Green synthesis, characterization, DFT, molecular docking, cytotoxicity, and DNA binding studies of mono- and polynuclear salpn Schiff base complexes

A Schiff base ligand, 3,3′-((1E,1′E)-(propane-1,3-diylbis(azaneylylidene))bis(methaneylylidene)) bis(benzene-1,2-diol) (AD), was synthesized via a green, microwave-assisted method. The ligand was coordinated with Pd(II) and Ni(II) ions to form mono-, di-, and tetranuclear complexes. This study aims to investigate the influence of nuclearity on the structural, electronic, and biological properties of the complexes. All compounds were characterized using elemental analysis, FTIR, UV–Vis, ¹H and ¹³C NMR, TGA, powder XRD, melting point, conductivity, and FESEM-EDX. Density Functional Theory (DFT) calculations supported the experimental findings. Cytotoxicity was evaluated against HCT116 colorectal cancer cells, while DNA binding was assessed via UV–Vis and circular dichroism spectroscopy. The results demonstrated that higher nuclearity led to enhanced cytotoxic activity. The study revealed that the ligand and its metal complexes exhibit an partial intercalation or mixed binding modes with ctDNA, with intrinsic binding constant values of 3.5 × 10⁶ – 5.3 × 10⁴, indicating moderate DNA binding affinity. Molecular docking further revealed strong interactions between the complexes and B-DNA, involving hydrogen bonding and hydrophobic contacts. Pd₄AD₂ and Pd₂AD demonstrated stable binding through hydrophobic interactions and hydrogen bonding, while PdAD showed distinct interactions with specific nucleotides. Ni₂AD demonstrates specific interactions with guanine bases and metal coordination bonding. Among all, Pd₄AD₂ and Pd₂AD showed the most potent biological activity.