The multifaceted behavior of electron attachment in 8-bromo-purine derivatives and the connection with DNA damage^†

This review summarizes the discoveries of 8-bromopurine nucleosides (8-Br-Pu), particularly 8-bromo-2'-deoxyadenosine (8-Br-dA) and 8-bromo-2'-deoxyguanosine (8-Br-dG), in chemistry and biology over the past two decades. It compiles available data on the reactions of hydrated electrons (e_aq^-) with various 8-bromopurines, as determined by pulse radiolysis and supported by theoretical studies. Three distinct mechanistic pathways are identified: dissociative electron attachment, sequential electron transfer-proton transfer, and concerted electron-proton transfer. This review also highlights the use of 8-Br-dA and 8-Br-dG in the synthesis of a library of 5',8-cyclopurine nucleosides (cPu) for quantifying them in genetic material and incorporating them into oligonucleotides (ODNs) for DNA repair research. Additionally, the summary covers the use of 8-Br-dA and 8-Br-dG embedded in various ODNs to study excess electron transfer (EET), their potential as radiosensitizers, and their formation in vivo via hypobromous acid.

Based on radiation chemistry, our understanding of the one-electron reduction of 8-Br-dA and 8-Br-dG has been enhanced substantially. This mechanistic background is crucial for a better understanding of and addressing their significant roles in the biological environment, such as DNA radiosensitizers for cancer radiation therapy or as biomarkers for early inflammation.