The rich solid-state phase behavior of L-Phenylalanine: disappearing polymorphs and high temperature forms

After years of controversy over the solid state structure of the essential amino acid L-phenylalanine, four different polymorphic forms were published recently. The common form I has symmetry P21 with four molecules in the asymmetric unit (Z = 4), similar to form III, but with a different arrangement of molecular bilayers. Form II, obtained from the hydrate at very low humidity is unrelated to forms I and III, as is the high-density form IV. The present investigation demonstrates that this prototype aromatic amino acid has two additional high-temperature phases Ih and IIIh obtained from form I and form III above 458 and 440 K, respectively, when flipping between two alternative side-chain conformations becomes dynamic and causes pairs of molecules, initially crystallographically independent, to become equivalent above a sharp transition temperature. These abrupt and reversible phase changes occur with a reduction of Z from 4 (low T ) to 2 (high T ) and modified crystal symmetry. We furthermore experienced...