I begin to think that if the system one works on is in solution, everything should be done with continuum solvent model applied. Fortunately, unlike not too long ago, there are some very robust implementations of continuum models available out there. Warts and all, it’s still better than doing calculations in vacuum.

This of course brings a contentious issue of doing vibrational frequency calculations with PCM-type models and using them to get thermodynamic data, a truly heretic idea for some researchers. Although I think I do understand their logic, form the experience we’ve seen many times that it works fine.

Indeed, for species that don’t change much in solution the frequencies and thermodynamic values hardly differ in the gas phase and in solution. In fact, a recent paper from Cramer and Truhlar groups have shown just that: DOI:10.1021/jp205508z