Walter Guild, Jr.' Penn Yan Academy Penn Yan, N e w York 14527
Theory of Sweet Taste
Various attempts have been made to rationalize the chemical basis of the taste sense. The purpose of this article is to review the studies of R. S. Shallenberger, New York State Agricultural Experiment Station, Geneva, New York, and his colleagues in order to acquaint the reader with the most recent approach they have taken to establish the molecular features common to compounds which taste sweet. I n 1963 Shallenberger (1) suggested that varying sweetness of sugars and the sugar anomers was due to intramolecularyly hydrogen-bonded hydroxyl groups. The sugar -OH group is recognized to be related to sugar sweetness (3). The saporous unit appears to be
Kuhn (3) recognized that adjacent -OH groups may have hydrogen bonds 0-H--0-H
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I
and Shallenberger (1) postulated that the occurrence of the hydrogen bond might restrict the ability of the sugar saporous group to elicit the sweet taste response, and that the varying sweetness of the sugars could be largely resolved on the basis of this consideration. When the distan~e~between two oxygen atoms is between 2.5 and 2.8 A, a substituent hydrogen atom would be attracted to and, due to delocalization of charge, "bond" the second oxygen atom, 0-H. . .O (4). Certain sugar OH groups may bond in this manner. Reeves (5) calculated that adjacent OH groups in five membered rings have an 0 . ..0 distance of 2.86 A when the groups are gauche. When the adjacent OH groups are eclipsed, the 0. . .0 distance is 2.51 A. Thus it would be expected that adjacent gauche
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HO
sugar OH groups would hydrogen bond when the ring conformation or ring flexing causes the projected angle between the OH groups to decrease, or if the adjacent groups exist in true cis (eclipsed) arrangement.
sorption band occurring at about 3222 cm-' is associated with 0-H stretch (6). Carboyhdrate OH groups may be bonded singly, 0-H.. .O, or doubly bonded, 0. . .H-0 (7). Infrared and X-ray diffraction (8) correlation showed that or-D-glucose has one singly bonded, and four doubly bonded hydroxyl groups. Stereochemical studies (9, 10) based on infrared analysis of sugar related tetrahydropyran-3-01, led Foster (11) to suggest that the axial hydroxyl substituent on carbon No. 4 in or-galactose, and carbon No. 2 in a-mannose (C-1 conformation) are sterically located to bond the ring oxygen.
The mutarotation of 8-fructose consists mainly of a pyranose to furanose ring conversion (13). At equilibrium, the mixture is composed of 31.6% furanose form and 68.4% pyranose form (15). OH
I n the planar furanose form, two hydroxyl groups are in a true cis (eclipsed) conformation. If these two OH groups should hydrogen bond, the sweetness of the compound would presumably be lowered. Evidence that the OH groups are closer is indicated by the instantaneous reaction of furanose compounds with lead tetraacetate (14). At elevated temperatures hydrogen bonds are severed. Therefore, a sugar not as sweet as a, second sugar should approach the sweetness of the second sugar at an elevated temperature. Regression equations showed that the sweetness of glucose increases with temperature but galactose with reference to glucose increased twice as fast. Thus the intramolecular hydrogen bonds in galactose are greater than glucose. However, the intermolecular hydrogen bonding can not be excluded. It is possible that intermolecular hydrogen-bonding affects the rapidity with which sweetness is perceived, and intramolecular hydrogeubonding influences sweetness intensity. It became apparent that two general problem areas concerning the sweetness of sugars should be investigated, configuration and conformation of hexose anomers (15).
OH
The infrared studies indicate that hydrogen bonding does occur in sugars. The strong composite OH ab-
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Address through June 1972: University of Maryland, College
Park, Maryland 20742 Volume 49, Number 3, March 1972
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Boeseken (16) showed that compounds with cis vicinal OH groups complex with boric acid to cause an increase in conductivity of the solution. For mutarotating hexoses, the conductance of the solutions decreased if the anomer forming has trans OH groups on the anomeric carbon and the adjacent carbon atom. Conductance will increase with time if the anomer forming has cis OH groups at these positions. When p-D-glucose is dissolved in water, a conformational change apparently alters its sweetness. Lentz and Heeschen (17) found that a-D-glucose still possessed the C-1 conformation in water solution, and the 8-Danomer appeared to have a half-chair conformation. Presumably an unknown amount of L C conformation is also present.
Thus, compounds which react more strongly with boric acid are less sweet due to the intramolecular hydrogen bonding. If the infrared absorption a t a wave length of about 3,u for glucose and galactose is observed, the hydrogen bond strength of galactose is twice that of glucose and galactose is about half as sweet as glucose (80). Thus, the configuration and conformation of the sugar molecule plays an important role in the degree of sweetness for sugars. Now we should recognize that sugar sweetness is inhibited by glycol intramolecular hydrogen bonds and that the primary mechanism for the sweet taste response is intermolecular hydrogen bonding between the glycol unit and the taste bud receptor site (16). Thus, Shallenberger points out that the sweet unit of the sugars can be viewed as a bifunctional entity with an AH and B component (81). In an AH, B system, A and B are electronegatixe atoms separated-by a distance of greater than 2.5 A, but less than 4 A. H is a hydrogen atom attached to one of the electronegative atoms by a covalent bond. Thus, sweet tasting compounds must have a slightly acidic proton within a specific distance of and electronegative orbital. Examples of sweet compounds and their AH, B systems are shown below.
Half Chair
p-D-glucose, when dissolved in boric acid solution, does not initially increase the conductivity but as the mutarotation proceeds the conductivity increases to indicate a slow increase of hydrogen bonding. a-Dglucose increases the conductance of boric acid solution immediately upon dissolution and conductance gradually decreases indicating a reduction in hydrogen bonding. Galactose and mannose were also treated with boric acid, and it was found that the p-anomers react most strongly. However, the mutarotation of galactose is not easily related to a-gpyranose anomer interconversion since there are more than two galactose isomers present in significant amounts. Mannose complexing ability was of the same magnitude as glucose, but galactose has a greater ability to complex with boric acid than glucose. Since neither cis nor trans vicinal sugar OH groups alone in the C-1 conformation appear to be able to form coordination compounds with boric acid,, by reference to Barton conformational analysis models (18) and Angyal and McHugh (19), that sugar conformation actually forming the complex with boric acid may be a boat form. The complex needed would be of tridentate structure. For a-n-glucose, this would be the B-3 conformation of Reeves (5).
8.o-Fructose
Unsaturated Alcohols
Saccharine
H Alanine
Chloroform
2-Amino4-Nitrobenzene
In p-n-fructopyranose all the vicinal OH groups appear to constitute sweet glycol units. However, the anomeric OH group possesses the most acidic hydrogen in the molecule, and constitutes an AH moiety. I n close proximity, and having free rotation, is the methylene OH group which could serve as the B moiety of the AH-B system.
OH
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The conformation of 8-n-galactose and mannose may be the 2-B and B-3 conformations, respectively. 172
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Journal of Chemical Edumfion
Three-dirnenrienol model of sweet receptor site containing (left1 D-leucine and (right) 1-leucine.
The moiety of saccharine is the NH group with two possible B moieties, the carbonyl oxygen atom and the sulfoxide oxygen atom. In chloroform, which is quite sweet, the high electronegativity of the chlorine atoms comprise the B unit to complete the bifunctional system. The unsaturated alcohols, (shown above) possess an OH group which is a to a double bond where the slightly acidic OH group is influenced by the acceptor, the unsaturated center. Alanine (shown above), whether n or L, is sweet (Z). The NHa+group in solution is the AH moiety, and the COO- group would serve as the proton acceptor site. Varying degrees of sweetness for the amino-acids depend upon size and the stereochemistry of the a carbon atom. The nitrohenzene compound, l-propoxy-2-amino-4nitrohenzene (shown above), tastes sweet. However, the sweetness is greatly affected by substitution on the benzene ring. Thus, the electron density at a specific point in the molecule will determine sweetness. The ortho hydrogen is the proton of the AH, B system and influence of other substituents on the nitroheneene ring alter sweetness by changing the acidity (or H bonding power) of the hydrogen mtho to the nitro group. The receptor site is also a bifunctional unit similar in nature to the AH-B system of a sweet compound. Thus, the interaction between the receptor site and the sweet unit is a "concerted interaction" involving two simultaneous hydrogen bonds.
This interaction is neither a proton transfer nor an electrostatic interaction, but probably involves London dispersion, the principle element of hydrogen bonds (ZZ), but i t could also be a protein amide group of glutamine or asparagine. Dastoli and Price (23) showed that a protein from bovine taste buds does indeed respond to sweet tasting compounds. The model shown above to describe the initial chemistry of sweet taste is two dimensional. However, data are available which demands the inclusion of a third dimension in the model. In the model (Zh), shown in the figure, an amino acid has fixed AH-B unit, and can make only one approach to the receptor site. If the side chain is larger than the ethyl group,
as it is in leucine, than a spatial barrier at a distance of about 3-4 A form the AH, B site serves to explain why the euantiomorphic amino acids yield differenttastes. The initial chemistry of sweet taste appears to be a concerted simultaneous interaction between an AH, B unit of a saporous compound, and an analogous AH, B unit a t the taste bud receptor site. The forces involved appear to be the formation of intermolecular hydrogen bonds. A bitter taste appears to be an interaction at the same site, but because the tastant is strongly hydrogen bonded intermolecularly, the interaction may be nonbonded, or repulsive. The reaction of a dissociated proton a t the negative dipole of the site through ionic forces may be the intial chemical basis of the sour taste response, while the reaction of a halide anion a t the positive dipole (AH) moiety of the site through ionic forces may be the initial chemical interaction for the salt taste response. Acknowledgment
An expression of gratitude to Dr. R. S. Shallenberger, New York State Agricultural Experiment Station, Geneva, New York, for his enthusiasm and interest that has been expressed to tbe Secondary Science Teachers and their students. It has been a pleasure to work with Dr. Shallenberger during the summer recess for the past decade. Literature Cited (1) S ~ ~ m a w s m aR. ~ nS., , . I . Food Sci., 28, 584 (1963). 12) Mo~cnrers.R. W.. "The Chemical Senses'' (2nd ed.). Leonard Hill, Ltd., oddo on, 1951. Kunn. L. Pl., J . Amer. Chcnr. Soc.. 74, 2492 (1952). PA~LINO L... "The Nature of the Chemical Bond" (3rd ed.). Cornell Uniu. Press, Ithhoa, N. Y.. 1960, p. 485. REEVEB, R. E., Aduan. Corbohrd. Chem.. 6, 107 (1951). KnHN, L. P., Anal. Chem.. 22,276 (1950). KONK~N A., A,, S H I ~ O R I N D.. N.. A N D NOOCIOTA. L. I., Zh. Fia. Khim.. 32, 894 (1958). M ~ n n n i m H. , J., A N D MAN" J., 3. A p d . Chern., 4 , 204 (1954). BRIMACOLIBE. J. 6.. FOBTEB. A. B.. STAOET. M., A N D WHIPPEN,D. H., Tekohcdron, 4 , 3 5 1 (1958). B*YEB. S. A,, Bnru*cOMn~,J. 8.. FOBTEB. A. B., W"IO~.EN.D. H., A N D ZVEIFEI.. G.. Tetrahedron. 7 , 10 (1959). FOSTER, A. B.. Ann. Re". Biochcm., 30, 45 (1961). Isnem, H. S.. m n P I ~ M * N W , . W., J . Rer. Nat. Bur. Stond.. 20, 773 (1958). (13) A ~ n ~ n s B., o ~AND . D E ~H.. . A d o . Chem. Scond.. 16, 215 (1962). (14) BARTON.D. H.,*NDCOOXBON. R. C.. Q"r271. RCY.London. 10.44 (1956). 115) SH.~LENDER~&R. B. 8.. ACREB. T. E.. AND GUILD. W. E.. .I. Food Sci.. 30, No. 3.560 (1965): (16) B o e s e a e ~J., , Aduon. Cmbohyd. Chem., 4, 189 (1949). J. P., J . Folym. S d . , 51,247 (1961). (17) LENT.,R. W., A N D HEEBCAEN, (18) B A ~ T O N D.. H. R.,Chem. Ind.. London. 1136 (1956). (19) ANWEL. S. J., McHaax. D. I., J . Cham. Soc.. London, 1423 (1957). (20) S H A L ~ ~ E N B E R. RS., ~ ENew R . Sci., 2,569 (1964). (21) S n * r . m ~ s ~ n a s nR. . 8.. AND ACREE.T. E.. N o t w e . 216, 480 (1967). (22) Wmeno. K. B.. "Phvsioal Organic Chemiatry." John Wiley 6; Sons, Inc.. New York, 1964, p. 141. (23) DASTOLI. F. R.. A N D P e ~ c r S.. . Science, 154. 905 (1966). o n S., n . ACREE.T. E.. AND LEE. C. Y.. N~IuI.,221, (24) S ~ ~ ~ r , e w e ~ n R. No. 5180. 555 (1969).
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