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 (Phi X174 DNA and in a 167-base-pair fragment of pBR322. O-18-Labeling studies confirm that the high-valent manganese-ore 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 O-2), a mechanism is proposed in which SO3.-, formed by oxidation with Mn-III, is trapped by O-2, leading to a species (SO5.-) capable of generating a Mn-V=O complex. Importantly, these studies point to the use of an alternative, biocompatible oxidation system compared to the preformed oxidant KHSO5.