基于离子液体及聚离子液体的磷脂酰丝氨酸分离方法研究

发布时间：2018-05-05 16:02

本文选题：磷脂酰丝氨酸 + 同系物分离　；参考：《浙江大学》2017年硕士论文

【摘要】：同系物分离是高纯度药物单体制备中的重要环节。磷脂酰丝氨酸是一类重要的药物和功能添加剂,其制备过程中的关键技术是磷脂酰丝氨酸与其它磷脂同系物的分离,但同系物之间结构性质相似、分离难度大。离子液体具有结构和性质可设计、分子识别能力强等特点,在结构相似物质的分离中有良好的应用前景。本文研究了磷脂酰丝氨酸(PS)、磷脂酰胆碱(PC)及其它磷脂同系物在离子液体液-液两相体系中的萃取平衡,合成具有介孔结构的聚离子液体研究其对磷脂同系物的吸附分离性能,探讨分离介质结构与分离性能的关系。研究了磷脂同系物在有机溶剂中的溶解特性,构建了离子液体/稀释剂-正己烷液-液两相体系,测定了 PS及磷脂同系物在离子液体两相体系中的萃取平衡,研究了离子液体结构、稀释剂种类、萃取温度和原料液初始浓度等因素对萃取分离性能的影响。结果表明,离子液体的阴离子结构显著影响分离性能,具有适宜氢键碱性的Br-为阴离子的离子液体表现出优异的分离选择性。离子液体的摩尔浓度仅为5%时,在1-乙基-3甲基咪唑溴盐([EMIm]Br)/甲醇-正己烷两相体系中,PC对PS的选择性分离系数高达29.48,显著优于常规有机溶剂体系。延长阳离子烷基侧链长度可有效提高PC的分配系数,当烷基侧链由乙基([EMIm]Br)延长至辛基([OMIm]Br)时,PC的分配系数由11.79提高至37.11。此外,研究表明离子液体与极性稀释剂之间存在明显的协同萃取效应,较低浓度的离子液体即可获得高的分配系数和分离选择性。采用量子化学计算和动态光散射法对离子液体和磷脂同系物之间的相互作用和微观聚集结构进行了研究,探讨其分离机理。结果表明,离子液体与磷脂之间形成了多重氢键和静电相互作用,其中,PC的P=O双键与[EMIm]Br中咪唑阳离子上的氢原子之间形成了三重氢键,且PC末端季胺结构中的多个H原子与[EMIm]Br中阴离子Br-有很强的静电作用,其氢键作用和静电作用均强于PS。离子液体-磷脂复合物的相互作用能的计算结果显示,PC与[EMIm]Br之间相互作用能为-129.45 kJ/mol,其作用强度显著大于PS与[EMIm]Br之间相互作用能(-91.70kJ/mol)。因此离子液体可选择性的分离PC与PS。进一步制备具有介孔结构的聚离子液体研究其对磷脂同系物的吸附分离性能。以具有不同长度烷基侧链的3-烷基-1-乙烯基咪唑溴盐([CmVIM]Br)为单体,通过交联聚合合成了 7种不同结构的多孔聚离子液体。采用吸附仪、扫描电子显微镜、红外光谱、元素分析、热重分析等手段,表征了所合成聚离子液体的结构、形貌、离子液体含量以及热稳定性。结果表明,制备的聚离子液体均为介孔材料,且聚离子液体的稳定性随其离子液体含量的增加而提高。介孔聚离子液体表现出良好的磷脂同系物的吸附分离性能,研究表明离子液体中咪唑溴盐烷基侧链长度的增加以及乙烯基苯DVB交联剂比例的降低,有利于提高介孔聚离子液体对磷脂同系物的吸附容量。当离子液体单体为1-辛基-3甲基咪唑溴盐[OVIM]Br 时,DVB 与[OVIM]Br 以摩尔比为 2:1 制备得到的 P(2DVB-OVIMBr)对PS、PC和磷脂酰乙醇胺的吸附容量较高,分别可达到17.05、7.58和7.20 mg·g-1,实现了 PS的选择性吸附。此外,初步研究了磷脂同系物上介孔聚离子液体上的吸附动力学,符合Lagergren 一级速率方程。
[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.

【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.6;O658

【参考文献】