Resonance Raman studies of HOO-Co(III)bleomycin and Co(III)bleomycin: identification of two important vibrational modes, nu(Co-OOH) and nu(O-OH)

Bleomycin is an antitumor agent whose cytotoxicity is dependent on its ability to bind DNA in the nucleus and effect double-stranded DNA cleavage, which is difficult for the cell to repair. In order for this DNA cleavage to occur, bleomycin must, through a series of reactions, form a low-spin Fe(III) complex, the putative "activated" form of the drug, HOO-Fe(III)bleomycin. The relative strengths of the bonds in the Fe(III)-OOH linkage have not been determined due to the weakness of the hydroperoxo-to-iron(III) charge-transfer transition. The much more stable HOO-Co(III)bleomycin has often been studied as a structural analogue of HOO-Fe(III)bleomycin, and hence, an understanding of the relative bond strengths in the Co-OOH linkage may serve to enhance our understanding of the analogous Fe-OOH linkage. In this report, we present resonance Raman data that identify two important vibrational modes in the Co-OOH linkage, the stretching modes, nu(Co-OOH) and nu(O-OH). Both of these vibrational modes were found to be unperturbed by complexation of the drug with calf thymus DNA. Advantage was also taken of the isostructural realtionship between Fe-bleomycin and Co-bleomycin to analyze and assign the high-frequency modes for HOO-Co(III)bleomycin and Co(III)bleomycin (A(2) and B(2)). These data could be useful for future studies of photoactivated Co-bleomycin and Co-bleomycin analogues in an attempt to characterize oxygen-independent DNA damage pathways.