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

• Published in: Crystal growth & design Vol. 11; no. 1; pp. 53 - 58
• Main Authors: Guo, Hui-Shi, Kim, Jong-Min, Pham, Xuan-Hung, Chang, Sang-Mok, Kim, Woo-Sik
• Format: Journal Article
• Language: English
• Published: Washington,DC American Chemical Society 05.01.2011
• Subjects: Condensed matter: structure, mechanical and thermal properties; Equations of state, phase equilibria, and phase transitions; Exact sciences and technology; Physics; Solid-solid transitions; Specific phase transitions; Differential scanning calorimetry; pH value; Phenylalanine; Cooling rate; Crystallization; Liquid chromatography; Contact angle; Racemates; Molecular assembly; Temperature effects; Resonance frequency; Sensors; Diastereomer; Quartz microbalance; X-ray photoelectron spectra
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/cg100275v

This study uses quartz crystal microbalance (QCM) chiral recognition as a novel approach to predict the chiral recognizability of a chiral selector for a racemate. The chiral selector (l-phenylalanine, l-Phe) was immobilized on a QCM sensor surface using a two-step assembly procedure. The modification of the l-Phe on the sensor surface was then characterized using several techniques, including resonant frequency detection, the contact angle, and X-ray photoelectron spectroscopy measurements. When examining the chiral recognizability of the l-Phe-modified QCM sensor for l-mandelic acid (l-MA) using a vapor diffused molecular assembly reaction technique, the chiral discrimination factor between l- and d-MA was about 8. The practical diastereomeric crystallization resolution of a MA racemic compound was then carried out using l-Phe as the resolving agent. The different properties of the diastereomer crystals of l-Phe-l-MA and l-Phe-d-MA were confirmed using high performance liquid chromatography (HPLC) and differential scanning calorimetry (DSC) analysis, plus the factors influencing the chiral resolution, such as molar ratio of MA to l-Phe, agitation speed, pH, cooling rate, and crystallization temperature were examined. The results showed that the diastereomeric crystallization separation of racemate MA using l-Phe as the resolving agent matched well with the QCM chiral recognition results. Therefore, the proposed method using QCM chiral recognition offers a simple solution to the challenge of screening a resolving agent for diastereomeric crystallization.