Quantum, Hirshfeld surface, crystal voids, energy framework and molecular docking analysis of two halogen-containing benzimidazole-2-thione structures

Abstract

The crystal structures of 4,5-Dichlorobenzimidazolene-2-thione (I) and 4-Fluoro benzimidazolene-2-thione (II) were computed by Density Functional Theory (DFT) and their optimized molecular geometry, atomic Mulliken charges, molecular electrostatic potential, HOMO-LUMO and other related molecular properties were analyzed using B3LYP/6-311 + G(d,p) level basic set. The optimized geometry of both structures varies slightly from the reported X-ray crystallographic structures. The HOMO-LUMO analyses of both crystal structures include the evaluation of molecular parameters, viz. chemical hardness, softness, electrophilicity index, chemical potential and electronegativity. The Hirshfeld surfaces analyses of both structures were carried out to explore and quantify the contributions of the distinct intermolecular interactions within the crystals. The analysis reveals that the maximum contribution to the Hirshfeld surface comes from the N-H…S interactions. The void volume occupancy in both structures is 6.06% and 7.11%, respectively. However, distinct intermolecular interaction energies were used to form energy frameworks in order to investigate the stability and kind of dominating energy in both structures. The inhibitory nature of both structures on estrogen receptors (ERs) was investigated by molecular docking procedures with breast cancer protein (PDB ID: 1GWR). The docking results suggest that the higher binding nature of both structures with target receptors may lead to the development of some novel drugs for the treatment of breast cancer.