A novel nitration product formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine: N-nitro-N'-[1-(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)- 2, 4-dioxoimidazolidin-5-ylidene]guanidine.
A novel nitration product, formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine, has been characterized using a combination of UV/vis, CD, and NMR spectroscopy and mass spectrometry. This compound has been identified as N-nitro-N'-[1-(2,3, 5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)-2, 4-dioxoimidazolidin-5-ylidene]guanidine (IV). Upon base hydrolysis, IV releases nitroguanidine (IVa) and an intermediate, 1-(2,3, 5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)-5-iminoimidazolidine -2, 4-dione (IVb). This intermediate is ultimately hydrolyzed to the stable 3-(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)oxaluric acid (IVc). IV can be reduced by sodium borohydride to a pair of stable diastereomers (IV(red)()). The formation of this product is rationalized in terms of initial oxidation of 2',3', 5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine to a quinonoid diimine intermediate, 3. Nucleophilic attack at C5 of 3 by peroxynitrite leads to formation of a C5-oxyl radical species, 5, which then undergoes a series of rearrangements to yield an ylidene radical, 7. Combination of this radical species with nitrogen dioxide results in the formation of product IV.
Niles
J C
JC
Division of Bioengineering and Environmental Health and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Wishnok
J S
JS
Tannenbaum
S R
SR
D002942:Circular Dichroism; D006146:Guanidines / Q000032:analysis*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009566:Nitrates / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
C410287:2',3',5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine; D006146:Guanidines; C410288:N-nitro-N'-(1-(2,3,5-tri-O-acetyl-erythro-pentofuranosyl)-2,4-dioxoimidazolidin-5-ylidene)guanidine; D009566:Nitrates; D016877:Oxidants; D006151:Guanosine; C039642:peroxynitric acid