Structures, Spectroscopic Properties, and Dioxygen Reactivity of 5- and 6-Coordinate Nonheme Iron(II) Complexes: A Combined Enzyme/Model Study of Thiol Dioxygenases.

The synthesis of four new Fe(NS(thiolate)) complexes as models of the thiol dioxygenases are described. They are composed of derivatives of the neutral, tridentate ligand triazacyclononane (RTACN; R = Me, iPr) and 2-aminobenzenethiolate (abt; X = H, CF), 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(MeTACN)(abt)(OTf) (1: X = H; 2: X = CF) and 5-coordinate (5-coord) complexes for Fe(iPrTACN)(abt) (3: X = H; 4: X = CF). Complexes 1-4 were examined by UV-vis, H/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 active site. Reaction of 1 or 2 with O at -95 °C leads to S-oxygenation of the abt ligand, and in the case of 2, a rare di(sulfinato)-bridged complex, Fe(μ-O)((2-NH) p-CFCHSO) ( 5), was obtained. Parallel enzymatic studies on the CDO variant C93G were carried out with the abt substrate and show that reaction with O 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 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.