Solution Properties of Metallobleomycins Related to the DNA Damage Reaction

Solution Properties of Metallobleomycins Related to the DNA Damage Reaction 

An elegant series of papers by Peisach, Horwitz and colleagues has demonstrated that in vitro DNA strand scission is dependent upon the presence of iron in the reaction mixture and involves the following pathway of activation of the drug to carry out the strand scission reaction  

Oxidation Damage by Bleomycin, Adriamycin and Other Cytotoxic Agents 

Reaction of H02 -Fe(m)Blm with DNA to produce a single strand break had been conceived of in two ways in the first, abstraction of the C4 hydrogen formally involves a species equivalent to a hydroxyl radical. As such, there is homolytic cleavage of the peroxide, leaving a ferryl species, equivalent to a hydroxyl radical and Fe(in)Blm, as the other product. 

As this C4 radical is converted into a hydroperoxide, an electron is required from some source in the reaction mixture. According to the other proposal, H02 -Fe(iii)Blm undergoes heterolytic cleavage to produce hydroxide and a perferryl species that does the hydrogen abstraction. The net reaction is the same as shown in Reaction 7  

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