Disease relevance of phenol

• Previous studies showed that the phenoxyl radical of etoposide can be generated by myeloperoxidase (MPO), an enzyme prevalent in myeloid progenitor cells that can derive myelogenous leukemias [1].
• Mechanisms of phenoxyl radical-induced generation of oxygen radicals potentially involved in toxicity of benzene were studied [2].

High impact information on phenol

• Myeloperoxidase (MPO)-catalyzed one-electron oxidation of the etoposide phenolic ring and/or interaction of this phenolic moiety with reactive radicals yields its phenoxyl radical, whose reactivity may determine the pro- or antioxidant effects of this molecule in cells [3].
• Combined optical and conductimetric measurements in aqueous solution indicate that at high pH (greater than or equal to 10).OH radicals react with the phenoxide form of 2,4-dihydroxybenzoic acid to form transiently phenoxyl radicals and a small amount of hydroxyeyclohexadienyl (HCHD) radicals by 150 ns [4].
• This reaction results in the complete reduction of the free radical of acetaminophen, whereas the glutathione reduction of the phenoxyl radical of acetaminophen was not complete on the fast-flow ESR time scale of milliseconds [5].
• A selectivity of 230:20:1 was determined for alkylation of phenol at oxygen, C-4 and C-2 to form 1-OPh and biphenyls 1-(4-C6H4OH) and 1-(2-C6H4OH), respectively, and of 2:2:1 for alkylation of the corresponding nucleophilic sites of phenoxide ion in diffusion-limited reactions [6].
• Coenzyme Q (CoQ) was previously demonstrated in vitro to indirectly act as an antioxidant in respiring mitochondria by regenerating alpha-tocopherol from its phenoxyl radical [7].

Biological context of phenol

• In reactions involving polar groups, such as alkylations of phenoxide ions or S(N)1 ionizations of alkyl halides, cosolvents in water can have other effects as well [8].
• Thus, Tyr150, as the phenoxide anion, would be the general base catalyst in acylation, as proposed by Oefner et al [9].
• Atmospheric pressure ionization (API) mass spectrometry: formation of phenoxide ions from chlorinated aromatic compounds [10].
• Under excess of phenol over the substrate, all the reactions obey pseudo-first-order kinetics and are first order in phenoxide anion [11].
• Metabolic activation of PAR via primary formation of a phenoxy radical seems the most likely mechanism [12].

Anatomical context of phenol

• These findings suggest a role for the OTA phenoxyl radical in OTA-mediated DNA adduction in vivo, provide a rationale for the tumorigenesis of OTA, and strengthen the OTA hypothesis in the etiology of BEN and the associated urinary tract tumors [13].
• Involvement of phenoxyl radical intermediates in lipid antioxidant action of myricetin in iron-treated rat hepatocyte culture [14].
• Antioxidant paradoxes of phenolic compounds: peroxyl radical scavenger and lipid antioxidant, etoposide (VP-16), inhibits sarcoplasmic reticulum Ca(2+)-ATPase via thiol oxidation by its phenoxyl radical [15].
• A simple and convenient method to follow phenoxyl radical reactions in liposomes and rat liver microsomes based on an enzymatic (lipoxygenase + linolenic acid) oxidation system was used to generate phenoxyl radicals from BHT and its homologues with substitutents in m- and p-positions [16].
• It is shown in this study that the initial protein radical, which is a tyrosine phenoxyl radical centered at position 103 in the protein, does not react rapidly with erythrocyte membranes [17].

Associations of phenol with other chemical compounds

• Tyrosine phenoxyl radical "repair" by superoxide and physiological antioxidants was examined by BT fluorescence quenching as well as pulse radiolysis [18].
• This was identified by time-resolved resonance Raman spectroscopy as the phenoxyl radical from probucol, formed by hydrogen atom or electron plus proton loss from one of the phenolic groups of probucol [19].
• These results show that a monomeric phenoxyl radical attacks the polymeric phenoxyl to induce the redistribution via a quinone ketal intermediate, leading to the substantial decrease in the molecular weight of PPO, which is much faster than the chain growth [20].
• NADPH quenched directly the EPR signal of phenoxyl radical of a phenolic antitumor drug, etoposide, in the absence of the OR [21].
• We found by liquid chromatography-ionspray mass spectrometry and electron spin resonance (ESR) that tyrosinase caused oxidation of VP-16 to its o-quinone and aromatized derivative via intermediate formation of the phenoxyl radical [22].

Gene context of phenol

• All phenolics were substrates for the enzymes, but MPx only weakly activated 4OHTAM to its phenoxyl radical [23].
• Spectroscopic analyses indicated that paracetamol, similar to tyrosine, could undergo peroxidase-induced phenoxyl radical formation, which was inhibited by the radical scavenger ascorbic acid as well as by heme poisons and catalase [24].
• The semidehydroascorbyl radical ESR signal preceded the quenching of the VP-16 phenoxyl radical by GSH and metallothionein [22].
• Formation of 4 was also specific for peroxidase activation that is known to oxidize PCP into the phenoxyl radical [25].
• The results reveal that imidazole substitution lowers the pK(a) of phenol and increases the E degrees of phenoxide due to its sigma-electron withdrawing ability (sigma(p)(-) = +0.21, sigma(m)(-) = +0.45) but decreases the O-H BDE and E degrees of phenol due to its pi-electron-donating ability (sigma(p)(+) = -0.45) [26].

Analytical, diagnostic and therapeutic context of phenol

• The phenoxyl radical spectra derived from the hydroxycinnamic acids were determined using pulse radiolysis of aqueous solutions and the reduction potentials were found to range from 534 to 596 mV [27].
• Multifrequency (X-, Q-, and W-band) electron spin resonance (ESR) spectroscopy has been used to characterize the phenoxyl radical produced from alpha-(3,5-di-tert-butyl-4-hydroxyphenyl)-N-tert-butylnitrone, which is a new spin-trapping reagent [28].
• Interactions of phenoxyl radical of antitumor drug, etoposide, with reductants in solution and in cell and nuclear homogenates: electron spin resonance and high-performance liquid chromatography [29].
• Three dimetallic monoethoxide complexes supported by a binucleating phenoxide ligand, LM(2)Cl(2)OEt (M = Zn, Co, or Mg), were prepared and shown by X-ray crystallography to be structurally analogous [30].

References