Paraoxon development

In a study of the metabolism of methyl parathion in intact and subcellular fractions of isolated rat hepatocytes, a high performance liquid chromatography (HPLC) method has been developed that separates and quantitates methyl parathion and six of its hepatic biotransformation products (Anderson et al. 1992). The six biotransformation products identified are methyl paraoxon, desmethyl parathion, desmethyl paraoxon, 4-nitrophenol, />nitrophenyl glucuronide, and /wiitrophenyl sulfate. This method is not an EPA or other standardized method, and thus it has not been included in Table 7-1. 

Previously, we have shown that functional secretion of OPH molecules into the periplasmic space induced about 2.8-fold higher specific whole cell OPH activity [10]. From the detail reaction kinetic studies in this work, we showed that this periplasmic space-secretion strategy provided much improved bioconversion capability and efficiency ( 1.8-fold) for Paraoxon as a model organophosphate compound. From these results, we confirmed that Tat-driven periplasmic secretion of OPH can be successfully employed to develop a whole cell biocatalysis system with notable enhanced bioconversion efficiency and capability for environmental toxic organophosphates. 

Recently, Noort et al developed a procedure that is based on straightforward isolation of adducted BuChE from plasma by means of affinity chromatography with a procainamide column, followed by pepsin digestion and LC/electrospray tandem MS analysis of a specific nonapeptide containing the phosphonylated active site serine-198 residue (5). This method surpasses the limitations of the fluoride-reactivation method, since it can also deal with dealkylated ( aged ) phosphonylated BuChE. The method allowed the positive analysis of several serum samples of Japanese victims of the terrorist attack in the Tokyo subway in 1995. Furthermore, the method could be applied for detection of ChE modifications induced by, e.g., diethyl paraoxon and pyridostigmine bromide, illustrating the broad scope of this approach. This new approach... 

Organophosphorsus inhibitors have been developed as insecticides (paraoxon, parathion) and for chemical warfare (soman, tabun, sarin). They are extremely toxic and lethal either by cardiac arrest of general paralysis and subsequent suffocation. 

A multiresidue method for analyzing 28 common organophosphorus pesticides and three of their main metabolites (paraoxon-ethyl, paraoxon-methyl, and malaoxon) in a variety of crop samples has been developed (59). The use of LC-DAD techniques allowed identification of both organophosphorus pesticides and metabolites by means of standard and spectral comparisons, respectively. A typical chromatogram for fortified apple extract is shown in Figure 4. 

Following the first reports in the literature of catalytic imprinted beads, a number of authors also reported applications of this polymer format to several imprinting systems. Busi et al. [64] reported the preparation of catalytic active beads for the Diels-Alder reaction using a TSA as a template. Jakubiak and co-workers developed imprinted beads for the oxidation of phenols based on a Cu(II) complex as catalytic centre [65]. Say and collaborators described the synthesis of microbeads also based on a Cu(II) complex with esterase activity towards paraoxon (60), a potent nerve agent [66]. The imprinted beads enhanced the rate of reaction over the non-imprinted polymer by a factor of 40, as resulted from the ratio of the corresponding kciil. 

A series of multielectrode sensors were developed based on Drosophila mutant AChE immobilised via photocrosslinking onto screen-printed carbon electrodes [8]. Four different mutant and wild-type AChE were evaluated for their sensitivity to the organophosphate paraoxon and the carbamate pesticide carbofuran. The response of the electrodes in thiocholine before and following a 15-min exposure to solutions of the pesticides was compared. The data was then processed using a feed-forward neural network generated with NEMO 1.15.02 as previously described [8,9]. Networks with the smallest errors were selected and further refined. This approach together with varying the AChE led to the construction of a sensor with capability to analyse the binary pesticide mixtures. 

In the body, parathion is converted to paraoxon (structure in Figure 18.8), which is a potent inhibitor of acetylcholinesterase. Because this conversion is required for parathion to have a toxic effect, symptoms develop several hours after exposure, whereas the toxic effects of TEPP or... 

Organophosphorus compounds are used not only as pesticides, but also as medicines. Organophosphorus medicines are most often used to treat glaucoma. Organophosphorus glaucoma medicines include paraoxon (min-takol) synthesised by G.Schrader, and armin, which was developed in the laboratoiy of Academician A.E. Arbuzov ... 

Gomaa HM, Faust SD. 1972. Chemical hydrolysis and oxidation of parathion and paraoxon in aquatic environments. In Fate of organic pesticides. Research and Development Division, Keramchemie (Canada) Ltd. and Department of Environmental Sciences, Rutgers, New Brunswick, NJ, 189-209. 

Figure 9.17. Organophosphate inhibitors of acetylcholinesterase. a The catalytic mechanism, shown here for diiso-propylfluorophosphate(DFP).b Stmcturesof soman and tabun. Like DFP, these were developed during world war II as nerve gases , c Stractures of the insecticides parathion and malathion, and of paraoxon, which is the achve metabolite of parathion. (Malathion likewise requires conversion to malaoxon.) The arrow above the malathione stmcture indicates the esterase cleavage sites in its leaving group esterase cleavage occurs in human plasma and renders the molecule non-toxic.

AChE was sandwiched with poly(diallyldimethyl-ammonium chloride) layers on the surface of CNTs. The OP biosensor thus developed was used to detect paraoxon (Figure 55.7) as low as 4 x 10 M with a 6 min response time in flow injection analysis. A high stability of the sensors was also a merit of this biosensor no deterioration in the response was observed after 1 week of eontinuous use of the sensor. Only a 15% deerease in the aetivity of the enzyme was observed after 3 weeks, though the authors... 

Selected Biological Aspects. - The catalytic antibody-mediated hydrolysis of the insecticide paraoxon (100) and analogues 101 have been investigated with a view to developing antibodies for use in the treatment of insecticide poisoning. Two-dimensional inverse NMR spectroscopy has been applied to the... 

A portable fluorescence system has been developed to measure beryllium in workplace air. Another design of fluorescence probe has been used to determine carbofuran and paraoxon in fruit and vegetable samples ... 

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