title: Combined QM/MM Molecular Dynamics Study on a Condensed-Phase SN2 Reaction at Nitrogen:  The Effect of Explicitly Including Solvent Polarization.
abstract: In a previous combined QM/MM molecular dynamics (MD) study from our laboratory on the identity SN2 reaction between a chloride anion and an amino chloride in liquid dimethyl ether (DME), an increase in the free energy activation barrier was observed in the condensed phase when compared to the gas-phase activation energy. Here we reproduce these findings, but when comparing the condensed-phase potential of mean force (PMF) with the free energy profile in the gas phase (obtained from Monte Carlo simulations), we observe a smaller solvent effect on the activation barrier of the reaction. In a next step, we introduce an explicit description of electronic polarization in the MM (solvent) part of the system. A polarizable force field for liquid DME was developed based on the charge-on-spring (COS) model, which was calibrated to reproduce thermodynamic properties of the nonpolarizable model in classical MD simulations. The COS model was implemented into the MNDO/GROMOS interface in a special version of the QM/MM software ChemShell, which was used to investigate the effect of solvent polarization on the free energy profile of the reaction under study. A higher activation barrier was obtained using the polarizable solvent model than with the nonpolarizable force field, due to a better solvation of and a stronger polarization of solvent molecules around the separate reactants. The obtained PMFs were subjected to an energy-entropy decomposition of the relative solvation free energies of the reactant complex along the reaction coordinate, to investigate in a quantitative manner whether the solvent (polarization) effects are mainly due to favorable QM-MM (energetic) interactions.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich, ETH, CH-8093 Zürich, Switzerland, and Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim, Germany.
authors.forename: Daan P
authors.initials: DP
authors.lastname: Geerke
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich, ETH, CH-8093 Zürich, Switzerland, and Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Thiel
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich, ETH, CH-8093 Zürich, Switzerland, and Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Thiel
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich, ETH, CH-8093 Zürich, Switzerland, and Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim, Germany.
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren