The carcinogens 4-aminobiphenyl and 2-aminofluorene are metabolized to hydroxylamine esters that undergo N-O heterolysis to produce arylnitrenium ions that react with DNA, especially at guanine residues. These nitrenium ions and a number of their derivatives have been studied by the laser flash photolysis technique, to provide direct kinetic information about the lifetimes of the electrophiles in water and their reactivities with added nucleophiles. Arylnitrenium ions ArNH+ are longer-lived in water than arylcarbenium analogs ArCH2+, in some cases significantly longer-lived. The nitrenium ions do react with azide ion at the diffusion limit (providing the cation is not highly stabilized). This behaviour completely parallels that of carbenium ions. The biphenylyl- and fluorenylnitrenium ions react with guanine derivatives such as 2-deoxyguanosine (dG) with rate constants that are close to or at the diffusion limit (2 × 109 M-1 s-1) for the more reactive cations. Thus, in spite of cation lifetimes of the order of 100 ns to a millisecond in water, dG effectively competes with the solvent. The product is a C8 adduct, the same adduct observed with carcinogenic arylamines and DNA. With delocalized carbenium ions that have similar lifetimes, guanine derivatives compete very poorly with water. Thus, arylnitrenium ions have high dG:water selectivities; arylcarbenium ions have low selectivities. Nitrenium ions and carbenium ions do have parallel reactivities with primary alkyl amines. More reactive cations show a greater reactivity with less basic amines and the rate constants level below the diffusion limit. This can be explained by hydrogen bonding of the amine lone pair. Using the NH2 group of the alkyl amines as a model for the C2-NH2 group of guanine shows why nitrenium ions show no detectable reactivity at this site. The rate constant for the nitrenium-guanine reaction that forms the C8 adduct is at least an order of magnitude greater than that of a nitrenium-NH2 reaction. Nitrenium ions do form a guanine-NH2 adduct in DNA, suggesting that incorporation into the polymer changes reactivity patterns. With imidazoles, nitrenium ions show reactivity trends that parallel the nitrenium-dG reaction, with rate constants levelling at the 2 × 109 limit for the more reactive cations. Imidazole itself and 1-methylimidazole are generally less reactive than dG, while 2-methylimidazole and 1,2-dimethylimidazole are very similar. A Brönsted-like plot incorporating points for dG, primary amines and imidazoles shows no correlation of nitrenium rate constants with nitrogen basicity. This is true even if only dG and imidazoles are considered. Thus a previous correlation of nitrenium reactivity with purine N7 basicity is suspect. The conclusion is that there is some feature of guanine that makes its reaction with nitrenium ions unusually fast. The reasons for this are not immediately apparent, especially since there is conflicting evidence as to the detailed nature of the mechanism of the reaction that forms the C8 adduct. Key words: nitrenium, aryl azide, guanine, DNA, carcinogen.
4-Azido-X'-substituted biphenyls (X' = 4'-MeO, 4'-Me, 4'-F, 3'-Me, 4'-Cl, H, 3'-MeO, 3'-Cl, 4'-CF3) have been prepared and subjected to 248 nm flash photolysis irradiation in 20:80 acetonitrile:water. Transient X'-substituted 4-biphenylylnitrenium ions 10 (Ar C6H4-N + H) are observed, with lifetimes ranging from 0.6 ms (4'-MeO) to 26 ns (4'-CF3). These cations are quenched by azide ion, with values of kaz ranging from 6 to 10 x 109 M-1 s-1, with the majority in the range (9-10) x 109. This near constant kaz provides further evidence that arylnitrenium ions are quenched by azide ion at the diffusion limit. The solvent reactivities, plotted in a single-parameter Hammett plot against σ sup + (X), exhibit a poor correlation, with the points for the para π-electron donors deviating from the correlation line based on the other substituents in the direction of requiring a more negative substituent parameter. The data are more satisfactorily fit to the two-parameter Yukawa-Tsuno equation; the parameter r + obtained in this fit is 2.8. Thus the resonance interaction of the para π -donor X'-substituents with the positive charge of the cation is underestimated by σ sup + , a situation that has previously been observed with benzylic-type carbenium ions. The conclusion is made that, in their reaction with water, 4-biphenylylnitrenium ions behave like benzyl cations bearing two additional stabilizing vinyl groups, i.e., as if they had the structure Ar-C + (C = C)2. The inherent reactivity and the pattern of the aryl substituent effects are in fact similar to those in the carbocation series Ar-C + (Ph)2.Key words: nitrenium, nitrene, aryl azide, photochemistry, lifetime.
This paper describes the behavior in aqueous solutions of the two electron oxidation products of the carcinogens benzidine and N,N-dimethylbenzidine. In biological systems there is evidence that these diamines are oxidized by peroxidases, and that a product of this oxidation may be partly responsible for carcinogenicity. Entry into the oxidation products in the present study was provided through the bis-perchlorate salts of dications obtained upon chemical oxidation and through the irradiation of 4'-amino and 4'-N,N-dimethylamino-4-azidobiphenyls. The benzidine oxidation product exists in three conjugate acid-base forms, a dication, a monocation and neutral bisimine, with pKa(1) = 5.0 and pKa(2) = 9.0. These values stand in marked contrast to ones previously obtained for the two electron oxidation product of p-phenylenediamine, pKa(1) < 1.5 and pKa(2) = 5.75. The dimethylamino derivative, blocked from forming the neutral form, exists as a dication and monocation, with pKa = 5.0. Both systems are quite long-lived in aqueous solution, but they do decay on the minutes-to-hours time scale. The kinetics can be explained by reactions of both the dication and the monocation with water, with a reaction of hydroxide and the monocation becoming important around pH 10. One surprising result is that the monocations are two orders of magnitude more reactive than the dications. Thus, at neutral pH the form that exists in both systems is the monocation, and this is the species that is the most reactive towards the solvent. One of the resonance contributors in the monocation is a 4-biphenylylnitrenium ion. Comparison with other 4'-substituted-4-biphenylylnitrenium ions studied by laser flash photolysis shows that the 4'-amino- and 4'-dimethylamino substituents are highly kinetically stabilizing. These cations, for example, are a billion-fold longer-lived in aqueous solution than the parent 4-biphenylylnitrenium ion.Key words: quinone bisimine, nitrenium, aryl azide.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.