Diastereomeric aggregates

What happens for a nonracemic mixture of enantiomers Is it possible to calculate the values of the chiral properties of the solution from knowledge of the properties of the enantiopure compound In principle, yes, on the condition that there is no autoassociation or aggregation in solution. Then, the observed properties will be simply the weighted combination of the properties of two enantiomers. A nice example of where this normal law may be broken was discovered by Horeau in 1967 it is the nonequivalence between enantiomeric excess (ee) and optical purity (op, with op = [a]exi/[ ]max) for 2,2-methylethyl-succinic acid. In chloroform op is inferior to ee, while in methanol op = ee. This was explained by the formation of diastereomeric aggregates in chloroform, while the solvation by methanol suppresses the autoassociation. 

The formation of diastereomeric aggregates may perturb the achiral properties as well, when compared to homochiral solutions, since the aggregation state will be not necessarily the same. It has been observed that the NMR spectra of racemic and enantiopure dihydroquinine in chloroform are significantly different. ... 

For a mixture of enantiomers it is thus possible to determine the ee-value without recourse to complicated calibration. The fact that the method is theoretically valid only if the g factor is independent of concentration and if it is linear with respect to ee has been emphasized repeatedly.84-89 However, it needs to be pointed out that these conditions may not hold if the chiral compounds form dimers or aggregates, because such enantiomeric or diastereomeric species would give rise to their own particular CD effects.88 Although such cases have yet to be reported, it is mandatory that this possibility be checked in each new system under study. 

The isolated enantiomers S (M ) and R (Mr) of a chiral molecule M exhibit the same spectral features since their physical properties are identical. However, their aggregation with a chiral chromophore of defined configuration (Cr/s) leads to the formation of two diastereomeric complexes with different spectral properties, i.e., and [C /yM ]. The lcR2PI spectroscopy is able to discriminate between Mj and by measuring the spectral shift of the diastereomeric [C /yM ] and [Cj5/5-Mj ] complexes with respect to that of the bare chromophore Cr/s- It is convenient to define the diastereomeric clusters as homochiral when the chromophore and the solvent have the same configuration, and heterochiral in the opposite case. 

One may consider a series of physical states ranging from the crystalline, where molecular aggregation and orientation are large, to the dilute gaseous state, where there are no significant orientational limits. States of intermediate order are represented by micelles, liquid crystals, monolayers, ion pairs, and dipole-dipole complexes. In the crystalline state, the differences between pure enantiomers, racemic modifications, and diastereomeric complexes are clearly defined both structurally and energetically (32,33). At the other extreme, stereospecific interactions between diastereomerically related solvents and solutes, ion pairs, and other partially oriented systems are much less clearly resolved. 

The chiral-bilayer-effect hypothesis has been evoked for the rationalization of the helical fibers formed from enantiomeric or diastereomeric surfactants (Fig. 54) [373], Different packing of the chiral surfactants in the crystals (head-to-tail) and in bilayer or micellar aggregates (tail-to-tail) is the basis for this postulate. Crystallization from aggregates requires an energetically costly, 180°... 

In order to form such an aggregate, the bis-melamine calix[4]arene 135 may assume either a C2-symmetrical (staggered) conformation, in which the residues R1 are in an identical environment, or a Cs-symmetrical (eclipsed) conformation with two different environments for the residues R1. As illustrated in Figure 35, three different diastereomeric boxes may be formed by combination of three molecules of 135 with six molecules 136.281... 

Figure 35. Three possible diastereomeric boxes and their symmetry. The combination of C2- and Cs-symmetrical bis-melamines is not possible in one aggregate.

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