Physical properties of enantiomers

If both enantiomers are present in a solid sample, the melting point and the solubility of the solid mixture are often found to be different than those of the pure enantiomers. This is due to the fact that the solid-state interaction of two R enantiomers or two S enantiomers is often different than the solid-state interaction of an R and an S enantiomer. (In fact, these interactions are diastereomeric.) The result is that three different scenarios are possible when a racemic mixture is crystallized from solution  

If an enantiomer has a greater affinity for molecules of opposite configuration, then crystals are produced which contain equal numbers of the (+) 

The usual physical properties such as density, melting point, and boiling point are identical within experimental error for both enantiomers of a chiral compound. 

Enantiomers can have striking differences, however, in properties that depend on the arrangement of atoms in space. Take, for example, the enantiomeric forms of car-vone. (/ )-( )-Carvone is the principal component of spearmint oil. Its enantiomer, (5 )-(+)-carvone, is the principal component of caraway seed oil. The two enantiomers do not smell the same each has its own characteristic odor. 

An article entitled When Drug Molecules Look in the Mirror in the June 1996 issue of the Journal of Chemical Education (pp. 481-484) describes numerous examples of common drugs in which the two enantiomers have different biological properties. 

The difference in odor between (R)- and (5 )-carvone results from their different behavior toward receptor sites in the nose. It is believed that volatile molecules occupy only those odor receptors that have the proper shape to accommodate them. Because the receptor sites are themselves chiral, one enantiomer may fit one kind of receptor while the other enantiomer fits a different kind. An analogy that can be drawn is to hands and gloves. Your left hand and your right hand are enantiomers. You can place your left hand into a left glove but not into a right one. The receptor (the glove) can accommodate one enantiomer of a chiral object (your hand) but not the other. 

The term chiral recognition refers to the process whereby some chiral receptor or reagent interacts selectively with one of the enantiomers of a chiral molecule. Very high levels of chiral recognition are common in biological processes. ( )-Nicotine, for example, is much more toxic than (+)-nicotine, and (+)-adrenaline is more active in the 

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Two compounds are diastereomers when they contain more than one chiral center. If the number of dissymmetric centers is given by N, then the number of possible diastereomers is given by 2N. Of these 2 v diastereomers, each will be characterized by its mirror image, so that the number of enantiomers is given by 2NI2. Whereas the physical properties of enantiomers in an achiral environment are necessarily identical, the physical properties (including solubility) of diastereomers are normally different. The differences arise since there is no structural requirement that the crystal lattices of different diastereomers be the same. For instance, the solubility of an (SS )-diastereomer could differ substantially from that of the (/ S)-diastereomer. However, it should be remembered that the solubility of the (SS)-diastereomer must be exactly identical to that of the (I 7 )-diastereomer, since these compounds are enantiomers of each other. At the same time, the solubilities of the (SI )-diastereomer and the (I S)-diastereomer must also be identical. 

The physical properties of enantiomers and race-mates, except for optical rotation and melting points, are... 

Although most physical properties of enantiomers are identical, pharmacological properties may be different. There are examples of compounds where ... 

Because the physical properties of enantiomers are identical, they seldom can be separated by simple physical methods, such as fractional crystallization or distillation. It is only under the influence of another chiral substance that enantiomers behave differently, and almost all methods of resolution of enantiomers are based upon this fact. We include here a discussion of the primary methods of resolution. 

Except for the property of rotating plane-polarized light in opposite directions, the physical properties of enantiomers of the same compound are identical. In addition, their chemical properties are identical, except when they are acted upon by another chiral molecule. One such kind of molecule consists of enzymes, large molecules of proteins that catalyze biochemical reactions. Therefore, many biochemical reactions involve chiral molecules. 

W. H. Pirkle, The nonequivalence of physical properties of enantiomers in Optically active solvents. Differences in nuclear magnetic resonance spectra. I, /. Am. Chem. Soc. 88 (1966), 1837. 

The physical properties of enantiomers are identical in an achiral environment. However, chemical reactions that add another asymmetric center create a diastereomeric pair, each of which has physical properties that are not completely the same. Therefore, although an enantiomeric pair cannot be separated by ordinary chromatographic means or fractional recrystallization, the diastereomeric pair can often be separated easily by these means, as is indicated in the chapter by Joseph Gal. After separation, the pure enantiomers can then be regenerated by chemical means. This is today the most fundamental way of resolving a racemate. 

Identical chemical and physical properties of enantiomers represent a potential source for enantiomer-enantiomer interactions at both pharmacokinetic and pharmacodynamic levels. Whether by competition for plasma- or tissue-binding sites or for drug-metabolizing enzymes, enantiomers may exhibit changes in pharmacokinetics when administered as a racemate compared to individual stereoisomers. The enantiomers of disopyramide exhibit similar clearance and volumes of distribution when given separately. " However, when administered as the racemate, the 5... 

The identity of most physical properties of enantiomers has one consequence of great practical significance. They cannot be separated by ordinary methods not by fractional distillation, because their boiling points are identical not by fractional crystallization, because their solubilities in a given solvent are identical (unless the solvent is optically active) not by chromatography, because they are held equally strongly on a given adsorbent (unless it is optically active). The separation of a racemic modification into enantiomers—the resolution of a racemic modification—is therefore a special kind of job, and requires a special kind of approach (Sec. 7.9). 

A molecule that cannot be superimposed on its mirror image is said to be chiral. When a carbon atom is bonded to four different atoms or groups of atoms, it is called a chiral carbon. Two stereoisomers that are nonsuperimposable mirror images of one another are a pair of enantiomers. As mentioned in Section 17.3, the chemical and physical properties of enantiomers are identical, with the exception that they rotate plane-polarized light to the same degree but in opposite directions. This is exactly the phenomenon that Pasteur observed with the mirror-image crystals of tartaric acid salts. 

Enantiomers share many of the same properties—they have the same boiling points, the same melting points, and the same solubilities. In fact, all the physical properties of enantiomers are the same except those that stem from how groups bonded to the asymmetric carbon are arranged in space. One of the properties that enantiomers do not share is the way they interact with polarized light. 

In the second example, we will imprint a chiral template, (R)-isoproterenol (as depicted in Fig. 9), which is another common asthma medication [41]. The synthesis of materials that can discriminate between enantiomers [24] demonstrates the vast potential of the imprinting technique. Because the chemical and physical properties of enantiomers are identical in anonchiral environment, the observation of enantios-electivity in MIPs can only be attributed to the three-dimensional arrangement of the functional monomers around the template molecule. Chiral selectivity in MIPs can be readily observed in batch-mode binding and competition studies [31] similar to the one described in the theophylline MIP protocol. In this case, however, we will present a procedure for evaluating the MIP as a HPFC packing material in order to... 

As pointed out previously, all of the amino acids prepared in this section are racemic. To obtain an enantiopure amino acid requires separation of the enantiomers via resolution. As discussed in Chapter 9 (Section 9.2), the physical properties of enantiomers are identical except for specific rotation. Because separation methods rely on differences in physical properties, this is a problem. It is overcome if the racemic amino acid mixture reacts with a reagent that has a stereogenic center. The resulting product will be a mixture of diastereomers, which have different physical properties and may be separated. 

The procedures in this chapter are chosen to study (a) separating diastereomers by chromatography (Sec. 7.2), (b) converting one diastereomer into another (Sec. 7.3), (c) evaluating some chemical and physical properties of enantiomers (Sec. 7.4), and (d) resolving a racemate (Sec. 7.6). A description of the technique of polarimetry is given in Section 7.5 to support this last study. 

The physical properties of the three stereoisomers of tartaric acid are listed in Table 4.2. The meso compound and either of the enantiomers are diastereomers. Notice that the physical properties of enantiomers are the same, whereas the physical properties of diastereomers are different. 

Most of the physical properties of enantiomers are the same. A major exception is their interaction with plane-polarized light One enantiomer will rotate the polarization plane clockwise (dextrorotatory), the other counterclockwise (levorotatory). This phenomenon is called optical activity. The extent of the rotation is measmed in degrees and is expressed by the specific rotation, [a]. Racemates and meso compounds show zero rotation. The enantiomer excess or optical purity of an unequal mixture of enantiomers is given by... 

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