Novel Tridentate Hydrazone of Heterocyclic N-oxide and Its Transition Metal Complexes: Evaluation of DNA/BSA Binding Interactions, In Vitro and In Silico Biological Properties

Abstract

Novel hydrazone ligand 2-(2-(2-hydroxy-5-methoxybenzylidene) hydrazinecarbonyl) pyridine 1-oxide was synthesized and characterized by spectral analyses. The assessment of number of dissociable protons in ligand and evaluation of corresponding values of pKa and the stability constants for M(II)-Ligand systems (M (II) = Cu, Co, Ni and Zn) in 30% DMF-water medium were done by adopting pH-metric method following Irving- Rossotti technique. To understand the chelation properties of hydrazone ligand, its contour maps of frontier molecular orbitals and their energies were computed using HyperChem 7.5 tools. The synthesized metal complexes of above hydrazone with Cu (II), Co (II), Ni (II) and Zn (II) were characterized with spectral and analytical techniques such as; FT-IR, 1H-NMR, LC-MS, TGA, UV-Vis, FE-SEM-EDX and ESR. The tridentate and dibasic nature of title ligand is ascertained from pH-metric studies as well as through the analyses of analytical and spectral data of complexes. The CT-DNA binding studies conducted adopting absorption and fluorescence titrations with metal complexes and ligand inferred their binding affinity through the mode of intercalation. The evaluated antioxidant and cytotoxicity properties revealed higher efficacy of copper complex. Furthermore, investigations employing molecular docking studies revealed non-covalent bonding interactions of synthesized compounds with chosen protein target CDK2.