Chiral Discrimination Using Ion Mobility Spectrometry and Their Applications to Chemical and Biological Studies

Abstract

Ion mobility spectrometry (IMS) has become an analytical technique for rapid chiral discrimination, offering significant potential to accelerate various studies such as drug discovery, clinical diagnostics, and bioimaging. This review highlights recent advancements in chiral discrimination using IMS, based on studies published from 2006 to 2024. The methods are categorized into three main approaches: (1) direct separation in a chiral environment, (2) non-covalent complexation, and (3) diastereomeric separation using a covalently bonded chiral tag (chiral derivatization). For each approach, landmark studies are discussed with emphasis on critical notes such as selection of the additive and the ion form for efficient separation. Subsequently, representative applications of chiral derivatization to asymmetric catalyst development, rapid bioanalysis, and biomolecular imaging are explained in detail. The enantioselective imaging of chiral metabolites is more challenging than others but attracts growing interest from biologists and analytical chemists, making the description regarding on-tissue charged chiral derivatization, which improves ionization efficiency and separation of analyte, particularly relevant. Independent studies have demonstrated that IMS, under optimized conditions, can achieve performance comparable to high-performance liquid chromatography (HPLC) in determining enantiomeric excess. Considering higher throughput and simplicity of IMS over HPLC, further instrumental and/or chemical advancements would make IMS a more versatile technique for chiral discrimination.