【摘要】：近紅外熒光成像以及近紅外熒光探針技術(shù)在診斷學(xué)、生物醫(yī)學(xué)、環(huán)境科學(xué)和材料化學(xué)等領(lǐng)域已經(jīng)成為重要的技術(shù)手段。發(fā)展具有高效的近紅外熒光探針在離子檢測、生物分子檢測、細(xì)胞成像和腫瘤治療等方面具有重要的意義。氟硼吡咯(BODIPY)具有良好的光穩(wěn)定性、熱穩(wěn)定性和生物相容性。此外,基于不同的功能特性可以對(duì)BODIPY的結(jié)構(gòu)修飾,以改變其光學(xué)性能應(yīng)用于近紅外熒光探針、電化學(xué)傳感以及生物成像等領(lǐng)域。本論文總結(jié)了氟硼吡咯的合成方法、氟硼吡咯類化合物在腫瘤治療上的應(yīng)用以及近紅外氟硼吡咯作為生物體內(nèi)熒光分子探針的運(yùn)用。設(shè)計(jì)合成了三種不同氟硼吡咯八號(hào)位(meso)位取代的化合物及其十個(gè)相關(guān)的共軛化合物,并研究了這些化合物的光學(xué)特性;進(jìn)一步制備了近紅外氟硼吡咯-離子液體復(fù)合物以及氟硼吡咯錳復(fù)合物,通過核磁、質(zhì)譜、元素分析、透射電鏡(TEM)等方法表征了配合物的結(jié)構(gòu),研究了它們的細(xì)胞成像、光致毒性以及錳復(fù)合物在腫瘤光動(dòng)力學(xué)治療方面的運(yùn)用。主要?jiǎng)?chuàng)新結(jié)果如下:(1)合成了三種不同八號(hào)位(meso)位取代的氟硼吡咯衍生物及其十個(gè)共軛化合物,比較了這些化合物紫外吸收、熒光量子產(chǎn)率、熒光壽命等光學(xué)特性與結(jié)構(gòu)之間的關(guān)系,發(fā)現(xiàn)3,5-位側(cè)鏈二甲胺基苯乙烯基取代的氟硼吡咯,其Stocks位移增大,同時(shí)熒光量子產(chǎn)率增高;meso位引入嗎啉基團(tuán)使該類化合物具有一定的親水性和質(zhì)子化能力,能運(yùn)用于細(xì)胞成像中。細(xì)胞毒性實(shí)驗(yàn)顯示,取代基對(duì)化合物的毒性有一定的影響。實(shí)驗(yàn)結(jié)果為構(gòu)建近紅外細(xì)胞成像劑提供了理論基礎(chǔ)。(2)合成了氟硼吡咯錳納米復(fù)合物PMnD,并研究其催化水氧化活性和光動(dòng)力學(xué)治療腫瘤方面的運(yùn)用。發(fā)現(xiàn)PMnD具有催化劑和光敏劑于一體的特點(diǎn),其與水作用釋放出氧氣,PMn D-水體系是較好的光驅(qū)動(dòng)氧釋放體。細(xì)胞實(shí)驗(yàn)結(jié)果表明PMnD具有線粒體靶向性、光激活的抗腫瘤活性和對(duì)HIF-ɑ的抑制性能,可望用于缺氧腫瘤的成像和光控制治療。(3)比較了2d、DTM和DTP三種BODPY衍生物對(duì)pH的響應(yīng),發(fā)現(xiàn)具有嗎啉基團(tuán)的化合物其質(zhì)子化效率高于異喹啉基團(tuán),化合物顏色隨pH變化肉眼可見,同時(shí)turn-on的熒光變化特性使DTP有望作為pH的熒光探針。(4)合成了一種新型的吡咯甲酮取代咪唑鹽,利用其帶正電荷性質(zhì)與DPD組裝獲得DPD-Ps復(fù)合物,DPD-Ps具有較好水溶性并被細(xì)胞吸收,DPD能作為核酸載體,DPD-Ps-核酸可作為腫瘤靶向成像劑。
[Abstract]:Near-infrared fluorescence imaging and near-infrared fluorescence probe technology have become important technical means in diagnostics, biomedicine, environmental science and material chemistry. The development of NIR fluorescent probes with high efficiency is of great significance in ion detection, biomolecular detection, cell imaging and tumor therapy. Fluoropyrrole (BODIPY) has good photostability, thermal stability and biocompatibility. In addition, the structure of BODIPY can be modified based on different functional characteristics to change its optical properties and be used in near infrared fluorescence probe, electrochemical sensing and biological imaging. In this paper, the synthesis method of fluoroboropyrrole, the application of fluorboropyrrole compounds in tumor therapy and the application of near infrared fluoropyrrole as fluorescence molecular probe in vivo were summarized. Three kinds of (meso) substituted compounds at the eighth position of fluorboron and their ten conjugated compounds were designed and synthesized. The optical properties of these compounds were studied. Near-infrared fluoropyrrole-ionic liquid complexes and fluorboropyrrolidene manganese complexes were further prepared. The complexes were characterized by NMR, mass spectrometry, elemental analysis and transmission electron microscopy (TEM), and their cellular imaging was studied. Phototoxicity and application of manganese complex in photodynamic therapy of tumor. The main innovative results are as follows: (1) three kinds of fluoroboropyrrole derivatives and their ten conjugated compounds were synthesized and their UV absorption and fluorescence quantum yields were compared. The relationship between the optical properties such as fluorescence lifetime and the structure shows that the Stocks shift increases with the substitution of fluoroboron pyrrole with dimethylamino styrene-group in the 3 ~ (5) -position side chain. At the same time, the introduction of morpholine group at meso site to increase the fluorescence quantum yield makes the compounds have certain hydrophilicity and protonation ability, and can be used in cell imaging. Cytotoxicity tests showed that the substituents had a certain effect on the toxicity of the compounds. The experimental results provide a theoretical basis for the construction of near infrared cell imaging agents. (2) the fluoroboropyrrole manganese nanocomposite PMnD, was synthesized and its catalytic water oxidation activity and photodynamic therapy were studied. It is found that PMnD has the characteristics of catalyst and Guang Min, and it is a good photo-driven oxygen releasing agent when it acts with water to release oxygen and PMN D- water system. The results of cell experiments showed that PMnD had mitochondrial targeting, photoactivated anti-tumor activity and inhibitory effect on HIF-. It is expected to be used in hypoxic tumor imaging and photocontrol therapy. (3) the responses of two BODPY derivatives of DTM and DTP to pH were compared. It was found that the protonation efficiency of the compounds with morpholine group was higher than that of isoquinoline group, and the color of the compounds varied with pH. At the same time, the fluorescence characteristics of turn-on make it possible to use DTP as a fluorescence probe for pH. (4) A novel pyrrolidone substituted imidazole salt was synthesized. The DPD-Ps complex DPD-Ps assembled with DPD with positive charge can be used as carrier of nucleic acid, DPD-Ps- nucleic acid can be used as tumor target imaging agent.
【學(xué)位授予單位】：江蘇大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O657.3;O626.13

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相關(guān)期刊論文 前1條

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本文編號(hào)：2250764