Catalysis of Phosphoryl Group Transfer. The Role of Divalent Metal Ions in the Hydrolysis of Lactic Acid O-Phenyl Phosphate and Salicylic Acid O-Aryl Phosphates

James J. Steffens, Iris J. Siewers, Stephen J. Benkovic

Research output: Contribution to journalArticle

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Abstract

The spontaneous hydrolyses of lactic acid O-phenyl phosphate (I) and, to a lesser extent, 3-hydroxybutyric acid O-phenyl phosphate (II) have been investigated and compared with similar intramolecular and bimolecular reactions. Compared to bimolecular nucleophilic reactions, the reactivity of II is similar to other systems involving the formation of a six-membered ring intermediate, which suggests that the electrostatic barrier to attack of an anionic nucleophile on a phosphate diester anion is fully present in II. The reactivity of I, as compared to that of II, would suggest that at least a partial overcoming of the electrostatic barrier takes place upon closer approximation of the two reacting centers. The Mn2+-catalyzed hydrolysis of I exhibits saturation kinetics, consistent with the enhanced reactivity of the metal ion-substrate complex. The binding constant for this complex, determined from kinetics, is in good agreement with that obtained by electron spin resonance (ESR) titration. It is argued that the complex of Mn2+ with II, as observed by pulsed Fourier transform nuclear magnetic resonance (NMR) techniques, is a precursor to the complex of catalytic significance. The hydrolysis of I as catalyzed by a variety of divalent metal ions suggests an optimal metal ion size. The spontaneous and metal ion catalyzed hydrolyses of salicylic acid O-aryl phosphates (IIIa-d) proceed through cyclic acyl phosphate intermediates after expulsion of phenol. Product studies on the parent compound have failed to detect phenyl phosphate as a product in either the spontaneous or metal ion catalyzed process. The dependence of the second-order rate constant for the metal-catalyzed hydrolysis on leaving group pKa1g, decreases significantly relative to β1g for the spontaneous hydrolysis. From the collective data a specific interaction of the metal ion with a pentacovalent intermediate is inferred in the rate-determining step for esters I and III. The probable consequences of these mechanistic postulates for phosphoryl transfer reactions in biological systems are discussed.

Original languageEnglish (US)
Pages (from-to)2431-2440
Number of pages10
JournalBiochemistry
Volume14
Issue number11
DOIs
StatePublished - Jun 1 1975

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Salicylic Acid
Catalysis
Metal ions
Hydrolysis
Lactic Acid
Metals
Phosphates
Ions
Static Electricity
Electrostatics
Nucleophiles
Kinetics
3-Hydroxybutyric Acid
Biological systems
Phenol
Titration
Electron Spin Resonance Spectroscopy
Fourier Analysis
Anions
Paramagnetic resonance

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

@article{aa72d2bc444a4188985b556ba146ec3b,
title = "Catalysis of Phosphoryl Group Transfer. The Role of Divalent Metal Ions in the Hydrolysis of Lactic Acid O-Phenyl Phosphate and Salicylic Acid O-Aryl Phosphates",
abstract = "The spontaneous hydrolyses of lactic acid O-phenyl phosphate (I) and, to a lesser extent, 3-hydroxybutyric acid O-phenyl phosphate (II) have been investigated and compared with similar intramolecular and bimolecular reactions. Compared to bimolecular nucleophilic reactions, the reactivity of II is similar to other systems involving the formation of a six-membered ring intermediate, which suggests that the electrostatic barrier to attack of an anionic nucleophile on a phosphate diester anion is fully present in II. The reactivity of I, as compared to that of II, would suggest that at least a partial overcoming of the electrostatic barrier takes place upon closer approximation of the two reacting centers. The Mn2+-catalyzed hydrolysis of I exhibits saturation kinetics, consistent with the enhanced reactivity of the metal ion-substrate complex. The binding constant for this complex, determined from kinetics, is in good agreement with that obtained by electron spin resonance (ESR) titration. It is argued that the complex of Mn2+ with II, as observed by pulsed Fourier transform nuclear magnetic resonance (NMR) techniques, is a precursor to the complex of catalytic significance. The hydrolysis of I as catalyzed by a variety of divalent metal ions suggests an optimal metal ion size. The spontaneous and metal ion catalyzed hydrolyses of salicylic acid O-aryl phosphates (IIIa-d) proceed through cyclic acyl phosphate intermediates after expulsion of phenol. Product studies on the parent compound have failed to detect phenyl phosphate as a product in either the spontaneous or metal ion catalyzed process. The dependence of the second-order rate constant for the metal-catalyzed hydrolysis on leaving group pKa,β1g, decreases significantly relative to β1g for the spontaneous hydrolysis. From the collective data a specific interaction of the metal ion with a pentacovalent intermediate is inferred in the rate-determining step for esters I and III. The probable consequences of these mechanistic postulates for phosphoryl transfer reactions in biological systems are discussed.",
author = "Steffens, {James J.} and Siewers, {Iris J.} and Benkovic, {Stephen J.}",
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Catalysis of Phosphoryl Group Transfer. The Role of Divalent Metal Ions in the Hydrolysis of Lactic Acid O-Phenyl Phosphate and Salicylic Acid O-Aryl Phosphates. / Steffens, James J.; Siewers, Iris J.; Benkovic, Stephen J.

In: Biochemistry, Vol. 14, No. 11, 01.06.1975, p. 2431-2440.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Catalysis of Phosphoryl Group Transfer. The Role of Divalent Metal Ions in the Hydrolysis of Lactic Acid O-Phenyl Phosphate and Salicylic Acid O-Aryl Phosphates

AU - Steffens, James J.

AU - Siewers, Iris J.

AU - Benkovic, Stephen J.

PY - 1975/6/1

Y1 - 1975/6/1

N2 - The spontaneous hydrolyses of lactic acid O-phenyl phosphate (I) and, to a lesser extent, 3-hydroxybutyric acid O-phenyl phosphate (II) have been investigated and compared with similar intramolecular and bimolecular reactions. Compared to bimolecular nucleophilic reactions, the reactivity of II is similar to other systems involving the formation of a six-membered ring intermediate, which suggests that the electrostatic barrier to attack of an anionic nucleophile on a phosphate diester anion is fully present in II. The reactivity of I, as compared to that of II, would suggest that at least a partial overcoming of the electrostatic barrier takes place upon closer approximation of the two reacting centers. The Mn2+-catalyzed hydrolysis of I exhibits saturation kinetics, consistent with the enhanced reactivity of the metal ion-substrate complex. The binding constant for this complex, determined from kinetics, is in good agreement with that obtained by electron spin resonance (ESR) titration. It is argued that the complex of Mn2+ with II, as observed by pulsed Fourier transform nuclear magnetic resonance (NMR) techniques, is a precursor to the complex of catalytic significance. The hydrolysis of I as catalyzed by a variety of divalent metal ions suggests an optimal metal ion size. The spontaneous and metal ion catalyzed hydrolyses of salicylic acid O-aryl phosphates (IIIa-d) proceed through cyclic acyl phosphate intermediates after expulsion of phenol. Product studies on the parent compound have failed to detect phenyl phosphate as a product in either the spontaneous or metal ion catalyzed process. The dependence of the second-order rate constant for the metal-catalyzed hydrolysis on leaving group pKa,β1g, decreases significantly relative to β1g for the spontaneous hydrolysis. From the collective data a specific interaction of the metal ion with a pentacovalent intermediate is inferred in the rate-determining step for esters I and III. The probable consequences of these mechanistic postulates for phosphoryl transfer reactions in biological systems are discussed.

AB - The spontaneous hydrolyses of lactic acid O-phenyl phosphate (I) and, to a lesser extent, 3-hydroxybutyric acid O-phenyl phosphate (II) have been investigated and compared with similar intramolecular and bimolecular reactions. Compared to bimolecular nucleophilic reactions, the reactivity of II is similar to other systems involving the formation of a six-membered ring intermediate, which suggests that the electrostatic barrier to attack of an anionic nucleophile on a phosphate diester anion is fully present in II. The reactivity of I, as compared to that of II, would suggest that at least a partial overcoming of the electrostatic barrier takes place upon closer approximation of the two reacting centers. The Mn2+-catalyzed hydrolysis of I exhibits saturation kinetics, consistent with the enhanced reactivity of the metal ion-substrate complex. The binding constant for this complex, determined from kinetics, is in good agreement with that obtained by electron spin resonance (ESR) titration. It is argued that the complex of Mn2+ with II, as observed by pulsed Fourier transform nuclear magnetic resonance (NMR) techniques, is a precursor to the complex of catalytic significance. The hydrolysis of I as catalyzed by a variety of divalent metal ions suggests an optimal metal ion size. The spontaneous and metal ion catalyzed hydrolyses of salicylic acid O-aryl phosphates (IIIa-d) proceed through cyclic acyl phosphate intermediates after expulsion of phenol. Product studies on the parent compound have failed to detect phenyl phosphate as a product in either the spontaneous or metal ion catalyzed process. The dependence of the second-order rate constant for the metal-catalyzed hydrolysis on leaving group pKa,β1g, decreases significantly relative to β1g for the spontaneous hydrolysis. From the collective data a specific interaction of the metal ion with a pentacovalent intermediate is inferred in the rate-determining step for esters I and III. The probable consequences of these mechanistic postulates for phosphoryl transfer reactions in biological systems are discussed.

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