Taylor Vortex Flow-Induced Homochiral Nucleation Enables Additive-Free Enantiopure Crystallization of Hippuric Acid

Abstract

Achieving enantiopure crystallization without the aid of chiral additives or grinding remains a significant challenge in crystallization-based chiral separation. This study demonstrates that periodic Taylor vortex flow (TVF) within a Couette–Taylor crystallizer can drive chiral symmetry breaking (CSB) during the early stages of crystallization, resulting in nearly 100% enantiomeric excess (ee) of hippuric acid as early as the induction period. This performance significantly exceeds that of conventional mixed-tank crystallizers operating under random turbulent flow (RTF). Supersaturation is found to critically influence the extent of CSB. While ee during the induction period under RTF diminishes rapidly with increasing supersaturation, periodic TVF sustains full ee up to a supersaturation of 1.8 and robustly facilitates the dominance of a single enantiomer across all tested conditions, despite the stochastic nature of handedness selection. CFD simulations reveal that Taylor vortices generate coherent flow structures and spatially organized thermal gradients during cooling crystallization, which collectively facilitate molecular alignment and the formation of homochiral prenucleation clusters. These effects favor initial nucleation of a single enantiomer and suppress stochastic, racemic pathways. Importantly, by emphasizing the roles of both homochiral primary nucleation and secondary nucleation, this work extends traditional CSB mechanisms and highlights structured hydrodynamics as a critical regulator of chiral outcomes. This work not only advances the mechanistic understanding of flow-mediated chiral crystallization but also presents a scalable, additive-free strategy for producing enantiopure materials, with broad relevance to pharmaceutical and fine chemical manufacturing.