Hydrolysis of phosphate diester

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

Mechanistic studies of the hydrolysis of phosphate diesters indicate similar possibilities, with alkyl metaphosphate (ROP02)-like transition states and 5 n2(P) pathways. The hydrolysis of m-nitrobenzyl uridine 3 -diphosphate, whose two potential leaving groups have equal pK s, is associated with isomerisation to the 2 -isomer in weakly acidic solution, which requires pseudorotation of a (probably neutral) phosphorane. ... 

Two different binuclear copperdi) complexes have been prepared recently, one with a bridging phenoxy ligand having two bis-benzi-midazole arms (12, Fig. 14), and the second having a bis-cyclen-naphthalene ligand (13, Fig. 15) (352, 353). Both of them show bimetallic cooperativity for the hydrolysis of phosphate diesters, contrary to studies with the dinuclear cobalt complex (354). The pseudo-first-order rate constants for hydrolysis of the para-nitrophenylphosphate ester of propylene glycol by bis-benzimidazole-based copper complexes... 

The most potent catalysts for the cleavage of phosphate diesters are octahedral Co(ni) complexes with cis-tetraamine and aquo ligands. These accelerate the hydrolysis of phosphate diesters with much more effect than they accelerate the hydrolysis of phosphate monoesters. Chin and Zou... 

Initial studies carried out in our laboratories served to confirm that the Eu(III) texaphyrin 8b is in fact capable of catalyzing the hydrolysis of phosphate diesters. For instance, using the ammonium salt of uridylyl-3, 5 -uridine (UpU) as a substrate, it was found that this particular texaphyrin is able to effect catalytic hydrolysis (as judged by a controlled HPLC product analysis) with a pseudo-zero order rate of (9.1 1.6) x lO mMh By comparison, under identical conditions, Eu(N03)3, was found to effect UpU hydrolysis with a pseudo-zero order rate of (2.7 0.2) X lO mMhwhile Morrow s Eu(III) hexaamine Schiff base complex ("EuHAM"),27e one of the better alternative systems known, induced hydrolysis with a corresponding rate of (4.1 0.4) x lO mMh- Additionally, these same studies served to confirm that the Eu(III) texaphyrin complex 8b is far more stable in solution than the corresponding HAM-derived product. Thus, from both a kinetic efficacy and intrinsic stability perspective, the Eu(III) texaphyrins appear to be the best metal-based systems for use in antisense applications. 

Chin, J. Banaszcyk, F. Jubian, V. Zou, X., Co(III) complex promoted hydrolysis of phosphate diesters Comparison in reactivity of rigid cis-diaquotetraazacoboalt(III) complexes. J Am Chem Soc 1989, 111, 186-190. 

For undetermined reasons, the optical density of DNA is less than the sum of the densities of the component nucleotides.Since DNA is a very long polymer, with a molecular weight of approximately 1,000,000, there is a decrease in viscosity on hydrolysis. The binding of basic dyes is characteristic only of large polymers, and has been used to assay hydrolysis. The most widely used assays, as with ribonuclease, measure either acid produced by hydrolysis of phosphate diesters or the formation of acid-soluble nucleotides. ... 

Catalysis of ester hydrolysis by metal cations is not restricted to esters of organic acids. Both magnesium(n) and zinc(n) cause marked rate enhancements of hydrolysis of phosphate diesters. Here there is parallel hydrolysis of the free ester and of its metal complex under the conditions examined. ... 

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). 

Stockbridge RB, Wolfenden R. The hydrolysis of phosphate diesters in cyclohexane and acetone. Chem Comm. 2010 46 4306-4308. 

These were differently affected by different procedures. For example, when the enzyme was activated at 55°, the increment in ki was slight, but k2 increased 3.5-fold. Similarly, in the presence of EDTA, fc, and k2 values decreased independently, suggesting that the sites for both activities were different. Center and Behai (5) found that with the P. mirabilis enzyme, cyclic 2, 3 -UMP competitively inhibited the hydrolysis of bis(p-nitrophenyl) phosphate. The Ki was 40 pAf very close to the Km for the cyclic nucleotide (Km, 75 yM) which indicated that the two compounds could serve as alternate substrates being hydrolyzed at the same active site. In contrast, 3 -AMP was a mixed inhibitor of cyclic 2, 3 -UMP and bis(p-nitrophenyl) phosphate hydrolysis. Adenosine was a mixed inhibitor of bis(p-nitrophenyl) phosphate hydrolysis but a competitive inhibitor of 3 -AMP hydrolysis. From such kinetic studies Center and Behai (5) suggested that two separate and adjacent sites A and B are involved in the hydrolysis of the diester and phos-phomonoester substrates. Site A serves as a binding site for hydrolysis of ribonucleoside 2, 3 -cyclic phosphates and together with site B catalyzes the hydrolysis of the diester bond. During this reaction 3 -... 

Phosphorus is essential to all living systems. Within biological systems the most abundant forms of phosphorus are phosphate diester bonds, which form the links within nucleic molecules. Phosphate is an indispensable portion of the ATP molecule. The hydrolysis of phosphate from ATP to ADP forms the basis of most energy transfer reactions within biological systems. Phospholipids and sugar phosphates are constituents of all living cells. 

Cryptate complexes with macrobicychc hgands containing three bipy units, in which the Ln + ion is contained within a hgand cavity, have been synthesized. Such hgands will complex Ln + ions, such as Eu + and Sm +, under conditions where Ln + ions are not. An application has been using lanthanide cryptates of the early lanthanides (La, Ce, Eu) as catalysts in the hydrolysis of phosphate monoesters, diesters, and triesters. Schiff base complexes can be synthesized by the reaction of a lanthanide salt with a diamine and a suitable carbonyl derivative such as 2,6-diacetylpyridine. 

Phosphoryl transfer reactions have essential roles throughout biochemistry. The enzymes that catalyze these reactions result in tremendous rate enhancements for their normally unreactive substrates. This fact has led to great interest in the enzymatic mechanisms, and debate as to whether the mechanisms for enzyme-catalyzed hydrolysis of phosphate esters differ from those of uncatalyzed reactions. This review summarizes the uncatalyzed reactions of monoesters, diesters and triesters. A selection of enzymatic phosphoryl transfer reactions that have been the most studied and are the best understood are discussed, with examples of phosphatases, diesterases, and triesterases. 

A cooperative effect of two mononuclear complexes has been observed in the hydrolysis of phosphate mono- or diesters, the reaction order being then two with respect to the metal (343-348). Hydrolysis of methyl para-nitrophenylphosphate diester doubly coordinated to a di-nuclear cobalt(III) complex was reported, and a crystalline compound of dimethylphosphate coordinated to the same cobalt complex was characterized [Co2 (l,4,7-triazacyclononane)2 (0H)2 02P(0CH3)2 ] ... 

The effectiveness of the binuclear complex 11 (Fig. 13), with two mononuclear cyclen-cobalt(III) units linked together by an anthra-cenyl spacer (cyclen = 1,4,7,10-tetraazacyclododecane), was compared with the monomer in the hydrolysis of phosphate monoesters (354). The reaction assisted by this rigid binuclear complex, having a phosphate-sized pocket, was 10 times faster than that promoted in the presence of two equivalents of the single cyclen-Co complex. In these experiments the substrate concentration was 25 pM and the total cobalt concentration was 2 mM at 25°C and neutral pH (354). No such cooperativity could be noted using a diester substrate because the pseudo-first-order rate constants were similar for both 11 and the mononuclear complex. With 11 as catalyst, an overall rate enhancement of 10 was achieved over the uncatalyzed hydrolysis of paranitrophenyl phosphate monoester as substrate. 

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