Regulating Access to Active Sites via Hydrogen Bonding and Cation-Dipole Interactions: A Dual Cofactor Approach to Switchable Catalysis

Hydrogen bonding networks are ubiquitous in biological systems and play a key role in controlling the conformational dynamics and allosteric interactions of enzymes. Yet in small organometallic catalysts, hydrogen bonding rarely controls ligand binding to the metal center. In this work, a hydrogen bonding network within a well-defined organometallic catalyst works in concert with cation-dipole interactions to gate substrate access to the active site. An ammine ligand acts as one cofactor, templating a hydrogen bonding network within a pendent crown ether in the secondary coordination sphere, an interaction which prevents the binding of nitriles to the nickel center. Sodium ions are a second cofactor, disrupting hydrogen bonding to enable ligand substitution reactions and substrate binding. Thermodynamic analyses provide insight into the energetic requirements of the different supramolecular interactions enabling substrate gating. Switchable ligand substitution and switchable hydroamination catalysis illustrate the dual cofactor approach.