Thymine anion radical

Although the reduction potentials argue for thymine, as the most easily reducable base in protic solvents like water, subsequent protonation reactions need to be considered as well. The coupling of single electron reduction with a subsequent protonation step will strongly affect the ease of single electron reduction. Table 2 contains the pKa-values of some nucleobases in their reduced and neutral states [37]. It is clear that the thymine radical anion, due to its rather neutral pKa-value of about 7 is unlikely to become pro-tonated either by water or by the adenine counter base in the DNA strand. 

J.M. Lu, J. Geimer, S. Naumov and D. Beckert, A Fourier transform EPR study of uracil and thymine radical anions in aqueous solution, Phys. Chem. Chem. Phys., 2001, 3, 952. 

The disulfide radical anions are also formed upon the reduction of the disulfide by C02- [reaction (41)] and the thymine radical anion (Willson 1970 Elliot et al. 1984). For example, the reducing hydroxymethyl radical can reduce the disulfide (Anderson et al. 1986), but the rate is only fast when the hydroxymethyl radical is deprotonated (Akhlaq et al. 1989) and thus its redox potential decreased. 

Davies MJ, Gilbert BC, Norman ROC (1984) Electron spin resonance, part 67. Oxidation of aliphatic sulphides and sulphoxides by the sulphate radical anion (S04 ) and of aliphatic radicals by the peroxydisulphate anion S Os2 ). J Chem Soc Perkin Trans 2 503-509 Dizdaroglu M, Gajewski E, Reddy P, Margolis SA (1989) Structure of a hydroxyl radical induced DNA-protein cross-link involving thymine and tyrosine in nucleohistone. Biochemistry 28 3625-3628... 

Deeble DJ, von Sonntag C (1985) TheUV absorption spectra of theC(5) and C(6) OH adduct radicals of uracil and thymine derivatives. A pulse radiolysis study. Z Naturforsch 40c 925-928 Deeble DJ, von Sonntag C (1987) Radioprotection of pyrimidines by oxygen and sensitization by phosphate a feature of their electron adducts. Int J Radiat Biol 51 791-796 Deeble DJ, Das S, von Sonntag C (1985) Uracil derivatives sites and kinetics of protonation of the radical anions and the UV spectra of theC(5) and C(6) H-atom adducts. J Phys Chem 89 5784-5788... 

Naumov S, Beckert D (2002) Reply to the Comment on A Fourier transform EPR study of uracil and thymine radical anions in aqueous solution)/ by DM Close. Phys Chem Chem Phys 4 45 Naumov S, Barthel A, Reinhold J, Dietz F, Geimer J, Beckert D (2000) Calculation of spin densities of radicals of pyrimidine-type bases by density functional theory. Influence of solvent and comparison with EPR results. Phys Chem Chem Phys 2 4207-4211 Naumov S, Hildenbrand K, von Sonntag C (2001) Tautomers of the N-centered radical generated by reaction of SO4 - with N(1)substituted cytosines in aqueous solution. Calculation of isotropic hyperfine coupling constants by a density functional method. J Chem Soc Perkin Trans 2 1648-1653... 

Nishimoto S, Hatta H, Ueshima H, Kagiya T (1992) 1-(5 -Fluoro-6 -hydroxy-5, 6 -dihydrouracil-5 -yl)-5-fluorouracil,a novel N(1)-C(5) linked dimer that releases 5-fluorouracil by radiation activation under hypoxic conditions. J Med Chem 35 2711-2712 Norman ROC, Storey PM, West PR (1970) Electron spin resonance studies, part XXV. Reactions of the sulphate radical anion with organic compounds. J Chem Soc (B) 1087-1095 Novais HM, Steenken S (1986) ESR studies of electron and hydrogen adducts of thymine and uracil and their derivatives and of 4,6-dihydroxypyrimidines in aqueous solution. Comparison with data from solid state. The protonation at carbon of the electron adducts. J Am Chem Soc 108 1-6... 

Sudha Sawargara M, Adinarayana M (2003) Kinetics and mechanism of protection of thymine from sulphate radical anion under anoxic conditions. Proc Indian Acad Sci (Chem Sci) 115 123-128 Sugiyama H.Tsutsumi Y, Fujimoto K, Saito I (1993) Photoinduced deoxyribose C2 oxidation in DNA. Alkali-dependent cleavage of erythrose-containing sites via a retroaldol reaction. J Am Chem Soc 115 4443-4448... 

Sugiyama H, Fujimoto K, Saito I (1995) Stereospecific 1,2-hydride shift in ribonolactone formation in the photoreaction of 2 -iododeooxyuridine. J Am Chem Soc 117 2945-2946 Sugiyama H, Fujimoto K, Saito I (1997) Preferential Cl hydrogen abstraction by a uracilyl radical in a DNA-RNA hybrid. Tetrahedron Lett 38 8057-8060 Svoboda P, Harms-Ringdahl M (1999) Protection or sensitation by thiols or ascorbate in irradiated solutions of DNA or deoxyguanosine. Radiat Res 151 605-616 Symons MCR(1990) ESR spectra for protonated thymine and cytidine radical anions their relevance to irradiated DNA. Int J Radiat Biol 58 93-96... 

An analogous stereoelectronic influence on the rate of the reductive repair process was also observed by Carell et al. [28]. The ring opening of the dimer radical anion also proceeds stepwise, but with the C(5)-C(5 ) bond being broken first. The C(5) and C(5 )-methyl groups of thymine-derived dimers, which were found to be repaired more slowly than the uracil-derived dimers, lead to distortion of the geometry, which results in deceased overlap of the n C(4)-0(4) orbital with the a C(5)-C(5 ) orbital. 

K. The three markers at the bottom are the positions of the Fremy Salt resonances, withyf = 2.0056 and = 2.0056. (B) to (E) are spectra used as benchmarks for deconvolution of the DNA spectrum. (B) One-electron oxidized guanine. (C) One-electron reduced cytosine (i.e. the protonated anion radical). (D) Thymine anion radical. (E) Composite spectrum of neutral sugar radicals. 

Triplet sensitized electron transfer from thymine to 9,10-anthraquinone-2,6-disulfonate in aqueous solution leads to the anthraquinone radical anion and the deprotonated thymine-1-yl radical, both of which are spin polarised by the... 

Based on the known chemistry of flavin photolysis reactions, it appears unlikely that thymine dimer cleavage occurs via a direct energy transfer mechanism (160). One proposal suggests that in the model reaction with 1-deazariboflavin, the thymine dimer radical anion is formed via electron donation from the excited sensitizer (164). Alternatively, electron abstraction by the excited flavin could occur, resulting in the thymine dimer radical cation (159, 160), although it is unlikely that reduced flavin would act as an electron acceptor. A schematic for this mechanism is illustrated in Scheme 33, where the initial formation of a sensitizer-dimer complex is consistent with the observed saturation kinetics. The complex is activated by excitation of the ionized sensitizer (pH > 7), and electron donation to the dimer forms the dimer radical anion and the zwitterionic, neutral 1-deazariboflavin radical (162). Thymine dimer radical would spontane-... 

Thymine and uracil behave similar to typical carbonyl compounds, i.e. the first intermediate is a radical anion [reaction (55)] which is in equilibrium with its oxygen-protonated conjugated acid [reaction (57)]. The other functional groups, especially the second carbonyl function, withdraw electron density, and hence the p a values of these oxygen-protonated radical anions are much lower (thymine p a = 6.9 [52]) than those of the corresponding radicals from simple carbonyl compounds. However, the C(6)-protonated isomers [cf. reaction (58)]... 

In guanosine after the rapid protonation of the electron adduct by water [86, 88] at the heteroatom [at O , N 3) or N(7) k > lO s ], a rapid transformation occurs which is catalysed by phosphate buffer and which has been attributed to a protonation at C(8) [88]. This assignment is based upon solid-state EPR data [91], where the C(8)-H-adduct radical appears as the thermodynamically most stable H-adduct radical. The high solvent-kinetic-isotope effect of kn/ki) = 8 is a strong indication that a proton is transferred in the rate-determining step. The magnitude of the rate of phosphate buffer catalysis points to a protonation at carbon (for a similar reaction observed with the thymine radical anion see above). Other purines, e.g. hypoxanthine/inosine, behave in a similar way [89]. 

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