Hydration-determined orientational preferences in aromatic association from benzene dimer free energy volumes

In this study of the thermodynamics of benzene association in water, we show that although the potential energy and enthalpy play an important role in the association of benzene dimers, they do not determine the relative orientation of these molecules on close contact in solution. We observe a large variation in the configurations that contribute to the vacuum (i.e., solvent-free) minimum free energy wells of the benzene contact pair. In water, fewer and smaller minimum free energy wells are observed. On examination, we find that fewer close contact configurations of benzene dimers populate these wells and that they are more energetically distinct from each other (compared with the vacuum case). The edge-over-edge configuration is most likely in solution and appears to evolve from the entropically favored side-by-side solvent shared configuration. Therefore, the relative orientation of the benzene molecules (i.e., parallel displaced, T-shaped, etc.) on association is a result of maximizing the contribution of the benzene-benzene entropy of association, to the solution free energy.