Synthetic analogues of [Fe4S4(Cys)3(His)] in hydrogenases and [Fe4S4(Cys)4] in HiPIP derived from all-ferric [Fe4S4{N(SiMe3)2}4].

The all-ferric [Fe(4)S(4)](4+) cluster [Fe(4)S(4){N(SiMe(3))(2)}(4)] 1 and its one-electron reduced form [1](-) serve as convenient precursors for the synthesis of 31-site differentiated [Fe(4)S(4)] clusters and high-potential iron-sulfur protein (HiPIP) model clusters. The reaction of 1 with four equivalents (equiv) of the bulky thiol HSDmp (Dmp = 2,6-(mesityl)(2)C(6)H(3), mesityl = 2,4,6-Me(3)C(6)H(2)) followed by treatment with tetrahydrofuran (THF) resulted in the isolation of [Fe(4)S(4)(SDmp)(3)(THF)(3)] 2. Cluster 2 contains an octahedral iron atom with three THF ligands, and its Fe(S)(3)(O)(3) coordination environment is relevant to that in the active site of substrate-bound aconitase. An analogous reaction of [1](-) with four equiv of HSDmp gave [Fe(4)S(4)(SDmp)(4)](-) 3, which models the oxidized form of HiPIP. The THF ligands in 2 can be replaced by tetramethyl-imidazole (Me(4)Im) to give [Fe(4)S(4)(SDmp)(3)(Me(4)Im)] 4 modeling the [Fe(4)S(4)(Cys)(3)(His)] cluster in hydrogenases, and its one-electron reduced form [4](-) was synthesized from the reaction of 3 with Me(4)Im. The reversible redox couple between 3 and [3](-) was observed at E(1/2) = -820 mV vs. Ag/Ag(+), and the corresponding reversible couple for 4 and [4](-) is positively shifted by +440 mV. The cyclic voltammogram of 3 also exhibited a reversible oxidation couple, which indicates generation of the all-ferric [Fe(4)S(4)](4+) cluster, [Fe(4)S(4)(SDmp)(4)].