A novel rearrangement of fluorescent human thymidylate synthase inhibitor analogues in ESI tandem mass spectrometry

Abstract

Cu(I) catalyzed alkyne-azide cycloaddition reaction was employed to synthesize a series of anthracene-based human thymidylate synthase (hTS) inhibitor analogues. The triazoloanthracene 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 triazoloanthracene 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 ␥ position rather than the ␣ or ␤ position of the anthracene moiety by an electrophilic substitution mechanism. (J Am Soc Mass Spectrom 2010, 21, 403-410)

Gas-Phase Chemistry of Benzyl Cations in Dissociation ofN-Benzylammonium andN-Benzyliminium Ions Studied by Mass Spectrometry

“…Consequently, a need for other examples of INC-mediated reactions is evident in order to better understand the fragmentation reactions in the contemporary ESI mass spectrometry, a method that has become one of the most popular analytical methods. Thus, renewed interest in studies on INC-mediated fragmentation reactions has emerged in recent years [8,[20][21][22][23][24][25][39][40][41][42][43][44][45][46][47].…”

N-Centered Odd-Electron Ions Formation from Collision-Induced Dissociation of Electrospray Ionization Generated Even-Electron Ions: Single Electron Transfer via Ion/Neutral Complex in the Fragmentation of ProtonatedN,N′-Dibenzylpiperazines and ProtonatedN-Benzylpiperazines

“…The well-documented reactions are isomerization, proton transfer and small alkyl carbocation transfer. In very recent years, several novel reactions were uncovered in ESI mass spectrometry, such as electrophilic aromatic substitution [18][19][20], hydride transfer [21,22], transacylation [23], formaldehyde loss [24], and ester group transfer [25].…”

“…In the present study, we focus on the mechanism for formation of OE ions from protonated Nbenzyl compounds and provide a novel perspective. Since the ion/neutral complexes had been designated and confirmed as intermediates for other reaction pathways in the fragmentation of N-benzyl compounds [19][20][21][22], it is reasonable that the N-centered OE ions also derive from the ion/ neutral complex intermediates. For the [benzyl cation/ piperazine] complex, benzyl cation is electron deficient while piperazine is apt to donate electron, thus the electron transfer between them is feasible.…”

Intramolecular Halogen Transfer via Halonium Ion Intermediates in the Gas Phase

“…The fragmentation reactions of organic compounds in multi-stage mass spectrometry are directly related to their structures, but the interpretation of mass spectra is not always straightforward because of many rearrangements that take place during fragmentation. In recent years, considerable research in ESI-MS has focused on studying the skeletal rearrangements of organic compounds, including alkyl transfer [24,25], benzyl cation transfer [26][27][28][29][30], benzoyl cation transfer [31], phosphate group migration [32], intramolecular electrophilic substitution [33,34], tosyl cation transfer [35], and ion/neutral complexmediated fragmentations [36][37][38][39].…”