The nerve agents can be classified as G agents (e.g. sarin, soman, tabun, etc.) and V agents (e.g. VX), and more recently as A agents (known as Novichok, a group of chemical warfare agents developed in the former Soviet Union that recently gained worldwide attention due to the Skripal and Navalny poisonings.

The international group of researchers, led by Yevgen Karpichev, a TalTech senior scientist in the department of chemistry and biotechnology, focused on neurotoxins, which are poisonous because of the phosphorus compounds they contain.

The body uses a molecule called acetylcholine (ACh), among others, to transmit nerve signals. But if the molecules that have already been fired are not constantly broken down and removed, the communication between nerve cells becomes a jumbled mess: the tissues no longer understand what exactly they are supposed to do.

So the work of the molecular tissue inhibitor that helps prevent this – acetylcholinesterase (AChE) – is what is targeted by organophosphorus (OP) neurotoxins, essentially either nerve agents or pesticides.

In severe cases, they cause nausea and vision problems. However, stronger toxins or larger doses could also cause difficulty breathing, muscle spasms, loss of muscle control, and severe central nervous system damage. Such neurological and respiratory failure can be fatal if left untreated.

Antidotes can be used to displace the nerve agent from the acetylcholinesterase, and the molecular coaxial machinery can begin to function again. But if left untreated, poisoning generally causes irreversible health damage.

Chemical warfare agents are a major concern in the age of terrorist activity, as is the risk of their use by a terrorist group or rogue regime, because a facility producing OP pesticides can be repurposed to produce nerve agents, or OP pesticides can be used in larger quantities for the same purpose as nerve agents.

They are the most likely weapons of choice for terrorists because they are deadly and easy to prepare even for the untrained.

Although the world's major powers have pledged to renounce chemical weapons and destroy their stockpiles, the key intermediates are relatively easy to synthesize, and there are still countries, such as North Korea and Syria, that have not ratified the Chemical Weapon Convention.

A Novichok poison was also used to poison both Russian exile Sergei Skripal and the recently deceased opposition leader Alexei Navalny.

Now, the antidotes described by Karpichev and his colleagues will help against VX, an extremely toxic synthetic chemical compound that is a thousand times more toxic than the chemical warfare nerve agent sarin developed before World War II.

Karpichev says the new compounds are more potent and effective than conventional antidotes. At the same time, they are safer for bacteria and fungi and less toxic to mammalian cells.

He said their work is significant because they were guided by the principles of green or sustainable chemistry in developing the antidotes.

Biodegradable ionic liquids and surfactant building blocks were used in their synthesis.

Series of AChE reactivators were synthesized using biodegradable ionic liquids-based molecular platforms.

The compounds are stable in blood plasma, while they degrade rapidly when released into the environment. "Our work represents the state of the art in this field and may be used in the future to improve human acetylcholinesterase reactivators, which are critical in the treatment of organophosphate poisoning," Karpichev said.

The study was published in the journal Chemico-Biological Interaction.

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