Antimicrobial, antibiofilm, antioxidant activities and molecular docking of Schiff base and its complexes of Cu(II), Co(II), Ni(II), Mn(II) and UO2(II).

The global escalation of multidrug-resistant pathogens demands the urgent development of multifunctional metallo-pharmaceuticals. Coordination compounds offer a unique advantage by combining ligand bioactivity with metal-centered redox potential. A novel tetradentate N2O2 Schiff base ligand (H2L) was synthesized via the condensation of 2,6-diaminopyridine and 2,4-dihydroxybenzaldehyde. Its coordination potential was explored through the synthesis of Cu(II), Co(II), Ni(II), Mn(II), and UO2(II) complexes. Comprehensive characterization was performed using spectroscopic (FT-IR, NMR, UV-Vis) and physicochemical techniques. Biological efficacy was quantified through antimicrobial (MIC/MMC), antibiofilm, and DPPH radical scavenging assays, supplemented by enzymatic (POX/CAT) profiling. Molecular docking studies using MOE 2019 targeted essential proteins from B. cereus, S. aureus, E. coli, and S. typhi (PDB: 1FEZ, 3Q8U, 3T88, and 6J90). Structural analysis confirmed the tetradentate dibasic nature of H2L. Metal complexation significantly enhanced biological potency; the UO2(II) and Cu(II) complexes exhibited superior antimicrobial effects, while the Mn(II) complex demonstrated the highest antioxidant potential (78.1% inhibition; IC50 = 64.10 µg/mL), acting as a functional SOD-mimic. Biofilm formation in S. aureus, B. cereus, and E. coli was suppressed by up to 50% at 100 µg/mL of ligand and its complexes. Computational analysis revealed that Co(II) and UO2(II) complexes achieved the most favorable binding affinities, stabilized by hydrogen bonding and π-cation interactions. These findings suggest that these complexes represent promising scaffolds for next-generation antimicrobial and antioxidant agents, with significant potential for therapeutic application in disrupting microbial redox homeostasis.