The properties of the hydrogenase-inspired [Ni(PNP)₂]²⁺ (PNP = Et₂PCH₂NMeCH₂PEt₂) catalyst for homogeneous hydrogen oxidation in acetonitrile solution are explored from a theoretical perspective for hydrogen production. The defining characteristic of this catalyst is the presence of pendent bases in the second coordination sphere that function as proton relays between the solution and the metal center. DFT calculations of the possible intermediates along proposed catalytic pathways are carried out and used to construct coupled Pourbaix diagrams of the redox processes and free-energy profiles along the reaction pathways. Analysis of the coupled Pourbaix diagrams reveals insights into the intermediate species and the mechanisms favored at different pH values of the solution. Consideration of the acid–base behavior of the metal hydride and H₂ adduct species imposes additional constraints on the reaction mechanism, which can involve intramolecular as well as intermolecular proton-coupled electron-transfer steps. The efficacy of the catalyst is shown to depend critically on the pK_a values of these potential intermediates, as they control both the species in solution at a given pH and the free-energy profile of reaction pathways. Optimal relationships among these pK_a values can be identified, and it is demonstrated that “proton management”, i.e., the manipulation of these pK_a values (e.g., through choice of metal or substituents on ligands), can serve as a design principle for improved catalytic behavior.