發(fā)布時(shí)間：2018-03-18 03:29

  本文選題：1　切入點(diǎn)：2　出處：《海南師范大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：1,2,3-三氮唑類化合物因其獨(dú)特的物理化學(xué)性質(zhì),一直以來備受化學(xué)家的重視,三氮唑可與其他取代基相綴合或并合形成多種類型的衍生物,又表現(xiàn)出良好的生物活性,在有機(jī)化學(xué)、有機(jī)金屬化學(xué)、藥物化學(xué)和材料化學(xué)等諸多領(lǐng)域具有廣闊的應(yīng)用前景。其中,對其進(jìn)行設(shè)計(jì)合成目標(biāo)產(chǎn)物來作為金屬離子探針的就是一個(gè)非常有實(shí)際意義的應(yīng)用。眾所周知,金屬離子過量或不足都會(huì)引起生物體正常生理功能的紊亂,尋找快速有效的檢測金屬離子的方法就顯得尤為重要。熒光分析方法操作簡單且檢測限低,設(shè)備儀器簡單并且不需要進(jìn)行復(fù)雜的多級樣本制備。而羅丹明類化合物具有量子產(chǎn)率高,摩爾消光系數(shù)大,發(fā)射波長長等優(yōu)點(diǎn),廣泛用于金屬離子的熒光顯色識別。尤其是探索新型1,2,3-三氮唑類化合物或其衍生物對金屬離子的顯色識別,有助于建立測定金屬離子的新方法。另外,鑒于對這些新型1,2,3-三氮唑類化合物有可能進(jìn)一步開發(fā)利用作為新型藥物,因此有必要進(jìn)行與生物大分子相互作用的研究。由于藥物在體內(nèi)所起的作用,本質(zhì)上都是其與機(jī)體組織中包括蛋白質(zhì)的重要功能生物大分子反應(yīng)的結(jié)果。蛋白質(zhì)是生命科學(xué)的重要研究對象,也是藥物的一種非常重要的運(yùn)輸載體,蛋白質(zhì)與藥物的相互作用不僅影響藥物在體內(nèi)分布,而且還影響藥物在體內(nèi)的代謝與排泄方式,因此研究藥物與蛋白質(zhì)的相互作用已成為生命科學(xué)、化學(xué)和臨床醫(yī)學(xué)研究領(lǐng)域的重要研究課題之一。本論文分為兩部分,第一部分選擇8種含有酯基或羧基的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,簡稱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,簡稱S2),5-苯基-2-鄰甲苯-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,簡稱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,簡稱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,簡稱S5),5-苯基-2-對甲苯-2H-1,2,3-三氮唑-4-羧酸乙酯(Ethyl 5-phenyl-2-(ptolyl)-2H-1,2,3-triazole-4-carboxylate,簡稱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,簡稱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,簡稱S8)作為反應(yīng)物,探索合適的反應(yīng)條件,與羅丹明B反應(yīng)生成含有1,2,3-三氮唑基團(tuán)的系列羅丹明B衍生物。通過核磁共振,高分辨質(zhì)譜對其結(jié)構(gòu)進(jìn)行了表征;并通過紫外吸收光譜和熒光光譜討論了化合物與15種金屬離子的作用。結(jié)果顯示,在一定濃度下,二甲基甲酰胺-水溶液體系中(pH 7.4),這8種化合物均對Hg2+的響應(yīng)比其他離子靈敏,使其熒光增強(qiáng),并且反應(yīng)時(shí)間很快。第二部分選擇三種1,2,3-三氮唑化合物(S1,S3,S6),以人血清蛋白、免疫球蛋白、牛血紅蛋白為模型蛋白,通過熒光光譜、紫外光譜及計(jì)算機(jī)分子對接方法分別研究了其與三種蛋白的相互作用。結(jié)果顯示三種化合物均能夠使三種蛋白質(zhì)的熒光增強(qiáng)并且熒光光譜發(fā)生紅移,說明化合物的加入改變了蛋白質(zhì)氨基酸微環(huán)境,變得更加親水;計(jì)算了不同溫度下化合物與三種蛋白相互作用的結(jié)合常數(shù),根據(jù)熱力學(xué)參數(shù)確定了作用力類型,并通過分子對接結(jié)果得到驗(yàn)證;通過同步熒光光譜及三維熒光光譜分析了化合物對三種蛋白質(zhì)二級結(jié)構(gòu)和氨基酸微環(huán)境的影響。這些結(jié)果首次從分子水平揭示了幾種三氮唑化合物的光譜活性及與球狀蛋白的作用機(jī)理,有助于了解它們在生物體體內(nèi)體外的性質(zhì)。
[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.

【學(xué)位授予單位】：海南師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O621.3;O657.3

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