New class of potent catalysts of O2.-dismutation. Mn(III) ortho-methoxyethylpyridyl- and di-ortho-methoxyethylimidazolylporphyrins

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-PyP(5+)), Mn(III)5,10,15,20-tetrakis[N-methyl-N'-(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTM,MOE-2-ImP(5+)) and Mn(III) 5,10,15,20-tetrakis[N,N'-di(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTDMOE-2-ImP(5+)). 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-PyP(5+), log k(cat)= 7.98 (E(1/2)=+356 mV) for MnTM,MOE-2-ImP(5+) and log k(cat)= 7.59 (E(1/2)=+365 mV) for MnTDMOE-2-ImP(5+). 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-PyP(5+)), Mn(III) 5,10,15,20-tetrakis(N-n-butylpyridinium-2-yl)porphyrin (MnTnBu-2-PyP(5+)) and Mn(III) 5,10,15,20-tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin (MnTDE-2-ImP(5+)). MnTMOE-2-PyP(5+) has side chains of the same length and the same E(1/2), as MnTnBu-2-PyP(5+)(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(cat)vs. 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 microM), and protected SOD-deficient E. coli in a concentration-dependent manner. At 3 microM levels, the MnTDMOE-2-ImP(5+), bearing an oxygen atom within each of the eight side chains, was the most effective and offered much higher protection than MnTE-2-PyP(5+), while MnTDE-2-ImP(5+) was of very low efficacy.     

Absorption spectrum of carbon dioxide at 4.3 μm

The absorption spectrum of carbon dioxide has been recorded in the wavenumber region 2395-2216 cm^?1 with a spectral resolution between 0.02 and 0.03 cm^?1. About twenty transitions have been identified and the molecular constants of the levels involved have been evaluated. In view of the interest of this region in atmospheric studies a map of the entire spectrum recorded by using a normal sample of carbon dioxide is presented including the identifications for the different bands. About 90% of the lines observed have been interpreted. Some of them have been assigned to transitions originating from higher excited states of ¹²C¹⁶O₂ not considered before in interpreting this spectral region. For the first time, bands of ¹²C¹⁶O¹⁷O have been identified in the 4.3-μm spectra obtained with the natural sample.     

New PEG-ylated Mn(III) porphyrins approaching catalytic activity of SOD enzyme

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'-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, E1/2 = +250 mV vs. NHE for MnTTEG-2-PyP5+ and E1/2 = + 412 mV vs. NHE for MnTDTEG-2-ImP5+. As expected, from established E1/2 vs. log kcat(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 kcat = 8.11 (MnTTEG-2-PyP5+) and log kcat = 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.     

DOES THE AEROBIC XANTHINE OXIDASE REACTION GENERATE SINGLET OXYGEN?*

Abstract— The aerobic xanthine oxidase reaction causes the co-oxidation of 2,5-dimethylfuran to cis-diacetylethylene and the bleaching of rubrene tetracarboxylate. These actions were suppressed by superoxide dismutase, catalase, desferoxamine and by benzoate and other hydroxyl radical scavengers. The bleaching of rubrene tetracarboxylate was not enhanced in D₂0. These results suggest that OHv, generated from O₂^- plus H₂O₂ by an iron-catalyzed Haber Weiss reaction, was the responsible agent and that singlet oxygen was not detectably involved. Control experiments, in which singlet oxygen was generated photochemically, demonstrated that replacement of H₂O by D₂O caused the expected enhancement of the chemical reactivity of singlet oxygen under the conditions of these experiments and that O₂^-, at concentrations achieved by the xanthine oxidase reaction, did not detectably quench singlet oxygen. We conclude that singlet oxygen, if produced at all during the aerobic xanthine oxidase reaction, cannot exceed 0.1% of the production of O₂^-.     

Production of O2- in photolyzed water demonstrated through the use of superoxide dismutase

Abstract— The photolysis of water has been studied using ferricytochrome c as the detector of reducing radicals and ferrocytochrome c as the detector of oxidizing radicals. Mannitol was used as a scavenger of hydroxyl radicals and superoxide dismutase was used to expose the specific involvement of superoxide radicals. Aerobic photolysis caused a reduction of ferricytochrome c, which was inhibited by superoxide dismutase and was enhanced by mannitol. Aerobic photolysis also caused the oxidation of ferrocytochrome c, which was inhibited by mannitol and augmented by superoxide dismutase. The presence of superoxide dismutase also eliminated the effects of mannitol on the aerobic oxidation of ferrocytochrome c. Photolysis in the absence of oxygen also caused the reduction of ferricytochrome c and the oxidation of ferrocytochrome c, but under these anaerobic conditions neither mannitol nor superoxide dismutase exerted significant effects. An explanation of these observations is offered in terms of the reactivities of H^., OH^. and O^-2 radicals.     

THE ROLE OF O2- IN THE CHEMILUMINESCENCE OF LUMINOL*

Abstract— The chemiluminescence of luminol in buffered aqueous solutions is inhibited by superoxide dismutase. This occurs whether the luminescence is induced by ferricyanide, persulfate, hypochlorite, or by the action of xanthine oxidase on xanthine. Since superoxide dismutase inhibits reactions which involve O₂^-, we conclude that this radical is a constant factor in the chemiluminescence of luminol in aqueous solutions. The kinetics of light production are discussed in terms of hypothetical mechanisms that fit the available data. The strong luminescence of luminol in aprotic solvents or in aqueous systems containing relatively high concentrations of H₂O₂ could not be explored in this way, because superoxide dismutase is inactive under such conditions.     

Strengths of single lines in the 12C16O2, ν3 band at 4.3 μm

Individual line strengths have been measured in the 4.3-μm ν₃ absorption band of ¹²C¹⁶O₂ from R46 to R90 using a vacuum grating spectrometer. Approximately 1100 measurements were made at pressures from 0.16 to 100.0 Torr, path lengths from 3.25 to 2331 cm, and temperatures from 246 to 338 K. The standard deviations of the measurements varied from 5 to 10%. The mean value of the vibrational dipole matrix element squared obtained is {R_if}² = 0.1103 ± 0.0085 D².     

Correcting measured line half-widths

A method is presented for correcting measured line half-widths for the error introduced by imprecise location of the 100% transmittance line. The method assumes a line shape—Lorentz or Voigt—and requires as input the measured central transmittance, the measured half-width, and the distance from line center to the assumed location of 100% transmittance.