Shapeshifting Nucleophile Singly Hydrated Hydroperoxide Anion Leads to the Occurrence of the Thermodynamically Unfavored S_N2 Product

Single water molecules alone may introduce unusual features into the kinetics and dynamics of chemical reactions. The singly hydrated hydroperoxide anion, HOO-(H2O), was found to be a shapeshifting nucleophile, which can be transformed to HO- solvated by hydrogen peroxide HO-(HOOH). Herein, we performed direct dynamics simulations of its reaction with methyl iodide to investigate the effect of individual water molecules. In addition to the normal S(N)2 product CH3OOH, the thermodynamically unfavored proton transfer-induced HO--S(N)2 path (produces CH3OH) was also observed, contributing similar to 4%. The simulated branching ratio of the HO--S(N)2 path exceeded the statistical estimation (0.6%) based on the free energy barrier difference. The occurrence of the HO--S(N)2 path was attributed to the shallow entrance channel well before a submerged saddle point, thus providing a region for extensive proton exchange and ultimately leading to the formation of CH3OH. In comparison, changing the leaving group from Cl to I increased the overall reaction rate as well as the proportion of the HO--S(N)2 path because the CH3I system has a smaller internal barrier. This work elucidates the importance of the dynamic effect introduced by a single solvent molecule to alter the product channel and kinetics of typical ion-molecule S(N)2 reactions.