4075-79-0Relevant articles and documents
Reactions of ester derivatives of carcinogenic N-(4-biphenylyl)hydroxylamine and the corresponding hydroxamic acid with purine nucleosides
Kennedy, Sonya A.,Novak, Michael,Kolb, Brent A.
, p. 7654 - 7664 (1997)
The nitrenium ions 3a,b derived from hydrolysis of N-(sulfonatooxy)-N-acetyl-4-aminobiphenyl (1a) and N-(4-biphenylyl)-O-pivaloylhydroxylamine (1b) are trapped by the purine nucleosides 2'-deoxyguanosine (dG), guanosine (G), 8-methylguanosine (8-MeG), adenosine (A), inosine (I), and xanthosine (X) with varying degrees of efficiency. Those nucleosides with a basic N-7 (pK(a)(N7-H+) ≤ 2.3) react with 3a,b with an apparently diffusion-limited rate constant at 20°C of ca. 2.0 x 109 M-1 s-1, determined from the experimental trapping ratios k(nuc)/k(s) and known values of k(s) for the two nitrenium ions. All nucleosides with a basic N-7, including 8-MeG, generate only C-8 adducts upon reaction with 3a,b. The reactions of 8-MeG with 3a,b produce metastable adducts, tentatively identified as 16a,b, that decompose over time into the stable 7,8-dihydroguanosine derivatives 8a,b. Our data, and those of other workers, are consistent with a mechanism that involves initial attack of N-7 on the nitrogen of the nitrenium ions followed by a 1,2 migration and deprotonation (Scheme 2b) to yield the final C-8 adducts. Nucleosides with a less basic N-7 react more slowly with the nitrenium ions and also produce adducts other than C-8 adducts. Inosine generates both the C-8 adducts 6a,b and the O-6 adducts 7a,b. Adenosine reacts with 3a,b to produce the unique azabicyclo[4.1.0]hepta-2,4-diene derivatives 11a,b. plots of log k(nuc) vs pK(a)(N7-H+) show that the β(nuc) for C-8 adduct formation is at least 0.7 for purine nucleosides with pK(a) ≤ 2.3. The purine and pyrimidine selectivity data conclusively demonstrate that the high abundance of C-8 dG adducts observed in DNA from in vivo or in vitro experiments is a consequence of the high selectivity of nitrenium ions for N-7 of dG. Other minor DNA adducts may be produced as a result of structure-dependent modification of site selectivity.
Ligands for metals and improved metal-catalyzed processes based thereon
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, (2008/06/13)
One aspect of the present invention relates to novel ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon-heteroatom and carbon-carbon bond-forming reactions. The subject methods provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, reaction conditions, and efficiency.
Reactions of glutathione with carcinogenic esters of N-arylhydroxamic acids
Novak, Michael,Lin, Jing
, p. 1302 - 1308 (2007/10/03)
The nitrenium ions 7a and 7b derived from hydrolysis of N-(sulfonatooxy)-N-acetyl-2-aminofluorene (1a) and N-(sulfonatooxy)-N-acetyl-4-aminobiphenyl (1b) are trapped by glutathione anion (GS-) with selectivity ratios, k(gs)-/k(s), of 8200 ± 600 M-1 and 300 ± 15 M-1, respectively. Since k(s) is known for both of these ions under our reaction conditions, k(gs)- can be calculated. For 7a, k(gs)- is 6.3 x 108 M-1 s-1, and for 7b, k(gs)- is 1.8 x 109 M-1 s-1. Under physiological conditions (50-100 μM GS-) neither ion would be efficiently trapped by GS-. Some of the GSH adducts isolated in this study (4 from 1a, 11 and 12 from 1b) are not derived from nitrenium ion trapping. They arise from GS- trapping of the quinol imines 8a and 8b, which are the initial products of trapping of 7a and 7b by H2O. This reaction is very efficient at physiological GS- concentrations and could lead to significant GSH depletion in vivo. Although it has been known for some time that quinol imines such as 8a and 8b are major hydrolysis products of carcinogenic esters of N-arylhydroxylamines and N-arylhydroxamic acids, no physiological role has been previously suggested for these materials.
