Decoding Proton-Coupled Electron Transfer with Potential-p K_a Diagrams: Applications to Catalysis

The applied potential at which [Ni^II(P₂^PhN₂^Bn)₂]²⁺ (P₂^PhN₂^Bn = 1,5-dibenzyl-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane) catalyzes hydrogen production is reported to vary as a function of proton source p K_a in acetonitrile. By contrast, most molecular catalysts exhibit catalytic onsets at p K_a-independent potentials. Using experimentally determined thermochemical parameters associated with reduction and protonation, a coupled Pourbaix diagram is constructed for [Ni^II(P₂^PhN₂^Bn)₂]²⁺. One layer describes proton-coupled electron transfer reactivity involving ligand-based protonation, and the second describes metal-based protonation. An overlay of this diagram with experimentally determined E _cat/2 values spanning 15 p K_a units, along with complementary stopped-flow rapid mixing experiments to detect reaction intermediates, supports a mechanism in which the proton-coupled electron transfer processes underpinning the p K_a-dependent catalytic processes involve protonation of the ligand, not the metal center. For proton sources with p K_a values in the range 6-10.6, the initial species formed is the doubly reduced, doubly protonated species [Ni⁰(P₂^PhN₂^BnH)₂]²⁺, despite a higher overpotential for this proton-coupled electron transfer reaction in comparison to forming the metal-protonated isomer. In this complex, each ligand is protonated in the exo position with the two amine moieties on each ligand binding a single proton and positioning it away from the metal center. This species undergoes very slow isomerization to form an endo-protonated hydride species [HNi^II(P₂^PhN₂^Bn)(P₂^PhN₂^BnH)]²⁺ that can release hydrogen to close the catalytic cycle. Importantly, this slow isomerization does not perturb the initially established proton-coupled electron transfer equilibrium, placing catalysis under thermodynamic control. New details revealed about the reaction mechanism from the coupled Pourbaix diagram and the complementary stopped-flow studies lead to predictions as to how this p K_a-dependent activity might be engendered in other molecular catalysts for multi-electron, multi-proton transformations.