Molecular dynamics simulation study of the influence of conformation on the solvation thermodynamics of 1,2-dimethoxyethane and 1,2-dimethoxypropane in aqueous solution

We have performed atomistic molecular dynamics simulations of 1,2-dimethoxyethane (DME) and 1,2-dimethoxypropane (DMP) in aqueous solution in order to compare the free energy, energy, and entropy of solvation of these ethers as well as to examine the influence of ether conformation on the thermodynamics of solvation. The free energy and energy of solvation were found to be highly favorable for both ethers, whereas the entropy of solvation was highly unfavorable, indicating that the ethers are strongly water-structuring. The free energy of solvation of DMP was found to be slightly more favorable than that of the smaller DME. However, scaling for molecular volume differences reveals that the solvation of DME is intrinsically more favorable than that of DMP. This difference was found to be energetic in origin, resulting from stronger water-ether interactions in the DME solution. DME was found to lead to a larger decrease in entropy upon solvation compared to DMP, indicating that a severe entropic penalty is associated with the stronger ether-water interactions. Similar conformation dependence of the free energy of solvation was observed for DME and DMP. The free energy of solvation for hydrophilic DME conformers was found to be 1.7 kcal/mol more favorable than that for hydrophobic conformers. The corresponding difference for DMP was found to be quite similar at 1.4 kcal/mol. In dilute solution, 88% of DME conformers were found to be hydrophilic, whereas only 78% of DMP conformers were hydrophilic, However, contrary to our previous speculation, only about 1/5 of the difference in DME and DMP solvation thermodynamics can be accounted for by the larger fraction of hydrophilic conformers in DME solutions.