Phosphate diester hydrolysis

Methyl-p-nitrophenyl phosphate coordinated to the two metal centers in 37 undergoes hydrolysis by a two-step addition-elimination mechanism [73]. The free phosphate hydrolyzes by a concerted mechanism. In both phosphate monoester and diester hydrolysis, the two Co(m) centers in 32 and 37 stabilize the five-coordinate phosphate species (transition state or intermediate) by bringing the phosphate and nucleophile together. This stabilization leads to a change in mechanism from dissociative to concerted for a phosphate monoester hydrolysis [96] and from concerted to stepwise for phosphate diester hydrolysis [73]. 

Reports which have clear applications in DNA hydrolysis include one of a dinuclear lanthanum(III) complex that catalyses phosphate diester hydrolysis to give unprecidented rates of reaction and one describing the preparation of two new dinuclear bisimidazolyl-Cu(II) calixarenes and an investigation of these complexes as metalloenzyme models for phosphate diester cleavage. The importance of tuning microenvironments when designing synthetic nucleases is illustrated by a report that intramolecular trans-esterification of 2-hydroxy-propyl-4-nitrophenyl phosphate (84) is up to 5000 times faster in organic solvents than in water/ ... 

The rate of hydrolysis of bis(4-nitrophenyl) phosphate is approximately 10-fold higher for a binuclear Zn2(OH)2 complex of the L22 ligand (Fig. 52) versus a mononuclear zinc hydroxide complex of the L23 ligand at 308 K.105 In this system, a monohydroxide binuclear zinc complex (Zn2(p-OH)) does not promote phosphate diester hydrolysis. The 10-fold rate enhancement found for the reaction involving the binuclear Zn2(OH)2 complex was explained via cooperative interaction between the zinc centers. As shown in Fig. 54, the reaction is proposed to take place via attack of a terminal Zn-OH moiety on a phosphate diester substrate that is interacting with both zinc centers. This suggests a cooperative role for the two zinc centers in the phosphate diester hydrolysis reaction. 

Kr et al. demonstrated that sapphyrin, an all-organic receptor for phosphate, could also be used as a catalyst for phosphate diester hydrolysis. Because nucleophilic displacement plays an important role in this particular... 

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

An estimate of the rate enhancement associated with the intramolecular phosphorylation can be made by using isopropyl p-nitrophenyl methyl-phosphonate as a model for the covalent intermediate formed in the initial step of the reaction of cycloheptaamylose with bis (p-nitrophenyl) me thy 1-phosphonate. The first-order rate constant for the alkaline hydrolysis of isopropyl p-nitrophenyl methylphosphonate at pH 9.86 can be obtained from the data of van Hooidonk and Groos (1970) kun = 1.4 X 10-5 sec-1. This value may be compared with the maximal rate constant for the reaction of cycloheptaamylose with bis(p-nitrophenyl) methylphosphonate— k2 = 1.59 X 10-1 sec-1 at pH 9.86—which must be a minimal value for the rate of the intramolecular phosphorylation. This comparison implies a kinetic acceleration of at least 104 which is similar to rate enhancements associated with the formation of cyclic phosphates from nucleoside phosphate diesters. 

Phosphate diesters of general structure 29 are among the most resistant species to hydrolysis due the reluctance of hydroxide or even water to attack an anionic... 

No phosphate was released when the fraction was treated with phosphomonoesterase, indicating the presence of a phosphoric diester. Hydrolysis of the unknown KDO derivative (1 M HC1 for 5 h at... 

As we shall see later, most catalytic antibodies achieve rate accelerations in the range 103 to 106. It follows that for a very slow reaction, e.g. the alkaline hydrolysis of a phosphate diester with A 0h 10-u m 1 s 1 direct observation of the reaction is going to be experimentally problematic. Given that concentrations of catalytic antibodies employed are usually in the 1-10 /am range, it has proved far more realistic to target the hydrolysis of an aliphatic ester, with /c0h 0.1 m-1 s-1 under ambient conditions. 

The classic case of assisted hydrolysis of phosphate diesters is neighbouring... 

Fig. 35 Hapten a ft-[102] was used to generate 25 mAbs from which 2G12 proved to catalyse the hydrolysis of the phosphate diester [103].

Phosphate diesters resist acid hydrolysis, and they are only inefficiently hydrolyzed in alkaline solutions. The exception is any five-membered ring containing a phos-phodiester, such as that formed upon alkaline treatment of RNA. Such five-membered cyclic phosphodiesters are rapidly hydrolyzed in alkaline solutions. 

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