Thymidine radical cations

Scheme 1 Reactions of the thymidine radical cation in aerated aqueous solution... 

Hydration of the thymidine radical cation leads to the predominant formation of the oxidizing 6-hydroxy-5,6-dihydrothymid-5-yl radical whereas deprotonation mostly generates the methyl-centered radical (Fig. 4). As already pointed out, these two pyrimidine radicals are also produced upon reaction with OH. However, the methyl-centered radical represented only 5% of base radicals when produced by OH while it corresponds to 30% of the thymidine radicals produced upon one-electron oxidation. Type I photosensitization of 2 -deoxy-cytidine leads to the formation of the 6-hydroxy-5,6-dihydro-2 -deoxycytidil-5-yl radical also produced upon reaction with OH. Additional oxidative pathways involve the formation of 2-deoxyribonolactone and free cytosine as well as production of 2 -deoxyuridine as the result of deprotonation ofthe pyrimidine radical cation at Cl and NH2 group, respectively. 

Wagner J.R., van Lier J.E., Johnston L.J., Quinone sensitized electron transfer photooxidation of nucleic acids Chemistry of thymine and thymidine radical cation in aqueous solution, Photochem. Photobiol., 1990,52, 333-343. 

Fig. 6 Hole injection into a guanine (G) in single strands, which is separated from the enol ether radical cation by various numbers of thymidines [T]n...

In a rare example of the use of phenylselenides as radical precursors in the generation of alkene radical cations by the fragmentation approach, Giese and coworkers generated a thymidine C3/,C4/ radical cation by expulsion of diethyl phosphate. Trapping experiments were conducted with methanol and with allyl alcohol (Scheme 16), when nucleophilic attack was followed by radical cyclization [66]. 

Scheme 16 Generation and trapping of a thymidine C3, C4 radical cation...

Scheme 2. Hole and spin transfer (ht) in the electron-loss path after y-irradiation of DNA. It should be noted that extensive recombination occurs after the initial ionizations. This scheme assumes that last recombination is equally efficient for all cationic radicals. Net hole transfer occurs ftom the adenine, cytosine and thymidine base cation radicals to guanine and from the sugar phosphate backbone to the...

One-electron oxidation reactions of pyrimidine bases are also well established, mostly through the study ofthe menadione-mediated type I photosensitization of 2 -deoxycytidine and thymidine [3]. The radical cations once formed may undergo two competitive pathways. 

Pulse radiolysis shows that the pyrimidine radical cations are fairly strong acids and rapidly deprotonate at a heteroatom [reaction (98)]. As protonation/deprotonation reactions at heteroatoms are easily reversible, the radical cations are regenerated upon reprotonation. Deprotonation at carbon or reaction with water yields the final free-radical products [reactions (99) - (101)]. It is noted that in thymidine [23] and 5 -thymidylic acid [104] the allylic thymine radical is observed by EPR and there is very little question that its precursor is the thymine radical cation. The identification of the C(6)-OH-5-yl radical by EPR supports the view [100] that reaction with water competes with the deprotonation at methyl. Due to the ready oxidation of the (reducing) C(5)-OH-6-yl by peroxodisulfate, this type of radical is only observed at low peroxodisulfate concentrations in these systems, i.e. the (oxidizing) C(6)-OH-5-yl radicals are correspondingly enriched under conditions favourable to a chain reaction [22]. In the case of 1,3-dimethyluracil the interesting characteristics of... 

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... 

The only azine cation-radical to have been characterized in solution by ESR seems to be that of 1,3,6,8-tetraazapyrene, (pyrimido[4,5,6-g/i]per-imidine) (103). The ESR spectrum of this radical is closely similar to that of 58, the corresponding (4n + 3)-electron radical, as would be expected.191 Sevilla has described cation-radicals from thymidine and various derivatives generated by photoionization in a glassy matrix.349... 

The oxidation of thymine and thymidine derivatives with superoxide ion in dimethyl sulfoxide (DMSO) or DMF gives ring-contracted imidazolones (88CC1171). Oxidation with sodium persulfate gives a mixture of 5-hy-droxymethyluracils and 5-formyluracils, perhaps by thymine cation radicals (86CL1319 88JOC3421) (Scheme 159). 

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