Activating Water: Important Effects of Non‐leaving Groups on the Hydrolysis of Phosphate Triesters

Kirby, Anthony J.; Medeiros, Michelle; Oliveira, Pedro Santos Mello de; Orth, Elisa S.; Brandão, Tiago A. S.; Wanderlind, Eduardo H.; Amer, Almahdi; Williams, Nicholas H.; Nome, Faruk

doi:10.1002/chem.201101926

Cited by 26 publications

(63 citation statements)

References 62 publications

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“…The IRC for triester 6a (Figure 3) shows a moderately stable intermediate with well-defined participation of water molecules in its formation and cleavage, consistent with proton inventory measurements and the substantial solvent deuterium isotope effect previously reported. 8 Using this TS as a model, potential energy surfaces were evaluated for the hydrolysis of all six triesters of Scheme 12. The activation parameters shown in Table 2 were obtained from stationary points characterizing reactant van der Waals complexes, transition states, and intermediates.…”

Section: Calculation: Triester Hydrolysismentioning

confidence: 99%

Fundamentals of Phosphate Transfer

Kirby¹,

Nome

2015

Acc. Chem. Res.

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Historically, the chemistry of phosphate transfer-a class of reactions fundamental to the chemistry of Life-has been discussed almost exclusively in terms of the nucleophile and the leaving group. Reactivity always depends significantly on both factors; but recent results for reactions of phosphate triesters have shown that it can also depend strongly on the nature of the nonleaving or "spectator" groups. The extreme stabilities of fully ionised mono- and dialkyl phosphate esters can be seen as extensions of the same effect, with one or two triester OR groups replaced by O(-). Our chosen lead reaction is hydrolysis-phosphate transfer to water: because water is the medium in which biological chemistry takes place; because the half-life of a system in water is an accepted basic index of stability; and because the typical mechanisms of hydrolysis, with solvent H2O providing specific molecules to act as nucleophiles and as general acids or bases, are models for reactions involving better nucleophiles and stronger general species catalysts. Not least those available in enzyme active sites. Alkyl monoester dianions compete with alkyl diester monoanions for the slowest estimated rates of spontaneous hydrolysis. High stability at physiological pH is a vital factor in the biological roles of organic phosphates, but a significant limitation for experimental investigations. Almost all kinetic measurements of phosphate transfer reactions involving mono- and diesters have been followed by UV-visible spectroscopy using activated systems, conveniently compounds with good leaving groups. (A "good leaving group" OR* is electron-withdrawing, and can be displaced to generate an anion R*O(-) in water near pH 7.) Reactivities at normal temperatures of P-O-alkyl derivatives-better models for typical biological substrates-have typically had to be estimated: by extended extrapolation from linear free energy relationships, or from rate measurements at high temperatures. Calculation is free from these limitations, able to handle very slow reactions as readily as very fast ones, and capable of predicting rate constants with levels of accuracy acceptable to the experimentalist. We present an updated overview of phosphate transfer, with particular reference to the mechanisms of the reactions of alkyl derivatives and triesters. The intention is to present a holistic (not comprehensive!) overview of the reactivity of typical phosphate esters, in terms familiar to the working chemist, at a level sufficient to support informed predictions of reactivity for structures of interest.

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Section: Calculation: Triester Hydrolysismentioning

confidence: 99%

Fundamentals of Phosphate Transfer

Kirby¹,

Nome

2015

Acc. Chem. Res.

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“…Piperidine and piperazine have been used in the deesterification of phenyl thionoacetate (Castro et al, 1993), poly(ethylenimine) has been used with substituted phenyl acetates (Arcelli and Concilio, 1996), and trihydroxymethylmethylamine has been used on substituted phenyl-alpha-furoates (Alwar, 2008). Pyridine is obviously ineffective in the present case since it is the solvent in the DECP reaction to give the diethyl ester (its inability to catalyze the hydrolysis of tris-2-pyridyl phosphate in an intramolecular reaction has been ascribed to low basicity) (Kirby et al, 2011). Dimethylamine was also found to be ineffective.…”

Section: Discussionmentioning

confidence: 70%

Development of a new ion-exchange/coordinating phosphate ligand for the sorption of U(VI) and trivalent ions from phosphoric acid solutions

Zhu

Alexandratos

2015

Chemical Engineering Science

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Polymer-bound monoprotic ligands developed for U(VI) sorption from 0.1 to 6 M H 3 PO 4 . Ligands are phosphorylated mono-and triethylene glycol monoethyl esters. Metal ion complexation by ion exchange through -OH and coordination through P ¼O. Decreased hydrogen bonding results in increased metal ion affinities. a b s t r a c tA polymer-bound monoprotic phosphoric acid ligand was developed for the sorption of U(VI) from 0.10 to 6.0 M phosphoric acid solutions. The ligands reported are new phosphorylated mono-and triethylene glycol ethyl esters (pEG1M and pEG3M) prepared by combining diethylchlorophosphate and 4-dimethylaminopyridine; they ion exchange through the acid site and coordinate through the phosphoryl oxygen. The binding mechanism is probed by comparing their results to coordinating phosphorylated mono-and triethylene glycol diethyl esters (pEG1 and pEG3) and the diprotic phosphonic acid (DPA) that operates by ion exchange. The affinities for Lu(III), La(III), Fe(III) and Al(III) were also determined. All metal ions were sorbed much more efficiently by the monoprotic ligand relative to the diprotic and coordinating ligands. It is proposed that a decrease in inter-ligand hydrogen bonding within the monoprotic ligand is responsible for the increased metal ion affinities. This is consistent with the FTIR spectra wherein the P¼O band appears at 1262 cm À 1 for pEG1 and this shifts down to 1229 cm À 1 in pEG1M and 1180 cm À 1 for DPA. Incorporating ether oxygen into the ligand further enhances metal affinities: pEG3M with three oxygen donors adjacent to the monoprotic site shows the highest affinity for metal ions. The increased affinities compared to pEG1M are due to complexation by the weakly binding ether oxygen donors. High metal ion affinities thus require both ion exchange with acidic protons and coordination with neutral donors. More rapid kinetics evident with pEG3M relative to DPA is further evidence for decreased hydrogen bonding which permits more rapid sorption. The affinity orders of the three acidic polymers are similar: U(VI), Lu(III)4Fe(III) 4La(III)4Al(III). Ligand strength is pEG3M4pEG1M4DPA4pEG34pEG1.

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“…O valor bastante negativo de entropia de ativação e resultados No entanto, resultados complementares mostraram que a hidrólise do TPP é sensível à presença de tampões, isto é, a hidrólise do substrato sofre catálise básica geral promovida por bases externas em reações intermoleculares. 17 Tais resultados contestam o mecanismo inicialmente proposto, já que reações intermoleculares geralmente não competem com reações intramoleculares altamente eficientes, que exibem vantagens, como proximidade e geometria apropriada entre grupos funcionais reativos. De fato, considerando a baixa basicidade do nitrogênio do grupo piridínio espectador (pK b = 13,78), uma contribuição mínima do mecanismo do Esquema 2 deve ser esperada.…”

Section: Hidrólise De Triésteres Fosfóricosunclassified

Recent Advances on the Decomposition of Neurotoxic Phosphorous Triesters

Wanderlind¹,

Medeiros²,

Souza³

et al. 2014

Revista Virtual De Química

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The anti-cholinesterase activity exhibited by several organophosphorus compounds brings interest to the development of new antidotes for poisoning cases with such chemicals. The advance of more efficient methods for destruction of stockpiles of chemical warfare agents is also currently important. In this sense, the aim of this work is to present a review of the recent progress in the investigation of the reactivity of phosphate triesters in several different systems, which can give insights into the development of novel strategies for application in chemical defense.

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Activating Water: Important Effects of Non‐leaving Groups on the Hydrolysis of Phosphate Triesters

Cited by 26 publications

References 62 publications

Fundamentals of Phosphate Transfer

Fundamentals of Phosphate Transfer

Development of a new ion-exchange/coordinating phosphate ligand for the sorption of U(VI) and trivalent ions from phosphoric acid solutions

Recent Advances on the Decomposition of Neurotoxic Phosphorous Triesters

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