Hydroxyl radical Fenton reaction

There is a more serious problem for the [Fe(H20)6]2+ complex in acidic medium, which needs more efficient oxidants than 02. In such a case H202 is sufficient for regenerating Fem with simultaneous formation of hydroxyl radicals (Fenton reaction) ... 

The octanol/water partition coefficient (log P) indicates the hydrophobiaty of a substrate. Fligher hydrophobicity of a chemical compound will decrease its aqueous solubility. Because hydroxyl radicals have reaction rates that are most likely diffusion controlled, the reaction rates of hydrophobic compounds in aqueous systems, such as Fenton s reaction, will be negatively affected. Figure 6.22 shows the effect of the octanol/partition coefficient on the oxidation rates of 2-chlorophenol, 2,4-dichlorophenol, 2,4,6-trichlorophe-nol, and pentachlorophenol. Pentachlorophenol has the lowest aqueous solubility and correspondingly its reaction rates are significantly affected. 

Although Fenton did not observe hydroxyl radical-mediated reactions for mixtures of Fe3+ and hydrogen peroxide, more recent work has illustrated that such systems can produce hydroxyl radical. Haber and Weiss [5] originally proposed a free radical mechanism for the Fe3+-catalyzed decomposition of hydrogen peroxide. These reactions include [3] ... 

It is possible to generate ferryl species by peroxide treatment of ferrous iron ions [18,249], The two-electron oxidation of ferrous (as opposed to ferric) iron does not require the formation of a cation radical, although subsequent reactions may generate hydroxyl radicals. These reactions therefore provide an alternative mechanism to the Fenton reaction for free radical damage associated with low-molecular-weight iron species. In the absence of a protective protein environment, however, such low-molecular-weight ferryl species are unstable and difficult to detect and therefore their existence is controversial [see the review by Koppenol in this volume (Chapter 1)]. 

FlGUEtE 10,24 One-electton oxidation of ferrous iron lo ferric iron. The xidatiDA of ferrous to ferric iron can lake place under a variety of conditions. One condition, shown here, involves the reduction of HOOH, producing a hydroxide anion and a hydroxyl radical. This reaction is the Fenton reaction. 

It has been suggested that the reactive species arc metal complexed hydroxy radicals rather than "free" hydroxyl radicals. The reactions observed show dependence on the nature of the metal ion and quite different product distributions can be obtained from reaction of organic substrates w ith Fc -H2O2 (Fenton s Reagent) and Ti " -H202. However, it is not clear whether these findings reflect the involvement of a different active species or simply the different rates and/or pathways for destruction of the initially formed intermediates." Metal ions in... 

Metal chelation may enhance or inhibit the Fenton reaction, depending on the metal and the chelator in question. Chelation of iron (II) by EDTA enhances the formation of hydroxyl radical, while deferoxamine, another chelator, reduces its formation. This is significant because peptides or proteins can chelate metals in the body, thus influencing the resulting degree of damage. The formation of hydroxyl radicals by nickel (II) and cobalt (II) is enhanced by this type of chelation. In addition to the Fenton and Haber-Weiss reactions, metals can also catalyze the formation of the hydroxyl radical via reaction with hypochlorite (HOCl), which is prodnced by neutrophils. ... 

Under some conditions, the active oxidant is Fe(IV)=0 and not the hydroxyl radical (101). Reactions entailing other low-valent transition-metal complexes that react like iron are called Fenton-like reactions (100,102,103). Fenton-like reactions were studied with Cu (aq) and its complexes, such as [Cu(D (phenanthroUnelal (102). The results of these studies indicate that transient complexes, Cu(I)-H202, are formed. However, OH is not formed directly as proposed in reaction (47) (103). 

Heterocyclic compounds have in most cases been hydroxylated by modified forms of Fenton s reagent. For instance, EDTA or pyrophosphate have been added to the system to complex the ferrous ions. It has been shown in the reactions of bcnzenoid compounds, however, that addition of complexing agents does not affect the distribution of isomers obtained by Fenton s reagent,and therefore the hydroxyl radical must still be the hydroxylating species. 

The reverse reaction (that is, the oxidation of a vinyl radical by Fe to the corresponding vinyl cation) may be involved in the reaction of the dimethyl ester of acetylenedicarboxyUc acid 261 with Fenton s reagent [Fe —H2O2, (217)] (216). When 261 was treated with Fe —H2O2 and the reaction mixture was extracted with ether, a small amount of furan 262 was isolated. A possible mechanism (216) for its formation may be addition of hydroxyl radical to the triple bond of 261, followed by addition of the intermediate vinyl radical to a second molecule of 261 and oxidation of the resulting radical with Fe to the corresponding vinyl cation, followed by cyclization to 262, as shown in Scheme XX. 

Floyd, R.A. Zs-Nagy (1984). Formation of long lived hydroxyl free radical adducts of proline and hydroxyproline in a Fenton reaction. Biochimica Bio-physica Acta, 790, 94-7. 

Fenton chemistry comprises reactions of H2O2 in the presence of iron species to generate reactive species such as the hydroxyl radical OH. These radicals ( = 2.73 V) lead to a more eflident oxidation chemistry than H2O2 itself (E° = 1.80 V). 

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. 

Indeed, when present in concentrations sufficient to overwhelm normal antioxidant defences, ROS may be the principal mediators of lung injury (Said and Foda, 1989). These species, arising from the sequential one-electron reductions of oxygen, include the superoxide anion radical, hydrogen peroxide, hypochlorous ions and the hydroxyl radical. The latter species is thought to be formed either from superoxide in the ptesence of iron ions (Haber-Weiss reaction Junod, 1986) or from hydrogen peroxide, also catalysed by ferric ions (Fenton catalysis Kennedy et al., 1989). 

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). 

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. 

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