Arylamine-nucleoside adduct formation: evidence for arylnitrene involvement in the reactions of an N-acetoxyarylamine

Chem Res Toxicol. 1994 Sep-Oct;7(5):684-9. doi: 10.1021/tx00041a014.

Abstract

N-Acetoxyarylamines are reactive metabolites that are produced from N-arylhydroxamic acids by N-arylhydroxamic acid N,O-acyltransferase and by the acetyl coenzyme A-dependent O-acetylation of N-arylhydroxylamines. Solvolytic decomposition of 7-acetyl-2-(N-acetoxyamino)fluorene (3) afforded 7-acetyl-2-aminofluorene (4) and 7,7'-diacetyl-2,2'-azofluorene (5). Solvolysis of 3 in the presence of 2'-deoxyguanosine resulted in formation of N-(deoxyguanosin-8-yl)-7-acetyl-2-aminofluorene (2), along with smaller yields of 4 and 5 than were obtained in the absence of 2'-deoxyguanosine. The inclusion of nitrene trapping agents, such as piperylene, triethyl phosphite, 1-chloro-4-nitrosobenzene, and oxygen, in the reaction medium with 3 and 2'-deoxyguanosine caused a reduction in the yields of 2, 4, and 5. Additionally, products that would be expected to be formed through reaction with an arylnitrene intermediate were obtained when triethyl phosphite, 1-chloro-4-nitrosobenzene, and oxygen were included in the incubations with 3 and 2'-deoxyguanosine. The results support the proposal that a nitrene intermediate is involved in the formation of 2, 4, and 5 from 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Azo Compounds / chemistry*
  • DNA Adducts / chemistry*
  • Deoxyguanosine / chemistry
  • Fluorenes / chemistry*
  • Nucleosides / chemistry*

Substances

  • 7-acetyl-N-acetoxy-2-aminofluorene
  • Amines
  • Azo Compounds
  • DNA Adducts
  • Fluorenes
  • Nucleosides
  • Deoxyguanosine