Enthalpy–Entropy Interplay in π-Stacking Interaction of Benzene Dimer in Water

Aromatic groups can engage in an interesting class of noncovalent interactions termed π–π interactions, which play a pivotal role in stabilizing a variety of molecular architectures, including nucleic acids, proteins, and supramolecular assemblies. When the aromatic compounds interact with each other in an aqueous environment, their association is facilitated by the hydrophobic effect–the trend of nonpolar solutes to aggregate in a polar solution. To develop an in-depth understanding of hydrophobic association, we investigate in the present work π–π interactions in water, employing as a paradigm the benzene dimer. Using DFT-CES, a mean-field QM/MM method recently developed by our group, we describe the benzene solute at a quantum-mechanical level. Full consideration of detailed solute-electron density enables an optimal description of the solute–solvent interactions, leading to an accurate prediction of hydration free energies. In π-stacking of benzene, we find an entropic stabilization associated with th...