Synthesis and in vitro antioxidant properties of manganese(III) β-octabromo-meso-tetrakis(4-carboxyphenyl)porphyrin

Manganese(III)meso-tetrakis(4-carboxypheny)porphyrin(MnTBAP) is a readily available and widely used agent to scavenge reactive oxygen species. A major limitation of MnTBAP is its relatively weak potency due to its low metal centered redox potential. The goal of these studies was to prepare a more potent analog of MnTBAP by increasing its redox potential through P-substitution on the porphyrin ring by bromination. Manganese(III) beta-octabromo-meso-tetrakis(4-carboxyphenyl)porphyrin (MnBr(8)TBAP) was prepared in three steps starting from the methyl ester of the free ligand meso-tetrakis(4-carboxyphenyl)porphyrin, with an overall yield of 50%. The superoxide dismutase (SOD)-like activity of MnBr(8)TBAP (IC50 = 0.7 muM) was the same as manganese(III) meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (MnTM-4-PyP5+), while the metal-centered redox potential of the first was considerably higher than the second (E-1/2 = + 128 and 0 mV vs. normal hydrogen electrode, respectively). However, a number of these cationic Mn-porphyrins (such as MnTM-4-pyp(5+)) redox-cycle with cytochrome P450 reductase in the presence of oxygen and NADPH whereas MnTBAP and its halogenated analog, MnBr(8)TBAP do not. The enhanced ability of MnBr(8)TBAP to inhibit paraquat- and hypoxia-induced injuries in vitro is also reported. In these in vitro models, in which cationic Mn-porphyrins exhibit very low activity, MnBr(8)TBAP appears to be at least eightfold more active than the non-brominated analog MnTBAP. (C) 2003 Elsevier Science Inc. All rights reserved.