More complex, less complicated? Explicit solvation of hydroxyl groups for the analysis of VCD spectra.

Solute-solvent interactions and in particular hydrogen bonding can significantly influence the appearance of vibrational spectra due to band shifts, intensity changes and band broadening. In VCD spectroscopy, solvation may also lead to sign changes and thus an overall drastic change in the spectral pattern. As the VCD spectral analysis relies heavily on the comparison with computed spectra, such solvent effects have to be accounted for in the calculations. For simple model systems with one stereocenter, we have previously shown for carboxylic acids and hydroxyl groups that considering solvation explicitly improves the match substantially. In the present study we evaluate if explicit solvation is always necessary and if larger, more complex molecules featuring several stereocenters show the same susceptibility to H-bonding induced spectral changes as the previously investigated model systems. We analyse the spectra of the diastereomeric pairs menthol/neomenthol and borneol/isoborneol and study both experimentally and computationally the influence of hydrogen bonding to dimethylsulfoxide-d6 (DMSO-d6) and acetonitrile-d3 (ACN-d3) on their VCD spectral signatures. Further chiral alcohols with tertiary hydroxyl group (terpinen-4-ol and cedrol) and more complex structures with multiple stereocenters (cholesterol) are investigated to show that solvent effects on the spectra become less pronounced. We related this to the increasing number of vibrational bands that are insensitive to solvation and thus overlap with actually affected modes. As a consequence, the analysis of the spectra does not require consideration of explicit solvation and in this respect becomes less complicated.