Other Fluorophosphates

Other fluorophosphates were synthesized and produced as chemical warfare agents (sarin and soman). However, DFP is less toxic than the G-series nerve agents and, therefore, easier to handle. DFP has been extensively used as a model compoxmd for xmderstanding the toxicity, mechanisms, and therapeutic strategy of the other fluoride-containing OPs. 

Other uses of Snp2 are in the synthesis of fluorophosphate glasses having low melting temperatures (13—15), in formation of transparent film (16), and in the preparation of optically active alcohols (17). 

Organophosphorus esters are known to react with a serine hydroxyl group in the active site of the acetylcholinesterase protein (Ecobichon 1991 Murphy 1986). Some organophosphorus esters (e.g., diisopropyl fluorophosphate, [DFP]) bind irreversibly, while others bind in a slowly reversible fashion, thereby leading to a slow reactivation (dephosphorylation) of the enzyme. A process known as "aging" has also been described in which reversibly bound compounds are changed with time to moieties that are essentially irreversibly... 

Many drugsbromides, morphine, cocaine, hashish, marijuana, mescaline, scopolamine, di-isopropyl fluorophosphate, ACTH, pervitin, sodium amytal, lysergic acid, reserpine and chlorpromazine are known to have marked effects on the mental processes of the individuals who receive them. These effects are varied and cannot be discussed here. Suffice it to say that some drugs produce symptoms which resemble those observed in mental disease others work in the opposite direction. There can be no doubt that enzyme systems are... 

The A-esterases now classified as diisopropyl fluorophosphatases (diiso-propyl-fluorophosphate fluorohydrolase, DFPase, somanase, EC 3.1.8.2) were previously listed under EC 3.8.2.1. These enzymes, which hydrolyze P-F and P-CN bonds such as those of nerve gases, should be described as organophosphorus acid anhydrolases rather than phosphatases [56]. Diisopropyl-fluoro-phosphatases exist in different forms with contrasting substrate specificities. One form is able to hydrolyze paraoxon at a low rate, while others have no paraoxonase activity. The different forms differ in their molecular weights and in their requirements for bivalent cations for activity [56]. 

In the reversed-phase mode, mixtures of aqueous buffer and acetonitrile are commonly used as mobile phase. Other modifiers are possible, but as shown in Figure 6, acetonitrile often produces the best separations and peak shapes. Several studies have shown the fundamental importance of keeping the chiral analytes neutral when working with polysaccharide stationary phases in the reversed-phase mode. ° ° Therefore, acidic compounds are preferably analyzed at low pFI while basic compounds will be analyzed either in basic media or at low pH in the presence of a chaotropic salt such as sodium perchlorate (NaC104) or potassium hexa-fluorophosphate Some illustrations of the effect of the addi-... 

Such an intermediate is known to be formed in reactions catalyzed by trypsin, chymotrypsin, thrombin, other enzymes of the blood-clotting cascade (except angiotensinconverting enzyme, which is an aspartic protease). An acyl-serine intermediate is also formed in the acetylcholinesterase reaction. The active site serine of this enzyme and the serine proteases can be alkylated by diisopropyl-fluorophosphate. See also Active Site Titration... 

Other chemicals which inhibit milk lipase include hydrogen peroxide, animal cephalin, sodium arsenite, diisopropyl fluorophosphate, 2,4 din-itro-l-fluorobenzene, p-hydroxymercuribenzoate, potassium dichromate, lauryl dimethyl benzyl ammonium chloride, aureomycin, penicillin, streptomycin, and terramycin (Schwartz 1974). 

The preceding experiments prove that there is an intermediate on the reaction pathway in each case, the measured rate constants for the formation and decay of the intermediate are at least as high as the value of kcat for the hydrolysis of the ester in the steady state. They do not, however, prove what the intermediate is. The evidence for covalent modification of Ser-195 of the enzyme stems from the early experiments on the irreversible inhibition of the enzyme by organo-phosphates such as diisopropyl fluorophosphate the inhibited protein was subjected to partial hydrolysis, and the peptide containing the phosphate ester was isolated and shown to be esterified on Ser-195.1516 The ultimate characterization of acylenzymes has come from x-ray diffraction studies of nonspecific acylenzymes at low pH, where they are stable (e.g., indolylacryloyl-chymotrypsin),17 and of specific acylenzymes at subzero temperatures and at low pH.18 When stable solutions of acylenzymes are restored to conditions under which they are unstable, they are found to react at the required rate. These experiments thus prove that the acylenzyme does occur on the reaction pathway. They do not rule out, however, the possibility that there are further intermediates. For example, they do not rule out an initial acylation on His-57 followed by rapid intramolecular transfer. Evidence concerning this and any other hypothetical intermediates must come from additional kinetic experiments and examination of the crystal structure of the enzyme. 

Many compounds have been tested simultaneously with (2-chloroethyl)tri-methylammonium chloride on Thatcher wheat, to ascertain, if possible, whether these chemicals were affecting a particular metabolic process. Other cholinesterase inhibitors such as eserine, diisopropyl fluorophosphate, and nitrogen mustard, neither negated the effect from (2-chloroethyl)trimethylammonium chloride nor altered the growth of the plant themselves. Many other substances were also without effect on the action of (2-chloroethyl)trimethylammonium chloride. A very slight reversal of the alteration by (2-chloroethyl)trimethylam-monium chloride was obtained by 10 2 and 10 3 M choline, betaine, and adenine. Only gibberellin completely and rapidly reversed the shorter growth pattern of a plant which had been treated with (2-chloroethyl)trimethylammonium chloride. 

It is found that the hydrolysis of fluorophosphate esters is also accelerated by transition metal ions and complexes. This would be an observation of little general interest, except for the fact that fluorophosphate esters form one of the more commonly encountered types of nerve gases (Fig. 4-51). The hydrolysis of fluorophosphate esters is increased dramatically in the presence of copper(n) and other transition metal complexes, and this sug-... 

Binding of sarin and soman to a tyrosine residue present in blood has been observed by Black et al. (51) When sarin or soman was incubated with human plasma, phosphonylated tyrosine was observed by LC/MS after Pronase digestion, in addition to phosphonylated serine. The precise site of this residue has not yet been confirmed but it is associated with the albumin fraction. A phosphonylated tryptic peptide [/-PrO(CH3)P(0)]-Tyr-Thr-Lys, consistent with albumin, has been identified but this sequence is also present in other proteins. Before the advent of modem mass spectrometry, diisopropyl fluorophosphate was reported to bind... 

It should be noted that fluorophosphates are usually highly toxic compounds and, for this reason, fluorination with tetrafluoro(phenyl)-3, -phosphane cannot be recommended. Moreover, other methods usually give better results. 

Gates, M., Renshaw, B. (1946). Fluorophosphates and other phosphorous-containing compoimds. In NDRC (National Defense Research Committee) Chemical Warfare Agents and Related Chemical Problems, Part /-// (Conant, J.B., Tolman, R.C., Chair and vice-Chair), Vol. 1, pp. 131-55. National Defense Research Committee, Division 9, Washington, DC. 

I returned early to the laboratory, by-passing imdergraduate students as they lined up to get into their one o clock class. John and I worked on the methyl fluorophosphate tests. The regular charcoal seemed satisfactorily to stop the first sample we tested, but we would have to do farther tests for several different flow rates, dilution, humidity, and other parameters. Dickinson and Stosick, talking together, got back somewhat before two o clock. The two of them turned to the left to inspect the Stoff-Stoff. 

Si 4H CP/MAS-NMR, 27A1 and 23Na MQ/MAS-NMR studies have been made of amorphous aluminium silicates, to determine local atomic struc-tures. A1 MAS-NMR (together with some other nuclei) studies have been carried out on novel porous sodium aluminophosphate-silicate and sodium ammonium fluorophosphates silicate 340 an ordered hexagonal mesoporous silica material (JLU-30) 341 mesoporous Al-MSU-X aluminosilicate 342 cubic mesoporous aluminosilicate A1MB48 343 and mesoporous Al-SBA-15.344... 

Nerve agents also react with a tyrosine residue associated with the albumin fraction in blood (Black et al, 1999) (Figure 10). Analysis of tryptic digests from plasma incubated with sarin identified a phosphylated tripeptide, MeP(0)(0 Pr)-Tyr-Thr-Lys, consistent with the protein being albumin (tyrosine residue 411), although this sequence is common and occurs in other proteins. Before the advent of modern mass spectrometry, diisopropyl fluorophosphate was reported to... 

Gates M and Renshaw BC (1946). Fluorophosphates and other phosphorus-containing compounds. In Summary Technical Report of Division 9, Vol. 1, Parts I, n, pp. 131, 155. Washington, DC, USA Office of Scientific Research and Development. 

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