Control of crystal polymorphism by tuning the structure of auxiliary molecules as nucleation inhibitors.: The β-polymorph of glycine grown in aqueous solutions

The control of crystal polymorphism of the trimorphic crystals of glycine (Gly) grown in aqueous solutions in the presence of alpha-amino acids operating as stereospecific nucleation inhibitors is reported. The presence of enantiopure alpha-amino acids phenylalanine (Phe), methionine (Met), and tryptophan (Trp) in the crystallizing aqueous solutions induces changes in the morphology of alpha-Gly leading to the formation of pyramidal instead of bipyramidal crystals. Increased concentrations of racemic Phe and Met inhibit both the alpha- and beta-polymorphs of glycine and induce precipitation of the thermodynamically most stable gamma-polymorph. alpha-Amino acids that bear bulky side groups such as racemic tryptophan (Trp), N-CH3-Trp, and alpha-naphthylalanine induce precipitation of the least stable beta-Gly polymorph. Quasi-racemic mixtures of R-Trp and S-Phe (or S-Met), for example, lead to the precipitation of one of the enantiomorphs of beta-Gly. The roles played by the different alpha-amino acids in affecting morphology and polymorphism. are discussed in terms of their interactions with and stereoselective occlusion in the various sectors of the {010} faces of the beta-Gly crystals.