Publications [#63233] of Mark W. Dewhirst

Papers Published

1. Batinic-Haberle, Ines and Spasojevic, Ivan and Stevens, Robert D. and Bondurant, Bruce and Okado-Matsumoto, Ayako and Fridovich, Irwin and Vujakovic, Zeljko and Dewhirst, Mark W., New PEG-ylated Mn(iii) porphyrins approaching catalytic activity of SOD enzyme, Dalton Transactions no. 4 (2006), pp. 617 - 624 [b513761f]
   (last updated on 2007/04/14)

   Abstract:
   Two new tri(ethyleneglycol)-derivatized Mn(iii) porphyrins were synthesized with the aim of increasing their bioavailability, and blood-circulating half-life. These are Mn(iii) tetrakis(N-(1-(2-(2-(2-methoxyethoxy)ethoxy)ethyl) pyridinium-2-yl)porphyrin, MnTTEG-2-PyP⁵⁺ and Mn(iii) tetrakis(N,N prime -di(1-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)imidazolium-2-yl) porphyrin, MnTDTEG-2-ImP⁵⁺. Both porphyrins have ortho pyridyl or di-ortho imidazolyl electron-withdrawing substituents at meso positions of the porphyrin ring that assure highly positive metal centered redox potentials, E_1/2 = +250 mV vs. NHE for MnTTEG-2-PyP⁵⁺ and E _1/2 = + 412 mV vs. NHE for MnTDTEG-2-ImP⁵⁺. As expected, from established E_1/2 vs. log k_cat(O₂ ^-) structure-activity relationships for metalloporphyrins (Batinic-Haberle et al., Inorg. Chem., 1999, 38, 4011), both compounds exhibit higher SOD-like activity than any meso-substituted Mn(iii) porphyrins-based SOD mimic thus far, log k_cat = 8.11 (MnTTEG-2-PyP⁵⁺) and log k_cat = 8.55 (MnTDTEG-2-ImP⁵⁺), the former being only a few-fold less potent in disproportionating O₂^- than the SOD enzyme itself. The new porphyrins are stable to both acid and EDTA, and non toxic to E. coli. Despite elongated substituents, which could potentially lower their ability to cross the cell wall, MnTTEG-2-PyP⁵⁺ and MnTDTEG-2-ImP⁵⁺ exhibit similar protection of SOD-deficient E. coli as their much smaller ethyl analogues MnTE-2-PyP⁵⁺ and MnTDE-2-ImP⁵⁺, respectively. Consequently, with anticipated increased blood-circulating half-life, these new Mn(iii) porphyrins may be more effective in ameliorating oxidative stress injuries than ethyl analogues that have been already successfully explored in vivo. © The Royal Society of Chemistry 2006.

   Keywords:
   Porphyrins;Polyethylene glycols;Catalyst activity;Enzymes;Redox reactions;Substitution reactions;