Optimized Structure, in Silico interaction and Molecular Docking Analysis of Two Benzimidazole-2-Thione Derivatives

The nitrogen containing heterocyclic compounds play a very important role in defining their biological and pharmacological properties. Two such important compounds having known crystal structure, viz. 5-Methoxy-1H-benzo[d]imidazole-2(3H)-thione (M1) and 4, 5- Dimethylbenzimidazolene-2-thione (M2), have been investigated for their optimal molecular geometry, atomic Mulliken charges, molecule electrostatic potential, HOMO (highest occupied molecular orbital)-LUMO (lowest unoccupied molecular orbital), and associated molecular characteristics using DFT (density functional theory). The optimized geometry of (M1) and (M2), slightly deviates from the X-ray structure. The N-H...S and N-H...O hydrogen bonding contribute to the Hirshfeld surface in the molecular structure M1 [24.2 % and 7.1 % of the overall contribution, respectively] while the N-H...S hydrogen bonding contribution is 25.4% in M2. The crystal void analysis has also been reported, besides the energy frameworks built using distinct intermolecular interaction energies. The computational antibacterial activity of both structures has been analyzed in silico with Staphylococcus epidermidis bacterial protein (PDB ID: 4EJV). The results indicate that M1 and M2 possess higher binding energy with more interactions as compared to the standard drug chloramphenicol with receptor complex and this observation leads us to the state that these two derivatives could be the potential candidates for the antibacterial drug development process. KEYWORDS: Crystal voids; Density Functional Theory; Hirshfeld surface; Interaction energy; Mulliken charges; Molecular orbital energy; Molecular docking