Production and Decontamination
Altogether there are four ingredients in Sarin:
In binary weapons, methylphosphoryldifluoride (DF) and isopropanol are used. The isopropanol is included in a mixture (OPA) with isopropylamine which binds the hydrogen fluoride generated.
Since sarin is farily volatile (comparable to water), the major action is via the respiratory organs. Due to its high solubility, sarin persists in the ground for a large amount of time, but this decomposes the molecule to a non-toxic phosphoric acid. As shown in the graph below, this action can be speeded up by alkali, or by a catalyst (eg hypochlorite ions from bleaching powder), providing the basis for decontamination.
It was VX's stability to alkali that made it more attractive than sarin, along with its greater power on inhalation.
A characteristic of nerve agents is that they are extremely toxic and that they have very rapid effect. The nerve agent, either as a gas, aerosol or liquid, enters the body through inhalation or through the skin.
The route for entering the body is of importance for the period required for the nerve agent to start having effect. It also influences the symptoms developed and, to some extent, the sequence of the different symptoms. Generally, the poisoning works faster when the agent is absorbed through the respiratory system than via other routes. This is because the lungs contain numerous blood vessels and the inhaled nerve agent can therefore rapidly diffuse into the blood circulation and thus reach the target organs. Among these organs, the respiratory system is one of the most important. If a person is exposed to a high concentration of nerve agent, e.g., 200 mg sarin/m3 death may occur within a couple of minutes.
Poisoning takes longer when the nerve agent enters the body through the skin. Nerve agents are more or less fat-soluble and can penetrate the outer layers of the skin. However, it takes some time before the poison reaches the deeper blood vessels. Consequently, the first symptoms do not occur until 20-30 minutes after the initial exposure but subsequently the poisoning process may be rapid if the total dose of nerve agent is high.
When exposed to a low dose of sarin, causing minor poisoning, characteristic symptoms are increased production of saliva, a running nose and a feeling of pressure on the chest. The pupil of the eye becomes contracted (miosis) which impairs night-vision. The accommodation capacity of the eye is also reduced so that short-range vision deteriorates and the victim feels pain when he tries to focus on an object nearby. This is accompanied by headache. Less specific symptoms are tiredness, slurred speech, hallucinations and nausea. Exposure to higher doses causes cramp, vomiting, involuntary urination. This is swiftly followed by muscle tremors and convulsions. A large dose would kill by suffocation in under a minute.
Click here for detailed, illustrated description of the reaction mechanism
The toxic effect of sarin depends on it becoming bound to an enzyme, and thereby inhibit this vital enzyme's normal biological activity in the cholinergic nervous system.
Click here for a PDB model of acetylcholinesterase. This model structure contains an inhibitor very similar to sarin, the poison from a bite from a monkey-snake. To see this more easily, change to colour to "chain".
The enzyme is responsible for breaking down the messenger molecule acetylcholine. It is found associated with the post-juctional membrane at the neuromuscular junction and in the cell bodies and processes of cholinergic neurons. Since the signals from the brain are not broken down, muscles go into constant spasms, including the diaphram which contracts leading to suffocation. The process requires two steps, acetylation by means of a serine in the active site and hydrolysis:
Enzyme-OH +
CH3C(=O)-O-(CH2)2-N+(CH3)3
reacts with the release of choline to give
Enzyme-O-C(=O)-CH3
which is rapidly hydrolysed to
Enzyme-OH + CH3COOH
Degradation of the signal substance in the cholinergic synapse takes place extremely rapidly depending on the enzyme being available in large amounts and also since it is extremely effective. Under optimum conditions, each enzyme molecule hydrolyses about 15 000 acetylcholine molecules per second. The reaction mechanism for sarin is similar but with the important difference that the rate of the final, hydrolysing step is negligible. Consequently, the enzyme becomes irreversibly inhibited, with the sarin covalently bound to the enzyme via the serine in the active site.
Enzyme-OH---X-P(=O)(R1)(-OR2)
releases X- to give
Enzyme-O-P(=O)(R1)(-OR2)
A simplified picture of a cholinergic synapse, with the nerve in which acetyllcholine is formed and the receiving side (muscles, glands, etc.) with receptors. Acetylcholine is formed and released from the nerve cell. On the other side of the synapse it binds to a muscle cell receptor for a split second. The signal has now been transferred from the nervous system to the performing muscle. In the presence of sarin the enzyme acetylcholinesterase, which is responsible for breaking down acetylcholine, is inhibited. The receptor keep on sending signals to the muscle cell, which leads to muscle cramp.