Investigation On The Fragmentation Behaviors Of Metal Ion Adducts Of Organic Compounds In Electrospray Tandem Mass Spectrometry

Electrospray ionization mass spectrometry(ESI-MS), especially tandem mass spectrometry(MS/MS), is an essential tool for structural characterization of organic compounds. In ESI-MS, compounds are usually ionized in the protonated, deprotonated or cationized forms. In the past decades, there are abundant research reports on the fragmentation behaviors of protonated and deprotonated molecules in ESI-MS. However, the fragmentation reactions of cationized molecules in ESI-MS have not yet been well investigated. Therefore, it is very important and necessary to explore and summarize the dissociation mechanisms of these metal ion-adducts. In this thesis, several typical organic compounds were selected as models to investigate the metal ion mediated gas-phase mechanistic dissociation reactions and to summarize the corresponding fragmentation rules, including the following four parts:1. Investigation on the alkali metal mediated MSn fragmentation behaviors:The fragmentation behaviors of alkali metal ion-adducts of β-anilinodidrochalcones and Si-69 have been investigated by electrospray ionization tandem mass spectrometry(ESI-MSn). Sodiated N-benzylidenebenzenamine(P1) was the main fragment ion of sodiated β-anilinodidrochalcones, which was facile to undergo solvation reactions with the residual ESI solvent molecules(H2O and CH3OH) in the vacuum system, as verified by MS3 and accurate MS analysis. The formed hydrated ions appears as an unusual leading peak in the profile spectrum, which results in a deviant decreasing mass shift of almost 1 Da. Mass shift of the hydrated ion was the result of the weak association in the complex and the unique operating manner of the mass analysis step in ion trap mass spectrometer. The same mass deviation phenomenon also occurred in the gas-phase dissociation of [S4+Li]+.2. Investigation on the gas phase chemistry of the Ni2+- mediated halogenated phenylmethylidene hydrazinecarbodithioates(MX):The complex ion [2MX – H + N i]+, which was produced from ESI of a diluted solution containing N iCl2 and halogenated phenylmethylidene hydrazinecarbodithioates(MX), undergo dissociation to afford an active complex [MX + SCH3 + Ni]+ ion in MS2 experiments. In MS3 experiments, complex ion [MX + SCH3 + Ni]+ undergoes ligand exchange reactions with residual gas molecules such as water, acetonitrile, and nitrogen in the ion trap. In addition, the o-isomers [Mo-X + SCH3 + Ni]+ have been found to undergo the characteristic HX elimination to afford several unique ions due to the “ortho effect”. The order of HX elimination reaction is: [Mo-Br + SCH3 + Ni]+ > [Mo-Cl + SCH3 + Ni]+ > [Mo-F + SCH3 + Ni]+. The three isomeric complexes of [MX + SCH3 + Ni]+ show significantly different MSn behaviors, which al ow evident assignment of these isomers.3. The distinction of positional isomers of OMe/Me/NO2 substituted phenylmethylidene hydrazinecarbodithioates(MR) mediated by Ni2+:Metal complexation and ESI-MSn analysis have been further applied for rapid differentiation of the isomeric phenylmethylidene hydrazinecarbodithioates(MR, R=OMe, Me, NO2). The active complex [MR + SCH3 + Ni]+ undergo ligand exchange reactions in MS3 experiments, with residual molecules such as H2 O, N2 and CH3 CN in the ion trap. The isomers have been completely differentiated based on the characteristic product ions and the significant difference in the distribution of product ions, due to their different reactivity and the ortho effect. These results are important to the MS-based isomeric differentiation and the proper interpretation of the mass spectra of the metal complex ions.4. Transition metal ion mediated chiral recognition of chiral drugs:A rapid and sensitive approach based on the MS kinetic method was applied for the chiral recognition and enantiomeric excess measurement of Rivaroxaban enantiomer. Transition metal bound trimeric complex ions containing the chiral alanalyte and chiral selector were generated by electrospray ionization mass spectrometry and subjected to collision- induced dissociations. The ratio of two product ions originated from two competitive dissociation of [CuII(L- Trp)2(AS/R)-H]+ is significantly different between the two isomers under the same CID conditions, Rchiral =2.06, indicating that the two isomeric compounds can be differentiated by tandem MS.