Tackling Solvent Effects by Coupling Electronic and Molecular Density Functional Theory.

Solvation effects can have a tremendous influence on chemical reactions. However, precise quantum chemistry calculations are most often done either in vacuum neglecting the role of the solvent or using continuum solvent model ignoring its molecular nature. We propose a new method coupling a quantum description of the solute using electronic density functional theory with a classical grand-canonical treatment of the solvent using molecular density functional theory. Unlike a previous work, both densities are minimized self-consistently, accounting for mutual polarization of the molecular solvent and the solute. The electrostatic interaction is accounted using the full electron density of the solute rather than fitted point charges. The introduced methodology represents a good compromise between the two main strategies to tackle solvation effects in quantum calculation. It is computationally more effective than a direct quantum mechanics/molecular mechanics coupling, requiring the exploration of many solvent configurations. Compared to continuum methods, it retains the full molecular-level description of the solvent. We validate this new framework onto two usual benchmark systems: a water solvated in water and the symmetrical nucleophilic substitution between chloromethane and chloride in water. The prediction for the free energy profiles are not yet fully quantitative compared to experimental data, but the most important features are qualitatively recovered. The method provides a detailed molecular picture of the evolution of the solvent structure along the reaction pathway.