[18O]‐Peroxides: Synthesis and Biological Applications

The peroxidation reactions of the main cellular targets including nucleic acids, proteins and unsaturated lipids have received major attention during the last two decades. This was particularly the case for the hydroperoxides generated by 1O2, one of the main reactive oxygen species that usually oxidizes biomolecules in a more specific way than either •OH or one-electron oxidants. Most of the endoperoxides and hydroperoxides produced by 1O2 have been shown to be unstable and therefore their identification is often difficult. The use of [18O]-labeled 1O2 released from thermolabile endoperoxides in association with HPLC-ESI-MS/MS analysis provides a highly suitable way to gain relevant mechanistic insights into the formation and the decomposition pathways of initially generated peroxidic compounds. The possibility of cell penetration afforded by suitable naphthalene endoperoxides has also been exploited for investigating the reaction of 1O2 with DNA for accrediting the mechanism of oxidation of guanine in the nucleus and providing an elegant approach for assessing the validity of DNA isolation methods used in the measurement of 8-oxo-7,8-dihydroguanine, an ubiquitous oxidation product. Further developments are expected both in mechanistic studies and applications in cells using [18O]-labeled 1O2 generators. Keywords: [18O]-Peroxides; hydroperoxides; [18O]-labeled singlet molecular oxygen; mass spectrometry; [18O]-labeled molecular oxygen; naphthalene endoperoxides; DNA; protein; cardiolipin; lipid