title: How does a CC double bond cleave in the gas phase? Fragmentation of protonated ketotifen in mass spectrometry.
abstract: In the literature, it is reported that the protonated ketotifen mainly undergoes CC double bond cleavage in electrospray ionization tandem mass spectrometry (ESI-MS/MS); however, there is no explanation on the mechanism of this fragmentation reaction. Therefore, we carried out a combined experimental and theoretical study on this interesting fragmentation reaction. The fragmentation of protonated ketotifen (m/z 310) always generated a dominant fragment ion at m/z 96 in different electrospray ionization mass spectrometers (ion trap, triple quadrupole and linear trap quadrupole (LTQ)-orbitrap). The mechanism of the generation of this product ion (m/z 96) through the CC double bond cleavage was proposed to be a sequential hydrogen migration process (including proton transfer, continuous two-step 1,2-hydride transfer and ion-neutral complex-mediated hydride transfer). This mechanism was supported by density functional theory (DFT) calculations and a deuterium labeling experiment. DFT calculations also showed that the formation of the product ion m/z 96 was most favorable in terms of energy. This study provides a reasonable explanation for the fragmentation of protonated ketotifen in ESI-MS/MS, and the fragmentation mechanism is suitable to explain other CC double bond cleavage reactions in mass spectrometry. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Tea Research Institute, Chinese Academy of Agricultural Sciences, 9 South Meiling Road, Hangzhou, 310008, PR China.|College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Yunfeng
authors: Y
authors: Chai
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Lu
authors: L
authors: Wang
authors: Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124, PR China.
authors: Lin
authors: L
authors: Wang
keywords: DFT calculation; double bond cleavage; hydride transfer; ion-neutral complex; ketotifen; proton transfer