Enantioselective high-performance liquid chromatography of aryl-substituted oxazolines as an efficient tool for determination of chiral purity of serine medicinal components.

A new approach for the evaluation of chiral purity of serine esterification products bearing long-chain alkyl substituents was developed. The compounds were simply converted to aryl-substituted oxazolines which: (i) facilitates effective chromatographic enantioseparation and (ii) enables direct detection using ultraviolet absorption. The method employs a polysaccharide-based chiral stationary phase and allows enantioseparation of highly stable oxazoline products in less than 6 min using a simple binary mobile phase. As opposed to the previously used normal phase method the developed method was performed in the reversed-phase mode. Aside from the benefits of switching to less hazardous solvents with regard to the principles of Green Chemistry, this has also led to a reduction in the analysis time. In comparison with known serine chromophores, the best enantioseparation of aryloxazoline rigid structure may be achieved only based on non-polar interactions with the chiral stationary phase. In contrast, the substitution of the chromophore moiety with hydroxyl substituent affected intra and intermolecular interactions that caused enantioseparation differences. Concurrently, we found high chirality retention of (R)- and (S)-configuration oxazoline standards (≥99% enantiomeric excess) during the introduction of the ultraviolet label. The method is suitable for rapid injection of the mixture containing the ultraviolet absorption marker without prior purification.

How mobile phase composition and column temperature affect enantiomer elution order of liquid crystals on amylose tris(3-chloro-5-methylphenylcarbamate) as chiral selector.

A comprehensive study into the effects of mobile phase composition and column temperature on enantiomer elution order was conducted with a set of chiral rod-like liquid crystalline materials. The analytes were structurally similar and comprised variances such as length of terminal alkyl chain, presence of chlorine, number of phenyl rings, and type of chiral center. Experiments were carried out in polar organic and reversed-phase modes using amylose tris(3-chloro-5-methylphenylcarbamate) immobilized on silica gel as the chiral stationary phase. For all liquid crystals, reversal of elution order of enantiomers was observed based on type of used cosolvent and/or its content in the mobile phase; for some of the liquid crystals a temperature-induced reversal was also observed. Both linear and nonlinear dependencies of natural logarithm of enantioselectivity on temperature were found. Tested mobile phases comprised pure organic solvents and binary and tertiary mixtures of acetonitrile with organic solvents and/or water. Effect of acidic/basic mobile phase additives was also tested. Effect of structure of chiral selector is briefly discussed.

Advantages of polar organic solvent chromatography for enantioseparation of chiral liquid crystals.

Three sets of fluorinated chiral liquid crystals were used to explore the polar organic solvent chromatography mode for their enantioseparation. The materials include a set of newly synthesized compounds with chiral center derived from 2-hexanol and two sets of compounds with chiral center derived from 2-/3-octanol. Baseline enantioseparation of all materials was achieved using binary mobile phases without additives. For some of the compounds exceedingly high values of enantioresolution (> 20) and enantioselectivity (> 4) were found. The chromatographic behavior of the sample set was studied on three different polysaccharide-based chiral columns - Chiralpak IA-U, IG-U and IB-U. Comparison of results from Chiralpak IA-U and IB-U shows the effect of amylose vs. cellulose polysaccharide backbone while comparison of Chiralpak IA-U and IG-U reveals the effect of 3,5-dimethylphenylcarbamate vs. 3­chloro-5-methylphenylcarbamate substituent. The mobile phases tested included whole range of acetonitrile/methanol mixtures to demonstrate that acetonitrile-rich and alcohol-rich mobile phases offer different enantiorecognition mechanisms and can provide complementarity to some extent. The effect of temperature on enantioseparation was investigated on Chiralpak IA-U by constructing van't Hoff plots for selected liquid crystals in pure acetonitrile and pure methanol as mobile phases.

Enantioseparation of liquid crystals and their utilization as enantiodiscrimination materials.

Liquid crystals can partake in enantioseparations in several different ways. Enantiomeric purity of chiral liquid crystals as analytes is often determined using enantioselective liquid or supercritical fluid chromatography. At the same time, chiral liquid crystalline materials can be applied as a chiral selector or they can function as an auxiliary material for a different chiral selector enabling enantioseparation of various solutes in miscellaneous separation techniques. They can also be used in fabrication of matrices or surfaces sensitive towards enantiomers or employed as chiral solvents for visualizing enantiomers in NMR. In this review, all of these aspects of relationship between liquid crystals and enantiodiscrimination are discussed in an effort to encompass their versatility and with emphasis on enantioseparations.

Enantiorecognition ability of different chiral selectors for separation of liquid crystals in supercritical fluid chromatography; critical evaluation.

Comprehensive study of enantioselective potential of eight different chiral stationary phases for chiral liquid crystal-forming molecules was conducted. The tested columns were: (i) polysaccharide-based Trefoil AMY1, CEL1 and CEL2 and (ii) superficially porous particles packed TeicoShell, VancoShell, TagShell, DMP-MaltoShell, and NicoShell. To test their enantioselective potential for these separations, twenty racemic mixtures of rod-like liquid crystalline materials comprising three different types of chiral centres and various other structural differences were used. Mobile phases consisting of supercritical carbon dioxide and alcohol as cosolvent were used; selected alcohols were methanol, ethanol and propan-2-ol. Effect of acidic and/or basic additives on enantioselectivity was also evaluated. Chiral stationary phases based on polysaccharides were found to have the greatest enantioselective potential for rod-like molecules that form liquid crystals, followed by TeicoShell, which proved suitable for enantioseparation of non-halogenated liquid crystals with lactic acid-based chiral centre.

Ultra-performance supercritical fluid chromatography: A powerful tool for the enantioseparation of thermotropic fluorinated liquid crystals.

A fast and simple supercritical fluid chromatography method for the enantioseparation of twenty newly synthesized orthoconic antiferroelectric liquid crystals is reported for the first time. The effects of alkoxy spacer length and fluorine atom presence and position in the phenyl ring on chromatographic behavior were investigated. Baseline enantioseparation of all compounds was achieved using simple mobile phases consisting of carbon dioxide and alcohol as cosolvent on (3,5-dimethylphenylcarbamate) derivative of amylose as chiral stationary phase. The analysis times ranged from 2 to 4 and from 4 to 7 min for most samples when using methanol and propane-2-ol, respectively. The significant effect of cosolvent type on the enantioseparation of these compounds was assessed and partial complementarity of methanol and propane-2-ol was observed.