Metal–Ligand Design of Co(II), Ni(II), Cu(II), and VO(II) Azo–Schiff Base Complexes: Structural Elucidation, DFT Insights, Promising Biological Activities and DNA Interactions

Abstract A new azo-Schiff base ligand, 2-ethoxy-4-(phenyldiazenyl)− 6-[(phenylimino)methyl]phenol (HL), was synthesized as a bidentate scaffold, giving rise to a new family of VO(II) (VOL), Co(II) (CoL), Ni(II) (NiL), and Cu(II) (CuL) complexes, then comprehensively characterized by CHN analysis, FT-IR, 1 H NMR, UV–Vis, magnetic characterization, TGA, mass spectroscopy, and powder X-ray diffraction (PXRD). From FT-IR data the shift of the azomethine ν(C=N) band from 1618 cm⁻ 1 in HL to 1633–1669 cm⁻ 1 in the complexes, together with the appearance of M–N and M–O vibrations, suggest bidentate coordination of the ligand through the azomethine nitrogen and deprotonated phenolic oxygen atoms. Magnetic susceptibility measurements gave μ eff values of 1.75, 3.92, 2.93, and 1.91 B.M. for VOL, CoL, NiL, and CuL, respectively, consistent with the proposed square-pyramidal geometry of VOL and distorted octahedral geometries of the CoL, NiL, and CuL complexes. CuL complex exhibit the smallest crystallite sizes (27.08 nm). Frontier molecular orbital analysis revealed that metal coordination reduced the energy gap of HL (ΔE = 5.93 eV). Among the complexes, VOL exhibited the lowest energy gap (ΔE = 2.78 eV) and higher softness (σ = 0.72 eV⁻ 1 ). The complexes displayed promising biological activities; CoL was the most active antimicrobial agent against Pseudomonas aeruginosa (AI = 183.3%) and Candida tropicalis (AI = 254.5%). NiL and VOL showed high radical scavenging efficiencies of 96.94% and 95.75%, and VOL exhibited the highest anti-inflammatory activity (IC₅₀ = 41.84 µg/mL), with CT-DNA binding affinity (K b = 2.28 × 10 5 M⁻ 1 ). Molecular docking against COX-2 enzyme showed that VOL complex displays the highest binding affinity (− 8.90 kcal/mol).