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-dimethoxy ethane (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 thermodyna mics of solvation. The free energy and energy of solvation were found to be highly favorable for both ethers, whereas the entropy of solvation was hig hly unfavorable, indicating that the ethers are strongly water-structuring. The free energy of solvation of DMP was found to be slightly more favorabl e than that of the smaller DME. However, scaling for molecular volume diffe rences reveals that the solvation of DME is intrinsically more favorable th an that of DMP. This difference was found to be energetic in origin, result ing from stronger water-ether interactions in the DME solution. DME was fou nd to lead to a larger decrease in entropy upon solvation compared to DMP, indicating that a severe entropic penalty is associated with the stronger e ther-water interactions. Similar conformation dependence of the free energy of solvation was observed for DME and DMP. The free energy of solvation fo r hydrophilic DME conformers was found to be 1.7 kcal/mol more favorable th an that for hydrophobic conformers. The corresponding difference for DMP wa s 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 conformer s were hydrophilic, However, contrary to our previous speculation, only abo ut 1/5 of the difference in DME and DMP solvation thermodynamics can be acc ounted for by the larger fraction of hydrophilic conformers in DME solution s.