Chemistry Everyday for Everyone edited by
applications and analogies
Ron DeLorenzo Middle Georgia College Cochran, GA 31014
Hot and Spicy vs. Cool and Minty as an Example of Organic Structure–Activity Relationships Doris R. Kimbrough Chemistry Department, Box 194, University of Colorado at Denver, P.O. Box 173364, Denver, CO 80217-3364 The relationship between molecular structure and molecular function or reactivity is integral to chemistry, particularly in the study of organic substances. Since many organic chemistry students are interested in the life sciences, using biological examples to illustrate the importance of functional groups is a convenient way to make organic chemistry relevant. Interesting examples of structure–activity relationships can be found in two classes of compounds responsible for the sensations that we normally associate with hot and spicy or cool and minty flavors. Humans have two types of neural receptors that are involved in temperature perception (1). Receptors that respond to warm stimuli have a peak sensitivity above normal body temperature; cool receptors function most efficiently below. These receptors are found inside the mouth as well as on the skin. They continue to respond to a stimulus as long as they are in contact with heat or cold. However, certain classes of compounds enable these receptors to respond at normal body temperature, outside of their peak range. The exact relationship between their molecular structure and neurological response is unknown, but there are clear analogies among the structures of substances with similar neural activity (2). The spices that we normally associate with “hot” food, such as peppers or curry, activate the warm receptors. Piperine (Fig. 1) is the active component of white and black pepper (Piper nigrum) and is presumably of use to the plant because of its insecticidal properties (2–4). Capsaicin (pronounced cap-SAY-shin) is the substance responsible for the spiciness associated with members of the genus Capsicum, which includes most of the red and green peppers used in Mexican, South American, Cajun, and some Asian foods (2, 4). Ginger is another “hot” spice common to Asian cuisine, and the substance responsible for its pungency is zingerone (2, 4). The structures of these three substances are remarkably similar. Each contains an aromatic ring with two ortho oxygen atoms (similar to vanillin), either in an ether–phenol combination, as in the case of capsaicin and zingerone, or as an acetal, as found in piperine. Bonded to the ring at position 4 is a long chain bearing a carbonyl group. The carbonyl group is located in the same position for capsaicin and zingerone—although the latter is a ketone, whereas capsaicin is an amide. The carbonyl is located further down the chain in piperine, which, like capsaicin, is an amide. These three compounds are listed by the Merck Index as ranging from sparingly soluble to virtually insoluble in water (3), as anyone who has ever failed to achieve comfort by drinking cold water to relieve the burning sensation from spicy food can attest. All three are soluble in organic solvents, and their oil solubility accounts for why sour cream is a popular accompaniment to hot foods. A “cool” sensation results from the presence of a substance that allows cool receptors to be activated outside
O O
N
O piperine
O H3CO
N H
HO
capsaicin
O H3CO HO zingerone
Figure 1. Structures of substances responsible for hot and spicy sensations.
CH3
CH3 O H OH
H H3C
CH3
menthol
H
CH3
H2C R -carvone
Figure 2. Structures of substances responsible for cool and minty sensations.
their normal temperature range in the warm environment of the mouth. Menthol and carvone, terpenes with similar skeletal structures, can cause this effect (Fig. 2). Menthol can be extracted from different mint plants and can also be synthesized from turpentine (2, 3). It is an optically active substance having three chiral carbons. The two enantiomers of carvone are often mentioned in organic chemistry classes to illustrate the chirality of olfactory receptors. R(–)-carvone is the principal component in oil of spearmint; its enantiomer, S-(+)-carvone, is responsible for the flavor of caraway oil (3, 5). It is significant that we do not associate the flavor of caraway with a cooling effect, indicating that the temperature-oriented neural receptors that respond to these substances must also have chirality. How the substances discussed above specifically interact with the corresponding heat- or cold-sensitive neural receptors is unclear, but the structural similarities within each group of compounds provide interesting examples of the structure–activity connections in organic functional groups.
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Chemistry Everyday for Everyone Literature Cited 1. Shepherd, G. M. Neurobiology, 3rd ed.; Oxford University: New York, 1994. 2. Atkins, P. W. Molecules; Freeman: New York, 1987. 3. The Merck Index, 9th ed.; Windholz, M. Ed.; Merck & Co.: Rahway, NJ, 1976. 4. Lehman, J. W. Operational Organic Chemistry, 2nd Ed.; Allyn & Bacon: Boston, 1988. 5. Carey, F. A. Organic Chemistry; McGraw-Hill: New York, 1987.
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