Mass spectrometry is a commonly used method for identifying molecules based on their mass. Recently, scientists have shown that it can also distinguish between chiral compounds. These compounds have identical atoms but their structures are mirror-images that cannot overlap each other.
The method, which is presented in Science today, may use in drug discovery in the future. Enantiomers, or distinct forms of chiral compounds, frequently differ greatly in their characteristics. This was tragically demonstrated by the medication thalidomide: whereas one enantiomer is tranquil, the other, when given during pregnancy, causes congenital defects. Because of this, enantiomer separation is an essential but frequently time-consuming step in the drug discovery process. The tools used by current approaches are specialized and maintain distinct protocols for every pair of enantiomers.
Separate ions
Mass spectrometry was utilized by a group of researchers at Tsinghua University in Beijing, under the direction of Zheng Ouyang, to separate the enantiomers of a class of chiral compounds known as binaphthyl-triflates.
Pairs of these propeller-shaped molecules were introduced into a mass spectrometer by the researchers, who then used it to evaporate, ionize, and transfer the molecules to an ion-trap mass analyzer. Based on the chirality of each enantiomer, the researchers subsequently used alternating currents to spin the ions, sending them spinning in slightly different directions.
“When they collide with background gas molecules, different enantiomeric forms experience different effects due to the collisions,” says Ouyang, which separates them. Then, when they are ejected at the other end of the spectrometer, the ions come out one at a time and can be detected separately. The machine can also determine the proportion of each enantiomer in a mixture — known as the enantiomeric excess (e.e.) and expressed as a percentage.
“Chemists can take a dip of a crude reaction product as sample, send it to a mass spectrometer, get both the e.e. of the enantiomers in addition to the confirmation of the molecular structures within a minute,” Ouyang says. Once scaled up, the mass-spectrometry system could also be used to prepare pure samples of enantiomers in larger quantities, he adds.
“I love this work,” says Perdita Barran, director of the Michael Barber Centre for Collaborative Mass Spectrometry at the University of Manchester, UK. She says that being able to simply separate enantiomers has been a “big quest”. “A go-to method to separate enantiomers has relevance for drug discovery and design,” she says.
