Singlet molecular oxygen generated from lipid hydroperoxides by the Russell mechanism:: Studies using 18O-labeled linoleic acid hydroperoxide and monomol light emission measurements

The decomposition of lipid hydroperoxides into peroxyl radicals is a potential source of singlet oxygen (O-1(2)) in biological systems. We report herein on evidence of the generation of O-1(2) from lipid hydroperoxides involving a cyclic mechanism from a linear tetraoxide intermediate proposed by Russell. Using O-18-labeled linoleic acid hydroperoxide (LA(18)O(18)OH) in the presence of Ce4+ or Fe2+, we observed the formation of O-18-labeled O-1(2) ((18)[O-1(2)]) by chemical trapping Of O-1(2) with 9,10-diphenylanthracene (DPA) and detected the corresponding O-18-labeled DPA encloperoxide (DPA(18)O(18)O) by high-performance liquid chromatography coupled to tandem mass spectrometry. Spectroscopic evidence for the generation Of O-1(2) was obtained by measuring (i) the dimol light emission in the red spectral region (lambda > 570 nm); (ii) the monomol light emission in the near-infrared (IR) region (lambda = 1270 nm); and (iii) the quenching effect of sodium azide. Moreover, the presence of O-1(2) was unequivocally demonstrated by the direct spectral characterization of the near-IR light emission. For the sake of comparison, O-1(2) deriving from the H2O2/OCl- and H2O2/MoO42- systems or from the thermolysis of the endoperoxide of 1,4-dimethylnaphthalene was also monitored. These chemical trapping and photoemission properties clearly demonstrate that the decomposition of LA(18)O(18)OH generates (18)[O-1(2)], consistent with the Russell mechanism and pointing to the involvement of O-1(2) in lipid hydroperoxicle mediated cytotoxicity.