A Structural and Functional Model for the Tris-Histidine Motif in Cysteine Dioxygenase

The iron(II) complexes [Fe(L)(MeCN)₃ ](SO₃ CF₃ )₂ (L are two derivatives of tris(2-pyridyl)-based ligands) have been synthesized as models for cysteine dioxygenase (CDO). The molecular structure of one of the complexes exhibits octahedral coordination geometry and the Fe-N_py bond lengths [1.953(4)-1.972(4) Å] are similar to those in the Cys-bound Fe^II -CDO; Fe-N_His : 1.893-2.199 Å. The iron(II) centers of the model complexes exhibit relatively high Fe^III/II redox potentials (E_1/2 =0.988-1.380 V vs. ferrocene/ferrocenium electrode, Fc/Fc⁺ ), within the range for O₂ activation and typical for the corresponding nonheme iron enzymes. The reaction of in situ generated [Fe(L)(MeCN)(SPh)]⁺ with excess O₂ in acetonitrile (MeCN) yields selectively the doubly oxygenated phenylsulfinic acid product. Isotopic labeling studies using ¹⁸ O₂ confirm the incorporation of both oxygen atoms of O₂ into the product. Kinetic and preliminary DFT studies reveal the involvement of an Fe^III peroxido intermediate with a rhombic S= $$ Fe^III center (687-696 nm; g≈2.46-2.48, 2.13-2.15, 1.92-1.94), similar to the spectroscopic signature of the low-spin Cys-bound Fe^III CDO (650 nm, g≈2.47, 2.29, 1.90). The proposed Fe^III peroxido intermediates have been trapped, and the O-O stretching frequencies are in the expected range (approximately 920 and 820 cm^-1 for the alkyl- and hydroperoxido species, respectively). The model complexes have a structure similar to that of the enzyme and structural aspects as well as the reactivity are discussed.