Some metal-organic frameworks (MOFs) incorporate nodes that are metal oxide clusters such as Zr6O8. Vacancies on the node surfaces, accidental or by design, act as catalytic sites. Here, we report elucidation of the chemistry of Zr6O8 nodes in the MOFs UiO-66 and UiO-67 having used infrared and nuclear magnetic resonance spectroscopies to determine the ligands on the node surfaces originating from the solvents and modifiers used in the syntheses and having elucidated the catalytic properties of the nodes for ethanol dehydration, which takes place selectively to make diethyl ether but not ethylene at 473-523 K. Density functional theory calculations show that the key to the selective catalysis is the breaking of node-linker bonds (or the accidental adjacency of open/defect sites) that allows catalytically fruitful bonding of the reactant ethanol to neighboring sites on the nodes, facilitating the bimolecular ether formation through an SN2 mechanism.