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

Two groups of Mn-based catalytic antioxidants are described in terms of the ir 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 radical anion dismutation (disproport ionation). 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 o dor potential (+2 metal oxidation state is stabilized) which exhibit a weak metal/ligand binding; although of high superoxide dismutase (SOD)-like act ivity, the compounds are not stable under physiological conditions. The sec ond generation of the potent O(2)radical anion scavengers are manganese com plexes with biliverdin IX and its derivatives which have an RO- functionali ty 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 = similar to + 0.46 V vs. NHE) beco mes coupled to the O(2)radical anion 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, metallobilive rdins still retain a high ligand affinity in solution. Independently of the ir charge (two neutral and the other two negatively charged) metallobiliver dins studied are of similar SOD-like activity comparable to the efficacy of highly charged manganese(III) ortho N-alkylpyridylporphyrins. These most p otent in vitro SOD-like Mn porphyrins are also reactive towards peroxynitri te, nitric oxide, hydrogen peroxide and oxygen. Since the fifth coordinatio n site of the metal center is occupied no reactivity of the manganese(III) biliverdin IX dimethyl ester towards NO. and H2O2 is observed. Thus, mangan ese(III) porphyrins and manganese(III) biliverdins are expected to differ w ith regards to their tissue localization and to the type and the concentrat ion of reactive oxygen species they would encounter in biological systems. Comparative kinetic and thermodynamic studies of these catalytic antioxidan ts would help us understand not only the prevalent mode of their in vivo bi ological action but the mechanism of oxidative stress injuries as well. (C) 2001 Elsevier Science B.V. All rights reserved.