248 - Catalysis of Sulfite Oxidation Adds to the Array of Biologically Relevant Reactions of Cationic Mn(III) Porphyrins, Widely Known as SOD-Mimics

Abstract

Sulfite is generated in vivo as a result of metabolism of sulfur containing amino acids methionine and cysteine. Sulfite is consumed as antioxidant/preservative in food, beverages and medications. We are also consuming it through exposure to major environmental pollutant - sulfur dioxide. The enzyme sulfite oxidase (SO) is responsible for the detoxification of sulfite to sulfate, which is subsequently excreted into urine. The SO deficiency is one of the most common causes of sulfite hypersensitivity and toxicity. Herein we report for the first time the ability of cationic Mn(III) N-substituted pyridyl(imidazolyl)-porphyrins (MnPs) to catalyze sulfite oxidation. Originally developed as SOD mimics, MnPs operate at Mn III P/Mn II P reduction potential that is highly compatible with reduction potentials of numerous biomolecules and reactive species, among them superoxide, peroxynitrite, oxygen, hydrogen peroxide, hypochlorite, nitric oxide, thiols, and ascorbate. At least 4 oxidation states of Mn in MnPs (+2, +3, +4 and +5) are involved in their actions which may occur via one- or two-electron transfers. We are here providing evidence, based on spectrophotometric measurements, that several analogs of MnP are able to catalyze sulfite oxidation one-electronically via employing Mn III P/Mn II P redox couple. The reaction proceeds through generation of sulfite radical anion as an intermediate species characterized by electron paramagnetic resonance (EPR) spin trapping studies using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Clark electrode measurements of the MnP/sulfite system indicated that molecular oxygen is also involved, both in regeneration of Mn III P and further oxidation of sulfite radical to sulfate. Such redox further substantiates tight connections of MnP bioeffects to sulfur biology and indicates that we are still in infancy with regards to fully understanding the plethora of reactions of redox-active drugs. The MnP/sulfite cycling is the reminiscence of redox behavior of MnP/ascorbate system, which has been used successfully in tumor models, suggesting its therapeutic potential. Support: NC Biotechnology# 2016-BIG-6518