Online-Monitoring of the Enantiomeric Ratio in Microfluidic Chip Reactors Using Chiral Selector Ion Vibrational Spectroscopy.

A novel experimental approach for the rapid online monitoring of the enantiomeric ratio of chiral analytes in solution is presented. The charged analyte is transferred to the gas phase by electrospray. Diastereomeric complexes are formed with a volatile chiral selector in a buffer-gas-filled ion guide held at room temperature, mass-selected, and subsequently spectrally differentiated by cryogenic ion trap vibrational spectroscopy. Based on the spectra of the pure complexes in a small diastereomer-specific spectral range, the composition of diastereomeric mixtures is characterized using the cosine similarity score, from which the enantiomeric ratio in the solution is determined. The method is demonstrated for acidified alanine solutions and using three different chiral selectors (2-butanol, 1-phenylethanol, 1-amino-2-propanol). Among these, 2-butanol is the best choice as a selector for protonated alanine, also because the formation ratio of the corresponding diastereomeric complexes is found to be independent of the nature of the enantiomer. Subsequently, a microfluidic chip is implemented to mix enantiomerically pure alanine solutions continuously and determine the enantiomeric ratio online with minimal sample consumption within one minute and with competitive accuracy.