Chirality: Why Is It Important? - Cengage

Chirality: Why Is It Important?

A molecule is said to be chiral if it can exist as isomers (called enantiomers) that are nonsuperimposable mirror images of each other. We often say these molecules exhibit "handedness," after our nonsuperimposable mirror image left and right hands. Enantiomers rotate plane-polarized light by the same angle but in opposite directions; however, the importance of this type of isomerism goes far beyond this rather curious behavior. In fact, many of the molecules produced by organisms exhibit a specific handedness. This is important because the response of an organism to a particular molecule often depends on how that molecule fits a particular site on a receptor molecule in the organism. Just as a left hand requires a left-handed glove, a left-handed receptor requires a particular enantiomer for a correct fit. Therefore, in designing pharmaceuticals, chemists must be concerned about which enantiomer is the active one--the one that fits the intended receptor.

Ideally, the pharmaceutical should consist of the pure active isomer. One way to obtain the compound as a pure active isomer is to produce the chemical by using organisms, because the production of biomolecules in organisms is stereospecific (yields a specific stereoisomer). For example, amino acids, vitamins, and hormones are naturally produced by yeast in the fermentation of sugar and can be harvested from the ferment. Biotechnology, in which the gene for a particular molecule is inserted into the DNA of a bacterium, provides another approach. Insulin is now produced in this way.

In contrast to the synthesis of biomolecules by organisms where a specific isomer is produced, when chiral molecules are made by "normal" chemical procedures (reactants are mixed and allowed to react), a mixture of the enantiomers is obtained. For example, when one chiral center is present in a molecule, normal chemical synthesis gives an equal mixture of the two mirror image isomers--called a racemic mixture. How does one deal with a pharmaceutical produced as a racemic mixture? One possibility is to administer the drug in its racemic form, assuming that the inactive form (50% of the mixture) will have no effect, positive or negative. In fact, this procedure is being followed for many drugs now on the market. However, it is a procedure that is growing increasingly controversial as evidence mounts that the "inactive" form of the drug may actually produce detrimental effects often totally unrelated to the effect of the active isomer. In effect, a drug administered as a racemic mixture contains a 50% impurity, the effects of which are not well understood.

The alternative to using racemic mixtures is to find a way to produce the substance as a pure isomer or a way to separate the isomers from the racemic mixtures. Both of these options are difficult and thus expensive. However, it is becoming increasingly clear that many pharmaceuticals must be administered as pure isomers to produce the desired results with no side effects. Therefore, a great deal of effort is now being directed toward the synthesis and separation of chiral compounds.

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