REACTIVITY OF THE 4-BIPHENYLYL AND 2-FLUORENYLNITRENIUM IONS WITH HETEROCYCLIC AND CARBON NUCLEOPHILES

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.