Hydrolysis Reactions of N-Sulfonatooxy-N-acetyl-1-aminonaphthalene and N-Sulfonatooxy-N-acetyl-2-aminonaphthalene:  Limited Correlation of Nitrenium Ion Azide/Solvent Selectivities with Mutagenicities of the Corresponding Amines

Abstract

The hydrolysis reactions of the title compounds N-sulfonatooxy-N-acetyl-1-aminonaphthalene, 2d, and N-sulfonatooxy-N-acetyl-2-aminonaphthalene, 2e, in 5% CH 3 CN-H 2 O (20 °C, pH 5.7-7.5, µ ) 0.5) appear to involve nitrenium ion intermediates that exhibit very small azide/solvent trapping efficiencies. The azide/solvent selectivities, S, were estimated from fitting azide-and solvent-derived product yields as a function of [N 3 -]. The derived values of S for the N-acetyl-N-(1-naphthyl)nitrenium ion (3d) of 0.7 ( 0.1 M -1 and the N-acetyl-N-(2-naphthyl)nitrenium ion (3e) of 1.5 ( 0.2 M -1 show that these ions have short lifetimes (ca. 10 -10 s) in aqueous solution. In turn, these results suggest that the hydrolysis reactions of 2d and 2e should proceed, in part, through ion-pair and/or preassociation pathways. The decrease in the yield of the rearrangement products N-acetyl-1-amino-2-sulfonatooxynaphthalene, 6, and N-acetyl-2-amino-1-sulfonatooxynaphthalene, 11, with increasing [N 3 -] indicates that this is the case. Plots of log(mutagenicity) toward Salmonella typhimurium TA 98 and TA 100 for a series of polycyclic and monocyclic aromatic amines vs log(S) for ArNAc + show that there is no general correlation of mutagenicity with nitrenium ion selectivity, but there does appear to be a limited correlation of these two quantities for five polycyclic amines for which there are reliable mutagenicity and nitrenium ion selectivity data. These results suggest that nitrenium ion selectivity is one of several factors that determines the mutagenicity of aromatic amines.

Quantification of Ultrasound‐Induced Chain Scission in PdII–Phosphine Coordination Polymers

“…Arylnitrenium ions are thought to have a key role in chemical carcinogenesis, and there is much interest in their chemical reactions and properties 1–18. Aromatic amines like 2‐acetylaminofluorene may be enzymatically converted into sulfate esters of the analogous N ‐hydroxylamines, and in aqueous environments a sulfate anion will spontaneously leave these esters to produce an arylnitrenium ion 13, 17. These arylnitrenium ions can in some cases (such as the 2‐fluorenylnitrenium ion) be selectively trapped by guanine bases in DNA, and this is thought to result in carcinogenic mutations 8–10, 14, 18.…”

Aryl Nitrenium Ions in Aqueous Solution

“…The azide/solvent selectivities of about 20 nitrenium ions were measured in water via the azide clock method from 1987 to 1999. 19,20,27,106,107,[109][110][111] The data showed a 10 5 -fold range of k az /k s , but evaluation of cation lifetimes required measurement of k az and k s for some representative ions.…”

“…107,[109][110][111]115,126 Since ion pairs in water have lifetimes about 100 ps, there is only a narrow range of k s (about 2 Â 10 8 s À1 to 10 10 s À1 ) in which ion pair mechanisms will be significant, and they are never the dominant reaction type. 110,127 For ions with aqueous solution lifetimes less than about 100 ps, preassociation mechanisms become dominant because the ions do not survive long enough for nonsolvent species to diffuse to them.…”

High‐Level Secretory Expression of Penicillin Amidase from Providenciarettgeri in Saccharomycescerevisiae: Purification and Characterization

“…The heterolytic scission of the NO bond of the latter species is thought to generate a transient arylnitrenium ion that covalently adds to guanine bases in DNA. The detailed mutagenic power of a given arylnitrenium ion strictly depends on a number of intrinsic and environmental factors, and various research groups are currently focusing intense interest on the experimental and theoretical investigation of the formation, structure, and reactivity of aromatic nitrenium ions 17–25. Strictly related to these studies is the experimental and theoretical investigation of the interaction between prototype nitrenium ions in their singlet state and simple nucleophiles of biological interest.…”