Theoretical Spectroscopy Aided Validation of the Hydration Structure of Trimethylamine N -Oxide (TMAO).

The molecular-level understanding of the hydration structure of external solutes is extremely challenging. In the context of molecular simulation, particularly sampling proper solvation structure by classical force fields remains always a matter of concern. In the present work, we use theoretical vibrational spectroscopy to understand the microscopic solvation structure of TMAO in water in the cases of five different classical force fields of TMAO. We find that the Netz ( , , 8310-8321) force field agrees better with the experimental results. We also observe that the O-H stretching frequency gets red-shifted compared to the bulk water response, suggesting that the TMAO-water forms stronger hydrogen bonds than water-water. We further investigate the O-H stretching frequency in different solvation shells and the hydrophobic and hydrophilic regions of TMAO. We find that, in the hydrophilic region, O-H stretching frequencies show a strong orientational correlation; however, that is absent in the hydrophobic region. These are further supplemented by hydrogen-bond analysis and local structure index data.