含糖膽固醇衍生物的合成及其膠凝行為.doc

含糖膽固醇衍生物的合成及其膠凝行為中文不同于化學(xué)凝膠，物理凝膠的三維網(wǎng)絡(luò)結(jié)構(gòu)是由膠凝劑分子通過(guò)氫鍵、范德華力、p-p堆積、疏溶劑、靜電以及偶極等分子間的弱相互作用維持的。物理凝膠的這種弱相互作用特征決定了其具有良好的熱可逆性以及一些奇特的性質(zhì)，因而在藥物緩釋、凝膠電池、組織工程支架和溫和分離等領(lǐng)域具有潛在的應(yīng)用價(jià)值。形成物理凝膠的膠凝劑可以是聚合物、無(wú)機(jī)微納米顆粒，或者小分子量化合物，其中以小分子量化合物備受人們關(guān)注。主要是由于：（1）與凝膠對(duì)應(yīng)的溶液態(tài)與純?nèi)軇┯兄嘟恼扯?；?）此類(lèi)膠凝劑相對(duì)容易獲得，且易于改性修飾，因此易于放大制備；（3）此類(lèi)膠凝劑在理論上可以燃燒，為凝膠的現(xiàn)實(shí)應(yīng)用奠定了基礎(chǔ)。糖類(lèi)化合物含有多羥基，分子間存在很強(qiáng)的氫鍵作用，其衍生物是一類(lèi)重要的兩親性小分子膠凝劑。由于膽固醇分子片段之間的范德華相互作用使得膽固醇類(lèi)衍生物易于在溶液中發(fā)生簇集，因此，膽固醇類(lèi)衍生物是一類(lèi)重要的小分子膠凝劑?；谶@些認(rèn)識(shí)，本學(xué)位論文立足于實(shí)驗(yàn)室對(duì)膽固醇類(lèi)小分子膠凝劑多年研究的基礎(chǔ)，將膽固醇和糖類(lèi)化合物結(jié)合，以?xún)捎H性小分子膠凝劑的研發(fā)為主要內(nèi)容，主要開(kāi)展了以下四個(gè)方面的論文工作：第一部分：通過(guò)連接臂的改變，設(shè)計(jì)合成了4種含有直鏈葡萄糖的膽固醇類(lèi)小分子膠凝劑（分別以化合物1，2，3，4表示）。利用核磁技術(shù)、紅外光譜和元素分析等方法對(duì)這些化合物的組成和結(jié)構(gòu)進(jìn)行了表征，均得到了比較滿(mǎn)意的結(jié)果，為系統(tǒng)地研究這些化合物的膠凝行為奠定了基礎(chǔ)。第二部分：系統(tǒng)考察了所合成的四種化合物在常見(jiàn)有機(jī)溶劑中的膠凝行為?；衔?-4都既可以膠凝質(zhì)子性溶劑（戊醇等），也可以膠凝非質(zhì)子性溶劑（二甲苯等）?；衔?，3，4在二甲苯中的膠凝濃度分別為0.09，0.022，0.016%（w/v），是二甲苯的超級(jí)膠凝劑，并且可以在二甲苯中形成罕見(jiàn)的超分子凝膠薄膜。各化合物膠凝溶劑的種類(lèi)隨連接臂的增長(zhǎng)而增加。凝膠的穩(wěn)定性研究發(fā)現(xiàn)，隨著連接臂的增長(zhǎng)，凝膠的相轉(zhuǎn)變溫度逐漸升高。凝膠的流體力學(xué)研究發(fā)現(xiàn)化合物的力學(xué)性能對(duì)化合物的連接臂以及化合物在體系中的濃度存在依賴(lài)性。掃描電鏡研究發(fā)現(xiàn)化合物連接臂的改變對(duì)凝膠的微觀形貌也有顯著的影響。第三部分：利用紅外光譜、變溫變濃度核磁共振等手段探討了凝膠的形成機(jī)理。利用X-射線(xiàn)衍射研究發(fā)現(xiàn)，化合物1在戊醇中的干凝膠是呈層狀堆積方式，與其在固體粉末中的堆積方式類(lèi)似。根據(jù)以上的探討，提出了化合物在凝膠中的堆積模型。第四部分：設(shè)計(jì)合成了4個(gè)含乳糖的膽固醇類(lèi)兩親型小分子膠凝劑，研究了所得化合物在多種有機(jī)溶劑中的膠凝行為、膠凝性質(zhì)以及成膠機(jī)理，相關(guān)數(shù)據(jù)見(jiàn)附錄。譯文Unlike chemical gels, physical gels only involve non-covalent interactions (e.g., hydrogen bonding, - stacking, van der Waals interaction, coordination interaction, etc.) between gelator molecules. Generally speaking, these gels are thermo-reversible and display fascinating properties of both fundamental and practical values including drug delivery devices, gel electrolyte based batteries, scaffolds for tissue engineering, and mild separation, etc. Within the physical gels, the gelators could be polymers, inorganic micro- nano- particles, and low-molecular mass compounds, which are called low-molecular-mass-gelators (LMMGs). LMMGs are more attractive than others due to a number of reasons: (1) dissolution of the gels formed by them may result in solution of similar viscosity to pure solvent; (2) these gelators are much easier to be modified and created, and thereby much more gelators and gels can be developed; (3) these gelators are, at least in theory, degradable and combustible, which bring gels more chances in real life applications.Sugar, which contains several free OH groups, has been used to make special amphiphilic gelators. At the same time, cholesterol derivatives have been the subject of attention in the field of low-molecular-mass-gelators due to their outstanding gelation? performances. Based upon the knowledge described above and as a continuation of our group studies of cholesterol derivatives as low molecular-mass organic gelators, a series of cholesterol-based and sugar-contained LMMGs were synthesized and studied. This dissertation is mainly composed of the following four parts: In the first part, four novel LMMGs containing both glucose and cholesterol unit, which are denoted as 1, 2, 3, and 4, respectively, have been synthesized. The structures and compositions of all these compounds are characterized by 1H NMR, FT-IR spectroscopy, and elemental analysis, and satisfied results have been obtained.In the second part, the gelation properties of the four compounds were examined systematically in common organic solvents. Clearly, Compounds 1-4 show similar gelation behaviors, they gel both protic and aprotic solvents, such as pentanol, xylene. The number of solvents gelled by the compounds increases along with increasing the linker length of them. 2, 3, and 4 in xylene are only 0.090%，0.022%，and 0.016% (w/v), respectively, which are significantly lower than 0.1% (w/v), a well recognized critical value for “super-gelators”. Interestingly, Compounds 2, 3, or 4 can form supramolecular gel films in xylene. Tgel and rheological studies revealed that the stability and porporties of the gels depend on the length of the spacers of the compounds. SEM studies revealed that the linker length has a great effect upon the aggregation mode of the gelators and the structures of the gel networks.In the third part, we studied the mechanisim of the formation of the gels. FT-IR and 1H NMR spectroscopy studies revealed that intermolecular hydrogen bonding formation plays an important role for the formation of the gels. XRD studies showed that 1 possesses a layered structure in its 1-pentanol gel, a similar structure to that of it in solid state. According to the discussion above, a structural model was proposed to describe the formation of gel network.In the forth part, four no