Spectroscopic and Computational Studies of (μ-Oxo)(μ-1,2-peroxo)diiron(III) Complexes of Relevance to Nonheme Diiron Oxygenase Intermediates

Abstract

With the goal of gaining insight into the structures of peroxo intermediates observed for oxygen activating nonheme diiron enzymes, a series of metastable synthetic diiron(III)-peroxo complexes with [FeIII2(µ-O)(µ-1,2-O2)] cores has been characterized by X-ray absorption and resonance Raman spectroscopy. EXAFS analysis shows that this basic core structure gives rise to an Fe-Fe distance of ~3.15 Å; the distance is decreased by 0.1 Å upon introduction of an additional carboxylate bridge. In corresponding resonance Raman studies, vibrations arising from both the Fe-O-Fe and the Fe-O-O-Fe units can be observed. A change in the Fe-Fe distance affects the ν(O-O) mode, as well as the νsym(Fe-O-Fe) and the νasym(Fe-O-Fe) modes. Indeed a linear correlation can be discerned between the ν(O-O) frequency of a complex and its Fe-Fe distance among the subset of complexes with [FeIII2(µ-OR)(µ-1,2-O2)] cores (R = H, alkyl, aryl, or no substituent). These experimental studies are complemented by a normal coordinate analysis and DFT calculations.

Crystal structure of CmlI, the arylamine oxygenase from the chloramphenicol biosynthetic pathway

“…The model angles are 126° (∠Fe1-O1-O2), 107° (∠Fe2-O2-O1) and dihedral −38° (∠Fe1-O1-O2-Fe2). These values compare well with other structurally characterized diferric cis µ -1,2-peroxo species in diiron proteins or model compounds (Table 2) [44–49]. Overall, the CmlIΔ33 iron-peroxo bond distances (1.8, 2.0 Å) are more similar to those observed in inorganic model complexes than in other diiron protein crystals, which exhibit longer bonds.…”

Human deoxyhypusine hydroxylase, an enzyme involved in regulating cell growth, activates O 2 with a nonheme diiron center

“…As the Fe-O-O angle is related to the FeϪFe distance, the (O-O) can reflect the FeϪFe distance. This mechanical coupling model is supported by a recent study of a series of synthetic (cis--1,2-peroxo)diiron(III) complexes (32). Indeed, a detailed spectroscopic and DFT analysis of the W48F/D84E R2 peroxo intermediate also questions the 2.5-Å FeϪFe distance deduced by EXAFS and favors an FeϪFe distance of 3.68 Å (18) that is closer to the 3.44 Å distance we have determined for hDOHH peroxo by EXAFS analysis.…”

“…Indeed a number of metastable synthetic complexes are characterized to have core structures like that shown in Fig. 6; some in fact are stable enough to have been crystallized (31)(32)(33)(34). As the target hydroxylation site of hDOHH resides on a protein substrate, it seems plausible that substrate binding triggers a conformation change that activates the ( -1,2-peroxo)diiron(III) intermediate to carry out eIF5A(Dhp) hydroxylation (Scheme 1).…”

Unprecedented (μ-1,1-Peroxo)diferric Structure for the Ambiphilic Orange Peroxo Intermediate of the Nonheme N-Oxygenase CmlI

“…82 Since the original 1989 study, examples of oxo-bridged diiron complexes with an additional μ -1,2-peroxo bridge (green squares) have been characterized, 32, 60–62, 83 as well as complexes with bis( μ -oxo)diiron diamond cores. 84–86 These new data have been included to the plot shown in Figure 6 and extend the correlation to entries with Fe–O–Fe angles approaching 90°.…”