RSC Publishing


Publishing

 

Cover image for Dalton Transactions, select for current issue

Dalton Transactions

The international journal for inorganic, organometallic and bioinorganic chemistry




Paper

Dalton Trans., 2007, 3676 - 3683, DOI: 10.1039/b704390b


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

Palanisamy Uma Maheswari, Kristian Lappalainen, Michael Sfregola, Sharief Barends, Patrick Gamez, Urho Turpeinen, Ilpo Mutikainen, Gilles P. van Wezel and Jan Reedijk


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 CuII 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 CuII ion is four-coordinated in a distorted square planar geometry. Both complexes promote the oxidative DNA cleavage of X174 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.

Graphical abstract image for this article  (ID: b704390b)