Glycosidic Bond Cleavage of Pyrimidine Nucleosides by Low-Energy Electrons:  A Theoretical Rationale

DNA damage by attachment of low-energy secondary electrons is a very interesting and important mechanism. Electron capture and subsequent base release are thought to be the elementary steps of this mechanism. The process of the N1-glycosidic bond breaking of anion radicals of pyrimidine nucleosides, specifically the 2'-deoxyribothymidine (dT) and 2'-deoxyribocytidine (dC) anions, has been investigated theoretically at the B3LYP/DZP++ level of theory. The release of nucleobases by the attachment of low-energy electrons depends on the formation of a stable anion radical of the nucleoside. The lower bond-breaking activation energy and the higher vertical electron detachment energy for dT enables the heterolytic cleavage of the N1-glycosidic bond. However, with the higher bond-breaking activation energy and the lower vertical electron detachment energy for dC, the release of cytosine might be impractical when the incident electrons have high kinetic energy. Furthermore, the release of cytosine would have a quantum yield much lower than that of dT when the incident electrons have lower kinetic energy. This study also demonstrates the importance of the proton at O5' of 2'-deoxyribose in the base release process. Extending this investigation from dT to dC advances the insight into the mechanism of the N1-glycosidic bond-breaking process. The information from this extensive investigation should be valuable for further experimental studies of cytosine release in irradiated DNA.