Oxidative DNA damage by manganese complexes

Additionally, the mechanistic similarities between bleomycin and cytochrome P450 45,159-162) led to the test of manganese bleomycin for DNA strand scission 163,164). 

Among the manganese complexes tested for oxidative DNA damage, the cationic manganese porphyrin, Mn -bis(aqua)meso-tetrakis(4-A -methylpyri-diniumyl)-porphyrin, Mn-TMPyP, (Fig. 19) proved to be the most efficient and will be described in more detail. 

Mn complexes are not strong oxidants and must be activated in order to become good oxidation catalysts. To mimic the catalytic cycle of heme enzymes, for which the active iron-oxo species is generated from Fe and H2O2 (peroxidase) or from Fe, a source of electrons and O2 (cytochrome P450), the activation of manganese complexes into high-valent 

The Mn =0 entity is a very powerful oxidant able to mediate two different types of oxidative reactions transfer of an oxygen atom on a substrate (mimic of cytochrome P450, Fig. 21A) or electron abstraction (mimic of peroxidase. Fig. 21B). It is formally written Mn =0 since it corresponds to a two-electron oxidation with respect to the initial Mn complex. However, 

The first detection of a Mn -oxo porphyrin intermediate under catalytic conditions was achieved by using rapid-mixing stopped-fiow techniques with Mn-TMPyP and mc a-chloroperbenzoic acid or KHSO5 (165). Furthermore, the Mn =0 derivative of the mcso-tetrakis-(2-A/ -methylpyridiniumyl)-porphyrin isomer was surprisingly stable (a few minutes) allowing its characterization by NMR (166). Recently, a direct proof of a manganese-oxo salen complex has been reported by mass spectrometry (167). 

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