Pyrimidine radical anions

In a comment on this work,39 Close expresses doubt regarding the DFT calculations that indicate a lack of planarity in pyrimidine radical anions, contrary to what is experimentally found in low temperature single crystal studies. He notes that using an extended basis set results in reasonable agreement between the experimental and calculated values of hyperfine coupling constant for the a-proton without the need to move the proton significantly out of the... 

Table 10.20. Rate constants for protonation of the pyrimidine radical anion at C(6) by H2P04 using various approaches of evaluating the data (Deeble et al. 1985) ...

Repair reactions of pyrimidine radical anions protonated at the C6 position... 

The following pyrimidine radical anions protonated at the C6 position were studied, U (C6H), T C6H, and C (C6H) (Chart 3), to monitor their repair reactions [reaction (5)] ... 

At pH < 7 the nitroxyl radicals do not undergo an observable heterolysis (khs 10 s ), but decay by bimolecular reactions. However, in basic solution an OH -catalyzed heterolysis takes place to yield the radical anion of the nitrobenzene and an oxidized pyrimidine. In the case of the nitroxyls substituted at N(l) by H (i.e. those derived from the free bases), the OH catalysis involves deprotonation at N(l) which is adjacent to the reaction site [= C(6)] (cf. Eq. 15) [26] ... 

An ab initio study on the structure and splitting of the uracil dimer anion-radical (see Scheme 3.72, R = H) gives preference to the one-step mechanism (Voityuk and Roesch 1997). Anion-radical anions of the pyrimidine dimers cleave with rate constants in excess of 10 s ... 

DNA, laced with an intercalator characterized by a high electron affinity, is y-ir-radiated and observed by EPR. The one-electron reduced intercalator presents an EPR spectrum that is readily distinguishable from that of the DNA-trapped radicals. A key example is mitoxantrone (MX), with an electron affinity of 6.25 eV and a radical anion spectrum that is a sharp singlet. Charges are injected into the DNA by y-irradiation at a preselected temperature (4 130 K). Holding the temperature constant, the EPR spectrum changes as a function of time (0.5-30 h). Thereby, a direct measure of the rate of electron transfer from one-electron reduced pyrimidines (Pryre) to the intercalator, e.g., MX, is measured. The turmeling rate is observed to depend on the electron affinity (EA) of the... 

The 77-SCF MO Cl method has also been used446 to interpret spectral transitions of a series of possible intermediates in the reaction of uracil and cytosine with the solvated electrons eaq, produced by radiolysis of water. Experimentally this reaction has been investigated by Hayon,447 who used the technique of flash radiolysis. Hayon measured the optical-absorption spectra of the transient species in the UV range to obtain information on the site of attack of eaq on the pyrimidine base. At pH 5.0 the solvated electrons react with the pyrimidine molecules mainly at the C-2 and C-4 carbonyls, and the intermediates are rapidly protonatcd to give the corresponding ketyl radicals. For uracil Hayon found two absorption maxima (at 305 and < 280 nm) at pH 5.1 and one peak at 310 nm at pH 11.7. In this last case, on ionization of one of the chromophores the ketyl radical anion of the other nondissociated carbonyl is formed. Several species, 44, 45, 46, have been suggested by... 

Hayon s suggestion 44, 45) and species 50 in alkaline solution (Hayon s suggestion 46). The calculation (the spectra as well as the INDO calculation446 of electron densities of uracil and cytosine radical anion) suggested that the solvated electron reacts with uracil and cytosine by addition to the lowest unoccupied molecular orbital, followed at neutral pH by protonation to form the C-4 ketyl radical of uracil and the C-2 ketyl radical of cytosine. The calculation on transition energies presented in ref. 446 cannot be treated as evidence that the species above is the one formed on pulse rediolysis of aqueous solutions of the pyrimidines. 

An ab initio study on the structure and splitting of the uracil dimer anion radical (see Scheme 3-66 and keep R = H) gives preference to the one-step mechanism (Voityuk Roesch 1997). Anion radical anions of the pyrimidine dimers cleave with rate constants in excess of 106 sec 1 (Yeh Falvey 1991). However, the cyclobutyl dimer of a quinone, dithymoquinone, also cleaves upon single-electron reduction but much more slowly than the pyrimidine dimers (Robbins Falvey 1993). It is truly an unresolved issue as to why the anion radical cleavage depicted in Scheme 3-66 is so facile. Water participation can probably decrease the barrier of the cycloreversion on physiological conditions (Saettel Wiest 2001). 

Hayon E (1969) Optical-absorption spectra of ketyl radicals and radical anions of some pyrimidines. J Chem Phys 51 4881-4892... 

The radical anions may be formed by reacting the nucleobases with eaq which may be either generated radiolytically or in a two-step reaction, e.g in the laser flash photolysis of anthraquinonedisulfonate in the presence of pyrimidines (yielding the pyrimidine radical cation and an anthraquinonedisulfonate radical anion) and subsequent photoionization of the anthraquinonedisulfonate radical anion (Lii et al. 2001). The latter approach, combined with Fourier transform EPR spectroscopy, yielded detailed information as to the conformation of the radical anions of Ura and Thy in aqueous solution (for a discussion see Close 2002 Naumov and Beckert 2002). Similarly valuable EPR information has been obtained from y-irradiated single crystals (cf. Box and Budzinski 1975 Boxet al. 1975 Sagstuen et al. 1998). 

Pyrimidines. The pyrimidines react with eaq at practically diffusion-controlled rates (Table 10.6). The ensuing reactions of the radical anions of Ura and Thy are very well understood, while with that of Cyt some open questions still remain. 

Single-crystals and powders. In Ura, the N(l)-centered radical is observed (Zeh-ner et al. 1976). Based on our present knowledge, one may suggest that it arises most likely from the deprotonation of the radical cation. The radical anion is protonated at 0(4). The C(5) -TP-adduct primarily formed is converted with light of A > 400 nm into the thermodynamically more stable C(6)-H -adduct [reaction (303)]. This is also observed with other pyrimidines (Flossmann et al. 1976). 

Chatgilialoglu C, loele M, Mulazzani QG (2005) Reactions of oxide radical anion (O -) with pyrimidine nucleosides. Radiat Phys Chem 72 251-256... 

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... 

Flatta FI, Zhou L, Mori M,Teshima S, Nishimoto S (2001) N(1)-C(5 )-linked dimer hydrates of 5-substi-tuted uracils produced by anodic oxidation in aqueous solution. J Org Chem 66 2232-2239 Flayon E (1969) Optical-absorption spectra of ketyl radicals and radical anions of some pyrimidines. J Chem Phys 51 4881-4892... 

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... 

Visscher KJ, de Haas MP, Loman H, Vojnovic B, Warman JM (1987) Fast protonation of adenosine and of its radical anion formed by hydrated electron attack a nanosecond optical and dc-conduc-tivity pulse radiolysis study. Int J Radiat Biol 52 745-753 Visscher KJ, Spoelder HJW, Loman H, Hummel A, Horn ML (1988) Kinetics and mechanism of electron transfer between purines and pyrimidines, their dinucleotides and polynucleotides after reaction with hydrated electrons a pulse radiolysis study. Int J Radiat Biol 54 787-802 von Sonntag C (1980) Free radical reactions of carbohydrates as studied by radiation techniques. Adv Carbohydr Chem Biochem 37 7-77... 

Despite uncertainty related to irreversible electrochemistry, the trend for the re-ducibility of the nucleobases was established as T,U C A > G [26], Because of this trend, we expect that the U radical anion should only be able to reduce adjacent pyrimidine bases. In accordance with this assumption we expect different emission quantum yield, depending on the nature of the adjacent DNA bases (Figure 4.6.11). In fact, duplex PI has a high emission quantum yield, because ET from the Py-dU group to the adjacent A is not expected. In contrast, significant quenching of the emission can be observed when a T or C is placed adjacent to the... 

In aprotic medium, on the other hand, pyrimidine gives a reversible diffusion-controlled le wave at a very negative potential, with formation of a radical anion which is deactivated via two pathways rapid formation of the anionic, probably 4,4 -, dimer, with a rate constant of 8 x 105 L mol-1 sec-1, and proton abstraction from residual water in the medium at a much lower rate constant, 7 L mol-1 sec-1 98). This is rapidly followed by a further le reduction to produce, ultimately, 3,4-dihydropyrimidine 98). In the presence of acid there is also a le reduction wave corresponding to formation of a free radical which, as in aqueous medium, dimerizes, most likely to 4,4 -Z w-(3,4-dihydropyrimidine). Examination of the mechanism of reduction in acetonitrile in the presence of acids supported the conclusion that reduction of pyrimidine in aqueous medium is preceded by its protonation98). 

Table 21-4. The relative electronic energies (AEr) and free energies (A( I)) at 298 K of stationary points on the reaction path leading from the radical anions (Y -dXOMPII Y = 3, 5, X=C,T) via transition states (TS) to the C3 -0 and C5 -0 bond broken complexes (Product complex) for electron induced dissociation of pyrimidine nucleotides. All values given in kcal/mol. (Table 2 of ref. [79] (Reprinted with permission. Copyright (2006) National Academy of Sciences, U.S.A.) and Table 1 of ref. [80] (Reprinted with permission. Copyright 2006 American Chemical Society.))...

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