrate examples of crystal engineering where one can build up from previous knowledge with a focus that is provided by the modern definition of the halogen bond. We also comment on the similarities and differences between halogen bonds and hydrogen bonds. These interactions are similar because the protagonist atomshalogen and hydrogenare both electrophilic in nature. The interactions are distinctive because the size of a halogen atom is of consequence when compared with the atomic sizes of, for example, C, N, and O, unlike that of a hydrogen atom. Conclusions may be drawn pertaining to the nature of X···X interactions from the Cambridge Structural Database (CSD). There is a clear geometric and chemical distinction between type I and type II, with only type II being halogen bonds. Cl/Br isostructurality is explained based on a geometric model. In parallel, experimental studies on 3,4-dichlorophenol and its congeners shed light on the nature of halogen···halogen interactions and reveal the chemical difference between Cl and Br. Variable temperature studies also show differences between type I and type II contacts. In terms of crystal design, halogen bonds offer a unique opportunity in the strength, atom size and interaction gradation; this may be used in the design of ternary cocrystals. Structural modularity in which an entire crystal structure is defined as a combination of modules is rationalized on the basis of the intermediate strength of a halogen bond. The specific directionality of the halogen bond makes it a good tool to achieve orthogonality in molecular crystals. Mechanical properties can be tuned systematically by varying these orthogonally oriented halogen···halogen interactions. In a further development, halogen bonds are shown to play a systematic role in organization of LSAMs (long range synthon aufbau module), which are bigger structural units containing multiple synthons. With a formal definition in place, this may be the right time to look at differences between halogen bonds and hydrogen bonds and exploit them in more subtle ways in crystal engineering.
Crystal Engineering has traditionally dealt with molecular crystals. It is 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 desired physical and chemical properties. We outline here five areas which come under the umbrella of Crystal Engineering and where we feel that a proper planning of research efforts could lead to higher dividends for science together with greater returns for humankind. We touch on themes and domains where science funding and translation efforts could be directed in the current climate of a society that increasingly expects applications and utility products from science and technology. The five topics are: 1) pharmaceutical solids; 2) industrial solid state reactions; 3) mechanical properties with practical applications; 4) MOFs and COFs framework solids; 5) new materials for solar energy harvesting and advanced polymers.
A promising future: Crystal engineering has led to the successful approval of two cocrystal–salt drugs by the USFDA in the past three years. At least three more drug candidates are in the regulatory passage. The low solubility challenge faced by almost 90 % of drugs in BCS classes II and IV can be met by using pharmaceutical cocrystals. Read more about this and other emerging applications of Crystal Engineering in the Viewpoint by A. K. Nangia and G. R. Desiraju.
Conspectus Mechanical properties of organic molecular crystals have been noted and studied over the years but the complexity of the subject and its relationship with diverse fields such as ...mechanochemistry, phase transformations, polymorphism, and chemical, mechanical, and materials engineering have slowed understanding. Any such understanding also needs conceptual advancessophisticated instrumentation, computational modeling, and chemical insightlack of such synergy has surely hindered progress in this important field. This Account describes our efforts at focusing down into this interesting subject from the viewpoint of crystal engineering, which is the synthesis and design of functional molecular solids. Mechanical properties of soft molecular crystals imply molecular movement within the solid; the type of property depends on the likelihood of such movement in relation to the applied stress, including the ability of molecules to restore themselves to their original positions when the stress is removed. Therefore, one is interested in properties such as elasticity, plasticity, and brittleness, which are linked to structural anisotropy and the degree to which a structure veers toward isotropic character. However, these matters are still by no means settled and are system dependent. While elasticity and brittleness are probably displayed by all molecular solids, the window of plasticity is perhaps the one that is most amenable to crystal engineering strategies and methods. In all this, one needs to note that mechanical properties have a kinetic component: a crystal that is elastic under slow stress application may become plastic or brittle if the same stress is applied quickly. In this context, nanoindentation studies have shown themselves to be of invaluable importance in understanding structural anisotropy. Several problems in solid state chemistry, including classical ones, such as the melting point alternation in aliphatic straight chain dicarboxylic acids and hardness modulation in solid solutions, have been understood more clearly with this technique. The way may even be open to picoindentation studies and the observation of molecular level movements. As in all types of crystal engineering, an understanding of the intermolecular interactions can lead to property oriented crystal design, and we present examples where complex properties may be deliberately turned on or off in organic crystals: one essentially fine-tunes the degree of isotropy/anisotropy by modulating interactions such as hydrogen bonding, halogen bonding, π···π interactions, and C–H···π interactions. The field is now wide open as is attested by the activities of several research groups working in the area. It is set to take off into the domains of smart materials, soft crystals, and superelasticity and a full understanding of solid state reactivity.
A strategy is outlined for the design of hand-twisted helical crystals. The starting point in the exercise is the one-dimensional (1D) plastic crystal, 1,4-dibromobenzene, which is then changed to a ...1D elastic crystal, exemplified by 4-bromophenyl 4′-chlorobenzoate, by introduction of a molecular synthon −O–CO– in lieu of the supramolecular synthon Br···Br in the precursor. The 1D elastic crystals are next modified to two-dimensional (2D) elastic crystals, of the type 4-bromophenyl 4′-nitrobenzoate where the halogen bonding and C–H···O hydrogen bonding are well-matched. Finally, varying the interaction strengths in these 2D elastic crystals gives plastic crystals with two pairs of bendable faces but without slip planes. Typical examples are 4-chlorophenyl and 4-bromophenyl 4′-nitrobenzoate. This type of 2D plasticity represents a new type of bendable crystals in which plastic behavior is seen with a fair degree of isotropic character in the crystal packing. The presence of two sets of bendable faces, generally orthogonal to each other, allows for the possibility of hand-twisting of the crystals to give grossly helical morphologies. Accordingly, we propose the name hand-twisted helical crystals for these substances.
The acid···amide dimer heterosynthon in cocrystals of aromatic acids and primary amides is identified by marker peaks in the IR spectra that are characteristic of individual N–H···O and O–H···O ...interactions and also of the extended synthon. The O–H···O hydrogen bond is crucial to heterodimer formation in contrast to the N–H···O bond. A combinatorial study, tuning the chemical nature of acid and amide functionalities, leads to 22 cocrystals out of 36 crystallization attempts. Four quadrants I–IV are defined based on acidity and basicity of the acid and amide components. The strong acid–strong base combination in quadrant I favors the planar acid···amide heterodimer in its eight cocrystals. Quadrant IV with its weak acid–weak base combination is the least favored for the planar heterosynthon and synthon diversity is observed in the eight cocrystals obtained. The strong–weak and weak–strong combinations in quadrants II and III are expectedly ambivalent. This exercise highlights the effect of molecular features on supramolecular behavior. Quadrant I crystals, with their propensity for the planar acid···amide heterodimer are suitable for the engineering of crystals that can be sheared. This quadrant favors the formation of elastic crystals too. The overall result is that 57% (4 in 7) of all crystals in this quadrant are deformable, compared with 14% (1 in 7) in the three other quadrants. This work is a complete crystal engineering exercise from synthon identification to a particular desired crystal packing to property selection. One can virtually anticipate the mechanical property of a putative acid···amide cocrystal from a knowledge of just the molecular structures of the constituent acid and amide molecules.
This recommendation proposes a definition for the term “chalcogen bond”; it is recommended the term is used to designate the specific subset of inter- and intramolecular interactions formed by ...chalcogen atoms wherein the Group 16 element is the electrophilic site.
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