Reaction of 6-yl radicals of uracil, thymine, and cytosine and their nucleosides and nucleotides with nitrobenzenes via addition to give nitroxide radicals. Hydroxide ion-catalyzed nitroxide heterolysis

Steenken, S.; Jagannadham, V.

doi:10.1021/ja00310a013

Cited by 59 publications

(31 citation statements)

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“…The carbon- centered radical at C-5' (structure 1), produced by hydrogenatom abstraction by a radical species of NCS-Chrom, forms a labile nitroxyl radical adduct (structure 2) with misonidazole (RNO2) (reaction 1). The addition of carboncentered radicals to the oxygen of the nitro group of tetranitromethane and nitrobenzenes to give intermediate nitroxide radicals has been documented by electron spinresonance spectroscopy and pulse-radiolysis methods (13)(14)(15). While such adducts can act as intermediates in one-electron oxidations, as has been described in radiationsensitization reactions with pyrimidines and their derivatives (15), they also can undergo fragmentation (reaction 2) to form oxy radicals (structure 3) and the nitroso reduction product of misonidazole, a two-electron process (16).…”

Section: Discussionmentioning

confidence: 99%

3'-Formyl phosphate-ended DNA: high-energy intermediate in antibiotic-induced DNA sugar damage.

Chin

Kappen

Goldberg

1987

Proc. Natl. Acad. Sci. U.S.A.

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Under anaerobic conditions where the nitroaromatic radiation-sensitizer misonidazole substitutes for dioxygen, DNA strand breakage (gaps with phosphate residues at each end) by the nonprotein chromophore of the antitumor antibiotic neocarzinostatin (NCS-Chrom) is associated with the generation of a reactive form of formate from the C-5' of deoxyribose of thymidylate residues. Such lesions account for a minority (10-15%) of the strand breakage found in the aerobic reaction without misonidazole. Amino-containing nucleophiles such as tris(hydroxymethyl)aminomethane (Tris) and hydroxylamine act as acceptors for the activated formate. The amount of [3H formyl hydroxamate produced from DNA labeled with [5'-3H]thymidine is comparable to the spontaneously released thymine. During the course of the reaction, misonidazole undergoes a DNA-dependent reduction and subsequent conjugation with glutathione used to activate NCSChrom. From these and earlier results, we propose a possible mechanism in which the carbon-centered radical formed at C-5' by hydrogen atom abstraction by thiol-activated NCSChrom reacts anaerobically with misonidazole to form a nitroxyl-radical-adduct intermediate, which fragments to produce an oxy radical at C-5'. j3-Fragmentation results in cleavage between C-5' and C-4' with the generation of 3'-formyl phosphate-ended DNA, a high-energy form of formate, which spontaneously hydrolyzes, releasing formate and creating a 3'-phosphate end, or transfers the formyl moiety to available nucleophiles. A similar mechanism, involving dioxygen addition, is probably responsible for the 10-15% DNA gap formation in the aerobic reaction.as to position the reactive ring system containing the two acetylenic bonds close to the C-5' of deoxyribose of mainly thymidylate residues.Upon activation by thiol [glutathione in the cell (2)], the DNA-bound drug is converted into a species, presumably free-radical form, that abstracts a hydrogen atom from C-5' to generate a carbon-centered radical, whether or not dioxygen is present (3). Addition of dioxygen to the radical at C-5' forms a peroxyl radical species that undergoes reduction by thiol to generate a DNA strand break with a nucleoside 5'-aldehyde group at the 5' end and a phosphate at the 3' end.Such lesions account for more than 80% of the strand breaks produced (4). The remaining 10-15% of the strand breaks are actually gaps with phosphates at both ends. The mechanism for their production has not been clear, although it has been thought to be related to the formation of formate from C-5' (5). In addition to single-strand breaks, DNA bases (mainly thymine) are also released (6, 7), in part generating abasic sites. When nitroaromatic radiation sensitizers, such as misonidazole, are substituted for dioxygen in the reaction, gaps with phosphates at both ends constitute the main form of DNA breakage (8), and this is associated with base (mainly thymine) release and a 4-to 5-fold increase (over the aerobic reaction) in the release of a soluble material labeled with tri...

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Section: Discussionmentioning

confidence: 99%

3'-Formyl phosphate-ended DNA: high-energy intermediate in antibiotic-induced DNA sugar damage.

Chin

Kappen

Goldberg

1987

Proc. Natl. Acad. Sci. U.S.A.

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“…16,17 In addition, transient absorption spectroscopy has been widely used for the direct observation of the carbon-centered radicals formed in the reactions. 1,5,9,15,18,19 Regarding the latter technique, the spectra related to the pyrimidine nucleobases 1, 9 and some of their derivatives as 5,6-dihydrouracil or 1,3-dimethyluracil 9 in aqueous solution were reported early in 1970s. For uracil, a broadband centered at around 3.26 eV (380 nm) was observed at pH 3.15.…”

Section: The Journal Of Chemical Physics 139 071101 (2013)mentioning

confidence: 99%

“…9 Since the C5OH adducts were demonstrated to be the major products, 2, 3, 15 the bands were assigned in the experimental studies to these regioisomers, 1, 2, 9 even in more complex systems as deoxyuridine. 18 A few theoretical attempts have been undertaken to assign the observed bands of the spectra. In 1993, Krauss and Osman 21 used first-order configuration interaction (FOCI) to study the electronic excited states of the · OH adducts of uracil.…”

Section: The Journal Of Chemical Physics 139 071101 (2013)mentioning

confidence: 99%

Communication: Electronic UV-Vis transient spectra of the ·OH reaction products of uracil, thymine, cytosine, and 5,6-dihydrouracil by using the complete active space self-consistent field second-order perturbation (CASPT2//CASSCF) theory

Francés‐Monerris

Merchán

Roca‐Sanjuán

2013

The Journal of Chemical Physics

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“…High-intensity laser excitation of DNA-bases may yield intermediates, which are also found in radiolysis, e.g. e,, electron-adducts, OH-adduct radicals to the base (produced by water addition to the radical cation and deprotonation), and H-abstraction radicals (Bansal and Fessenden, 1978;Fujita and Steenken, 1981;Steenken and Jagannadham, 1985;v. Sonntag, 1987).…”

Section: Introductionmentioning

confidence: 99%

TRANSIENTS OF URACIL and THYMINE DERIVATIVES and THE QUANTUM YIELDS OF ELECTRON EJECTION and INTERSYSTEM CROSSING UPON 20 ns PHOTOLYSIS AT 248 nm

Görner

1990

Photochem & Photobiology

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Transients of uracil and a series of 17 correlated pyrimidines, e.g. methylated bases, nucleosides, nucleotides, and polyuridylic acid [poly(U)] were studied after 248 nm excitation by 20 ns laser pulses. The transient absorption spectra in aqueous solution at room temperature reveal the triplet state and the hydrated electron (e-aq), while the corresponding radical cation could not be observed at pH 6-7. Fast loss of the chromophore in the 260-290 nm range within 0.1 microsecond was observed in aqueous solution in some cases [e.g. poly(U), 5'-UMP, uridine, uracil] and in others (thymine, thymidine) virtually not. This photobleaching is assigned to formation of the photohydrate. The concentration of e-aq shows a quadratic dependence on the laser pulse intensity (IL) in the range (0.2-2) x 10(7) W cm-2 and the quantum yield of electron ejection (phi c-) thus depends linearly on IL. This behaviour, suggesting that the photoionization involves a two-step absorption process, was found for poly(U) and all pyrimidine monomers examined. At a constant IL value of 2 x 10(7) W cm-2, phi c- ranges from 3 x 10(-3) for 1,3-dimethylthymine to 4 x 10(-2) for poly(U). The triplet state shows a much larger transient absorbance (delta A, typically in a broad range, e.g. 290-500 nm) than that of the neutral radical resulting from the radical cation. The triplet state in organic solvents (acetonitrile and ethanol) shows generally a significantly larger delta A value than in aqueous solution. The estimated quantum yields of intersystem crossing at room temperature are compared with those of phosphorescence at -196 degrees C.

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Reaction of 6-yl radicals of uracil, thymine, and cytosine and their nucleosides and nucleotides with nitrobenzenes via addition to give nitroxide radicals. Hydroxide ion-catalyzed nitroxide heterolysis

Cited by 59 publications

References 1 publication

3'-Formyl phosphate-ended DNA: high-energy intermediate in antibiotic-induced DNA sugar damage.

3'-Formyl phosphate-ended DNA: high-energy intermediate in antibiotic-induced DNA sugar damage.

Communication: Electronic UV-Vis transient spectra of the ·OH reaction products of uracil, thymine, cytosine, and 5,6-dihydrouracil by using the complete active space self-consistent field second-order perturbation (CASPT2//CASSCF) theory

TRANSIENTS OF URACIL and THYMINE DERIVATIVES and THE QUANTUM YIELDS OF ELECTRON EJECTION and INTERSYSTEM CROSSING UPON 20 ns PHOTOLYSIS AT 248 nm

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