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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Condensed Matter Physics
- Physical and Theoretical Chemistry