Enantiomeric solutes, interaction with

The magnitude of nonequivalence exhibited by diastereomeric salts depends on solvent polarity (57,60,64), this effect stemming from dissociation of the ion pairs. Equations [4] and [5] describe the equilibria that occur in systems of diastereomeric sdts. When weakly basic enantiomeric solutes interact with weakly acidic CSAs, the dissociation of the diastereomeric solvates AHS and A HS into... 

In certain instances, enantioselectivity can be influenced by the addition of a second chiral additive such as alkylhydroxyalkyl cellulose [3,4], hexadecyltrimethyl ammonium bromide or cetylpyridinium chloride [3]. Extra additives, will not only introduce a different enantiomeric selectivity, but it will also increase the probability of the solute interacting with a chiral center and thus increase the selectivity. This... 

Crown ethers have also been used in capillary zone electrophoresis and have been established as suitable for separating optically active primary amines by LC [11,12]. In addition, they have been used in conjunction with the cyclodextrins [13,14] to improved chiral separations. As already discussed, the introduction of a second chiral agent would be expected to improve the enantiomeric resolution, as, in addition to introducing a second type of chiral selectivity, it would also increase the probability of the solute interacting with a chiral center. 

Both the N- (a-methylbenzy 1) stearamide and phospholipid systems as detailed above proved to be difficult systems with which to work. The inability of N- a-methylbenzy 1)stearamide to form stable monolayers or even to spread from the crystal on anything but very acidic subphases presents a significant technical challenge despite the presence of a chiral headgroup that is unobstructed by other molecular features. On the other hand, the phospholipid surfactants that spread to form stable films both from solution and from their bulk crystals on pure water subphases at ambient temperatures displayed no discernible enantiomeric discrimination in any film property. The chiral functionality on these biomolecules is apparently shielded from intermolecular interactions with other chiral centers to the extent... 

Since the first report of the nonequivalence phenomenon, approximately 40 chiral substances have been reported to induce enantiomeric nonequivalence in the NMR spectra of a host of solutes. These CSAs are encountered in subsequent discussions. Two qualities considered to be essential in the design of the first reported experiment (3) are evident in nearly all CSA-solute combinations. In all cases, the CSA and the solute have the common feature of complementary functionality, which permits their interaction. Both are in general hydrogen bond donors or acceptors the CSAs are acids, amines, alcohols, sulfoxides, or cyclic compounds such as cyclodextiins, crown ethers, or peptides, which attractively interact with appropriate enantiomeric solutes, engendering different spatial environments for their nuclei. In nearly every case the CSA contains a group of high diamagnetic anisotropy near its asymmetric center, a feature... 

Equations [1] and [2] describe the interaction of enantiomeric solutes A and A with chiral solvating agent S. Solvates (or association complexes) are formed that are diastereomeric and thus can, in principle, have different properties. Relevant differences are those in... 

Mechanism of Separation. There are several requirements for chiral recognition. (/) Formation of an inclusion complex between the solute and the cydodextrin cavity is needed (4,10). This has been demonstrated by performing a normal-phase separation, eg, using hexane—isopropanol mobile phase, on a J3-CD column. The enantiomeric solute is then restricted to the outside surface of the cydodextrin cavity because the hydrophobic solvent occupies the interior of the cydodextrin. (2) The inclusion complex formed should provide a rdatively "tight fit" between the hydrophobic species and the cydodextrin cavity. This is evident by the fact that J3-CD exhibits better enantioselectivity for molecules the size of biphenyl or naphthalene than it does for smaller molecules. Smaller compounds are not as rigidly held and appear to be able to move in such a manner that they experience the same average environment. (5) The chiral center, or a substituent attached to the chiral center, must be near to and interact with the mouth of the cydodextrin cavity. When these three requirements are fulfilled the possibility of chiral recognition is favorable. 

That both phenomena arise as a consequence of macroscopic solvent order and not Intimate solvent-solute Interactions Is clear Saeva and 01In (75) have shown that solute LCICD spectra can be observed In twisted nematic phases only Nakazaki et al. (76) find an excess of one enantiomer of hexahelicene Is produced photochemlcally from achiral precursors In twisted nematic phases no LCICD spectra or optical Induction occurs In untwisted nematic phases and the handedness of the twist can be correlated with the sign of the LCICD and the preferred product enantiomer. Furthermore, Isotropic phases of cholesteric mixtures display no discernible LCICD spectra (12, 67) and the enantiomeric excesses In products of photolablle reactants In Isotropic phases are near zero (51). 

Type IV includes chiral phases that usually interact with the enantiomeric analytes through the formation of metal complexes. There are usually used to separate amino acid enantiomers. These types of phases are also called ligand exchange phases. The transient diastereomeric complexes are ternary metal complexes between a transitional metal (usually Cu +), an amino acid enantiomeric analyte, and another compound immobilized on the CSP which is able to undergo complexation with the transitional metal (see also the ligand exchange section. Section 22.5). The two enantiomers are separated based on the difference in the stability constant of the two diastereomeric species. The mobile phases used to separate such enantiomeric analytes are usually aqueous solutions of copper (II) salts such as copper sulfate or copper acetate. To modulate the retention, several parameters—such as the pH of the mobile phase, the concentration of the copper ion, or the addition of an organic modifier such as acetonitrile or methanol in the mobile phase—can be varied. 

Enantiomeric separations of amino acids and short peptides are performed using either a direct or the indirect approach [10]. The indirect approach employs chiral reagents for diasteromer formation and their subsequent separation by various modes of CE. The direct approach uses a variety of chiral selectors that are incorporated into the electrolyte solution. Chiral selectors are optically pure compounds bearing at least one functional group with a chiral center (usually represented by an asymmetric carbon atom) which allows sterically selective interactions with the two enantiomers. Among others, cyclodextrins (CDs) are the... 

Capillaries with chiral polymer coatings have been applied in CE for resolution of enantiomers. Possibly because of its inclusive effect, cyclodextrin seems to be an effective chiral selective agent when bonded to a fused-silica capillary surface. In this case, the purpose of the modification is to induce interactions with the chiral material on the surface. Certainly, the cyclodextrin moiety lowers EOF like other wall modifications because it diminishes the number of silanols. The lower EOF allows for slower migration of the solute through the column and, hence, more time for interaction with the chiral selector. The diminished number of silanols also results in less nonspecific interactions with the fused-silica surface, which would tend to degrade the enantiomeric separation. 

The conditions of validity of this isotherm model are the same as those of the competitive Langmuir isotherm, ideal behavior of the mobile phase and the adsorbed layer, localized adsorption, and equal column saturation capacities of both t3q>es of sites for the two components. The excellent results obtained with a simple isotherm model in the case of enantiomers can be explained by the conjunction of several favorable circumstances [26]. The interaction energy between two enantiomeric molecules in solutions is probably very close to the interaction energy between two R or two S molecules and their interactions with achiral solvents are... 

Transition metal complexes can interact with the DNA biomolecule either covalently, as with c/i-platin, or noncovalently, when coordinatively saturated octahedral [Ru (dimine)3] " complexes or related are employed. The latter exists in two enantiomeric forms designated as the A and A optical isomers (Figure 4.15). In solution at room temperature they are configurationally stable and kinetically inert to ligand substitution. Due to their geometry these compounds are ideally suited for DNA binding studies. There are three kinds of noncovalent interactions ... 

Before discussing actual application examples, the nature of the interaction between a chiral solute and a chiral stationary phase needs to be considered further and in particular, elution order. If the stationary phase contains a substance with a particular spatial orientation, then either of a pair of enantiomeric solutes may be able to penetrate closest to the phase and, although chiral selectivity may be anticipated, the elution order of the enantiomeric pair will be unknown. In addition, the chiral substance used as the stationary phase will not be the same as the solutes and so can not predictively interact more closely with one specific enantiomer. It is important to understand a (J)-isomer in the stationary phase will not determine that the (/) or d) isomer of the solute will be... 

Incorporating the chirally selective material into a phenylpolysiloxane polymer raises the operating temperature significantly and, in addition, the polarizability of the phenyl group allows induced dipole interactions (ti interactions) with polar solutes. Materials based on the phenylsiloxane polymers can be used up to temperatures (conservatively) of about 180°C. These materials are suitable for the separation of enantiomers that are essentially polar but, insufficiently polar to render them involatile. Derivatives of polar substances would also separate well on phenylpolysiloxane polymer stationary phases, but the derivatizing procedure must not effect the enantiomeric ratio. 

Enantiomeric ions can be separated in normal phase liquid-solid systems with one antipode of a chiral counter-ion added to the non-polar mobile phase. The chiral selector should have properties such that several interaction points with the enantiomeric solutes are obtained. Electrostatic interaction, hydrogen bonding and a steric influence from a bulky structure in the vicinity of the asymmetric centre seem to be needed. Pettersson has developed systems for the separation of enantiomers of amino alcohols used as /8-adrenoceptor blocking drugs, with (-l-)-lO-camphorsulfonic acid [54] and a dipeptide derivative, N-benzoxycarbonylglycyl-L-proline [25], as selectors, the latter giving higher chiral selectivity. 

Once again, isomeric and enantiomeric forms of polar compounds can be effectively separated using NP supports and alkane-based mobile phases. When anhydrous alkanes are used as the mobile phase, active silanol groups can strongly interact with solutes. These interactions can cause peak broadening or can catalyze chemical reactions. Therefore, the choice of mobile phase modifier is critical—the modifier governs the overall surface interactions and dictates the selectivity of the separation. The only concern in using alkane-based solvent systems is the limited solubility some analytes will have in the mobile phase used. 

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