title: New class of potent catalysts of O2.-dismutation. Mn(III) ortho-methoxyethylpyridyl- and di-ortho-methoxyethylimidazolylporphyrins.
abstract: Three new Mn(III) porphyrin catalysts of O2.-dismutation (superoxide dismutase mimics), bearing ether oxygen atoms within their side chains, were synthesized and characterized: Mn(III) 5,10,15,20-tetrakis[N-(2-methoxyethyl)pyridinium-2-yl]porphyrin (MnTMOE-2-PyP(5+)), Mn(III)5,10,15,20-tetrakis[N-methyl-N'-(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTM,MOE-2-ImP(5+)) and Mn(III) 5,10,15,20-tetrakis[N,N'-di(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTDMOE-2-ImP(5+)). Their catalytic rate constants for O2.-dismutation (disproportionation) and the related metal-centered redox potentials vs. NHE are: log k(cat)= 8.04 (E(1/2)=+251 mV) for MnTMOE-2-PyP(5+), log k(cat)= 7.98 (E(1/2)=+356 mV) for MnTM,MOE-2-ImP(5+) and log k(cat)= 7.59 (E(1/2)=+365 mV) for MnTDMOE-2-ImP(5+). The new porphyrins were compared to the previously described SOD mimics Mn(III) 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)), Mn(III) 5,10,15,20-tetrakis(N-n-butylpyridinium-2-yl)porphyrin (MnTnBu-2-PyP(5+)) and Mn(III) 5,10,15,20-tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin (MnTDE-2-ImP(5+)). MnTMOE-2-PyP(5+) has side chains of the same length and the same E(1/2), as MnTnBu-2-PyP(5+)(k(cat)= 7.25, E(1/2)=+ 254 mV), yet it is 6-fold more potent a catalyst of O2.-dismutation , presumably due to the presence of the ether oxygen. The log k(cat)vs. E(1/2) relationship for all Mn porphyrin-based SOD mimics thus far studied is discussed. None of the new compounds were toxic to Escherichia coli in the concentration range studied (up to 30 microM), and protected SOD-deficient E. coli in a concentration-dependent manner. At 3 microM levels, the MnTDMOE-2-ImP(5+), bearing an oxygen atom within each of the eight side chains, was the most effective and offered much higher protection than MnTE-2-PyP(5+), while MnTDE-2-ImP(5+) was of very low efficacy.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. ibatinic@duke.edu
authors.forename: Ines
authors.initials: I
authors.lastname: Batinić-Haberle
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojević
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Peter
authors.initials: P
authors.lastname: Hambright
authors.forename: Pedatsur
authors.initials: P
authors.lastname: Neta
authors.forename: Ayako
authors.initials: A
authors.lastname: Okado-Matsumoto
authors.forename: Irwin
authors.initials: I
authors.lastname: Fridovich
mesh_terms: D002384:Catalysis; D004563:Electrochemistry; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D007700:Kinetics; D008345:Manganese / Q000737:chemistry*; D008665:Metalloporphyrins / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D018716:Molecular Mimicry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013482:Superoxide Dismutase; D013481:Superoxides / Q000378:metabolism*
chemical_list: D008665:Metalloporphyrins; D013481:Superoxides; D008345:Manganese; D013482:Superoxide Dismutase