Miniature polymeric tubes separate enantiomers

Separations using tiny polymer-based devices could offer an alternative to chromatography for purifying of chiral compounds. Serena Arnaboldi of the University of Milan and coworkers initially reported the tubular devices late last year (Chem 2023, DOI: 10.1016/j.chempr.2023.11.001), and the team has now shown that the devices can isolate enantiomers of multiple compounds in a single sample (Anal. Chem. 2024, DOI: 10.1021/acs.analchem.3c05544).

The tubes are about 1 cm long and 300 μm in diameter, and they feature a two-layer structure. The inner tubular layer, which is made of a chiral oligomer, interacts with the molecules in a sample as they flow through the tube. That interaction—in which the oligomer grips one enantiomer more strongly than the other—gives the device its separation power.

The outer layer, which is made of polypyrrole, pumps the sample through the tube. The pumping action stems from polypyrrole’s ion-exchange properties: they make the layer swell and contract under an electric field. The researchers place the tubes in a buffer-filled electrochemical cell that allows them to control the electric field and thus the fluid flow.

The researchers injected a mixture of R- and S-carvone and both enantiomers of a chiral ferrocenyl compound into one end of the tube, and they isolated fractions of the four molecules as they emerged from the device. The team analyzed the fractions by high-performance liquid chromatography to verify the separation.

In tubes lined with the R oligomer of the chiral selector, the S-carvone and the R-carvone were eluted in the first and second fractions, respectively. The enantiomers of the ferrocenyl compound were more strongly retained; they were eluted in the third and fourth fractions after several minutes. The team was able to change the elution order of the enantiomers by using an inner layer made of the S oligomer of the chiral selector.

Arnaboldi doesn’t anticipate that the devices will replace chiral chromatography, partially because of the difficulty in scaling them up. But “the systems can be really supportive for rapid screening because they are small,” she says. “Also, they work wirelessly, so you don’t need to connect everything to a big power supply.”

Sara Grecchi, a postdoctoral fellow in Arnaboldi’s group, is currently working to improve the devices’ separation power by making the tubes longer and forming them into other shapes. “It’s really tricky, but she’s obtaining a really nice helix,” Arnaboldi says.