Radical anion guanine

The high pKa-value of the cytosine radical anion, however, will enforce rapid protonation in water and maybe also by the guanine counterbase in a DNA double strand, as depicted in Scheme 3 [38]. In fact, it is currently be-... 

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]. 

P.C. Mishra et al., Interaction of singlet oxygen and superoxide radical anion with guanine and formation of its mutagenic modification 8-oxoguanine. Int. J. Quantum Chem. 102, 282-301 (2005)... 

C. Crean et al., Oxidation of guanine and 8-oxo-7, 8-dihydroguanine by carbonate radical anions Insight from oxygen-18 labeling experiments. Angew. Chem. Int. Ed. 44, 5057-5060 (2005)... 

At the time Steenken s review article was written, the radical anion of guanine had not been fully studied in aqueous solution [5], This was considered in a later study which showed that radical anion G — rapidly protonates at N3 or N7 followed by tautomerization to give a radical protonated at C8 G(C8+H) [51], Many of the solid-state studies of guanine derivatives report these H-addition radicals even at low temperatures [37, 52],... 

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. 

Joffe, A., Geacintov, N.E., and Shafirovich, V. (2003) DNA lesions derived from the site-selective oxidation of guanine by carbonate radical anions. Chem. Res. Toxicol., 16, 1528-1538. 

Yadav A, MishraPC (2011) Quantum theoretical study of mechanism of the reaction between guanine radieal eation and carbonate radical anion formation of 8-oxoguanine. Int J Quantum Chem 112 2000-2008... 

Joffe A, Geacintov NE, Shafirovich V (2003) DNA lesions derived from the site selective oxidation of guanine by carbonate radical anions. Chem Res Toxicol 16 1528 1538 Masuda M, Suzuki T, Friensen MD, Ravanat JL, Cadet J, Pignattelli B, Nishino H, Ohshi-ma H (2001) Chlorination of guanosine and other nucleosides by hypochlorous acid and myeloperoxidase of activated human neutrophils catalysis by nicotine and trimethylamine. J Biol Chem 276 40486 10496... 

Fig. 13 Results from the quantum calculations on the duplex sequence 5 -GAGG-3. In a, the sodium ions and their solvating water molecules are located at positions near the phosphate anions of the DNA backbone. In b, one sodium ion is moved from near a phosphate anion to N-7 of a guanine, which molecular dynamics calculations show to be a preferred site. The balloons represent the hole density on the GAGG sequences with the two different sodium ion orientations. The radical cation clearly changes its average location with movement of the sodium ion...

With the site-selective hole injection and the hole trapping device established, the efficiency of the hole transport between the hole donor and acceptor, especially with respect to the distance and sequence dependence, were examined. Our experiments showed that hole transport between two guanines was extremely inefficient when the intervening sequence consisted of more than 5 A-T base pairs [1]. Hole injection into the DNA n-stack using photoexcited dCNBPU was accompanied by the formation of dCNBPU anion radical. Therefore, hole transport would always compete with the back electron transfer (BET). To minimize the effect of BET, we opted for hole transport between G triplets, that are still lower in oxidation potential than G doublet. With this experimental system, we researched the effect of the bridging sequence between two G triplets on the efficiency of hole transport [2]. 

Therefore, the N(9) radical should be more stable than the N(6) one. That is why both radicals coexist in the system and both N(9) and N(6) deprotonations take place. In the case of the guanine cation-radical, the presence of the carbonyl group in the pyridazine ring brings about two additional effects Deprotonation infringes on this ring exclusively, and double deprotonation leads to the formation of a distonic anion-radical. Scheme 1.25 depicts the differences mentioned. Adhikary et al. (2006) substantiated it experimentally (ESR and UV) and theoretically (B3LYP). 

The previous section outlined the typical e loss and e gain products observed in the nucleic acid bases in the solid state. These studies can be applied to the study of the radiation chemistry of DNA. The relevance of the study of model systems is shown by considering the following remarkable observations. Years ago, Ehrenberg et al. showed the EPR spectra of the 5,6-dihydrothymine-5-yl radical observed in thymine, thymidine, and DNA. The spectra are nearly identical [46]. The reduction product observed in cytosine monohydrate is the N3 protonated anion. In solution, this reduction product gives rise to a 1.4-mT EPR doublet. The same feature is present in irradiated DNA at 77 K. Likewise, the result of e loss in guanine bases is characterized by a broad EPR singlet. The same feature is also evident in the EPR spectrum of DNA irradiated and observed at 77 K. 

---