Departamento de Ciências Naturais, Universidade Federal de São João del-Rei, 36301-160, São João del-Rei, MG, Brazil.
J Phys Chem B. 2013 May 30;117(21):6487-97. doi: 10.1021/jp311504d. Epub 2013 May 16.
The mechanism of neutral hydrolysis of ester has long been explored by theoretical studies. However, reliable theoretical calculations show that the usual bifunctional catalysis mechanism reported by different authors cannot explain the experimental kinetics. An important advance was recently reported by Gunaydin and Houk, suggesting that ions are involved in the mechanism and the process initiates by water autoionization followed by protonation of the ester (W(AI)A mechanism). However, this mechanism does not explain the hydrolysis of activated esters. In this work, we have used ab initio calculations, continuum solvation models, and intrinsic reaction coordinate method to support the W(AI)A mechanism for normal ester. In the case of activated esters, the process can also be viewed as water autoionization with formation of hydroxide ion aided by a second water molecule acting as a general base (W(AI)B mechanism). This is the mechanism that was proposed by Jencks and Carriuolo 50 years ago. Our analysis point out that the usual method for exploring mechanisms, searching for saddle points, may not work for problems like the present one, since there are no saddle points on the reaction pathway. Rather, the formation of a pair of ions from a neutral species may have an asymptotic barrier. The approach used in this paper allows the calculation of the free energy profile and enable us to explain the mechanism and kinetics of the neutral hydrolysis of normal (methyl acetate) and activated (methyl trifluoroacetate) esters. In addition, the present study suggests that formation of a pair of ions should always be considered in reactions in aqueous solution.
酯的中性水解机制长期以来一直是理论研究探索的课题。然而，可靠的理论计算表明，不同作者报道的通常的双功能催化机制不能解释实验动力学。最近，Gunaydin 和 Houk 报告了一项重要进展，表明离子参与了该机制，该过程由水自身离解引发，随后酯质子化（W(AI)A 机制）。然而，该机制并不能解释活化酯的水解。在这项工作中，我们使用从头算计算、连续溶剂化模型和内禀反应坐标方法来支持 W(AI)A 机制对普通酯的水解。对于活化酯，该过程也可以看作是水自身离解，同时形成氢氧根离子，由第二个水分子作为广义碱辅助（W(AI)B 机制）。这是 Jencks 和 Carriuolo 50 年前提出的机制。我们的分析指出，探索机制的常用方法，即寻找鞍点，对于像目前这样的问题可能不起作用，因为在反应途径上没有鞍点。相反，中性物质形成一对离子可能具有渐近势垒。本文中使用的方法允许计算自由能轮廓，并使我们能够解释普通（乙酸甲酯）和活化（三氟乙酸甲酯）酯的中性水解的机制和动力学。此外，本研究表明，在水溶液中的反应中，应该始终考虑形成一对离子。
