动态调控一步乳化高内相双乳液模板构建高活性硼亲和多孔印迹聚合物 选择性分离纯化莽草酸

Production of shikimic acid with high purity has been a big problem for a long time, which in a great extent restricted the pharmacological research and application of shikimic acid and its derivatives. This project intends to design the self-assembly system of PS-b-P4VP with phenylselenyl bromide and trifluoroacetic acid. By tailoring of the amphiphilicity of the originally hydrophobic block co-polymer, the high internal phase double emulsions template will be formed via dynamic regulation and one-step method. Based on the strategy of reducing pKa values of phenylboronic acid ligands, highly active boronate-affinity monomers which are proper to covalent affinity with shikimic acid will be prepared. By introduction of shikimic acid and highly active boronate-affinity monomers into the middle phase of the high internal phase double emulsions template, highly active boronate-affinity porous imprinted polymers will be synthesized, and the boronate-affinity and imprinted double recognition sites will also be realized. Through adjusting the microstructure, the optimized porous imprinted polymers will be adopted to selective recognition of shikimic acid, and their binding equilibrium, kinetics and thermodynamic performances will be investigated. Then the mechanism and synergetic effect of imprinted binding sites with double recognition abilities for the enhancement of selectivity will also be investigated. Finally, a new strategy for the selective separation and purification of shikimic acid from star anise extracts will be established.

莽草酸高纯产品的生产长期以来是一大难题，这在很大程度上制约了莽草酸及其衍生物的药理研究和应用开发。本项目拟设计苯乙烯-b-聚-4乙烯基吡啶(PS-b-P4VP)二嵌段共聚物与苯基溴化硒、三氟乙酸的共价自组装体系，实现二嵌段共聚物向两亲性共聚物的可控转变，从而以动态调控策略一步乳化高内相双乳液模板；结合降低苯硼酸配基pKa值的策略，设计合成适合于共价亲和莽草酸的高活性苯硼酸单体，并将其与模板分子莽草酸等引入乳液模板的中间相，引发聚合制备高活性硼亲和多孔印迹聚合物(MIP)，构建硼亲和/分子印迹二元识别位点；可控调节高活性硼亲和多孔MIP的微结构，探索其选择性分离纯化莽草酸过程的平衡、动力学和热力学行为；揭示高活性硼亲和多孔MIP对莽草酸的二元识别机制，建立相应的分离与纯化新方法。

莽草酸作为生产抗禽流感病毒的唯一武器—专利药物GS4104(达菲)的原料，具有极高的医药价值。我国一些植物如八角茴香资源丰富，若以此为原料来提取和生产莽草酸，将产生很好的经济效益和社会效益。然而，由于从植物中提取的基质复杂，开发合适的提取与分离纯化莽草酸的新材料是当前亟待解决的问题。本项目利用硼亲和/分子印迹二元识别体系，设计合成了一系列具有特异选择性的高活性硼亲和分子印迹复合材料。通过设计与合成适合于共价亲和莽草酸的高活性苯硼酸聚合单体，并将其与模板分子莽草酸等引入分子印迹体系，热引发聚合制备高活性硼亲和印迹聚合物，构建硼亲和/分子印迹二元识别位点，得到具有高硼亲和特性的分子印迹复合材料；研究结果表明该类高活性硼亲和印迹聚合物材料对莽草酸分子具有良好的选择性识别和吸附分离性能。结合实验数据和量化计算结果，深入分析了高活性硼亲和印迹聚合物材料的微观结构、材料形貌以及主客体印迹效果等对识别和吸附分离性能的影响，总结了其结构和性能之间的构效关系。本项目的研究，为环境天然产物中的活性成分的选择性识别和吸附分离提供了科学依据，也促进了化学、材料和环境等学科的交叉融合。