May 3, 2012  2  US 2012/0108878 Al  phosphate toxants work by inhibiting acetylcholinesterase,  leading to excess acetylcholine at the neuromuscular junction  which can, in turn, cause paralysis of the muscles needed for  breathing and stopping the beating of the heart. Many orga› nophosphates have neurotoxic effects on developing organ› isms, even at low exposure levels. Their toxicity is not limited  to an acute phase, however, and chronic effects have long  been noted.  [0013]  Some organophosphate compounds are also potent  pesticides and are classified as weapons of mass destruction  by the United Nations according to UN Resolution 687  (passed in April 1991 ). Their production and stockpiling was  outlawed by the Chemical Weapons Convention of 1993,  which officially took effect on Apr. 29, 1997.  [0014]  The term "organophosphate" has, in recent years,  also been used more generically to describe virtually any  organic phosphorus (V)-containing compound, especially  when dealing with neurotoxic compounds. Many compounds  that are included within the organophosphate class actually  contain carbon-phosphate bonds. For instance, the nerve  agent sarin has the IUPAC name 0-isopropyl meth› ylphosphonofluoridate, and is derived from phosphorous acid  (HP(O)(OH)$_{2}$ ), rather than phosphoric acid (P(O)(OH) 3 ).  Also, many compounds that are derivatives of phosphinic  acid are used as neurotoxic organophosphates. Organophos› phate pesticides, as well as sarin and the VX nerve agent,  irreversibly inactivate acetylcholinesterase, which is essen› tial to nerve function in insects, humans, and many other  animals. Organophosphate pesticides affect this enzyme in  varied ways, and thus vary in their potential for poisoning. For  example, parathion, one of the first organophosphates com› mercialized, is many times more potent than malathion, an  insecticide used in combating the Mediterranean fruit fly  (Med-fly) and West Nile Virus-transmitting mosquitoes.  [0015]  Many, but not all, organophosphate pesticides  degrade rapidly by hydrolysis on exposure to sunlight, air,  and soil. However, small amounts of these compounds can  still be detected in food and drinking water. The ability to  degrade over time has made them an attractive alternative to  the persistent organochloride pesticides, such as DDT, aldrin,  and dieldrin. Although organophosphates degrade faster than  the organochlorides, they have greater acute toxicity, posing  risks to people who may be exposed to large amounts of these  compounds. Common organophosphates which have been  used as pesticides include parathion, malathion, methyl par› athion, chlorpyrifos, diazinon, dichlorvos, phosmet, tetra› chlorvinphos, and azinphos methyl.  [0016]  VX is an extremely toxic organophosphate and is so  dangerous, even in extremely small volumes, that its only  application is in chemical warfare as a nerve agent. VX is also  the most toxic of the deployed chemical weapons and is  classified as a weapon of mass destruction by the United  Nations in UN Resolution 687. Like other organophosphorus  nerve agents, VX may be destroyed by reaction with strong  nucleophiles such as pralidoxime. The reaction ofVX with  concentrated aqueous sodium hydroxide results in competing  cleavage of P---0 and P-S esters, with P-S cleavage domi› nating. This can be a problem when hydrogen peroxide is  used as a decontaminant, since one by-product of P---0 bond  cleavage (named EA 2192) is nearly as toxic as VX itself and  is far more persistent in the environment. In contrast, reaction  with the anion of percarboxylic acids (perhydrolysis) leads to  exclusive cleavage of the P-S bond:  [0017]  The H-class (known as "blister agents" or "sulfur  mustards") are not organophosphates. Rather, these com› pounds are a class of cytotoxic, vesicant CBW agents with the  ability to form large blisters on exposed skin. Vesicants are  highly active corrosive materials, even at extremely low con› centrations. Compounds of this type comprise the structural  element BCH$_{2}$CH$_{2}$X, where B is any leaving group and X is  a Lewis base. Such compounds can form cyclic "onium" ions  (sulfonium, ammoniums, etc.), which are good alkylating  agents. Examples of blister agents include, but are not limited  to, bis(2-chloroethyl)ether, the (2-haloethyl) amines (nitro› gen mustards) and sulfur sesquimustard, which has two  ~-chloroethyl thioether groups (CIH$_{2}$C----CH$_{2}$-S-) con› nected by an ethylene (----CH$_{2}$CH$_{2}$ -) group. These com› pounds have a similar ability to alkylate DNA, but their physi› cal properties, e.g., melting point, can vary considerably.  Some of these compounds have melting points well below the  freezing point of water. The most well known of these com› pounds is commonly referred to as "mustard gas" (bis-(2- chloroethyl) sulfide or 1,1’-thiobis(2-chloroethane)), and, in  its pure form, is a colorless, odorless, viscous liquid desig› nated as HD, which is a ~-chloro thioether with the formula  C$_{4}$H$_{8}$Cl$_{2}$ S. HD is a liquid at room temperature and has melt› ing point of 14°  C. (57°  F.).  [0018]  These vesicant agents can be quite deadly as they  have a high solubility in lipids ( e.g., fatty tissues). Symptoms  of exposure to mustard gas include conjunctivitis, blindness,  cough, edema of the eyelids, and erythema or necrosis of the  skin. When inhaled, this can severely and irreparably damage  the respiratory tract. In addition, mustard gas is also a car› cinogen. Vesicants have other uses besides chemical warfare,  however, the vesicating properties of these compounds are an  undesirable/unwanted side effect. For example, some chemo› therapy drugs are mild vesicants, as are a variety of industri› ally useful chemical intermediates.  [0019]  The term "biopathogen" encompasses CBW agents  that are infectious biological agents which can cause disease  P-S Cleavage  P-S Cleavage  NaOH(aq)  0  II  ,, P,,,  ~  HO,....  \’’O 