This controversial theory is an alternative to the more widely accepted docking theory of olfaction (formerly termed the shape theory of olfaction), which proposes that a molecule's smell character is due to a range of weak non-covalent interactions between its protein odorant receptor (found in the nasal epithelium), such as electrostatic and Van der Waals interactions as well as H-bonding, dipole attraction, pi-stacking, metal ion, Cation–pi interaction, and hydrophobic effects, in addition to the molecule's conformation.
benzaldehyde, that gives the same scent to both almonds and/or cyanide), the shape "lock and key" model is not quite sufficient to explain what is going on.
[10] A PNAS paper in 2011 by Turin, Efthimios Skoulakis, and colleagues at MIT and the Alexander Fleming Biomedical Sciences Research Center reported fly behavioral experiments consistent with a vibrational theory of smell.
[3][12][13][14][15][16][17][18] 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.
Such isotope effects are exceedingly common, and so it is well known that deuterium substitution will indeed change the binding constants of molecules to protein receptors.
When these trained flies were then presented with a completely new and unrelated choice of normal vs. deuterated odorants, they avoided or preferred deuterium as with the previous pair.
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.
[21] The study failed to support the prediction that isotopes should smell different, with untrained human subjects unable to distinguish acetophenone from its deuterated counterpart.
[19] 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.
[36] Bill Hansson, an insect olfaction specialist, raised the question of whether deuterium could affect hydrogen bonds between the odorant and receptor.
[37] In 2013, Turin and coworkers confirmed Vosshall and Keller's experiments showing that even trained human subjects were unable to distinguish acetophenone from its deuterated counterpart.
To account for the different results seen with acetophenone and cyclopentadecanone, Turin and coworkers assert that "there must be many C-H bonds before they are detectable by smell.
This results in more than 3 times the number of vibrational modes involving hydrogens than in acetophenone, and this is likely essential for detecting the difference between isotopomers.
Vosshall, in commenting on Turin's work, notes that "the olfactory membranes are loaded with enzymes that can metabolise odorants, changing their chemical identity and perceived odour.
Ultimately, any attempt to prove the vibrational theory of olfaction should concentrate on actual mechanisms at the level of the receptor, not on indirect psychophysical testing.
The authors conclude: "These and other concerns about electron transfer at olfactory receptors, together with our extensive experimental data, argue against the plausibility of the vibration theory."
In commenting on this work, Vosshall writes "In PNAS, Block et al.... shift the "shape vs. vibration" debate from olfactory psychophysics to the biophysics of the ORs themselves.
[42] Recently, Saberi and Allaei have suggested that a functional relationship exists between molecular volume and the olfactory neural response.