A Potent Superoxide Dismutase Mimic: Manganese β-Octabromo-meso-tetrakis-(N-methylpyridinium- 4-yl) Porphyrin

Variously modified metalloporphyrins offer a promising route to stable and active mimics of superoxide dismutase (SOD). Here we explore bromination on the pyrroles as a means of increasing the redox potentials and the catalytic activities of the copper and manganese complexes of a cationic porphyrin. Mn(II) and Cu(II) octabrominated 5,10,15,20-tetrakis-(N-methylpyridinium-4-yl) porphyrin, MnIIOBTMPyP4+, and CuIIOBTMPyP4+were prepared and characterized. The rate constants for the porphyrin-catalyzed dismutation of O•−2as determined from the inhibition of the cytochrome c reduction arekcat= 2.2 × 108and 2.9 × 106m−1s−1, i.e., IC50was calculated to be 12 nmand 0.88 μm, respectively. The metal-centered half-wave potential wasE1/2= +0.48 V vs NHE for the manganese compound. CuIIOBTMPyP4+proved to be extremely stable, while its Mn(II) analog has a moderate stability, logK= 8.08. Nevertheless, slow manganese dissociation from MnIIOBTMPyP4+enabled the complex to persist and exhibit catalytic activity even at the nanomolar concentration level and at biological pH. The corresponding MnIIIOBTMPyP5+complex exhibited significantly increased stability, i.e., demetallation was not detected in the presence of a 400-fold molar excess of EDTA at micromolar porphyrin concentration and at pH 7.8. The β-substituted manganese porphyrin facilitated the growth of a SOD-deficient strain ofEscherichia coliwhen present at 0.05 μmbut was toxic at 1.0 μm. The synthetic approach used in the case of manganese and copper compounds offers numerous possibilities whereby the interplay of the type and of the number of β substituents on the porphyrin ring would hopefully lead to porphyrin compounds of increased stability, catalytic activity, and decreased toxicity.