Versatile Method for Chiral Recognition by the Quartz Crystal Microbalance: Chiral Mandelic Acid as the Detection Model

Abstract

Chiral recognition is considered to be the most important, fundamental basis in the development of separation technology for chiral isomers in the pharmaceutical and biotechnology fields. However, the selective detection of individual enantiomers is still one of the most difficult analytical tasks because of the close similarity of the molecular configurations between chiral isomers. This study presents a versatile vapor-diffused molecular assembly (VDMA) reaction approach for chiral recognition by the quartz crystal microbalance (QCM). Chiral L/D-mandelic acid (MA) was used as the detection model, and L-phenylalanine (L-Phe) was used as the selector. The construction of the L-Phe-modified QCM sensor involved a four-step layer-by-layer assembly procedure. Each modification step was analyzed by cyclic voltammetry, the contact angle, and a resonance frequency measurement. The chiral recognizability of the L-Phe-modified QCM sensor to L-mandelic acid was then examined by resonance frequency measurement using the novel VDMA technique and also investigated by atomic force microscope (AFM) measurements. A chiral discrimination factor of up to approximately 9 between L- and d-MA on the L-Phe-modified QCM sensor was obtained by using this gaseous-phase reaction technique. AFM results also showed obvious selective aggregation of L-MA on the L-Phe-modified surface but no noticeable aggregation of D-MA during the VDMA reaction. Both of the QCM and AFM results confirmed the usefulness of this proposed VDMA technique for the study of chiral recognition. The main advantage of the proposed method is that it offers a universal simple application scheme for the QCM detection of small resonance frequency changes due to chiral molecular recognition by a chiral selector immobilized on the QCM sensor surface.