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Cyclofructans as Chiral Selectors: An Overview

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Chiral Separations

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1985))

Abstract

Cyclofructans are cyclic oligosaccharides made of β-2,1-linked fructofuranose units. They have been utilized as chiral selectors, usually after derivatization, with high-performance liquid chromatography (HPLC), gas chromatography (GC), capillary electrophoresis (CE), and supercritical fluid chromatography (SFC). The focus herein will be directed to their development and applications as chiral selectors in various chiral separation techniques. Discussion of their use in hydrophilic liquid interaction chromatography (HILIC) will be limited. Their use in liquid chromatography, especially their improvements with the use of superficially porous particles (SPPs) will be emphasized. Method parameters and future directions are also discussed.

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References

  1. Kawamura M, Uchiyama T, Kuramoto T, Tamura Y, Mizutani K (1989) Enzymic formation of a cycloinulo-oligosaccharide from inulin by an extracellular enzyme of Bacillus circulans OKUMZ 31B. Carbohydr Res 192:83–90

    Article  CAS  Google Scholar 

  2. Kushibe S, Sashida R, Morimoto Y (1994) Production of cyclofructan from inulin by Bacillus circulans MCI-2554. Biosci Biotechnol Biochem 58:1136–1138

    Article  CAS  Google Scholar 

  3. Yoshie N, Hamada H, Takada S, Inoue Y (1993) Complexation of cycloinulonexaose with some metal ions. Chem Lett 22:353–356

    Article  Google Scholar 

  4. Shizuma M, Takai Y, Kawamura M, Takeda T, Sawada M (2001) Complexation characteristics of permethylated cycloinulohexaose, cycloinuloheptaose, and cycloinulooctaose with metal cations. J Chem Soc Perkin Trans 2:1306–1314

    Article  Google Scholar 

  5. Takai Y, Okumura Y, Tanaka T, Sawada M, Takahashi S, Shiro M, Kawamura M, Uchiyama T (1994) Binding characteristics of a new host family of cyclic oligosaccharides from inulin: permethylated cycloinulohexoase and cycloinuloheptaose. J Org Chem 59:2967–2975

    Article  CAS  Google Scholar 

  6. Uchiyama T, Kawamura M, Uragami T, Okuno H (1993) Complexing of cycloinulo-oligosaccharides with metal ions. Carbohydr Res 241:245–248

    Article  CAS  Google Scholar 

  7. Sawada M, Takai Y, Shizuma M, Takeda T, Adachi H, Uchiyama T (1998) Measurement of chiral amino acid discrimination by cyclic oligosaccharides: a direct FAB mass spectrometric approach. Chem Commun 14:1453–1454

    Article  Google Scholar 

  8. Sun P, Wang C, Breitbach ZS, Armstrong DW (2009) Development of new chiral stationary phases based on native and derivatized cyclofructans. Anal Chem 81:10215–10226

    Article  CAS  Google Scholar 

  9. Sawada M, Tanaka T, Takai Y, Hanafusa T, Hirotsu K, Higuchi T, Kawamura M, Uchiyama T (1990) Crystal structure of cycloinulohexaose. Chem Lett 19:2011–2014

    Article  Google Scholar 

  10. Sawada M, Tanaka T, Takai Y, Hanafusa T, Taniguchi T, Kawamura M, Uchiyama T (1991) The crystal structure of cycloinulohexaose produced from inulin by cycloinulo-oligosaccharide fructanotransferase. Carbohydr Res 217:7–17

    Article  CAS  Google Scholar 

  11. Wang C, Breitbach ZS, Armstrong DW (2010) Separations of cycloinulooligosaccharides via hydrophilic interaction chromatography (HILIC) and ligand-exchange chromatography. Sep Sci Technol 45:447–452

    Article  CAS  Google Scholar 

  12. Immel S, Schmitt GE, Lichtenthaler FW (1998) Cyclofructins with six to ten β-(1→2)-linked fructo-furanose units: geometries, electrostatic profiles, lipophilicity patterns, and potential for inclusion complexation. Carbohydr Res 313:91–105

    Article  CAS  Google Scholar 

  13. Armstrong DW, DeMond W (1984) Cyclodextrin bonded phases for the liquid chromatographic separation of optical geometrical, and structural isomers. J Chromatogr Sci 22:411–415

    Article  CAS  Google Scholar 

  14. Wang C, Sun P, Armstrong DW (2010) Cyclofructans, a new class of chiral stationary phases. In: Berthod A (ed) Chiral recognition in separation methods. Springer, Heidelberg

    Google Scholar 

  15. Sun P, Armstrong DW (2010) Effective enantiomeric separations of racemic primary amines by the isopropyl carbamate-cyclofructan6 chiral stationary phase. J Chromatogr A 1217:4904–4918

    Article  CAS  Google Scholar 

  16. Sun P, Wang C, Padivitage NLT, Nanayakkara YS, Perera S, Qiu H, Zhang Y, Armstrong DW (2011) Evaluation of aromatic-derivatized cyclofructans 6 and 7 as HPLC chiral selectors. Analyst 136:787–800

    Article  CAS  Google Scholar 

  17. Aranyi A, Bagi Á, Ilisz I, Pataj Z, Fülöp F, Armstrong DW, Péter A (2012) High-performance liquid chromatographic enantioseparation of amino compounds on newly developed cyclofructan-based chiral stationary phases. J Sep Sci 35:617–624

    Article  CAS  Google Scholar 

  18. Gondová T, Petrovaj J, Kutschy P, Armstrong DW (2013) Stereoselective separation of spiroindoline phytoalexins on R-naphthylethyl cyclofructan 6-based chiral stationary phase. J Chromatogr A 1272:100–105

    Article  Google Scholar 

  19. Hrobonova K, Moravcik J, Lehotay J, Armstrong DW (2015) Determination of methionine enantiomers by HPLC on the cyclofructan chiral stationary phase. Anal Methods 7:4577–4582

    Article  CAS  Google Scholar 

  20. Ilisz I, Grecsó N, Forró E, Fülöp F, Armstrong DW, Péter A (2015) High-performance liquid chromatographic separation of paclitaxel intermediate phenylisoserine derivatives on macrocyclic glycopeptide and cyclofructan-based chiral stationary phases. J Pharm Biomed Anal 114:312–320

    Article  CAS  Google Scholar 

  21. Majek P, Krupcik J, Breitbach ZS, Dissanayake MK, Kroll P, Ruch AA, Slaughter LM, Armstrong DW (2017) Determination of the interconversion energy barrier of three novel pentahelicene derivative enantiomers by dynamic high resolution liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 1051:60–67

    Article  CAS  Google Scholar 

  22. Moravčík J, Hroboňová K (2013) High-performance liquid chromatographic method for enantioseparation of underivatized α-amino acids using cyclofructan-based chiral stationary phases. Nova Biotechnol Chim 12:108–119

    Article  Google Scholar 

  23. Moskaľová M, Kozlov O, Gondová T, Budovská M, Armstrong DW (2017) HPLC enantioseparation of novel spirobrassinin analogs on the cyclofructan chiral stationary phases. Chromatographia 80:53–62

    Article  Google Scholar 

  24. Moskaľová M, Petrovaj J, Gondová T, Budovská M, Armstrong DW (2016) Enantiomeric separation of new phytoalexin analogs with cyclofructan chiral stationary phases in normal-phase mode. J Sep Sci 39:3669–3676

    Article  Google Scholar 

  25. Padivitage NLT, Dodbiba E, Breitbach ZS, Armstrong DW (2014) Enantiomeric separations of illicit drugs and controlled substances using cyclofructan-based (LARIHC) and cyclobond I 2000 RSP HPLC chiral stationary phases. Drug Test Anal 6:542–551

    Article  CAS  Google Scholar 

  26. Woods RM, Patel DC, Lim Y, Breitbach ZS, Gao H, Keene C, Li G, László K, Armstrong DW (2014) Enantiomeric separation of biaryl atropisomers using cyclofructan based chiral stationary phases. J Chromatogr A 1357:172–181

    Article  CAS  Google Scholar 

  27. Qiu H, Padivitage NLT, Frink LA, Armstrong DW (2013) Enantiomeric impurities in chiral catalysts, auxiliaries, and synthons used in enantioselective syntheses. Part 4. Tetrahedron Asymmetry 24:1134–1141

    Article  CAS  Google Scholar 

  28. Shu Y, Breitbach ZS, Dissanayake MK, Perera S, Aslan JM, Alatrash N, MacDonnell FM, Armstrong DW (2015) Enantiomeric separations of ruthenium (II) polypyridyl complexes using HPLC with cyclofructan chiral stationary phases. Chirality 27:64–70

    Article  CAS  Google Scholar 

  29. Kalíková K, Janečková L, Armstrong DW, Tesařová E (2011) Characterization of new R-naphthylethyl cyclofructan 6 chiral stationary phase and its comparison with R-naphthylethyl β-cyclodextrin-based column. J Chromatogr A 1218:1393–1398

    Article  Google Scholar 

  30. Lim Y, Breitbach ZS, Armstrong DW, Berthod A (2016) Screening primary racemic amines for enantioseparation by derivatized polysaccharide and cyclofructan columns. J Pharm Anal 6:345–355

    Article  Google Scholar 

  31. Vozka J, Kalíková K, Janečková L, Armstrong DW, Tesařová E (2012) Chiral HPLC separation on derivatized cyclofructan versus cyclodextrin stationary phases. Anal Lett 45:2344–2358

    Article  CAS  Google Scholar 

  32. Khan MM, Breitbach ZS, Berthod A, Armstrong DW (2016) Chlorinated aromatic derivatives of cyclofructan 6 as HPLC chiral stationary phases. J Liq Chromatogr R T 39:497–503

    Article  CAS  Google Scholar 

  33. Padivitage NL, Smuts JP, Breitbach ZS, Armstrong DW, Berthod A (2015) Preparation and evaluation of HPLC chiral stationary phases based on cationic/basic derivatives of cyclofructan 6. J Liq Chromatogr R T 38:550–560

    Article  CAS  Google Scholar 

  34. Hilton M, Armstrong DW (1991) Evaluation of a crown etheric column for the separation of racemic amines. J Liq Chromatogr 14:9–28

    Article  CAS  Google Scholar 

  35. Janečková L, Kalíková K, Vozka J, Armstrong DW, Bosáková Z, Tesařová E (2011) Characterization of cyclofructan-based chiral stationary phases by linear free energy relationship. J Sep Sci 34:2639–2644

    Article  Google Scholar 

  36. Woods RM, Breitbach ZS, Armstrong DW (2014) Comparison of enantiomeric separations and screening protocols for chiral primary amines by SFC and HPLC. LCGC N Am 32:742–745

    CAS  Google Scholar 

  37. Breitbach AS, Lim Y, Xu QL, Kürti L, Armstrong DW, Breitbach ZS (2016) Enantiomeric separations of α-aryl ketones with cyclofructan chiral stationary phases via high performance liquid chromatography and supercritical fluid chromatography. J Chromatogr A 1427:45–54

    Article  CAS  Google Scholar 

  38. Geryk R, Vozka J, Kalíková K, Tesařová E (2013) HPLC method for chiral separation and quantification of antidepressant citalopram and its precursor citadiol. Chromatographia 76:483–489

    Article  CAS  Google Scholar 

  39. Kalíková K, Šlechtová T, Vozka J, Tesařová E (2014) Supercritical fluid chromatography as a tool for enantioselective separation; a review. Anal Chim Acta 821:1–33

    Article  Google Scholar 

  40. Vozka J, Kalíková K, Roussel C, Armstrong DW, Tesařová E (2013) An insight into the use of dimethylphenyl carbamate cyclofructan 7 chiral stationary phase in supercritical fluid chromatography: the basic comparison with HPLC. J Sep Sci 36:1711–1719

    Article  CAS  Google Scholar 

  41. Dolzan MD, Spudeit DA, Breitbach ZS, Barber WE, Micke GA, Armstrong DW (2014) Comparison of superficially porous and fully porous silica supports used for a cyclofructan 6 hydrophilic interaction liquid chromatographic stationary phase. J Chromatogr A 1365:124–130

    Article  CAS  Google Scholar 

  42. Spudeit DA, Dolzan MD, Breitbach ZS, Barber WE, Micke GA, Armstrong DW (2014) Superficially porous particles vs. fully porous particles for bonded high performance liquid chromatographic chiral stationary phases: isopropyl cyclofructan 6. J Chromatogr A 1363:89–95

    Article  CAS  Google Scholar 

  43. Patel DC, Breitbach ZS, Wahab MF, Barhate CL, Armstrong DW (2015) Gone in seconds: praxis, performance, and peculiarities of ultrafast chiral liquid chromatography with superficially porous particles. Anal Chem 87:9137–9148

    Article  CAS  Google Scholar 

  44. Patel DC, Wahab MF, Armstrong DW, Breitbach ZS (2016) Advances in high-throughput and high-efficiency chiral liquid chromatographic separations. J Chromatogr A 1467:2–18

    Article  CAS  Google Scholar 

  45. Barhate CL, Breitbach ZS, Pinto EC, Regalado EL, Welch CJ, Armstrong DW (2015) Ultrafast separation of fluorinated and desfluorinated pharmaceuticals using highly efficient and selective chiral selectors bonded to superficially porous particles. J Chromatogr A 1426:241–247

    Article  CAS  Google Scholar 

  46. Barhate CL, Joyce LA, Makarov AA, Zawatzky K, Bernardoni F, Schafer WA, Armstrong DW, Welch CJ, Regalado EL (2017) Ultrafast chiral separations for high throughput enantiopurity analysis. Chem Commun 53:509–512

    Article  CAS  Google Scholar 

  47. Hellinghausen G, Roy D, Lee JT, Wang Y, Weatherly CA, Lopez DA, Nguyen KA, Armstrong JD, Armstrong DW (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

    Article  CAS  Google Scholar 

  48. Broeckhoven K, Cabooter D, Desmet G (2013) Kinetic performance comparison of fully and superficially porous particles with sizes ranging between 2.7 μm and 5 μm: intrinsic evaluation and application to a pharmaceutical test compound. J Pharm Anal 3:313–323

    Article  CAS  Google Scholar 

  49. Bruns S, Stoeckel D, Smarsly BM, Tallarek UJ (2012) Influence of particle properties on the wall region in packed capillaries. J Chromatogr A 1268:53–63

    Article  CAS  Google Scholar 

  50. Gritti F, Farkas T, Heng J, Guiochon G (2011) On the relationship between band broadening and the particle-size distribution of the packing material in liquid chromatography: theory and practice. J Chromatogr A 1218:8209–8221

    Article  CAS  Google Scholar 

  51. Gritti F, Guiochon G (2012) Facts and legends about columns packed with sub-3-μm core-shell particles. LCGC N Am 30:586–595

    CAS  Google Scholar 

  52. DeStefano JJ, Langlois TJ, Kirkland JJ (2008) Characteristics of superficially-porous silica particles for fast HPLC: some performance comparisons with sub-2-microm particles. J Chromatogr Sci 46:254–260

    Article  CAS  Google Scholar 

  53. Qiu H, Loukotková L, Sun P, Tesařová E, Bosáková Z, Armstrong DW (2011) Cyclofructan 6 based stationary phases for hydrophilic interaction liquid chromatography. J Chromatogr A 1218:270–279

    Article  CAS  Google Scholar 

  54. Shu Y, Lang JC, Breitbach ZS, Qiu H, Smuts JP, Kiyono-Shimobe M, Yasuda M, Armstrong DW (2015) Separation of therapeutic peptides with cyclofructan and glycopeptide based columns in hydrophilic interaction liquid chromatography. J Chromatogr A 1390:50–61

    Article  CAS  Google Scholar 

  55. Wang Y, Wahab MF, Breitbach ZS, Armstrong DW (2016) Carboxylated cyclofructan 6 as a hydrolytically stable high efficiency stationary phase for hydrophilic interaction liquid chromatography and mixed mode separations. Anal Methods 8:6038–6045

    Article  CAS  Google Scholar 

  56. Padivitage NLT, Dissanayake MK, Armstrong DW (2013) Separation of nucleotides by hydrophilic interaction chromatography using the FRULIC-N column. Anal Bioanal Chem 405:8837–8848

    Article  CAS  Google Scholar 

  57. Padivitage NLT, Armstrong DW (2011) Sulfonated cyclofructan 6 based stationary phase for hydrophilic interaction chromatography. J Sep Sci 34:1636–1647

    Article  CAS  Google Scholar 

  58. Eastwood H, Xia F, Lo MC, Zhou J, Jordan JB, McCarter J, Barnhart WW, Gahm KH (2015) Development of a nucleotide sugar purification method using a mixed mode column & mass spectrometry detection. J Pharm Biomed Anal 115:402–409

    Article  CAS  Google Scholar 

  59. Kozlík P, Šímová V, Kalíková K, Bosáková Z, Armstrong DW, Tesařová E (2012) Effect of silica gel modification with cyclofructans on properties of hydrophilic interaction liquid chromatography stationary phases. J Chromatogr A 1257:58–65

    Article  Google Scholar 

  60. Qiu H, Kiyono-Shimobe M, Armstrong DW (2014) Native/derivatized cyclofructan 6 bound to resins via “click” chemistry as stationary phases for achiral/chiral separations. J Liq Chromatogr R T 37:2302–2326

    Article  CAS  Google Scholar 

  61. Hellinghausen G, Readel ER, Wahab MF, Lee JT, Lopez DA, Weatherly CA, Armstrong DW (2019) Mass spectrometry compatible enantiomeric separations of 100 pesticides using core-shell chiral stationary phases and evaluation of iterative curve fitting models for overlapping peaks. Chromatographia 82(1):221–233

    Article  CAS  Google Scholar 

  62. 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

    Article  CAS  Google Scholar 

  63. Zhang YJ, Huang MX, Zhang YP, Armstrong DW, Breitbach ZS, Ryoo JJ (2013) Use of sulfated cyclofructan 6 and sulfated cyclodextrins for the chiral separation of four basic pharmaceuticals by capillary electrophoresis. Chirality 25:735–742

    Article  CAS  Google Scholar 

  64. Weatherly CA, Na YC, Nanayakkara YS, Woods RM, Sharma A, Lacour JÔ, Armstrong DW (2014) Reprint of: enantiomeric separation of functionalized ethano-bridged Tröger bases using macrocyclic cyclofructan and cyclodextrin chiral selectors in high-performance liquid chromatography and capillary electrophoresis with application of principal component analysis. J Chromatogr B Analyt Technol Biomed Life Sci 968:40–48

    Article  CAS  Google Scholar 

  65. Na YC, Berthod A, Armstrong DW (2015) Cation-enhanced capillary electrophoresis separation of atropoisomer anions. Electrophoresis 36:2859–2865

    Article  CAS  Google Scholar 

  66. Přibylka A, Švidrnoch M, Tesařová E, Armstrong DW, Maier V (2016) The empirical comparison of cyclofructans and cyclodextrins as chiral selectors in capillary electrophoretic separation of atropisomers of R,S-1,1′-binaphthalene-2,2′-diyl hydrogen phosphate. J Sep Sci 39:973–979

    Article  Google Scholar 

  67. Reijenga JC, Verheggen TPEM, Chiari M (1999) Use of cyclofructan as a potential complexing agent in capillary electrophoresis. J Chromatogr A 838:111–119

    Article  CAS  Google Scholar 

  68. Wang C, Yang SH, Wang J, Kroll P, Schug KA, Armstrong DW (2010) Study of complexation between cyclofructans and alkali metal cations by electrospray ionization mass spectrometry and density functional theory calculations. Int J Mass Spectrom 291:118–124

    Article  CAS  Google Scholar 

  69. Wang L, Chai Y, Sun C, Armstrong DW (2012) Complexation of cyclofructans with transition metal ions studied by electrospray ionization mass spectrometry and collision-induced dissociation. Int J Mass Spectrom 323–324:21–27

    Article  Google Scholar 

  70. Wang L, Li C, Yin Q, Zeng S, Sun C, Pan Y, Armstrong DW (2015) Construction the switch binding pattern of cyclofructan 6. Tetrahedron 71:3447–3452

    Article  CAS  Google Scholar 

  71. Wang L, Li Y, Yao L, Sun C, Zeng S, Pan Y (2014) Evaluation and determination of the cyclofructans-amino acid complex binding pattern by electrospray ionization mass spectrometry. J Mass Spectrom 49:1043–1049

    Article  CAS  Google Scholar 

  72. Maier V, Kalíková K, Přibylka A, Vozka J, Smuts J, Švidrnoch M, Ševčík J, Armstrong DW, Tesařová E (2014) Isopropyl derivative of cyclofructan 6 as chiral selector in liquid chromatography and capillary electrophoresis. J Chromatogr A 1338:197–200

    Article  CAS  Google Scholar 

  73. Smuts JP, Hao XQ, Han Z, Parpia C, Krische MJ, Armstrong DW (2014) Enantiomeric separations of chiral sulfonic and phosphoric acids with barium-doped cyclofructan selectors via an ion interaction mechanism. Anal Chem 86:1282–1290

    Article  CAS  Google Scholar 

  74. Stavrou IJ, Breitbach ZS, Kapnissi-Christodoulou CP (2015) Combined use of cyclofructans and an amino acid ester-based ionic liquid for the enantioseparation of huperzine A and coumarin derivatives in CE. Electrophoresis 36:3061–3068

    Article  CAS  Google Scholar 

  75. Xie SM, Yuan LM (2017) Recent progress of chiral stationary phases for separation of enantiomers in gas chromatography. J Sep Sci 40:124–137

    Article  CAS  Google Scholar 

  76. Zhang Y, Breitbach ZS, Wang C, Armstrong DW (2010) The use of cyclofructans as novel chiral selectors for gas chromatography. Analyst 135:1076–1083

    Article  CAS  Google Scholar 

  77. Zhang Y, Armstrong DW (2011) 4,6-Di-O-pentyl-3-O- trifluoroacetyl/propionyl cyclofructan stationary phases for gas chromatographic enantiomeric separations. Analyst 136:2931–2940

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, USA

    Garrett Hellinghausen & Daniel W. Armstrong

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  1. Garrett Hellinghausen
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  2. Daniel W. Armstrong
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Correspondence to Daniel W. Armstrong .

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  1. Department of Pharmaceutical Chemistry, University of Jena, Jena, Germany

    Gerhard K. E. Scriba

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Hellinghausen, G., Armstrong, D.W. (2019). Cyclofructans as 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_11

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  • DOI: https://doi.org/10.1007/978-1-4939-9438-0_11

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