A reaction density functional theory study of solvent effect in the nucleophilic addition reactions in aqueous solution

Whereas the proper choice of reaction solvent constitutes the cornerstone of the green solvent concept, solvent effects on chemical reactions are not mechanistically well understood due to the lack of feasible molecular models. Herein, by taking the case study of nucleophilic addition reaction in aqueous solution, we extend the proposed multiscale reaction density functional theory (RxDFT) method to investigate the intrinsic free energy profile and total free energy profile, and study the solvent effect on the activation and reaction free energy for the nucleophilic addition reactions of hydroxide anion with methanal and carbon dioxide in aqueous solution. The predictions of the free energy profile in aqueous solution for these two nucleophilic addition reactions from RxDFT have a satisfactory agreement with the results from the RISM and MD-FEP simulation. Meanwhile, the solvent effect is successfully addressed by examining the difference of the free energy profile between the gas phase and aqueous phase. In addition, we investigate the solvent effect on the reactions occurred near solid-liquid interfaces. It is shown that the activation free energy is significantly depressed when reaction takes place in the region within 10 angstrom distance to the substrate surface owing to the decrease of hydration free energy at the solid-liquid interface. (C) 2020 Institute of Process Engineering, Chinese Academy of Sciences. Publishing services by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.