Modelling solute–solvent interactions in VCD spectra analysis with the micro-solvation approach

Abstract

Vibrational circular dichroism (VCD) spectroscopy has become an important part of the (stereo-)chemists’ toolbox as a reliable method for the determination of absolute configurations. Being the chiroptical version of infrared spectroscopy, it has also been recognized as being very sensitive to conformational changes and intermolecular interactions. This sensitivity originates from the fact that the VCD spectra of individual conformers are often more different than their IR spectra, so that changes in conformational distributions or band positions and intensities become more pronounced. What is an advantage for studies focussing on intermolecular interactions can, however, quickly turn into a major obstacle during AC determinations: solute–solvent interactions can have a strong influence on spectral signatures and they must be accurately treated when simulating VCD and IR spectra. In this perspective, we showcase selected examples which exhibit particularly pronounced solvent effects. It is demonstrated that it is typically sufficient to model solute–solvent interactions by placing single solvent molecules near hydrogen bonding sites of the solute and subsequently use the optimized structures for spectra simulations. This micro-solvation approach works reasonably well for medium-sized, not too conformationally flexible molecules. We thus also discuss its limitations and outline the next steps that method development needs to take in order to further improve the workflows for VCD spectra predictions.