Synthesis, Structural Elucidation, Electronic Properties, and Enhanced Bioactivity of Co(II), Ni(II), and Cu(II) Complexes Derived From Nifuroxazide and 4‐Chloro‐pyridine‐2‐carboxylic Acid: Structural, DFT and Molecular Docking Studies

This study explores the structural, physicochemical, and biological properties of Co(II), Ni(II), and Cu(II) metal complexes (CoPCNF, NiPCNF, and CuPCNF), synthesized using Nifuroxazide (NF) and 4‐chloro‐pyridine‐2‐carboxylic acid (PC) ligands. The molar conductivity measurements indicate non‐electrolyte behavior for CoPCNF and CuPCNF, with NiPCNF acting as a 1:1 electrolyte. Infrared spectroscopy confirms ligand coordination via hydroxyl, carbonyl, and azomethine groups, supporting octahedral geometries for CoPCNF and CuPCNF, and a tetrahedral configuration for NiPCNF. UV–vis spectra further validate these geometries, with magnetic moment values consistent with the expected low‐spin Co(II), high‐spin Ni(II) configurations. DFT calculations reveal favorable electronic properties for CoPCNF and CuPCNF, with CoPCNF demonstrating the highest reactivity, indicating strong potential for biological activity. TD‐DFT calculations using the B3LYP functional provided electronic transition data that closely matched the experimental UV–vis spectra, offering deeper insight into the coordination geometries of the CoPCNF, NiPCNF, and CuPCNF complexes. Biological evaluations demonstrate that the metal complexes exhibit superior antibacterial, antifungal, and anti‐inflammatory activity compared to the free ligands. CuPCNF shows the highest antibacterial potency, with inhibition zones of 30 mm against Gram‐positive bacteria and 29 mm against Gram‐negative bacteria, and the lowest MIC of 80 µM. In antifungal tests, CuPCNF achieves the highest inhibition zones (19.0 mm) and the lowest MIC of 100 µM. The anti‐inflammatory IC 50 of CuPCNF is 85.09 µM, outperforming the free ligands. Molecular docking studies with the E. coli FabH‐CoA complex (1HNJ) and cyclooxygenase‐2 (6COX) reveal that CuPCNF has the highest binding affinity to both targets, with binding energies of −9.70 (1HNJ) and −9.50 kcal/mol (6COX), supported by extensive hydrogen bonds, electrostatic interactions, and hydrophobic contacts. These findings emphasize the enhanced biological efficacy of the metal complexes, particularly CuPCNF, as a promising dual antibacterial and anti‐inflammatory agent.