Peroxo-Type Intermediates in Class I Ribonucleotide Reductase and Related Binuclear Non-Heme Iron Enzymes

Kasper Planeta Kepp, Caleb B. Bell, MIchael D. Clay, Edward I. Solomon

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We have performed a systematic study of chemically possible peroxo-type intermediates occurring in the non-heme di-iron enzyme class la ribonucleotide reductase, using spectroscopically calibrated computational chemistry. Density functional computations of equilibrium structures, Fe-O and O-O stretch frequencies, Mossbauer isomer shifts, absorption spectra, J-coupling constants, electron affinities, and free energies Of O-2 and proton or water binding are presented for a series of possible intermediates. The results enable structure-property correlations and a new rationale for the changes in carboxylate conformations occurring during the O-2 reaction of this class of non-heme iron enzymes. Our procedure identifies and characterizes various possible candidates for peroxo intermediates experimentally observed along the ribonucleotide reductase dioxygen activation reaction. The study explores how water or a proton can bind to the di-iron site of ribonucleotide reductase and facilitate changes that affect the electronic structure of the iron sites and activate the site for further reaction. Two potential reaction pathways are presented: one where water adds to Fe1 of the cis-mu-1,2 peroxo intermediate P causing opening of a bridging carboxylate to form intermediate P' that has an increased electron affinity and is activated for proton-coupled electron transfer to form the Fe(Ill)Fe(IV) intermediate X; and one that is more energetically favorable where the P to P' conversion involves addition of a proton to a terminal carboxylate. ligand in the site which increases the electron affinity and triggers electron transfer to form X. Both pathways provide a mechanism for the activation of peroxy intermediates in binuclear non-heme iron enzymes for reactivity. The studies further show that water coordination can induce the conformational changes observed in crystal structures of the met state.
Original languageEnglish
JournalJournal of the American Chemical Society
Issue number34
Pages (from-to)12155-12171
Publication statusPublished - 2009

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