【作者】 陈志涛；

【导师】 夏之宁；

【作者基本信息】 重庆大学 ， 生物医学工程， 2011， 博士

【摘要】 毛细管电泳具有分析速度快、分离效率高、样品用量少等特点。室温离子液体由于低熔点、良好的导电性、电化学窗口宽、特殊溶解性,已广泛应用于毛细管电泳分离分析。咪唑型离子液体因其独特结构,能吸附在毛细管壁,影响毛细管电泳电渗流大小和方向。离子液体与其它分子间存在广泛分子间作用,如:静电作用、氢键、范德华力、色散力、n-π作用,π-π作用等,作为毛细管电泳添加剂,能与介质中包括分析物、环糊精、表面活性剂等成分作用,改变分析物Z/M值或分配特性,提供一种新的分离机制,所以咪唑型离子液体是毛细管电泳方法应用最多一种类型。论文在总结离子液体相关性质和应用基础上,第一部分尝试以非手性离子液体作辅助添加剂,探讨其对手性药物分离分析影响;第二部分通过疏水离子液体1-丁基-3-甲基咪唑六氟磷酸盐([BMIM]PF6)与表面活性剂作用形成水包离子液体微乳液或者离子液体修饰胶束,与毛细管微乳液电动色谱(MEEKC)或胶束电动色谱(MEKC)相结合,研究这种新型微乳液和胶束在手性和非手性分离中的特性。具体内容主要有:(1)建立了以水溶性非手性离子液1-正丁基-3-甲基咪唑盐酸盐([BMIM]C1)为添加剂,β-环糊精及其衍生物作为手性选择剂的毛细管区带电泳方法,分离了氯霉素前体、普萘洛尔、沙丁胺醇三种手性药物对映体。结果表明:缓冲液中没有添加[BMIM]CI的条件下,药物只能部分分离,添加离子液体后三种药物都实现了基线分离,在此基础上考察了手性选择剂浓度、离子液体种类和浓度、缓冲溶液pH、分离电压等因素对手性分离度的影响。(2)为了探讨非手性离子液体对手性药物分离的影响机理,应用荧光光谱方法测定了缓冲液介质加入离子液体条件下,两种氯霉素前体对映体与β-环糊精结合常数,与无离子液体条件结合常数比较,并从微观上分析探索作用机制。(3)吐温-20(Tween-20)作为非离子型表面活性剂本身对中性化合物不能实现分离,通过与离子液体之间作用使胶束带有电荷。建立了基于以非离子型Tween-20为表面活性剂,1-丁基-3-甲基咪唑六氟磷酸盐([BMIM]PF6)为油相形成水包离子液体微乳液分离四种中性化合物和四种喹诺酮药物MEEKC新方法。并对缓冲液pH值、离子浓度和表面活性剂用量、离子液体用量等因素对分离的选择性进行了讨论。在此基础上,比较其与环己烷为油相、SDS为表面活性剂组成的微乳液对分离对象选择性异同。(4)以非离子型Tween-20为表面活性剂,1-丁基-3-甲基咪唑六氟磷酸盐([BMIM]PF6)为油相形成水包离子液体微乳液,把这种新型微乳液引入毛细管微乳液电动色谱(MEEKC),以β-环糊精衍生物作为手性选择剂,建立了在酸性条件下分离氯霉素前体、氧氟沙星手性药物毛细管微乳液电动色谱方法,同时考察微乳液组成等条件对分离的影响,并对其分离机制进行了初步研究。该方法保留了毛细管微乳液电动色谱可控条件多、理论塔板数高等优点,由于采用非离子型表面活性剂避免了对电渗流的抑制,可在酸性环境中对药物实现分离。(5)通过阴离子表面活性剂十二烷基硫酸钠(SDS)与疏水性离子液体1-正丁基-3-甲基咪唑六氟磷酸盐之间作用形成了离子液体修饰的SDS胶束,建立了新的胶束毛细管电动色谱方法,采用该方法分离8种喹诺酮药物混合物,并对微乳液PH值、缓冲液离子浓度、表面活性剂量、离子液体量等因素对分离的选择性进行了讨论。结果表明这种新型胶束与未被修饰SDS对分离的选择性存在差异。更多还原

【Abstract】 Capillary electrophoresis (CE) is an effective analytical technique, which permits rapid, efficient separation and a small sample volume. Due to low melting point, good conductivity, wide electrochemical window, special solubility, room-temperature ionic liquids (RTILs) are widely applied in capillary electrophoresis. Imidazole ionic liquids can be absorbed into capillary wall affecting the quantity and direction of electroosmotic flow (EOF). What’s more, because of its unique structure, the interactions between ILs and other molecular are listed as electrostatic forces, hydrogen bonding, van der Waals forces, dispersion forces, n-πandπ-πinteraction, and so on. As additives in buffer, it can interaction with analytes, cyclodextrin and surfactant affecting the Z/M value of analytes or distribution characteristics, which show another separation mechanism for CE. Therefore, imidazole ionic liquid is the most widely applied in CE. Summarizing the structure, properties and applications of imidazole ionic liquid, IL as additive in CE was investigated. The thesis content consists of two part. The first part is that achiral ionic liquid as auxiliary additives is utilized for separation chiral drugs. The second part is that oil-in-water microemulsion containing IL and micelles modified hydrophobic ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM]PF6) were introduced into microemulsion electrokinetic chromatography (MEEKC) and micellar electrokinetic chromatography (MEKC) for separation chiral or achiral compounds. The separation selectivities of the novel MEEKC and MEKC on analytes were studied. Specific contents are listed as follows:(1) A capillary zone electrophoresis (CZE) method that the enantiomers of three chiral drugs (chloramphenicol precursors, propranolol, salbutamol) were separated on condition that water-soluble achiral ionic liquid 1-butyl-3-methyl-imidazole hydrochloride ([BMIM]C1) was used as an additive,β-cyclodextrin or its derivatives as chiral selectors in buffer was established. The results indicated that the three drugs can be baseline separated in the presence of ionic liquid. However, the above enantiomers can be partly separated if there exist no ionic liquid in buffer. On this basis, the effects of chiral selector concentration, type and concentration of ionic liquid, pH in buffer and separation voltage on the separation were further investigated.(2)In order to discuss the influence mechanism of achiral IL on the separation of chiral drugs, fluorescence spectroscopy was employed to determine binding constants between the each enantiomer of precursors of chloramphenicol andβ-cyclodextrin in the presence of IL, compared with the absence of IL. From the microscopic perspective, brief analysis and discussion were made in light of the results.(3)Neutral compounds can not be achieved separation by MEEKC using a nonionic surfactant Tween-20 as surfactant. However, Tween-20 micelles can share charge by interacting with hydrophobic ionic liquid formed similar mixed micelles. A novel microemulsion, Tween-20 as surfactant and 1-butyl-3-methylimidazolium hexafluorophosphate([BMIM]PF6) as oil phase, was applied in MEEKC for separation of four neutral compounds and four fluoroquinolones . The effect of pH in buffer, ionic stength, concentration of surfactant and ionic liquid on the separation selectivity were discussed. Compared with the microemulsion containing cyclohexane as oil phase and sodium dodecyl sulfate (SDS) as surfactant, two microemulsion have differences in the distribution mechanism and separation selectivities.(4)Microemulsion containing IL was formed by using nonionic Tween-20 as surfactant and [BMIM]PF6 as oil phase. The microemulsion was introduced into MEEKC, and chiral drugs (chloramphenicol precursor and ofloxacin) were successfully separated by the novel MEEKC method under acidic conditions andβ-cyclodextrin derivatives as chiral selector. Besides, the effect of microemulsion composition on separation was investigated. The separation mechanism was briefly discussed as well. The method permits many adjustable factors, high theoretical plate number like tradition MEEKC method. Nonionic surfactant avoided inhibition of electroosmotic flow (EOF), The MEEKC method can realize separation of compounds in the acidic environment.(5) By the interaction between anionic surfactant sodium dodecyl sulfate (SDS) and hydrophobic ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate, a novel micelles electrokinetic chromatography method was established. Mixture of eight kinds of quinolone drugs was successfully separated. Moreover, impacting factors on separation selectivity, such as pH, amount of surfactant and ionic liquid were discussed. The results show that the separation selectivity by using mixed micelles is different from that which SDS micelles was not modified by ionic liquid.更多还原