Designing Co-Crystals of Pharmaceutically Relevant Compounds That Crystallize with Z′ > 1
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- 作者：Kirsty M. Anderson ; Michael R. Probert ; Christopher N. Whiteley ; Adrian M. Rowland ; Andrs E. Goeta ; Jonathan W. Steed
- 刊名：Crystal Growth & Design
- 出版年：2009
- 出版时间：February 4, 2009
- 年：2009
- 卷：9
- 期：2
- 页码：1082-1087
- 全文大小：242K
- 年卷期：v.9,no.2(February 4, 2009)
- ISSN：1528-7505
文摘
Molecules which crystallize with Z′ > 1 show a markedly stronger tendency to form co-crystals than compounds that crystallize in the pure form with Z′ = 1. The proportion of bioactive compounds with Z′ = 1 which form co-crystals is 4.8% as opposed to 7.1% for compounds crystallizing with Z′ > 1 in the pure state. Moreover, the Z′ > 1 percentage of the distinct set of molecules in the entire Cambridge Structural Database (CSD) that form co-crystals is 17.7% compared to the CSD average for organic molecules of 11.5%. This tendency is demonstrated experimentally by the design and preparation of a new 1:1 co-crystal of Ornidazole (Z′ = 3 in pure form) with 3,5-dinitrobenzoic acid. Two new pure structures with Z′ > 1 are also predicted and prepared from molecules known to form co-crystals, namely, 2,3,4-trihydroxybenzophenone and 6-phenyl-3(2H)-pyridazinone. These compounds crystallize in their pure form with Z′ = 2 and 3, respectively.