Ions as Substituents: A Supramolecular Hammett Approach for Electrostatic Control of Acidity

Controlling chemical reactivity by engineering the immediate electrostatic and solvation microenvironment of a reactant is a central goal of chemistry. Crown ethers covalently attached to reactive centers have emerged as a versatile supramolecular motif for modulating reactivity by selectively positioning metal ions near functional groups and generating localized electrostatic fields without altering covalent structure. Here, we demonstrate ion-controlled modulation of acidity in an archetypal benzoic acid system covalently functionalized with a metal-binding crown ether. Experimental pK_a measurements, supported by density functional theory calculations, show that encapsulated metal ions act as effective electron-withdrawing units that stabilize the carboxylate conjugate base. We show that the induced acidity change depends on metal-ion identity, charge, size complementarity with crown ether, and hydration energy. This study establishes a quantitative framework for defining Hammett-like parameters for metal ions and provides design principles and limitations for controlling acid-base chemistry using crown ether motifs. More broadly, it demonstrates a general supramolecular strategy for tuning reactivity via noncovalent electrostatic effects.