Enantioseparation and molecular docking study of selected chiral pharmaceuticals on a commercialized phenylcarbamate-β-cyclodextrin column using polar organic mode

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Due to the different pharmacokinetic and pharmacodynamic effect of enantiomers, to develop novel enantioselective methods are crucial. The gold standard in the field is direct liquid chromatography using chiral stationary phase. Cyclodextrins (CDs) are indeed widely used in various technological applications, and they are also commonly employed as chiral selectors in analytical chemistry. At present native CD-based columns as well as acetylated β-, permethylated β-, dimethlyated β- hydroxypropylated β-, napthylethylcarbamated β-, 3,5-dimethylphenylcarbamate-β-, and perphenylcarbamate-β-CD are commercially available on the market as CSPs from different vendors. One of the key advantages of using CD-based CSPs in chiral separations is the ability to utilize multimodal elution, which enables the resolution of a wide range of stereoisomeric compounds through the combination of different elution modes, including reversed-phase, normal-phase, and polar organic-mode. However, up until now, the use of the polar organic mode, where neat alcohol or acetonitrile was employed as the mobile phase, has not been successful or recommended for these columns. Polar organic mode offers several advantages, including shorter run times, high efficiency, easier mass spectrometric coupling, and enhanced solubility of the analytes in the mobile phase. Additionally, polar organic mode is suitable for both analytical and preparative applications. In a very recent article, Dobó et al. investigated the chiral separation capability of commercialized Chiral-CD-Ph column, containing phenylcarbamate-β-cyclodextrin as the chiral selector in polar organic mode. A total of twenty-five compounds with different structures and acid-base properties were evaluated, and twenty of them were separated using acetonitrile or methanol as eluent. The high success rate in separating the tested compounds highlights the effectiveness of the Chiral CD-Ph column in polar organic mode, especially when using methanol as the mobile phase. The authors investigated how chromatographic parameters influence the enantiorecognition, and it was found that the main factor is the mobile phase composition. The enantiomer recognition ability at the atomic level was also investigated through a molecular docking study, which revealed surface binding in polar organic mode instead of inclusion complexation. The work proves that the phenylcarbamate-β-cyclodextrin-based chiral stationary phase can be effectively used in polar organic mode for the chiral separation of structurally diverse compounds. Furthermore, it is important to note that the study demonstrated that surface binding is responsible for the formation of supramolecular complexes in certain cyclodextrin derivatives.

Dobó, M., Ádám, M., Fiser, B., Papp, L. A., Dombi, G., Sekkoum, K., Szabó Z.-I., Tóth, G. (2023). Enantioseparation and molecular docking study of selected chiral pharmaceuticals on a commercialized phenylcarbamate-β-cyclodextrin column using polar organic mode. Scientific Reports13(1), 14778.

The article is available here: https://www.nature.com/articles/s41598-023-41941-5

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