Skip to main content
SpringerLink
Log in

Study on the separation of ofloxacin enantiomers by hydroxyl-propyl-β-cyclodextrin as a chiral selector in capillary electrophoresis: a computational approach

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

Hydroxypropyl-β-cyclodextrin (HPβCD) has been used successfully as a chiral additive to separate ofloxacin (OFL) enantiomers in a capillary electrophoresis system. Using electrospray-mass spectrometry (ESI–MS) it was revealed that OFL forms an inclusion complex with HPβCD at 1:1 stoichiometry. The interaction of the enantiomers with the host was further investigated by molecular modeling using molecular mechanics dockings, PM7 semiempirical calculations and molecular dynamics simulations. Calculations using PM7 semiempirical methods indicated that the separation is brought about by a large difference in the binding energies (∆∆E) of 15 kcal mol−1 between R-OFL-HPβCD and S-OFL-HPβCD inclusion complexes. S-OFL was predicted to be eluted first by the PM7 method which corroborates the experimental results. Moreover, the molecular dynamic simulations show that the formation of stable R-OFL-HPβCD is because it is more deeply inserted into the cavity of the host. The study also revealed the absence of the role of strong hydrogen bonding in the enantioseparations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Zhao, M., Cui, Y., Yu, J., Xu, S., Guo, X.: Combined use of hydroxypropyl-β-cyclodextrin and ionic liquids for the simultaneous enantioseparation of four azole antifungals by CE and a study of the synergistic effect. J. Sep. Sci. 37, 151 (2014)

    Article  CAS  Google Scholar 

  2. Chen, B., Zhang, Y., Xie, H.L., Chen, Q.M., Mai, Q.H.: Chiral separation of ofloxacin enantiomers by microchip capillary electrophoresis with capacitively coupled contactless conductivity detection. J. Chin. Chem. Soc. 61, 432 (2014)

    Article  CAS  Google Scholar 

  3. Jáč, P., Scriba, G.K.E.: Recent advances in electrodriven enantioseparations. J. Sep. Sci. 36, 52 (2013)

    Article  Google Scholar 

  4. Elbashir, A.A., Aboul-Enein, H.Y.: Capillary electrophoresis and molecular modeling as a complementary technique for chiral recognition mechanism. Crit. Rev. Anal. Chem. 43, 131 (2013)

    Article  CAS  Google Scholar 

  5. Scriba, G.K.E.: Fundamental aspects of chiral electromigration techniques and application in pharmaceutical and biomedical analysis. J. Pharm. Biomed. Anal. 55, 688 (2011)

    Article  CAS  Google Scholar 

  6. Dixit, S., Park, J.H.: Application of antibiotics as chiral selectors for capillary electrophoretic enantioseparation of pharmaceuticals: a review. Biomed. Chromatogr. 28, 10 (2014)

    Article  CAS  Google Scholar 

  7. Domínguez-Vega, E., Pérez-Fernández, V., Crego, A.L., García, M.Á., Marina, M.L.: Recent advances in CE analysis of antibiotics and its use as chiral selectors. Electrophoresis 35, 28 (2014)

    Article  Google Scholar 

  8. Tsioupi, D.A., Stefan-vanStaden, R.-I., Christodoulou, C.P.K.: Chiral selectors in CE: recent developments and applications. Electrophoresis 34, 178 (2013)

    Article  CAS  Google Scholar 

  9. Mangelings, D., Vander, Heyden Y.: Enantioselective capillary electrochromatography: recent developments and new trends. Electrophoresis 32, 2583 (2011)

    Article  CAS  Google Scholar 

  10. Al Azzam, K.M., Saad, B., Adnan, R., Aboul-Enein, H.Y.: Enantioselective analysis of ofloxacin and ornidazole in pharmaceutical formulations by capillary electrophoresis using single chiral selector and computational calculation of their inclusion complexes. Anal. Chim. Acta 674, 249 (2010)

    Article  CAS  Google Scholar 

  11. Mofaddel, N., Krajian, H., Villemin, D., Desbane, P.L.: Enantioseparation of binaphthol and its mono derivatives by cyclodextrin-modified capillary zone electrophoresis. J. Chromatogr. A 1211, 142 (2008)

    Article  CAS  Google Scholar 

  12. Juvancz, Z., Kendrovics, R.B., Iványi, R., Szente, L.: The role of cyclodextrins in chiral capillary electrophoresis. Electrophoresis 29, 1701 (2008)

    Article  CAS  Google Scholar 

  13. Scriba, G.K.E.V.: Cyclodextrins in capillary electrophoresis enantioseparations—recent developments and applications. J. Sep. Sci. 31, 1991 (2008)

    Article  CAS  Google Scholar 

  14. Chankvetadze, B.: Enantioseparations by using capillary electrophoretic techniques. The story of 20 and a few more years. J. Chromatogr. A 1168, 45 (2007)

    Article  CAS  Google Scholar 

  15. Chankvetadze, B., Lindner, W., Scriba, G.K.E.: Enantiomer separations in capillary electrophoresis in the case of equal binding constants of the enantiomers with a chiral selector: commentary on the feasibility of the concept. Anal. Chem. 76, 4256 (2004)

    Article  CAS  Google Scholar 

  16. Rizzi, A.: Fundamental aspects of chiral separations by capillary electrophoresis. Electrophoresis 22, 3079 (2001)

    Article  CAS  Google Scholar 

  17. Rizzi, A.M., Kremser, L.: pKa shift-associated effects in enantioseparations by cyclodextrin-mediated capillary zone electrophoresis. Electrophoresis 20, 2715 (1999)

    Article  CAS  Google Scholar 

  18. Elbashir, A.A., Suliman, F.O.: Computational modeling of capillary electrophoretic behavior of primary amines using dual system of 18-crown-6 and β-cyclodextrin. J. Chromatogr. A 1218, 5344 (2011)

    Article  CAS  Google Scholar 

  19. Prapasawat, T., Lothongkum, A.W., Pancharoen, U.: Modelling and experimental validation of enantioseparation of racemic phenylalanine via a hollow fibre-supported liquid membrane. Chem. Papers 68, 180 (2014)

    Article  CAS  Google Scholar 

  20. Ortuso, F., Alcaro, S., Menta, S., Fioravanti, R., Cirilli, R.: A chromatographic and computational study on the driving force operating in the exceptionally large enantioseparation of N-thiocarbamoyl-3-(4′-biphenyl)-5-phenyl-4,5-dihydro-(1H) pyrazole on a 4-methylbenzoate cellulose-based chiral stationary phase. J. Chromatogr. A 1324, 71 (2014)

    Article  CAS  Google Scholar 

  21. Shi, J.H., Su, Y.H., Jiang, W.: Enantioseparation and chiral recognition of a-cyclohexylmandelic acid and methyl a-cyclohexylmandelate on hydroxypropyl-b-cyclodextrin as chiral selector: HPLC and molecular modeling. J. Chromatogr. Sci. 51, 8 (2013)

    Article  CAS  Google Scholar 

  22. Suliman, F.O., Elbashir, A.A.: Enantiodifferentiation of chiral baclofen by β-cyclodextrin using capillary electrophoresis: a molecular modeling approach. J. Mol. Struct. 1019, 43 (2012)

    Article  CAS  Google Scholar 

  23. Li, W., Tan, G., Zhao, L., Chen, X., Zhang, X., Zhu, Z., Chai, Y.: Computer-aided molecular modeling study of enantioseparation of iodiconazole and structurally related triadimenol analogues by capillary electrophoresis: chiral recognition mechanism and mathematical model for predicting chiral separation. Anal. Chim. Acta 718, 138 (2012)

    Article  CAS  Google Scholar 

  24. Li, W., Liu, C., Tan, G., Zhang, X., Zhu, Z., Chai, Y.: Molecular modeling study of chiral separation and recognition mechanism of b-adrenergic antagonists by capillary electrophoresis. Int. J. Mol. Sci. 13, 710 (2012)

    Article  CAS  Google Scholar 

  25. Shi, J.H., Ding, Z.J., Hu, Y.: Experimental and theoretical studies on the enantioseparation and chiral recognition of mandelate and cyclohexylmandelate on permethylated β-Cyclodextrin chiral stationary phase. Chromatographia 74, 319 (2011)

    Article  CAS  Google Scholar 

  26. Bikádi, Z., Fodor, G., Hazai, I., Hári, P., Szemán, J., Szente, L., Fülöp, F., Péter, A., Hazai, E.: Molecular modeling of enantioseparation of phenylazetidin derivatives by cyclodextrins. Chromatographia 71, S21 (2010)

    Article  Google Scholar 

  27. Varghese, B., Al-Busafi, S.N., Suliman, F.O., Al-Kindy, S.M.Z.: Study on the spectral and inclusion properties of a sensitive dye, 3-naphthyl-1-phenyl-5-(5-fluoro-2-nitrophenyl)-2-pyrazoline, in solvents and β-cyclodextrin. Spectrochimica Acta Part A 136, 661 (2015)

    Article  CAS  Google Scholar 

  28. Zimnicka, M., Troć, A., Ceborska, M., Jakubczak, M., Koliński, M., Danikiewicz, W.: Structural elucidation of specific noncovalent association of folic acid with native cyclodextrins using an ion mobility mass spectrometry and theoretical approach. Anal. Chem. 86, 4249 (2014)

    Article  CAS  Google Scholar 

  29. Rajendiran, N., Mohandoss, T., Venkatesh, G.: nvestigation of inclusion complexes of sulfamerazine with α- and β-cyclodextrins: an experimental and theoretical study. Spectrochimica Acta Part A 124, 441 (2014)

    Article  CAS  Google Scholar 

  30. Asensi-Bernardi, L., Escuder-Gilabert, L., Martin-Biosca, Y., Medina-Hernandez, M.J., Sagrado, S.: Modeling the chiral resolution ability of highly sulfated b-cyclodextrin for basic compounds in electrokinetic chromatography. J. Chromatogr. A 1308, 152 (2013)

    Article  CAS  Google Scholar 

  31. Eid, E.E., Abdul, A.B., Suliman, F.O., Sukari, M.A., Rasedee, A., Fatah, S.S.: Characterization of the inclusion complex of zerumbone with hydroxypropyl-β-cyclodextrin. Carbohydr. Polym. 83, 1707 (2011)

    Article  CAS  Google Scholar 

  32. Toth, G., Mohacsi, R., Racz, A., Rusu, A., Horvath, P., Szente, L., Beni, S., Noszai, B.: Equilibrium and structural characterization of ofloxacin-cyclodextrin complexation. J. Incl. Phenom. Macrocycl. Chem. 77, 291 (2013)

    Article  CAS  Google Scholar 

  33. Elbashir, A.A., Saad, B., Aboul-Enein, H.Y.: Recent developments of enantioseparations for fluoroquinolones drugs using liquid chromatography and capillary electrophoresis. Curr. Pharm. Anal. 6, 246 (2010)

    Article  CAS  Google Scholar 

  34. Yan, H., Row, K.H.: Rapid chiral separation and impurity determination of levofloxacin by ligand-exchange chromatography. Anal. Chim. Acta 584, 160 (2007)

    Article  CAS  Google Scholar 

  35. Zhou, S., Ouyang, J., Baeyens, W.R.G., Zhao, H., Yang, Y.: Chiral separation of four fluoroquinolone compounds using capillary electrophoresis with hydroxypropyl-βcyclodextrin as chiral selector. J. Chromatogr. A 1130, 296 (2006)

    Article  CAS  Google Scholar 

  36. Stewart, J.J.P.: Optimization of parameters for semiempirical methods VI: more modifications to the NDDO approximations and re-optimization of parameters. J. Mol. Model. 19, 1 (2013)

    Article  CAS  Google Scholar 

  37. Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., Olson, A.J.: In. The Scripps Research Institute, La Jolla (2009)

    Google Scholar 

  38. Sanner, M.F., Huey, R., Dallakyan, S., Lindstorm, W., Morris, G.M., Norledge, A., Omelchenko, A., Stoffler, D., Vareille, G.: In. The Scripps Institute, La Jolla (2007)

    Google Scholar 

  39. Gasteiger, J., Marsili, M.: Iterative partial equalization of orbital electronegativity—a rapid access to atomic charges. Tetrahedron 36, 3219 (1980)

    Article  CAS  Google Scholar 

  40. Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W., Klein, M.L.: Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926 (1983)

    Article  CAS  Google Scholar 

  41. Phillips, J.C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R.D., Kale, L., Schulten, K.: Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781 (2005)

    Article  CAS  Google Scholar 

  42. MacKerell Jr, A.D., Bashford, D., Bellott, M., Dunbrack Jr, R.L., Evanseck, J.D., Field, M.J., Fischer, S., Gao, J., Guo, H., Ha, S., Joseph-McCarthy, D., Kuchnir, L., Kuczera, K., Lau, F.T.K., Mattos, C., Michnick, S., Ngo, T., Nguyen, D.T., Prodhom, B., Reiher, W.E., Roux, B., Schlenkrich, M., Smith, J.C., Stote, R., Straub, J., Watanabe, M., Wiórkiewicz-Kuczera, J., Yin, D., Karplus, M.: All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 102, 3586 (1998)

    Article  CAS  Google Scholar 

  43. Pedretti, A., Villa, L., Vistoli, G.: VEGA: a versatile program to convert, handle and visulize molecular structure on Windows-based PCs. J. Mol. Graph. Model. 21, 47 (2002)

    Article  CAS  Google Scholar 

  44. Humphrey, W., Dalke, A., Schulten, K.: VMD—visual molecular dynamics. J. Mol. Graph. Model. 14, 33 (1996)

    Article  CAS  Google Scholar 

  45. Rao, C.T., Pitha, J., Lindberg, B., Lindberg, J.: Distribution of substituents in O-(2-hydroxypropyl) derivatives of cyclomalto-oligosaccharides (cyclodextrins): influence of increasing substitution, of the base used in the preparation, and of macrocyclic size. Carbohydr. Res. 223, 99 (1992)

    Article  CAS  Google Scholar 

  46. Rusu, A., Tóth, G., Szőcs, L., Kökösi, J., Kraszni, M., Gyéresi, Á., Noszál, B.: Triprotic site-specific acid–base equilibria and related properties of fluoroquinolone antibacterials original research article. J. Pharm. Biomed. Anal. 66, 50 (2012)

    Article  CAS  Google Scholar 

  47. Babić, S., Horvat, A.J.M., Pavlović, D.M., Kaštelan-Macan, M.: Determination of pKa values of active pharmaceutical ingredients. Trends Anal. Chem. 26, 1043 (2007)

    Article  Google Scholar 

  48. Li, J., Zhang, X.: Preparation and characterization of the inclusion complex ofofloxacin with bCD and HP-bCD. J. Incl. Phenom. Macrocycl. Chem. 69, 173 (2011)

    Article  CAS  Google Scholar 

  49. Ghosh, B.C., Deb, N., Mukherjee, A.K.: Determination of individual proton affinities of ofloxacin from its UV − Vis absorption, fluorescence and charge-transfer spectra: effect of inclusion in β-cyclodextrin on the proton affinities. J. Phys. Chem. B 114, 9862 (2010)

    Article  CAS  Google Scholar 

  50. Raymo, F.M., Bartberger, M.D., Houk, K.N., Stoddart, J.F.: The magnitude of [C–H···O] hydrogen bonding in molecular and supramolecular assemblies. J. Am. Chem. Soc. 123, 9264 (2001)

    Article  CAS  Google Scholar 

  51. Desiraju, G.R.: The C–H···O hydrogen bond: structural implications and supramolecular design. Acc. Chem. Res. 29, 441 (1996)

    Article  CAS  Google Scholar 

  52. Añibarro, M., Geßler, K., Usón, I., Sheldrick, G.M., Saenger, W.: X-ray structure of β-cyclodextrin-2,7-dihydroxy-naphthalene·4.6 H2O: an unusually distorted macrocycle. Carbohydr. Res. 333, 251 (2001)

    Article  Google Scholar 

  53. Nakagawa, T., Immel, S., Lichtenthaler, F.W., Lindner, H.J.: Topography of the 1:1 α-cyclodextrin–nitromethane inclusion complex. Carbohydr. Res. 324, 141 (2000)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, College of Science, Sultan Qaboos University, Box 36, Al-Khod 123, Muscat, Oman

    FakhrEldin O. Suliman

  2. Department of Chemistry, Faculty of Science, University of Khartoum, Box 321, Khartoum, Sudan

    Abdalla A. Elbashir

  3. Applied Analytical Chemistry, Faculty of Chemistry, University of Duisburg-Essen, Essen, Germany

    Oliver J. Schmitz

Authors
  1. FakhrEldin O. Suliman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdalla A. Elbashir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oliver J. Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to FakhrEldin O. Suliman.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Suliman, F.O., Elbashir, A.A. & Schmitz, O.J. Study on the separation of ofloxacin enantiomers by hydroxyl-propyl-β-cyclodextrin as a chiral selector in capillary electrophoresis: a computational approach. J Incl Phenom Macrocycl Chem 83, 119–129 (2015). https://doi.org/10.1007/s10847-015-0547-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-015-0547-2

Keywords

Search

Navigation