Bioactive Cr(III), Co(II), and Mn(II) Complexes with N′((3-Hydroxynaphthalen-2-yl)methylene)picolinohydrazide: Structural, Computational, and Biological Studies

The present study focuses on the synthesis and characterization of novel bioactive complexes of Cr(III), Co(II), and Mn(II) derived from N′-((3-hydroxynaphthalen-2-yl)methylene)picolinohydrazide (H₂L), a Schiff-base ligand featuring multifunctional donor sites. The primary objective was to investigate the coordination behavior, stability, and biological efficacy of these metal chelates. The complexes were synthesized via direct metal–ligand reactions and characterized using elemental analysis, FT-IR spectroscopy, UV–Vis, PXRD,¹H NMR spectroscopy, MS, magnetic susceptibility measurements, and thermogravimetric analysis. Spectroscopic evidence supported tetrahedral geometries for the Co(II) and Mn(II) complexes, while the Cr(III) complex exhibited an octahedral arrangement. Thermogravimetric and kinetic studies yielded positive activation free energy (ΔG*) values, indicating nonspontaneous decomposition pathways and high thermal stability. Quantum Theory of Atoms in Molecules (QTAIM) and reduced density gradient (RDG) analyses were performed to elucidate the nature of ligand–receptor interactions. Biological assessments revealed promising results, as DNA degradation assays demonstrated notable nuclease-like activity, particularly for the Co(II) complex. Antibacterial potency was evaluated via minimum inhibitory concentration (MIC), where the Mn(II) complex exhibited the strongest activity (0.313 mg/mL), followed by Co(II) and Cr(III) (0.625 mg/mL each), and the free ligand (1.250 mg/mL). Cytotoxicity testing against HeLa, HCT-116, and MCF-7 cancer cell lines showed high anticancer efficacy for the [CoL]·2H₂O complex with IC₅₀values of 7.76  ±  0.4, 10.23  ±  0.8, and 6.88  ±  0.4 μM, respectively. Molecular docking studies using an induced fit protocol highlighted the strong noncovalent interactions of the complexes with DNA targets relevant to each cell line.