Modeling the Syn Disposition of Nitrogen Donors in Non-Heme Diiron Enzymes. Synthesis, Characterization, and Hydrogen Peroxide Reactivity of Diiron(III) Complexes with the Syn N-Donor Ligand H₂BPG₂DEV

Abstract

In order to model the syn disposition of histidine residues in carboxylate-bridged non-heme diiron enzymes, we prepared a new dinucleating ligand, H2BPG2DEV, that provides this geometric feature. The ligand incorporates biologically relevant carboxylate functionalities, which have not been explored as extensively as nitrogen-only analogs. Three novel oxo-bridged diiron(III) complexes [Fe2(μ-O)(H2O)2-(BPG2DEV)](ClO4)2 (6), [Fe2(μ-O)(μ-O CAriPrO)(BPG2DEV)](ClO4) (7), and [Fe2(μ-O)(μ-CO3)(BPG2DEV)] (8) were prepared. Single crystal X-ray structural characterization confirms that two pyridines are bound syn with respect to the Fe–Fe vector in these compounds. The carbonato-bridged complex 8 forms quantitatively from 6 in a rapid reaction with gaseous CO2 in organic solvents. A common maroon-colored intermediate (λmax = 490 nm; ε = 1500 M−1 cm−1) forms in reactions of 6, 7, or 8 with H2O2 and NEt3 in CH3CN/H2O solutions. Mass spectrometric analyses of this species, formed using 18O-labeled H2O2, indicate the presence of a peroxide ligand bound to the oxo-bridged diiron(III) center. The Mössbauer spectrum at 90 K of the EPR-silent intermediate exhibits a quadrupole doublet with trueδ. = 0.58 mm/s and ΔEQ = 0.58 mm/s. The isomer shift is typical for a peroxodiiron(III) species, but the quadrupole splitting parameter is unusually small compared to related complexes. These Mössbauer parameters are comparable to those observed for a peroxo intermediate formed in the reaction of reduced toluene/o-xylene monooxygenase hydroxylase (ToMOH) with dioxygen. Resonance Raman studies reveal an unusually low-energy O–O stretching mode in the peroxo intermediate that is consistent with a short diiron distance. Although peroxodiiron(III) intermediates generated from 6, 7, and 8 are poor O-atom transfer catalysts, they display highly efficient catalase activity, with turnover numbers up to 10,000. In contrast to hydrogen peroxide reactions of diiron(III) complexes that lack a dinucleating ligand, the intermediates generated here could be reformed in significant quantities after a second addition of H2O2, as observed spectroscopically and by mass spectrometry.

Current challenges of modeling diiron enzyme active sites for dioxygen activation by biomimetic synthetic complexes

“…The more recently introduced BPG 2 DEV 2− ligand affords three oxo-bridged diiron(III) complexes, [Fe 2 ( μ -O)(H 2 O) 2 -BPG 2 DEV](ClO 4 ) 2 , [Fe 2 ( μ -O)( μ -O 2 CAr i PrO )BPG 2 DEV]-(ClO 4 ), and [Fe 2 ( μ -O)( μ -CO 3 )BPG 2 DEV], which form a peroxodiiron(III) species upon reaction with hydrogen peroxide 72. The spectroscopic properties of these inter-mediates differ significantly from those of related ( μ -oxo)( μ -peroxo)diiron(III) species,73 which may be due to the rigid scaffold that restrains the diiron distance to shorter values or to protonation of the peroxo species.…”

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

“…Indeed in the past twenty years many synthetic peroxodiferric complexes have been trapped and spectroscopically characterized from the reactions of diiron(II) precursors with O 2 or diiron(III) complexes with H 2 O 2 . 27,36–51 Some of these intermediates are stable enough to have been crystallized, and crystal structures of five such complexes have been reported. 39–41,45 In each case, there is a ( cis -μ-1,2-peroxo)diferric center that is supported by one or two additional bridging groups such as oxo, hydroxo, alkoxo and/or a bidentate carboxylate, which constrain the Fe•••Fe distances to a range from 3.2 – 4 Å (Table 1).…”

Evolution of strategies to prepare synthetic mimics of carboxylate-bridged diiron protein active sites

“…Lippard, Unpublished work]. Such undesired [Fe II 2 ( syn N -donor) 2 ] species were avoided by the use of ligands bearing polydentate nitrogen-rich metal binding groups [109]. Only diiron(III) complexes, however, could be prepared from these ligands.…”