Calculation of Solvation Free Energies of Charged Solutes Using Mixed Cluster/Continuum Models

We derive a consistent approach for predicting the solvation free energies of charged solutes in the presence of implicit and explicit solvents. We find that some published methodologies make systematic errors in the computed free energies because of the incorrect accounting of the standard state corrections for water molecules or water clusters present in the thermodynamic cycle. This problem can be avoided by using the same standard state for each species involved in the reaction under consideration. We analyze two different thermodynamic cycles for calculating the solvation free energies of ionic solutes: (1) the cluster cycle with an n water cluster as a reagent and (2) the monomer cycle with n distinct…