Purine radical anions

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... 

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)]. ... 

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... 

The reaction of hydrated electrons formed by radiolysis with peroxydisulfate yields the sulfate radical anion SO4 which is a strong chemical oxidant (Eqx = 2.4 V/NHE) [50, 58]. The oxidation of both purine and pyrimidine nucleotides by S04 occurs with rate constants near the diffusion-controlled limit (2.1-4.1 x 10 M s ). Candeias and Steenken [58a] employed absorption spectroscopy to investigate acid-base properties of the guanosine cation radical formed by this technique. The cation radical has a pKa of 3.9, and is rapidly deprotonated at neutral pH to yield the neutral G(-H) . Both G+ and G(-H) have broad featureless absorption spectra with extinction coefffcients <2000 at wavelengths longer than 350 nm. This has hampered the use of transient absorption spectra to study their formation and decay. Candeias and Steenken [58b] have also studied the oxidation of di(deoxy)nucleoside phosphates which contain guanine and one of the other three nucleobases by SO4 , and observe only the formation of G+ under acidic conditions and G(-H) under neutral conditions. 

The rate constants for the single steps of the chain reaction, namely the coupling of radical with nucleophile, the electron transfer to the aromatic compound and the dissociation of the radical anion have been determined by electroanalytical techniques, and its scope by way of cathodic induction has been demonstrated [159]. The reaction has been extended to substrates other than aromatics. For example, perfluoroalkylation of purine and pyrimidine bases can be achieved by cathodic initiation [160[. 

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]. 

Tile low-temperature ESR spectrum of the anion radical of purine disclosed that about 45% of the spin density is localized at position 6 (80BCJ1252), although a single very broad signal for N(7) and N(9) did not allow discussion of the tautomerism. 

Comparing electrochemical behavior and biological transformations of purine bases, Japanese chemists (Yao and Musha 1974, Ohya-Nishiguchi et al. 1980) have considered the anion-radicals of purine, its 8-deutero and 6,8-dideutero derivatives. As it turned out, up to 40% of the total spin density is localized in position 6 of the purine anion-radical (see Scheme 3.7). Ohya-Nishiguchi et al. (1980) noted that such a large localized spin density is very rare in a n electron system of the purine s size and should have important application in relation to its chemical reactivity. Protonation should... 

Moorthy PN, Hayon E (1975) Free-radical intermediates produced from the one-electron reduction of purine, adenine and guanine derivatives in water. J Am Chem Soc 97 3345-3350 Mori M, Teshima S-l, Yoshimoto H, Fujita S-l, Taniguchi R, Hatta H, Nishimoto S-l (2001) OH Radical reaction of 5-substituted uracils pulse radiolysis and product studies of a common redox-ambivalent radical produced by elimination of the 5-substituents. J Phys Chem B 105 2070-2078 Morin B, Cadet J (1995) Chemical aspects of the benzophenone-photosensitized formation of two lysine - 2 -deoxyguanosine cross-links. J Am Chem Soc 117 12408-12415 Morita H, Kwiatkowski JS,TempczykA(1981) Electronic structures of uracil and its anions. Bull Chem Soc Jpn 54 1797-1801... 

In non-aqueous media (DMF, DMSO, acetonitrile), purine and some of its 6-sub-stituted derivatives (adenine, 6-methylpurine, 6-methylaminopurine, 6-methoxypurine, 6-dimethylaminopurine) undergo an initial le reduction to form the corresponding anionic free radical, followed by dimerization with rate constantsof 103—10s lmol l l64. The free radical nature of the le reduction product was independently established by ESR spectroscopy l69>. This behaviour is to be contrasted with the 2e and 4e reductions undergone by these compounds in aqueous media. s6-99-155. ... 

The lung also possesses nonenzymatic antioxidants such as vitamin E, beta-carotene, vitamin C, and uric acid. Vitamin E is lipid-soluble and partitions into lipid membranes, where it is positioned optimally for maximal antioxidant effectiveness. Vitamin E converts superoxide anion, hydroxyl radical, and lipid peroxyl radicals to less reactive oxygen metabolites. Beta-carotene also accumulates in cell membranes and is a metabolic precursor to vitamin A. Furthermore, it can scavenge superoxide anion and react directly with peroxyl-free radicals, thereby serving as an additional lipid-soluble antioxidant. Vitamin C is widely available in both extracellular and intracellular spaces where it can participate in redox reactions. Vitamin C can directly scavenge superoxide and hydroxyl radical. Uric acid formed by the catabolism of purines also has antioxidant properties and primarily scavenges hydroxyl radical and peroxyl radicals from lipid peroxidation. 

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. ... 

The electron affinities (EA) of the nucleobases have not been determined experimentally. Calculated values for the vertical and adiabatic EA obtained by scaling experimental and calculated values for other aromatic molecules are summarized in Table 1 [33a]. The vertical values follow the order U>T>C>A>G, with U having the largest (most positive) EA. The calculated adiabatic EA for C is less positive than the values for T or U. Chen and Chen [36] have asserted that the electron affinities of the purines are larger than those of the pyrimidines. However, this claim appears to be based upon questionable reduction potential measurements (see p. 114). The nucleobase anion radicals are estimated to be stabilized by c. 3 eV in aqueous solution. 

The adenine anion has also been determined to be protonated in single crystals at very low temperatures. The main protonation site in single crystals is N3, which is supported by DFT calculations [4]. Furthermore, protonation can occur at both C2 and C8, where these sites are favorable under conditions where N3 is not involved in a hydrogen bond in single crystals [15]. In the aqueous state, the adenine anion has been shown to accept a proton from N3 in thymine at the N1 position [101]. This can be followed by a 1,2-shift to form the A(C2H) product [92]. Only the A(N3H) product has been assigned in oriented DNA [76]. However, a product has been identified in randomly oriented DNA and assigned to a net radical addition product at C 8 in one of the purines [78], which could be associated with A(C8H). 

Ethylene and thioformaldehyde are the products of irradiation of matrix-isolated thietane at lOK. Sulphur-carbon bond homolysis has also been observed on irradiation of the nucleoside membrane transport inhibitor, 6-[ (4-nitrobenzyl) thio] -9- (/8-D-ribofuranosyl) -purine (94), and the oxazolidin-2-one (95) has been converted into the allyl derivative (96) by photochemically induced radical allylation.Efficient conversion of cyclic thioacetals into the corresponding carbonyl compounds under neutral conditions has been achieved by 2,4,6-triphenylpyrylium tetrafluoroborate-sensitised irradiation in moist dichloromethane,and diaryl sulphides and the corresponding sulphoxides and sulphones have been reported to undergo anion-promoted carbon-sulphur bond photocleavageboth processes appear to involve an initial electron transfer. Sulphur-hydrogen bond horaolysis has been reported in t-butanethiol and is also responsible for the photoinitiated thiylation of fluorobromoethylenes and of trialkylethynylsilanes and t-butylacetylene. 

Electro chemically reducible nitro- and cyanoarenes are used as mediators for SRN1 per-fluoroalkylation of heteroaromatics such asuracils (17) [15], purines (18), pyrimidines (19) [16], indoles (20), and imidazoles (21) [17] where the electroreductively generated arene anion radicals initiate the SET reaction [18] (Scheme 2.37). 

---