Synthesis and structure determination of the adducts formed by electrochemical oxidation of Dibenzo[a,l]pyrene in the presence of adenine.
Because the radical cations of polycyclic aromatic hydrocarbons (PAH) are involved in tumor initiation, determination of the structures of biologically formed PAH-DNA adducts is important and relies on comparison of their properties with those of synthesized adducts. One of the possible sites of adduct formation is the N-3 position of Ade, but this depurinating adduct is not obtained by one-electron oxidation of dibenzo[a,l]pyrene (DB[a,l]P) in the presence of deoxyadenosine. Therefore, we turned to electrochemical oxidation of DB[a,l]P in the presence of Ade in dimethylformamide and produced the following adducts: DB[a,l]P-10-N1Ade (47%), DB[a, l]P-10-N3Ade (5%), DB[a,l]P-10-N7Ade (2%), and DB[a,l]P-10-N(6)Ade (6%). In Me(2)SO, this reaction afforded the same four adducts, but in slightly different yields: DB[a,l]P-10-N1Ade (44%), DB[a, l]P-10-N3Ade (9%), DB[a,l]P-10-N7Ade (1%), and DB[a,l]P-10-N(6)Ade (3%). These adducts were purified by reverse-phase HPLC, and the subtle differences between the isomers were revealed by NMR, tandem mass spectrometry, and fluorescence line-narrowing spectroscopy. The relative yields of the N1Ade, N3Ade, and N7Ade adducts reflect the nucleophilicity and steric accessibility of these three nitrogen atoms in Ade.
Li
K M
KM
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Byun
J
J
Gross
M L
ML
Zamzow
D
D
Jankowiak
R
R
Rogan
E G
EG
Cavalieri
E L
EL
D000225:Adenine / Q000737:chemistry*; D001580:Benzopyrenes / Q000737:chemistry*; D002273:Carcinogens / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D004126:Dimethylformamide / Q000737:chemistry; D004563:Electrochemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D013050:Spectrometry, Fluorescence
D001580:Benzopyrenes; D002273:Carcinogens; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D004126:Dimethylformamide; C041517:dibenzo(a,l)pyrene; D000225:Adenine