Dimethyl phosphate, hydrolysis

The hydrolysis in acid or base of five-membered cyclic esters of phosphoric acid proceed some 10 times faster than their acyclic analogs or the six- and seven-membered cyclic phosphates 55 56. Unlike that of dimethyl phosphate, the hydrolysis of hydrogen ethylene phosphate is accompanied by rapid oxygen exchange into the unreacted substrate57, viz-... 

DFT analysis of the hydrolysis of dimethyl phosphate by hydroxide ion and water in the gas phase and in water was reported.57 The kinetics of the acid hydrolysis at 97 °C of 4-bromo-2,6-dimethylphenyl phosphate were reported.58... 

Further ab initio molecular orbital calculations on the reaction profile for the base-catalyzed hydrolysis of dimethyl phosphate in various ester conformations have provided support for this theory (5 6) ... 

Figure I. Reaction profiles for hydroxide-catalyzed hydrolysis of dimethyl phosphate (5).

To understand the role of metal ions in hydrolysis reactions, it is useful to first consider the background hydrolysis reactions. Table 6.1 lists the second-order rate constants for hydroxide-catalyzed hydrolysis of various substrates. The reactivity of methyl acetate (first entry in Table 6.1) [16] is comparable to those of other unactivated esters found in nature (e.g. acetyl choline and carboxyl esters in phospholipids). The reactivity of N-methylacetamide (second entry in Table 6.1) [17] is comparable to those of typical peptides (1.1 x 10 6 m-1 s 1) [18] and that of dimethyl phosphate (P-O bond... 

Preparation of the DHAP analogue, 4-hydroxy-3-oxobutylphosphonic acid, which is an effective donor substrate, is accomplished in four steps from glycidol.29 Glycidol is silyl protected then its epoxide is opened by dimethyl methylphosphonate. The secondary alcohol was oxidized under the Dess-Martin conditions. Deprotection of the alcohol followed by phosphate hydrolysis, generated the DHAP phosphonate analogue (Scheme 5.9). 

Other docking studies have been completed with tetronic acid derivatives in the active site of VHR results indicate that on dissociation, the 3-acyltetronic acid anion can bind tightly to the active site through several hydrogen bonds in a manner similar to that of phosphotyrosine (43). Finally, rhodanine and thiazolidinone cores have been shown to bind at or near the phosphate-binding site in modeling studies of various proteins (57), and they share many commonalities with compounds believed to mimic the pentavalent transition state of phosphate hydrolysis. Core structure electron-density isosurfaces for both rhodanine and thiazolidinone portray this well, as compared with the electron density structure of dissociated dimethyl phosphate. At this time, crystal structures of proteins complexed with these novel cyclic phosphate mimics have not been published. 

P-O bond fission is the usual mode of attack by nucleophiles on phosphodiesters, although there are exceptions. The labile diester methyl-2,4-dinitrophenyl phosphate shows significant amounts of attack at aromatic carbon (nucleophilic aromatic substitution, with loss of methyl phosphate) in competition with attack at phosphorus, most notably with hydroxide and with primary amines.46 Due to the small size of the methyl group it is sterically susceptible to nucleophilic attack in phosphate esters the hydrolysis of the dimethyl phosphate anion occurs almost exclusively by C-O bond fission.4 With larger or less labile leaving groups, even... 

Bluegill and catfish were both able to hydrolyze DFP, dichlorvos, and dimethyl 2,2,2-trichloro-l-n-butyryloxyethyl phosphonate (butonate). Catfish enzymes were also able to hydrolyze paraoxon and methyl 3-hydroxy-alpha-cronate dimethyl phosphate (mevinphos) although at a very slow rate. Kms calculated for the enzymes of both species indicated that each had a greater affinity for DFP than dichorvos. Sulfhydryl reagents and Cu2+ were found to inhibit the enzymatic activity of both organisms. Paraoxon had no effect. Cleavage products were identified as dimethyl phosphate and 2,2-dichloroacetaldehyde from dichlorovos hydrolysis and diisopropyl phosphate from the hydrolysis of DFP. 

OP.v are unstable in aqueous solution and even more so in blood owing to the presence of esterase. After ingestion, OP.v decompose in the human body to yield alkyl phosphates. Typical degradation products are dimethyl phosphate (DMP), dimethyl phosphorothionate (DMTP), dimethyl phosphorodithioate (DMDTP), diethyl phosphate (DEP), diethyl phosphorothionate (DETP) and diethylphosphorodithioate (DEDTP), which are formed by the hydrolysis of the ester bond in the OP molecule. In Figure 9.5 the chemical structures of the respective alkylphosphates are shown. ... 

From the point of view of application, mevinphos has the important distinctive property of being rapidly hydrolysed by enzymes in the plant. Hydrolysis products are phosdrinic acid, demethyl phosdrinic acid and dimethyl phosphate ... 

DIMETHYLAMINO)-l-METHYL-3-OXO-l-PROPENYL DIMETHYL PHOSPHATE (141-66-2) May react violently with antimony(V) pentafluoride. Inconqjatible with nitrates. Corrosive to cast iron, mild (low carbon) steel, brass, and stainless steel 304. Slow hydrolysis in water. Deconqjoses in storage at tenqjeratures above 135°F/55°C. Incompatible with... 

In order to propose a kinetic anomeric effect in nucleophilic substitution reactions at phosphorus, it is necessary (i) to extend the observations of a generalized anomeric effect in the TBP intermediate and the tetrahedral ground state to the transition state, and (ii) to show that the effect is amplified in the transition state. Consequently, Gorenstein et al. (1979) constructed models of the transition states for hydrolysis of dimethyl phosphate monoanion and subjected these to similar ab initio STO-3G calculations. The reactive intermediates along this hypothetical reaction coordinate are derived from the dimethoxy hydroxyphosphoranes [56] [58]. 

Fig. 6 Reaction profile for hydroxide-catalysed hydrolysis of dimethyl phosphate. The reaction coordinate is defined by the P-OH distance and P-OfijCHj...

The spontaneous cleavage of DNA in neutral solution is a reaction that has probably never been measured or even observed. Since the bulk of DNA phosphate linkages are unactivated phosphate diesters, it can be expected that DNA will be very stable. This is consistent with its role in retaining genetic information. The determination of the success of any material as a catalyst requires that the rate in the presence of the catalyst be compared with the rate in the absence of catalysts. Since the hydrolysis of DNA is slow, the rate constant for the standard is unknown. Guthrie (1977) estimated the rate constant for the reaction of water with dimethyl phosphate at phosphorus at 25°C to be 2 X 10 s based on extrapolation of the data reported by Bunton et al. (1960) at 100°C. The observed rate constant at pH 4 and 100°C is 10 s . If the rate decreases by an order of magnitude for each 25° decrease in temperature then at pH 4 the rate constant would be 10 s and the rate at pH 7 would be what is estimated by Guthrie. However, on the basis of the other data presented, this rate appears to contain a component due to acid catalysis, so that the rate constant due to... 

These predictions are consistent with experimental data on the competition between dealkylation and hydrolysis for the reactions of HS" and OH with dimethyl phosphate (Schmidt, 1975). 

Oxidative -demethylation is a pathway involved in the metabolism of some amide-substituted organophosphates. Dicrotophos is A-demethylated to monocrotophos via the iV-methylol derivative [156,157]. Monocrotophos, itself an active inhibitor of cholinesterase used in pest control, is further A-demethylated to its iV-methylol and finally to the unsubstituted amide [157]. This latter step is of only minor significance [158]. The principal degradative metabolite of dicrotophos, dimethyl phosphate, produced by hydrolysis of the vinyl-phosphate linkage was found to exceed the production of 0-demethylmonocrotophos by a ratio of approximately 4 lwhile only trace amounts of the iV-demethylated metabolite were detected [158]. 

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