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Mechanistic Principles in Chiral Separations Using Liquid Chromatography and Capillary Electrophoresis

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Abstract

Due to the importance of chiral separations of drugs, pharmaceuticals, agrochemicals and xenobiotics by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE), it is important to have the knowledge of the enantiomeric recognition mechanisms so that scientists may design and module the new chiral selectors for rapid, inexpensive and reproducible chiral separations; specially at preparative scale. The mechanisms of the chiral separation by HPLC and CE using polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, Pirkle type, ligand exchangers, crown ethers and other several types of chiral selectors have been discussed. Various complex formation and different types of interactions responsible for chiral resolution have been presented in detail.

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References

  • Easson EH, Stedman E (1993) Biochem J 27:1257–1266

    Google Scholar 

  • Mesecar AD, Koshland DE (2000) Jr Nature 403:614–615

    CAS  Google Scholar 

  • Testa B (1986) Trends in Pharmacol Sci 60–64

  • Ariëns EJ (1986) Trends in Pharmacol Sci 200–205

  • Simonyi M, Fitos I, Visy J (1986) Trends in Pharmacol Sci 112–116

  • Cannon JG, Moe ST, Long JP (1991) Chirality 3:19–23

    Article  CAS  Google Scholar 

  • Allenmark S (1991) Chromatographic Enantioseparation:Methods and Applications 2nd Ed. Ellis Horwood Ltd. New York

    Google Scholar 

  • Aboul-Enein HY, Wainer IW (Eds) (1997) The Impact of Stereochemistry on Drugs Development and Use John Wiley & Sons, New York, Vol. 142

  • Beesley TE, Scott RPW (1998) Chiral Chromatography John Wiley & Sons, New York

  • Aboul-Enein HY, Ali I (2003) Chiral separations by liquid chromatography and related technologies Marcel Dekker, Inc., New York

  • Ali I, Aboul-Enein HY (2004) Chiral pollutants:Distribution, toxicity and analysis by chromatography and capillary electrophoresis John Wily & Sons, Chichester

    Google Scholar 

  • Stinson SC, (1994) Chem & Eng News 72:38–72

    Google Scholar 

  • Witte DT, Ensing K, Franke JP, de Zeeuw RA (1993) Pharm. World Sci. 15:10–16.

    Google Scholar 

  • Rauws AG, Groen K (1994) Chirality 6:72–75

    Article  CAS  Google Scholar 

  • Krstulovic AM (1989) Chiral separations by HPLC:Applications to Pharmaceutical Compounds Ellis Horwood Ltd. New York

    Google Scholar 

  • Stinson SC (2000) Chem Eng News 76:83–1043

    Google Scholar 

  • Chankvetadze B (1997) Capillary electrophoresis in chiral analysis John Wiley & Sons

  • Hesse G, Hagel R (1976) Liebigs Ann Chem 966–1008

  • Francotte E, Wolf RM, Lohmann D, Mueller RJ (1985) Chromatogr 347:25–37

    Article  CAS  Google Scholar 

  • Ellington JJ, Evans JJ, Prickett KB (2001) Champion WL Jr J Chromatogr A 928:145–154

    Article  CAS  Google Scholar 

  • Wolf RM, Francotte E, Lohmann DJ (1988) Chem. Soc. Perkin Trans II 893–901

  • Okamoto Y, Aburatani R, Hatada K (1987) J Chromatogr, 389:95–102

  • Wainer IW, Alembic M (1986) J Chromatogr 358:85–93

    Article  CAS  Google Scholar 

  • Wainer IW, Stiffin RM, Shibata T (1987) J Chromatogr 411:139–151

    Article  CAS  Google Scholar 

  • Okamoto Y, Kaida Y (1994) J Chromatogr A 666:403–419

    Article  CAS  Google Scholar 

  • Yashima E (2001) J Chromatogr A 906:105–125

    Article  CAS  Google Scholar 

  • Vogt U, Zugenmaier P (1985) Ber Bunsenges Phys Chem 89:1217–1224

    CAS  Google Scholar 

  • Lipkowitz KB (1994) Modeling Enantioseparation in Chiral Chromatography. In: A Practical Approach to Chiral Separations by Liquid Chromatography:Subramanian G (Ed) VCH Verlagsgesellschaft mbH, Weinheim

  • Lipkowitz KB (1995) J Chromatogr A 694:15–37

    Article  CAS  Google Scholar 

  • Yashima E, Yamada M, Kaida Y, Okamoto Y (1995) J Chromatogr A 694:347–354

    Article  CAS  Google Scholar 

  • Yamamoto C, Yashima E, Okamoto Y (1999) Bull Chem Soc Jpn 72:1815–1825

    Article  CAS  Google Scholar 

  • Theodorou DN, (1985) Suter UW Macromolecules 18:1467–1478

    Article  CAS  Google Scholar 

  • Aboul-Enein HY, Ali IJ (2001) Biochem & Biophys Methods 48:175–188

    Google Scholar 

  • Aboul-Enein HY, Ali I (2002) Chirality 14 47–50

    Google Scholar 

  • Aboul-Enein HY, Ali I (2002) J Pharm Biomed Anal 27:441–446

    Article  CAS  Google Scholar 

  • Lipkowitz KB, Green K, Yang JA (1992) Chirality, 4:205–215

  • Armstrong DW, Ward TJ, Armstrong RD (1986) Beesley TE.Science, 222:1132–1135

    Google Scholar 

  • Hamilton JA, Chen L (1988) J Am Chem Soc, 110: 5833–5841

    Google Scholar 

  • Street KW Jr (1987) J Liq Chromatogr, 10:655–562

    Google Scholar 

  • Lipkowitz KB, Stoehr CM (1996) Chirality 8:341–350

    Article  CAS  Google Scholar 

  • Boeham RE, Martire DE (1988) Anal Chem 60:522–528

    Article  Google Scholar 

  • Linnemayr K, Rizzi A, Günther A (1997) J Chromatogr A 791:299–306

    Article  CAS  Google Scholar 

  • Morin N, Guillaumine YC, Rouland JC (1998) Chromatographia 48:388–394

    CAS  Google Scholar 

  • Redondo J, Blazquez MA, Torrens A (1999) Chirality 11:694–700

    Article  CAS  Google Scholar 

  • Lipkowitz KB (2001) J Chromatogr A 906:417–442

    Article  CAS  Google Scholar 

  • Armstrong DW, Chang CD, Lee SH (1991) J Chromatogr A 539:83–90

    Article  CAS  Google Scholar 

  • Armstrong DW, Yang XF, Han SM, Menges RA (1987) Anal Chem 59:2594–2596

    Article  CAS  Google Scholar 

  • Berthod A, Chang SC, Armstrong DW (1992) Anal Chem 64:395–404

    Article  CAS  Google Scholar 

  • Han SM, Armstrong DW (1989) HPLC Separation of Enantiomers and other Isomers with Cyclodextrin Bonded Phases In: Rule for Chiral Recognition in Chiral Separations by HPLC, Krstulovic AM (Ed) Ellis Howrood, Chichester

    Google Scholar 

  • Stalcup AM (1994) Cyclodextrin Bonded Chiral Stationary Phases in Enantiomer Separations. In: A Practical Approach to Chiral Separations by Liquid Chromatography, Subramanian G (Ed) VCH Publ. Weinheim

  • Tarr MA, Nelson G, Patonay G, Warner IM (1988) Anal Lett 21:843–856

    CAS  Google Scholar 

  • Armstrong DW, Chang SC, Wang Y, Ibrahim H, Reid III GR (1997) Beesley T.E. J. Liq Chromatogr & Rel Technol 20:3279–3308

    Google Scholar 

  • Seeman JI, Secor HV, Armstrong DW, Timmons KD, Ward TJ (1988) Anal Chem 60:2120–2127

    Article  CAS  Google Scholar 

  • Armstrong DW, Tang Y, Chen S, Zhou Y, Bagwill C (1994) Anal Chem 66:1473–1484

    Article  CAS  Google Scholar 

  • Chirobiotic Handbook (1999) Guide to Using Macrocyclic Glycopeptide Bonded Phases for Chiral LC Separations, 2nd ed, Advance Separation Tech Inc, Whippany, N.J. USA

  • Aboul-Enein HY, Ali I (2000) Chromatographia 52:679–691

    CAS  Google Scholar 

  • Maier NM, Franco P, Linder W (2001) J Chromatogr A 906:3–33

    Article  CAS  Google Scholar 

  • Yashima E, Okamoto Y (1997) Chiral recognition mechanisms of polysaccharides chiral stationary phases In: The impact of stereochemistry on drug development and use, Aboul-Enein HY, Wainer IW, (Eds.), J Wiley & Sons, Inc, New York

    Google Scholar 

  • Lee JT, Beesley TE (2001) 13th International Symposium on Chirality 2001 Orlando, USA Abstract No:62, 225

  • Berthod A, Liu Y, Bagwill C, Armstrong DW (1996) J Chromatogr A 731:123–137

    Article  CAS  Google Scholar 

  • Hage DS (2001) J Chromatogr A 906:459–481

    Article  CAS  Google Scholar 

  • Haginaka J (2001) J Chromatogr A 906:253–273

    Article  CAS  Google Scholar 

  • Allenmark S (1994) Separation of Enantiomers by Protein Based Chiral Phases. In: A Practical Approach to Chiral Separations by Liquid Chromatography Subramanian G (Ed) Wiley VCH, Weinheim

  • Haddadian F, Billiot EJ, Shami SA, Warner IM (1999) J Chromatogr A 858:219–227

    Article  CAS  Google Scholar 

  • Kaliszan R Nasal A Turowski M (1995) Biomed Chromatogr 9:211–215

    Article  CAS  Google Scholar 

  • He XM, Carter DC (1992) Nature 358:209–215

    Article  CAS  Google Scholar 

  • Yang Y, Hage DS (1993) J Chromatogr A 645:241–250

    Article  CAS  Google Scholar 

  • Yang Y, Hage DS (1996) J Chromatogr A 725:273–285

    Article  CAS  Google Scholar 

  • Yang Y, Hage DSJ (1997) Chromatogr A, 766:15–25

  • Peryn E, Guillaume YC, Guinchard C (1998) J Chromatogr Sci 36:97–103

    Google Scholar 

  • Peryn E, Guillaume YC, Guinchard C (1998) Anal Chem 70:4235–4240

    Article  Google Scholar 

  • Kremer JMH, Wilting J, Janssen LHM (1988) Pharmacol Rev 40:1–47

    Article  CAS  Google Scholar 

  • Haupt D, Pettersson C, Westulund D (1995) Chirality 7:23–27

    Article  CAS  Google Scholar 

  • Water MS, Sidler DR, Simon AJ, Middaugh CR, Thompson R, August LJ, Bicker G, Perpall HJ, Grinberg N:Chirality 1999, 11, 224–232

    Google Scholar 

  • Shiono H, Shibukawa A, Kuroda Y, Nakagawa T (1997) Chirality 9:291–296

    Article  CAS  Google Scholar 

  • Kuroda Y, Shibukawa A, Nakagawa T (1999) Anal Biochem 268:9–14

    Article  CAS  Google Scholar 

  • Haginaka J, Matsunaga H (2001) Enantiomer 5:37–45

    Google Scholar 

  • Pinkerton TC, Howe WJ, Urlich EL, Comiskey JP, Haginaka J, Murashima T, Walkenhorst WF, Westler WM, Markley JL (1995) Anal Chem 67:2354–2367

    Article  CAS  Google Scholar 

  • Haginaka J, Seyama C, Murashima T (1995) J Chromatogr A 704:279–287

    Article  CAS  Google Scholar 

  • Haginaka J, Matsunaga H (1999) Chirality 11:426–431

    Article  CAS  Google Scholar 

  • Haginaka J, Matsunaga H. (1999) Anal Commun 36:39–41

    Article  CAS  Google Scholar 

  • Haginaka J, Takehira H (1997) J Chromatogr A 777:241–247

    Article  CAS  Google Scholar 

  • Haginaka J, Kagawa C, Matsunaga H (1999) J Chromatogr A 858:155–165

    Article  CAS  Google Scholar 

  • Haginaka J, Okazaki Y, Matsunaga H (1999) J Chromatogr A 840:171–181

    Article  CAS  Google Scholar 

  • Oda Y, Ohe H, Asakawa N, Yoshida Y, Sato T, Nakagawa T. (1992) J. Liq Chromatogr 15:2997–3012

    CAS  Google Scholar 

  • Felix G, Descorps V (1999) Chromatographia 49:595–605

    CAS  Google Scholar 

  • Norin M Hult K (1993) Biocatalysis 7:131–147

    CAS  Google Scholar 

  • Marle I, Jonsson S, Isaksson R, Pettersson C, Pettersson G (1993) J Chromatogr A 648:333–347

    Article  CAS  Google Scholar 

  • Divne C, Stahlberg J, Reinikainen T, Ruohonen L, Pettersson G, Knowles J, Teeri T, Jones TA (1994) Science 265:524–528

    CAS  Google Scholar 

  • Divne C, Stahlberg J, Teeri T, Jones TA (1998) J Mol Biol 275:309–325

    Article  CAS  Google Scholar 

  • Hyun MH, Jin JS, Lee W (1998) J Chromatogr A 822:155–161

    Article  Google Scholar 

  • Steffeck RJ, Zelechonok Y, Gahm KH (2002) J Chromatogr A 947:301–305

    Article  CAS  Google Scholar 

  • Pedersen CJ (1967) J Am Chem Soc 89:2495–2496

    Article  CAS  Google Scholar 

  • Kyba EP, Timko JM, Kaplan JL, de Jong F, Gokel GW, Cram DJJ (1978) Am Chem Soc 100:4555–4568

    Article  CAS  Google Scholar 

  • Peacock SC, Domeier LA, Gaeta FCA, Helgeson RC, Timko JM, Cram DJ (1978) J Am Chem Soc 100:8190–8202

    Article  CAS  Google Scholar 

  • Peacock SC, Walba DM, Gaeta FCA, Helgeson RC, Timko JM, Cram DJ (1980) J Am Chem Soc 102:2043–2025

    Article  CAS  Google Scholar 

  • Linggenfelter DS, Helgeson RC, Cram DJ (1981) J Org Chem 46:393–406

    Article  Google Scholar 

  • Pocsfalvi G, Liptak M, Huszthy P, Bradshaw JS, Izatt RM, Vekey K (1996) Anal Chem 68:792–795

    Article  CAS  Google Scholar 

  • Machida Y, Nishi H, Nakamura K (1999) Chirality 11:173–178

    Article  CAS  Google Scholar 

  • Shibukawa A, Nagakawa T (1989) The use of chiral crown ethers in liquid chromatography In: Chiral separations by HPLC, Krstulovic AM (Ed) Ellis Howrood Ltd., New York

    Google Scholar 

  • Aboul-Enein HY, Ali I, Hyun MH, Cho YJ, Jin JS (2002) J Biochem & Biophys Methods 54:407–413

    Google Scholar 

  • Macaudiere P, Lienne M, Tambute A, Caude M (1989) Pirkle Type and Related Chiral Stationary Phases for Enantiomeric Resolution In: Chiral Separations by HPLC, Krstulovic AM (Ed) Ellis Horwood Ltd., A Division of John Wiley & Sons, New York

  • Pirkle WH, Hyun MH, Tsipouras A, Hamper BC, Bank B (1984) J Pharm & Biomed Anal 2:173–181

    Google Scholar 

  • Pirkle WH, Hyun MH, Bank B (1984) J Chromatogr 316:585–604

    Article  CAS  Google Scholar 

  • Vinkovic V, Kontrec D, Sunjic V, Navarini L, Zanetti F, Azzolina O (2001) Chirality 13:581–587

    Article  CAS  Google Scholar 

  • Hyun MH, Kang MH, Han SC (2000) J Chromatogr A 868:31–39

    Article  CAS  Google Scholar 

  • Altomare C, Cellamare S, Carotti A, Barrreca ML, Chimirri A, Monforte AM, Gasparrini F, Villani C, Cirilli M, Mazza F (1996) Chirality 8:556–566

    Article  CAS  Google Scholar 

  • Fukushima T, Kato M, Santa T, Imai K (1995) Biomed Chromatogr 9:10–17

    Article  CAS  Google Scholar 

  • Pirkle WH, Pochapsky TC (1987) J Am Chem Soc 109:5975–5982

    Article  CAS  Google Scholar 

  • Quaglia MG, Mai A, Artico SM, Ragno R, Massa S, Piano DD, Setzu G, Doratiotto S, Cotichini V (2001) Chirality 13:75–80

    Article  CAS  Google Scholar 

  • Lipkowitz KB, Demeter DA, Parish CA, Darden T (1987) Anal Chem 59:1731–1733

    Article  CAS  Google Scholar 

  • Norinder U, Sundholm EG (1987) J Liq Chromatogr 10:2825–2844

    CAS  Google Scholar 

  • Suzuki T, Timofei S, Iuras BE, Uray G, Verdino P, Walter MF (2001) J Chromatogr A 922:13–23

    Article  CAS  Google Scholar 

  • Pirkle WH, Däppen R (1987) J Chromatogr 404:107–115

    Article  CAS  Google Scholar 

  • Wainer IW, Alembic MC (1986) J Chromatogr 367:59–68

    Article  CAS  Google Scholar 

  • Pirkle WH, Welch CJ (1992) J Liq Chromatogr 15:1947–1955

    CAS  Google Scholar 

  • Rogozhin SV, Davankov VA (1969) German Patent 1932190

  • Davankov VA (1994) J Chromatogr 666:55–76

    Article  CAS  Google Scholar 

  • Rogozhin SV, Davankov VA (1971) Chem Lett 490

  • Gübitz G, Jellenz WJ (1981) Chromatogr 203:377–384

    Article  Google Scholar 

  • Aboul-Enein HY, Ali I (2001) Chromatograhia 54:200–202

    CAS  Google Scholar 

  • Allenmark SG, Andersson S, Möller P, Sanchez D (1995) Chirality 7:248–256

    Article  CAS  Google Scholar 

  • Franco P, Lämmerhofer M, Klaus PM, Lindner W (2000) J Chromatogr A 869:111–127

    Article  CAS  Google Scholar 

  • Bartsch RA, Maeda M (Eds) (1998) Molecular and Ionic Recognition with Imprinted Polymers, ACS Symposium Series No. 703, Oxford University Press, Washington DC

  • Sellergren B (2001) J Chromatogr A 906:227–252

    Article  CAS  Google Scholar 

  • Wulf G (1995) Angew Chem Int Ed Eng 34:1812–1832

    Article  Google Scholar 

  • Spivak D, Gilmore MA, Shea KJ (1997) J Am Chem Soc 119:4388–4393

    Article  CAS  Google Scholar 

  • Sellergren B, Shea KJ (1993) J Chromatogr A 654:17–28

    Article  CAS  Google Scholar 

  • Dauwe C, Sellergren B (1996) J Chromatogr A 753:191–200

    Article  CAS  Google Scholar 

  • Andersson, L.I. Anal. Chem. 1996, 68, 111–117

  • Huang X, Zou H, Chen X, Luo Q, Kong L (2003) J Chromatogr A 984:273–282

    Article  CAS  Google Scholar 

  • Lämmerhofer M, Lindner W (2001) J Chromatogr A 839:167–182

    Google Scholar 

  • Fanali S, Catarcini P, Blaschke G, Chankvetadze B (2001) Electrophoresis, 22:3131–3151

  • Gübitz G, Schmid MG (1997) J Chromatogr A 792:179–225

    Article  Google Scholar 

  • Spegel P, Nilsson J, Nilsson S (2004) Methods Mol Biol 243:411–424

    CAS  Google Scholar 

  • Vespalec R, Bocek P (2000) Chem Rev 100:3715–3753

    Article  CAS  Google Scholar 

  • Zerbinati O, Trotta F, Giovannoli C (2000) J Chromatogr A 875:423–430

    Article  CAS  Google Scholar 

  • Chankvetadze B, Burjanadze N, Pintore G, Bergenthal D, Bergander K, Mühlenbrock C, Breitkreuz J, Blaschke G (2000) J Chromatogr A 875:471–484

    Article  CAS  Google Scholar 

  • Gasper MP, Berthod A, Nair UB, Armstrong DW (1996) Anal Chem 68:2501–2514

    Article  CAS  Google Scholar 

  • Kuhn R, Stoeklin F, Erni F (1992) Chromatographia 33:32–36

    Article  CAS  Google Scholar 

  • Kuhn R, Steinmetz C, Bereuter T, Haas P, Erni F (1994) J Chromatogr A 666:367–373

    Article  CAS  Google Scholar 

  • Kuhn R, Hoffstetter-Kuhn S (1992) Chromatographia 34:505–512

    Article  CAS  Google Scholar 

  • Koide T, Ueno K (2001) J Chromatogr A 923:229–239

    Article  CAS  Google Scholar 

  • Lin JM, Nkagama T, Wu XZ, Uchiyama K, Hobo T (1997) Fresenius J Anal Chem 357: 130–132

    Article  CAS  Google Scholar 

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Ali, I., Kumerer, K. & Aboul-Enein, H.Y. Mechanistic Principles in Chiral Separations Using Liquid Chromatography and Capillary Electrophoresis. Chroma 63, 295–307 (2006). https://doi.org/10.1365/s10337-006-0762-5

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