Peculiar DNA partial threading intercalative ability of tetradentate copper complex based on ONO hydrazone backbone and an ancillary ligand

Abstract

Multidentate copper metal complexes have been in the limelight in the area of DNA interaction studies exhibiting intercalation, groove binding and cross linking modes. Design of metal complex based on the versatile ligands decides their mode of DNA binding behavior. Based on this, a tetradentate Copper (II) complex, [Cu(L)(4,4’-bpy)], is synthesized using ONO hydrazone ligand and ancillary ligand, 4,4’-bipyridine. It is characterized by physico-chemical and UV-Visible, FTIR, Mass and EPR spectroscopic techniques. The binding pattern of the characterized complex with DNA has been assessed by UV absorption and fluorescence spectral titrations as well as viscosity studies and it has exhibited peculiar threading intercalation. The binding constant, K_b value of the synthesized complex was found to be (4.38 ± 0.09) × 10⁴ M⁻¹, greater than that of the hydrazone ligand (K_b = 2.29 × 10⁴ M⁻¹) and lesser than the classical intercalator ethidium bromide - EtBr (K_b = 10⁷). The fluorescence quenching assays in the presence of ethidium bromide and viscometric studies show threading intercalative mode of binding of the complex to the DNA base pairs. Molecular docking studies further supports such a binding pattern with the bipyridine ring of the complex intercalating with deoxycytosine nucleobase of DNA. ADME (Absorption, Distribution, Metabolism and Excretion) parameters of the complex and ligand were predicted to get an idea of drug likeliness and to correlate the structural properties with semi DNA intercalative pattern of the same.

Keywords:

• Copper complex
• hydrazone
• DNA interaction
• DNA binding
• threading intercalation
• docking