Iron peroxide complex

MnP is the most commonly widespread of the class II peroxidases [72, 73], It catalyzes a PLC -dependent oxidation of Mn2+ to Mn3+. The catalytic cycle is initiated by binding of H2O2 or an organic peroxide to the native ferric enzyme and formation of an iron-peroxide complex the Mn3+ ions finally produced after subsequent electron transfers are stabilized via chelation with organic acids like oxalate, malonate, malate, tartrate or lactate [74], The chelates of Mn3+ with carboxylic acids cause one-electron oxidation of various substrates thus, chelates and carboxylic acids can react with each other to form alkyl radicals, which after several reactions result in the production of other radicals. These final radicals are the source of autocataly tic ally produced peroxides and are used by MnP in the absence of H2O2. The versatile oxidative capacity of MnP is apparently due to the chelated Mn3+ ions, which act as diffusible redox-mediator and attacking, non-specifically, phenolic compounds such as biopolymers, milled wood, humic substances and several xenobiotics [72, 75, 76]. 

The hexanuclear complex (Table VI), although somewhat beyond the scope of this review, deserves mention inasmuch as it is the only structurally characterized synthetic iron peroxide complex thus far (162). It contains a (jL-peroxo species coordinated to two Fe30 units via two of the three iron atoms in each trinuclear unit. The peroxide in this complex appears to be sufficiently stabilized as to be unreactive. 

Heme (C34H3204N4Fe) represents an iron-porphyrin complex that has a protoporphyrin nucleus. Many important proteins contain heme as a prosthetic group. Hemoglobin is the quantitatively most important hemoprotein. Others are cytochromes (present in the mitochondria and the endoplasmic reticulum), catalase and peroxidase (that react with hydrogen peroxide), soluble guanylyl cyclase (that converts guanosine triphosphate, GTP, to the signaling molecule 3, 5 -cyclic GMP) and NO synthases. 

In related work, the reactions of hydrogen peroxide with iron(II) complexes, including Feu(edta), were examined.3 Some experiments were carried out with added 5.5"-dimethyl-1-pyrroline-N-oxide (DMPO) as a trapping reagent fa so-called spin trap) for HO. These experiments were done to learn whether HO was truly as free as it is when generated photochemically. The hydroxyl radical adduct was indeed detected. but for some (not all) iron complexes evidence was obtained for an additional oxidizing intermediate, presumably an oxo-iron complex. 

Another iron porphyrin complex with 5,10,15,20-tetrakis(2, 6 -dichloro-3 -sulfonatophenyl)porphyrin was applied in ionic liquids and oxidized veratryl alcohol (3,4-dimethoxybenzyl alcohol) with hydrogen peroxide in yields up to 83% to the aldehyde as the major product [145]. In addition, TEMPO was incorporated via... 

Iron(II) complexes of flavonoids like quercetin could, however, be involved in the reduction of peroxides ... 

Extensive studies have established that the catalytic cycle for the reduction of hydroperoxides by horseradish peroxidase is the one depicted in Figure 6 (38). The resting enzyme interacts with the peroxide to form an enzyme-substrate complex that decomposes to alcohol and an iron-oxo complex that is two oxidizing equivalents above the resting state of the enzyme. For catalytic turnover to occur the iron-oxo complex must be reduced. The two electrons are furnished by reducing substrates either by electron transfer from substrate to enzyme or by oxygen transfer from enzyme to substrate. Substrate oxidation by the iron-oxo complex supports continuous hydroperoxide reduction. When either reducing substrate or hydroperoxide is exhausted, the catalytic cycle stops. 

How does nature prevent the release of hydrogen peroxide during the cytochrome oxidase-mediated four-electron reduction of dioxygen It would appear that cytochrome oxidase behaves in the same manner as other heme proteins which utilize hydrogen peroxide, such as catalase and peroxidase (vide infra), in that once a ferric peroxide complex is formed the oxygen-oxygen bond is broken with the release of water and the formation of an oxo iron(IV) complex which is subsequently reduced to the ferrous aquo state (12). Indeed, this same sequence of events accounts for the means by which oxygen is activated by cytochromes P-450. 

In 1989, we showed [142] that the Fe2+(rutin)2 complex is a more effective inhibitor than rutin of asbestos-induced erythrocyte hemolysis and asbestos-stimulated oxygen radical production by rat peritoneal macrophages. Later on, to evaluate the mechanisms of antioxidant activities of iron rutin and copper-rutin complexes, we compared the effects of these complexes on iron-dependent liposomal and microsomal lipid peroxidation [165], It was found that the iron rutin complex was by two to three times a more efficient inhibitor of liposomal peroxidation than the copper-rutin complex, while the opposite tendency was observed in NADPH-dependent microsomal peroxidation. On the other hand, the copper rutin complex was much more effective than the iron rutin complex in the suppression of microsomal superoxide production, indicating that the copper rutin complex indeed acquired additional SOD-dismuting activity because superoxide is an initiator of NADPH-dependent... 

In 1988 Bast and Haenen [201] reported that both LA and DHLA did not affect iron-stimulated microsomal lipid peroxidation. However, Scholich et al. [202] found that DHLA inhibited NADPH-stimulated microsomal lipid peroxidation in the presence of iron-ADP complex. Inhibitory effect was observed only in the presence of a-tocopherol, suggesting that some interaction takes place between these two antioxidants. Stimulatory and inhibitory effects of DHLA have also been shown in other transition metal-stimulated lipid peroxidation systems [203,204]. Later on, the ability of DHLA (but not LA) to react with water-soluble and lipid-soluble peroxyl radicals has been proven [205], But it is possible that the double (stimulatory and inhibitory) effect of DHLA on lipid peroxidation originates from subsequent reactions of the DHLA free radical, capable of participating in new initiating processes. 

Several studies suggest that LA and DHLA form complexes with metals (Mn2+, Cu2+, Zn2+, Cd2+, and Fe2+/Fe3+) [215-218]. However, in detailed study of the interaction of LA and DHLA with iron ions no formation of iron LA complexes was found [217]. As vicinal dithiol, DHLA must undoubtedly form metal complexes. However, the high prooxidant activity of DHLA makes these complexes, especially with transition metals, highly unstable. Indeed, it was found that the Fe2+-DHLA complex is formed only under anerobic conditions and it is rapidly converted into Fe3+ DHLA complex, which in turn decomposed into Fe2+ and LA [217]. Because of this, the Fe3+/DHLA system may initiate the formation of hydroxyl radicals in the presence of hydrogen peroxide through the Fenton reaction. Lodge et al. [218] proposed that the formation of Cu2+ DHLA complex suppressed LDL oxidation. However, these authors also found that this complex is unstable and may be prooxidative due to the intracomplex reduction of Cu2+ ion. 

The inhibition of lipid peroxidation by metalloporphyrins apparently depends on metal ions because only compounds with transition metals were efficient inhibitors. Therefore, the most probable mechanism of inhibitory effects of metalloporphyrins should be their disuniting activity. Manganese metalloporphyrins seem to be more effective inhibitors than Trolox (/5o = 204 pmol I 1) and rutin (/50 112 pmol I 1), and practically equal to SOD (/50= 15 pmol I 1). The mechanism of inhibitory activity of manganese and zinc metalloporphyrins might be compared with that of copper- and iron-flavonoid complexes [167,168], which exhibited enhanced antiradical properties due to additional superoxide-dismuting activity. 

The mechanism shown in Scheme 5 postulates the formation of a Fe(II)-semi-quinone intermediate. The attack of 02 on the substrate generates a peroxy radical which is reduced by the Fe(II) center to produce the Fe(III) peroxide complex. The semi-quinone character of the [FeL(DTBC)] complexes is clearly determined by the covalency of the iron(III)-catechol bond which is enhanced by increasing the Lewis acidity of the metal center. Thus, ultimately the non-participating ligand controls the extent of the Fe(II) - semi-quinone formation and the rate of the reaction provided that the rate-determining step is the reaction of 02 with the semiquinone intermediate. In the final stage, the substrate is oxygenated simultaneously with the release of the FemL complex. An alternative model, in which 02 attacks the Fe(II) center instead of the semi-quinone, cannot be excluded either. 

This behavior, as well as complementary observations, can be explained on the basis of the reaction mechanism depicted in Scheme 5.3. The main catalytic cycle involves three successive forms of the enzyme in which the iron porphyrin prosthetic group undergoes changes in the iron oxidation state and the coordination sphere. E is a simple iron(III) complex. Upon reaction with hydrogen peroxide, it is converted into a cation radical oxo complex in which iron has a formal oxidation number of 5. This is then reduced by the reduced form of the cosubstrate, here an osmium(II) complex, to give an oxo complex in which iron has a formal oxidation number of 4. 

An interesting alternative to the use of chromium(VI) oxidants for the conversion of 1 to 2 involves the use of a low-valent iron reagent prepared in situ by the action of hydrogen peroxide on an iron(II) complex of 1 (73). Vinblastine (as the free base) is treated with 2 equiv of perchloric acid in acetonitrile at -20°C. Ferrous perchlorate is then added, followed by the addition of excess 30% hydrogen peroxide. Work-up of the reaction mixture with a saturated solution of ammonium hydroxide gives 2 in yields of 35-50% after chromatography. 

On the other hand, Tilley et al. have reported a synthesis of a well-defined tris(tert-butoxy)siloxy-iron(lll) complex [13] as well as respective molecular siloxide complexes of cobalt [14] and copper [15], which appear to become precursors for their grafting onto silica and application as catalysts for oxidation of alkanes, alkenes and arenes by hydrogen peroxide. 

The dibenzotetraaza[14]annulene-iron(III) cation (144) shows catalase-like activity, converting hydrogen peroxide into dioxygen under physiological conditions. The iron(II) complex of... 

Reviews of kinetics and mechanisms deal with long-range electron transfer and with the uptake and release of dioxygen species, especially uptake from organic peroxides. " " The photochemistry of iron porphyrin complexes has been documented." ... 

The bis-hydroxylamine adduct [Fe (tpp)(NH20H)2] is stable at low temperatures, but decomposes to [Fe(tpp)(NO)] at room temperature. [Fe(porphyrin)(NO)] complexes can undergo one-and two-electron reduction the nature of the one-electron reduction product has been established by visible and resonance Raman spectroscopy. Reduction of [Fe(porphyrin)(NO)] complexes in the presence of phenols provides model systems for nitrite reductase conversion of coordinated nitrosyl to ammonia (assimilatory nitrite reduction), while further relevant information is available from the chemistry of [Fe (porphyrin)(N03)]. Iron porphyrin complexes with up to eight nitro substituents have been prepared and shown to catalyze oxidation of hydrocarbons by hydrogen peroxide and the hydroxylation of alkoxybenzenes. ... 

The second reaction achieved notoriety as a possible source of hydroxyl radicals, but the reaction proceeds extremely slowly. Iron(III) complexes may catalyze this reaction in this case, Fe(III) would first be reduced by the superoxide, followed by oxidation by hydrogen peroxide. See also Fenton Reaction... 

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