Metal-peroxo intermediates

McLain, J. L. Lee, J. Groves, J. T. Biomimetic oxygenations related to cytochrome P450 metal- and metal-peroxo intermediates, Biomimetic Oxidations Catalyzed by Transition Metal Complexes , Ed. Meunier, B. Imperial College Press London, 2000, pp. 91-169. 

Metal-peroxo intermediates of different structures were often implicated in the catalytic cycles of oxidative enzymes (see Figures 4.32 1.35 for representative examples). In most cases, however, these peroxo complexes are incompetent oxidants for native substrates. Instead, they undergo further reactions (usually, 0-0 bond cleavage that generates high-valent metal-oxo species) yielding more reactive, kinetically competent oxidants. Nevertheless, some peroxides can react with substrates in both enzymatic and synthetic systems. 

McLain, J., X Lee, and XT. Groves (1999). Biomimetic oxygenations related to cytochrome P450 Metal-oxo and metal-peroxo intermediates. In B. Meunier (ed.), Biomimetic Oxidations. ICP Publishers, pp. 91-170. 

Figure 21.2. Activation of O2 or H2O2 by POMs, through the formation of oxene intermediates (upper right) or metal-peroxo intermediates (lower right).

AH of the commercial inorganic peroxo compounds except hydrogen peroxide are described herein, as are those commercial organic oxidation reactions that are beheved to proceed via inorganic peroxo intermediates. Ozonides and superoxides are also included, but not the dioxygen complexes of the transition metals. 

Transition-metal-catalyzed oxidations may or may not proceed via peroxocomplexes. Twelve important industrial organic oxidation processes catalyzed by transition metals, many of which probably involve peroxo intermediates, have been tabulated (88). Even when peroxo intermediates can be isolated from such systems, it does not necessarily foUow that these are tme intermediates in the main reaction. 

The metal-alcoholate mechanism is well established for allylic alcohol epoxidation in the presence of Ti and V catalysts. [41, 51, 52, 111-113], In principle, it can provide a viable pathway also for catalysis by a Re complex. In fact, allylic alcohols may add, at least formally, to either an oxo-Re or peroxo-Re moiety (e.g. of 5a or 5b) in a process which is referred to as metal-alcoholate binding this mechanism gives rise to metal-alcoholate intermediates. We identified four intermediates of alcohol addition to di(peroxo) complexes two resulting transition states, S-8 and S-9b, are shown in Figure 11. All metal-alcoholate intermediates he significantly higher in energy (by 10-22 kcal/mol) than 5b + propenol, except the... 

It is instructive to compare the properties of metal peroxo and alkyl (or hydro) peroxo groups for the case of Ti because experimental structures of both types are known [117, 119-121] and Ti compounds are catalysts for such important processes as Sharpless epoxidation [22] and epoxidation over Ti-silicalites [122], where alkyl and hydro peroxo intermediates, respectively, are assumed to act as oxygen donors. Actually, the known Ti(t 2-02) complexes are not active in epoxidation. [121-124] However, there is evidence [123] that (TPP)Ti(02) (TPP = tetraphenylporphyrin) becomes active in epoxidation of cyclohexene when transformed to the cis-hydroxo(alkyl peroxo) complex (TPP)Ti(OH)(OOR) although the latter has never been isolated. 

The metal-peroxo species are considered to have a side-on structure (bidentate coordination of the peroxide ligand) and to be very unstable in protic medium (8). Under physiological conditions, after the first protonation and formation of a hydroperoxo intermediate (Scheme 2), the second protonation of this intermediate can proceed in two distinctly different pathways. In one case the second protonation results in the release of hydrogen peroxide from the metal center, leaving the metal oxidation state unchanged (Scheme 2). This is a crucial step in the catalytic cycles of SODs and SORs, especially in the catalytic mechanism of manganese SODs, which exist in the hydrophobic mitochondrial matrix. If protonation is not efficient, the... 

The metal peroxo species is thus formed in solution and, in general, it can be isolated by adding to the reaction mixture a suitable ligand (equation 2). This procedure does not vary much with the metal or with the nature of the ligand and it is still based on the old method reported by Mimoun and coworkers about 30 years ago. The intermediate formation of a hydroperoxy species has been postulated and in some cases observed (see below). 

The metallacycle mechanism can also be considered a concerted mechanism. It is analogous to the one proposed for metal peroxo complexes and is based on the assumed formation of a cyclic intermediate that includes the peroxo group, the reactant molecule, and the metal ion (Mimoun, 1982, 1987 Huybrechts et al., 1992). For alkene epoxidation, the sequence of events would be represented as follows [Eq. (31)] ... 

The present view is that cytochrome a is the acceptor of electrons from cytochrome c, but that a simple linear electron-transfer sequence from cytochrome a to Cua and then to the cytochrome 03/Cub centre is unlikely. Instead the sequence shown in equation (63) holds, where cytochrome a is in rapid equilibrium with Cua. These views depend largely upon pre-steady-state kinetics of the redox half reactions of the enzyme with its two substrates, ferrocytochrome c and O2. However, these conclusions are not in accord with kinetic studies under conditions when both substrates are bound to the enzyme, and which show maximal rates of electron transfer from cytochrome c to O2. In particular some of the cytochrome c is oxidized at a faster rate than a metal centre in the oxidase. In contrast, at high ionic strength conditions, where the cytochrome c and the cytochrome oxidase are mainly dissociated, oxidation of cytochrome c occurs only slowly following the complete oxidation of the oxidase. These results for the fast oxidation of cytochrome c have been interpreted in terms of direct electron transfer from cytochrome c to the bridged peroxo intermediate involving 03 and Cub, or to a two-electron transfer to O2 from cytochromes a and 03 during the initial phase of the reaction. 

As discussed in previous sections, direct reactions of low-valent metal compounds with O2 afford various metal-oxygen intermediates, including superoxo, peroxo, and high-valent metal-oxo species. However, with the exception of superoxides and dinuclear peroxides, alternative methods of generating these intermediates are more generally applicable, and often produce better results.15 16... 

Hydrogen peroxide and organic hydroperoxides are relatively poor oxidants in the absence of radical initiators or other specific reagents. No reaction occurs with alkenes unless a reagent capable of producing electrophilic intermediates, such as a peracid or metal peroxo complex, is used. 

In Mechanism I, which is favored for the SOD enzymes and most redox-active metal complexes with SOD activity, superoxide reduces the metal ion in the first step, and then the reduced metal ion is reoxidized by another superoxide, presumably via a metal-peroxo complex intermediate. In Mechanism II, which is proposed for nonredox metal complexes but may be operating in other situations as well, the metal ion is never reduced, but instead forms a superoxo complex, which is reduced to a peroxo complex by a second superoxide ion. In both mechanisms, the peroxo ligands are protonated and dissoeiate to give hydrogen peroxide. 

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