Assessing the Potential for Chiral Separation by Crystallization Using Crystal Energies

A racemic mixture of chiral molecules generally crystallizes as a racemic compound, but in some instances as a conglomerate of enantiopure crystals. Achiral molecules generally form achiral crystals but occasionally chiral structures. In both cases, crystallization breaks the symmetry of the initial achiral liquid, with implications on the origin of life and chiral separation. We analyze the relative energies of the chiral and achiral crystals for systems that do and do not undergo chiral separation on crystallization. In the cases where crystallization can generate chirality, the chiral crystal usually has lower energy than the achiral crystal, while the opposite is true if no chiral separation occurs. This simple result, though intuitive, is not obvious given that many factors influence crystallization and polymorph selection; it helps to assess the potential for a given system to undergo chiral separation by crystallization. Although our analysis has treated chiral and achiral molecules separately, no significant difference is seen between the two groups, suggesting that the two groups are profitably investigated together to understand chirality generation by crystallization.

Automated summary

A racemic mixture of chiral molecules can crystallize either as a racemic compound or as a conglomerate of enantiopure crystals. Achiral molecules usually form achiral crystals, but occasionally exhibit chiral structures. The relative energies of chiral and achiral crystals are analyzed, revealing that chiral crystals generally have lower energy when chiral separation occurs on crystallization, while achiral crystals have lower energy when no chiral separation occurs. This analysis suggests that chiral and achiral molecules should be studied together to better understand chirality generation by crystallization.