SYNTHESIS OF METAL-COMPLEXES OF 2,9-BIS(2-HYDROXYPHENYL)-1,10-PHENANTHROLINE AND THEIR DNA-BINDING AND CLEAVING ACTIVITIES

A series of metal complexes that combine the structure of phenanthroli ne and salen have been synthesized and characterized by electron param agnetic resonance spectroscopy. The effects of the 2,9-bis(2-hydroxyph enyl)-1,10-phenanthroline compounds complexed with Cu-II,Ni-II, Co-II or Mn-III on the temperature-dependent helix-to-coil transition of DNA have been measured. The interaction with DNA is metal-dependent and t he highest stabilization is observed with the Co complex, The DNA clea ving activities have been studied with plasmid DNA and/or with a P-32- labelled duplex oligonucleotide depending on the redox properties of t he complexes. The Cu complex is inactive whereas the Co chelate effici ently cleaves DNA in the presence of a reducing agent. Cleavage of DNA by the Mn complex can occur either in the presence of a reducing agen t via the production of oxygen radicals (which are detected by EPR spe ctroscopy) or in the presence of an oxidant such as KHSO5. In both cas es, the cleavage of nucleic acids is very efficient whereas no cleavag e is observed with the Ni complex. The complexes of bis(hydroxyphenyl) phenanthroline with Mn and Co complement the tool-box of reagents avai lable for cleavage of DNA.