When chemists need to separate one chiral molecule from a mixture of enantiomers—for instance, when synthesizing potential drug molecules—they often turn to high-performance liquid chromatography (HPLC). A new study suggests an alternative to this approach. The authors report that magnetic fields could separate enantiomers in a racemic mixture (Science 2018, DOI: 10.1126/science.aar4265).
This effect is possible because electrons don’t behave the same way in one enantiomer as they do in another. Electrons and other elementary particles have an intrinsic property called spin. In the case of electrons, the particles are either spin up or spin down. In a chiral molecule, these spin states affect electron motion. Electrons in one spin state will move more easily than those in the other state. Ron Naaman of Weizmann Institute of Science and Yossi Paltiel of Hebrew University of Jerusalem call that phenomenon chiral-induced spin selectivity (CISS).
Now they’ve shown how CISS could be exploited to separate enantiomers in a racemic mixture. When molecules approach a surface, they become polarized, which involves electrons moving through the molecule. Because of the CISS effect, if the molecule is chiral, electrons with one spin state are more favored to move than those in the other state. That causes a concentration of electrons in one spin state where the molecule interacts with the surface.
If the surface is magnetized, the spin states of the material’s electrons will align parallel to the magnetic field. Electrons with like spin states repel each other. A chiral molecule approaching the surface will either be attracted or repelled depending on the spin state of the electrons that concentrated at the end facing the surface. As a result, the researchers say, one enantiomer will preferentially adsorb to a magnetized surface, while the other chiral molecule will not.
They demonstrated the effect with silicon dioxide nanoparticles decorated with enantiomers of a polyalanine oligomer and a magnetized, gold-coated surface. Through scanning electron microscope images, the team observed that the l-alanine oligomer nanoparticles adsorbed eight times as well as the d-alanine particles when the magnetic field pointed up from the surface, and the d-alanine nanoparticles adsorbed four times as well when the field pointed down. Paltiel says their group has tried other chiral molecules and have yet to find enantiomers that don’t show preferential adsorption.
This preferential adsorption could help separate chiral molecules, the scientists say. HPLC separations employ columns filled with a chiral material that adsorbs one enantiomer over the other. “Our idea is people will be able to replace [the columns] they have now in HPLC with a magnetic column,” Naaman says.
A lot of work needs to be done to show this effect can efficiently resolve racemic mixtures, “but it could prove to be very important,” says David Waldeck, a physical chemist at the University of Pittsburgh, who was not involved with the research but has collaborated with Naaman on CISS.