X-Files' Freezing Catalyst: Digging Deeper

A random Friday afternoon link at Chemjobber's place clued me into Mitch's post, about a random NMR encountered in an old episode of '90s sci-fi classic The X-Files. By some odd coincidence I, too, was watching the episode sometime in early April, though I didn't get my notes and pictures together in time. Alas.

(Before we get too hung up on the episode's premise - that in 1996 computational chemists at MIT were performing in silico calculations on a "catalyst" intended for rapid body freezing - let's also remember that this episode shows us protagonist Lisa, a wunderkind doctor / chemist / radiologist, strutting out of her lab sans questioning after her patient spontaneously combusts!)

Now, to the structure of "Compound X" - I took a close-up of the computer terminal Lisa's working on, right around 17:00. Yes, folks, that's 1,2-dichloro-1,1,2,2-tetrahelio-ethane. Carbon-helium bonds can't exist, shout the skeptics? Well, 1993 marked production of the first He@C60 clathrate (story here), and friend of the blog Henry Rzepa had a theoretical paper in 2010 discussing charge-shift C-He bonding. True, isolable heliocarbons are still at large, for anyone seeking a high-risk, high-reward tenure project [ducks].

Molecular modeling has always looked best on Macs. There, I said it.
Fox Broadcasting Corp.

In his post, Mitch calls attention to the NMR, though I found the second analytical spectrum more entertaining, since it has an actual reference printed across the top. Turns out the producers did their homework for this one - this spectrum is an example of spectral linear combination to quantify small amounts of metabolites in blood plasma - good call!

Real science! In a sci-fi show! Who knew?
Fox Broadcasting Corp.

Back to the (flimsy) plot: certain details are over-the-top cheesy, like the "hand scanner" Jason uses to access his facility - it looks like it was built from an old dot-matrix calculator screen screwed into a subway post:

State-of-the-art security for the "MIT Biomedical Research Facility"
Alternate caption: I spent a weekend building this prop, and they used it for 4 seconds of footage.
Fox Broadcasting Corp.

The writers have also presaged the warm-liquid-goo-phase meme from Austin Powers, as the antidote to the freezing catalyst seems to be epinephrine, DMSO, electroshock...and complete-body immersion in a human-sized deep fryer:

Warm liquid goo phase - Complete!
Fox Broadcasting Corp.

Spoiler alert - the concluding scene, a conflagration in the "MIT computer mainframe," would likely have set the Schrock and Buchwald groups back quite a number of years.


Finally, I'll leave you with a silly futuristic quote: "The technology to engineer [Compound X] is still 5, 10 years away..." Sorry, Dr. Lisa - it's been 23 years since this episode aired, and to my knowledge, we're still not making per-heliated small molecules. Maybe check back in another three decades.

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If you enjoyed this post, try some of the others in the Chemistry Movie Carnival from 2013.

A Cage-y Déjà Vu

I love finding molecular "diamonds in the rough." Especially when they look, well, a bit like diamonds.

While strolling through the literature, I did a double-take at this polycyclic caged structure reported by Santiago Vázquez  (Universitat de Barcelona) and coworkers. Wow!

Source: ACIEE 2014, Vasquez et. al.

Spawned from a "highly pyramidalized" (nonplanar) olefin dimerization, it features three cyclobutanes, four "envelope" cyclopentanes, and four cyclohexanes locked in their "boat" conformations (Even worse? All those eclipsing methyl groups on each end . . .jeepers). One might expect a thing like that to fall apart in a minute with a little heat, but, amazingly, the compound remains stable up to 500 degrees Celsius.

Model of the "highly-pyramidalized" olefin monomer.
Phil Baran used to say that you could judge the strain based
on how badly your model's bonds bent...

A little reference digging proved that similar caged olefins were first produced almost half a century ago at Smith Kline & French, using a seven-step prep reliant on chloroketals and long-duration sulfuric acid stirs (yuck). A major step forward came in 1970, when Avila and Silva (San Fernando Valley State U) realized that blasting UV light at a double-Diels Alder adduct of acetylene dicarboxylic acid led to a symmetric anhydride precursor.

Vázquez extended this little gem of a starting material towards finding active antiviral analogues of amantadine. Using the imide version of Silva's anhydride, Vázquez produced a caged secondary amine (see right) that exhibits activity against mutant versions of the H1N1 flu virus. His compound also inhibits the influenza A wild-type proton channel; molecular dynamics simulations indicate that it performs a "flip" relative to bound amantadine that plugs up this pore more effectively.

Let's just hope that these new polycycles get an easier-to-pronounce nickname. 
Octopane? Rocketane? Congestane? I'm open to suggestions!

Friday Fun: Insane in the Membrane

...CARBORANES in the Brain!*

Source: ACS Chemical Neuroscience | Sydney University 

From the pages of the (relatively new) journal ACS Chemical Neuroscience, comes this report about development of new antidepressants with rather...interesting appendages. The adamantyl (1) and Cookson's diketone (3) molecules shouldn't surprise, but the rest? You're not imagining things - those are blood-brain barrier-penetrant lead molecules based on cubane (2) and closo- and nido-carboranes (4,5). At 20 mg/kg, compounds 2 and 5 restore significant function to mice following stress tests. The authors indicate that, although the caged compounds look pretty huge, they're actually fairly isosteric (similar size) to a phenyl group, yet possess rugged metabolic stability.

*With apologies to Cypress Hill