Catalytic Inhibition of Base-Mediated Reactivity by a Self-Assembled Metal-Ligand Host

Spacious M₄ L₆ tetrahedra can act as catalytic inhibitors for base-mediated reactions. Upon adding only 5 % of a self-assembled Fe₄ L₆ 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 Fe₄ L₆ 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 Fe₄ L₆ hosts with spacious internal cavities: minimal inhibition is seen with smaller tetrahedra or Fe₂ L₃ 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.