镧系离子与生物大分子和药物相互作用的荧光特性研究及应用
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摘要
蛋白质和核酸是生命现象的物质基础，执行生物体内各种生理功能，维持生物机体的新陈代谢，是生物性状的直接表达者。研究药物分子与蛋白质、核酸的作用机理，建立灵敏、简便的分析方法，对在分子水平上阐明生命的本质、新型药物的研制、药理和毒理的研究等方面都具有重要的意义。目前，对以药物为配体的稀土荧光固体配合物的荧光特性及药物配合物抗菌活性的改善的研究倍受关注。
本文以建立新方法和合成新型配合物为研究目的，利用荧光技术、吸收光谱技术、红外光谱技术等为研究手段，探讨了镧系离了、药物分子与生物大分子的作用机理，体系的荧光特性，并运用荧光光度法建立了分析蛋白质和药物灵敏、简便的测定方法。合成了以药物为配体的镧系离子三元固体荧光配合物，进行了光谱表征。论文分为三章：
第一章，运用荧光分光光度法研究药物与(Eu~(3+)、Tb~(3+))存在分子能量转移，而人血清蛋白(HSA)可以显著增加体系的荧光强度，表明HSA与药物及镧系离子之间发生了相互作用，将其作为荧光探针测定HSA。本章研究了HSA对诺氟沙星、环丙沙星-Tb~(3+)；对美他环素-Eu~(3+)体系的荧光增强特性及其影响因素，建立了测定HSA的方法。
第二章，利用药物可以敏化镧系离子与HSA、DNA体系的荧光发光效率的特性，研究了药物对(Eu~(3+)、Tb~(3+))—HSA体系的荧光增强作用，据此改进了测定药物的荧光测定方法，并成功应用于环丙沙星、诺氟沙星及美他环素的测定。
第三章，选择Eu~(3+)、Tb~(3+)为络合物中心离子；以Eu~(3+)、Tb~(3+)有效荧光敏化体环丙沙星、乙酰丙酮为配体，合成了三元固体荧光配合物，并进行了光谱表征，初步确定配合物的组成，解释了配合物的荧光特性及发光机理。
Nucleic acid and protein are the material base of life. Protein has the various physiological functions. It not only sustains the metabolism of life, but also the direct expresser of biological shape and properties. It is very important for researchers to expound the essence of life in the molecular lever, to design the new functional medicine, to study the pharmacology and toxicity of the new medicine. It is of special value for the purpose of establishing the sensitive and succinct method to research the interaction mechanism of medicine and biomacromolecule. At present, the lanthanide complexes with medical ligand. are paid close attention the fluorescence property and improving efficacy of medicine.
in this paper, according to the purposes of founding new research methods and new complexes, using molecule spectroscopy (fluorescenc and UV spectroscopy) and IR spectrum , we have studied the interaction among lanthanide ions, drug and biomacromolecule and explained the properties of flurescence. The surveying methods havd been established, which have the sensitive and succinct features. The lanthanide compexes with medical ligand havd been synthetized and characterized the spectroscopic properties, respectively. There are three chapters.
First,we have studied the transition of inter molecule energy between the medical and the lanthanide ions Tb and Eu3+ and the complexes can emit the characteristic fluorescence of Tb3+ and Eu3+, so the complexes of them can be used to determin HSA as a kind of fluorescent probe. In this chapter we have studied the effects for the fluoresence intensity of the HSA-Tb3+-Ciprofloxacin, HSA-Tb3+-Norfloxacin and HSA-Eu3+-Metacycline systems
and explained the interaction mechanism and founded methods used for selective determination of HSA.
Second, the fluorescent intensity of the system composing of lanthanide and biomolecule can enhance remarkably with increasing concentration of drugs. By using this properties we studied the interaction mechanism of them and improved the surveying methods of drugs, furthermore, these methods have been applied to the deterimination of drug samples and the results are satisfactory.
Third, we synthetized the solid lanthanide complexes with the ligands of acetylacetone and ciprofloxacin. Based on the characteristic of spectroscopic properties, we defined the components of the complexes preliminarily and explained the properties of fluoresence and the emitting mechanism.
本文以建立新方法和合成新型配合物为研究目的，利用荧光技术、吸收光谱技术、红外光谱技术等为研究手段，探讨了镧系离了、药物分子与生物大分子的作用机理，体系的荧光特性，并运用荧光光度法建立了分析蛋白质和药物灵敏、简便的测定方法。合成了以药物为配体的镧系离子三元固体荧光配合物，进行了光谱表征。论文分为三章：
第一章，运用荧光分光光度法研究药物与(Eu~(3+)、Tb~(3+))存在分子能量转移，而人血清蛋白(HSA)可以显著增加体系的荧光强度，表明HSA与药物及镧系离子之间发生了相互作用，将其作为荧光探针测定HSA。本章研究了HSA对诺氟沙星、环丙沙星-Tb~(3+)；对美他环素-Eu~(3+)体系的荧光增强特性及其影响因素，建立了测定HSA的方法。
第二章，利用药物可以敏化镧系离子与HSA、DNA体系的荧光发光效率的特性，研究了药物对(Eu~(3+)、Tb~(3+))—HSA体系的荧光增强作用，据此改进了测定药物的荧光测定方法，并成功应用于环丙沙星、诺氟沙星及美他环素的测定。
第三章，选择Eu~(3+)、Tb~(3+)为络合物中心离子；以Eu~(3+)、Tb~(3+)有效荧光敏化体环丙沙星、乙酰丙酮为配体，合成了三元固体荧光配合物，并进行了光谱表征，初步确定配合物的组成，解释了配合物的荧光特性及发光机理。
Nucleic acid and protein are the material base of life. Protein has the various physiological functions. It not only sustains the metabolism of life, but also the direct expresser of biological shape and properties. It is very important for researchers to expound the essence of life in the molecular lever, to design the new functional medicine, to study the pharmacology and toxicity of the new medicine. It is of special value for the purpose of establishing the sensitive and succinct method to research the interaction mechanism of medicine and biomacromolecule. At present, the lanthanide complexes with medical ligand. are paid close attention the fluorescence property and improving efficacy of medicine.
in this paper, according to the purposes of founding new research methods and new complexes, using molecule spectroscopy (fluorescenc and UV spectroscopy) and IR spectrum , we have studied the interaction among lanthanide ions, drug and biomacromolecule and explained the properties of flurescence. The surveying methods havd been established, which have the sensitive and succinct features. The lanthanide compexes with medical ligand havd been synthetized and characterized the spectroscopic properties, respectively. There are three chapters.
First,we have studied the transition of inter molecule energy between the medical and the lanthanide ions Tb and Eu3+ and the complexes can emit the characteristic fluorescence of Tb3+ and Eu3+, so the complexes of them can be used to determin HSA as a kind of fluorescent probe. In this chapter we have studied the effects for the fluoresence intensity of the HSA-Tb3+-Ciprofloxacin, HSA-Tb3+-Norfloxacin and HSA-Eu3+-Metacycline systems
and explained the interaction mechanism and founded methods used for selective determination of HSA.
Second, the fluorescent intensity of the system composing of lanthanide and biomolecule can enhance remarkably with increasing concentration of drugs. By using this properties we studied the interaction mechanism of them and improved the surveying methods of drugs, furthermore, these methods have been applied to the deterimination of drug samples and the results are satisfactory.
Third, we synthetized the solid lanthanide complexes with the ligands of acetylacetone and ciprofloxacin. Based on the characteristic of spectroscopic properties, we defined the components of the complexes preliminarily and explained the properties of fluoresence and the emitting mechanism.
引文
[1] Mengsu Yang, Mark E., Mc Govern etc., Anal. Chim. Acta, 1997, 346: 256-275
[2] Yunxiang Ci, Yuanzong Liu, Anal. Chem., 1995, 67(11): 1785-1788
[3] Cunguo Lin, Jinghe Yang, Xia Wu, Guiling Zhang, Rutao Liu, Xihui Cao, Rongjing Han, Anal. Chim. Acta, 2000, 403: 219-224
[4] Jacquelinek, Barton, Jonathan M.Golberg, Challa V. Kumar etc. J. Am. Chem. Soc. 1986,108:2081-2088
[5] Kumar C. V., Emma H. Asuncion, J. Am. Chem. Soc. 1993,115:8547-8553
[6] Eckhard Nrdmeier, J. Plays. Chem.1992,96:6045-6055
[7] 何宏山，化学进展，2001，13(6)：201—223
[8] 吴厚铭，化学进展，2000，12(4)：423—430
[9] 陈蓓，唐宏武，陈观铨，叶勇，曾云鹗，分析科学学报，1997，13(1)：1—5
[10] 刘劲刚，许亮年，无机化学学报，2000，16(2)：195—203
[11] 林辉祥，李克良，戴桂林，毕琼斯，愈汝勤，中国科学B辑，1992，7：730—735
[12] 唐宏武，陈蓓，陈观铨，曾云鹗，高校化学学报，1997，18(2)：1960—1962
[13] 李来生，黄伟东，王瑞京，化学学报，1990，57(6)：572—577
[14] 林万明，核酸探针杂交实验技术，北京，中国科学技术出版社，1991
[15] Hurskainenp, Journal of alloys and Compounds, 1995, 225(1-2): 489-491
[16] Justo GZ, Livotto PR, Durann, Radical biology and Medicine, 1995, 19(4): 431-440
[17] Rossetto FE, Nieboer E., J. of Inorg. Biochem.,1994,54(3):167-186
[18] Patty K-L, Fu and Claudia Turro, J. Aem. Chem. Soc., 1999, 121: 1-7
[19] 金林培 北京师范大学学报(自然科学版) 1992，28：194．
[20] 李文连 化学通报 1991，(8)：1
[21] 苏锵 发光学报 1986，7：1
[22] 吴淑鸰 华南理工大学学报 1993，21(1)：108
[2] Yunxiang Ci, Yuanzong Liu, Anal. Chem., 1995, 67(11): 1785-1788
[3] Cunguo Lin, Jinghe Yang, Xia Wu, Guiling Zhang, Rutao Liu, Xihui Cao, Rongjing Han, Anal. Chim. Acta, 2000, 403: 219-224
[4] Jacquelinek, Barton, Jonathan M.Golberg, Challa V. Kumar etc. J. Am. Chem. Soc. 1986,108:2081-2088
[5] Kumar C. V., Emma H. Asuncion, J. Am. Chem. Soc. 1993,115:8547-8553
[6] Eckhard Nrdmeier, J. Plays. Chem.1992,96:6045-6055
[7] 何宏山，化学进展，2001，13(6)：201—223
[8] 吴厚铭，化学进展，2000，12(4)：423—430
[9] 陈蓓，唐宏武，陈观铨，叶勇，曾云鹗，分析科学学报，1997，13(1)：1—5
[10] 刘劲刚，许亮年，无机化学学报，2000，16(2)：195—203
[11] 林辉祥，李克良，戴桂林，毕琼斯，愈汝勤，中国科学B辑，1992，7：730—735
[12] 唐宏武，陈蓓，陈观铨，曾云鹗，高校化学学报，1997，18(2)：1960—1962
[13] 李来生，黄伟东，王瑞京，化学学报，1990，57(6)：572—577
[14] 林万明，核酸探针杂交实验技术，北京，中国科学技术出版社，1991
[15] Hurskainenp, Journal of alloys and Compounds, 1995, 225(1-2): 489-491
[16] Justo GZ, Livotto PR, Durann, Radical biology and Medicine, 1995, 19(4): 431-440
[17] Rossetto FE, Nieboer E., J. of Inorg. Biochem.,1994,54(3):167-186
[18] Patty K-L, Fu and Claudia Turro, J. Aem. Chem. Soc., 1999, 121: 1-7
[19] 金林培 北京师范大学学报(自然科学版) 1992，28：194．
[20] 李文连 化学通报 1991，(8)：1
[21] 苏锵 发光学报 1986，7：1
[22] 吴淑鸰 华南理工大学学报 1993，21(1)：108