1. Nerve Agents, Tabun and VX gas: Chemical Weapons of Mass Destruction Joe Lach VX Gas Tabun Gas

2. Other Common Nerve Agents Sarin Cyclosarin CS (Tear Gas)

3. Dimethylamidoethoxyphosphotyl cyanide Least Deadly, but most volatile: Volatility: v.p. 0.07 mmHg at 25°C Solubility: Water, but rapidly hydrolyzed S-(2-Diisopropylaminoethyl) O-ethyl methylphosphonothiolate Most Deadly, but least volatile: Volatility: v.p. 7.0 × 10 -4 mmHg Solubility: Water: 30 g/l

4. Tabun VX Important Similarities needed Understand the Mechanism of Nerve Agents

5. Representation of Acetylcholine in the binding site of a receptor Activity of Acetylcholine Receptor following Binding How do Nerve Agents Work?

6. Why don’t the receptors stay on all the time? Acetylcholine Esterase Proper Function of AChE

7. What are the Nerve Agents Doing? Example using Diisopropyl phosphofluoridate (DIPF) Acetylcholine Esterase constitutively binds the Nerve Agent’s phosphate and is then rendered inactive

8. Pathway of Poisoning 1.Contact with VX 2.Headache and Drowsiness 3.Nausea and Diarrhea 4.Altered BP and Breathing 5.Loss of Consciousness 6.Convulsions 7.Paralysis 8.Death 1.Contact with Tabun 2.Headache and Drowsiness 3.Nausea and Diarrhea 4.Altered BP and Breathing 5.Loss of Consciousness 6.Convulsions 7.Paralysis 8.Death After Contact with a Lethal Dose (LD) = What’s the difference?...

9. Differences Concentration in Air Tabun LD500 ppb VX LD20-30 ppb Carbon Dioxide375 ppm Methane1750 ppb Nitrous Oxide300 ppb Moderate DoseTime for full effect Tabun6-12 hrs VX30min-2hrs Lethal Dose is determined by measuring the quantity needed to kill half the rats and then multiplying by an average body mass index to determine dangerous levels for humans. Lethal DoseTime till death Tabun5-10min VX15sec-1min

10. Treatment Atropine Sulfate – Acetylcholine Blocker, blocks other acetylcholine-like compounds by binding the Acetylcholine receptor in such a way as to NOT activate the Na channel.

11. Any Current Threat? Newport – Located in Indiana only stores VX gas reserves and these are kept in steel drums under 24 hours protection. As of 9/11 most of this supply has supposedly been scheduled for destruction. http://www.cma.army.mil/newport.aspx

12. http://www.defenselink.mil/releases/1996/b012496_bt024-96.html www.unc.edu/news/archives/apr03/hce040703.html www.cmbi.kun.nl/samsam/visualisatie/4.gif www.nimr.mrc.ac.uk/physbiochem/hulme/fig/ http://www.cdc.gov/page.do http://cdiac.ornl.gov/pns/current_ghg.html Gangolli, S. (2005). Dictionary of Substances and Their Effects (DOSE, 3rd Electronic Edition). Royal Society of Chemistry. Access through http://www.knovel.com/knovel2/Toc.jsp?BookID=527&VerticalID=0 Pohanish, R.P. (2002). Sittig's Handbook of Toxic and Hazardous Chemicals and Carcinogens (4th Edition). William Andrew Publishing/Noyes. Access through http://www.knovel.com/knovel2/Toc.jsp?BookID=421&VerticalID=0 Arie Ordentlich, Dov Barak, Gali Sod-Moriah, Dana Kaplan, Dana Mizrahi, Yoffi Segall, Chanoch Kronman, Yishai Karton, Arie Lazar,. (2004) Stereoselectivity toward VX Is Determined by Interactions with Residues of the Acyl Pocket as Well as of the Peripheral Anionic Site of AChE. Biochemistry, 43 (35), 11255 -11265 Ramesh C. Gupta, Gary T. Patterson and Wolf-D. Dettbarn. (1987). Acute tabun toxicity; biochemical and histochemical consequences in brain and skeletal muscles of rat. Toxicology. Vol. 46-3, 329-341. J. Heath, Andrew MD PhD. (2002). Antidotes for Poisoning by Organophosporus Pesticides. International Programme on Chemical Safety Evaluation. Works Cited pics

13. Questions?