(253a) Resolving Experimentally-Inferred Solvophobic Interactions in the Overlap Region

Solvent-mediated interactions between non-polar atoms is a principal driving force in molecular self-assembly. Experimental measurement of two atomsâ?? solvent-mediated interactions is difficult; such a measurement when two atoms are overlapping is impossible. In the 1970â??s, however, Ben-Naim derived useful experimental estimates of the solvent-mediated contribution of the potential-of-mean-force (PMF) for two methanes at distances within the overlap region. By approximating two methanes separated by 1.54 Ã?â??the bond length of an ethaneâ??as a single ethane, he could calculate the free energy of solvation of both ethane and methane, and therefore calculate the potential of mean force at 1.54 Ã? as: μ^ex_ethane â?? 2μ^ex_methane.
In this study we use simulations to revisit Ben-Naimâ??s results. By using previous work on interpolating and calculating the solvent-mediated interactions of methanes in the overlap region, we are able to quantitatively compare simulation results with experimental estimates. We compare methane interaction free energies, entropies, and enthalpiesâ??in water and in ethanolâ??with Ben Naimâ??s estimates.
By using accurate force field modelsâ??TraPPE-UA and TIP4P2005â??we are able to reproduce Ben-Naimâ??s experimental estimates. We observe, however, that such results understimate the solvent-mediated contribution to the PMF in the overlap region. When we perform a free-energy perturbation on the ethane, transforming the methyl groups into methanes the results become consistent with previous simulation work on solvent-mediated contributions in the overlap region.