80106-09-8Relevant articles and documents
Shapiro,Rohl
, p. 448,453 (1968)
Role of nitrite on nitration of 2′-deoxyguanosine by nitryl chloride
Chen, Hauh-Jyun Candy,Wang, Tze-Fan,Chen, Yuan-Mao
, p. 275 - 281 (2007/10/03)
Nitryl chloride and peroxynitrite are reactive nitrogen species generated by activated phagocytes against invading pathogens during infections and inflammation. In our previous report, formation of 8-nitroxanthine and 8-nitroguanine was observed in reaction of 2′-deoxyguanosine or calf thymus DNA with nitryl chloride generated by mixing hypochlorous acid (HOCl) with nitrite (NO2-). The present study investigates factors controlling the yields of 8-nitroxanthine and 8-nitroguanine formation in nitration of 2′-deoxyguanosine by nitryl chloride. We found that the yields of 8-nitroxanthine and 8-nitroguanine in reaction of 2′- deoxyguanosine with nitryl chloride were highly dependent on the ratio of NO2- versus HOCl concentration. The yields of 8-nitroxanthine and 8-nitroguanine reached a plateau when the ratio of NO 2- versus HOCl concentration was higher than 2. A possible mechanism was postulated to explain this observation. While 8-nitroguanine is not stable in the presence of peroxynitrite, 8-nitroxanthine is sensitive to HOCl. The stability of these two nitrated adducts might be a factor on their final yields in this reaction. Since HOCl is produced by neutrophils at sites of inflammation where the level of NO2- is elevated, it is conceivable that nitryl chloride contributes to DNA base nitration in vivo, forming 8-nitroxanthine and 8-nitroguanine.
Analysis of peroxynitrite reactions with guanine, xanthine, and adenine nucleosides by high-pressure liquid chromatography with electrochemical detection: C8-nitration and -oxidation
Sodum, Rama S.,Fiala, Emerich S.
, p. 438 - 450 (2007/10/03)
Peroxynitrite, the reaction product of nitric oxide and superoxide anion, and a powerful oxidant, was found to nitrate as well as oxidize adenine, guanine, and xanthine nucleosides. A highly sensitive reverse-phase HPLC method with a dual-mode electrochemical detector, which reduces the nitro product at the first electrode and detects the reduced product by oxidation at the second electrode, was applied to detect femtomole levels of 8-nitroguanine and 8-nitroxanthine. This method was used to separate and identify the products of nitration and oxidation from the reactions of nucleosides with peroxynitrite. Peroxynitrite nitrates deoxyguanosine at neutral pH to give the very unstable 8-nitrodeoxyguanosine, in addition to 8-nitroguanine. 8-Nitrodeoxyguanosine, with a half-life of ～10 min at room temperature and ≤3 min at 37 °C, hydrolyzes at pH 7 to 8-nitroguanine. A decrease in the reaction pH resulted in a decrease in the level of C8-nitration. Peroxynitrite also oxidizes deoxyguanosine in a pH-dependent manner, to give 8-oxodeoxyguanosine with a maximum yield (0.5-0.7%) at pH 5. Guanosine and xanthosine exhibit reactivity similar to that of deoxyguanosine toward peroxynitrite at neutral pH, producing only the corresponding 8-nitronucleosides as well as 8-nitroguanine and 8-nitroxanthine, respectively. 8-Nitroguanosine at pH 7, with a half-life of several weeks at 5 °C and 5 h at 37 °C, was much more stable than 8-nitrodeoxyguanosine. C8-nitration was confirmed by dithionite reduction to the corresponding amino nucleosides, which cochromatographed with synthesized 8-amino nucleoside standards. In contrast to guanine nucleosides, adenine nucleosides undergo peroxynitrite-mediated C8 oxidation even at neutral pH to give the corresponding 8-oxoadenine nucleosides in ～0.3% yield. Adenine nitration, though minor compared to C8-oxidation, appears to occur at both C2 and C8 positions of the adenine ring. Lowering the reaction pH from 7 to 5 results in 2.4- and 2.2-fold increases in the yields of 8-oxo-dA and 8-oxo-Ado, respectively, but the level of nitration is not altered.
