Chiral recognition complexes

Systems exhibiting chiral recognition. Complexation of an optically active guest molecule (+)G or (-)G by a chiral host (—)H may be represented as follows ... 

The dependence of chiral recognition on the formation of the diastereomeric complex imposes constraints on the proximity of the metal binding sites, usually either an hydroxy or an amine a to a carboxyHc acid, in the analyte. Principal advantages of this technique include the abiHty to assign configuration in the absence of standards, enantioresolve non aromatic analytes, use aqueous mobile phases, acquire a stationary phase with the opposite enantioselectivity, and predict the likelihood of successful chiral resolution for a given analyte based on a weU-understood chiral recognition mechanism. 

The chiral recognition mechanism for these types of phases was attributed primarily to hydrogen bonding and dipole—dipole interactions between the analyte and the chiral selector in the stationary phase. It was postulated that chiral recognition involved the formation of transient five- and seven-membered association complexes between the analyte and the chiral selector (117). 

Although the chiral recognition mechanism of these cyclodexttin-based phases is not entirely understood, thermodynamic and column capacity studies indicate that the analytes may interact with the functionalized cyclodextrins by either associating with the outside or mouth of the cyclodextrin, or by forming a more traditional inclusion complex with the cyclodextrin (122). As in the case of the metal-complex chiral stationary phase, configuration assignment is generally not possible in the absence of pure chiral standards. 

In order to reduce or eliminate off-line sample preparation, multidimensional chromatographic techniques have been employed in these difficult analyses. LC-GC has been employed in numerous applications that involve the analysis of poisonous compounds or metabolites from biological matrices such as fats and tissues, while GC-GC has been employed for complex samples, such as arson propellants and for samples in which special selectivity, such as chiral recognition, is required. Other techniques include on-line sample preparation methods, such as supercritical fluid extraction (SFE)-GC and LC-GC-GC. In many of these applications, the chromatographic method is coupled to mass spectrometry or another spectrometiic detector for final confirmation of the analyte identity, as required by many courts of law. 

GC-GC has typically been employed for complex samples or those requiring additional chemistry, such as chiral recognition, to be employed along with classical GC separation. Typical GC-GC systems employ multiple capillary columns connected... 

This is because the increased turbulence from higher flow rates decreases the possibility for inclusion complexation, a necessary event for chiral recognition in reversed phase. Some effect has also been observed in the new polar organic mode when (capacity factor) is small (< 1). Flow rate has no effect on selectivity in the typic normal-phase system, even at flow rates up to 3 inL miir (see Fig. 2-11). 

Kuhn, R., Emi, F., Bereuter, T., and Hausler, J., Chiral recognition and enantiomeric resolution based on host-guest complexation with crown ethers in capillary zone electrophoresis, Anal. Chem., 64, 2815, 1992. 

The possibility to resolve the two enantiomers of 27a (or 26) by crystalline complexa-tion with optically active 26 (or 27a) is mainly due to differences in topological complementarity between the H-bonded chains of host and guest molecules. In this respect, the spatial relationships which affect optical resolution in the above described coordination-assisted clathrates are similar to those characterizing some optically resolved molecular complexes S4). This should encourage additional applications of the lattice inclusion phenomena to problems of chiral recognition. 

A particularly elegant example of cluster formation involving chiral recognition and retention of chirality through an increasingly complex hierarchical series of clusters is that of rubrene on Au l 1 1 [9] illustrated in Figure 1.5... 

From the atomic to the macroscopic level chirality is a characteristic feature of biological systems and plays an important role in the interplay of structure and function. Originating from small chiral precursors complex macromolecules such as proteins or DNA have developed during evolution. On a supramolecular level chirality is expressed in molecular organization, e.g. in the secondary and tertiary structure of proteins, in membranes, cells or tissues. On a macroscopic level, it appears in the chirality of our hands or in the asymmetric arrangement of our organs, or in the helicity of snail shells. Nature usually displays a preference for one sense of chirality over the other. This leads to specific interactions called chiral recognition. 

A system exhibiting chiral recognition. The chiral macrotricyclic tet-raamide (250) (Lehn, Simon Moradpour, 1978) has been used for the complexation, extraction and transport of primary ammonium salts. The tetraamide was used rather than the corresponding tetraamine because of the lower basicity of the nitrogens in the former ligand. This avoids the possibility of proton transfer occurring from the primary ammonium substrates R-NH3+ used as guests. In a typical experiment, a solution of a primary ammonium salt, such as naphthylethyl ammonium or phenylalanine methylester hydrochloride in hydrochloric acid was... 

Fig. 14. Dynamic chiral recognition of 9-ethylguanine by chiral ruthenium-arene complex 9.

One may use the stronger term chirality discrimination when a substantial suppression of one intermolecular diastereomer with respect to the other occurs. This requires multiple strong interactions between the two molecular units and therefore more than simple monofunctional alcohols. Some examples where one of the molecules involved is a chiral alkanol are reported in Refs. 112 and 119 121. Pronounced cases of higher-order chirality discrimination have been observed in clusters of hydroxy esters such as methyl lactate tetramers [122] and in protonated serine octamers [15,123,124]. The presence of an alcohol functionality appears to be favorable for accentuated chirality discrimination phenomena even in these complex systems [113,123,125,126]. Because the border between chirality recognition and discrimination is quite undefined, it is suggested that the two may be used synonymously whenever both molecular partners are permanently chiral [127]. 

Most of the work on chiral recognition in the ground state deals with salts having chiral, primary alkylammonium cations. Another approach is the chiral discrimination between two enantiomeric anions present as counterions in metal-cation complexes (Lehn et al., 1978). Discrimination between enantiomeric transition states will be dealt with in the next section together with non-chiral mimicry of enzymic catalysis. 

---