Singlet molecular oxygen: generation, reactivity, identification and biological effects

Electronically excited singlet molecular oxygen ((1)O2)) is of great importance in chemical and biological systems due to its high reactivity and involvement in physiological and pathological processes. It is a simple and useful reagent in organic synthesis of peroxides, endoperoxides, hydroperoxides, and dioxetanes. In biological systems, (1)O2 has been implicated in: i) Defense mechanisms of living organisms such as phagocytosis; ii) degradative oxidation of endogenous hallucinogens; iii) hormonal activity of prostaglandins; iv) photochemotherapy utilizing the photodynamic action of synthetic dyes; v) photosensitivity to drugs like chlorpromazine and vi) inborn errors of metabolism exemplified by erythropoietic porphyria. The high reactivity of (1)O2 with unsaturated compounds, sulfides and amines arises from its high electrophilicity and relatively long lifetime (2-4 ms in H2O and ~700 ms in CCI4). Thus, biological targets for (1)O2 having the above functional groups include unsaturated fatty acids, proteins, and DNA. Extensively conjugated biomolecules such as carotenoids act as chemical and physical quenchers of (1)O2 and hence provide protective mechanisms against the deleterious effects of this excited state of molecular oxygen. However, due to the difficulties involved in obtaining (1)O2 free from other reactive contaminants, there is a paucity of detailed studies on the mentioned aspects of (1)O2 biochemistry. Chemical and dye-sensitized photophysical methods are available to prepare (1)O2. The aim of this work is to give a general view on (1)O2 with regard to its chemical generation, reactivity with biologically important compounds, detection and its role in biological systems.

Enolizable carbonyl and imino metabolites may act as endogenous sources of reactive oxygen species

Highly reactive oxyradicals and electronically excited triplet carbonyls can be generated in vitro by iron complexes and heme enzyme-catalyzed aerobic oxidation of synthetic or naturally occurring substances capable of enolization in aqueous medium. Monoenols and enamines, obtained by (alpha-methyne-carbonyl and -imine enolization, undergo dioxygen insertion and ultimately originate triplet species; e.g., isobutanal, 3-methylacetoacetone, Schiff bases. In turn, (alpha-hydroxy- and (alpha-aminocarbonyls (e.g., carbohydrates, 5-aminolevulinic acid) tautomerize to enediols and enolamines and yield oxyradicals, initiated by electron transfer to dioxygen, as polyphenols (e.g., 6-hydroxydopamine) and polyphenolamines do. Free radicals and excited species have been implicated in several normal and pathological processes. We here briefly review our contributions to this research area, emphasizing a possible in vivo prooxidant role for 5-aminolevulinic acid, the heme precursor accumulated in several porphyric disorders (e.g., lead poisoning, acut intermittent porphyria, tyrosinosis).