title: A novel hydrogen migration of dialkylphosphonic acid esters using electrospray ionization tandem mass spectrometry.
abstract: 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.
authors: Department of Chemistry and the Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, PR China.
authors: Zhiping
authors: Z
authors: Zeng
authors: Ping
authors: P
authors: Luo
authors: Yao
authors: Y
authors: Jiang
authors: Yan
authors: Y
authors: Liu
authors: Guo
authors: G
authors: Tang
authors: Pengxiang
authors: P
authors: Xu
authors: Yufen
authors: Y
authors: Zhao
mesh_terms: D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D041961:Deuterium Exchange Measurement / Q000379:methods*; D008968:Molecular Conformation; D063065:Organophosphonates / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013816:Thermodynamics
chemical_list: D063065:Organophosphonates; D047428:Protein Kinase Inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases