Studies On The Fragmentation Mechanisms Of Electron-Impact And Electrospray Ionization Organic Mass Spectrometry By Quantum Chemistry

Mass spectrometry has become an indispensable instrument in modern analytical technology due to its high sensitivity in rapidly and accurately identifying unknown compounds. Particluarly when coupled to the high separation efficency of different kinds of gas chromatography (GC), it becomes a powerful tool for complex mixtures analysis. However, the interpretion of mass spectral fragmentation patterns, in terms of structural elucidation of the preionization molecules, is still a challenging puzzle for many compound classes.The aim of this work is to study on the fragmentation mechanisms of Electron-Impact and Electrospray ionization Organic mass spectrometry by quantum chemistry based on the electron transfer law and point of view of energy, through mass spectral interpretation of indole alkaloid derivatives and protonated belactosin derivatives under the electron-impact and electrospray ionization conditions, respectively. At the same time, a new EEM approach, which could be fast and more accurately used to calculate atomic charges in large biological molecues, has been developed to help to interpret mass spectra. The thesis is mainly referred to following aspects:1. To predict preferred decomposition pathways in electron-impact mass spectrometry, a new approach, which is applied to determine the most likely initial ionization site by the natural spin density and the change of the charges and molecular structures from neutral to cationic form based on the DFT theory at B3LYP/6-31+G (d, p) level, has been proposed for the first time in this study (chapter 3). The characteristic mass spectral fragmentation of simple indole alkaloids are elucidated by determining the localization of intial ionization site using this method and the predicted results are in good agreement with the experimental mass spectra from National Institute of Standards and Technology (NIST). Results show that this method is superior to the traditional method, which is based on the ionization energy of comparable functional groups.2. To further test the reliability and accuracy of this new method, the energy and structural properties of reactants, products, neutral fragments, and transition states related to the dissociation of indole alkaloid derivatives in EI source are calculated and analysed based on the Density Functional Theory (DFT) at the B3LYP/6-31+(d, p) level(chapter 3). Results show that the method presented in this study is feasible and reliable for determination of favorable ionization site in EI mass spectra. More importantly, it has been further demonstrated that for those compounds containing hereatoms such as nitrogen, the main primaryα-cleavage fragmentations could be directly determined as long as the initial ionization site is assured.3.To unravel the fragmentation mechnisms of electrospray ionization organic mass spectrometry, the Gas-phase dissociation mechanisms of protonated belactosin precursor have been investigated by density functional theory (DFT) at the B3LYP/6-31+G (d, p) level(chapter 4). The possible protonation sites have been determined by comparing with Fukui functions, gas-phase basicity (GB), and relative Gibbs energies of all possible protonated species. Possible fragmentation pathways for protonated precursor of belactosin derivatives [M+H]+ are proposed on the basis of the theoretical calculations.4. Determination of atomic charge distribution in ionized molecule is an initial key step to predict its favorable fragmentatation pathways, especially helpful for EI and ESI mass spectral interpretation. On the basis of the Electronegativity equalization method (EEM), a modified Electronegativity equalization method (MEEM), which could be used to fast and more accurately calculate atomic charges for large biological molecules, has been presented in this research (chapter 5). Results show that the accuracy of the modified EEM method improves significantly as compared to that of the original EEM method.5. To further improve the accuracy of the EEM, a Fragment-Combination EEM (FCEEM) method, which is applied to fast calculation of atomic charges specifically for polypeptides, has been proposed using Natural Population Analysis (NPA) based on the Bader's concept of fragment transferability of electron density and derived properties (including atomic charges)(chapter 6). Results show that a significant improvement of predicted atomic charges is obtained by FCEEM method for test polypeptides, compared to the previous and modified EEM methods. This is very useful for predicting the fragmentation mechanisms of polypeptides produced by ESI mass spectrometry.