The Haber-Weiss Reaction

In their brilliant papers, Haber and Weiss (1932, 1934) studied the iron-catalyzed decomposition of H202 and proposed the reaction of H02 with H202 as a single step [reaction (100)]. This has since been shown to proceed in two steps [reactions (101) and (102) Czapski and Ilan 1978 Bielski 1985 Rush and Bielski 1985], 

In contrast to the Haber-Weiss reaction, the reaction of 02 with HOC1 [reaction (103)] proceeds without transition metal catalysis (Candeias et al. 1993). 

This reaction is considered to be an important step in the phagocytic killing of microorganisms by free-radical processes (Saran et al. 1999). In this reaction, also Cl was considered to play a role (for the complexities of OH/Cl reactions in aqueous solution, see Yu and Barker 2003a,b Yu et al. 2004). 

Adamic K, Howard JA, Ingold KU (1969) Absolute rate constants for hydrocarbon autoxidation. XVI. 

Reactions of peroxy radicals at low temperatures. Can J Chem 47 3803-3808 Adams GE, Willson RL (1969) Pulse radiolysis studies on the oxidation of organic radicals in aqueous solution. Trans Faraday Soc 65 2981-2987 

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Immunohistochemical studies carried out in our laboratories have demonstrated the presence of xanthine oxidase in synovial endothelial cells (Stevens etal., 1991). As expected, the activity of this enzyme per unit weight of tissue is generally higher in synovia taken from RA patients due to their increased vascularity (Allen et al., 1987). In addition, it has also been shown that rheumatoid synoviocytes contain increased levels of iron-saturated ferritin (Morris et d., 1986). Xanthine oxidase (but not dehydrogenase) is able to mobilize iron from ferritin, supplying the necessary transition metal catalyst for the Haber-Weiss reaction and promoting OH formation (Biemond eta/., 1986). 

Cuprous and cupric ions may substitute for ferrous and ferric ions in the Haber-Weiss reaction [22]. Peroxynitrite can be formed from the reaction of NO with 02 ... 

In the presence of trace amounts of iron, superoxide can then reduce Fe3+ to molecular oxygen and Fe2+. The sum of this reaction (13.2) plus the Fenton reaction (13.1) produces molecular oxygen, hydroxyl radical and hydroxyl anion from superoxide and hydrogen peroxide, in the presence of catalytic amounts of iron. This is the Haber-Weiss reaction (13.3), originally described by Haber and Weiss (1934), but manifestly impossible from thermodynamical considerations in the absence of catalytic amounts of redox metals such as iron and copper ... 

However, the formation of either 02 or OH by the myeloperoxidase system is debatable, and it has even been proposed that myeloperoxidase can actually lower OH formation by decreasing the concentration of H202 available for the Haber-Weiss reaction ( 5.4.2.5). 

Metal-catalyzed nitration by peroxynitrite also provides an alternative explanation to the Haber-Weiss reaction for the role of transition metals in oxidative tissue injury. The rate of peroxynitrite reaction with Fe " EDTA is 5700 M , which is in the same range as the rate of hydrogen peroxide reacting with... 

The production of ethylene from methional (3-thiomethylpropanal) was induced by the oxidation of xanthine by dioxygen catalysed by xanthine oxidase The second-order rate constant for the reaction of hydroxyl radicals with methional was estimated by pulse radiolysis to amount to 8.2 x lO s while the superoxide anion reacted more slowly The short lag period of the ethylene production induced by the oxidation of xanthine could be overcome by the addition of small amounts of hydrogen peroxide. The reaction was inhibited by SOD or by catalase, and by scavengers of hydroxyl radicals, so that the Haber-Weiss reaction was implicated... 

Further reduction of H2O2 yields the hydroxyl radical, OH, indeed a powerful but indiscriminant and very unstable oxidant. Superoxide anion may itself serve as the reductant of H2O2 to form OH in the presence of ionic iron in a reaction called the Haber-Weiss reaction... 

However, under certain circumstances, such as in the presence of transition metal ions, hydroxyl radicals may result from either the Haber-Weiss reaction or the Fenton reaction, which cause lipid peroxidation and cell injury (Fig. 6.10). 

Rush JD, Bielski BHJ (1985) Pulse radiolytic studies of the reactions of H02/02 with Fe(ll)/Fe(lll) ions. The reactivity of H02/02 with ferric ions and its implication on the occurrence of the Haber-Weiss reaction. J Phys Chem 89 5062-5066... 

Weinstein J, Bielski BHJ (1979) Kinetics of the interaction of HO2 and O2 radicals with hydrogen peroxide. The Haber-Weiss reaction. J Am Chem Soc 101 58-62 Winterbourn CC, Metodiewa D (1994) The reaction of superoxide with reduced glutathione. Arch Biochem Biophys 314 284-290... 

J.P. Kehrer, The Haber-Weiss reaction and mechanisms of toxicity. Toxicology 149,43-50... 

Sutton HC. Efficiency of chelated iron compounds as catalysts for the Haber-Weiss reaction. J Free Radic Biol Med 1985 1 195-202. 

Egan TJ, Barthakur SR, Aisen P. Catalysis of the Haber-Weiss reaction by iron-diethylenetriaminepentaacetate. J Inorg Biochem 1992 48 241-249. 

During a cell s normal life cycle under aerobic conditions, some of the consumed oxygen is reduced to highly reactive molecules called reactive oxygen species (ROS). Transition metal ions such as iron, with their frequently unpaired electrons, act as excellent catalysts for the creation of ROS. The body s inability to modulate free iron availability creates an environment prone to the formation of ROS and free-radical induced cellular damage in the event of iron overload. The classical reaction between Fe3+ and superoxide (02 ) is known as the Haber-Weiss reaction ... 

Besides the above hypothesis, there are only a few documented cases where superoxide toxicity does not involve H2O2 and/or metal ions. Accordingly, for the last decade, it was repeatedly stated that 02" served as a precursor of a much more reactive and oxidizing species such as OH. Because the Haber-Weiss reaction was extremely slow, it was suggested that 02 triggered OH production by recycling the reduced form of transition metal ions involved in Fenton reactions [42] ... 

Superoxide is also a product of various enzyme reactions catalyzed by the flavin oxidases (e.g., xanthine oxidase and monoamine oxidase). In addition, 07 is a product of the noncatalytic oxidation of oxyhemoglobin, of which about 3% is converted each day to methemoglobin. Moreover, 02 is readily formed in phagocytic cells (i.e., neutrophils and monocytes) during the respiratory burst. Furthermore, in addition to the Fenton reaction, the Haber-Weiss reaction results in the conversion of 02 to the potent HO via the following reactions (H3) ... 

Mello-Eilho AC, Meneghini R. In vivo formation of single-strand breaks in DNA by hydrogen peroxide is mediated by the Haber-Weiss reaction. Biochim. Biophys. Acta. 1984 781 56-63. 

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