Uracil hydroperoxides

Tandem base modifications thymine hydroperoxides, 933 uracil hydroperoxides, 935, 936 Tantalum(V) complexes... 

Only limited information is available on uracil hydroperoxides that are likely to be generated in a similar way to thymine analogues by initial OH radical addition in aerated aqueous solutions. This is likely due to the higher instability of these peroxides. Evidence has been recently provided for the implication of the 5-peroxy-5,6-dihydrouracil-6-yl radical in the formation of tandem base lesions. 

Unsaturated triglycerides hydroperoxide determination, 680, 689 reference derivatives, 739 Upregulation of metabolism, 610 Uracil... 

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.

DNA is also susceptible to free radical attack during oxidative stress. The participation of GST isoenzymes in the detoxification and repair of the potentially mutagenic radical damage to DNA has been studied by Ketterer and his colleagues. Both thymine hydroperoxides and DNA peroxidized by ionizing radiation in the presence of oxygen have been shown to serve as substrates for rat GST (T3, T4). However, these workers reported that the specificity of rat GST isoenzymes toward the peroxidized DNA differs from that toward the free thymine hydroperoxide, 5-hydroxymethyl uracil. From their data, Ketterer et al. (K7, K9) propose that GST act in concert with DNA glycosylase to repair oxidized DNA. 

In a previous section (p. 194), the thermal electrocyclization of 5-aryIazo-6-ethoxymethyieneamino-uracils to 8-arylamino-theophyllines was noted. Related are the 6-dimethylaminomethyleneamino-derivatives (353), which on irradiation under anaerobic conditions also cyclize to 8-arylamino-theophyllines (242). However, in the presence of oxygen, photocyclization of (353) affords 6-aryl-6,7-dihydro-6-azalumazin-7-ones (355). A mechanistic rationale has been proposed (Scheme 81) involving the initial formation of the 5,6-dihydroazalumazine (354) followed either by formation of hydroperoxide (path a) or ring contraction (path b), depending on the reaction conditions. Thermolysis of (353) produces a mixture of the 5,6-dihydro-azalumazine (354) and theophylline (242). 

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