Radicals, oxygen trapping

The endoperoxy hydroperoxide (36) results from the hydroperoxide (35) by sequential peroxy radical generation, (>-exo trig cyclisation and oxygen trapping <96SL349>. 

Carotenoids are of physiological interest because some of them are precursors of vitamin A. They have been in the news recently because many exhibit radical or single oxygen trapping ability and as such have potential antioxidant activity in vivo. They may reduce the risk of cardiovascular disease, lung cancer, cervical... 

At low temperature, propene behaves like another alkene and undergoes a simple addition of a halogen across the double bond to form 1,2-dichlo-ropropane. These conditions minimize the possibility of forming chlorine atoms (chlorine free radicals), and the presence of oxygen traps the few that do form. However, when the conditions promote the formation of chlorine atoms, a substitution occurs to produce 3-chloropropene. 

Scheme 10.11 shows a PRE-mediated 5-exo-trig radical cyclisation in which the controlled thermal formation of active radicals from the dormant alkoxyamine 2 is facilitated by steric compression of the alkoxyamine C—O bond by the bulky N-alkyl and O-alkyl groups [8]. Intramolecular H-bonding between a —CH2—OH and the nitroxyl oxygen of the incipient nitroxide in a six-membered cyclic transition structure further facilitated the dissociation of 2. After cyclisation, the resultant primary cyclopentylmethyl radical was trapped by the free nitroxide to form the new dormant isomerised alkoxyamine 3, which is more stable than 2 since the O-alkyl is now primary. The same reaction using TEMPO as the nitroxide component did not work presumably because the C—O bond in the alkoxyamine precursor is much stronger. 

MPTP decreases glutathione levels and increases the levels of reactive oxygen species and the degree of lipid peroxidation in mouse brain slices in vitro and increases the levels of reactive oxygen species in mouse brain in vivo. MPTP neurotoxicity in vitro is reduced by glutathione. In vitro studies have shown that MPP neurotoxicity can be reduced by vitamin E, vitamin C, coenzyme Q, and mannitol (but not by superoxide dismutase, catalase, allopurinol, or dimethyl sulfoxide). P-Carotene, vitamin C, and /V-acctylcystcine partially protect against the neurotoxic effects of MPTP in mice, as do nicotinamide, coenzyme Q, and the free-radical spin trap A-tert-butyl-a-(sulfophenyl) nitrone. 

These data suggest that oxygen is necessary for the solid-state photochemical reaction to occur. It was proposed that oxygen traps the metal radicals produced in the photolysis of the metal-metal bonds, thereby preventing radical recombination (eq. 25). If oxygen diffusion is rate limiting then... 

As previously mentioned, when hydrophilic free radicals are trapped by GSH, superoxide will act as a free radical sink and SOD should then behave as a terminal antioxidant [189]. The simultaneous presence of the two antioxidants will result in an optimal sparing effect on both GSH and oxygen consumptions in superoxide- or GS -dependent chain oxidations of metabolites or xenobiotics. 

Fig. 1. Two-compartment model to describe the metabolism of oxygen-derived free radicals in myocardial tissue. This figure depicts the progressive reduction of intracellular oxygen during the cycle of ischemia and reperfusion. Inhibitors of radical metabolism are shown in dashed boxes. Radical spin traps are shown in closed boxes.

In spite of the increased activities of SOD-1 and GPx and normal catalase activity, increased lipid peroxides in the blood plasma of DS patients have been reported (K10), as has as an increased accumulation rate of age pigments (i.e., lipofuscin and ceroid, known products of lipid peroxidation) (K9). In addition, an early study showed increased lipid peroxides in the cerebral cortex of DS fetal brains (B15). More recently, cortical neurons from fetal DS and age-matched normal brains were shown to differentiate normally early in cell cultures. However, DS neurons subsequently degenerated and underwent apoptosis, whereas the normal cells remained viable (B18). In addition, the DS neurons exhibited a three- to fourfold increase in reactive oxygen species and increased lipid peroxidation that preceded cell death. Importantly, DS neuron degeneration could be prevented by treatment with the free radical spin trap A-ferf-butyl-2-sulphophenylnitrone, the... 

Vice versa, siloxycarbenes have been generated as short lived intermediates by irradiation of acylsilanes [27-29]. Irradiation of matrix isolated acylsilanes 14c, e and f resulted both in the a-cleavage to give radical pairs and in the rearrangement to siloxycarbenes 13 [29]. Since the formation of these intermediates is reversible, the radical pairs and carbenes 13 could only be identified by oxygen trapping. 

Support for a free-radical mechanism for dextrinization is afforded by comparison of the processes conducted in air with those carried out under a neutral atmosphere and under vacuum. The absence of oxygen accelerates dextrinization, and thus, the overall process yielding dextrins is not merely oxidation furthermore, free radicals are trapped by molecular oxygen, a biradical. Pyrolysis of a-D-glucose at 300° to 1,4 3,6-dianhydro-f -D-... 

In another experiment, the irradiated sample was photobleached with IR radiation and then maintained at room temperature in the absence of oxygen until 90% of the radicals had decayed. If the sample was then re-irradiated, the maximum concentration of 4.2 x 1016 electron g 1 was restored after absorption of 3.0x1019 eVg-1. The decrease of the trapped electron concentration was thus assigned by Keyser et al. to a reaction of free radicals with trapped electrons. If the G value for alkyl radicals obtained by Waterman and Dole [214] for linear polyethylene at 77°K is used (G = 3.3), it can be calculated that the concentration of free radicals is 1.5 x 10-3 mole l-1 if the absorbed dose is 3 x 101 9 eV g-1. Scavenging of electrons in hydrocarbon glasses by biphenyl shows that, in this case, 1.5 x 10-3 mole l-1 biphenyl scavenges 50% of the ejected electrons [215]. 

---