Richard J. Hooley

Spacious M 4 L 6 tetrahedra can act as catalytic inhibitors for base‐mediated reactions. Upon adding only 5 % of a self‐assembled Fe 4 L 6 cage complex, the conversion of the conjugate addition between ethylcyanoacetate and β‐nitrostyrene catalyzed by proton sponge can be reduced from 83 % after 75 mins at ambient temperature to <1 % under identical conditions. The mechanism of the catalytic inhibition is unusual: the octacationic Fe 4 L 6 cage increases the acidity of exogenous water in the acetonitrile reaction solvent by favorably binding the conjugate acid of the basic catalyst. The inhibition only occurs for Fe 4 L 6 hosts with spacious internal cavities: minimal inhibition is seen with smaller tetrahedra or Fe 2 L 3 helicates. The surprising tendency of the cationic cage to preferentially bind protonated, cationic ammonium guests is quantified via the comprehensive modeling of spectrophotometric titration datasets.