Dissertation > Mathematical sciences and chemical > Chemistry > Organic Chemistry > Organic Chemistry general issues > Properties of organic compounds > Chemical properties of organic reactions

Formation and Fragmentation of Protonated N-containing Organic Compounds in Atmospheric Pressure Ionization Mass Spectrometry

Author ChaiYunFeng
Tutor PanYuanJiang
School Zhejiang University
Course Chemistry
Keywords atmospheric pressure ionization mass spectrometry electrospray ionization atmospheric pressure chemical ionization protonation proton transfer ion/neutralcomplex benzyl cation
CLC O621.25
Type PhD thesis
Year 2013
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Atmospheric pressure ionization mass spectrometry (API-MS) is one of the important tools for analysis and structure elucidation of organic compounds. The protonated ion of organic compounds is the most common quasi-molecular ion in API-MS, which provides molecular weight and structural information. Therefore, understanding the formation and fragmentation mechanism of protonated ions is the core issue of organic mass spectrometry. In this dissertation, using typical N-containing compounds as models, two aspects including the generation mechanism of protonated ions in the ion source and the fragmentation rules of protonated ions in tandem mass spectrometry were studied, which specifically includes the following four parts:1. Using p-(dimethylamino)chalcone as a model compound, the kinetically controlled protonation reaction in atmospheric pressure chemical ionization (APCI) was reported for the first time. The most basic site ofp-(dimethylamino)chalcone in solution is the N, while the most stable protonation site of it in the gas phase is the carbonyl O. Thus according to the conventional understanding, the O-protonated ion should be dominantly formed in APCI. However, when acetonitrile/water is used as the solvent and the infusion rate is relatively high, the N-protonated ion is preferentially produced. The proposed explanation is that under the present ionization conditions highly solvated N-protonated ions are formed, which is close to the situation in liquid phase. This finding will help us better understand the mechanism of APCI.2. Using1,4-diphenyl-3-benzoyl-1,4-dihydropyridines as model compounds, a rare dehydrogenation reaction in electrospray ion source was reported. When a protic solvent is used, the [M+H]+ion is mainly formed; when an aprotic solvent is used, the generation of [M-H]+ion is dominant. With the aid of a variety of experimental methods, it is proved that the dehydrogenation reaction is an electrochemical oxidation reaction induced by the high voltage in the spray needle, in which the1,4-dihydropyridine ring is oxidized to a pyridine ring. This is a special case of ion suppression. 3. Using N-benzyl lactams as model compounds, the proton transfers in the fragmentation of their proton adducts were studied. The fragmentation of protonated N-benzyl lactams requires the ionizing proton migrating from the thermodynamically stable carbonyl oxygen to the lactam nitrogen or the ipso position of the phenyl ring. Experimental and theoretical studies indicate that a direct1,5-H shift is responsible for the proton transfer from the carbonyl oxygen to the ipso position of the phenyl ring. However, the proton transfer from the carbonyl oxygen to the lactam nitrogen is not achieved via a classical1,3-H shift. In fact, the proton first migrates from the carbonyl oxygen to the ortho position of the phenyl ring and then to the lactam nitrogen, in which the phenyl ring acts as a catalyst (intramolecular proton-transport catalysis). Further studies found that the present fragmentation reaction model is applicable to other N-benzyl amides and drugs containing such a skeleton structure.4. Using N-benzyl piperidine and N-benzyl piperazine as model compounds, the fragmentation rules of protonated N-benzyl structure-containing compounds were systematically studied and five kinds of ion/neutral complex-mediated benzyl cation-involved reactions were concluded including hydride ion transfer, electrophilic substitution, electron transfer, proton transfer, and nucleophilic aromatic substitution. This study prompts us to obtain comprehensive understanding on the reactivity of the benzyl cations. The fragmentation rules summarized in this study have been well applied by other domestic and foreign mass spectrometrists in their researches. These fragmentation rules also can be used to rationalize the generation of special fragment ions in the fragmentation of related drugs.In addition, the ionization mechanism of atmospheric pressure ionization source was briefly summarized and the important rearrangements of protonated ions generated by API-MS in collision-induced dissociation were reviewed.

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