Metal-organic frameworks (MOFs) are porous 3-dimensional crystalline structures that have shown promise for a variety of applications including adsorption, catalysis, and sensing. Modern warfare has placed chemical warfare agent (CWA) destruction at the forefront of chemical applications for MOFs. However, experiments involving CWAs can only be performed by a small number of highly trained individuals as they are extremely dangerous and available only to certain laboratories. As such, it is imperative that suitable chemical simulants and reaction conditions are determined for CWAs of interest. In this work, we determine the reaction rate for heterogeneous catalytic hydrolysis of eight commonly used G-agent simulants with zirconium-based MOFs. Of the simulants tested, only dimethyl chlorophosphate (DMCP), diisopropylfluorophosphate (DFP), and dimethyl p-nitrophenylphosphate (DMNP) exhibit the ability to be catalytically hydrolyzed in a manner similar to the G-agents by the MOFs studied. Two different base-catalyzed reaction mechanisms are proposed for the hydrolysis reaction on the different MOF secondary building units, and the effect of pH and buffer properties is determined using an N-ethylmorpholine (NEM) buffer at pH 8-10 and a 3-(cyclohexylamino)-1-propanesulofinic acid (CAPS) buffer at pH 10-11.