Proton Transfer And Fragmentation Reaction In ESI-MS~n

Soft ionization methods combined with tandem mass spectrometry, especially ESI-MS", are widely used nowadays in the structural analysis of organic and biologic compounds. However, unlike the cases in EI-MS, protonated molecules MH+ in ESI are even-electron ions, and the reactions of the MH+ ions are directed by the formal charge. Corresponding theoretical systems for elucidating the phenomena in ESI-MSn are still rather insufficient. This study tries to find some rules for the gas-phase fragmentation reaction in ESI-MSn based on the inverstigation of several types of model compounds, including the following four subjects:1. Dissociative protonation and proton transfersa,β-unsaturated aromatic ketones (chalcones) were used as model compounds. In the mass spectrometry of protonated chalcones, phCO+ and ph'CH=CHCO+ were observed as the major fragments. It was found that the carbonyl oxygen was the most favorable site for protonation, and proton transfer to a "dissociative protonation site" was a regulator of the overall reactions. The substituent effect was used as a probe to examine the reaction mechanisms. The proton transfer intermediate was confirmed by the fragmentation of 1,5-diketone compounds. The proton transfer mechanisms were also investigated by theoretical calculations and isotope labeling experiments. Besides, intermediate MH-3 was found as an ion-neutral complex, which was a direct evidence for "dissociative protonation site". The model of "dissociative protonation site" can be used for discussing the fragmentation reaction from the protonated molecules MH+ in ESI mass spectrometry.2. Retro Friedel-Crafts reaction of several heterocyclic drugsRetro Friedel-Crafts reaction could be observed, and sometimes it was the main fragmentation reaction for the heterocyclic drugs. "Dissociative protonation site" model could be well used to discuss the deacylation, dealkylation and desulfonation reactions. Only when the proton attached to the dissociative site would arouse the retro-friedel crafts reaction. Besides, High resolution mass spectrometer (HRMS) and isotope labeling experiments were applied to investigate several INC-mediated fragmentation reactions.3. INC -mediated charge transfer reactionA series of phenyl-, benzenesulfonamide compounds were used as a model to study a new type of INC-mediated charge transfer reaction. Different from amides, the most stable protonation site for sulfonamides was N atom, and the S-N bond dissociate spontaneously when the proton attached the N atom to form a ion-neutral complex: [benzenesulfonyl cation, aniline]. Similar to the H-transfer, electron can also transfer in the ion-neutral complex with a charge shift between the two parts, made the aniline radical cation RC6H4NH2+·become the main fragment ion, which disobeyed the "even-electon rules". The charge transfer reaction is related to the ionization abilities of the partners.4. Study on rearrangement reaction by substituent effectRearrangement reactions are often observed in mass spectrometry, and the substituent effect is a helpful method to investigate the reaction mechanism. We studied the substituent effect on the SO2 elimination from N-arylbenzenesulfonamides, and found the curve in the plot of ln[(M-H-SO2)-/(M-H)-] vsσp-.Two routes of nucleophilic reactions were proposed. This mechanism was also supported by ESI-MSn experiments and theoretical calculation.Besides, this study sums up the researches of the soft ionization mass spectrometry (especially ESI-MS) and the theories related to ESI-MS.