Sekai Iwama

Chiral Symmetry Breaking Phenomenon Caused by a Phase Transition

Rui Tamura *, Sekai Iwama and Hiroki Takahashi Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan; E-Mails: w.sekai2@gmail.com (S.I.); takahashi@mbox.kudpc.kyoto-u.ac.jp (H.T.) * Author to whom correspondence should be addressed; E-Mail: tamura-r@mbox.kudpc.kyoto-u.ac.jp. Received: 30 December 2009; in revised form: 9 February 2010 / Accepted: 15 February 2010 / Published: 17 February 2010 Abstract: We report the mechanism and scope of “preferential enrichment”, which is an unusual symmetry-breaking enantiomeric resolution phenomenon that is initiated by the solvent-assisted solid-to-solid transformation of a metastable polymorphic form into a thermodynamically stable one during crystallization from the supersaturated solution of certain kinds of racemic mixed crystals ( i.e. , solid solutions or pseudoracemates) composed of two enantiomers. The mechanism can well be interpreted in terms of a symmetry-breaking complexity phenomenon involving multistage processes that affect each other. Keywords: preferential enrichment; enantiomeric resolution; optical resolution; chiral separation; polymorphic transition; epitaxial transition; mixed crystal 1. Introduction Nowadays, a concept of nonlinear “complexity” theor y has been recognized to govern various dynamic behaviors in both natural and social sciences. In the complexity system, symmetry is easily broken by the phase transition between two chaotic or metastable states [1-3]. Therefore, it might be possible to observe the symmetry-breaking as a chemical complexity phenomenon by using appropriate probes such as chirality (Figure 1). Crystallization can be regarded as an event of complexity in terms of the kinetic behavior, far from thermal equilibrium, involving formation of metastable prenucleation molecular aggregates, nucleation and crystal growth, and polymorphic transition. Furthermore, these processes affect each other in

Highly efficient chiral resolution of DL-arginine by cocrystal formation followed by recrystallization under preferential-enrichment conditions.

An excellent chiral symmetry-breaking spontaneous enantiomeric resolution phenomenon, denoted preferential enrichment, was observed on recrystallization of the 1:1 cocrystal of dl-arginine and fumaric acid, which is classified as a racemic compound crystal with a high eutectic ee value (>95 %), under non-equilibrium crystallization conditions. On the basis of temperature-controlled video microscopy and in situ time-resolved solid-state (13) C NMR spectroscopic studies on the crystallization process, a new mechanism of phase transition that can induce preferential enrichment is proposed.

Preferential Enrichment of DL-Leucine Using Cocrystal Formation With Oxalic Acid Under Nonequilibrium Crystallization Conditions.

By utilizing the preferential enrichment (PE) technique, we achieved an improved enantiomeric resolution of DL-leucine (Leu) using a 1:1 cocrystal (DL-) of DL-Leu and oxalic acid. The crystal structure analysis of DL- indicated the occurrence of a novel type of phase transition and subsequent preferential redissolution of one enantiomer from the resulting crystals into solution.

A Kinetic/Thermodynamic Origin of Regular Chiral Fluctuation or Symmetry Breaking Unique to Preferential Enrichment.

The kinetic/thermodynamic origin of preferential enrichment (PE), which is a spontaneous enantiomeric resolution phenomenon applicable to racemic crystals, is described. The mechanism of PE, which was unveiled with respect to the first-generation of chiral organic compounds showing PE, has been interpreted in terms of a nonlinear complexity phenomenon including two unique processes: a solvent-assisted solid-to-solid polymorphic transition and subsequent selective redissolution of the excess one enantiomer from the transformed disordered crystals into the mother liquor. The present works confirm that PE takes place because of the unique nonlinear solubility properties of the two enantiomers after the occurrence of a polymorphic transition under PE crystallization conditions at high supersaturation. Furthermore, a ternary phase diagram that is consistent with the mechanism of PE is proposed.