Conformation and configuration at the central amine nitrogen of a nucleotide adduct of the carcinogen 2-(acetylamino)fluorene as studied by 13C and 15N NMR spectroscopy.
The conformation and configuration at the central nitrogen of the adduct 8-(N-fluoren-2-ylamino)-2'-deoxyguanosine 5'-monophosphate has been investigated by high-field 13C and 15N NMR spectroscopy. One-bond nitrogen-hydrogen coupling constants and 13C chemical shifts for the adduct as well as for the model compounds diphenylamine, 4-nitrodiphenylamine and 2-aminofluorene have been measured in nonaqueous solutions. The data indicate a near planar configuration at the amine nitrogen that links the guanine and fluorene rings of the adduct. The orientations about the guanyl-nitrogen and fluorenyl-nitrogen bonds place the two ring systems in either perpendicular (Type A) or helical (Type B) conformations. It is suggested, based on structural similarities to diarylamines, that the G-N-C bond angle of the adduct is greater than 120 degrees in order to reduce unfavorable steric interactions between the two ring systems. Space-filling molecular models of the adduct in duplex DNA show that the aminofluorene moiety can be oriented into both Type A and Type B conformations within the major groove. The configuration at nitrogen of diphenylamine, 4-nitrodiphenylamine and 2-aminofluorene has also been examined.
Evans
F E
FE
Division of Chemistry, Food and Drug Administration, Jefferson, AR 72079.
Levine
R A
RA
D015073:2-Acetylaminofluorene; D004247:DNA; D003848:Deoxyguanine Nucleotides; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009584:Nitrogen
D003848:Deoxyguanine Nucleotides; C062988:8-(N-fluoren-2-ylamino)-2'-deoxyguanosine 5'-monophosphate; C007257:2'-deoxyguanosine 5'-phosphate; D004247:DNA; D015073:2-Acetylaminofluorene; D009584:Nitrogen