It’s no secret that the sense of smell plays a large role in how people perceive the world, affecting everything from the taste of food to attraction. Upon casual observation, it’s not immediately obvious that the experience of a high-end perfume is somehow connected to the whirlwind of calculus and seemingly impossible ideas of quantum mechanics. However, new models and experimental evidence have once again brought new, fascinating discoveries.
The widest proposed idea of how olfaction works is the Docking theory, also called Shape Theory. The idea is that aromatic ligands fit into protein receptors in the nose that are shaped for a specific molecule, and that the intermolecular interactions of the two initiate the signal transduction pathway to the brain. Odotope theory is a subset of the Docking theory that proposes that nasal receptors only recognize parts of a molecule that are common to groups of compounds. It was proposed as a result of having only a few hundred known types of nasal receptors but humans being able to register tens of thousands of distinct odors; However, the different perceived aromas of isomers (molecules with the same composition but different arrangement of their atoms), such as vanillin and isovanillin, challenge the theory.
The modern vibration theory of olfaction was proposed by Luca Turin in a 1996 paper published by University College London. Turin suggests that olfaction uses a process similar to Inelastic Electron Tunneling Spectroscopy (IETS), which relies on two key principles: molecular vibration and electron tunneling.
The internal thermal of atoms causes them to constantly vibrate, and the bonds between atoms in a molecule also constantly vibrate, similarly to a spring connecting two balls. From Hooke’s law, it’s derived that the vibrational frequency of the bond is dependent upon the masses of the atoms in a bond, and the bond’s strength.
Electron tunneling is a quantum phenomenon in which a flowing electron can disappear from one side of a small gap or barrier and appear on the other side in a way that is impossible for classical particles. It can sort of be thought of as being able to teleport short distances. The behavior arises as a result of subatomic particles' wave behavior. However, a condition is required for tunneling. The other side of the barrier that the electron crosses must be able to hold it at the same energy level that the electron was previously. If a space for the electron is available only at a lower energy level, it can’t tunnel because there’s nowhere for the excess energy to go.
IETS exploits this limitation of electron tunneling to identify molecules. In the gap between the two metallic electrodes with different energy levels available, a molecule can be placed there. If the energy needed to vibrate one of the molecule’s resonances is equal to the difference in energy levels, then the electron can transfer its excess energy to the molecule, causing it to vibrate, and it can then tunnel to the other side.
A proposed mechanism by Turin functions similarly. NADPH supplies electrons to a receptor protein with two different available energy levels on each side of the protein’s binding site. When an odorant binds to the receptor, the electrons tunnel to the other side and flow, transferring energy to the odorant causing it to vibrate. Through a zinc ion, the electrons reduce a disulphide bridge holding a G-protein in place, causing it to break and allowing the G-protein to carry out the next step of the transduction pathway.
There exists sizable evidence for the proposed models of Vibration Theory and Turin’s mechanism. Experiments have been carried out involving compounds containing hydrogen and their deuterated counterparts, where the hydrogen in the molecules is a heavier form of hydrogen called deuterium. By Hooke’s law, altering the mass of one of the bond members alters the bond’s and therefore the molecule’s vibrational frequency and energy needed to resonate it. One test involving human subjects with benzaldehyde and benzaldehyde-d6 showed a statistically significant difference in odor perception. Similarly, experiments suggest that honey bees are able to differentiate between ACP, BNZ, OCT, and their deuterated forms. The known involvement of zinc in olfaction also suggests evidence for the occurrence of electron tunneling and electron flow in nasal receptor proteins, as zinc is known to form bridges between proteins and is present in enzymes involved in electron transfers.
While experimental evidence shows support for the Theory, there are a few known issues. Some experimental evidence has shown no significant difference in perception between molecules and their deuterated forms. Another issue is enantiomers, forms of molecules that are non-superimposable mirror images, a property known as chirality. These molecules should smell identical since their bond vibrations would be the same, but have been shown to be perceived differently. It is likely that the sense of smell lies both in shape theory and vibration theory.
The Vibration Theory of Olfaction is an intriguing idea on how living beings perceive the world around them; While it is not perfect, it shows the deep connection between the branches of science, and how science continues to evolve and fascinate.
Haffenden, L., Yaylayan, V., & Fortin, J. (2001, February 28). Investigation of vibrational theory of olfaction with variously labelled benzaldehydes. Retrieved September 13, 2020, from https://www.sciencedirect.com/science/article/abs/pii/S0308814600002879
Hoehn, R., Nichols, D., Neven, H., & Kais, S. (2018, February 28). Status of the Vibrational Theory of Olfaction. Retrieved September 13, 2020, from https://www.frontiersin.org/articles/10.3389/fphy.2018.00025/full
Muthyala, R, Butani, D, Nelson, M, & Tran, K. (2017).
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Turin, L. (1996). A Spectroscopic Mechanism for Primary Olfactory Reception. London, UK. Department of Anatomy and Developmental Biology, University College London.