Energy difference, chiral recognition

The results reviewed in this section demonstrate that chiral recognition in complexes between chiral crown ethers and racemic ammonium salts and vice versa occurs both in polar and in apolar solvents. The maximum values of 2.9 found for the enantiomeric distribution constants correspond to a difference in free energy of the two diastereomeric complexes of 0.6 kcal mol-1. 

With amino-acid salts the effect of the medium is considerably larger. Peacock and Cram (1976) reported that the degree of chiral recognition of DL-phenylglycine perchlorate by crown ether [285] depends on the ratio of acetonitrile and chloroform. The observed EDC values vary from 6 to 52, which corresponds to a difference in free energy of —1.15 kcal mol-1 (Table 72). The optimum is very sharply defined (23.1% of acetonitrile) and is... 

In practice it means that the exchange of one enantiomer for another is accompanied by the loss or profound change of at least one of these interactions. The study of enantioselective receptors consists in the measurement of the difference in Gibb s free energy caused by these two processes. The magnitude of this difference is directly proportional to the efficiency of chiral recognition. 

HPLC-CSPs are based on molecules of known stereochemical composition immobilized on liquid chromatographic supports. Single enantiomorphs, diastereomers, diastereomeric mixtures, and chiral polymers (such as proteins) have been used as the chiral selector. The chiral recognition mechanisms operating on these phases are the result of the formation of temporary diastereomeric complexes between the enantiomeric solute molecules and immobilized chiral selector. The difference in energy between the resulting diastereomeric solute/CSP complexes determines the magnitude of the observed stereoselectivity, whereas the sum total of the interactions between the solute and CSP chiral and achiral, determines the observed retention and efficiency. 

Chiral separation can be observed when there is a suitable difference between free energies (AG) of diastereomeric associates formed by R- and S-enantiomers of selectand and a chiral selector (SO). The energy differences can be directly attributed to the chiral recognition phenomena, involving complementarity of size, shape, and molecular interaction of SO and SA molecules. These factors are also controlled by experimental conditions such as temperature, mobile phase... 

The ability to predict recognition by CyDs would be of great practical value, especially for drug manufacturers. Consequently, several models of chiral recognition by CyDs have been proposed in the literature, neglecting the complexity of the complexation process involving very small energy differences between the complexes with enantiomeric species. The models critically reviewed later in this chapter are mostly based on very few experimental data and some of them contradict... 

There is justifiable skepticism concerning the validity of any mechanism purporting to explain such small energy differences, despite a strong tendency among workers in the field to advance chiral recognition rationales, even when comparatively few data are available upon which to base such a rationale Typically, chromatographic separation of enantiomers in-... 

A thermodynamic term describing chiral recognition is determined by the difference between the formation free energies of the transient diastereomeric complexes between the enantiomers and a chiral selector. Therefore, exact calculation of the absolute energy values is not necessarily required in molecular modeling studies related to enantioseparations. This simplifies the calculations (the opposite opinion on this topic is expressed in Chapter 11). On the other hand, due to the... 

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