1,3-Diene Probes for Detection of Triplet Carbonyls in Biological Systems

Abstract

Electronically excited triplet carbonyls are formed during the oxidative degradation of polyunsaturated fatty acids, amino acids, and beta-dicarbonyl metabolites. Due to their long lifetime and high alkoxyl radical-like reactivity, triplet carbonyls may initiate deleterious reactions in biological systems. Here we study the quenching properties of conjugated dienes, specifically 2,4-hexadienoate (sorbate) and its alkyl ester, on triplet acetone generated chemically (thermolysis of tetramethyl-1,2-dioxetane) or enzymatically (horseradish peroxidase-catalyzed aerobic oxidation of isobutanal). Triplet acetone quenching rates were near diffusion control ( k q = 10 (8)-10 (9) M (-1) s (-1)) and accompanied by diene cis-trans isomerization. None of the dienes displays antioxidant activity in classical systems known to generate reactive oxygen species: superoxide anion radical, hydroxyl radical, alkoxyl and alkylperoxyl radicals, or singlet oxygen. Experiments with model systems used widely to study lipid peroxidation showed that sorbate can inhibit mitochondrial swelling induced by enzymically formed triplet benzophenone and quench the chemiluminescence of microsome preparations challenged with iron and ascorbate. Altogether, our data indicate that conjugated dienes can be used as specific quenchers of triplet carbonyls formed in biological systems during oxidative stress. Moreover, they suggest that the well-known food preservative properties of sorbate may be due to its triplet carbonyl quenching activity.

Unanticipated role of melanin in causing carcinogenic cyclobutane pyrimidine dimers

“…2 Furthermore, indisputable evidence of excited triplet carbonyls came from inhibition of dark CPDs in the presence of sorbate, a specific quencher of triplet energy. 9 Addition of 9,10-dibromoanthracene-2-sufonate (DBAS), which diverts the energy of excited triplets to luminescence, 9 also reduced the number of dark CPDs. Moreover, cell-free oxidation of synthetic melanin with peroxynitrite, or with hydrogen peroxide and peroxidase, generated ultraweak chemiluminescence.…”

Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure

“…The lifetime of triplet carbonyls is ~10 μs (24), so a signal persistent over the course of hours indicates ongoing creation. To test whether this triplet state is required for dark CPD, we added ethyl sorbate, a specific quencher of triplet states (26), to intact melanocytes after UVA exposure. We found that this treatment prevented production of dark CPD (Fig.…”

Fontes vegetais naturais de antioxidantes

“…É interessante notar que espécies carbonílicas no estado triplete, produzidas na termólise de dioxetanos e dismutação de radicais alcoxilas e peroxilas, formadas com altos rendimentos durante a peroxidação lipídica e outras oxidações biológicas, têm sido negligenciadas na literatura apesar de, in vitro, terem exibido reatividade similar à de radicais alcoxila. 5,6 Espécies reativas são formadas continuamente durante os processos metabólicos -normais ou patogênicos -ou são provenientes de fontes exógenas físicas e químicas. Tais espécies atuam como mediadores da transferência de elétrons e em vários processos bioquímicos, 7 como a fagocitose, fenômeno em que espécies reativas de oxigênio, H 2 O 2, ClO − e 1 O 2 *, são produzidas para eliminar o agente agressor por oxidação.…”