title: Synthesis and in vitro antioxidant properties of manganese(III) beta-octabromo-meso-tetrakis(4-carboxyphenyl)porphyrin.
abstract: 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 beta-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 (IC(50)=0.7 microM) was the same as manganese(III) meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (MnTM-4-PyP(5+)), 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.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Remy
authors.initials: R
authors.lastname: Kachadourian
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Flaherty
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Crumbliss
authors.forename: Manisha
authors.initials: M
authors.lastname: Patel
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Day
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D015227:Lipid Peroxidation; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008665:Metalloporphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008665:Metalloporphyrins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D013482:Superoxide Dismutase; D009251:NADPH-Ferrihemoprotein Reductase; D010269:Paraquat