Phosphorothionates

Chambers JE, Ma T, Boone JS, et al. 1994. Role of detoxication pathways in acute toxicity levels of phosphorothionate insecticides in the rat. Life Sci 54 1357-1364. 

This process of aging is believed to be critical in the development of delayed neuropathy, after NTE has been phosphorylated by an OP (see Chapter 10, Section 10.2.4). It is believed that most, if not all, of the B-esterases are sensitive to inhibition by OPs because they, too, have reactive serine at their active sites. It is important to emphasize that the interaction shown in Fignre 2.11 occurs with OPs that contain an oxon group. Phosphorothionates, which contain instead a thion group, do not readily interact in this way. Many OP insecticides are phosphorothionates, but these need to be converted to phosphate (oxon) forms by oxidative desulfuration before inhibition of acetylcholinesterase can proceed to any significant extent (see Section 2.3.2.2). 

Phosphorothionates OP compounds containing thion groups (cf. organophos-phates that contain oxon groups). 

Lawrence, L.J and Casida, J.E (1984). Interactions of lindane, toxaphene, and cyclodienes with brain-specific t-bntyl phosphorothionate receptor. Life Science 35, 171. 

Data presentations should include the parent compound and all toxic transformation products. This is particularly important for oxidation of sulfide linkages to sulfoxides or sulfones. These products are often equally toxic to the parent with increased availability. Attention should also be given to oxidative desulfuration of phosphorothionate esters. 

Dionex Nucleopak PA-100185 Formamide-LiBr Phosphorothionate oligonucleotides... 

Chemical names Phosphorothioic acid 0-[4-[(dimethylamino) sulfonyl], phenyl] 0,0-dimethyl ester Phosphorothioic acid, 0,0-dimethyl-, O-ester with p-hydroxy-/V,/V-dimethylbenzene sulfonamide Phosphorothioic acid, 0,0-dimethyl O-p-(dimethylsulfamoyl) phenyl ester O-Dimethyl hydrogen phosphorothioate, O-ester with p-hydroxy-/V,/V-dimethylbenzenesulfonamide 0-[4-1 (Dimethylamino) sulfonyl] phenyl phosphorothioic acid O.O-dimethyl ester O,O-Dimethyl O, p-(N,N-dimethylsulfamoyl) phenyl phosphorothioate O, p-(Dimethylsulfamoyl) phenyl O.O-dimethyl phosphorothioate p-(Dimethylsulfamoyl)phenyl dimethyl phosphorothioate O.O-dimethyl 0-[p-(dimethylsulfamoyl)-phenyl] phosphorothioate Dimethyl p-(dimethylsulfamoyl) phenyl phosphorothionate O.O-dimethyl-O, p-(dimethylsulfamoyl) phenyl phosphorothionate... 

Casida, J.E. and LJ. Lawrence. 1985. Structure-activity correlations for interactions of bicyclophosphorus esters and some polychlorocycloalkane and pyrethroid insecticides with the brain-specific t-butylcyclo-phosphorothionate receptor. Environ. Health Perspec. 61 123-132. 

The active constituent of this insecticide is stated to be 00 -diethyl 0"-ethylmercaptoethyl phosphorothionate,... 

Parathion (OO -diethyl 0"-p-nitropheny 1 phosphorothionate) is known to isomerize to 08-diethyl O -p-nitrophenyl thiophos-... 

It was shown that systox indeed consisted of 00 diethyl (S-ethylmercaptoethyl phosphorothiolate (VIII) and OO -di-ethyl O -ethylmercaptoethyl phosphorothionate (VII). (Compound (IX) was not present, and in any case it does not seem to have been fully characterized.) It seems that at room temperature (VII) isomerizes to (VIII), the half-life being about 3 years. Furthermore, the P=S compound is much less effective than the P=0 compound as an insecticide. 

Among phosphorus insecticides containing also nitrogen and sulphur we may mention 00 -diethyl-/S-/ -diethylaminoethyl phosphorothiolate (X). It was prepared (i) from diethyl phos-phorochloridate1 and sodium / -diethylaminoethyl mercaptide, (ii) from sodium diethyl phosphite and / -diethylaminoethyl thiocyanate, (iii) by the isomerization of OO -diethyl-O"-/ -diethylaminoethyl phosphorothionate (XI) obtained from / -diethylaminoethoxide and diethyl phosphorochloridothionate. 

Three different pathways are associated with the metabolism of disulfoton (I) oxidation of the thioether sulfur to produce sulfoxides and sulfones (2) oxidation of the thiono sulfur to produce the oxygen analogs and (3) hydrolysis of the P-S-C linkage to produce the corresponding phosphorothionate or phosphate (WHO 1976) (see Figure 2-3). These pathways have been elucidated from data obtained in humans exposed to disulfoton and from in vivo and in vitro metabolism studies in rats and mice. 

Synonyms AI3-27311 BRN 1545756 Brodan Caswell No. 219AA CCRIS 7144 Chloryrifos-ethyl Coroban Detmol U.A. 0,0-Diethyl-0-3,5,6-trichloro-2-pyridyl phosphorothioate Dowco-179 Dursban Dursban F EINECS 220-864-4 ENT 27311 Eradex Grofo Killmaster Lentrek Lorsban NA 2783 QMS 971 Phosphorothionic acid, 0,0-diethyl 0-(3,5,6-trichloro-2-pyridyl) ester Pyrinex Terial UN 2783 XRM 429 XRM 5160. 

At 87 °C and pH 2.5, malathion degraded in water to malathion a-monoacid and malathion P-monoacid. From the extrapolated acid degradation constant at 27 °C, the half-life was calculated to be >4 yr (Wolfe et al., 1977a). Under alkaline conditions (pH 8 and 27 °C), malathion degraded in water to malathion monoacid, diethyl fumarate, ethyl hydrogen fumarate, and QO-dimethyl phosphorodithioic acid. At pH 8, the reported half-lives at 0, 27, and 40 °C are 40 d, 36 h, and 1 h, respectively. However, under acidic conditions, it was reported that malathion degraded into diethyl thiomalate and 0,0-dimethyl phosphorothionic acid (Wolfe et al, 1977a). 

Synonyms AAT AATP AC 3422 ACC 3422 AI3-15108 Alkron Aileron American Cyanamide 3422 Aphamite Aralo B 404 Bay E-605 Bayer E-605 Bladan Bladan F BRN 2059093 C-06604 Caswell No. 637 CCRIS 493 Compound 3422 Corothion Corthion Corthione Danthion DDF 0,0-Diethyl-0-4-nitrophenyl phosphorothioate 0,0-Diethyl 0-p-nitrophenyl phosphorothioate Diethyl-4-nitrophenyl phosphorothionate Diethyl-p-nitrophenyl thionophosphate 0,0-Di-ethyl-0-4-nitrophenyl thionophosphate 0,0-Diethyl-O-p-nitrophenyl thionophosphate Diethyl-p-nitrophenyl thiophosphate 0,0-Diethyl-O-p-nitrophenyl... 

Diethylmethane. see Pentane Diethylmethylmethane. see 3-Methylpentane Diethyl-4-nitrophenyl phosphorothionate. see Parathion 0,0-Diethyl-O-4-nitrophenyl phosphorothioate. see Parathion... 

Phosphorothionic acid, 00-diethyl 0-(3,5,6-trichloro-2-pyridyl) ester, see Chlorpyrifos Phosphostigmine, see Parathion Phosphothion, see Malathion Phosvit, see Dichlorvos Phthalandione, see Phthalic anhydride... 

Dimethyl phosphorodithioic acid, see Malathion 0,0-Dimethyl phosphorophosphate, see Methoate Dimethyl phosphorothioate, see Malathion, Parathion 0,0-Dimethyl phosphorothioate, see Malathion 0,5-Dimethyl phosphorothioate, see Acephate Dimethyl phosphorothioic acid, see Dimethoate Dimethyl phosphorothionic acid, see Malathion 0,0-Dimethyl phosphorothionic acid, see Malathion Dimethyl sulfide, see Methyl mercaptan Dimethyl thiophosphate, see Malathion Dimethyl thiophosphoric acid, see Malathion Dimethyl triclopyr-aspartate, see Triclonvr Dimethyl triclopyr-glutamate, see Triclopvr... 

Loos MA (1975) Phenoxyalkanoic acids. In Kemey PC, Kaufman DD (eds) Herbicides chemistry, degradation and mode of action, vol 1. Marcel Dekker New York, pp 1-128 Lovley DR (1993) Dissimilatory metal reduction. Annual Review of Microbiology 47 263-290 Macalady DL, Wolfe NL (1983) New perspectives on the hydrolytic degradation of the organo-phosphorothionate insecticide chloropyrifos. J Agric Food Chem 31 1139-1147 Macalady DL, Wolfe NL (1985) Effects of sediment sorption and abiotic hydrolysis. J Agric Food Chem 33 167-173... 

The discovery of prontosil was fortuitous and was not based on rationale design. There are a large number of pesticides which fall in the same category as prontosil, i.e., they are active by virtue of their susceptibility to metabolic or chemical modification to active intermediates. The classical example of an insecticide of this type is parathion, a phosphorothionate ester which in animals or plants is oxidatively desulfurated to the potent anticholinesterase paraoxon O). The insecticidal activity of parathion was known for several years before the purified material was shown to be a poor anticholinesterase and that metabolic activation to paraoxon was necessary for intoxication. 

Chemical Mechanisms of the Cytochrome P-450 Monooxygenase-Catalyzed Metabolism of Phosphorothionate Triesters... 

One of the most extensively studied phosphorothionate esters from the standpoint of mammalian metabolism is the insecticide parathion. The majority of this paper will center on what is known of the mechanism of mammalian microsomal metabolism of this compound. 

Parathion is one of a class of phosphorothionate triesters widely used as insecticides. These compounds exert their toxic effects in insects and mammals by inhibiting the enzyme acetylcholinesterase. The phosphorothionates, in general, are relatively poor inhibitors of acetylcholinesterase but are converted by the cytochrome P-450-containing monooxygenase enzyme systems in insects and mammals to the corresponding phosphate triesters that are potent inhibitors of this enzyme. 

---