Synthesis, characterization, antibacterial evaluation, molecular docking, and DFT analysis of biphenyl-based Bis(tetrazoline) and Bis(imidazolidin-4-one) derivatives

The present study involves the synthesis of a novel series of heterocyclic derivatives featuring 2,5-dihydro-1H-tetrazole and 5-oxoimidazolidine cores, prepared from Schiff base precursors via conventional synthetic protocols. The chemical structures of the synthesized derivatives were thoroughly characterized using FT-IR, 1 H NMR spectroscopy, and elemental analysis (C, H, N). The in vitro antibacterial activity of the synthesized compounds was evaluated against two pathogenic bacterial strains, Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), using the agar-well diffusion method. Among the series, compound S2, bearing the nitrogen-dense 2,5-dihydro-1H-tetrazole core, exhibited the most prominent growth-inhibitory activity, particularly against E. coli, with a maximum zone of inhibition of 46 mm at 0.01 mg. mL − 1 . Furthermore, computational molecular docking simulations of active derivatives (S2–S4) were performed to propose working hypotheses regarding potential binding interactions within the active sites of bacterial target enzymes (PDB ID: 3JZF for E. coli Biotin Carboxylase and PDB ID: 4DQ2 for S. aureus Biotin Protein Ligase). Notably, compound S2 displayed the most favorable interactions, forming key hydrogen bonds and non-covalent contacts within the active-site cavity. Qualitative DFT quantum chemical calculations provided complementary electronic profiling, describing variations in energy gaps (ΔE) and chemical hardness (η). Overall, integrating experimental in vitro screening with supportive in silico docking and DFT profiling highlights 2,5-dihydro-1H-tetrazole derivatives as useful scaffolds for the design of potential antibacterial agents.