Vibration theory of olfaction

The Vibration theory of smell proposes that a molecule's smell character is due to its vibrational frequency in the infrared range. The theory is opposed to the more widely accepted shape theory of olfaction, which proposes that a molecule's smell character is due to its shape.

Introduction
The current vibration theory has recently been called the "swipe card" model, in contrast with "lock and key" models based on shape theory. As proposed by Luca Turin, the odorant molecule must first fit in the receptor's binding site. Then it must have a vibrational energy mode compatible with the difference in energies between two energy levels on the receptor, so electrons can travel through the molecule via inelastic electron tunneling, triggering the signal transduction pathway.

The odour character is encoded in the ratio of activities of receptors tuned to different vibration frequencies, in the same way that colour is encoded in the ratio of activities of cone cell receptors tuned to different frequencies of light. Although vibration theory explains odour character, it does not explain intensity: why some odours are stronger than others at the same concentrations.

Some studies support vibration theory while others challenge its findings.

Major proponents and history
The theory was first proposed by Malcolm Dyson in 1937 and expanded by Robert H. Wright in 1954, after which it was largely abandoned in favor of the competing shape theory. A 1996 paper by Turin revived the theory by proposing a mechanism, speculating that the G-protein-coupled receptors discovered by Linda Buck and Richard Axel were actually measuring molecular vibrations using inelastic electron tunnelling, rather than responding to molecular keys that work by shape alone. The theory remains controversial.

Explaining differences in stereoisomer scents
Carvone presented a perplexing situation to vibration theory. Carvone has two isomers, which have identical vibrations, yet one smells like mint and the other like caraway (for which the compound is named).

An experiment by Turin filmed by the BBC Horizon documentary "A Code in the Nose" consisted of mixing the mint isomer with butanone, on the theory that the shape of the G-protein-coupled receptor prevented the carbonyl group in the mint isomer from being detected by the "biological spectroscope". The experiment succeeded with the trained perfumers used as subjects, who perceived that a mixture of 60% butanone and 40% mint carvone smelled like caraway.

The sulfurous smell of boranes
According to Turin's original paper in the journal Chemical Senses, the well documented smell of borane compounds is intensely sulfurous, though these molecules contain no sulfur. He proposes to explain this by the similarity in frequency between the vibration of the B-H bond and the S-H bond.

Isotope effects
A major prediction of Turin's theory is the isotope effect: that the normal and deuterated versions of a compound should smell different, although they have the same shape. A 2001 study by Haffenden et al showed humans able to distinguish benzaldehyde from its deuterated version. In addition, tests with animals have shown fish and insects able to distinguish isotopes by smell.

Consistency with physics
Biophysical simulations published in Physical Review Letters in 2006 suggest that Turin's proposal is viable from a physics standpoint.

Correlating odor to vibration
A 2004 paper published in the journal Organic Biomolecular Chemistry by Takane and Mitchell shows that odor descriptions in the olfaction literature correlate more strongly with vibrational frequency than with molecular shape.

Lack of antagonists
Turin points out that traditional lock-and-key receptor interactions deal with agonists, which increase the receptor's time spent in the active state, and antagonists, which increase the time spent in the inactive state. In other words, some ligands tend to turn the receptor on and and some tend to turn it off. As an argument against the traditional lock-and-key theory of smell, no olfactory antagonists have yet been found.

Additional challenges to shape theory

 * Similarly shaped molecules with different molecular vibrations have different smells (metallocene experiment and deuterium replacement of molecular hydrogen)
 * Differently shaped molecules with similar molecular vibrations have similar smells (replacement of carbon double bonds by sulphur atoms and the disparate shaped amber odorants)
 * Hiding functional groups does not hide the group's characteristic odor

Challenges to vibration theory
Three predictions by Luca Turin on the nature of smell, using concepts of vibration theory, were addressed by experimental tests published in Nature Neuroscience in 2004 by Vosshall and Keller. The study failed to support the prediction that isotopes should smell different, with human subjects unable to distinguish acetophenone and its deuterated counterpart. In addition, Turin's description of the odor of long-chain aldehydes as alternately (1) dominantly waxy and faintly citrus and (2) dominantly citrus and faintly waxy was not supported by tests on untrained subjects, despite anecdotal support from fragrance industry professionals who work regularly with these materials. Vosshall and Keller also presented a mixture of guiacol and benzaldehyde to subjects, to test Turin's theory that the mixture should smell of vanillin. Vosshall and Keller's data did not support Turin's prediction.