Molecular Vibration-Sensing Component in Human Olfaction

Abstract

Whether olfaction recognizes odorants by their shape, their molecular vibrations, or both remains an open and controversial question. A convenient way to address it is to test for odor character differences between deuterated and undeuterated odorant isotopomers, since these have identical ground-state conformations but different vibrational modes. In a previous paper (Franco et al. (2011) Proc Natl Acad Sci USA 108:9, 3797-802) we showed that fruit flies can recognize the presence of deuterium in odorants by a vibrational mechanism. Here we address the question of whether humans too can distinguish deuterated and undeuterated odorants. A previous report (Keller and Vosshall (2004) Nat Neurosci 7:4, 337-8) indicated that naive subjects are incapable of distinguishing acetophenone and d-8 acetophenone. Here we confirm and extend those results to trained subjects and gas-chromatography [GC]-pure odorants. However, we also show that subjects easily distinguish deuterated and undeuterated musk odorants purified to GC-pure standard. These results are consistent with a vibrational component in human olfaction.

Implausibility of the vibrational theory of olfaction

“…Gane et al (14) have framed the argument for olfactory discrimination of hydrogen isotopomers as one of "shape" vs. "vibration."…”

“…For example, benzaldehyde is converted to benzoic acid (32), a reaction potentially subject to significant primary isotope effects (2,33,34), which could explain the difference in odor perception for the benzaldehyde isotopomers. Earlier claims that human subjects can distinguish odors of acetophenone isotopomers (9,35) have been shown to be untrue (14,31). Recent studies indicate that Drosophila melanogaster can distinguish acetophenone isotopomers (36,37) and that Apis mellifera L., the honey bee, can be trained to discriminate pairs of isotopomers (38).…”

“…In 1996-1997, Turin (9-12) elaborated on the undulatory theory of smell, as considered in more detail below, and suggested that a mechanism analogous to inelastic electron tunneling spectroscopy (13) may be involved, where tunneling electrons in the receptor probe the vibrational frequencies of odorants. In 2013, Gane et al (14) commented that "whether olfaction recognizes odorants by their shape, their molecular vibrations, or both remains an open and controversial question" and that "a convenient way to address [this question] is to test for odor character differences between deuterated and nondeuterated odorant isotopomers since these have identical ground-state conformations but different vibrational modes." Gane et al (14) also stated that a particularly appropriate test case would involve odorants containing "more CH group.…”

Dissipation enhanced vibrational sensing in an olfactory molecular switch

“…In fact, obtaining a deeper understanding of olfaction, the mechanism for which is still being actively debated, [21][22][23][24][25][26][27][28][29][30] is an important problem in its own right for both fundamental science and industry. [31][32][33][34][35] The prevailing theory, known as the lock-and-key model, explains how the odorant size and shape can provide discrimination in the receptor.…”

“…may be possible to distinguish the scents of some very similar odorants, for example between those that are deuterated and non-deuterated. 26,30,37 It was suggested as early as 1938 that the sensing of vibrational spectra of molecules [38][39][40] -later proposed to occur via electron transfer 21,22 -could play an important role in olfaction, supplementing (rather than replacing) the existing lockand-key model. Recent work, focussing on constructing and exploring model systems that capture the important physical processes, 24,27 has shown that this is indeed a viable proposition.…”