DFT Study of the Active Site of the XoxF-Type Natural, Cerium-Dependent Methanol Dehydrogenase Enzyme

Rare‐earth metal cations have recently been demonstrated to be essential co‐factors for the growth of the methanotrophic bacterium Methylacidiphilum fumariolicum SolV. A crystal structure of the rare‐earth‐dependent methanol dehydrogenase (MDH) includes a cerium cation in the active site. Herein, the Ce–MDH active site has been analyzed through DFT calculations. The results show the stability of the CeIII–pyrroloquinoline quinone (PQQ) semiquinone configuration. Calculations on the active oxidized form of this complex indicate a 0.81 eV stabilization of the PQQ0 LUMO at cerium versus calcium, supporting the observation that the cerium cation in the active site confers a competitive advantage to Methylacidiphilum fumariolicum SolV. Using reported aqueous electrochemical data, a semi‐empirical correlation was established based on cerium(IV/III) redox potentials. The correlation allowed estimation of the cerium oxidation potential of +1.35 V versus saturated calomel electrode (SCE) in the active site. The results are expected to guide the design of functional model complexes and alcohol‐oxidation catalysts based on lanthanide complexes of biologically relevant quinones. The electronic structure of the active site of the XoxF‐type, natural cerium‐dependent methanol dehydrogenase enzyme was studied by using DFT. A semi‐empirical correlation was developed to gauge the Lewis acidity of the central cerium cation. The correlation predicted an oxidation potential of +1.35 V versus a saturated calomel electrode (SCE); this is expected to guide in the design of biomimetic rare‐earth catalysts for the oxidation of alcohols and aldehydes (see figure).