Chemists just reported that it is possible to use mass spectrometry — a technique commonly used to identify molecules by mass — to separate chiral molecules, those that exist as different forms with identical atoms but mirror-image structures that cannot be superimposed on each other.
The novel technique, described in February in Science Magazin (1), could find real applications in the drug discovery. The different enantiomers often have very different properties in vivo. We all remember that thalidomide, an API showed this to tragic effect: one enantiomer was an efficient sedative, but the other caused serious congenital disabilities, when taken by early pregnant women. As a result, separating and distinguishing enantiomers has been a crucial part of early drug discovery. This step is, however, costly and laborious. Currently, special equipment, use of chiral recognition agents and protocols are required to separate and identify enantiomers. Readers of this blog certainly are aware of the dominant role of cyclodextrins in the separation and detection of enantiomeric species, though no preparative scale of the enantioseparation was achieved, yet. (See CDN blogs )
A research team at Tsinghua University in Beijing, reported on the use of mass spectrometry to separate enantiomers for a group of chiral molecules called binaphthyl-trifluoromethanesulfonates. The researchers put pairs of these propeller-shaped molecules into a mass spectrometer, where they were vaporized, ionized and transferred to an ion-trap mass analyser. The team then applied alternating currents to the ions, sending each enantiomer spinning on a slightly different path, on the basis of its chirality. If these species collide with background gas molecules, then the different enantiomeric forms experience different effects due to the collisions, which finally separates them. Should this novel MS-technique become available broadly, it will be possible to take a small sample of a crude reaction product, send it to a mass spectrometer, get both the enantiomeric excess of the enantiomers in addition to the confirmation of the molecular structures accomplished, within minutes.
Xioaoyu Zhou, et al. Science 383, 612–618 (2024). DOI: 10.1126/science.adj8342