Iron-hydroperoxide species

The oxidation of peroxidases by hydroperoxide leads to a ferryl iron-oxo species as well as a radical cation on the porphyrin ring, which is sometimes transferred to an adjacent amino acid. This species is referred to as compound I. Compound I can oxidize substrates directly by a two-electron process to regenerate the native peroxidase, but, more commonly, it oxidizes substrates by an one-electron process to form compound II where the porphyrin radical cation has been reduced. Compound II, in turn, can perform a second one-electron... 

In fact, the role of copper and oxygen in the Wacker Process is certainly more complicated than indicated in equations (151) and (152) and in Scheme 10, and could be similar to that previously discussed for the rhodium/copper-catalyzed ketonization of terminal alkenes. Hosokawa and coworkers have recently studied the Wacker-type asymmetric intramolecular oxidative cyclization of irons-2-(2-butenyl)phenol (132) by 02 in the presence of (+)-(3,2,10-i -pinene)palladium(II) acetate (133) and Cu(OAc)2 (equation 156).413 It has been shown that the chiral pinanyl ligand is retained by palladium throughout the reaction, and therefore it is suggested that the active catalyst consists of copper and palladium linked by an acetate bridge. The role of copper would be to act as an oxygen carrier capable of rapidly reoxidizing palladium hydride into a hydroperoxide species (equation 157).413 Such a process is also likely to occur in the palladium-catalyzed acetoxylation of alkenes (see Section 61.3.4.3). 

Complementary DFT calculations were performed to interpret the observed 180 KIE in the context of 180 EIEs expected for potential intermediates and products. Included in the analysis were iron(III) hydroperoxide species, including those with hydrogen bonds between both oxygen atoms and a nearby histidine, as well as the iron... 

Epoxidation of cyclooctene with hydrogen peroxide, catalysed by the methoxide-ligated form of iron(III) tetrakispentafluorophenyl [F20TPPFe(III)] porphyrin, is proposed to involve a reaction of F20TPPFe(in) with hydrogen peroxide to form an iron(III) hydroperoxide species, which then undergoes both heterolytic and homolytic cleavage to form iron(IV) n -radical cations and iron(IV) oxo species, respectively. 

In early attempts to produce an iron-oxo species (20) from typical porphyrins like chloro-a,/3,y,8-tetraphenylporphinatoiron(III) [Fe(III)TPP-Cl] and chloroferriprotoporphyrin(IX)[Fe(III)PPIX-Cl], we examined the reaction of t-butyl hydroperoxide and peroxy-acids with alkanes and olefins in the presence of these catalysts. With peroxyacids, decomposition of the porphyrin ring was observed, while with the f-butyl hydroperoxides, product distributions were indistinguishable from free-radical chain reactions initiated photochem-ically in the absence of any metals. 

The first step of peroxidase catalysis involves binding of the peroxide, usually H2C>2, to the heme iron atom to produce a ferric hydroperoxide intermediate [Fe(IE)-OOH]. Kinetic data identify an intermediate prior to Compound I whose formation can be saturated at higher peroxide concentrations. This elusive intermediate, labeled Compound 0, was first observed by Back and Van Wart in the reaction of HRP with H2O2 [14]. They reported that it had absorption maxima at 330 and 410 nm and assigned these spectral properties to the ferric hydroperoxide species [Fe(III)-OOH]. They subsequently detected transient intermediates with similar spectra in the reactions of HRP with alkyl and acyl peroxides [15]. However, other studies questioned whether the species with a split Soret absorption detected by Back and Van Wart was actually the ferric hydroperoxide [16-18], Computational prediction of the spectrum expected for Compound 0 supported the structure proposed by Baek and Van Wart for their intermediate, whereas intermediates observed by others with a conventional, unsplit Soret band may be complexes of ferric HRP with undeprotonated H2O2, that is [Fe(III)-HOOH] [19]. Furthermore, computational analysis of the peroxidase catalytic sequence suggests that the formation of Compound 0 is preceded by formation of an intermediate in which the undeprotonated peroxide is coordinated to the heme iron [20], Indeed, formation of the [Fe(III)-HOOH] complex may be required to make the peroxide sufficiently acidic to be deprotonated by the distal histidine residue in the peroxidase active site [21],... 

It has been widely accepted that the high-valent iron oxo complex 1 is the active oxidant in metalloporphyrin systems and in non-porphyrin iron complex systems as well. A high-valent iron oxo species can be formed via heterolytic 0-0 bond cleavage of the iron-hydroperoxide 2 or of the iron-peroxyacid species 4 (Figure 5, pathway A). Recently, elegant proof of this heterolytic 0-0 bond cleavage of hydrogen peroxide, MCPBA, and f-butyl hydroperoxide has been provided by Traylor et al in iron porphyrin... 

The participation of the two mechanisms is indicated by the effect of added dimethyl sulfide. The presence of dimethyl sulfide suppressed formation of cyclohexanol, cyclohexanone and halocyclohexane but did not affect the production of r-butylperoxy-cyclohexane. In place of the former products, dimethyl sulfoxide was found. Since sulfides can act as a trap for a two-electron oxidant such as an iron-peroxo or an iron-oxo species, the formation of alcohol, ketone and haloalkane must involve heterolysis of the alkyl hydroperoxide, i.e. 

Fe(II)(DTPA)] (diethylenetriamine-N,N, N",iV" -pentaacetate) and H2O2 clearly established that the oxidizing species produced is not the hydroxyl radical but an iron-oxo species such as the ferryl ion. This species is formed by a bimolecular reaction, first order in both [H2O2] and [Fe(II)(DTPA) ] with a rate constant of k = 1.37 0.07 x 10 M s The peroxidatic activity of the heme octapeptide from cytochrome c, microperoxidase-8, was measured at 25 C and pH The active form of the substrate was shown to be the hydroperoxide... 

Guajardo and Mascharak have found that the iron complexes [Fe(PMA)] (n = 1, 2) (84, 85) shown in Fig. 23, which are synthesized as iron bleomycin analogues, promote facile lipid peroxidation in the presence of O2 or H2O2 [140]. Reaction of linoleic acid (59) with O2 catalyzed by 84 and 85 gives the 13-OOH product in the selectivity of 80 and 75%, respectively. In the reaction of arachidonic acid, (86), the 15-OOH product is also selectively formed (80%) by the two complexes. The peroxidation is also promoted by H2O2. As a possible intermediate, a low-spin (hydroperoxo)-iron(III) species, [(PMA)Fe -OOH], has been detected by X-band EPR. The EPR spectrum is identical to that of the activated bleomycin. The reaction has been explained in terms of the radical mechanism, which involves H atom abstraction from lipid (LH) by [(PMA)Fe -OOH]. Peroxidized linoleic acid (L-00 ) has been detected by UV absorption at 234 nm, and a chain propagation reaction by the peroxy radical to produce lipid hydroperoxide (L-OOH) has been proposed. 

Reactions of some lacunar and some novel binuclear iron(II) complexes with O2 are only partly reversible and occur with the formation of free O2, as shown by ESR spectroscopy. Reversible one-electron transfer occurs between O2 and the pentacoordinated Fe(II) complex, followed by the coordination of a base (pyridine or 1-methylimidazole) yielding hexacoor-dinated Fe(III). The reaction of O2 with Fe(II) complexes of bis(j8-diimine)-containing macrocyclic ligands produces diketone ligands through the intermediacy of HO2 and hydroperoxide species. " ... 

Metal-Catalyzed Oxidation. Trace quantities of transition metal ions catalyze the decomposition of hydroperoxides to radical species and greatiy accelerate the rate of oxidation. Most effective are those metal ions that undergo one-electron transfer reactions, eg, copper, iron, cobalt, and manganese ions (9). The metal catalyst is an active hydroperoxide decomposer in both its higher and its lower oxidation states. In the overall reaction, two molecules of hydroperoxide decompose to peroxy and alkoxy radicals (eq. 5). 

Alkyliron(lll) porphyrin complexes are air. sensitive, and when exposed to oxygen under ambient conditions the products are the very stable iron(IIl) /t-oxo dimers, [Fe(Por)]20. A more careful investigation revealed that the reaction of the alkyl complexes with oxygen proceeds via insertion of O2 into the Fe—C bond. " When a solution of Fe(Por)R (R = Me, Et, i-Pr) is exposed to O2 at —70 C, the characteristic H NMR spectrum of the low spin iron alkyl complex disappears and is replaced by a new, high spin species. The same species can be generated from the reaction of an alkyl hydroperoxide with Fe(Por)OH, and is formulated as... 

The conversion of hydroperoxide/peroxide to superoxide is a one-electron redox reaction and requires the presence of transition metals having accessible multiple oxidation states as in biological iron or manganese clusters (e.g., Fe(II, III, IV) clusters of monooxygenase or the Mn(II, HI, IV) clusters of photosystems). Ti is usually not reduced at ambient temperatures. The various possibilities that could facilitate the transformation of hydroperoxo/peroxo to superoxo species are as follows ... 

Such a species cannot be ruled out in reactions of iron-EDTA complexes with hydroperoxides recently described by Bruice and coworkers (27). On the other hand, a hydroperoxide complex that reacts with the substrate such that bond formation fiom O to substrate is concerted with 0-0 bond breaking, as proposed by Klinman for dopamine P-monooxygenase (18), could provide compensation for the cost of 0-0 bond cleavage in the transition state. In fact, it is interesting to speculate that for each of these enzymes, the mechanism by which the substrate is oxidized may be dependent on the reactivity of the substrate. One could envision certain substrates that would react with the metal-bound hydroperoxide ligand prior to or concerted with 0-0 bond cleavage. This possibility is difficult to assess because of our lack of information concerning the reactivity of HQ2" when complexed to different metal ions. 

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