[¹⁸O]‐Peroxides: Synthesis and Biological Applications

Abstract

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 1 O 2 , 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 [ 18 O]‐labeled 1 O 2 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 1 O 2 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 [ 18 O]‐labeled 1 O 2 generators.

Type I and Type II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways

“…That is, we do not account for species formed in type I and type II reactions as interim products, which lack high enough stability downstream as quantifiable end points. One example is photogenerated hydroperoxides (,) that can subsequently react and produce 1 O 2 in the dark via Russell rearrangements. Superoxide can also dismutate biologically to form H 2 O 2 and 1 O 2 in a secondary reaction.…”

Oxidatively Generated Damage to Cellular DNA by UVB and UVA Radiation,

“…One‐electron oxidation reactions give rise directly or indirectly after hole transfer within the DNA chain to the predominant formation of modified guanine lesions including 8‐oxoGua and FapyGua without, however, DNA cleavage . Investigations using a suitable derivatized naphthalene endoperoxide as a chemical source of 1 O 2 have shown that the latter ROS reacts in a highly specific way with the guanine moiety of both isolated and cellular DNA to produce exclusively 8‐oxoGua according to a Diels‐Alder [2 + 4] cycloaddition mechanism (Fig. ) without inducing detectable amounts of strand breaks .…”

31P NMR Evidence for Peroxide Intermediates in Lipid Emulsion Photooxidations: Phosphine Substituent Effects in Trapping

“…Because of the use of Intralipid in photodynamic therapy (PDT) and its tissue‐simulating properties , there is interest in the reactivity of its alkene bonds with reactive oxygen species (ROS), particularly singlet oxygen ( 1 O 2 ). Current knowledge of 1 O 2 reactivity is limited to constituents of such as the individual fatty acids and alkenes, and membranes rather than the Intralipid emulsions themselves. Intralipid emulsions consist of soybean oil alkenes and polyenes, egg yolk phospholipids, glycerin and water.…”

“…The potential for O ‐atom trapping of photooxidized Intralipid samples is yet unexplored. We envisioned that Intralipid photoperoxides likely exist because membrane photoperoxides exist . We sought to develop an Intralipid peroxide trapping process.…”