168701-80-2Relevant articles and documents
Role of nitrite on nitration of 2′-deoxyguanosine by nitryl chloride
Chen, Hauh-Jyun Candy,Wang, Tze-Fan,Chen, Yuan-Mao
, p. 275 - 281 (2002)
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.
8-Nitroxanthine, an adduct derived from 2′-deoxyguanosine or DNA reaction with nitryl chloride
Chen, Hauh-Jyun Candy,Chen, Yuan-Mao,Wang, Tze-Fan,Wang, Kuang-Sian,Shiea, Jentaie
, p. 536 - 546 (2001)
Activated phagocytic cells generate reactive nitrogen species, including nitryl chloride and peroxynitrite, for host defense against invading pathogens. It has been proposed that these reactive nitrogen species may cause DNA damage and thus contribute to the multistage carcinogenesis process associated with chronic infections and inflammation. Previous studies showed that peroxynitrite reacted with guanine, 2′-deoxyguanosine, or DNA forming 8-nitroguanine. We herein report formation of 8-nitroxanthine as the major nitration product in reactions of 2′-deoxyguanosine or calf thymus DNA with nitryl chloride produced by mixing nitrite with hypochlorous acid, and 8-nitroguanine was a minor product in these reactions. 8-Nitroxanthine was characterized by its NMR and laser desorption ionization mass spectra and by deamination of 8-nitroguanine. Formation of 8-nitroxanthine was also detected by xanthine reaction with various reactive nitrogen species, including nitryl chloride, peroxynitrite, nitronium tetrafluoroborate, and heated nitric and nitrous acid. The identity of 8-nitroxanthine in nitryl chloride-treated dG and DNA was confirmed by co-injection with synthetic 8-nitroxanthine and by its reduction to 8-aminoxanthine. Levels of 8-nitroxanthine and 8-nitroguanine in these reactions were quantified by reversed-phase HPLC with photodiode array detection. Once formed, 8-nitroxanthine was spontaneously removed from DNA with a half-life of 2 h at 37 °C and pH 7.4. Therefore, 8-nitroxanthine might be an important DNA lesion derived from reactive nitrogen species in vivo.
Base modification and strand breakage in isolated calf thymus DNA and in DNA from human skin epidermal keratinocytes exposed to peroxynitrite or 3- morpholinosydnonimine
Spencer, Jeremy P. E.,Wong, Jon,Jenner, Andrew,Aruoma, Okezie I.,Cross, Caroll E.,Halliwell, Barry
, p. 1152 - 1158 (1996)
Exposure of isolated calf thymus DNA and human skin epidermal keratinocytes to peroxynitrite or the peroxynitrite generator, 3- morpholinosydnonimine (SIN-1), led to extensive DNA base modification. Large increases in xanthine and hypoxanthine, possible deamination products of guanine and adenine, respectively, and in 8-nitroguanine were observed, but only small changes in some oxidized base products were seen. This pattern of damage suggests that hydroxyl radicals were not major contributors to base modification caused by peroxynitrite, as OH· is known to cause multiple oxidative modifications to all four DNA bases. Instead, it seems that reactive nitrogen species play a much greater role in the mechanism of base damage, producing both nitration and deamination of purine bases when DNA or whole cells are exposed to peroxynitrite. If this pattern of damage is unique to peroxynitrite, it might act as a marker of cellular damage by this species in vivo.
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 (2001)
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.
Nitration of 2′-deoxyguanosine by a NO/O2 gas mixture: Identification and characterization of N2-nitro-2′ -deoxyguanosine
Yamada, Masaki,Suzuki, Toshinori,Kanaori, Kenji,Tajima, Kunihiko,Sakamoto, Shunji,Kodaki, Tsutomu,Makino, Keisuke
, p. 3173 - 3176 (2003)
(Matrix presented) A gas mixture of NO and O2 was bubbled into 2′-deoxyguanosine solution at neutral pH and 37°C. A novel nitrated nucleoside was generated in the reaction mixture in addition to 8-nitroguanine, 8-nitroxanthine, 2′-deoxyxanthosine, xanthine, and guanine. The novel nucleoside was identified as N2-nitro-2′-deoxyguanosine by spectrometric data.
Peroxynitrite reacts with 8-oitropurines to yield 8-oxopurines
Lee, Joseph M.,Niles, Jacquin C.,Wishnok, John S.,Tannenbaum, Steven R.
, p. 7 - 14 (2007/10/03)
Peroxynitrite reacts with 2′-deoxyguanosine to yield several major products, including 8-oxo2′-deoxyguanosine (8-oxodG) and 8-nitroguanine (8-nitroGua). While the terminal products formed during the reaction of 8-oxodG with peroxynitrite have been previously characterized, those formed from 8-nitroGua have not. To identify these products, 9-ethyl-8-nitroxanthine was used as a model for 8-nitroGua, since the former could be easily synthesized in high yield, and facilitated reversed-phase HPLC separation of the resulting products. Using this model substrate, the products formed during the peroxynitrite reaction were identified as the ethyl derivatives of oxaluric acid, 5-iminoimidazolidin-2,4-dione, III, [N-nitro-N'-[2,4-dioxo-imidazolidine-5-ylidene]-urea, V, dehydroallantoin, parabanic acid, cyanuric acid, and uric acid. Upon the basis of the previous studies with 8-oxodG, these products were recognized as those expected to arise from peroxynitrite-mediated uric acid oxidation. Furthermore, the presence of uric acid in the reaction mixture led us to propose a model in which the 8-nitropurine is first converted to the 8-oxopurine which is further oxidized by peroxynitrite to give the observed final products. We have also provided evidence suggesting that the peroxynitrite anion, acting as a nucleophile, might be responsible for the initial conversion of the 8-nitropurine to the 8-oxopurine and that a hydroxyl radical or oxidative process is less likely to explain this conversion.
