Understanding the role of Zn2+ in the hydrolysis of glycylserine: a mechanistic study by using density functional theory |
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Authors: | Jose R Mora Oswaldo Nuñez Luis Rincón F Javier Torres |
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Institution: | 1. Instituto de Simulación Computacional (ISC-USFQ), Universidad San Francisco de Quito (USFQ), Quito, Ecuador;2. Departamento de Ingeniería Química, Grupo de Química Computacional y Teórica (QCT-USFQ), Universidad San Francisco de Quito (USFQ), Quito, Ecuador;3. Departamento de Ingeniería Química, Laboratorio de Fisicoquímica orgánica y Química ambiental, Universidad Simón Bolívar, Caracas, Venezuela;4. Departamento de Química, Facultad de Ciencias, Universidad de Los Andes, Mérida, Venezuela |
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Abstract: | The hydrolysis mechanism of glycylserine in the presence of Zn2+ was theoretically studied by means of density functional theory calculations. Two possible reaction mechanisms are proposed for the hydrolysis reaction: (1) the first one involves a stepwise reaction with an initial attack of the serine –OH to the amide carbonyl group through a general base catalysis of a water molecule, which undergoes to a proton transfer to the carboxylate group to give a cyclic intermediate. Its further rearrangement finally forms an ester that hydrolyses to yield products. (2) The second mechanism involves a general base catalysis by the carboxylate group for the water attack to the amide carbonyl group to generate a tetrahedral intermediate. Upon comparison of both mechanisms, it is observed that the former is favoured; furthermore, its first step is the rate-limiting step in a bicyclic asynchronous transition state with evolution of 86% in C(1)–O(2) bond. The crucial role of Zn2+ in this hydrolysis process can be rationalised in terms of the inductive effect and the formation of a rigid structure that increases the electrophilicity of the amide carbonyl group. The calculations presented in this report are in good agreement with reported values for the activation barrier. |
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Keywords: | Glycylserine hydrolysis transition state peptide bond |
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