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.