Tuesday, October 28, 2014

Theories of Odorant Structure-Function Relationships: The Future for Designing Fragrance Compounds?

“Perfume is decidedly not about two things: it isn’t about memory and it isn’t about sex. Perfume is about beauty and intellect. A perfume is a message in a bottle—not a smell—and the message is written by the perfumer and read by the person who smells it.”1

"I think everyone (scientist or not) at some point wonders how smell works. The Italian physicist Giorgio Careri told me that Enrico Fermi in his presence once sniffed the air while frying onions and said “wouldn’t it be nice to know how that works?” I started reading up on smell and it gradually became clear to me that there were big gaps in our knowledge, so I started thinking about it."2
-Luca Turin

Upon getting back into the Chemistry and Technology of Flavors and Fragrances text, I discovered (via Chapter 11) just how much we don't know about how to design odorants. The discovery process of flavor and fragrance molecules throughout history has been haphazard and involving a great deal of luck. The author of this section identifies one of the main methods of finding novel odorants as "Serendipity." While humorous, the fact that scientists consider this a legitimate method for finding new compounds is telling of how little we actually understand the process. It's funny to see how differently contributors to this book speak about our level of understanding of the olfactory system; in this section, internationally recognized biophysicist and perfumer Luca Turin presents two major theories - stress: theories - behind rational odorant design: vibration and shape.


In 1946, Linus Pauling suggested for the first time that the shape of molecules affected their function. This idea has proved to be critical to chemistry but when applied to the flavor and fragrance industry it doesn't always pan out. If the character of odorants relied entirely on their structure they could be designed just like pharmaceuticals. Unfortunately, it's more of a trial-and-error process. In the first place, there's a lack of understanding about the exact structure of olfactory receptors. Receptor antagonists, for example, are important in pharmacology for turning receptors "off." No odorant has been found to do this which means there's something amiss in our comprehension. The olfactory receptors must be somehow different than those that absorb drugs. Additionally, there are a number of  little contingencies like the fact that we can accurately identify functional groups no matter what the rest of the structure looks like. In every case, "rules" about structure-character relationships are broken; catalogues which have tried to place odorants into structural categories are essentially "catalogues of exceptions." 

The counter-theory is that molecules with similarities in vibrational spectra should be similarly perceived by the nose. It should be noted that Turin believed pretty ardently in this theory, even to the point of founding a company called Flexitral, Inc. based on the concept. This theory is supported by evidence of things like boranes and thiols: IR spectra shows that they exhibit the same frequency range and they also smell a lot alike. However, chemically they're completely different…so there's another mystery. Vibration theory only accounts for odorant character so the cause of varying intensity of odorants remains mysterious. Additionally, no one has proven that receptors can respond based on vibrations of molecules and the theory is essentially untested at this point. 

Both theories have their strengths and weaknesses (there's a lot more to them than what I've summarized here). It's possible that human olfaction operates through a combination of both theories, or something altogether different. What was most astounding to me about this chapter is that we understand so poorly something so commonplace yet we're crashing protons together and trying to identify the tiniest bits of matter that seem so distant from our day-to-day reality. That's certainly not to say one area of study is more important than the other, simply that there's an incredible amount that we don't know. With continued research, it's possible we'll find some of the answers right under our noses.


Ashley
1 Suhrawardi, Rebecca. "Style.com/Arabia Pulls Fragrance Legend Luca Turin As Its Fragrance Critic," The Fragrance Foundation Jan 7, 2014. Web. Accessed Oct. 28, 2014.


2 Sinatra, Nina. "Opinion: The Science of Smell; Luca Turin on the Vibration Theory of Scent," The Tech, Online Edition. Massachusetts Institute of Technology: Cambridge, Massachusetts. Apr. 23, 2010. Web. Accessed Oct. 28, 2014. 

Rowe, David J (ed.) (2005) Chemistry and Technology of Flavors and Fragrances. Blackwell Publishing: Poole. Ch.11.

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