Intermolecular interactions of cytosine DNA nucleoside base with Gallic acid and its Methylgallate and Ethylgallate derivatives

Abstract

3,4,5‐trihydroxybenzlic acid (gallic acid) and its derivatives exist mostly as secondary metabolites of the phenol family found in plants. Herein, the interaction of gallic acid ( GA), methylgallic acid ( MGA), ethylgallic acid ( EGA) with cytosine (the most reactive part of DNA) has been studied in detail using first principle density functional theory (DFT). Several interaction configurations between the gallic acid and selected derivatives have been investigated using DFT at the M06‐2X/6‐31+G(d,p) theoretical method, topological analysis based on quantum theory of atoms‐in‐molecule (QTAIM), and the noncovalent interaction (NCI) which aid in the understanding of interactions between studied compounds. The results obtained from the interaction energy and energy decomposition analysis (EDA) show that methylgallate ( GA) has the largest interaction energy with cytosine, along with the strongest H‐bond interaction and is best suited for drug design due to its lowest value of stabilization energy at the interaction site 1.Similarly, weak interactions were observed between EGA and cytosine of DNA between −0.02 to 0.01 a.u with a sparing trace of H bond with the aid of non‐covalent interaction (NCI). The reactivity of the studied compound depicts GA to be the most reactive. Although gallic acid competes favorably, this study, however, revealed the great potential of its derivatives: EGA and MGA having great potential for drug design. Their applications are vast and mostly hinged on antioxidant properties, especially in the pharmaceutical industry and, hence, form the basis of an effective class of phytomedicines.