Organophosphate
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Reverted edits by [[Special:Contributions/131.230.29.18|131.230.29.18]] ([[User talk:131.230.29.18|talk]]) to last version by 206.205.112.130
An '''organophosphate''' (sometimes abbreviated '''OP''') is the general name for [[ester]]s of [[phosphoric acid]]. Phosphates are probably the most pervasive [[organophosphorus compound]]s. Many of the most important biochemicals are organophosphates, including [[DNA]] and [[RNA]] as well as many [[cofactor (biochemistry)|cofactor]]s that are essential for life. Organophosphates are also the basis of many [[insecticide]]s, [[herbicide]]s, and [[nerve gas]]es. Organophosphates are widely used as [[solvent]]s, [[plasticizer]]s, and [[EP additives]].
Organophosphates are widely employed both in natural and synthetic applications because of the ease with which organic groups can be linked together. Being a triprotic acid, phosphoric acid can form tri[[ester]]s whereas carboxylic acids only form monoesters. Esterification entails the attachment of organic groups to phosphorus through oxygen linkers. The precursors to such esters are [[alcohol]]s. Encompassing many thousands of natural and synthetic compounds, alcohols are diverse and widespread.
:OP(OH)<sub>3</sub> + ROH → OP(OH)<sub>2</sub>(OR) + H<sub>2</sub>O
:OP(OH)<sub>2</sub>(OR) + R'OH → OP(OH)(OR)(OR') + H<sub>2</sub>O
:OP(OH)(OR)(OR') + R"OH → OP(OR)(OR')(OR") + H<sub>2</sub>O
The phosphate esters bearing OH groups are [[acid]]ic and partially [[deprotonation|deprotonated]] in aqueous solution. For example DNA and RNA are polymers of the type [PO<sub>2</sub>(OR)(OR')<sup>-</sup>]<sub>n</sub>. Polyphosphates also form esters. An important example of an ester of a polyphosphate is [[adenosine triphosphate|ATP]], which is the monoester of triphosphoric acid (H<sub>5</sub>P<sub>3</sub>O<sub>10</sub>).
Alcohols can be detached from phosphate esters by [[hydrolysis]], which is the reverse of the above reactions. For this reason, phosphate esters are common carriers of organic groups in [[biosynthesis]].
== Organophosphate pesticides ==
In health, agriculture, and government, the word "organophosphates" refers to a group of [[insecticides]] or nerve agents acting on the enzyme [[Cholinesterase enzyme|acetylcholinesterase]] (the pesticide group [[carbamates]] also act on this enzyme, but through a different mechanism). The term is used often to describe virtually any organic phosphorus(V)-containing compound, especially when dealing with neurotoxins. Many of the so called organophosphates contain C-P bonds. For instance, [[sarin]] is ''O''-isopropyl methylphosphonofluoridate, which is formally derived from [[phosphorous acid]] (HP(O)(OH)<sub>2</sub>), not phosphoric acid (P(O)(OH)<sub>3</sub>). Also, many compounds which are derivatives of [[phosphinic acid]] are used as organophosphorus neurotoxins.
Organophosphate pesticides (as well as [[sarin]] and [[VX (nerve agent)|VX]] nerve gas) irreversibly inactivate acetylcholinesterase, which is essential to nerve function in insects, humans, and many other animals. Organophosphate pesticides affect this enzyme in varied ways, and thus in their potential for poisoning. For instance, [[parathion]], one of the first OPs commercialized, is many times more potent than [[malathion]], an insecticide used in combatting the [[Mediterranean fruit fly]] (Med-fly) and [[West Nile Virus]]-transmitting mosquitoes.
Organophosphate pesticides degrade rapidly by hydrolysis on exposure to sunlight, air, and soil, although small amounts can be detected in food and drinking water. Their ability to degrade 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 (see the Toxicity section below).
Commonly used organophosphates have included parathion, malathion, [[methyl parathion]], [[chlorpyrifos]], [[diazinon]], [[dichlorvos]], [[phosmet]], [[tetrachlorvinphos]], and [[azinphos methyl]].
==Organophosphate neurotoxins==
===History of nerve gases===
Early pioneers in the field include [[Jean Louis Lassaigne]] (early 1800s) and [[Philip de Clermount]] (1854). In 1932, German chemist Willy Lange and his graduate student, Gerde von Krueger, first described the [[cholinergic]] nervous system effects of organophosphates, noting a choking sensation and a dimming of vision after exposure. This discovery later inspired German chemist [[Gerhard Schrader]] at company [[I.G. Farben]] in the 1930s to experiment with these compounds as insecticides. Their potential use as chemical warfare agents soon became apparent, and the Nazi government put Schrader in charge of developing organophosphate (in the broader sense of the word) nerve gases. Schrader's laboratory discovered the G series of weapons, which included [[Sarin]], [[Tabun]], and [[Soman]]. The Nazis produced large quantities of these compounds, though did not use them during World War II (likely because they feared the Allies possessed similar weapons). British scientists experimented with a [[cholinergic]] organophosphate of their own, called [[diisopropylfluorophosphate]] (DFP), during the war. The British later produced [[VX (nerve agent)|VX]] nerve gas, which was many times more potent than the G series, in the early 1950s.
After World War II, American companies gained access to some information from Schrader's laboratory, and began synthesizing organophosphate pesticides in large quantities. [[Parathion]] was among the first marketed, followed later by [[malathion]] and azinphosmethyl. The popularity of these insecticides increased after many of the [[organochlorine]] insecticides like [[DDT]], [[dieldrin]], and [[heptachlor]] were banned in the 1970s.
===Structural features of organophosphate neurotoxins===
Effective organophosphate neurotoxins have the following structural features:
* A terminal [[oxygen]] connected to phosphorus by a double bond, i.e. a phosphoryl group
* Two lipophilic groups bonded to the phosphorus
* A [[leaving group]] bonded to the phosphorus, often a [[halide]]
====Terminal oxygen vs. terminal sulfur====
Thiophosphoryl compounds, those bearing the P=S functionality, are much less toxic than related phosphoryl derivatives, which includes as [[sarin]], [[VX (nerve agent)|VX]] and [[tetraethyl pyrophosphate]]. Thiophosphoryl compounds are not active [[Enzyme inhibitor|inhibitors]] of [[acetylcholinesterase]] in either [[mammals]] or insects; in mammals, [[metabolism]] tends to remove [[lipophilic]] side groups from the phosphorus atom while in insects it tends to [[oxidize]] the compound, thus removing the terminal sulfur and replacing it with a terminal oxygen, which allows the compound to more efficiently act as an acetylcholinesterase inhibitor.
====Fine tuning====
Within these requirements, a large number of different lipophilic and leaving groups have been used. The variation of these groups is one means of fine tuning the toxicity of the compound. A good example of this chemistry are the ''P''-[[thiocyanate]] compounds which use an [[aryl]] (or [[alkyl]]) group and an alkylamino group as the lipophilic groups. The thiocyanate is the leaving group.
[[Image:FcPthiocyanate2.jpg|right|thumb|One of the products of the reaction of Fc<sub>2</sub>P<sub>2</sub>S<sub>4</sub> with dimethyl cyanamide]]
It was claimed in a German patent that the reaction of 1,3,2,4-dithiadiphosphetane 2,4-disulfides with dialkyl cyanamides formed plant protection agents which contained six membered (P-N=C-N=C-S-) rings. It has been proven in recent times by the reaction of diferrocenyl 1,3,2,4-dithiadiphosphetane 2,4-disulfide (and Lawesson's reagent) with dimethyl [[cyanamide]] that, in fact, a mixture of several different phosphorus-containing compounds is formed. Depending on the concentration of the dimethyl cyanamide in the reaction mixture, either a different six membered ring compound (P-N=C-S-C=N-) or a nonheterocylic compound (FcP(S)(NR2)(NCS)) is formed as the major product; the other compound is formed as a minor product.
In addition, small traces of other compounds are also formed in the reaction. It is unlikely that the ring compound (P-N=C-S-C=N-) {or its isomer} would act as a plant protection agent, but (FcP(S)(NR2)(NCS)) compounds can act as [[nerve]] poisons in [[insects]].
==Organophosphate poisoning==
{{Main|Organophosphate poisoning}}
Many ''organophosphates'' are potent [[neurotoxin]]s, functioning by inhibiting the action of acetylcholinesterase (AChE) in nerve [[cell (biology)|cells]]. They are one of the most common causes of poisoning worldwide, and are frequently intentionally used in suicides in agricultural areas. Their toxicity is not limited to the acute phase, however, and chronic effects have long been noted. Neurotransmitters such as [[acetylcholine]] (which is affected by organophosphate pesticides) are profoundly important in the brain's development, and many OPs have [[neurotoxic]] effects on developing organisms even from low levels of [[exposure]].
==See also==
*[[Activity based protein profiling]] using organophosphate-containing activity based probes
*[[Mark Purdey]]
*[[Pesticide toxicity to bees]]
*[[Toxic Oil Syndrome|Toxic Syndrome (Spain)]]
==References==
* Costa LG. ''Current issues in organophosphate toxicology''. Clin Chim Acta. 2006 Apr;366(1-2):1-13. Epub 2005 [[December 6]]. Review. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=citation&list_uids=16337171&query_hl=27&itool=pubmed_docsum PMID: 16337171].
==External links==
* [http://www.atsdr.cdc.gov/csem/cholinesterase ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Pesticides and Chemical Warfare Nerve Agents] U.S. [[Department of Health and Human Services]]
* [http://www.pan-uk.org/pestnews/actives/organoph.htm Organophosphate insecticides fact sheet]
* [http://www.emedicine.com/neuro/topic286.htm Organophosphates - an article by Frances M Dyro, MD]
* [http://www.panna.org/campaigns/opsCampaignPartners.html Pesticides Action Network, North America]
* [http://www.nytimes.com/2006/08/04/washington/04pest.html NYTimes: E.P.A. Recommends Limits On Thousands of Pesticides]
* [http://www.epa.gov/pesticides/cumulative/common_mech_groups.htm#op EPA OP pesticide site]
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