Chiral Amplification in Crystallization under Ultrasound Radiation

Abstract

The discovery of the importance of stereochemistry and the resolution of enantiomers dates back to the days of Pasteur, and since then the study of chirality has been of fundamental importance for both scientific and applicative purposes. [1,2] Resolution of enantiomers can be achieved by various processes based on physical, chemical, and biological techniques. [3] Nevertheless, all these techniques require the presence of optically-active molecules in order to achieve chiral resolution.During the last two decades there has been much progress in the field of chiral amplification and resolution of a symmetric chemical system in the absence of any asymmetric (chiral) environment. First experimental evidence for the spontaneous emergence of homochirality was reported by Havinga in 1954 [4] for a spontaneous homochiral phase that arises in the crystallization of methyl-ethyl-allyl-anilinium iodide. Later Kondepudi et al. induced total chiral discrimination by stirred crystallization of sodium chlorate and other chiral systems. [5][6][7][8] More recent examples of symmetry breaking during crystallization are reported in the work of Viedma, who showed in a series of papers [9][10][11] that asymmetric amplification can be achieved by the abrasive grinding of saturated solutions of enantiomorphous crystals (sodium chlorate) to obtain crystals with single-handedness. Recently, Vlieg and Blackmond [12][13][14][15] have shown that in the stirred crystallization of a suspension of nearly racemic amino acid, derivative crystals can result in a single chiral crystal of one of the enantiomeric pair in a chemical system in which enantiomers can racemize. Blackmond and Viedma in a joint publication [16] illustrated the evolution of total enantioenrichment of the solid phase of aspartic acid by solutionphase racemization. The authors also investigated the mechanism for this transformation, showing that the process occurs even in the absence of the attrition enhancement. [16] In this Communication, we describe the effect of ultrasound radiation on the kinetic resolution of enantiomers during crystallization. It should be mentioned that the ability of ultrasound radiation to serve as a false chiral force was first proposed by Cintas [17] and the concept of enantioselective crystallization under ultrasound was later demonstrated by Chen and co-workers [18] in the crystallization of sodium chlorate in the presence of seed crystals. In a more recent paper Cintas [19] emphasized the potential of ultrasound irradiation in enantioselective crystallization.Herein we demonstrate that the application of ultrasound radiation to the crystallization of amino acids affects crystallization kinetics, crystal morphology, and causes chiral amplification. To demonstrate the effect of ultrasounds on chiral amplification in a crystallization process, a model for chiral crystallization has to be selected. We selected dlthreonine as a model system for conglomerate crystallization. We have to point out that our experimental system has two unique propertie...

Molecular Chirality in Meteorites and Interstellar Ices, and the Chirality Experiment on Board the ESA Cometary Rosetta Mission

“…This reaction clearly does not occur under prebiotic conditions, but it is an important example of the absolute asymmetric synthesis of enantiomerically enriched products. This strategy has proven to be effective for threonine, [89] aspartic acid, and glutamic acid, [90] as well as for valine. [86] Its kinetic model has been studied in detail by the groups of Blackmond [87] and Buhse.…”

“…[88] Another example of the Frank model is the amplification of an initial enantiomeric disproportion through physical processes, such as evaporation, crystallization, or sublimation under "far-from-equilibrium" conditions. This strategy has proven to be effective for threonine, [89] aspartic acid, and glutamic acid, [90] as well as for valine. [91] The autocatalysis based on equilibrium phase behavior is fully reflected in crystallization under "near-equilibrium" conditions as described by Viedma.…”

A Mechanochemical Approach to Deracemization

“…[4][5][6][7][8][9][10][11] An ideal solution to this problem is to reconfigure the stereochemistry of the undesired enantiomer during the resolution process. While dynamic kinetic resolution (DKR) [5][6][7][8][9][10][11] or attrition-enhanced deracemization [12][13][14][15] methods may be used to overcome this fundamental limitation, the substrate scope for these methods is confined to compounds that can be chemically or thermally racemized. Given the recent advances in mechanochemistry, [16,17] where the mechanical force generated under ultrasound may be used to surmount thermally inaccessible isomerization barriers, [18][19][20][21][22] we envisioned a new method for enriching the enantiopurity of optically active species.…”

On the Physical Basis of Asymmetry and Homochirality

“…Stirring drives the system far from the equilibrium, a situation that can also be attained under other forms of agitation such as an ultrasonic field. In a recent study by Mastai et al , amplification experiments were conducted from supersaturated solutions of DL‐threonine (an amino acid that crystallizes as conglomerate) when exposed to pulsed ultrasound irradiation . This field is clearly a falsely chiral influence, although it largely accelerates the crystallization and reduces the average crystal size.…”

“…This field is clearly a falsely chiral influence, although it largely accelerates the crystallization and reduces the average crystal size. Starting from slightly enriched solutions of threonine (2.5%–5% ee of the L‐enantiomer or D‐enantiomer), a significant amplification (up to 87% ee ) could be detected under ultrasonic irradiation …”