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The Equally Important Role of Adenine Derivatives to That of Pyrimidine Derivatives in Near‐0 eV Electron‐Induced DNA Lesions
Author(s) -
Wang Shoushan,
Zhao Peiwen,
Zhang Changzhe,
Bu Yuxiang
Publication year - 2016
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201600002
Subject(s) - pyrimidine , dna , chemistry , electron , computational chemistry , photochemistry , combinatorial chemistry , stereochemistry , biochemistry , physics , quantum mechanics
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 N 7 ‐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—N 7 ‐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 N 9 −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 N 9 −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 C 8 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 N 9 ‐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 N 1 ‐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.