A molecular dynamics simulation study with a combined quantum mechanical and molecular mechanical potential energy function: Solvation effects on the conformational equilibrium of dimethoxyethane

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Abstract
Solvent effects on the conformational equilibria of dimethoxyethane (DME, CH3–O–CH2–CH2–O–CH3) have been studied using molecular dynamics simulation with a combined molecular mechanical and semiempirical quantum mechanical potential energy function. The potential of mean force around the central O–C–C–O dihedral angle of DME in water was determined using umbrella sampling, with the DME molecule treated by the modified intermediate neglect of diatomic differential overlap (MNDO) method and water molecules described using the extended simple point charge model. This potential of mean force shows the same bias as the gas phase potential energy surface calculated by MNDO: the heights of the barriers are underestimated and the stability of the gauche conformation with respect to the trans conformation is overestimated. However, the calculated stabilization of the gauche state by solvation is in good agreement with experimental results, suggesting a quite reasonable description of this system by the combined potential energy function. The solute–water atom pair distributions and the averaged percentage of solute–water hydrogen bonding does not change much when the central dihedral angle changes, but in the gauche conformation one water hydrogen can be hydrogen bonded with the two solute oxygen atoms simultaneously. The interactions between DME and its explicit water environment favor the gauche over the trans conformation much more than predicted by the reaction field model, although the overall relative stabilities predicted by the latter model are not so biased due to compensation of errors. The trans conformation of the outer C–O–C–C dihedral angles is most favored during the simulations, which is qualitatively different from the reaction field prediction that the trans–gauche+–gauche− would be the most stable conformer in solution.