Aryloxyl Radicals Research Articles

An active-site model of prostaglandin H synthase: an iron "twin-coronet" porphyrin with an aryloxyl radical overhang and its catalytic oxygenation of 1,4-diene.

An active-site model of prostaglandin H synthase: an iron "twin-coronet" porphyrin with an aryloxyl radical overhang and its catalytic oxygenation of 1,4-diene.

A method for thermal generation of aryloxyl radicals at ambient temperatures: application to low-density lipoprotein (LDL) oxidation.

A method for thermal generation of aryloxyl radicals at ambient temperatures: application to low-density lipoprotein (LDL) oxidation.

Antioxidant Action of 2,2,4,6-Tetra-Substituted 2,3-Dihydro-5-hydroxybenzofuran Against Lipid Peroxidation: Effects of Substituents and Side Chain

With increasing evidence suggesting the involvement of oxidative stress in various disorders and diseases, the role of antioxidants in vivo has received much attention. 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di- tert -butylbenzofuran (BO-653) was designed, synthesized and has been evaluated as a novel antiatherogenic drug. In order to further understand the action of BO-653 and also radical-scavenging antioxidants in general, the dynamics of inhibition of oxidation by BO-653 were compared with those of the related compounds, 2,3-dihydro-5-hydroxy-2,2-dimethyl-4,6-di- tert -butylbenzofuran (BOB), 2,3-dihydro-5-hydroxy-2,2,4,6-tetramethylbenzofuran (BOM), f -tocopherol and 2,2,5,7,8-pentamethyl-6-chromanol (PMC), aiming specifically at elucidating the effects of substituents and side chain length of the phenolic antioxidants. These five antioxidants exerted substantially the same reactivities toward radicals and antioxidant capacities against lipid peroxidation in organic solution. When compared with di-methyl side chains, the di-pentyl side chains of BO-653 reduced its inter-membrane mobility but exerted less significant effect than the phytyl side chain of f -tocopherol on the efficacy of radical scavenging within the membranes. Di- tert -butyl groups at both ortho-positions made BO-653 and BOB more lipophilic than di-methyl substituents and reduced markedly the reactivity toward Cu(II) and also the synergistic interaction with ascorbate. The results of the present study together with those of the previous work on the effect of substituents on the stabilities of aryloxyl radicals suggest that tert -butyl group is more favorable than methyl group as the substituent at the ortho-positions and that di-pentyl side chains may be superior to a phytyl side chain.

Stability and Reactivity of Aryloxyl Radicals Derived from a Novel Antioxidant BO-653 and Related Compounds. Effects of Substituent and Side Chain in Solution and Membranes

2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653) is a novel antioxidant designed as a drug for inhibition of lipid peroxidation in vivo. To understand the dynamics of action of BO-653 as an antioxidant, the effects of substituents and side chains on the stability and reactivity of the BO-653 derived radical were studied and compared with the aryloxyl radicals derived from related compounds including α-tocopherol. The rate constants for the reactions of the aryloxyl radicals with themselves, lipid, hydroperoxide, and ascorbate were measured with a stopped-flow electron spin resonance (ESR) spectroscope equipped with a rapid mixing device. The ortho substituents exerted profound effects on the rate of bimolecular decay reactions and the reaction with ascorbic acid, while the effects on the reactions with methyl linoleate and tert-butyl hydroperoxide were much less significant. The side chain at the 2-position did not exert any effect in organic solution but the two pentyl side chains, when compared with two methyl side chains, diminished the apparent reactivities in the liposomal membranes.

Theoretical Calculation of Substituent Effects on the O−H Bond Strength of Phenolic Antioxidants Related to Vitamin E

Calculations on phenol and a large number of phenols substituted with methyl, methoxyl, and amino groups have yielded reliable gas-phase O−H bond dissociation energies, BDE(ArO−H)gas. Geometries for the phenol, ArOH, and aryloxyl radical, ArO, were optimized at the (semiempirical) AM1 level followed by single point density functional theory (DFT) calculations using a 6-31G basis set supplemented with p-functions on the hydrogen atom and the B3LYP density functional. This gave BDE(PhO−H)gas = 86.46 kcal/mol, which is in good agreement with the experimental value of 87.3 ± 1.5 kcal/mol. All but one of the compounds and conformations examined had weaker O−H BDE's than phenol, the exception being o-methoxyphenol with the O−H group pointing toward this substituent (BDE = 87.8 kcal/mol). Where comparison was possible, calculated differences in O−H BDE's were in excellent agreement with experiment (better than 1 kcal/mol). A simple group additivity scheme also gave excellent agreement with calculated BDE (ArO−H)...

Aryl Oxalate Derivatives as Convenient Precursors for Generation of Aryloxyl Radicals.

The use of aryloxy oxalyl chlorides (AOCs), aryloxy oxalyl tert-butyl peroxides (AOBs), and diaryl oxalates (DAOs) for unimolecular generation of phenoxyl-based radicals under solution and rigid matrix conditions is described. AOCs are usable for photochemical generation of phenoxyl radicals, but are only conveniently stable as precursors when 2,6-di-tert-butylated derivatives are used. AOBs may be used as thermal precursors to aryloxyl radicals, since they typically decompose within 2-3 h at 60-85 degrees C to give phenols. (1)H-NMR solution kinetic studies find that DeltaH() = 31 kcal/mol, and DeltaS() = +3.4 cal/mol-K for decomposition of phenoxyoxalyl tert-butyl peroxide, consistent with substantial concertedness in peroxide bond cleavage. AOBs and the more stable DAOs are also convenient photochemical phenoxyl radical precursors. AOBs yield phenoxyl radicals more readily by photolysis than do corresponding DAOs, but the DAOs have fewer side reactions that can quench the product phenoxyl radicals.

Organophosphorus antioxidants action mechanisms and new trends

AbstractPhosphite and phosphonite esters can act as antioxidants by three basic mechanisms depending on their structure, the nature of the substrate to be stabilized and the reaction conditions. All phosph(on)ites are hydroperoxide‐decomposing secondary antioxidants. Their efficiency in hydroperoxide reduction decreases in the order phosphonites > alkylphosphites > arylphosphites > hindered arylphosphites. Five‐membered cyclic phosphites are capable of decomposing hydroperoxides catalytically due to the formation of acidic hydrogen phosphates by hydrolysis and peroxidolysis in the course of reaction. Hindered aryl phosphites can act as chain‐breaking primary antioxidants being substituted by alkoxyl radicals and releasing hindered aryloxyl radicals which terminate the radical chain oxidation. At ambient temperatures, the chain‐breaking antioxidant activity of aryl phosphites is lower than that of hindered phenols, because the rate of their reaction with peroxyl radicals and their stoichiometric inhibition factors are lower than those of phenols. In oxidizing media at medium temperatures, however, hydrolysis of aryl phosph(on)ites takes place giving hydrogen phosph(on)ites and phenols which are effective chain‐breaking antioxidants.2,2,6,6‐Tetramethyl‐ and 1,2,2,6,6‐Pentamethylpiperidinyl phosphites and phosphonites (HALS‐phosph(on)ites) surpass many common phosphites, phenols and HALS compounds as stabilizers in the thermo‐ and photo‐oxidation of polymers. Their superior efficiency is probably due to an intramolecular synergistic action of the HALS and the phosph(on)ite moieties of their molecules.

Convenient unimolecular sources of aryloxyl radicals. III - photolysis of bis(aryloxy)phosphine azides

Photolysis of sterically hindered bis(aryloxy)phosphine azides in solution, frozen matrix, or neat solid states leads to facile unimolecular production of aryloxyl radicals.

Diaryl oxalates as convenient unimolecular sources of aryloxyl radicals

Diaryl oxalates are readily synthesized, stable, convenient unimolecular sources for aryloxyl radicals under solution and rigid-phase photochemical conditions.

The mechanism of biological C–C bond formation to methoxy groups; biomimetic cyclisation via alkyloxyl radicals

Aryl(methylene)oxyl radicals generated by decarboxylation of the thiohydroxamate ester (8) undergo 6-endo cyclisation, yielding ketones (9) and (11), mimicking an unusual biosynthetic conversion.

Convenient unimolecular sources of aryloxyl radicals II — aryloxyoxalyl tert-butylperoxides

UV photolysis and mild thermolysis of aryloxyoxalyl tert-butylperoxides provides a new unimolecular source of aryloxyl radicals, as shown by ESR and UV-vis spectroscopy.

Convenient unimolecular sources of aryloxyl radicals I -- aryloxyoxalyl chlorides

UV photolysis of readily synthesized aryloxyoxalyl chloride half-esters provides a new unimolecular source of aryloxyl radicals, as shown by ESR and UV-vis spectroscopy.

Organophosphorus antioxidants part IX—Inhibition of the oxidation of hydrocarbons by hindered aryl phosphites

Sterically hindered aryl phosphites inhibit the AIBN-initiated oxidation of cumene and tetralin at 65°C by trapping peroxyl radicals to give hindered aryloxyl radicals. The stoichiometric factors of inhibition depend on the oxidisability of the hydrocarbon and on the phosphite concentration, decreasing from one at high concentrations to zero at low concentrations. An apparent critical antioxidant concentration is observed. These peculiarities are due to the oxidation of the phosphites by hydroperoxides formed in the reaction. Kinetic schemes which take into account this reaction and the participation of peroxyl radicals derived from the initiator, allow one to evaluate consistent rate constants for the reaction of alkylperoxyl radicals with phosphites. These are of the order of 10 2 to 10 3 litres/mol/s at 65°C depending on the structures of the phosphite and of the hydrocarbon substrate.

Chain-breaking antioxidant activity of phosphite esters

The inhibition of the autoxidation of hydrocarbons and polypropylene by aliphatic, aromatic, sterically hindered and cyclic phosphites has been studied by means of volumetric and 31P-NMR techniques. The antioxidant activity of phosphites depends on the rate of their reactions with peroxyl radicals and on the way they react with alkoxyl radicals. Only those phosphites which react by substitution to give free aryloxyl radicals are effective as chain-breaking antioxidants. The reaction modes of various phosphites with various peroxyl and alkoxyl radicals have been studied in some model reactions and the relationship between structure, reaction mechanism and antioxidant activity has been elucidated.

Mechanisms of antioxidant action: Evidence for a regenerative cycle during the melt stabilisation of polypropylene by galvinoxyl

Evidence is presented to show that galvinoxyl (G·), a ‘stable’ aryloxyl radical, is converted to the corresponding phenol(GH) in polypropylene during processing. The redox couple (G·/GH) is a catalytic CB-A/CB-D antioxidant and is capable of deactivating 50 kinetic chains, thus effectively protecting polypropylene against oxidative chain scission for up to 20 min at 200°C in a closed mixer. A reciprocal alternation of the concentration of G· and GH is accounted for by changing conditions in the mixer and G· is slowly and irreversibly destroyed by alkylperoxyl radicals.

Oxidative coupling of phenols. Part 10. The role of steric effects in the formation of C–O coupled products

The formation of C–O coupled products in the oxidative coupling of phenols is hindered by bulky ortho-substituents in the aryloxyl radical intermediates as shown by the predominant formation of the ortho-ortho-C–C coupling products in the oxidation of o-t-butyl- and 2,4-di-t-butyl-phenol. 3,5-Di-t-butyl-phenol gives exclusively the ortho-O-dimeric product as steric effects prevent the sandwich approach of two aryloxyl radicals necessary for C–C coupling.

Electrophilic aromatic substitution. Part 28. The mechanism of nitration of some 4-substituted anisoles and phenols, and of rearrangement of the intermediate 4-nitro-4-substituted-cyclohexa-2,5-dienones

The kinetics of nitration in sulphuric acid of 2-chloro-4-methyl-, 4-chloro-, 2,4-dichloro-, and 4-fluoroanisole and of the corresponding phenols have been determined. The reaction products from the anisoles and from 2-chloro-4-methyl- and 4-fluoro-phenol have been determined. Results for 4-methylanisole supplementary to earlier ones are also reported. Generally the anisoles give the 2-nitro-derivatives and the 2-nitrophenols, and from 2-chloro-4-methylanisole, 2-chloro-4-methyl-4-nitrocyclohexa-2,5-dienone was formed as an intermediate. The decomposition of this dienone in sulphuric acid, like those of others, changes from a non-acid-catalysed to an acid-catalysed form with increasing acidity. The first form is regarded as a decomposition into an aryloxyl radical and nitrogen dioxide which can recombine to give the 2-nitrophenol. The formation of a small amount of 2-(4-fluorophenoxy)-4-fluorophenol in the nitration of 4-fluorophenol is seen as support for this view. The acid-catalysed form is regarded as the decomposition of the protonated dienone into a phenol–nitronium ion encounter-pair which can give the nitrophenol. A consequence of the mechanism is that if the phenol were nitrated at less than the encounter rate, the phenol itself would in appropriate conditions be a product of the ipso-nitration of the original anisole. 4-Methyl-, 2-chloro-4-methyl-, and 4-chloro-phenol have been so identified. Quantitative analysis of the results allows evaluation of the partitioning of dienone decomposition between the two modes. The mechanism accounts for the formation from 2,4-dichloro-anisole of both 2,4-dichloro-6- and 2,4-dichloro-5-nitroanisole, but only 2,4-dichloro-6-nitrophenol.

Flash photolysis study of phenyl-substituted phenols, quinones, and corresponding free radicals. Part 3. Intermediates in the photolysis of phenyl-substituted phenols

Aryloxyl radicals are formed on photoexcitation of phenyl-substituted phenols in a biphotonic process involving the triplet excited state. These aryloxyl radicals are also formed on photolysis of the corresponding phenolate ions in the presence of oxygen involving the singlet excited state.

Further nitroxide-producing reactions of aromatic C-nitroso-compounds in benzene solution

E.s.r. studies show that nitrosobenzene and 2,4,6-trichloronitrosobenzene react slowly in benzene solution under nitrogen with many carbonyl compounds to give moderately stable nitroxides formed by additions to their enolic tautomers. The formation of nitroxides from diethyl and di-isopropyl ketones may involve a further molecular rearrangement. Short lived arylnitroxides ArNHO· are probably formed also and sometimes can be detected as transient initial products of reactions between nitroso-compounds and arylhydroxylamines, hydrazobenzene, thiols, and a few phenols. Thiophenols react with these nitroso-compounds to give thionitroxide radicals ArN(O·)SAr′, but alkylated phenols yield first the corresponding aryloxyl radicals and then either benzylic or nuclear-substituted nitroxides, depending on the structures of their substituent groups.

The Addition Reaction of Acyl Radicals to 9,10-Phenanthrenequinone in the Presence of the Corresponding Aldehydes. A Support for the In-Cage Mechanism of the Photochemical Reaction of 9,10-Phenanthrenequinone with Aldehydes

Abstract Regarding the photochemical reaction of 9,10-phenanthrenequinone, 1, with acetaldehyde, 2, two reaction mechanisms have been proposed: the in-cage mechanism (Eq. 1) and the radical chain mechanism involving an acyl radical as the chain carrier (Eq. 2). For the establishment of the true reaction mechanism, the thermal addition reaction of an acyl radical to 9,10-phenanthrenequinone was investigated. The products in the thermal reaction were the dimeric isomers of the aryloxyl radical, 6, i.e., 4 and 5, which were quite different from the product of the photochemical reaction of 9,10-phenanthrenequinone with acetaldehyde, i.e., 9-acetoxy-10-hydroxyphenan-threne, 3. These results, as well as the estimation of the quantum efficiency for the photochemical reaction, exclude the radical chain mechanism (Eq. 2) and strongly support the in-cage mechanism (Eq. 1) for the photochemical reaction of 9,10-phenanthrenequinone with aldehyde.