Iron(II)-Thiolate S-Oxygenation by O2: Synthetic Models of Cysteine Dioxygenase

The synthesis of structural and functional models of the active site of the nonheme iron enzyme cysteine dioxygenase (CDO) is reported. A bis(imino)pyridine ligand scaffold was employed to synthesize a mononuclear ferrous complex, FeII(LN3S)(OTf) (1), which contains three neutral nitrogen donors and one anionic thiolato donor. Complex 1 is a good structural model of the Cys-bound active site of CDO. Reaction of 1 with O2 results in oxygenation of the thiolato sulfur, affording the sulfonato complex FeII(LN3SO3)(OTf) (2) under mild conditions. Isotope labeling studies show that O2 is the sole source of O atoms in the product and that the reaction proceeds via a dioxygenase-type mechanism for two out of three O atoms added, analogous to the dioxygenase reaction of CDO. The zinc(II) analog, Zn(LN3S)(OTf) (4), was prepared and found to be completely unreactive toward O2, suggesting a critical role for FeII in the oxygenation chemistry observed for 1. To our knowledge, S-oxygenation mediated by an FeII−SR complex and O2 is unprecedented.