The Fenton reaction

The most celebrated example of this process is the Fenton reaction which is discussed at some length to illustrate the general characteristics of such reductions. An interesting recent example is the reduction of organic halides, viz. 

At low peroxide/Fe(II) ratios only (92) and (93) occur. As the ratio increases, OH- increasingly attacks H2O2 to give the observed kinetic deviation and evolution of O2. At high ratios the competition between Fe(II) and Fe(ril) for H02-dominates and the evolution of O2 becomes independent of peroxide concentration. The effect of Cu(ri) is ascribed to reactions 

The main alternative to the modified Haber-Weiss theory is a two-equivalent oxidation of Fe by peroxide , viz. 

This has received support from work with 0-labelled peroxide under conditions when O2 is evolved , but a stopped-flow examination indicated the immediate product to be at least 99% Fe -t-FeOH in contrast, reduction of HOCl and O3 gave significant quantities of the dimeric (FeOH)2 formed very probably as follows 

The absence of dimer in the Fenton reaction is regarded as evidence for almost complete one-equivalent reduction. 

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The discussion above refers to the classical dark conditions where the chemical activation is achieved thermally. Fenton requires a moderate thermal activation, resulting in a reaction temperature ranging from 25 to 90 °C. The oxidizing capacity of the Fenton reaction can be increased by UV or UV-vis Hght irradiation [160, 161]. The increase is interpreted by means of the photoreduction ability of Fe ... 

This concerted reduction by two ferrous species eliminates H02- (or O2 ) as an intermediate and explains the weak catalysis by Cu(II) (which is strong for V([II) and V(IV) autoxidations). Weiss has suggested that the species Fe. 02.Fe may be a stable intermediate, but Wells explains the presence of two Fe(Il) species in the rate law in terms of a pre-existing dimeric form of Fe(lf) containing an H2O bridge, for which there is evidence . The reduction is completed via the Fenton reaction vide infra). The hydrogen peroxide dianion is probably never free but is protonated whilst complexed to Fe(III). 

Hardwick has compared his own data with those of several groups on the rate of the Fenton reaction. The following equations fit most data... 

The stoichiometry of the reduction by Fe(ll) of cumene hydroperoxide is 1 1 (in contrast to reduction of H2O2) but the ratio A[Fe(II)]/A[ROOH] increases greatly in the presence of oxygen. The Arrhenius parameters for reduction of this and related hydroperoxides are quite similar to those of the Fenton reaction (Table 21). The production of acetophenone and ethane in high yield and the simple, second-order kinetics are consistent with the scheme... 

The reduction of NH2OH is one stage in the reduction of N03 to NH3- It is formally closely related to the Fenton reaction, the stoichiometry in acidic solution being... 

As strong metal ion chelators due to their catechol structure, tea flavonoids are able to bind and thus decrease the level of free cellular ferric and ferrous ions, which are required for the generation of reactive oxygen radicals via the Fenton reaction (Yang and Wang, 1993). 

Gutteridge, J.M.C. (1986). Iron promoters of the Fenton reaction and lipid peroxidation can be released from haemoglobin by peroxides. FEBS Lett. 201, 291-298. 

Humans Hydrogen peroxide has been used as an enema or as a cleaning agent for endoscopes and may cause mucosal damage when applied to the surface of the gut wall. Hydrogen peroxide enteritis can mimic an acute ulcerative, ischaemic or pseudomembranous colitis, and ranges from a reversible, clinically inapparent process to an acute, toxic fulminant colitis associated with perforation and death (Bilotta and Waye, 1989). It is conceivable that anecdotal reports of exacerbation of IBD by iron supplementation (Kawai et al. 1992) are mediated by hydroxyl radical production by the Fenton reaction. 

The antiulcer agent rebamipide ((2-(4-chlorobenzoy-lamino)-3-[2(lH)-quinolinon-4-yl]propionic acid) dose-dependently decreased hydroxyl radical signal generated by the Fenton reaction in an e.s.r. study. Rebamipide is active as a hydroxyl radical scavenger and inhibitor of superoxide production by neutrophils (Yoshikawa etal., 1993). 

Spin trapping EPR technique and UV-Vis spectroscopy have been used (Polyakov et al. 2001b) to determine the relative rates of reaction of carotenoids with OOH radicals formed by the Fenton reaction in organic solvents. The Fe3+ species generated via the Fenton reaction... 

FIGURE 9.1 EPR spectra of spin adducts recorded during the Fenton reaction in DMSO at different H202 concentrations ([FeClJ = 1 mM), (1), (2), and (3) are OH, OOH, and CH3 radicals, respectively. 

In the presence of trace amounts of iron, superoxide can then reduce Fe3+ to molecular oxygen and Fe2+. The sum of this reaction (equation 2) plus the Fenton reaction (equation 1) produces molecular oxygen plus hydroxyl radical, plus hydroxyl anion from superoxide and hydrogen peroxide, in the presence of catalytic amounts of iron - the so-called Haber-Weiss reaction (equation 3) (Haber and Weiss, 1934). 

Ferrous iron, by its reaction with hydrogen peroxide in the Fenton reaction, can yield the toxic hydroxyl radical, OH, which will further potentiate oxygen toxicity. 

Trace amounts of copper are essential for life. However, as with iron, excess copper is also toxic, on account of its capacity to catalyse the Fenton reaction. There are analogies and differences between these two elements successively selected by Nature as it was obliged to adapt life to the first general irreversible pollution of the earth, namely the advent of dioxygen. 

The equivalent reaction is not observed with iron. Cu(I) catalyses the Fenton reaction with hydrogen peroxide, just as Fe(II) does. The Cu(I) state exhibits the ability to bind and activate dioxygen via Cu2(p-ri2 ri2-02) and Cu2(p-0)2 species. 

Reactions of Hydroxyl and Hydroxyl-Like Radicals Produced by the Fenton Reaction with Nucleic Acids... 

For a long time one question remained unanswered the efficiency of the Fenton reaction as the in vivo producer of hydroxyl radicals due to the low rate of Reaction (2) (the rate constant is equal to 42.11 mol 1 s 1 [18]). It is known that under in vitro conditions the rate of Fenton reaction can be sharply enhanced by chelators such as EDTA, but for a long time no effective in vivo chelators have been found. From this point of view new findings obtained by Chen and Schopfer [19] who found that peroxidases catalyze hydroxyl radical formation in plants deserve consideration. These authors showed that horseradish peroxidase (HRP) compound III is a catalyst of the Fenton reaction and that this compound is one to two orders of magnitude more active than Fe EDTA. 

The formation of hydroxyl or hydroxyl-like radicals in the reaction of ferrous ions with hydrogen peroxide (the Fenton reaction) is usually considered as a main mechanism of free radical damage. However, Qian and Buettner [172] have recently proposed that at high [02]/ [H202] ratios the formation of reactive oxygen species such as perferryl ion at the oxidation of ferrous ions by dioxygen (Reaction 46) may compete with the Fenton reaction (2) ... 

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