Radical Purine

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

Overall, these results show that attachment of the phenolic ring to dG expands the redox chemistry of the nucleoside to generate the phenolic radical instead of the purine radical cation that reacts with water. Given that the 5-(2 -deoxyuridinyl)methyl radical (T(—H) ) generates the fate of the phe-... 

The purine radical cations are strong Bronsted acids, and thus rapidly de-protonate in neutral aqueous solutions [47, 48]. For instance, the adenosine radicals generated by reaction with S04 radicals were identified as neutral radicals, A(-H) . A change in pH from 1 to 13 does not affect the transient absorption spectra of these species based on this result, it was inferred that the pKa of A is <1 [49]. The solution pH exerts pronounced effects on the transient absorption spectra of the 2AP radicals assigned to the following equilibrium ... 

A common feature of heteroatom-centered radicals is that they react reversibly, only slowly or not at all with 02 (Schuchmann and von Sonntag 1997), and this property is shared by the purine radicals G and A (Chap. 10.2). 

The properties of the purine radical anions formed by their reaction with eaq resemble those of the Cyt radical anion. Because the pKa values of the heteroatom-protonated conjugate acid of the purine radical anions are very high, the purine radical anion are rapidly protonated by water (Hissung et al. 1981a Visscher et al. 1987 von Sonntag 1991 Candeias and Steenken 1992a Candeias et al. 1992 Aravindakumar et al. 1994). For example, the dAdo radical anion... 

As with other reducing agents, G reacts with 02 (Chap. 10.2) which is the most abundant freely diffusing peroxyl radical. Upon two-photon excitation of a 2-aminopurine-containing ss- and dsODN in air-saturated solutions, photoionization leads to the formation of eaq (and subsequently 02 ) and the 2-amino-purine radical cation oxidizes a neighboring G (leading to G plus H+ Misiaszek et al. 2004). G and 02 react with one another (ssDNA k = 4.1 x 108 dm3 mol-1 s 1 dsDNA 2.7 x 108 dm3 mol-1 sH). In the majority of these events G is reformed, but with an efficiency of 15% Iz and, to a minor extent, 8-oxo-G are formed. The suggested mechanism is shown in Chapter 10.2. 

Similar to Cyt, the purine radical anions are also rapidly protonated by water [cf. reaction (15)]. The primary H adducts thus formed rmdergo a series of tautomerization reactions, eventually reaching thermodynamically more favorable H adducts [cf. reactions (16) and (17)]. ... 

Purine radical cations are relatively stable, so that the highest intensity ion in the mass spectrum is due to the molecular ion. Subsequent fragmentation depends on the nature of the substituents. The only common fragmentation reaction to all purines appears to be the elimination of HCN from the molecular or fragment ions. Multiple expulsions of HCN also occur as major processes in the mass spectra of a number of purine analogs, including 6-sulfanyl-purine, 7-deazaadenine, or purine itself. ... 

Among the species produced upon radiolysis of water, hydroxyl radical ( OH) is the most reactive. Indeed, its reaction rate with the four bases and related nucleosides is diffusion-controlled. The main reactive sites of hydroxyl radicals on nucleobases are the double-bonds of the heterocycles. Accordingly, addition of OH at the C8 position of adenine and guanine yields the corresponding reducing 8-hydroxy-7,8-dihydropurin-7-yl radical (Fig. 2). Oxidation of this intermediate leads to the formation of related 8-hydroxypurines that are in dynamic equilibrium with their more stable 8-oxo-7,8-dihydropurine tautomeric form. Competitive reduction of the latter purine radical gives rise to imidazole ring opened compounds the... 

Independent Generation and Reactivity of Neutral Purine Radicals 186... 

NCS. See Neocarzinostatin (NCS) Neocarzinostatin (NCS), 124—125, 125f Neutral purine radicals, generation and reactivity of, 187... 

Hydroxyl radical addition to the purine bases can in principle occur at Cl, C4, C5 and C8 (cf Fig. 1). Of these, addition to position C4, C5 and C8 in guanine and adenine are known to result in ring opening, ring saturation, or hydroxylation [15]. The most well-characterized purine radicals in irradiated DNA are 8-hydroxy-... 

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