Shapeshifting Nucleophile Singly Hydrated Hydroperoxide Anion Leads to the Occurrence of the Thermodynamically Unfavored SN2 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 SN2 product CH3OOH, the thermodynamically unfavored proton transfer-induced HO–-SN2 path (produces CH3OH) was also observed, contributing ∼4%. The simulated branching ratio of the HO–-SN2 path exceeded the statistical estimation (0.6%) based on the free energy barrier difference. The occurrence of the HO–-SN2 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–-SN2 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 SN2 reactions.孤立的单个水分子，可使化学反应的动力学与动态演化呈现异常特征。研究发现，单水合过氧氢根阴离子（HOO–(H2O)）是一种构象可变的亲核试剂，可转化为被过氧化氢溶剂化的氢氧根离子（HO–(HOOH)）。本文中，我们针对其与碘甲烷的反应开展直接动力学模拟，以探究单个水分子对反应的影响。除常规双分子亲核取代（SN2）产物（CH3OOH）外，本文还观测到热力学上不利的质子转移诱导型HO–-SN2路径（产物为CH3OH），其贡献占比约为4%。模拟得到的HO–-SN2路径分支比，超出了基于自由能垒差得到的统计估算值（0.6%）。HO–-SN2路径的发生，可归因于其在潜鞍点前存在较浅的入口通道势阱，该区域为广泛的质子交换提供了条件，最终促成CH3OH的生成。相较而言，将离去基团从氯（Cl）替换为碘（I）后，整体反应速率以及HO–-SN2路径的占比均有所提升，这是由于碘甲烷体系的内势垒更小。本研究阐明了单个溶剂分子引入的动态效应可改变典型离子-分子SN2反应的产物通道与动力学过程，凸显了该动态效应的重要价值。