Synthesis, characterization, and comparative conformational analysis of N-(deoxyguanosin-8-yl)aminopyrene adducts derived from the isomeric carcinogens 1-, 2-, and 4-nitropyrene

Document Type


Date of Original Version



Nitrated polycyclic aromatic hydrocarbons are mutagens/carcinogens that undergo in vivo activation by ring-oxidation and nitro-reduction pathways. We report the syntheses and comparative conformational analyses of N- (deoxyguanosin-8-yl)-n-aminopyrene adducts (dG-C8-n-AP, n = 1, 2, 4) derived from the three isomeric mononitropyrenes (1-, 2-, and 4-NP). The C8-amine nitrogens of these adducts have been enriched with 15N to examine the conformation about the pyrenyl-nitrogen and guanyl-nitrogen bonds that link the guanine and the pyrene moiety. These adducts are structurally isomeric, thus providing an interesting opportunity for systematic probing of the isomeric adduct conformations. Spectroscopic data indicated that the three isomeric aminopyrene adducts favor anti-glycosyl conformations, with C2'- endo (S) sugar puckering and a nearly planar conformation at the central amine nitrogen. The data further indicated differences in the extent of π- electron conjugations about the pyrenyl-nitrogen bond, depending on the location of aminopyrene substitution. Thus while the 1- and 4-isomers both have substitution adjacent to a fused aromatic ring, the 2-isomer is highly symmetric and less sterically hindered. The 2-isomer adopts the most planar conformation, thereby having the most efficient π-electron delocalization between the guanine and pyrene rings. The isomeric dG-C8-AP adducts and their nitro and amino precursors display physicochemical properties (HPLC retention time, UV pattern, 1H NMR data, mass fragmentation, etc.) distinctly dependent on their structures (1- and 4-isomers versus 2-isomer).

Publication Title

Chemical Research in Toxicology