- Mechanistic studies of fluorescent sensors for the detection of reactive oxygen species
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Two new sensors for the detection of reactive oxygen species have been synthesized and characterized; they contain the 4-amino-7-nitrobenzofurazan (ABF) moiety covalently tethered to a phenol. Comparison of sensors ABFhd and dABFhd (the latter containing two ortho-methyl groups) shows that introduction of steric bulk leads to an improvement of fluorescent sensor performance, thus confirming our previous predictions based on computational chemistry. ABFhd and dABFhd are new tools for biological applications involving reactive oxygen species, in particular oxygen-centered radicals. This journal is The Royal Society of Chemistry.
- Heyne, Belinda,Ahmed, Sara,Scaiano
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p. 354 - 358
(2008/10/09)
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- Nitrosation of phenolic compounds: Effects of alkyl substituents and solvent
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Nitrosation reactions of phenol, o-cresol, 2,6-dimethylphenol, o-tert-butylphenol, 2-hydroxyacetophenone, and 2-allylphenol in water and water/acetonitrile were studied. Kinetic monitoring of the reactions was accomplished by spectrophotometric analysis of the nitrosated products at 345 nm. The dominant reaction was C-nitrosation via a mechanism consisting of an attack on the nitrosatable substrate by NO+/NO2H2+ followed by a slow proton transfer. The values of the rate constants of phenolic C-nitrosation were increased by electron donating substituents, and a good Hammett correlation was observed with ρ=-6.1. The results also revealed the strong effect of pH and the permitivity of the reaction medium on the rate constant, whose maximum values were observed for pH≈3, decreasing strongly for higher pH values. The study in water/acetonitrile with up to 25% acetonitrile showed that it is possible to inhibit the reaction strongly by increasing the percentage of the organic component. The conclusions drawn show that (i) it is possible to predict the rate of nitrosation of phenolics as a function of the meta-substituents on the phenol ring and (ii) the nitrosation of phenolics can be strongly inhibited by increasing the pH of the reaction medium as well as by lowering its dielectric constant.
- Gonzalez-Mancebo, Samuel,Lacadena, Javier,Garcia-Alonso, Yolanda,Hernandez-Benito, Jesus,Calle, Emilio,Casado, Julio
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p. 157 - 166
(2007/10/03)
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- A study of the reaction of different phenol substrates with nitric oxide and peroxynitrite
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The reactivity of different phenol substrates with nitric oxide and peroxynitrite was investigated. In general, nitration is the major reaction with peroxynitrite, while reactions with aqueous solutions of nitric oxide led to mixtures of nitro and nitroso derivatives depending upon the phenol. Nitrosation occurs on phenol substrates bearing a free para- position with respect to the OH group with the exception of 1-naphthol, which afforded a 1:1 mixture of the 2- and the 4-nitroso derivatives. Chromans 7 and 8 showed the highest reactivity with peroxynitrite, which suggests that they can act as efficient scavengers of this toxic intermediate. In both cases the corresponding 5-nitro derivative was the only reaction product detected. Finally, the fact that chroman 8 reacts with nitric oxide to afford the p- quinone derivative 22a in 90% yield suggests that this antioxidant could also be of potential use as specific nitric oxide tracer in biological tissues.
- Yenes, Susana,Messeguer, Angel
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p. 14111 - 14122
(2007/10/03)
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- Reactivity of phenolic nucleophiles towards nitroso compounds. Part 2. Reaction with alkyl nitrites (O-nitroso compounds)
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Second-order rate constants, k, have been measured for the reaction of substituted phenolate ions with alkyl nitrites in aqueous solution at 25 deg C. The final products of this reaction were identified as aromatic C-nitroso compounds and/or NO2-. Nitrosation of the phenolate ion yields ca. 90 percent of the p-nitroso product. However, methylation of the activated position of the ring (as in 4-methylphenol) does not result in the decrease in the overall reaction rate that would be expected. The reactivity of all the phenolate ions studied correlates well with their basicity, with the Hammett ?- constant and with their reactivity in other reactions in which they are known to act as O-nucleophiles. All these facts suggest that the reaction of aryloxide ions with alkyl nitrites always occurs through the oxygen atom to yield an unstable O-nitroso compound. This intermediate is likely to undergo an internal rearrangement of the NO group to give the corresponding C-nitroso product, competing with homolysis of the O-NO bond to yield nitric oxide. Oxidation of NO in the presence of O2 gives N2O3, which could act as a nitrosating agent towards ArO-. Hydrolysis of N2O3 in basic media accounts for the presence of the nitrite ion as one of the products.
- Leis, J. Ramon,Rios, Ana,Rodriguez-Sanchez, Luiza
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p. 2729 - 2734
(2007/10/03)
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- Nitrosation and Nitrous Acid-catalysed Nitration of Anisole and 2,6-Dimethylanisole
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Rate-acidity profiles have been obtained for the nitrosation of anisole, 2,6-dimethylanisole (DMA), and 2,6-dimethylphenol (DMP) in aqueous sulphuric acid.The phenol is more reactive than the corresponding anisole, and DMA has a more shallow profile than anisole.A deuterium kinetic isotope effect (KH/kD) of 4.0 for 2H>anisole indicates that the product of nitrosation of anisole in 46.5percent sulphuric acid (p-nitrosophenol) is formed by slow proton loss from the Wheland intermediate.Intense colours were associated with the nitrosation of these compounds when nitrous acid was in excess.The kinetics of nitrous acid-catalysed nitration of anisole were studied in 43.0 and 47.0percent sulphuric acid; the product is p-nitrophenol.Nitrosation followed by oxidation by NV was the major pathway at these acidities.The other pathway has a kinetic form given by kC=k3III>V>, consistent with a process where oxidation by NV is rate-limiting.Product studies show that p-nitrophenol is formed at lower acidities and o- and p-nitroanisole at higher acidities.A mechanism is suggested involving a radical cation species, which would predominate at higher acidities and account for the kC pathway at lower acidities.The nitrous acid-catalysed nitration of DMA gives 2,6-dimethyl-4-nitroanisole in higher yield as the acidity increases.
- Dix, Leslie R.,Moodie, Roy B.
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p. 1097 - 1102
(2007/10/02)
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- Studies on the mechanism of toxicity of acetaminophen. Synthesis and reactions of N-acetyl-2,6-dimethyl- and N-acetyl-3,5-dimethyl-p-benzoquinone imines
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N-Acetyl-2,6-dimethyl-p-benzoquinone imine and N-acetyl-3,5-dimethyl-p-benzoquinone imine were prepared from 2,6-dimethylacetaminophen and 3,5-dimethylacetaminophen by oxidation with lead tetraacetate. Reaction of N-acetyl-2,6-dimethyl-p-benzoquinone imine with hydrochloric acid gave 3'-chloro-2',6'-dimethyl-4'-hydroxyacetanilide, whereas ethanethiol, aniline, and ethanol gave tetrahedral adducts resulting from addition to the imine carbon. Water gave 2,6-dimethyl-p-benzoquinone. With N-acetyl-3,5-dimethyl-p-benzoquinone imine, water and aniline gave substitution on the imine carbon, yielding 2,6-dimethyl-p-benzoquinone and 3,5-dimethyl-N-phenyl-p-benzoquinone imine, respectively. Ethanethiol gave 3',5'-dimethyl-2'-(ethylthio)-4'-hydroxyacetanilide. The toxicity of 2,6-dimethylacetaminophen and 3,5-dimethylacetaminophen was examined histologically in mice and rats. 3,5-Dimethylacetaminophen was slightly more nephrotoxic but showed a similar hepatotoxicity to acetaminophen. 2,6-Dimethylacetaminophen, like N-methylacetaminophen, showed very little tissue damage.
- Fernando,Calder,Ham
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p. 1153 - 1158
(2007/10/02)
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