Synthesis of metal complexes of 2,9-bis(2-hydroxyphenyl)-1,10-phenanthroline and their DNA binding and cleaving activities

Abstract

A series of metal complexes that combine the structure of phenanthroline and salen have been synthesized and characterized by electron paramagnetic resonance spectroscopy. The effects of the 2,9-bis(2-hydroxyphenyl)-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 the highest stabilization is observed with the Co complex. The DNA cleaving activities have been studied with plasmid DNA and/or with a ³²P-labelled duplex oligonucleotide depending on the redox properties of the complexes. The Cu complex is inactive whereas the Co chelate efficiently 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 agent via the production of oxygen radicals (which are detected by EPR spectroscopy) or in the presence of an oxidant such as KHSO₅. In both cases, the cleavage of nucleic acids is very efficient whereas no cleavage is observed with the Ni complex. The complexes of bis(hydroxyphenyl)phenanthroline with Mn and Co complement the tool-box of reagents available for cleavage of DNA.