界面聚合手性高分子复合膜研究

The optical resolution membrane is a popular subject of the materials. It is very important and significant that chiral pharmaceuticals are separated by the membrane. At present, enantioselective membranes are not used in business, the separatical technology of optical resolution membranes also has not been applied in production. Polymeric composite membranes, prepared by using interfacial polymerization, have many potential advantages in comparison, for example, they have high throughput, better selectivity and good separation effects, so they become another milestone of membrane science and technology. In this study, β-cyclodextrin , Macrocyclic antibiotics, protein, enzyme and chiral complex will be chosen as chiral monomer in the top surface of polymeric enantioselective membranes. In order to optimize the properties and preparation technology of polymeric enantioselective membrane with interfacial polymerization, the influences of different parameters such as the number of monomer functional groups, concentration, polymeric time, temperature, medium, the kinds of basic membrane and aperture will be investigated. The structure of the membrane will be examined by electron microscopy. The aperture and performance of the membrane, for example the properties of adsorbability and diffusion, enantioselectivity, stability and flux will be determined by using physical and chemical methods. The optical resolution principle will be discussed. The resulting membranes, which have a high flux and better selectivity, will be used to isolate some enantiomers, some plant components and isomers. We shall solve the problem of the application of polymeric enantioselective membranes in production,on the other hand, the resulting membranes will also be used in sample pretreatment.

手性膜分离材料属国际研究热点，手性药物的膜分离分析研究具有重要的实际意义。国内外尚无商品化的手性膜，手性膜分离技术也远没有实际应用。界面聚合制备高分子复合膜法因所得膜的通量大、分离效果好已成为膜科学与技术领域的又一里程碑。本项目将利用环糊精、大环抗菌素、蛋白质、酶以及手性配合物作为复合膜皮层的手性单体，利用界面聚合法详细研究手性高分子复合膜的制备技术，考察单体的功能团的数目、浓度大小、缩聚时间、温度、介质、基质膜种类和孔径等多种因素对手性复合膜制备的影响。采用电镜研究膜结构，利用物理化学方法测试手性膜的孔径，测定膜的吸附-扩散特性、手性选择性能、稳定性和通量，探讨膜的手性分离机理。最终成功研究出对手性样品拆分选择性较宽、通量高、并对一些植物成分和位置异构体具有一定分离作用的手性高分子膜，解决手性高分子膜的实际应用问题，并探索手性高分子膜技术在手性样品前处理中的应用。

手性膜分离材料属于国际研究热点，手性药物的膜分离生产具有巨大的经济和社会效益。但国内外尚无商品化的手性膜，手性膜分离技术也还未产业化。界面聚合制备高分子复合膜法因所得膜的通量大、分离效果好已成为膜科学与技术领域的又一里程碑。项目选用羟丙基-β-环糊精、环己二胺、万古霉素、替考拉宁、β-环糊精、海藻酸钠、壳聚糖等作为手性单体，利用界面聚合法详细研究了手性高分子复合膜的制备技术，考察单体功能团的数目、浓度大小、缩聚时间、温度、介质、基质膜种类、交联剂种类和膜尺寸大小等因素对手性膜制备的影响。采用电镜研究膜结构，利用物理化学方法测试手性膜的吸附-扩散特性、手性选择性能、稳定性和通量。最终从制得的15种手性复合膜中成功地研究出3种稳定性好、通量较高、选择性高的手性高分子复合膜，他们可用于青霉素及头孢类药物合成的重要中间体苯甘氨酸、对羟基苯甘氨酸的手性拆分，为手性高分子复合膜的工业化应用打下了一定的理论和技术基础。以1,6-己二异腈酸酯为交联剂，分别以替考拉宁、万古霉素和羟丙基-β-环糊精作为手性单体，采用界面聚合法制备了替考拉宁-异腈酸酯聚砜复合膜、万古霉素-异腈酸酯聚砜复合膜和羟丙基-β-环糊精-异氰酸酯聚砜复合膜，通过优化膜材料浓度、制膜条件及外消旋体溶液浓度等分离参数后，可分别达到渗析分离D,L-对羟基苯甘氨酸90%的对映体过剩值(e.e.)、分离D-苯甘氨酸70 %的e.e.、分离D,L-对羟基苯甘氨酸59.1%的e.e.。并探讨了膜的手性分离机理。通过比较研究手性膜吸附、固相萃取、膜色谱、膜渗析和膜超滤过程，根据在多种膜研究中观察到“手性膜优先吸附的对映体并不是各种模式下优先透过的对映体”的实验事实，结合外消旋体的缔合特性，首次提出了“吸附-缔合-扩散”的手性膜分离机理。这个新的机理是对以往膜分离理论的颠覆和补充，对膜分离理论的发展是非常有价值的。