Ferryl ion

If a dilute solution of hydrogen peroxide in dry acetonitrile is added to a solution of a sulphoxide and an iron(II) salt in dry acetonitrile then the sulphone is produced in quantitative yield34. This latter reaction works equally well for aliphatic and aromatic sulphoxides and is thought to involve oxygen transfer by the reaction of a ferryl ion with the sulphoxide, as shown in equation (12). 

Then the ferryl ion either reacts with water to form the hydroxyl radical, or oxidizes another Fe2+ ion [14,16],... 

Thus, two routes of transformation are possible for the Fe2+(H202) complex one-electron transfer to form the hydroxyl radical and two-electron transfer to form the ferryl ion. It is difficult to prove experimentally the formation of the ferryl ions because they are very reactive, so that this route of interaction of H202 with Fe2+ remains hypothetical to a great extent. Another change in the mechanism of H202 decomposition with increasing pH is related to the acidic dissociation of H02 (pKa = 4.4)... 

This mode of superoxide-dependent free radical-mediated damaging activity remains an important one although the nature of the generated reactive species (free hydroxyl radicals or perferryl, or ferryl ions) is still obscure. However, after the discovery of the fact that many cells produce nitric oxide in relatively large amounts (see below), it became clear that there is another and possibly a more portent mechanism of superoxide-induced free radical damage, namely, the formation of highly reactive peroxynitrite. 

It has been recognized Teel et al. 2001) that one of the attractiveness of Fenton chemistry approach is its near-stoichiometric generation of a strong oxidant (probably a mixture of OH, HO2, FeO ). If the ferryl ion hypothesis is taken into account, one molecule of H2O2 will give another FeO (see equations 18 or 20), the ferryl ion in turn can accept two electrons in acid medium according to ... 

Hence, the stoichiometric conversion of 1 mole of RB5 to CO2 requires up to 76 mole of hydrogen peroxide (and therefore 76 mole ferryl ion, if equations 20, 24 and 30 are 100% efficient). The color of the dyestuff is a function of the conjugated length of the double bonds... 

In fact, spectroscopic measurements indicate that form P contains an oxo-ferryl ion with the second oxygen of the original 02 converted to an OH ion and probably coordinated with CuB.136a 136c 142/142a c P may also contain an organic radical, perhaps formed from tyrosine 244 as indicated in Fig. 18-11. 

Jacobsen F, Flolcman J, Sehested K (1997a) Activation parameters of ferryl ion reactions in aqueous acid solutions. Int J Chem Kinet 29 17-24... 

These theoretical suggestions were found to be very useful for further stages in the development of the oxidation mechanism up to now ferryl-ion (Fe2+0) has been considered in biooxidation as the intermediate hydroxiding intermediate [10]. 

F. Ferryl Ion or Other High-Valent Iron Species... 

The importance of Fe02+ (the ferryl ion) as an alternate oxidant, instead of hydroxyl radical, has been extensively debated. Much of the debate exists due to difficulty in definitively detecting the ferryl ion and the hydroxyl radical. Because of their low concentrations and short lifetimes, these species are detected through indirect methods. 

Although there is still debate as to whether hydroxyl radicals or ferryl species are the key oxidants in Fenton systems, most literature reports on the mechanisms of degradation of organic compounds invoke the hydroxyl radical. Based on the reports discussed above, it seems likely that hydroxyl radical is a major oxidant during Fenton degradations. Although ferryl ions or other highly oxidized forms of iron may occur, either to a limited extent or more abundantly under specific conditions, this section will deal with documented reaction pathways and kinetics for hydroxyl radical or species assumed to be hydroxyl radical. The reader should keep in mind that ferryl pathways may need to be considered under certain conditions. 

Koppenol WF1, Liebman JF (1984) The oxidizing nature of the hydroxyl radical - a comparison with the ferryl ion (Fe02+). J Phys Chem 88 99-101... 

Progressive fibro-proliferative diseases (e.g. liver cirrhosis, pulmonary fibrosis, rheumatoid arthritis) result in a dramatic increase in collagen synthesis [227], This is preceded by inflammation that correlates with an increased activity of proline and lysine hydroxylase [228], Although they are unlikely to be the primary initiators of these diseases the increased activities of these enzymes may cause other problems. For example, in vitro the enzyme can turn over in the absence of a peptide substrate (but the presence of the 2-oxoglutarate cofactor). In this case stoichiometric amounts of ascorbate are required, probably to reduce the ferryl ion back to ferrous [229]. In vivo, lower concentrations of ascorbate are utilised [229,230], possibly to reactivate the enzyme after a non-productive activation (for example in the presence of a peptide that can bind to the active site, but cannot be hydroxylated). As the amount of proline-hydroxylase activity increases in the fibro-proliferative diseases, the concentration of ascorbate might not be sufficient to reduce these inactive complexes, resulting in the formation of potentially reactive ferryl intermediates. 

It is interesting to note that several research groups propose the oxidizing intermediate to be an iron(IV) species such as the ferryl ion (Fe02+),27 especially when the iron centre is attached to a porphyrin ring. Figure 2.12 illustrates a possible alternative mechanism involving the ferryl ion to that outlined above. 

Although this is a most satisfying mechanism for such induced oxida- tions, there is an important alternative, suggested originally by Bray and Gorin in 1932, involving the formation of Fe(IV) rather than OH. This is usually written as the formation of the aquo ferryl ion, Fe02+ [4.11]. 

Studies in MeCN suggest that an iron(IV) ferryl ion, Fe02+, is initially formed that is,... 

Iron being a redox-active metal, it most hkely exerts its toxic effects through the generation of hydroxyl radical or by generation of ferryl ion. In iron loaded condition, there is generation of radical species leading to hpid peroxidation. Lipid peroxidation of cellular membrane would have deleterious effects on their function and hence on the function of the cell. There is also irreversible oxidation of ascorbic acid. Deficiency of ascorbic acid can lead to a reduction in the amount of iron available for erythropoiesis. 

The conversion P F (Figure 7) is accompanied by an electron equilibration between Cua and cytochrome a, and its rate is pH-dependent [60] and displays a kinetic isotope effect in D2O [60b]. Consequently, it has been suggested [51, 60a,c] that the formation of F is controlled by the protonation of the binuclear site. The conclusion that F really is a ferryl ion intermediate is supported by resonance-Raman measurements [61]. 

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