Rational Tuning of the Thiolate Donor in Model Complexes of Superoxide Reductase: Direct Evidence for a trans Influence in Fe^III−OOR Complexes

Abstract

Iron peroxide species have been identified as important intermediates in a number of non-heme iron as well as heme-containing enzymes, yet there are only a few examples of such species either synthetic or biological that have been well characterized. We describe the synthesis and structural characterization of a new series of five-coordinate (N 4 S(thiolate))Fe II complexes that react with tert-butyl hydroperoxide (tBuOOH) or cumenyl hydroperoxide (CmOOH) to give metastable alkylperoxo-iron(III) species (N 4 S(thiolate)Fe III -OOR) at low temperature. These complexes were designed specifically to mimic the non-heme iron active site of superoxide reductase, which contains a five-coordinate iron(II) center bound by one Cys and four His residues in the active form of the protein. The structures of the Fe II complexes are analyzed by X-ray crystallography, and their electrochemical properties are assessed by cyclic voltammetry. For the Fe III -OOR species, lowtemperature UV-vis spectra reveal intense peaks between 500 -550 nm that are typical of peroxide to iron(III) ligand-to-metal charge-transfer (LMCT) transitions, and EPR spectroscopy shows that these alkylperoxo species are all low-spin iron(III) complexes. Identification of the vibrational modes of the Fe III -OOR unit comes from resonance Raman (RR) spectroscopy, which shows ν(Fe-O) modes between 600 -635 cm −1 and ν(O-O) bands near 800 cm −1 . These Fe-O stretching frequencies are significantly lower than those found in other low-spin Fe III -OOR complexes. Trends in the data conclusively show that this weakening of the Fe-O bond arises from a trans influence of the thiolate donor, and DFT calculations support these findings. These results suggest a role for the cysteine ligand in SOR, and are discussed in light of the recent assessments of the function of the cysteine ligand in this enzyme.

Thioether-ligated iron(ii) and iron(iii)-hydroperoxo/alkylperoxo complexes with an H-bond donor in the second coordination sphere

“…Monitoring the reaction by UV-vis spectroscopy shows the isosbestic conversion of the peaks corresponding to 1 , into a new spectrum (λ max = 600 nm, ε = 1670 M −1 cm −1 ) that is characteristic of an alkylperoxo-to-iron( iii ) LMCT band and is in good agreement with similar compounds reported in the literature. 14,29 The UV-vis spectra reveal that 1 reacts with t BuOOH to form 6 within 10 min, but is only stable for a short period and begins to decay after 15 min. The new species ( 6 ) is assigned as the alkylperoxo complex [Fe III (OO t Bu)(N3PySR)] 2+ .…”

Proton-Coupled Electron Transfer in Organic Synthesis: Fundamentals, Applications, and Opportunities

“…Moreover, the axial ligation of the metal oxo in iron heme proteins has been demonstrated to have a profound effect on the pK a of the Fe IV oxo form of the enzyme [49] as well as the Fe-O bond strength observed in model systems [50].…”

Synthesis and reactivity of a 4His enzyme model complex

“…In this mechanism, the iron(II) center in 1 first becomes oxidized to Fe(III) (due to the presence of ambient oxygen and possibly forming an LFe III -O 2 − species 59 ) and reacts with the hydrogen peroxide to form what is believed, based on spectroscopic characteristics, to be a LFe III -OOH species. 60-62 The protonated superoxide species would be displaced. Since triphenylmethyl is known to form the stable triphenylmethyl radical (Ph 3 C·), 63 we hypothesize that this species exchanges with the hydroperoxo group and forms LFe III -OOCPh 3 which along with LFe III -OOH could account for the dark brown-purple intermediate species.…”