Mono-oxygenase model

Role of Ascorbic Acid in a Mono-oxygenase Model (Udenfriend s System)... 

J. Razenberg, A. W. Vandermade, J. W. H. Smeets, R. J. M. Nolte, Cyclohexene epoxidation by the mono-oxygenase model (tetraphenylporphyrinato)manganese(in) acetate-sodium hypochlorite, J. Mol. Catal. 31 (1985) 271. 

Iley, J., L. Constantino, F. Norberto, and E. Rosa (1990). Oxidation of the methyl groups of N,N-dimethylbenzamides by a cytochrome P450 mono-oxygenase model system. Tetrahedron Lett. 31,4921 922. 

More recently, research concerning catalytic oxidation reactions has emerged on one side from bioinorganic chemistry with cytochrome P450 models and non-por-phyrinic methane mono-oxygenase models, and on the other side, from organic chemistry with asymmetric epoxidation and dihydroxylation. 

This mechanism represents a shortcut in biological mono-oxygenase enzyme systems that use O2 as oxygen atom sources and whose mechanism is much more complex because of the requirement to cleave O2. Non-porphyrinic binuclear methane mono-oxygenase model complexes are also able to activate methane in the same way (see Chap. 19). When S = RH, Groves originally proposed the well-known rebound mechanism in which the Fe =0 species removes an H atom from RH, then transfers OH to produce the alcohol ROH ... 

Copper enzymes are involved in reactions with a large number of other, mostly inorganic substrates. In addition to its role in oxygen and superoxide activation described above, copper is also involved in enzymes that activate methane, nitrite and nitrous oxide. The structure of particulate methane mono-oxygenase from the methanotrophic bacteria Methylococcus capsulatus has been determined at a resolution of 2.8 A. It is a trimer with an a3P33 polypeptide arrangement. Two metal centres, modelled as mononuclear and dinuclear copper, are located in the soluble part of each P-subunit, which resembles CcOx subunit II. A third metal centre, occupied by Zn in the crystal, is located within the membrane. 

Atom Transfer Reactions. The apparent catalysis of the auto-oxidation of triphenylphos-phine by (Ph3P)2Pt02 aroused considerable interest as a possible model for enzymatic mono-oxygenase reactions. This reaction was recently reinvestigated by Halpem and Sen who showed that intramolecular oxygen transfer does not occur. The reaction takes place via coordination of free phosphine to the platinum followed by loss of H2O2 or HO2 which can react with free phosphine. The Pt(II) species can be reduced to Pt(0) and may react with molecular oxygen. The reaction of triphenylphosphine with dioxo-... 

J. R. Lindsay Smith, D. N. Mortimer, The oxidation of organic compounds with lodosylbenzene catalysed by tetra(4-N-methylpyridyl)porphyrinatoiron(III) pentacation A polar model system for the cytochrome P450 dependent mono-oxygenases, J. Chem. Soc. Chem. Commun. (1985) 410. 

N. Kitajima, H. Fukui, Y. Morooka, A model for methane mono-oxygenase Dioxygen oxidation of alkanes by use of a /e-oxo binuclear iron complex, ]. Chem. Soc. Chem. Commun. (1988) 485. 

A recent summary25 of the activation of O2 by cytochrome P-450 (an iron(III)-heme protein with a axial cysteine thiolate ligand) concludes that the reactive form of this mono-oxygenase also contains an oxene-ferryl group (RS)(por)FeV=O. The mono-oxygenase chemistry of cytochrome P-450 has been modeled via the use of (TPP)Fei lCl(TPP=tetraphenylporphyrin) and (OEP)Fe JCl (OEP=octaethylporphyrin) with peracids,26,27 iodosobenzene,26,27... 

Table 6-4 Mono-oxygenation and Dehydrogenation of Organic Substrates via a Model System for the Cytochrome P-450 Mono-oxygenase/Reductase Enzymes"...

Cytochrome P-450, which is the most extensively studied of the mono-oxygenase proteins, has a heme-iron active center with an axial thiol ligand (a cysteine residue). However, most chemical-model investigations s ugg simple iron(III) porphyrins without thiolate ligands. As a result, model mechanisms for cytochrome P-450 invoke a reactive intermediate that is formulated to be equivalent to Compound I of horseradish peroxidase, (por+ )Fe =O, with a high-potential porphyrin cation radical. Such a species would be reduced by thiolate, and therefore is an unreasonable formulation for the reactive center of cytochrome P-450. 

M at 35°C (73, 74). The dioxygen adducts react with added substrates such as benzene, toluene, and anisole to produce hydroxylated products of organic substrates, except with nitrobenzene. This suggests that the activated O2 species has an electrophilic character (73). The dioxygen adducts of Ni(II) complexes are proposed as the models of mono-oxygenase because the complexes are able to activate the dioxygen. 

The classical endo-exo deconstruction model of pure cellulose is undergoing revision in light of the recent discovery of a family of copper-dependent polysaccharide mono-oxygenases from the GH61 family (Table 4.1) (Harris et al., 2010 Quinlan et al., 2011). These enzymes represent a novel mechanism to deconstruct cellulose in that they cleave cellulose oxidatively, unlike traditional acid/base catalyzed enzyme systems. Family GH61 enzymes can also provide powerful synergistic benefits to cocktails of traditional GH5, GH6, and GH7 enzyme mixtures (Harris et al., 2010). 

Carbonyl oxides e.g. (8), produced via singlet oxygen oxidation of diazo-compounds, can epoxidize olefins. It is considered that such intermediates can serve as useful chemical models for the mono-oxygenase enzymes. 

Thus, as in the case of alkenes in the preceding chapter, we start with the radical type of activation that is much older. Transition-metal compounds play a key role in radical activation, because they provide very strong oxidants that can oxidize hydrocarbons either by (reversible) electron transfer or H-atom transfer (more rarely by hydride transfer). Biological oxidation of hydrocarbons involves reactive metal-0X0 species in methane mono-oxygenases and many related synthetic models, and a number of simple metal-oxo complexes also work. The clear criterion of distinction between an organometallic C-H activation and a radical activation is the above selectivity in activated C-H bonds. 

Interaction of dioxygen species with Fe aq and with Fe " aq has been very briefly reviewed. In relation to 0x0-, peroxo-, and superoxo-complexes as models for intermediates in oxygenase activity, a brief report on a 2000 symposium on activation of oxygen summarizes the then-current situation in the search for a mechanism common to mono- and dinuclear iron sites, mono- and dinuclear copper sites, and copper-iron sites. The outline proposals comprise ... 

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