J Incl Phenom Macrocycl Chem
deprotonated analytes were not favorable for the formation
of inclusion complex with b-CD [45]. This finding further
support the role of inclusion complex formation in enan-
tioseparation of b-CD based CSPs. Meanwhile, the reten-
tion time of pindolol and atenolol was reduced at pH 4 and
2. Wilson, A.G., Brooke, O.G., Lloyd, H.J., Robinson, B.F.:
Mechanism of action of b-adrenergic receptor blocking agents in
angina pectoris: comparison of action of propranolol with dex-
propranolol and practolol. Br. Med. J. 4, 399–401 (1969)
3. Borchard, U.: Pharmacological properties of beta-adrenoceptor
blocking drugs. J. Clin. Bas. Cardiol. 1, 5–9 (1998)
4
. Hoffman, B.B.: Catecholamines, sympathomimetic drugs, and
adrenergic receptor antagonists, The pharmacological basis of
therapeutics (1996)
9
as compared to pH 7. Due to both of analytes and b-CD-
BIMOTs CSP acquiring positive charges at pH 4, the
electrostatic repulsion occurred and reduced the retention
time. At basic pH, the abundance of TEAA species reduces
the retention time due to the competition between TEAA
and protonated analytes.
5. Armstrong, D.W.: Direct enantiomeric separations in liquid
chromatography and gas chromatography. In: Issaq, H.J. (ed.) A
Century of Separation Science, pp. 555–578. Marcel Dekker,
New York (2002)
6
7
8
. Stoschitzky, K., Lindner, W., Zernig, G.: Racemic beta-blockers-
fixed combinations of different drugs. J. Clin. Bas. Cardiol. 1,
1
5–19 (1998)
. Hedeland, M., Isaksson, R., Pettersson, C.: Cellobiohydrolase I as
a chiral additive in capillary electrophoresis and liquid chro-
matography. J. Chromatogr. A 807, 297–305 (1998)
. Aboul-Enein, H.Y., Abou-Basha, L.I.: HPLC separation of
nadolol and enantiomers on chiralcel OD column. J. Liq. Chrom.
Rel. Techno. 19, 383–392 (1996)
Conclusion
In this study, the b-CD-BIMOTs and native b-CD was
successfully synthesized and immobilized onto the modified
silica to obtain CSPs. The enantioseparation of b-blockers
using b-CD-BIMOTs CSP with ionic liquid moiety was
found to be better than native b-CD CSP. This proved the
critical role of ionic liquid in enhancing the enantiosepara-
tion for some of b-blockers. Propranolol and metoprolol
obtained good enantioresolution compared to atenolol and
pindolol. The results suggested that the lipophilic property
and the structure of propranolol and metoprolol that enable
the formation of inclusion complex contribute to better
9. Armstrong, D.W., DeMond, W.: Cyclodextrin bonded phases for
the liquid chromatographic separation of optical, geometrical,
and structural isomers. J. Chromatogr. Sci. 22, 411–415 (1984)
0. Armstrong, D.W., Ward, T.J., Armstrong, R.D., Beesley, T.E.:
Separation of drug stereoisomers by the formation of beta-cy-
clodextrin inclusion complexes. Science 232, 1132–1135 (1986)
1. Stalcup, A.M., Chang, S.C., Armstrong, D.W., Pitha, J.: (S)-2-
Hydroxyprophyl-b-cyclodextrin, a new chiral stationary phase for
reversed-phase liquid chromatography. J. Chromatogr. A 513,
1
1
1
81–194 (1990)
12. Armstrong, D.W., Stalcup, A.M., Hilton, M.L., Duncan, J.D.,
Faulkner Jr., J.R., Chang, S.C.: Separation of metallocene enan-
tiomers by liquid chromatography: chiral recognition via
cyclodextrin bonded phases. Anal. Chem. 57, 481–484 (1985)
3. Scriba, G.K., Altria, K.: Using cyclodextrins to achieve chiral and
non-chiral separations in capillary electrophoresis. LC GC
EUROPE. 22, 420 (2009)
4. Hinze, W.L., Riehl, T.E., Armstrong, D.W., Demond, W., Alak,
A., Ward, T.: Liquid chromatography separation of enantiomers
using a chiral b-cyclodextrin bonded stationary phase and con-
ventional aqueous-organic mobile phase. Anal. Chem. 57,
1
enantioseparation. This observation was proven by H NMR
and NOESY of b-CD-BIMOTs-b-blockers inclusion com-
plexes. According to H NMR and NOESY, propranolol and
1
1
metoprolol showed the interaction at the interior torus of b-
CD-BIMOTs which indicates the formation of inclusion
complex. However, atenolol and pindolol showed the strong
interaction at exterior torus of b-CD-BIMOTs and resulting
in the poor enantioseparation.
1
2
37–242 (1985)
1
1
5. Daffe, V., Fastrez, J.: Cyclodextrin-catalysed hydrolysis of oxa-
zol-5(4H)-ones. Enantioselectivity of the acid-base and ring-
opening reactions. J. Chem. Soc. Perkin Trans. 2, 789–796 (1983)
6. Juvancz, Z., Szejtli, J.: The role of cyclodextrins in chiral
selective chromatography. Trends Anal. Chem. 21, 379–388
Acknowledgments Authors would like to seize this opportunity to
express their gratitude to the University Malaya for the IPPP grant
PG027/2013A and UMRG grant (RP006A-13SUS and RP011B-
14SUS). The authors also acknowledge Ministry of Higher Education
MOHE) for providing fellowship to one of the authors-cum-re-
(
searchers, Ms. NurulYani Rahim.
(
2002)
1
1
7. Szejtli, J.: Medicinal applications of cyclodextrins. Med. Res.
Rev. 14, 353–386 (1994)
Comliance with ethical standards
8. Wang, Y., Young, D.J., Tan, T.T.Y., Ng, S.C.: ‘‘Click’’ immo-
bilized perphenylcarbamated and permethylated cyclodextrin
stationary phases for chiral high-performance liquid chromatog-
raphy application. J. Chromatogr. A 1217, 5103–5108 (2010)
9. Poon, Y.F., Muderawan, I.W., Ng, S.C.: Synthesis and applica-
tion of mono-2 A-azido-2 A-deoxyperphenylcarbamoylated b-
cyclodextrin and mono-2 A-azido-2 A-deoxyperacetylated b-cy-
clodextrin as chiral stationary phases for high-performance liquid
chromatography. J. Chromatogr. A 1101, 185–197 (2006)
0. Ahuja, S.: Chiral Separations by Chromatography. American
Chemical Society, Oxford University Press, Oxford (2000)
1. Zhou, Z., Li, X., Chen, X.: Synthesis of ionic liquids function-
alized b-cyclodextrin-bonded chiral stationary phases and their
Conflict if interest The authors declare that they have no conflict of
interest.
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