Synthetic Models of the Reduced Active Site of Superoxide Reductase

We report the synthesis, structural and spectroscopic characterization, and magnetic and electrochemical studies of a series of iron(II) complexes of the pyridyl-appended diazacyclooctane ligand L(8)py(2), including several that model the square-pyramidal [Fe(II)(N(his))(4)(S(cys))] structure of the reduced active site of the non-heme iron enzyme superoxide reductase. Combination of L(8)py(2) with FeCl(2) provides [L(8)py(2)FeCl(2)] (1), which contains a trigonal-prismatic hexacoordinate iron(II) center, whereas a parallel reaction using [Fe(H(2)O)(6)](BF(4))(2) provides [L(8)py(2)Fe(FBF(3))]BF(4) (2), a novel BF(4)(-)-ligated square-pyramidal iron(II) complex. Substitution of the BF(4)(-) ligand in 2 with formate or acetate ions affords distorted pentacoordinate [L(8)py(2)Fe(O(2)CH)]BF(4) (3) and [L(8)py(2)Fe(O(2)CCH(3))]BF(4) (4), respectively. Models of the superoxide reductase active site are prepared upon reaction of 2 with sodium salts of aromatic and aliphatic thiolates. These model complexes include [L(8)py(2)Fe(SC(6)H(4)-p-CH(3))]BF(4) (5), [L(8)py(2)Fe(SC(6)H(4)-m-CH(3))]BF(4) (6), and [L(8)py(2)Fe(SC(6)H(11))]BF(4) (7). X-ray crystallographic studies confirm that the iron(II)-thiolate complexes model the square-pyramidal geometry and N(4)S donor set of the reduced active site of superoxide reductase. The iron(II)-thiolate complexes are high spin (S = 2), and their solutions are yellow in color because of multiple charge-transfer transitions that occur between 300 and 425 nm. The ambient temperature cyclic voltammograms of the iron(II)-thiolate complexes contain irreversible oxidation waves with anodic peak potentials that correlate with the relative electron donating abilities of the thiolate ligands. This electrochemical irreversibility is attributed to the bimolecular generation of disulfides from the electrochemically generated iron(III)-thiolate species.