Scavengers which convert

Irradiation of dilute aqueous solutions results in the interaction ofthe ionizing radiation with water molecules. The radiolysis of water produces hydrated electrons (eaq ", G = 2.8), hydrogen atoms (G = 0.6) and hydroxyl radicals (G = 2.8) which react with the molecules of the solutes. The use of special scavengers can convert one species to another, e.g. 

A different approach, recently introduced by Kaldor et al. [130, 131] and Virgilio [132], consists of using solid supported materials which function either as scavengers, sequestering from the solution reaction mixture an excess of reagents or some reaction byproducts, or as quenchers which convert unstable library components or intermediates into stable compounds, thus making simpler the purification/work-up procedures. 

This side reaction is relatively innocuous because the by-product is irreversibly bound to the polymer and only the yield is affected not the purity of the synthetic peptide. More disturbing is the succinimide ring formation at aspartyl residues exposed to HF. Alkylation of the indole ring in tryptophan, the phenolic side chain in tyrosine and the sulfur atom in methionine must be suppressed by the addition of scavengers. The often appUed anisole is less than unequivocal in this role it can be the source of methyl groups which convert the methionine thioether to a tertiary sulfonium derivative. The acid stable thioanisole seems to be a better scavenger. 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

All mammalian cells contain a thiol called glutathione Glutathione protects the cell by scavenging harmful oxidants It reacts with these oxidants by forming a disul fide which is eventually converted back to glutathione... 

The reactions described so far do not require the involvement of the apo-B protein, neither would they necessarily result in a significant amount of protein modification. However, the peroxyl radical can attack the fatty acid to which it is attached to cause scission of the chain with the concomitant formation of aldehydes such as malondialdehyde and 4-hydroxynonenal (Esterbauer et al., 1991). Indeed, complex mixtures of aldehydes have been detected during the oxidation of LDL and it is clear that they are capable of reacting with lysine residues on the surface of the apo-B molecule to convert the molecule to a ligand for the scavenger receptor (Haberland etal., 1984 Steinbrecher et al., 1989). In addition, the lipid-derived radical may react directly with the protein to cause fragmentation and modification of amino acids. 

Anti-oxidants can be divided into two classes depending on which part of the radical chain they quench. Primary anti-oxidants are radical scavengers and will react with alkyl chain radicals (R ) or hydroperoxides (ROOH). Secondary antioxidants work in combination with primary anti-oxidants and principally act by converting peroxide radicals (ROO ) into non-radical stable products. Synergism often works when both classes are used together. 

Regarding the proposed mechanisms of carvedilol antioxidative activity, membrane stabilization through the biophysical interaction of carvedilol with the membrane seems to be the most reliable one. However, a higher antioxidant activity of the metabolite SB 211475 leads to another explanation. In contrast to the parent carvedilol, SB 211475 has the active free radical scavenging phenolic hydroxyl, which is apparently responsible for its enhanced antioxidant activity. Thus, we may suggest that the in vivo antioxidant activity of carvedilol is due to its converting into active metabolites, which, for example, may be formed in the reactions with primary free radicals such as hydroxyl radicals. 

In neutral water the radiation chemical yields G are 2.7 x 10 7 mol J-1 for the hydrated electron, 2.8 x ] 0 7 mol, 1 1 for the "OH radical and 6 x 10 x mol J-1 for the H atom. These values vary slightly with the solute concentration, due to increased reaction with the solute in the radiation spurs. In order to study the reaction of one radical without interference of the others, scavengers have to be added to the system. The best scavengers are those which will convert the unwanted radical to the studied one. This can be done with eaq, which can be converted to "OH or to H by the addition of N2O or H+, respectively (equations 3 and 4). 

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