Molecular Docking, DFT, and Structural Characterization of Cr(III), Mn(II), and Fe(III) Mixed‐Ligand Complexes With Nifuroxazide and 4‐Chloro‐Pyridine‐2‐Carboxylic Acid: New Perspectives on Antibacterial and Anti‐Inflammatory Activity

ABSTRACT The development of metal‐based therapeutics offers a promising strategy to overcome antimicrobial resistance and enhance anti‐inflammatory efficacy. In this study, three new mixed‐ligand complexes of Cr(III), Mn(II), and Fe(III) with nifuroxazide (NF) and 4‐chloro‐pyridine‐2‐carboxylic acid (CP) were synthesized and comprehensively characterized. Spectroscopic, magnetic, and thermal analyses, supported by DFT calculations, confirmed octahedral coordination geometries, with CrPCNF and FePCNF behaving as 1:1 electrolytes ( Λ m = 40.52 and 40.55 Ω −1 cm 2 mol −1 , respectively), while MnPCNF ( Λ m = 11.32 Ω −1 cm 2 mol −1 ) was non‐electrolytic. Density functional theory revealed reduced HOMO‐LUMO energy gaps and high electrophilicity indices for MnPCNF (3.14 eV; ω = 19.44) and FePCNF (2.71 eV; ω = 20.53), indicating enhanced chemical reactivity relative to the free ligands. Biological evaluation demonstrated a pronounced improvement in antibacterial, antifungal, and anti‐inflammatory activities upon metal complexation. Notably, the FePCNF complex exhibited the highest antibacterial activity (31.0 mm against Bacillus subtilis and 30 mm against Klebsiella pneumoniae ; MIC = 80 µM), superior antifungal efficacy (20 mm inhibition zones; MIC = 100 µM), and the strongest anti‐inflammatory response (25.07% inhibition at 500 µM; IC 50 = 71.23 µM). Molecular docking against Escherichia coli FabH and COX‐2 enzymes corroborated the experimental results, with FePCNF showing the most favorable binding affinities (−8.90 and −9.50 kcal mol −1 , respectively). Overall, these findings proposed that the Fe(III) mixed‐ligand complex might be a promising multifunctional candidate drug for further development as an antimicrobial and anti‐inflammatory agent.