The hydroxyl radical (•OH) is a highly reactive oxygen species (ROS) that efficiently reacts with nearby biomolecules at diffusion-controlled rates of reaction. The generation of •OH by Fenton type-driven reactions is believed to take place in a site-specific manner, for example, involving metal ions in close proximity or bound to DNA (Cadet J & Wagner JR 2013).
Hydroxyl radical reacts with both the basepairs of DNA and the sugar moiety in the oligonucleotides (Dedon PC 2008; Cadet J & Wagner JR 2014). •OH reacts with 2'-deoxyribose in DNA by H abstraction from all its carbons leading to five C-centered radicals (Dedon PC 2008; Cadet J & Wagner JR 2013). The abstraction at C1' gives 2-deoxyribonolactone, the abstraction at C5′ gives 3′-phosphoglycoaldehyde, and abstraction at C4′ gives an intermediate unsaturated dialdehyde that can couple with cytosine to form a DNA inter- or intrastrand cross-link (Dedon PC 2008; Sczepanski JT et al. 2011; Cadet J & Wagner JR 2013). In addition, the C5′-centered radicals of 2-deoxyribose can react with the purine ring in the same nucleoside to produce 8,5'-cyclo-2′-deoxyguanosine (8,5'-cyclo-dGuo) or 8,5'-cyclo-2′-deoxyadenosine (8,5'-cyclo-dAdo), which are among the major lesions in DNA that are formed by attack of hydroxyl radical (Jaruga P et al. 2002; Chatgilialoglu C et al. 2011).