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, Fe(II)(LN(3)S)(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 O(2) results in oxygenation of the thiolato sulfur, affording the sulfonato complex Fe(II)(LN(3)SO(3))(OTf) (2) under mild conditions. Isotope labeling studies show that O(2) 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(LN(3)S)(OTf) (4), was prepared and found to be completely unreactive toward O(2), suggesting a critical role for Fe(II) in the oxygenation chemistry observed for 1. To our knowledge, S-oxygenation mediated by an Fe(II)-SR complex and O(2) is unprecedented.
Jiang
Yunbo
Y
Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21212, USA.
Widger
Leland R
LR
Kasper
Gary D
GD
Siegler
Maxime A
MA
Goldberg
David P
DP
D055162:Biocatalysis; D018360:Crystallography, X-Ray; D050558:Cysteine Dioxygenase / Q000737:chemistry / Q000378:metabolism*; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D005296:Ferrous Compounds; D013438:Sulfhydryl Compounds; D050558:Cysteine Dioxygenase; D010100:Oxygen