Quinones reactions with superoxide

There are two kinds of redox interactions, in which ubiquinones can manifest their antioxidant activity the reactions with quinone and hydroquinone forms. It is assumed that the ubiquinone-ubisemiquinone pair (Figure 29.10) is an electron carrier in mitochondrial respiratory chain. There are numerous studies [235] suggesting that superoxide is formed during the one-electron oxidation of ubisemiquinones (Reaction (25)). As this reaction is a reversible one, its direction depends on one-electron reduction potentials of semiquinone and dioxygen. 

Although many polyphenolic compounds can quench DPPH215 218 and scavenge radicals in competition with spin traps,225 232,278 consideration must also be given to the fate of the resultant phenoxyl radicals, which can include their direct reaction with important biomolecules, further oxidation to cytotoxic quinones and, in the case of semiquinones, their reduction of oxygen to superoxide. Thus,... 

The prototropic equilibrium constant (pRa) for the equilibrium between 0 and HO radicals is 4.7. Therefore at physiological pH, the superoxide radicals exist predominantly in the form of O radicals. HO radicals are more reactive than Oj radicals, and react with substrates by hydrogen abstraction or by addition to the double bonds. 0 radicals do not exhibit these reactions but participate in a number of redox reactions with metal ions and substrates like quinone, ascorbate, etc. The rate constants for these reactions are considerably lower than diffusion-controlled limits (10 to 10 s ). Oj ... 

Brunmark and Cadenas (27A15) reviewed the major mechanisms that are involved in quinone-induced cytotoxicity in 1989. The redox chemistry of quinoid compounds was surveyed in terms of (1) reactions involving only electron transfers, such as those accomplished during the enzymatic reduction of quinones and nonenzymatic interaction with redox couples generating semiquinones, and (2) nucleophilic addition reactions. In their explanation of the mechanisms involved, quinone is reduced to the hydroquinone or semiqui-none radical by cellular reductase. The semiquinone radical then undergoes rapid autooxidation with the generation of the parent quinone and concomitant formation of superoxide. The hydroquinone reacts rapidly with superoxide to form H2O2 and the semiquinone. 

Carbon dioxide radical anions, C02 , are commonly used in aqueous chemistry as a reducing agent for metalloporphyrins or as intermediate in the formation of superoxide anion. COf has been reported to undergo efficient electron transfer reactions with methyl violo-gen, quinones, alkyl halides, fumarates, nitro and nitrosobenzenes and chlorinated benzaldehydes. With nitrobenzenes and chlorinated benzaldehydes, electron attachment occurs on the nitro and aldehyde groups, respectively. CO2 radicals have also been reported to add to some unsaturated compounds such as acrylamide and pyridin-3-ol. Efficient hydrogen abstraction from mercaptobenzenes have also been reported. 

It is extremely important that the interaction of quinones with XO (Reaction (3)) is reversible that can lead to receiving erroneous results at the measurement of superoxide production by SOD-inhibitable cytochrome c reduction [28,29] (see also Chapter 27). Lusthof et al. [30] demonstrated that 2,5-bis(l-aziridinyl)-l,4-benzoquinones are directly reduced by XO. Interestingly at quinone concentrations greater than 25pmol I 1, quinones entirely suppressed one-electron reduction of dioxygen, and cytochrome c was completely reduced by the semiquinones formed. It is well known that cytochrome c and lucigenin are effective superoxide scavengers and due to that, these compounds are widely used in the quantitative assays of superoxide detection. Nonetheless, under certain experimental conditions they can be directly reduced by XO [31]. 

As hydroxyl or hydroxyl-like radicals are produced by the superoxide-driven Fenton reaction, superoxide overproduction must also occur in thalassemic cells. First, it has been shown by Grinberg et al. [382], who demonstrated that thalassemic erythrocytes produced the enhanced amount of superoxide in comparison with normal cells in the presence of prooxidant antimalarial drug primaquine. Later on, it has been found that the production of superoxide and free radical-mediated damage (measured through the MetHb/Hb ratio) was much higher in thalassemic erythrocytes even in the absence of prooxidants, although quinones (menadione, l,4-naphthoquinone-2-methyl-3-sulfonate) and primaquine further increased oxidative stress [383]. Overproduction of superoxide was also observed in thalassemic leukocytes [384]. 

Possible errors due to the competition of cytochrome c reduction with the reversible reduction of quinones by superoxide are frequently neglected. For example, it has been found that quinones (Q), benzoquinone (BQ), and menadione (MD) enhanced the SOD-inhibitable cytochrome c reduction by xanthine oxidase [6]. This seems to be a mystery because only menadione may enhance superoxide production by redox cycling ( °p)"]/ [MD] =-0.20 V against ,0[02 ]/[02] 0.16 V) via Reactions (3) and (4), whereas for... 

However, a more discouraged fact is that benzoquinone accelerated SOD-inhibitable part of cytochrome c reduction, which is usually considered as a reliable proof of superoxide formation. Such a phenomenon has been first shown by Winterbourn [7], who suggested that SOD may shift the equilibrium of Reaction (4) to the right even for nonredox cycling quinones. The artificial enhancement of superoxide production by SOD in the presence of quinones was demonstrated in the experiments with lucigenin-amplified CL, in which benzoquinone was inhibitory [6],... 

The most common addition reaction is to a carbonyl group without an adequate leaving group. Examples include the reaction of HO and 02 with CO2 and quinones. A common feature of these reactions is the formation of an adduct that is sufficiently stable to be isolated or characterized (see Scheme 18). The same orange-colored species results from the reaction of solid tetramethylammonium superoxide with gaseous CO2 and with neat CCLt, and is believed to be an anion radical, 000(0)0 . ... 

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