DFT Study of Molecular Stability and Reactivity on Some Hydroxamic Acids: An Approach by Hirshfeld Population Analysis

Abstract

Several studies have been carried out on the structure of hydroxamic acids as histone deacetylase inhibitors. Scientists discovered that the (-CONHOH) moiety of hydroxamic acids was responsible for the chelation of the zinc ion into the active site of histone deacetylases thereby inhibiting the activity of these. In this work, we conducted a study using the new dual descriptor from the conceptual DFT to determine the atoms responsible for zinc chelation in order to propose new, more active molecules. The calculations were performed to determine the local reactivity of the hydroxamic acids studied using Fukui functions by the Hirshfeld method. Global parameters were also determined to predict the relative stability and reactivity of hydroxamic acids. The work was conducted at computational level B3LYP / 6-311G (d, p). The most polarizable compound has an energy gap of 3.933 eV. The analysis of the local indices of reactivity as well as the dual descriptors revealed that an oxygen of these compound is the most favorable site vis-à-vis electrophilic attack.