The Equally Important Role of Adenine Derivatives to That of Pyrimidine Derivatives in Near‐0 eV Electron‐Induced DNA Lesions

The role of adenine (A) derivatives in DNA damage is scarcely studied due to the low electron affinity of base A. Experimental studies demonstrate that low‐energy electron (LEE) attachment to adenine derivatives complexed with amino acids induces barrier‐free proton transfer producing the neutral N₇‐hydrogenated adenine radicals rather than conventional anionic species. To explore possible DNA lesions at the A sites under physiological conditions, probable bond ruptures in two models—N₇‐hydrogenated 2′‐deoxyadenosine‐3′‐monophosphate (3′‐dA(N7H)MPH) and 2′‐deoxyadenosine‐5′‐monophosphate (5′‐dA(N7H)MPH), without and with LEE attachment—are studied by DFT. In the neutral cases, DNA backbone breakage and base release resulting from C_3′?O_3′ and N₉?C_1′ bond ruptures, respectively, by an intramolecular hydrogen‐transfer mechanism are impossible due to the ultrahigh activation energies. On LEE attachment, the respective C_3′?O_3′ and N₉?C_1′ bond ruptures in 3′‐dA(N7H)MPH]^? and 5′‐dA(N7H)MPH]^? anions via a pathway of intramolecular proton transfer (PT) from the C_2′ site of 2′‐deoxyribose to the C₈ atom of the base moiety become effective, and this indicates that substantial DNA backbone breaks and base release can occur at non‐3′‐end A sites and the 3′‐end A site of a single‐stranded DNA in the physiological environment, respectively. In particular, compared to the results of previous theoretical studies, not only are the electron affinities of 3′‐dA(N7H)MPH and 5′‐dA(N7H)MPH comparable to those of hydrogenated pyrimidine derivatives, but also the lowest energy requirements for the C_3′?O_3′ and N₉‐glycosidic bond ruptures in 3′‐dA(N7H)MPH]^? and 5′‐dA(N7H)MPH]^? anions, respectively, are comparable to those for the C_3′?O_3′ and N₁‐glycosidic bond cleavages in corresponding anionic hydrogenated pyrimidine derivatives. Thus, it can be concluded that the role of adenine derivatives in single‐stranded DNA damage is equally important to that of pyrimidine derivatives in an irradiated cellular environment.