title: Reactivity and selectivity of the N-acetyl-Glu-P-1, N-acetyl-Glu-P-2, N-acetyl-MeIQx, and N-acetyl-IQx nitrenium ions: comparison to carbocyclic N-arylnitrenium ions.
abstract: The model ultimate carcinogens 1a-d, related to the metabolites of the food-derived carcinogenic heterocyclic amines Glu-P-1, Glu-P-2, MeIQx, and IQx, spontaneously decompose in neutral aqueous solution to generate the heterocyclic nitrenium ions, 2a-d. The less reactive esters 1a and 1b also undergo acid-catalyzed ester hydrolysis to generate the corresponding hydroxamic acids at pH <2, while the more reactive 2c and 2d are prone to rearrangement in nonaqueous solvents. The reactions of the nitrenium ions with AcO(-), HPO(4)(2-), N(3)(-), and 2'-deoxyguanosine (d-G) were characterized in aqueous solution by using a combination of competitive trapping methods and product isolation and identification. The reactions with N(3)(-) and d-G generally follow patterns previously established for carbocyclic nitrenium ions, but the reactions with AcO(-) and HPO(4)(2-) are unusual. Similar reactions have previously only been reported for heterocyclic 1-alkyl-2-imidazolium ions. The N(3)(-)/solvent selectivities of these ions (5.1 x 10(6) M(-1) for 2a, 2.3 x 10(6) M(-1) for 2b, 1.2 x 10(5) M(-1) for 2c, and 5.2 x 10(4) M(-1) for 2d) are comparable to those of highly selective carbocyclic nitrenium ions. If k(az) for these ions is diffusion limited at ca. 5 x 10(9) M(-1) s(-1) the aqueous solution lifetimes of these ions range from 10 micros (2d) to 1 ms (2a). These ions are also highly selective for trapping by d-G, but comparisons to other nitrenium ions show that they are 10- to 50-fold less selective for trapping by d-G than they would be if both the N(3)(-) and d-G reactions were diffusion limited. This is not a consequence of their heterocyclic structures. Several carbocyclic ions show similar behavior. The relatively inefficient trapping of 2c and 2d by d-G may account for the observation of the unusual minor N-2 d-G adduct that is isolated for both of these nitrenium ions, but has not previously been observed for the reactions of other nitrenium ions with monomeric d-G.
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio 45056, USA. novakm@muohio.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Novak
authors.forename: Krisztina
authors.initials: K
authors.lastname: Toth
authors.forename: Sridharan
authors.initials: S
authors.lastname: Rajagopal
authors.forename: Michael
authors.initials: M
authors.lastname: Brooks
authors.forename: Lora L
authors.initials: LL
authors.lastname: Hott
authors.forename: Matthew
authors.initials: M
authors.lastname: Moslener
mesh_terms: D000107:Acetylation; D002273:Carcinogens / Q000737:chemistry* / Q000633:toxicity; D003849:Deoxyguanosine / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry* / Q000633:toxicity; D007700:Kinetics; D011804:Quinolines / Q000737:chemistry* / Q000633:toxicity; D011810:Quinoxalines / Q000737:chemistry* / Q000633:toxicity
chemical_list: D002273:Carcinogens; D007093:Imidazoles; D011804:Quinolines; D011810:Quinoxalines; C049870:N-acetyl-2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D003849:Deoxyguanosine; C045421:3,4,8-trimethylimidazo(4,5-f)quinoxalin-2-amine