Spectroscopic Characterization of the Initial C8 Intermediate in the Reaction of the 2-Fluorenylnitrenium Ion with 2‘-Deoxyguanosine

Abstract

Irradiation of 2-azidofluorene in an aqueous solution containing 2‘-deoxyguanosine (dG) gives good yields of 8-(2-fluorenylamino)dG. This is the C8 adduct implicated in the carcinogenicity of 2-aminofluorene, and formed in vivo from the reaction of DNA-guanine and an ester of N-hydroxy-2-aminofluorene. Flash photolysis of the azide reveals two intermediates on the pathway that forms this adduct, the 2-fluorenylnitrenium ion, and a subsequent longer-lived species formed in the reaction of this ion with dG. A number of pieces of evidence identify this later intermediate as the initial C8 adduct derived from addition of the nitrenium ion to the C8 carbon prior to loss of the C8 proton. Both spectroscopic and kinetic analyses show that the latter actually exists in both a cationic acid form and a base form, with a pK a for the acid of 3.9. The base form is a tautomer of the final product and is the species present at pH 7. There is also evidence that the reaction of the nitrenium ion and dG that forms this intermediate proceeds directly by addition at C8. In other words, the substitution of ArNH+ for H+ at the C8 position of 2‘-deoxyguanosine is a straightforward electrophilic aromatic substitution.

Structural Stability and Vibrational Analyses of Haloselenonyl Azides, XSeO2-NNN, where X is F, Cl, Br

“…The very high reactivity and the application of organoazides in synthetic chemistry and many important industries [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] has drawn the attention to investigate the structure and conformational behavior of vinyl azide, CH2=CH-NNN [37] and formyl azide, CHO-NNN [38], by DFT and ab initio MP2 calculations. Both molecules were predicted to have a cis/trans conformational equilibrium with the gauche form being the transition state.…”

Aryl Nitrenium Ions in Aqueous Solution

“…The preference for formation of iminoquinols 9 and the tendency of p-nucleophiles to attack N, as in 7, are known characteristics of nitrenium ions. [13][14][15][16][17][18][19][20][21][32][33][34][35][36] The modern formulation of the nitrenium ion mechanism is due to Heller, Hughes, and Ingold who showed in 1951 that the rate of rearrangement of 3 is proportional to the concentration of protonated hydroxylamine, reaching a constant value in sufficiently acidic solutions, and that the rate is independent of [Cl À ] in aqueous HCl under conditions in which 5b and 6b are major products. 8 Others showed through hydrolysis in 18 OÀ ÀH 2 O that 4 is produced by an intermolecular process, and that no 18 O is incorporated into 3 during the reaction.…”

“…The suggestion in the late 1960s that 1 is the reactive intermediate responsible for the carcinogenicity of metabolites of aromatic amines, 12 and the substantiation of that proposal during the 1990s, [13][14][15][16][17] spurred research into the reactions of 1 in water. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Many reactive examples of 1 have lifetimes in water in the microsecond range making it possible to detect and characterize the cations during laser flash photolysis experiments.…”

“…22,30 Aryl nitrenium ions can be generated in water by heterolytic cleavage of NÀ ÀX bonds under solvolysis conditions, and by photolysis of various precursors. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Under solvolysis conditions, 1 is generated as a steady-state intermediate that does not reach directly detectable concentrations, but it can be studied by indirect methods. 13,14,18,19,27,29 Laser flash photolysis provides the opportunity to directly observe the cation.…”

“…13,14,18,19,27,29 Laser flash photolysis provides the opportunity to directly observe the cation. [15][16][17][20][21][22][23][24][25][26]28,30,31 Results from both types of studies are discussed and compared herein.…”