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MrSamosa
December 26th, 2004, 10:22 PM
Friends, Chemists, Cadres! Lend me your eyes! I'm not Shakespeare, but long time no see :) . After a long time away from the beloved E&W Forum, I have not come back empty-handed or empty-minded. Nay, I have goodies for you to feast your minds upon...

Bicyclic Phosphates. I first came across this while doing research on a paper about Chemical Warfare in WW1 from the following site http://www.asanltr.com/ASANews-98/chemistry.html . The structure, as you see, is very unique, and isn't so easy to convey on a 2D plane, something along the lines of

O=P(O-C)3C-R

the Phosphorus and Carbon forms a sort of 3-pronged cage with the three OC's. The nomenclature for them is "Alkyl Bicyclic Phosphate," according to the R. The most dangerous of them is Isopropyl Bicyclic Phosphate, which has a toxicity on par with Sarin, according to ASA. Unfortunately, information concerning these compounds is very sparse online. Nevertheless, I have managed to glean some useful information.

Of all the Nerve Agents, I feel these are the most accessable . First of all, the synthesis of Ethyl Bicyclic Phosphate is extraordinarily simple, and is often made accidentally; not to mention the precursors are not watched materials. Trimethylol Propane is simply heated together with Aluminum Phosphate. Alternately, Trimethylol Propane can be reacted with Sodium Acid Phosphate. For other Bicyclic Phosphates, I imagine Aluminum Phosphate can be reacted with variants of Trimethylol Propane. Secondly, the treatment is pretty simple: benzodiazepines. You can buy them from the friendly local drug dealer :p
Thirdly, they aren't nearly as volatile as other OP's, such as DFP or TEPP or Sarin, provided they aren't pulverized too finely. They are crystalline solids, you see. It would still be prudent to avoid all contact with them, though.

As you imagine, these are a bit different from the OP's we are all familiar with. Intoxication is slightly different (and not well-described by my sources..), and treatment is also different. Of interest is that Atropine (the typical nerve agent treatment) is ineffective against Bicyclic Phosphate poisoning and there is no specific antidote/treatment.

...Fun fun fun...

FUTI
December 27th, 2004, 12:45 PM
I'm confused....I know that number of cytotoxic agent are bicyclic phosphates so their toxicity is easily understandable...but in this post you stated that benzodiazepines are simple treatment, and then later you said that there is no good treatment.

EDIT: I just saw teshilo's post and realise that although the doctrine of CW use state that it is better to use volatile/gaseous compound on field against armed forces, actually for terorist purpose that isn't relevant. Pulverised form can actually be better...longer onset time enables victims to change location and since they will have different sensitivity to agent (mostly because its action would depend on sweating and exposure means) it will generate a random map based on the occurence of the first simptoms victims noted making cause of it hard to locate and identify in real-time (I'm not saying that's easy task even in classic warfare). It will be some kind of sneak attack that enable terorist to leave the crime scene unnoticed. There are reports about CW agent can be spread by wind on carrier as for example desert sand so being crystaline compound in this case can be usefull.

teshilo
December 27th, 2004, 02:47 PM
[. Of all the Nerve Agents, I feel these are the most accessable . First of all, the synthesis of Ethyl Bicyclic Phosphate is extraordinarily simple, and is often made accidentally; not to mention the precursors are not watched materials. Trimethylol Propane is simply heated together with Aluminum Phosphate. Alternately, Trimethylol Propane can be reacted with Sodium Acid Phosphate. For other Bicyclic Phosphates, I imagine Aluminum Phosphate can be reacted with variants of Trimethylol Propane. Secondly, the treatment is pretty simple: benzodiazepines. You can buy them from the friendly local drug dealer :p
Thirdly, they aren't nearly as volatile as other OP's, such as DFP or TEPP or Sarin, provided they aren't pulverized too finely. They are crystalline solids, you see. It would still be prudent to avoid all contact with them, though.

...Fun fun fun...[/QUOTE]
Yes yes very simple search on the Google give result about Trimethylol Propane This NOT restricted chemical :)
1,1,1-TRIMETHYLOLPROPANE
PRODUCT IDENTIFICATION

CAS NO. 77-99-6

EINECS NO. 201-074-9
FORMULA C2H5C(CH2OH)3
MOL WT. 134.18
H.S. CODE 2905.41
TOXICITY
Oral rat LD50: 14100 mg/kg
SYNONYMS 2-Ethyl-2-(hydroxymethyl)-1,3-propanediol;
Trimethylol propane; propylidynetrimethanol; 1,1,1-Tris(hydroxymethyl)propane; Ethriol; Ethyltrimethylolmethane; Hexaglycerine; 2,2-Bis(hydroxymethyl)-1-butanol; Propylidintrimethanol (German); Propilidintrimetanol (Spanish); Propylidynetrimťthanol (French);
DERIVATION

CLASSIFICATION


PHYSICAL AND CHEMICAL PROPERTIES

PHYSICAL STATE white flakes

MELTING POINT 55 - 59 C
BOILING POINT
SPECIFIC GRAVITY 1.17 - 1.18
SOLUBILITY IN WATER Freely soluble (Soluble in alcohol, glycerin. Insoluble in hydrocarbon solvents)
pH 4 - 7

VAPOR DENSITY 4.8
AUTOIGNITION 295 C

NFPA RATINGS
REFRACTIVE INDEX

FLASH POINT

STABILITY Stable under ordinary conditions. Hygroscopic.
APPLICATIONS

Trimethylolpropane, containing three primary hydroxyl groups in a quaternary mole structure, is a white crystalline solid or clear liquid in molten form at high temperature; melting at 57 C; soluble in water, alcohol, glycerin; insoluble in hydrocarbon solvents. It is prepared by the hydrogenation reaction of aldehyde n-butyraldehyde and formaldehyde It is used as an important raw material in manufacturing polyesters, alkyd and urethane resins. It improves heat resistance, color stability, balance between toughness and flexibility. It is also used in lubricating oils and plasticizers as well as in radiation curing monomers or oligomers.
SALES SPECIFICATION
APPEARANCE
white flakes

PURITY
99.0% min

HYDROXYL VALUE 1230 min ( mg KOH/kg)

ASH
0.005% max

WATER
0.1% max

TRANSPORTATION
PACKING 25KGS in bag and big bag
HAZARD CLASS Not regulated

Possible synth these stuff in dirty home lab :D
I read about Bicyclo Phosphates in book about future CW .Solid state these compounds his caltrops on way good weaponization .
With return Samosa ;) ;) .Good luck in New 2 :D :D 5 YEAR...

MrSamosa
December 28th, 2004, 01:07 AM
I should clarify what I said about treatment, because apparently it was a bit convoluted. According to ASA, there is no effective treatment for poisoning by Bicyclic Phosphates and from what I gathered from them, their action isn't even fully understood. However, they did mention that "relatively good" results were obtained from Benzodiazepines.

This in itself is not surprising because benzodiazepines have long been used to treat conventional Nerve Agent poisoning. While Atropine keeps people alive for a few minutes longer by antagonizing acetylcholine, Pralidoxime destroys the Nerve Agent molecules, and Valium is used to control tremors and other discomforts.

Also of interest: a more familiar potential precursor for Bicyclic Phosphates is Pentaerythritol. However, this would form a "weird" structure in that it's not quite what we are looking to create:

O=P(O-C)3-C-CH2-OH

This may or may not be a complete loss. Again, information on Bicyclic Phosphates (Bicyclic Phosphites, too) is pretty sparse, so it will be difficult to find anything on the toxicity of such a compound or its derivatives (which I think would be of most interest).

Maybe the above product could be chlorinated, to replace the COH with CCl ? From there, it could be alkylated to form a secondary carbon chain, which could be quite toxic.

nbk2000
December 28th, 2004, 02:05 AM
...the Phosphorus and Carbon forms a sort of 3-pronged cage...


While reading up on TETS, I noticed mention of it being part of a class of poisons called "Cage Convulsants" because the core molecule is a carbon cage with the rest of the stuff attached to it.

TETS and the bicyclic phospates are both (suspected) GABA antigonists.

OH! IDEA!

Given the commonality of high toxicity, cage molecule, and not commonly thought of as weapons, what about using acetonitrile to add the -CN molecule to the cage, and possibly forming a Novichok agent an order of magnitude of toxicity greater than VX?

It's supposedly piss easy to make (comparatively), uses chemicals not thought of as CW precursors, and have agricultural utility (rodenticides?). And I haven't seen stated anywhere that Novichok is not a solid. Everyone assumes OPA's to be liquids, though that's not true.

c0deblue
December 28th, 2004, 02:56 AM
Given TETS' stability you presumably wouldn't have to worry about interaction if different agents were mixed with it. At the very least I'd think that would confound accurate diagnosis until death ensued from one or the other.

OT, but I wonder why TETS - alone or in combination - hasn't been identified as a battlefield weapon (but who's to say it hasn't?). Dirt cheap to produce compared with some of the more exotic agents and with the potential to completely neutralize an opposing force without any of the classic warning signs until it's too late. Interspersed with regular artillery rounds, TETS shells wouldn't be readily distinguished. Troops under artillery fire are trained to stay low and breath plenty of dust, so they wouldn't even know they'd been poisoned until they all started seizing or falling unconscious. Even then, those around them would merely think that those first-affected had been hit by shrapnel if the shelling were still going on.

Of course there'd be no question of physically moving in to "capture" the enemy positions, but you wouldn't have to!

MrSamosa
December 28th, 2004, 03:59 PM
NBK-- When you mention adding a -CN group to the molecule, are you referring to a structure like:

O=P(O-C)3-C-X , where X = CN?

Because such a substance would be extremely interesting, particularly where X is Chlorine or Fluorine. Its own toxicity wouldn't be of much interest, but it could be used to create other Bicyclic Phosphates such as Isopropyl Bicyclic Phosphate (with an LD50 of .18 mg/kg in rats).

Also of interest--Bicyclic Phosphates do not have to be inhaled. They work very well through dermal exposure, from what I'd read somewhere (sorry, but I can't find that source anymore). If that's the case, they are then ideal dusty agents themselves without having to be absorbed by some carrier.

On the note of Novichoks, I, along with some members of sciencemadness (notably Fritz) did a bit of collaborative fact-finding on them, which we have neatly compiled here (in Microsoft Word format):

http://www.geocities.com/hammsterr/FritzNovResearch.doc

http://www.geocities.com/hammsterr/NovDAGVGP.doc

From what I can tell, they don't look so easy to prepare. They do, however, look pretty similar to the GV and GP agents. GV and GP themself confirm that there are a new generation of Chemical Weapons and that Novichoks aren't simply Cold War rumors.

c0deblue-- You should look up Iraq's chemical weapons strategy in the Iran-Iraq War; when I read your post, that's just what I thought about. Saddam demonstrated the applications of Chemicals on the battlefield very well for us to study.

Of interest, though, is that he did not gas a position and then send the troops in to take it, so much, at least in the case of the Kurdish attacks. There, he simply gassed a village, bulldozed the whole place, and relocated the population. In the case of Halabja (then under Iranian control), he opened up with all kinds of crazy weapons--Napalm, Phosphorus, Mustard, and G-Agents. When the Iranians fled the city following that initial defeat, Saddam did NOT send his government workers or soldiers back in. When the Iranians sent "Human Waves," the Iraqis responded with massive gas attacks to break them up--"We will use bug spray instead of a fly swat," as one Iraqi leader put it.

As you see, Chemical Weapons in today's battlefield are more of area-denial weapons. So if an enemy position is saturated in poisonous dust, it would be time-consuming and wasteful to retake/decontaminate it. Gas it, and move on or completely level it. Total warfare, as you see. Naturally, there are exceptions to this rule...in the Al-Faw campaign (which ended just prior to the squashing of the Kurds), the Iraqis were alleged to have used Chlorine, "Yellow Rain," and other chemicals... But they did move up to take the positions once the Iranians fled.

As always, there's a weapon for each need on the battlefield...Chemicals can't simply be described as a "one-situation" weapon. But I hope you enjoyed my bit of history :)

megalomania
December 29th, 2004, 12:59 AM
I believe current US military doctrine (or at least Vietnam era) was to deploy chemical weapons should it become necessary to retreat from a base in a hurry. This would deny the enemy valuable hardware and materials should there be no time to deatroy them. With the 3 week toxicity window of VX they could use that time to retake the position, or later destroy it through airstrikes/artillery.

You have given me lots of good data to chew on MrSamosa. If there are any journals or books you require to furthur your research of these compounds I would be happy to obtain them for you. Email me...

simply RED
December 31st, 2004, 10:38 AM
More precize on the synthesis:
How to prepare alluminium ortophosphate (AlPO4)?
One possible way is to mix equimolar solutions of alluminium nitrate
(Al(NO3)3.xH2O) and sodium phosphate Na3PO4. The alluminium phosphate should precipitate.
Al (3+) + PO4 (3-) = AlPO4 (precipitate)
Maybe additional acid should be used to insure that the phosphate will not hydrolize? Too much acid may dissolve the phosphate ...
AlPO4 + H3PO4 = Al (3+) + HPO4 (2-) + H2PO4 (-)
Someone tried this reaction?

More precize on the condensation-cyclization.

AlPO4 is mixed with trimethylolpropane (this forms a suspension) and heated (what temperature is needed?) .
The reaction should be: AlPO4 + C2H5C(CH2OH)3 = Al(OH)3 +
C2H5C(CH2O)3P=O. All the products are solid. What yield do we expect?
Trimethylolpropane is insoluble in water AlPO4(hydrolyses?) and Al(OH)3 too. What about the bicyclo-organic phosphate?
Is it possible to prepare the compound from H3PO4,P2O5 and Trimethylolpropane?
If yes, bicyclo-organic phosphate should form at room temperature and become ultra-easy-to-use binary agent !!!

What about tris bufer NH2-C(CH2OH)3 and AlPO4 ? or forming bicyclo-organic phosphate with methilated tris:
Cl(-) (CH3)3N(+)-C(CH2OH)3 .
Cl(-) (CH3)3N(+)-C(CH2O)3P=O. It looks like VX, doesn't it ?
I know it has different mode of action though...
Poor rats.......

simply RED
January 1st, 2005, 06:36 AM
More precize on the mechanism.
The bicyclophosphates bind unreversibly to the GABA receptors.
So they are GABA receptor antagonosts.
It could be proposed that the bicyclophosphate part of the molecule blocks the receptor. So the other part of the molecule should be made to look like the known GABA receptor antagonists. They all contain C-C-C-NX chain like GABA.

XN-C--C-C---XOOH --- GABA receptor antagonist.

H2N-C(-C-0-)3P=O --- Possily extremely toxic bicyclophosphate.

H atoms not shown.

As we see - here is part of the tris buffer.
View the pdf for more info on GABA receptors, agonists and antagonists.
(I prepher the word inhibitor.)

simply RED
January 3rd, 2005, 06:19 AM
Theory suggests that tris hydrochloride and phosphorous oxitrichloride will react at room temperature (possible solvent trichloromethane - anyone has data on tris and its salts solubility?) to produce the desired ultratoxic compound with near 100% yield.

O=PCl3 + (HO-CH2)3C-NH3Cl = O=P(O-CH2)3C-NH3Cl + 3HCl (gas)

Acidic media and diluted solutions favorize cyclisation over polymerization, but as the nucleophilic reagent R-:O:-H attacks the very near Phosphorous atom (sigma + ). The cyclisation will be favorized over polymerization anyway.

MrSamosa
January 4th, 2005, 06:18 PM
Simply RED, I've had to read over your posts several times because they've made me think. You've brought up something very interesting, which I hadn't even considered--using tertiary amines instead of variants of trimethylol propane. It opens up possibilities...for example, instead of having:

O=P(OC)3-R

We could get:

O=P(OC2)3-R

[Hydrogens not shown]

By using Triethanolamine. But let's not get too theoretical, as this is the Explosives & Weapons Forum :P.

What would be call that structure that you presented? Aminobicyclic Phosphate? Well, whatever it is, it has really caught my interest because again, at least one of the precursors is very easy to obtain and the reaction is straight forward.

From my reading on esterifying phosphates, a strong organic base is usually used to facilitate the reaction between the alcohol and the Acyl Chloride (whatever it may be--Phosphorus Trichloride or Oxychloride, as it is in this case). Triethanolamine, which has legitimate uses, could be employed here. As you mentioned, it would make sense then to use the Hydrochloride salt of Tris so as to avoid competition in the acid-base neutralization.

But afterward, you would have Aminobicyclic Phosphate Hydrochloride... This may be useful in that it could be water-soluble, which increases its ability to be weaponized (conversely, it would mean that it is more susceptible to weather). But being purists, the finished product could be reacted with a weak basic solution, e.g. Sodium Carbonate, to precipitate the pure Aminobicyclic Phosphate.

But if we don't mind using watched reagents such as POCl3 (this is kinda getting away from my original goal of using OTC precursors), then we have plenty of room for experimentation. For example, we could try Thiobicyclic Phosphates and investigate dermal toxicity. It may be higher, it may not; I'm just drawing possible extensions from what we know about Thiosarin vs. Sarin and Thiosoman vs. Soman.

simply RED
January 5th, 2005, 08:51 PM
P2O5 may also work, it is easy to find (here).
One mol P4O10 (this is the actual molecule) and one mol tris or another triol should be tried first.
Do you have a synthesis with phosphate, i mean described procedure?

You know the small medicine "bottles" that have unique rubber plugs.
A needle penetrates the plug and when the needle is drown away, the plug does not permit any liquid or gas.
Such could be used to make safe tests with these compounds.
The rector will be such bottle, one needle will be stuck in it, this needle will lead to solid NaOH column (for degasation - never use liquid solutions bacause if the gas dissolves in water it will lower the pressure and fill your container with liquid). The tris is in the bottle. The phosphorous compound is injected via another needle.
After the reaction is complete some liquid is drown away and injected directly in rat. I would use hamster instead, cause they are cheaper. I have tested parathion, malathion, bi-58, cyanide, lambda cyhalothrine, galantamine(nivalin).... on hamster and it does the trick well. Injection with some percents over LD 50 of lambda cyhalothrine is most fun anyway ( its eyes plug out :) ).
Working with toxins require different skills from explosives. Anyone who does not have it - will die during an attempt with the former chemicals.

FUTI
January 6th, 2005, 06:07 AM
to simply Red: I agree that P4O10 can be used instead but since it is solid it should be inside the vial and then I would add triol to the vial by syringe. Also did you considered using some base to neutralise the acid formed in reaction. This can be tricky since phosphate esters of this kind aren't stabile and easy hydrolise from triester to diester form (God knows do you understand what I wanted to say in my sloppy english), it may not be of much importance since you don't make it for recording NMR or MS spectra but pH range may be needed little fine tunning.

simply RED
January 6th, 2005, 06:42 AM
During the reaction no water forms. Thus no way the product to hydrlolize.
Equimolar equation:
P4O10 + (HO-CH2)3C-NH3Cl = O=P(OCH2)3C-NH3Cl + P3O9H3 (CycloTriorthophosphoric acid).
P4O10 will be dissolved in something and then added.

It could be possible even to use a mix of H3PO4, P4O10 and solvent.
It is a great chance to get the cylco compound with 80% + yield.
Even the well known polyphosphoric acids may produce some product.
H3PO4, and sodium tripolyphosphate could be used, it is so cheap...
H3PO4 will be formed as a byproduct.
As long as the media is anhydridous it is a great chance to have decent yield.

This may have toxicity like LD 100 - 0,2-0,1 mg/kg so careful experimenting with it is prefered.

MrSamosa
January 6th, 2005, 04:21 PM
As we all know, Amines are basic and, accordingly, form salts with acids. Aminobicyclic Phosphate would also be a Lewis base, as I pointed out earlier, since it would form a hydrochloride salt.

But let's be creative, in the name of rogue science. Why should we settle with a mere hydrochloride salt? Suppose we were to neutralize the Aminobicyclic Phosphate with a toxic acid, maybe Fluoroacetic Acid, or even Hydrofluoric Acid? Therefore, we would have Aminobicyclic Phosphate Fluoroacetate/Hydrofluoride.

My knowledge of pathology is limited, and I will acknowledge that...but from my limited knowledge, in an aqueous solution, wouldn't these be double-action poisons?? The Aminobicyclic Phosphate portion would antagonize GABA receptors while the Fluoroacetate would interfere with the Citric Acid cycle, or the Hydrogen Fluoride would decalcify the bone.

Possibly, if the acid used to make the salt is particularly corrosive, then dermal toxicity might be increased. Well, maybe not so much dermal toxicity of the product, but it could cause skin damage which would allow the bicyclic phosphate to be administered via the bloodstream.

FUTI
January 10th, 2005, 01:19 PM
to MrSamosa: HF have a number of effects on organism. First it doesn't need any aditional molecule to cross cell membrane...it is so poor acid that is mostly in molecular form has low MW and its abillity to form eg. trimeric form that resemble to benzene molecule in structure and properties make HF perfect membrane penetrating agent. Second you would have a very good time for bone decalcification to happen, but first thing you would notice if your skin is exposed to it is swelling and incredible muscle pain and spasm (little applied chemistry;) Ca2+ is precipitated/sequestered with fluoride ion which affects neural impulses - it also can dissable several Ca2+ dependent enzymes).

As for the fluoroacetic acid it may be benefitial to its properties, as I remember main disadvantage of fluoro-acetic acid is its good water solubility. I don't question the benefitial effect of salt formation on bicyclic phosphate proposed here - I must say I love idea simple RED gave here involving tris.

nbk2000
January 23rd, 2005, 11:25 PM
While I was researching TETS, I found this reference to bicyclophosphorus esters...

+++++++++++++++

Modulation of gamma-aminobutyric acid-stimulated chloride influx by bicycloorthocarboxylates, bicyclophosphorus esters, polychlorocycloalkanes and other cage convulsants [published erratum appears in Journal of Pharmacology and Experimental Therapeutics 1988 Oct;247(1):397]

T Obata, HI Yamamura, E Malatynska, M Ikeda, H Laird, CJ Palmer and JE Casida

Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.


Inhibition by derivatives of t- butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) depended on the substituents at both positions 1 and positions 4. Among them, the 4-cyano-phenyl analog of TBOB was the most potent inhibitor with an IC50 value of 40 nM. Other cage convulsants such as picrotoxinin, tetramethylenedisulfotetramine and p- chlorophenylsilatrane were less potent than TBOB and TBPS.

megalomania
April 7th, 2005, 12:49 AM
I find it curious that in the paper Mr Samosa provided, http://www.geocities.com/hammsterr/NovDAGVGP.doc that the review of the book "Handbook of Chemical and Biological Warfare Agents" is no longer at amazon.com. I went there a few days ago to see about buying the book (screw that is too expensive) because EVERY copy in the network of libraries is either restricted or checked out for the next several months. I would like to know what kind of person can check out a book for months at a time :(

Anyway, I looked over the reviews to see if there was anything else, and imagine my suprise to see nothing for December 14, 2003. In fact there is nothing from Anatoly Kuntsevich. It looks like Amazon has censored the review. I see they have a complaint system in place to rat on undesirable articles. Perhaps the review hit a little too close to home for some government stooge to tolerate.

megalomania
April 7th, 2005, 12:49 AM
I find it curious that in the paper Mr Samosa provided, http://www.geocities.com/hammsterr/NovDAGVGP.doc that the review of the book "Handbook of Chemical and Biological Warfare Agents" is no longer at amazon.com. I went there a few days ago to see about buying the book (screw that is too expensive) because EVERY copy in the network of libraries is either restricted or checked out for the next several months. I would like to know what kind of person can check out a book for months at a time :(

Anyway, I looked over the reviews to see if there was anything else, and imagine my suprise to see nothing for December 14, 2003. In fact there is nothing from Anatoly Kuntsevich. It looks like Amazon has censored the review. I see they have a complaint system in place to rat on undesirable articles. Perhaps the review hit a little too close to home for some government stooge to tolerate.

megalomania
April 7th, 2005, 12:49 AM
I find it curious that in the paper Mr Samosa provided, http://www.geocities.com/hammsterr/NovDAGVGP.doc that the review of the book "Handbook of Chemical and Biological Warfare Agents" is no longer at amazon.com. I went there a few days ago to see about buying the book (screw that is too expensive) because EVERY copy in the network of libraries is either restricted or checked out for the next several months. I would like to know what kind of person can check out a book for months at a time :(

Anyway, I looked over the reviews to see if there was anything else, and imagine my suprise to see nothing for December 14, 2003. In fact there is nothing from Anatoly Kuntsevich. It looks like Amazon has censored the review. I see they have a complaint system in place to rat on undesirable articles. Perhaps the review hit a little too close to home for some government stooge to tolerate.

simply RED
April 7th, 2005, 07:28 AM
The process using tris and POCl3 or P2O5 is very interesting as
theory suggests - cyclic product will be formed with high yield.
(theory of antiperiplanar groups, quantum calculations, thermodinamics - delta

G less than zero , general organic reactions theory ( metaphase formation )


Solvent maybe ether (or THF) + H3PO4. In proportions to produce homogenous mix.

simply RED
April 7th, 2005, 07:28 AM
The process using tris and POCl3 or P2O5 is very interesting as
theory suggests - cyclic product will be formed with high yield.
(theory of antiperiplanar groups, quantum calculations, thermodinamics - delta

G less than zero , general organic reactions theory ( metaphase formation )


Solvent maybe ether (or THF) + H3PO4. In proportions to produce homogenous mix.

simply RED
April 7th, 2005, 07:28 AM
The process using tris and POCl3 or P2O5 is very interesting as
theory suggests - cyclic product will be formed with high yield.
(theory of antiperiplanar groups, quantum calculations, thermodinamics - delta

G less than zero , general organic reactions theory ( metaphase formation )


Solvent maybe ether (or THF) + H3PO4. In proportions to produce homogenous mix.

MrSamosa
April 10th, 2005, 09:42 PM
Curse censorship, but thank God for Google caches and cheap websites who copy reviews from Amazon.com :) . Fear not Mega, all is not lost. But it is being lost faster than I thought... I used to find copies of that review all over Google, but the numbers are dwindling. So for safe-keeping, I'll put the original reviews right here in this thread; as you will see, most of my editing was for the sake of clarity--fixing grammar, rewording sentences, adding pictures.

Novichok(s), dusty agents and GV/GP agents, December 14, 2003
Reviewer: Anatoly Kuntsevich from Moscow, Russia
Although this book is missing the chemistry of the Novichok class of nerve agents it summarizes the physico-chemical data of the known CWAs. Most of the data are taken from the older Field Manual FM 3-9 (1990). The expert may find that some of the data are only estimated, but not indicated as such. Only the details of GV-4 alias EA-5414 (CAS RN 158847-17-7) and GP/GV alias EA-5365 (CAS RN 141102-74-1) are new revelations to the public.

The Novichok class of chemical warfare agents belongs to those organophosporus compounds containing also a dihaloformaldoxime group: -O-N=C(X)Y group (X,Y = Cl, F, Br or even stable pseudohalogens such as C#N). Two examples of Novichok compounds are
a) Smiles: P(F)(=O)(O\N=C(/Cl)F)OCCCl with CAS RN 26102-97-6 and
b) Smiles: F/C(Cl)=N\OP(=O)(OCC)N(C)CCCl with CAS RN 26102-99-8
as published in Kruglyak, Yu. L.; Malekin, S. I.; Leibovskaya, G. A.; Khromova, Z. I.; Sretenskaya, I. I.; Martynov, I. V.: Reaction of alpha-chloronitrosoalkanes with phospholanes and iminophosphites, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 4th (1972), Meeting Date: 1969, p. 307-312. Editor: Grechkin, N. P. Publisher: Nauka, Moscow, USSR. In fact the group of Novichok CWAs is quite large and it would be difficult to protect soldiers and civil personnel, when many different chemicals belonging this class of CWA could be used in chemical warfare with rogue nations or terrorists.

Several Russian chemists as P.P. Kirpichev, R.K. Bal'chenko, I.V. Martynov, Yu.A. Kruglyak, S.I. Malekin, and N.F. Privezentseva from the Moscow institutes GosNIIOKhT and INEOS developed
the principle of these extremely toxic OP haloformaldoximes already during the mid 60's. Rapid progress toward supertoxic variants was seen in the early 70's and the synthesis details were indeed published mainly in the Journal of General Chemistry (Zhurnal Obshchei Khimii), although absolutely no toxicity data of the Novichoks were revealed. All activities were covered as research for pesticides at that time. All publication activities of these authors ceased at the end of 1972.

Michael Crichton alias John Lange published in 1972 the thriller "Binary" which alarmed Russian politicians and military personnel to act quickly on the looming threat of US binary chemical weapons. In 1973 the further activities in the USSR under the new Foliant program were disguised again as a pesticide research program but kept secret until 1986 when some of the researches could publish more details about chemical and biological effects of phosphorylated oximes (e.g. Raevskii, 0. A.; Chapysheva, N. V.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Effect of alkyl substituents in phosphorylated oximes, Zhurnal Obshchei Khimii (1987), 57(12), 2720-2723 and Raevskii, O. A.; Grigor'ev, V. Yu.; Solov'ev, V. P.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Electron-donor functions of ethyl methylchloroformimino methylphosphonate, Zhurnal Obshchei Khimii (1987), 57(9), 2073-8)). It became clear that Novichoks do resist strongly poisoned Acetylcholinesterase/Butyrylcholinesterase reactivation by other common oximes (e.g. 2-PAM/EA-2170, TMB-4/EA-1814) as used so far by the American military forces. The final details to US authorities were given by Vil S. Mirzayanov alias Kenneth (Ken) Alibek who was responsible to detect any Novichok traces in the environment of the GosNIIOKhT branch no. 4 (CWA plant for Novichok) at Vol'sk-17 by gas chromatography. He, as an long standing expert in gas chromatography having the details of what he had to look for in the analyses defected to the US in 1992.

Since the beginning of the 90's US chemical demilitarization programs in the former GUS also included joint research on Novichoks. Now in order to develop effective detectors, detoxifiers, reactivators and bioscavengers (including BuChE). All such programs were named under activities versus "Fourth Generation Agents" (FGA) or "Non-Traditional Agents" (NTA). It seems each year is now coming up with a new disguising term in order not to use "Novichok" in public US documents. "Dusty agents" are also not covered in Ellison's handbook but should be seen in conjunction with the Novichok developments during the 70's and 80's. The Russian researchers V.A. Pasechnik, O.I. Stuzhuk, and Ye.A. Gayev contributed to this development. O.I. Stuzhuk proposed special minerals and diatoms for being contaminated with CWAs, whereas Ye. A. Gayev developed the physical CWA spraying/aerosol system and V.A. Pasechnik contributed to the development and application of "dusty agents" containing biological weapons.


More details would be fine, November 16, 2003
Reviewer: Anatoly Kuntsevich (Moscow, Russia) - See all my reviews
Although this book does not reveal the precise chemical formulas for the Novichok class of nerve agents it introduces into the hidden world of russian chem-bio weapon designers. The intelligence still fears to make public that Novichoks belong to organophosporus compounds containing the double halogenated oxime like -O-N=C(F)Cl group and that beside P.P.Kirpichev also I.V.Martnov and Yu.A.Kruglak from GosNIOKhT developed the principle of these extremely toxic OP oximes during the mid 60's already (and published also) which resist reactivation by other oximes. These chemicals an be made by heating only of substituted 1,3,2-dioxaphospholanes indicated slighly in this book. Hopefully int'l organizations will make public more details for the protection of other citizens than just army soldiers soon. (Review for Cassidy's Run: The Secret Spy War over Nerve Gas (Thorndike Press Large Print Core Series) [LARGE PRINT] )

MrSamosa
April 10th, 2005, 09:42 PM
Curse censorship, but thank God for Google caches and cheap websites who copy reviews from Amazon.com :) . Fear not Mega, all is not lost. But it is being lost faster than I thought... I used to find copies of that review all over Google, but the numbers are dwindling. So for safe-keeping, I'll put the original reviews right here in this thread; as you will see, most of my editing was for the sake of clarity--fixing grammar, rewording sentences, adding pictures.

Novichok(s), dusty agents and GV/GP agents, December 14, 2003
Reviewer: Anatoly Kuntsevich from Moscow, Russia
Although this book is missing the chemistry of the Novichok class of nerve agents it summarizes the physico-chemical data of the known CWAs. Most of the data are taken from the older Field Manual FM 3-9 (1990). The expert may find that some of the data are only estimated, but not indicated as such. Only the details of GV-4 alias EA-5414 (CAS RN 158847-17-7) and GP/GV alias EA-5365 (CAS RN 141102-74-1) are new revelations to the public.

The Novichok class of chemical warfare agents belongs to those organophosporus compounds containing also a dihaloformaldoxime group: -O-N=C(X)Y group (X,Y = Cl, F, Br or even stable pseudohalogens such as C#N). Two examples of Novichok compounds are
a) Smiles: P(F)(=O)(O\N=C(/Cl)F)OCCCl with CAS RN 26102-97-6 and
b) Smiles: F/C(Cl)=N\OP(=O)(OCC)N(C)CCCl with CAS RN 26102-99-8
as published in Kruglyak, Yu. L.; Malekin, S. I.; Leibovskaya, G. A.; Khromova, Z. I.; Sretenskaya, I. I.; Martynov, I. V.: Reaction of alpha-chloronitrosoalkanes with phospholanes and iminophosphites, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 4th (1972), Meeting Date: 1969, p. 307-312. Editor: Grechkin, N. P. Publisher: Nauka, Moscow, USSR. In fact the group of Novichok CWAs is quite large and it would be difficult to protect soldiers and civil personnel, when many different chemicals belonging this class of CWA could be used in chemical warfare with rogue nations or terrorists.

Several Russian chemists as P.P. Kirpichev, R.K. Bal'chenko, I.V. Martynov, Yu.A. Kruglyak, S.I. Malekin, and N.F. Privezentseva from the Moscow institutes GosNIIOKhT and INEOS developed
the principle of these extremely toxic OP haloformaldoximes already during the mid 60's. Rapid progress toward supertoxic variants was seen in the early 70's and the synthesis details were indeed published mainly in the Journal of General Chemistry (Zhurnal Obshchei Khimii), although absolutely no toxicity data of the Novichoks were revealed. All activities were covered as research for pesticides at that time. All publication activities of these authors ceased at the end of 1972.

Michael Crichton alias John Lange published in 1972 the thriller "Binary" which alarmed Russian politicians and military personnel to act quickly on the looming threat of US binary chemical weapons. In 1973 the further activities in the USSR under the new Foliant program were disguised again as a pesticide research program but kept secret until 1986 when some of the researches could publish more details about chemical and biological effects of phosphorylated oximes (e.g. Raevskii, 0. A.; Chapysheva, N. V.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Effect of alkyl substituents in phosphorylated oximes, Zhurnal Obshchei Khimii (1987), 57(12), 2720-2723 and Raevskii, O. A.; Grigor'ev, V. Yu.; Solov'ev, V. P.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Electron-donor functions of ethyl methylchloroformimino methylphosphonate, Zhurnal Obshchei Khimii (1987), 57(9), 2073-8)). It became clear that Novichoks do resist strongly poisoned Acetylcholinesterase/Butyrylcholinesterase reactivation by other common oximes (e.g. 2-PAM/EA-2170, TMB-4/EA-1814) as used so far by the American military forces. The final details to US authorities were given by Vil S. Mirzayanov alias Kenneth (Ken) Alibek who was responsible to detect any Novichok traces in the environment of the GosNIIOKhT branch no. 4 (CWA plant for Novichok) at Vol'sk-17 by gas chromatography. He, as an long standing expert in gas chromatography having the details of what he had to look for in the analyses defected to the US in 1992.

Since the beginning of the 90's US chemical demilitarization programs in the former GUS also included joint research on Novichoks. Now in order to develop effective detectors, detoxifiers, reactivators and bioscavengers (including BuChE). All such programs were named under activities versus "Fourth Generation Agents" (FGA) or "Non-Traditional Agents" (NTA). It seems each year is now coming up with a new disguising term in order not to use "Novichok" in public US documents. "Dusty agents" are also not covered in Ellison's handbook but should be seen in conjunction with the Novichok developments during the 70's and 80's. The Russian researchers V.A. Pasechnik, O.I. Stuzhuk, and Ye.A. Gayev contributed to this development. O.I. Stuzhuk proposed special minerals and diatoms for being contaminated with CWAs, whereas Ye. A. Gayev developed the physical CWA spraying/aerosol system and V.A. Pasechnik contributed to the development and application of "dusty agents" containing biological weapons.


More details would be fine, November 16, 2003
Reviewer: Anatoly Kuntsevich (Moscow, Russia) - See all my reviews
Although this book does not reveal the precise chemical formulas for the Novichok class of nerve agents it introduces into the hidden world of russian chem-bio weapon designers. The intelligence still fears to make public that Novichoks belong to organophosporus compounds containing the double halogenated oxime like -O-N=C(F)Cl group and that beside P.P.Kirpichev also I.V.Martnov and Yu.A.Kruglak from GosNIOKhT developed the principle of these extremely toxic OP oximes during the mid 60's already (and published also) which resist reactivation by other oximes. These chemicals an be made by heating only of substituted 1,3,2-dioxaphospholanes indicated slighly in this book. Hopefully int'l organizations will make public more details for the protection of other citizens than just army soldiers soon. (Review for Cassidy's Run: The Secret Spy War over Nerve Gas (Thorndike Press Large Print Core Series) [LARGE PRINT] )

MrSamosa
April 10th, 2005, 09:42 PM
Curse censorship, but thank God for Google caches and cheap websites who copy reviews from Amazon.com :) . Fear not Mega, all is not lost. But it is being lost faster than I thought... I used to find copies of that review all over Google, but the numbers are dwindling. So for safe-keeping, I'll put the original reviews right here in this thread; as you will see, most of my editing was for the sake of clarity--fixing grammar, rewording sentences, adding pictures.

Novichok(s), dusty agents and GV/GP agents, December 14, 2003
Reviewer: Anatoly Kuntsevich from Moscow, Russia
Although this book is missing the chemistry of the Novichok class of nerve agents it summarizes the physico-chemical data of the known CWAs. Most of the data are taken from the older Field Manual FM 3-9 (1990). The expert may find that some of the data are only estimated, but not indicated as such. Only the details of GV-4 alias EA-5414 (CAS RN 158847-17-7) and GP/GV alias EA-5365 (CAS RN 141102-74-1) are new revelations to the public.

The Novichok class of chemical warfare agents belongs to those organophosporus compounds containing also a dihaloformaldoxime group: -O-N=C(X)Y group (X,Y = Cl, F, Br or even stable pseudohalogens such as C#N). Two examples of Novichok compounds are
a) Smiles: P(F)(=O)(O\N=C(/Cl)F)OCCCl with CAS RN 26102-97-6 and
b) Smiles: F/C(Cl)=N\OP(=O)(OCC)N(C)CCCl with CAS RN 26102-99-8
as published in Kruglyak, Yu. L.; Malekin, S. I.; Leibovskaya, G. A.; Khromova, Z. I.; Sretenskaya, I. I.; Martynov, I. V.: Reaction of alpha-chloronitrosoalkanes with phospholanes and iminophosphites, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 4th (1972), Meeting Date: 1969, p. 307-312. Editor: Grechkin, N. P. Publisher: Nauka, Moscow, USSR. In fact the group of Novichok CWAs is quite large and it would be difficult to protect soldiers and civil personnel, when many different chemicals belonging this class of CWA could be used in chemical warfare with rogue nations or terrorists.

Several Russian chemists as P.P. Kirpichev, R.K. Bal'chenko, I.V. Martynov, Yu.A. Kruglyak, S.I. Malekin, and N.F. Privezentseva from the Moscow institutes GosNIIOKhT and INEOS developed
the principle of these extremely toxic OP haloformaldoximes already during the mid 60's. Rapid progress toward supertoxic variants was seen in the early 70's and the synthesis details were indeed published mainly in the Journal of General Chemistry (Zhurnal Obshchei Khimii), although absolutely no toxicity data of the Novichoks were revealed. All activities were covered as research for pesticides at that time. All publication activities of these authors ceased at the end of 1972.

Michael Crichton alias John Lange published in 1972 the thriller "Binary" which alarmed Russian politicians and military personnel to act quickly on the looming threat of US binary chemical weapons. In 1973 the further activities in the USSR under the new Foliant program were disguised again as a pesticide research program but kept secret until 1986 when some of the researches could publish more details about chemical and biological effects of phosphorylated oximes (e.g. Raevskii, 0. A.; Chapysheva, N. V.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Effect of alkyl substituents in phosphorylated oximes, Zhurnal Obshchei Khimii (1987), 57(12), 2720-2723 and Raevskii, O. A.; Grigor'ev, V. Yu.; Solov'ev, V. P.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Electron-donor functions of ethyl methylchloroformimino methylphosphonate, Zhurnal Obshchei Khimii (1987), 57(9), 2073-8)). It became clear that Novichoks do resist strongly poisoned Acetylcholinesterase/Butyrylcholinesterase reactivation by other common oximes (e.g. 2-PAM/EA-2170, TMB-4/EA-1814) as used so far by the American military forces. The final details to US authorities were given by Vil S. Mirzayanov alias Kenneth (Ken) Alibek who was responsible to detect any Novichok traces in the environment of the GosNIIOKhT branch no. 4 (CWA plant for Novichok) at Vol'sk-17 by gas chromatography. He, as an long standing expert in gas chromatography having the details of what he had to look for in the analyses defected to the US in 1992.

Since the beginning of the 90's US chemical demilitarization programs in the former GUS also included joint research on Novichoks. Now in order to develop effective detectors, detoxifiers, reactivators and bioscavengers (including BuChE). All such programs were named under activities versus "Fourth Generation Agents" (FGA) or "Non-Traditional Agents" (NTA). It seems each year is now coming up with a new disguising term in order not to use "Novichok" in public US documents. "Dusty agents" are also not covered in Ellison's handbook but should be seen in conjunction with the Novichok developments during the 70's and 80's. The Russian researchers V.A. Pasechnik, O.I. Stuzhuk, and Ye.A. Gayev contributed to this development. O.I. Stuzhuk proposed special minerals and diatoms for being contaminated with CWAs, whereas Ye. A. Gayev developed the physical CWA spraying/aerosol system and V.A. Pasechnik contributed to the development and application of "dusty agents" containing biological weapons.


More details would be fine, November 16, 2003
Reviewer: Anatoly Kuntsevich (Moscow, Russia) - See all my reviews
Although this book does not reveal the precise chemical formulas for the Novichok class of nerve agents it introduces into the hidden world of russian chem-bio weapon designers. The intelligence still fears to make public that Novichoks belong to organophosporus compounds containing the double halogenated oxime like -O-N=C(F)Cl group and that beside P.P.Kirpichev also I.V.Martnov and Yu.A.Kruglak from GosNIOKhT developed the principle of these extremely toxic OP oximes during the mid 60's already (and published also) which resist reactivation by other oximes. These chemicals an be made by heating only of substituted 1,3,2-dioxaphospholanes indicated slighly in this book. Hopefully int'l organizations will make public more details for the protection of other citizens than just army soldiers soon. (Review for Cassidy's Run: The Secret Spy War over Nerve Gas (Thorndike Press Large Print Core Series) [LARGE PRINT] )

simply RED
April 13th, 2005, 07:56 AM
Quite impressive !
by the way...
I found genuine military toxicology report (Varshava pact) from 1971.
Novichok is not lised but anyway.
Hope will be interesting.
translation of the interesting part :

" We managed to test VX series contaning sulphur or nitrogen but not
holine part. They found out to be 10 to 100 times more toxic than normal VX gas even without fluorine in their molecules.
Normal VX (methylfluorophosphorylholine LD50 = 0,1 mg/kg )

Samples included:
GD-7

(C2H50)(CH3)(P=O)-S-CH2-CH2-S-C2H5

GD-42

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
LD50 = 0,032 mg/kg

We tested organophosphorous sulphur comatining series (proposed by K. Los)

Samples included

Compound-2

(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5)
LD 50 = 0,07 mg/kg

Compound-4

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg
{{{{{simple isn't it !!!}}}}}

EDEMO

O-ethyl-S-/2-diethylaminoethyl/methylthiophosphonate
LD 50 = O,02 mg/kg
And other compounds. {{{{{{not listed!!! sh**!!!}}}}}

We estimated 0,1-1 mg to be the absolute lethal dose (inhalation) for human of the new VX series.
VX gas "MEDETFK" was absolutely always lethal (animal - Cat) in dose 0,03 mg/kg.
We estimated binary reagents could be prepared by mixing

Compund 1
(CH30)2(P=O)-S-CH2-CH2-S-C2H5
LD = 65 mg/kg {{{{ yes sixtyfive, like dimethoate or lambda cyhalothrine }}}}
with dimethylsulphate :
{{{{ Reaction written by me
(CH30)2(P=O)-S-CH2-CH2-S-C2H5 + (CH30)2SO2 =
(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5) CH3SO4(-)
LD = 0,07 mg/kg }}}}

Replacing sulphur with oxygen in any parts lowers the toxicity 1000 times.
{{{{{ this is about nerve gasses }}}}}
............................................

Our next goal is to test "crabaminoylcholinechloride" and "fluoroglucine"
{{{{{ translated 1:1 as they were misspelled }}}}}
for which we have intelligence data to be "tried" by the americans .


Somebody know how to prepare compound 1 ? :)

simply RED
April 13th, 2005, 07:56 AM
Quite impressive !
by the way...
I found genuine military toxicology report (Varshava pact) from 1971.
Novichok is not lised but anyway.
Hope will be interesting.
translation of the interesting part :

" We managed to test VX series contaning sulphur or nitrogen but not
holine part. They found out to be 10 to 100 times more toxic than normal VX gas even without fluorine in their molecules.
Normal VX (methylfluorophosphorylholine LD50 = 0,1 mg/kg )

Samples included:
GD-7

(C2H50)(CH3)(P=O)-S-CH2-CH2-S-C2H5

GD-42

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
LD50 = 0,032 mg/kg

We tested organophosphorous sulphur comatining series (proposed by K. Los)

Samples included

Compound-2

(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5)
LD 50 = 0,07 mg/kg

Compound-4

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg
{{{{{simple isn't it !!!}}}}}

EDEMO

O-ethyl-S-/2-diethylaminoethyl/methylthiophosphonate
LD 50 = O,02 mg/kg
And other compounds. {{{{{{not listed!!! sh**!!!}}}}}

We estimated 0,1-1 mg to be the absolute lethal dose (inhalation) for human of the new VX series.
VX gas "MEDETFK" was absolutely always lethal (animal - Cat) in dose 0,03 mg/kg.
We estimated binary reagents could be prepared by mixing

Compund 1
(CH30)2(P=O)-S-CH2-CH2-S-C2H5
LD = 65 mg/kg {{{{ yes sixtyfive, like dimethoate or lambda cyhalothrine }}}}
with dimethylsulphate :
{{{{ Reaction written by me
(CH30)2(P=O)-S-CH2-CH2-S-C2H5 + (CH30)2SO2 =
(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5) CH3SO4(-)
LD = 0,07 mg/kg }}}}

Replacing sulphur with oxygen in any parts lowers the toxicity 1000 times.
{{{{{ this is about nerve gasses }}}}}
............................................

Our next goal is to test "crabaminoylcholinechloride" and "fluoroglucine"
{{{{{ translated 1:1 as they were misspelled }}}}}
for which we have intelligence data to be "tried" by the americans .


Somebody know how to prepare compound 1 ? :)

simply RED
April 13th, 2005, 07:56 AM
Quite impressive !
by the way...
I found genuine military toxicology report (Varshava pact) from 1971.
Novichok is not lised but anyway.
Hope will be interesting.
translation of the interesting part :

" We managed to test VX series contaning sulphur or nitrogen but not
holine part. They found out to be 10 to 100 times more toxic than normal VX gas even without fluorine in their molecules.
Normal VX (methylfluorophosphorylholine LD50 = 0,1 mg/kg )

Samples included:
GD-7

(C2H50)(CH3)(P=O)-S-CH2-CH2-S-C2H5

GD-42

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
LD50 = 0,032 mg/kg

We tested organophosphorous sulphur comatining series (proposed by K. Los)

Samples included

Compound-2

(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5)
LD 50 = 0,07 mg/kg

Compound-4

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg
{{{{{simple isn't it !!!}}}}}

EDEMO

O-ethyl-S-/2-diethylaminoethyl/methylthiophosphonate
LD 50 = O,02 mg/kg
And other compounds. {{{{{{not listed!!! sh**!!!}}}}}

We estimated 0,1-1 mg to be the absolute lethal dose (inhalation) for human of the new VX series.
VX gas "MEDETFK" was absolutely always lethal (animal - Cat) in dose 0,03 mg/kg.
We estimated binary reagents could be prepared by mixing

Compund 1
(CH30)2(P=O)-S-CH2-CH2-S-C2H5
LD = 65 mg/kg {{{{ yes sixtyfive, like dimethoate or lambda cyhalothrine }}}}
with dimethylsulphate :
{{{{ Reaction written by me
(CH30)2(P=O)-S-CH2-CH2-S-C2H5 + (CH30)2SO2 =
(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5) CH3SO4(-)
LD = 0,07 mg/kg }}}}

Replacing sulphur with oxygen in any parts lowers the toxicity 1000 times.
{{{{{ this is about nerve gasses }}}}}
............................................

Our next goal is to test "crabaminoylcholinechloride" and "fluoroglucine"
{{{{{ translated 1:1 as they were misspelled }}}}}
for which we have intelligence data to be "tried" by the americans .


Somebody know how to prepare compound 1 ? :)

akinrog
April 13th, 2005, 09:05 AM
Compound 4 seems dubious to me.

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg

How Sulfur may have three bonds (like -S(+)(C2H5)(C2H5))?

Maybe a typo if sulfur is nitrogene then everything fits and we have VX :)

akinrog
April 13th, 2005, 09:05 AM
Compound 4 seems dubious to me.

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg

How Sulfur may have three bonds (like -S(+)(C2H5)(C2H5))?

Maybe a typo if sulfur is nitrogene then everything fits and we have VX :)

akinrog
April 13th, 2005, 09:05 AM
Compound 4 seems dubious to me.

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg

How Sulfur may have three bonds (like -S(+)(C2H5)(C2H5))?

Maybe a typo if sulfur is nitrogene then everything fits and we have VX :)

megalomania
April 15th, 2005, 06:49 PM
It has occured to me that a little social networking is in order to track down all possible scientific articles about Novichok agents and chemical weapons in general. Thanks to the papers provided by Samosa and Fritz I have used the names of the authors in those articles as a basis for a search for all of their respective articles.

The theory is whoever publishes an article about a chemical weapon has probably published other articles on chemical weapons. The theory also stipulates whoever he co-authored these papers with also probably work in chemical weapons, so their articles are likely to be related to chemical weapons research.

The end result is I have nearly 1000 articles published by the top dozen names, leading me to dozens more authors. I now have to sift through the first batch of all the articles to weed out any unrelated publications, and to find out who the co-authors of the good articles are.

I also read a tidbit in Tobiasons Scientific Principles, the chemical weapons volume, that the Soviets intentionally published large amounts of chemical weapons information in the open literature in the 1950s and 1960s with the hope some rogue nation would use the information to attack the US. The goal here was for the rogue state to finish the job for the Soviet Union, or at least inflict massive American casualities. Now all I need to do is find out what journals they published this stuff in. Zhurnal Obshchei Khimii is probably a good place to start since it has an English translation.

Also, in the paper by Mr Samosa the molecular structures for the two examples of Novichok compounds are incorrect. I donít know if the CAS numbers are wrong for the right structures, or if the structures are wrong for the right CAS number. I think the wrong structures were used for the right CAS numbers.
(see attached image)

One name that seems to pop up a lot is I. V. Martynov. He has published about 500 journal articles in his lifetime to date. Indeed there are many about phosphorus compounds, but those type of articles cease after 1972. He publishes many articles about molecular refraction after that. In 1984 he resumes publication of phosphorus related articles.

One article in particular caught my eye:
Synthesis and anticholinesterase activity of fluorochloronitroacetic acid esters. Ivanov, Yu. Ya.; Brel, V. K.; Postnova; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1985), 19(8), 968-71.

There are a few earlier articles about fluorochloronitroacetic acid esters. These are important in the systhesis of Novichoks I would imagine. Samosa did mention in his paper (NovDAGVGP.doc attached earlier) that dihaloformaldoxime are critical parts of Novichok agents, and fluorochloronitroacetic acid should form those.

Another article Martynov published related to bicyclic phosphates. There is another thread Samosa started about those. I donít know enough about them to say if this article is of interest. The abstract mentions this compound is a chloride blocker, it blocks GABA-independent Cl- channels specificially. Perhaps someone with knowledge of biology can say if blocking those is lethal. The article is:
4-Methyl- and 4-ethylbicyclophosphates, blockers of chloride channels. Fetisov, V. I.; Redkozubov, A. E.; Lyubimov, V. S.; Sokolov, V. S.; Martynov, I. V.. USSR. Biologicheskie Membrany (1986), 3(9), 968-70.
4-Methyl- (I; R = Me) [1449-89-4] and 4-ethylbicyclophosphate (I; R = Et) [1005-93-2] were effective blockers of GABA-independent Cl- channels (of Limnaea stagnalis giant neurons). Both potential and thermoregulation of the Cl- channels were affected.


Here is another article of potential use in the preparation of Novichok agents. This compound is similar to fluorochloronitroacetic acid from which this substance is made:
Synthesis of chlorofluoronitronitrosomethane. Martynov, I. V.; Brel, V. K.; Uvarova, L. V. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (4), 952-3.
Decarboxylation-nitrosation of ClFC(NO2)CO2H with HNO3 gave 52% ClFC(NO)NO2

Here is another possible tidbit as it relates to insecticides and plant growth regulation. We know they disguised their research under the guise of agrichemicals:
Synthesis and pesticidal activity of chloronitroacetic acid esters. Martynov, I. V.; Yurtanov, A. I.; Ivanov, Yu. J.; Kulish, E. V.; Uvarova, L. V.; Andreeva, E. I.; Rozhkova, N. G.; Zhirmunskaya, N. M. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1986), 289(1), 109-13 [Chem.].
A series of 31 O2NCRR1CO2R [e.g., R, R1, R2 = H, Cl, n-C7H15 (I); F, Cl, ClCH2CH2; Br, Cl, Et] was tested for insecticidal and, in some cases, plant growth regulatory activity. Eight of the compds., e.g., I, were active insecticides. Twelve of the compds. were new but no prepn. details were given.

Here is another possible Novichok variant:
Reaction of phosphorus trichloride with 1,1,2-trichloro-1-nitrosoethane in sulfur dioxide. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (9), 2158.
Reaction of ClCH2CCl2NO with PCl3 in SO2 gave 58% ClCH2CCl:NOP(O)Cl2.


Here is yet another possible Novichok variant:
Reaction of dialkyl phosphites with 1,1-dichloronitrosoalkanes. Ivanov, A. N.; Epishina, T. A.; Goreva, T. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (1), 226-8.
(RO)2P(O)ON:CClR1 (R = Bu, Me2CHCH2, pentyl, Me, Et; R1 = Me, Et, Pr, Me2CH, Bu, Me2CHCH2) were prepd. in 44-67% yields by treating (RO)2POH with ONCCl2R1 in EtOH at 20.

Here is a toxicity study done on animals and humans for some pesticides. Yeah, pesticides, thatís the ticket:
Delayed neurotoxicity from organophosphorus pesticides. Makhaeva, G. F.; Malygin, V. V.; Martynov, I. V.. USSR. Agrokhimiya (1987), (12), 103-24.
A review with 123 refs. on 8 clin. intoxication symptoms, pathmorphol., mechanisms of initiation of delayed neurotoxicity by organophosphorus pesticides (OPP) structure-activity relations of OPP, monitoring of the delayed neurotoxicity of OPP in animals and humans, etc.

Here is another possible Novichok variant:
Reaction of O-alkyl methylphosphonites with 1,1-dichloro-1-nitrosopropane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(4), 952-3.
Reaction of ROP(O)HMe (R = Me2CH, Bu, pentyl) with EtCCl2NO in Et2O gave 50-52% ROP(O)MeON:CClEt (I; same R). Treating MeP(OR)2 with EtCCl2NO also gave I.

Here is an interesting reference, although I doubt this would have very high human toxicity due to the two large aryl groups attached to phosphorus. Still, it gives enlightenment as to where they are headed:
Reaction of diphenylphosphinous acid with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Epishina, T. A.; Ivanov, A. N.; Kharitonov, A. V.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1658-9.
Treating Ph2P(O)H with RCCl2NO (R = Et, Pr, Me2CH) in Et2O gave 62-75% Ph2P(O)ON:CClR (same R).


Another Novichok possibility:
Synthesis and the structure of dialkylfluoroformiminophosphates. Martynov, I. V.; Brel, V. K.; Uvarov, V. I.; Yarkov, A. V.; Novikov, V. P.; Chepakova, L. A.; Raevskii, O. A. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (4), 857-60.
Syn- And anti-(RO)2P(O)N:CHF (R = Me, Et, Pr, Bu) were prepd. in 11-25% yields by treating (RO)3P with ClCHFNO2.

Here is some nasty looking stuff that may be of interest:
Reaction of (-aminoalkyl)phosphonates with perfluoro-2-azapropene. Aksinenko, A. Yu.; Pushin, A. N.; Sokolov, V. B.; Gontar, A. F.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1177-9.
(RO)2P(O)CMeR1N:C:NCF3 (R = Me, R1 = Et; R = Et, R1 = Et, Pr, Bu; R = Me2CHCH2, R1 = Et) were prepd. in 40-60% yields by condensing CF2:NCF3 with (RO)2P(O)CMeR1(NH2) in the presence of KF.

Here is another variant:
Reaction of polychloronitrosoethanes with phosphorous acid derivatives. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1086-9.
The title reaction gave 20-93% of 22 o-phosphorylated alkyl chloroformimines. Thus, treating ONCCl2R (R = Me, CH2Cl, CHCl2) with (R1O)3P (R1 = Me, Pr, Bu, Me2CHCH2, pentyl, ClCH2CH2) gave (R1O)2P(O)ON:CClR.

Of all the other compounds I have previously referenced this particular compound looks like it may be the deadliest. It has some similarities to most other nerve gasses in that it uses the simplest alkyl groups, and has a direct alkyl and a direct halogen attachment to phosphorus. I would replace those chlorines with fluorine to increase the toxicity:
Reaction of dichloromethylphosphine with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1659-60.
MePCl2 reacted with RCCl2NO (R = Et, Pr, Me2CH) in SO2 to give 27-37% RCCl:NOP(O)ClMe.

This compound looks like a good precursor for organophosphorus agents like the previous compound. The chlorines can be replaced by F, and one of the fluorines can form an ester or something else. The second compound is an example of what could be made, and I just bet that stuff is pretty toxic.
Interaction of 2,2,3,3-tetrafluoropropyl dichlorophosphite with 1,1,2-trichloro-1-nitrosoethane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (6), 1422-3.
Refluxing CHF2CF2CH2OPCl2 (I) with CH2ClCCl2NO (II) in Et2O gave 67.8% Cl2P(O)ON:CClCH2Cl. Treating I with II in SO2 at 20 gave 48.2% (CHF2CF2CH2O)ClP(O)ON:CClCH2Cl.

We might have a real winner with this one as it has similarities with VX nerve gas. The second compound in particular has a =S group. If that could be isomerized, like it is done in making VX, then we have a thioester. The two isobutyl groups are probably too large to make this particular compound all that toxic. I am sure they could be replaced with methyls instead.
Reaction of diisobutylchlorophosphine with 1,1-dichloro-1-nitrosoalkanes in presence of sulfur dioxide and ethyl mercaptan. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2586-8.
Treating (Me2CHCH2)2PCl with RCCl2NO (R = Me, Et, Pr, Me2CH) in Et2O contg. SO2 gave 61-74% (Me2CHCH2)2P(O)ON:CRCl (same R). When Et2SH was used instead of SO2, 44% (Me2CHCH2)2P(S)ON:CRCl (R = Me) was obtained.

Another phenyl attached compound:
Synthesis and molecular structure of (O-isopropylchloroformimino) diphenylphosphinate. Martynov, I. V.; Chekhlov, A. N.; Ivanov, A. N.; Epishina, T. A.; Makhaev, V. D.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2595-7.
Treating Ph2PH with Me2CHCCl2NO in C6H6 gave 58% Ph2P(O)ON:CClCHMe2, the structure of which was detd. by x-ray crystallog.

This compound has some VX similarities too:
O,O-Dialkyl O-(dialkylformimino) thiophosphates. Chepakova, L. A.; Brel, V. K.; Pushin, A. N.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(12), 2716-19.
Twelve (R1O)2P(S)ON:CMeR (R = Me, Et, Pr; R1 = Me, Et, Pr, Bu) were prepd. in 41-62% yields by treating (R1O)2PHS with ONCClMeR or HON:CMeR.

These compounds are similar to the last journal reference except the R and Rí groups are switched. Isomerize that S and we may have something far more toxic.
O-(Alkylchloroformimino) O,O-dialkyl thiophosphates. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (12), 2854-5.
Seven (RO)2P(S)ON:CClR1 (R = Et, Me2CH; R1 = Me, Et, Pr, Me2CH, ClCH2) were prepd. in 33-54% yields by condensing (RO)2PSH with R1Cl2CNO in THF.

Martynov has 64 publications in 1988 alone, his best year. In no particular order here are some highlights:

Molecular and crystal structure of O,O-diethyl 1-[N2-(trifluoromethyl)fluoroformamidino]-1-methylethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Korenchenko, O. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 302(4), 855-8 [Chem.].
The crystal and mol. structure of (EtO)2P(O)CMe2NHCFNCF3 was detd.

Reaction of (N-acetyl-N-ethylamido)alkylphosphonic acid chlorides with cesium fluoride. Krolevets, A. A.; Adamov, A. V.; Popov, A. G.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2628-9.
RP(O)F(NEtCH:CH2) (R = Me, Me2CH) were prepd. in 45, 50% yields, resp., by treating RPCl(NEtAc) (I) with CsF. I were prepd. in 60, 65% yields, resp., by treating RPCl2 with Me3SiNEtAc.

Stable alkoxyfluorophosphoranes. Krolevets, A. A.; Popov, A. G.; Adamov, A. V.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2626-7.
RPF2(OR1)2 (R = BuCHClCH2, R1 = Me3C; R = Me2CClCH2, R1 = Et) were prepd. in 45, 40% yields, resp., by treating RPF4 with Me3SiOR1.

O-(Alkylchloroformimidoyl) o-alkyl methylphosphonates. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1128-30.
Nine (RO)MeP(O)ON:CClR1 (R = Et, Pr, Bu, Me2CH, pentyl; R1 = Me, Et, Pr, Bu, Me2CH) were prepd. in 41-67% yields by treating R1CCl2NO with MeP(OR)2 or MeP(O)H(OR).

Reaction of 1,1-dichloro-1-nitrosoalkanes with phosphorus(III) chlorides. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (9), 2128-32.
The title reaction was studied. Thus, R1R2P(O)ON:CRCl (R = Me, Et, Pr, Me2CH; R1 = R2 = Cl, Me2CHCH2; R1 = Cl, R2 = Me) were prepd. in 34-74% yields by reaction of RCCl2NO with R1R2PCl in the presence of SO2.

Synthesis and x-ray diffraction study of N-(diisopropoxythiophosphoryl)thioacetamide. Solov'ev, V. N.; Chekhlov, A. N.; Zabirov, N. G.; Cherkasov, R. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 300(6), 1386-9 [Chem.].
Treating MeCSNH2 with Me3COK in MeCN and then with ClP(S)(OCHMe2)2 gave 15% MeCSNHP(S)(OCHMe2)2, the structure of which was detd. by x-ray crystallog.

Reaction of 1,1-dichloro-1-nitrosoethane with phosphorus oxychloride in the presence of zinc. Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (7), 1691.
Cl2P(O)ON:CClMe was prepd. in 26.6% yield by treating MeCCl2NO with POCl3 in the presence of Zn.

Comparative studies on the interaction of acetylcholinesterases from human erythrocytes and housefly heads with phosphorylated alkylchloroformoxims. Shataeva, G. A.; Makhaeva, G. F.; Yankovskaya, V. L.; Sokolov, V. B.; Ivanov, A. N.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Zhurnal Evolyutsionnoi Biokhimii i Fiziologii (1988), 24(6), 791-6.
Among Valexon analogs, 6 (RO)2P(O)ON:CClMe (I), 6 (RO)2P(O)ON:C(Cl)CH2Cl (II), and 5 (RO)2P(O)ON:C(Cl)CHCl2 (III, R = Me, Et, Pr, iso-Bu, Bu, amyl), and 4 (EtO)2P(O)ON:C(Cl)R1 (IV, R1 = Me, Et, Pr, Bu), I-III (R = Et) were highly selective insecticides, having rate consts. of bimol. reaction with acetylcholinesterase (KII) of human erythrocytes (HE) lower by 1 magnitude order than with that from housefly heads (FL). Inhibition of both HE and FL followed the order I < II < III. Phosphorylation capacity of II 1.6-fold exceeded that of I. Replacing Me by Et, increased the effect of I-III on FL 3-8-fold and decreased that on HE 1.7-4-fold. Further increases in hydrophobicity abolished the specificity of I-III. The selectivity of IV decreased in order of R1: Me > Et > Bu; IV (R1 = Pr) showed no selectivity.

Fluorination of some phosphoric acid derivatives. Zavorin, S. I.; Lermontov, S. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka., USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1174-6.
Dialkyl fluorophosphates were prepd. by the title fluorination with Et3N.3HF (I). Thus, fluorination of (EtO)2P(O)ON:CCl2 with I in MeCN gave 83.5% (EtO)2P(O)F.

Reaction of fluorine-containing acetylenic alcohols with phosphorus trichloride. Brel, V. K.; Chekhlov, A. N.; Ionin, B. I.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1988), 58(4), 750-7.
Treating RC.tplbond.CCMe(OH)CH2F (I; R = Ph) with PCl3 in Et2O gave 45% Cl2P(O)CR:C:CMeCH2F (II; R = Ph) and 24% E- and Z-Cl2P(O)CHPhCCl:CMeCH2F (III). Under the same conditions, I (R = MeOCH2) gave a mixt. of II (R = MeOCH2) and Cl2P(O)C(:CH2)CCl:CMeCH2F. Treating I (R = Ph) with MeOH and then with Br2 gave oxaphospholene IV. The structure of III was detd. by x-ray crystallog.

Synthesis and anticholinesterase activity of fluorochloronitroacetic acid thioesters. Ivanov, Yu. Ya.; Uvarov, V. I.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(5), 538-40.
Treating O2NCFClCOX (I; X = OH) with PCl5 gave I (X = Cl), which reacted with RSH (R = Et, Bu) to give 35-55% I (X = SR; same R) (II). II were less effective acetylcholinesterase inhibitors than I (X = OR; same R) but had comparable activity vs. butyrylcholinesterase with lower toxicity.

Synthesis and antiesterase activity of sulfur-containing phosphorylated oximes. Chepakova, L. A.; Bret, V. K.; Makheva, G. F.; Yankovskaya, V. L.; Beznosko, B. K.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(2), 143-6.
Reaction of (RS)2POEt (R = Et, Pr, iso-Bu, Bu or amyl) with O:NCFCl2 gave the corresponding (RS)2P(:O)ON:CClF (I). An increase in the hydrophobicity of I did not alter the anticholinesterase activity of I, while the butyrylcholinesterase and carboxylesterase activity were increased.

O-substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov Iu Ia; Sokolov V B; Epishina T A; Martynov I V Doklady Akademii nauk SSSR (1990), 310(5), 1253-5.

Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid. Kuusk V V; Morozova I V; Agabekian R S; Aksinenko A Iu; Epishina T A; Sokolov V B; Kovaleva N V; Razdol'skiy A N; Fetisov V N; Martynov I V Bioorganicheskaia khimiia (1990 Nov), 16(11), 1500-8.
A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.

Reaction of 1,1-dichloro-1-nitrosobutane with (N,N-dimethylamido)dichlorophosphite. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (6), 1416-18.
Reaction of PrCCl2NO with Me2NPCl2 in Et2O or in SO2 gave 36% Me2NPCl4 or 30% Me2NP(O)ClON:CClPr, resp. Treating Me2NPCl4 with SO2 gave 91% Me2NP(O)Cl2. Reaction of PrCCl2NO with Me2NPCl2 in Et2O, and then with Ph3P and distn. gave Ph3PO and PrCN.

Alkyl chlorofluoroformimino perfluoroalkylphosphonates. Chepakova, L. A.; Brel, V. K.; Martynov, I. V.; Maslennikov, I. G. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(6), 1455-6.
Treating RP(OR1)2 (R = CF3, R1 = Pr, Bu; R = CF3CF2, R1 = Me, Bu) with CFCl2NO in Et2O gave 76-88% title compds. R1OP(O)RON:CFCl.

Synthesis of dialkyl (3-alkyl-1,3-alkadien-2-yl)phosphonates. Brel, V. K.; Abramkin, E. V.; Martynov, I. V.; Ionin, B. I. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(9), 2142-3.
(RO)2P(O)C(:CH2)CR1:CMe2 (R = Et, Pr; R1 = Me, Et) were prepd. in 41-73% yields by the Grignard reaction of (RO)2P(O)C(CH2OMe):C:CMe2 with R1X (X = halo).

Synthesis and antiesterase activity of O,O-dialkyl S-(ethoxycarboxyl)chloromethyl thiophosphates. Khaskin, B. A.; Makhaeva, G. F.; Torgasheva, N. A.; Ishmuratov, A. S.; Yankovskaya, V. L.; Fetisov, V. I.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovko, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2741-6.
The title compds. (RO)2P(O)SCHClCO2Et (I; R = alkyl homologs) were prepd. in 82-95% yields in the reaction of (RO)2P(O)SCl with N2CHCO2Et at -25 (in Et2O) or 6-7 (in benzene), presumably via a noncarbene mechanism. I irreversibly inhibited acetylcholinesterase, butyrylcholinesterase, and carboxylesterase; antibutyrylcholinesterase activity increased in the homologous series of R, with max. at R = Bu. An antiesterase MSBAR of I was fulfilled with parameters representing hydrophobicity and steric properties of R.

Synthesis and cholinesterase hydrolysis of O-acylated alkylchloroformoximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Agabekyan, R. S.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1989), 23(11), 1317-20.
The title compds., RCO2N:CClR1 (R = Me, Et, Pr or CH2Cl and R1 = Me, Et, Pr, or iso-Pr) were prepd. e.g., by the reaction of 1,1-dichloro-1-nitrosobutane with AcCl in the presence of Zn. These compds. were good substrates for acetyl- and butyrylcholinesterases. The kinetic parameters (Km, Vmax and ac) of these compds. in the hydrolysis reactions were comparable to those with acetylcholine. The acute toxicity was 79-381 mg/kg in mice given drugs orally.

Synthesis and structure of O,O-dialkyl 2-[(ethoxycarbonyl)amino]hexafluoroisopropylphosphonates. Aksinenko, A. Yu.; Chekhlov, A. N.; Korenchenko, O. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(1), 61-5.
The title compds. (RO)2P(O)C(CF3)2NHCO2Et (I; R = Me, Et, CHMe2) were prepd. in 54-76% yields in the reaction of (RO)2P(O)H with (CF3)2C:NCO2Et. The crystal and mol. structure of I (R = Et) was detd.

O-Substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1990), 310(5), 1253-5 [Biochem.].
The ability of O-substituted alkylchloroformoximes to serve as substrates for acetylcholinesterase (ACE, EC 3.1.1.7) and butyrylcholinesterase (BCE, EC 3.1.1.8) and to inhibit acetylcholine hydrolysis by these enzymes was detd., along with the LD50 of these compds. in mice. The compds. tested were O-acylated alkylchloroformoximes of the general formula R1C(O)ON:C(Cl)R2 [R1 = R2 = Me; R1 = Me, R2 = Et; R1 = Me, R2 = Pr; R1 = Et, R2 = Me; R1 = Et, R2 = iso-Pr; R1 = Pr, R2 = iso-Pr; R1 = CH2Cl, R2 = Pr (I); R1 = CH2Cl, R2 = iso-Pr (II)], O-carbonylated alkylchloroformoximes of the general formula EtOC(O)ON:C(Cl)R [R = Me (III), iso-Pr (IV)], and O-carbamoylated alkylchloroformoximes of the general formula (Me)2NC(O)ON:C(Cl)R [R = Me (V), iso-Pr (VI)]. All of the compds. except for I and II were good substrates for the enzymes, with Km values for ACE ranging (0.3-11.0)  10-4M and for BCE ranging (0.5-13.0)  10-4M (the Km values of ACE and BCE with acetylcholine were 1.3  10-4 and 5.4  10-4M, resp.). III and IV were competitive (Ki 1.6  10-4M) and mixed-type (Ki 4.2  10-4M) inhibitors, resp., of ACE. V and VI were effective inhibitors of both ACE and BCE, with bimol. rate consts. for inhibition (kII) of 5.7  103 and 1.4  105 M-1 min-1, resp., for ACE, and 9.8  103 and 5.4  106 M-1 min-1, resp., for BCE. The LD50 values for the tested compds. ranged 60-381 mg/kg body wt.

O-(alkylchloroformimino)(methyl)thiophosphonic acid chlorides. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2865-6.
Treating the adduct from RCCl2NO and MePCl2 with H2S gave 21-35% MeP(S)ClON:CRCl.

Interaction of 1,1-dichloro-1-nitrosoalkanes with S-ethylmethylphosphonous chloride in the presence of sulfur dioxide. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (2), 464-5.
EtSP(O)MeON:CClR (R = Me, Et, Pr) were prepd. in 42-47% yields by treating RCCl2NO with EtSPMeCl in the presence of SO2.

O-(alkylchloroformimino)-O-alkylphosphoric acid chlorides. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (5), 1122-5.
Reaction of (ON)CCl2R with (R'O)2PCl (R, R' = alkyl) afforded the title compds. (R'O)ClP(O)ON:CRCl (I) in up to 69% yield. Hydrolysis of I led to substitution of P-, and not C-bound Cl, resulting in (R'O)(NH4O)P(O)ON:CRCl.

Reaction of the adduct of methyldichlorophosphine and 1,1-dichloro-1-nitrosoethane with thioacetic acid. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(8), 1923-4.
Treating MePCl2 with MeCCl2NO in PhMe, followed by addn of 1 or 2 equiv AcSH gave 56% MeP(S)ClON:CMeCl or 32% MeP(S)ClON:CMeSAc, resp.

Inhibition of cholinesterase activity by fluorine-containing derivatives of -aminoalkylphosphonic acids. Kuusk, V. V.; Morozova, I. V.; Agabekyan, R. S.; Aksinenko, A. Yu.; Epishina, T. A.; Sokolov, V. B.; Kovaleva, N. V.; Razdol'skii, A. N.; Fetisov, V. I.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Bioorganicheskaya Khimiya (1990), 16(11), 1500-8.
A series of O,O-diethyl-1-(N--hydrohexafluoroisobutyryl)aminoalkylphosphonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate consts. and the enzyme-inhibitor intermediate dissocn. consts. are calcd. The quant. structure-activity relationships including both hydrophobic and calcd. steric parameters of substituents are developed for APh-ChE interactions. Mol. mechanics (program MM2) was used for detg. steric parameters (Es). On the basis of QSAR models anal. it was concluded that hydrophobic interactions play an essential role in APh-AChE binding, whereas for APh-BuChE binding steric interactions are essential. Presence of at least two APh binding centers on the surface of AChE and BuChE is suggested.

Synthesis and anticholinesterase activity of O-carbamoylated alkylchloroform oximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshestva, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1991), 25(4), 33-4.
Treating ClCO2N:CClR (R = Me, Et, Pr, CHMe2) with NHR1R2 (R1 = R2 = H, Me, Et; R1 = H, R2 = Me) in Et2O gave 50-69% R1R2NCO2N:CClR (same R-R3), which are acetyl- and butyrylcholinesterase inhibitors (k11 = 1.1  10-2 to 5.4  10-6 M-1 min-1). Acute oral toxicity in mice ranged from 32 to 565 mg/kg.

O-Alkyl O-methylchloroformimino phenylphosphonates - effective inhibitors of the hen brain neurotoxic esterase. Makhaeva, G. F.; Kononova, I. V.; Malygin, V. V.; Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1991), 317(4), 1009-12 [Biochem.].
The title phosphonates were effective inhibitors of neurotoxic esterase; with increasing hydrophobicity the compds. showed pronounced and selective biol. activity towards brain neurotoxic esterase compared to acetylcholinesterase. Thus, the structure of phenylphosphonate played a major role in the inhibitory effects of these potential pesticides towards neurotoxic esterase or acetylcholinesterase.

Synthesis and anticholinesterase activity of fluorine-containing -aminophosphoryl compounds. Korenchenko, O. V.; Ivanov, Yu. Ya.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Khimiko-Farmatsevticheskii Zhurnal (1992), 26(6), 21-3.
Reaction of R2P(O)H (R = MeO, EtO, PrO, Me2CHO, Ph) with (CF3)2C:NCOR1 (R1 = OEt, OCH2Ph, OPr, OBu, OCH2CH2CHMe2, CF3) in Et2O gave 44-93% R2P(O)C(CF3)2NHCOR1. Treating a 1,4,2-oxazaphospholine deriv. with alcs. gave Me(R)P(O)C(CF3)2NHCO2Et (R = BuO, Me2CHO). Bimol. rate consts. for inhibition of cholinesterases by these compds. were detd.

Synthesis and insecticidal and acaricidal activity of O-alkylchloroformimine O,O-dialkyl phosphates and O,O-dialkylthiophosphates. Ivanov, A. M.; Ivanova, G. B.; Sokolova, V. B.; Epishina, T. N.; Goreva, T. V.; Beznosko, B. K.; Martynov, I. V.. Inst. Fiziol. Okl. Veshchestv., Chernogolovka, Russia. Fiziologicheski Aktivnye Veshchestva (1991), 23 58-62.
Of 26 title compds., those having ethoxy group at P were both insecticides and acaricides, whereas those having their methoxy group showed insecticidal activity only. Increasing hydrophobicity of the alkoxy substituents decreased i.m. toxicity to mice, but also the effectiveness. O replacement by S also decreased toxicity. Synthesis is indicated.

Paradoxical toxic effect and calcium antagonism of the cholinesterase inhibitors O-(N-arylcarbamoyl)acylhydroximoyl chlorides. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 328(6), 744-6 [Biochem.].
N-phenylcarbamates and aliph. analogs of the formula R R1N(O)ON::C(Cl)R2 [where R = Et, Me, and Ph; R1 = H, Me; R2 = Et, Pr, iso-Pr] were examd. for their acetylcholinesterase and butyrylcholinesterase inhibition, for their acute toxicity and their action on selective organs. The enzyme inhibition depended on their mol. structure. Paradoxical effects (higher dose and low toxicity and vice versa) were noted.

Similar sensitivity of rat and hen brain neurotoxic esterase to inhibition by O-alkyl-O-alkylchloroformiminophenylphosphonates. Makhaeva, G. F.; Filonenko, I. V.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 332(5), 650-3.
Quant. structure-neurotoxic esterase (NTE)-inhibiting activity relationship of the title phosphonates was examd. against both rat and chicken enzyme. The phosphonates effectively inhibited the enzyme from both the sources. The anti-NTE activity of the compds. increased with the length of alkyl radical in the phosphoryl portion. The introduction of branched substituent, esp. in the -position, decreased the antienzyme activity. Math. equations are derived to describe the effects of steric factors on the NTE inhibition. PI50 = -lg I50, where I50 is the concn. of the inhibitor required to cause 50% inhibition, was calcd. for these compds.; the values are tabulated.

Crystal and molecular structures and synthesis of O,O-diisopentyl 1-(phenylsulfonamido)-1-(trifluoromethyl)-2,2,2-trifluoroethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Ross. Akad. Nauk, Chernogolovka, Russia. Doklady Akademii Nauk (1995), 345(3), 360-363.
Reaction of (CF3)2C:NSO2Ph and (Me2CHCH2CH2O)2P(O)H in Et2O gave 85% title compd. (Me2CHCH2CH2O)2P(O)C(CF3)2NHSO2Ph, the structure of which was detd. by x-ray crystallog.

Assessment of the neurotoxic potential of some methyl- and phenylphosphonates using a stable preparation of neuropathy target esterase from chicken brain. Makhaeva G F; Malygin V V; Martynov I V Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow Oblast, 142432 Russia Doklady. Biochemistry and biophysics (2001 Mar-Apr), 377 68-71.

megalomania
April 15th, 2005, 06:49 PM
It has occured to me that a little social networking is in order to track down all possible scientific articles about Novichok agents and chemical weapons in general. Thanks to the papers provided by Samosa and Fritz I have used the names of the authors in those articles as a basis for a search for all of their respective articles.

The theory is whoever publishes an article about a chemical weapon has probably published other articles on chemical weapons. The theory also stipulates whoever he co-authored these papers with also probably work in chemical weapons, so their articles are likely to be related to chemical weapons research.

The end result is I have nearly 1000 articles published by the top dozen names, leading me to dozens more authors. I now have to sift through the first batch of all the articles to weed out any unrelated publications, and to find out who the co-authors of the good articles are.

I also read a tidbit in Tobiasons Scientific Principles, the chemical weapons volume, that the Soviets intentionally published large amounts of chemical weapons information in the open literature in the 1950s and 1960s with the hope some rogue nation would use the information to attack the US. The goal here was for the rogue state to finish the job for the Soviet Union, or at least inflict massive American casualities. Now all I need to do is find out what journals they published this stuff in. Zhurnal Obshchei Khimii is probably a good place to start since it has an English translation.

Also, in the paper by Mr Samosa the molecular structures for the two examples of Novichok compounds are incorrect. I donít know if the CAS numbers are wrong for the right structures, or if the structures are wrong for the right CAS number. I think the wrong structures were used for the right CAS numbers.
(see attached image)

One name that seems to pop up a lot is I. V. Martynov. He has published about 500 journal articles in his lifetime to date. Indeed there are many about phosphorus compounds, but those type of articles cease after 1972. He publishes many articles about molecular refraction after that. In 1984 he resumes publication of phosphorus related articles.

One article in particular caught my eye:
Synthesis and anticholinesterase activity of fluorochloronitroacetic acid esters. Ivanov, Yu. Ya.; Brel, V. K.; Postnova; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1985), 19(8), 968-71.

There are a few earlier articles about fluorochloronitroacetic acid esters. These are important in the systhesis of Novichoks I would imagine. Samosa did mention in his paper (NovDAGVGP.doc attached earlier) that dihaloformaldoxime are critical parts of Novichok agents, and fluorochloronitroacetic acid should form those.

Another article Martynov published related to bicyclic phosphates. There is another thread Samosa started about those. I donít know enough about them to say if this article is of interest. The abstract mentions this compound is a chloride blocker, it blocks GABA-independent Cl- channels specificially. Perhaps someone with knowledge of biology can say if blocking those is lethal. The article is:
4-Methyl- and 4-ethylbicyclophosphates, blockers of chloride channels. Fetisov, V. I.; Redkozubov, A. E.; Lyubimov, V. S.; Sokolov, V. S.; Martynov, I. V.. USSR. Biologicheskie Membrany (1986), 3(9), 968-70.
4-Methyl- (I; R = Me) [1449-89-4] and 4-ethylbicyclophosphate (I; R = Et) [1005-93-2] were effective blockers of GABA-independent Cl- channels (of Limnaea stagnalis giant neurons). Both potential and thermoregulation of the Cl- channels were affected.


Here is another article of potential use in the preparation of Novichok agents. This compound is similar to fluorochloronitroacetic acid from which this substance is made:
Synthesis of chlorofluoronitronitrosomethane. Martynov, I. V.; Brel, V. K.; Uvarova, L. V. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (4), 952-3.
Decarboxylation-nitrosation of ClFC(NO2)CO2H with HNO3 gave 52% ClFC(NO)NO2

Here is another possible tidbit as it relates to insecticides and plant growth regulation. We know they disguised their research under the guise of agrichemicals:
Synthesis and pesticidal activity of chloronitroacetic acid esters. Martynov, I. V.; Yurtanov, A. I.; Ivanov, Yu. J.; Kulish, E. V.; Uvarova, L. V.; Andreeva, E. I.; Rozhkova, N. G.; Zhirmunskaya, N. M. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1986), 289(1), 109-13 [Chem.].
A series of 31 O2NCRR1CO2R [e.g., R, R1, R2 = H, Cl, n-C7H15 (I); F, Cl, ClCH2CH2; Br, Cl, Et] was tested for insecticidal and, in some cases, plant growth regulatory activity. Eight of the compds., e.g., I, were active insecticides. Twelve of the compds. were new but no prepn. details were given.

Here is another possible Novichok variant:
Reaction of phosphorus trichloride with 1,1,2-trichloro-1-nitrosoethane in sulfur dioxide. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (9), 2158.
Reaction of ClCH2CCl2NO with PCl3 in SO2 gave 58% ClCH2CCl:NOP(O)Cl2.


Here is yet another possible Novichok variant:
Reaction of dialkyl phosphites with 1,1-dichloronitrosoalkanes. Ivanov, A. N.; Epishina, T. A.; Goreva, T. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (1), 226-8.
(RO)2P(O)ON:CClR1 (R = Bu, Me2CHCH2, pentyl, Me, Et; R1 = Me, Et, Pr, Me2CH, Bu, Me2CHCH2) were prepd. in 44-67% yields by treating (RO)2POH with ONCCl2R1 in EtOH at 20.

Here is a toxicity study done on animals and humans for some pesticides. Yeah, pesticides, thatís the ticket:
Delayed neurotoxicity from organophosphorus pesticides. Makhaeva, G. F.; Malygin, V. V.; Martynov, I. V.. USSR. Agrokhimiya (1987), (12), 103-24.
A review with 123 refs. on 8 clin. intoxication symptoms, pathmorphol., mechanisms of initiation of delayed neurotoxicity by organophosphorus pesticides (OPP) structure-activity relations of OPP, monitoring of the delayed neurotoxicity of OPP in animals and humans, etc.

Here is another possible Novichok variant:
Reaction of O-alkyl methylphosphonites with 1,1-dichloro-1-nitrosopropane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(4), 952-3.
Reaction of ROP(O)HMe (R = Me2CH, Bu, pentyl) with EtCCl2NO in Et2O gave 50-52% ROP(O)MeON:CClEt (I; same R). Treating MeP(OR)2 with EtCCl2NO also gave I.

Here is an interesting reference, although I doubt this would have very high human toxicity due to the two large aryl groups attached to phosphorus. Still, it gives enlightenment as to where they are headed:
Reaction of diphenylphosphinous acid with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Epishina, T. A.; Ivanov, A. N.; Kharitonov, A. V.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1658-9.
Treating Ph2P(O)H with RCCl2NO (R = Et, Pr, Me2CH) in Et2O gave 62-75% Ph2P(O)ON:CClR (same R).


Another Novichok possibility:
Synthesis and the structure of dialkylfluoroformiminophosphates. Martynov, I. V.; Brel, V. K.; Uvarov, V. I.; Yarkov, A. V.; Novikov, V. P.; Chepakova, L. A.; Raevskii, O. A. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (4), 857-60.
Syn- And anti-(RO)2P(O)N:CHF (R = Me, Et, Pr, Bu) were prepd. in 11-25% yields by treating (RO)3P with ClCHFNO2.

Here is some nasty looking stuff that may be of interest:
Reaction of (-aminoalkyl)phosphonates with perfluoro-2-azapropene. Aksinenko, A. Yu.; Pushin, A. N.; Sokolov, V. B.; Gontar, A. F.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1177-9.
(RO)2P(O)CMeR1N:C:NCF3 (R = Me, R1 = Et; R = Et, R1 = Et, Pr, Bu; R = Me2CHCH2, R1 = Et) were prepd. in 40-60% yields by condensing CF2:NCF3 with (RO)2P(O)CMeR1(NH2) in the presence of KF.

Here is another variant:
Reaction of polychloronitrosoethanes with phosphorous acid derivatives. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1086-9.
The title reaction gave 20-93% of 22 o-phosphorylated alkyl chloroformimines. Thus, treating ONCCl2R (R = Me, CH2Cl, CHCl2) with (R1O)3P (R1 = Me, Pr, Bu, Me2CHCH2, pentyl, ClCH2CH2) gave (R1O)2P(O)ON:CClR.

Of all the other compounds I have previously referenced this particular compound looks like it may be the deadliest. It has some similarities to most other nerve gasses in that it uses the simplest alkyl groups, and has a direct alkyl and a direct halogen attachment to phosphorus. I would replace those chlorines with fluorine to increase the toxicity:
Reaction of dichloromethylphosphine with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1659-60.
MePCl2 reacted with RCCl2NO (R = Et, Pr, Me2CH) in SO2 to give 27-37% RCCl:NOP(O)ClMe.

This compound looks like a good precursor for organophosphorus agents like the previous compound. The chlorines can be replaced by F, and one of the fluorines can form an ester or something else. The second compound is an example of what could be made, and I just bet that stuff is pretty toxic.
Interaction of 2,2,3,3-tetrafluoropropyl dichlorophosphite with 1,1,2-trichloro-1-nitrosoethane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (6), 1422-3.
Refluxing CHF2CF2CH2OPCl2 (I) with CH2ClCCl2NO (II) in Et2O gave 67.8% Cl2P(O)ON:CClCH2Cl. Treating I with II in SO2 at 20 gave 48.2% (CHF2CF2CH2O)ClP(O)ON:CClCH2Cl.

We might have a real winner with this one as it has similarities with VX nerve gas. The second compound in particular has a =S group. If that could be isomerized, like it is done in making VX, then we have a thioester. The two isobutyl groups are probably too large to make this particular compound all that toxic. I am sure they could be replaced with methyls instead.
Reaction of diisobutylchlorophosphine with 1,1-dichloro-1-nitrosoalkanes in presence of sulfur dioxide and ethyl mercaptan. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2586-8.
Treating (Me2CHCH2)2PCl with RCCl2NO (R = Me, Et, Pr, Me2CH) in Et2O contg. SO2 gave 61-74% (Me2CHCH2)2P(O)ON:CRCl (same R). When Et2SH was used instead of SO2, 44% (Me2CHCH2)2P(S)ON:CRCl (R = Me) was obtained.

Another phenyl attached compound:
Synthesis and molecular structure of (O-isopropylchloroformimino) diphenylphosphinate. Martynov, I. V.; Chekhlov, A. N.; Ivanov, A. N.; Epishina, T. A.; Makhaev, V. D.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2595-7.
Treating Ph2PH with Me2CHCCl2NO in C6H6 gave 58% Ph2P(O)ON:CClCHMe2, the structure of which was detd. by x-ray crystallog.

This compound has some VX similarities too:
O,O-Dialkyl O-(dialkylformimino) thiophosphates. Chepakova, L. A.; Brel, V. K.; Pushin, A. N.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(12), 2716-19.
Twelve (R1O)2P(S)ON:CMeR (R = Me, Et, Pr; R1 = Me, Et, Pr, Bu) were prepd. in 41-62% yields by treating (R1O)2PHS with ONCClMeR or HON:CMeR.

These compounds are similar to the last journal reference except the R and Rí groups are switched. Isomerize that S and we may have something far more toxic.
O-(Alkylchloroformimino) O,O-dialkyl thiophosphates. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (12), 2854-5.
Seven (RO)2P(S)ON:CClR1 (R = Et, Me2CH; R1 = Me, Et, Pr, Me2CH, ClCH2) were prepd. in 33-54% yields by condensing (RO)2PSH with R1Cl2CNO in THF.

Martynov has 64 publications in 1988 alone, his best year. In no particular order here are some highlights:

Molecular and crystal structure of O,O-diethyl 1-[N2-(trifluoromethyl)fluoroformamidino]-1-methylethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Korenchenko, O. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 302(4), 855-8 [Chem.].
The crystal and mol. structure of (EtO)2P(O)CMe2NHCFNCF3 was detd.

Reaction of (N-acetyl-N-ethylamido)alkylphosphonic acid chlorides with cesium fluoride. Krolevets, A. A.; Adamov, A. V.; Popov, A. G.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2628-9.
RP(O)F(NEtCH:CH2) (R = Me, Me2CH) were prepd. in 45, 50% yields, resp., by treating RPCl(NEtAc) (I) with CsF. I were prepd. in 60, 65% yields, resp., by treating RPCl2 with Me3SiNEtAc.

Stable alkoxyfluorophosphoranes. Krolevets, A. A.; Popov, A. G.; Adamov, A. V.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2626-7.
RPF2(OR1)2 (R = BuCHClCH2, R1 = Me3C; R = Me2CClCH2, R1 = Et) were prepd. in 45, 40% yields, resp., by treating RPF4 with Me3SiOR1.

O-(Alkylchloroformimidoyl) o-alkyl methylphosphonates. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1128-30.
Nine (RO)MeP(O)ON:CClR1 (R = Et, Pr, Bu, Me2CH, pentyl; R1 = Me, Et, Pr, Bu, Me2CH) were prepd. in 41-67% yields by treating R1CCl2NO with MeP(OR)2 or MeP(O)H(OR).

Reaction of 1,1-dichloro-1-nitrosoalkanes with phosphorus(III) chlorides. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (9), 2128-32.
The title reaction was studied. Thus, R1R2P(O)ON:CRCl (R = Me, Et, Pr, Me2CH; R1 = R2 = Cl, Me2CHCH2; R1 = Cl, R2 = Me) were prepd. in 34-74% yields by reaction of RCCl2NO with R1R2PCl in the presence of SO2.

Synthesis and x-ray diffraction study of N-(diisopropoxythiophosphoryl)thioacetamide. Solov'ev, V. N.; Chekhlov, A. N.; Zabirov, N. G.; Cherkasov, R. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 300(6), 1386-9 [Chem.].
Treating MeCSNH2 with Me3COK in MeCN and then with ClP(S)(OCHMe2)2 gave 15% MeCSNHP(S)(OCHMe2)2, the structure of which was detd. by x-ray crystallog.

Reaction of 1,1-dichloro-1-nitrosoethane with phosphorus oxychloride in the presence of zinc. Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (7), 1691.
Cl2P(O)ON:CClMe was prepd. in 26.6% yield by treating MeCCl2NO with POCl3 in the presence of Zn.

Comparative studies on the interaction of acetylcholinesterases from human erythrocytes and housefly heads with phosphorylated alkylchloroformoxims. Shataeva, G. A.; Makhaeva, G. F.; Yankovskaya, V. L.; Sokolov, V. B.; Ivanov, A. N.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Zhurnal Evolyutsionnoi Biokhimii i Fiziologii (1988), 24(6), 791-6.
Among Valexon analogs, 6 (RO)2P(O)ON:CClMe (I), 6 (RO)2P(O)ON:C(Cl)CH2Cl (II), and 5 (RO)2P(O)ON:C(Cl)CHCl2 (III, R = Me, Et, Pr, iso-Bu, Bu, amyl), and 4 (EtO)2P(O)ON:C(Cl)R1 (IV, R1 = Me, Et, Pr, Bu), I-III (R = Et) were highly selective insecticides, having rate consts. of bimol. reaction with acetylcholinesterase (KII) of human erythrocytes (HE) lower by 1 magnitude order than with that from housefly heads (FL). Inhibition of both HE and FL followed the order I < II < III. Phosphorylation capacity of II 1.6-fold exceeded that of I. Replacing Me by Et, increased the effect of I-III on FL 3-8-fold and decreased that on HE 1.7-4-fold. Further increases in hydrophobicity abolished the specificity of I-III. The selectivity of IV decreased in order of R1: Me > Et > Bu; IV (R1 = Pr) showed no selectivity.

Fluorination of some phosphoric acid derivatives. Zavorin, S. I.; Lermontov, S. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka., USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1174-6.
Dialkyl fluorophosphates were prepd. by the title fluorination with Et3N.3HF (I). Thus, fluorination of (EtO)2P(O)ON:CCl2 with I in MeCN gave 83.5% (EtO)2P(O)F.

Reaction of fluorine-containing acetylenic alcohols with phosphorus trichloride. Brel, V. K.; Chekhlov, A. N.; Ionin, B. I.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1988), 58(4), 750-7.
Treating RC.tplbond.CCMe(OH)CH2F (I; R = Ph) with PCl3 in Et2O gave 45% Cl2P(O)CR:C:CMeCH2F (II; R = Ph) and 24% E- and Z-Cl2P(O)CHPhCCl:CMeCH2F (III). Under the same conditions, I (R = MeOCH2) gave a mixt. of II (R = MeOCH2) and Cl2P(O)C(:CH2)CCl:CMeCH2F. Treating I (R = Ph) with MeOH and then with Br2 gave oxaphospholene IV. The structure of III was detd. by x-ray crystallog.

Synthesis and anticholinesterase activity of fluorochloronitroacetic acid thioesters. Ivanov, Yu. Ya.; Uvarov, V. I.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(5), 538-40.
Treating O2NCFClCOX (I; X = OH) with PCl5 gave I (X = Cl), which reacted with RSH (R = Et, Bu) to give 35-55% I (X = SR; same R) (II). II were less effective acetylcholinesterase inhibitors than I (X = OR; same R) but had comparable activity vs. butyrylcholinesterase with lower toxicity.

Synthesis and antiesterase activity of sulfur-containing phosphorylated oximes. Chepakova, L. A.; Bret, V. K.; Makheva, G. F.; Yankovskaya, V. L.; Beznosko, B. K.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(2), 143-6.
Reaction of (RS)2POEt (R = Et, Pr, iso-Bu, Bu or amyl) with O:NCFCl2 gave the corresponding (RS)2P(:O)ON:CClF (I). An increase in the hydrophobicity of I did not alter the anticholinesterase activity of I, while the butyrylcholinesterase and carboxylesterase activity were increased.

O-substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov Iu Ia; Sokolov V B; Epishina T A; Martynov I V Doklady Akademii nauk SSSR (1990), 310(5), 1253-5.

Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid. Kuusk V V; Morozova I V; Agabekian R S; Aksinenko A Iu; Epishina T A; Sokolov V B; Kovaleva N V; Razdol'skiy A N; Fetisov V N; Martynov I V Bioorganicheskaia khimiia (1990 Nov), 16(11), 1500-8.
A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.

Reaction of 1,1-dichloro-1-nitrosobutane with (N,N-dimethylamido)dichlorophosphite. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (6), 1416-18.
Reaction of PrCCl2NO with Me2NPCl2 in Et2O or in SO2 gave 36% Me2NPCl4 or 30% Me2NP(O)ClON:CClPr, resp. Treating Me2NPCl4 with SO2 gave 91% Me2NP(O)Cl2. Reaction of PrCCl2NO with Me2NPCl2 in Et2O, and then with Ph3P and distn. gave Ph3PO and PrCN.

Alkyl chlorofluoroformimino perfluoroalkylphosphonates. Chepakova, L. A.; Brel, V. K.; Martynov, I. V.; Maslennikov, I. G. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(6), 1455-6.
Treating RP(OR1)2 (R = CF3, R1 = Pr, Bu; R = CF3CF2, R1 = Me, Bu) with CFCl2NO in Et2O gave 76-88% title compds. R1OP(O)RON:CFCl.

Synthesis of dialkyl (3-alkyl-1,3-alkadien-2-yl)phosphonates. Brel, V. K.; Abramkin, E. V.; Martynov, I. V.; Ionin, B. I. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(9), 2142-3.
(RO)2P(O)C(:CH2)CR1:CMe2 (R = Et, Pr; R1 = Me, Et) were prepd. in 41-73% yields by the Grignard reaction of (RO)2P(O)C(CH2OMe):C:CMe2 with R1X (X = halo).

Synthesis and antiesterase activity of O,O-dialkyl S-(ethoxycarboxyl)chloromethyl thiophosphates. Khaskin, B. A.; Makhaeva, G. F.; Torgasheva, N. A.; Ishmuratov, A. S.; Yankovskaya, V. L.; Fetisov, V. I.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovko, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2741-6.
The title compds. (RO)2P(O)SCHClCO2Et (I; R = alkyl homologs) were prepd. in 82-95% yields in the reaction of (RO)2P(O)SCl with N2CHCO2Et at -25 (in Et2O) or 6-7 (in benzene), presumably via a noncarbene mechanism. I irreversibly inhibited acetylcholinesterase, butyrylcholinesterase, and carboxylesterase; antibutyrylcholinesterase activity increased in the homologous series of R, with max. at R = Bu. An antiesterase MSBAR of I was fulfilled with parameters representing hydrophobicity and steric properties of R.

Synthesis and cholinesterase hydrolysis of O-acylated alkylchloroformoximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Agabekyan, R. S.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1989), 23(11), 1317-20.
The title compds., RCO2N:CClR1 (R = Me, Et, Pr or CH2Cl and R1 = Me, Et, Pr, or iso-Pr) were prepd. e.g., by the reaction of 1,1-dichloro-1-nitrosobutane with AcCl in the presence of Zn. These compds. were good substrates for acetyl- and butyrylcholinesterases. The kinetic parameters (Km, Vmax and ac) of these compds. in the hydrolysis reactions were comparable to those with acetylcholine. The acute toxicity was 79-381 mg/kg in mice given drugs orally.

Synthesis and structure of O,O-dialkyl 2-[(ethoxycarbonyl)amino]hexafluoroisopropylphosphonates. Aksinenko, A. Yu.; Chekhlov, A. N.; Korenchenko, O. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(1), 61-5.
The title compds. (RO)2P(O)C(CF3)2NHCO2Et (I; R = Me, Et, CHMe2) were prepd. in 54-76% yields in the reaction of (RO)2P(O)H with (CF3)2C:NCO2Et. The crystal and mol. structure of I (R = Et) was detd.

O-Substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1990), 310(5), 1253-5 [Biochem.].
The ability of O-substituted alkylchloroformoximes to serve as substrates for acetylcholinesterase (ACE, EC 3.1.1.7) and butyrylcholinesterase (BCE, EC 3.1.1.8) and to inhibit acetylcholine hydrolysis by these enzymes was detd., along with the LD50 of these compds. in mice. The compds. tested were O-acylated alkylchloroformoximes of the general formula R1C(O)ON:C(Cl)R2 [R1 = R2 = Me; R1 = Me, R2 = Et; R1 = Me, R2 = Pr; R1 = Et, R2 = Me; R1 = Et, R2 = iso-Pr; R1 = Pr, R2 = iso-Pr; R1 = CH2Cl, R2 = Pr (I); R1 = CH2Cl, R2 = iso-Pr (II)], O-carbonylated alkylchloroformoximes of the general formula EtOC(O)ON:C(Cl)R [R = Me (III), iso-Pr (IV)], and O-carbamoylated alkylchloroformoximes of the general formula (Me)2NC(O)ON:C(Cl)R [R = Me (V), iso-Pr (VI)]. All of the compds. except for I and II were good substrates for the enzymes, with Km values for ACE ranging (0.3-11.0)  10-4M and for BCE ranging (0.5-13.0)  10-4M (the Km values of ACE and BCE with acetylcholine were 1.3  10-4 and 5.4  10-4M, resp.). III and IV were competitive (Ki 1.6  10-4M) and mixed-type (Ki 4.2  10-4M) inhibitors, resp., of ACE. V and VI were effective inhibitors of both ACE and BCE, with bimol. rate consts. for inhibition (kII) of 5.7  103 and 1.4  105 M-1 min-1, resp., for ACE, and 9.8  103 and 5.4  106 M-1 min-1, resp., for BCE. The LD50 values for the tested compds. ranged 60-381 mg/kg body wt.

O-(alkylchloroformimino)(methyl)thiophosphonic acid chlorides. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2865-6.
Treating the adduct from RCCl2NO and MePCl2 with H2S gave 21-35% MeP(S)ClON:CRCl.

Interaction of 1,1-dichloro-1-nitrosoalkanes with S-ethylmethylphosphonous chloride in the presence of sulfur dioxide. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (2), 464-5.
EtSP(O)MeON:CClR (R = Me, Et, Pr) were prepd. in 42-47% yields by treating RCCl2NO with EtSPMeCl in the presence of SO2.

O-(alkylchloroformimino)-O-alkylphosphoric acid chlorides. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (5), 1122-5.
Reaction of (ON)CCl2R with (R'O)2PCl (R, R' = alkyl) afforded the title compds. (R'O)ClP(O)ON:CRCl (I) in up to 69% yield. Hydrolysis of I led to substitution of P-, and not C-bound Cl, resulting in (R'O)(NH4O)P(O)ON:CRCl.

Reaction of the adduct of methyldichlorophosphine and 1,1-dichloro-1-nitrosoethane with thioacetic acid. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(8), 1923-4.
Treating MePCl2 with MeCCl2NO in PhMe, followed by addn of 1 or 2 equiv AcSH gave 56% MeP(S)ClON:CMeCl or 32% MeP(S)ClON:CMeSAc, resp.

Inhibition of cholinesterase activity by fluorine-containing derivatives of -aminoalkylphosphonic acids. Kuusk, V. V.; Morozova, I. V.; Agabekyan, R. S.; Aksinenko, A. Yu.; Epishina, T. A.; Sokolov, V. B.; Kovaleva, N. V.; Razdol'skii, A. N.; Fetisov, V. I.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Bioorganicheskaya Khimiya (1990), 16(11), 1500-8.
A series of O,O-diethyl-1-(N--hydrohexafluoroisobutyryl)aminoalkylphosphonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate consts. and the enzyme-inhibitor intermediate dissocn. consts. are calcd. The quant. structure-activity relationships including both hydrophobic and calcd. steric parameters of substituents are developed for APh-ChE interactions. Mol. mechanics (program MM2) was used for detg. steric parameters (Es). On the basis of QSAR models anal. it was concluded that hydrophobic interactions play an essential role in APh-AChE binding, whereas for APh-BuChE binding steric interactions are essential. Presence of at least two APh binding centers on the surface of AChE and BuChE is suggested.

Synthesis and anticholinesterase activity of O-carbamoylated alkylchloroform oximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshestva, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1991), 25(4), 33-4.
Treating ClCO2N:CClR (R = Me, Et, Pr, CHMe2) with NHR1R2 (R1 = R2 = H, Me, Et; R1 = H, R2 = Me) in Et2O gave 50-69% R1R2NCO2N:CClR (same R-R3), which are acetyl- and butyrylcholinesterase inhibitors (k11 = 1.1  10-2 to 5.4  10-6 M-1 min-1). Acute oral toxicity in mice ranged from 32 to 565 mg/kg.

O-Alkyl O-methylchloroformimino phenylphosphonates - effective inhibitors of the hen brain neurotoxic esterase. Makhaeva, G. F.; Kononova, I. V.; Malygin, V. V.; Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1991), 317(4), 1009-12 [Biochem.].
The title phosphonates were effective inhibitors of neurotoxic esterase; with increasing hydrophobicity the compds. showed pronounced and selective biol. activity towards brain neurotoxic esterase compared to acetylcholinesterase. Thus, the structure of phenylphosphonate played a major role in the inhibitory effects of these potential pesticides towards neurotoxic esterase or acetylcholinesterase.

Synthesis and anticholinesterase activity of fluorine-containing -aminophosphoryl compounds. Korenchenko, O. V.; Ivanov, Yu. Ya.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Khimiko-Farmatsevticheskii Zhurnal (1992), 26(6), 21-3.
Reaction of R2P(O)H (R = MeO, EtO, PrO, Me2CHO, Ph) with (CF3)2C:NCOR1 (R1 = OEt, OCH2Ph, OPr, OBu, OCH2CH2CHMe2, CF3) in Et2O gave 44-93% R2P(O)C(CF3)2NHCOR1. Treating a 1,4,2-oxazaphospholine deriv. with alcs. gave Me(R)P(O)C(CF3)2NHCO2Et (R = BuO, Me2CHO). Bimol. rate consts. for inhibition of cholinesterases by these compds. were detd.

Synthesis and insecticidal and acaricidal activity of O-alkylchloroformimine O,O-dialkyl phosphates and O,O-dialkylthiophosphates. Ivanov, A. M.; Ivanova, G. B.; Sokolova, V. B.; Epishina, T. N.; Goreva, T. V.; Beznosko, B. K.; Martynov, I. V.. Inst. Fiziol. Okl. Veshchestv., Chernogolovka, Russia. Fiziologicheski Aktivnye Veshchestva (1991), 23 58-62.
Of 26 title compds., those having ethoxy group at P were both insecticides and acaricides, whereas those having their methoxy group showed insecticidal activity only. Increasing hydrophobicity of the alkoxy substituents decreased i.m. toxicity to mice, but also the effectiveness. O replacement by S also decreased toxicity. Synthesis is indicated.

Paradoxical toxic effect and calcium antagonism of the cholinesterase inhibitors O-(N-arylcarbamoyl)acylhydroximoyl chlorides. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 328(6), 744-6 [Biochem.].
N-phenylcarbamates and aliph. analogs of the formula R R1N(O)ON::C(Cl)R2 [where R = Et, Me, and Ph; R1 = H, Me; R2 = Et, Pr, iso-Pr] were examd. for their acetylcholinesterase and butyrylcholinesterase inhibition, for their acute toxicity and their action on selective organs. The enzyme inhibition depended on their mol. structure. Paradoxical effects (higher dose and low toxicity and vice versa) were noted.

Similar sensitivity of rat and hen brain neurotoxic esterase to inhibition by O-alkyl-O-alkylchloroformiminophenylphosphonates. Makhaeva, G. F.; Filonenko, I. V.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 332(5), 650-3.
Quant. structure-neurotoxic esterase (NTE)-inhibiting activity relationship of the title phosphonates was examd. against both rat and chicken enzyme. The phosphonates effectively inhibited the enzyme from both the sources. The anti-NTE activity of the compds. increased with the length of alkyl radical in the phosphoryl portion. The introduction of branched substituent, esp. in the -position, decreased the antienzyme activity. Math. equations are derived to describe the effects of steric factors on the NTE inhibition. PI50 = -lg I50, where I50 is the concn. of the inhibitor required to cause 50% inhibition, was calcd. for these compds.; the values are tabulated.

Crystal and molecular structures and synthesis of O,O-diisopentyl 1-(phenylsulfonamido)-1-(trifluoromethyl)-2,2,2-trifluoroethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Ross. Akad. Nauk, Chernogolovka, Russia. Doklady Akademii Nauk (1995), 345(3), 360-363.
Reaction of (CF3)2C:NSO2Ph and (Me2CHCH2CH2O)2P(O)H in Et2O gave 85% title compd. (Me2CHCH2CH2O)2P(O)C(CF3)2NHSO2Ph, the structure of which was detd. by x-ray crystallog.

Assessment of the neurotoxic potential of some methyl- and phenylphosphonates using a stable preparation of neuropathy target esterase from chicken brain. Makhaeva G F; Malygin V V; Martynov I V Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow Oblast, 142432 Russia Doklady. Biochemistry and biophysics (2001 Mar-Apr), 377 68-71.

megalomania
April 15th, 2005, 06:49 PM
It has occured to me that a little social networking is in order to track down all possible scientific articles about Novichok agents and chemical weapons in general. Thanks to the papers provided by Samosa and Fritz I have used the names of the authors in those articles as a basis for a search for all of their respective articles.

The theory is whoever publishes an article about a chemical weapon has probably published other articles on chemical weapons. The theory also stipulates whoever he co-authored these papers with also probably work in chemical weapons, so their articles are likely to be related to chemical weapons research.

The end result is I have nearly 1000 articles published by the top dozen names, leading me to dozens more authors. I now have to sift through the first batch of all the articles to weed out any unrelated publications, and to find out who the co-authors of the good articles are.

I also read a tidbit in Tobiasons Scientific Principles, the chemical weapons volume, that the Soviets intentionally published large amounts of chemical weapons information in the open literature in the 1950s and 1960s with the hope some rogue nation would use the information to attack the US. The goal here was for the rogue state to finish the job for the Soviet Union, or at least inflict massive American casualities. Now all I need to do is find out what journals they published this stuff in. Zhurnal Obshchei Khimii is probably a good place to start since it has an English translation.

Also, in the paper by Mr Samosa the molecular structures for the two examples of Novichok compounds are incorrect. I donít know if the CAS numbers are wrong for the right structures, or if the structures are wrong for the right CAS number. I think the wrong structures were used for the right CAS numbers.
(see attached image)

One name that seems to pop up a lot is I. V. Martynov. He has published about 500 journal articles in his lifetime to date. Indeed there are many about phosphorus compounds, but those type of articles cease after 1972. He publishes many articles about molecular refraction after that. In 1984 he resumes publication of phosphorus related articles.

One article in particular caught my eye:
Synthesis and anticholinesterase activity of fluorochloronitroacetic acid esters. Ivanov, Yu. Ya.; Brel, V. K.; Postnova; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1985), 19(8), 968-71.

There are a few earlier articles about fluorochloronitroacetic acid esters. These are important in the systhesis of Novichoks I would imagine. Samosa did mention in his paper (NovDAGVGP.doc attached earlier) that dihaloformaldoxime are critical parts of Novichok agents, and fluorochloronitroacetic acid should form those.

Another article Martynov published related to bicyclic phosphates. There is another thread Samosa started about those. I donít know enough about them to say if this article is of interest. The abstract mentions this compound is a chloride blocker, it blocks GABA-independent Cl- channels specificially. Perhaps someone with knowledge of biology can say if blocking those is lethal. The article is:
4-Methyl- and 4-ethylbicyclophosphates, blockers of chloride channels. Fetisov, V. I.; Redkozubov, A. E.; Lyubimov, V. S.; Sokolov, V. S.; Martynov, I. V.. USSR. Biologicheskie Membrany (1986), 3(9), 968-70.
4-Methyl- (I; R = Me) [1449-89-4] and 4-ethylbicyclophosphate (I; R = Et) [1005-93-2] were effective blockers of GABA-independent Cl- channels (of Limnaea stagnalis giant neurons). Both potential and thermoregulation of the Cl- channels were affected.


Here is another article of potential use in the preparation of Novichok agents. This compound is similar to fluorochloronitroacetic acid from which this substance is made:
Synthesis of chlorofluoronitronitrosomethane. Martynov, I. V.; Brel, V. K.; Uvarova, L. V. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (4), 952-3.
Decarboxylation-nitrosation of ClFC(NO2)CO2H with HNO3 gave 52% ClFC(NO)NO2

Here is another possible tidbit as it relates to insecticides and plant growth regulation. We know they disguised their research under the guise of agrichemicals:
Synthesis and pesticidal activity of chloronitroacetic acid esters. Martynov, I. V.; Yurtanov, A. I.; Ivanov, Yu. J.; Kulish, E. V.; Uvarova, L. V.; Andreeva, E. I.; Rozhkova, N. G.; Zhirmunskaya, N. M. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1986), 289(1), 109-13 [Chem.].
A series of 31 O2NCRR1CO2R [e.g., R, R1, R2 = H, Cl, n-C7H15 (I); F, Cl, ClCH2CH2; Br, Cl, Et] was tested for insecticidal and, in some cases, plant growth regulatory activity. Eight of the compds., e.g., I, were active insecticides. Twelve of the compds. were new but no prepn. details were given.

Here is another possible Novichok variant:
Reaction of phosphorus trichloride with 1,1,2-trichloro-1-nitrosoethane in sulfur dioxide. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (9), 2158.
Reaction of ClCH2CCl2NO with PCl3 in SO2 gave 58% ClCH2CCl:NOP(O)Cl2.


Here is yet another possible Novichok variant:
Reaction of dialkyl phosphites with 1,1-dichloronitrosoalkanes. Ivanov, A. N.; Epishina, T. A.; Goreva, T. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (1), 226-8.
(RO)2P(O)ON:CClR1 (R = Bu, Me2CHCH2, pentyl, Me, Et; R1 = Me, Et, Pr, Me2CH, Bu, Me2CHCH2) were prepd. in 44-67% yields by treating (RO)2POH with ONCCl2R1 in EtOH at 20.

Here is a toxicity study done on animals and humans for some pesticides. Yeah, pesticides, thatís the ticket:
Delayed neurotoxicity from organophosphorus pesticides. Makhaeva, G. F.; Malygin, V. V.; Martynov, I. V.. USSR. Agrokhimiya (1987), (12), 103-24.
A review with 123 refs. on 8 clin. intoxication symptoms, pathmorphol., mechanisms of initiation of delayed neurotoxicity by organophosphorus pesticides (OPP) structure-activity relations of OPP, monitoring of the delayed neurotoxicity of OPP in animals and humans, etc.

Here is another possible Novichok variant:
Reaction of O-alkyl methylphosphonites with 1,1-dichloro-1-nitrosopropane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(4), 952-3.
Reaction of ROP(O)HMe (R = Me2CH, Bu, pentyl) with EtCCl2NO in Et2O gave 50-52% ROP(O)MeON:CClEt (I; same R). Treating MeP(OR)2 with EtCCl2NO also gave I.

Here is an interesting reference, although I doubt this would have very high human toxicity due to the two large aryl groups attached to phosphorus. Still, it gives enlightenment as to where they are headed:
Reaction of diphenylphosphinous acid with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Epishina, T. A.; Ivanov, A. N.; Kharitonov, A. V.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1658-9.
Treating Ph2P(O)H with RCCl2NO (R = Et, Pr, Me2CH) in Et2O gave 62-75% Ph2P(O)ON:CClR (same R).


Another Novichok possibility:
Synthesis and the structure of dialkylfluoroformiminophosphates. Martynov, I. V.; Brel, V. K.; Uvarov, V. I.; Yarkov, A. V.; Novikov, V. P.; Chepakova, L. A.; Raevskii, O. A. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (4), 857-60.
Syn- And anti-(RO)2P(O)N:CHF (R = Me, Et, Pr, Bu) were prepd. in 11-25% yields by treating (RO)3P with ClCHFNO2.

Here is some nasty looking stuff that may be of interest:
Reaction of (-aminoalkyl)phosphonates with perfluoro-2-azapropene. Aksinenko, A. Yu.; Pushin, A. N.; Sokolov, V. B.; Gontar, A. F.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1177-9.
(RO)2P(O)CMeR1N:C:NCF3 (R = Me, R1 = Et; R = Et, R1 = Et, Pr, Bu; R = Me2CHCH2, R1 = Et) were prepd. in 40-60% yields by condensing CF2:NCF3 with (RO)2P(O)CMeR1(NH2) in the presence of KF.

Here is another variant:
Reaction of polychloronitrosoethanes with phosphorous acid derivatives. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1086-9.
The title reaction gave 20-93% of 22 o-phosphorylated alkyl chloroformimines. Thus, treating ONCCl2R (R = Me, CH2Cl, CHCl2) with (R1O)3P (R1 = Me, Pr, Bu, Me2CHCH2, pentyl, ClCH2CH2) gave (R1O)2P(O)ON:CClR.

Of all the other compounds I have previously referenced this particular compound looks like it may be the deadliest. It has some similarities to most other nerve gasses in that it uses the simplest alkyl groups, and has a direct alkyl and a direct halogen attachment to phosphorus. I would replace those chlorines with fluorine to increase the toxicity:
Reaction of dichloromethylphosphine with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1659-60.
MePCl2 reacted with RCCl2NO (R = Et, Pr, Me2CH) in SO2 to give 27-37% RCCl:NOP(O)ClMe.

This compound looks like a good precursor for organophosphorus agents like the previous compound. The chlorines can be replaced by F, and one of the fluorines can form an ester or something else. The second compound is an example of what could be made, and I just bet that stuff is pretty toxic.
Interaction of 2,2,3,3-tetrafluoropropyl dichlorophosphite with 1,1,2-trichloro-1-nitrosoethane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (6), 1422-3.
Refluxing CHF2CF2CH2OPCl2 (I) with CH2ClCCl2NO (II) in Et2O gave 67.8% Cl2P(O)ON:CClCH2Cl. Treating I with II in SO2 at 20 gave 48.2% (CHF2CF2CH2O)ClP(O)ON:CClCH2Cl.

We might have a real winner with this one as it has similarities with VX nerve gas. The second compound in particular has a =S group. If that could be isomerized, like it is done in making VX, then we have a thioester. The two isobutyl groups are probably too large to make this particular compound all that toxic. I am sure they could be replaced with methyls instead.
Reaction of diisobutylchlorophosphine with 1,1-dichloro-1-nitrosoalkanes in presence of sulfur dioxide and ethyl mercaptan. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2586-8.
Treating (Me2CHCH2)2PCl with RCCl2NO (R = Me, Et, Pr, Me2CH) in Et2O contg. SO2 gave 61-74% (Me2CHCH2)2P(O)ON:CRCl (same R). When Et2SH was used instead of SO2, 44% (Me2CHCH2)2P(S)ON:CRCl (R = Me) was obtained.

Another phenyl attached compound:
Synthesis and molecular structure of (O-isopropylchloroformimino) diphenylphosphinate. Martynov, I. V.; Chekhlov, A. N.; Ivanov, A. N.; Epishina, T. A.; Makhaev, V. D.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2595-7.
Treating Ph2PH with Me2CHCCl2NO in C6H6 gave 58% Ph2P(O)ON:CClCHMe2, the structure of which was detd. by x-ray crystallog.

This compound has some VX similarities too:
O,O-Dialkyl O-(dialkylformimino) thiophosphates. Chepakova, L. A.; Brel, V. K.; Pushin, A. N.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(12), 2716-19.
Twelve (R1O)2P(S)ON:CMeR (R = Me, Et, Pr; R1 = Me, Et, Pr, Bu) were prepd. in 41-62% yields by treating (R1O)2PHS with ONCClMeR or HON:CMeR.

These compounds are similar to the last journal reference except the R and Rí groups are switched. Isomerize that S and we may have something far more toxic.
O-(Alkylchloroformimino) O,O-dialkyl thiophosphates. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (12), 2854-5.
Seven (RO)2P(S)ON:CClR1 (R = Et, Me2CH; R1 = Me, Et, Pr, Me2CH, ClCH2) were prepd. in 33-54% yields by condensing (RO)2PSH with R1Cl2CNO in THF.

Martynov has 64 publications in 1988 alone, his best year. In no particular order here are some highlights:

Molecular and crystal structure of O,O-diethyl 1-[N2-(trifluoromethyl)fluoroformamidino]-1-methylethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Korenchenko, O. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 302(4), 855-8 [Chem.].
The crystal and mol. structure of (EtO)2P(O)CMe2NHCFNCF3 was detd.

Reaction of (N-acetyl-N-ethylamido)alkylphosphonic acid chlorides with cesium fluoride. Krolevets, A. A.; Adamov, A. V.; Popov, A. G.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2628-9.
RP(O)F(NEtCH:CH2) (R = Me, Me2CH) were prepd. in 45, 50% yields, resp., by treating RPCl(NEtAc) (I) with CsF. I were prepd. in 60, 65% yields, resp., by treating RPCl2 with Me3SiNEtAc.

Stable alkoxyfluorophosphoranes. Krolevets, A. A.; Popov, A. G.; Adamov, A. V.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2626-7.
RPF2(OR1)2 (R = BuCHClCH2, R1 = Me3C; R = Me2CClCH2, R1 = Et) were prepd. in 45, 40% yields, resp., by treating RPF4 with Me3SiOR1.

O-(Alkylchloroformimidoyl) o-alkyl methylphosphonates. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1128-30.
Nine (RO)MeP(O)ON:CClR1 (R = Et, Pr, Bu, Me2CH, pentyl; R1 = Me, Et, Pr, Bu, Me2CH) were prepd. in 41-67% yields by treating R1CCl2NO with MeP(OR)2 or MeP(O)H(OR).

Reaction of 1,1-dichloro-1-nitrosoalkanes with phosphorus(III) chlorides. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (9), 2128-32.
The title reaction was studied. Thus, R1R2P(O)ON:CRCl (R = Me, Et, Pr, Me2CH; R1 = R2 = Cl, Me2CHCH2; R1 = Cl, R2 = Me) were prepd. in 34-74% yields by reaction of RCCl2NO with R1R2PCl in the presence of SO2.

Synthesis and x-ray diffraction study of N-(diisopropoxythiophosphoryl)thioacetamide. Solov'ev, V. N.; Chekhlov, A. N.; Zabirov, N. G.; Cherkasov, R. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 300(6), 1386-9 [Chem.].
Treating MeCSNH2 with Me3COK in MeCN and then with ClP(S)(OCHMe2)2 gave 15% MeCSNHP(S)(OCHMe2)2, the structure of which was detd. by x-ray crystallog.

Reaction of 1,1-dichloro-1-nitrosoethane with phosphorus oxychloride in the presence of zinc. Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (7), 1691.
Cl2P(O)ON:CClMe was prepd. in 26.6% yield by treating MeCCl2NO with POCl3 in the presence of Zn.

Comparative studies on the interaction of acetylcholinesterases from human erythrocytes and housefly heads with phosphorylated alkylchloroformoxims. Shataeva, G. A.; Makhaeva, G. F.; Yankovskaya, V. L.; Sokolov, V. B.; Ivanov, A. N.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Zhurnal Evolyutsionnoi Biokhimii i Fiziologii (1988), 24(6), 791-6.
Among Valexon analogs, 6 (RO)2P(O)ON:CClMe (I), 6 (RO)2P(O)ON:C(Cl)CH2Cl (II), and 5 (RO)2P(O)ON:C(Cl)CHCl2 (III, R = Me, Et, Pr, iso-Bu, Bu, amyl), and 4 (EtO)2P(O)ON:C(Cl)R1 (IV, R1 = Me, Et, Pr, Bu), I-III (R = Et) were highly selective insecticides, having rate consts. of bimol. reaction with acetylcholinesterase (KII) of human erythrocytes (HE) lower by 1 magnitude order than with that from housefly heads (FL). Inhibition of both HE and FL followed the order I < II < III. Phosphorylation capacity of II 1.6-fold exceeded that of I. Replacing Me by Et, increased the effect of I-III on FL 3-8-fold and decreased that on HE 1.7-4-fold. Further increases in hydrophobicity abolished the specificity of I-III. The selectivity of IV decreased in order of R1: Me > Et > Bu; IV (R1 = Pr) showed no selectivity.

Fluorination of some phosphoric acid derivatives. Zavorin, S. I.; Lermontov, S. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka., USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1174-6.
Dialkyl fluorophosphates were prepd. by the title fluorination with Et3N.3HF (I). Thus, fluorination of (EtO)2P(O)ON:CCl2 with I in MeCN gave 83.5% (EtO)2P(O)F.

Reaction of fluorine-containing acetylenic alcohols with phosphorus trichloride. Brel, V. K.; Chekhlov, A. N.; Ionin, B. I.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1988), 58(4), 750-7.
Treating RC.tplbond.CCMe(OH)CH2F (I; R = Ph) with PCl3 in Et2O gave 45% Cl2P(O)CR:C:CMeCH2F (II; R = Ph) and 24% E- and Z-Cl2P(O)CHPhCCl:CMeCH2F (III). Under the same conditions, I (R = MeOCH2) gave a mixt. of II (R = MeOCH2) and Cl2P(O)C(:CH2)CCl:CMeCH2F. Treating I (R = Ph) with MeOH and then with Br2 gave oxaphospholene IV. The structure of III was detd. by x-ray crystallog.

Synthesis and anticholinesterase activity of fluorochloronitroacetic acid thioesters. Ivanov, Yu. Ya.; Uvarov, V. I.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(5), 538-40.
Treating O2NCFClCOX (I; X = OH) with PCl5 gave I (X = Cl), which reacted with RSH (R = Et, Bu) to give 35-55% I (X = SR; same R) (II). II were less effective acetylcholinesterase inhibitors than I (X = OR; same R) but had comparable activity vs. butyrylcholinesterase with lower toxicity.

Synthesis and antiesterase activity of sulfur-containing phosphorylated oximes. Chepakova, L. A.; Bret, V. K.; Makheva, G. F.; Yankovskaya, V. L.; Beznosko, B. K.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(2), 143-6.
Reaction of (RS)2POEt (R = Et, Pr, iso-Bu, Bu or amyl) with O:NCFCl2 gave the corresponding (RS)2P(:O)ON:CClF (I). An increase in the hydrophobicity of I did not alter the anticholinesterase activity of I, while the butyrylcholinesterase and carboxylesterase activity were increased.

O-substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov Iu Ia; Sokolov V B; Epishina T A; Martynov I V Doklady Akademii nauk SSSR (1990), 310(5), 1253-5.

Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid. Kuusk V V; Morozova I V; Agabekian R S; Aksinenko A Iu; Epishina T A; Sokolov V B; Kovaleva N V; Razdol'skiy A N; Fetisov V N; Martynov I V Bioorganicheskaia khimiia (1990 Nov), 16(11), 1500-8.
A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.

Reaction of 1,1-dichloro-1-nitrosobutane with (N,N-dimethylamido)dichlorophosphite. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (6), 1416-18.
Reaction of PrCCl2NO with Me2NPCl2 in Et2O or in SO2 gave 36% Me2NPCl4 or 30% Me2NP(O)ClON:CClPr, resp. Treating Me2NPCl4 with SO2 gave 91% Me2NP(O)Cl2. Reaction of PrCCl2NO with Me2NPCl2 in Et2O, and then with Ph3P and distn. gave Ph3PO and PrCN.

Alkyl chlorofluoroformimino perfluoroalkylphosphonates. Chepakova, L. A.; Brel, V. K.; Martynov, I. V.; Maslennikov, I. G. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(6), 1455-6.
Treating RP(OR1)2 (R = CF3, R1 = Pr, Bu; R = CF3CF2, R1 = Me, Bu) with CFCl2NO in Et2O gave 76-88% title compds. R1OP(O)RON:CFCl.

Synthesis of dialkyl (3-alkyl-1,3-alkadien-2-yl)phosphonates. Brel, V. K.; Abramkin, E. V.; Martynov, I. V.; Ionin, B. I. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(9), 2142-3.
(RO)2P(O)C(:CH2)CR1:CMe2 (R = Et, Pr; R1 = Me, Et) were prepd. in 41-73% yields by the Grignard reaction of (RO)2P(O)C(CH2OMe):C:CMe2 with R1X (X = halo).

Synthesis and antiesterase activity of O,O-dialkyl S-(ethoxycarboxyl)chloromethyl thiophosphates. Khaskin, B. A.; Makhaeva, G. F.; Torgasheva, N. A.; Ishmuratov, A. S.; Yankovskaya, V. L.; Fetisov, V. I.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovko, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2741-6.
The title compds. (RO)2P(O)SCHClCO2Et (I; R = alkyl homologs) were prepd. in 82-95% yields in the reaction of (RO)2P(O)SCl with N2CHCO2Et at -25 (in Et2O) or 6-7 (in benzene), presumably via a noncarbene mechanism. I irreversibly inhibited acetylcholinesterase, butyrylcholinesterase, and carboxylesterase; antibutyrylcholinesterase activity increased in the homologous series of R, with max. at R = Bu. An antiesterase MSBAR of I was fulfilled with parameters representing hydrophobicity and steric properties of R.

Synthesis and cholinesterase hydrolysis of O-acylated alkylchloroformoximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Agabekyan, R. S.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1989), 23(11), 1317-20.
The title compds., RCO2N:CClR1 (R = Me, Et, Pr or CH2Cl and R1 = Me, Et, Pr, or iso-Pr) were prepd. e.g., by the reaction of 1,1-dichloro-1-nitrosobutane with AcCl in the presence of Zn. These compds. were good substrates for acetyl- and butyrylcholinesterases. The kinetic parameters (Km, Vmax and ac) of these compds. in the hydrolysis reactions were comparable to those with acetylcholine. The acute toxicity was 79-381 mg/kg in mice given drugs orally.

Synthesis and structure of O,O-dialkyl 2-[(ethoxycarbonyl)amino]hexafluoroisopropylphosphonates. Aksinenko, A. Yu.; Chekhlov, A. N.; Korenchenko, O. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(1), 61-5.
The title compds. (RO)2P(O)C(CF3)2NHCO2Et (I; R = Me, Et, CHMe2) were prepd. in 54-76% yields in the reaction of (RO)2P(O)H with (CF3)2C:NCO2Et. The crystal and mol. structure of I (R = Et) was detd.

O-Substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1990), 310(5), 1253-5 [Biochem.].
The ability of O-substituted alkylchloroformoximes to serve as substrates for acetylcholinesterase (ACE, EC 3.1.1.7) and butyrylcholinesterase (BCE, EC 3.1.1.8) and to inhibit acetylcholine hydrolysis by these enzymes was detd., along with the LD50 of these compds. in mice. The compds. tested were O-acylated alkylchloroformoximes of the general formula R1C(O)ON:C(Cl)R2 [R1 = R2 = Me; R1 = Me, R2 = Et; R1 = Me, R2 = Pr; R1 = Et, R2 = Me; R1 = Et, R2 = iso-Pr; R1 = Pr, R2 = iso-Pr; R1 = CH2Cl, R2 = Pr (I); R1 = CH2Cl, R2 = iso-Pr (II)], O-carbonylated alkylchloroformoximes of the general formula EtOC(O)ON:C(Cl)R [R = Me (III), iso-Pr (IV)], and O-carbamoylated alkylchloroformoximes of the general formula (Me)2NC(O)ON:C(Cl)R [R = Me (V), iso-Pr (VI)]. All of the compds. except for I and II were good substrates for the enzymes, with Km values for ACE ranging (0.3-11.0)  10-4M and for BCE ranging (0.5-13.0)  10-4M (the Km values of ACE and BCE with acetylcholine were 1.3  10-4 and 5.4  10-4M, resp.). III and IV were competitive (Ki 1.6  10-4M) and mixed-type (Ki 4.2  10-4M) inhibitors, resp., of ACE. V and VI were effective inhibitors of both ACE and BCE, with bimol. rate consts. for inhibition (kII) of 5.7  103 and 1.4  105 M-1 min-1, resp., for ACE, and 9.8  103 and 5.4  106 M-1 min-1, resp., for BCE. The LD50 values for the tested compds. ranged 60-381 mg/kg body wt.

O-(alkylchloroformimino)(methyl)thiophosphonic acid chlorides. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2865-6.
Treating the adduct from RCCl2NO and MePCl2 with H2S gave 21-35% MeP(S)ClON:CRCl.

Interaction of 1,1-dichloro-1-nitrosoalkanes with S-ethylmethylphosphonous chloride in the presence of sulfur dioxide. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (2), 464-5.
EtSP(O)MeON:CClR (R = Me, Et, Pr) were prepd. in 42-47% yields by treating RCCl2NO with EtSPMeCl in the presence of SO2.

O-(alkylchloroformimino)-O-alkylphosphoric acid chlorides. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (5), 1122-5.
Reaction of (ON)CCl2R with (R'O)2PCl (R, R' = alkyl) afforded the title compds. (R'O)ClP(O)ON:CRCl (I) in up to 69% yield. Hydrolysis of I led to substitution of P-, and not C-bound Cl, resulting in (R'O)(NH4O)P(O)ON:CRCl.

Reaction of the adduct of methyldichlorophosphine and 1,1-dichloro-1-nitrosoethane with thioacetic acid. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(8), 1923-4.
Treating MePCl2 with MeCCl2NO in PhMe, followed by addn of 1 or 2 equiv AcSH gave 56% MeP(S)ClON:CMeCl or 32% MeP(S)ClON:CMeSAc, resp.

Inhibition of cholinesterase activity by fluorine-containing derivatives of -aminoalkylphosphonic acids. Kuusk, V. V.; Morozova, I. V.; Agabekyan, R. S.; Aksinenko, A. Yu.; Epishina, T. A.; Sokolov, V. B.; Kovaleva, N. V.; Razdol'skii, A. N.; Fetisov, V. I.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Bioorganicheskaya Khimiya (1990), 16(11), 1500-8.
A series of O,O-diethyl-1-(N--hydrohexafluoroisobutyryl)aminoalkylphosphonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate consts. and the enzyme-inhibitor intermediate dissocn. consts. are calcd. The quant. structure-activity relationships including both hydrophobic and calcd. steric parameters of substituents are developed for APh-ChE interactions. Mol. mechanics (program MM2) was used for detg. steric parameters (Es). On the basis of QSAR models anal. it was concluded that hydrophobic interactions play an essential role in APh-AChE binding, whereas for APh-BuChE binding steric interactions are essential. Presence of at least two APh binding centers on the surface of AChE and BuChE is suggested.

Synthesis and anticholinesterase activity of O-carbamoylated alkylchloroform oximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshestva, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1991), 25(4), 33-4.
Treating ClCO2N:CClR (R = Me, Et, Pr, CHMe2) with NHR1R2 (R1 = R2 = H, Me, Et; R1 = H, R2 = Me) in Et2O gave 50-69% R1R2NCO2N:CClR (same R-R3), which are acetyl- and butyrylcholinesterase inhibitors (k11 = 1.1  10-2 to 5.4  10-6 M-1 min-1). Acute oral toxicity in mice ranged from 32 to 565 mg/kg.

O-Alkyl O-methylchloroformimino phenylphosphonates - effective inhibitors of the hen brain neurotoxic esterase. Makhaeva, G. F.; Kononova, I. V.; Malygin, V. V.; Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1991), 317(4), 1009-12 [Biochem.].
The title phosphonates were effective inhibitors of neurotoxic esterase; with increasing hydrophobicity the compds. showed pronounced and selective biol. activity towards brain neurotoxic esterase compared to acetylcholinesterase. Thus, the structure of phenylphosphonate played a major role in the inhibitory effects of these potential pesticides towards neurotoxic esterase or acetylcholinesterase.

Synthesis and anticholinesterase activity of fluorine-containing -aminophosphoryl compounds. Korenchenko, O. V.; Ivanov, Yu. Ya.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Khimiko-Farmatsevticheskii Zhurnal (1992), 26(6), 21-3.
Reaction of R2P(O)H (R = MeO, EtO, PrO, Me2CHO, Ph) with (CF3)2C:NCOR1 (R1 = OEt, OCH2Ph, OPr, OBu, OCH2CH2CHMe2, CF3) in Et2O gave 44-93% R2P(O)C(CF3)2NHCOR1. Treating a 1,4,2-oxazaphospholine deriv. with alcs. gave Me(R)P(O)C(CF3)2NHCO2Et (R = BuO, Me2CHO). Bimol. rate consts. for inhibition of cholinesterases by these compds. were detd.

Synthesis and insecticidal and acaricidal activity of O-alkylchloroformimine O,O-dialkyl phosphates and O,O-dialkylthiophosphates. Ivanov, A. M.; Ivanova, G. B.; Sokolova, V. B.; Epishina, T. N.; Goreva, T. V.; Beznosko, B. K.; Martynov, I. V.. Inst. Fiziol. Okl. Veshchestv., Chernogolovka, Russia. Fiziologicheski Aktivnye Veshchestva (1991), 23 58-62.
Of 26 title compds., those having ethoxy group at P were both insecticides and acaricides, whereas those having their methoxy group showed insecticidal activity only. Increasing hydrophobicity of the alkoxy substituents decreased i.m. toxicity to mice, but also the effectiveness. O replacement by S also decreased toxicity. Synthesis is indicated.

Paradoxical toxic effect and calcium antagonism of the cholinesterase inhibitors O-(N-arylcarbamoyl)acylhydroximoyl chlorides. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 328(6), 744-6 [Biochem.].
N-phenylcarbamates and aliph. analogs of the formula R R1N(O)ON::C(Cl)R2 [where R = Et, Me, and Ph; R1 = H, Me; R2 = Et, Pr, iso-Pr] were examd. for their acetylcholinesterase and butyrylcholinesterase inhibition, for their acute toxicity and their action on selective organs. The enzyme inhibition depended on their mol. structure. Paradoxical effects (higher dose and low toxicity and vice versa) were noted.

Similar sensitivity of rat and hen brain neurotoxic esterase to inhibition by O-alkyl-O-alkylchloroformiminophenylphosphonates. Makhaeva, G. F.; Filonenko, I. V.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 332(5), 650-3.
Quant. structure-neurotoxic esterase (NTE)-inhibiting activity relationship of the title phosphonates was examd. against both rat and chicken enzyme. The phosphonates effectively inhibited the enzyme from both the sources. The anti-NTE activity of the compds. increased with the length of alkyl radical in the phosphoryl portion. The introduction of branched substituent, esp. in the -position, decreased the antienzyme activity. Math. equations are derived to describe the effects of steric factors on the NTE inhibition. PI50 = -lg I50, where I50 is the concn. of the inhibitor required to cause 50% inhibition, was calcd. for these compds.; the values are tabulated.

Crystal and molecular structures and synthesis of O,O-diisopentyl 1-(phenylsulfonamido)-1-(trifluoromethyl)-2,2,2-trifluoroethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Ross. Akad. Nauk, Chernogolovka, Russia. Doklady Akademii Nauk (1995), 345(3), 360-363.
Reaction of (CF3)2C:NSO2Ph and (Me2CHCH2CH2O)2P(O)H in Et2O gave 85% title compd. (Me2CHCH2CH2O)2P(O)C(CF3)2NHSO2Ph, the structure of which was detd. by x-ray crystallog.

Assessment of the neurotoxic potential of some methyl- and phenylphosphonates using a stable preparation of neuropathy target esterase from chicken brain. Makhaeva G F; Malygin V V; Martynov I V Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow Oblast, 142432 Russia Doklady. Biochemistry and biophysics (2001 Mar-Apr), 377 68-71.

simply RED
April 16th, 2005, 07:16 AM
The sulphur, like nitrogen, phosphorous ..... exists in quaternized form.
Anyway, strong methylating agent like dimethy sulphate is needed to quaternize it.

NH3 + BrCH3 = CH3NH3+Br-

CH3SH + (CH3)2SO4 = (CH3)2SH+ CH3SO4-

It is not a type mistake!
Anyway, these compound are sold as pesticides

http://environmentalchemistry.com/yogi/chemicals/cn/Demeton.html
http://www.inchem.org/documents/pds/pds/pest60_e.htm
http://www.inchem.org/documents/jmpr/jmpmono/v065pr15.htm
http://www.hclrss.demon.co.uk/demeton-s.html

systox, demeton ....

So we have VX with only one reaction. Just buy the pesticide, purify the
main ingredient, dissolve in THF or ether and add the dimethyl sulphate.
(C2H5O)2P=OSC2H4-S-C2H5 + (CH3)2SO4 =
(C2H5O)2P=OSC2H4-(S+)-(C2H5)(CH3) CH3SO4(-)
Toxicity LD50 = 0,017 mg/kg !!!!!!!!!!!!!!!!
With dietyl sulphate LD50 = 0,01 !
If the solvent contains no OH groups... Add the dimethyl sulphate directly!

" Quaternizing the sulphur we have structure maximal near "choline with quaternized nitrogen". Sulphur does the task of fluorine as it is easily hydrolisable by the enzyme . (my colegues tried to explain why it works so good - hahahaha ) "

Actually i never tried it, but everything elese in this report was 100% true plus things i tried myself ....


" THE PARTICULAR SULPHUR VX COMPOUNDS WERE 100-1000 TIMES MORE EASILY ABSORBED THROUGH THE SKIN THAN ESERINE AND SOMAN. 100MG SOMAN CAUSED DEATH AS WE COMPLETED WITH 5MG GD - 42 "
{{{{{{hm.... it is only 20 heh...}}}}}}

" BEWARE ! 5 MILIGRAMS VX ON THE SKIN CAUSES DEATH ! THIS PARTICULAR VX DOES NOT HYDROLISE BEFORE PH 10 !!! "

" THE BEST ANTIDOTE WE TRIED DEMINISHED THE TOXICITY ONLY TWO TIMES - SO - WE CONSIDER NO ANTIDOTE EXISTS FOR THE UPPER COMPOUNDS "


" INJECTING MEDETFK INTER-VEINS OR INTER-MUSCULAR CAUSED IMMEDIATE DEATH "
{{{{{ sure, I tried BI - 58 (dimetoate) with the same resault }}}}}

p.s. The report continues with psycho chemical experiments but i found nothing of any interest there ... (the trivial compounds - LSD, mescaline, neavy amfetamine molecules ... )

simply RED
April 16th, 2005, 07:16 AM
The sulphur, like nitrogen, phosphorous ..... exists in quaternized form.
Anyway, strong methylating agent like dimethy sulphate is needed to quaternize it.

NH3 + BrCH3 = CH3NH3+Br-

CH3SH + (CH3)2SO4 = (CH3)2SH+ CH3SO4-

It is not a type mistake!
Anyway, these compound are sold as pesticides

http://environmentalchemistry.com/yogi/chemicals/cn/Demeton.html
http://www.inchem.org/documents/pds/pds/pest60_e.htm
http://www.inchem.org/documents/jmpr/jmpmono/v065pr15.htm
http://www.hclrss.demon.co.uk/demeton-s.html

systox, demeton ....

So we have VX with only one reaction. Just buy the pesticide, purify the
main ingredient, dissolve in THF or ether and add the dimethyl sulphate.
(C2H5O)2P=OSC2H4-S-C2H5 + (CH3)2SO4 =
(C2H5O)2P=OSC2H4-(S+)-(C2H5)(CH3) CH3SO4(-)
Toxicity LD50 = 0,017 mg/kg !!!!!!!!!!!!!!!!
With dietyl sulphate LD50 = 0,01 !
If the solvent contains no OH groups... Add the dimethyl sulphate directly!

" Quaternizing the sulphur we have structure maximal near "choline with quaternized nitrogen". Sulphur does the task of fluorine as it is easily hydrolisable by the enzyme . (my colegues tried to explain why it works so good - hahahaha ) "

Actually i never tried it, but everything elese in this report was 100% true plus things i tried myself ....


" THE PARTICULAR SULPHUR VX COMPOUNDS WERE 100-1000 TIMES MORE EASILY ABSORBED THROUGH THE SKIN THAN ESERINE AND SOMAN. 100MG SOMAN CAUSED DEATH AS WE COMPLETED WITH 5MG GD - 42 "
{{{{{{hm.... it is only 20 heh...}}}}}}

" BEWARE ! 5 MILIGRAMS VX ON THE SKIN CAUSES DEATH ! THIS PARTICULAR VX DOES NOT HYDROLISE BEFORE PH 10 !!! "

" THE BEST ANTIDOTE WE TRIED DEMINISHED THE TOXICITY ONLY TWO TIMES - SO - WE CONSIDER NO ANTIDOTE EXISTS FOR THE UPPER COMPOUNDS "


" INJECTING MEDETFK INTER-VEINS OR INTER-MUSCULAR CAUSED IMMEDIATE DEATH "
{{{{{ sure, I tried BI - 58 (dimetoate) with the same resault }}}}}

p.s. The report continues with psycho chemical experiments but i found nothing of any interest there ... (the trivial compounds - LSD, mescaline, neavy amfetamine molecules ... )

simply RED
April 16th, 2005, 07:16 AM
The sulphur, like nitrogen, phosphorous ..... exists in quaternized form.
Anyway, strong methylating agent like dimethy sulphate is needed to quaternize it.

NH3 + BrCH3 = CH3NH3+Br-

CH3SH + (CH3)2SO4 = (CH3)2SH+ CH3SO4-

It is not a type mistake!
Anyway, these compound are sold as pesticides

http://environmentalchemistry.com/yogi/chemicals/cn/Demeton.html
http://www.inchem.org/documents/pds/pds/pest60_e.htm
http://www.inchem.org/documents/jmpr/jmpmono/v065pr15.htm
http://www.hclrss.demon.co.uk/demeton-s.html

systox, demeton ....

So we have VX with only one reaction. Just buy the pesticide, purify the
main ingredient, dissolve in THF or ether and add the dimethyl sulphate.
(C2H5O)2P=OSC2H4-S-C2H5 + (CH3)2SO4 =
(C2H5O)2P=OSC2H4-(S+)-(C2H5)(CH3) CH3SO4(-)
Toxicity LD50 = 0,017 mg/kg !!!!!!!!!!!!!!!!
With dietyl sulphate LD50 = 0,01 !
If the solvent contains no OH groups... Add the dimethyl sulphate directly!

" Quaternizing the sulphur we have structure maximal near "choline with quaternized nitrogen". Sulphur does the task of fluorine as it is easily hydrolisable by the enzyme . (my colegues tried to explain why it works so good - hahahaha ) "

Actually i never tried it, but everything elese in this report was 100% true plus things i tried myself ....


" THE PARTICULAR SULPHUR VX COMPOUNDS WERE 100-1000 TIMES MORE EASILY ABSORBED THROUGH THE SKIN THAN ESERINE AND SOMAN. 100MG SOMAN CAUSED DEATH AS WE COMPLETED WITH 5MG GD - 42 "
{{{{{{hm.... it is only 20 heh...}}}}}}

" BEWARE ! 5 MILIGRAMS VX ON THE SKIN CAUSES DEATH ! THIS PARTICULAR VX DOES NOT HYDROLISE BEFORE PH 10 !!! "

" THE BEST ANTIDOTE WE TRIED DEMINISHED THE TOXICITY ONLY TWO TIMES - SO - WE CONSIDER NO ANTIDOTE EXISTS FOR THE UPPER COMPOUNDS "


" INJECTING MEDETFK INTER-VEINS OR INTER-MUSCULAR CAUSED IMMEDIATE DEATH "
{{{{{ sure, I tried BI - 58 (dimetoate) with the same resault }}}}}

p.s. The report continues with psycho chemical experiments but i found nothing of any interest there ... (the trivial compounds - LSD, mescaline, neavy amfetamine molecules ... )

simply RED
April 16th, 2005, 06:48 PM
GD-42 was found in the net also ...

http://www.rand.org/publications/MR/MR1018.5/MR1018.5.chap4.html

Gd-42 (O-ethyl S-2-(S'S'-methylethylsulphonio)ethyl methylphosphonothiolate methosulphate)

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
Right :) ...

simply RED
April 16th, 2005, 06:48 PM
GD-42 was found in the net also ...

http://www.rand.org/publications/MR/MR1018.5/MR1018.5.chap4.html

Gd-42 (O-ethyl S-2-(S'S'-methylethylsulphonio)ethyl methylphosphonothiolate methosulphate)

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
Right :) ...

simply RED
April 16th, 2005, 06:48 PM
GD-42 was found in the net also ...

http://www.rand.org/publications/MR/MR1018.5/MR1018.5.chap4.html

Gd-42 (O-ethyl S-2-(S'S'-methylethylsulphonio)ethyl methylphosphonothiolate methosulphate)

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
Right :) ...

MrSamosa
April 17th, 2005, 10:06 PM
New and interesting information regarding Organophosphates is popping up all over the place. Simply RED, in the link you posted, there was a reference to "Tri-ortho-cresyl Phosphate" (TOCP). I had come across that earlier while looking for information on Bicyclic Phosphates (and how the two might be a potential exhaust hazard from jets) but forgot to post anything on it.

It turns out that TOCP is quite toxic to the spinal cord. In the 1930's, there was a case where homebrewed alcohol was adultered with TOCP (since it is odorless, tasteless, and alcohol soluble), poisoning its consumers.

Once again, another "Poor Man's Nerve Agent"--a simple triester of Phosphoric Acid.

MrSamosa
April 17th, 2005, 10:06 PM
New and interesting information regarding Organophosphates is popping up all over the place. Simply RED, in the link you posted, there was a reference to "Tri-ortho-cresyl Phosphate" (TOCP). I had come across that earlier while looking for information on Bicyclic Phosphates (and how the two might be a potential exhaust hazard from jets) but forgot to post anything on it.

It turns out that TOCP is quite toxic to the spinal cord. In the 1930's, there was a case where homebrewed alcohol was adultered with TOCP (since it is odorless, tasteless, and alcohol soluble), poisoning its consumers.

Once again, another "Poor Man's Nerve Agent"--a simple triester of Phosphoric Acid.

MrSamosa
April 17th, 2005, 10:06 PM
New and interesting information regarding Organophosphates is popping up all over the place. Simply RED, in the link you posted, there was a reference to "Tri-ortho-cresyl Phosphate" (TOCP). I had come across that earlier while looking for information on Bicyclic Phosphates (and how the two might be a potential exhaust hazard from jets) but forgot to post anything on it.

It turns out that TOCP is quite toxic to the spinal cord. In the 1930's, there was a case where homebrewed alcohol was adultered with TOCP (since it is odorless, tasteless, and alcohol soluble), poisoning its consumers.

Once again, another "Poor Man's Nerve Agent"--a simple triester of Phosphoric Acid.

simply RED
April 20th, 2005, 05:01 PM
This is answer to the other topic (GP, GV) but i post it here as the other topic is about GP GV and not GD :) .



Indeed the toxic nerve gasses must have choline- like structures.

One thing is also sure - the phosphorous group has tetrahedrical configuration (like CH4). The carbon acetyl group in acetylcholine has planar configuration (they are not allike).
Also binding to the enzyme is a complex process. 100% right simulation of it is difficult for nowdays chemistry.

I don't rememer exactly but one of the 1971 nerve gasses has the fragment -CH2-CH2-CH2-N+(CH3)3 and is 10 times more toxic than the same compound with -CH2-CH2-N+(CH3)3 fragment.
The sulphur compounds, in difference, have greatest toxicity when
-CH2-CH2-S+(C2H5)2 fragment is presented.
And S+ (upper) compounds are 1000 times more toxic than the same compounds with
-CH2-CH2-S-C2H5 fragment.
( I would say this is a perfect option to binarize as the yield will always be 100%, reaction should be fast and the beginning products are not that toxic- some pesticide and dimethylsulphate )
What is the LD-50 of novichok and the P-N compounds (interaperitoneal)?

" For the novel VX compounds we measured LD-50 values of intervenous, interaperitoneal, peroral, skin absorbtion not to differ much. In other words the soldiers will be harmed by droplets of VX fallen on the skin and should always wear protective clothes in combination to the gas masks. "
" Sulphur containing VX formulations GD 42, Amaton - 4, EDEMO, MEDETFK are not hydrlozed by any means in the nature. "
(they are hydrolized by 10 pH NaOH)
" In 3 minutes MEDETFK blocked the nerve conductivity 100% "
(I have 4 pages for MEDETFK but not the formula, anyway it is less or the same toxic as EDEMO and GD 42)
I would scan the graphic of the nerve conductivity (MEDETFK) measured in a cat,
but immagine the face of the computer operator who would do it for me :) ....


Isn't triortocresyl phosphate refered in "Silent Spring" as the cause of the "gingifile paralysis" during the dry regime in the US. Th smuggler used it to manufacture fake liquer?

simply RED
April 20th, 2005, 05:01 PM
This is answer to the other topic (GP, GV) but i post it here as the other topic is about GP GV and not GD :) .



Indeed the toxic nerve gasses must have choline- like structures.

One thing is also sure - the phosphorous group has tetrahedrical configuration (like CH4). The carbon acetyl group in acetylcholine has planar configuration (they are not allike).
Also binding to the enzyme is a complex process. 100% right simulation of it is difficult for nowdays chemistry.

I don't rememer exactly but one of the 1971 nerve gasses has the fragment -CH2-CH2-CH2-N+(CH3)3 and is 10 times more toxic than the same compound with -CH2-CH2-N+(CH3)3 fragment.
The sulphur compounds, in difference, have greatest toxicity when
-CH2-CH2-S+(C2H5)2 fragment is presented.
And S+ (upper) compounds are 1000 times more toxic than the same compounds with
-CH2-CH2-S-C2H5 fragment.
( I would say this is a perfect option to binarize as the yield will always be 100%, reaction should be fast and the beginning products are not that toxic- some pesticide and dimethylsulphate )
What is the LD-50 of novichok and the P-N compounds (interaperitoneal)?

" For the novel VX compounds we measured LD-50 values of intervenous, interaperitoneal, peroral, skin absorbtion not to differ much. In other words the soldiers will be harmed by droplets of VX fallen on the skin and should always wear protective clothes in combination to the gas masks. "
" Sulphur containing VX formulations GD 42, Amaton - 4, EDEMO, MEDETFK are not hydrlozed by any means in the nature. "
(they are hydrolized by 10 pH NaOH)
" In 3 minutes MEDETFK blocked the nerve conductivity 100% "
(I have 4 pages for MEDETFK but not the formula, anyway it is less or the same toxic as EDEMO and GD 42)
I would scan the graphic of the nerve conductivity (MEDETFK) measured in a cat,
but immagine the face of the computer operator who would do it for me :) ....


Isn't triortocresyl phosphate refered in "Silent Spring" as the cause of the "gingifile paralysis" during the dry regime in the US. Th smuggler used it to manufacture fake liquer?

simply RED
April 20th, 2005, 05:01 PM
This is answer to the other topic (GP, GV) but i post it here as the other topic is about GP GV and not GD :) .



Indeed the toxic nerve gasses must have choline- like structures.

One thing is also sure - the phosphorous group has tetrahedrical configuration (like CH4). The carbon acetyl group in acetylcholine has planar configuration (they are not allike).
Also binding to the enzyme is a complex process. 100% right simulation of it is difficult for nowdays chemistry.

I don't rememer exactly but one of the 1971 nerve gasses has the fragment -CH2-CH2-CH2-N+(CH3)3 and is 10 times more toxic than the same compound with -CH2-CH2-N+(CH3)3 fragment.
The sulphur compounds, in difference, have greatest toxicity when
-CH2-CH2-S+(C2H5)2 fragment is presented.
And S+ (upper) compounds are 1000 times more toxic than the same compounds with
-CH2-CH2-S-C2H5 fragment.
( I would say this is a perfect option to binarize as the yield will always be 100%, reaction should be fast and the beginning products are not that toxic- some pesticide and dimethylsulphate )
What is the LD-50 of novichok and the P-N compounds (interaperitoneal)?

" For the novel VX compounds we measured LD-50 values of intervenous, interaperitoneal, peroral, skin absorbtion not to differ much. In other words the soldiers will be harmed by droplets of VX fallen on the skin and should always wear protective clothes in combination to the gas masks. "
" Sulphur containing VX formulations GD 42, Amaton - 4, EDEMO, MEDETFK are not hydrlozed by any means in the nature. "
(they are hydrolized by 10 pH NaOH)
" In 3 minutes MEDETFK blocked the nerve conductivity 100% "
(I have 4 pages for MEDETFK but not the formula, anyway it is less or the same toxic as EDEMO and GD 42)
I would scan the graphic of the nerve conductivity (MEDETFK) measured in a cat,
but immagine the face of the computer operator who would do it for me :) ....


Isn't triortocresyl phosphate refered in "Silent Spring" as the cause of the "gingifile paralysis" during the dry regime in the US. Th smuggler used it to manufacture fake liquer?

nbk2000
April 21st, 2005, 12:13 PM
...as the cause of the "'gingifile paralysis"...


Do you mean 'Infantile Paralysis'? If so, that's caused by the Polio virus, not TOCP. Wasn't silent spring written prior to the discovery of the cause of polio?

nbk2000
April 21st, 2005, 12:13 PM
...as the cause of the "'gingifile paralysis"...


Do you mean 'Infantile Paralysis'? If so, that's caused by the Polio virus, not TOCP. Wasn't silent spring written prior to the discovery of the cause of polio?

nbk2000
April 21st, 2005, 12:13 PM
...as the cause of the "'gingifile paralysis"...


Do you mean 'Infantile Paralysis'? If so, that's caused by the Polio virus, not TOCP. Wasn't silent spring written prior to the discovery of the cause of polio?

simply RED
April 21st, 2005, 03:22 PM
I mean "Silent Spring" by Rachel Carson. The book that criticizes the pesticides misuse.
There was a chapter about organophosphates and TOCP was listed as a cause of paralysis that takes place when somebody drinks fake alcohol made with it.

http://www.inchem.org/documents/ehc/ehc/ehc110.htm

"""
In the spring of 1930, in mid-western and south-
western USA, an outbreak of paralysis characterized by
bilateral foot- and wrist-drop appeared suddenly (Burley,

1930; Merritt & Moor, 1930). Ultimately 50 000 people were
poisoned by a popular substitute for alcohol called
"Ginger Jake" (Morgan, 1982). Smith et al. (1930) proved
that the adulterated beverage contained about 2% TOCP and
that this caused the paralysis. """

Gingifile was a bad translation from bulgarian and it should be "Ginger Jake".

simply RED
April 21st, 2005, 03:22 PM
I mean "Silent Spring" by Rachel Carson. The book that criticizes the pesticides misuse.
There was a chapter about organophosphates and TOCP was listed as a cause of paralysis that takes place when somebody drinks fake alcohol made with it.

http://www.inchem.org/documents/ehc/ehc/ehc110.htm

"""
In the spring of 1930, in mid-western and south-
western USA, an outbreak of paralysis characterized by
bilateral foot- and wrist-drop appeared suddenly (Burley,

1930; Merritt & Moor, 1930). Ultimately 50 000 people were
poisoned by a popular substitute for alcohol called
"Ginger Jake" (Morgan, 1982). Smith et al. (1930) proved
that the adulterated beverage contained about 2% TOCP and
that this caused the paralysis. """

Gingifile was a bad translation from bulgarian and it should be "Ginger Jake".

simply RED
April 21st, 2005, 03:22 PM
I mean "Silent Spring" by Rachel Carson. The book that criticizes the pesticides misuse.
There was a chapter about organophosphates and TOCP was listed as a cause of paralysis that takes place when somebody drinks fake alcohol made with it.

http://www.inchem.org/documents/ehc/ehc/ehc110.htm

"""
In the spring of 1930, in mid-western and south-
western USA, an outbreak of paralysis characterized by
bilateral foot- and wrist-drop appeared suddenly (Burley,

1930; Merritt & Moor, 1930). Ultimately 50 000 people were
poisoned by a popular substitute for alcohol called
"Ginger Jake" (Morgan, 1982). Smith et al. (1930) proved
that the adulterated beverage contained about 2% TOCP and
that this caused the paralysis. """

Gingifile was a bad translation from bulgarian and it should be "Ginger Jake".

nbk2000
April 21st, 2005, 03:34 PM
I know what book you were referring to. It was the 'gingifile' reference that had me confused.

nbk2000
April 21st, 2005, 03:34 PM
I know what book you were referring to. It was the 'gingifile' reference that had me confused.

nbk2000
April 21st, 2005, 03:34 PM
I know what book you were referring to. It was the 'gingifile' reference that had me confused.

simply RED
April 21st, 2005, 03:39 PM
It is very funny when such words are translated into different languages.
It's okay now .

simply RED
April 21st, 2005, 03:39 PM
It is very funny when such words are translated into different languages.
It's okay now .

simply RED
April 21st, 2005, 03:39 PM
It is very funny when such words are translated into different languages.
It's okay now .

simply RED
April 27th, 2005, 08:55 AM
I made an interesting test.

In a very small syringe (0,5 ml - used for diabetics). First suck 0,1 ml clear water. Then 0,1 ml (coloured) solution of KMnO4.
And observed will they mix, despite the small (2-3 mm) diameter of the syringe.

They mixed perfectly for 3,4 seconds...
:)

simply RED
April 27th, 2005, 08:55 AM
I made an interesting test.

In a very small syringe (0,5 ml - used for diabetics). First suck 0,1 ml clear water. Then 0,1 ml (coloured) solution of KMnO4.
And observed will they mix, despite the small (2-3 mm) diameter of the syringe.

They mixed perfectly for 3,4 seconds...
:)

simply RED
April 27th, 2005, 08:55 AM
I made an interesting test.

In a very small syringe (0,5 ml - used for diabetics). First suck 0,1 ml clear water. Then 0,1 ml (coloured) solution of KMnO4.
And observed will they mix, despite the small (2-3 mm) diameter of the syringe.

They mixed perfectly for 3,4 seconds...
:)

MrSamosa
April 28th, 2005, 01:31 AM
I've finally found some toxicity data on Bicyclic Phosphates and Phosphites. I've also found that it is more fruitful to use the words "Bicyclophosphate" and "Bicyclophosphite" in Google searches.

According to the EPA, Trimethylolpropane Bicyclophosphite (Ethyl Bicyclophosphite) has an LD50 of 2.5 mg/kg orally in cats. Not too shabby at all--that's more toxic than Parathion and at the same level as some Dialkyl Fluorophosphates.

http://www.navy.al.wpafb.af.mil/resabs/lindsey1.html This site has some details about the neurological action of Ethyl Bicyclophosphate at levels of .20-.60 mg/kg in rats.

http://www.jneurosci.org/cgi/content/abstract/5/9/2432 This is about t-butylbicyclophosphorothionate (TBPS)--of interest is that it mentions it having a toxicity comparable to picrotoxin.

It appears a convulsive dose for TMPP (Trimethylolpropane Bicyclophosphate--a nice abbreviation) is a mere .6 mg/kg! Not bad at all, considering its ease of production.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2996180&dopt=Citation

This line really stood out to me:

4-Alkylbicyclophosphates, R1C(CH2O)3P(O), with suitable R1 substituents (e.g., t-butyl, isopropyl, or cyclohexyl) are highly toxic compounds [mouse intraperitoneal (ip) LD50 values 0.036-0.52 mg/kg] and are potent noncompetitive gamma-aminobutyric acid (GABA) antagonists.

MrSamosa
April 28th, 2005, 01:31 AM
I've finally found some toxicity data on Bicyclic Phosphates and Phosphites. I've also found that it is more fruitful to use the words "Bicyclophosphate" and "Bicyclophosphite" in Google searches.

According to the EPA, Trimethylolpropane Bicyclophosphite (Ethyl Bicyclophosphite) has an LD50 of 2.5 mg/kg orally in cats. Not too shabby at all--that's more toxic than Parathion and at the same level as some Dialkyl Fluorophosphates.

http://www.navy.al.wpafb.af.mil/resabs/lindsey1.html This site has some details about the neurological action of Ethyl Bicyclophosphate at levels of .20-.60 mg/kg in rats.

http://www.jneurosci.org/cgi/content/abstract/5/9/2432 This is about t-butylbicyclophosphorothionate (TBPS)--of interest is that it mentions it having a toxicity comparable to picrotoxin.

It appears a convulsive dose for TMPP (Trimethylolpropane Bicyclophosphate--a nice abbreviation) is a mere .6 mg/kg! Not bad at all, considering its ease of production.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2996180&dopt=Citation

This line really stood out to me:

4-Alkylbicyclophosphates, R1C(CH2O)3P(O), with suitable R1 substituents (e.g., t-butyl, isopropyl, or cyclohexyl) are highly toxic compounds [mouse intraperitoneal (ip) LD50 values 0.036-0.52 mg/kg] and are potent noncompetitive gamma-aminobutyric acid (GABA) antagonists.

MrSamosa
April 28th, 2005, 01:31 AM
I've finally found some toxicity data on Bicyclic Phosphates and Phosphites. I've also found that it is more fruitful to use the words "Bicyclophosphate" and "Bicyclophosphite" in Google searches.

According to the EPA, Trimethylolpropane Bicyclophosphite (Ethyl Bicyclophosphite) has an LD50 of 2.5 mg/kg orally in cats. Not too shabby at all--that's more toxic than Parathion and at the same level as some Dialkyl Fluorophosphates.

http://www.navy.al.wpafb.af.mil/resabs/lindsey1.html This site has some details about the neurological action of Ethyl Bicyclophosphate at levels of .20-.60 mg/kg in rats.

http://www.jneurosci.org/cgi/content/abstract/5/9/2432 This is about t-butylbicyclophosphorothionate (TBPS)--of interest is that it mentions it having a toxicity comparable to picrotoxin.

It appears a convulsive dose for TMPP (Trimethylolpropane Bicyclophosphate--a nice abbreviation) is a mere .6 mg/kg! Not bad at all, considering its ease of production.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2996180&dopt=Citation

This line really stood out to me:

4-Alkylbicyclophosphates, R1C(CH2O)3P(O), with suitable R1 substituents (e.g., t-butyl, isopropyl, or cyclohexyl) are highly toxic compounds [mouse intraperitoneal (ip) LD50 values 0.036-0.52 mg/kg] and are potent noncompetitive gamma-aminobutyric acid (GABA) antagonists.

MrSamosa
May 1st, 2005, 10:07 PM
Extending on my earlier idea of using Pentaerythritol...

The toxicity of Bicyclic Phosphates is dependent on the R-chain, and the toxicity varies in much the same way it does with conventional G-Agents.

Let me clarify a bit. t-butyl Bicyclophosphate is more toxic than Isopropyl Bicyclophosphate, which is more toxic than Ethyl Bicyclophosphate: the toxicity increases from primary alcohols to secondary alcohols to tertiary alcohols.

Therefore, it seems reasonable to conclude that high toxicities might come from aminoalcohol groups. And this makes finding a suitable precursor all the easier!

Pentaerythritol. Instead of nitrating those alcohol groups, why not halogenate them? And then react the product with Silver Phosphate to get Chloromethyl Bicyclophosphate. In turn, this could be reacted with Dimethylamine yielding Dimethylaminomethyl Bicyclophosphate.

It wouldn't be quite the same R chain we see in VX or in GV/GP Agents, but it might still be of interest.

MrSamosa
May 1st, 2005, 10:07 PM
Extending on my earlier idea of using Pentaerythritol...

The toxicity of Bicyclic Phosphates is dependent on the R-chain, and the toxicity varies in much the same way it does with conventional G-Agents.

Let me clarify a bit. t-butyl Bicyclophosphate is more toxic than Isopropyl Bicyclophosphate, which is more toxic than Ethyl Bicyclophosphate: the toxicity increases from primary alcohols to secondary alcohols to tertiary alcohols.

Therefore, it seems reasonable to conclude that high toxicities might come from aminoalcohol groups. And this makes finding a suitable precursor all the easier!

Pentaerythritol. Instead of nitrating those alcohol groups, why not halogenate them? And then react the product with Silver Phosphate to get Chloromethyl Bicyclophosphate. In turn, this could be reacted with Dimethylamine yielding Dimethylaminomethyl Bicyclophosphate.

It wouldn't be quite the same R chain we see in VX or in GV/GP Agents, but it might still be of interest.

MrSamosa
May 1st, 2005, 10:07 PM
Extending on my earlier idea of using Pentaerythritol...

The toxicity of Bicyclic Phosphates is dependent on the R-chain, and the toxicity varies in much the same way it does with conventional G-Agents.

Let me clarify a bit. t-butyl Bicyclophosphate is more toxic than Isopropyl Bicyclophosphate, which is more toxic than Ethyl Bicyclophosphate: the toxicity increases from primary alcohols to secondary alcohols to tertiary alcohols.

Therefore, it seems reasonable to conclude that high toxicities might come from aminoalcohol groups. And this makes finding a suitable precursor all the easier!

Pentaerythritol. Instead of nitrating those alcohol groups, why not halogenate them? And then react the product with Silver Phosphate to get Chloromethyl Bicyclophosphate. In turn, this could be reacted with Dimethylamine yielding Dimethylaminomethyl Bicyclophosphate.

It wouldn't be quite the same R chain we see in VX or in GV/GP Agents, but it might still be of interest.

simply RED
May 5th, 2005, 04:46 AM
What V gas (intervenous) does to a cat - see the attachment:

The upper graphic shows bronchial spasm. The graphic below shows arterial pressure drop - and death. Everything happens for 2,5 minutes.

-----

Everything about bicyclophosphates seems very good and right!
Only the synthesis you mentioned has a drawback :
ester with halogen in R chain could not be reacted with amine, basic solution
( NaCO3, NaHCO3, pyridine, NaOH ) is needed for this , the high pH hydrolises the ester.

simply RED
May 5th, 2005, 04:46 AM
What V gas (intervenous) does to a cat - see the attachment:

The upper graphic shows bronchial spasm. The graphic below shows arterial pressure drop - and death. Everything happens for 2,5 minutes.

-----

Everything about bicyclophosphates seems very good and right!
Only the synthesis you mentioned has a drawback :
ester with halogen in R chain could not be reacted with amine, basic solution
( NaCO3, NaHCO3, pyridine, NaOH ) is needed for this , the high pH hydrolises the ester.

simply RED
May 5th, 2005, 04:46 AM
What V gas (intervenous) does to a cat - see the attachment:

The upper graphic shows bronchial spasm. The graphic below shows arterial pressure drop - and death. Everything happens for 2,5 minutes.

-----

Everything about bicyclophosphates seems very good and right!
Only the synthesis you mentioned has a drawback :
ester with halogen in R chain could not be reacted with amine, basic solution
( NaCO3, NaHCO3, pyridine, NaOH ) is needed for this , the high pH hydrolises the ester.

simply RED
May 26th, 2005, 07:52 AM
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~uONr6f:12

SYNTHESIS AND INSECTICIDAL ACTIVITY OF BICYCLIC PHOSPHOROTHIONATES AND RELATED MONOCYCLIC PHOSPHOROTHIONATES
Authors:

WU S-Y

HIRASHIMA A

TAKEYA R

ETO M

Source: J FAC AGRIC KYUSHU UNIV; 33 (3-4). 1988. 275-286.


Could somebody find this article? It would be of great use !!!!

simply RED
May 26th, 2005, 07:52 AM
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~uONr6f:12

SYNTHESIS AND INSECTICIDAL ACTIVITY OF BICYCLIC PHOSPHOROTHIONATES AND RELATED MONOCYCLIC PHOSPHOROTHIONATES
Authors:

WU S-Y

HIRASHIMA A

TAKEYA R

ETO M

Source: J FAC AGRIC KYUSHU UNIV; 33 (3-4). 1988. 275-286.


Could somebody find this article? It would be of great use !!!!

simply RED
May 26th, 2005, 07:52 AM
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~uONr6f:12

SYNTHESIS AND INSECTICIDAL ACTIVITY OF BICYCLIC PHOSPHOROTHIONATES AND RELATED MONOCYCLIC PHOSPHOROTHIONATES
Authors:

WU S-Y

HIRASHIMA A

TAKEYA R

ETO M

Source: J FAC AGRIC KYUSHU UNIV; 33 (3-4). 1988. 275-286.


Could somebody find this article? It would be of great use !!!!

FUTI
May 26th, 2005, 04:06 PM
simply RED the data you posted about choline resemblance started another idea in my head. If CW that has -S-CH2-CH2-S(CH3)2+ group is most active in its group, and -S-(CH2)3-N(CH3)3+ is the most active in other group this could indicate that targeted enzyme has deeper binding pocket as when you compare the length two sulfur atom in the first case and sulfur and nitrogen due to longer C-S bond they are very close to each other. So making longer chain make better fit for a deeper pocket. Anyway it all started with a sound in my head that I heard somewhere about butyryl-choline esterase enzyme...maybe its dead end but since you have access to good data maybe you can give us a few pro et contra for this theory.

FUTI
May 26th, 2005, 04:06 PM
simply RED the data you posted about choline resemblance started another idea in my head. If CW that has -S-CH2-CH2-S(CH3)2+ group is most active in its group, and -S-(CH2)3-N(CH3)3+ is the most active in other group this could indicate that targeted enzyme has deeper binding pocket as when you compare the length two sulfur atom in the first case and sulfur and nitrogen due to longer C-S bond they are very close to each other. So making longer chain make better fit for a deeper pocket. Anyway it all started with a sound in my head that I heard somewhere about butyryl-choline esterase enzyme...maybe its dead end but since you have access to good data maybe you can give us a few pro et contra for this theory.

FUTI
May 26th, 2005, 04:06 PM
simply RED the data you posted about choline resemblance started another idea in my head. If CW that has -S-CH2-CH2-S(CH3)2+ group is most active in its group, and -S-(CH2)3-N(CH3)3+ is the most active in other group this could indicate that targeted enzyme has deeper binding pocket as when you compare the length two sulfur atom in the first case and sulfur and nitrogen due to longer C-S bond they are very close to each other. So making longer chain make better fit for a deeper pocket. Anyway it all started with a sound in my head that I heard somewhere about butyryl-choline esterase enzyme...maybe its dead end but since you have access to good data maybe you can give us a few pro et contra for this theory.

simply RED
May 27th, 2005, 12:48 PM
Don't know about longer chains.

The longest chain I have data on is :

-S-CH2-CH2-S(+)-(CH2-CH3)2 and it is one of the most active...

It could be tried with one more methylene group anyway :) .

simply RED
May 27th, 2005, 12:48 PM
Don't know about longer chains.

The longest chain I have data on is :

-S-CH2-CH2-S(+)-(CH2-CH3)2 and it is one of the most active...

It could be tried with one more methylene group anyway :) .

simply RED
May 27th, 2005, 12:48 PM
Don't know about longer chains.

The longest chain I have data on is :

-S-CH2-CH2-S(+)-(CH2-CH3)2 and it is one of the most active...

It could be tried with one more methylene group anyway :) .

FUTI
May 29th, 2005, 02:24 PM
Thanks simply RED you have just answered with info that makes it posible. Only question now is: Is the higher activity caused by higher lipophylic character of compound or better match to target? But you are right until someone doesn't try that through experiment nobody will know.

FUTI
May 29th, 2005, 02:24 PM
Thanks simply RED you have just answered with info that makes it posible. Only question now is: Is the higher activity caused by higher lipophylic character of compound or better match to target? But you are right until someone doesn't try that through experiment nobody will know.

FUTI
May 29th, 2005, 02:24 PM
Thanks simply RED you have just answered with info that makes it posible. Only question now is: Is the higher activity caused by higher lipophylic character of compound or better match to target? But you are right until someone doesn't try that through experiment nobody will know.

simply RED
May 30th, 2005, 09:10 AM
Always welcome!
Yes, only trial may show...

Another thing to spot is the positive charge of the " choline - N " analog atom as we see in the most active toxins.

(CH3)3N+ ; (R)2S+ ; -N=C(sigma+)ClF

simply RED
May 30th, 2005, 09:10 AM
Always welcome!
Yes, only trial may show...

Another thing to spot is the positive charge of the " choline - N " analog atom as we see in the most active toxins.

(CH3)3N+ ; (R)2S+ ; -N=C(sigma+)ClF

simply RED
May 30th, 2005, 09:10 AM
Always welcome!
Yes, only trial may show...

Another thing to spot is the positive charge of the " choline - N " analog atom as we see in the most active toxins.

(CH3)3N+ ; (R)2S+ ; -N=C(sigma+)ClF

Chris The Great
August 17th, 2005, 11:20 PM
Very interesting stuff, I wish I had sources as good as that! Nonetheless, I have a large amount of information myself, and am trying to deduce the effects on toxicity different structures have. It's quite difficult, as the lesser known V agents (VM, VE, VS) do not have any toxicity data available, just "in the same range as VX". That doesn't help anyone see if a CH3-P group is more toxic than a C2H5-P group, etc.
Actually, if anyone has toxicity info for VS than it would solve the question, as it is VX but with the methyl replaced by ethyl...

While choline type structures seem to have the best toxicity, remember that nerve agents do not exclusively attack AChE. It has been found that when AChE is completely protected, nerve agents still produce extremely toxic effects.
See http://www.rand.org/publications/MR/MR1018.5/MR1018.5.chap5.html

I also read a journal about this topic, I don't know where it is right now, anyway... basically they tested VX toxicity against mice without AChE (yes, they can actually live!). They found that they where twice as sensitive to VX poisoning, and exhibited the same symtoms as normal mice.
http://jpet.aspetjournals.org/cgi/content/full/299/2/528

Suddenly, the picture becomes much more complicated!


Anyway, has anybody found any toxicity information for those lesser known V-agents? It would help a huge amount in designing new nerve agents to have ultra-high toxicities. By seeing what difference in toxicity a change makes, we could estimate the toxicities of new agents simply by looking at the structure (no, it won't be right on, but it will give an idea of relative toxicity).


From what I can see so far, it seems that giving the amino group a positive charge will give a more toxic agent than the S atom, probably because the amino group agents are already extremely toxic. The isopropyl group should have the highest toxicity, although larger groups may be more toxic.... no agent like that has been made as far as I know however so it is pure speculation that a pincolyl group would be more toxic than an isopropyl group in that location on the molecule...

(and since this is getting off topic, perhaps a new thread should be created for the discussion that stemmed from simply RED's post about the new V agents? It would tidy things up a bit.)

FUTI
August 18th, 2005, 08:53 AM
Chris blood and tissues are full of diferent esterase enzymes. It is recomended in drug design to avoid esters for that reason. Not that they won't be active one but they will have awkward ADME. Now I don't think that there are such issues in CW program - but mild esterase inhibitor can make things worse. Since AChE is serin protease, I suspect that the other esterase enzyme that should be targeted is whithin the same family since CW show efect on them to. I would be suprised if metaloprotease is involved - but than the job of making things worse is easier.

FUTI
August 29th, 2005, 10:32 AM
Another thing to spot is the positive charge of the " choline - N " analog atom as we see in the most active toxins.

(CH3)3N+ ; (R)2S+ ; -N=C(sigma+)ClF

It just crossed my mind. Last compound is some Novichok derivative. Does anyone has the info about skin penetration of this class compared to others? It looks more oil soluble to me than the rest.

simply RED
October 8th, 2005, 11:15 AM
Synthesis of tret-butyl bicyclophosphate:
From the original source (Ozoe and Eto)

3,2 g O=PCl3 in 10ml acetonitrile was added dropwise to a solution of
3,4g (CH3)3C-C(CH2OH)3 and 5g pyridine in 50 ml acetonitrile - cooled in ice bath. The mixture is stirred at room temperature for 12 hours and then at 50 degrees C for 5 hours. The sloution is evaporated to give 2,2 g chrystal mass which is rechrystalized from ether-chloroform - to give pure tret-butyl bicyclophosphate.
Yield: (CH3)3C-C(-CH2O-)3P=O

Comment:
Instead of rechrystalisation, the yield could be mixed with DMSO and directly weaponized. Ozoe and Eto have tested wide range of byc. phosphates but not any amino-bicyclophosphate derivate - which theory suggest will be most toxic.

(CH3)2N-C(-CH2O-)3P=O should be synth. the absolutely same way.

With NH groups in basic environment, the NH will not be protonized and will be active too, so the reaction should be carried out in acidic conditions, HCl should be extracted, it is a gas anyway...

It is incredibly hard to post these days, btw.

Chris The Great
November 23rd, 2005, 12:12 AM
I noticed nbk had posted a useful chart that included relative toxicty of several nerve agents and other poisons, along with names so that the structure could be easily determined.
I found the increase in toxicity by including a N+(Me)3 group over a normal N(R)2 group to be quite startling, as it seems that since adding an extra methyl group is just as simple as adding methyl iodide, why didn't anyone do that in the cold war? I am guessing the information simply hasn't had time to make it's way around to us.

My point is that it seems that an extremely high toxicity would depend on several main factors:

The type of agent. V agents are more toxic than the corresponding G agent. By V agents I mean agents that have an -S-R structure and lack fluorine, by G agents I mean agents that have fluorine attacked to the central phosphorus. This is a simplification but it helps in understanding.
The presence of an -O/S-R-N(R)2 group give high toxicity, and quaternizing it to -O/S-R-N+(R)3 gives another large increase in toxicity. -S-R-S+(R)2 groups also give high toxicity, though not as high as the nitrogen group.
The alkyl group on the V agent will also increase toxicity. VR has a higher toxicity than VX, and simply replaces the ethyl group with an isopropyl group. Replacing it with even more active groups, such as cyclohexanol or pinacolyl, would most likely give even more toxic versions of the original V agent.
Replacing the sulfur in a V agent with selenium MAY give an increase in toxicity, I say this because VE with a selenium atom is more toxic than VX, and I would expect the normal VE is to be about roughly equal in toxicity.
The length of the chain leading to the -N(R)2 group also determines toxicity. With an ethyl group, toxicity is of course high, but replacing it with a propyl group gives a LARGE increase in toxicity (undoutably because of the structural similarity to choline). The most toxic agent listed on that chart would be considered a G agent, and has a LD lower than dioxin (which is nearly as toxic as iv VX by oral exposure, and is no doubt even more toxic by the iv route in which it is compared on the chart), which is simply amazing.

So, from the above patterns I've noticed after looking at lots of toxicity information (that handy chart by nbk coupled with all sorts of bits and pieces I've found over the years), I have several ideas.
First, we change over to a V agent. Toxicity should go up by maybe 5 times. Second, we use a cyclohexanol group for our alkyl group, since cyclosarin is already 40% as toxic as VX. If using selenium is indeed more toxic than sulfur, use that as well. We should end up with an agent a good 25 to 100 times more toxic than VX (not accurate since I really am just making educated guesses here, but you get the genera idea).

If I had the equipment and capability, I'd whip some up as well as some VX and test them on mice ($1 each at the store for snake food) but unfortunately I am limited to reading and making educated guesses. Maybe there should be a thread on making a glove box suitable for making and working with nerve agents? Then maybe we could get something practical done. Such an agent would not be illegal in Canada under the CW act, and might not be in other countries as well.

Thought you guys might be interested in having something new to read (and some forum activity).