Alteration of Polymorphic Selectivity through Different Crystallization Mechanisms Occurring in the Same Crystallization Solution

We report a case in which two different crystallization mechanisms occurring in the same crystallization experiment are found to yield different polymorphic outcomes. In particular, we focus on crystallization of glycine from neutral aqueous solution. Crystallization in the bulk solution gives only the metastable alpha-polymorph, as observed in previous studies, whereas crystallization by evaporation of a thin film of the solution on the walls of the crystallization vessel is found to give rise to the thermodynamically stable gamma-polymorph, and furthermore produces an uncharacteristic crystal morphology for this polymorph. A detailed set of control experiments are described that elucidate mechanistic details relating to the latter crystallization process. The fact that crystallization on the walls of a crystallization vessel can yield a different polymorphic outcome from crystallization in the bulk solution in the same experiment has potentially much wider significance with regard to other polymorphic systems.