Oxidative guanine

Also, the distance of the injection system from the first oxidized guanine influences the product ratio Pggg/Pgu because the injection system itself can influence the water trapping rate of the nearby Gf+. Therefore, the experimentally detected efficiencies of the charge transfer (measured by the ratio of the chemical products) depend upon the special injection system and the reaction conditions. This has to be taken into account if the experimental results obtained under different reaction conditions are to be compared with each other. 

Fig. 9 Long-range oxidative damage in DNA is regulated by the structure of the DNA n-stack. Photoexcited [Rh(phi)2(bpy )]3+ intercalated within B-DNA oxidizes guanine doublets positioned 17 A and 40 A away with approximately equal efficiency. When a bulge is introduced in the DNA oxidation at the distal guanine doublet is inhibited. As shown by the NMR structure, bulges introduce local distortions in the DNA r-stack, although the kinking of the helical actually positions the distal guanine closer to the Rh(III) photooxidant...

Correlation between Electrochemical and Biological Oxidation Guanine... 

The kinetics and mechanisms of the oxidation of DNA, nucleic acid sugars, and nucleotides by [Ru(0)(tpy)(bpy)] and its derivatives have been reported. " The Ru =0 species is an efficient DNA cleavage agent it cleaves DNA by sugar oxidation at the 1 position, which is indicated by the termini formed with and without piperidine treatment and by the production of free bases and 5-methylene-2(5//)-furanone. Kinetic studies show that the I -C— activation is rate determining and a hydride transfer mechanism is proposed. The Ru =0 species also oxidizes guanine bases via an 0x0 transfer mechanism to produce piperidine-labile cleavages. 

It is not clear what the structure of one-electron oxidized guanine is in DNA. The amino-deprotonated product observed in 5-dGMP does not seem to fit parameters of the oxidation species observed in DNA. Recently, Reynisson and Steenken have proposed that the one-electron oxidized species found in ds DNA is the radical cation [41]. 

Electron and Hole Transfer to Oxidized Guanine Sites. 124... 

Guanine is the most easily oxidizable natural nucleic acid base [8] and many oxidants can selectively oxidize guanine in DNA [95]. Here, we focus on the site-selective oxidation of guanine by the carbonate radical anion, COs , one of the important emerging free radicals in biological systems [96]. The mechanism of COs generation in vivo can involve one-electron oxidation of HCOs at the active site of copper-zinc superoxide dismutase [97, 98], and homolysis of the nitrosoperoxycarbonate anion (0N00C02 ) formed by the reaction of peroxynitrite with carbon dioxide [99-102]. 

Building films a layer at a time allowed us to incorporate catalytic metallopolyion catalysts for DNA oxidation into reagentless toxicity biosensors. Two polyions containing Ru(bpy)2+ were used that are capable of cat-alytically oxidizing guanines in DNA. The one shown below, denoted Ru-PVP, has 6 Ru-N bonds and reversible oxidation at 1.15 V vs. SCE. 

Figure 24.12. Examples of DNA adducts and oxidized guanine nucleotide. (A) Benzo[a]pyrene-7,8-diol-9,10-epoxide-M-2 guanine adduct. (B) Aflatoxin epoxide N7 guanine adduct. (C) 8-Oxoguanine is commonly produced by reactive oxygen species, dR = deoxyribose.

It seems then that one-electron oxidized guanine in the solid-state deprotonates at the amino group. There is however no good evidence that this occurs in aqueous solution. A study of guanine derivatives in aqueous solution using pulse radiolytic techniques concluded that one-electron oxidized guanine deprotonated at Nl [55], Early ab initio calculations on guanine concluded that G(N1-H) is the more stable than G(N2-H) [56], However more recent DFT and molecular dynamics calculations have come to the opposite conclusion [57], Calculations have also been performed on G C base pairs. Hutter and Clark have concluded that proton transfer... 

Scheme 20-2. The numbering scheme and prototropic equilibria of one-electron oxidized guanine cation radical (G +), the mono- deprotonated species, (G(N1-H) and G(N2-H), in syn and anti- conformers with respect to the N3 atom) and the di- deprotonated species, G(-2H) . (Reprinted with permission from ref. [189], J. Phys. Chem. (2006) American Chemical Society.)...

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