Atomic-Level Mechanism, Solvent Effect, and Potential of the Mean Force of the F + CHCHCl S2 Reaction in Aqueous Solution.

We investigate the bimolecular nucleophilic substitution (S2) reaction of F with CHCHCl in aqueous solution using combined multilevel quantum mechanism (ML-QM) theories with molecular mechanics (MM). The synchronized, atomic-level structural and charge evolutions are analyzed along the reaction path. The potential mean force along the reaction path in water is calculated at high-accuracy CCSD(T)/aug-cc-pVTZ/MM level of theory with a free energy barrier of 16.8 kcal/mol and a free energy of reaction of -9.7 kcal/mol. The water solvent hinders the reactivity by raising its reaction barrier by 15.1 kcal/mol, of which 13.6 kcal/mol comes from solvent energy contribution and 1.5 kcal/mol comes from the polarization effect. This indicates that the water solvent plays an essential role on this reaction in aqueous solution. We also predict the potential mean force profile based on the gas-phase reaction path and the solvation free energies of the stationary points; the comparison between our calculated result at CCSD(T)/MM level shows an excellent agreement with the predicted one with the free energy barrier at 16.2 kcal/mol and the free energy of reaction at -8.3 kcal/mol.