本文選題：磷脂酰絲氨酸 + 同系物分離　； 參考：《浙江大學(xué)》2017年碩士論文

【摘要】：同系物分離是高純度藥物單體制備中的重要環(huán)節(jié)。磷脂酰絲氨酸是一類重要的藥物和功能添加劑,其制備過(guò)程中的關(guān)鍵技術(shù)是磷脂酰絲氨酸與其它磷脂同系物的分離,但同系物之間結(jié)構(gòu)性質(zhì)相似、分離難度大。離子液體具有結(jié)構(gòu)和性質(zhì)可設(shè)計(jì)、分子識(shí)別能力強(qiáng)等特點(diǎn),在結(jié)構(gòu)相似物質(zhì)的分離中有良好的應(yīng)用前景。本文研究了磷脂酰絲氨酸(PS)、磷脂酰膽堿(PC)及其它磷脂同系物在離子液體液-液兩相體系中的萃取平衡,合成具有介孔結(jié)構(gòu)的聚離子液體研究其對(duì)磷脂同系物的吸附分離性能,探討分離介質(zhì)結(jié)構(gòu)與分離性能的關(guān)系。研究了磷脂同系物在有機(jī)溶劑中的溶解特性,構(gòu)建了離子液體/稀釋劑-正己烷液-液兩相體系,測(cè)定了 PS及磷脂同系物在離子液體兩相體系中的萃取平衡,研究了離子液體結(jié)構(gòu)、稀釋劑種類、萃取溫度和原料液初始濃度等因素對(duì)萃取分離性能的影響。結(jié)果表明,離子液體的陰離子結(jié)構(gòu)顯著影響分離性能,具有適宜氫鍵堿性的Br-為陰離子的離子液體表現(xiàn)出優(yōu)異的分離選擇性。離子液體的摩爾濃度僅為5%時(shí),在1-乙基-3甲基咪唑溴鹽([EMIm]Br)/甲醇-正己烷兩相體系中,PC對(duì)PS的選擇性分離系數(shù)高達(dá)29.48,顯著優(yōu)于常規(guī)有機(jī)溶劑體系。延長(zhǎng)陽(yáng)離子烷基側(cè)鏈長(zhǎng)度可有效提高PC的分配系數(shù),當(dāng)烷基側(cè)鏈由乙基([EMIm]Br)延長(zhǎng)至辛基([OMIm]Br)時(shí),PC的分配系數(shù)由11.79提高至37.11。此外,研究表明離子液體與極性稀釋劑之間存在明顯的協(xié)同萃取效應(yīng),較低濃度的離子液體即可獲得高的分配系數(shù)和分離選擇性。采用量子化學(xué)計(jì)算和動(dòng)態(tài)光散射法對(duì)離子液體和磷脂同系物之間的相互作用和微觀聚集結(jié)構(gòu)進(jìn)行了研究,探討其分離機(jī)理。結(jié)果表明,離子液體與磷脂之間形成了多重氫鍵和靜電相互作用,其中,PC的P=O雙鍵與[EMIm]Br中咪唑陽(yáng)離子上的氫原子之間形成了三重氫鍵,且PC末端季胺結(jié)構(gòu)中的多個(gè)H原子與[EMIm]Br中陰離子Br-有很強(qiáng)的靜電作用,其氫鍵作用和靜電作用均強(qiáng)于PS。離子液體-磷脂復(fù)合物的相互作用能的計(jì)算結(jié)果顯示,PC與[EMIm]Br之間相互作用能為-129.45 kJ/mol,其作用強(qiáng)度顯著大于PS與[EMIm]Br之間相互作用能(-91.70kJ/mol)。因此離子液體可選擇性的分離PC與PS。進(jìn)一步制備具有介孔結(jié)構(gòu)的聚離子液體研究其對(duì)磷脂同系物的吸附分離性能。以具有不同長(zhǎng)度烷基側(cè)鏈的3-烷基-1-乙烯基咪唑溴鹽([CmVIM]Br)為單體,通過(guò)交聯(lián)聚合合成了 7種不同結(jié)構(gòu)的多孔聚離子液體。采用吸附儀、掃描電子顯微鏡、紅外光譜、元素分析、熱重分析等手段,表征了所合成聚離子液體的結(jié)構(gòu)、形貌、離子液體含量以及熱穩(wěn)定性。結(jié)果表明,制備的聚離子液體均為介孔材料,且聚離子液體的穩(wěn)定性隨其離子液體含量的增加而提高。介孔聚離子液體表現(xiàn)出良好的磷脂同系物的吸附分離性能,研究表明離子液體中咪唑溴鹽烷基側(cè)鏈長(zhǎng)度的增加以及乙烯基苯DVB交聯(lián)劑比例的降低,有利于提高介孔聚離子液體對(duì)磷脂同系物的吸附容量。當(dāng)離子液體單體為1-辛基-3甲基咪唑溴鹽[OVIM]Br 時(shí),DVB 與[OVIM]Br 以摩爾比為 2:1 制備得到的 P(2DVB-OVIMBr)對(duì)PS、PC和磷脂酰乙醇胺的吸附容量較高,分別可達(dá)到17.05、7.58和7.20 mg·g-1,實(shí)現(xiàn)了 PS的選擇性吸附。此外,初步研究了磷脂同系物上介孔聚離子液體上的吸附動(dòng)力學(xué),符合Lagergren 一級(jí)速率方程。
[Abstract]:The separation of homologues is an important link in the preparation of high purity drugs. Phosphatidylserine is an important kind of drug and functional additive. The key technology in the preparation process is the separation of phosphatidyl serine and other phospholipid homologues, but the structural properties of the homologues are similar, and the separation is difficult. The ionic liquid has the structure and properties. This paper has studied the extraction equilibrium of phosphatidylcholine (PS), phosphatidylcholine (PC) and other phosphatidylcholine homologues in the liquid liquid two phase system of ionic liquids. The synthesis of polyionic liquids with mesoporous structure for the study of phosphatidylcholine homologous The relationship between the adsorption and separation of the material and the relationship between the structure of the separation medium and the separation performance was discussed. The dissolution characteristics of the phospholipid homologues in the organic solvents were studied. The ionic liquid / diluent - hexane liquid - liquid two phase system was constructed. The extraction equilibrium of PS and phospholipid homologues in the ionic liquid two phase system was measured, and the structure of ionic liquids was studied. The effects of the types of diluents, the extraction temperature and the initial concentration of the raw material on the separation performance. The results show that the anion structure of the ionic liquid significantly affects the separation performance. The Br- with the suitable hydrogen bond alkalinity shows excellent separation selectivity for the ionic liquid of the anion. The molar concentration of the ionic liquid is only 5% at 1- B. In the base -3 methyl imidazolium bromide salt ([EMIm]Br) / methanol n-hexane two-phase system, the selective separation coefficient of PC to PS is up to 29.48, which is significantly better than the conventional organic solvent system. Prolonging the length of the cationic alkyl side chain can effectively improve the PC distribution coefficient. When the alkyl side chain is extended from ethyl ([EMIm] Br) to octyl ([OMIm]Br), the distribution coefficient of PC is 11.7. 9 to 37.11., the study shows that there is an obvious synergistic extraction effect between ionic liquid and polar diluent. High distribution coefficient and separation selectivity can be obtained by the lower concentration of ionic liquid. The interaction and microaggregation of ionic liquids and phospholipid homologues by quantum chemical calculation and dynamic light scattering are used. The results show that the multiple hydrogen bonds and electrostatic interactions between the ionic liquids and phospholipids have formed between the PC P=O double bonds and the hydrogen atoms of the imidazole cations in [EMIm]Br, and the multiple H atoms in the PC terminal quaternary amine structure are strongly associated with the anion Br- in the [EMIm]Br. The interaction energy of the PS. ionic liquid phospholipid complex is stronger than the interaction energy of the ionic liquid phospholipid complex. The results show that the interaction between PC and [EMIm]Br can be -129.45 kJ/mol, and its action strength is significantly greater than the interaction energy between PS and [EMIm]Br (-91.70kJ/ mol). Therefore, the ionic liquid can selectively separate PC and PS.. A polyionic liquid with mesoporous structure was further prepared to study the adsorption and separation properties of the phospholipid homologues. The 3- alkyl -1- vinyl imidazolium bromide ([CmVIM]Br) with different alkyl side chains of different lengths was used as a monomer, and 7 different structures were synthesized by crosslinking polymerization. The structure, morphology, ionic liquid content and thermal stability of the synthesized polyionic liquids were characterized by external spectra, elemental analysis and thermogravimetric analysis. The results showed that the prepared polyionic liquids were mesoporous materials, and the stability of the polyionic liquids increased with the increase in the content of ionic liquids. The mesoporous polyionic liquids showed good performance. The adsorption and separation performance of the phospholipid homologues shows that the increase in the alkyl side chain length of the imidazolium bromide in the ionic liquid and the decrease in the proportion of the vinyl benzene DVB crosslinker are beneficial to the enhancement of the adsorption capacity of the mesoporous polyionic liquid to the phospholipid homologue. When the ionic liquid monomer is 1- octyl -3 methyl imidazolium bromide [OVIM]Br, DVB and [OVIM The adsorption capacity of P (2DVB-OVIMBr) prepared by the mole ratio of P (2DVB-OVIMBr) to PS, PC and phosphatidyl ethanolamine was higher, which could reach 17.05,7.58 and 7.20 mg. G-1 respectively. The selective adsorption of PS was achieved. In addition, the adsorption kinetics on the mesoporous polyionic liquid on the phospholipid homologues was preliminarily studied, which accords with the Lagergren first order rate equation.

【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：TQ460.6;O658

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