Spontaneous and Controlled Macroscopic Chiral Symmetry Breaking by Means of Crystallization

Abstract

In this paper, macroscopic chiral symmetry breaking refers to as the process in which a mixture of enantiomers departs from 50–50 symmetry to favor one chirality, resulting in either a scalemic mixture or a pure enantiomer. In this domain, crystallization offers various possibilities, from the classical Viedma ripening or Temperature Cycle-Induced Deracemization to the famous Kondepudi experiment and then to so-called Preferential Enrichment. These processes, together with some variants, will be depicted in terms of thermodynamic pathways, departure from equilibrium and operating conditions. Influential parameters on the final state will be reviewed as well as the impact of kinetics of the R ⇔ S equilibrium in solution on chiral symmetry breaking. How one can control the outcome of symmetry breaking is examined. Several open questions are detailed and different interpretations are discussed.

The unexpected dominance of secondary over primary nucleation

“…12 Viedma ripening is a particular deracemization process, where a racemic mixture of chiral crystals can be deracemized by attrition under isothermal conditions. 13 Enantioselective secondary nucleation in a process with an enantiopure seed suspension would generate only new crystals with the same handedness as that of the seed crystals, while unselective primary nucleation in such a process would result in the loss of product chirality, as crystals with both handednesses are formed. While deracemization by Viedma ripening is haunted by a relatively low productivity, in terms of units of product weight per units of time and volume, due to the relatively low supersaturations during the process, temperature cycling induced deracemization (TCID) 14,15 and second order asymmetric transformation (SOAT) 16 processes allow an improvement in productivity, as the supersaturations achieved for crystallization are higher, while primary nucleation can be avoided.…”

Spontaneous and induced chiral symmetry breaking of stereolabile pillar[5]arene derivatives upon crystallisation

“…Overall, this work provides new strategies to manipulate the handedness of inherently chiral pillar[5]arene macrocycles. These pillararene-based chiral crystalline materials will be of interest for further studies of symmetry breaking during crystallisation, 28 new routes to absolute asymmetric synthesis, 14 and their chiroptical, pyroelectric, or piezoelectric properties. 29…”

Nucleation behaviour of racemic and enantiopure histidine

“…These observations are consistent with a report on limited preferential enrichment observed for histidine 31 and would explain the weak SHG effect in line with symmetry breaking through crystallisation. 32,33 It also explains, in the case of the racemic compound, why CNT may not work as the nucleation is clearly not a simply homogeneous process.…”