Ra. Mcclelland et al., REACTIVITY OF THE 4-BIPHENYLYL AND 2-FLUORENYLNITRENIUM IONS WITH HETEROCYCLIC AND CARBON NUCLEOPHILES, Journal of physical organic chemistry, 9(6), 1996, pp. 355-360
The carcinogens 4-aminobiphenyl, 2-aminofluorene and their N-acetyl de
rivatives form DNA adducts in vivo with the aryl nitrogen attached at
C-8 of guanine. These adducts are proposed to arise through the reacti
on with the DNA base of a nitrenium ion obtained by N-O heterolysis of
a hydroxylamine ester obtained metabolically by oxidation and esterif
ication. Routes have now been discovered for the photochemical generat
ion of these nitrenium ions, the N-acetyl derivatives via a photoheter
olysis reaction and the N-H derivatives by protonation of the singlet
nitrene photochemically generated from the azide precursor. The nitren
ium ions are observed as transient intermediates with laser flash phot
olysis, and the kinetics of their reaction with various nucleophiles d
irectly monitored. These results, coupled with competition kinetics ex
periments, show that the nitrenium ions derived from the above amines
and amides are relatively long-lived in water, with a remarkably high
selectivity in water for reaction with 2'-deoxyguanosine and its 5'-ph
osphate. The C-8 adduct is the product of this reaction. These behavio
urs differ considerably from those of analogous carbenium ions. Reacti
ons with vinyl ethers have also been investigated, and also show signi
ficant differences between the two types of electrophile.