Quantitative Chiral Analysis by Molecular Rotational Spectroscopy Using Noncovalent Derivatization

Recent advances in experimental and theoretical physical chemistry have provided a path for a new technique for routine chiral analysis of small organic molecules. Chiral tag rotational spectroscopy uses chiral derivatization to convert the enantiomers of an analyte into spectroscopically distinct diastereomers. The derivatization is achieved by forming molecular complexes between the analyte and a small, chiral molecule-the tag-via noncovalent interactions. These chiral tag complexes are formed in the molecular beam expansion used to inject samples into Fourier transform microwave spectrometers. Rotational spectroscopy analysis, guided by computational chemistry methods that model the geometries of the low-energy isomers of the tag complexes, is used to assign the absolute configuration of the analyte. Intensity changes in the rotational spectrum between measurements using racemic and enantiopure tag samples are used to determine the enantiomeric excess. A key feature of chiral tag rotational spectroscopy is that chiral analysis can be performed without any reference samples of the analyte.