Four related mixed-ligand nickel(II) complexes: effect of steric encumbrance on the structure, DNA/BSA binding, DNA cleavage and cytotoxicity

Four closely related mononuclear nickel(II) complexes [Ni(L)(diimine) Cl](ClO4) (1-4), where L is a tridentate polypyridyl ligand of 4-methyl-N, N-bis(pyridin-2-ylmethyl) aniline and diimine is 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d: 20,30-f] quinoxaline (dpq, 3) or dipyrido[3,2-a: 20,30-c]-phenazine (dppz, 4), have been synthesized and characterized using various physico-chemical techniques. All Ni centers adopt a distorted octahedral geometry with N5Cl donor sets. From 1 to 4, the dihedral angles between the benzene ring of L and the plane of the diimine gradually decline (52.5-6.8 degrees), leading to increasing steric encumbrance. The interactions of the complexes with CT-DNA and BSA have been explored using absorption and emission spectral methods. These complexes display binding propensity to CT-DNA in the order: 4 (dppz) > 3 (dpq) > 2 (phen) > 1 (bpy), and the quenching mechanisms of BSA by all the complexes are static procedures. In the absence of any external agents, only 1 (bpy) and 4 (dppz) exhibit apparent DNA cleavage activity, while with the addition of GSH or on the irradiation with UV-A light of 365 nm, the DNA cleavage abilities of the complexes are obviously enhanced, which vary as 1 > 2 > 3 > 4 (GSH) and 4 > 3 > 2 > 1 (UV-A). In addition, the in vitro cytotoxicity of the complexes on tumor cells lines (MCF-7, HepG-2 and SGC-7901) have been examined by MTT and the morphological assessment obtained using Hoechst 33342 staining reveals that 4 induces apoptosis against HepG-2.