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DTPA—堿基衍生物—Eu配合物在分析與檢測堿基化合物中的應(yīng)用

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  本文選題:氨基多羧酸-銪配合物 + 設(shè)計和合成 ; 參考:《遼寧大學(xué)》2017年碩士論文


【摘要】:本論文通過改進的實驗方法合成了兩種氨基多羧酸化合物配體(Dtpa-bis(guanine)和Dtpa-bis(cytosine)),并將其與稀土金屬銪離子絡(luò)合形成了兩種銪配合物((Eu-dtpa-bis(guanine)和Eu-dtpa-bis(cytosine)),作為熒光探針分別探測腺嘌呤和6-硫代鳥嘌呤。在本文中,腺嘌呤和6-硫代鳥嘌呤分別作為與Eu-dtpa-bis(guanine)和Eu-dtpa-bis(cytosine)結(jié)合的研究對象,為了驗證這兩種銪配合物作為熒光探針的專一性,鳥嘌呤、腺嘌呤、胞嘧啶、次黃嘌呤、黃嘌呤、胸腺嘧啶、尿嘧啶、尿酸和6-巰嘌呤被選擇作為干擾物質(zhì)。Eu-dtpa-bis(guanine)和Eu-dtpa-bis(cytosine)配合物作為熒光探針檢測腺嘌呤和6-硫代鳥嘌呤的結(jié)合模式和檢測機理是本論文研究的重點。這對了解腺嘌呤和6-硫代鳥嘌呤作為藥物治療疾病時因為劑量或者生物體內(nèi)殘留濃度而引發(fā)的疾病等生物效應(yīng)有著重要的意義,因此在生理學(xué)和臨床醫(yī)學(xué)等領(lǐng)域,腺嘌呤和6-硫代鳥嘌呤的濃度檢測與分析被認為是一項極具挑戰(zhàn)性的重要任務(wù)。堿基化合物不僅僅參與遺傳物質(zhì)的合成,在生命過程中起到非常重要的作用,也在細胞代謝中履行各種功能。近幾年,堿基化合物及其衍生物作為藥物被應(yīng)用于臨床醫(yī)學(xué)用來治療一些腫瘤性疾病。例如,腺嘌呤作為藥物用于治療由于腫瘤化療引起的白血球減少癥和急性粒細胞減少癥等疾病。此外,人體內(nèi)腺嘌呤濃度的異常也預(yù)示著由某些疾病引起的免疫系統(tǒng)的突變和缺陷,包括癲癇、癌癥、腫瘤、精神發(fā)育遲滯,艾滋病感染、帕金森氏癥與肝癌等疾病。6-硫代鳥嘌呤是鳥嘌呤的一種衍生物,在結(jié)構(gòu)上與鳥嘌呤具有相似性。在50年代早期,6-硫代鳥嘌呤就已經(jīng)作為藥物應(yīng)用于臨床醫(yī)學(xué)并首次用于病人身上。在過去的20年里,6-硫代鳥嘌呤是非常有名的用于治療白血病的藥物。最近幾年,它被用于治療乳腺癌以及由于免疫反應(yīng)引起的炎癥性疾病,比如潰瘍性結(jié)腸炎、皮炎和類風(fēng)濕性關(guān)節(jié)炎。因此對堿基化合物分子的研究一直是生物分子研究中備受關(guān)注的焦點。本文中,通過熒光光譜法和紫外-可見分光光度法研究了Eu-dtpa-bis(guanine)和Eu-dtpa-bis(cytosine)配合物作為熒光探針檢測腺嘌呤與6-硫代鳥嘌呤的反應(yīng)過程和檢測機理。論文一共分為以下兩個部分:1、第一部分通過改進實驗方法合成了新型氨基多羧酸Dtpa-bis(guanine)配體,同時該配體與稀土金屬Eu(Ш)合成了Eu-dtpa-bis(guanine)配合物。這部分主要研究了Eu-dtpa-bis(guanine)配合物作為熒光探針檢測腺嘌呤的反應(yīng)過程和檢測機制。通過熒光光譜法,我們還研究了腺嘌呤濃度的改變對Eu-dtpa-bis(guanine)配合物熒光光譜的影響,此外,我們還研究了鳥嘌呤,黃嘌呤,次黃嘌呤,尿酸對檢測和分析腺嘌呤時的干擾,發(fā)現(xiàn)它們并不能干擾到腺嘌呤的檢測與分析。通過熒光光譜和紫外可見吸收光譜,我們還研究了Eu-dtpa-bis(guanine)配合物與腺嘌呤、鳥嘌呤、黃嘌呤、次黃嘌呤、尿酸等堿基化合物分子結(jié)合的方式。通過以上實驗的描述,我們預(yù)測并分析了Eu-dtpa-bis(guanine)配合物作為熒光探針能夠檢測腺嘌呤的反應(yīng)過程以及機理。2、第二部分通過改進實驗方法合成了新型氨基多羧酸Dtpa-bis(cytosine)配體,同時該配體與稀土金屬Eu(Ш)合成了Eu-dtpa-bis(cytosine)配合物。這部分主要考察了Eu-dtpa-bis(cytosine)配合物作為熒光探針檢測6-硫代鳥嘌呤的反應(yīng)過程和反應(yīng)機制。通過熒光光譜法,我們還研究了6-硫代鳥嘌呤濃度的改變對Eu-dtpa-bis(cytosine)配合物熒光光譜的影響,同時,我們還研究了胞嘧啶,鳥嘌呤,腺嘌呤,黃嘌呤,次黃嘌呤,胸腺嘧啶,尿嘧啶和尿酸對檢測和分析6-硫代鳥嘌呤的干擾,發(fā)現(xiàn)它們并不能干擾到6-硫代鳥嘌呤的檢測與分析。此外,我們還研究了溶液pH對Eu-dtpa-bis(cytosine)配合物熒光光譜的影響。通過熒光光譜和紫外光譜,我們了解到Eu-dtpa-bis(cytosine)配合物以不同的方式與6-硫代鳥嘌呤、鳥嘌呤、胞嘧啶、腺嘌呤、黃嘌呤、次黃嘌呤,胸腺嘧啶、尿嘧啶和尿酸等堿基化合物分子結(jié)合。通過以上實驗的描述,我們預(yù)測并分析了銪配合物(Eu-dtpa-bis(cytosine)作為熒光探針能夠檢測6-硫代鳥嘌呤的反應(yīng)過程與機理。此外,我們還在實際尿液中進行了6-硫代鳥嘌呤的測定,發(fā)現(xiàn)Eu-dtpa-bis(cytosine)配合物作為熒光探針在實際尿液中能夠可靠并有效的檢測到6-硫代鳥嘌呤。
[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.
【學(xué)位授予單位】:遼寧大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:O641.1

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