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How We Smell Those Delightful Little Sulfur Compounds

We humans have a huge number of different smell receptors, but some of the most famous are the ones that are sensitive to thiols. We don’t miss out on many low oxidation state sulfur compounds: S-alkyl and SH groups reek to the skies as far as our noses are concerned (as do the corresponding selenium compounds). One classic example is ethanol versus ethanethiol, SH for OH on a two-carbon chain. Ethanol smells quite pleasant, even for those of us who don’t drink it, but ethanethiol is something else again. It’s the prototype Sulfur Smell, sort of like what you’d get if someone tried to extinguish a smoldering tractor tire by dumping dead skunks on it. A lot of the lower-molecular-weight thiols fall somewhere on that burning rubber/angry skunk axis, but other delightful notes creep in as well (Major Spill at the Garlic Factory. . .Ah, That’s Why People Don’t Make Hard-Boiled Eggs By Grilling Them In Their Shells. . .Who Left All This Shredded Cabbage Under This Tarp. . .I’ve Eaten Nothing But Raw Broccoli and Green Onions For Six Days Now. . .that sort of thing). Once in a while this can also show up as a drug side effect and there’s not much to be done.

We’ve developed our insane sensitivity to these compounds – the human nose can detect ethanethiol at levels at least one hundred million times lower than we can ethanol, and this effect is used deliberately so that we can smell natural gas leaks. Sulfur compounds like these are the smell of things that will kill us – rotten food, dangerous vapors, probably carnivore excretion/body odors as well. Evolutionarily, there’s clearly been a very strong selection pressure away from such substances, and we’re descended from a long, long time of creatures that put time and effort into avoiding them. But how does that sensitivity work?

This new paper has an interesting answer: copper atoms. Robert Crabtree had proposed this mechanism years ago, and it appears that he’s right. The OR2T11 receptor, known to be sensitive to short-chain thiols, seems to have a very pronounced dependence on copper for it to work at all. A close look at its structure shows two very likely metal binding sites near its receptor pocket as well, and NMR experimental results are consistent with the mechanism. Not all the thiol receptors show this copper effect (human odor sensing is very complex), but this one certainly does.

25 comments on “How We Smell Those Delightful Little Sulfur Compounds”

  1. Jeff says:

    Of course you would post this the very morning our neighborhood skunk family had a block party under our bedroom window at 3am…

  2. Curious Wavefunction says:

    Didn’t Luca Turin’s vibrational theory of smell also posit the presence of a metalloenzyme?

  3. anonymous says:

    If copper had an important role to play may be then the key experiment to do was “EDTA complexation” of copper followed by olfactory response to thiols? May be it is easier suggested than actually to carry out these and other suggestions when it comes olfactory science.

    1. loupgarous says:

      Complexation of copper by in vivo chelation is a risky business, not just because copper’s a trace nutrient, but because you’d probably have complexed more vital trace metals such as zinc and iron on the way to getting enough copper out of the system under study (I hope to God no IRB would sign off on a study like that in humans just to indulge curiosity as to whether we need copper to smell thiols) to damage the organism at least temporarily.

      Like the early animal studies of tranquilizers, you’d have your work cut out just determining how to measure what an animal smells and how much of it they smell. I’m thinking instrumentation of olfactory nerves to measure response would be involved, and a modern IRB might not think the knowledge would be worth the pain to the animal.

  4. Barry says:

    I’ve never understood the vibrational theory. Wouldn’t it predict that replacing hydrogen with deuterium on a small molecule would change its smell? It certainly changes its vibrational modes/IR spectrum.

    1. Mr. Eldritch says:

      You’re correct that the vibrational theory of smell predicts that deuterated compounds would smell different from non-deuterated compounds; its proponents claim that they actually *do*, and that this is evidence for the vibrational theory.

      1. peptoid says:

        Hmm, never come across that theory myself before, but to my nose our deuterated methanol smells somewhat stronger and more ‘fruity’ than our regular stuff…

    2. TWS says:

      Always been a bit dubious about that theory as well – I’ve some experience with IR absorption spectroscopy of H2S gas (and gas phase complexes of it) and I have to say it is a really awful IR absorber (one of the many ways it’s so vastly different to its lighter, O-based analogue beside the awful smell, toxicity, low melting and boiling points etc.). The other low molecular weight thiols have similarly weak S-H absorptions, although less weak than H2S.

      Of course, binding to some hypothetical ‘vibrational olfactory receptor’ could enhance the oscillator strength I suppose, and of course there is no reason why IR absorption strength should correlate to a ‘smell strength’, but I suppose it’s always made me a bit suspicious.

  5. Anon says:

    Are there any well-known and available agents which can effectively mask sulfur/thiol smells? Does activate charcoal work on thiols? How would they react?

    1. b says:

      My grad school group worked with a lot of sulfides/thiols, and we had a group-wide established “stench technique”. Almost nothing ever left the hood after handling them, and anything that did had better have seen a good dose of bleach, or you were in big trouble with those around you.

      1. ShPh says:

        I have a theory that exposure to thiolphenols can lead to autism like symptoms. I’ll try to find the paper.

    2. CMCguy says:

      Having previously a dog who appaerntly liked playing with neighborhood skunks (usually at 3AM no less) we obtained a recipe as partial remediation that worked well: Hydrogen Peroxide, Baking soda and Dawn Liq detergent made a paste/syrup and rub in well, the a thorough rinse, possibly repeat. We learned the hard way not to first try to bath the dog which only set the smell and made subsequent treatment less effective. It did a good job overall however is hard to totally eliminate the smell with lingering hits from transfers to towels and even persons doing the job (which got the treatment alos). Even a few days afterwards if the dog laid in the sun a while then walked past the odor would be faintly noted.

      1. John Wayne says:

        Here is the scene: we have guests over and I come back in from the back yard holding the dog by the collar. “Do we smell like skunk?” Everybody in the room nods. “Okay, I wasn’t sure if she got hit. Sweetie (to my wife), please bring all the dish soap, baking soda and peroxide.” I lead to dog into the bathroom and out the door flies the following: the bath mats, the towels, some bag left in there, the cloth shower curtain, and all my clothes. Worked awesome; sometimes, it is good to be a chemist.

        If you have to do this yourself, you really can’t use too much dish soap; I used almost a whole bottle on a 50 lb dog.

  6. Anon says:

    So why do my socks smell so bad?

    1. Ed says:

      Butyric acid mostly.

    2. Some idiot says:

      Not long enough in the bleach (my personal experience (of my socks, not yours…) )

      1. Falanx says:

        Which destroys cotton fibres over time, though…

  7. MTK says:

    Isn’t there a story of Gilbert Stork spilling some dithiane on a pair of pants he was wearing as he walked through the lab one day. He decided that oxidizing the dithiane using the lab’s ozone generator was the way to destink them. Later that day he was at a meeting and the pants began to go to tatters on him.

    I’m sure the whole thing is apocryphal, but who cares? It’s funny.

    1. Milkshake says:

      unsubstituted 1,3-dithiane in diluted form smells almost pleasant, with piercing terpenic odor, rather similar to thiophosgene… Also trisulfane HSSSH is supposed to smell nicely – in pure, very diluted form.

      1. Nick K says:

        I was told many years ago that one of the main components of roast chicken aroma is dimethyl trisulfide.

  8. steve says:

    I wonder what the copper content is of beans after they’ve gone through the digestive tract. Though none of them are chemists, my family seems to think that I become a thiol generator.

    1. HONClBrIF says:

      Bismuth subsalicylate causes dark colored stool because it precipitates bismuth sulfide in the GI tract. May be possible to head stinky farts off at the pass by taking a large dose of Pepto after a windy meal by locking them up in the solid phase.

  9. Digitalis says:

    Apparently, there is a rather inventive use for smelly compounds:

  10. Barry says:

    I wonder if those coppers are involved in the particularly awful smell of trimethylphosphine, too

  11. Oblarg says:

    I’m not sure I’d say that ethanol smells quite pleasant, and this is as someone who does, indeed, occasionally drink it (certainly not for flavor, however).

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