DOI: 10.1021/cg100152c
Observation of the Preferential Enrichment Phenomenon for Essential r-Amino Acids with a Racemic Crystal Structure
2010, Vol. 10 2668–2675
Sekai Iwama,† Masahiro Horiguchi,† Hiroyasu Sato,‡ Yoshiaki Uchida,† Hiroki Takahashi,† Hirohito Tsue,† and Rui Tamura*,† †
Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan, and Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima-shi, Tokyo 196-8666, Japan
‡
Received February 1, 2010
ABSTRACT: The preferential enrichment phenomenon has been observed for two neutral R-amino acids, leucine and alanine, by applying kinetic crystallization conditions using high concentrations and appropriate solvents. The mechanism of preferential enrichment of leucine and alanine is proposed on the basis of (i) the difference in solubility between the racemic and enantiomerically pure samples, (ii) the observation of polymorphic transition during crystallization by in situ attenuated total reflection infrared spectroscopy, (iii) the characterization of deposited crystals by X-ray crystallographic analysis, and (iv) the optical microscopic or atomic force microscopy observation of the crystal shape or surface, respectively.
Table 1. X-ray Analytical Data for Leucine and Alanine
Introduction
*Corresponding author. Telephone: þ81-75-753-6815. Fax: þ81-75-7537915. E-mail:
[email protected]. pubs.acs.org/crystal
Published on Web 04/29/2010
crystal system space group a, A˚ b, A˚ c, A˚ R, deg β, deg γ, deg V, A˚3 Z Re, Rwf
leucinea form a
leucineb form b
alaninec needles
d DL-alanine
triclinic P1 (No. 2) 14.1178(3) 5.40675(11) 5.19308(11) 111.1860(10) 96.9701(11) 86.4257(12) 366.798(14) 2 0.039, 0.120
triclinic P1 (No. 2) 13.9853(15) 5.3995(14) 5.154(4) 111.471(6) 96.760(8) 86.579(7) 359.6(3) 2 0.078, 0.234
orthorhombic Pna21 (No. 33) 12.0067(16) 6.0290(6) 5.8318(6) 90 90 90 422.15(8) 4 0.047, 0.116
orthorhombic Pna21 (No. 33) 12.0263(17) 6.0321(9) 5.829(2) 90 90 90 422.858(19) 4 0.025, 0.072
)
a b c d e D-rich, 2.5% ee. 0% ee. 0% ee. Quoted from ref 23. R = Σ F0| ; |Fc /Σ|F0| for I > 2.0σ(I) data. f Rw = [Σw(|F0| ; |Fc|)2/Σw|F02|]1/2.
)
Nowadays, the concept of nonlinear “complexity” theory 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.1,2 This is true for crystallization processes, too.3,4 In fact, we reported the first symmetrybreaking enantiomeric resolution phenomenon, referred to as “preferential enrichment”, that is initiated by the solventassisted 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 without the aid of any external chiral element.4-7 Most notably, this polymorphic transition process is followed by partial crystal disintegration inside the transformed crystal lattice to release the excess enantiomer into solution until the deposited crystals are slightly enriched with the opposite enantiomer (
