Mechanistic studies of La3+- and Zn2+-catalyzed methanolysis of aryl phosphate and phosphorothioate triesters. Development of artificial phosphotriesterase systems

Abstract

The methanolyses of a series of O,O-diethyl O-aryl phosphates (2,5) and O,O-diethyl S-aryl phosphorothioates (6) promoted by methoxide and two metal ion systems, (La3+)2(-OCH3)2 and 4:Zn2+:-OCH3 (4 = 1,5,9-triazacyclododecane) has been studied in methanol at 25 degrees C. Brønsted plots of the logk2 values vs. pKa for the phenol leaving groups give beta(lg) values of -0.70, -1.43 and -1.12 for the methanolysis of the phosphates and -0.63, -0.87 and -0.74 for the methanolysis of the phosphorothioates promoted by the methoxide, La3+ and Zn2+ systems respectively. The kinetic data for the metal-catalyzed reactions are analyzed in terms of a common mechanism where there is extensive cleavage of the P-XAr bond in the rate-limiting transition state. The relevance of these findings to the mechanism of action of the phosphotriesterase enzyme is discussed.

The RNA‐Cleaving Bipartite DNAzyme Is a Distinctive Metalloenzyme

“…[22] Moreover, cases of bimetallic catalysts and the necessity of removing two protons from them to generate an active species have been reported in other systems. [23] The falling part [5] of the bell-shaped pH profile (at pH > 8.0) can be comfortably fit to a single ionization event [pK a3 = 8.93 AE 0.07, obtained by using Equation (4)]. …”

Catalytic Decomposition of Simulants for Chemical Warfare V Agents: Highly Efficient Catalysis of the Methanolysis of Phosphonothioate Esters

“…A turnover experiment was conducted in solution with methanol, the concentrations were 3.62 m M for 5 a and 0.36 m M for La(OTf) 3 (Tf=trifluoromethylsulfonyl) buffered with N ‐ethyl morpholine at ${{{\hfill {\rm s}\atop \hfill {\rm s}}}}$ pH 9.1, in which the dominant catalytically active form in solution was probably the bis(methoxy)‐bridged dimer [{La 3+ ( − OCH 3 )} 2 ], which we had shown earlier makes a contribution of >90 % toward the catalysis of phosphate ester methanolysis at that ${{{\hfill {\rm s}\atop \hfill {\rm s}}}}$ pH value 8a,b. None of the starting material, which has a 31 P NMR signal at δ =50.37 ppm, was evident within the five minutes required to obtain the spectrum: only a single peak at δ =30.6 ppm, which corresponds to O‐ ethyl O ‐methyl methylphosphonate, was observed.…”

Transition from concerted to stepwise processes as a function of leaving group ability: density functional theory and experimental study of lyoxide‐promoted cleavages of phosphorothioate and phosphate triesters in water and methanol

“…Because of their environmental accumulation, health threats, and possible use as ‘weapons of opportunity’ by terrorist organizations, detailed studies of their decomposition mechanisms are warranted, as is the development of efficient catalytic means for their decontamination. Recent contributions to the latter area from our labs have disclosed the results of metal‐catalyzed methanolytic cleavages of phosphorothioate ( 1 ) and phosphate triesters ( 2 ) where substantial rate accelerations over the background reactions at ambient temperature and essentially neutral pH (in alcohol) are observed. The present report is an extension of these studies but deals with new aspects of the mechanism of the base‐promoted solvolysis.…”