I recently finished reading Luca Turin’s The Secret of Scent, and wanted to get my thoughts down before they faded to nonexistence. The book is very compelling, being that the subject matter is about human olfaction. The mechanism of how humans and other animals detect odor is still up for grabs, and there are several competing theories, such as the “lock-and-key” mechanism, or shape-based detection. The author’s central thesis is that the nose operates through a mechanism known as quantum electron tunneling, and he gives a detailed history of the development of the theory. The book is aimed at laymen, and is written for a nonscientific audience. As a chemist, I was very impressed by Turin’s coverage of the basics of organic chemistry, given that all the popular fragrance molecules in use today are small organic molecules! It is noteworthy that Turin is not an organic chemist by training; he got his PhD in biophysics. Turin posits that the odor of molecules as detected by the nose can be correlated with their IR (infrared) frequencies, and one of the biggest pieces of evidence he describes is the similarity of the smell of decaborane and thiols (B-H and S-H bonds both have IR frequencies around 2500 cm-1). Any organic chemist will be all too familiar with the vile smell of divalent sulfur compounds, such as H2S, thiols, thiolate salts, disulfides, and sulfides. However, the moment the sulfur is oxidized, the smell vanishes. Sulfoxides and sulfones do not smell bad at all. Recently, I have been working with aryl-SF5 compounds as part of my graduate research work, and those smell very pleasant, often reminiscent of their -CF3 analoges! Thus, according to Turin’s theory, they should have similar IR frequencies, which I am unfortunately too lazy to look up.
Turin explains that deuterated and non-deuterated molecules smell different when properly purified (by GC methods) and that the smell can be distinguished by trained individuals (he writes about his attempt to demonstrate this with acetophenone and acetophenone-d8). This is due to the isotope effect, which is most pronounced with D-H substitution, since deuterium is twice the mass of protium.
He also attempts to explain the difference in odor between the enantiomers of carvone, suggesting that the C=O stretch in one enantiomer may not be detected as well as other (which is entirely feasible when one considers that molecules in the nose are detected in a protein receptor, which is an inherently chiral environment). His experiment to prove this theory involves mixing simple ketones (such as acetone or MEK) and one enantiomer of carvone to see if the smell matches the other.
The above experiments call for reproduction by interested individuals, and it is noteworthy that Dr. Turin has wriiten about these experiments in detail in a book intended for laymen. His passion for the subject shines through every paragraph in the book.
That being said, here’s another shameless plug (for fluorine and fluorine chemistry). Selective fluorination may be another way to intelligently design new fragance molecules. While it is known that C-F bonds, due to their inherent polarity, are stronger than C-H bonds (and thus vibrate differently), organofluorine compounds are also often more volatile than their nonfluorinated counterparts. This could be useful for designing new “headnote” fragrances, which are the smells one initially detects when applying perfume; they only last for a few minutes or so.