Electronic Structure, Hydrogen Bonding Dynamics and Bioactive Potential of 2-(5-Bromo-2-(trifluoromethoxy)phenyl)-5-(3-bromophenyl)-1,3,4-oxadiazole: A DFT, Spectroscopic and Docking Investigation

Abstract

The structural, electronic and biological properties of 2-(5-bromo-2-(trifluoromethoxy)phenyl)-5-(3-bromophenyl)-1,3,4-oxadiazole were investigated via density functional theory (DFT), vibrational and NMR spectroscopy, Natural Bond Orbital (NBO) analysis, frontier molecular orbital (FMO) mapping, molecular electrostatic potential (MEP) analysis, Nucleus-Independent Chemical Shift (NICS) aromaticity calculations and molecular docking. Geometry optimization at the B3LYP/6-31G(d,p) level revealed an extended π-conjugated framework with localized distortions near halogenated moietiesVibrational and NMR analyses were carried out using Density Functional Theory (DFT) to provide a detailed understanding of the structural and electronic features of the studied compounds. These computational results further supported the interpretation of their spectroscopic characteristics. NBO analysis revealed strong π→π* and n→π* delocalization, enhancing intramolecular charge transfer, consistent with the narrow HOMO–LUMO gap (0.163 eV). MEP mapping confirmed electrophilic regions at hydrogen donors and nucleophilic sites at oxygen, nitrogen and halogens, correlating with docking results against prostate cancer target 6XXO (binding affinity –7.3 kcal/mol, two hydrogen bonds). NICS calculations revealed modest aromaticity in the five-membered oxadiazole ring. The integrated spectroscopic, computational, and docking results demonstrate titled compound’s potential as a multifunctional bioactive scaffold.