DNA/HSA binding and anticancer properties of pendant acetate bearing mono-nuclear Ni(II) and bridging acetate bearing di-nuclear Cu(II) Schiff base complexes: an experimental and molecular docking study

One mono-nuclear Ni(II) complex [NiL(CH3COO)] (1) and one di-nuclear Cu(II) complex, [Cu2L2(CH3-COO)2] (2), with pendant and bridging acetate moieties, respectively, have been synthesized using a novel N,N,O donor Schiff base ligand HL, 1-(((piperidine-2-ylmethyl)imino)methyl)naphthalene-2-al, prepared by the simple condensation of 2-hydroxy-1-naphthaldehyde and 2-amino methyl piperidine. With the aid of numerous spectroscopic studies, the three compounds described above have been properly characterized. The single crystal data analyses of both the complexes reveal that in complex 1, one deprotonated ligand, one pendant acetate ion, and one Ni(II) ion form a mononuclear distorted square planar geometry and in complex 2, each Cu(II) center connects with one deprotonated ligand and a double mu 1.1-acetato-bridge forming a distorted trigonal bipyramidal geometry, while two acetate bridges connect two Cu(II) centers forming a dinuclear complex. After rigorous characterization, both the complexes are investigated to check their binding efficacy with biomacromolecules like DNA and HSA, and the results, obtained from a variety of biophysical studies like absorption, fluorescence, and circular dichroism-based titrations, clearly disclose that both the complexes have an affinity for binding with DNA and HSA. Fluorescence displacement analysis and a DNA melting study demonstrate different modes of binding for the two complexes with the DNA host, namely intercalative mode associated with groove binding for complex 1 and only groove binding for complex 2. Circular dichroism spectral analysis of HSA during interaction with the complexes confirms some structural changes in HSA upon binding. Determination of the thermodynamic parameters implies the binding interactions of HSA with the two complexes to be spontaneous. After a convincing study of the complex-biomacromolecule binding interactions, an MTT assay study on both cancer and normal cells reveals that of the two complexes, complex 2 is the better one, showing superior anticancer properties together with low toxicity to a normal cell. Finally, an apoptotic cell-killing pathway of the studied complexes has been confirmed by a nuclear staining study.