Design and Synthesis of Co-crystals

2 Co-crystals Solid-state Targets for Non-covalent Synthesis 

What is the most likely outcome when a solution containing different molecular solutes is allowed to evaporate to dryness Unless a chemical reaction driven by the formation of covalent bonds takes place between the solutes, one would normally expect the appearance of separate molecular solids. This is a demonstration of the innate structural selfishness of molecules [60], and it is utilized every time recrystallization is employed as a method of purification. Recrystallizations are per- 

This section will provide some practical approaches to the design of binary and ternary supermolecules and co-crystals by outlining supramolecular synthetic strategies based upon modular hydrogen-bond driven approaches. 

Crystal engineering is a highly interdisciplinary area, which to some extent explains why unambiguous definitions and systematic nomenclatures have yet to be fully developed. The term co-crystal is not well-defined, and the existing literature contains terms such as molecular complexes, co-crystals, molecular adducts, 

Only compounds constructed from discrete neutral molecular species will be considered as co-crystals, and all solids containing ions, including complex transition-metal ions, are excluded from this overview. 

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Scheme 2.5.23 Design, implementation, and evaluation of supramolecular synthesis of co-crystals.

The study of pharmaceutical co-crystals is also a re-emerging and exciting field of academic research in the context of crystal engineering and rational design of molecular assemblies. Most, if not all, fundamental aspects have been reviewed in this book, from the role of weak interactions in co-crystals to mechanochemical methods of synthesis, including insights into solubility and thermodynamic stability or phase diagrams of co-crystals. 

A set of molecules that rank high after this process would be synthesized and subject to biological tests, i.e., in vitro enzymatic assay or binding affinity experiments, in order to confirm design rationales. Simultaneously, X-ray co-crystal structures of these ligands in complex with the target are to be determined to further corroborate modeling results. Positive results from such approaches are decisive for selection of next set of compounds for synthesis and the future directions of lead optimization. 

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