DNA cleavage activities of tetraazamacrocyclic oxamido nickel(II) complexes

Abstract

The DNA cleavage activities of nickel(II) ion and four closely related macrocyclic nickel(II) complexes NiL 1 ∼ NiL 4 in the absence of any added redox cofactors are compared and the structure of NiL 3 methanol solvate has been characterized by single crystal X-ray analysis, where L 1 ∼ L 4 are the dianions of tetraazamacrocyclic oxamido Schiff bases. In NiL 3·MeOH, the macrocyclic [N 4] ligand coordinates to the central Ni(II) ion forming a distorted square–planar geometry. The adjacent mononuclear molecules are linked by O–H⋯O hydrogen bonds and Ni⋯O and Ni⋯L van der Waals forces into 2D supramolecular structure. Agarose gel electrophoresis studies indicate that the ability of these nickel(II) complexes to cleave DNA is highly dependent upon the ligand employed. In the absence of any added oxidizing agents, only NiL 3 is a relatively good DNA cleavage agent, and the process of plasmid DNA cleavage is much sensitive to ionic strength and pH value. The NiL 3-mediated DNA cleavage reaction is a typical pseudo-first-order consecutive reaction, and the rate constants of 0.148 ± 0.007 h −1 ( k 1) and 0.0118 ± 0.0018 h −1 ( k 2) for the conversion of supercoiled to nicked DNA and nicked to linear DNA are obtained in presence of 0.5 mmol L −1 NiL 3. The results of DNA cleavage experiments, combining with those of circular dichroism (CD) and fluorescence spectroscopy indicate that the main binding modes between DNA and the complexes should be groove binding and electrostatic interaction.