Homochiral interaction

The chiral discrimination in the self-association of chiral l,3a,4,6a-tetrahydroi-midazo[4,5-d]imidazoles 3 has been studied using density functional theory methods [37], (Scheme 3.20). Clusters from dimers to heptamers have been considered. The heterochiral dimers (RR SS or SS RR) are more stable than the homochiral ones (RR RR or SS SS) with energy differences up to 17.5 kJ mol-1. Besides, in larger clusters, the presence of two adjacent homochiral molecules imposes an energetic penalty when compared to alternated chiral systems (RR SS RR SS...). The differences in interaction energy within the dimers of the different derivatives have been analyzed based on the atomic energy partition carried out within the AIM framework. The mechanism of proton transfer in the homo- and heterochiral dimers shows large transition-state barriers, except in those cases where a third additional molecule is involved in the transfer. The optical rotatory power of several clusters of the parent compound has been calculated and rationalized based on the number of homochiral interactions and the number of monomers of each enantiomer within the complexes. 

Vapor Pressure. Differences in vapor pressure (i.e., in the heat of sublimation [Ai/subiim]) have been observed for enantiomers and racemates. It has been suggested that heterochiral interactions between solid enantiomers (as in a racemic compound) can be either stronger or weaker than the homochiral interactions, i.e., between the crystals of the 1 1 mechanical mixture [32]. These interactions have not been widely investigated in pharmaceutical formulations containing racemates or enantiomers. The difference in A/fsubiim can also be used to separate enantiomers from a mixture, and it is thought to be a better method of separation, at least in some cases, than recrystallization. 

Racemic species contain equal amounts of two enantiomers and raise various issues concerning how to count the number of substances present in a sample. Most racemic species are distinct compounds (racemates) one solid compound forms, because heterochiral interactions dominate. Racemic molecules (or complexes ) may exist in the liquid state. Enantiomers may also form solid solutions or racemic conglomerates. The latter are eutectic mixtures of (-h) and (—) enantiomers two separate solid phases form, each crystal type comprises a single enantiomer (because homochiral interactions dominate). In practice, spectra of racemic and enantiomeric forms are indistinguishable, although one would be inclined to consider the racemate and the separate enantiomers as three different species. In the solid state, properties such as melting point, solubility behaviour, and density are different for the racemate and the respective enantiomers. Hence, some of their thermodynamic properties must be different. 

Enantiomers (M)- and (P)-helicenebisquinones [32] 93 have been synthesized by high pressure Diels-Alder reaction of homochiral (+)-(2-p-tolylsulfo-nyl)-l,4-benzoquinone (94) in excess with dienes 95 and 96 prepared from the common precursor 97 (Scheme 5.9). The approach is based on the tandem [4 + 2] cycloaddition/pyrolitic sulfoxide elimination as a general one-pot strategy to enantiomerically enriched polycyclic dihydroquinones. Whereas the formation of (M)-helicene is explained by the endo approach of the arylethene toward the less encumbered face of the quinone, the formation of its enantiomeric (P)-form can be the result of an unfavourable interaction between the OMe group of approaching arylethene and the sulfinyl oxygen of 94. 

The carboxylic acid functionality is not involved in any significant interaction with the gold substrate but rather dominates the pairing interaction between enantiomers. This three-point bonding of each molecule, Au—S, Au—N, and O—H—O, drives the self-recognition preference for homochiral pairs [58]. 

Figure 1.17 The left-hand STM image shows homochiral adenine rows aligned in low symmetry but mirror image azimuths on a Cu(l 1 0) surface. On the right, adenine rows in the (1,2) direction are decorated with double rows of S-phenylglycine molecules, while no such interaction occurs with (1, -2) rows. (Adapted with permission from Ref. [60], Copyright 2000, Macmillan Publishers Ltd.)...

Another hypothesis on homochirality involves interaction of biomolecules with minerals, either at rock surfaces or at the sea bottom thus, adsorption processes of biomolecules at chiral mineral surfaces have been studied. Klabunovskii and Thiemann (2000) used a large selection of analytical data, provided by other authors, to study whether natural, optically active quartz could have played a role in the emergence of optical activity on the primeval Earth. Some researchers consider it possible that enantioselective adsorption by one of the quartz species (L or D) could have led to the homochirality of biomolecules. Asymmetric adsorption at enantiomor-phic quartz crystals has been detected L-quartz preferentially adsorbs L-alanine. Asymmetrical hydrogenation using d- or L-quartz as active catalysts is also possible. However, if the information in a large number of publications is averaged out, as Klabunovskii and Thiemann could show, there is no clear preference in nature for one of the two enantiomorphic quartz structures. It is possible that rhomobohedral... 

The application of a chiral auxiliary or catalyst, in either stoichiometric or catalytic fashion, has been a common practice in asymmetric synthesis, and most of such auxiliaries are available in homochiral form. Some processes of enantiodifferentiation arise from diastereomeric interactions in racemic mixtures and thus cause enhanced enantioselectivity in the reaction. In other words, there can be a nonlinear relationship between the optical purity of the chiral auxiliary and the enantiomeric excess of the product. One may expect that a chiral ligand, not necessarily in enantiomerically pure form, can lead to high levels of asymmetric induction via enantiodiscrimination. In such cases, a nonlinear relationship (NLE) between the ee of the product and the ee of the chiral ligand may be observed. 

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