A structure determination protocol based on combined analysis of 3D-ED data, powder XRD data, solid-state NMR data and DFT-D calculations reveals the structure of a new polymorph of -tyrosine

We report the crystal structure of a new polymorph of l -tyrosine (denoted the β polymorph), prepared by crystallization from the gas phase following vacuum sublimation. Structure determination was carried out by combined analysis of three-dimensional electron diffraction (3D-ED) data and powder X-ray diffraction (XRD) data. Specifically, 3D-ED data were required for reliable unit cell determination and space group assignment, with structure solution carried out independently from both 3D-ED data and powder XRD data, using the direct-space strategy for structure solution implemented using a genetic algorithm. Structure refinement was carried out both from powder XRD data, using the Rietveld profile refinement technique, and from 3D-ED data. The final refined structure was validated both by periodic DFT-D calculations, which confirm that the structure corresponds to an energy minimum on the energy landscape, and by the fact that the values of isotropic 13 C NMR chemical shifts calculated for the crystal structure using DFT-D methodology are in good agreement with the experimental high-resolution solid-state 13 C NMR spectrum. Based on DFT-D calculations using the PBE0-MBD method, the β polymorph is meta-stable with respect to the previously reported crystal structure of l -tyrosine (now denoted the α polymorph). Crystal structure prediction calculations using the AIRSS approach suggest that there are three other plausible crystalline polymorphs of l -tyrosine, with higher energy than the α and β polymorphs. A new polymorph of l -tyrosine is reported, with the crystal structure determined by combined analysis of 3D-ED data and powder XRD data, augmented by information from periodic DFT-D calculations and solid-state 13 C NMR data.