Wednesday, April 21, 2010

An Apology to Socrates

I was watching House M.D. yesterday, and one of the interim solutions to the mysterious ailments experienced by the patient of the week (who was a swords and sorcerers playacting fanatic) was Hemlock poisoning. Sure, everyone knows about Hemlock – it was the sentence for one of the most famous trials of all time – but when House storms out of the apothecary shop with his brilliant Hemlock deduction, his team immediately responds with “Okay, I’ll check for piperidine alkaloids”.

“Piperidine alkaloids!” I exclaim, “I have some of those, and the MSDS didn’t mention anything about notorious neurotoxicity causing death of premodern philosophers! To Wikipedia, batman!”

So hemlock leaves (and roots) are chock full of a bunch of different piperidine alkaloids which are more or less all poisonous, their neurotoxicity stemming from being competitive agonists to the active site of certain nicotinic receptors, causing muscular paralysis, preventing breathing, and resulting in eventual death. Other molecules which do the same thing (to lesser and greater degrees, respectively) are nicotine and cobra poison.


For those interested in the structures of these badboys. Taken from some ancient ACS paper (Leete, E, “Biosynthesis of the hemlock and related piperidine alkaloids”, Accounts of Chemical Research 1971 4 (3), 100-107)

Well anyway, for reasons outside the scope of this post (and more importantly, inside several NDAs), I happen to have a supply of conveniently azide functionalized piperidine alkaloid (very similar structurally to coniine, which is the most active and poisonous of the chemicals contained in hemlock). So naturally, as I didn’t have anything better to do today, I decided to make the ultimate philosopher killing machine. It’s a piece of molecular art, really. I call it “Hypervalent Hemlock”.


Just in case it wasn't deadly enough already.

Yes, that’s a 3rd generation triazole dendrimer chock full of piperidine alkaloid goodness. I have no idea about the actual mechanism behind the binding of coniine to the nicotinic receptors, and so whether the right side of the molecule is sticking out here, but I like to think that this molecule can agonize a dozen receptors in one go, thereby increasing its Socrates killing power 12-fold.


Its not so pretty IRL, guys.

Science is awesome. Think I can make a work term report out of this?

1 comment:

  1. A few years ago a bunch of us were certain you would go on to create something you could use to kill people who were smarter than you. Now you've done it!

    It brings a tear to my eye.

    ReplyDelete