Similarity and Differences of Dasatinib Solvates: A Crystallographic Perspective

Detailed crystallographic and computational analysis of solvates of dasatinib (DAS), an inhibitor of multiple tyrosine kinases, was performed by confirming the high structural similarity of most of the DAS crystal structures and identifying the differences in molecular conformation, hydrogen bonding, and molecular packing. The crystal structures of 14 new DAS solvates are presented, allowing the crystallographic analysis of 23 DAS solvates and one nonsolvated phase. The analysis of molecular conformation revealed that in most of the structures DAS adopts three slightly different conformations, even though computational analysis indicated the existence of alternative energetically competitive conformations. In almost all structures, DAS molecules form identical hydrogen-bonded layers. The lack of structural variation is believed to be the result of the limited ways for efficient packing of the large sized and specifically shaped DAS molecules. Detailed analysis, however, revealed three similar but somewhat different ways these layers are packed, resulting in the classification of DAS solvates in three structure groups I, II, and III. The different arrangements of the layers result in different hydrogen bonds formed by O1–H and the space available for the solvent, but, interestingly, this is not linked with the exact DAS conformation or solvent functionality, properties, or bonding with DAS molecules.