nitroglycol
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Effect of leaving group on organophosphate toxicity
As I understand it, the primary reason for the toxicity of these compounds lies in the fact that they bind covalently to cholinesterase and other
enzymes. But it strikes me that most of them also have fluoride as a leaving group (or cyanide in the case of tabun). Will the leaving group have an
impact on the toxicity, or is it the case that by the time you got enough of it building up you'd already be dead because of the cholinesterase
inhibition?
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Sauron
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You are talking about first generation chemical weapons.
1) The forum proprietor prefers that this topic be shunned, as with all weapon related topics.
2. Y9ou are talking 1930s technology. There are many such agents that contain neither F nor psuedohalogen (-CN).
I suggest you read Saunders' book from the forum library if you are interested in this subject, also UTFSE for the thread on Sartori's supplement to
THE WAR GASES published in Chemical Reviews. There is a link to the article there.
3. Lots of other material is in the literature.
Most tests on enzymology will touch on this.
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nitroglycol
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| Quote: | Originally posted by Sauron
1) The forum proprietor prefers that this topic be shunned, as with all weapon related topics. |
Sorry about that, my bad. Don't worry though, I wasn't planning on making any of these things.
| Quote: | | 2. Y9ou are talking 1930s technology. There are many such agents that contain neither F nor psuedohalogen (-CN). |
Right you are again; parathion seems to be one of them. Sorry for asking dumb questions.
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Sauron
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Not to worry.
When I first joined I posted about some of these, but since then I have realized (and been advised) it is not so wise to do so. So I still post about
phosphorus chemistry, which is fascinating, but I stick to the innocuous.
Parathion is an insecticide and not a military OPA at all. So that one I would not hesitate to discuss.
I generally stick to the chemistry and let the technology sort itself out.
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nitroglycol
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| Quote: | Originally posted by Sauron
Parathion is an insecticide and not a military OPA at all. So that one I would not hesitate to discuss. |
Of course, but I think the mechanism of action is pretty much the same. From a biochemical point of view, they're the same sort of agent.
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Sauron
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There's more than one sort of human AChE
And more than one mode of action.
More than one aspect to the nervous systems of mammalian life. Central vs peripheral, for example.
Just because something is said to inhibit acetylcholineesterase does not mean that its activity is of the same nature as another inhibitor.
For example, Hemicholinium-3 (q.v.) acts in a very different fashion than any of the others.
This is a complex subject involving physiology, enzymology, biochemistry, and all I do is chemistry. So, if you reckon you have this down pat, I
salute you. Because no one does. We are still learning new things about the action of 70 year old agents. The Gulf War taught us a few new lessons.
Namly that these things are active in terms of chronic effects at far smaller doses than ever expected - just to name one.
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nitroglycol
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The Gulf War? Who used nerve agents then? I know that the Iraqis used some sort of chemical weapons during the war with Iran in the 1980s, but I
thought it was mustard that they used, and I haven't heard of them being used since then.
I agree that the subject is very complex, and I certainly don't claim to be an expert. And certainly, a compound like succinylcholine works quite
differently (I think it binds to the enzyme reversibly, rather than irreversibly), but I thought parathion worked more like the nastier nerve agents
like tabun and sarin, just with a different leaving group.
[Edited on 2/10/2007 by nitroglycol]
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Sauron
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There were, or so I am told, low level exosures of troops that occurred due to strikes on some of Saddam's stockpiles.
Nobody "used" anything but that is neither here nor there.
I'm not sure that parathion has any leaving group.
And no, succinylcholine, which is not an enzyme inhibitor, has nothing in common any of the OPAs. Only that chemical idiot Tom Clancy thinks
succinylcholine is anything exotic. Clearly he never went deer hunting with a bow and arrow. A sackful of succinylcholine is employed in that fashion
to paralyze the deer. Otherwise wounded deer have a tendency to want to disembowel the hapless hunter.
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nitroglycol
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Hmm, I'd thought succinylcholine was a competitive inhibitor of ACE. I guess I was wrong again.
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Sauron
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Succinylcholine acts as a depolarizing neuromuscular blocker. It imitates the action of acetylcholine at the neuromuscular junction, but it is not
degraded by acetylcholinesterase but by pseudocholinesterase, a plasma cholinesterase.
Acetylcholine is a neurotransmitter not a neuroclocker.
If you inhibit acetylchloineesterase, then acetylcholine builds up and the junction fires uncontrollably (spasms).
Succinylcholine blocks the junction so if you want to call that competitive inhibition of acetylcholine, fine, but that is not the same as any sort of
inhibition of acetylcholineesterase, in fact, succinylcholine and acetylcholineesterase do not interact.
Remember, the basic choline backbone is -N-CH2-Ch2-O-. Anytime you see that substructure, look again. You will find it all over the place in medicinal
chemistry and biochemistry, and not infrequently in orhanic chemistry (think ethanolamine and substituted ethanolamines esp. the di-Me.) Look at
atropine and scopolamine. Then recall that atropine in an antidote for some but not all AChE inhibitors.
Look at beta blockers, lots of things.
You will see that we built s choline-like side chain as a thioester -S-CH2-CH2-N- into some insecticides and also some related military OPAs so do you
reckon that was a coincidence?
No F, no CN.
Now go look at the quaternary aldoxime series of antidotes for OPAs starting with 2PAM 2-pyridinium aldoxide methiodide and current variations.
The Russians in their latest generation OPAs have built THAT substructure in, combines with highly electronetative substituents like F, CN, or both
(!) in order to defeat the NATO antidotes, not to mention mount an entire class of agents not covered by existing anti-CW treaties.
Quite clever really but also quite scary.
Sorry if I am dancing around the topic but I am not going to tell anyone How To Do.
[Edited on 3-10-2007 by Sauron]
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nitroglycol
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OK, thanks for clearing that up. And no, I don't have any desire to try any of these... just like I don't really care to try to replicate this guy's work, brilliant and fascinating though it was.
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Sauron
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No problem.
Glad to clarify.
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