High-valent oxo intermediates

FIGURE 3. Generic radical rebound mechanism of monooxygenases such as MMO and P450. X is a species that can provide one electron to stabilize the high valent oxo intermediate such as a second iron in the case of MMO or a porphyrin macrocycle in the case of P450. 

The second question is about how the the high-valent oxo intermediate forms in both enzymes. For catalase and peroxidase, the evidence indicates that hydrogen peroxide binds to the ferric center and then undergoes heterolysis at the... 

High-valent oxo-complexes, isolated or in situ-generated, interact most often with electron-rich n -systems 1 or suitable C-H bonds with low bond dissociation energy (BDE) in substrates 3 (Fig. 2). These reactions may occur concerted via transition states 1A or 3A leading to epoxides 2 or alcohols 4. On the other hand, a number of epoxidation reactions, such as the Jacobsen-Katsuki epoxidation, is known to proceed by a stepwise pathway via transition state IB to radical intermediate 1C [39]. Similarly, hydrocarbon oxidation to 4 can proceed by a hydrogen abstraction/S ... 

The reactions of iron-containing enzymes with O2 often involve high oxidation states of the metal. Generally, the initial reaction of dioxygen with both heme and mononuclear non-heme ferrous enzymes results in the formation of Fe -superoxide intermediates. Highly reactive Fe =0 intermediates often are employed often for C-H activation. The mechanism of substrate oxidation by binuclear non-heme enzymes involves high valent, oxo-bridged species, with Fe in the -i-3 or +4 oxidation state. 

High-valent iron intermediates have been proposed as the active species in OAT and C-H oxidation reactions for nonheme iron enzymes. In some cases, such intermediates have been trapped by rapid fireeze-quench studies and characterized. In ribonucleotide reductase from E. coli and MMO, intermediates X and Q with Fem-( l-0)2-Ferv and Ferv-( 0,-O)2-FeIV diamond core, respectively, have been characterized (Figure 3.11).35 Also, Fe,v oxo intermediates have been observed for mononuclear proteins such as taurine/2-oxoglutarate dioxygenase (TauD) (Figure 3.11).36... 

Regarding the iron coordination geometry, the most active catalysts exhibit two available cis-coordination sites that facilitate the activation of the oxidant. Conversely, relatively inactive complexes usually show only one available coordination site or have two available sites in a trans position. As stated before, iron-based enzymatic systems in nature involve the formation of high-valent metal intermediates within the catalytic cycle. Similarly, oxo-iron complexes have been proposed as the main intermediate for artificial oxidation processes. Depending on the iron complex, the type of oxidant and substrate and the mechanism involved in the oxidation process, this intermediate could be a Fe =0 or H0-Fe =0 species. Wieghard et al. 

Guo, C.C., J.X. Song, X.B. Chen, and G.R Jiang (2000). A new evidence of the high-valent oxo-metal radical cation intermediate and hydrogen radical abstract mechanism in hydrocarbon hydroxylation catalyzed by metalloporphyrins. J. Mol. Cat. A 157, 31-40. 

The catalytic cycle of peroxidases (Fig. 5) begins with the oxidation of the high-spin, pentacoordinate ferric native enzyme 10) by hydrogen peroxide to form a semi-stable intermediate called Compound I (//). Compound I is a high-valent oxo-iron complex that is two oxidation equivalents above ferric horseradish peroxidase. Although formally an Fe heme. Compound 1 is generally thought to be an Fe porphyrin 71-cation radical [51, 52]. 

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]. 

EXAFS analysis of a peroxide compound of beef heart cytochrome c oxidase has also revealed the presence of a short Fe=0 bond with a bond length of 1.71 A [ 157]. A catalytic role for the ferryl-oxo species of cytochrome c oxidase has been postulated [158-161]. In this case, the prosthetic group is no longer protoporphyrin IX, but is instead heme a [162]. The observation of an Fe=0 bond for this intermediate of cytochrome oxidase further illustrates the generality of the short, 1.65 A, Fe =0 bond for high-valent oxo-iron states (Table 2). 

Because there exist a number of reviews which deals with the structural and mechanistic aspects of high-valent iron-oxo and peroxo complexes [6,7], we focus in this report on the application and catalysis of iron complexes in selected important oxidation reactions. When appropriate we will discuss the involvement and characterization of Fe-oxo intermediates in these reactions. 

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