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A novel hydrogen migration of dialkylphosphonic acid esters using electrospray ionization tandem mass spectrometry
Author(s) -
Zeng Zhiping,
Luo Ping,
Jiang Yao,
Liu Yan,
Tang Guo,
Xu Pengxiang,
Zhao Yufen
Publication year - 2011
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.5215
Subject(s) - chemistry , mass spectrometry , electrospray ionization , tandem mass spectrometry , fragmentation (computing) , deuterium , transition state , kinetic isotope effect , computational chemistry , hydrogen–deuterium exchange , medicinal chemistry , organic chemistry , chromatography , catalysis , physics , quantum mechanics , computer science , operating system
In this paper, attention is focused on analysis of the fragmentation of α‐hydroxy‐β‐amino phosphonate esters designed as inhibitors of protein kinase A. An interesting proton migration mechanism in the cleavage of the P‐C bond is investigated by electrospray ionization tandem mass spectrometry. A possible rearrangement mechanism is proposed and verified by high‐resolution mass spectra using isotope deuterium/hydrogen‐exchange technology and additionally checked by detailed DFT calculation based on Gaussian software. The result clearly indicates that this mechanism proceeds by a five‐membered ring concerted transition state with activation energy 11.3 kcal mol −1 for the compound 3f. The overall reaction is endothermic with an energy 13.2 kcal mol −1 . The effect of different substituents and different metal ions for rearrangement of these esters is studied by experiment and theory. It is concluded that this rearrangement process is energetically unfavorable and hence only occurs in the mass spectrometer. Copyright © 2011 John Wiley & Sons, Ltd.