Buffer-Induced Acceleration and Inhibition in Polyoxometalate-Catalyzed Organophosphorus Ester Hydrolysis

Abstract

The Zr-containing polyoxometalates (POMs), including (Et2NH2)8{[α-PW11O39Zr­(μ–OH)­(H2O)]2}·7H2O (1), effectively catalyze the hydrolysis of nerve agent simulants at near-neutral pH. Analogous Zr-containing heterogeneous systems are much-studied and effective nerve-agent hydrolysis catalysts, but due to their heterogeneous nature, it is very challenging to know the exact structure of the catalytic sites during turnover and to clarify at the molecular level the elementary mechanistic processes. Here, under homogeneous conditions, hydrolysis rates of the nerve-agent simulant methyl paraoxon catalyzed by 1 are examined as a function of pH, ionic strength, catalyst, and substrate concentrations. In addition, the specific effect of three commonly used buffers is examined, revealing that acetate functions as a co-catalyst, phosphate inhibits hydrolytic activity, and 2-(N-morpholino)­ethanesulfonic acid (MES) has no effect on the hydrolysis rate. Spectroscopic (31P nuclear magnetic resonance) and computational studies demonstrate how each of these buffers interacts with the catalyst and offer explanations of their impacts on the hydrolysis rates. The impact of the nerve-agent hydrolysis product, methyl phosphonic acid, is also examined, and it is shown to inhibit hydrolysis. These results will aid in the design of future Zr-based hydrolysis catalysts.

Selective Hydrolysis of Ovalbumin Promoted by Hf(IV)-Substituted Wells-Dawson-Type Polyoxometalate

“…The absence of hydrolysis might be due to the presence of precipitation which was observed under both these pH conditions and which probably resulted in the loss of Hf1-WD2 catalyst (see Figure S1). In addition, the presence of different buffers might also contribute to the observed changes in the reactivity, similarly to the recently reported inhibition and activation effect of buffers on the catalytic activity of Zr-POMs (Collins-Wildman et al, 2018).…”

Selective Hydrolysis of Transferrin Promoted by Zr-Substituted Polyoxometalates

“…Solutions of transferrin (7.5 µM) was incubated with each Zr-substituted POM (7.5 mM) in phosphate buffer (10 mM, pH 7.4) at 60 °C over the course of a week. Although previous studies have shown that phosphate buffer may impact POM reactivity [ 37 ], it ensures pH stability and pH conditions which are pertinent to physiological conditions.…”

“…Solutions of transferrin (7.5 µM) was incubated with each Zr-substituted POM (7.5 mM) in phosphate buffer (10 mM, pH 7.4) at 60 °C over the course of a week. Although previous studies have shown that phosphate buffer may impact POM reactivity [37], it ensures pH stability and pH conditions which are pertinent to physiological conditions. Aliquots of the reaction mixture were taken at different time intervals and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) on separate gels for each Zr-POM by plotting the different time increments next to each other (Figures S1-S6).…”

Synthesis, Characterization, and Phosphoesterase Activity of a Series of 4f- and 4d-Sandwich-Type Germanotungstates [(n-C4H9)4N]l/mH2[(M(H2O)3)(γ-GeW10O35)2] (M = CeIII, NdIII, GdIII, ErIII, l = 7; ZrIV, m = 6)

“…A stepwise disappearance of the singlet corresponding to the substrate DMNP and gradual appearance of a singlet attributed to the hydrolysis side product dimethyl phosphate (DMP) can be observed ( Figure 3 ). 28 The corrected rate constant after subtracting the rate constant obtained from reaction mixtures lacking the POM catalyst ( k uncat = 4.01 (±0.10) × 10 –5 min –1 ) - under elsewise identical reaction conditions considering autohydrolysis of the substrate - gives a value of k corr = 2.42 (±0.10) × 10 –4 min –1 ( Figure S17 ) which is about seven times higher than the values obtained for the uncatalyzed reaction ( k uncat = 4.01 (±0.10) × 10 –5 min –1 ) and control experiments containing the [GeW 10 O 36 ] 8– precursor ( k corr = 3.37 (±0.12) × 10 –5 min –1 ) ( Figure S18 ), respectively. Concentration dependent experiments on the phosphoesterase activity of [Ce(H 2 O) 3 (GeW 10 ) 2 ] 9– and [Zr(H 2 O) 3 (GeW 10 ) 2 ] 8– toward NPP and DMNP were carried out, and the substrate conversion for a specific reaction time (45.6 h, 49 h, and 25 h) under varying catalyst concentrations (0.5 mM, 1.0 mM, 1.25 mM, 2.5 mM) was recorded and compared ( Table S20 ).…”