Wednesday, January 30, 2013

Nitration Surprise

(File under "Learn something new every day")

Boom goes the peptide!

For some light bedtime reading, I chose Life Technologies' Molecular Probes handbook, a 1,000-page opus of how to make anything and everything biological light up in brilliant hues of Texas Red or Cascade Blue. Flipping to Chapter 1, I quickly glanced at the very first scheme in the entire catalog, and did a double-take: tyrosine tetranitromethane!

TNM: First time's the charm!
Source: Molecular Probes Handbook
Not to tread on Derek - who has a good thing going with his "Things I Won't Work With" tales - but doesn't this look like it should be grandfathered in to his list?

"Rule of Six" violation? Check. Potentially explosive byproducts? Check Check. A brief glance at the MSDS shows some of the more exciting Hazard Codes ("H330 - Fatal if Inhaled"), and the Merck Index (#9305) ain't much better: TNM "attacks iron, copper, brass, and rubber" and "Has been proposed as [an] irritant war gas."


But, lest I lapse into my own fit of hypocritical chemophobia, I should point out that this compound is apparently 'par for the course' for stalwart chemical biologists - it's been used since the 1920s to label proteins, and a 1966 JACS article dubs it "stable, specific, and gentle." Even PubMed brings up >600 references, so I suppose my initial gut-check was a bit unwarranted - TNM looks OK when used in dilute solutions. But, I'd still say you should think twice before considering it for routine bench work.


  1. For the longest time peptide chemists were big users of HF too. They don't play around.

  2. I had no idea that was an actual reagent - I'm on the case! Thanks for the tip. . .

  3. as much as i never want to see a bottle of this stuff, how is it made?

  4. I'm always a bit baffled by biochemists/mol. biologists' attitudes to chemicals. On the one hand you have this, and as Brandon points out, use of HF. On the other hand, when I took a biology lab course, the fuss over ethidium bromide was outrageous. Entire section of the lab cordoned off, incredibly strict containment. Not that that's a bad thing, but it seems an over-reaction in contrast to "sure, lob some tetranitromethane at it!".

  5. TNM can be made by nitration of acetic anhydride, first with cooling on ice and then at room temperature for several days - the required combo of fuming nitric acid and Ac2O is however notoriously temperamental and may end up in self-accelerated thermal runaway, or boom if overheated.

    TNM is relatively mild nitration agent as it disproportionates to NO2(+) and (NO2)3C(-) and it is not as big explosion hazard even neat, if reasonably pure, or when handled in CCl4. The mixtures with flammable organics like toluene are however viciously explosive, and the byproduct trinitromethane (nitroform) is very shock sensitive on its own, and makes variety of explosive salts with bases

  6. The chemistry blogosphere: 40% chemophobia since forever.

  7. Tetranitromethane is a really stable compound what is widely used as a nitrating agent and it is perfectly safe, it won't explode even if used in pure form, only if it contacts with base and forms the corresponding trinitromethane salt.

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