Effects of Inorganic Salts and Volume Reduction on Glycine Polymorphism

Studies have demonstrated that inorganic salts can drive polymorphic selectivity of glycine from the metastable α-polymorph to the stable γ-polymorph. Here, we explore the effect of NaCl and CaCl₂ together with volume reduction on glycine nucleation. The salts were added to supersaturated aqueous solutions of glycine at a 2:1 Gly:NaCl/CaCl₂ ratio at volumes from 1000 μL to 50 μL. Analysis showed that a primary γ-glycine nucleation event occurs for Gly:NaCl systems, with observed increase in induction times as volume was decreased. However, β-glycine primary nucleation was also detected for Gly:NaCl systems. Interestingly, it was observed that β-glycine nucleation is preferred over the salt-directed γ-glycine nucleation at a certain volume. The increase in induction times combined with a decrease in probability for γ-glycine nucleation may have allowed preferred nucleation of the β-polymorph. On the other hand, no nucleation events were observed for Gly:CaCl₂ systems at a time span of 48 hours. These results provide insight on how polymorph modifiers act in confined environments.