Metal catalyzed Fenton reaction

As mentioned above, in contrast to classic antioxidant vitamins E and C, flavonoids are able to inhibit free radical formation as free radical scavengers and the chelators of transition metals. As far as chelators are concerned their inhibitory activity is a consequence of the formation of transition metal complexes incapable of catalyzing the formation of hydroxyl radicals by the Fenton reaction. In addition, as shown below, some of these complexes, for example, iron- and copper-rutin complexes, may acquire additional antioxidant activity. 

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). 

H202 may also undergo homolytic cleavage of the peroxide catalyzed by transition metals, such as Fe2 +, Cu2 +, Mn2 +, Ni2 +, and Cr5 +, via the Fenton reaction, to produce the highly reactive OH radical and the hydroxyl anion (OH-). 

Moreover, metallic ions like Fe2+ are pro-oxidants as they catalyze Fenton s reaction, inducing formation of strongly reactive hydroxyl radical OH- [13,14] ... 

ROS produced by sugars and glycated protein autoxidation participate in oxidizing of already glycated proteins and affect other proteins (H24). These reactions are catalyzed by metal ions (W17). The presence of metal ions may, moreover, initiate the Fenton reaction and produce hydroxyl radicals. A carbon-centered 1-hydroxyalkyl radical was found during autoxidation of glyceraldehyde (T12). 

Fig. 5.8 Examples of oxidative water treatment technologies used in industry, research and development [adapted from FIGAWA (1997), and supplemented by novel methods]. The numbers 1 to 9 refer to the generalized reaction sequences presented in Figure 5-9. a) Oxidation at elevated temperatures between 220°C < T <300°C or supercritical water oxidation at AT >374°C, Ap >221 bar (221000 kPa) (cf Chapter 1) b) oxidation in the presence of bimetallics Fe°/Ni° or Zn°/Ni° (Cheng and Wu, 2001) or heterogeneous oxidation in supercritical water catalyzed by metals Me = Cu, Ag, Au/Ag-alloy c) Fenton reaction at pH <5 d) photo-assisted Fenton reaction, irradiation in the UV-B/VIS range e) the mixture of oxidants O3/H2O2 is called PEROXONE f) ozonation using solid-bed catalysts with conditioned activated carbon (AC) g) vacuum-UV photolysis of water.

Iron is an essential micronutrient (see Nutritional Aspects of Metals Trace Elements) but in order to obtain sufficient iron and then to handle it in a safe way, biological organisms have evolved complex transport proteins for iron. A major reason for this is that iron bound to low molecular weight ligands can be highly toxic owing to its ability to catalyze Fenton-type reactions, which produce free radicals, as in reactions (1) and (2) below. 

In terms of potential chemical interactions, the effects of NO on ROS-induced injury are multiple, and some effects can be classified as prooxidant and others may be classified as antioxidant still others can be classified as both. In terms of the metal-catalyzed Haber-Weiss reaction, there are two primary effects of -NO. The binding of NO to metal ions will prevent the Fenton reaction and thus results in an antioxidant action. Another important antioxidant action of NO (and its oxidized product N02) is its reaction with hpid radicals, thus resulting in radical chain termination. ... 

CH Activation is sometimes used rather too loosely to cover a wide variety of situations in which CH bonds are broken. As Sames has most recently pointed out, the term was first adopted to make a distinction between organic reactions in which CH bonds are broken by classical mechanistic pathways, and the class of reactions involving transition metals that avoid these pathways and their consequences in terms of reaction selectivity. For example, radicals such as RO- and -OH readily abstract an H atom from alkanes, RH, to give the alkyl radical R. Also in this class, are some of the metal catalyzed oxidations, such as the Gif reaction and Fenton chemistry see Oxidation Catalysis by Transition Metal Complexes). Since this reaction tends to occur at the weakest CH bond, the most highly substituted R tends to be formed, for example, iPr-and not nPn from propane. Likewise, electrophilic reagents such as superacids see Superacid), readily abstract a H ion from an alkane. The selectivity is even more strongly in favor of the more substituted carbonium ion product such as iPr+ and not nPr+ from propane. The result is that in any subsequent fimctionalization, the branched product is obtained, for example, iPrX and not nPrX (Scheme 1). 

There is now substantial evidence that the metal-oxygen complexes described above do indeed form hypervalent intermediates that catalyze both radical and nonradical oxidations (63, 69-78). Most is known about Fe(lV) and Fe(V) complexes, providing support for the idea that hypervalent iron is at least one catalyst in Fenton reactions (79) analogous complexes have been identified for Cu (73, 80) and... 

Hydroxyl radical, HO Three-electron reduction product of O2 generated by Fenton reaction transition metal (iron, copper)-catalyzed Haber-Weiss reaction formed by decomposition of peroxynitrite produced by the reaction of O2 with NO . 

Hydrogen peroxide, although not acmally a radical, is a weak oxidizing agent that is classified as an ROS because it can generate the hydroxyl radical (OH ). Transition metals, such as Fe or Cu, catalyze formation of the hydroxyl radical from hydrogen peroxide in the nonenzymatic Fenton reaction (see Fig. 24.4.). 

A number of aglycone flavonoids are potent inhibitors of in vitro oxidative modification of LDL [44]. Phenolic compounds isolated from red wine inhibit the copper-catalyzed oxidation of LDL in vitro (10 mmol/L), significantly more than a-tocopherol [45], possibly by regenerating a-tocopherol [44], Alternatively, chelation of divalent metal ions by flavonoids may reduce formation of free radicals induced by Fenton reactions [42]. Hydroxylation of the flavone nucleus appears to be advantageous because flavone itself is a poor inhibitor of LDL oxidation, whereas polyhydroxylated flavonoids such as quercetin, morin, hypoleatin, fisetin, gossypetin, and galangin are potent inhibitors of LDL oxidation [44],... 

The superoxide dismutation can be spontaneous or can be catalyzed and therefore significantly accelerated by the enzyme superoxide dismutase (SOD). The superoxide not only generates lydrogen peroxide (H2O2) but also stimulates its conversion into OH radicals, which are actually extremely strong oxidizers very effective in sterilization through a chain oxidation mechanism (to be especially discussed in Section 12.1.5). The H2O2 conversion into OH, known as the Fenton reaction, proceeds as a redox process provided by oxidation of metal ions (for example, Fe +) ... 

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. ... 

In turn, the very same catalyst is also likely to exhibit catalase activity, i.e., the reversal of 02 activation, thereby depleting the free 0) equivalents necessarily formed as intermediates Reaction 8). Moreover, metal-catalyzed decomposition of peroxides according to Reaction 8b often involves radical pathways e.g., Fenton chemistry), thereby increasing the risk of the occurrence of non-selective pathways. Accordingly, systems for selective mediation of reactions with 02 need to display a delicate balance of rate constants if, for example. Reactions 7a and 8 a have to be fast compared with all possible competing chaimels. 

---