Spectroscopic Characterization, DFT Calculation, and Docking Analysis for Understanding Molecular Interaction Mechanism of Propiconazole and DNA

Abstract

This research presents a theoretical analysis based on structural and spectral data to elucidate the molecular interaction mechanism of propiconazole, a fungicide. The optimization, vibration bands, and electronic structure analysis were conducted using the B3LYP level density functional theory with the aug-ccpVDZ basis set. Additionally, molecular docking simulations were performed to uncover the mechanism and modes of interaction between the propiconazole pesticide and DNA (PDB ID: 1BNA). The investigation revealed that the compound exhibits reactivity and polarizability, as indicated by the HOMO-LUMO energy range. The analysis of the molecular electrostatic potential surface (MEPS) and electrostatic potential surface (ESPS) demonstrated that the N6 and N7 atoms possess negative potential and serve as active sites for nucleophilic attacks. Similar observations were made for the oxygen and chlorine atoms. The molecular docking analysis indicated a preference for the propiconazole ligand to bind to DNA at sites involving nitrogen, oxygen, and chlorine atoms, specifically with guanine (G)-cytosine (C) interactions. Notably, the remarkable concordance between the MEP and molecular insertion results further supports these findings. These results provide valuable insights into the mechanism of DNA damage and the toxicological effects of the pesticide. Furthermore, the molecular docking analysis led to observations of changes in the optimized structure of the propiconazole molecule. For instance, the bond length between Cl1–C15, which was initially determined as 1.73 Å in the optimized structure, was recalculated as 1.77 Å following the molecular docking analysis.