DTPA—碱基衍生物—Eu配合物在分析与检测碱基化合物中的应用

发布时间：2018-05-19 02:23

本文选题：氨基多羧酸-铕配合物 + 设计和合成　；参考：《辽宁大学》2017年硕士论文

【摘要】：本论文通过改进的实验方法合成了两种氨基多羧酸化合物配体(Dtpa-bis(guanine)和Dtpa-bis(cytosine)),并将其与稀土金属铕离子络合形成了两种铕配合物((Eu-dtpa-bis(guanine)和Eu-dtpa-bis(cytosine)),作为荧光探针分别探测腺嘌呤和6-硫代鸟嘌呤。在本文中,腺嘌呤和6-硫代鸟嘌呤分别作为与Eu-dtpa-bis(guanine)和Eu-dtpa-bis(cytosine)结合的研究对象,为了验证这两种铕配合物作为荧光探针的专一性,鸟嘌呤、腺嘌呤、胞嘧啶、次黄嘌呤、黄嘌呤、胸腺嘧啶、尿嘧啶、尿酸和6-巯嘌呤被选择作为干扰物质。Eu-dtpa-bis(guanine)和Eu-dtpa-bis(cytosine)配合物作为荧光探针检测腺嘌呤和6-硫代鸟嘌呤的结合模式和检测机理是本论文研究的重点。这对了解腺嘌呤和6-硫代鸟嘌呤作为药物治疗疾病时因为剂量或者生物体内残留浓度而引发的疾病等生物效应有着重要的意义,因此在生理学和临床医学等领域,腺嘌呤和6-硫代鸟嘌呤的浓度检测与分析被认为是一项极具挑战性的重要任务。碱基化合物不仅仅参与遗传物质的合成,在生命过程中起到非常重要的作用,也在细胞代谢中履行各种功能。近几年,碱基化合物及其衍生物作为药物被应用于临床医学用来治疗一些肿瘤性疾病。例如,腺嘌呤作为药物用于治疗由于肿瘤化疗引起的白血球减少症和急性粒细胞减少症等疾病。此外,人体内腺嘌呤浓度的异常也预示着由某些疾病引起的免疫系统的突变和缺陷,包括癫痫、癌症、肿瘤、精神发育迟滞,艾滋病感染、帕金森氏症与肝癌等疾病。6-硫代鸟嘌呤是鸟嘌呤的一种衍生物,在结构上与鸟嘌呤具有相似性。在50年代早期,6-硫代鸟嘌呤就已经作为药物应用于临床医学并首次用于病人身上。在过去的20年里,6-硫代鸟嘌呤是非常有名的用于治疗白血病的药物。最近几年,它被用于治疗乳腺癌以及由于免疫反应引起的炎症性疾病,比如溃疡性结肠炎、皮炎和类风湿性关节炎。因此对碱基化合物分子的研究一直是生物分子研究中备受关注的焦点。本文中,通过荧光光谱法和紫外-可见分光光度法研究了Eu-dtpa-bis(guanine)和Eu-dtpa-bis(cytosine)配合物作为荧光探针检测腺嘌呤与6-硫代鸟嘌呤的反应过程和检测机理。论文一共分为以下两个部分:1、第一部分通过改进实验方法合成了新型氨基多羧酸Dtpa-bis(guanine)配体,同时该配体与稀土金属Eu(Ш)合成了Eu-dtpa-bis(guanine)配合物。这部分主要研究了Eu-dtpa-bis(guanine)配合物作为荧光探针检测腺嘌呤的反应过程和检测机制。通过荧光光谱法,我们还研究了腺嘌呤浓度的改变对Eu-dtpa-bis(guanine)配合物荧光光谱的影响,此外,我们还研究了鸟嘌呤,黄嘌呤,次黄嘌呤,尿酸对检测和分析腺嘌呤时的干扰,发现它们并不能干扰到腺嘌呤的检测与分析。通过荧光光谱和紫外可见吸收光谱,我们还研究了Eu-dtpa-bis(guanine)配合物与腺嘌呤、鸟嘌呤、黄嘌呤、次黄嘌呤、尿酸等碱基化合物分子结合的方式。通过以上实验的描述,我们预测并分析了Eu-dtpa-bis(guanine)配合物作为荧光探针能够检测腺嘌呤的反应过程以及机理。2、第二部分通过改进实验方法合成了新型氨基多羧酸Dtpa-bis(cytosine)配体,同时该配体与稀土金属Eu(Ш)合成了Eu-dtpa-bis(cytosine)配合物。这部分主要考察了Eu-dtpa-bis(cytosine)配合物作为荧光探针检测6-硫代鸟嘌呤的反应过程和反应机制。通过荧光光谱法,我们还研究了6-硫代鸟嘌呤浓度的改变对Eu-dtpa-bis(cytosine)配合物荧光光谱的影响,同时,我们还研究了胞嘧啶,鸟嘌呤,腺嘌呤,黄嘌呤,次黄嘌呤,胸腺嘧啶,尿嘧啶和尿酸对检测和分析6-硫代鸟嘌呤的干扰,发现它们并不能干扰到6-硫代鸟嘌呤的检测与分析。此外,我们还研究了溶液pH对Eu-dtpa-bis(cytosine)配合物荧光光谱的影响。通过荧光光谱和紫外光谱,我们了解到Eu-dtpa-bis(cytosine)配合物以不同的方式与6-硫代鸟嘌呤、鸟嘌呤、胞嘧啶、腺嘌呤、黄嘌呤、次黄嘌呤,胸腺嘧啶、尿嘧啶和尿酸等碱基化合物分子结合。通过以上实验的描述,我们预测并分析了铕配合物(Eu-dtpa-bis(cytosine)作为荧光探针能够检测6-硫代鸟嘌呤的反应过程与机理。此外,我们还在实际尿液中进行了6-硫代鸟嘌呤的测定,发现Eu-dtpa-bis(cytosine)配合物作为荧光探针在实际尿液中能够可靠并有效的检测到6-硫代鸟嘌呤。
[Abstract]:In this paper, two amino polycarboxylic carboxylic compounds (Dtpa-bis (guanine) and Dtpa-bis (cytosine)) were synthesized by improved experimental methods, and they were complex with rare earth metal europium ions to form two EU complexes (Eu-dtpa-bis (guanine) and Eu-dtpa-bis (cytosine)), which were used as fluorescence probes to detect adenine and 6- thioguanine respectively. In this paper, adenine and 6- thioguanine are used to study the combination of Eu-dtpa-bis (guanine) and Eu-dtpa-bis (cytosine) respectively. In order to verify the specificity of these two europium complexes as a fluorescent probe, guanine, adenine, cytosine, hypoxanthine, xanthopurinx, thymine, uracil, uric acid and 6- mercaptopurine were selected as dry ones. The binding patterns and detection mechanisms of perturbed.Eu-dtpa-bis (guanine) and Eu-dtpa-bis (cytosine) complexes as fluorescence probes for the detection of adenine and 6- thioguanine are the focus of this paper. This is a disease caused by understanding of adenine and 6- thioguanine as a drug treatment disease due to dose or residual concentration of living organisms. Biological effects, such as disease, are of great significance. Therefore, in the fields of physiology and clinical medicine, the detection and analysis of adenine and 6- thioguanine is considered as a very challenging and important task. Base compounds not only participate in the synthesis of genetic material, but also play a very important role in the life process, and also in the cell generation. In recent years, basic compounds and their derivatives have been used as drugs in clinical medicine for the treatment of some tumor diseases. For example, adenine is used as a drug to treat diseases such as leukopenia and acute granulocytopenia caused by chemotherapy for cancer. In addition, the abnormal concentration of adenine in the human body is abnormal. It also indicates mutations and defects of immune systems caused by certain diseases, including epilepsy, cancer, cancer, mental retardation, AIDS infection, Parkinson's disease and liver cancer,.6- thioguanine is a derivative of guanine, which is structurally similar to guanine. In the early 50s, 6- thioguanine had been made. For the first time, 6- thioguanine is a very famous drug for the treatment of leukemia for the past 20 years. In recent years, it has been used in the treatment of breast cancer and inflammatory diseases caused by immune responses, such as ulcerative colitis, dermatitis and rheumatoid arthritis. In this paper, the reaction process and detection mechanism of Eu-dtpa-bis (guanine) and Eu-dtpa-bis (cytosine) complexes as fluorescent probes for the detection of adenine and 6- thioguanine were studied by fluorescence and UV spectrophotometry. It is divided into two parts as follows: 1, in the first part, a novel amino polycarboxylic acid Dtpa-bis (guanine) ligand was synthesized by improved experimental method, and the ligand was synthesized with Eu-dtpa-bis (guanine) complex with the rare earth metal Eu. This part mainly studied the reaction process of the Eu-dtpa-bis (guanine) complex as a fluorescence probe for the detection of adenine. In addition, we also studied the interference of guanine, xanthine, hypoxanthine, uric acid to the detection and analysis of adenine, and found that they did not interfere with the detection and analysis of adenine. Through the fluorescence spectrum, we also studied the effect of the change of adenine concentration on the fluorescence spectra of Eu-dtpa-bis (guanine) complexes. We also studied the combination of Eu-dtpa-bis (guanine) complexes with adenine, guanine, xanthine, hypoxanthine, uric acid and other basic compounds. Through the description of the above experiments, we predicted and analyzed the Eu-dtpa-bis (guanine) complex as a fluorescence probe to detect adenine The reaction process and mechanism.2, the second part syntheses the new amino polycarboxylic acid Dtpa-bis (cytosine) ligand by improving the experimental method and syntheses the Eu-dtpa-bis (cytosine) complex with the rare earth metal Eu. This part mainly investigates the reaction of the Eu-dtpa-bis (cytosine) complex as a fluorescent probe for the detection of 6- thioguanine. We also studied the effect of the change of 6- thioguanine concentration on the fluorescence spectra of Eu-dtpa-bis (cytosine) complexes by fluorescence spectrometry. At the same time, we also studied cytosine, guanine, adenine, xanthine, hypoxanthine, thymine, uracil and uric acid for the detection and analysis of 6- thioguanine. It is found that they do not interfere with the detection and analysis of 6- thioguanine. In addition, we also studied the effect of solution pH on the fluorescence spectra of Eu-dtpa-bis (cytosine) complexes. By fluorescence and UV spectra, we know that Eu-dtpa-bis (cytosine) complexes are in different ways with 6- thioguanine, guanine, cytosine, The combination of adenine, xanthine, hypoxanthine, thymine, uracil, uric acid and other base compounds. Through the description of the above experiments, we predict and analyze the reaction process and mechanism of the Eu-dtpa-bis (cytosine) as a fluorescent probe for the detection of 6- thioguanine. In addition, we have also carried out 6- in the actual urine. Determination of thiguanine showed that Eu-dtpa-bis (cytosine) complex could be used as a fluorescent probe to detect 6- thiguanine reliably and effectively in real urine.
【学位授予单位】：辽宁大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O641.1

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