Radicals transition metal peroxide oxidation

Key Words Lewis acid adducts, Radical oxidations, Epoxidation, Hydrogen peroxide, Bond dissociation energy, Catalyst durability, Methyltrioxorhenium, Cross-bridged cyclam, Mn(IV), Late transition metal. Propylene oxide. Titanium silicalite (TS-1) catalyst, Ethylanthrahydroquinone/H2 process, Polyoxometallates, Mn(IV) catalyst. Hydrogen abstraction. Rebound mechanism, Isotopic label, t-BuOOH, Peroxide adduct. 2008 Elsevier B.v. 

Oxidation of polyunsaturated fatty acids (PUFA) in lipoproteins may be mediated by reactive species such as radicals, transition metals, other electrophiles, and by enzymes. Once initiated, oxidation of lipids may proceed by a chain reaction, illustrated in Fig. 4 (R5). In step I, an oxidant captures an electron from a PUFA to produce a lipid radical. In step 2, after rearrangement, the conjugated diene radical reacts rapidly with singlet oxygen to produce a lipid peroxide radical, which is the kinetically preferred reaction (step 3) (B5). The chain can be terminated if the lipid radical reacts with an antioxidant to produce a stable peroxide (step 4). Otherwise, the peroxyl radical can react with another polyunsaturated fatty acid as shown in step 5 to perpetuate a chain reaction. The chain reaction requires production of lipid peroxides, giving it the name peroxidation. Fatty acids oxidized in the core are largely triglycerides and cholesterol esters, while toward the outer layer fatty acids in phospholipids are oxidized. 

A second approach uses transition metal pro-oxidant catalysts as an additive (Pablos et al., 2010 Roy et al., 2009). Several photodegradable and oxo-biodegradable plastic products rely on this approach. Transition metals can act as redox catalysts to accelerate degradation via catalyzed peroxide decomposition into radicals. 

Chemical Properties. Higher a-olefins are exceedingly reactive because their double bond provides the reactive site for catalytic activation as well as numerous radical and ionic reactions. These olefins also participate in additional reactions, such as oxidations, hydrogenation, double-bond isomerization, complex formation with transition-metal derivatives, polymerization, and copolymerization with other olefins in the presence of Ziegler-Natta, metallocene, and cationic catalysts. All olefins readily form peroxides by exposure to air. 

The decomposition of diacyl peroxides (36) is catalyzed by various transition metal salts,46,167 for example, Cu+ (Scheme 3.28).168,169 A side reaction is oxidation of alkyl radicals by the oxidized fonn of the metal salt e.g. Cu2+). 

So-called reverse ATRP has been described where a conventional radical initiator (e.g. AIBN) and a transition metal complex in its Higher oxidation state are used. 85"288 One of the first systems explored was ( uBr- 133 AIBN VI VIA. It is important that the initiator is completely consumed early in the polymerization. The use of peroxide initiators in reverse ATRP can be problematical depending on the catalyst used and the reaction temperature.286 289 The system CuBr2/133/BPO/MMA at 60°C was found to provide no control,286 In ATRP at lower temperatures (40 °C), the system CuCl/133/BPO/MMA was successful though dispersities obtained were relatively broadf89 Radicals are produced from the redox reaction between the catalyst in its reduced form and BPO. 

In this reaction scheme, the steady-state concentration of peroxyl radicals will be a direa function of the concentration of the transition metal and lipid peroxide content of the LDL particle, and will increase as the reaction proceeds. Scheme 2.2 is a diagrammatic representation of the redox interactions between copper, lipid hydroperoxides and lipid in the presence of a chain-breaking antioxidant. For the sake of clarity, the reaction involving the regeneration of the oxidized form of copper (Reaction 2.9) has been omitted. The first step is the independent decomposition of the Upid hydroperoxide to form the peroxyl radical. This may be terminated by reaction with an antioxidant, AH, but the lipid peroxide formed will contribute to the peroxide pool. It is evident from this scheme that the efficacy of a chain-breaking antioxidant in this scheme will be highly dependent on the initial size of the peroxide pool. In the section describing the copper-dependent oxidation of LDL (Section 2.6.1), the implications of this idea will be pursued further. 

Injury to cells and tissues may enhance the toxicity of the active oxygen species by releasing intracellular transition metal ions (such as iron) into the surrounding tissue from storage sites, decompartmentalized haem proteins, or metalloproteins by interaction with delocalized proteases or oxidants. Such delocalized iron and haem proteins have the capacity to decompose peroxide to peroxyl and alkoxyl radicals, exacerbating the initial lesion. 

Although atherosclerosis and rheumatoid arthritis (RA) are distinct disease states, both disorders are chronic inflammatory conditions and may have common mechanisms of disease perpetuation. At sites of inflammation, such as the arterial intima undergoing atherogen-esis or the rheumatoid joint, oxygen radicals, in the presence of transition-metal ions, may initiate the peroxidation of low-density lipoprotein (LDL) to produce oxidatively modified LDL (ox-LDL). Ox-LDL has several pro-inflammatory properties and may contribute to the formation of arterial lesions (Steinberg et /., 1989). Increased levels of lipid peroxidation products have been detected in inflammatory synovial fluid (Rowley et /., 1984 Winyard et al., 1987a Merry et al., 1991 Selley et al., 1992 detailed below), but the potential pro-inflammatory role of ox-LDL in the rheumatoid joint has not been considered. We hypothesize that the oxidation of LDL within the inflamed rheumatoid joint plays a pro-inflammatory role just as ox-LDL has the identical capacity within the arterial intima in atherosclerosis. 

Ascorbate is known to act as a water-soluble antioxidant, reacting rapidly with superoxide, hydroxyl and peroxyl radicals. However, reduced ascorbate can react non-enzymatically with molecular oxygen to produce dehydroascorbate and hydrogen peroxide. Also, ascorbate in the presence of light, hydrogen peroxide and riboflavin, or transition metals (e.g. Fe, Cu " ), can give rise to hydroxyl radicals (Delaye and Tardieu, 1983 Ueno et al., 1987). These phenomena may also be important in oxidative damage to the lens and subsequent cataract formation. 

Several studies suggest that LA and DHLA form complexes with metals (Mn2+, Cu2+, Zn2+, Cd2+, and Fe2+/Fe3+) [215-218]. However, in detailed study of the interaction of LA and DHLA with iron ions no formation of iron LA complexes was found [217]. As vicinal dithiol, DHLA must undoubtedly form metal complexes. However, the high prooxidant activity of DHLA makes these complexes, especially with transition metals, highly unstable. Indeed, it was found that the Fe2+-DHLA complex is formed only under anerobic conditions and it is rapidly converted into Fe3+ DHLA complex, which in turn decomposed into Fe2+ and LA [217]. Because of this, the Fe3+/DHLA system may initiate the formation of hydroxyl radicals in the presence of hydrogen peroxide through the Fenton reaction. Lodge et al. [218] proposed that the formation of Cu2+ DHLA complex suppressed LDL oxidation. However, these authors also found that this complex is unstable and may be prooxidative due to the intracomplex reduction of Cu2+ ion. 

Thus, the mechanism of MT antioxidant activity might be connected with the possible antioxidant effect of zinc. Zinc is a nontransition metal and therefore, its participation in redox processes is not really expected. The simplest mechanism of zinc antioxidant activity is the competition with transition metal ions capable of initiating free radical-mediated processes. For example, it has recently been shown [342] that zinc inhibited copper- and iron-initiated liposomal peroxidation but had no effect on peroxidative processes initiated by free radicals and peroxynitrite. These findings contradict the earlier results obtained by Coassin et al. [343] who found no inhibitory effects of zinc on microsomal lipid peroxidation in contrast to the inhibitory effects of manganese and cobalt. Yeomans et al. [344] showed that the zinc-histidine complex is able to inhibit copper-induced LDL oxidation, but the antioxidant effect of this complex obviously depended on histidine and not zinc because zinc sulfate was ineffective. We proposed another mode of possible antioxidant effect of zinc [345], It has been found that Zn and Mg aspartates inhibited oxygen radical production by xanthine oxidase, NADPH oxidase, and human blood leukocytes. The antioxidant effect of these salts supposedly was a consequence of the acceleration of spontaneous superoxide dismutation due to increasing medium acidity. 

The superoxide anion radical and hydrogen peroxide are not particularly harmful to cells. It is the product of hydrogen peroxide decomposition, the hydroxyl radical (HO ), that is responsible for most of the cytotoxicity of oxygen radicals. The reaction can he catalyzed hy several transition metals, including copper, manganese, cohalt, and iron, of which iron is the most ahimdant in the human body (Reaction 2 also called the Fenton reaction). To avoid iron-catalyzed reactions, iron is transported and stored chiefly as Fe(III), although redox active iron can be formed in oxidative reactions, and Fe(III) can be reduced by semiquinone radicals (Reaction 3). 

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