Double dioxygenation

Fig. 4. Mono- and dihydroxylated derivatives of arachidonic acid, formed by single or double dioxygenation followed by reduction.

This enzyme has recently been isolated from the prostaglandin synthetase complex (775) and has three C-20 fatty acids as substrates similar to the C-18 substrates of lipoxygenases, but containing one, two or three extra non-conjugated cis double bonds (163). The overall transformation (eq. 41) resembles lipoxygenation, except that double dioxygenation occurs, giving an endo-peroxy hydroperoxide (163, 176). 

Reactivities of SLO-1 with various substrates other than linoleic acid have been reported. Bis-homo-y-linolenic acid (all-cw-8,l 1,14-eicosatrienoic acid) and arachidonic acid (all-cw-5,8,11,14-eicosatetraenoic acid) yield 15-hydroperoxy compound exclusively [257]. In the presence of a relatively high concentration of SLO-1, a double dioxygenation product, 8,15-dihydroperoxy-5,9,ll,13-eicosatetraenoic acid, is formed from arachidonic acid [eq. (18)] [225, 258]. The double dioxygenation of linoleic acid [246, 259] and a-linolenic acids has also been reported. In the latter case, the dioxygenation proceeds stepwise and the mono- and dihydroperoxy compounds are converted to 9(S),10- and 9(5), 16-dihydroxy products, respectively. 

The single and double dioxygenations of polyenoic fatty acids. The LOX activity is commonly abundant in higher plant species. Usual substrates of LOX are methylene-interrupted polyenoic fatty acids, in plants presumably linoleic and linolenic acids. Most of LOX act regio-and stereospecifically [1,2]. Like soybean LOX, many of plant enzymes convert linoleic and linolenic acids into corresponding 13(5)-hydroperoxides. At the same time, many plant tissues, in particular, potato tubers and tomatoes, possess the activity of 9-LOX. Such enzymes are able to form double hydroperoxide of a-linolenic acid via intermediary formation of 9(iS)-HPOT [3]. The double dioxygenation of linolenate occurs in potato tubers [3], rice and wheat seeds and in other tissues, exhibiting the 9-LOX activity. 

Recent work has revealed that lipoxygenases from some plant tissues oxidize a-ketols of a-linolenic acid to hydroperoxides of a-ketols [3]. This paper deals with the formation of similar products by the other way by hydroperoxide dehydration of double dioxygenation products. Incubation of 9-hydroxy-16-hydroperoxy-10( ),12(Z),14( )-[l-l C]octadecatrienoic acid with enzyme preparation from com seeds led to the formation of three polar metabolites. After RP- and SP-HPLC purifications two of these polar metabolites were identified by UV spectroscopy and electron-impact mass spectrometry as a- and y-ketols of 9-hydroxy derivative of a-linolenic acid 9,16-dihydroxy-15-oxo-I0(, 12(Z)-octadecadienoic acid and 9,12-dihydroxy-15-oxo-I0(jE, 13( )-octadecadienoic acid, respectively. Stmcture of the most polar metabolite is discussed. 

Recent work has demonstrated that hydroperoxides of a-ketols are formed from the corresponding hydroperioxide precursors by conversion of hydroperoxides into a-ketols and following lipoxygenase oxidation of a-ketols [3]. The present work has revealed that the similar metabolites (a- and y-ketols of hydroxy derivatives) may be formed from double dioxygenation products by dehydration of hydroperoxide groups and further hydrolysis of hydroxy allene oxides. 

Analysis Disregarding the remote and unhelpful double bond, we can disconnect as a 1,3-dioxygenated compound (frames 94-107). 

The hexamethylbenzene complex could be similarly deprotonated [54, 57] but the red complex obtained is then stable and its x-ray crystal structure could be recorded [55], showing a dihedral angle of 32° between the cyclohexadienyl plane and the exocyclic double bond (Fig. 5). This complex can also be cleanly obtained by the reaction of dioxygen with the 19e wostructural complex Fe CpfCgMeg) as shown in the preceding section. 

Representations showing electrons in molecules seem to suggest localisation of the valence electrons, but there are problematic issues in this regard. For example, we might ask if dioxygen has a double bond and two lone pairs on each O atom (as in Table 1.1) - a stmcture that does not reconcile with the paramagnetic nature of the substance - or a single bond and an odd number of electrons localised on each atom, as shown here ... 

Compared with monocyclic aromatic hydrocarbons and the five-membered azaarenes, the pathways used for the degradation of pyridines are less uniform, and this is consistent with the differences in electronic structure and thereby their chemical reactivity. For pyridines, both hydroxylation and dioxygenation that is typical of aromatic compounds have been observed, although these are often accompanied by reduction of one or more of the double bonds in the pyridine ring. Examples are used to illustrate the metabolic possibilities. 

Bimolecular and Trimolecular Reactions of Dioxygen with the Double Bond of Olefin... 

Radicals also exhibit high activity in addition reactions. For example, the peroxyl radical of oxidizing styrene adds to the double bond of styrene with the rate constant k = 68 Lmol-1 s-1, and dioxygen adds with k = 5.6x 10-10Lmol-1 s-1 (298 K). As in the case of abstraction reactions, the distinction results from the fact that the first reaction is... 

The reactions of nitrogen dioxide addition to the double bond of olefins occur much more rapidly. However, this reaction is reversible and, hence, the formed radical is stabilized due to the addition of the dioxygen molecule ... 

In addition to the reaction with the C—H bond, dioxygen attacks the double bond of olefin with free radical formation [9]. 

The bimolecular addition of dioxygen to the double bond of nonsaturated ester. This reaction seems to be preceded by CTC formation. 

Free radical formation in oxidized organic compounds occurs through a few reactions of oxygen bimolecular and trimolecular reactions with the weakest C—H bond and double bond (see Chapter 4). The study of free radical generation in polymers (PE, PP) proved that free radicals are produced by the reaction with dioxigen. The rate of initiation was found to be proportional to the partial pressure of oxygen [6,97]. This rate in a polymer solution is proportional to the product [PH] x [02]. The values of the apparent rate constants (/ti0) of free radical formation by the reaction of dioxygen (v 0 = k 0[PH][O2]) are collected in Table 13.8. 

The oxidation of PIB occurs mainly via intramolecular addition of dioxygen to double bonds of polymer. The reaction of peroxyl radical addition to the phenoxyl radical leads to the formation of quinolide peroxide (see Chapter 15). This peroxide is unstable, and its decomposition provokes the degradation of PIB. Another reaction predominates in case of aromatic diamine. 

A less common reactive species is the Fe peroxo anion expected from two-electron reduction of O2 at a hemoprotein iron atom (Fig. 14, structure A). Protonation of this intermediate would yield the Fe —OOH precursor (Fig. 14, structure B) of the ferryl species. However, it is now clear that the Fe peroxo anion can directly react as a nucleophile with highly electrophilic substrates such as aldehydes. Addition of the peroxo anion to the aldehyde, followed by homolytic scission of the dioxygen bond, is now accepted as the mechanism for the carbon-carbon bond cleavage reactions catalyzed by several cytochrome P450 enzymes, including aromatase, lanosterol 14-demethylase, and sterol 17-lyase (133). A similar nucleophilic addition of the Fe peroxo anion to a carbon-nitrogen double bond has been invoked in the mechanism of the nitric oxide synthases (133). 

This enzyme catalyzes the NADPH- and dioxygen-dependent insertion of cis double bonds into the methylene region of fatty acyl structures covalently attached to the phosphopantetheine portion of an acyl carrier protein. 

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