Manganese(III) complexes with porphyrins and related compounds as catalytic scavengers of superoxide

Abstract

Two groups of Mn-based catalytic antioxidants are described in terms of their catalytic activities and electrochemical properties. In the first group, manganese porphyrins, phthalocyanine, and porphyrazine employ the Mn(III)/Mn(II) couple in the catalysis of O 2 − dismutation (disproportionation). The catalytic rate constant is dependent upon the metal-centered redox potential, as shown previously for water-soluble Mn porphyrins. The limitation of this simple relation becomes obvious with compounds of high redox potential (+2 metal oxidation state is stabilized) which exhibit a weak metal/ligand binding; although of high superoxide dismutase (SOD)-like activity, the compounds are not stable under physiological conditions. The second generation of the potent O 2 − scavengers are manganese complexes with biliverdin IX and its derivatives which have an RO − functionality as a fifth coordination to the metal center in a dimeric structure. Such a coordination pattern stabilizes the +4 oxidation state of the manganese so that the Mn(III)/Mn(IV) redox ( E 1/2=∼+0.46 V vs. NHE) becomes coupled to the O 2 − dismutation. More importantly, despite operating at a high positive metal-centered redox potential and having the+3 oxidation state as the resting state of the metal center, metallobiliverdins still retain a high ligand affinity in solution. Independently of their charge (two neutral and the other two negatively charged) metallobiliverdins studied are of similar SOD-like activity comparable to the efficacy of highly charged manganese(III) ortho N-alkylpyridylporphyrins. These most potent in vitro SOD-like Mn porphyrins are also reactive towards peroxynitrite, nitric oxide, hydrogen peroxide and oxygen. Since the fifth coordination site of the metal center is occupied no reactivity of the manganese(III) biliverdin IX dimethyl ester towards NO and H 2O 2 is observed. Thus, manganese(III) porphyrins and manganese(III) biliverdins are expected to differ with regards to their tissue localization and to the type and the concentration of reactive oxygen species they would encounter in biological systems. Comparative kinetic and thermodynamic studies of these catalytic antioxidants would help us understand not only the prevalent mode of their in vivo biological action but the mechanism of oxidative stress injuries as well.