One of the major requirements in solid acids and bases catalyzed reactions is that the reactants, intermediates or activated complexes cooperate with several functions of catalyst support. In this work the remarkable bifunctional behavior of the defective UiO-66(Zr) metal organic framework is shown for acid-base pair catalysis. The active site relies on the presence of undercoordinated zirconium sites, which may be tuned by removing framework linkers and by removal of water from the inorganic bricks using a dehydration treatment. To elucidate the amphoteric nature of defective UiO-66, the Oppenauer oxidation of primary alcohols has been theoretically investigated using density functional theory (DFT) and the periodic approach. The presence of acid and basic centers within molecular distances has been shown crucial for determining the catalytic activity of the material. Hydrated and dehydrated bricks have a distinct influence on modulation of the acidity and basicity of the active sites. In any case both functions need to cooperate in a concerted way to enable the chemical transformation.