Singlet Molecular Oxygen Reactions with Nucleic Acids, Lipids, and Proteins

Singlet oxygen (O-1(2)) is a biologically relevant reactive oxygen species capable of efficiently reacting with cellular constituents. The resulting oxidatively generated damage to nucleic acids, membrane unsaturated lipids, and protein components has been shown to be implicated in several diseases, including arthritis, cataracts, and skin cancer. Singlet oxygen may be endogenously produced, among various possibilities, by myeloperoxidase, an enzyme implicated in inflammation processes, and also efficiently in skin by the UVA component of solar radiation through photosensitization reactions. Emphasis is placed in this Review on the description of the main oxidation reactions initiated by O-1(2), and the resulting modifications within key cellular targets, including guanine for nucleic acids, unsaturated lipids, and targeted amino acids. Most of these reactions give rise to peroxides and dioxetanes, whose formation has been rationalized in terms of [4+2] cycloaddition and 1,2-cycloaddition with dienes + olefins, respectively. The use of [O-18]-labeled thermolabile endoperoxides as a source of [O-18] -labeled O-1(2) has been applied to study mechanistic aspects and preferential targets of O-1(2) in biological systems. A relevant major topic deals with the search for the molecular signature of the O-1(2) formation in targeted biomolecules within cells. It may be anticipated that [O-18] -labeled O-1(2) and labeled peroxides in association with sensitive mass spectrometric methods should constitute powerful tools for this purpose.