Angew.Chem.Int.Ed.http://doi.org/f2s3wh(2014)

Credit: © 2014 WILEY

When enantioselective syntheses of drug molecules or natural products are impossible, impractical or prohibitively expensive, chiral separation of a racemic product or intermediate offers a viable alternative. Many chiral separations are chromatography-based, and rely on a series of interactions between the racemate and a chiral stationary phase. The net result is separation of the two enantiomers, but the process can be time-consuming and wasteful of the mobile phase.

Now, a team led by Andreas Hauser and Peter Schwerdtfeger from the University of California, Berkeley and Massey University, respectively, have shown that it is theoretically possible to use a nanoporous membrane instead of a stationary phase to achieve chiral separation. This means that, for each molecule, only one event — either passing through a pore or not — would be needed to achieve macroscopic separation, rather than the multiple interactions with the stationary phase that occur in chiral chromatography. However, a chiral pore alone cannot discriminate between enantiomers because the molecules can approach from either 'above' or 'below' the pore.

To overcome this problem, the team modelled a nanopore in graphene with an added out-of-plane single-enantiomer 'gatekeeper' molecule attached to the pore rim. They show that the gatekeeper molecule (1-aminoethanol) forms dimers with free R- or S-1-aminoethanol — with a difference in binding energy that would be too small to achieve chiral separation by itself. However, the small differences in size and orientation of the dimers are enough to greatly amplify the difference in free energy required to pass through the nanopore. The net result is that one enantiomer 'fits' through the pore, and one is blocked due to the size of the dimer formed with the gatekeeper molecule. Although the system modelled is based upon a single pore in a graphene sheet, the approach could be extended to other nanoporous membranes and other gatekeeper molecules, provided the pore size is carefully chosen and controlled. If this approach proves experimentally viable, then it could be a useful alternative to preparative chromatography for chiral separations.