Catecholase activity, DNA cleavage and cytotoxicity of six Zn(II) complexes synthesized from designed Mannich ligands: higher reactivity of mononuclear over dinuclear

Six zinc(II) complexes have been synthesized from two designed Mannich-base ligands which consist of three dinuclear complex [Zn-2(L-1)(2)X-2] (1-3) and three mononuclear complex [ZnH(L-2)X-2] (4-6), respectively, where X = Cl- (1,4), Br- (2,5), I- (3,6), as reported earlier by us (Sanyal et al., Inorg Chem 53:85-96, 2014). The catecholase activity of the complexes has been investigated under completely aerobic conditions in DMF-water medium (9:1) at pH 8.5 against the model substrate 3,5-di-tert-butylcatechol (3,5-DTBC). Saturation kinetic studies show that the order of conversion of substrate to product (quinone) follows the trend 5 > 4 > 2 > 1 while 3 and 6 are inactive. The generation of phenoxyl radicals, confirmed by UV-vis and EPR spectral studies, is supposed to be responsible for the oxidation of 3,5-DTBC. The in vitro evaluation of 1-6 comprises the study of their DNA-cleaving ability using plasmid DNA and the assessment of their cytotoxic activity against Jurkat (T cell lymphoma) cell line by MTT assay. The mechanisms of toxicity appeared to be predominantly by reactive oxygen species (ROS). The comparative analysis helps to arrive at the following facts under experimental conditions: (1) mononuclear species prevail over the dinuclear ones, unlike the behavior in phosphatase activity as reported in Inorganic Chemistry; (2) the halide substituents at the active site control the overall activity in the order: (a) In catecholase activity, Cl- < Br- (dinuclear) and Cl- > Br- (mononuclear) and (b) in biological activity, Cl- > Br- > I- regardless of nuclearity.