离子液体选择性萃取分离磷脂酰丝氨酸和磷脂酰胆碱
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摘要
同系物分离是高纯度药物单体和化学品制备中的重要环节,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他磷脂同系物的分离,但同系物之间结构相似、分离难度大。报道了以离子液体为介质选择性萃取分离磷脂酰丝氨酸和磷脂酰胆碱的方法,系统研究了离子液体结构和浓度、萃取温度对分离性能的影响。研究表明,离子液体的阴离子结构显著影响同系物的分离选择性,且离子液体与极性稀释剂之间存在协同萃取效应,离子液体的摩尔浓度仅为5%时,1-乙基-3-甲基咪唑溴/甲醇-正己烷两相体系中的磷脂酰丝氨酸和磷脂酰胆碱的选择性高达29.48。采用量子化计算初步研究了萃取机理,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,从而促进了磷脂同系物之间的选择性分离。
Homologues separation is a key process in the production of high-purity drugs and chemicals. High-purity phosphatidylserine(PS) is widely used as drugs and functional additives; however PS often appears in a mixture with structurally similar homologues and the selective separation of phospholipid homologues remains challenging. Here, a novel extraction method was developed to separate PS and phosphatidylcholine(PC) with ionic liquids(ILs) as extractants. The effects of structure and concentration of ILs and temperature on extraction performance were investigated. The results showed that the structure of the IL's anion had a significant impact on the separation selectivity, and an obvious synergistic extraction effect between IL and polar diluent was observed. In 1-ethyl-3-methylimidazolium bromide([EMIm]Br)-methanol-hexane biphasic systems, the selectivity of PC to PS(SPC/PS) reached up to 29.48, when the mole fraction of IL was only 5%. Additionally, ab initio calculations were used to explore the extraction mechanism, and the results indicated that the multiple hydrogen-bonding and electrostatic interactions were formed between phospholipids and ILs, which is probably beneficial for the selective separation of phospholipid homologues.
Homologues separation is a key process in the production of high-purity drugs and chemicals. High-purity phosphatidylserine(PS) is widely used as drugs and functional additives; however PS often appears in a mixture with structurally similar homologues and the selective separation of phospholipid homologues remains challenging. Here, a novel extraction method was developed to separate PS and phosphatidylcholine(PC) with ionic liquids(ILs) as extractants. The effects of structure and concentration of ILs and temperature on extraction performance were investigated. The results showed that the structure of the IL's anion had a significant impact on the separation selectivity, and an obvious synergistic extraction effect between IL and polar diluent was observed. In 1-ethyl-3-methylimidazolium bromide([EMIm]Br)-methanol-hexane biphasic systems, the selectivity of PC to PS(SPC/PS) reached up to 29.48, when the mole fraction of IL was only 5%. Additionally, ab initio calculations were used to explore the extraction mechanism, and the results indicated that the multiple hydrogen-bonding and electrostatic interactions were formed between phospholipids and ILs, which is probably beneficial for the selective separation of phospholipid homologues.
引文
[1]LEIROS I,MCSWEENEY S,HOUGH E.The reaction mechanism of phospholipase D from Streptomyces sp.strain PMF snapshots along the reaction pathway reveal a pentacoordinate reaction intermediate and an unexpected final product[J].Mol.Biol.,2004,339(4):805-820.
[2]JORISSE B L.Safety of soy-derived phosphatidyl-serine in elderly people[J].Nutreurosci,2002,5(5):337-343.
[3]HELLHAMMER J.Effects of soy lecithin phosphatidic acid phosphatidylserine complex(PAS)on the endocrine and psychological responses tomental stress[J].Stress,2004,7(2):119-126.
[4]DELWAIDE P J.Double-blind randomized controlled study of phosphatidylserine in senile demented patients[J].Acta Neurologica Scandinavica,1986,73(2):136-140.
[5]BRAMBILLA F,MAGGIONI M.Blood levels of cytokines in elderly patients with major depressive disorder[J].Acta Psychiatrica Scandinavica,1998,97(4):309-313.
[6]司朝勇,吴素芳,许海丹,等.含水量对氧化铝柱色谱法同时分离纯化卵磷脂和脑磷脂的影响[J].化工学报,2005,56(4):689-693.SI C Y,WU S F,XU H D,et al.Effects of water content on simultaneous purification of PC and PE by alumina column chromatography[J].Journal of Chemical Industry and Engineering(China),2005,56(4):689-693.
[7]HANAHAN D J,CHACKOFF I L.Analysis of phospholipase D[J].Biol.Chem.,1974:169-199.
[8]龚雁.磷脂化合物的分离制备和测定方法研究[D].北京:北京化工大学,2006.GONG Y.Studies on phospholipids preparation and analysis[D].Beijing:Beijing University of Chemical Technology,2006.
[9]夏玉宇.化学实验室手册[M].北京:化学工业出版社,2004:507-510.XIA Y Y.Handbook of Chemistry Lab[M].Beijing:Chemical Industry Press,2004:507-510.
[10]曹栋,裘爱泳,王兴国.超临界流体分离大豆磷脂酰胆碱[J].中国油脂,2002,27(3):72-74.CAO D,QIU A Y,WANG X G.Separation of soybean phosphatidylcholine by supercritical carbon dioxide/ethanol[J].China Oils and Fats,2002,27(3):72-74.
[11]金文彬,邢华斌,任其龙,等.离子液体在结构相似物分离中的进展[J].中国科学:化学,2016,46:1251-1263.JIN W B,XING H B,REN Q L,et al.Separation of structurally-related compounds with ionic liquids[J].Sci.Sin.Chim.,2016,46(12):1251-1263.
[12]曹领帝,曾少娟,张锁江,等.离子液体吸收分离硫化氢进展[J].化工学报,2015,66(S1):1-9.CAO L D,ZENG S J,ZHANG S J,et al.Progress on hydrogen sulfide removal using ionic liquids[J].CIESC Journal,2015,66(S1):1-9.
[13]ROUT A,WELLENS S,BINNEMANS K.Separation of rare earths and nickel by solvent extraction with two mutually immiscible ionic liquids[J].RSC Adv,2014,4(11):5753-5758.
[14]MEINDERSMA G W,HAAN A B.Coneeptual process design for aromatic/aliphatic separation with ionic 1iquids[J].Chemical Engineering Research and Design,2008,86(7):745-752.
[15]YANG Q W,XING H B,YANG Y W,et al.Selective separation of tocopherol homologues by liquid-liquid extraction using ionic liquids[J].Ind.Eng.Chem.Res.,2009,48(13):6417-6422.
[16]JIN W B,YANG Q W,HUANG B B,et al.Enhanced solubilization and extraction of hydrophobic bioactive compounds using water/ionic liquid mixtures[J].Green Chemistry,2016,18(12):3549-3557.
[17]MATSUMOTO M,INOMOTO Y,KONDO K.Selective separation of aromatic hydrocarbons through supported liquid membranes based on ionic liquids[J].Journal of Membrane Science,2005,246(1):77-81.
[18]LARRIBA M,NAVARRO P,GARCIA J,et al.Liquid-liquid extraction of toluene from heptane using[EMIM][DCA],[BMIM][DCA],and[EMIM][TCM]ionic liquids[J].Industrial and Engineering Chemistry Research,2013,52(7):2714-2720.
[19]ZHAO X,YANG Q W,XU D,et al.Design and screening of ionic liquids for C2H2/C2H4 separation by COSMO-RS and experiments[J].AICh E Journal,2015,61(6):2016-2027.
[20]LIU X X,YANG Q W,BAO Z B,et al.Nonaqueous lyotropic ionic liquid crystals:preparation,characterization,and application in extraction[J].Chemistry—A European Journal,2015,21(25):9150-9156.
[21]LI M,PHAM P J,PITTMAN C U,et al.SBA-15-supported ionic liquid compounds containing silver salts:novel mesoporous7t-complexing sorbents for separating polyunsaturated fatty acid methyl esters[J].Microporous and Mesoporous Materials,2009,117(1):436-443.
[22]JIN W B,YANG Q W,ZHANG Z G,et al.Self-assembly induced solubilization of drug-like molecules in nanostructured ionic liquids[J].Chemical Communications,2015,51(67):13170-13173.
[23]CAO Y F,XING H B,YANG Q W,et al.High performance separation of sparingly aqua-/lipo-soluble bioactive compounds with an ionic liquid-based biphasic system[J].Green Chemistry,2012,14(9):2617-2625.
[24]BINI R,BORTOLINI O,CHIAPPE C,et al.Development of cation/anion“interaction”scales for ionic liquids through ESI-MS measurements[J].The Journal of Physical Chemistry B,2007,111(3):598-604.
[25]SHIROTA H,CASTNER E W.Why are viscosities lower for ionic liquids with-CH2Si(CH3)3 vs-CH2C(CH3)3 substitutions on the imidazolium cations?[J].The Journal of Physical Chemistry B,2005,109(46):21576-21585.
[26]贺杠.磷脂酶D催化合成磷脂酰丝氨酸(PS)的色谱分离研究[D].西安:西北大学,2011.HE G.The chromatographic separation study of phosphatidylserine enzymatic synthetised by phospholipase D[D].Xi’an:Northwest University,2011.
[27]XU D,YANG Q W,SU B G,et al.Enhancing the basicity of ionic liquids by tuning the cation-anion interaction strength and via the anion-tethered strategy[J].The Journal of Physical Chemistry B,2014,118(4):1071-1079.
[28]DONG K,ZHANG S J.Hydrogen bonds:a structural insight into ionic liquids[J].Chemistry—A European Journal,2012,18(10):2748-2761.
[29]CAMMARATA L,KAZARIAN S G,SALTER P A,et al.Molecular states of water in room temperature ionic liquids[J].Physical Chemistry Chemical Physics,2001,3(23):5192-5200.
[30]CLAUDIO A F M,SWIFT L,HALLETT J P,et al.Extended scale for the hydrogen-bond basicity of ionic liquids[J].Physical Chemistry Chemical Physics,2014,16(14):6593-6601.
[31]YANG Q W,XING H B,SU B G,et al.Improved separation efficiency using ionic liquid-cosolvent mixtures as the extractant in liquid-liquid extraction:a multiple adjustment and synergistic effect[J].Chemical Engineering Journal,2012,181:334-342.
[32]NI X L,XING H B,YANG Q W,et al.Selective liquid-liquid extraction of natural phenolic compounds using amino acid ionic liquids:a case ofα-tocopherol and methyl linoleate separation[J].Ind.Eng.Chem.Res.,2012,51(18):6480-6488.
[33]ZHANG J Z,YU K,YANG Q W,et al.Selective separation of zwitterionic phospholipid homologues with functional ionic liquids as extractants[J].RSC Adv,2015,5(95):77581-77588.
[34]YANG Q W,XING H B,SU B G,et al.The essential role of hydrogen-bonding interaction in the extractive separation of phenolic compounds by ionic liquid[J].AICh E Journal,2013,59(5):1657-1667.
[35]孙奇,管生洲,王晓武,等.咪唑及其衍生物N-1H保护基的研究进展[J/OL].[2010-03-10].http://jonline.nwu.edu.cn/wenzhang/210008.pdf.SUN Q,GUAN S Z,WANG X W,et al.General trends in N-1H protection of imidazole and its derivatives[J/OL].[2010-03-10].http://jonline.nwu.edu.cn/wenzhang/210008.pdf.
[36]SHIRLEY D A,ALLEY P W.The metalation of 1-methyl-,1-benzyland 1-phenylimidazole with n-butyllithium[J].Journal of the American Chemical Society,1957,79(18):4922-4927.
[2]JORISSE B L.Safety of soy-derived phosphatidyl-serine in elderly people[J].Nutreurosci,2002,5(5):337-343.
[3]HELLHAMMER J.Effects of soy lecithin phosphatidic acid phosphatidylserine complex(PAS)on the endocrine and psychological responses tomental stress[J].Stress,2004,7(2):119-126.
[4]DELWAIDE P J.Double-blind randomized controlled study of phosphatidylserine in senile demented patients[J].Acta Neurologica Scandinavica,1986,73(2):136-140.
[5]BRAMBILLA F,MAGGIONI M.Blood levels of cytokines in elderly patients with major depressive disorder[J].Acta Psychiatrica Scandinavica,1998,97(4):309-313.
[6]司朝勇,吴素芳,许海丹,等.含水量对氧化铝柱色谱法同时分离纯化卵磷脂和脑磷脂的影响[J].化工学报,2005,56(4):689-693.SI C Y,WU S F,XU H D,et al.Effects of water content on simultaneous purification of PC and PE by alumina column chromatography[J].Journal of Chemical Industry and Engineering(China),2005,56(4):689-693.
[7]HANAHAN D J,CHACKOFF I L.Analysis of phospholipase D[J].Biol.Chem.,1974:169-199.
[8]龚雁.磷脂化合物的分离制备和测定方法研究[D].北京:北京化工大学,2006.GONG Y.Studies on phospholipids preparation and analysis[D].Beijing:Beijing University of Chemical Technology,2006.
[9]夏玉宇.化学实验室手册[M].北京:化学工业出版社,2004:507-510.XIA Y Y.Handbook of Chemistry Lab[M].Beijing:Chemical Industry Press,2004:507-510.
[10]曹栋,裘爱泳,王兴国.超临界流体分离大豆磷脂酰胆碱[J].中国油脂,2002,27(3):72-74.CAO D,QIU A Y,WANG X G.Separation of soybean phosphatidylcholine by supercritical carbon dioxide/ethanol[J].China Oils and Fats,2002,27(3):72-74.
[11]金文彬,邢华斌,任其龙,等.离子液体在结构相似物分离中的进展[J].中国科学:化学,2016,46:1251-1263.JIN W B,XING H B,REN Q L,et al.Separation of structurally-related compounds with ionic liquids[J].Sci.Sin.Chim.,2016,46(12):1251-1263.
[12]曹领帝,曾少娟,张锁江,等.离子液体吸收分离硫化氢进展[J].化工学报,2015,66(S1):1-9.CAO L D,ZENG S J,ZHANG S J,et al.Progress on hydrogen sulfide removal using ionic liquids[J].CIESC Journal,2015,66(S1):1-9.
[13]ROUT A,WELLENS S,BINNEMANS K.Separation of rare earths and nickel by solvent extraction with two mutually immiscible ionic liquids[J].RSC Adv,2014,4(11):5753-5758.
[14]MEINDERSMA G W,HAAN A B.Coneeptual process design for aromatic/aliphatic separation with ionic 1iquids[J].Chemical Engineering Research and Design,2008,86(7):745-752.
[15]YANG Q W,XING H B,YANG Y W,et al.Selective separation of tocopherol homologues by liquid-liquid extraction using ionic liquids[J].Ind.Eng.Chem.Res.,2009,48(13):6417-6422.
[16]JIN W B,YANG Q W,HUANG B B,et al.Enhanced solubilization and extraction of hydrophobic bioactive compounds using water/ionic liquid mixtures[J].Green Chemistry,2016,18(12):3549-3557.
[17]MATSUMOTO M,INOMOTO Y,KONDO K.Selective separation of aromatic hydrocarbons through supported liquid membranes based on ionic liquids[J].Journal of Membrane Science,2005,246(1):77-81.
[18]LARRIBA M,NAVARRO P,GARCIA J,et al.Liquid-liquid extraction of toluene from heptane using[EMIM][DCA],[BMIM][DCA],and[EMIM][TCM]ionic liquids[J].Industrial and Engineering Chemistry Research,2013,52(7):2714-2720.
[19]ZHAO X,YANG Q W,XU D,et al.Design and screening of ionic liquids for C2H2/C2H4 separation by COSMO-RS and experiments[J].AICh E Journal,2015,61(6):2016-2027.
[20]LIU X X,YANG Q W,BAO Z B,et al.Nonaqueous lyotropic ionic liquid crystals:preparation,characterization,and application in extraction[J].Chemistry—A European Journal,2015,21(25):9150-9156.
[21]LI M,PHAM P J,PITTMAN C U,et al.SBA-15-supported ionic liquid compounds containing silver salts:novel mesoporous7t-complexing sorbents for separating polyunsaturated fatty acid methyl esters[J].Microporous and Mesoporous Materials,2009,117(1):436-443.
[22]JIN W B,YANG Q W,ZHANG Z G,et al.Self-assembly induced solubilization of drug-like molecules in nanostructured ionic liquids[J].Chemical Communications,2015,51(67):13170-13173.
[23]CAO Y F,XING H B,YANG Q W,et al.High performance separation of sparingly aqua-/lipo-soluble bioactive compounds with an ionic liquid-based biphasic system[J].Green Chemistry,2012,14(9):2617-2625.
[24]BINI R,BORTOLINI O,CHIAPPE C,et al.Development of cation/anion“interaction”scales for ionic liquids through ESI-MS measurements[J].The Journal of Physical Chemistry B,2007,111(3):598-604.
[25]SHIROTA H,CASTNER E W.Why are viscosities lower for ionic liquids with-CH2Si(CH3)3 vs-CH2C(CH3)3 substitutions on the imidazolium cations?[J].The Journal of Physical Chemistry B,2005,109(46):21576-21585.
[26]贺杠.磷脂酶D催化合成磷脂酰丝氨酸(PS)的色谱分离研究[D].西安:西北大学,2011.HE G.The chromatographic separation study of phosphatidylserine enzymatic synthetised by phospholipase D[D].Xi’an:Northwest University,2011.
[27]XU D,YANG Q W,SU B G,et al.Enhancing the basicity of ionic liquids by tuning the cation-anion interaction strength and via the anion-tethered strategy[J].The Journal of Physical Chemistry B,2014,118(4):1071-1079.
[28]DONG K,ZHANG S J.Hydrogen bonds:a structural insight into ionic liquids[J].Chemistry—A European Journal,2012,18(10):2748-2761.
[29]CAMMARATA L,KAZARIAN S G,SALTER P A,et al.Molecular states of water in room temperature ionic liquids[J].Physical Chemistry Chemical Physics,2001,3(23):5192-5200.
[30]CLAUDIO A F M,SWIFT L,HALLETT J P,et al.Extended scale for the hydrogen-bond basicity of ionic liquids[J].Physical Chemistry Chemical Physics,2014,16(14):6593-6601.
[31]YANG Q W,XING H B,SU B G,et al.Improved separation efficiency using ionic liquid-cosolvent mixtures as the extractant in liquid-liquid extraction:a multiple adjustment and synergistic effect[J].Chemical Engineering Journal,2012,181:334-342.
[32]NI X L,XING H B,YANG Q W,et al.Selective liquid-liquid extraction of natural phenolic compounds using amino acid ionic liquids:a case ofα-tocopherol and methyl linoleate separation[J].Ind.Eng.Chem.Res.,2012,51(18):6480-6488.
[33]ZHANG J Z,YU K,YANG Q W,et al.Selective separation of zwitterionic phospholipid homologues with functional ionic liquids as extractants[J].RSC Adv,2015,5(95):77581-77588.
[34]YANG Q W,XING H B,SU B G,et al.The essential role of hydrogen-bonding interaction in the extractive separation of phenolic compounds by ionic liquid[J].AICh E Journal,2013,59(5):1657-1667.
[35]孙奇,管生洲,王晓武,等.咪唑及其衍生物N-1H保护基的研究进展[J/OL].[2010-03-10].http://jonline.nwu.edu.cn/wenzhang/210008.pdf.SUN Q,GUAN S Z,WANG X W,et al.General trends in N-1H protection of imidazole and its derivatives[J/OL].[2010-03-10].http://jonline.nwu.edu.cn/wenzhang/210008.pdf.
[36]SHIRLEY D A,ALLEY P W.The metalation of 1-methyl-,1-benzyland 1-phenylimidazole with n-butyllithium[J].Journal of the American Chemical Society,1957,79(18):4922-4927.
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