Anal. Chem. 1997, 69, 4773-4782
A Persubstituted Cationic â-Cyclodextrin for Chiral
Separations
Frank O’Keeffe,† Shahab A. Shamsi,‡ Raphael Darcy,† P. Schwinte´,† and Isiah M. Warner*,‡
Laboratory for Carbohydrate and Molecular Recognition Chemistry, Department of Chemistry, University College Dublin,
National University of Ireland, Dublin 4, Ireland, and Department of Chemistry, Louisiana State University,
Baton Rouge, Louisiana 70803
γ-11-16) CDs and neutral derivatized (hydroxypropyl-,17-20 ethy-
lated,21 and methylated22-26) CDs as chiral additives in CE.
The recently developed applications of charged CDs for chiral
separations in CE offer at least two important advantages over
those with neutral CDs. First, neutral racemates that lack
electrophoretic mobility as well as the charged racemates can be
enantioresolved with charged CDs. Second, introduction of
ionogenic groups on the CD rim or connected with it via a short
alkyl chain enhances the solubility of charged CDs in aqueous
media. Although the applications of negatively charge (car-
boxylated,27-29 sulfated,30-37 and phosphated38) CDs for the separa-
tion of both neutral and charged chiral racemates have currently
The applications of a novel polycationic derivative of
â-cyclodextrin (â-CD), heptakis(6 -hydroxyethylamino-6 -
deoxy-â-cyclodextrin) (â-CD-EA), as a chiral host-guest
additive for the enantioseparation of various classes of
chiral anionic analytes are presented. The cationic â-CD
described in this paper is persubstituted with seven
ethanolamine side arms at the primary rim of each
cyclodextrin (CD) molecule. It is found that the electro-
phoretic mobility of â-CD-EA can be adjusted to influence
the chiral selectivity by changing the pH of the background
electrolyte. Most of the observed CD capillary zone
electrophoresis (CZE) separations of anionic drugs and
herbicides were accomplished in the pH range of 4 .0 -
7 .0 with a reverse polarity configuration. At pH 5 .0 ,
enantioseparation of a mixture of three structurally related
antiinflammatory agents (fenoprofen, flurbiprofen, and
ibuprofen) was possible in about 3 0 min. However, other
chiral acids, such as a series of phenoxypropionic acid
herbicides and dansylated amino acids (glutamic acid and
aspartic acids), were best separated at pH 6 .0 or 7 .0 . An
impressive separation of a mixture of six structurally
related anionic herbicides [(()-2 -phenoxypropionic acid,
(()-2 -(2 -chlorophenoxy)propionic acid, (()-2 -(3 -chlo-
rophenoxy)propionic acid, (()-2 -(4 -chlorophenoxy)pro-
pionic acid, (()-2 -(2 ,4 -dichlorophenoxy)propionic acid,
and (()-2 -(2 ,4 ,5 -trichlorophenoxy)propionic acid] was
achieved for the first time in about 1 5 min during a single
run with 2 0 mM â-CD-EA. The analytical applicability of
this cationic CD molecule for chiral separations is dis-
cussed in detail.
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The ability of cyclodextrins (CDs) to engage in chiral recogni-
tion through inclusion complexes is well known in high-
performance liquid chromatography.1 With this property in mind,
Fanali was the first to show the utility of CDs for chiral separations
in capillary electrophoresis (CE).2 Since that report, there has
been an explosive increase in the use of native (R-,3,4 â-,5-11 and
† National University of Ireland.
‡ Louisiana State University.
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S0003-2700(97)00370-3 CCC: $14.00 © 1997 American Chemical Society
Analytical Chemistry, Vol. 69, No. 23, December 1, 1997 4773