New class of potent catalysts of O2.- dismutation.: Mn(III) ortho-methoxyethylpyridyl- and di-ortho-methoxyethyl-imidazolylporphyrins

Three new Mn(III) porphyrin catalysts of O-2(circle-) 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-PyP5+), Mn(III) 5,10,15,20-tetrakis[ N-methyl-N'-(2-methoxyethyl) imidazolium-2yl] 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(circle-) 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-PyP5+, 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(III) 5,10,15,20-tetrakis(N-n-butylpyridinium-2-yl) porphyrin (MnTnBu-2-PyP5+) and Mn(III) 5,10,15,20-tetrakis( N,N'-diethylimidazolium-2-yl) porphyrin (MnTDE-2-ImP(5+)). MnTMOE-2-PyP5+ has side chains of the same length and the same E-1/2, as MnTnBu-2-PyP5+ (k(cat)=7.25, E-1/2=+254 mV), yet it is 6-fold more potent a catalyst of O-2(circle-) 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 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-PyP5+, while MnTDE-2-ImP(5+) was of very low efficacy.