For phosphate monoesters

Figure 11 A possible mechanism for phosphate monoester hydrolysis catalyzed by PPPs. ...

Figure 12 Possible mechanisms for phosphate monoester hydrolysis catalyzed by eukaryotic (a) and prokaryotic (b) PPMs. The representation for eukaryotic PPMs is based on the crystal structure of PP2Ca bound to phosphate (PDB code 1A6Q). In the published structure the phosphate anion is not directly coordinated to the metal ions and it has been modified here to represent a catalytic complex analogous with that implicated by the crystal structure of the homologue MspP bound to phosphate (PDB code 2JFR) see text for details. The octahedral coordination of metals Ml and M2 are completed by bridging carboxylate residues Asp60 in PP2Ca, and Asp35 in MspP (not shown for clarity). Water molecules complete the octahedral coordination at third metal site of the prokaryotic MspP.

A second periplasmic phosphatase, PhoV, in the same organism (Wagner et ah, 1995) has substrate specificity for phosphate monoesters and requires zinc ions for activ-... 

Phosphoric acid diesters are prepared by treating a liquid slurry of phosphate monoester with epoxides in the presence of alkali compounds. Thus a mixture of monolauryl phosphate sodium salt and triethyl amine in water was treated with glycidol at 80°C for 8 h to give 98% lauryl(2,3-dihydroxypropyl)phosphate sodium salt [13]. 

Compound (1) phosphorylates phosphate monoesters and alcohols, although with the latter a considerable excess of alcohol is necessary to obtain satisfactory yields. In the absence of mercuric ions the milder phosphorylating species (3) can be isolated which converts monoalkyl phosphates to pyrophosphate diesters in good yield but does not react appreciably with alcohols unless catalytic amounts of boron trifluoride are added. Amine salts of (3) are converted to phosphoramidates on heating. In the presence of silver ions, O-esters of thiophosphoric acid behave as phosphorylating agents and a very mild and convenient procedure suitable for preparing labile unsymmetrical pyrophosphate diesters, such as the... 

Other workers have concluded that, for the solvolysis of phosphate monoesters, the bonding between nucleophile and mecaphosphate is not far developed in the transition state and... 

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... 

A similar reaction mechanism was proposed by Chin et al. [32] for the hydrolysis of the biological phosphate monoester adenosine monophosphate (AMP) by the complex [(trpn) Co (OH2)]2+ [trpn = tris(ami-nopropyl)amine]. Rapid cleavage is observed only in the presence of 2 equiv metal complex. It is evident from 31P NMR spectra that on coordination of 1 equiv (trpn)Co to AMP a stable four-membered chelate complex 4 is formed. The second (trpn)Co molecule may bind to another oxygen atom of the substrate (formation of 5) and provide a Co-OH nucleophile which replaces the alkoxy group. The half-life of AMP in 5 is about 1 h at pD 5 and 25 °C. 

The highest rate acceleration in the nonenzymatic hydrolysis of a phosphate monoester was reported by Chin s group [35]. In the dinuclear cobalt(III) complex 9 the metal ions are much more rigidly preorganized than in complexes 6 and 8. At pH 7 and 25 °C coordinated phenyl phosphate (PP) hydrolyzes 1011 times faster than free PP under the same conditions. There is good evidence for a reaction mechanism which has already been suggested for 2. The higher reactivity of 9 compared to 2 may be attributed to the proximity of substrate and M-OH nucleophile. 

Starch liquefaction, 10 287-288 Starch molecule, techniques for characterizing, 20 562 Starch phosphates, 4 724t Starch sodium phosphate monoesters, 4 721... 

Fig. 19 Bond length-reactivity plots for phosphate triesters and for monoester dianions. Note the increased slope for the monoesters, which undergo SNl(P)-type P-O cleavage in solution. Reprinted with permission from Jones and Kirby (1984). Copyright 1984 American Chemical Society.

Solvolysis studies of meta- and para-substituted phenyl phosphates (240) in anhydrous Bu OH and in Am OH have revealed that generally reactions of dianions are much faster in alcohols than in water. For example, the dianion of p-nitrophenyl phosphate (240 X = 4-NO2) reacts 7500- and 8750-fold faster in Bu OH and Am OH, respectively, than in water." The results of a theoretical study of the reactivity of phosphate monoester anions in aqueous solution do not support the generally accepted view that Brpnsted coefficients fhg = —1.23 and jSnuc = 0.13 determined more than 30 years ago for the uncatalysed reaction of water and a monophosphate dianion (241) represent conclusive evidence for the dissociative mechanism. It is suggested that, instead, the observed LFERs could correspond to a late transition state in the associative mechanism." ... 

The phosphitylation procedure (step a) proceeds in the presence of EtN(i-Pr)2 (DPEA) and the subsequent oxidation by TBHP (step b). The cyclic phosphate is deprotected stepwise (steps c and d) and serves as a model for the physiological milieu . It has been possible to deliver phosphate monoesters via steps c and d in a controllable manner from cyclic phosphotri-esters at physiological pH. 

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 ... 

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