Scheme IX.

Reactivity of Mn(III) ortho N-substituted pyridylporphyrins towards different low-molecular weight reactive species. In late 1990s, along with growing awareness of highly oxidizing species, ONOO^–, it became obvious that all potent SOD mimics can effectively reduce ONOO⁻ either one- (if starting from Mn^IIIP) or two-electronically (if starting from Mn^IIP), producing either highly oxidizing ^•NO₂ or benign NO₂⁻, respectively. The ONOO⁻ reduction by MnP is only few-fold slower than the catalysis of O₂^•− dismutation, demonstrating that all potent SOD mimics are potent peroxynitrite scavengers. Compounds which cannot dismute O₂^•−, such as MnTBAP³⁻, could be oxidized with strong oxidant, such as ONOO⁻, in a 1st step and reduced with either ascorbate or thiol or O₂^•− in a 2nd step. If O₂^•− is involved in a 2nd step, such compounds can affect in vivo levels of O₂^•−. Yet, the lower the SOD-like activity, the lower is the ability to reduce ONOO⁻. Indeed, MnTBAP³⁻ is ~2 orders of magnitude less able reductant of ONOO⁻ than is MnTE-2-PyP⁵⁺. Coupling of ONOO⁻ reduction to O₂^•− oxidation, has been explored with MnTM-4-PyP⁵⁺[25], and may be operative with other compounds. Coupling of ONOO⁻ reduction to cellular reductants is likely operative with potent SOD mimics also (Scheme X). Due to high levels of carbonate in vivo, ONOO⁻ forms an adduct with CO₂. The ONOOCO₂⁻ adduct degrades to CO₃^•− and ^•NO₂ radicals. Due to its radical nature, all potent SOD mimics react rapidly with CO₃^•− in a pH-dependent manner, log k_red(CO₃^•-) ranging between 8 and 9 (Scheme X, Eqs. 5 and 6). Most of the rate constants provided here were based on those determined for MnTE-2-PyP⁵⁺. The linear relationship between log k_cat(O₂^•−) and log k_red(ONOO⁻) allows for calculations of other k_red(ONOO⁻) (see Scheme XIV).