Radicals phenoxyl

Phenoxyl radicals are oxidizing radicals (for a compilation of redox potentials see Wardman 1989). Thus, in their reactions with 02 (E7 = -0.3 V) there is ample driving force for a reduction by ET [cf. reaction (16)], and this has been thought for a long time to be the only (Hunter et al. 1989) or at least a major process, depending on the reduction potential of the (substituted) phenoxyl radical (Jonsson et al. 1993). Yet in the tyrosine system, despite of the high reduction potential of tyrosine phenoxyl radical (E7 = 0.64 V), the by far dominating process is addition, and the intermediate adduct is locked in by a Mannich reaction [reactions (14) and (15) Jin et al. 1993], 

Reduction of a phenoxyl radical by CV can nevertheless occur by an addition/ elimination sequence as shown in reactions (17) and (18) (d Alessandro et al. 2000). In the given case, the pfCa value of the hydroperoxide is 11.3 [equilibrium (19)], and 02 elimination occurs only from the anion [reaction (18) k = 1.3 x 105 s 1 at 23 °C, a = 105 kj mol1]. 

In addition to the 02 elimination reaction (17) and the Mannich reaction (14), phenoxyl/CV combination products can undergo a water elimination if the position where 02- has added to carries an H atom [e.g., reactions (20 and (21) d Alessandro et al. 2000]. 

As mentioned above, these reactions are potentially of some heuristic importance also for DNA in so far as little is known about the fate of G (notably its bimolecular decay Chap 10.2). Both G- and phenoxyl radicals share quite some properties they are aromatic with high spin density at oxygen, reasonably strong oxidants, do not react with 02 at an appreciable rate, but quite readily with 02-. 

Many antioxidants quoted as potential protective agents against free-radical-induced DNA damage have more than one phenolic group. Their chemistry is, therefore, also of some interest in the present context. The semiquinone radicals, derived from hydroquinone by one-electron oxidation or from 1,4-benzoqui-none by one-electron reduction, are in equilibrium with their parents (Roginsky et al. 1999), and these equilibria play a role in the autoxidation of hydroquinone (Eyer 1991 Roginsky and Barsukova 2000). Superoxide radials are intermediates in these reactions. 

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Tripathi G N R and Schuler R H 1984 The resonance Raman spectrum of phenoxyl radical J. Chem. Phys. 81 113-21... 

The effect substitution on the phenolic ring has on activity has been the subject of several studies (11—13). Hindering the phenolic hydroxyl group with at least one bulky alkyl group ia the ortho position appears necessary for high antioxidant activity. Neatly all commercial antioxidants are hindered ia this manner. Steric hindrance decreases the ability of a phenoxyl radical to abstract a hydrogen atom from the substrate and thus produces an alkyl radical (14) capable of initiating oxidation (eq. 18). 

Allyl (27, 60, 119-125) and benzyl (26, 27, 60, 121, 125-133) radicals have been studied intensively. Other theoretical studies have concerned pentadienyl (60,124), triphenylmethyl-type radicals (27), odd polyenes and odd a,w-diphenylpolyenes (60), radicals of the benzyl and phenalenyl types (60), cyclohexadienyl and a-hydronaphthyl (134), radical ions of nonalternant hydrocarbons (11, 135), radical anions derived from nitroso- and nitrobenzene, benzonitrile, and four polycyanobenzenes (10), anilino and phenoxyl radicals (130), tetramethyl-p-phenylenediamine radical cation (56), tetracyanoquinodi-methane radical anion (62), perfluoro-2,l,3-benzoselenadiazole radical anion (136), 0-protonated neutral aromatic ketyl radicals (137), benzene cation (138), benzene anion (139-141), paracyclophane radical anion (141), sulfur-containing conjugated radicals (142), nitrogen-containing violenes (143), and p-semi-quinones (17, 144, 145). Some representative results are presented in Figure 12. 

Rapid oxidation by acidic hexachloriridate of phenol and 2,6-dimethylphenol takes place to give the corresponding phenoxyl radical . At low Ir(iri) concen-... 

Trisacetylacetonecobalt(III) oxidises phenols to phenoxyl radicals at 71-120 °C in chlorobenzene with simple second-order kinetics, E = 33 kcal.mole" and AS = 13.6 eu) . When 2,4,6-tcrt-butylphenol was employed, the characteristic ESR spectrum of the phenoxyl radical was obtained with an intensity corresponding to almost quantitative conversion, viz. 

Fig. 16.4 Interaction between quercetin (Quer) and iron and the balance between pro-oxidative and antioxidative effects. Quercetin may reduce Fe(H20) to yield Fe(H20) active in the Fenton region forming hydroxyl radicals ( OFI) or alkoxyl radicals ( OR), in effect being pro-oxidative. In contrast, quercetin may form a complex with iron(II), inactive in reducing FI2O2 to OFI, but rather oxidised in the quercetin ligand, in effect being antioxidative. Quer (-H) is the phenoxyl radical.

The electron transfer mechanism for antioxidant activity corresponding to eq. 16.5 makes the standard reduction potentials of interest for evaluation of antioxidative activity. The standard reduction potential of the phenoxyl radical of several flavonoids has been determined and forms the basis for correlation of rate of electron transfer for various oxidants from the flavonoid (Jovanovic etal., 1997 Jorgensen and Skibsted, 1998). The standard reduction potentials have also been used to establish antioxidant hierarchies. 

The reaction of eq. 16.9 will regenerate the antioxidant Arj-OH at the expense of the antioxidant At2-OH. Despite the fact that such regeneration reactions are not simple electron transfer reactions, the rate of reactions like that of eq. 16.9 has been correlated with the E values for the respective Ar-0. Thermodynamic and kinetic effects have not been clearly separated for such hierarchies, but for a number of flavonoids the following pecking order was established in dimethyl formamid (DMF) by a combination of electrolysis for generating the a-tocopherol and the flavonoid phenoxyl radicals and electron spin resonance (ESR) spectroscopy for detection of these radicals (Jorgensen et al, 1999) ... 

Fig. 16.5 Synergistic regeneration of a-tocopherol by quercetin at a lipid-water interphase. a-tocopherol is reacting with a lipid peroxyl radical in a chain-breaking reaction. According to the standard reduction potential, the phenoxyl radical of quercetin can further be regenerated by ascorbate.

TTx represents the hydrophobicity of the substituents at position 10. Its positive coefficient (+0.75) suggests that the presence of highly hydrophobic substituents at position 10 increases the activity. The outlier (X = OH) is much more active than expected by 11 times the standard deviation. This may be due to the formation of a phenoxyl radical that interacts with DNA [48]. The other derivative (X = NH2) is also considered as an outher due to being much more active than expected by 14 times the standard deviation. This anomalous behavior may be attributed to its nature as an aniline. This could result in hydrogen abstraction, or involve microsomal N-oxidation [48,49]. 

Kalyanaraman, B., Darley-Usmar, V.M., Wood, J., Joseph, J. and Parathasarathy, S. (1992). Synergistic interaction between the probucol phenoxyl radical and ascorbic acid in inhibiting the oxidation of LDL. J. Biol. Chem. 267, 6789—6795. 

Compound 1 (Fig. 18.18) reversibly forms an analogous ferric-superoxo/Cu adduct at 60 °C, as demonstrated by resonance Raman spectroscopy. However, warming the sample to 40 °C results in a rapid four-electron reduction of the bound O2 ligand, generating a ferryl/Cu /phenoxyl radical derivative (Fig. 18.18) [Collman et al., 2007a]. 

The spin density of tocopheroxyl radical 2, a classical phenoxyl radical, is mainly concentrated at oxygen 0-6, which is the major position for coupling with other C-centered radicals, leading to chromanyl ethers 5. These products are found in the typical lipid peroxidation scenarios. Also at ortho- and para-positions of the aromatic ring, the spin density is increased. At these carbon atoms, coupling with other radicals, especially O-centered ones, proceeds. Mainly the para-position (C-8a) is involved (Fig. 6.3), leading to differently 8a-substituted chromanones 6. 

Also for the reaction that was described as dimerization of the chromanol methide radicals 10 to the ethano-dimer of a-tocopherol 12, the involvement of the C-centered radicals has been disproven and these intermediates lost their role as key intermediates in favor of the o-QM 3. It was experimentally shown that ethano-dimer 12 in hydroperoxide reaction mixtures of a-tocopherol was formed according to a more complex pathway involving the reduction of the spiro dimer 9 by a-tocopheroxy 1 radicals 2, which can also be replaced by other phenoxyl radicals (Fig. 6.10).11 Neither the hydroperoxides themselves, nor radical initiators such as AIBN, nor tocopherol alone were able to perform this reaction, but combinations of tocopherol with radical initiators generating a high flux of tocopheroxyl radicals 2 afforded high yields of the ethano-dimer 12 from the spiro dimer 9. 

The central feature of this mechanism is, therefore, that the phenoxyl radical is reversibly reduced and re-oxidised this leads to the continuous consumption of macroalkyl radicals. The phenoxyl radical can, therefore, react with polypropylene radicals and compete with PP-MA adduct formation in the stabilised polymer (Figure 3, curve MA-S). 

The binding of phenoxyl radical species to zinc has been observed. The pendent arm macro-cyclic ligand 1-ethyl-4,7-t-bis(3-butyl-5-methoxy-2-hydroxybenzyl)-l,4,7-triazacyclononane... 

Pendent arm 1,4,7-triazacyclononane macrocycles (91) and (92) have been used to stabilize the zinc-to-phenoxyl bond allowing characterization of these compounds.477 The interest in the zinc complexes comes from the wide potential range in which it is redox stable allowing observation of the ligand-based redox processes, this allows study of the radical by EPR and the electronic spectra is unperturbed by d-d transitions. Macrocycles of the type l,4,7-tris(2-hydroxybenzyl)-1,4,7-triazacylononane form a bound phenoxyl radical in a reversible one-electron oxidation of the ligand. The EPR, resonance Raman, electronic spectra, and crystal structure of the phenoxide complexes were reported. This compound can be compared to a zinc complex with a non-coordinated phenoxyl radical as a pendent from the ligand.735... 

With 2,4,6-trialkylphenols used as inhibitors, the formed phenoxyl radicals produce quinolide peroxides by the reactions with peroxyl radicals. At sufficiently high temperatures, quinolide peroxides decompose giving rise to free radicals [18,31,32,53,54] ... 

Phenoxyl radicals with alkoxyl substituents in the ortho- and pnra-positions decompose with the formation of alkyl radicals [55],... 

A) Phenols of this group react with peroxyl radicals, hydroperoxide, and dioxygen, while respective phenoxyl radicals can react with RH and ROOH. Reactions of these phenols with R02 most commonly give rise to quinones the breakdown of phenoxyls does not produce active radicals. This group includes all phenols, except 2,6-di-/er/-alky I phenols and alkoxy-substituted phenols. Phenols of this group can inhibit oxidation by mechanisms I-VII. 

B) Phenols of this group slowly react with hydroperoxide and dioxygen. Respective phenoxyl radicals are relatively unreactive toward RH and ROOH, but can react with R02 giving rise to peroxides and then to free radicals. For these phenols, appropriate inhibitory mechanisms are I III and VI VIII. 

C) This group includes phenols with alkoxy substituents. Respective phenoxyl radicals decompose with the formation of chain-propagating alkyl radicals. In addition to inhibitory mechanisms determined by substituents, these phenols can realize mechanism IX. 

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