The importance of relative growth rates in the preponderance of alpha- over gamma-glycine during solution crystallisation has been confirmed. Most surprisingly tailor-made additives drastically accelerated the growth of gamma-glycine--an unexpected and key factor in the polymorphic outcome of glycine crystallisation.

The growth kinetics of γ-glycine and dl-alanine crystals in pure aqueous solutions was studied systematically using in situ microscopic observations on single crystal seeds. It was found that the growth behaviors of these two polar crystals are very similar. A fairly large dead supersaturation zone is observed respectively for their growth along the polar c-axis. Over a wide supersaturation range, the growth of these crystals along the polar c-axis remains remarkably slower than that along other axes, leading to a drastic morphological change from needle-like to prismatic pyramidal shape. This slow growth and the existence of the dead zone are attributed to the preferential adsorption of solvent water at the polar c ends, which is supported by predicted binding energies for solvent−surface interactions. With the increase in supersaturation, however, the growth along the polar c-axis, predominantly at the −c end, changes from the slowest to the fastest thereby yielding the usual needle-shaped morphology. This observed growth acceleration is explained based on structural features of the faces. The implication of these growth phenomena for the previously reported competitive formation of α-glycine and γ-glycine is discussed.

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 pK 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.