Probing the Mechanism of Hydrolytic Degradation of Nerve Agent Simulant with Zirconium-Based Metal–Organic Frameworks

Metal–organic frameworks (MOFs) have been reported to effectively detoxify chemical warfare agents (CWAs) and their simulants. Early studies of Zr-MOF-catalyzed hydrolytic degradation of an organophosphoester type CWA, Sarin, and its simulant, dimethyl-4-nitrophenylphosphate (DMNP), suggested that the activity originates from ZrIV–OH–ZrIV moieties that resemble the structure of the active-site phosphotriesterase enzyme. Measurements of pKa values for hexa-zirconium-node-sited bridging hydroxo, terminal hydroxo, and aqua ligands reveal essentially complete conversion of mu-hydroxo ligands to substitution-inert mu-oxo ligands at alkaline pHs, ruling out a primary role for ZrIV–OH–ZrIV moieties, despite the resemblance to the phosphotriesterase enzyme active-site. The measurements also rule out a secondary role as a hydrogen bond donor/stabilizer of bound DMNP. Additionally, the measurements show that reactant-displaceable node-aqua ligands become increasingly scarce in increasingly alkaline environments. Here, the rates of the catalyzed hydrolysis reaction were examined experimentally to ascertain reaction orders and, in turn, interrogate the mechanism. In striking contrast to the ubiquitous Zr-MOF, UiO-66, for which simulant displacement of water as a node ligand is rate-determining, and the rate of catalysis (in alkaline environments) increases with decreasing pH, catalysis by NU-1000 is rate-limited by solution hydroxide attack of the nitrophenoxide–phosphorus bond of the MOF-activated simulant, with the overall hydrolysis rate being remarkably insensitive to pH (or pOH). Underlying the unusually weak sensitivity of rates of hydrolysis to pH is almost exact counterbalancing of the prevalence of catalyst active-sites (Zr–OH2 sites) with activity of the reaction nucleophile, free hydroxide ion, as a function of pH. We ascribe the residual pH dependence of the overall rate to a charge-based modulation of the equilibrium constant for simulant binding to the node. In contrast to overall hydrolysis rates, the catalyst turnover frequencies per Zr–OH2 active-site are strongly pH dependent, exceeding 30,000 s–1 at pH 10.5.