Oxy Radical Intermediates

The second mechanism is due to Kozarich and co-workers [39] (Figure 11). The initial step here is the abstraction of a hydrogen atom from Cys419 by the glycyl radical, forming a transient thiyl radical. Addition of this thiyl radical to the keto group of the pyruvate results in the formation of a tetrahedral oxy-radical intermediate. This intermediate collapses into an acetylated cysteine and... 

The next step is the addition of the thiyl radical to the carbonyl carbon of pyruvate, yielding a tetrahedral oxy-radical intermediate. The calculated energy of this intermediate, relative to the free reactants, is +9.9 kcal/mol, and the barrier for its formation is calculated to 12.3 kcal/mol. The barrier for the dissociation of the radical intermediate into acetylated cysteine and formyl radical is calculated to be only 2.8 kcal/mol with an exothermicity of 3.9 kcal/mol. Taken together, the total reaction ... 

Figure 13. Formation and collapse of the tetrahedral oxy-radical intermediate. Optimized structures for A) transition state of the thiyl radical addition to pyruvate (TSl), B) tetrahedral oxy-radical intermediate, and C) transition state of the dissociation of formyl radical (TS2). The energies of these species are 12.3 kcal/mol, 9.9 kcal/mol, and 12.7 kcal/mol, respectively, relative the energy of (methylthiyl + pyruvic acid).

To move the acetyl group homolytically between the cysteines has a computed barrier of quite reasonable 11.6 kcal/mol. In Figure 15, the transition state structure for this reaction is presented. This thermoneutral occurs without the intermediacy of tetrahedral oxy radical intermediate. 

Scheme 25 Ring expansion to 2-(5i3)-furanone induced by oxy-radical intermediate [118]...

The deoxygenation of epoxides with the metal complexes mentioned above all seem to proceed via intermediate /i-melal oxy radicals. The reaction path after their trapping seems, however, to depend on the Lewis acidity of the ET reagent. 

As indicated in Scheme VII/32, cyclononanone (VII/165) is transformed into hydroperoxide hemiacetal, VII/167, which is isolated as a mixture of stereoisomers. The addition of Fe(II)S04 to a solution of VII/167 in methanol saturated with Cu(OAc)2 gave ( )-recifeiolide (VII/171) in quantitative yield. No isomeric olefins were detected. In the first step of the proposed mechanism, an electron from Fe2+ is transferred to the peroxide to form the oxy radical VII/168. The central C,C-bond is weakened by antiperiplanar overlap with the lone pair on the ether oxygen. Cleavage of this bond leads to the secondary carbon radical VII/169, which yields, by an oxidative coupling with Cu(OAc)2, the alkyl copper intermediate VII/170. If we assume that the alkyl copper intermediate, VII/170, exists (a) as a (Z)-ester, stabilized by n (ether O) —> <7 (C=0) overlap (anomeric effect), and (b) is internally coordinated by the ester to form a pseudo-six-membered ring, then only one of the four -hydrogens is available for a syn-//-elimination. [111]. This reaction principle has been used in other macrolide syntheses, too [112] [113]. 

Recently, Wahl and Orme-Johnson reported their studies on the characterization and mechanism of the pymvate flavodoxin (ferredoxin) oxidoreductase from Klebsiella pneumoniae and Clostridium thermoacetium (214). These oxi-doreductases appear to be closely related to that from C. acidiurici (215) in that the iron is present in two Fe4S4 clusters, which act as election acceptors in the catalytic mechanism. However the K. pneumoniae and C. thermoaceticum enzymes may be mechanistically distinct from the H. halobium oxidoreductase (213) in that free radical intermediates are not detected for the former enzymic reaction. EPR signals in the Klebsiella or C. thermoaceticum oxidoreductases are only observed in the fully reduced enzyme when the reductants dithionite or pyruvate and CoASH are present (214). The suggested mechanism for the pyruvate oxidoreductase from K. pneumoniae and C. thermoaceticum is initially similar to the mechanism for all TPP enzymes in that decarboxylation of pyra-vate leads to the formation of hydroxyethyl-TPP. Two one-electron transfers to each of the two Fe-S clusters occur on the binding of CoASH. However, the mechanism for the formation of acetyl-CoA from the hydroxyethyl-TPP intermediate and of the CoASH-induced electron transfers is not yet clear. 

They postulated that the initiating event was a radical addition of a hydroxyl (or lipid oxy) radical to the indole ring however, others (33, 34) have demonstrated that formation of a hydroperoxy group at carbon-3 of the indole ring was intermediate in the oxidation of indole derivatives by various oxidants. This latter pathway seems a more plausible route to the products observed by Yong et al. (32). Schaich and Karel... 

The decomposition reactions result in a number of unsaturated oxy-hydrocarbon intermediates and radical products, for which thermochemistry is not available. The Group Additivity method (GA) [2, 20] is a fast and reliable method to estimate or check the thermochemistry of unknown or large molecules. In this work we also develop a series of new groups (for use in group additivity (GA)) to aid our evaluation of enthalpies of formation for our system. 

Oxy radicals (RO) are important intermediates in all VOC oxidation chains. They are formed in the chain propagating channels of the reactions of RO2 radicals with NO and in the self-reactions of RO2. Three principal reaction pathways for RO radicals have been identified under atmospheric conditions ... 

As can be seen from Fig. 1 the oxidation of alkenes generally corresponds to the alkane oxidation. However, it has to be considered that in this case the chlorine atom, which is used as a primary oxidant, predominantly adds to the double bond. Therefore, chlorine containing intermediates are formed. However, as a consequence of the oxidation mechanism only -Cl oxy radicals are formed which are not expected to show significant deviations from the reactivity of their non-substituted analogues. In Table 2 the experimental results for alkenes are summarised when k 0>2) is fixed to 8 x 10 cmVs. 

There is good evidence for the existence of radical intermediates in this process. Treatment of the Mg/RX reaction mixture with the stable organic radical 2,2,6,6-tetramethylpiperidinyl-l-oxy (TEMPO, see structure below) results in high yields of a TEMPO-R adduct, strongly indicating the intermediacy of alkyl radicals ... 

The profiles of the curves are explained by the oxy-reduction interactions of the catalysts and with the radical intermediates. 

Matrix isolation was also used to identify the radical intermediates in the partial methanol oxidation reaction over a Pt/Si02 catalyst. Methyl peroxy radicals (CH3OO ) and methyl oxy radicals (CH3OO ) were discriminated between, based on their different stability to photolysis (142). By combining EPR and in situ IR spectroscopy, it was shown that the radical species form super equilibrium concentrations under reaction conditions at the platinum/support interface region (143). 

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