where x is a vector of reaction coordinates, U 0 (x) the gas phase energy obtained quantum mechanically and V (x, P ) is obtained via eq. 21 by neglecting its pressure dependence. While this approach leads to activation volumes in good agreement with experimental data and model systems, it cannot describe the response of the electronic wave function to the compression, limiting the applicability to spectroscopic properties. This can be achieved by embedded-cluster (EC) methods, such as the embedded cluster reference interaction site model (EC-RISM). In the EC-RISM methodology, the solvent is approximated by point charges surrounding the solute and adding the interaction term to the Hamiltonian of the solute. This changes the wave function of the solute and, accordingly, the polarization of the solvent, which again changes the point charges. This procedure is continued until the wave function of the solute converges. To calculate the point charges, the pure solvent susceptibility χ is needed, which is extracted from a previous MD or integral equation based RISM calculation. Thus, the pressure can be modeled indirectly by adjusting the box volume of the underlying MD/RISM calculation. EC-RISM calculations have successfully been used to calculate pressure-dependent Raman and NMR shifts. The model was recently adapted to predict pressure-dependent free solvation energies. Further applications are pointed out in Section 3.2.