Influence of solution speciation of impurities on polymorphic nucleation in glycine

Abstract

Nucleation of polymorphs is a phenomenon in which a chemical compound crystallizes with different molecular packing arrangements in the solid state. Glycine, the simplest amino acid, usually crystallizes as the metastable α-polymorph from pure aqueous solution. Based on our previous studies (Poornachary et al. Cryst. Growth Des. 2007, 7 (2), 254), we predict that "certain" impurities (viz. L-, D-, and DL-aspartic (Asp) and -glutamic (GIu) acids) can operate as stereospecific nucleation inhibitors and in doing so impact polymorphic nucleation in glycine. In line with this prediction, we observed that the thermodynamically stable γ-polymorph crystallized from solutions containing trace amounts of these impurities. Asp and Glu, with pKa values lower than the isoelectric point (pi 5.9) of glycine, dissociate in glycine solution, forming charged molecular species. From this known solution chemistry and the crystal morphologies of α- and γ-polymorphs, it is hypothesized that the interactions between charged molecular species and the developing crystal nuclei resulted in the crystallization of γ-glycine. Supporting this hypothesis, metastable zone width measurements of pure and impure solutions of glycine indicated that these impurities may cause nucleation inhibition of the a-form. This demonstration of screening impurities using morphological and kinetic data is a step directed toward the control of polymorphic crystallization in industrial systems. © 2008 American Chemical Society.