Crystal engineering and polymorphism

Braga, D. and Grepioni, F. (2005) Making crystals from crystals a green route to crystal engineering and polymorphism. Chem. Commun., 3635-3645. 

The controlled preparation and characterization of different crystal forms of the same substance has become one of the major issues of modern crystal engineering and solid-state chemistry. Even though the discovery of polymorphs of molecular crystals or of their diverse solvate forms (pseudo-polymorphs) is often serendipitous, crystal polymorphism can, to some extent, be controlled. The existence of more than one packing arrangement for the same molecular or ionic components) could be a major drawback for the purposed bottom-up construction of functional solids. Rather than attempting a thorough review of the subject, this... 

Thus, the preceding theoretical analysis provides a molecular view of disappearing polymorphs common in crystal engineering. However, many experimental factors such as temperature and rates of precipitation may control the ultimate formation of the polymorphs. From the discussion, it is also quite evident that there is a close resemblance between protein folding and crystal engineering, and both share a common physical chemistry basis. 

An understanding of crystallization is important for the systematic development of crystal engineering, but it is not a simple phenomenon and many would agree that it is still far too difficult to study in a rigorous way, either experimentally or theoretically. However, indirect approaches to the study of crystallization are evolving. Three possible types of crystals that may be pertinent to this endeavor are (1) polymorphs - these represent cases of alternative crystallization, (2) pseudosymmetric structures with multiple molecules in the asymmetric unit - these could represent cases of incomplete crystallization, and (3) solvated crystals or pseudopolymorphs -these may represent cases of interrupted crystallization. These three scenarios are now sketched very briefly and the treatment given is necessarily selective. 

The molecular packing of MOMs results from a precise and subtle balance of several intermolecular interactions within a narrow cohesion energy range of less than 1 eV molec . This is the reason why crystal engineering is so powerful because this balance can be intentionally modified but at the same time it implies that MOMs are soft materials and that polymorphism is favoured. Detailed descriptions on the fundamentals of interatomic and intermolecular interactions can be found in many books (see e.g., Kitaigorodskii, 1961). Here we briefly describe the relevant interactions for MOMs and give a new approach supported on the nanoscience perspective. 

An interesting example of a mineral featuring remarkable hardness anisotropy and considerable hardness scatter is silicon carbide, SiC, widely used in electronic, electrical engineering and machining industries. It can crystallize in two polymorphous varieties, namely cubic / -SiC and hexag-... 

The central problem in organic solid-state photochemistry is the preorganization of molecules satisfying the topochemical postulates. Schmidt coined the term crystal engineering for this problem of supramolecular assembly. Indeed, the importance of crystal engineering is fundamental to areas as diverse as nonlinear optics, high- /) superconductors, and the generation of polymorph forms in pharmaceuticals. 

The topic of polymorphism is of tremendous and increasing academic and industrial importance in modern crystal chemistry and crystal engineering. The industrial interest stems from the pharmaceutical industry and has stimulated wide-ranging academic study. Legally, a molecule (termed an active pharmaceutical Ingredient, API) with particular biological activity in vivo can be patented as a new invention. Moreover, particular crystal forms of that molecule (polymorphs) can be separately patented as distinct inventions. If particular polymorphs are patented after the original API patent then upon the... 

Moulton, B., Zaworotko, M. J., From molecules to crystal engineering Supramolecular isomerism and polymorphism in network solids. Chem. Rev. 2001,101, 1629-1658. 

Pseudo-polymorphs [12b, 19], relevant for the following discussion, are characterized by the presence of solvent molecules that may differ in type and quantity and, of course, in the way of bonding within the crystal. Therefore, there is a difference in chemical composition between different solvates and between these and the unsolvated forms. Whether this would lead to a different behaviour in solution will depend on the nature of the encapsulated guest molecule in relation to that constituting the solvent. If the focus is on the chemically relevant species, the presence of solvent molecules will not be relevant however, for the purposes of crystal engineering, the solvent molecules present in pseudo-polymorphs will not be innocent partners. The guest molecules participate in determining crystal properties, even if the structure of the chemically relevant molecule or ion is not influenced. 

Single-crystal diffraction methods (whether based on X-ray or neutron sources) are those that carry the most complete information on the intimate nature of the crystals and therefore provide the most valuable tools for identification, characterization and comparison of polymorphs and pseudo-polymorphs. It is difficult to deny that one of the reasons for the outpouring of new results in the field of crystal engineering is the quantum leap represented by the commercial availability of single-crystal diffractometers equipped with area detectors. These devices have not only reduced the time of data collection by an order of magnitude with... 

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