Basicity of MnIII-Hydroxo Complexes Controls the Thermodynamics of Proton-Coupled Electron Transfer Reactions

Several manganese-dependent enzymes utilize Mn^III-hydroxo units in concerted proton–electron transfer (CPET) reactions. We recently demonstrated that hydrogen bonding to the hydroxo ligand in the synthetic [Mn^III(OH)(PaPy₂N)]⁺ complex increased rates of CPET reactions compared to the [Mn^III(OH)(PaPy₂Q)]⁺ complex that lacks a hydrogen bond. In this work, we determine the effect of hydrogen bonding on the basicity of the hydroxo ligand and evaluate the corresponding effect on CPET reactions. Both [Mn^III(OH)(PaPy₂Q)]⁺ and [Mn^III(OH)(PaPy₂N)]⁺ react with strong acids to yield Mn^III-aqua complexes [Mn^III(OH₂)(PaPy₂Q)]²⁺ and [Mn^III(OH₂)(PaPy₂N)]²⁺, for which we determined pK_a values of 7.6 and 13.1, respectively. Reactions of the Mn^III-aqua complexes with one-electron reductants yielded estimates of reduction potentials, which were combined with pK_a values to give O–H bond dissociation free energies (BDFEs) of 77 and 85 kcal mol^–1 for the Mn^II-aqua complexes [Mn^II(OH₂)(PaPy₂Q)]⁺ and [Mn^II(OH₂)(PaPy₂N)]⁺. Using these BDFEs, we performed an analysis of the thermodynamic driving force for phenol oxidation by these complexes and observed the unexpected result that slower rates are associated with more asynchronous CPET. In addition, reactions of acidic phenols with the Mn^III-hydroxo complexes show rates that deviate from the thermodynamic trends, consistent with a change in mechanism from CPET to proton transfer.