Structural Theories Applied to Taste Chemistry Tseng Kuang-chih and tie Hua-zhong Shanghai Institute of Organic Chemistry, Academia Sinica, Shanghai, China The mechanism of taste phenomena is still largely unknown. Nevertheless, numerous chemical structures of molecules with various tastes, the basic ones of which are sour, salty, sweet, and hitter, are known. This paper is an attempt to explain these phenomena from viewpoints of structural theories in chemistry. I t is generally agreed that tastes are experienced when tastants contact the taste receptors on the taste buds of an animal. In terms of structural chemistry, the tastant and receptor form a guestihost complex, which produces a sense of taste. There should be no covalent hond formation; otherwise, it would he an irreversible process destroying the taste sensor. Our present best guess about this biochemical recognition process of taste sensing may be illustrated schematically by Figure 1 We shall not delve in the latter steps, since the first one alone involves the recognition of a chemical structure.
wm
Bitter sensitive Sour sensitive
Salty sensitive
Sweet sensitive Sour receptor (Head of PL) Salty receptor -1(Head Bitter Toste of receptor PL)
The Nature ol the Chemlcal Bond Because taste quality and intensity of sourness or saltiness denend uoon the whole molecule of acid or salt.. resoectivelv, . .. the assertion that the primary reaction for each is a rapid reversible, but selective ion exchange reaction related to a difference in their ionic radii is probably not far from reality (2,3).However, not all acids are sour, and not all salts are salty. For instance, both picric acid and cesium salt are bitter, which, however, can be explained by their size and nature of chemical bond (see helow). Bitter compounds are widely distributed and are the most complex. They include compounds with a hydrophobic part not much thicker than that of a half length of the phospholipid outer layer of a hiomembraue bilayer, for example, radon gas, heavy metal salts to complex lipids, alkaloids, glycosides, and polypeptides. Circumstantial evidence suggests that the bitter receptor is a high-enthalpy water hole in which inclusion compounds can he formed with nonpolar molecules or polar molecules with a hydrophobic moiety such as highly polarizable radon gas, olefins, crown ethers, heavy salts, picric acid, sulfonium and ammonium salts, etc. Sweet compounds also are widespread although not as numerous as the hitter ones. They are limited to those molecules with a dipolar distance of -2.8 to 5.4 &, that may result from the pure formal charges of an ion pair, a betaine molecule, H-bond donor-acceptor pair of sugars, dipolar structure of alkyl halides, or a mixed form of valency like the following three octenols, which involve a positive H-bond donor and a negative a-electron donor (4):
Acid ,base
stimuli
( P L poiyene tail) Sweet receptor (Peripheral protein)
Hydropho-
OMe
Coulomb attraction
t
.
A change of the PL &/or protein conformation on the villi of t a s t e cell membrane
Domains of t a s t e cell membrane excited by low frequency phonon 150 3
at the basalposition of the taste cell where the nerve ending is located
300 4
T h e H bond is especially important in taste chemistry as is exemplified by Shallenherger's theory of sweet taste (5)and Kuhota-Kubo's theory on hitter taste (6-8), viz., an H-bond donor-acceptor pair separated by 2 . 8 4 0 A capable of forming an intermolecular H-bond complex is an attribute of a molecule to he attracted to the sweet receptor while one of a similar pair separated less tha 2.8 A and that favors a tight intramolecular H hond, is an attribute of a molecule to he
I
H Transmission of the toste signal by the nerve axon
Limbic area of cerebrum perceiving the t a s t e
Figure 1. A schematic representation of the steps in taste perception.
I It must be noted that there are no clear demarcation lines between taste modalities, mainly because tastants can often be competitively accepted simultaneously by different taste receptors. Here PL stands for phospholipid.
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so 0.74
Note: sw = sweet, so = sour, & bi = bitter
Li '-B
GlucOPr > GlucOEt > GlucOMe in bitterness, where gluc stands for glucosyl(23). However, an energy of dehydration that is too high to allow the molecule to interact with the taste receptor will cause the molecule to he tasteless, or, in some cases, sour due to the tunnelling effect of protons in aqueous media. For i n s t a n c e , i n s w e e t n e s s , 1-CHzC0NHNHz)z > H ~ N H N C O C H Z C H O H C O N H N H ~> (-CHOHCONHNHz)? > (-CHOHCHOHCONHNHZ)~,the latter of which is flat. Compounds RCH(CONHNHZ)~are sweet when R is less than three C atoms, bitter when R = C4to C7 and flat when R is too large to be soluble or is too hydrophilic, such as an additional NHNH? group. The presence of a free carboxylic group in any of the above compounds will imnart a sour taste (24). some compoundsmay have to he properly hydrated before they can impart a taste, for example, chloral hydrate CI;ICCH(OH)~ is bitter, while hydrated acetone MezC(OH)~ is sliphtly sweet. Inorganic cations Na+. K+, A13+. etc.. are sweet oniy in dilute sointions or in mineral water. ~ s ~ e c i a l l y sour are metal ions and acidic oxides. Resonance Effect The range of dipolar distances for the glucophore apparently is limited to 2.8-5.4 A; beyond this point substances usually have a hitter taste. Saturated hydrocarbons are flat. Only their unsaturated and oxidized products can have a taste. Charred food stuffs are always hitter due mainly to the formation of hydrophobic conjugated unsaturated camnounds. Boiled cereals can be sweet owine to deeraded saccharides. The structures of the pyrolytFc compounds are hard to analyze. Althoueh - the aforementioned three octen01s are sweet, the two similarly conjugated hydroxy compounds with a longer resonance structure (25) are hitter.
Just as a cross conjugation is needed to break the rigid peptide bond resonance to effect a taste simulation for aspartyl anilide sweeteners, a complete conjugation of the auxogluc with the glncophore for many other types of sweeteners is also undesirable except where polymolecular stimulation can be accommodated (21,22): (1) Phyllodulcin-type (26, 27) sweeteners are very sweet, for example,
COOH
while their conjugated derivatives are tasteless.
(2) For dihydrochalcone-type (28) compounds, the partly crossconjugated one is not as sweet as the nonconjugated one.
(3) Flavanone-type (29, 30) compounds can be sweet (+), bitter (-) or both (*),
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but the flavone 14 is tasteless and rboifobn 15
The observed trend for 20-22 must be due to F(face) strain and i-BuNtH3 (&-BusNtHz)i-BuaN+H, etc. due to B(hack) strain. All neutral amino acids with less than four C atoms are sweet owing mainly to an electrostatic attraction with the sweet receptor, which is a protein composed of L-amino acids. Those with larger side alkvl or arvl chains are hitter cxtcpt the nmpr
