Cooperative interactions in the hydration of dimethyl ether (DME) relative to its purely hydrophobic analog, propane, are analyzed by expressing the free energy of hydration in terms of an "inner-shell" contribution from water molecular packing and chemical association, and an "outer-shell" contribution described by the mean binding energy of the solute to the solution and fluctuations in this binding energy. We find that nonadditive, cooperative interactions associated with strong correlations in the binding energy fluctuations of the methyl groups and ether oxygen play a dominant role in the hydration of DME relative to propane. The electrostatic nature of these interactions is revealed in a multi-Gaussian analysis of hydration substates, which shows that the formation of favorable ether oxygen-water hydrogen bonds is correlated with less favorable methyl group-water interactions, and vice versa. We conclude that the group additive distinction between the hydrophobic hydration of the DME methyl groups and hydrophilic hydration of the ether oxygen is lost in the context of these cooperative interactions. Our results also suggest that the binding energy fluctuations of constituent hydrophobic/hydrophilic groups are more sensitive than local water density fluctuations for characterizing the hydration of heterogeneous interfaces.

We calculate hydration free energies of 1,2-dimethoxyethane (DME) conformations in water at 298 K and 1 bar. We find that the preference for the two most abundant tgt and tgg conformations derives from favorable nonspecific (i.e., long-range) solute–water interactions that are partially offset by unfavorable free energies of forming cavities in water to accommodate these conformations. The much lower population of the third most abundant tg + g – conformation, the most abundant conformation in the ideal gas at 298 K, is attributed to less favorable long-range solute–water interactions. We also find that long-range methyl/methylene group–water and ether oxygen–water interactions make significant nonadditive contributions to the free energy of DME hydration and propose a method based on quasichemical theory for reducing these nonadditive contributions by identifying constituent groups of DME that minimize the covariance in the long-range methyl/methylene group–water and ether oxygen–water interactions. We apply this method to show that the decomposition of DME into its constituent dimethyl ether groups is a better approximation of group additivity than decompositions based on distinguishing hydrophobic/hydrophilic constituent groups.