Secondary Peroxyl Radicals Research Articles

Gas-Phase Peroxyl Radical Recombination Reactions: AComputational Study of Formation and Decomposition of Tetroxides.

The recombination (“dimerization”) of peroxyl radicals (RO2•) is one of the pathways suggested in the literature for the formation of peroxides (ROOR′, often referred to as dimers or accretion products in the literature) in the atmosphere. It is generally accepted that these dimers play a major role in the first steps of the formation of submicron aerosol particles. However, the precise reaction pathways and energetics of RO2• + R′O2• reactions are still unknown. In this work, we have studied the formation of tetroxide intermediates (RO4R′): their formation from two peroxyl radicals and their decomposition to triplet molecular oxygen (3O2) and a triplet pair of alkoxyl radicals (RO•). We demonstrate this mechanism for several atmospherically relevant primary and secondary peroxyl radicals. The potential energy surface corresponds to an overall singlet state. The subsequent reaction channels of the alkoxyl radicals include, but are not limited to, their dimerization into ROOR′. Our work considers the multiconfigurational character of the tetroxides and the intermediate phases of the reaction, leading to reliable mechanistic insights for the formation and decomposition of the tetroxides. Despite substantial uncertainties in the computed energetics, our results demonstrate that the barrier heights along the reaction path are invariably small for these systems. This suggests that the reaction mechanism, previously validated at a multireference level only for methyl peroxyl radicals, is a plausible pathway for the formation of aerosol-relevant larger peroxides in the atmosphere.

The Fate of the Peroxyl Radical in Autoxidation: How Does Polymer Degradation Really Occur?

Bolland and Gee's basic autoxidation scheme (BAS) for lipids and rubbers has long been accepted as a general scheme for the autoxidation of all polymers. This scheme describes a chain process of initiation, propagation, and termination to describe the degradation of polymers in the presence of O2. Central to this scheme is the conjecture that propagation of damage to the next polymer chain occurs via hydrogen atom transfer with a peroxyl radical. However, this reaction is strongly thermodynamically disfavored for all but unsaturated polymers, where the product allylic radical is resonance-stabilized. Paradoxically, there is no denying that the autocatalytic degradation and oxidation of saturated polymers still occurs. Critical analysis of the literature, described herein, has begun to unravel this mystery. One possibility is that the BAS still holds for saturated polymers but only at unsaturated defect sites, where H transfer is thermodynamically favorable. Another is that peroxyl termination rather than H transfer is dominant. If this were the case, tertiary peroxyl radicals (formed at quaternary centers or quaternary branching defects) may terminate to form alkoxy radicals, which can much more readily undergo chain transfer. This process would lead to the creation of hydroxy groups on the degraded polymer. On the other hand, primary and secondary peroxyl radicals would terminate to form nonradical products and halt further degradation. As a result, under this scenario the degree of branching and substitution would have a major effect on polymer stability. Herein we survey studies of polymer degradation products and of the effect of polymer structure on stability and show that indeed peroxyl termination is competitive with peroxyl transfer and possibly dominant under some conditions. It is also feasible that oxygen may not be the only reactive atmospheric species involved in catalyzing polymer degradation. Herein we outline plausible mechanisms involving ozone, hydroperoxyl radical, and hydroxyl radical that have all been suggested in the literature and can account for the experimentally observed formation of hydroperoxides without invoking peroxyl transfer. We also show that oxygen itself has even been reported to slow the degradation of poly(methyl methacrylate)s, which might be expected if peroxyl radicals are unreactive toward hydrogen transfer. Discrepancies between the rate of oxidation and the rate of degradation have been observed for polyolefins and also support the counterintuitive notion that oxygen stabilizes these polymers against degradation. We show that together these studies support alternative mechanisms for polymer degradation. A thorough assessment of kinetic studies reported in the literature indicates that they are limited by their propensity to use models based on the BAS, disregarding the chemical differences intrinsic to each class of polymer. Thus, we propose that further work must be done to fully grasp the complex mechanism of polymer degradation under ambient conditions. Nonetheless, our analysis of the literature points to measures that can be used to enhance or prevent polymer degradation and indicates that we should focus beyond just the role of oxygen toward the specific chemical nature and environment of the polymer at hand.

Do garlic-derived allyl sulfides scavenge peroxyl radicals?

The chain-breaking antioxidant activities of two garlic-derived allyl sulfides, i.e. diallyl disulfide (1), the main component of steam-distilled garlic oil, and allyl methyl sulfide (3) were evaluated by studying the thermally initiated autoxidation of cumene or styrene in their presence. Although the rate of cumene oxidation was reduced by addition of both 1 and 3, the dependence on the concentration of the two sulfides could not be explained on the basis of the classic antioxidant mechanism as with phenolic antioxidants. The rate of oxidation of styrene, on the other hand, did not show significant changes upon addition of either 1 or 3. This unusual behaviour was explained in terms of the co-oxidant effect, consisting in the decrease of the autoxidation rate of a substrate forming tertiary peroxyl radicals (i.e. cumene) upon addition of little amounts of a second oxidizable substrate giving rise instead to secondary peroxyl radicals. The relevant rate constants for the reaction of ROO(.) with 1 and 3 were measured as 1.6 and 1.0 M(-1) s(-1), respectively, fully consistent with the H-atom abstraction from substituted sulfides. It is therefore concluded that sulfides 1 and 3 do not scavenge peroxyl radicals and therefore cannot be considered chain-breaking antioxidants.

Reactions of Halogenated Hydroperoxides and Peroxyl and Alkoxyl Radicals from Isoflurane in Aqueous Solution

Model systems, based on aqueous solutions containing isoflurane (CHF(2)OCHClCF(3)) as an example, have been studied in the presence and absence of methionine (MetS) to evaluate reactive fates of halogenated hydroperoxides and peroxyl and alkoxyl radicals. Primary peroxyl radicals, CHF(2)OCH(OO*)CF(3), generated upon 1-e-reduction of isoflurane react quantitatively with MetS via an overall two-electron oxidation mechanism to the corresponding sulfoxide (MetSO). This reaction is accompanied by the formation of oxyl radicals CHF(2)OCH(O*)CF(3) that quantitatively rearrange by a 1,2-hydrogen shift to CHF(2)OC*(OH)CF(3). According to quantum-chemical calculations, this reaction is exothermic (DeltaH = -5.1 kcal/mol) in contrast to other potentially possible pathways. These rearranged CHF(2)OC*(OH)CF(3) radicals react further via either of two pathways: (i) direct addition of oxygen or (ii) deprotonation followed by fluoride elimination resulting in CHF(2)OC(O)CF(2)*. Route i yields the corresponding CHF(2)OC(OO*)(OH)CF(3) peroxyl radicals, which eliminate H+/O(2)*-. The resulting ester, CHF(2)OC(O)CF(3), hydrolyzes further, accounting for the formation of HF, trifluoroacetic acid, and formic acid with a contribution of 45% and 80% in air- and oxygen-saturated solutions, respectively. A competitive pathway (ii) involves the reactions of the secondary peroxyl radicals, CHF(2)OC(O)CF(2)OO*. The two more stable of the three above mentioned peroxyl radicals can be distinguished through their reaction with MetS. Although the primary CHF(2)OCH(OO*)CF(3) oxidizes MetS to MetSO in a 2-e step, the majority of the secondarily formed CHF(2)OC(O)CF(2)OO* reacts with MetS via a 1-e transfer mechanism, yielding CHF(2)OC(O)CF(2)OO-, which eventually suffers a total breakup into CHF(2)O- + CO(2) + CF(2)O. Quantum-chemical calculations show that this reaction is highly exothermic (DeltaH = -81 kcal/mol). In air-saturated solution this pathway accounts for about 35% of the overall isoflurane degradation. Minor products (10% each), namely, oxalic acid and carbon monoxide originate from oxyl radicals, CHF(2)OC(O)CF(2)O* and CHF(2)OCH(O*)CF(3). An isoflurane-derived hydroperoxide CHF(2)OCH(OOH)CF(3) in high yield was generated in radiolysis of air-saturated solutions containing isoflurane and formate either via a H-atom abstraction from formate by the isoflurane-derived peroxyl radicals or by their cross-termination reaction with superoxide O(2)*-. CHF(2)OCH(OOH)CF(3), is an unstable intermediate whose multistep hydrolysis is giving H(2)O(2) + 2HF + HC(O)OH + CF(3)CH(OH)(2). In the absence of MetS, about 55% of CHF(2)OCH(OO*)CF(3) undergo termination via the Russell mechanism and 27% are involved in cross-termination with superoxide (O(2)*-) and peroxyl radicals derived from t-BuOH (used to scavenge *OH radicals). The remaining 18% of the primary peroxyl radicals undergo termination via formation of alkoxyl radicals, CHF(2)OCH(O*)CF(3).

Hydroxyl and Peroxyl Radical Trapping by the Monoamine Oxidase-B Inhibitors deprenyl and MDL 72,974A: Implications for Protection of Biological Substrates

We have examined in vitro radical trapping by the monoamine oxidase-B (MAO-B) inhibitor deprenyl and compared it to the specific MAO-B inhibitor MDL 72,974A. The capacity for the compounds to prevent ·OH-mediated oxidation of biological substrates was examined by determining their ability to inhibit oxidation of 2-deoxyribose and phosphatidylcholine liposomes using the thiobarbituric acid reactive substances (TBARS) assay. MDL 72,974A gave a dose-dependent inhibition of 2-deoxyribose oxidation, while deprenyl generated a strong false positive TBARS reaction with both the sugar and the liposomes. When lipid peroxidation was monitored by conjugated diene formation, deprenyl inhibited oxidation while MDL 72,974A was without effect suggesting that trapping of ·OH was not responsible for activity. Deprenyl inhibited liposomal peroxidation initiated with the water-soluble peroxyl radical generator 2,2′-azobis (2-amidinopropane) (ABAP) with an IC50 of 78 μM as compared to 4.2 mM for MDL 72,974A. A similar difference was observed using the lipophilic peroxyl radical generator 2,2′-azobis (2,4-dimethylvaleronitrile) (AMVN). The data indicate that radical trapping by the MAO-B inhibitors provides differential protection against biological substrates and may involve trapping of secondary peroxyl radicals rather than ·OH.Copyright © 1997 by Elsevier Science Inc.

Free radicals and the etiology of colon cancer

This hypothesis paper reviews diverse evidence suggesting that intracolonic production of oxygen radicals may play a role in carcinogenesis. The hypothesis began to evolve when the author made the chance discovery that 1/10,000 dilutions of feces generated detectable quantities of highly reactive hydroxyl radicals (HO·). The rate of HO· formation, detected using DMSO as a molecular probe, was quite remarkable, corresponding to that which would be produced by over 10,000 rads of gamma irradiation per day, absorbed in the periphery of the fecal mass adjacent to the mucosa. The relatively high concentrations of iron in feces, together with the ability of bile pigments to act as iron chelators that support Fenton chemistry, may very well permit efficient HO· generation from superoxide and hydrogen peroxide produced by bacterial metabolism. Such free radical generation in feces could provide a missing link in our understanding of the etiology of colon cancer: the oxidation of procarcinogens either by fecal Ho·, or by secondary peroxyl radicals (ROO·) to form active carcinogens or mitogenic tumor promotors. Intracolonic free radical formation may explain the high incidence of cancer in the colon and rectum, compared to other regions of the GI tract, as well as the observed correlations of a higher incidence of colon cancer with red meat in the diet, which increases stool iron, and with excessive fat in the diet, which may increase the fecal content of procarcinogens and bile pigments.

Lipid peroxidation during the oxidation of haemoproteins by hydroperoxides. Relation to electronically excited state formation.

The formation of electronically excited states during hydroperoxide metabolism is analysed in terms of recombination reactions involving secondary peroxyl radicals and scission of the O-O bond of peroxides by haemoproteins, mainly myoglobin. Both processes may be sequentially interrelated, for the cleavage of H2O2 by metmyoglobin leads to the formation of a strong oxidizing equivalent with the capability to promote peroxidation of polyunsaturated fatty acids. The decomposition of lipid hydroperoxides by ferryl-hydroxo complexes, as that formed during the oxidation of metmyoglobin by H2O2, is a source of peroxyl radicals, the recombination of which proceeds with elimination of a conjugated triplet carbonyl or singlet oxygen.

Fenton reactions in lipid phases.

Metal catalysis of membrane lipid oxidation has been thought to occur only at cell surfaces. However, conflicting observations of the pro-oxidant activity of ferric (Fe3+) vs ferrous (Fe2+) forms of various chelates have raised questions regarding this dogma. This paper suggests that the solubilities of iron complexes in lipid phases and the corresponding abilities to initiate lipid oxidation there, either directly or via Fenton-like production of reactive hydroxyl radicals, are critical determinants of initial catalytic effectiveness. Partitioning of Fe3+ and Fe2+ complexes and chelates into bulk phases of purified lipids was quantified by atomic absorption spectroscopy. mM solutions of iron salts partitioned into oleic acid at levels of about micromolar. Ethylenediamine tetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) chelates were somewhat less soluble, while adenosine diphosphate (ADP) chelates, and ferrioxamine were soluble as chelates at greater than 10(-5) M. Solubilities of all iron compounds in methyl linoleate were 10- to 100-fold lower. To determine whether Fenton-like reactions occur in lipid phases, H2O2 and either Fe2+ or Fe3+ and a reducing agent were partitioned into the lipid along with the spin-trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and free radical adducts were recorded by electron paramagnetic resonance (EPR). Hydroxyl radicals (OH.) adducts were observed in oleic acid, but in lipid esters secondary peroxyl radicals predominated, and the presence of OH. adducts was uncertain.

Reactions of alkylperoxyl radicals in solution. Part 2.—A kinetic and product study of self-reactions of 2-propylperoxyl radicals between 253 and 323 K

The self-reactions of 2-propylperoxyl radicals have been studied between 253 and 323 K in decane solution. The ratio of the major products, propanone and propan-2-ol, as a function of temperature is in good agreement with the behaviour of other secondary peroxyl radicals in solution. The roles played by the solvent are considered by comparison with previous studies of this radical in the gas phase. It is concluded that the increase in ketone production relative to the alcohol as the temperature is lowered is best explained by the inclusion of the bimolecular reaction of the peroxyl radical producing propanone and hydrogen peroxide. It is suggested that this reaction has Arrhenius parameters of A≈ 106 dm3 mol–1 s–1 and Ea≈ 5 kJ mol–1.

Reactions of alkylperoxyl radicals in solution. Part 1.—A kinetic study of self-reactions of 2-propylperoxyl radicals between 135 and 300 K

Absolute rate constants for the self-reaction of 2-propylperoxyl radicals in solution have been obtained over a wide temperature range and in four solvents. The kinetic behaviour is in agreement with that reported for other secondary peroxyl radicals in solution, but is not entirely consistent with the corresponding data for the 2-propylperoxyl radical in the gas phase. The thermodynamics of the equilibrium between the radicals and their dimer have been investigated to interpret their behaviour below 200 K.

Distinct temporal relation among oxygen uptake, malondialdehyde formation, and low-level chemiluminescence during microsomal lipid peroxidation

An oxystat system was employed in conjunction with a single-photon counting apparatus for simultaneous monitoring of oxygen uptake, oxidative decomposition of membrane lipids, and occurrence of electronically excited species during microsomal lipid peroxidation. During NADPH/ADP-iron-promoted lipid peroxidation at a steady state oxygen partial pressure (pO 2) of 30 mm Hg, complex time relationships among oxygen uptake, malondialdehyde (MDA) formation, and low-level chemiluminescence were observed. While the first two parameters occurred nearly simultaneously, low-level chemiluminescence occurred with a significant delay. A decrease of the steady state pO 2 to 3 mm Hg led to significant increases of the lag phases of all three parameters and a further enhancement of the time displacement of low-level chemiluminescence in relation to oxygen uptake and MDA formation. At a pO 2 of 0.5 mm Hg, the lowest pO 2 maintained during this study, no low-level chemiluminescence was observed while oxygen uptake and MDA formation were still detected. In contrast, during NADPH/CCl 4-promoted lipid peroxidation at a pO 2 of 0.5 mm Hg a sudden drastic rise of low-level chemiluminescence accompanying oxygen uptake and MDA formation was observed. At pO 2 between 0.5 and 3 mm Hg all three parameters occurred nearly concomitantly during the entire incubation. At pO 2 levels above 3 mm Hg all three parameters showed principally the same behavior. However, the respective maxima of low-level chemiluminescence were reached with some delay. The present observations support the assumption that the decomposition of membrane lipid peroxyl radicals to MDA and the formation of electronically excited species proceed via different pathways. The time displacement between oxygen uptake and MDA formation, on the one hand, and low-level chemiluminescence, on the other hand, depends on the type of initiating radical system and on the steady state pO 2 level. It is suggested that the differences are due to distinct subsets (chemical or spatial) of secondary peroxyl radicals in the membrane.