Guangjun Han

Resolving the longstanding riddle of pH-dependent outcome of glycine polymorphic nucleation

We have experimentally studied the nucleation of acidic and basic glycine aqueous solutions using in situ Raman spectroscopy and hence resolved the longstanding riddle of pH-dependent polymorphic outcome. We have found that typical inorganic acids and bases accelerate the nucleation rates of both α- and γ-glycine, with γ-glycine promoted to a greater extent hence formed preferentially over α-glycine. We hypothesize that glycine ions, readily formed in an acidic or basic environment, induce head-to-tail molecular ordering which structurally matches γ-glycine and primarily directs nucleation path from α-glycine to γ-glycine.

Salt-dependent growth kinetics in glycine polymorphic crystallization

Mechanistic exploration of the salt-dependent polymorphic outcome of solution crystallization of an important classical model compound, glycine, was carried out by measuring the growth rates of α-glycine and γ-glycine single seed crystals in the presence of typical inorganic salts. The most surprising finding was that all the three divalent cation salts examined here inhibited the growth of γ-glycine far more severely than that of α-glycine, thereby reinforcing the preferential formation of α-glycine. This strongly indicates that crystal (nucleus) growth kinetics plays an important role in determining the outcome of glycine polymorphic crystallization in the presence of these associated divalent cation salts. On the other hand, monovalent cation salts of different cations (Na+, K+ and NH4+), in general, do not significantly change the relative growth competitiveness of α-glycine and γ-glycine but they readily alter the polymorphic selectivity from α-glycine to γ-glycine. It is therefore inferred that nucleation phenomena (e.g., clustering and ordering of solute molecules in solution) also make a great contribution to directing the path of glycine polymorphic crystallization. As such, the observations from this study provide new insights into additive-directed glycine polymorphic crystallization.