Open AccessCollision-Induced Dissociation Studies of Protonated Ions of Alkylated Thymidine and 2′-Deoxyguanosine
Author(s) -
Yuxiang Cui,
Jun Yuan,
Pengcheng Wang,
Jun Wu,
Yang Yu,
Yinsheng Wang
Publication year - 2020
Publication title -
journal of the american society for mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.961
H-Index - 127
eISSN - 1879-1123
pISSN - 1044-0305
DOI - 10.1021/jasms.9b00147
Subject(s) - chemistry , protonation , alkyl , tandem mass spectrometry , nucleobase , alkylation , alkene , adduct , deoxyadenosine , fragmentation (computing) , dissociation (chemistry) , medicinal chemistry , collision induced dissociation , stereochemistry , mass spectrometry , photochemistry , ion , dna , organic chemistry , chromatography , biochemistry , catalysis , computer science , operating system
Mass spectrometry and tandem MS (MS/MS) have been widely employed for the identification and quantification of damaged nucleosides in DNA, including those induced by alkylating agents. Upon collisional activation, protonated ions of alkylated nucleosides frequently undergo facile neutral loss of a 2-deoxyribose in MS/MS, and further cleavage of the resulting protonated nucleobases in MS 3 can sometimes be employed for differentiating regioisomeric alkylated DNA lesions. Herein, we investigated systematically the collision-induced dissociation (CID) of the protonated ions of O 4 -alkylthymidine ( O 4 -alkyldT), O 2 -alkyldT, O 6 -alkyl-2'-deoxyguanosine ( O 6 -alkyldG), and N 2 -alkyldG through MS 3 analysis. The MS 3 of O 2 - and O 4 -MedT exhibit different fragmentation patterns from each other and from other O 2 - and O 4 -alkyldT adducts carrying larger alkyl groups. Meanwhile, elimination of alkene via a six-membered ring transition state is the dominant fragmentation pathway for O 2 -alkyldT, O 4 -alkyldT, and O 6 -alkyldG adducts carrying larger alkyl groups, whereas O 6 -MedG mainly undergoes elimination of ammonia. The breakdown of N 2 -alkyldG is substantially influenced by the structure of the alkyl group, where the relative ease in eliminating ammonia and alkene is modulated by the chain length and branching of the alkyl groups. We also rationalize our observations with density functional theory (DFT) calculations.