Photosensitized Reaction of 8-Oxo-7,8-dihydro-2‘-deoxyguanosine:  Identification of 1-(2-Deoxy-β-d-erythro-pentofuranosyl)cyanuric Acid as the Major Singlet Oxygen Oxidation Product

Abstract

The main photosensitized oxidation product in aqueous solution of 8-oxo-7,8-dihydro-2‘-deoxyguanosine (1) has been isolated by HPLC and characterized as 1-(2-deoxy-β-d-erythro-pentofuranosyl)-cyanuric acid (7) and its precursor, 1,3,5-triazine-1(2H)-carboximidamide, 3-(2-deoxy-β-d-erythro-pentofuranosyl)tetrahydro-2,4,6-trioxo- (6). This was achieved by carrying out extensive spectroscopic measurements including FAB mass spectrometry, 1H and 13C NMR analyses. The formation of the photooxidized nucleoside 7 is accounted for by a type II mechanism through initial [2+2] cycloaddition across the C-4−C-5 ethylenic bond of 1. The 1,2 bond cleavage of the transient dioxetanes gives rise to the modified nucleoside 6 through a nine-membered ring oxidized intermediate nucleoside. The derivative 6 further decomposes into the stable cyanuric acid nucleoside 7 by the hydrolysis of the guanidino residue with the concomitant release of urea 8. Photosensitizers such as methylene blue and rose Bengal were found to efficiently photooxidize 8-oxodGuo 1 via a type II mechanism (1O2), whereas riboflavin and benzophenone, which act mostly by a type I mechanism, were far less efficient.

Peroxynitrite reaction products of 3′,5′-di -O- acetyl-8-oxo-7,8-dihydro-2′-deoxyguanosine

“…In 150 mM KH 2 PO 4 , 25 mM Na 2 CO 3 , pH 7.2 and at ambient temperature, II has a half-life of 5 hr. This compound is therefore relatively more labile than I whose half-life previously was determined to be days (30). However, IIc is quite stable and little degradation occurs even after days of incubation at room temperature in pH 7.2 buffer.…”

“…Photooxidation of 8-oxodGuo leads to the formation of 1,3,5-triazine-1(2H)-carboximidamide, 3-(2-deoxy-␤-D-erythro-pentofuranosyl)tetrahydro-2,4,6-trioxo-(I) as the major product. This compound then undergoes basemediated hydrolysis to yield 1-(2-deoxy-␤-D-erythro-pentofuranosyl)cyanuric acid (Ia) (30).…”

Nickel(II)-catalysed oxidative guanine and DNA damage beyond 8-oxoguanine

“…[37][38][39][40] The retention time of the peak at m/z 156 was just over 6 min. A peak of m/z 157 was also detected.…”

Interactions of Amino Acids with Oxidized Guanine in the Gas Phase Associated with the Protection of Damaged DNA

“…In addition, G · + can participate in irreversible reactions with a large variety of chemical and physical agents which may lead to oxidative damage. [15,16] For example, G · + reacts with H 2 O or a strong chemical oxidant at certain sites, giving rise to 8-oxo-7,8-dihydroguanine and other G lesions products. [17][18][19][20] Many efforts have been devoted to explore the protective mechanism of damaged G. The main strategies, which include repairing damaged DNA, [21] packaging DNA with lipid-like compounds, [22] and driving the radical cations away from the coding regions [23] have been described in detail.…”