Probing Molecular Crystals by Combined Inelastic Neutrons Scattering (INS) Experiments and First-principle Techniques

Fundamental properties of molecular crystals depend on both the arrangement of molecules, and the molecular interactions within the solid. We have combined state-of-art density functional theory calculations with inelastic neutron scattering (INS) experiments on the nucleic acid nitrogenous bases, simple pharmaceuticals and pharmaceuticals cocrystals (PC) using the VISION vibrational spectrometer at SNS, revealing details about intermolecular interactions as well as the performance of various computational methods. VISION provides an invaluable probe into molecular motions at atomic-level details; the physical formalism describing INS is rather simple, thus a near-exact estimate of the experimental data is possible by DFT-based normal mode calculations. This synergistic relationship is exploited to probe the vibrational signatures of molecular motions and interactions in these crystals, and changes induced due to the co-crystallization, to develop a predictive computational method for use in applications. The crucial thermal effects are investigated by employing the quasi-harmonic approximation. This comparative study is important to a deeper understanding of biomolecular systems as well as drug design in the field of pharmaceuticals.