New class of potent catalysts of O_2 dismutation.Mn(III)ortho-methoxyethylpyridyl-and di-ortho-methoxyethyl-imidazolylporphyrins

摘要

Three new Mn(III)porphyrin catalysts of O_2 dismutation(superoxide dismutase mimics),bearing ether oxygen atoms within their side chains,were synthesized and characterized: Mn(II)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 O_2~-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-PyP5),Mn(in)5,10,15,20-tetrakis(yV-/7-butylpyridinium-2-yl)porphyrin(MnTnBu-2-PyP~5+)and Mn(in)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 O_2~-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 coll in the concentration range studied(up to 30 muM),and protected SOD-deficient E.coli in a concentration-dependent manner.At 3 muM 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.