Reactivity and selectivity of nitrenium ions derived from ester derivatives of carcinogenic N-(4-biphenylyl)hydroxylamine and the corresponding hydroxamic acid

Novák, Michael; Kahley, Mary Jo; Eiger, Emily; Helmick, John S.; Peters, Hope E.

doi:10.1021/ja00074a010

Cited by 89 publications

(173 citation statements)

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“…In this case, significant quantities of oxidation products are formed even with rigorous dearation (7,9) and these complicate the analysis. One approach we considered was to move to a phenylhydroxylamine derivative where the phenylnitrenium ion forms by simple ionization, as has been done by the Novak group (21)(22)(23). This, however, adds the complication of trapping at the stage of an ion pair (23,25).…”

Section: Nhoh Nhoh Nhohmentioning

confidence: 99%

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Halide ion trapping of nitrenium ions formed in the Bamberger rearrangement of N-arylhydroxylamines. Lifetime of the parent phenylnitrenium ion in water

Fishbein¹,

McClelland²

1996

Can. J. Chem.

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The acid reactions of five arylhydroxylamines (Ar = 2,6-Me2C6H3, 2,5-Me2C6H3, 2-MeC6H4, 2-C1C6H4, and C6H5) have been studied at constant ionic strength (NaC104) in the presence of varying amounts of NaBr and NaCI. Each system resulted in the corresponding p-aminophenol, the product of Bamberger rearrangement, as the only detectable product in the absence of halide. ' The addition of halide ion reduced the yield of this product, with the appearance of the corresponding p-haloaniline, o-haloaniline (where appropriate), and the parent aniline (predominantly with bromide). Rate constants for the reaction were measured in the case of the parent and 2,6-dimethyl systems and showed small decreases (chloride) or increases (bromide) with increasing halide concentration. These changes did not correlate with the change in products, implying that the rate variations were caused by specific salt effects. Product data were analyzed by a mechanism involving rate-limiting formation of the appropriate arylnitrenium ion followed by product-determining steps involving trapping by the solvent or by the added halide. The possibility that a portion of the halide-trapped products were derived from a pre-association mechanism was also included. Kinetic analyses then produced kBr:kw and kcl:kw ratios for two limiting cases, one involving pre-association with an equilibrium constant K,, = 0.3, and one ignoring pre-association. From an azide:water ratio (kAz:kw) previously determined for the 2,6-dimethylphenylnitrenium, kBr was concluded to lie in the range (4-5) x lo9 M-I s-I for all of the nitrenium ions of this study. This range for kB, then led to k, values of (1-2) x lo9 s-I (2.5-Me2), (2-3) x 10' s-' (2-Me), and (4-8) x lo9 s-' (parent and 2-Cl), where the ranges reflect uncertainties in the exact value of kBr and in the contribution from pre-association. The lifetime of the parent phenylnitrenium ion in water at one molar ionic strength is concluded to lie in the range 125-250 ps.

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Section: Nhoh Nhoh Nhohmentioning

confidence: 99%

“…The Novak group has more recently applied the azide-clock approach to a number of arylnitrenium ions formed in the solvolysis of sulfate, pivalate, and N-chloro derivatives (21)(22)(23). With the above assumption for azide, they found lifetimes varying from the picosecond to the microsecond region.…”

mentioning

confidence: 99%

Halide ion trapping of nitrenium ions formed in the Bamberger rearrangement of N-arylhydroxylamines. Lifetime of the parent phenylnitrenium ion in water

Fishbein¹,

McClelland²

1996

Can. J. Chem.

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“…2 Using this method, we have recently shown that certain carcinogenic esters of N-arylhydroxylamines and N-arylhydroxamic acids (1) decompose in aqueous solution into nitrenium ions (2) that react very selectively with N 3 À . 3,4 These ions also react efficiently with 2'-deoxyguanosine (d-G). 5 Direct measurements of the aqueous solution lifetimes of 2a-c confirm that the ions have lifetimes in the range 0.1-10 ms, and that they react with N 3 À with rate constants of ca 5 Â 10…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of DNA structure on the efficiency of reaction of guanosine moieties with a nitrenium ion

Novák

Kennedy

1998

J. Phys. Org. Chem.

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“…N-OH-arylamines undergo N-O bond heterolysis to form nitrenium ions, which react with an aqueous solvent (34). This rapid exchange of […”

Section: H]abz To [mentioning

confidence: 99%

Peroxygenase Metabolism of N-Acetylbenzidine by Prostaglandin H Synthase

Zenser

Lakshmi

Hsu

et al. 1999

Journal of Biological Chemistry

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Synthesis of prostaglandin H 2 by prostaglandin H synthase (PHS) results in a two Prostaglandin H synthase (PHS)1 catalyzes the metabolism of arachidonic acid in the presence of molecular oxygen to form prostaglandin (PG) H 2 (1). PGH 2 is the common substrate utilized to synthesize a family of biologically important compounds referred to as prostanoids. There are two PHS isozymes, COX-1 and COX-2, which are encoded by two different genes (2, 3). COX-1 is the constitutive enzyme, whereas COX-2 is inducible. Whereas these isozymes differ substantially with respect to their expression and biology, they have a similar structure and express the same two catalytic activities (for a review, see Ref. 4). Both isozymes catalyze a cyclooxygenase (bis-oxygenase) reaction in which arachidonic acid is converted to PGG 2 and a peroxidase reaction in which PGG 2 undergoes a two-electron reduction to PGH 2 . The two-electron oxidation of PHS yields the peroxidase spectral intermediate I that must be reduced to regenerate the resting enzyme (5). A reducing cofactor(s) accomplishes this task and is required for the peroxidase reaction. By donating electrons to the oxidized PHS intermediate, reducing cofactors undergo co-oxidation. The peroxidase activity of both PHS isozymes is essential for biological activity. The biological reducing cofactor(s) for the peroxidatic activity of PHS is unknown. Many naturally occurring compounds have been tested for their efficiency in functioning as reducing cofactors (6). These compounds include NADPH, NADH, glutathione, methionine, tryptophan, epinephrine, ascorbic acid, lipoic acid, and uric acid. Whereas the last four compounds were efficient cofactors, uric acid was considered the most likely endogenous candidate. A large number of synthetic chemicals were also found to exhibit significant reducing cofactor activity.During reduction of the 15-hydroperoxy group of PGG 2 to a hydroxy group (PGH 2 ), prostaglandin hydroperoxidase oxidizes, reducing cofactors by electron or oxygen transfer (for a review, see Ref. 7). Most reducing cofactors donate an electron. Nitrogen-, carbon-, and sulfur-centered free radicals have been detected. For some cofactors, the radical product can undergo a second one-electron oxidation to form a two-electron oxidation product. In addition, the initial free radical product may disproportionate to give a two-electron oxidation product, i.e. an iminium cation, and the original substrate (8). Other radical products may couple, forming dimers or trimers. With sulfide cofactors, the hydroperoxidase catalyzes peroxide reduction by the direct transfer of the peroxide oxygen to the acceptor molecule (9, 10). Except for sulfide reducing cofactors, no other peroxygenase reaction has been reported for PHS.Aromatic and heterocyclic amines represent an important

show abstract

Reactivity and selectivity of nitrenium ions derived from ester derivatives of carcinogenic N-(4-biphenylyl)hydroxylamine and the corresponding hydroxamic acid

Cited by 89 publications

References 1 publication

Halide ion trapping of nitrenium ions formed in the Bamberger rearrangement of N-arylhydroxylamines. Lifetime of the parent phenylnitrenium ion in water

Halide ion trapping of nitrenium ions formed in the Bamberger rearrangement of N-arylhydroxylamines. Lifetime of the parent phenylnitrenium ion in water

Inhibitory effect of DNA structure on the efficiency of reaction of guanosine moieties with a nitrenium ion

Peroxygenase Metabolism of N-Acetylbenzidine by Prostaglandin H Synthase

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