Expanding the Solid-State Landscape of L-Phenylalanine: Discovery of Polymorphism and New Hydrate Phases, with Rationalization of Hydration/Dehydration Processes

To date, only one crystal structure of L-phenylalanine has been reported, with no confirmed report of polymorphism of this material. In the present work, we report the discovery of a new polymorph of L-phenylalanine, with the structural properties determined directly from powder X-ray diffraction data. The new polymorph of L-phenylalanine is stable only under rigorously dry conditions. In addition, two new solid hydrate phases of L-phenylalanine have been discovered: a monohydrate and a hemihydrate. The hemihydrate is susceptible to partial water deficiency. The crystal structures of the monohydrate and hemihydrate phases have also been determined directly from powder X-ray diffraction data. On the basis of results from dynamic vapor sorption and other experiments, we demonstrate that the three new solid forms are readily interconvertible as a function of relative humidity.