Protonation of a Peroxodiiron(III) Complex and Conversion to a Diiron(III/IV) Intermediate: Implications for Proton-Assisted O–O Bond Cleavage in Nonheme Diiron Enzymes

Abstract

Oxygenation of a diiron(II) complex,[FeII2(μ-OH)2(BnBQA)2(NCMe)2]2+ (2) (where BnBQA is N-benzyl-N,N-bis(2-quinolinylmethyl)amine) results in the formation of a metastable peroxodiferric intermediate (3). Treatment of 3 with strong acid affords its conjugate acid 4 in which the (μ-oxo)(μ-1,2-peroxo)diiron(III) core of 3 is protonated at the oxo bridge. The core structures of 3 and 4 are characterized in detail by UV-vis, Mössbauer, resonance Raman, and X-ray absorption spectroscopies. Complex 4 is shorter lived than 3 and decays to generate in 20–25% yield a diiron(III/IV) species (5) that can be identified by EPR and Mössbauer spectroscopy. This reaction sequence demonstrates for the first time that protonation of the oxo bridge of a (μ-oxo)(μ-1,2-peroxo)diiron(III) complex leads to the cleavage of the peroxo O–O bond and formation of a high-valent diiron complex, thereby mimicking the steps involved in the formation of intermediate X in the activation cycle of ribonucleotide reductase.

X-ray absorption spectroscopic characterization of the diferric-peroxo intermediate of human deoxyhypusine hydroxylase in the presence of its substrate eIF5a

“…Our data suggests that dioxygen is likely bound to the diiron(III) center as a 1,2-peroxo bridge [20]. Based on the available structures for synthetic peroxo-bridged diiron(III) complexes [50, 51, 70–72], such a ligand would be expected to have Fe–O bond distances of 1.87 – 1.98 Å, consistent with our observed distance of 1.98 Å.…”

“…This value is consistent with our previously published data [20] and higher than observed for hDOHH- R . hDOHH- P is likely 6-coordinate by comparison to synthetic 6-coordinate diferric peroxo complexes, which have pre-edge values that range from 13 – 16 units [50–52]. In contrast, hDOHH- P • S has a pre-edge feature centered higher in energy at 7114.1 eV with an area of 16.2 units, increased from hDOHH- P , indicating that the addition of substrate has decreased the symmetry around the diiron center.…”

Reactivity of the Binuclear Non-Heme Iron Active Site of Δ9 Desaturase Studied by Large-Scale Multireference Ab Initio Calculations

“…As the starting point, we consider the direct abstraction of the C 10 −H hydrogen atom by the "unactivated" P intermediate having the 1,2-μ peroxo structure (Scheme 2, path 1). Eight alternative reaction pathways are evaluated (paths 2−9), which involve a reactant that is derived from P via activation by a proton (2,4,5), water molecule (3), electron (6), electron/proton couple (7 and 8), or electron and water molecule (9). These pathways are discussed below.…”

Transition Metal Complexes and the Activation of Dioxygen

“…In work aimed at understanding how this might occur, reactions of (μ-1,2-peroxo)diiron(III,III) complexes with protic acids have been explored. Treatment of 70 ( Figure 35) with HClO 4 or HNO 3 was shown to result in initial protonation of the oxo bridge (71), followed by decay to the (μ-oxo)-diiron(III,IV) complex 72 that models intermediate X in ribonucleotide reductase [245]. Mechanistic details such as the source of the reducing equivalent required or how proton transfer from the hydroxo group induces breaking of the peroxo O-O bond in this system have yet to be elucidated.…”