Structure and DNA cleavage properties of two copper(ii) complexes of the pyridine-pyrazole-containing ligands mbpzbpy and Hmpzbpya

Abstract

The DNA-cleavage properties of the two copper(II) complexes, [Cu(mbpzbpy)Br₂](H₂O)_2.5 (1) and [Cu(mpzbpya)Cl](CH₃OH) (2), obtained from the ligands 6,6′-bis(3,5-dimethyl-N-pyrazolmethyl)-2,2′-bipyridine) (mbpzbpy) and 6′-(3,5-dimethyl-N–pyrazolmethyl)-2,2′-bipyridine-6-carboxylic acid) (Hmpzbpya), respectively, are reported. Upon coordination to Cu^II chloride in methanol, one arm of the ligand mbpzbpy is hydrolyzed to form mpzbpya. Under the same experimental conditions, the reaction of mbpzbpy with CuBr₂ does not lead to ligand hydrolysis. The ligand mpzbpya is coordinated to a copper(II) ion generating a CuN₃OCl chromophore, resulting in a distorted square-pyramidal environment, whereas with the N₄ mbpzbpy ligand, the Cu^II ion is four-coordinated in a distorted square planar geometry. Both complexes promote the oxidative DNA cleavage of ϕX174 phage DNA in the absence of reductant. The oxidative nature of the DNA cleavage reaction has been confirmed by religation and cell-transformation experiments. Studies using standard radical scavengers suggest the involvement of hydroxyl radicals in the oxidative cleavage of DNA. Although both compounds do convert form I (supercoiled) DNA to form II (nicked, relaxed form), only complex 1 is able to produce small amounts of form III (linearized DNA). This observation may be explained either by the attack of the copper(II) complexes to only one single strand of DNA, or by a single cleavage event. Statistical analysis of relative DNA quantities present after the treatment with both copper(II) complexes supports a random mode of DNA cleavage.