Design of Azomethine based Metalloorganic Complexes and their Binding Interactions with Nucleic Acid and Protein

Abstract

Mononuclear nickel, copper, and zinc complexes based on salen type (ONNO) donor acting as a tetradentate ligand obtained by the condensation of 4-methyl-o-phenylenediamine and 5-fluoro salicylaldehyde in 1:2 ratios. The compounds are characterized using UV-visible, FT-IR, 1H, 13C-NMR, HR-MS, Elemental (CHN) analyses ESR spectral techniques, and single crystal X-ray diffraction studies (SC-XRD). The binding interactions of the metal complexes with deoxyribonucleic acid (DNA) and bovine serum albumin (BSA) are monitored using UV absorption titration and tryptophan emission quenching techniques, respectively. The complexes possess strong binding propensities with DNA and prefer groove binding, as indicated by the hyperchromic effect. The complexes quench the intrinsic fluorescence of BSA with increasing amounts of the complex concentration in a dose-dependent manner. The gel electrophoresis was carried out against pBR322 to analyze the cleaving ability of the complexes. The results of the NBO (natural bond orbitals) analysis performed in combination with the Time-dependent Density Functional Theory (TD-DFT) calculations provided a good explanation of their electronic and structural characteristics. Further, the predictions of molecular docking studies support the experimental observations. The Gel electrophoresis study reveals the cleaving ability of the complexes by their interactions with DNA. In addition, the cell viability of the complexes is assessed based on MTT assay and the results indicate that they have a good antiproliferative activity only on liver cancer cell-line HepG-2 and does not show cytotoxic effect on normal vero cell lines with 90% viability.