Tuning Bro̷nsted Acidity by up to 12 pK_a Units in a Redox-Active Nanopore Lined with Multifunctional Metal Sites

Electrostatic interactions, hydrogen bonding, and solvation effects can alter the free energies of ionizable functional groups in proteins and other nanoporous architectures, allowing such structures to tune acid-base chemistry to support specific functions. Herein, we expand on this theme to examine how metal sites (M = H₂, Zn^II, Co^II, Co^I) affect the pK_a of benzoic acid guests bound in discrete porphyrin nanoprisms (M) in CD₃CN. These host-guest systems were chosen to model how porous metalloporphyrin electrocatalysts might influence H⁺ transfer processes that are needed to support important electrochemical reactions (e.g., reductions of H⁺, O₂, or CO₂). Usefully, the cavities of the host-guest complexes become hydrated at low water concentrations (10-40 mM), providing a good representation of the active sites of porous electrocatalysts in water. Under these conditions, Lewis acidic Co^II and Zn^II ions increase the Bro̷nsted acidities of the guests by 4 and 8 pK_a units, respectively, while reduction of the Co^II sites to anionic Co^I sites produces an electrostatic potential that lowers acidity by ca. 4 units (8 units relative to the Co^II state). Lacking functional metal sites, HTriCage increases the acidity of the guests by just 2.5 pK_a units despite the 12+ charge of this host and contributions from other factors (hydrogen bonding, hydration) that might stabilize the deprotonated guests. Thus, the metal sites have dominant effects on acid-base chemistry in the MTriCages, providing a larger pK_a range (12.75 to ≥24.5) for an encapsulated acid than attained via other confinement effects in proteins and artificial porous materials.