Mentioning the C. S. Sell article on odors and molecules the other day leads me to talk about Luca Turin. I don't think you can seriously take up the topic of chemicals and their smells without mentioning him, although those mentions tend to be anything but neutral.
Turin is (in)famous for suggesting that there's more to smell than molecular shapes and functional groups. He has an impressive list of structures that provide almost the same scent, but have very different shapes, along with a complementary set of nearly identical molecules with very different ones. These, along with several other arguments (vide infra) have led him to propose that the human body responds not only to shapes, but to vibrational spectra. Your nose, by this theory, is smelling the infrared spectra of the molecules that reach it.
This isn't a new idea - it was first proposed in 1938, and again in the early 1980s. Both times it was shot down, though, primarily by counterexamples such as enantiomeric molecules (mirror-image, for the non-chemists) which smell different while having identical vibrational spectra. Another problem was that no one could figure out how an olfactory receptor could be sensing vibrational spectra, since, to the best of human knowledge, the majority of noses contain neither a source nor detector of infrared light.
Luca proposed that electron tunnelling might provide the answer, and took a cue from solid state electronics. If the receptor was senstive to electron flow, it could function as a switch. An unoccupied receptor would have no current, but if a molecule whose vibrational mode energy was the same as the energy gap between its filled and unfilled levels, then electrons could drop to the lower state by tunnelling across. The receptors wouldn't scan the range themselves - rather, each one would be tuned to a different energy gap. Whether or not a given molecule worked for a given receptor would depend on its size and shape (to fit into the active site) but also on its charge distribution (and thus its functional groups) and its vibrational spectrum. The most complete published version of his theory can be found here.
In 2003, a book came out extolling Luca's work: The Emperor of Scent. It goes into detail about how the vibrational theory was received, which was mostly with great scepticism. Reviews of the book itself were all over the place, from enthusiastic to vitriolic. In that last category was the one from Nature Neuroscience (subscriber link here). The author, Chandler Burr, must have known that he was going to be in for a rough time when the reviewer started things off by quoting "Good Vibrations" by the Beach Boys.
I'll say this for the idea: this theory is well-made, because it's wide-ranging enough to accommodate a lot of the puzzling data about chemical odors, while at the same time making some specific predictions. Counterexamples can be found to just about any simple theory of odor, but this one is harder to get rid of. Not that people haven't tried, though. In 2004, a group at Rockefeller University reported some tests of Luca's predictions in Nature Neuroscience, a journal that must have been happy to see their manuscript. Three of his proposals took a good pounding: that mixtures of guiacol and benzaldehyde take on a vanilla odor not found in either compound alone, that straight-chain aldehydes with an odd number of carbons smell different from even-numbered ones, and that deuterated acetophenone smells different from the parent compound. The group reported failure on all three counts. The accompanying editorial was especially nasty, and to my mind, rather uncalled-for.
Turin has addressed some of these results, and it can be inferred that he didn't care for the Rockefeller group's experimental design. (He's partnered with a British statistician to analyze past data in the field and propose new designs for such tests). It does seem though, from the available data, that many animals from insects to dogs can in fact distinguish deuterated compounds from their lighter analogs. Turin's also proposed deuterated/nondeutreated dimethyl sulfide as a more distinguishable pair of compounds (see this long but interesting review article). That one's from 2003, before the latest results, but even at that point he's pointing out that vibrational theory, taken by itself, can't explain many important things about odors (such as their perceived intensity). At the same time, though, he maintains that the standard "odotope" theory is even more lacking.
Turin has now come out with a book of his own, which is getting better treatment from the scientific press so far (here's the Science review for subscribers). He's also put his money where his, er, nose is by forming his own company, Flexitral, with the intention of finding new odorants more efficiently. So far, the company has several commercial products, which are claimed to be improvements over the existing analogs in stability and allergenicity.
As for me, I'm willing to believe that vibrational spectra might be a component of odor, although shape is clearly a factor, too. But I'm betting that downstream neural processing will be just as large an influence, if not greater. For now, I'm going to see if I can get some deuterated dimethyl sulfide, and if I do, I'll report back.