Bivalent metal-isoniazid hydrazone complexes: Synthesis, spectroscopy, docking, and antibacterial activity

The novel Schiff base ligand ( E )-N′-((4-bromonaphthalen-1-yl)methylene) isonicotinohydrazide (BmnisOH) was synthesized from isoniazid and 4-bromo-1-naphthaldehyde. Complexation with metal ions Hg²⁺, Zn²⁺, Cd²⁺, Pd²⁺, and Pt²⁺ afforded complexes of the type [MCl 2 (BmnisOH)], where {M²⁺= Pd( 1 ), Pt( 2 ), Zn( 3 ), Cd( 4 ), and Hg( 5 )}. These were obtained as a solo product in high yield (77–97%). The compounds were characterized by FT-IR, ¹H NMR, ¹ ³C-NMR, mass spectrometry, C.H.N. microanalysis, and molar conductivity. The complexes displayed mononuclear tetrahedral geometries for Zn(II), Cd(II), and Hg(II) via pincer ON chelation. In contrast, Pd(II) and Pt(II) exhibited square-planar configurations via two NO modes. Biological tests indicated that both the ligand and its metal complexes possess antibacterial properties. The platinum(II) complex showed the highest efficacy, followed by the palladium(II) and zinc(II) complexes. The antibacterial activity of selected complexes ( 1 - 3 ) with the free ligand was evaluated against Escherichia coli and Staphylococcus aureus . Although less effective than tetracycline, their activity, particularly against E. coli , suggests potential for further exploration as antibacterial agents. Molecular docking studies of BmnisOH and its metal complexes against biotin carboxylase revealed stronger binding affinity for the complexes compared to the free ligand. Binding energies ranked as Pt > Pd > Zn > ligand. The platinum complex demonstrated the highest binding affinity (–9.6 kcal/mol), which correlated with its superior antibacterial activity. RMSD values (1.969–4.402 Å) confirmed the reliability of the docking poses.