Malathion structure

C03-0019. Determine the molar mass of malathion, an insecticide whose line structure and chemical formula appear in the margin. 

The toxicity of an insecticide not only depends upon its molecular structure but also the way it is metabolised. A good example of this is Malathion (77), which is metabolised very differently by insects and humans and is therefore only toxic to insects. The mildly active Malathion (77) is rapidly oxidised in insects converting it into the strongly active oxidation product 79 (Equation 84), and this is only broken down very slowly by hydrolysis to give the weakly active 81. In contrast, oxidation of Malathion in mammals is slow, but hydrolysis of the ester group occurs very rapidly to give the inactive non-toxic compound 80 (Equation 84).1,169... 

Currently there are few insecticides registered as surface treatments to control stored-product insects. For years the organophosphate insecticide malathion was used as a surface treatment for structural facilities, but stored-product insects throughout the world have developed extensive resistance to malathion (Subramanyam and Hagstrum, 1996). Most of the resistance reports were generated from studies with bulk grains, but in the United States, resistance has been documented for field populations of the red flour beetle, T. castaneum (Herbst), and the confused flour beetle, T. confusum (DuVal), collected from flour mills (Arthur and Zettler, 1991, 1992 Zettler, 1991). Populations of the Indianmeal moth, the almond moth, and the red flour beetle collected from bulk peanuts and empty warehouses were also highly resistant to malathion (Arthur et al., 1988 Halliday et al., 1988). 

Several hundred-pesticide compounds of diverse chemical structures are widely used in the United States and Europe for agricultural and non-agricultural purposes (Fig. 10). Some are substitutes for organochlorines, which were banned due to their toxicity, persistence, and bioaccumulation in environmental matrices. According to a report published by the US-EPA, a total of 500,000 tons of pesticides was used in 1985 [144, 145, 148]. As far as specific pesticides are concerned, worldwide consumption of Malathion and Atrazine in 1980 amounted to 24,000 and 90,000 tons, respectively [149,150]. In the Mediterranean countries, 2100 tons of Malathion (active ingredient) were sprayed during the same period compared to 9700 tons in Asia [150]. 

Chen, P.R., Tucker, W.P., and Dauterman, W.C. Structure of biologically produced malathion monoacid. J. Agrlc. Food Chem., 17(l) 86-90, 1969. 

Structures of some organophosphate cholinesterase inhibitors. The dashed lines indicate the bond that is hydrolyzed in binding to the enzyme. The shaded ester bonds in malathion represent the points of detoxification of the molecule in mammals and birds. 

Malathion is the best-known phosphorodithioate insecticide. It shows how differences in structural formula can cause pronounced differences in the properties of organophosphate pesticides. 

Different OP compounds have structural similarities within classes. The phosphorus compounds have the characteristic phosphoryl bond, P=0. Most OP compounds have a phosphoryl bond or a thiophosphoryl bond (P=S). All OP compounds are esters of phosphorus with varying combinations of oxygen, carbon, sulfur, and nitrogen attached. These are classified as (1) phosphates (2) phos-phonates (3) phosphorothioates (4) phosphorodithioates (5) phosphorothiolates and (6) phosphoramidates. Further, the OP compounds are categorized as (1) aliphatic (2) phenyl and (3) heterocyclic derivatives. The aliphatic are carbon chainlike in structure. TEPP, which was used in agriculture for the first time in 1946, is a member of this group. Others include malathion, trichlorfon, monocrotophos, dimethoate, oxydemetonmethyl, dimethoate, dicrotophos, disulfoton, dichlorvos, mevinphos, methamidophos, and acephate. 

Many organic derivatives of phosphates have been synthesized from the phosphites and are used as insecticides although details of the preparations will not be given here. One such compound is malathion that has the structure... 

Figure 4.5 Structures of malathion impurities compound A, 0,0,S-trimethyl phosphorodithioate compound B, 0,0,S-trimethyl phosphorothioate compound C, 0,S,S-trimethyi phosphorodithioate compound D, 0,S-dimethyl S-l,2-di (ethoxycarbonyl) ethyl phosphorodithioate (also known as isoma lath ion).

They experimented with four other proteins as carriers rabbit serum albumin, bovine serum albumin, bovine fibrinogen fraction I, and bovine )8-globulin fraction III. The structurally related derivatives of DDT and malathion, DDA, and 0,0-dimethyl S-carboxy-carboxyethyl phosphoro-dithioate (malathion half ester), respectively, were used as the specific haptens attached to these carrier proteins. These compounds contain free carboxyl groups, which when they reacted with thionylchloride, provide a means of coupling of the hapten to the amino groups of the protein carrier. 

The toxic effects of some pesticide mixtures are additive, particularly when their toxic mechanisms are identical. The additive effects of the organophosphates chlorpyrifos and diazanon were demonstrated in one study. T Another study found the s-triazine herbicides atrazine and cyanazine to show additive toxic effects. Not all mixtures of similar pesticides produce additive effects, however. In one study, mixtures of five organophos-phate pesticides (chlorpyrifos, diazinon, dimethoate, acephate, and malathion) were shown to produce greater than additive effects when administered to laboratory animals. Another article discusses nonsimple additive effects of pyrethroid mixtures. Despite the similarities in their chemical structure, pyrethroids act on multiple sites, and mixtures of these produce different toxic effects. 10 ... 

Fortunately, however, certain types of bacteria manufacture an enzyme called phospho-triesterase (PTE) that inactivates sarin and other organophosphate molecules like it, some of which are found in certain insecticides but are hundreds of times less toxic to people. Certain organophosphates, such as the common insecticide malathion, kill insects because, unlike animals, bugs lack an enzyme that breaks down this chemical. For many years Frank Raushel of Texas A M University in College Station has studied the PTE enzyme, and recently he and his colleague Hazel Holden of the University of Wisconsin-Madison cleared a substantial hurdle They identified the three-dimensional structure— a molecular snapshot —of what this enzyme looks like. This information will help scientists understand how the enzyme works—and could reveal how to engineer one that works even better. 

Fig. 8.2. Organophosphorous compounds. Malathion and parathion are organophosphorous insecticides. Nausea, coma, convulsions, respiratory failure, and death have resulted from the use of parathion by farmers who have gotten it on their skin. Malathion is similar in structure to parathion, but not nearly as toxic. The nerve gas Sarin, another organophospho-rus compound, was used in a terrorist attack in a Japanese subway.

Since l-n-dodecyl-3-(hydroxyiminomethyl)pyridinium iodide was indicated to be a more effective nucleophilic reagent for the hydrolysis of organophosphorus compounds, it was examined in addition to 2-PAM, 2-PAD, histidine hydrochloride, and succinyl choline as possible coatings (55,56). Among these, 3-PAD was found to be the best coating for compounds with the G agent structure, and histidine hydrochloride for compounds of the malathion type. Table 3. 

Malathion, an insecticide of low toxicity to hiimans, is made by a Michael addition. Given the structure of malathion, suggest the immediate precursors for its synthesis. 

OP insecticide with a structure similar to malathion, which is not a substrate for PON (Li et aL, 2000). As also predicted, PON mice showed a dramatically increased sensitivity to chiorpyrifos-oxon and diazoxon (Shih et ai., 1998 Li et ai, 2000). PONl mice showed an intermediate sensitivity to diazoxon toxicity (Li ef al, 2000). PONl null mice showed only a slight increase in sensitivity to the toxicity of chlorpyrifos and diazinon (Shih et a ., 1998 Li el al., 2000). The most surprising observation was that PONl null mice did not show an increased sensitivity to paraoxon, the substrate after which the enzyme was named, despite having no paraoxonase activity in plasma and liver (Li ei ai. 2000). 

---