A comparison of two-electron chemistry performed by the manganese and iron heterodimer and homodimers

Two-electron chemistry with an iron dimer, a manganese dimer, and a manganese–iron dimer as a catalyst has been modeled using B3LYP* hybrid density functional theory. The recently discovered MnFe proteins form (at least) two functionally distinct groups, performing radical generation (class Ic ribonucleotide reductase subunit II) and substrate oxidations (subunit II-like ligand-binding oxidases, R2lox), respectively. Proteins from the latter group appear to be functionally similar to the diiron carboxylate proteins that perform two-electron oxidations of substrates, such as methane monooxygenase. To qualitatively determine the potential role of a MnFe center in R2lox, methane hydroxylation with the MnFe heterodimer and with the FeFe and MnMn homodimers is studied. The redox potential of the active state of the Mn(IV)Fe(IV) heterodimer is about 7 kcal mol⁻¹ lower than that of the active state of the Fe(IV)Fe(IV) homodimer, leading to a high barrier for the rate-limiting hydrogen abstraction with the MnFe site. If the entropy loss is not included, the barriers are lower, and the MnFe heterodimer can therefore have a role in R2lox as an oxidase for larger substrates exergonically bound to the protein. A MnMn center has a high barrier both with and without entropy loss. The higher stability of Fe(IV) in the presence of Mn(IV) in the other site compared with a second Fe(IV) suggests an explanation for the presence of the MnFe site in R2lox: to provide a metal center that is capable of two-electron chemistry, and which is more stable and less sensitive to external reductants than an Fe(IV)Fe(IV) site.