Reaction path optimization and vibrational frequency analysis via ab initio QM/MM free energy gradient (FEG) method: application to isomerization process of glycine in aqueous solution

Abstract

For the purpose to explore reaction paths accurately for chemical reaction systems in solution, we have proposed the free energy gradient (FEG) method combined with ab initio QM/MM–MD calculation, i.e., the ab initio QM/MM–FEG method. For demonstration, the method has been applied to the isomerization reaction of glycine in aqueous solution, i.e., the intramolecular proton transfer reaction from zwitterion (ZW) to the neutral form (NF). Including the solvent effect explicitly by the ab initio QM/MM–FEG method, those stable-state structures were found different from those obtained in gas phase and by an implicit dielectric continuum model at the same ab initio QM level. Additionally, by the vibration frequency analysis with the “free energy (FE)” hessian in solution, the calculated vibrational frequencies were in good agreement with the experimental ones in the range from low to middle frequency of ZW. Furthermore, the FE of activation from ZW to NF was found in very good agreement with not only the estimation by the Car-Parrinello MD method but also by the previous experimental one. It is concluded that the ab initio QM/MM–FEG method is promising and should provide a better description of chemical reaction systems in solution in comparison with a number of conventional approaches by using the mean field approximations.