Chemistry 257

Experiment 6:NMR Analysis, IR Analysis and Smell Testing


Authors: Regina F. Frey and Maureen J. Donlin
Department of Chemistry, Washington University
St. Louis, MO

Introduction

The detection of small molecules plays an important role in the survival of most animals, which use odor for identifying and evaluating their food, predators, and territory. For many years, scientists have been very successful in synthesizing fragrances. Many types of industry today have synthetic fragrances in their materials; for example, inks, paints, soaps, cleaning products, and foods. However, the detection and processing of odor by the body is not well understood. Despite the importance of olfaction (sense of smell) to our daily lives, the chemical aspect to olfaction was not given much attention by the scientific community until the 1980's.

What happens when we inhale?

The initial detection of odors takes place at the back of the nose in a small region known as the olfactory epithelium. Dissolved molecules interact with specialized receptors called odorant-binding proteins. (Odorants are molecules that stimulate the olfactory receptors.) The binding of the molecules to these receptors initiate an electrical signal that transmits to the olfactory bulbs and higher brain centers for processing of the olfactory information. Precisely how the olfactory system detects and processes the numerous scents is still being explored.

In 1991, researchers used gene-cloning techniques and isolated genes encoding the odor receptors. This research suggests that odor discrimination involves a large number of distinct olfactory receptors (as many as 1000). Each of these receptors seems capable of responding to a small number of odorants and each odor must bind to several receptors. Scientists believe that various receptors respond to discrete parts of an odor's structure and that an odor usually consists of several chemical groups that each activates a characteristic receptor. To distinguish the smell, the brain must then determine the precise combination of receptors that are activated by a particular odor.

The process that we are going to examine is the physiology of the sense of smell. There is a variety of theories proposed to explain olfaction, but there is no general agreement. Most evidence supports a stereochemical theory of odor. Amoore et al. (in 1952) proposed that the sense of smell is based largely on the geometry of the odorant molecules. In this theory, there are a small number of primary odors that are detected by complementary receptor sites in the nose. Molecules that fit into a similar primary odor family do not necessarily have similar structural formulas, but they do have roughly the same molecular shape and size. Sometimes, charge is an additional important component. When a molecule of the correct size and shape fits into a complementary receptor site, an impulse is initiated (Figure 1). Complex odors result when a molecule fits into more than one kind of site (i.e., sideways into a wide receptor site and end-on into a narrow receptor site). X-ray diffraction, infrared spectroscopy, and electron-beam probes have enabled scientists to build models of the seven primary odors.

Figure 1:

A sketch of a molecular shape fitting into
a receptor site.


Questions:

  1. For a molecule to possess a scent, it must have at least two qualities. What are they? Answer: It must be volatile at ambient temperature, so that the molecule can reach the nose. It must interact with the protein odorant receptor sites in the nose.
  2. If a compound is odorant, is the compound ionic or nonionic? Answer: Odorants are nonionic compounds. (Recall that odorants must be volatile. Ionic compounds have high boiling points and therefore are not volatile.) They are usually organic compounds with a molecular weight of less than 300.

Odor Classes

In this experiment, we will be examining four odor classes. Table 1 contains examples of molecules in three of these classes and Table 2 contains the molecules in your smell kit.

Note: To download the 3-D coordinates for these structures, please click on the 3-D shape. You may use RasMol to rotate the molecules and to view the molecules in CPK representation.

Download RasMol.

Table 1 (Examples of Molecules in Different Odor Classes):

Smell Molecule Name Chemical Formula Shape
Fruity ethyl octanoate C10H20O2
Minty beta-cyclocitral C10H13O
Minty p-anisaldehyde C8H8O2
Nutty,Medicinal 2,6-dimethyl pyrazine C6H8N2
Nutty,Medicinal 4-heptanolide C7H12O2
Nutty,Medicinal p-cresol C7H8O

Table 2 (Molecules in your Smell Kit):

Vial Letter Molecule Name Chemical Formula Shape
A Benzyl acetate C9H10O2
B l-carvone or (-)-carvone C10H14O
C Ethyl propionate C5H10O2
D Isoamyl acetate C7H14O2
E d-carvone or (+)-carvone C10H14O
F l-methone C10H16O
G 2,5-dimethyl pyrazine C6H8N2

What to look for when viewing the molecules.

Remember that molecular shape and size are major factors in the odor a molecule has. To see the similarities between molecules within the same primary odor class, download the molecules and view them in the CPK representation. (The CPK representation gives an approximate volume and three-dimensional shape of the molecule.) Compare whether the molecules within a given class are all flat or have a group that bends out of the plane. Also compare whether the molecules would fit into a narrow receptor site or a wide receptor site.


Questions:

  1. For each primary class we are studying, are the molecules flat or bent? Answer: Molecules in the Minty class are not flat; molecules in the fruity class are flat; and molecules in the nutty/medicinal class are flat.
  2. For each primay class we are studying, would the molecules fit into a narrow or wide receptor site? Answer: Molecules in the Minty class would fit into a wide receptor site; molecules in the fruity class would fit into a narrow receptor site; and molecules in the nutty/medicinal class would fit into a wide receptor site.

CAUTION: While you are comparing the molecules, remember that the odors of most molecules are very complex and that a number of receptor sites are typically used to completely distinguish a molecule's odor. The comparisons we are making in this tutorial are a first approximation to the similarities within a odor class.


Additional References

Flavornet at Cornell University has an extensive smell database. This database can be searched and pdb files for all of the structures can be obtained.

An interesting article on smell is "The Molecular Logic of Smell" by R. Axel (Scientific American, Oct. 1995, p. 154).


Copyright 1998, Washington University, All Rights Reserved.

Comments can be directed to: chemistry@wustl.edu
Last modified: June 15, 2006