Trichloromethylperoxyl Radicals Research Articles

Radical reactions of C84

Pulse radiolysis and steady-state radiolysis experiments describing the radical and electron transfer reactions of C84 are reported here for the first time. C84 reacts readily with radiolytically generated chloromethyl (•CCl3) and trichloromethylperoxyl (CCl3OO•) radicals in CCl4. The formation of the radical adduct has been confirmed from its characteristic absorption in the UV (320 nm) and visible (480 nm). Radical-induced oxidation in 1,2-dichloroethane (1,2-DCE) resulted in a short lived transient absorbing at 920 nm. Reduction of C84 in toluene/2-propanol/acetone could be conveniently followed by formation of an absorption band with an absorption maximum at 960 nm.

An evaluation of the antioxidant and antiviral action of extracts of rosemary and provençal herbs

Extracts of herbs and spices are increasingly of interest in the food industry because they retard oxidative degradation of lipids. There is also increasing interest in the antiviral activity of plant products. A liquid, deodorized rosemary extract and an oily extract of a mixture of Provençal herbs were tested for antioxidant and antiviral action in vitro. The rosemary extract (Herbor 025) and the extract of Provençal herbs (Spice Cocktail) inhibited peroxidation of phospholipid liposomes with 50% inhibition concentration values of 0.0009% (v/v) and 0.0035% (v/v), respectively. Herbor 025 and the spice cocktail (at 0.2%, v/v) reacted with trichloromethylperoxyl radical with calculated rates of 2.7 × 10 4 s −1 and 1.5 × 10 3 s −1, respectively. The main active components in the herbal preparations, carnosol and carnosic acid, at 0.05% (v/v) react with rate constants of (1–3) × 10 6 M −1 sec −1 and 2.7 × 10 7 M −1 sec −1, respectively. Both extracts show good antioxidant activity in the Rancimat test, especially in lard. Herbor 025 and the spice cocktail inhibited human immunodeficiency virus (HIV) infection at very low concentrations which were also cytotoxic. However, purified carnosol exhibited definite anti-HIV activity at a concentration (8μM) which was not cytotoxic. Both preparations promoted some DNA damage in the copper-phenanthroline and the bleomycin-iron systems. The two herbal preparations possess antioxidant properties that may make them useful in the food matrix.

Evaluation of the pro-oxidant and antioxidant actions of L-DOPA and dopamine in vitro: implications for Parkinson's disease.

The antioxidant and pro-oxidant properties of L-DOPA and dopamine were investigated in vitro. Both compounds inhibited the peroxidation of ox-brain phospholipids, with IC50 values of 8.5 microM for dopamine and 450 microM for L-DOPA. Dopamine and L-DOPA reacted with trichloromethyl peroxyl radicals (CCl3O2.) with rate constants of 2.1 x 10(7)M-1s-1 and 1.3 x 10(7)M-1s-1 respectively. The effects of dopamine and L-DOPA on iron ion-dependent hydroxyl radical generation from H2O2 were complex. In general, low concentrations stimulated OH. formation in the presence of ferric-EDTA and, in the case of L-DOPA, ferric-ADP and ferric citrate chelates. Both compounds also reacted with superoxide radical and hypochlorous acid. The products of the reaction with HOCl could still inhibit alpha 1-antiproteinase and appear to be 'long lived' chloramine-type oxidizing species. Our results suggest that L-DOPA and dopamine might have a complex mixture of pro- and anti- oxidant effects, which could contribute to tissue damage due to oxidative stress in Parkinson's disease and other neurological disorders.

Evaluation of the antioxidant activity of melatonin in vitro

Melatonin is being increasingly promoted as a treatment for “jet lag” and insomnia and has been suggested to act as an antioxidant in vivo. The antioxidant and potential pro-oxidant activities of melatonin were investigated in vitro. Melatonin was able to scavenge hypochlorous acid (HOC1) at a rate sufficient to protect catalase against inactivation by this molecule. Melatonin could also prevent the oxidation of 5-thio-2-nitrobenzoic acid by HOC1. Melatonin decreased the peroxidation of ox-brain phospholipids with a calculated IC 50 of (210 ± 2.3) μM. In contrast, serotonin which also scavenged HOCI, was much more effective in decreasing phospholipid peroxidation (IC 50 15 ±5 μM). Both compounds reacted with trichloromethylperoxyl radical (CCl 3O 2) with rate constants of (2.7 ± 0.2) × 10 8 and (1.2 ± 0.1) × 10 8 M −1 s −1 respectively. Melatonin did not scavenge superoxide radical and weakly protected DNA against damage by the ferric bleomycin system. By contrast serotonin was weakly pro-oxidant in the ferric-bleomycin system and strongly pro-oxidant in the Fe 3+-EDTA/H 2O 2-deoxyribose system. Solubility restrictions precluded examination of melatonin in this system. Our data show that melatonin exerts only limited direct antioxidant activities.

5-Methylcytosine attack by hydroxyl free radicals and during carbon tetrachloride promoted liver microsomal lipid peroxidation: structure of reaction products

We recently reported that trichloromethyl and trichloromethylperoxyl radicals attack 5-methylcytosine (5MC) to give several products derived from hydroxylation, deamination or halogenation reactions. Hydroxyl radicals and lipid peroxidation (LP) are more frequently involved in deleterious pathological or toxicological processes than those CCl 4 derived radicals and thus we considered it of interest to test whether they also alter 5MC. We observed that ' OH radicals generated by 0.1 mM Fe 2+/2.5 mM H 2O 2 at 25 °C for 1 h led to the production of 5-hydroxymethylcytosine (5HMC). When OH generation was performed with UV light (254 nm, 3400 μWatt/cm 2) and 2 mM H 2O 2 during 4 min at 25 °C the following products were observed: 5-hydroxy-5-methylhydantoin, 5-hydroxyhydantoin, 5HMC, thymine glycol (two isomers) and 5-hydroxymethyl-6-hydroxycytosine. When 5MC was exposed to liver microsomal suspensions in the presence of NADPH generating system and carbon tetrachloride during 1 h at 37 °C and under air, the formation of only 5HMC was observed. Detection and identification of all reaction products was done by GC/MS analysis of trimethylsilyl derivatives of the bases. If similar reactions occurred in DNA, these results might be of relevance to gene control, differentiation and carcinogenesis.

Cholesterol interaction with free radicals produced from carbon tetrachloride or bromotrichloromethane by either catalytic decomposition or via liver microsomal activation

The reaction between cholesterol (Ch) and trichloromethyl or trichloromethyl peroxyl radicals was studied. The latter were generated from CCl 4 either by benzoyl peroxide (BP) catalysis or via thermal activation or by liver microsomal NADPH-dependent biotransformation of CBrCl 3. The structure of the products formed was elucidated by gas chromatography-mass spectrometry (GC/MS). Under aerobic conditions and using thermal activation of CCl 4, the formation of 6 products was observed. Two (I and II) were dehydrated Ch derivatives (one also having a third double bond) (I). Another product was a Δ 5-3 ketone derivative of Ch (III). Two additional reaction products were determined as ketocholesterols (IV and V). One chloro Ch was also formed (VI). At low concentrations of BP, reaction was more extensive than under thermal activation, and the formation of peaks I to IV was also observed. When the reaction was conducted anaerobically and using thermal activation of CCl 4 to generate radicals, only products I and II were formed in low yield. Under anaerobic conditions, but using catalyst, compounds I and III were produced plus two new isomeric ketocholesterol derivatives (VIII and IX) and also a compound having an extra hydroxyl group on the Ch structure (X). In order to check whether similar reactions are observable under biological experimental conditions, we used activation of CBrCl 3 by liver microsomes. The incubation using only microsomes (without CBrCl 3 or NADPH) showed two ketocholesterol peaks (A and B). In the presence of CBrCl 3 we could detect peak B and hydroxycholesterol (C) and two others, ketocholesterols (D and E). D was the only peak showing close similarity (spectrum and retention time) to one of those observed in the chemical reaction system (V). The reaction of CBrCl 3 in the presence of NADPH showed peaks B, C, D and E, in low abundance and a 7-ketocholesterol (F). If some of the reaction products reported here were formed during the intoxication with these haloalkanes, significant biological consequences might be expected.

Reaction of plant-derived and synthetic antioxidants with trichloromethylperoxyl radicals.

The rate constants for reaction of several lipid-soluble antioxidants with trichloromethylperoxyl radicals are tabulated.

Proline Interaction with Trichloromethyl and Tri-Chloromethyl Peroxyl Free Radicals in a Model System: Studies about The Nature of the Reaction Products Formed

Trichloromethyl and trichloromethyl peroxyl radicals are known to be produced during CCl4 biotransformation and are considered to be critical for deleterious effects of this haloalkane. In this work we describe our studies on the interaction of both free radicals with a lipid-soluble derivative of the amino acid proline in a model system. The analysis of the reaction products formed by gas chromatography-mass spectrometry of the sylilated derivatives revealed the formation of at least 11 reaction products under anaerobic conditions and 13 under aerobic atmosphere. All of them were tentatively identified and all but 2 were proline analogs. Only 3 incorporated in their structure CCl3 or CCl2 portions of the CCl4 molecule and, consequently, most of the adducts formed would be missed during regular procedures most toxicologists use to determine CCl4. Results were analyzed in relation to the known role of proline in collagen metabolism and of this protein in liver cirrhosis.

Solvent Effects on Rate Constants for One-Electron Oxidation of Porphyrins

Absolute rate constants for one-electron oxidation of free base porphyrins (hematoporphyrin-IX, mesoporphyrin-IX dimethyl ester) by the trichloromethylperoxyl radical and by the radical cation of N-methylindole have been determined in a variety of solvents by the pulse radiolysis technique. All solvents were air-saturated and contained CCl[sub 4] as a source for the CCl[sub 3]O[sub 2][sup [sm bullet]] radicals. The rate constants for reactions of these radicals were measured by following the formation of the porphyrin [pi]-radical cation optical absorption at 700 nm as a function of porphyrin concentration. The rate constants for reaction of CCl[sub 3]O[sub 2][sup [sm bullet]] with the porphyrin were found to vary by an order of magnitude in the different solvents and were correlated with the solvent cohesive energy density. In the second set of experiments, N-methylindole was used in addition to CCl[sub 4] so that CCl[sub 3]O[sub 2][sup [sm bullet]] radicals oxidize this solute to its radical cation, which in turn oxidizes the porphyrin. The variations of the rate constants for oxidation of the porphyrin by the N-methylindole radical cation in the different solvents exhibited different trends than those for oxidation by CCl[sub 3]O[sub 2][sup [sm bullet]] radicals. 39 refs., 1 fig., 6 tabs.

Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation.

A detailed evaluation of the antioxidant and pro-oxidant properties of lipoic acid (LA) and dihydrolipoic acid (DHLA) was performed. Both compounds are powerful scavengers of hypochlorous acid, able to protect alpha 1-antiproteinase against inactivation by HOCl. LA was a powerful scavenger of hydroxyl radicals (OH.) and could inhibit both iron-dependent OH. generation and peroxidation of ox-brain phospholipid liposomes in the presence of FeCl3-ascorbate, presumably by binding iron ions and rendering them redox-inactive. By contrast, DHLA accelerated iron-dependent OH. generation and lipid peroxidation, probably by reducing Fe3+ to Fe2+. LA inhibited this pro-oxidant action of DHLA. However, DHLA did not accelerate DNA degradation by a ferric bleomycin complex and slightly inhibited peroxidation of arachidonic acid by the myoglobin-H2O2 system. Under certain circumstances, DHLA accelerated the loss of activity of alpha-antiproteinase exposed to ionizing radiation under a N2O/O2 atmosphere and also the loss of creatine kinase activity in human plasma exposed to gas-phase cigarette smoke. Neither LA nor DHLA reacted with superoxide radical (O.2-) or H2O2 at significant rates, but both were good scavengers of trichloromethylperoxyl radical (CCl3O2.). We conclude that LA and DHLA have powerful antioxidant properties. However, DHLA can also exert pro-oxidant properties, both by its iron ion-reducing ability and probably by its ability to generate reactive sulphur-containing radicals that can damage certain proteins, such as alpha 1-antiproteinase and creatine kinase.

ChemInform Abstract: Solvent Effects on the Rate Constants for Reaction of Trichloromethylperoxyl Radicals with Organic Reductants

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Evaluation of the antioxidant and prooxidant actions of gallic acid and its derivatives

The antioxidant and prooxidant activities of gallic acid and its propyl, methyl, and (where solubility allowed) lauryl esters were investigated. Gallic acid (GA), propyl gallate (PG), and gallic acid methyl ester (GM) were able to scavenge hypochlorous acid at a rate sufficient to protect α-1-antiproteinase against inactivation by this molecule. When dissolved in ethanol, gallic acid lauryl ester (GL), PG, and GM decreased the peroxidation of or brain phospholipids. GA had only a weak inhibitory effect. GM, GL, and PG reacted with CCl 3 O 2 . (trichloromethyl peroxyl radical) with rate constants of 1.23×140 7 , 2.33×10 7 , and 1.67×10 7 M -1 s -1 , respectively. Gallic acid was much less reactive with a rate constants of 1.23×10 7 , of 4.47×10 5 M -1 s -1

Solvent effects on the rate constants for reaction of trichloromethylperoxyl radicals with organic reductants

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolvent effects on the rate constants for reaction of trichloromethylperoxyl radicals with organic reductantsZ. B. Alfassi, R. E. Huie, and P. NetaCite this: J. Phys. Chem. 1993, 97, 28, 7253–7257Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://doi.org/10.1021/j100130a022RIGHTS & PERMISSIONSArticle Views289Altmetric-Citations21LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (549 KB) Get e-Alerts

Evaluation of the antioxidant actions of ferulic acid and catechins.

We have evaluated the abilities of ferulic acid, (+/-) catechin, (+) catechin and (-) epicatechin to scavenge the reactive oxygen species hydroxyl radical (OH.), hypochlorous acid (HOCl) and peroxyl radicals (RO2.). Ferulic acid tested at concentrations up to 5 mM inhibited the peroxidation of phospholipid liposomes. Both (+/-) and (+) catechin and (-) epicatechin were much more effective. All the compounds tested reacted with trichloromethyl peroxyl radical (CCl3 O2.) with rate constants > 1 x 10(6) M-1 s-1. A mixture of FeCl3-EDTA, hydrogen peroxide (H2O2) and ascorbic acid at pH 7.4, has often been used to generate hydroxyl radicals (OH.) which are detected by their ability to cause damage to the sugar deoxyribose. Ferulic acid, (+) and (+/-) catechin and (-) epicatechin inhibited deoxyribose damage by reacting with OH. with rate constants of 4.5 x 10(9)M-1 s-1, 3.65 x 10(9) M-1 s-1, 2.36 x 10(9) M-1 s-1 and 2.84 x 10(9) M-1 s-1 respectively. (-) Epicatechin, ferulic acid and the (+) and (+/-) catechins exerted pro-oxidant action, accelerating damage to DNA in the presence of a bleomycin-iron complex. On a molar basis, ferulic acid was less effective in causing damage to DNA compared with the catechins. A mixture of hypoxanthine and xanthine oxidase generates O2-. which reduces cytochrome c to ferrocytochrome c. (+) Catechin and (-) epicatechin inhibited the reduction of cytochrome c in a concentration dependent manner. Ferulic acid and (+/-) catechin had only weak effects. All the compounds tested were able to scavenge hypochlorous acid at a rate sufficient to protect alpha-1-antiproteinase against inactivation. Our results show that catechins and ferulic acid possess antioxidant properties. This may become important given the current search for "natural" replacements for synthetic antioxidant food additives.

Reaction of trichloromethyl and trichloromethylperoxyl radicals with C 60. A pulse radiolysis study

Both trichloromethyl ( CCl 3) and trichloromethylperoxyl (CCl 3OO ) radicals react with C 60. The bimolecular rate constants are (2.7 ± 0.5) × 10 8 mol −1 dm 3 s −1 and 2 × 10 6 mol −1 dm 3 s −1, respectively. The transient absorption spectra of the radical adducts are presented.

Radiation chemistry of cyanine dyes: oxidation and reduction of merocyanine 540

Merocyanine 540 (MC) shows promise as a treatment for certain types of leukemia. It is shown that MC readily undergoes one-electron reduction under pulse radiolytic conditions. The {pi}-radical anion, produced by reduction with hydrated electrons and 2-hydroxypropyl radicals, disproportionates rapidly (k = 1.9 {times} 10{sup 9} M{sup {minus}1}s{sup {minus}1}) under anaerobic conditions but reduces O{sub 2} to superoxide ions (k = 1.6 {times} 10{sup 9} M{sup {minus}1}s{sup {minus}1}) in aerated solution. The dye reacts with trichloromethylperoxyl radicals (k = 9 {times} 10{sup 8} M{sup {minus}1}s{sup {minus}1}) to form several products, one of which is believed to be an adduct formed by addition of CCl{sub 3}OO{sup {sm bullet}} to the bridgehead carbon atom of the benzoxazole subunit. This species decays via first-order kinetics (k = 4.0 {times} 10{sup 3} s{sup {minus}1}) under pulse radiolytic conditions to form cleavage products. A second primary product is believed to arise from addition of CCl{sub 3}O{sub 2}{sup {sm bullet}} to the polymethine chain to form an {alpha}-amino carbon-centered radical capable of reducing O{sub 2} to superoxide ions. Preliminary studies indicate that the breakdown products are cytotoxic and could be important intermediates for the known antiviral activity of MC.

Halogenated peroxyl radicals as multi-electron oxidants: pulse radiolysis study on the reaction of trichloromethyl peroxyl radicals with iodide

CCl3OO˙ radicals are shown to oxidize three equivalents of iodide ions to yield one I2 molecule (showing up as I3– in aqueous solution) and one I˙ atom (showing up as I2˙–) per peroxyl unit; the mechanism is considered to proceed via a protonated CCl3OO˙I– adduct radical as the primary intermediate and subsequent nucleophilic (SN2) attack by a second iodide accompanied by electron localization in the hydroperoxide moiety leads to I2 and CCl3O˙ with the latter being responsible for the oxidation of the third iodide.

Reactivity of ebselen and related selenoorganic compounds with 1,2-dichloroethane radical cations and halogenated peroxyl radicals

The reactivity of ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)one, and structurally related analogues was studied by pulse radiolysis. The rate constant for the reaction of ebselen with trichloromethylperoxyl radicals was determined to be 2.9 × 10 8 m −1 s −1, while its sulfur analogue, 2-phenyl-1,2-benzisothiazol3(2H)one, was oxidized at much lower rates, k ⩽ 10 7M −1S −1. Among several derivatives studied, the only other compound that exhibited a high rate constant was 2-(methylseleno)-benzoic acid- N-phenylamide. Oxidation of ebselen by other halogenated peroxyl radicals was also carried out and revealed a direct relationship between rate constant and the degree of halogenation of the oxidant. The transient radicals generated during oxidation of ebselen and the analogues were characterized by optical absorption and conductivity measurements and were attributed to one-electron-oxidized radical cations. The oxidation potentials were determined by cyclic voltammetry. Comparative evaluation of the in vitro behavior during microsomal lipid peroxidation revealed ebselen to be the most potent antioxidant of the compounds investigated. 2-(Methylseleno)benzoic acid- N-phenylamide, despite its high rate constant for oxidation by halogenated peroxyl radicals, was found to be a poor antioxidant. The rate constant of oxidation of ebselen by trichloromethylperoxyl radicals is comparable to that of α-tocopherol under similar conditions, underscoring the potential pharmacological interest of ebselen as an antioxidant.

Trichloromethyl peroxyl radical (Cl 3COO•) mediated oxidation of cholesterol

Oxidation of cholesterol was studied in situ in a Cl 3COO• generating system via a heterogenous reaction of carbon tetrachloride (CCl 4), KO 2 and 18-crown-6 in aprotic solvent (acetonitrile) at 10°C. The reaction mixture without CCl 4 served as a control. Reaction performed with CCl 4 showed the formation of products more polar than cholesterol which were separated by preparative thin layer chromatography (TLC) and purified by normal phase high performance liquid chromatography (HPLC). The data obtained collectively from TLC, HPLC and ammonia chemical ionization mass spectrometry confirmed the formation of 3ß-hydroxy-5-cholesten-7-one, 5-cholesten-3ß, 7ß- and 3ß, 7α-diols and possibly 3ß-hydroxy-5, 6ξ-epoxy-5ξ-cholestan-7-one as Cl 3COO• mediated oxidation products of cholesterol.

Promethazine inhibits the formation of aldehydic products of lipid peroxidation but not covalent binding resulting from the exposure of rat liver fractions to CCl4.

Promethazine is known to have protective activity in relation to CCl4-induced liver necrosis. This hepatoprotective property has been investigated with regard to the free radical scavenging and antioxidant properties of promethazine using isolated hepatocytes and microsomal suspensions. CCl4 is activated in both systems to free radical metabolites that bind covalently to lipid and protein, and initiate lipid peroxidation. A large number of carbonyl products is produced during CCl4-induced lipid peroxidation; promethazine strongly inhibits the production of all classes of carbonyl compounds in both microsomal suspensions and isolated hepatocytes. In contrast, promethazine is a very weak inhibitor of the covalent binding of metabolites of CCl4. We conclude that promethazine acts by scavenging the trichloromethylperoxyl radical and lipid peroxyl radicals, and is a weak scavenger of the trichloromethyl radical. These data, when considered together with the hepatoprotective effects of promethazine, suggest that lipid peroxidation is of relatively more importance than covalent binding in the pathogenesis of CCl4-induced liver necrosis.