Iron catalyzed oxygen insertion

The committed biosynthetic path to the leukotrienes begins (see Fig. 5.2) with the action of 5-lipoxygenase (5-LO)[EC 1.13.11.34] (14)on arachidonic acid. Purified human 5-LO is an unstable, 78,000-Da protein that has been isolated and cloned (15,16). It contains a tightly bound, nonheme iron that is essential for enzymatic activity (17). Like all known lipoxygenases, 5-LO catalyzes the insertion of molecular oxygen into a l,4-cis,cis-pentadiene unit. The effect of 5-LO on AA is to abstract stereospecifically the pro-S hydrogen at position C7 and to insert molecular oxygen at... 

As to the mechanistic pathway of aerobic oxidations of this type Httle evidence of any details has emerged as yet [ 18]. However, it seems quite reasonable to assume the intermediacy of peracids being formed by autoxidation of the aldehydes [ 19,20]. Metals can be involved in various stages of oxidation processes like the described nickel(II)- or iron(III)-catalyzed reactions [21] acyl radicals may be produced by metals from aldehydes which then participate in the autoxidation of the aldehydes. Metals can direct the oxygen insertion itself, too, or promote other catalytic pathways as well as even inhibit catalytic turnover. 

Though the detailed mechanism of olefin epoxidation is still controversial, Scheme 8 depicts possible intermediates, metallacycle (a), K-cation radical (b), carbocation (c), carbon radical (d), and concerted oxygen insertion (e) [2, 216, 217]. As discussed above, the intermediacy of metallacycle has been questioned. One of the most attractive mechanism shown in Scheme 8 is the involvement of one electron transfer process to form the olefin 7C-cation radicals (b). Observation of rearranged products of alkenes, known to form through the intermediacy of the alkene cation radicals, in the course of oxidation catalyzed by iron porphyrin complexes is consistent with this mechanism [218, 219]. A -alkylation during the epoxidation of terminal olefins is also well explained by the transient formation of olefin cation radical [220]. A Hammett p value of -0.93 was reported in the epoxidation of substitute styrene by Fe (TPP)Cl/PhIO system, suggesting a polar transition state required for cation radical formation [221] Very recently, Mirafzal et al. have applied cation radical probes as shown in Scheme 9 to... 

The same aldehyde is formed in the oxygenation of quadricyclane catalyzed by cytochrome P-450 [88]. The mechanism of the cytochrome P-450-catalyzed reaction has been reported as follows the oxygenation is initiated by one electron transfer from quadricyclane to an electron deficient iron-oxene intermediate, which is followed by insertion of an oxygen atom into a C-C bond rather than a C-H bond. The electron transfer from substrate to the iron-oxene intermediate may be reasonable because of a high ionization potential of quadricyclane. Since the diagnostic aldehyde is a sole product in both sMMO and cytochrome P-450 systems, it is likely that the same reaction mechanism is applicable to these two enzymatic reactions. A plausible mechanism for the sMMO-catalyzed oxygenation of quadricyclane is shown in Scheme 4. 

Molybdenum hydroxylases (i.e., AO and XO) are flavoproteins that contain in addition to a FAD, a pterine cofactor coordinated to a molybdenum atom, and an iron sulfur center for their catalytic activity. They catalyze the two-electron oxidation of substrates with transfer to molecular oxygen to produce H2O2, and insert an atom of oxygen from water into a wide range of N-hctcrocycies and aldehydes via two-electron redox reaction as shown in equation 1.4 ... 

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