Computational Aspects of Organochlorine Compounds: DFT Study and Molecular Docking Calculations

Abstract

The paper and pulp industry generates enormous amounts of wastewater containing high quantities of chlorinated toxicants. These volatile organochlorine compounds are widespread toxic chemicals that may cause harmful effects on humans via interaction with human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (hACMSD) which is a vital enzyme of the kynurenine pathway in tryptophan metabolism. It averts the accumulation of quinolinic acid (QA) and supports the maintenance of the basal Trp-niacin ratio. Herein, we report the optimization of organochlorine compounds employing density functional theory (DFT) with B3LYP/6- 311G+(d,p) basis set to elucidate their frontier molecular orbitals as well as the chemical reactivity descriptors. The DFT outcome revealed that organochlorine compounds show a lower HOMO-LUMO gap as well as a higher electrophilicity index and basicity as compared to the substrate analogue, Dipicolinic acid. To assess the structure-based inhibitory action of organochlorine compounds, these were docked into the active site cavity of hACMSD. The docking simulation studies predicted that organochlorine compounds require lower binding energy (-3.86 to -6.42 kcal/mol) which is in good agreement with the DFT calculations and might serve as potent inhibitors to hACMSD comparable with its substrate analogue, Dipicolinic acid which has a binding affinity of -4.41 kcal/mol. Organochlorine compounds interact with key residues such as Arg47 and Trp191 and lie within the active site of hACMSD. The high binding affinity of organochlorine compounds was attributed to the presence of several chlorine atoms, important for hydrophobic interactions between the organochlorine compounds and the critical amino acid residues of the receptor (hACMSD). The results emphasized that organochlorine compounds can structurally mimic the binding pattern of Dipicolinic acid to hACMSD.