Influence of Solution Speciation of Impurities on Polymorphic Nucleation in Glycine

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 (Glu) 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 p K a 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 α-form. This demonstration of screening impurities using morphological and kinetic data is a step directed toward the control of polymorphic crystallization in industrial systems.