Phenol-derived phenoxyl radicals

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). 

Recently, a somewhat different synthetic approach has been reported. Halcrow et al. (215) synthesized a series of five-coordinate copper(II) complexes comprising a tridentate tris(pyrazolyl)borate ligand and a bidentate phenol derivative. Neutral complexes [Cun(TpPh)(bidentate phenolate)] were synthesized and structurally characterized [Tpph] = hydrido-tris(3-phenylpyrazol-l-yl)borate. The species [Cun(TpPh)(2-hydroxy-5-methyl-3-methylsulfanylbenzaldehydato)] can electro-chemically be converted to the (phenoxyl)copper(II) monocation, which has been characterized in solution by UV-vis spectroscopy. It displays two intense absorption maxima at 907 nm (e = 1.2 x 103 M 1 cm-1), and 1037 (1.1 x 103 M l cm-1), resembling in this respect the radical cofactor in GO (Fig. 7). 

Phenol-induced oxidative stress mediated by thiol oxidation, antioxidant depletion, and enhanced free radical production plays a key role in the deleterious activities of certain phenols. In this mode of DNA damage, the phenol does not interact with DNA directly and the observed genotoxicity is caused by an indirect mechanism of action induced by ROS. A direct mode of phenol-induced genotoxicity involves covalent DNA adduction derived from electrophilic species of phenols produced by metabolic activation. Oxidative metabolism of phenols can generate quinone intermediates that react covalently with N-1,N of dG to form benzetheno-type adducts. Our laboratory has also recently shown that phenoxyl radicals can participate in direct radical addition reactions with C-8 of dG to form oxygen (O)-adducts. Because the metabolism of phenols can also generate C-adducts at C-8 of dG, a case can be made that phenoxyl radicals display ambident (O vs. C) electrophilicity in DNA adduction. 

How can we keep our health against these reactive oxygen radicals Fortunately, vitamin C (hydrophilic), vitamin E (hydrophobic), flavonoids, and other polyphenols can function as anti-oxidants. These anti-oxidants are phenol derivatives. Phenol is a good hydrogen donor to trap the radical species and inhibits radical chain reactions. The formed phenoxyl radical is actually stabilized by the resonance effect as shown in eq. 1.8. Thus, phenol and polyphenol derivatives are excellent hydrogen donors to inhibit the radical reactions and, therefore, they are called radical inhibitors. 

Photoelectron transfer oxidation of phenols, 3,5-dunethyl and 2,6-dunethylphenol, takes place using 2-nitrofluorene as the electron-accepting sensitizer in both acetonitrile and cyclohexane solution. In acetonitrile the anion radical of 2,6-dimethylphenol is observed as the final product . Other phenols such as the 2,4,6-trunethyl derivative also undergo electron transfer reactions with 1,1 -, 1,2 - and 2,2 -dinaphthyl ketones. Other sensitizers such as 1,4-dicyanonaphthalene with biphenyl as a co-sensitizer in acetonitrile have also been used. The resultant phenol radical cations (4a-h) have absorption maxima in the 410-460 nm region with the exception of 4i that absorbs at 580 nm. When the reactions are carried out in the presence of a trace of water, the radical cations are not observed. Instead, phenoxyl radicals are detected. This presumably is due to the reaction shown in equation 2. 

The very rapid oxidation of phenols by solvent radical cations can be expected to yield phenol radical cations as the first products. These species are short-lived, except in highly acidic solutions, and were not observed in the microsecond pnlse radiolysis experiments described above. They were detected, however, in frozen matrices and with nanosecond pulse radiolysis Gamma irradiation of phenols in w-butyl chloride or in l,l,2-trichloro-l,2,2-trifluoroethane (Freon 113) at 77 K produced phenol radical cations, which were detected by their optical absorption and ESR spectra . Annealing to 133 K resulted in deprotonation of the radical cations to yield phenoxyl radicals. Pulse radiolysis of p-methoxyphenol and its 2,6-di-fert-butyl derivative in w-butyl chloride at room temperature produced both the phenol radical cations and the phenoxyl radicals. The phenol radical cations were formed very rapidly k = 1.5 x 10 ° M s ) and decayed in a first-order process k = 2.2 x 10 s ) to yield the phenoxyl radicals. The phenoxyl radicals were partially formed in this slower process and partially in a fast process. The fast process of phenoxyl formation probably involves proton transfer to the solvent along with the electron transfer. When the p-methoxy group was replaced with alkyl or H, the stability of the phenol radical cation was lower and the species observed at short times were more predominantly phenoxyl radicals. 

In a more recent study pulse radiolysis was utilized to produce the phenoxyl radical in the gas phase and to measure some reaction kinetics. The irradiated gas mixmre contained mainly SFe (at 980 to 1000 mbar), which served as a source of F atoms. Phenol was present at 0.1 mbar. The rate constant for reaction of phenol with F atoms was determined to be 1.9 X 10" M s. This reaction led to formation of the phenoxyl radical (45%) and other products, probably fluorine-adducts to the ring. When HCl (20 mbar) was added to the mixture, most fluorine atoms reacted with HCl to produce chlorine atoms and these reacted with phenol to produce the phenoxyl radical as the predominant product. The rate constant for reaction of chlorine atoms with phenol, derived from several competition kinetic experiments, was 1.2 x 10" M s, slightly lower than the value for fluorine atoms. The spectrum of the phenoxyl radical in the gas phase was very similar to that recorded in aqueous solutions. It exhibits several peaks between 350 nm and 400 nm and much more intense absorptions in the UV, the main peak being at 235 nm (molar absorption coefficient 2.3 x 10 M cm ). By following the decay... 

Phenoxyl and semiquinone radicals are important intermediates in numerous biological systems and ESR spectroscopy has been used to detect and identify them in such systems. Studies were carried out on enzymatic reduction of quinone derivatives and enzymatic oxidation of hydroquinone and phenol derivatives. This topic has been reviewed... 

Phenoxyl radicals (Ph-0 ) are known not to iiutiate radical polymerization in most cases (2) and may be RTCP catalysts if they can activate Polymer-I. Based on this idea, we attempted to use phenol derivatives as catalysts, thus extending the element of the catalyst to O (Figure 1). Notably, the phenols include common antioxidants for foods and resins and natural compounds such as vitamins (Figure 1). Their commonness (hence cheapness) and environmental safety may be highly attractive for practical applications. In this paper, we will present the results of the styrene and methyl methacrylate (MMA) polymerizations, along with a mechanistic study. 

Irradiation of PP in air leads to oxidative degradation, evidenced by discoloration and embrittlement. The extent of the degradation depends on crystallinity, MW, MWD, and chain mobility [Kadir et al., 1989 Kashiwabara and Seguchi, 1992 Williams, 1992]. Neat PP does not discolor on irradiation up to 100 kGy [Williams, 1992]. The antioxidants should be selected so as not to cause the discoloration. However, most commercial preparations containing phenolic antioxidants turn yellow on irradiation. Phenolic antioxidants produce stable phenoxyl radicals that convert into colored quinonoids. Other stabilizers and antioxidants are compounds that contain either phosphorous [Bentrude, 1965 de Paolo and Smith, 1968], sulfur [Jirackova and Pospisil, 1979], or hindered piperidine derivatives [Carlsson, et al., 1980 Felder et al., 1980 Allen et al., 1981]. A comprehensive list of stabilizers and their mode of action was given by Dexter [1992]. It is noteworthy that antioxidants and stabilizers are excluded from the crystalline regions [Winslow et al., 1966] thus they would provide protection only within the amorphous domains. 

The formation of the phenoxyl radical was proposed to occur in the presence of acetic acid by coupling the two-electron, two-proton reduction of molecular oxygen to H2O2 [85]. In some way this process is reminiscent of the half reaction observed in GAO. The unusual aspect, however, was its identification in the activated HKR reaction system, although there was no evidence for its involvement in the hydrolysis of epoxides [85]. As Wieghardt noted in earlier works, bulky substituents are required for stabilization of metal-coordinated phenolate radicals [66]. We confirmed this by activation of a Co-salen derivative, [Co(12)] (Fig. 3). In the absence... 

The free radical reactivity of methylated flavan-3 -ols has been investigated using a flash photolysis experiment for the photochemical generation of radicals and their characterization through the monitoring of their UY-visible spectra [29,31,39]. Phenoxyl radicals have been generated by different techniques (1) by direct photoionization of the polyphenol derivatives in their basic form and (2) by H-atom abstraction from phenolic OH by tert-butoxyl radicals generated by the photoionization of fert-butyl peroxide in aprotic media (Fig. 1). 

---