Abstract
Stereospecific recognition of chiral molecules plays an important role in nature as the basis of the interaction of chiral bioactive compounds with the chiral target structures. In separation sciences such as chromatographic and capillary electromigration techniques, interactions between chiral analytes and chiral selectors, i.e., the formation of transient diastereomeric complexes in thermodynamic equilibria, are the basis for chiral separations. Due to the large structural variety of chiral selectors, different structural features contribute to the overall chiral recognition process. This introductory chapter briefly summarizes the present understanding of the structural enantioselective recognition processes for various types of chiral selectors.
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References
Carrol L (1871) Through the looking-glass and what Alice found there. Macmillan, London
Berthod A (2010) Chiral recognition in separation methods. Springer, Heidelberg
Scriba GKE (2013) Chiral recognition in separation science: an overview. In: Scriba GKE (ed) Chiral separations: methods and protocols, 2nd edn. Humana Press, New York
Ciogli A, Kotoni D, Gasparrini F et al (2013) Chiral supramolecular selectors for enantiomer differentiation in liquid chromatography. Top Curr Chem 349:73–106
Scriba GKE (2013) Differentiation of enantiomers by capillary electrophoresis. Top Curr Chem 340:209–276
Berthod A (2006) Chiral recognition mechanisms. Anal Chem 78:2093–2099
Lämmerhofer M (2010) Chiral recognition by enantioselective liquid chromatography: mechanisms and modern chiral stationary phases. J Chromatogr A 1217:814–856
Scriba GKE (2012) Chiral recognition mechanisms in analytical separation sciences. Chromatographia 75:815–838
Scriba GKE (2016) Chiral recognition in separation science – an update. J Chromatogr A 1467:56–78
Lang C, Armstrong DW (2017) Chiral surfaces: the many faces of chiral recognition. Curr Opin Colloid Interface Sci 32:94–107
Schneider HJ (2009) Binding mechanisms in supramolecular complexes. Angew Chem Int Ed 48:3924–3977
Peluso P, Mamane V, Cossu S (2015) Liquid chromatography enantioseparations of halogenated compounds on polysaccharide-based chiral stationary phases: role of halogen substituents in molecular recognition. Chirality 27:667–684
Biedermann F, Nau WM, Schneider JH (2014) The hydrophobic effect revisited - studies with supramolecular complexes imply high-energy water as noncovalent driving force. Angew Chem Int Ed 53:11158–11171
Yang G, Xu Y (2011) Vibrational circular dichroism spectroscopy of chiral molecules. Top Curr Chem 298:189–236
Uccello-Barretta G, Vanni L, Balzano F (2010) Nuclear magnetic resonance approaches to the rationalization of chromatographic enantiorecognition processes. J Chromatogr A 1217:928–940
Salgado A, Chankvetadze B (2016) Applications of nuclear magnetic resonance spectroscopy for the understanding of enantiomer separation mechanisms in capillary electrophoresis. J Chromatogr A 1467:95–114
Lipkowitz KB (2001) Atomistic modeling of enantioselection in chromatography. J Chromatogr A 906:417–442
Del Rio A (2009) Exploring enantioselective molecular recognition mechanisms with chemoinformatic techniques. J Sep Sci 32:1566–1584
Elbashir AA (2012) Combined approach using capillary electrophoresis and molecular modeling for an understanding of enantioselective recognition mechanisms. J Appl Sol Chem Model 1:121–126
Sardella R, Ianni F, Macciarulo A et al (2018) Elucidation of the chromatographic enantiomer elution order through computational studies. Mini Rev Med Chem 18:88–97
Chen X, Yamamoto C, Okamoto Y (2007) Polysaccharide derivatives as useful chiral stationary phases in high-performance liquid chromatography. Pure Appl Chem 79:1561–1573
Ikai T, Okamoto Y (2009) Structure control of polysaccharide derivatives for efficient separation of enantiomers by chromatography. Chem Rev 109:6077–6101
Shen J, Okamoto Y (2016) Efficient separation of enantiomers using stereoregular chiral polymers. Chem Rev 116:1094–1138
Okamoto Y, Ikai T (2008) Chiral HPLC for efficient resolution of enantiomers. Chem Soc Rev 37:2593–2608
Chankvetadze B (2012) Recent developments on polysaccharide-based chiral stationary phases for liquid-phase separation of enantiomers. J Chromatogr A 1269:26–51
Yamamoto C, Yashima E, Okamoto Y (2002) Structural analysis of amylose tris(3,5-dimethylphenylcarbamate) by NMR relevant to its chiral recognition mechanism in HPLC. J Am Chem Soc 124:12583–12589
Ma S, Shen S, Lee H et al (2009) Mechanistic studies on the chiral recognition of polysaccharide-based chiral stationary phases using liquid chromatography and vibrational circular dichroism. Reversal of elution order of N-substituted alpha-methyl phenylalanine esters. J Chromatogr A 1216:3784–3793
Kim BH, Lee SU, Moon DC (2012) Chiral recognition of N-phthaloyl, N-tretrachlorophthaloyl, and N-naphthaloyl α-amino acids and their esters on polysaccharide-derived chiral stationary phases. Chirality 24:1037–1046
Peluso P, Mamane V, Aubert E et al (2016) Insights into halogen bond-driven enantioseparations. J Chromatogr A 1467:228–238
Dallocchio R, Dessi A, Solinas M et al (2018) Halogen bond in high-performance liquid chromatography enantioseparations: description, features and modelling. J Chromatogr A 1563:71–81
Wenslow RM, Wang T (2001) Solid-state NMR characterization of amylose tris(3,5-dimethylphenylcarbamate) chiral stationary-phase structure as a function of mobile-phase composition. Anal Chem 73:4190–4195
Wang T, Wenslow RM (2003) Effects of alcohol mobile-phase modifiers in the structure and chiral selectivity of amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase. J Chromatogr A 1015:99–110
Kasat RB, Zvinevich Y, Hillhouse HW et al (2006) Direct probing of sorbent-solute interactions for amylose tris(3,5-dimethylphenylcarbamate) using infrared spectroscopy, x-ray diffraction, solid-state NMR, and DFT modeling. J Phys Chem B 110:14114–14122
Zhao B, Oroskar PA, Wang X et al (2017) The composition of the mobile phase affects the dynamic chiral recognition of drug molecules by the chiral stationary phase. Langmuir 33:11246–11256
Layton C, Ma S, Wu L et al (2013) Study of enantioselectivity on an immobilized amylose carbamate stationary phase under subcritical fluid chromatography. J Sep Sci 36:3941–3948
Kasat RB, Wang NHL, Franses EI (2008) Experimental probing and modeling of key sorbent-solute interactions of norephedrine enantiomers with polysaccharide-based chiral stationary phases. J Chromatogr A 1190:110–119
Kasat RB, Franses EI, Wang NHL (2010) Experimental and computational studies of enantioseparation of structurally similar chiral compounds on amylose tris(3,5-dimethylphenylcarbamate). Chirality 22:565–579
Tsui HW, Franses EI, Wang NHL (2014) Effect of alcohol aggregation on the retention factors of chiral solutes with an amylose-based sorbent: modeling and implications of the adsorption mechanism. J Chromatogr A 1328:52–65
Ortuso F, Alcaro S, Menta S et al (2014) A chromatographic an computational study on the driving force operating in the exceptionally large enantioseparation of N-thicarbamoyl-3-(4′-biphenyl)-5-phenyl-4,5-dihydro-(1H) pyrazole on a 4-methylbenzoate cellulose-based chiral stationary phase. J Chromatogr A 1324:71–77
Hu G, Huang M, Luo C et al (2016) Interactions between pyrazole derived enantiomers and Chiralcel OJ: prediction of enantiomer absolute configurations and elution order by molecular dynamics simulations. J Mol Graph Model 66:123–132
Tsui HW, Wang NHL, Franses EI (2013) Chiral recognition mechanism of acyloin-containing chiral solutes by amylose tris[(S)-α-methylbenzylcarbamate]. J Phys Chem 117:9203–9216
Ma S, Tsui HW, Spinelli E et al (2014) Insights into chromatographic enantiomeric separation of allenes on cellulose carbamate stationary phase. J Chromatogr A 1362:119–128
Alcaro S, Bolasco A, Cirilli R et al (2014) Computer-aided molecular design of asymmetric pyrazole derivatives with exceptional enantioselective recognition toward the Chiralcel OJ-H stationary phase. J Chem Inf Model 52:649–654
Ali I, Al-Othman ZA, Al-Warthan A et al (2014) Enantiomeric separation and simulation studies on pheniramine, oxybutynin, cetirizine and brinzolamide chiral drugs on amylose-based columns. Chirality 26:136–143
Ali I, Sahoo DR, Al-Othman ZA et al (2015) Validated chiral high performance liquid chromatography separation method and simulation studies of dipeptides on amylose chiral column. J Chromatogr A 1406:201–209
Shedania Z, Kavaka R, Volonerio A et al (2018) Separation of enantiomers of chiral sulfoxides in high-performance liquid chromatography with cellulose-based chiral selectors using methanol and methanol-water mixtures as mobile phases. J Chromatogr A 1557:62–74
Gogaladze K, Chankvetadze L, Tsintsadze M et al (2015) Effect of basic and acidic additives on the separation of some basic drug enantiomers on polysaccharide-based chiral columns with acetonitrile as mobile phase. Chirality 27:228–234
Matarashvili I, Chankvetadze L, Tsintsadze T et al (2015) HPLC separation of enantiomers of some chiral carboxylic acid derivatives using polysaccharide-based chiral columns and polar organic mobile phases. Chromatographia 78:473–479
Mosiashvili L, Chankvetadze L, Farkas T, Chankvetadze B (2013) On the effect of basic and acidic additives on the separation of the enantiomers of some basic drugs with polysaccharide-based chiral selectors and polar organic mobile phases. J Chromatogr A 1317:167–174
Matarashvili I, Ghughunishvili D, Chankvetadze L et al (2017) Separation of enantiomers of chiral weak acids with polysaccharide-based chiral columns and aqueous-organic mobile phases in high-performance liquid chromatography: typical reversed-phase behavior? J Chromatogr A 1483:86–92
Mskhiladze A, Karchkhadze M, Dadianidz A et al (2013) Enantioseparation of chiral antimycotic drugs by HPLC with polysaccharide-based chiral columns and polar organic mobile phases with emphasis on enantiomer elution order. Chromatographia 76:1449–1458
Beridze N, Tsutskiridze E, Takaishvili N et al (2018) Comparative enantiomer-resolving ability of coated and covalently immobilized versions of two polysaccharide-base chiral selectors in high-performance liquid chromatography. Chromatographia 81:611–621
Yashima E, Ida H, Okamoto Y (2013) Enantiomeric differentiation by synthetic helical polymers. Top Curr Chem 340:41–72
Biwer A, Antranikian G, Heinzle E (2002) Enzymatic production of cyclodextrins. Appl Microbiol Biotechnol 59:609–617
Rekharsky MV, Inoue Y (1998) Complexation thermodynamics of cyclodextrins. Chem Rev 98:1875–1917
Bilensoy E (2011) Cyclodextrins in pharmaceutics, cosmetics and biomedicine. In: Current and future industrial applications. John Wiley & Sons, Hoboken
Dodziuk H (2006) Cyclodextrins and their complexes: chemistry, analytical methods, applications. Wiley-VCH, Weinheim
Crini C (2014) A history of cyclodextrins. Chem Rev 114:10940–10975
Zhang X, Zhang Y, Armstrong DW (2012) Chromatographic separations and analysis: cyclodextrin-mediated HPLC, GC and CE enantiomeric separations. In: Carreira EM, Yamamoto H (eds) Comprehensive chirality, vol 8. Elsevier, Amsterdam, pp 177–199
Schurig V (2010) Use of derivatized cyclodextrins as chiral selectors for the separation of enantiomers by gas chromatography. Ann Pharm Franc 68:82–98
Xiao Y, Ng SC, Tan TT, Wang Y (2012) Recent development of cyclodextrin chiral stationary phases and their applications in chromatography. J Chromatogr A 1269:52–68
Rezanka P, Navratilova K, Rezanka M et al (2014) Application of cyclodextrins in chiral capillary electrophoresis. Electrophoresis 35:2701–2721
Escuder-Gilabert L, Martin-Biosca Y, Medina-Hernandez MJ, Sagrado S (2014) Cyclodextrins in capillary electrophoresis: recent developments and new trends. J Chromatogr A 1357:2–23
Saz JM, Marina ML (2016) Recent advances on the use of cyclodextrins in the chiral analysis of drugs by capillary electrophoresis. J Chromatogr A 1467:79–94
Zhu Q, Scriba GKE (2016) Advances in the use of cyclodextrins as chiral selectors in capillary electrokinetic chromatography: fundamentals and applications. Chromatographia 79:1403–1435
Dodziuk H, Kozinsky W, Ejchart A (2004) NMR studies of chiral recognition by cyclodextrins. Chirality 16:90–105
Chankvetadze B (2004) Combined approach using capillary electrophoresis and NMR spectroscopy for an understanding of enantioselective recognition mechanisms by cyclodextrins. Chem Soc Rev 33:337–347
Mura P (2014) Analytical techniques for characterization of cyclodextrin complexes in aqueous solution: a review. J Pharm Biomed Anal 101:238–250
Mura P (2015) Analytical techniques for characterization of cyclodextrin complexes in the solid state: a review. J Pharm Biomed Anal 113:226–238
Hazai E, Hazai I, Demko L et al (2010) Cyclodextrin knowledgebase a web-based service managing CD-ligand complexation data. J Comput Aided Mol Des 24:713–717
Salgado A, Tatunashvili E, Gologashvili A et al (2017) Structural rationale for the chiral separation and migration order reversal of clenpenterol enantiomers in capillary electrophoresis using two different β-cyclodextrins. Phys Chem Chem Phys 19:27935–27939
Gogolashvili A, Tatunashvili E, Chankvetadze L et al (2017) Separation of enilconazole enantiomers in capillary electrophoresis with cyclodextrin-type chiral selectors and investigation of structure of selector-selectand complexes by using nuclear magnetic resonance spectroscopy. Electrophoresis 38:1851–1859
Fonseca MC, Santos da Silva RC, Soares Nascimento C Jr, Bastos Borges K (2017) Computational contribution to the electrophoretic enantiomer separation mechanism and migration order using modified β-cyclodextrins. Electrophoresis 38:1860–1868
Recio R, Elhalem E, Benito JM et al (2018) NMR study on the stabilization and chiral discrimination of sulforaphane enantiomers and analogues by cyclodextrins. Carbohyd Polym 187:118–125
Cucinotta V, Messina M, Contino A et al (2017) Chiral separation of terbutaline and non-steroidal anti-inflammatory drugs by using a new lysine-bridged hemispherodextrin in capillary electrophoresis. J Pharm Biomed Anal 145:734–741
Szabo ZI, Szöcs L, Horvath P et al (2016) Liquid chromatography with mass spectrometry enantioseparation of pomalidomide on cyclodextrin-bonded chiral stationary phases and the elucidation of the chiral recognition mechanisms by NMR spectroscopy and molecular modeling. J Sep Sci 39:2941–2949
Szabo ZI, Mohammadhassan F, Szöcs L et al (2016) Stereoselective interactions and liquid chromatographic enantioseparation of thalidomide on cyclodextrin-bonded stationary phases. J Incl Phenom Macrocycl Chem 85:227–236
Szabo ZI, Toth G, Völgyi G et al (2016) Chiral separation of asenapine enantiomers by capillary electrophoresis and characterization of cyclodextrin complexes by NMR spectroscopy, mass spectrometry and molecular modeling. J Pharm Biomed Anal 117:398–404
Yao Y, Song P, Wen X et al (2017) Chiral separation of 12 pairs of enantiomers by capillary electrophoresis using heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin as the chiral selector and the elucidation of the chiral recognition mechanism by computational methods. J Sep Sci 40:2999–3007
Fejös I, Varga E, Benkovics G et al (2016) Comparative evaluation of the chiral recognition potential of single isomer sulfated beta-cyclodextrin synthesis intermediates in non-aqueous capillary electrophoresis. J Chromatogr A 1467:454–462
Krait S, Salgado A, Chankvetadze B et al (2018) Investigation of the complexation between cyclodextrins and medetomidine enantiomers by capillary electrophoresis, NMR spectroscopy and molecular modeling. J Chromatogr A 1567:198–210
Li X, Yao X, Xiao Y, Wang Y (2017) Enantioseparation of single layer native cyclodextrin chiral stationary phases: effect of cyclodextrin orientation and a modeling study. Anal Chim Acta 990:174–184
Chankvetadze B, Burjanadze N, Maynard DM et al (2002) Comparative enantioseparations with native β-cyclodextrin and heptakis-(2-O-methyl-3,6-di-O-sulfo)-β-cyclodextrin in capillary electrophoresis. Electrophoresis 23:3027–3034
Servais AC, Rousseau A, Fillet M et al (2010) Separation of propranolol enantiomers by CE using sulfated β-CD derivatives in aqueous and non-aqueous electrolytes: comparative CE and NMR study. Electrophoresis 31:1467–1474
Servais AC, Rousseau A, Dive G et al (2012) Combination of capillary electrophoresis, molecular modeling and nuclear magnetic resonance to study the interaction mechanism between single-isomer anionic cyclodextrin derivatives and basic drug enantiomers in methanolic background electrolyte. J Chromatogr A 1232:59–64
Chankvetadze L, Servais AC, Fillet M et al (2012) Comparative enantioseparation of talinolol in aqueous and non-aqueous capillary electrophoresis and study of related selector-selectand interactions by nuclear magnetic resonance spectroscopy. J Chromatogr A 1267:206–216
Lomsadze K, Salgado A, Calvo E et al (2011) Comparative NMR and MS studies on the mechanism of enantioseparation of propranolol with heptakis(2,3-diacetyl-6-sulfo)-β-cyclodextrin in capillary electrophoresis with aqueous and non-aqueous electrolytes. Electrophoresis 32:1156–1163
Riesova M, Svobodova J, Tosner Z et al (2013) Complexation of buffer constituents with neutral complexation agents: part I. Impact on common buffer properties. Anal Chem 85:8518–8525
Beni M, Riesova M, Svobodova J et al (2013) Complexation of buffer constituents with neutral complexation agents: part II. Practical impact in capillary zone electrophoresis. Anal Chem 85:8526–8534
Melani F, Giannini I, Pasquini B et al (2011) Evaluation of the separation mechanism of electrokinetic chromatography with a microemulsion and cyclodextrins using NMR and molecular modeling. Electrophoresis 32:3062–3069
Pasquini B, Melani F, Caprini C et al (2017) Combined approach using capillary electrophoresis, NMR and molecular modeling for ambrisentan related substances analysis: investigation of intermolecular affinities, complexation and separation mechanism. J Pharm Biomed Anal 144:220–229
Vargas C, Schönbeck C, Heimann I, Keller S (2018) Extracavity effect in cyclodextrin/surfactant complexation. Langmuir 34:5781–5787
Alvira E (2013) Molecular dynamics study of the influence of solvents on the chiral discrimination of alanine enantiomers by β-cyclodextrin. Tetrahedron Asymmetry 24:1198–1206
Alvira E (2015) Theoretical study of the separation of valine enantiomers by β-cyclodextrin with different solvents: a molecular mechanics and dynamics simulation. Tetrahedron Asymmetry 26:853–860
Alvira E (2017) Influence of solvent polarity on the separation of leucine enantiomers by β-cyclodextrin: a molecular mechanics and dynamics simulation. Tetrahedron Asymmetry 28:1414–1422
Soares Nascimento C Jr, Fedoce Lopes J, Guimaraes L, Bastos Borges K (2014) Molecular modeling study of the recognition mechanism and enantioseparation of 4-hydroxypropranolol by capillary electrophoresis using carboxymethyl-β-cyclodextrin as the chiral selector. Analyst 139:3901–3910
Zhang Y, Breitbach ZS, Wang C, Armstrong DW (2010) The use of cyclofructans as novel chiral selectors for gas chromatography. Analyst 135:1076–1083
Sun P, Wang C, Breitbach ZS et al (2009) Development of new HPLC chiral stationary phases based on native and derivatized cyclofructans. Anal Chem 81:10215–10226
Jiang C, Tong MY, Breitbach ZS, Armstrong DW (2009) Synthesis and examination of sulfated cyclofructans as a novel class of chiral selectors for CE. Electrophoresis 30:3897–3909
Immel S, Schmitt RG, Lichtenthaler FW (1998) Cyclofructins with six to ten β(1→2)-linked fructofuranose units: geometries, electrostatic profiles, lipophilicity pattern, and potential for inclusion complexation. Carbohydr Res 313:91–105
Wang L, Li Y, Yao L et al (2014) Evaluation and determination of the cyclofructans-amino acid complex binding pattern by electrospray ionization mass spectrometry. J Mass Spectrom 49:1043–1049
Wang L, Li C, Yin Q et al (2015) Construction the switch binding pattern of cyclofructans 6. Tetrahedron 71:3447–3452
Smuts JP, Hao XQ, Han Z et al (2014) Enantiomeric separations of chiral sulfonic and phosphoric acids with barium-doped cyclofructan selectors via an ion interaction mechanism. Anal Chem 86:1282–1290
Hellinghausen G, Roy D, Lee JT et al (2018) Effective methodologies for enantiomeric separations of 150 pharmacology and toxicology related 1°, 2°, and 3° amines with core-shell chiral stationary phases. J Pharm Biomed Anal 155:70–81
Dominguez-Vega E, Montealegre C, Marina ML (2016) Analysis of antibiotics by CE and their use as chiral selectors: an update. Electrophoresis 37:189–211
Genar M, Castro-Puyana M, Garcia MA, Marina ML (2018) Analysis of antibiotics by CE and CEC and their use as chiral selectors: an update. Electrophoresis 39:235–259
Ilisz I, Pataj Z, Aranyi A, Peter A (2012) Macrocyclic antibiotic selectors in direct HPLC enantioseparations. Sep Purif Rev 41:207–249
Berthod A (2009) Chiral recognition mechanisms with macrocyclic glycopeptide selectors. Chirality 21:167–175
Fernandes C, Tiritn ME, Cass Q et al (2012) Enantioseparation and chiral recognition mechanism of new chiral derivatives of xanthones on macrocyclic antibiotic stationary phases. J Chromatogr A 1241:60–68
Ravichandran S, Collins JR, Singh N, Wainer IW (2012) A molecular model of the enantioselective liquid chromatographic separation of (RS)-ifosfamide and its N-dechloroethylated metabolites on a teicoplanin aglycone chiral stationary phase. J Chromatogr A 1269:218–225
He X, Lin R, He H et al (2012) Chiral separation of ketoprofen on a Chirobiotic T column and its chiral recognition mechanisms. Chromatographia 75:1355–1363
Phyo YZ, Cravl S, Palmeira A et al (2018) Enantiomeric resolution and docking studies of chiral xanthonic derivatives on Chirobiotic columns. Molecules 23:E142. https://doi.org/10.3390/molecules23010142
Bertucci C, Tedesco D (2018) Human serum albumin as chiral selector in enantioselective high-performance liquid chromatography. Curr Med Chem 24:743–757
Bocain S, Skoczylas M, Biszewski B (2016) Amino acids, peptides, and proteins as chemically bonded stationary phases - a review. J Sep Sci 39:83–92
Haginaka J (2011) Mechanistic aspects of chiral recognition on protein-based stationary phases. In: Grushka E (ed) Advances in chromatography, vol 49. CRC Press, Boca Raton, pp 37–69
Haginaka J (2008) Recent progress in protein-based chiral stationary phases for enantioseparations in liquid chromatography. J Chromatogr B 875:12–19
Ghuman J, Zunszain PA, Petitpas I et al (2005) Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol 353:38–52
Fernandes C, Tiritan ME, Pinto M (2013) Small molecules as chromatographic tools for HPLC enantiomeric resolution: Pirkle-type chiral stationary phase evolution. Chromatographia 76:871–897
Fernandes C, Phyo YZ, Sulva AS et al (2018) Chiral stationary phases based on small molecules: an update of the last 17 years. Sep Purif Rev 47:89–123
Carraro ML, Palmeira A, Tiritan ME et al (2017) Resolution, determination of enantiomeric purity and chiral recognition mechanism of new xanthone derivatives on (S,S)-Whelk-O1 stationary phase. Chirality 29:247–256
Fernandes C, Palmeira C, Santos A et al (2013) Enantioresolution of chiral derivatives of xanthones on (S,S)-whelk-O1 and l-phenylglycine stationary phases and chiral recognition mechanism by docking approach for (S,S)-Whelk-O1. Chirality 25:89–100
Zhao C, Cann NM (2007) The docking of chiral epoxides on the Whelk-O1 stationary phase: a molecular dynamics study. J Chromatogr A 1149:197–218
Zhao C, Cann NM (2008) Molecular dynamics study of chiral recognition for the Whelk-O1 chiral stationary phase. Anal Chem 80:2426–2438
Zhao CF, Dimert S, Cann NM (2009) Rational optimization of the Whelk-O1 chiral stationary phase using molecular dynamics simulations. J Chromatogr A 1216:5968–5978
Koscho ME, Spence PL, Pirkle WH (2005) Chiral recognition in the solid state: crystallographically characterized diastereomeric co-crystals between a synthetic chiral selector (Whelk-O1) and a representative chiral selector. Tetrahedron Asymmetry 16:3147–3153
Ilisz I, Bajtai A, Lindner W, Peter A (2018) Liquid chromatographic enantiomer separations applying chiral ion-exchangers based on Cinchona alkaloids. J Pharm Biomed Anal 159:127–152
Lämmerhofer M (2014) Liquid chromatographic enantiomer separation with special focus on zwitterionic chiral ion-exchangers. Anal Bioanal Chem 406:6095–6103
Lämmerhofer M, Lindner W (2008) Liquid chromatographic enantiomer separation and chiral recognition by Cinchona alkaloid-derived enantioselective separation materials. Adv Chromatogr 46:1–107
Hoffmann CV, Lämmerhofer M, Lindner W (2007) Novel strong cation-exchange type chiral stationary phase for the enantiomer separation of chiral amines by high-performance liquid chromatography. J Chromatogr A 1161:242–251
Maier NM, Schefzick S, Lombardo GM et al (2002) Elucidation of the chiral recognition mechanism of Cinchona alkaloid carbamate-type receptors for 3,5-dinitrobenzoyl amino acids. J Am Chem Soc 124:8611–8629
Zhang T, Holder E, Franco P, Lindner W (2014) Zwitterionic chiral stationary phases based on cinchona and chiral sulfonic acids for the direct stereoselective separation of amino acids and other amphoteric compounds. J Sep Sci 37:1237–1247
Pell R, Sic S, Lindner W (2012) Mechanistic investigations of Cinchona alkaloid-based zwitterionic chiral stationary phases. J Chromatogr A 1269:287–296
Ianni F, Sardella R, Carotti A (2016) Quinine-based zwitterionic chiral stationary phase as a complementary tool for peptide analysis: Mobile phase effects on enantio- and stereoselectivity of underivatized oligopeptides. Chirality 28:5–16
Sardella R, Macchiarulo A, Urbinati F et al (2018) Exploring the enantiorecognition mechanism of Cinchona alkaloid-based zwitterionic chiral stationary phases and the basic trans-paroxetine enantiomers. J Sep Sci 41:1199–1207
Ianni F, Pucciarini L, Carotti A et al (2018) Improved chromatographic diastereoresolution of cyclopropyl dafachronic acid derivatives using chiral anion exchangers. J Chromatogr A 1557:20–27
Grecso N, Kohout M, Carotti A et al (2016) Mechanistic considerations of enantiorecognition on novel Cinchona alkaloid-based zwitterionic chiral stationary phases from the aspect of the separation of trans-paroxetine enantiomers as model compounds. J Pharm Biomed Anal 124:164–173
Ianni F, Carotti A, Marinozzi M et al (2015) Diastereo- and enantioseparation of a Nα-Boc amino acid with a zwitterionic quinine-based stationary phase: focus on the stereorecognition mechanism. Anal Chim Acta 885:174–782
Sardella R, Lisanti A, Carotti A et al (2014) Ketoprofen enantioseparation with a Cinchona alkaloid based stationary phase: Enantiorecognition mechanism and release studies. J Sep Sci 37:2696–2703
Schmid MG, Gübitz G (2011) Enantioseparation by chromatographic and electromigration techniques using ligand-exchange as chiral separation principle. Anal Bioanal Chem 400:2305–2316
Zhang H, Qi L, Mao L, Chen Y (2012) Chiral separation using capillary electromigration techniques based on ligand exchange principle. J Sep Sci 35:1236–1248
Hyun MH (2018) Liquid chromatographic ligand-exchange chiral stationary phases based on amino alcohols. J Chromatogr A 1557:28–42
Natalini B, Giacche N, Sardella R et al (2010) Computational studies for the elucidation of the enantiomer elution order of amino acids in chiral ligand-exchange chromatography. J Chromatogr A 1217:7523–7527
Mofaddel N, Adoubel AA, Morin CJ et al (2010) Molecular modelling of complexes between two amino acids and copper(II): correlation with ligand-exchange capillary electrophoresis. J Mol Struct 975:220–226
EchevarrÃa RN, Franca CA, Tascon M et al (2016) Chiral ligand-exchange chromatography with Cinchona alkaloids. Exploring experimental conditions for enantioseparation of α-amino acids. Microchem J 129:104–110
Kapnissi-Christodoulou CP, Stavrou IJ, Mavroudi MC (2014) Chiral ionic liquids in chromatographic and electrophoretic separations. J Chromatogr A 1363:2–10
He S, He Y, Cheng L et al (2018) Novel chiral ionic liquids stationary phases for the enantiomer separation of chiral acid by high-performance liquid chromatography. Chirality 30:670–679
Zhang Q (2018) Ionic liquids in capillary electrophoresis enantioseparations. Trends Anal Chem 100:145–154
Bang E, Jung JW, Lee W et al (2001) Chiral recognition of (18-crown-6)-tetracarboxylic acid as a chiral selector determined by NMR spectroscopy. J Chem Soc Perkin Trans 2:1685–1692
Lee W, Bang E, Baek CS, Lee W (2004) Chiral discrimination studies of (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid by high-performance liquid chromatography and NMR spectroscopy. Magn Res Chem 42:389–395
Nagata H, Nishi H, Kamagauchi M, Ishica T (2008) Guest-dependent conformation of 18-crown-6 tetracarboxylic acid: relation to chiral separation of racemic amino acids. Chirality 20:820–827
Nagata H, Machida Y, Nishi H et al (2009) Structural requirement for chiral recognition of amino acid by (18-crown-6)-tetracarboxylic acid: binding analysis in solution and solid states. Bull Chem Soc Jpn 82:219–229
Tóth T, Németh T, Leveles I et al (2017) Structural characterization of the crystalline diastereomeric complex of enantiopure dimethylacridino-18-crown-6 ether and the enantiomers of 1-(1-napthyl)ethylamine hydrogen perchlorate. Struct Chem 28:289–296
Lovely A, Wenzel TJ (2008) Chiral NMR discrimination of amines: analysis of secondary, tertiary, and prochiral amines using (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. Chirality 20:370–378
Hyun MH (2015) Development of HPLC chiral stationary phases based in (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid and their applications. Chirality 27:576–588
Hyun MH (2016) Liquid chromatographic enantioseparations on crown ether-based chiral stationary phases. J Chromatogr A 1467:19–32
Adhikari S, Lee W (2018) Chiral separation using chiral crown ethers as chiral selectors. J Pharm Invest 48:225–231
Elbashir AA, Aboul-Enein HY (2010) Application of crown ethers as buffer additives in capillary electrophoresis. Curr Pharm Anal 6:101–113
Yashima E, Maeda K, Idea H et al (2009) Helical polymers: synthesis, structures and functions. Chem Rev 109:6102–6211
Yashima E, Maeda K (2008) Chirality-responsive helical polymers. Macromolecules 41:3–12
Cui Y, Li B, He H et al (2016) Metal-organic frameworks as platforms for functional materials. Acc Chem Res 49:483–493
Xue M, Li B, Qiu S, Chen B (2016) Emerging functional chiral microporous materials: synthetic strategies and enantioselective separations. Mater Today 19:503–515
Duerinck T, Denayer JFM (2015) Metal-organic frameworks as stationary phases for chiral chromatographic and membrane separations. Chem Eng Sci 124:179–187
Peluso P, Mamane V, Cossu S (2014) Homochiral metal-organic frameworks and their application in chromatography enantioseparations. J Chromatogr A 1363:11–16
Bhattacharjee S, Khan MI, Li X et al (2018) Recent progress in asymmetric catalysis and chromatographic separation by chiral metal-organic frameworks. Catalysts 8:120. https://doi.org/10.3390/catal8030120
Li X, Chang V, Wang X et al (2014) Applications of homochiral metal-organic frameworks in the enantioselective adsorption and chromatography separation. Electrophoresis 35:2733–2743
Xie SM, Zhang M, Fei ZX, Yuan LM (2014) Experimental comparison of chiral metal-organic framework used as stationary phase in chromatography. J Chromatogr A 1363:137–143
Xie SM, Yuan LM (2017) Recent progress of chiral stationary phases for separation of enantiomers in gas chromatography. J Sep Sci 40:124–127
Peng Y, Gong T, Zhang K et al (2014) Engineering chiral porous metal-organic frameworks for enantioselective adsorption and separation. Nat Commun 5:4406. https://doi.org/10.1038/ncomms5406
Rong F, Li P (2012) Study of the weakest interaction model for chiral resolution using molecularly imprinted polymer. Adv Mater Res 391-392:111–115
Cheong WJ, Ali F, Choi JH et al (2013) Recent applications of molecular imprinted polymers for enantioselective recognition. Talanta 106:45–59
Cheong WJ, Yang SH, Ali F (2013) Molecular imprinted polymers for separation science: a review of reviews. J Sep Sci 36:609–628
Greno M, Marina ML, Castro-Puyana M (2018) Enantioseparation by capillary electrophoresis using ionic liquids as chiral selectors. Crit Rev Anal Chem 48:429–446
Ding J, Armstrong DW (2005) Chiral ionic liquids. Synthesis and applications. Chirality 17:281–292
Wang J, Warner IM (1994) Chiral separations using micellar electrokinetic capillary chromatography and a polymerized chiral micelle. Anal Chem 66:3773–3776
Dobashi A, Hamada M, Dobashi Y, Yamaguchi J (1995) Enantiomeric separation with sodium dodecanoyl-l-amino acidate micelles and poly(sodium(10-undecanoyl)-l-valinate) by electrokinetic chromatography. Anal Chem 67:3011–3017
Morris KF, Billiot EJ, Billiot FH et al (2012) Investigation of chiral molecular micelles by NMR spectroscopy and molecular dynamic simulation. Open J Phys Chem 2:240–251
Morris KF, Billiot EJ, Billiot FH et al (2013) A molecular dynamics simulation study of two dipeptide based molecular micelles: effect of amino acid order. Open J Phys Chem 3:20–29
Morris KF, Billiot EJ, Billiot FH et al (2014) A molecular dynamics simulation study of the association of 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate enantiomers with a chiral molecular micelle. Chem Phys 439:36–43
Morris KF, Billiot EJ, Billiot FH et al (2015) Molecular dynamics simulation and NMR investigation of the association of the β-blockers atenolol and propranolol with a chiral molecular micelle. Chem Phys 457:133–146
Morris KF, Billiot EJ, Billiot FH et al (2018) Investigation of chiral recognition by molecular micelles with molecular dynamics simulations. J Disper Sci Technol 39:45–54
Yaghoubnejad S, Tabar Heydar K, Ahmadi SH, Zadmard R (2018) Preparation and evaluation of a chiral HPLC stationary phase based on cone calix[4]arene functionalized at the upper rim with l-alanine. Biomed Chromatogr 32:e4122
Chelvi SKT, Zhao J, Chen L et al (2014) Preparation and characterization of 4-isopropylcalix[4]arene-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles as chiral stationary phase for high-performance liquid chromatography. J Chromatogr A 1324:104–108
Chelvi SKT, Yong EL, Gong Y (2008) Preparation and evaluation of calyx[4]arene-capped β-cyclodextrin-bonded silica particles as chiral stationary phase for high-performance liquid chromatography. J Chromatogr A 1203:54–58
Krawinkler KH, Maier NM, Sajovic E, Lindner W (2004) Novel urea-linked cinchona-calixarene hybrid-type receptors for efficient chromatographic enantiomer separation of carbamate-protected cyclic amino acids. J Chromatogr A 1053:119–131
Sanchez Pena M, Zhang Y, Warner IM (1997) Enantiomeric separations by use of calixarene electrokinetic chromatography. Anal Chem 69:3239–3242
Grady T, Joyce T, Smyth MR et al (1998) Chiral resolution of the enantiomers of phenylglycinol using (S)-di-naphthylprolinol calyx[4]arene by capillary electrophoresis and fluorescence spectroscopy. Anal Commun 35:123–125
Zhang JH, Xie SM, Wang BJ et al (2018) A homochiral porous organic cage with large cavity and pore window for the efficient gas chromatography separation of enantiomers and positional isomers. J Sep Sci 41:1385–1394
Zhang JH, Xie SM, Wang BJ et al (2015) Highly selective separation of enantiomers using a chiral porous organic cage. J Chromatogr A 1426:174–182
Xie SM, Zhang JH, Fu N et al (2016) A chiral porous organic cage for molecular recognition using gas chromatography. Anal Chim Acta 903:156–163
Chen LJ, Riss PS, Chong SY et al (2014) Separation of rare gases and chiral molecules by selective binding in porous organic cages. Nat Mater 13:954–960
Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822
Ellington AD, Szostak JW (1992) Selection in vitro of single-stranded DNA molecules that fold into specific ligand-binding structures. Nature 355:850–852
Peyrin E (2009) Nucleic acid aptamer molecular recognition principles and application in liquid chromatography and capillary electrophoresis. J Sep Sci 32:1531–1536
Ravelet C, Peyrin E (2006) Recent developments in the HPLC enantiomeric separation using chiral selectors identified by a combinatorial strategy. J Sep Sci 29:1322–1331
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Scriba, G.K.E. (2019). Recognition Mechanisms of Chiral Selectors: An Overview. In: Scriba, G.K.E. (eds) Chiral Separations. Methods in Molecular Biology, vol 1985. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9438-0_1
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