Phenoxyl reduction potential

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. 

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.

The one-electron reduction potentials, (E°) for the phenoxyl-phenolate and phenoxyl-phenol couples in water (pH 2-13.5) have been measured by kinetic [pulse radiolysis (41)] and electrochemical methods (cyclic voltammetry). Table I summarizes some important results (41-50). The effect of substituents in the para position relative to the OH group has been studied in some detail. Methyl, methoxy, and hydroxy substituents decrease the redox potentials making the phe-noxyls more easily accessible while acetyls and carboxyls increase these values (42). Merenyi and co-workers (49) found a linear Hammett plot of log K = E°l0.059 versus Op values of substituents (the inductive Hammett parameter) in the 4 position, where E° in volts is the one-electron reduction potential of 4-substituted phenoxyls. They also reported the bond dissociation energies, D(O-H) (and electron affinities), of these phenols that span the range 75.5 kcal mol 1 for 4-amino-... 

One-Electron Reduction Potentials (E°) of the Phenoxyl-Phenolate and Phenoxyl-Phenol Couples... 

Jovanovic, S.V., Steenken, S., Hara, Y., and Simic, M.G., Reduction potentials of flavonoid and model phenoxyl radicals. Which ring in flavonoids is responsible for antioxidant activity J. Chem. Soc. Perkin Trans. 2, 2497, 1996. 

Land EJ, Ebert M (1967) Pulse radiolysis studies of aqueous phenol. Water elimination from dihy-droxycyclohexadienyl radicals to form phenoxyl. Trans Faraday Soc 63 1181-1190 Lind J, Shen X, Eriksen TE, Merenyi G (1990) The one-electron reduction potential of 4-substituted phenoxyl radicals in water. J Am Chem Soc 112 479-482 Loft S, Poulsen HE (1999) Markers of oxidative damage to DNA antioxidants and molecular damage. Methods Enzymol 300 166-184... 

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],... 

Tryptophan and its derivatives such as the Hoechst compounds (Adhikary et al. 2000) have reduction potentials below that of G (tryptophan E7 = 1.0 V Jovanovic and Simic 1985) and thus are capable of repairing some of the DNA damage (for a review on indol free-radical chemistry see Candeias 1998 for the thermochemistry of N-centered radicals see Armstrong 1998). In these reactions, radical cations and N-centered radicals are formed. Similar to phenoxyl radicals, these radical react with 02- mainly by addition despite the large difference in the redox potential which would allow an ET as well (Fang et al. 1998). 

Armstrong D, Sun Q, Schuler RH (1996) Reduction potentials and kinetics of electron transfer reactions of phenylthiyl radicals comparisons with phenoxyl radicals. J Phys Chem 100 9892-9899 Asmus K-D (1979) Stabilization of oxidized sulfur centers in organic sulfides. Radical cations and odd-electron sulfur-sulfur bonds. Acc Chem Res 12 436-442 Asmus K-D (1990a) Sulfur-centered free radicals. Methods Enzymol 186 168-180 Asmus K-D (1990b) Sulfur-centered three-electron bonded radical species. In Chatgilialoglu C, Asmus K-D (eds) Sulfur-centered reactive intermediates in chemistry and biology. Plenum, New York, pp 155-172... 

Reaction between phenol and hydroxyl yields the dihydroxybenzenes, which can then undergo further oxidation (hydroquinone to benzoquinone, further hydroxylated to hydroxybenzoquinone, catechol and resorcinol to trihydroxybenzenes [79,100]). The condensation products, phenoxyphenols and dihydroxybiphenyls, most likely originate from the reaction between phenol and the phenoxyl radical [101]. Their presence indicates that some phenoxyl forms in the system, due to the reaction of phenol with OH or NO2. The possibility for NO2 to oxidise phenol to phenoxyl has been the object of a literature debate [102,103] in the context of nitration processes. The problem can be tackled upon consideration of the reduction potentials of the various species. The reduction potential of phenoxyl to undissociated phenol is E = 1.34 V - 0.059 pH [104], while for the reduction of nitrogen dioxide to nitrite it is E = 0.90 V [105]. Accordingly oxidation of phenol to phenoxyl would be possible above pH 7.5, and of course in the presence of phenolate (pH > 10 [106]). 

The antioxidants studied can be classified into two broad types phenolic antioxidants and non-phenolic antioxidants. Phenolic antioxidants have been found to be more promising as they are obtained from dietary sources.Vitamin E (a-tocopherol), the first known chainbreaking antioxidant, is also an o-methoxy phenol. Pulse radiolysis studies of vitamin E and its water-soluble analogue, trolox C, have been reported several years ago. a-tocopherol reacts with almost all the oxidizing free radicals, and the phenoxyl radicals produced during oxidation reactions absorb at -460 nm (Fig. 1). The regeneration reaction of a-tocopherol phenoxyl radicals back to a-tocopherol by water-soluble antioxidant ascorbic acid was also first reported by pulse radiolysis method. The one-electron reduction potential of vitamin E is -0.48 V vs. NHE. Both a-tocopherol and trolox C are used as standards for evaluating the antioxidant ability of new compounds. 

Phenoxyl radicals react rapidly with 02 radicals (Table 9)360-362 -pjjg reaction has been suggested to proceed via two parallel mechanisms addition of the 02 to the ortho or para positions of phenoxyl, followed by rearrangement and possibly ring opening, and electron transfer from 02 to phenoxyl to form O2 and phenolate ion. The contribution of the latter reaction depends on the reduction potential of the phenoxyl... 

Phenoxyl radicals can oxidize various compounds by electron transfer. These reactions depend on the reduction potential of the phenoxyl radical and the other reactant and may appear as equilibrium reactions or may proceed predominantly in one direction. Examples of the latter group of reactions are shown in Table 9 and examples of equilibrium reactions are in Table 10. 

Rate constants for electron transfer equilibrium reactions of phenoxyl radicals (Table 10) have been determined in conjunction with measurements of reduction potentials of phenoxyl radicals. Since most phenoxyl radicals in aqueous solutions are relatively short-lived, it was not possible to determine their reduction potentials by cyclic voltammetry. Therefore, it was necessary to utilize the pulse radiolysis technique to determine the reduction potentials from equilibrium constants, using a reference compound with which a phenoxyl radical can establish equilibrium conditions. Equilibrium concentrations were determined at short times, after the electron transfer equilibrium was achieved but before any significant decay of the radicals took place. The equilibrium constants were determined either from the concentrations at equilibrium, derived from absorbance, or from the rate constants for the forward and reverse reactions, derived from the rate of approach to equilibrium. Further details were given before . 

The dependence on substituent of the reduction potential and other properties of p-substituted phenoxyl radicals has been compared with the properties of the analogous phenylthiyl radicals. From this comparison it is evident that the electronic interaction... 

Transient phenoxyl radicals Formation and properties in aqueous solutions 1141 TABLE 11. Reduction potentials of phenoxyl radicals (PhO + Ref PhO + Ref") ... 

TABLE 12. Reduction potentials of phenoxyl radicals and O—H bond dissociation energies of phenols... 

The reduction potential changes with pH if either the radical or the molecule undergoes protonation or deprotonation upon pH change. For example, for dihydroxy compounds, where the two OH groups have dissociation constants K and Ki, and the phenoxyl radical has a dissociation constant for the second OH group, the potential at any pH, E, is related to the potential at pH 0, Eq, according to equation 38. 

Using such equations and known pATj values, the pH dependencies of the reduction potentials of phenoxyl radicals have been calculated for a number of cases. 

From the reduction potentials at pH 0 and estimated values for the free energies of solvation of phenol and phenoxyl in water, gas-phase O—H bond dissociation energies have been calculated. The values derived from such calculations are given in Table 12. They are comparable to values determined by other methods which are discussed in Chapter 3. 

Aliphatic alkoxyl radicals have reduction potentials of about 1600 mV vs SHE at pH 7 making them better oxidising agents than alkyl peroxyl radicals (E 1000 mV SHE) [130], Phenoxyl radicals usually have even lower reduction potentials, e.g. phenoxyl radical (CsHsO ) with E7 900 mV vj SHE and tocopheroxyl radical with E 500 mV vj SHE [130], and these can also be produced in vivo via the oxidation of phenols, such as the amino acid tyrosine, flavenoids and other phenolic antioxidants (e.g. tocopherols), or via the reduction of quinones. 

The reduction of a-tocopheroxyl radical by polyphenols is dependent on their structure. This has been critically shown for hydroxycinnamates, caflfeic, and /t-coumaric acids, the latter missing one of the -OH groups of the catecholic moiety. Although caffeic acid efficiently reduces a-tocopheroxyl radical to a-TOH, />-coumaric acid increases the rate of a-TOH consumption, and a clear synergistic protection of LDL from oxidation is observed only with caffeic acid plus a-TOH (Laranjinha et al, 1995). This effect of j9-coumaric acid was interpreted in terms of the stability of hydroxycinnamates-derived phenoxyl radicals and is supported by the higher reduction potential of /t-coumaric radical as compared with that of caffeic radical (Foley et al, 1999). Thus, conversely to caffeic acid o-semiquinone radical, j7-coumaric acid phenoxyl radical was able to oxidize a-TOH. 

Along these lines, We have explored the possibility that red wine and red wine phenolics (e.g., anthocyanin fraction) promoted the formation of NO from nitrite in a pH-dependent and concentration-dependent way. This has been substantiated in vivo in healthy volunteers by measuring NO in the air expelled from the stomach, following consumption of wine and nitrate, as measured by chemiluminescence (Gago et al, 2007). Structure-activity studies revealed that the formation of NO from nitrite directly correlates with the reduction potential of the several phenols tested, including dimers B2, B5, B8, catechin, epicatechin, and quercetin, among others (results not published). EPR studies showed that, mechanistically, the reaction involves the one-electron reduction of nitrite to NO by the polyphenols and the concomitant formation of phenol-derived phenoxyl radicals (Gago et al, 2007) (Fig. 11.1). 

Jovanovic SV, Steenken S, Hara Y, Simic MG. Reduction potentials of flavonoid and model phenoxyl radicals which ring in Havonoids is responsible for antioxydant activity J Chem Soc Perkin Trans 2 1996 11 2497 2504. 

Reduction potentials have also been determined for para-substituted phenyl thiyl radicals from equilibration with phenoxyl radical/phenolate couples in equilibrium (36) and with other standards [37]. 

Misleading conclusions can be drawn if only the reduction potentials of, for example, the GS, HVGSH and PhO, H /PhOH couples are considered and the law of mass action is ignored. Rate constants for repair of phenoxyl radicals by GSH, producing thiyl radicals, of < 10 dm moP s have been estimated in the cases of 1-naphthol [67] or acetaminophen [68]. The latter phenol was oxidized by thiyl radicals (cysteine) with 5 ca. 7x10 dm moP s at pH 7, an estimate of the reduction potential of the acetaminophen phenoxyl radical, (PhO, H /PhOH) = 0.71 V confirming that reaction (5), as an equilibrium, is well over to the left [69]. In spite of this, thiyl radicals are undoubtedly formed during peroxidase catalysed oxidation of acetaminophen in the presence of thiols [64,70]. Similar results were obtained with 4-ethoxyaniline (p-pheneti-dine) [71]. 

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