Mass Spectrometry Behavior And Quantum Chemistry Studies On Diester-diterpenoid Alkaloids(DDA) Of Bioactive Components From Chinese Medicinal Herbs

Traditional Chinese Medicine (TCM) has a long history for thousands years. It has been proved practically that TCM grew out of a desire to maintain good health and from the need to treat various conditions and diseases. TCM must have a scientific base however is still not clearly understood. Most materials used in TCM are natural herbs which usually contains bioactive alkaloids. Electrospray ionization mass spectrometry (ESI-MS) is a commercially available analytical tool, which has been widely used in trace analysis of organic compounds such as Berberine, due to the high sensitivity, high throughput and high specificity. Calculations based on quantum chemistry theory have been used to facilitate the interpretation, prediction and analysis of data obtained in MS, especially results obtained in tandem mass spectrometry.In this work, a newly developed quantum chemistry DFT-B3LYP method is employed to predicate the fragmentation patterns of Berberine and the stability of the fragments generated in collision-induced dissociation (CID) of protonated Berberine in ESI-MS. The quantum chemistry DFT-B3LYP method is also used to elucidate the mechanism of hydrolysis of Berberine and to understand the intrinsic correspondence of the ESI signal intensity of peptides to the hydrophobicity of peptides in a molecular level. The success of this work provides a theoretical guide on how to fast screen useful intermediates and molecular structures of bioactivity, showing a new methodology for new drug design and resulting in an enrichment of theory and method for modernization of TCM. Basically, research work is composed of four major sections as below.1)Quantum chemistry DFT-B3LYP method for prediction of fragmentation pattern of Berberine. Berberine, commonly found in Chinese herbs such as Huanglian and Huangbai, is one of the alkaloids widely used as effective antibiotics. However, the mechanism of dissociation of Berberine is still unknown, and no research has been done in the literature by using quantum chemistry and mass spectrometry to study the dissociation mechanism. In this section, quantum chemistry DFT-B3LYP method is used to predict the fragmentation pattern of Berberine and the fragmentation sequence in terms of stability of the fragments produced from tandem MS so that the mechanism of dissociation of Berberine is elucidated for the first time. Experimental data provide an exploration on how to theoretically screen useful intermediates and molecular structures of bioactivity for potential drugs, showing a new methodology for new drug design and resulting in an enrichment of theory and method for modernization of TCM. On the other hand, data show that quantum chemistry-based methods including ab initio calculation, DFT etc. are useful tools for mechanism studies, providing complementary information which is usually not available from experimental procedures.2)Elucidation of the bioactivity and toxicity of alkaloids using tandem MS. Quantum chemistry methods are used to explain the mechanism of fragmentation of alkaloids (i.e.Diester-diterpenoid Alkaloids) using tandem MS data obtained from CID processes undergone low collision energy. Molecular geometries of the six DDAs are optimized at the...