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Proton‐bound complex mediating retro‐Michael‐type fragmentation of protonated 3‐substituted oxindoles in the Orbitrap high‐energy collisional dissociation cell
Author(s) -
Cao Xiaoji,
Zhu Kundan,
Song Qingbao,
Wang Chenlu,
Wang Ye,
Cai Ruonan,
Lin Yan,
Tang Fangliang,
Zhang Ming,
Mo Weimin
Publication year - 2015
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.7128
Subject(s) - chemistry , orbitrap , protonation , fragmentation (computing) , proton affinity , tandem mass spectrometry , computational chemistry , dissociation (chemistry) , mass spectrometry , electrospray ionization , collision induced dissociation , ion , organic chemistry , chromatography , computer science , operating system
Rationale Oxindole derivatives are valuable building blocks for indole chemistry. Systematically exploring the fragmentation behavior of the protonated 3‐pyrazole‐substituted oxindoles by kinetic methods combined with density functional theory (DFT) calculations is useful for further understanding their basic properties, and might provide some insights into their reactivity trends in synthesis and metabolism. Methods All high‐resolution high‐energy collision‐induced dissociation tandem mass spectrometry (CID‐MS/MS) experiments were carried out using electrospray ionization hybrid Quadrupole‐Orbitrap mass spectrometry in positive ion mode. Theoretical calculations were carried out by the DFT method at the B3LYP level with the 6‐311G (d, p) basis set in the Gaussian 03 package of programs. Results In the fragmentation of protonated 3‐pyrazole‐substituted oxindoles, the characterized protonated 3‐(3‐methyl‐5‐oxo‐1 H ‐pyrazol‐4(5 H )‐ylidene)indolin‐2‐one derivatives and the protonated 5‐methylpyrazolone were observed, which were proposed from the cleavage of the C β –C γ bond in a retro‐Michael reaction. With the kinetic plot, a linear correlation was established between the intensities of this two competitive product ions and the difference in proton affinities of the corresponding neutral molecules, which demonstrated that the retro‐Michael reaction was mediated by a proton‐bound complex. Conclusions Using the kinetic method combined with theoretical calculations, a proton‐bound complex mediating retro‐Michael reaction was proposed for the fragmentation of protonated 3‐pyrazole‐substituted oxindoles in the high‐energy collisional dissociation tandem mass spectrometry for the first time, which provided potential evidence to further understand their intrinsic bioactivities. Copyright © 2015 John Wiley & Sons, Ltd.