Open AccessA novel rearrangement of fluorescent human thymidylate synthase inhibitor analogues in ESI tandem mass spectrometry
Author(s) -
Yi Chen,
Céline Le Droumaguet,
Kai Li,
William E. Cotham,
Norman Lee,
Mike Walla,
Qin Wang
Publication year - 2010
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 - 10.1016/j.jasms.2009.11.004
Subject(s) - chemistry , thymidylate synthase , tandem mass spectrometry , mass spectrometry , fluorescence , chromatography , tandem , medicine , fluorouracil , surgery , chemotherapy , physics , materials science , quantum mechanics , composite material
Cu(I) catalyzed alkyne-azide cycloaddition reaction was employed to synthesize a series of anthracene-based human thymidylate synthase (hTS) inhibitor analogues. The triazolo-anthracene derivatives were characterized by ESI-MS/MS and a novel rearrangement reaction in ESI-MS/MS was observed. The mechanism is proposed whereby the protonated triazolo-anthracene derivative forms a carbocation, and then the carbocation electrophilically attacks an anthracene moiety resulting in formation of a rearrangement ion. Moreover, the carbocation prefers to attack the gamma position rather than the alpha or beta position of the anthracene moiety by an electrophilic substitution mechanism.