A concerted two-prong approach to the in situ allosteric regulation of bifunctional catalysis

Herein, we report the reversible in situ “on–off” allosteric regulation of hydrogen-bond-donating (HBD)–Lewis base co-catalytic activity via a concerted two-prong methodology entailing cooperative acid–base chemistry and a structurally addressable coordination complex. Specifically, a heteroligated Pt(ii) weak-link approach (WLA) tweezer complex containing both a hemilabile squaramide–piperidine-based catalytic ligand and a sodium sulfonate hydrogen-bond-accepting (HBA) ligand was synthesized. Due to the hemilabile nature of the catalyst-containing ligand, the heteroligated complex can be reversibly toggled in situ between a flexible, semi-open state and a rigid, fully closed state upon the addition of elemental ion cues. (1)H NMR spectroscopy titration studies show that in the semi-open state interligand hydrogen-bonding prevents substrate recognition by the squaramide unit, while in the fully closed state ligand–ligand interactions are prevented. This results in a catalytically active closed state, whereas in the semi-open state, when the piperidine tertiary amine is deliberately protonated, no catalytic activity is observed. Reversible interconversion between the active fully closed state and the dormant protonated semi-open state is achieved in the presence of substrate upon the concerted addition and abstraction of both a proton and a coordinating elemental anion. In this work, allosteric regulation of catalytic activity is demonstrated for both the Michael addition of nitroethane to β-nitrostyrene and the ring-opening of l-(–)-lactide. Taken together, this work details a potentially generalizable platform for the “on–off” allosteric regulation of a family of HBD–Lewis base co-catalysts capable of catalyzing a broad scope of reactions, including the living ring-opening polymerization of cyclic esters.