High Resolution of Chiral Compounds Using Protein-Multilayered Porous Membranes

手性分离是生产安全有效药物的重要技术。目前，选择结晶法和手性色谱法用于分离各种外消旋化学物质；后者更通用，因为手性配体可以固定在支撑基质上。我们描述了一种牛血清白蛋白(BSA)-多层吸附多孔中空纤维膜作为固定相，使手性分离在高分辨率和高速率。采用辐射诱导接枝聚合的方法，将含环氧基团的接枝链均匀地固定在多孔中空纤维膜的孔表面。随后，一个二乙胺基作为阴离子交换基团被引入接枝链中，这使得接枝链由于相互静电排斥而向孔的内部扩展。扩展的聚合物链为BSA作为手性选择剂提供了多层结合位点。在流动相（Tris-HCl缓冲液）中注入dl -色氨酸外消旋溶液，通过BSA多层多孔膜渗透时，BSA具有4种特异性识别的l -色氨酸的多层结合程度，分离因子为6.6。此外，无论流动相的流速如何，分离因子都是恒定的，因为接枝链可以忽略色氨酸对牛血清白蛋白的扩散传质阻力。

Chiral separation is an essential technology for producing effective and safe pharmaceuticals. At present, selective crystallization and chiral chromatography are used to resolve various racemic chemicals ; the latter is more versatile in that the chiral ligands can be immobilized on supporting matrices.We describe a bovine serum albumin (BSA)-multilayer-adsorbed porous hollow-fiber membrane as a stationary phase that enables chiral separations at a high resolution and high rate. Epoxy-group-containing graft chains were uniformly immobilized on the surface of pores throughout a porous hollow-fiber membrane by radiation-induced graft polymerization. Subsequently, a diethylamino group as an anion-exchange moiety was introduced to the graft chains, which caused the chains to expand toward the interior of the pores due to mutual electrostatic repulsion. The expanding polymer chains provided multilayer binding sites for BSA as a chiral selector. BSA with a degree of multilayer binding of four specifically recognized L-tryptophan with a separation factor of 6.6 during permeation by a mobile phase (Tris-HCl buffer) injected with a racemic solution of DL-tryptophan through the BSA-multilayered porous membrane. In addition, the separation factor was constant irrespective of flow rates of the mobile phase because of negligible diffusional mass-transfer resistance of tryptophan to BSA multilayered by the graft chains.