Hydrolysis organophosphates

Organophosphate hydrolysis is frequently observed as the initial reaction for pesticides having organophosphate bonds, such as methyl parathion, chlorpyrifos (9) (eq. 13), diazinon, and coumaphos (19). Several genera of organophosphate-hydrolyzing bacteria have been identified, including... 

Figure 22,2 Mechanism of enzyme-catalyzed organophosphate hydrolysis.

For [Co2(C02EtL2)(CH3COO)2] the pH dependence with one equivalent nitrocefin resulted in a sigmoidal profile with pKai = 8.47 0.14 (Fig. 6.38) the pKa is similar to that observed for organophosphate hydrolysis, and in the absence of the alkoxide the nucleophile is likely to be a terminal water molecule. 

To investigate whether MR would take up Zn(II) ions, which could potentially catalyze organophosphate hydrolysis, unsubstituted resin was also subjected to the aforementioned treatment... 

Khare, S.D., Kipnis, Y, Greisen Jr., R, et al., 2012. Computational redesign of a mononuclear zinc metalloenzyme for organophosphate hydrolysis. Nat. Chem. Biol 8, 294-300. 

Carboxyhc acid ester, carbamate, organophosphate, and urea hydrolysis are important acid/base-catalyzed reactions. Typically, pesticides that are susceptible to chemical hydrolysis are also susceptible to biological hydrolysis the products of chemical vs biological hydrolysis are generally identical (see eqs. 8, 11, 13, and 14). Consequentiy, the two types of reactions can only be distinguished based on sterile controls or kinetic studies. As a general rule, carboxyhc acid esters, carbamates, and organophosphates are more susceptible to alkaline hydrolysis (24), whereas sulfonylureas are more susceptible to acid hydrolysis (25). 

Organophosphates and carbamates containing a pyrazole ring, useful as insecticides as discussed earlier (Section 4.04.4.1.2), are metabolized mainly through hydrolysis of the ester function (B-80MI40406). 

FIGURE 5.46 Interaction of the serine hydroxyl residue in the catalytically active site of acetylcholinesterase enzyme with esters of organophosphates or carbamates. The interaction leads to binding of the chemical with the enzyme, inhibition of the enzyme, inhibition of acetylcholine hydrolysis, and thus accumulation of acetylcholine in the synapses. 

There is a second type of cholinesterase called butyrylcholinesterase, pseudocholinesterase, or cholinesterase. This enzyme is present in some nonneural cells in the central and peripheral nervous systems as well as in plasma and serum, the liver, and other organs. Its physiologic function is not known, but is hypothesized to be the hydrolysis of esters ingested from plants (Lefkowitz et al. 1996). Plasma cholinesterases are also inhibited by organophosphate compounds through irreversible binding this binding can act as a detoxification mechanism as it affords some protection to acetylcholinesterase in the nervous system (Parkinson 1996 Taylor 1996). 

Cowart RP, Bonner FL, Epps EA Jr. 1971. Rate of hydrolysis of seven organophosphate pesticides. 

Wolfe NL. 1980. Organophosphate and organophosphorothionate esters Application of linear free energy relationships to estimate hydrolysis rate constants for use in environmental fate assessment. Chemosphere 9 571-579. 

Table 10-1. Standard free energy of hydrolysis of some organophosphates of biochemical importance. ...

Dumas DP, IR Wild, FM Raushel (1989) Diisopropylfluorophosphate hydrolysis by an organophosphate anhydrase from Pseudomonas diminuta. Biotechnol Appl Biochem 11 235-243. 

Munnecke DM (1976) Enzymatic hydrolysis of organophosphate insecticides, a possible pesticide disposal method. Appl Environ Microbiol 32 7-13. 

In soil, the chances that any enzyme will retain its activity are very slim indeed, because inactivation can occur by denaturation, microbial degradation, and sorption (61,62), although it is possible that sorption may protect an enzyme from microbial degradation or chemical hydrolysis and retain its activity. The nature of most enzymes, particularly size and charge characteristics, is such that they would have very low mobility in soils, so that if a secreted enzyme is to have any effect, it must operate close to the point of secretion and its substrate must be able to diffuse to the enzyme. Secretory acid phosphatase was found to be produced in response to P-deficiency stress by epidermal cells of the main tap roots of white lupin and in the cell walls and intercellular spaces of lateral roots (63). Such apoplastic phosphatase is safe from soil but can be effective only when presented with soluble organophosphates, which are often present in the soil. solution (64). However, because the phosphatase activity in the rhizo-sphere originates from a number of sources (65), mostly microbial, and is much higher in the rhizosphere than in bulk soil (66), it seems curious that plants would have a need to secrete phosphatase at all. 

However, there are some data on interactions of phosphate esters with other compounds. Cocaine undergoes metabolism by three major routes one of these routes involves hydrolysis by liver and plasma cholinesterases to form ecgonine methyl ester. It has been suggested that cocaine users with serious complications tend to have lower plasma cholinesterase levels. Thus, it is possible that individuals with decreased plasma cholinesterase levels (such as resulting from organophosphate ester exposure) may be highly sensitive to cocaine (Cregler and Mark 1986 Hoffman et al. 1992). However, there are no experimental data to support this hypothesis. 

Hydrolysis appears to be the most important abiotic degradative mechanism for organophosphate esters under basic pH conditions. Under neutral and acidic conditions, the reaction slows considerably and could become an insignificant removal mechanism. The hydrolysis proceeds by a stepwise mechanism in which one alcohol group is removed at a time. The first step is cleavage of a P-OR bond (where "R" is an aryl or alkyl group) to produce a diester of phosphoric acid, which, under basic conditions, becomes an anion. 

This property of organophosphate esters may be of environmental importance since phosphoric acid diesters are much more soluble and very little is known concerning the environmental toxicity of these compounds. The available data do not provide sufficient descriptions of the experimental methods to determine if the rates are reliable (Barnard et al. 1961 Ciba-Geigy 1984e, 1986 Howard and Deo 1979 Mayer et al. 1981 Wolfe 1980). The majority of reports provide only a minimum of information and exclude important facts such as the duration of the experiments and the concentration of buffers. Despite the lack of experimental detail, published rate constants for base-catalyzed hydrolysis appear to be reasonably consistent and suggest that the hydrolytic half-life of triphenyl phosphate will vary from... 

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