Chiral Separations in Nonaqueous Media - Chiral Separations by Capillary Electrophoresis - page 278

literature of other solvents that have only been used for achiral separations in non-
aqueous media, such as N -, N -dimethylacetamide, butanol [36], nitromethane [37],
and tetrahydrofurane in mixtures with MeOH [38] or a combination of MeOH and
acetonitrile (ACN) [39]. These solvents might also prove to be useful for chiral
separations.
Important properties for a BGE solvent are (1) low volatility, (2) high solubility
of the electrolytes and the samples, (3) having a rather high self-dissociation con-
stant ( K a,solvent ), (4) having a reasonably low dielectric constant and (5) low viscos-
ity. One difference between the achiral and the chiral separations in NACE is that
solvents with a higher > 30) are more commonly used in the achiral separations,

especially in comparison with the solvents used for the ion-pair selectors [23]. The
ion-pair formation is more pronounced in a solvent with a low

ε ( ε

often
promotes the separation when ion-pair selectors are used. But, as already mentioned
above, if the value of

ε , as a low ε

is too low, it will suppress the ionization of the species (the
analyte and/or the selector) in the nonaqueous solvent, which results in the loss of
enantioselectivity since uncharged molecules have no net velocity in an electrical
i eld. The competing nonstereoselective ion-pair formation in the solvents with a
low

ε

might be another complicating factor that cause difi culties in the design of
separation conditions, since the proper choice of the other electrolytes in the BGE (in
addition to the choice of the selector) is of major importance for the separation [40].
Commonly used electrolytes for chiral separations in nonaqueous media are listed in
Table 10.3. The problem with nonstereoselective ion-pair formation in the BGE will
be discussed further in Section 10.3.
For safety reasons, all l ammable and toxic solvents should be avoided in the
BGE, and if ultraviolet (UV) detection is used, the solvent should have as low a UV
cutoff as possible. Of course, using a high purity solvent is also preferable. In this
context, it should be stressed that the term “nonaqueous” is slightly misleading, since
many of the organic solvents, e.g., EtOH, and some of the more common electro-
lytes, e.g., ammonia (NH 3 ), contains small amounts of water or produce water in
the BGE by neutralization. Furthermore, some of the solvents, e.g., dichloromethane
(DCM), and electrolytes, e.g., sodium hydroxide (NaOH), are hygroscopic, which
needs to be taken into account since it might cause problems with the repeatability
and reproducibility of the method if the water content changes during the analy-
sis. Addition of small amounts of water may reduce these problems. Tjørnlund and
Hansen [41] investigated the inl uence of water on an achiral separation by using
four different organic solvents (MeOH, ACN, dimethylsulfoxide [DMSO], and
N -methylformamide [NMF]). They found that the reproducibility increased with
only a minor effect being observed on the selectivity, efi ciency, and EOF when 0.5%
water was added to the BGE. The addition of small amounts (i.e., 0.5%) of water
has also shown to improve the repeatability of the method for a chiral separation of
β

ε

-blockers in an EtOH-based BGE [40]. However, the addition of higher concentra-
tions of water often decreases and even ruins the enantioresolution when ion-pair
selectors are used [21]. The inl uence of water when ion-pair selectors are used is
discussed further in Section 10.3.
Alterations in the organic solvent composition in the BGE give rise to simultane-
ous changes in several different parameters, including the p K a * value of the solutes,