系列1,2,3-三氮唑化合物与罗丹明B的合成、显色反应及其与球状蛋白的相互作用

发布时间：2018-03-18 03:29

本文选题：1　切入点：2　出处：《海南师范大学》2017年硕士论文　论文类型：学位论文

【摘要】：1,2,3-三氮唑类化合物因其独特的物理化学性质,一直以来备受化学家的重视,三氮唑可与其他取代基相缀合或并合形成多种类型的衍生物,又表现出良好的生物活性,在有机化学、有机金属化学、药物化学和材料化学等诸多领域具有广阔的应用前景。其中,对其进行设计合成目标产物来作为金属离子探针的就是一个非常有实际意义的应用。众所周知,金属离子过量或不足都会引起生物体正常生理功能的紊乱,寻找快速有效的检测金属离子的方法就显得尤为重要。荧光分析方法操作简单且检测限低,设备仪器简单并且不需要进行复杂的多级样本制备。而罗丹明类化合物具有量子产率高,摩尔消光系数大,发射波长长等优点,广泛用于金属离子的荧光显色识别。尤其是探索新型1,2,3-三氮唑类化合物或其衍生物对金属离子的显色识别,有助于建立测定金属离子的新方法。另外,鉴于对这些新型1,2,3-三氮唑类化合物有可能进一步开发利用作为新型药物,因此有必要进行与生物大分子相互作用的研究。由于药物在体内所起的作用,本质上都是其与机体组织中包括蛋白质的重要功能生物大分子反应的结果。蛋白质是生命科学的重要研究对象,也是药物的一种非常重要的运输载体,蛋白质与药物的相互作用不仅影响药物在体内分布,而且还影响药物在体内的代谢与排泄方式,因此研究药物与蛋白质的相互作用已成为生命科学、化学和临床医学研究领域的重要研究课题之一。本论文分为两部分,第一部分选择8种含有酯基或羧基的1,2,3-三氮唑化合物,包括2,5-二苯基-2H-1,2,3-三氮唑-4-羧酸乙酯(Ethyl 2,5-diphenyl-2H-1,2,3-triazole-4-carboxylate,简称S1),5-苯基-2-(3-三氟甲苯)-2H-1,2,3-三氮唑-4-羧酸乙酯(Ethyl 5-phenyl-2-(3-(trifluoromethyl)phenyl)-2H-1,2,3-triazole-4-carboxylate,简称S2),5-苯基-2-邻甲苯-2H-1,2,3-三氮唑-4-羧酸乙酯(Ethyl 5-phenyl-2-(o-tolyl)-2H-1,2,3-triazole-4-carboxylate,简称S3),5-苯基-2-(4-甲氧基)-2H-1,2,3-三氮唑-4-羧酸乙酯(Ethyl 2-(4-methoxyphenyl)-5-phenyl-2H-1,2,3-triazole-4-carboxylate,简称S4),2-苯基-5-三氟甲基-2H-1,2,3-三氮唑-4-羧酸乙酯(Ethyl 2-phenyl-5-(trifluoromethyl)-2H-1,2,3-triazole-4-carboxylate,简称S5),5-苯基-2-对甲苯-2H-1,2,3-三氮唑-4-羧酸乙酯(Ethyl 5-phenyl-2-(ptolyl)-2H-1,2,3-triazole-4-carboxylate,简称S6),5-甲基-2-苯基-2H-1,2,3-三氮唑-4-羧酸(5-methyl-2-phenyl-2H-1,2,3-triazole-4-carboxylic acid,简称S7),5-甲基-1-苯基-1H-1,2,3-三氮唑-4-羧酸(5-methyl-1-phenyl-1H-1,2,3-triazole-4-carboxylic acid,简称S8)作为反应物,探索合适的反应条件,与罗丹明B反应生成含有1,2,3-三氮唑基团的系列罗丹明B衍生物。通过核磁共振,高分辨质谱对其结构进行了表征;并通过紫外吸收光谱和荧光光谱讨论了化合物与15种金属离子的作用。结果显示,在一定浓度下,二甲基甲酰胺-水溶液体系中(pH 7.4),这8种化合物均对Hg2+的响应比其他离子灵敏,使其荧光增强,并且反应时间很快。第二部分选择三种1,2,3-三氮唑化合物(S1,S3,S6),以人血清蛋白、免疫球蛋白、牛血红蛋白为模型蛋白,通过荧光光谱、紫外光谱及计算机分子对接方法分别研究了其与三种蛋白的相互作用。结果显示三种化合物均能够使三种蛋白质的荧光增强并且荧光光谱发生红移,说明化合物的加入改变了蛋白质氨基酸微环境,变得更加亲水;计算了不同温度下化合物与三种蛋白相互作用的结合常数,根据热力学参数确定了作用力类型,并通过分子对接结果得到验证;通过同步荧光光谱及三维荧光光谱分析了化合物对三种蛋白质二级结构和氨基酸微环境的影响。这些结果首次从分子水平揭示了几种三氮唑化合物的光谱活性及与球状蛋白的作用机理,有助于了解它们在生物体体内体外的性质。
[Abstract]:1,2,3- three triazole compounds because of its unique physical and chemical properties, has attracted much attention of three triazole chemists, and other substituted phase conjugated or combined to form a variety of types of derivatives, and showed good biological activity in organic chemistry, organometallic chemistry, and has broad application prospects and medicinal chemistry materials chemistry and other fields. Among them, the design and synthesis of the target product as the metal ion probe is a very practical application of the metal ion. As everyone knows, excess or deficiency will cause the disorder of the normal physiological function of organism, methods for detecting metal ions effectively the fluorescence analysis is particularly important. The method has the advantages of simple operation and low detection limit, simple equipment and does not require complex multistage sample preparation. Luo Danming compounds with high quantum yield , large molar extinction coefficient, long wavelength emission advantages, widely used in metal ion fluorescent color recognition. Especially the exploration of color recognition model 1,2,3- three triazole compounds or derivatives for metal ions, a new method is helpful to establish the determination of metal ions. In addition, in May on the new 1,2,3- three triazole compounds for further development and utilization of new drugs, so it is necessary to study the interaction with biological macromolecules. Due to the drug effect in vivo is essentially the body tissues including protein to biological macromolecular reaction results. The protein is an important research object of life science that is a very important carrier is drugs, protein drug interaction not only affects the distribution of the drugs in the body, but also affect drug metabolism in vivo and discharge mode Therefore, the interaction between drugs and protein has become one of the important research topics in life sciences, chemistry and clinical medical research field. This thesis is divided into two parts, the first part of 8 kinds of containing ester or carboxyl 1,2,3- three triazole compounds, including 2,5- two -2H-1,2,3- three phenyl triazole carboxylic acid ethyl ester (Ethyl 2,5-diphenyl-2H-1,2,3-triazole-4-carboxylate -4-, referred to as S1), 5- (3- phenyl -2- three fluorine toluene) -2H-1,2,3- three triazole carboxylic acid ethyl ester (-4- Ethyl 5-phenyl-2- (3- (trifluoromethyl) phenyl) -2H-1,2,3-triazole-4-carboxylate, referred to as S2), 5- phenyl -2- toluene -2H-1,2,3- three triazole carboxylic acid ethyl ester (-4- Ethyl 5-phenyl-2- (o-Tolyl) -2H-1,2,3-triazole-4-carboxylate, referred to as S3), 5- phenyl -2- (4- methoxy) -2H-1,2,3- three triazole carboxylic acid ethyl ester (-4- Ethyl 2- (4-methoxyphenyl) -5-phenyl-2H-1,2,3-triazole-4-carboxylate, referred to as S4), 2- phenyl -5- methyl -2H-1,2,3- three fluorine triazole carboxylic acid ethyl ester (three -4- Ethyl 2-phenyl-5- (trifluoromethyl) -2H-1,2,3-triazole-4-carboxylate, referred to as S5), 5- -2- of -2H-1,2,3- three toluene phenyl triazole carboxylic acid ethyl ester (-4- Ethyl 5-phenyl-2- (ptolyl) -2H-1,2,3-triazole-4-carboxylate, referred to as S6), 5- methyl -2- phenyl -2H-1,2,3- three triazole carboxylic acid (5-methyl-2-phenyl-2H-1,2,3-triazole-4-carboxylic acid, referred to as -4- S7), 5- methyl -1- phenyl -1H-1,2,3- three triazole carboxylic acid -4- (5-methyl-1-phenyl-1H-1,2,3-triazole-4-carboxylic acid, referred to as S8) as reactants, explore the appropriate reaction conditions, the reaction with Luo Danming B Luo Danming B 1,2,3- three series derivatives containing triazole groups. Through high resolution NMR, the structure was characterized by UV and mass spectrometry; outside the absorption spectrum and fluorescence spectrum were discussed and 15 kinds of metal ions Effect. The results show that in a certain concentration, two methyl formamide water solution (pH 7.4), the 8 compounds were the response to Hg2+ than other ion sensitive, the fluorescence enhancement, and the reaction time soon. In the second part, three kinds of 1,2,3- three triazole compounds (S1, S3, S6), human serum protein, immunoglobulin, bovine hemoglobin as a model protein by fluorescence spectroscopy, UV spectroscopy and computer molecular docking were investigated by means of its interaction with the three proteins. The results showed that three compounds were able to make three kinds of protein fluorescence enhancement and fluorescence spectrum shift that compound changed with the addition of protein amino acid micro environment, becomes more hydrophilic; the binding constants at different temperatures and three kinds of compound protein interaction were calculated according to thermodynamic parameters of force were determined, and by molecular docking node If verified; compound effects on three kinds of protein and amino acids of two level structure micro environment was analyzed by synchronous fluorescence and three-dimensional fluorescence spectra. These results are the first from the molecular level reveals the mechanism spectrum activity of several triazole compounds and three globular proteins, helps to understand the nature of the organism in vivo and in vitro. They are.

【学位授予单位】：海南师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.3;O657.3

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