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by jmblpati 2985 days ago
Your claim about fluorine being essential for organophosphate nerve agents is incorrect. The original nerve agent, tabun, contains no fluorine at all for example. Neither do VX, parathion, or paraoxon.

The mechanism behind organophosphate poisoning lies entirely in the phosphate part of the molecule. Among the enzymes present in the human body are a large class known as serine hydrolases. These enzymes hydrolyze chemical bonds in a wide variety of compounds (such as sugars, proteins, and lipids), and their function critically depends on a nucleophillic serine amino acid in the enzyme's structure. This serine attacks the bond to be hydrolyzed, freeing one half of the victim molecule and leaving the other half attached to the enzyme. Then water comes in and breaks the bond between the serine and the second half to restore the enzyme and in sum hydrolyze the original bond.

Organophosphate nerve agents act by entering the active site of a serine hydrolase. They are attacked by the active site serine to release a counterion (which depends on the specific nerve agent) and a phosphate ester of the enzyme. However, this enzyme ester can only be hydrolyzed extremely slowly-- the enzyme cannot be restored to its original form, and the entire enzyme is nonfunctional.

Now, the released counterion could be many things (it just needs to be something that will leave if pushed out by the hydrolase serine). On the other hand, it should not be too eager to leave like something like chlorine would be: if it was the potential nerve agent would be attacked by things like water before getting to the hydrolase, wasting the agent. Thus, a balance needs to be struck between something easy to displace but not too easy to displace. This gives the classic functional groups present in most nerve agents and organophosphate pesticides: fluoride, cyanide, thiols, and phenolates.

By the way, fluorides and fluoride minerals are virtually impossible to regulate trade in: they have a large variety of legitimate uses from toothpaste to aluminum production, and fluorspar is a fairly common mineral in the world. What is usually regulated instead are the phosphorus precursors such as phosphorus trichloride and red phosphorus as well as some chlorinating agents like thionyl chloride.

2 comments

Your claim about fluorine being essential for organophosphate nerve agents is incorrect. The original nerve agent, tabun, contains no fluorine at all for example. Neither do VX, parathion, or paraoxon.

Sarin does, and the article is talking about sarin. Either way I’m sure you’d agree that isopropanol isn’t a precursor to sarin, yes? You’d also probably admit that you’re not getting methylphosphonyldifluoride from fucking toothpaste. Lecture about the mechanisms of organophosphates on AChE aside.

Just for your information, the mechanism of organophosphate nerve agent toxicity does not involve serine hydrolyases. It involves acetylcholinesterase.

https://chemm.nlm.nih.gov/nerveagents.htm

...which is a serine hydrolase.
I stand corrected... I was thinking of serine hydrolyases more generally, most of which are not significantly affected by organophosphate neurotoxins.

https://en.wikipedia.org/wiki/Serine_hydrolase

No, pretty much all serine hydrolases are affected by organophosphates (assuming they can reach the active site). For example, the compounds IDFP[0] and MAFP[1] can both be used to inhibit serine hydrolase activity in vitro. Diisopropyl fluorophosphate can also be used, although that one actually is pretty much a nerve agent (it's volatile).

The only reason the wholesale disruption of hydrolases is not the thing that kills you with nerve agents is that acetylcholinesterase is particularly susceptible to organophosphates (wide open active site) and essential to nerve signal conduction. Thus although sarin (for example) will wreck most hydrolases in your body, this won't really matter when you'll be dead in a few minutes from your nervous system being unable to tell your lungs to breathe.

[0] https://en.wikipedia.org/wiki/IDFP

[1] https://en.wikipedia.org/wiki/Methoxy_arachidonyl_fluorophos...

"The dose makes the poison". It would be too broad to claim that all serine hydrolyases are susceptible to all organophosphate compounds.

For example many pesticides are organophosphates, yet have little effect on humans.