Separating enantiomers through the art of levitation

Scientists from the Massachusetts Institute of Technology (MA, USA), in collaboration with Harvard University (MA, USA), have described the successful separation of enantiomers using sequential magnetic levitation (MagLev) separation.

Chiral separation is of particular significance in the pharmaceutical industry where it is important to separate the therapeutically active enantiomer from the other, which may be inactive or even toxic. Currently, isolation of pure enantiomers is often carried out using solution-based separation techniques, such as HPLC.

“Chiral resolution, especially during drug discovery, requires tedious method development by an experienced scientist to achieve efficient separation,” said Syed Rizvi, a chiral separations and pharmaceutical analysis expert at Nova Southeastern University (FL, USA).

An alternative to this technique is to purify the desired enantiomer from a mixture of crystals of enantiomerically pure and racemic compounds.

As enantiopure and racemic crystals generally have different densities due to distinct packing arrangements of the molecules, they can be levitated in a paramagnetic solution to different heights by the balance of magnetic and gravitational forces and then separated.

In a study led by Allan Myerson, a scientist at the Massachusetts Institute of Technology, the team successfully applied this approach, purifying a 1:1 mixture of S- and RS-ibuprofen to 99.2% ee using four sequential MagLev separations.

According to the team, relative to solution-based separation, the MagLev technique is quite simple and inexpensive and, as such, has great potential to become a routine method for chiral separation.

Despite its simplicity, the use of MagLev on a large scale presents a number of challenges: “As it requires that the racemic crystal forms reliably, does not stick to enantiomerically pure crystals, and has a different density, it is more likely to be used in an analytical laboratory setting engaged in preclinical studies of a compound,” said Myerson.

The team is currently working to apply MagLev to the purification of other chiral compounds and is aiming to extend their technique to the separation of cocrystals.

Source: Yang X, Wong SY, Bwambok DK et al. Separation and enrichment of enantiopure from racemic compounds using magnetic levitation. Chem. Commun. 50, 7548–7551 (2014).