Support Vibration theory of olfaction

1 support

1.1 isotope effects
1.2 explaining differences in stereoisomer scents
1.3 sulfurous smell of boranes
1.4 consistency physics
1.5 correlating odor vibration
1.6 lack of antagonists
1.7 additional challenges shape theory

support
isotope effects

a major prediction of turin s theory isotope effect: normal , deuterated versions of compound should smell different, although have same shape. 2001 study haffenden et al. showed humans able distinguish benzaldehyde deuterated version. however, study has been criticized lacking double-blind controls eliminate bias , because used anomalous version of duo-trio test. in addition, tests animals have shown fish , insects able distinguish isotopes smell.

it should noted, however, deuteration changes heats of adsorption , boiling , freezing points of molecules (boiling points: 100.0 °c h2o vs. 101.42 °c d2o; melting points: 0.0 °c h2o, 3.82 °c d2o), pka (i.e., dissociation constant: 9.71×10 h2o vs. 1.95×10 d2o, cf. heavy water) , strength of hydrogen bonding. such isotope effects exceedingly common, , known deuterium substitution indeed change binding constants of molecules protein receptors. binding interaction of odorant molecule olfactory receptor therefore show isotope effect upon deuteration, , observation of isotope effect in no way argues exclusively vibrational theory of olfaction.

a study published in 2011 franco, turin, mershin , skoulakis shows both flies can smell deuterium, , flies, carbon-deuterium bond smells nitrile, has similar vibration. study reports drosophila melanogaster (fruit fly), ordinarily attracted acetophenone, spontaneously dislikes deuterated acetophenone. dislike increases number of deuteriums. (flies genetically altered lack smell receptors not tell difference.) flies trained electric shocks either avoid deuterated molecule or prefer normal one. when these trained flies presented new , unrelated choice of normal vs. deuterated odorants, avoided or preferred deuterium previous pair. suggested flies able smell deuterium regardless of rest of molecule. determine whether deuterium smell due vibrations of carbon-deuterium (c-d) bond or unforeseen effect of isotopes, researchers looked nitriles, have similar vibration c-d bond. flies trained avoid deuterium , asked choose between nitrile , non-nitrile counterpart did avoid nitrile, lending support idea flies smelling vibrations. further isotope smell studies under way in fruit flies , dogs.

explaining differences in stereoisomer scents

carvone presented perplexing situation vibration theory. carvone has 2 isomers, have identical vibrations, yet 1 smells mint , other caraway (for compound named).

an experiment turin filmed 1995 bbc horizon documentary code in nose consisted of mixing mint isomer butanone, on theory shape of g-protein-coupled receptor prevented carbonyl group in mint isomer being detected biological spectroscope . experiment succeeded trained perfumers used subjects, perceived mixture of 60% butanone , 40% mint carvone smelled caraway.

the sulfurous smell of boranes

according turin s original paper in journal chemical senses, documented smell of borane compounds intensely sulfurous, though these molecules contain no sulfur. proposes explain similarity in frequency between vibration of b-h bond , s-h bond.

consistency physics

biophysical simulations published in physical review letters in 2006 suggest turin s proposal viable physics standpoint. however, block et al. in 2015 paper in proceedings of national academy of sciences indicate theoretical analysis shows proposed electron transfer mechanism of vibrational frequencies of odorants suppressed quantum effects of nonodorant molecular vibrational modes .

correlating odor vibration

a 2004 paper published in journal organic biomolecular chemistry takane , mitchell shows odor descriptions in olfaction literature correlate eva descriptors, loosely correspond vibrational spectrum, better descriptors based on 2 dimensional connectivity of molecule. study did not consider molecular shape.

lack of antagonists

turin points out traditional lock-and-key receptor interactions deal agonists, increase receptor s time spent in active state, , antagonists, increase time spent in inactive state. in other words, ligands tend turn receptor on , tend turn off. argument against traditional lock-and-key theory of smell, no olfactory antagonists have yet been found until recently.

in 2004, japanese research group published oxidation product of isoeugenol able antagonize, or prevent, mice olfactory receptor response isoeugenol.

additional challenges shape theory

similarly shaped molecules different molecular vibrations have different smells (metallocene experiment , deuterium replacement of molecular hydrogen). challenge contrary results obtained silicon analogues of bourgeonal , lilial, despite differences in molecular vibrations have similar smells , activate responsive human receptor, hor17-4, , studies showing human musk receptor or5an1 responds identically deuterated , non-deuterated musks.
differently shaped molecules similar molecular vibrations have similar smells (replacement of carbon double bonds sulfur atoms , disparate shaped amber odorants)
hiding functional groups not hide group s characteristic odor. not case, since ortho-substituted arylisonitriles , thiophenols have far less offensive odors parent compounds.




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