Zbynek Kobliha

Modified Cholinesterase Technology in the Construction of Biosensors for Organophosphorus Nerve Agents and Pesticides Detection

Organophosphorus compounds are a wide-spread group of agents which can be used among others as pesticides, especially insecticides, or chemical warfare agents. These extremely toxic compounds irreversibly inhibit the enzymes of hydrolases class, which have the catalytic capability of hydrolyzing their specific neurotransmitters in synaptic clefts of the nervous system. The organophosphorus pesticides and carbamates are agents used in agriculture very often, because of their relatively low stability. Many of them, however, have very high acute toxicity for warm-blooded animals. The group of organophosphorus compounds also includes nerve agents with their dominant position among chemical warfare agents. The discovery of their effects was made more or less accidentally in the 30-ies of the last century during the research of fluoroorganic compounds in IG Farben, a German company, by Dr. Gerhard Schrader. The first synthesized agent was ethyl-(dimethylamido)phosphorocyanidate, designated as trilon 83 or tabun. However, it was not the first known agent with a cholinergic effect. Back in 1854 a French chemist, Phillip de Clermont, synthesized the first organophosphate – tetraethyl pyrophosphate (de Clermont, 1855, as cited in Holmstedt, 2000). Gradually more agents with N-P, P-CN or C-F bonds were synthesized in order to produce insecticides and later also nerve agents (Holmstedt, 2000). After verifying the effects of tabun for warm-blooded animals, a synthesis of other, even more toxic, agents followed (Pitschmann, 1999). In 1939 isopropyl-methylphosphonofluoridate was discovered, also called trilon 46 or sarin, and in 1944 (3,3-dimethylbutane-2-yl)-methylphosphonofluoridate, the so-called soman, followed. These agents belong to the so-called G-series of nerve agents. The origin of a new V-series dates back to the end of 50-ies. This group of agents has increased toxicity when penetrating the skin. The principal representative is S-[2-(diisopropylamino)ethyl]-O-ethylmethylphosphonothioate, also known as VX, and S-[2-(diethylamino)ethyl]-O-isobutylmethylphosphonothioate with the code designation R-33. In the 70-ies up to 90-ies another group of nerve agents was discovered in the former USSR within the so-called Foliant program. These are compounds based on phosphorylated and phosphonylated oximes and amidases. According to unauthorized sources they reach at least the toxicity of VX, some are even 5 to 8 times more toxic. In a case like this there could be a problem with their detection.