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-PyP⁵⁺), Mn(III)5,10,15,20-tetrakis[N-methyl-N′-(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTM,MOE-2-ImP⁵⁺) and Mn(III) 5,10,15,20-tetrakis[N,N′-di(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTDMOE-2-ImP⁵⁺). 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-PyP⁵⁺, log k_cat = 7.98 (E_1/2 = +356 mV) for MnTM,MOE-2-ImP⁵⁺ and log k_cat = 7.59 (E_1/2 = +365 mV) for MnTDMOE-2-ImP⁵⁺. 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-ImP⁵⁺). 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 O₂˙⁻ dismutation, presumably due to the presence of the ether oxygen. The log k_catvs. 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 μM), and protected SOD-deficient E. coli in a concentration-dependent manner. At 3 μM levels, the MnTDMOE-2-ImP⁵⁺, 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-ImP⁵⁺ was of very low efficacy.