One-Electron Oxidation of Nucleobases

HOCl Acid-Mediated Halogenation of Pyrimidine and Purine Bases 

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The water-soluble compound 2-amino[l,8]naphthyridine is a novel DNA-binding photosensitizer, which may be employed for the one-electron oxidation of DNA. It is also reported to be an excellent chromophore for the design of artificial electron-accepting nucleobases <1999TL6029>. 

There is abundant evidence that 8-oxo-G is ubiquitous in cellular DNA as discussed in detail by Cadet et al. in Chapter 3 [82, 83], The major pathway of formation of this important marker of oxidative DNA damage involves the one-electron oxidation of 8-HO-G radicals derived from either the hydration of the G +/G(-H) radicals or the addition of OH radicals to the C8 position of G [62, 84], In DNA, the redox potential of 8-oxo-G at pH 7, E7 = 0.74 V versus NHE, indicates that it is more easily oxidized than any of the four natural nucleobases [85], The primary... 

In this context, in the narrow sense the term nucleobase radical cation signifies a species identical to that which is produced upon one-electron oxidation of the base. Its deprotonation leads to a radical whose unpaired spin is largely heteroatom-sited. Reprotonation of this radical could in principle give rise to radical cations that are not identical but tautomeric to the original radical cation. 

Major emphasis has been on the isolation and identification of the main decomposition products arising from one electron oxidation reactions with the pyrimidine and purine bases of isolated DNA and related model compounds13,14D. In recent years, major interest has been devoted on the delineation of the mechanistic features of charge transfer within double stranded DNA. This is mostly achieved using defined-sequence oligonucleotides in which radical cations are generated in most cases by photo-ionization of selected nucleobases and 2-deoxyribose. For more information on these systems, the reader is encouraged to read the recent review article by Cadet et al.134 and other references mentioned there in. 

In DNA free-radical chemistry, N-centered radicals are generated from some nucleobases upon one-electron oxidation (followed by II+ loss). They are also considered as important intermediates in the purine free-radical chemistry. It is, therefore, worthwhile to address very briefly some of the chemistry of N- centered radicals that were encountered in amines and amino acids. 

Deeble DJ, Schuchmann MN, Steenken S, von Sonntag C (1990) Direct evidence for the formation of thymine radical cations from the reaction of SO/" with thymine derivatives a pulse radiolysis study with optical and conductance detection. J Phys Chem 94 8186-8192 DeFelippis MR, Murthy CP, Faraggi M, Klapper MH (1989) Pulse radiolytic measurement of redox potentials the tyrosine and tryptophan radicals. Biochemistry 28 4847-4853 Delatour T, Douki T, D Ham C, Cadet J (1998) Photosensitization of thymine nucleobase by benzo-phenone through energy transfer, hydrogen abstraction and one-electron oxidation. J Photo-chem Photobiol 44 191-198... 

The -N02 radical does not react with any of the nucleobases, but when G- is formed by one-electron oxidation, e.g., by C(V , in the presence of-N02, recombination occurs thereby forming 8-nitroguanine (Joffe et al. 2003a). 

Much research has been carried out towards the identification of DNA-derived radicals formed after reaction with OH radicals or other one-electron oxidants. The main features of DNA free radical chemistry have been reasonably well established from studies performed on DNA itself as well as on model systems including nucleobases, sugars, nucleosides and nucleotides, poly-U, poly-A, and DNA oligomers. ... 

Direct hydrogen atom abstraction occurs less frequently from the nucle-obases, despite the expected modest carbon—hydrogen bond dissociation energy of the carbon—hydrogen bonds in the methyl groups of thymidine and 5-methyl-2 -deoxycytidine due to resonance stabilization of the incipient radicals. The respective radicals are also formed by deprotonation of the nucleobase radical cations, intermediates involved in electron transfer that are produced via one-electron oxidation. Amine radicals are also postulated as intermediates produced from the spontaneous decomposition of chloramines that arise from reactions of nucleosides with hypochlorous acid." " However, the majority of nucleobase radical intermediates arise from the... 

However, the biochemical significance of the latter studies is challenged by the fact that the transformation of transient purine and pyrimidine radicals into diamagnetic decomposition products is oxygen-independent in the solid state. Therefore, it is necessary to study the chemistry of one-electron nucleobase intermediates in aerated aqueous solutions in order to investigate the role of oxygen in the course of reactions that give rise to oxidation products within DNA and model compounds. In this respect, type I photo-... 

The reaction of hydrated electrons formed by radiolysis with peroxydisulfate yields the sulfate radical anion SO4 which is a strong chemical oxidant (Eqx = 2.4 V/NHE) [50, 58]. The oxidation of both purine and pyrimidine nucleotides by S04 occurs with rate constants near the diffusion-controlled limit (2.1-4.1 x 10 M s ). Candeias and Steenken [58a] employed absorption spectroscopy to investigate acid-base properties of the guanosine cation radical formed by this technique. The cation radical has a pKa of 3.9, and is rapidly deprotonated at neutral pH to yield the neutral G(-H) . Both G+ and G(-H) have broad featureless absorption spectra with extinction coefffcients <2000 at wavelengths longer than 350 nm. This has hampered the use of transient absorption spectra to study their formation and decay. Candeias and Steenken [58b] have also studied the oxidation of di(deoxy)nucleoside phosphates which contain guanine and one of the other three nucleobases by SO4 , and observe only the formation of G+ under acidic conditions and G(-H) under neutral conditions. 

If quinones are used as the oxidant, the reaction of the OH radical adducts of the nucleobases proceeds by outer sphere electron transfer to yield a carbocation but not an adduct [118]. The rate constant for this interaction shows a strong dependence on the one-electron reduction potential of the quinone. This reaction does not lead to ssb induction in poly C in the presence of benzoquinone but to a reduction in the yield of ssb. 

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