Anal. Chem. 2000, 72, 310-317
A Fa m ily o f S in g le -Is o m e r, S u lfa t e d γ-Cyc lo d e x t rin
Ch ira l Re s o lvin g Ag e n t s fo r Ca p illa ry
Ele c t ro p h o re s is . 1 .
Oc t a k is (2 ,3 -d ia c e t yl-6 -s u lfa t o )-γ-c yc lo d e x t rin
We nhong Zhu a nd Gyula Vigh*
Department of Chemistry, Texas A&M University, College Station, Texas, 77842-3012
2
The first member of the single-isomer, sulfated γ-cyclo-
dextrin family, the sodium salt of octakis(2 ,3 -diacetyl-6 -
sulfato)-γ-cyclodextrin (ODAS-γCD) has been synthesized,
analytically characterized, and used to separate, by capil-
lary electrophoresis, a variety of neutral, acidic, basic, and
amphoteric enantiomers in low pH background electro-
lytes. The anionic effective mobilities of the neutral and
anionic analytes were found to increase with the concen-
tration of ODAS-γCD. For weakly binding cationic ana-
lytes, the effective mobilities went from cationic high
values, through zero, to increasingly larger anionic values
as the concentration of ODAS-γCD was increased. For the
strongly complexing cationic analytes, the effective mobili-
ties became anionic even at very low ODAS-γCD concen-
trations and became smaller as the ionic strength of the
background electrolyte increased with the increasing
ODAS-γCD concentration. Separation selectivity followed
the predictions of the charged resolving agent migration
model: for neutral analytes it decreased as the concentra-
tion of ODAS-γCD was increased. For cationic analytes,
selectivities were found to increase as the cationic effective
mobilities approached zero, then decreased as the con-
centration of ODAS-γCD was increased further. The extent
of peak resolution that could be realized with ODAS-γCD
strongly depended on the magnitude of separation selec-
tivity and the normalized electroosmotic flow mobility.
ODAS-γCD proved to be a broadly applicable chiral
resolving agent.
differed in their degree and loci of substitution. Recently, single-
isomer anionic 7 and cationic10,11 â-cyclodextrins were developed
to eliminate both the batch-to-batch compositional variations and
the associated, undesirable mobility and selectivity variations. The
single-isomer anionic CDs were also meant to facilitate molecular-
level studies of the chiral recognition process via NMR spectros-
-9
5
6
copy, crystallography, and molecular modeling . These single-
isomer charged CDs were successfully used in aqueous,7
hydroorganic,14 and nonaqueous15,16 background electrolytes
(BEs) to separate the enantiomers of strong and weak acids,
strong and weak bases, and amphiprotics. To provide single-
isomer, sulfated cyclodextrin resolving agents with a larger cavity,
the first member of the single-isomer, sulfated γ-cyclodextrin
family, octakis(2,3-diacetyl-6-sulfato)-γ-cyclodextrin, was synthe-
sized, analytically characterized, and used for CE enantiomer
separations, as described in this paper.
-13
EXPERIMENTAL SECTION
Synthesis of the sodium salt of octakis(2 ,3 -diacetyl-6 -
sulfato)-γ-cyclodextrin. All the reagents used were obtained from
Aldrich Chemical Co. (Milwaukee, WI), except γ-cyclodextrin,
which was a generous gift from Cerestar USA (Hammond, IN).
The synthetic procedure, a modification of what was used for the
7
synthesis of the analogous â-cyclodextrin derivative, is shown in
Figure 1. The purity of every intermediate was monitored by
gradient elution HPLC using a home-built system consisting of a
Star 9010 ternary gradient pump (Varian, Walnut Creek, CA), a
Rheodyne 7125 injection valve (Rheodyne, Cotati, CA), a UV 2050
variable wavelength UV detector (Varian), a DDL-31 evaporative
During the last five years, charged cyclodextrins (CDs) became
reliable, widely used chiral resolving agents in capillary electro-
phoresis (CE).1 Though both weak and strong electrolyte
charged CDs yielded spectacular CE separations, the strong
electrolyte CDs became favored because they could be used over
(5) Chankvetadze, B.; Endresz, G.; Blaschke, G. Chem. Soc. Rev. 1 9 9 6 , 25,
141-162.
-4
(
(
6) Lipkovitz, K. B. Chem. Rev. 1 9 9 8 , 98, 1829-1873.
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1 9 9 7 , 69, 4226-4233.
(
8) Vincent, J. B.; Kirby, D.; Nguyen, T. V.; Vigh, Gy. Anal. Chem., 1 9 9 7 , 69,
2
a broad pH range without changes in their charge-states . Most
of these charged CDs were complex mixtures of isomers which
4419-4428.
(
9) Cai, H.; Nguyen, T. V.; Vigh, Gy. Anal. Chem. 1 9 9 8 , 70, 580-589.
(
10) O’Keeffe, F.; Shamsi, S. A.; Darcy, R.; Schwinte, P.; Warner, I. M. Anal.
Chem. 1 9 9 7 , 69, 4773-4782.
*
Corresponding author. Phone: 409-845-2456. Fax: 409-845-4719. E-mail:
vigh@mail.chem.tamu.edu.
(11) Haynes, J. L.; Shamsi, S. A.; O’Keefe, F.; Darcey, R.; Warner, I. M. J.
(
(
1) Beale, S. C. Anal. Chem. 1 9 9 8 , 70, 279R-300R.
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FL, 1997.
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310 Analytical Chemistry, Vol. 72, No. 2, January 15, 2000
10.1021/ac991039t CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/17/1999