Literature Review: Homochiral Porous Organic Cage with High Selectivity for the Separation of Racemates in Gas Chromatography

The chirality of a molecule can vastly alter the reactions and chemical behaviors of that molecule, especially in stereospecific environments.  There have been a variety of examples demonstrating that a change in chirality can make seemingly identical molecules either medically helpful or equally very detrimental to human health.  With this distinction, it becomes necessary to develop efficient and specific techniques that can, with good resolution, separate molecules that differ by as little as a single chiral center.  Naturally, because these molecules share many common molecular properties, such as boiling point or intermolecular interactions, this task can become very difficult.

Because typical intermolecular interactions for these isomers are almost always going to be the same or too similar to induce reliable separation by usual chromatographic methods, different sorts of molecular interactions must be utilized to accomplish the desired result.  There are columns which have already accomplished these types of separations. Chirasil-L-Val, which is primarily useful for the separation of amino acids and their derivatives, as well as β-DEX 120, which is reportedly one of the best enantioselective columns used in Gas Chromatography (GC), are some columns which are already established and used for enantioselective separations.  In class we have discussed briefly chiral stationary phases which rely upon very stereospecific three point interactions between atoms on complementary chiral centers for good separation of isomers, but this paper takes a somewhat different approach to solving the separation problem.

Using homochiral porous organic cages (POCs) diluted with polysiloxane as a stationary phase for GC, this paper demonstrates that a wide variety of small chiral molecules and isomers can be separated using a single column.  The general separation behavior of this new stationary phase was determined by elution of a linear series of alkanes, alcohols and aromatic hydrocarbons, demonstrating that these compounds could all be separated with good resolution and were eluted by boiling point.  Following this basic characterization, the column was used to separate a variety of positional isomers of disubstituted benzene derivatives where substituents were all small functionalities.  Typically, positional isomers would elute in order of boiling point as well, with meta-isomers eluted first followed by ortho– and para-isomers.  However, with this new stationary phase, ortho- and para-isomers were eluted in the correct order, but meta-isomers were eluted last in all cases, demonstrating a preference for retention of meta-isomers over the other two positional isomers for this particular stationary phase.  This preference was attributed to better matching of the meta-isomer geometry to the cavity geometry of the POCs used.

Finally, a variety of chiral molecules were also separated—including alcohols, diols, amines, esters, ketones, ethers, halohydrocarbons, acids, amino acid methyl esters and sulfoxides—and most reached baseline separation, some with very high resolution.  The overall ability to separate a large variety of molecules was compared to the other two columns previously mentioned.  As Chiral-L-Val seems specifically tuned towards separation of amino acid isomers, it is unsurprising that it cannot separate the broad range of different compounds that the POC stationary phase has.  It should be noted, however, that there was no comparison of the ability of the new stationary phase to separate amino acids more efficiently than Chiral-L-Val, only that it has broader applications.  However, when compared to the β-DEX 120 column, more compounds could be separated, and the paper gives the impression that the resolution was higher for their new column in all cases.

Overall, this new stationary phase therefore has the potential to offer a column which can be used for a variety of applications in GC and may be more efficient than some of the currently available columns already used. Nevertheless, it should be noted that there are some limitations.  There are many applications—such as in the cases of pesticides or chemicals used in the fragrance or cosmetics industries—that use large chiral molecules which not only may not be GC-compatible, but may not be POC compatible because they may not interact favorably in a geometric sense.  For techniques beyond a broad range of small organic chiral molecules with relatively low boiling points, the column would not only need to be adapted to allow for Liquid Chromatography to handle non-GC-compatible molecules, but the stationary phase itself might need to be adjusted such that the POCs would still be compatible with the analytes of interest.

Zhang, J.; Xie, S.; Chen, L.; Wang, B.; He, P.; Yuan, L.  Anal. Chem.201587 (15), pp 7817-7824.

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