Reinvestigating the Preferential Enrichment of DL-Arginine Fumarate: New Thoughts on the Mechanism of This Far from Equilibrium Crystallization Phenomenon

Clément de Saint Jores (1) , Clement Brandel (1) , Marie Vaccaro (1) , Najla Gharbi (1) , Isabelle Schmitz-Afonso (2) , Pascal Cardinael (1) , Rui Tamura (3) , Gérard Coquerel (1)

1 SMS - Sciences et Méthodes Séparatives
2 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
3 Kyoto University

Preferential enrichment (PE) is a crystallization process, starting from either a racemic of slightly enantio-enriched solution (ca. +5%) that results in a high enantiomeric excess in the liquid phase (>+90%ee) and a slight opposite excess in the deposited crystals (−2 to −5%ee). The mechanism(s) of this symmetry-breaking phenomenon is (are) still a matter of debate since it eludes rationalization by phase diagram formalism. In this publication, we thoroughly reinvestigate the PE phenomenon of arginine fumarate by using a new approach: the process is monitored by introducing isotopically labeled arginine enantiomers into the crystallization medium to better understand the mass exchanges during crystallization. These experiments are supported by chiral HPLC-MS/MS. This study permits re-evaluating the criteria that were thought mandatory to perform PE. In particular, we show that PE occurs by a continuous exchange between the solution and the crystals and does not require the occurrence of a solvent-mediated solid–solid phase transition.

Mots clés: crystallization; chiral resolution; symmetry breaking; preferential enrichment

Domaines: Chimie analytique; Cristallographie

Clément de Saint Jores, Clement Brandel, Marie Vaccaro, Najla Gharbi, Isabelle Schmitz-Afonso, et al.. Reinvestigating the Preferential Enrichment of DL-Arginine Fumarate: New Thoughts on the Mechanism of This Far from Equilibrium Crystallization Phenomenon. Molecules, 2022, 27 (24), pp.8652. ⟨10.3390/molecules27248652⟩. ⟨hal-03926061⟩