Autoxidation of sulfite is catalyzed by the water-soluble complex (meso-tetrakis(4-N-methylpyridiniumyl)porphyrinato)manganese(III) (Mn-TMPyP), leading to an intermediate species capable of hydroxylation of p-isopropylbenzoic acid, epoxidation of carbamazepine, and generation of single-strand breaks both in plasmid ΦX174 DNA and in a 167-base-pair fragment of pBR322. 18O-Labeling studies confirm that the high-valent manganese−oxo intermediate undergoes oxo−hydroxo tautomerism in competition with oxidation of substrate or reduction by excess sulfite. In contrast to the classical reductive activation of dioxygen by metalloporphyrins (dithiothreitol or ascorbate in the presence of O2), a mechanism is proposed in which SO3 •-, formed by oxidation with MnIII, is trapped by O2, leading to a species (SO5 •-) capable of generating a MnVO complex. Importantly, these studies point to the use of an alternative, biocompatible oxidation system compared to the preformed oxidant KHSO5.

A series of manganese(II) and manganese(III) salts and oxides were investigated for their ability to catalyze the autoxidation of sulfite resulting in oxidative damage to DNA. Experiments directed at identifying the reactive intermediates responsible for DNA oxidation included the trapping of a sulfite radical adduct during EPR studies, alcohol quenching studies of free radical intermediates, comparisons of relative reactivities toward conversion of Type I to Type II plasmid DNA and cleavage of a duplex DNA restriction fragment. The studies support previous work on the mechanism of manganese(III)-catalyzed sulfite autoxidation and provide evidence that simple manganese salts are capable of mediating substantial DNA damage in conjunction with sulfite.

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