Comprehensive Theoretical, Spectroscopic, Solvent, Topological and Antimicrobial investigation of...

This study presents comprehensive theoretical, spectroscopic, and biological investigations of the compound 5-Chloro-6-fluoro-2-(2-pyrazinyl)-1H-benzimidazole (5CF2PB). Density Functional Theory (DFT) calculations were performed at the B3LYP/6-311 +  + G(d,p) level, and a Potential Energy Scan (PES) was carried out to identify the most stable conformer and its optimized geometry. Theoretical vibrational frequencies and Potential Energy Distribution (PED) analysis were correlated with experimental FT-IR and FT-Raman spectra, showing excellent agreement. Experimental UV-Vis and ¹H-¹³C NMR spectra were recorded and compared with theoretical predictions using the IEF-PCM solvation model in DMSO, chloroform, and water. Frontier Molecular Orbital (FMO) analysis revealed a HOMO-LUMO energy gap of 4.043 eV, consistent with moderate chemical reactivity and optical absorption. The compound's chemical reactivity descriptors, Molecular Electrostatic Potential (MEP), and topological parameters were analyzed through QTAIM, ELF, LOL, IRI, and RDG methods, providing insights into electronic structure and non-covalent interaction regions. Hirshfeld surface and 2D fingerprint analyses confirmed the dominance of halogen-hydrogen and halogen-nitrogen interactions in crystal packing. In-vitro antimicrobial screening demonstrated that 5CF2PB exhibits potent antibacterial and antifungal activities, particularly against Pseudomonas aeruginosa and Aspergillusniger, showing better efficacy than the standard drug ciprofloxacin. The PASS prediction suggested significant anti-mycobacterial potential, which was validated by molecular docking studies against the protein targets 6TE7 and 5O4L, yielding strong binding affinities and inhibition constants. Molecular dynamics simulations further confirmed the stability of the ligand-protein complexes. Overall, the integrated computational, spectroscopic, and biological analyses establish 5CF2PB as a promising multifunctional compound with potential pharmacological applications.