Chirality is an essential property of nature. Most biochemical processes take place in chiral environments, which leads to totally different pharmacological interactions with a pair of enantiomers. People have never stopped seeking for more efficient methods to generate optically pure compounds to meet the huge demand in modern pharmaceutics. Among all the methods, selective crystallization is still the most economical and convenient one to provide large-scale chiral compounds. Since Louis Pasteur separated the enantiomeric crystals of sodium ammonium tartrate by using a magnifier and tweezers, several strategies have been developed, including spontaneous crystallization, diastereomer crystallization, preferential crystallization (including heteronucleation assisted by nanoparticles) and tailor-made additives for stereoselective inhibition, to improve chiral separation efficiency. However, either low transformation ratio or high labor is unavoidable in practical applications. Collection of two optically pure enantiomeric crystals in a single unit operation remains a challenge. Crystallization-induced asymmetric transformation and Viedma ripening involving a racemization process can obtain optically pure crystals with 100% yield, but an in-situ chemical transformation is always needed.

Inspired by the magnetic beneficiation, we present herein a magnetic separation strategy to obtain both optically pure enantiomers from conglomerates by making one enantiomeric crystal magnetic-responsive and leaving the other non-magnetic. For this purpose, a kind of nano-material called magnetic “nano-splitters” is designed, which consists of Fe₃O₄ nanoparticles as the core and the polymeric inhibitors with high stereoselectivity to the target crystals as the shell. Thus, selectively embedding magnetic nanoparticles into one polymorph is realized. Taking asparagine monohydrate as an example, this strategy shows high ee% values for both enantiomers (99.1 ee% for R-a.a. and 95.2 ee% for S-a.a.) and high crystallization yield (95.1%) in a one-step crystallization process. This simple strategy is fundamentally different from traditional selective crystallization that leads to enantiomorphs with the same physical properties, which may open a window for developing much more efficient chiral resolution methods that allow for a low cost, recyclable way for different scales.

For more details, please check our paper “Enantiomer-selective magnetization of conglomerates for quantitative chiral separation” on Nature Communications (2019, 10: 1964,  https://doi.org/10.1038/s41467-019-09997-y) .