Deoxyribose-derived radical reactions

From substituent and solvent effects on reactions such as Eq. 20 it was concluded [84] that these reactions are of the SnI type, i.e. that alkoxyalkene (enol ether) type radical cations are intermediates. The lifetimes of these radical cations were estimated [84] to be of the order of nanoseconds, much shorter than those [78, 79, 81] of the corresponding l,l-radical cations. This shows the importance of the additional (second) alkoxy group in stabilizing the positive charge on the carbon skeleton. On the basis of these mechanistic model studies, very detailed suggestions could be made [84] regarding the deoxyribose-derived radical reactions that lead to chain breaks in DNA (see below). 

The reactions of these radicals in aqueous solution are particularly interesting, because of their model character with respect to deoxyribose-derived radicals in DNA [83], which lead to strand breaks of this macromolecule. These model reactions have been studied in detail [84], by use of a large number of substrates, with the help of in-situ photolysis ESR, time-resolved conductance, and product-analysis techniques. From the results it is evident that the primarily formed a-alkoxy-jff-chlor-oalkyl radicals in aqueous solution undergo heterolysis of the jff-C-Cl bond with rates A het > 10 s to give rise, finally, to the y -OH-substituted analogs which were identified by ESR. 

Octahedral d, 18 e Co complex containing an L3X corrin ligand, and in apical position, an L benzimidazole ligand and an X ligand bonded to Co by a carbon atom [weak bond 28.6 kcal-mol (119.5 kj-mol ) whose facile homolytic cleavage leads to the adenosyl radical]. Vitamin B12 coenzyme catalyzes radical reactions such as the isomerization of halogenated derivatives (for instance coenzyme A), the methylation of a substrate such as homocysteine and the conversion of ribose to deoxyribose. 

The radicals derived from 2-deoxyribose (ribose) upon Oil-attack yield 37% (23%) PNAP-", and it has been concluded that ET only occurs from the C(l ) radicals (Michaels et al. 1976). With CH20H/CH20- the rate of reaction with PNAP is only fast with the anion, CH20 (Adams and Willson 1973). Whether the radicals formed at the other sites in 2-deoxyribose and ribose give (slowly) rise to adducts cannot be deduced from the reported data. Yet, the fact that PNAP enhances the yield of free phosphate in the radiolysis of GMP (Greenstock et al. 1973a) is an indication that such adducts are likely to be formed, but the rate of reaction is very slow with a-phosphatoalkyl radicals (< 5 x 107 dm3 mol 1 s 1 Schuchmann et al. 1995). 

The main oxidation reactions of the 2-deoxyribose of DNA are mediated by "OH that are able to abstract hydrogen atoms from most of the positions with the exception of the methylene group at C2, which is a poorly reactive site [12, 14, 112], An abundant literature is available on the degradation pathways that are derived from the reactions of osidic carbon-centered radicals and that lead in most cases to the formation of strand breaks [12, 14, 112], However, there is one major exception that concerns the chemical reactions of the CT radical that is the precursor of 2-deoxyribonolactone [113]. Here, emphasis is placed on reactions of C4 and C5 radicals that may lead to the formation of base modifications either as tandem lesions or clustered damage. 

The majority of the detailed mechanistic chemistry on DNA ssb is derived from studies with OH radicals. In the cell, about 40% of the ssb are induced by the direct effects of radiation. Although esr studies [10] indicate that the major radicals formed are located at the bases, it is established that the guanine radical cation does not lead to ssb by radical transfer to the sugar moiety. There is little mechanistic information on ionisation of the sugar phosphate backbone of DNA. Direct energy deposition in the deoxyribose moiety will cause ionisation provided the energy is sufficient to cause ionisation as shown in reactions (6-8). 

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