Control of Crystal Polymorphism by Tuning the Structure of Auxiliary Molecules as Nucleation Inhibitors. The β-Polymorph of Glycine Grown in Aqueous Solutions

Abstract

The control of crystal polymorphism of the trimorphic crystals of glycine (Gly) grown in aqueous solutions in the presence of α-amino acids operating as stereospecific nucleation inhibitors is reported. The presence of enantiopure α-amino acids phenylalanine (Phe), methionine (Met), and tryptophan (Trp) in the crystallizing aqueous solutions induces changes in the morphology of α-Gly leading to the formation of pyramidal instead of bipyramidal crystals. Increased concentrations of racemic Phe and Met inhibit both the α- and β-polymorphs of glycine and induce precipitation of the thermodynamically most stable γ-polymorph. α-Amino acids that bear bulky side groups such as racemic tryptophan (Trp), N-CH3-Trp, and α-naphthylalanine induce precipitation of the least stable β-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 β-Gly. The roles played by the different α-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 β-Gly crystals.