Catalysis of phosphoryl group transfer. 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 approimation of the two reacting centers. The Mn-2+-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 Mn-2+ 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 salicyclic 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, beta-1-g, decreases significantly relative to beta-1-g for the spontaneous hydrolysis. From the collective data a specific interation 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.

Unusual Catalyst Concentration Effects in the Hydrolysis of Phenyl Phosphate Esters and of DNA: A Systematic Investigation of the Lanthanide Series1

“…(Figure ). Such a correlation has also been found for the catalytic effect of other metal cations in substitution reactions at phosphorus. The ion diameter dependence is in accord with most of the known 12 possible mechanisms for the observed rate accelerations, as both the water and the phosphoryl activation should be enhanced by higher charge density of the cation.…”

Sugar non-specific endonucleases

“…Carboxylate groups are known to be effective nucleophilic catalysts in the intramolecular hydrolysis of phosphate esters [202]. The mechanism of staphylococcal nuclease suggested by Cotton et al [175] requires that the γ‐carboxylate group of Glu43 acts as a general base, facilitating the attack of water on the scissile phosphodiester bond.…”

Sugar non-specific endonucleases

“…Carboxylate groups are known to be e¡ective nucleophilic catalysts in the intramolecular hydrolysis of phosphate esters [202]. The mechanism of staphylococcal nuclease suggested by Cotton et al [175] requires that the Qcarboxylate group of Glu43 acts as a general base, facilitating the attack of water on the scissile phosphodiester bond.…”