Tuning Brønsted Acidity by up to 12 pKa 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 enclosed porous architectures, allowing these nanostructures to tune acid-base chemistry as needed to support specific functions. Herein, we expand on this theme to examine how metal sites (M = H2, ZnII, CoII, CoI) affect the pKa of benzoic acid guests bound in discrete porphyrin nanoprisms (M3TriCage), which were chosen as model systems for better understanding how porous metalloporphyrin electrocatalysts might influence H+ transfer processes that are needed to support many important electrochemical reactions (e.g., reductions of H+, O2, or CO2). Lewis acidic CoII and ZnII ions increase the Brønsted acidities of the guests by 4 and 8 pKa units, respectively, while reduction of the CoII sites to anionic CoI sites produces an electrostatic potential that lowers acidity by ca. 4 units (8 units relative to the CoII state). Lacking functional metal sites, H6TriCage increases the acidity of the guests by just 2.5 pKa units despite the 12+ charge of the host and contributions from other factors (hydrogen bonding, pore hydration) that might stabilize the depro-tonated guests. Thus, the metal sites have dominant effects on acid-base chemistry in the M3TriCages, providing a larger pKa range (12.75 to ≥24.5 in CD3CN) for the encapsulated acid than attained via other confinement effects in proteins and artificial porous materials.