Calculations of the Gibbs Energy of Formation of Cavities in Water

The Gibbs energy Δ cav G of formation of cavities in water was calculated by thermodynamic integration. The cavities corresponded to organic molecules of various volumes and shapes with characteristic radii of 3–7 Å and spheres of radii 3–6 Å. Statistical integrals were calculated by the Monte Carlo simulation of an ensemble of water molecules with periodic boundary conditions at 25°C and pressure 1 atm. Interaction between water molecules was described by the TIP4P four-point nonpolarizable model. It was found that the proportionality of Δ cav G to cavity volume V obtained earlier for spheres with radii not exceeding 5 Å remained valid for cavities corresponding to organic molecules of different volumes and shapes, including cavities with the characteristic radii exceeding 5 Å. A possible explanation of the retention of the Δ cav G ∞ V dependence at large characteristic radii was suggested in terms of the two-peak binomial model of the cavitation effect. The conclusion was drawn that the Δ cav G = α V dependence could be used for calculating the nonpolar part of the Gibbs energy of solvation in implicit water models.