Novel water-soluble 4,4-disubstituted ruthenium(III)-salen complexes in DNA stranded scission

Salen-type Ru(III) complexes are found to be capable of reacting with physiologically acceptable oxi-dants. The water solubility and DNA affinity of these Ru(III)-salen complexes are enhanced by the utilization of a variety of charged groups through the formation of peptide bonds. In the presence of hydrogen per-oxide, modified Ru(III)-salen complexes are capable of nicking DNA. In addition, the reactivity in DNA cleavage increases along with the total number of positive charges retaining in Ru(III)-salen complexes and less influence in the electronic effect. Using 32P-end-labeled oligonucleotides and high resolution polyacrylamide gel electrophoresis, Ru(III)-salen complexes are found to randomly cleave DNA regardless of the DNA secondary conformation such as bulge, inter-loop, or double-stranded regions. The possible reactive species of Ru(III)-salen complexes in DNA cleavage is considered as the hydroxyl radical and high valent oxoruthenium(IV) species according to the UV titration, quenching studies, and reaction with varied oxidants.