Characterization of 5-Hydroxy-8-oxo-7,8-dihydroguanosine in the Photosensitized Oxidation of 8-Oxo-7,8-dihydroguanosine and Its Rearrangement to Spiroiminodihydantoin

Abstract

The photosensitized oxidation of 2',3',5'-tris-(O-tert-butyldimethylsilyl)-8-oxo-7,8-dihydroguanosine (8-oxoG) with singlet oxygen was studied by low-temperature NMR. A stable intermediate was characterized at -60 degrees C by (13)C, 2D NMR HMBC spectra, and chemical shifts calculated by hybrid Hartree-Fock density functional theory which agreed with the structure 5-hydroperoxy-8-oxo-7,8-dihydroguanosine. Reduction of this intermediate at low temperature afforded the corresponding alcohol, the long-postulated 5-hydroxy-8-oxo-7,8-dihydroguanosine, the last intermediate in the formation of spiroiminodihydantoin. Upon warming to room temperature, this alcohol rearranges to form the spiroiminodihydantoin in good yield within 2 h.

Structural and Thermodynamic Features of Spiroiminodihydantoin Damaged DNA Duplexes

“…The R and S spiroiminodihydantoin (Sp) stereoisomers ( Figure 1A) result from the direct oxidation of guanine and the further oxidation of 8-oxoG (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Recently, Sp was detected in Nei-deficient Escherichia coli following chromate exposure (33).…”

Use of Short Duplexes for the Analysis of the Sequence‐Dependent Cleavage of DNA by a Chemical Nuclease, a Manganese Porphyrin

“…The new M+16 product was stable upon incubation during 30 min at 0 8C; consequently, it did not correspond to compound 9, an unstable common precursor of 5 and 6, that would also have a mass corresponding to an increase of 16 amu compared to the mass of guanine (Scheme 7). [52] Reaction of the 5'-OH group as a nucleophile on the C8 carbon atom of guanine after oxidation of the latter has been reported previously for the guanine oxidation pathway leading to cyclic analogues of 4. [53,54] Furthermore, this reaction is favored by the anti conformation of the base in the double-stranded duplex.…”

Singlet Oxygen as a Reagent in Organic Synthesis

“…Compounds 15,98,101,103, and 107 led to the formation of bisperoxides. Growing experimental data has been accumulated for singlet oxygen reactions, which give rise to spiro compounds [82,83,[127][128][129][130], or yield bis-or polyperoxides, or polyepoxides [42,58,[114][115][116][117][118][119][120]131].…”

“…In addition to the NMR spectroscopy evidence for 129 and 130, X-ray crystallography data was obtained for one of the diastereomers of ( þ )-premnalane 130. Unlike guanosine 59 (as described in Section 11.3.4.3 [78]), the reaction of singlet oxygen with 2 0 ,3 0 ,5 0 -tris-(O-tert-butyldimethylsilyl)guanosine (131) produced spirodiimidohydantoin (135) [127]. A facile rearrangement occurred because the guanosine peroxide bore a 8-H substituent.…”