Oxenoid transfer

The equivalence of the O-insertion step to similar reactions of carbenes and nitrenes prompted Hamilton [24] to coin the term oxenoid transfer or in general oxenold mechanism . Subsequently, cytochrome P-450 was referred to as oxene transferase [25]. These terms reflect the ability of the enzyme to abstract an O-atom from 0 and insert it... 

A more detailed study of the biological oxidation of sulphoxides to sulphones has been reported165. In this study cytochrome P-450 was obtained in a purified form from rabbit cells and was found to promote the oxidation of a series of sulphoxides to sulphones by NADPH and oxygen (equation 56). Kinetic measurements showed that the process proceeds by a one-electron transfer to the activated enzymatic intermediate [an oxenoid represented by (FeO)3+] according to equation (57). 

Metal-oxenoid (oxo metal) species and metal-nitrenoid (imino metal) species are isoelectronic and show similar reactivity both species can add to olefins and be inserted into C—H bonds. Naturally, the study of nitrene transfer reactions began with metalloporphyrins, which were originally used as the catalysts for oxene transfer reactions. 

Hamilton674 proposed the oxenoid mechanism shown in Scheme 5 for both the model and enzymatic systems. (The iron-dioxygen complex is assumed to react as an oxenoid species and transfer an oxygen atom to the substrates S.)... 

The current understanding of oxygen activation by P-450 is summarized as follows (Scheme II) (Ic, 5a, b) (i) incorporation of a substrate to the resting ferric state (1) of the active site of the enzyme to afford the ES complex (2) (//) one-electron reduction of the heme from NAD(P)H via an associated reductase enzyme (Hi) reaction of the reduced heme (3) with O2 to form an oxy complex (4a, 4b) (iv) one-electron reduction of the oxy complex to yield a peroxo complex (5) (v) protonation (or possibly acylation) of the peroxo oxygen (vi) the formation of active species, the so-called oxenoid [FeO + (7)], by heterolytic 0-0 bond cleavage of (6) (v/7) oxygen transfer to the substrate. Thus, the overall stoichiometry can be expressed as in Eq. (2), where R is orR C(0) ... 

Pd-coordinated oxygen first attacks the carbonyl carbon as a nucleophile to form a Pd metallacycle, which readily eliminates X to afford an acylperoxopalladium species, the precursor of the Pd oxenoid. Epoxidation occurs via oxene transfer and the same route is operative for the observed sulfide to sulfoxide transformation. 

The mechanism of aromatic hydroxylation is of special interest in view of its relevance to monooxygenase action. The "oxenoid" mechanism proposed by Hamilton involves the transfer of an oxygen atom from the active intermediate (an oxometal species) formed from the catalyst. This type of mechanism is supported by the NIH-shift, i.e, migration of an H-atom from the hydroxylation site to the adjacent position via an arene oxide intermediate. The NIH-shift has been observed in non-enzymatic hydroxylations, pointing to the involvement of oxometal species in various oxygenations (dehyrogenations). 

Despite the attractiveness of this proposal, peroxy acids such as (83) and (84) are unlikely to function as the critical oxenoid intermediates in the enzymic process. Peroxysuccinic acid has been added to both the proline-4-hydroxylase and thymidine-2 -hydroxylase systems, but it does not replace the requirement for oxygen and 0x0 glutarate 253). Furthermore, it is unlikely that such a peroxy acid would have sufficient reactivity to carry out the specified hydroxylation. Moreover, we have prepared the peroxy acid (84) and have found that it too is incapable of performing the required intramolecular oxene transfer. No products like (85), (86) or (87) are formed 287). 

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