Mechanistic Dissymmetry between Crystal Growth and Dissolution Drives Ratcheted Chiral Amplification
Sjoerd W. van Dongen, Jin Maeda, Bernard Kaptein, Pascal Cardinaël, Adrian E. Flood, Gérard Coquerel, Willem L. Noorduin
Abstract
Complete chiral amplification of the solid phase arises when mixtures of self-sorting enantiopure crystals undergo cycles of crystal growth and dissolution under solution-phase racemizing conditions. However, despite extensive studies and widespread use, the mechanism underlying such crystallization-induced deracemization remains insufficiently understood, hindering its optimization and broader application. Here, we experimentally dissect the individual contributions of crystal growth and dissolution and use a mass-balance to expose crystal dynamics. Regardless of the racemization rate, we always find a dissymmetry between the growth and the dissolution of the enantiomer populations. These experiments suggest that a fundamental difference between the mechanisms of crystal growth and dissolution enables a ratchet effect that drives chiral amplification. These insights advance our understanding of chiral crystallization mechanisms and provide guidance for optimizing crystallization-induced deracemizations, particularly by separately optimizing growth and dissolution steps to maximize the chiral amplification and deracemization efficiency.