Every living organism needs information for the maintenance of its life and species. To gather this information all animals possess senses. By means of these senses they can communicate with their environment. With the senses of smell and taste the animal-world communicates via chemicals. Chemical communication plays an important role in finding food and in interindividual relations (social and sexual) and in detecting danger. With the chemical senses one may assume that a chemical substance (or mixture) interacts with a biological system resulting in a response. For centuries attempts have been made to correlate the structures of odourant molecules with their olfactory responses. After a study of the structural features of these compounds some general remarks with respect to the primary olfaction process can be made. These general remarks are discussed below.
The primary process of olfaction is not yet completely understood. The discovery of a multigene family of odourant receptors as a molecular basis for odour recognition by Buck and Axel (Cell, Vol. 65,175-187, 1991) is a big step in the good direction.
From our studies we can make the following remarks regarding the primary process of odour perception. Receptor sites seem to be flexible and dynamic, and odourant molecules are either flexible or rigid. Therefore, both may contribute to an optimal fit. Different fit-possibilities may exist with flexible odourant molecules (more odour aspects for one molecule).
One odourant molecule interacts with one receptor site. If a receptor site could interact with a large number of molecules, structure-activity relationships would not exist. Both the odourant molecule and the receptor site are chirally active. Since humans can distinguish between optical isomers (R and S enantiomers), some type of a diastereo-isomeric interaction between optical active stimulus and optical active receptor site has to occur.
The interaction between stimulus and receptor site may be only electronic (strong polar molecules), or steric (spherical molecules), but is usually a combination of both factors. The first interaction (association) can often be electronic (dipole interaction, van der Waals forces, hydrogen bridges), but this is not always necessary (alkanes, spherical molecules).
After more or less chemical interaction the dynamic receptor site 'measures' the profile of the odourant molecule (handgrip-model). Some parts of the molecule are important only as steric, or spacefilling, elements (possible replacement of polar by apolar groups). The electrical impulse (Na+/K+ exchange across the cell membrane) is generated after blocking of the receptor site.
The generation of the impulse may be either direct or indirect due to enzymatic processes. The generated impulse is a function of the electronic interaction (stimulus to site) and the space occupied at the receptor site.
Detailed studies about structure-activity relationships in human olfaction are available.
Reprinted by Leffingwell & Associates, 2006, with Permission