本文關(guān)鍵詞： 氧雜環(huán)丁烷 四苯基乙烯 順反異構(gòu)體 光交聯(lián) 納米粒子 特異性標(biāo)記 超分辨熒光成像　出處：《吉林大學(xué)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：作為典型的聚集誘導(dǎo)發(fā)光分子,四苯基乙烯自發(fā)現(xiàn)以來,由于結(jié)構(gòu)簡單、合成方便、易于修飾等優(yōu)點而得到了廣泛的研究和應(yīng)用。但是相關(guān)領(lǐng)域仍然存許多問題需要進一步研究和解決,例如四苯基乙烯順反異構(gòu)體難以分離的問題和小尺寸聚集誘導(dǎo)發(fā)光納米粒子制備和特異性標(biāo)記問題,本文將圍繞這兩個問題進行研究解決。為了解決四苯基乙烯順反異構(gòu)體分離困難的問題,我們在第三章中設(shè)計合成了氧雜環(huán)丁烷取代的四苯基乙烯分子,通過簡單的柱層析分離得到了單一構(gòu)型的異構(gòu)體,具有較高的分離產(chǎn)率。而且通過質(zhì)譜、紅外和核磁等測試方法,證明這兩個分離的產(chǎn)物的確為異構(gòu)體。借助二維核磁,實現(xiàn)了對兩個分子構(gòu)型的確定。這兩個異構(gòu)體在適當(dāng)?shù)墓?熱刺激下會發(fā)生異構(gòu)化,相互轉(zhuǎn)化。重要的是與反式異構(gòu)體相比,順式異構(gòu)體在固體狀態(tài)下具有更加紅移的發(fā)射和更高的量子效率,順式異構(gòu)體量子效率是反式異構(gòu)體的五倍。通過理論計算可以發(fā)現(xiàn),兩種異構(gòu)體最大發(fā)射波長和量子效率的差別來自于兩種異構(gòu)體不同的發(fā)光機理,其中反式異構(gòu)體呈現(xiàn)的是局域激發(fā)態(tài)發(fā)射,而順式異構(gòu)體呈現(xiàn)的是電荷轉(zhuǎn)移態(tài)發(fā)射。這兩個異構(gòu)體都是優(yōu)良的力刺激變色材料,因為在力刺激下它們不僅會發(fā)生熒光顏色的變化,而且存在明顯的力刺激熒光亮度增加的現(xiàn)象,因而在力刺激下具有較高的對比度,通過一定的處理又可以恢復(fù)到初始狀態(tài)。此外,反式異構(gòu)體呈現(xiàn)出一定的自修復(fù)能力,其可以自發(fā)的從研磨后的無定型狀態(tài)回到初始的結(jié)晶態(tài),伴隨著熒光發(fā)射的恢復(fù)。在溶液中,順式異構(gòu)體聚集體仍然具有較高的量子效率,利用兩種異構(gòu)體制備的納米粒子也存在明顯的區(qū)別。通過細胞標(biāo)記實驗可以發(fā)現(xiàn),相比于反式異構(gòu)體,順式異構(gòu)體制備的納米粒子具有更高的細胞標(biāo)記亮度。因此,通過簡單反應(yīng)我們實現(xiàn)了四苯基乙烯順反異構(gòu)體的宏觀分離,進一步加深了我們對四苯基乙烯順反異構(gòu)體的理解,對進一步設(shè)計合成不同功能的四苯基乙烯分子具有一定的指導(dǎo)意義。在第四章中,我們通過合理的結(jié)構(gòu)調(diào)整,設(shè)計合成了三個分別具有藍色、綠色、紅色發(fā)射的氧雜環(huán)丁烷修飾的四苯基乙烯衍生物分子,最大發(fā)射波長分別為479 nm、503 nm和612 nm。這三個分子呈現(xiàn)典型的聚集誘導(dǎo)發(fā)光性質(zhì),都具有較高的熒光量子效率,固體狀態(tài)下量子效率分別為69%、63%和57%。利用氧雜環(huán)丁烷修飾的聚苯乙烯衍生物作為基質(zhì),通過納米再沉淀法制備了三種小尺寸(≈16 nm)、穩(wěn)定的、高亮度的熒光納米粒子。隨后,利用氧雜環(huán)丁烷的光交聯(lián)特性,將納米粒子進行交聯(lián)。光交聯(lián)后的納米粒子中會產(chǎn)生新的共價網(wǎng)絡(luò),因此納米粒子的穩(wěn)定性得到明顯的改善,在多種生理條件甚至是極端有機溶劑條件下都具有一定的穩(wěn)定性。通過控制交聯(lián)條件,不僅可以明顯改善納米粒子的穩(wěn)定性,而且可以維持納米粒子的小尺寸。得益于高亮度、小尺寸、超穩(wěn)定等優(yōu)勢,這三種納米粒子水溶液可以直接作為熒光墨水應(yīng)用于噴墨打印機中,實現(xiàn)熒光圖案化和熒光防偽。在生物成像方面,首先利用酰胺化反應(yīng)進行納米粒子的生物功能化,得到鏈霉親合素修飾的三種納米粒子。利用抗原抗體相互作用,實現(xiàn)了對細胞膜表面蛋白的特異性標(biāo)記。首次實現(xiàn)了聚集誘導(dǎo)發(fā)光納米粒子對亞細胞結(jié)構(gòu)微管的標(biāo)記,具有較高的分辨率。更重要的是實現(xiàn)了聚集誘導(dǎo)發(fā)光納米粒子在受激輻射損耗超分辨熒光成像中的應(yīng)用,成像分辨率得到明顯提高,定量分析表明半峰寬由190 nm縮減至95 nm,。通過除氧系統(tǒng)的引入,進一步提高了納米粒子在成像中的穩(wěn)定性,為進一步的長期熒光定位追蹤奠定了基礎(chǔ)。總之,我們設(shè)計合成了一系列氧雜環(huán)丁烷修飾的四苯基乙烯類分子,利用氧雜環(huán)丁烷的結(jié)構(gòu)特點,我們實現(xiàn)了四苯基乙烯順反異構(gòu)體的宏觀分離。通過詳細的對比研究,進一步揭示了順反異構(gòu)對分子性質(zhì)的影響,對未來分子的設(shè)計合成具有重要的指導(dǎo)意義。利用氧雜環(huán)丁烷的光交聯(lián)特性,我們發(fā)展了一種新的制備納米粒子的方法,制備了小尺寸、高亮度、超穩(wěn)定的熒光納米粒子。通過生物功能化,真正實現(xiàn)了聚集誘導(dǎo)發(fā)光納米粒子的特異性標(biāo)記,實現(xiàn)了對細胞膜表面蛋白和亞細胞結(jié)構(gòu)微管的特異性標(biāo)記。利用超分辨熒光成像技術(shù),進一步提高了成像的分辨率。
[Abstract]:As a typical molecular aggregation induced emission, four phenyl vinyl since the discovery, because of its simple structure, easy synthesis, easy modification and other advantages and has been widely studied and applied in related fields. But still many problems need to be further studied and solved, such as the four benzene vinyl CIS trans isomers difficult separation problems and small size the AIE nanoparticles preparation and specific markers, this paper will study and solve on the two issues. In order to solve the difficult problem of four phenyl ethylene CIS trans isomer separation, we design four phenyl ethylene oxetane substituted were synthesized in the third chapter, the single isomer configuration obtained by column chromatography is simple, the separation efficiency is higher. And by mass spectrometry, IR and NMR measurements, proved that the product of these two separate indeed isomers. With the help of 2D NMR, the determination of the two molecular configurations. The two isomers in the proper light / heat stimulation occurs under isomerization, into each other. The important thing is compared with the trans isomer, the cis isomer is more red shifted emission and higher quantum efficiency in solid state the cis isomer, the quantum efficiency is five times of the trans isomer. Through theoretical calculations can be found, two isomers of the maximum emission wavelength and quantum efficiency differences from the two isomers of different luminescence mechanism, the trans isomer is the locally excited state emission, and cis isomers show the charge transfer state emission. The two isomers are excellent photochromic materials stress stimulation, because of changes in force under the stimulation of them will not only bring the fluorescent color, and there are obvious stimulation fluorescence to increase the brightness of the phenomenon, so in force thorn High contrast with shock, through certain processing and can be restored to the initial state. In addition, the trans isomer showed a certain self-healing ability, it can spontaneously from non crystalline state back to the initial setting after grinding, with the recovery of fluorescence emission. In the solution, with quantum efficiency isomer aggregates are still high, the use of two kinds of heterogeneous nanoparticles preparation has obvious difference. Through cell labeling experiments can be found, compared to the trans isomers, cis isomers with nanoparticles prepared cells were labeled with higher brightness. Therefore, the macro separated by simple reaction we achieved four phenyl ethylene CIS trans isomers, and further enhance our CIS trans isomers of four phenyl vinyl understanding, has certain guidance for further design and synthesis of four phenyl ethylene molecules with different functions Meaning. In the fourth chapter, we through reasonable structural adjustment, designed and synthesized three respectively with blue, green, four phenyl ethylene derivatives oxetane theemission modification, the maximum emission wavelength were 479 nm, 503 nm and 612 nm. three molecules that are typical of aggregation induced emission properties and have high fluorescence quantum efficiency, quantum efficiency of solid state were 69%, 63% and 57%. using polystyrene derivatives oxetane modified as matrix, three kinds of small size were prepared by nano re precipitation (about 16 nm), stable, high brightness fluorescent nanoparticles. Then, using light crosslinking characteristics oxetane, the nanoparticles were cross-linked nanoparticles. Light after crosslinking will produce new covalent network, so the stability of nanoparticles have been significantly improved in various physiological conditions or even extremely The end has a certain stability in organic solvent conditions. By controlling the cross-linking conditions, not only can improve the stability of nanoparticles, and the nanoparticles can maintain small size. Due to the high brightness, small size, high stability and other advantages, these three kinds of nanoparticles aqueous solution can be directly used as fluorescent ink used in inkjet printers, realize fluorescence and fluorescence. Patterned in biological imaging, biological function, first by amidation reaction of nanoparticles, obtained the streptavidin affinity of three kinds of nanoparticles was modified. The anti body interaction with antigen, the specific marker of cell surface proteins. For the first time labeled AIE nanoparticles on subcellular structure microtubules, with high resolution. The more important is to realize aggregation induced emission of nanoparticles in the stimulated radiation loss of super resolution The application of fluorescence imaging, the imaging resolution was improved and the quantitative analysis showed that the half peak width from 190 nm down to 95 nm. Through the introduction of deaerator system, further improve the stability of nanoparticles in imaging, which laid the foundation for long-term follow-up fluorescence localization. In short, we designed and synthesized a series of oxygen oxetane modified four phenyl ethylene molecules, based on the structural characteristics of the oxetane, macro separation we achieved four phenyl ethylene CIS trans isomers. Through detailed comparative study, further reveals the CIS trans isomerization effect on molecular properties, has an important guiding significance for the future design of synthetic molecules. Using light crosslinking characteristics of oxetane, we developed a new method for preparation of nanoparticles, preparation of small size, high brightness, ultra stable fluorescent nanoparticles by biological function. The specific markers of aggregated induced luminescent nanoparticles were realized, and the specific markers for the surface proteins and subcellular microtubules of cell membrane were achieved. The resolution of imaging was further improved by super-resolution fluorescence imaging technology.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：O48

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