Phosphate esters hydrolysis

Gomez GA, Morisseau C, Hammock BD, Christianson DW. Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis. Biochemistry 2004 43 4716-23. 

J. P. Guthrie, Hydration and Dehydration of Phosphoric Acid Derivatives Free Energies of Formation of the Pentacoordinate Intermediates for Phosphate Ester Hydrolysis and of Monomeric Metaphosphate, J. Am. Chem. Soc. 1977, 99, 3391. 

Ivie 1980) and quantification of its urinary metabolites in various animal species (Bucci et al. 1992 Hart 1976 Ivie 1980 Snodgrass and Metker 1992 Weiss et al. 1994). Hydrolysis of one of the two phosphate ester bonds liberates isopropanol and converts diisopropyl methylphosphonate to IMPA. The locations of the enzymes capable of catalyzing diisopropyl methylphosphonate phosphate ester hydrolysis have not been identified. 

The mechanism of phosphate ester hydrolysis by hydroxide is shown in Figure 1 for a phosphodiester substrate. A SN2 mechanism with a trigonal-bipyramidal transition state is generally accepted for the uncatalyzed cleavage of phosphodiesters and phosphotriesters by nucleophilic attack at phosphorus. In uncatalyzed phosphate monoester hydrolysis, a SN1 mechanism with formation of a (POj) intermediate competes with the SN2 mechanism. For alkyl phosphates, nucleophilic attack at the carbon atom is also relevant. In contrast, all enzymatic cleavage reactions of mono-, di-, and triesters seem to follow an SN2... 

The higher coordinating ability and Lewis acidity of Zn(H) ion in addition to the low pK of the metal-bound water molecule and the appearance of this metal ion in native phosphatases inspired a number of research groups to develop Zn(II)-containing dinuclear artificial phosphatases. In contrast, very few model compounds have been published to mimic the activity of Fe(III) ion in dinuclear centers of phosphatase enzymes. Cu(II) or lanthanide ions are not relevant to natural systems but their chemical properties in certain cases allow extraordinarily high acceleration of phosphate-ester hydrolysis [as much as 108 for copper(II) or 1013 for lanthanide(III) ions]. 

Dejaegere, A., Liang, X. and Karplus, M. Phosphate ester hydrolysis calculation of gas-phase reaction paths and solvation effects, J.Chem.Soc., Faraday Trans., 90 (1994), 1763-1770... 

The last work pertaining to the discovery of new catalysts is perhaps the most novel approach to be reported thus far. In one of the earliest approaches taken toward catalyst development, Menger et al. (61) attempted to find catalysts for phosphate ester hydrolysis. A series of eight functionalized carboxylic acids were attached to polyallylamine in various combinations. Each of these polymers were then treated with one of three metals, Mg2+, Zn2+, or Fe3+. The different members of each library were identified by the relative percentages of each carboxylic acid attached to the polyamine. For example, one polymer possessed 15% Oct, 15% Imi, 15% Phe, and 5% Fe3+. There is no attempt to identify the location of the various carboxylic acids in a given polymer. This approach is novel since each system consists of an ensemble of different ligands with the carboxylic acids positioned in various locations. Each polymer within a given ratio of carboxylic acids consists of a combinatorial library of potential catalysts. 

Vanadium is beneficial and possibly essential for humans. It is certainly essential for a number of organisms. Vanadate (oxidation state V) and its derivatives are phosphate analogues, showing both ground state and transition state analogy (both structural and electronic) with phosphorus compounds. The analogy of five-coordinate vanadium compounds with the transition state of phosphate ester hydrolysis is well documented, and explains why so many vanadium compounds are potent inhibitors of phosphatases, ribonucleases and ATPases. 

The half-life of Fe2(OH)2" at room temperature is a few seconds. An improved model for the kinetics of dissociation of this dinuclear cation recognizes significan articipation by Fe2(OH)3 + at higher pHs, thus clearing up earlier slight anomalies in this area. Phosphate ester hydrolysis at the di-iron center of uteroferrin has now been shown to involve nucleophilic attack by bridging hydroxide (as proposed but not conclusively demonstrated for several M—OH—M-containing catalytic species) rather than by hydroxide bonded to just one Fe. ... 

Fig. 3 Mechanisms for enzymatic supramolecular polymerisation (a) Formation of supramolecular assembly via bond cleavage, (b) Formation of supramolecular assemblies via bond formation. Examples are shown of biocatalytic supramolecular polymerisation of aromatic peptide amphiphiles via (i) phosphate ester hydrolysis, (ri) alkyl ester hydrolysis, and (iii) amide condensation or reversed hydrolysis using protease...

The two-step mechanism of phosphate ester hydrolysis by the (Znn)2-containing alkaline phosphatase (AP) (7) is thus somewhat mimicked by 24. The phosphoryl intermediate 25 is generated by nucleophilic attack of the alkoxide moiety in 24b at BNP" and is hydrolyzed by the intramolecular Zn11—OH" species in 25b. Thus, the attack at the BNP... 

L.A. (2005) Estimation of phosphate ester hydrolysis rate constants. I. Alkaline hydrolysis. QSAR Comb. Sci., 25 (2), 123-133. 

Surface-catalyzed dark and photoassisted phosphate ester hydrolysis (P—O bond rupture) in aqueous suspensions of TiO2 has been proposed [6,7,41]. A number of products indicative of radical cationic pathways have been reported in the TiO2 photocatalysis of benzyl phosphonic acid [44]. 

As an explanation of the phosphoryltransferase activity of mammalian phosphatases, Morton (117) had earlier advanced the idea that phosphate ester hydrolysis catalyzed by the nonspecific phosphatases occurs in two catalytic steps similar to that shown by Wilson et al. (118) for cholinesterase. The first step is the formation of a phosphoryl enzyme with the splitting out of the alcohol group. The second step is the hydrolysis of the phosphoryl enzyme. 

The ability of tris and ethanolamine to serve as acceptors does not vary greatly with pH (SO, 128) even though phosphate ester hydrolysis depends very much upon pH. Also, Trentham and Gutfreund (98) found that hydroxylamine does not serve as an acceptor at pH 8.0, but it does at pH 5.8. 

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