Metal-hydroperoxo species

Transition metal hydroperoxo species are well established as important intermediates in the oxidation of hydrocarbons (8,70,71). As they relate to the active oxygenating reagent in cytochrome P-450 monooxygenase, (porphyrin)M-OOR complexes have come under recent scmtiny because of their importance in the process of (poiphyrin)M=0 formation via 0-0 cleavage processes (72-74). In copper biochemistry, a hydroperoxo copper species has been hypothesized as an important intermediate in the catalytic reaction of the copper monooxygenase, dopamine P-hydroxylase (75,76). A Cu-OOH moiety has also been proposed to be involved in the disproportionation of superoxide mediated by the copper-zinc superoxide dismutase (77-78). Thus, model Cun-OOR complexes may be of... 

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... 

Akita and coworkers established a dehydrative condensation procedure, starting from hydroxo metal precursors containing the hydrotris(3,5-diisopropylpyrazolyl) borato ligand, and they were able to obtain dinuclear (/r-peroxo)Pd complexes, as indicated in Scheme 4. With the same procedure peroxo and hydroperoxo species (for Pd and Rh) and alkyl peroxides (for Mn, Co, Ni and Pd) complexes may be obtained. 

Metal(V) species derived from the complexes in Table I are rare. In fact, only one such species, L1Cr(V) (presumably a dioxo or hydro-oxo species), has been observed and characterized by ESR and UV-visible spectroscopies (45,69), Figs. 5 and 6. This Cr(V) species, which has a lifetime of several seconds at room temperature, was generated from a hydroperoxo precursor by an intramolecular transformation that closely resembles the proposed, but so far unobserved step in the chemistry of cytochrome P450, whereby the hydroperoxoiron(III) is transformed to the FeIV(P + ) form also known as oxene (P += porphyrin radical cation). All the steps in Scheme 1 for the L1Cr(H20)2+/02 reaction have been observed directly (45,69). 

Hydroperoxo species intervene as reactive species in the Group VIII metal-catalyzed oxidation of alkenes by 02 or H202. 

The metal peroxo complexes are equivalent through addition of water across the 0-0 bond to form hydroxo hydroperoxo species (Figure 2.27). 

The Tpx ligands can mimic the coordination environment created by three imidazolyl groups from histidine residues, which is frequently found in the active sites of metalloenzymes. Higher valent bis(ix-oxo) species, [(Tpx)M( i-0)2M(Tpx)] via 0-0 cleavage of [(Tpx)M( x-r 2 r 2-02)M(Tpx)] intermediates, but also peroxo, hydroperoxo, and alkylperoxo species, active species undergoing oxidative C-C cleavage reaction, stable hydrocarbyl complexes, and dinuclear xenophilic complexes, [(Tpx)M-M L71], are all relevant to chemical and biological processes, most of which are associated with transition metal catalytic species. 

Thus a non-diffusible species such as Cu -hydroperoxo species can be generated as in Eq. (26) in Fig. 16 by Cu complexes in the presence of O2 and an electron (by first fixation of O2 on the metal center then reduction or by reaction with a beforehand-formed superoxide anion). This intermediate... 

The most notable reaction is that of metal-oxygen species with substrate. In the case of heme iron monooxygenases, high-valent iron-oxo species such as 3 or 4 in Fig. 5 are believed to react with substrates. On the other hand, both hydroperoxo (2) and 0x0 (3) are proposed for reactions by nonheme iron oxygenases. There are discussions on whether the iron-oxo species (3) is stabilized in the nonheme oxygenases in the absence of a porphyrin ligand which is effective to form 4. However, the iron-oxo species is attractive for explanation of the results obtained by monooxygenations by nonheme model iron systems. 

The conversion of hydroperoxide/peroxide to superoxide is a one-electron redox reaction and requires the presence of transition metals having accessible multiple oxidation states as in biological iron or manganese clusters (e.g., Fe(II, III, IV) clusters of monooxygenase or the Mn(II, HI, IV) clusters of photosystems). Ti is usually not reduced at ambient temperatures. The various possibilities that could facilitate the transformation of hydroperoxo/peroxo to superoxo species are as follows ... 

The first step consists of the formation of the dioxygen adduct which can have either a superoxo structure (1) if the metal is a potential one-electron donor, or a peroxo structure (2) if the metal is a potential two-electron donor. These superoxo or peroxo complexes can be considered as the formal, but not chemical, analogs of the superoxide 02 and peroxide 022- anions. The superoxo complex (1) can further react with a second reduced metal atom to give the /x-peroxo species (3), which can cleave itself into the oxo species (4), which may be hydrolyzed to give the hydroxo species (6) or react with a second metal atom to give the p.-oxo species (5). The alkylperoxo (7) and hydroperoxo (8) species can result from the alkylation or protonation of the peroxo species (2), or from anion exchange from metal salts by alkyl hydroperoxides or hydrogen peroxide. 

Hydroperoxo complexes are prepared75 by protonation of peroxo complexes, by insertion of dioxygen into metal-hydrogen bonds, by hydrogen abstraction by metal dioxygen complexes, by reduction of superoxo complexes or by reaction of the metal ion with hydrogen peroxide. Well-defined stable species have been characterized for Cu,76 Ir, Pt, and other metals, for example, by syntheses of the type ... 

In the case of copper complexes, the chemistry is less well understood. High valent copper-oxo species are not likely to be formed, consequently copper-hydroperoxo or copper-hydroxo species are usually proposed as active species in DNA oxidation. These species are thus more susceptible to homo-lytic cleavage of the peroxide or the metal-hydroxo bond and consequently, to 1-electron oxidation mechanism. However, the labeling of the product of deoxyribose oxidation at Cl by Cu(l,10-phenanthroline)2 clearly demonstrated that these complexes can mediate a 2-electron oxidation mechanism of DNA damage since the oxygen atom incorporated in DNA originates from H2O. 

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