Rational tuning of the thiolate donor in model complexes of superoxide reductase: Direct evidence for a trans influence in Fe^III-OOR complexes

Iron peroxide species have been identified as important intermediates in a number of nonheme 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 (N₄S(thiolate))Fe^II complexes that react with tert-butyl hydroperoxide (^tBuOOH) or cumenyl hydroperoxide (CmOOH) to give metastable alkylperoxo-iron(III) species (N₄S(thiolate)Fe^III-OOR) at low temperature. These complexes were designed specifically to mimic the nonheme 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, low-temperature 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 density functional theory (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.