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ESI-MS和CE-ICP-MS研究金属抗癌药物KP1019与体内细胞质中的具有还原性物质的反应

摘要第4-6页
ABSTRACT第6-7页
Abbreviations:第10-11页
1. Literature part第11-49页
    1.1 Introduction第11-12页
    1.2 Metallodrugs第12-13页
    1.3 Metallodrugs with potential anticancer properties第13-22页
        1.3.1 Platinum-based drugs第13-18页
        1.3.2 Ruthenium-based drugs第18-20页
        1.3.3 Gallium-based drugs第20-21页
        1.3.4 Other metallodrugs with potential anticancer properties第21-22页
    1.4 Selected component of blood第22-25页
        1.4.1 Human serum albumin第22-23页
        1.4.2 Human serum transferrin第23页
        1.4.3 Different conditions in blood and tumor cells第23-25页
    1.5 Analytical techniques used to investigate the anticancer metallodrugs第25-35页
        1.5.1 Determination of metals' total content第25-26页
        1.5.2 Identification of anticancer metallodrugs species第26-35页
            1.5.2.1 Separation techniques第26-32页
                1.5.2.1.1 High-performance liquid chromatography第27-28页
                1.5.2.1.2 Capillary electrophoresis第28-29页
                1.5.2.1.3 Comparison between CE and HPLC used in anticancermetallodrugs researches第29-32页
            1.5.2.2 Mass spectrometry detectors第32-35页
                1.5.2.2.1 Electrospray ionization mass spectrometry第32-33页
                1.5.2.2.2 Inductively coupled plasma mass spectrometry第33-35页
    1.6 Anticancer metallodrug analysis-selected problems第35-48页
        1.6.1 Analytical studies of platinum anticancer complexes第36-40页
            1.6.1.1 Hydrolysis of platinum complexes第36-37页
            1.6.1.2 Binding of platinum complexes to human transport serum proteins第37-39页
            1.6.1.3 Binding of platinum complexes to DNA第39-40页
        1.6.2 Analytical studies of gallium anticancer complexes第40页
        1.6.3 Analytical studies of ruthenium anticancer complexes第40-48页
            1.6.3.1 Stability of ruthenium complexes第40-41页
            1.6.3.2 Binding of ruthenium complexes to human serum proteins第41-43页
            1.6.3.3 Binding of ruthenium-complexes to DNA第43-44页
            1.6.3.4 State of art of in KP1019 investigations第44-48页
    1.7 Purposes第48-49页
2. Experimental part第49-55页
    2.1 Equipment(Instrumentation)第49页
    2.2 Methods第49-51页
        2.2.1 ESI-MS第49-50页
        2.2.2 CE-ICP-MS第50-51页
    2.3 Chemicals and materials第51-52页
    2.4 Preparation of solutions第52-55页
        2.4.1 Solutions used in ESI-MS experiments第52-53页
        2.4.2 Solutions used in ICP-MS experiments第53-55页
3. Results and discussions第55-75页
    3.1 Hydrolysis of KP1019 at pH 7.4-ESI-MS studies第55-58页
    3.2 Kinetic studies of binding of KP1019 towards holo-transferrin第58-63页
    3.3 The influence of cytosol components and conditions on KP1019-holo-transferrinadduct dissociation第63-75页
        3.3.1 The behavior of KP1019-holo-transferrin adduct at pH 6.0第63-64页
        3.3.2 The behavior of KP1019-holo-transferrin adduct at pH 6.0 in the presence ofreductive agent-glutathione第64-68页
        3.3.3 The behavior of KP1019-holo-transferrin adduct in pH 6.0 and in thepresence of reductive agent - ascorbic acid第68-70页
        3.3.4 The behavior of KP1019-holo-transferrin adduct in pH 6.0 and in thepresence of complexing agent-citric acid第70-72页
        3.3.5 The behavior of KP1019-holo-transferrin adduct at pH 6.0 and in thepresence of three agents-glutathione, ascorbic and citric acids第72-75页
4. Conclusions and outlook第75-77页
    4.1 Conclusions第75-76页
    4.2 Outlook第76-77页
References第77-89页
Acknowledgments第89-90页
攻读学位期间发表的学术论文目录第90页

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