石英晶体微天平用于预测非对映体盐结晶分离手性扁桃酸的分离效率

Prediction of Enantioseparation Efficiency of Chiral Mandelic Acid in Diastereomeric Crystallization Using a Quartz Crystal Microbalance

研究了以石英晶体微天平(QCM)手性识别结果预测手性选择剂对外消旋物的手性识别能力的新方法。经过两步组装方式将手性选择剂L-苯丙氨酸(L-Phe)组装到QCM电极表面。通过检测电极共振频率、接触角和X射线光电子能谱的变化对组装结果进行了表征。应用蒸气扩散分子组装(VDMA)方式检测L-Phe修饰QCM电极对L-扁桃酸(MA)的手性识别能力,其手性识别选择性系数约为8。随后用L-Phe作为拆分剂试验了非对映体盐结晶法拆分手性扁桃酸,并优化了手性拆分条件。结果显示,以L-Phe作为拆分剂进行非对映体盐结晶法拆分手性扁桃酸的结果与QCM手性识别结果高度吻合,表明QCM手性识别可用作辅助筛选和预测非对映体盐结晶手性拆分法的手性拆分剂。

A quartz crystal microbalance （QCM） chiral recognition method was used to predict the ehiral recognizability of a ehiral selector for a racemate. The chiral selector of L-phenylalanine （L- Phe） was immobilized on the surface of a QCM sensor by a two-step assembly procedure. The L-Phe modified sensor surface was characterized using several techniques, including resonant frequency detection, the eontact angle and X-ray photoelectron spectroscopy measurements. The ehiral recognizability of the L-Phe-modified QCM sensor for L-mandelic acid （MA） was examined by the vapor diffused molecular assembly reaction technique, and the ehiral discrimination factor between L- and D- MA was obtained to be about 8. The practical diastereomeric crystallization resolution of a MA raeemie mixture was then carried out using L-Phe as resolving agent. The different properties of the diastereomer crystals of L-Phe - L-MA and L-Phe - D-MA were confirmed by HPLC, morphology and DSC detection. The factors influencing the diastereomerie crystallization resolution were investigated. Under the optimal conditions, the results showed that the diastereomerie crystallization separation of raeemate MA with L-Phe as resolving agent matched well with that by the QCM chiral recognition method. Therefore, the proposed method using QCM chiral recognition can offer a simple solution to the challenge of screening a resolving agent for diastereomeric crystallization.