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.cite web |url=http://www.nature.com/news/2006/061204/full/news061204-10.html |title=Access : Rogue theory of smell gets a boost : Nature News |accessdate=2008-04-11 |format= |work=] 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.cite journal |author=Turin L |title=A spectroscopic mechanism for primary olfactory reception |journal=Chem. Senses |volume=21 |issue=6 |pages=773–91 |year=1996 |pmid=8985605 |url=http://www.flexitral.com/research/chemical_senses_complete.pdf |doi=]

The odor character is encoded in the ratio of activities of receptors tuned to different vibration frequencies, in the same way that color is encoded in the ratio of activities of cone cell receptors tuned to different frequencies of light. Although vibration theory explains odor character, it does not explain intensity: why some odors 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 tunneling, rather than responding to molecular keys that work by shape alone.cite journal |author=Turin L |title=A spectroscopic mechanism for primary olfactory reception |journal=Chem. Senses |volume=21 |issue=6 |pages=773–91 |year=1996 |pmid=8985605 |url=http://www.flexitral.com/research/chemical_senses_complete.pdf |doi=] The theory remains controversial.

upport

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.cite journal |author=Turin L |title=A spectroscopic mechanism for primary olfactory reception |journal=Chem. Senses |volume=21 |issue=6 |pages=773–91 |year=1996 |pmid=8985605 |url=http://www.flexitral.com/research/chemical_senses_complete.pdf |doi=]

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.cite journal |author= Haffenden LJ, Yaylayan VA, Fortin J|title=Investigation of vibrational theory of olfaction with variously labelled benzaldehydes |journal=Food Chem. |volume=73 |issue=1 |pages=67–72 |year=2001|doi=10.1016/S0308-8146(00)00287-9] cite web |url=http://www.inference.phy.cam.ac.uk/mackay/smell/ |title=David MacKay: Smells: Summary |accessdate=2008-04-11 |format= |work=] In addition, tests with animals have shown fish and insects able to distinguish isotopes by smell cite journal |author=Havens BR, Melone CD |title=The application of deuterated sex pheromone mimics of the american cockroach (Periplaneta americana, L.), to the study of wright's vibrational theory of olfaction |journal=Dev. Food. Sci. |volume=37 |issue=1 |pages=497–524 |year=1995|doi=10.1016/S0167-4501(06)80176-7 |url=http://flexitral.com/research/Meloan_1995.pdf] cite journal |author=Hara J |title=Olfactory discrimination between glycine and deuterated glycine by fish |journal=Experientia |volume=33 |issue=5 |pages=618–9 |year=1977 |pmid=862794 |doi=]

Consistency with physics

Biophysical simulations published in Physical Review Letters in 2006 suggest that Turin's proposal is viable from a physics standpoint.cite journal |author=Brookes JC, Hartoutsiou F, Horsfield AP, Stoneham AM |title=Could humans recognize odor by phonon assisted tunneling? |journal=Phys. Rev. Lett. |volume=98 |issue=3 |pages=038101 |year=2007 |pmid=17358733 |doi=] cite web |url=http://www.sciencedaily.com/releases/2007/02/070204162541.htm |title=Rogue Odour Theory Could Be Right |accessdate=2008-04-11 |format= |work=]

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.cite journal |author=Takane SY, Mitchell JB |title=A structure-odour relationship study using EVA descriptors and hierarchical clustering |journal=Org. Biomol. Chem. |volume=2 |issue=22 |pages=3250–5 |year=2004 |pmid=15534702 |doi=10.1039/B409802A]

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 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 until 2004. A japanese research group published that an oxidation product of eugenol is able to antagonize, i.e. prevent, the smell of eugenol.cite journal |author=Oka Y, Nakamura A, Watanabe H, Touhara K |title=An odorant derivative as an antagonist for an olfactory receptor |journal=Chem. Senses |volume=29 |issue=9 |pages=815–22 |year=2004 |pmid=15574817 |doi=10.1093/chemse/bjh247]

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 sulfur 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 untrained human subjects unable to distinguish acetophenone from its deuterated counterpart.cite journal |author=Brookes JC, Hartoutsiou F, Horsfield AP, Stoneham AM |title=Could humans recognize odor by phonon assisted tunneling? |journal=Phys. Rev. Lett. |volume=98 |issue=3 |pages=038101 |year=2007 |pmid=17358733 |doi=] cite journal |author= |title=Testing a radical theory |journal=Nat. Neurosci. |volume=7 |issue=4 |pages=315 |year=2004 |pmid=15048113 |doi=10.1038/nn0404-315] cite web |url=http://www.sciencedaily.com/releases/2007/02/070204162541.htm |title=Rogue Odour Theory Could Be Right |accessdate=2008-04-11 |format= |work=] 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 guaiacol 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.

References

*
*Flexitral website [http://flexitral.com]
* [http://www.rockefeller.edu/pubinfo/news_notes/rus_032604_b.php Newsletter report] , Rockefeller University Scientist.
*Zyga, Lisa. Quantum mechanics may explain how humans smell. "PhysOrg.com" (2007). [http://www.physorg.com/news89542035.html]