Hydrophobic interactions: conformational equilibria and the association of non-polar molecules in water

Abstract

Recently developed proximity approximations have been used to calculate inhomogeneous water density profiles around non-polar molecular solutes. Relative Helmholtz energies of hydrophobic hydration are calculated from these density profiles using two inherently different approaches: Helmholtz energy perturbation and a multiparticle correlation function expansion. Entropic contributions to the hydration Helmholtz energy are also calculated using the multiparticle correlation function expansion for the entropy truncated at the level of pair correlations. We show that the proximity approximations describe water structure around a tetramethylammonium ion in good agreement with neutron diffraction experiments, and provide an accurate description of water structure around simple alkanes and benzene as reflected in their entropies of hydration. Further, we reproduce two important features of hydrophobic interactions: a highly favoured contact minimum and a solvent separated minimum in the PMFs for methane–methane and neopentane–neopentane association in water. Our calculations also show that the more compact conformations of n-butane and n-pentane are favoured in water, as expected based on traditional ideas regarding hydrophobic interactions.