Iron-oxo intermediate

In a similar system, the reaction of the ferric(edta) complex with peroxycarboxylic acids was probed by adding 2,4,6-tri-fe/r-butyl phenol, ArOH.2 This experiment gave rise to the aryloxyl radical, ArO, which persisted for hours and was detected by its characteristic spectrum. It was indeed formed in the reaction mentioned, at a rate that was independent of [ArOH], It was proposed that ArO results from a reactive oxo-iron intermediate, tentatively (edta)FevO. 

A second class of heme enzymes that has a high-valent oxo-iron intermediate is the catalase group [81]. Most catalases have iron protoporphyrin IX as the prosthetic group (Fig. 1) and axial tyrosinate ligation [82-86]. However, both the catalase from Neurospora crassa [87, 88] and the HPII catalase from Escherichia coli [89] are likely to have iron chlorins as prosthetic groups [87-91]. 

As discussed above, the oxygen activation by P-450 begins with one electron reduction of the ferric heme (resting state) followed by the binding of molecular oxygen to afford the oxy intermediate. Introduction of the second electron is believed to form an active oxo-iron intermediate equivalent to compound I via the transient production of a peroxo-iron(III) species. Unfortunately, the subsequent intermediates to the oxy-iron complex have never been observed in biological systems [27, 28]. Therefore, the structures, reactivities, and their spectroscopic characteristics must be studied by their model systems. 

N—Fe(IV)Por complexes. Oxo iron(IV) porphyrin cation radical complexes, [O—Fe(IV)Por ], are important intermediates in oxygen atom transfer reactions. Compound I of the enzymes catalase and peroxidase have this formulation, as does the active intermediate in the catalytic cycle of cytochrome P Q. Similar intermediates are invoked in the extensively investigated hydroxylations and epoxidations of hydrocarbon substrates cataly2ed by iron porphyrins in the presence of such oxidizing agents as iodosylbenzene, NaOCl, peroxides, and air. 

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. 

I. M.C.M., Reversible formation of high-valent-iron-oxo prophyrin intermediates in heme-based catalysis revisiting the kinetic model for horseradish peroxidase, Inorg. Chim. Acta, 275/276, 98-105, 1998. 

The structural chemistry of oxo-iron aggregates is dominated by the presence of and /<3-oxo groups which, in conjunction with other ligands, confer stability to the polynuclear core. For structurally characterized synthetic complexes, the degree of aggregation varies to date from three to eleven, but neither a decanuclear nor any odd numbered intermediate size is known. 

Locating minima is not always straightforward since a reaction surface is usually complex, and a geometry optimization calculation will only locate minima close to the starting point. It is usually not feasible to systematically explore all possible conformers, so chemical intuition and corroborative evidence from experiment play important roles. A nice example is the identification of the coordination geometry of oxo-iron(IV) intermediate in TauD (22). As mentioned above, during optimization of enzyme active sites, key atoms are sometimes fixed to mimic the constraints that the protein environment exerts on the active site (20). 

The product ratios 36/37 obtained from incubations of 34, and 35 (Fig. 8) are reasonably well explained assuming a rather masked intramolecular isotope effect (/cH//cD)exo (kH//cD)eBdo = 2, and a twofold preference for the abstraction of exo-H over endo-H This observation suggests that the oxo-iron(I V) intermediate assumes a position, different from the CO complex, dissecting the H-C(5)-H angle unsymmetrically, being slightly closer to the exo-hydrogen. For this... 

The mechanism of epoxidation has been studied in detail both with P450 enzymes [68] and synthetic metal porphyrins [69], The problem finding a conclusive answer on how the enzymatic reaction proceeds is due to the fact that intermediates have not been detected but inferred by investigating the stereochemistry of product formation. By and large it is safe to say that the reaction depends on the steric hindrance imposed by the olefin s substitutents, the electron donating character of the olefin, and the electron demand of the oxo-iron(IV) porphyrin used. In particular the last aspect makes it difficult to draw conclusions from reactions with model compounds, since these metal porphyrins behave quite differently from native P450 due to the distinct electronic nature of both the metal and the porphyrin. 

Furthermore, the approach of olefins to the oxygen of the oxo-iron(IV) intermediate generated from face protected porphyrins is likely to be distinct from native P450 due to steric interactions. 

In conclusion it looks as if the reactive oxo-iron(IV) intermediate of the catalytic cycle of cytochrome P450 operates by different mechanisms depending on the structure and electronic nature of the unsaturated substrates. 

Ye S, Neese F. Nonheme oxo-iron(IY) intermediates form an oxyl radical upon approaching the C-H bond activation transition state. Proc Natl Acad Sci USA. 2011 108 1228-33. 

Fig. 21. Typical intermediates in hemoprotein enzyme active sites. The iron protoporphyrin IX cofactor (heme) forms dioxygen adducts termed oxy-species. In the course of oxygen activation and catalytic redox transformations, the oxy form can be consecutively converted into hydroperoxo- and oxo-type intermediates, which are usually referred to as compound 0, compound I, and compound II. Reproduced with permission from Ref (183). Copyright Nature Publishing Group.

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