Purine radical cations

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 ... 

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. 

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. ... 

Steenken, S. (1989). Purine bases, nucleosides and nucleotides aqueous solution redox chemistry and transformation reactions of their radical cations and e" and OH adducts. Chem. Rev. 89, 503-520. 

A different strategy has been applied in our work, that emphasizes the importance of DNA stability on hole transfer within double-stranded DNA. This work is based on determination of the overall yield of oxidized nucleosides that arise from the conversion of initially generated purine and pyrimidine radical cations within DNA exposed to two-photon UVC laser pulses. On the one hand, this work benefits from the excellent current knowledge of chemical reactions involving the radical cations of DNA bases, and on the other hand, from major analytical improvements that include recent availability of the powerful technique of high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (CLHP-ESI-MS/MS) [16-18]. 

The two overwhelming oxidation products of the purine moiety of dGuo 37 arising from the transformation of guanine radical cations 38 were isolated and identified as 2,2-diamino-4-[(2-deoxy-/l-D-eryfhro-pentofura-nosyl)amino]-5(2H)-oxazolone (41) and its precursor 2-amino-5-[(2-deoxy-... 

GG8, the radical cation must traverse five A/T base pairs. Electrochemical measurements in solution have shown that the purine bases (A and G) have considerably lower Eox than the pyrimidines (C and T), with the Eox of G estimated to be about 0.25 V below that of A [20]. It is not very likely that the Eox of bases in DNA will be the same as they are in solution, but it is generally assumed that the order of Eox will remain the same. Consequently, the radical cation at Gi of AQ-DNA(l) must traverse a bridge of five A bases to reach GG8. The process whereby the radical cation crosses such bridges has been a major point of debate in consideration of long distance radical cation migration mechanisms in DNA this issue will be discussed fully below. 

The primary conclusion that follows from the effect of base sequence on the efficiency of radical cation migration through duplex DNA is that base pairs cannot be considered in isolation. For example, the effect of placing a T in a sequence of purines depends critically on the nature and number of purines. In this regard, the effect of base sequence on radical cation transport emerges from examination of collective properties of the DNA. This is a clear indication that the charge is delocalized over several base pairs, a conclusion that is supported by extensive quantum calculations. 

The hydroxyl radical can also abstract a single electron from dG to generate the base radical cation (G ). In duplex DNA, the G " " will be stabilized by its delocalization into adjacent bases. Both calculations and kinetic measurements " indicate that GG sequences have a lower oxidation potential than an isolated G. Nucleo-bases on the 3 -side of G determine the extent of G formation, and here purines are more effective than pyrimidines at lowering the oxidation potential of G, which accounts for the GG effect and that GA sites are also reactive. ... 

Major emphasis has been on the isolation and identification of the main decomposition products arising from one electron oxidation reactions with the pyrimidine and purine bases of isolated DNA and related model compounds13,14D. In recent years, major interest has been devoted on the delineation of the mechanistic features of charge transfer within double stranded DNA. This is mostly achieved using defined-sequence oligonucleotides in which radical cations are generated in most cases by photo-ionization of selected nucleobases and 2-deoxyribose. For more information on these systems, the reader is encouraged to read the recent review article by Cadet et al.134 and other references mentioned there in. 

Gua has the lowest reduction potential among the four nucleobases (Table 10.2), and hence it is preferentially oxidized to its radical cation (for the calculation of ionization potentials of the DNA bases see Close 2004 Crespo-Hernandez et al. 2004), and this property makes Gua and its derivatives to stick out of the other nucleobases with respect to its different free-radical chemistry. In contrast, Thy and Cyt are good electron acceptors, while the purines are only poor ones in comparison (for the calculation of electron affinities, see Richardson et al. 2004). This is of special importance in the effects caused by the absorption of ionizing radiation by DNA. 

Photooxidation of purine nucleosides and also of Cyt by pyrimido[5,4-g]pteridine N-oxide under argon affords in high yields the 5 -0,8-cyclopurine nucleosides and 5 -0,6-cyclocytidne, whereby the N-oxidc is reduced (Sako et al. 1986). Nucleobase radical cations are believed to be the intermediates in this surprising oxidation reaction. 

Shi Y, Fluang C, Wang W, Kang J, Yao S, Lin N, Zheng R (2000a) Electron transfer from purine de-oxynucleotides to deoxynudeotides deprotonated radical cations in aqueous solution. Radiat... 

Steenken S (1988) Electron transfer between radicals and organic molecules via addition/elimina-tion. An inner-sphere path. In Rice-Evans C, Dormandy T (eds) Free radicals chemistry, pathology and medicine. Richelieu Press, London, pp 53-71 Steenken S (1989) Purine bases, nucleosides and nucleotides Aqueous solution redox chemistry and transformation reactions of their radical cations e and OH adducts. Chem Rev 89 503-520 Steenken S (1992) Electron-transfer-induced acidity/basicity and reactivity changes of purine and pyrimidine bases. Consequences of redox processes for DNA base pairs. Free Radical Res Commun 16 349-379... 

Transformation reactions of purines and purine nucleoside and nucleotide radical cations and E- and OH-adducts haye been reviewed <89CRV503>. 

The fluorescence polarization excitation spectrum has been measured for thymine in aqueous solution. " The depolarization at the red edge is attributed to the hidden n, ir transition. Ionization of the lowest excited singlet and triplet states have been determined by the effect of pH on the absorption, fluorescence, and phosphorescence spectra of purines and pyrimidines. " Spectral, polarization, and quantum yield studies of cytidylyl-(3, 5 )-adenosine have also been published. Intermediates in the room-temperature flash photolysis of adenine and some of its derivatives have been identified hydrated electron, radical cations and anions, and neutral radicals resulting from their reactions have been assigned. Photoionization occurs via the triplet state. FMN encapsulated in surfactant-entrapped water pools interacts with polar head groups, entrapped water molecules, and outer apolar solvent. ... 

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