Solid-state structural properties of alloxazine determined from powder XRD data in conjunction with DFT-D calculations and solid-state NMR spectroscopy: unravelling the tautomeric identity and pathways for tautomeric interconversion - data

We report the solid-state structural properties of alloxazine, a tricyclic ring system found in many biologically important molecules, with structure determination carried out directly from powder X-ray diffraction (XRD) data. As the crystal structures containing the alloxazine and isoalloxazine tautomers both give a high-quality fit to the powder XRD data in Rietveld refinement, other techniques are required to establish the tautomeric form in the solid state. In particular, high-resolution solid-state ¹⁵N NMR data support the presence of the alloxazine tautomer, based on comparison between isotropic chemical shifts in the experimental ¹⁵N NMR spectrum and the corresponding values calculated for the crystal structures containing the alloxazine and isoalloxazine tautomers. Furthermore, periodic DFT-D calculations at the PBE0-MBD level indicate that the crystal structure containing the alloxazine tautomer has significantly lower energy. We also report computational investigations of the interconversion between the tautomeric forms in the crystal structure via proton transfer along two intermolecular N–H...N hydrogen bonds; DFT-D calculations at the PBE0-MBD level indicate that the tautomeric interconversion is associated with a lower energy transition state for a mechanism involving concerted (rather than sequential) proton transfer along the two hydrogen bonds. However, based on the relative energies of the crystal structures containing the alloxazine and isoalloxazine tautomers, it is estimated that under conditions of thermal equilibrium at ambient temperature, more than 99.9% of the molecules in the crystal structure will exist as the alloxazine tautomer.

Data presented are the crystal structure for the new polymorph, powder XRD and solid-state NMR data, NMR parameters calculated by DFT from the crystal structure and the energies from DFT calculations (using several different exchange-correlation functionals) of structures involved in the transition between tautomers.

Research results based upon these data are pubilshed at https://doi.org/10.1021/acs.cgd.1c01114