Singlet oxygen guanine oxidation

Figure 3.1 Singlet oxygen oxidation of the guanine moiety in DNA.

CT-induced damage, consistent with theoretical predictions that the HOMO of guanine doublets is localized on the 5 -G [90]. Conversely, non-specific oxidation of both guanines is indicative of an alternative chemistry, for instance reaction with singlet oxygen. 

H-atom abstraction has been demonstrated to be the mechanism of action of excited uranyl ions, and in this case negligible base oxidation is found. Nucleo-base (especially guanine) oxidation is the principal reaction caused by singlet oxygen and this reactive species can be generated by a number of the complexes (e.g. many Ru(II)polypyridyls and porphyrins). It is worth pointing out, however, that the yield of may be lower when the sensitiser is bound to DNA, and it is the authors view that some of the reactions claimed to proceed via 62 may be caused by direct reaction of the photo-oxidised sensitiser with the DNA. 

Guanine is a preferential DNA target to several oxidants it shows the lowest ionization potential among the different purine and pyrimidine nucleobases and it is the only nucleic acid component that exhibits significant reactivity toward singlet oxygen ( O2) at neutral pH. ... 

It is well established that singlet oxygen is able to oxidise DNA with a much higher specificity than hydroxyl radical. The main stable oxidation products of the reaction of O2 with 2-deoxyribose guanine were identified as the and 4S diastereoisomers of 4-hydroxy-8-oxo-4,8-dihydro-2 -deoxy-guanosine on the basis of extensive NMR and mass spectrometry measurements (Ravanat et al. 1992, Ravanat and Cadet 1995). Similar oxidation products were generated by the type II photooxidation reaction of 2 -deoxyguanosylyl -(3 -5 )-thymidine (Buchko et al. 1992). 

Cui L, Ye WJ, Prestwich EG, Wishnok JS, Taghizadeh K, Dedon PC, Tannenbaum SR (2013) Comparative analysis of four oxidized guanine lesions from reaetions of DNA with peroxyni-trite, singlet oxygen, and gamma-radiation. Chem Res Toxieol 26 195-202... 

The main oxidising agent of DNA is the hydroxyl radical (HO ), which oxidises the purine and pyrimidine bases and deoxyribosyl residues. The main oxidation products are 5-(hydroxymethyl)uracil (3-153) and S-hydroxyguanine (3-154), which is formed by reaction of guanine with singlet oxygen. In the presence of transition metals, the main compound that is attacked is adenine. The reaction product is adenine-N -oxide (3-155). 

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