An unusual dearomatized adduct formed by reaction of 4'-fluoro-4-(acetylamino)biphenyl N-sulfate with deoxyadenosine.
The sulfate ester of the liver carcinogen N-hydroxy-4'-fluoro-4-(acetylamino)biphenyl (FAABP-N-sulfate) is believed to be a reactive intermediate in the male rat liver in vivo. After reaction of FAABP-N-sulfate with double-stranded calf thymus DNA in vitro, 30% of the adducts was identified as N-(deoxyguanosin-8-yl)-4'-fluoro-4-(acetylamino)biphenyl(dG-C8- FAABP) and 16% was suggested to be 3-(deoxyguanosin-N2-yl)-4'-fluoro-4-(acetylamino)biphenyl. To investigate the identity of the remaining adducts, FAABP-N-sulfate was reacted with deoxyadenosine. Two adducts could be isolated, which were identified by 1H NMR and mass spectrometry as 3-(deoxyadenosin-N6-yl)-4'-fluoro-4-(acetylamino)biphenyl (3-dA-N6-FAABP) and -(deoxyadenosin-N6-yl)-4'-fluoro-4-(acetylimino)-3, 4-dihydrobiphenyl (3-dA-N6-FHAIBP). An additional center of chirality is introduced at C3 (biphenyl) in the latter adduct. Therefore, 3-dA-N6-FHAIPB exists as a pair of two diastereomers with H-3 (biphenyl) in the alpha or beta position. Hydrogen bonding between the proton on N6 (adenine) and the imine nitrogen or the acetylimino oxygen is suggested to stabilize 3-dA-N6-FHAIBP and to prevent its conversion to 3-dA-N6-FAABP by restoration of the aromatic system. The adduct 3-dA-N6-FHAIBP was also formed in the reaction of N-OSO3H-FAABP with DNA; it accounted for 3-6% of total covalent binding.
van de Poll
M L
ML
Division of Toxicology, Sylvius Laboratories, University of Leiden, The Netherlands.
Venizélos
V
V
Niessen
W M
WM
Meerman
J H
JH
D000611:Aminobiphenyl Compounds / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry; D004277:DNA, Single-Stranded / Q000737:chemistry; D003839:Deoxyadenosines / Q000737:chemistry*; D006868:Hydrolysis; D014269:Trifluoroacetic Acid / Q000737:chemistry; D014316:Tritium
D000611:Aminobiphenyl Compounds; D004277:DNA, Single-Stranded; D003839:Deoxyadenosines; D014316:Tritium; C071145:N-hydroxy-4'-fluoro-4-(acetylamino)biphenyl sulfate; D004247:DNA; D014269:Trifluoroacetic Acid