Phosphorothioate and

The rat LD qS are 13, 3.6 (oral) and 21, 6.8 (dermal) mg/kg. Parathion is resistant to aqueous hydrolysis, but is hydroly2ed by alkah to form the noninsecticidal diethjlphosphorothioic acid and -nitrophenol. The time required for 50% hydrolysis is 120 d ia a saturated aqueous solution, or 8 h ia a solution of lime water. At temperatures above 130°C, parathion slowly isomerizes to 0,%diethyl 0-(4-nitrophenyl) phosphorothioate [597-88-6] which is much less stable and less effective as an insecticide. Parathion is readily reduced, eg, by bacillus subtilis ia polluted water and ia the mammalian mmen to nontoxic 0,0-diethyl 0-(4-aminophenyl) phosphorothioate, and is oxidized with difficulty to the highly toxic paraoxon [511-45-5] diethyl 4-nitrophenyl phosphate d 1.268, soluble ia water to 2.4 mg/L), rat oral LD q 1.2 mg/kg. 

Finally, non-racemic phosphorothioic and phosphonothioic acids 98 were obtained via a PTE-catalysed stereoselective hydrolysis of the prochiral substrates 97 (Equation 48). ° The absolute configurations of the thioacids 98 depended on whether native PTE or its mutants were used. 

Snyder et al. [94] compared supercritical extraction with classical sonication and Soxhlet extraction for the extraction of selected organophosphorus insecticides from soil. Samples extracted with supercritical carbon dioxide modified with 3% methanol at 350atm and 50°C gave a =85% recovery of Diazinon (diethyl-2-isopropyl-6-methyl-4-pyrimidinyl phosphorothiodate or 0,0 diethyl-0-(2-isopropyl-6-methyl-4-pyrimidyl) phosphorothioate). Ronnel (or Fenchlorphos) 0,0-dimethyl-0-2,4,5 trichlorophenol phosphorothiodate), Parathion ethyl (diethyl-p-nitrophenyl (phosphorothioate), Tetrachlorovinphos (trans,-2-chloro-l-(2,4,5 trichlorophenyl) vinyl (chlorophenyl-O-methylphenyl phosphorothioate) and Methiadathion. Supercritical fluid extraction with methanol modified carbon dioxide has been applied to the determination of organophosphorus insecticides in soil [260]. 

Phosphinates are a class of organophosphorus compounds, the metabolism of which has received less attention than that of phosphates (see above) or phosphorothioates and P-halidc compounds (see below). Many phosphinates are rapid but transient inhibitors of acetylcholinesterase and carboxyl-esterases. And like organophosphates and phosphonates, phosphinates are substrates of arylesterases (EC 3.1.1.2). This is exemplified by 4-nitrophen-yl ethyl(phenyl)phosphinate (9.62), whose (-)-enantiomer was hydrolyzed by rabbit serum arylesterase almost 10 times faster than the (+)-enantiomer [133],... 

Phosphorothioates and phosphonothioates are of particular significance as insecticides. Schematically, it can be stated that these xenobiotics undergo activation by oxidative desulfuration, and detoxification by hydrolytic cleavage. Oxidative desulfuration transforms phosphorothioates and phosphonothioates to the corresponding oxon derivatives (see Chapt. 7 in [59]), which are highly toxic as potent inactivators of acetylcholinesterase [69]. This route of toxification can be competitive with and/or followed by cleavage reactions, which can be either hydrolytic or oxidative. 

Parathion degraded on both glass surfaces and on bean plant leaves. Metabolites reported were paraoxon, 4-nitrophenol, and a compound tentatively identified as 5-ethyl parathion (El-Refai and Hopkins, 1966). Upon exposure to high intensity UV light, parathion was altered to the following photoproducts paraoxon, 0,5-diethyl 0-4-nitrophenyl phosphorothioate, 0,0-diethyl 5-4-nitrophenyl phosphorothioate, 0,0-bis(4-nitrophenyl) 0-ethyl phosphorothioate, 0,0-bis(4-nitrophenyl) 0-ethyl phosphate, 0,0-diethyl 0-phenyl phosphorothioate, and 0,0-diethyl 0-phenyl phosphate (Joiner et al., 1971). 

Diazinon and Ronnel. The conclusion that neutral hydrolysis of sorbed chlorpyrifos is characterized by a first-order rate constant similar to the aqueous phase value is strengthened and made more general by the results for diazinon, 0,0-diethyl 0-(2-iso-propyl-4-methyl-6-pyrimidyl) phosphorothioate, and Ronnel, 0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphorothioate (10). The results for the pH independent hydrolysis at 35°C for these compounds in an EPA-26 sediment/water system (p=0.040) are summarized in Table IV. Because the aqueous (distilled) values of k for diazinon and Ronnel are similar in magnitude to the value for chlorpyrifos, and because these values were shown by the chlorpyrifos study to be slow compared to sorption/desorption kinetics, computer calculations of were not deemed necessary and were not made for these data. 

Figure 5.12. Chemical structure of antisense oligodeoxynucleotides (AS-ODN). Phosphorothioate and methylphosphonate AS-ODN have a sulfur atom and a methyl group respectively, substituted for a nonbridging oxygen atom to increase stability to nucleases.

Grunweller A, Wyszko E, Bieber B et al (2003) Comparison of different antisense strategies in mammalian cells using locked nucleic acids, 2 -O-methyl RNA, phosphorothioates and small interfering RNA. Nucleic Acids Res 31 3185-3193... 

In general, AMP aminohydrolase specificities have not been thoroughly defined perhaps because of difficulties until recently in obtaining pure enzyme. In addition to AMP and dAMP, the muscle enzyme catalyzes the deamination of V -methyl AMP, iV -ethyl AMP, for-mycin-5 -monophosphate, adenosine-5 -monosulfate, adenosine-5 -phos-phoramidate, adenosine, ADP (133), adenosine-5 -phosphorothioate, and 6-chloropurine 5 -ribonucleotide (124) ATP, GMP, CMP, 2 -AMP, 3 -AMP, 3, 5 -cyclic AMP, 3-iso-AMP, V-methyl AMP, toyocamycin-5 -monophosphate, tubercidin-5 -monophosphate, and 6-mercaptopurine-5 -ribonucleotide are not deaminated (133). The elasmobranch fish muscle, carp muscle, and avian brain enzymes appear to be specific for AMP and dAMP (123, 125, 126). Extracts from pea seed and erythrocytes and the purified calf brain enzyme are specific for AMP (48, 131, 134). 

Diethyl - 0 - (6 - m ethoxy - 3 - benzo[ ]thienyl)phosphorothioate and a number of related compounds may be prepared similarly.607 These compounds exhibit pesticidal activity. 

Reaction of 2-chloromethyl-4//-pyrido[l,2-a]pyrimidin-4-ones 385 with O.O-dialkyl phosphorothioates and phosphorodithioates in a mixture of ethanol and toluene in the presence of potassium hydroxide at 60-70°C gave insectidical or nematocidal phosphorus derivative 386 (83EUP81945). 

Chemicals Used. Chemicals used in this study were technical grade products or better, dissolved in xylene with 5% emulsifying agent. The chemicals used included an oil soluble red dye, Dino-seb (2-sec-butyl-4,6 dinitrophenol), pentachlorophenol (PCP), Isopropyl N-(3-chlorophenyl) carbamate (CIPC or Chlorpropham), Iso-octyl 2,4,5- trichlorophenoxy acetate (2,4,5-T), chlorpyrifos (0, 0-diethyl 0-(3,4,6-trichloro 2-pyridyl) - phosphorothioate), and Ronnel (0-dimethyl 0-2, 4,5-trichlorophenyl) phosphorothioate) for application as a spray. The emulsifiable concentrate was diluted in water comparable to 50 gallons of spray to contain the following amounts respectively 2 lbs. for chloropryifos 4 lbs. for 2,4,5-T 3 lbs. CIPC and 2 lbs. for PCP. 

In a recent series of studies focused on the synthetic utility of alkenyliodo-nium salts, ( )-/J-phenylethenyl(phenyl)- and ( )-l-hexenyl(phenyl)iodonium tetrafluoroborates, 22 and 23, were utilized for alkenylations of a range of soft, anionic nucleophiles (Scheme 45) [128-135]. In all cases but one, alkenylations with 22 occurred with retention of configuration, while alkenylations with 23 occurred with inversion of configuration. Only the dialkyl phosphoroselenolate salts gave mixtures of (Z)- and (fj)-products with 22 [132]. Furthermore, although cuprous iodide was used to catalyze the reactions of 22 and 23 with the phosphorothioate and -dithioate salts, the stereochemical results were the same [131,133]. It was generally assumed that retention was an outcome of the ligandcoupling or addition-elimination pathways, while stereochemical inversion was attributed to the vinylic... 

Figure 18.7 Phosphates, phosphorothiolate, phosphorothioate, and phosphorodithioate insecticides distinguished by the numbers and orientations of the sulfur atoms around the phosphorus.

Dickson, W. (1956) The vapour pressure of l l p p -dichlorodiphenyl trichloroethane (D.D.T.). Trans. Farad. Soc. 52, 31-35. Dierberg, F.E., Pfeuffer, RJ. (1983) Fate of ethion in canals draining a Florida citrus grove. J. Agric. Food Chem. 31, 704—709. Dilling, W.L., Lickly, L.C., Lickly, T.D., Murphy, P.G., McKellar, R.L. (1984) Organic photochemistry. 19. Quantum yields for 0,0-diethyl 0-(3,5,6-trichloro-2-pyridinal) phosphorothioate and 3,5,6-trichloro-2-pyridinol in dilute aqueous solutions and their environmental transformation rates. Environ. Sci. Technol. 18, 540-543. 

Nearly all synthesis of phosphate esters, phosphorothioates and phosphoroamidoates use as starting materials one of the following... 

Animals. In mice and rats, the parent compound, O-ethyl-O-(3-oxo-2-phenyl-277-pyridazine-6-yl) phosphorothioate and the corresponding phosphate are found... 

A claim that the stereochemical course of cyclic AMP phosphodiesterase action on 3, 5 -cyclic AMPS and 3, 5 -cyclic AMP, l80 differed, inversion for the chiral cyclic phosphorothioate and retention for the chiral cyclic phosphate, resulted from... 

Portions of the 6 and 15% Florisil eluate were injected into the DC200 and DEGS columns with the coulometer equipped with the sulfur-detecting cell. No peaks were obtained from the 15% eluate injection. Of the several peaks that appeared on the DC200 and DEGS columns from the 6% eluate injection, one was identified as Ronnel DC200 reference 1.00, sample 1.00, DEGS, reference 1.00, sample 1.00, and concentration 0.2 p.p.m. Ronnel is chemically 0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphorothioate and thus should yield a peak with both the chloride and sulfur detectors. Identification was assured since a peak was found at the proper retention times with both detector cells one column was used for the chloride, and two columns were used for the sulfur detector cells. 

The Gl ribozyme reaction depends on the presence of divalent metal ions but as indicated above, the binding of these ions plays multiple roles that include folding and enhancing substrate binding affinities (59). The rate of the chemical step is Mg(2- -) dependent, but these data do not distinguish between direct or indirect roles, or a combination of both. As indicated above, distinguishing active site metal ions from what has been referred to as the sea of other functionally important metal ion interactions presents a considerable challenge. For the GI ribozyme and other catalytic RNAs, site-specific evidence for active site metal interactions comes primarily from analyses of thiophilic metal ion rescue of phosphorothioate and other substrate modifications (e.g.. References 60 and 61). These analyses rely on the fact that substitution of a substrate phosphate by a phosphorothioate weakens the affinity of coordinated Mg(2- -) ions... 

To aid hepato-cellular uptake of antisense ODNs, the phosphoramidites of cholic and taurocholic acids were prepared and added to the 5 -end of antisense oligomers." The oligonucleotides were further modified by the inclusion of phosphorothioate and benzylphosphonate internucleotide linkages. The bile acid conjugated oligomers exhibited enhanced lipophilicity as determined by HPLC, and when incorporated into duplexes no destabilisation was observed. An antisense phosphorothioate ODN targeted to the HIV-1 gag-mKNA was... 

---