Three-dimensional reference interaction site model solvent combined with a quantum mechanical treatment of the solute

We implemented and applied a hybrid approach for modeling the solvation of molecules where we combined a three-dimensional reference interaction site model (3D RISM) with quantum mechanical (QM) calculations of the solute. The electrostatic potential induced by the solute is derived directly from its electron density. For neutral solutes, we analyzed the accuracy of calculated solvation free energies which is mainly determined by the cavity formation energy. In an aqueous medium the solute electronic structure relaxation also has a noticeable influence on the results of SCF-RISM calculations. We apply a known partial molar volume correction for which we give an alternative interpretation. The results of this hybrid model agree well with experiment and results of a polarizable continuum model (PCM). As a model with an atomic solvent representation, RISM accounts for the effect of discrete hydrogen bonds which in PCM models are included on average only.