DNA cleavage activities of tetraazamacrocyclic oxamido nickel(II) complexes

The DNA cleavage activities of nickel(II) ion and four closely related macrocyclic nickel(II) complexes NiL1 similar to NiL4 in the absence of any added redox cofactors are compared and the structure of NiL3 methanol solvate has been characterized by single crystal X-ray analysis, where L-1 similar to L-4 are the dianions of tetraazamacrocyclic oxamido Schiff bases. In NiL3 center dot 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 center dot center dot center dot O hydrogen bonds and Ni center dot center dot center dot O and Ni center dot center dot center dot 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 NiL3 is a relatively good DNA cleavage agent, and the process of plasmid DNA cleavage is much sensitive to ionic strength and pH value. The NiL3-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 NiL3. 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. (C) 2009 Elsevier Ltd. All rights reserved.