Heterochiral molecules

The term chiralty is broadly used within chemistry and drug development however, the terms chiralty or chiral are not always well understood by the reader. To clarify the matter, we can consider that two main situations exist. In the first case a sample consists of equal numbers of molecules having an opposite sense of chiralty (heterochiral molecules). This sample is said to be chiral but racemic. The second case occurs when a sample is made up of molecules that all have the same sense of chiralty (homochiral molecules). In this case the sample is said to be chiral and non-racemic. 

Random versus Partially Ordered Solid Solutions.—One of the points that needed to be clarified in order to understand the nature of the interactions at the microscopic level within the disordered phase is whether the heterochiral molecules are randomly distributed in the crystals, in which case the contacts are of (RR), (SS), and RS) natures, or if they are ordered in homochiral stacks, where the contacts are mainly of (RR) and (S5) natures. ... 

The three water ligands located at meridional positions of the J ,J -DBFOX/Ph aqua complexes may be replaced by another molecule of DBFOX/Ph ligand if steric hindrance is negligible. Based on molecular model inspection, the hetero-chiral enantiomer S,S-DBFOX/Ph looks like a candidate to replace the water ligands to form the heterochiral meso-2 l complex J ,J -DBFOX/Ph-S,S-DBFOX/... 

On the other hand, in the single crystals prepared from equivalent amounts of heterochiral 1 1 complexes, a pair of two heterochiral 1 1 complexes are incorporated in a unit cell to form a layered structure with alternate layer distances of 7.33 and 7.6 A. Two perchlorate ions stay in the narrower gap, and two additional acetone molecules as crystallization solvent occupy the wider gap. The perchlorate ions interact with two axial water ligands by hydrogen bonds (3.71 and 3.77 A) to construct a layered structure. The adjacent two molecules of heterochiral 1 1 com-... 

Fig. 13 Force/area curves of dipalmitoylphosphatidyl choline monolayers spread on pure water at 25°C (solid line) and 45°C (dashed line). The compression rate is 7.2 A2/molecule per minute. The shape of the isotherms is identical for homochiral and heterochiral films.

When compressed to surface pressures greater than their stability limits (see Table 10), diastereomeric mixtures of /V-(a-methylbenzyl)stearamides with both stearoylalanine and stearoylserine methyl esters provided clear evidence of chiral discrimination. Force-area isotherms at 35°C for homochiral and heterochiral pairs of N-(a-methylbenzyl)stearamide and stearoylalanine methyl ester show differences in both their lift-off and touchdown (the area per molecule where the surface pressure returns to zero on the expansion arm of the isotherm) areas per molecule (Fig. 32). In addition, monolayers of the heterochiral pair could be compressed to lower areas per molecule than monolayers of the homochiral pair. 

Heterochiral mixtures of JV-(a-methylbenzyl)stearamide and stearoylserine methyl ester show a collapse of the film at 20 k2/molecule to some unstable state (Fig. 33). The homochiral mixture can be compressed to a higher... 

This rather amazing result at first seems impossible. As indicated in Figure 8.37, the ShiCaPf structure is composed of heterochiral adjacent layer pairs. By pure symmetry it must be the case that the unichiral molecules have a lower free energy in either the (+) or the (—) layers. The free-energy difference between these diastereomeric layer structures could be small. But, the layers possess a collective free energy. A priori it is expected that the thermodynamic phase would possess only layers of the lower free-energy chirality. 

For skeletons in category (a), with respect to a particular classification, molecules belonging to the same region (R or L) of the 2-space are referred to as homochiral , those belonging to different regions as heterochiral . Thus, all right shoes are homochiral with one another. 

J. Paul, I. Hearn, and B. J. Howard, Chiral recognition in a single molecule A study of homo and heterochiral butan 2,3, diol by Fourier transform microwave spectroscopy. Mol. Phys. 105, 825 839 (2007). 

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. 

At the beginning of this paragraph, it has been mentioned the application of the kinetic method to characterize chiral ions. If A is an unknown chiral molecule and ref is a reference molecule of defined configuration, the stability difference between their homochiral and heterochiral complexes with I, [A -Lref] and [A -Lref], can be determined by the dissociation of the corresponding [A -L(ref)2] and [A -L(ref)2] clusters (Scheme 4). 

Ruch5 revived Lord Kelvin s idea and extended it in order to allow sorting of objects, e.g., snail shells, by helicity. Accordingly, in relation to chiral similarity, (M)j(M) and (M) (P) hexahelieene/heptahelieene molecule pairs would be regarded as homochirally and heterochirally similar, respectively. 

It was soon recognized that in specific cases of asymmetric synthesis the relation between the ee of a chiral auxiliary and the ee of the product can deviate from linearity [17,18,72 - 74]. These so-called nonlinear effects (NLE) in asymmetric synthesis, in which the achievable eeprod becomes higher than the eeaux> represent chiral amplification while the opposite case represents chiral depletion. A variety of NLE have been found in asymmetric syntheses involving the interaction between organometallic compounds and chiral ligands to form enantioselective catalysts [74]. NLE reflect the complexity of the reaction mechanism involved and are usually caused by the association between chiral molecules during the course of the reaction. This leads to the formation of diastereoisomeric species (e.g., homochiral and heterochiral dimers) with possibly different relative quantities due to distinct kinetics of formation and thermodynamic stabilities, and also because of different catalytic activities. 

---