BAOCHAU DINH CHEM 12B MAY 3RD, 2006

I. Sarin

A. Background

B. Structure

C. Chemical Characteristics

II. Synthesis of Sarin

III. Mechanism of Action of Acetyl Cholinesterase

IV. Mechanism of Toxicity of Sarin

V. Bibliography

Sarin or GB (O-Isopropyl methylphosphonofluoridate), discovered in 1938 in Wuppertal-Elberfeld in the Ruhr valley of Germany by two German scientists while attempting to create stronger pesticides, is a human-made chemical warfare agent classified as a nerve agent – the most toxic and rapidly acting of the known chemical warfare agents. It is a member of the organophosphate family which was previously used as pesticides before their effects were fully known. Sarin possesses the typical organophosphate characteristics of stability, high toxicity, and is an easily dispersed agent that acts extremely quickly when absorbed through the skin or inhaled. Even at very low concentrations, sarin can be fatal. Death may follow in one minute after direct ingestion of about 0.01 milligram per kilogram of body weight

Background Sarin gas was released in the

Tokyo subway system by the Aum Shinrikyo Cult, creating more than 5,000 victims and causing 12 deaths.

The same cult had released sarin in an apartment complex in Matsumoto in 1994, killing seven and injuring more than 600 people.

In Tokyo, sarin was concealed in lunch boxes and bags. The terrorists punctured the bags with

umbrellas and ran out of the subway tunnel.

Structure of Sarin Chemical formula: C4H10FO2P Chemical name: 2-(fluoro-methyl-phosphoryl oxypropane) Molecular weight: 146.1 g Density (g/cm-3 at 298K) : 1.09 Alternative names:

GB Zarin Phosphonofluoridic acid, methyl-, isopropyl ester Phosphonofluoridic acid, methyl-, 1- methyl ethyl ester Isopropyl methylphosphonofluoridate Isopropyl ester of methylphosphonofluoridic acid Methylisoproposfluorophosphine oxide Isopropyl Methylfluorophosphonate O-Isopropyl Methylisopropoxfluorophosphine oxide O-Isopropyl Methylphosphonofluoridate Methylfluorophosphonic acid, isopropyl ester Isoproposymethylphosphonyl fluoride

Chemical CharacteristicsChemical Family Fluorinated organophosphorus compound

Boiling point 158 °C

Freezing/Melting point

-56 °C

Vapor pressure 2.9 at 25 °C

Vapor relative density (Air=1)

4.86

Liquid density 1.0887 g/cm³ at 25 °C 1.102 g/cm³ at 20 °C

Solubility in water Complete

Appearance & color Colorless liquid. Odorless in pure form

Chemical Synthesis of Sarin The first stage of this process involves reagents that

are not particularly dangerous and to get the reaction to complete no special conditions are required. The only problem with this reaction is that it produces Hydrochloric acid, a dangerous compound and so special care is needed to be taken when disposing of the waste products.

Phosphorus trichloride

Trimethylphosphate

Chemical Synthesis of Sarin (con.)

The second stage of this reaction process involves the heating of the reactant which would result in the transformation as shown.

Heat

Trimethylphosphate Dimethylmethylphosphonate

Chemical Synthesis of Sarin (con.)

Stage three also involves the use of hazardous reactants and products. To start with, Chlorine gas is used, which in itself was used as a chemical weapon during World War I, and then more Hydrochloric acid is produced during the reaction that needs to be disposed of safely after the products have been seperated using fractional distillation.

Dimethylmethylphosphonate Methylphosphonyl Dichloride

Chemical Synthesis of Sarin (con.)

In the fourth stage of the reaction process, Hydrofluoric acid

(or Sodium Fluoride, or Potassium Fluoride) is used as a source of Fluoride ions, which in itself is very toxic by inhalation, by contact with skin and if swallowed and it causes severe burns. Also, more Hydrochloric acid is produced which would have to be disposed of safely.

Methylphosphonyl Dichloride

Methylphosphonyl Difluoride

Chemical Synthesis of Sarin (con.) The fifth and final stage in the making of Sarin is usually

carried out inside the warhead during flight to the enemy because the products of this final stage is far more dangerous than the reactants and so for safety reasons the reactants are stored ready for use instead of Sarin itself.

Methylphosphonyl Difluoride

MethylphosphonylDichloride

Sarin

Mechanism of Action of Acetyl

cholinesterase When a functioning motor nerve is stimulated, it releases the

neurotransmitter acetylcholine to transmit the impulse to a muscle or organ. Once the impulse has been sent, the enzyme acetylcholinesterase inactivates the acetylcholine by breaking it down so that the nerve impulse is only transmitted once as required.

Acetylcholine vs. Acetyl cholinesterase

Acetylcholine: CH3COOCH2CH2N+

(CH3)3 2-(acetyloxy)-N, N, N- trimethylethanaminium an ester of acetic acid and choline abbreviated as ACh, was the first neurotransmitter to be identified. It is a chemical transmitter in both

the peripheral nervous system (PNS)

and central nervous system.

Acetyl cholinesterase A glycoprotein catalyze the hydrolysis of the

neurotransmitter acetylcholine into choline and acetic acid - a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.

Mechanism of Toxicity Sarin disrupts the nervous system by inhibiting

Acetylcholinesterase by forming a covalent bond with the site of this enzyme where acetylcholine normally undergoes hydrolysis. This allows acetylcholine to accumulate and continue to act so that any nerve impulses are, in effect, continually transmitted.

This has various unpleasant effects leading to paralysis (where accumulation occurs at motor neurons) and eventually death by means such as asphyxiation

Mechanism of Toxicity (con.) Sarin works by phosphorylating the serine hydroxyl at

the active site of the enzyme 

This inhibition causes the Acetylcholine levels to accumulate in the peripheral and central nervous systems leading to malfunction or possibly death.

Bibliography “Sarin”. The University of Sheffield. Apr 20, 2006.

http://www.chem.shef.ac.uk/chm131-2002/cha02sra/sarin.html “Sarin”. Wikipedia, the Free Encyclopedia. Apr 22, 2006. http://en.wikipedia.org/wiki/Sarin Harrison, Karl. “A Nerve Gas”. 3DChem.com. Apr 19, 2006. http://www.3dchem.com/molecules.asp?ID=25 “Nerve Agents”. Brookside Associates Medical Education Division. April 19,

2006. http://www.brooksidepress.org/Products/OperationalMedicine/DATA/operationalmed/Manuals/RedHandbook/006NerveAgents.htm

“Facts About Sarin.” Center For Disease Control and Prevention. May 17, 2004. Arp 20, 2006. http://www.bt.cdc.gov/agent/sarin/basics/facts.asp

“Sarin Nerve Gas.” SC-EMS. April 19, 2006. http://sc-ems.com/ems/NuclearBiologicalChemical/Sarin/sarin.htm

Sharp, David. "Long-term Effects of Sarin.(Comment)." The Lancet 367.9505 (Jan 14, 2006): 95(3). Expanded Academic ASAP. Thomson Gale. CCL San Jose City College. 01 May 2006 <http://0-find.galegroup.com.library.sjeccd.org:80/itx/infomark.do?&contentSet=IAC-Documents&type=retrieve&tabID=T002&prodId=EAIM&docId=A141438773&source=gale&srcprod=EAIM&userGroupName=san61858&version=1.0>.