Four closely related mononuclear nickel(II) complexes [Ni(L)(diimine)Cl](ClO 4 ) (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 by using various physico-chemical techniques. All Ni centers adopt distorted octahedral geometry with N 5 Cl donor sets. From 1 to 4, the dihedral angles between benzene ring of L and the plane of the diimine exhibit gradually decline (52.5-6.8°), leading to the increasing steric encumbrance. The interactions of the complexes with CT-DNA and BSA have been explored by using absorption and emission spectral methods. These complexes display binding propensity to the CT-DNA giving a relative order: 4 (dppz) > 3 (dpq) > 2 (phen) > 1 (bpy), and the quenching mechanisms of BSA by all 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 vitro Corresponding authors. 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 by using Hoechst 33342 staining reveals that 4 against HepG-2 induces apoptosis.