Thymine oxidation

Hydroxyl radical-mediated thymine oxidation products. 976... 

There is not much discussion of thymine oxidation products since they are viewed as unimportant in the radiation chemistry of DNA, the feeling being that in DNA, most of the holes will be trapped by the purines. However, when model systems are used, there are several known pathways that involve oxidation of the thymine base. When a thymine base is ionized, the resulting thymine cation is an acid with for deprotonation in... 

Figure 3. OH radical-induced degradation of thymine. Oxidation involves either OH addition to the C5-06 double bond or OH-mediated hydrogen abstraction from the methyl group. Molecular oxygen then adds to the resulting carbon-centered radicals. This reaction yields hydroperoxide that further evolves into stable products, such as thymidine glycol (ThdGly), 5-hydroxymethyl-uracil (HMdUrd) and 5 formyl-uracil (5-FordUrd). N- represents the bond to the DNA backbone.

Scheme 7 Structure of the decarboxylation product of thymine oxidation, 5-hydroxy-hydantoin...

Table V Hyperfine Coupling Parameters for Thymine Oxidation Products ...

In contrast, the photochemistry of uracil, thymine and related bases has a large and detailed literature because most of the adverse effects produced by UV irradiation of tissues seem to result from dimer formation involving adjacent thymine residues in DNA. Three types of reaction are recognizable (i) photohydration of uracil but not thymine (see Section 2.13.2.1.2), (ii) the oxidation of both bases during irradiation and (iii) photodimer formation. 

The best laboratory synthesis of thymine (947) is probably from 3-methylmalic acid (945) which gives 2-formylpropionic acid (946 R = H) in situ by decarboxylation and oxidation in fuming sulfuric acid prior to condensation with urea (46JA912) a similar method from ethyl 2-formylpropionate (946 R = Et) is also described (68IZV918). 

Interestingly, one-electron oxidants partly mimic the effects of OH radicals in their oxidizing reactions with the thymine moiety of nucleosides and DNA. In fact, the main reaction of OH radicals with 1 is addition at C-5 that yields reducing radicals in about 60% yield [34, 38]. The yield of OH radical addition at C-6 is 35% for thymidine (1) whereas the yield of hydrogen abstraction on the methyl group that leads to the formation of 5-methyl-(2 -de-oxyuridylyl) radical (9) is a minor process (5%). Thus, the two major differences in terms of product analysis between the oxidation of dThd by one-electron oxidants and that by the OH radical are the distribution of thymidine 5-hydroxy-6-hydroperoxide diastereomers and the overall percentage of methyl oxidation products. 

Fig. 11 Thymine dimer repair at a distance by DNA-mediated charge transport. Here photoexcitation of intercalated [Rh(phi)2bpy/]3+ tethered to the 3 -end of a DNA duplex oxidizes a remote thymine dimer (>34 A away) within the helix leading to dimer repair. The arrows mark the sites of intercalation of the phi ligand. Adapted from [149]...

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