Designer co-crystals

Water motifs have been classified systematically using a system of nomenclature somewhat analogous to graph set analysis (Section 8.3.1). in this scheme water structures are discussed in terms of particular classes, listed below. 

C infinite chains in 1 dimension involving no rings T infinite tapes in 1 dimension involving rings L infinite layers in 2 dimensions 

In addition about 4% of compounds were unclassified (U or network, N) showing cross-linking within rings. The D and C patterns prove to be by far the most common, accounting for 61 % and 

Work by Neil Champness of the University of Nottingham, UK, has resulted in a strategy for encouraging the formation of extended water arrays in molecules such as 8.43 that contain a 1,4-dihydroquinoxaline- 

Should solid-state molecular packing have to obey the rules of crystallographic symmetry , Cryst. Eng. Comm. 2003, 5, 169-179. 

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K.M. Anderson, M.R. Probert, C.N. Whiteley, A.M. Rowland, A.E. Goeta, J.W. Steed, Designing co-crystals of pharmaceutically relevant compounds that crystallize with Z > 1, Cryst. Growth Des. 9 (2009) 1082-1087. 

How to design co-crystal formers using crystal engineering and prepare them using green methodologies ... 

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. 

Fig. 16.1. Progress of two rounds of Chk1 targeted libraries. Cpd-1 is the original HTS hit with a broad kinase inhibition profile and based on which the first round library was designed and synthesized. 1808-1 is the best hit from the first round targeted library with improved kinase selectivity profile, based on which the second round library was designed and synthesized. 1819-1 is the best lead with improved potency, kinase selectivity, and solubility. Co-crystal structures of Chkl kinase domain and corresponding lead compounds were solved and extensively utilized in structure-based singleton and library designs. For details of the X-ray co-Crystal structures, please refer to the publications from Ming and et al (4a) and Foloppe and et al for details (4b).

Elements and Principles of Design. 46 min. Aspen, CO Crystal Productions, 1989. Elements of Design. 30 min. Glenview, IL Crystal Productions, 1996. 

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