Abstract
The synthesis of four new Fe(II)(N(4)S(thiolate)) complexes as models of the thiol dioxygenases are described. They are composed of derivatives of the neutral, tridentate ligand triazacyclononane (R(3)TACN; R = Me, iPr) and 2-aminobenzenethiolate (abt(x); X = H, CF(3)), a non-native substrate for thiol dioxygenases. The coordination number of these complexes depends on the identity of the TACN derivative, giving 6-coordinate (6-coord) complexes for Fe(II)(Me(3)TACN)(abt(x))(OTf) (1: X = H; 2: X = CF(3)) and 5-coordinate (5-coord) complexes for [Fe(II)(iPr(3)TACN)(abt(x))](OTf) (3: X = H; 4: X = CF(3)). Complexes 1-4 were examined by UV-vis, (1)H/(19)F NMR, and Mössbauer spectroscopies, and density functional theory (DFT) calculations were employed to support the data. Mössbauer spectroscopy reveals that the 6-coord 1-2 and 5-coord 3- 4 exhibit distinct spectra, and these data are compared with that for cysteine-bound CDO, helping to clarify the coordination environment of the cys-bound Fe(II) active site. Reaction of 1 or 2 with O(2) at -95 °C leads to S-oxygenation of the abt ligand, and in the case of 2, a rare di(sulfinato)-bridged complex, [Fe(2)(III)(μ-O)((2-NH(2)) p-CF(3)C(6)H(3)SO(2))(2)](OTf)(2) ( 5), was obtained. Parallel enzymatic studies on the CDO variant C93G were carried out with the abt substrate and show that reaction with O(2) leads to disulfide formation, as opposed to S-oxygenation. The combined model and enzyme studies show that the thiol dioxygenases can operate via a 6-coord Fe(II) center, in contrast to the accepted mechanism for nonheme iron dioxygenases, and that proper substrate chelation to Fe appears to be critical for S-oxygenation.