Computational Modeling of Metal–Organic Frameworks for the Catalytic Hydrolysis of Nerve Agents and Their Simulants


The effective capture and detoxification of chemical warfare agents (CWAs) is a pressing need in the modern world. Materials are needed for both the destruction of weapon stockpiles and personal protection via fabric coatings or respirators. Attractive candidates for these applications include metal–organic frameworks (MOFs) – highly crystalline materials composed of metal nodes connected by organic linkers – due to their high porosity, large surface area, high concentration of active sites, and chemical functionality that can be tailored towards specific target molecules. Previous experiments, performed in buffered solution, have shown that Zr(IV)-MOFs can catalytically degrade organophosphate-based nerve agents into nontoxic products within minutes via hydrolysis of the phosphate ester bond. This dissertation uses a molecular modeling approach to study the detailed reaction mechanisms and binding interactions involved in MOF-catalyzed nerve agent hydrolysis to help elucidate experimental observations and screen for promising candidate materials with potentially better performance for CWA detoxification. By performing density functional theory (DFT) calculations, we explore the effects of temperature-induced node dehydration and distortion as well as varying node topologies, connectivities, and metal identities on the catalytic activity of M(IV)-MOFs for solution-phase organophosphate hydrolysis. To address the recent experimental observation of product inhibition in gas-phase nerve agent hydrolysis by Zr-MOFs, we examine the promising alternative of depositing single-atom transition-metal catalysts on MOF nodes to facilitate catalytic turnover. Additionally, we perform a DFT screening to identify highly predictive nontoxic simulant molecules as candidates for safer and more accurate experimental studies of nerve agent hydrolysis. Throughout the dissertation, we also derive quantitative structure-activity relationship models and perform statistical analyses to determine the most important features for describing the hydrolysis barriers and binding energetics involved in organophosphate hydrolysis reactions. Broadly, the body of work described in this dissertation establishes design principles that can be used to guide future experimental testing for the optimization of MOF catalysts for nerve agent hydrolysis.

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