Gamma radiolysis of thymine in oxygen-free aqueous solution in the presence of electron affinic radiosensitizers: identification of stable products.
Radiosensitizers react with nucleic radicals by addition and by electron transfer reactions. We report the steady-state gamma radiolysis of 1 mM thymine in oxygen-free aqueous solutions containing different classes of radiosensitizing drugs: N-oxyl-free radicals (TAN and TMPN), quinones (menadione and naphtoquinone), nitroheterocyclic compounds (metronidazole and 5-nitro-2-furoic acid) and N-ethylmaleimide. Two classes of thymine degradation products were isolated by thin-layer chromatography and characterized by spectroscopic measurements. The main products, irrespective of radiosensitizers, resulting from oxidation reaction were identified as the cis and trans isomers of 5,6-dihydroxy-5,6-dihydrothymine, N-pyruvyl-N'-formylurea, 6-hydroxy-5,6-dihydrothymine and 5-hydroxy-5,6-dihydrothymine. In the experimental conditions used only N-oxyls and to a lesser extent NEM reacted with 5-hydroxy-5,6-dihydrothymin-6-yl radical, giving stable covalently-bonded addition products with a high yield. TAN showed a higher binding ability with respect to TMPN, which is in good agreement with the rate-constants previously reported for these bimolecular reactions.
D003497:Cyclic N-Oxides; D005033:Ethylmaleimide; D005720:Gamma Rays; D008795:Metronidazole; D009285:Naphthoquinones; D009581:Nitrofurans; D010100:Oxygen; D011838:Radiation-Sensitizing Agents; D013941:Thymine / Q000528:radiation effects*; D014216:Triacetoneamine-N-Oxyl; D014812:Vitamin K
D003497:Cyclic N-Oxides; D009285:Naphthoquinones; D009581:Nitrofurans; D011838:Radiation-Sensitizing Agents; D014812:Vitamin K; D008795:Metronidazole; D014216:Triacetoneamine-N-Oxyl; D005033:Ethylmaleimide; D013941:Thymine; D010100:Oxygen