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More VSC Voodoo

OK, it’s been a few years since I blogged about this particular weirdness, so let’s do some more. There have been a couple more recent reports of the effects of “vibrational strong coupling” on chemical reaction rates. What the heck is that? There’s some background in that link, but we can hand-wave our way through by saying that under certain conditions you can form what would have to be called hybrid states of light and matter (“polaritons”). These conditions obtain, for example, with molecules that have particularly strong IR absorption bands, when at high concentration inside a very small cavity that confines light to particular wavelengths. It’s a quantum mechanical effect and has been observed and validated many times by experiment in simple model systems. But we’re only in recent years finding ourselves able to apply such effects to organic molecules.

Here’s one from last fall, showing enzyme rate changes under the influence of strong coupling of water vibrational modes. The model system was pepsin, where a water molecule is involved in the enzyme’s active site. Coupling of OH stretching band, a whopper familiar to anyone who’s ever taken an IR spectrum, decreased the rate constant by nearly five-fold, whereas strong coupling to the bending vibrational mode had no effect. The mechanistic basis for this difference is frankly not clear: there’s something about the detailed mechanism of water in that active site that can distinguish these effects, and it’s hard to imagine another analytical technique that would have revealed it.

And here’s a paper that just came out on the Prins reaction, familiar to most synthetic organic chemists. It’s certainly familiar to me! In this case, as in the water one above, running the reaction under conditions of vibrational strong coupling to the carbonyl stretching vibration slow down the reaction rate by up to 70%. The rate change follows the amount of VSC very closely; you can actually scan along the CO absorption band wavenumber by wavenumber and see it max out right where the absorption does.

As the authors say, “While broadly attributed to the re-shaping of the reaction potential energy landscape by hybrid light-matter states, a clear picture of the effect of VSC on organic chemistry is still lacking.” Given the mechanism of the Prins, the slower rate is what you would expect if you had somehow made the carbonyl bond less polar than before (less of a positive charge on the carbonyl carbon). It’s interesting that the earlier example linked in the first paragraph, the deprotection of TMS-acetylene, also involved a slowdown of the reaction rate, and that also could (in theory) be ascribed to making the C-Si bond less polar. In both cases, there’s no evidence of a larger change in the mechanistic pathway, just a weird tuning of the one that’s already in effect.

This work, for now, has no practical application whatsoever. But it represents a tool for both changing reaction dynamics and investigating reaction mechanisms that we’ve never really investigated before. I’ve always had a weakness for physical organic chemistry (as my old grad school professor Ned Arnett figured out when I took his course at Duke), a weakness that fortunately rarely extends so far as actually wanting to do any of it in the lab. But I’m a big fan of the stuff from afar, and I will be interested to see what comes of VSC.

18 comments on “More VSC Voodoo”

  1. Adrian Roitberg says:

    Interesting… Can you link to the Prins paper please ?

    1. Derek Lowe says:

      Whoops. Link added – thanks!

  2. Thoryke says:

    Oh, please keep the home0pathy folks from running mad with this! Anything that mentions vibrations and water seems to attract them…

    1. Vader says:

      See, this is why we can’t have nice things.

  3. David Gooden says:

    Ned…..a true rock star in physical organic chemistry. 21 years ago I was tutoring an undergrad in Gross Chem and he happened to walk across the lobby. i had a copy of March and i quickly turned to all of the entries for his name in the back of the book. i said to the student “look that’s this guy”. the intended effect was not observed. he is still around. I don’t see him in the department anymore but he does show up in emails from time to time.

    1. tally ho says:

      Glad to hear that Ned is still kickin’ – he was old school before there was was old school. It’s sad that fundamental physical organic chemistry is no longer fashionable nor fundable, even though it’s as important as ever to drug design.

  4. John says:

    I’m incredibly sorry to ask an unrelated question, but I’m having trouble finding answers to this.
    What would I need to do to safely store about a pint of 99% isopropyl alcohol in a dorm room? Do I need a fire safety cabinet, just a dark drawer, or what? Thank you.

    1. DCM says:

      I hope you’re behind 7 proxies because I’m tracking your IP address and reporting you to your RA!!

    2. Fire Marshall says:

      this is NOT a joke – at that high of a concentration you are highly likely to form dangerous explosive peroxides. If it has ever been exposed to air in any form then you need to call the fire department and pull the fire alarm to immediately evacuate your dorm.

      This is not a joke, I hope you have learned your lesson.

      1. doc says:

        Nonsense. Here’s the MSDS.

        http://websites.retailcatalog.us/1424/mm/isopropyl-alcohol.pdf

        OP: store cool and away from flame.A pint or so would probably give any dorm RA absolute fits. Even though it’s not materially more dangerous than a bottle of high test white lightnin’. Use a safety cabinet if you’d store your booze in one as well.

    3. loupgarous says:

      If it was absolute undenatured ethanol, sharing with your RA in a 1:3 solution with Coca-Cola couldn’t hurt (A friend of mine with access to her lab’s science stores account had decent success with this)

      But with 99% IPA? Only if you really hate the guy.

    4. Derek Freyberg says:

      A bottle.
      Seriously, you can buy pints of 90% isopropyl alcohol at Safeway (or your pharmacy of choice); I can’t imagine 99% is any different.
      It’ll burn if given the chance, but your medicine cabinet is just fine for storage.

  5. Morten says:

    Layman here, possibly with a noob question: could this be used to impede the formation of selected byproducts, or is it far too non-specific for that?

    1. Steve says:

      This occurred to me too. It might be possible if say there were two sites on a molecule that could react (say reduction of a ketone vs an ester) – it might be able to slow the ketone reduction so the ester react first (though would need more than a 60% reduction)

    2. Derek Lowe says:

      Depends on what sorts of functional groups are involved, and what their IR absorptions are. I think in same cases you might be able to do that, but whether or not it can ever be useful in any sort of preparative way, well, that’s another question. . .

  6. A spurious connection I know, but: Hey! Luca Turin is right!

    1. Ian Malone says:

      I have no idea whether Turin is right or not (about the molecular vibrational basis of scent), but I have a feeling people who enjoy the occasional humour in Derek’s writing might also find Turin and Sanchez’s book “Perfumes The A-Z Guide” entertaining…

      On Chanel no. 22:
      “No. 22 is above all an exercise in heavy lifting. Aldehydes are said to give “lift” to a fragrance, meaning they offset the sweetness and heaviness of whatever else is in there. Like its Antonov namesake, Chanel’s 22 goes for the maximum-payload record as follows: (1) Determine the largest dose of aldehydes a human can stand without fainting. (2) Load it up with as much sweetness as the aldehydes can bear. (3) Round it off with a note of iris to make it look easy. (4) Stand back and watch the whole thing lumber off into the sky after a three-mile takeoff roll. LT”

      1. eub says:

        Like its Antonov namesake

        I am amused.

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