In continuation of our efforts to synthesize a highly dedicated strong cation exchanger, we introduce four chiral stationary phases based on a laterally substituted naphthalene core featuring chiral 2-aminocyclohexansulfonic acid as the chiral cation-exchange site. The selectors were modified with two different terminal units, which enabled immobilization to the silica support by thiol-ene radical reaction or azide-yne click chemistry. The chromatographic parameters of these chiral stationary phases were determined using a set of chiral amines, mainly from the family of β-blocker pharmaceuticals. The chiral stationary phases immobilized by means of click chemistry were found to be superior to those possessing the sulfide linker to the silica support. The chromatographic results and visualization of density functional theory-calculated conformations of the selectors hint at a combination of a steric and electronic effect of the triazole ring in the course of chiral resolution of the target analytes.

Department of Analytical Chemistry University of Chemistry and Technology Prague Prague Czech Republic

Department of Analytical Chemistry University of Vienna Vienna Austria

Department of Organic Chemistry University of Chemistry and Technology Prague Prague Czech Republic

Department of Physical Chemistry University of Chemistry and Technology Prague Prague Czech Republic

Institute of Chemical Process Fundamentals Czech Academy of Sciences Prague Czech Republic

Zobrazit více v PubMed

Chankvetadze B. Recent developments on polysaccharide-based chiral stationary phases for liquid-phase separation of enantiomers. J Chromatogr A. 2012;1269:26-51

Lämmerhofer M. Chiral recognition by enantioselective liquid chromatography: Mechanisms and modern chiral stationary phases. J Chromatogr A. 2010;1217:814-56.

Scriba GKE. Chiral recognition in separation science - an update. J Chromatogr A. 2016;1467:56-78.

Lämmerhofer M. Liquid chromatographic enantiomer separation with special focus on zwitterionic chiral ion-exchangers. Anal Bioanal Chem. 2014;406:6095-103.

Armstrong DW, Tang Y, Chen S, Zhou Y, Bagwill C, Chen J-R. Macrocyclic antibiotics as a new class of chiral selectors for liquid chromatography. Anal. Chem. 1994;66:1473-84.

Armstrong DW, Liu Y, Ekborgott KH. A covalently bonded teicoplanin chiral stationary phase for HPLC enantioseparations. Chirality 1995;7:474-97.

Ilisz I, Berkecz R, Peter A. HPLC separation of amino acid enantiomers and small peptides on macrocyclic antibiotic-based chiral stationary phases: A review. J. Sep. Sci. 2006;29:1305-21.

Nair UB, Chang SSC, Armstrong DW, Rawjee YY, Eggleston DS, McArdle JV. Elucidation of vancomycin's enantioselective binding site using its copper complex. Chirality. 1996;8:590-5.

Zhao J, Wu H, Wang D, Wu H, Cheng L, Jin Y, Ke Y, Liang X. Improvement of chiral stationary phases based on cinchona alkaloids bonded to crown ethers by chiral modification. J. Sep. Sci. 2015;38:3884-90.

Malanga M, Fejős I, Varga E, Benkovics G, Darcsi A, Szemán J, Béni S. Synthesis, analytical characterization and capillary electrophoretic use of the single-isomer heptakis-(6-O-sulfobutyl)-beta-cyclodextrin. J. Chromatogr. A. 2017;1514:127-33.

Armstrong DW, Li W, Chang CD, Pitha J. Polar-liquid, derivatized cyclodextrin stationary phases for the capillary gas chromatography separation of enantiomers. Anal. Chem. 1990;62:914-23.

Lämmerhofer M, Lindner W. Quinine and quinidine derivatives as chiral selectors I. Brush type chiral stationary phases for high-performance liquid chromatography based on cinchonan carbamates and their application as chiral anion exchangers. J. Chromatogr. A. 1996;741:33-48.

Lämmerhofer M, Lindner W. Liquid chromatographic enantiomer separation and chiral recognition by cinchona alkaloid-derived enantioselective separation materials. Adv. Chromatogr. 2008;46:1-107.

Calderón C, Lämmerhofer M. Chiral separation of short chain aliphatic hydroxycarboxylic acids on cinchonan carbamate-based weak chiral anion exchangers and zwitterionic chiral ion exchangers. J. Chromatogr. A. 2017;1487:194-200.

Kohout M, Wernisch S, Tůma J, Hettegger H, Pícha J, Lindner W. Effect of different immobilization strategies on chiral recognition properties of Cinchona-based anion exchangers. J. Sep. Sci. 2018;41:1355-64.

Wernisch S, Bisi F, Cazzato AS, Kohout M, Lindner W. 2-Acyl-dimedones as UV-active protective agents for chiral amino acids: Enantiomer separations of the derivatives on chiral anion exchangers. Anal. Bioanal. Chem. 2013;405:8011-26.

Mahut M, Lindner W, Lämmerhofer M. Molecular recognition principles and stationary-phase characteristics of topoisomer-selective chemoaffinity materials for chromatographic separation of circular plasmid DNA topoisomers. J. Am. Chem. Soc. 2012;134:859-62.

Hebenstreit D, Bicker W, Lämmerhofer M, Lindner W. Novel enantioselective strong cation exchangers based on sulfodipeptide selectors: Evaluation for enantiomer separation of chiral bases by nonaqueous capillary electrochromatography. Electrophoresis 2004;25:277-89.

Preinerstorfer B, Lubda D, Lindner W, Lämmerhofer M. Monolithic silica-based capillary column with strong chiral cation-exchange type surface modification for enantioselective non-aqueous capillary electrochromatography. J. Chromatogr. A. 2006;1106:94-105.

Veigl E, Böhs B, Mandl A, Krametter D, Lindner W. Evaluation of silica gel-based brush type chiral cation exchangers with (S)-N-(3,5-dinitrobenzoyl)tyrosine as chiral selector: Attempt to interpret the discouraging results. J. Chromatogr. A. 1995;694:151-61.

Zarbl E, Lämmerhofer M, Woschek A, Hammerschmidt F, Parenti C, Cannazza G, Lindner W. Strong versus weak chiral cation exchangers: Comparative evaluation for enantiomer separation of chiral bases by non-aqueous CEC. J. Sep. Sci. 2002;25:1269-83.

Zheng J, Bragg W, Hou J, Lin N, Chandrasekaran S, Shamsi SA. Sulfated and sulfonated polysaccharide as chiral stationary phases for capillary electrochromatography and capillary electrochromatography-mass spectrometry. J. Chromatogr. A. 2009;1216:857-72.

Hoffmann CV, Lämmerhofer M, Lindner W. Separation of Cinchona alkaloids on a novel strong cation-exchange-type chiral stationary phase-comparison with commercially available strong cation exchanger and reversed-phase packing materials. Anal. Bioanal. Chem. 2009;393:1257-65.

Hoffmann CV, Laemmerhofer M, Lindner W. Novel strong cation-exchange type chiral stationary phase for the enantiomer separation of chiral amines by high-performance liquid chromatography. J. Chromatogr. A. 2007;1161:242-51.

Lajkó G, Grecsó N, Megyesi R, Forró E, Fülöp F, Wolrab D, Lindner W, Péter A, Ilisz I. Enantioseparation of ß-carboline derivatives on polysaccharide- and strong cation exchanger-based chiral stationary phases. A comparative study. J. Chromatogr. A. 2016, 1467, 188-98.

Hoffmann CV, Pell R, Lämmerhofer M, Lindner W. Synergistic effects on enantioselectivity of zwitterionic chiral stationary phases for separations of chiral acids, bases, and amino acids by HPLC. Anal. Chem. 2008;80:8780-9.

Wolrab D, Kohout M, Boras M, Lindner W. Strong cation exchange-type chiral stationary phase for enantioseparation of chiral amines in subcritical fluid chromatography. J. Chromatogr. A. 2013;1289:94-104.

Wolrab D, Macíková P, Boras M, Kohout M, Lindner W. Strong cation exchange chiral stationary phase-a comparative study in high-performance liquid chromatography and subcritical fluid chromatography. J. Chromatogr. A. 2013;1317:59-66.

Wolrab D, Frühauf P, Kohout M, Lindner W. Click chemistry immobilization strategies in the development of strong cation exchanger chiral stationary phases for HPLC. J. Sep. Sci. 2013;36:2826-37.

Wolrab D, Frühauf P, Moulisová A, Kuchař M, Gerner C, Lindner W, Kohout M. Chiral separation of new designer drugs (Cathinones) on chiral ion-exchange type stationary phases. J. Pharm. Biomed. Anal. 2016;120:306-15.

Kohout M, Svoboda J, Novotna V, Pociecha D, Glogarova M, Gorecka E. A nematic-polar columnar phase sequence in new bent-shaped liquid crystals based on a 7-hydroxynaphthalene-2-carboxylic acid core. J. Mater. Chem. 2009;19:3153-60.

Tůma J, Kohout M. Silica gel-immobilized multidisciplinary materials applicable in stereoselective organocatalysis and HPLC separation. RSC Adv. 2018;8:1174-81.

Bouř P, Maloň P, The MCM Program, Czech Academy of Sciences, Prague, Czech Republic, 1995-2009.

Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA Jr., Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG,Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA, Gaussian 03, Revision C.02. Gaussian, Inc., Wallingford CT, 2004.

Kohout M, Svoboda J, Novotná V, Pociecha D. Non-symmetrical bent-shaped liquid crystals based on a laterally substituted naphthalene central core with four ester groups. Liq. Cryst. 2011;38:1099-110.

Wamhoff H, In: 1,2,3-Triazoles and their Benzo Derivatives. Katritzky, A. R., Rees, C. W. (Eds.), Comprehensive Heterocyclic Chemistry. Pergamon, Oxford 1984, pp. 669-732.

4-Isobutylmethcathinone-A Novel Synthetic Cathinone with High In Vitro Cytotoxicity and Strong Receptor Binding Preference of Enantiomers