Polymorphism as a vehicle for crystallization research: Structure-property relationships and selective nucleation

IEC 78

Lian Yu, Eli Lilly and Company, Eli Lilly and Company, Lilly Research Labs, Lilly Corporate Center, Indianapolis, IN 46285
Polymorphism, the existence of multiple crystallization pathways leading to different solid structures, enables molecular-level studies of structure-property relationships and selective nucleation. Using the polymorphs of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile, the current record holder for the highest number of polymorphs of known structures, we studied how thermodynamic stability and crystal color depend on crystal structure and demonstrated how epitaxy with single-crystal substrates aids the discovery and selective nucleation of polymorphs. We elucidated how pH change causes glycine to crystallize into different polymorphs and salts as a result of complex acid-base and agglomeration equilibria in solution. References: Yu, L.; Ng, K. J. Pharm. Sci. 2002, 91, 2367. Yu, L. J. Phys. Chem. A 2002, 106, 544. Mitchell, C. A.; Yu, L.; Ward, M. D. J. Am. Chem. Soc. 2001, 123, 10830. Yu, L. et al. J. Am. Chem. Soc. 2000, 122, 585.