SOD-like activity of Mn(II) β-octabromo-meso-tetrakis(N-methylpyridinium-3-yl)porphyrin equals that of the enzyme itself

摘要: Abstract Mn porphyrins are among the most efficient SOD mimics with potency approaching that of enzymes. The potent ones, Mn(III) N-alkylpyridylporphyrins bear positive charges in a close proximity to metal site, affording thermodynamic and kinetic facilitation for reaction negatively charged superoxide. addition electron-withdrawing bromines onto β-pyrrolic positions dramatically improves O 2 • - dismutation. We have previously characterized para isomer, MnIIBr8TM-4-PyP4+ [Mn(II) β-octabromo-meso-tetrakis(N-methylpyridinium-4-yl)porphyrin]. Herein we fully its meta analogue, MnIIBr8TM-3-PyP4+ respect UV/vis spectroscopy, electron spray mass spectrometry, electrochemistry, dismutation, metal–ligand stability, ability protect SOD-deficient Escherichia coli comparison analogue. increased electron-deficiency center stabilizes +2 oxidation state. metal-centered MnIII/MnII reduction potential, E½ = +468 mV vs NHE, is by 416 mV non-brominated MnIIITM-3-PyP5+ only 12 mV less than isomer. Yet, complex significantly more stable towards loss As expected, based on structure–activity relationships, an increase E½ results higher catalytic rate constant log kcat ⩾ 8.85; 1.5-fold IC50 was calculated be ⩽3.7 nM. Manipulation cationic porphyrin resulted, therefore, highest kcat ever reported metalloporphyrin, being essentially identical superoxide dismutases (log kcat = 8.84–9.30). salt effect points unexpected, unique first time recorded behavior β-octabrominated when compared other studied thus far. When species opposing react, ionic strength invariably decreased constant; brominated opposite found true. 3.5-fold greater which discussed closer quaternary nitrogens isomer corroborated vivo studies, where 500 nM allows E. grow >60% growth wild type; at concentrations ⩾5 μM it exhibits toxicity. Our work shows exceptionally high disproportionation can achieved not N5-type coordination motif, as rationalized aza crown ether (cyclic polyamines) complexes, but also N4-type motif case; both motifs sharing “up-down-up-down” steric arrangement.