The log k(cat) values for the dismutation of O-2(.-) by a series of monohydroxoiron(III) and aquamanganese(III) porphyrins, including ortho, meta, and para isomers of 5,10,15,20-tetrakis(N-alkylpyridiniumyl) were found to vary linearly with the metal-centered redox potentials (E-1/2) for the M(III)/M(II) couple. Each 120 mV increase in E-1/2 imparted a 10-fold increase in k(cat). The observed behavior is in accord with the Marcus equation for outer-sphere electron-transfer reactions, suggesting that the same mechanism is operative for iron and manganese porphyrins. The Marcus plot enabled us to estimate the self-exchange late constants of monohydroxoiron porphyrins to be similar to 1 order of magnitude higher than those of aquamanganese porphyrins. Furthermore, E-1/2 values for all of the metalloporhyrins investigated were linearly related to the acid dissociation constants (pK(a3)) of the pyrrolic nitrogen of the metal-free porphyrins, indicating that either E1/2, or the more readily measured pK(a3), may be useful in predicting SOD activity in vitro. The most potent compounds investigated, with respect to SOD activity, are those of the ortho N-alkylpyridiniumyl series. Ortho N-alkylpyridiniumyl groups are more electron withdrawing than are the meta or para groups, thus imparting a more positive redox potential and a correspondingly higher SOD activity. Sufficiently positive potentials, or sufficiently low pK(a3) values, are necessary for useful SOD activity, but so is the absence of toxicity. Despite their favorable redox potentials and SOD activities, all Fe(III) porphyrins investigated were toxic to Escherichia coli under both aerobic and anaerobic conditions and to both SOD-deficient and SOD-proficient strains. Only the ortho and meta manganese isomers of the N-alkylpyridiniumyl series (Mn-III-TE-2-PyP5+, (MnTM)-T-III-2-PyP5+ and (MnTM)-T-III-3-PyP5+) significantly protected SOD-deficient E. coli and allowed growth in an aerobic minimal medium. In previous work, we established that the lower toxicity of these compounds is due to diminished ability to bind to nucleic acids. The Mn(III) complexes are preferable to the Fe(III) complexes for SOD mimics possibly due to a lower tendency for axial ligation. We propose E-1/2 greater than or equal to +0.05 V vs NHE and/or pK(a3) less than or equal to 2.0 as necessary requirements for Mn porphyrins to be considered useful SOD mimics.