Aryl phosphate monoesters

Grzyska PK, Czyryca PG, Purcell J, Hengge AC. Transition state 42. differences in hydrolysis reactions of alkyl versus aryl phosphate monoester monoanions. J. Am. Chem. Soc. 2003 125 13106-13111. 

Converging lines of evidence have led to a general acceptance of the monomeric metaphosphate mechanism for the hydrolysis of phosphate monoester monoanions. The pH rate profile for aryl and alkyl phosphate monoester hydrolyses commonly exhibits a rate maximum near pH 4. where the concentration of the monoanion is at a maximum. The proposed mechanism is based on these principal points of evidence (a) a general observation of P-O bond cleavage (b) the entropies of activation for a series of monoester monoanions are all close to zero, which is consistent with a unimolecular rather than a bi-molecular solvolysis where entropies of activation are usually more negative by 20 eu7 (c) the molar product composition (methyl phosphate inorganic phosphate) arising from the solvolysis of the monoester monoanion in a mixed methanol-water solvent usually approximates the molar ratio of methanol ... 

The electrostatic model for the micellar effect on the hydrolysis of phosphate monoesters is also consistent with the results of inhibition studies (Bunton et al., 1968, 1970). The CTAB catalyzed hydrolysis of the dinitrophenyl phosphate dianions was found to be inhibited by low concentrations of a number of salts (Fig. 9). Simple electrolytes such as sodium chloride, sodium phosphate, and disodium tetraborate had little effect on the micellar catalysis, but salts with bulky organic anions such as sodium p-toluenesulfonate and sodium salts of aryl carboxylic and phosphoric acids dramatically inhibited the micelle catalysis by CTAB. From equation 14 and Fig. 10, the inhibitor constants, K, were calculated (Bunton et al., 1968) and are given in Table 9. The linearity of the plots in Fig. 10 justifies the assumption that the inhibition is competitive and that incorporation of an inhibitor molecule in a micelle prevents incorporation of the substrate (see Section III). Comparison of the value of for phenyl phosphate and the values of K for 2,4-and 2,6-dinitrophenyl phosphates suggests that nitro groups assist the... 

Figure 1 On the left are the structures of a phosphate monoester, diester, and triester. The first pK of an alkyl phosphate monoester, and the pKa of a dialkyl diester, are typically between 1 and 2. The second pKa of an alkyl monoester is approximately 6.8, and from one to two units lower for aryl esters. At the right are the structures of a sulfate monoester and diester. Sulfate monoesters have a very low pKa values and as a result are always ionized at physiological pH.

APs are nonspecific metalloenzymes that hydrolyze phosphate monoesters optimally at alkaline pH. They liberate inorganic phosphate from many types of molecules including nucleotides, proteins and other biomolecules, and synthetic alkyl and aryl phosphate esters. Probably the most-studied phosphatase of all is the AP from... 

Liquid aryl phosphate esters have found use as components of rust prevention compositions. Various monoester compositions of type R0((CH2) 0 , P(0)(0H)2, together with their corresponding di- and triester derivatives, have been patented as metal degreasing and cleaning agents. 

Reactions of less activated (aliphatic) phosphates were also investigated by the Wolfenden group.In case of these phosphates, the solvent used was cyclohexane, which is stiU aprotic (as DMSO) but also nonpolar, and the phosphates were synthesized as their tetrabutylammonium salts (as for reactions of aryl monoesters). The previous results strongly suggested an enthalpic contribution for the reactions of pNPP", whereas results for the hydrolysis of neopentyl phosphate monoester dianion (NP ) in wet cyclohexane su ested a significant entropic contribution to the overall 2.5 X 10 rate acceleration. In this solvent, the monoanionic and dianionic species of NP reacted with the same rate this result was attributed to the removal of water molecules proposed to assist hydrolysis of monoester monoanions in aqueous solution. Unsurprisingly, hydrolysis of phosphate diesters was also accelerated by cyclohexane, with a rate acceleration of 10 -fbId for dineopentyl phosphate at 25 °C, and by acetone, with a rate acceleration of 5 X 10 -fbId. The reduced amount of catalysis in case of alkyl diesters, relative to alkyl monoester dianions, parallels what was observed with the corresponding aryl species (see above). 

There are comparatively few studies addressing the structure-metabolism relationships of phosphoric acid monoester hydrolysis. For example, kinetics of decomposition in rat whole blood were examined for the phosphoric acid monoesters of estrone, 17a- and 17/J-testosterone, 3-(hydroxyme-thyl)phenytoin (see Fig. 9.7,a), and 1-phenylvinyl alcohol (9.28, the enolic form of acetophenone) [87]. As a general trend, the rate of hydrolysis increased with the acidity of the leaving hydroxylated compound. In other words, hydrolysis was the fastest for the phosphoric acid aryl monoester (estrone 3-phosphate), and slowest for the two testosterone phosphoric acid... 

A new one-pot method has been developed by Kraszewski for the synthesis of aryl nucleoside phosphate (3a-p) and phosphorothioate (4a-p) diesters. This method, based on H-phosphonate chemistry, employed diphenyl phosphoroch-loridate and a series of phenols. Depending on the substituents present on the phenols, oxidation conditions were optimized to avoid competing hydrolysis. A versatile procedure that permits easy access to H-phosphonoselenoate monoesters (5) has been developed by Stawinski. These monoesters, obtained by selenisation of a phosphinate using triphenylphosphine selenide in combination with trimethylsilyl chloride, reacted with a suitable nucleoside in pyridine/acetonitrile in the presence of diphenyl phosphorochloridate to yield... 

The elimination-addition reaction for phosphate esters was first proposed to account for the shape of the pH-rate profile of alkyl monoesters (40), which are most reactive at the maximum concentration of the monoanion, that is, pH 4. The explanation for this observation was that the reaction proceeded via a metaphosphate intermediate by the expulsion of an alcohol group with the proton for the alcohol being transferred from the phosphate as the reaction proceeds. Further studies of the reactions of monoesters have implied that the above mechanism operates for all alkyl and aryl monoesters where the p fa of the leaving group exceeds about... 

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