A Family of Single-Isomer Chiral Resolving Agents
for Capillary Electrophoresis. 3.
Heptakis(2,3-dimethyl-6-sulfato)--cyclodextrin
Hong Cai, Thanh V. Nguyen, and Gyula Vigh*
Department of Chemistry, Texas A&M University, College Station, Texas 77845-3255
The third member of a new family of single-isomer charged
cyclodextrins, the sodium salt of heptakis(2,3-dimethyl-
6-sulfato)--cycldextrin, has been synthesized, character-
ized, and used for the capillary electrophoretic separation
of the enantiomers of neutral, acidic, basic, and zwitteri-
onic analytes. Though heptakis(2,3-dimethyl-6-sulfato)-
-cyclodextrin complexes much less strongly with any of
the analytes tested here than the previously synthesized
heptakis(2,3-diacetyl-6-sulfato)--cyclodextrin and hep-
takis-6-sulfato--cyclodextrin, it offers excellent enanti-
oselectivities, complementary to those of the other two
single-isomer, differently functionalized charged cyclo-
dextrins. Confirming the predictions of the charged
resolving agent migration model, heptakis(2,3-dimethyl-
6-sulfato)--cyclodextrin allowed for the reversal of the
migration order of the enantiomers of neutral analytes as
the cyclodextrin concentration was increased. Just as
with the previous two single-isomer charged resolving
agents, separation selectivity for the acidic, basic, and
zwitterionic analytes could increase, decrease, or pass a
maximum as the cyclodextrin concentration was in-
creased, depending on the respective binding strength of
the enantiomers and the ionic mobilities of both the
complexed and noncomplexed forms of the enantiomers.
In view of the increasing role of capillary electrophoresis (CE)
in the efficient separation of enantiomers,
1,2
our laboratory initiated
a long-term project with multiple objectives: (i) to provide a
comprehensive theoretical framework for the description of the
electrophoretic migration of the enantiomers in order to identify
the operating variables and their ranges that are most likely to
offer successful separations (implemented in the charged resolving
agent migration model, or the CHARM model
3
), (ii) to synthesize
charged cyclodextrins that offer unique intermolecular interactions
by having different functional groups connected to the 2- and
3-carbon atoms of the glucopyranose subunits of cyclodextrins,
4,5
and (iii) to eliminate the most common drawback of the com-
mercially available charged cyclodextrins, namely the presence
of numerous isomers which makes these preparations ill-defined
complex mixtures with ill-defined mixed properties.
6-14
In parts
1 and 2 of this series,
4,5
we described the synthesis and use of
single-isomer -cyclodextrin derivatives which are completely
sulfated in the 6-positions and completely substituted on their
larger rims with hydrophilic (hydroxy)
5
and moderately hydro-
phobic (acetyl) functional groups.
4
This paper describes the
synthesis, characterization, and use of the third member of the
new single-isomer, fully charged cyclodextrin family, a derivative
which carries the hydrophobic methyl functional group on its
larger rim, heptakis(2,3-dimethyl-6-sulfato)--cyclodextrin.
EXPERIMENTAL SECTION
Synthesis of Heptakis(2,3-dimethyl-6-sulfato)--cyclodex-
trin. Except for -cyclodextrin (CD), which was a gift from
Cerastar (Hammond, IN), all chemicals were purchased from
Aldrich Chemical Co. (Milwaukee, WI). The sodium salt of
heptakis(2,3-dimethyl-6-sulfato)--cyclodextrin was synthesized
according to Figure 1. First, heptakis-6-dimethyl-tert-butylsilyl--
cyclodextrin was obtained by reacting -CD with dimethyl-tert-
butylchlorosilane according to ref 15 and purifying the raw
reaction mixture by preparative gradient elution column chroma-
tography
16
using a silica gel column and the n-hexane/ethyl
acetate/ethanol eluent system.
15
(The 50-mm-i.d., 300-mm-long
preparative HPLC column packed with 30-nm pore size, 10-μm
irregular silica (Merck, Darmstadt, Germany) was generously
loaned to us by Dr. Y. Y. Rawjee of Smith-Kline Beecham, King
of Prussia, PA.)
The pure intermediate was then methylated with iodomethane
in the presence of NaH,
15
and the resulting reaction mixture was
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Anal. Chem. 1998, 70, 580-589
580 Analytical Chemistry, Vol. 70, No. 3, February 1, 1998 S0003-2700(97)00822-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/06/1998