A synthetic analogue of the active site of Fe-containing nitrile hydratasewith carboxamido N and thiolato S as donors: Synthesis, structure, and reactivities

As part of our work on models of the iron(III) site of Fe-containing nitril e hydratase, a designed ligand PyPSH4 with two carboxamide and two thiolate donor groups has been synthesized. Reaction of (Et4N)-[FeCl4] with the dep rotonated form of the ligand in DMF affords the mononuclear iron(III) compl ex (Et4N)-[Fe-III(PyPS)] (1) in high yield. The iron(III) center is in a tr igonal bipyramidal geometry with two deprotonated carboxamido nitrogens, on e pyridine nitrogen, and two thiolato sulfurs as donors. Complex 1 is stabl e in water and binds a variety of Lewis bases at the sixth site at low temp erature to afford green solutions with a band around 700 nm. The iron(III) centers in these six-coordinate species are low-spin and exhibit EPR spectr a much like the enzyme. The pK(a) of the water molecule in [Fe-III(PyPS)(H2 O)](-) is 6.3 +/- 0.4. The iron(III) site in 1 with ligated carboxamido nit rogens and thiolato sulfurs does not show any affinity toward nitriles. It thus appears that at physiological pH, a metal-bound hydroxide promotes hyd ration of nitriles nested in close proximity of the iron center in the enzy me. Redox measurements demonstrate that the carboxamido nitrogens prefer Fe (III) to Fe(II) centers. This fact explains the absence of any redox behavi or at the iron site in nitrile hydratase. Upon exposure to limited amount o f dioxygen, 1 is converted to the bis-sulfinic species. The structure of th e more stable O-bonded sulfinato complex (Et4N)[Fe-III(PyP{SO2}(2))] (2) ha s been determined. Six-coordinated low-spin cyanide adducts of the S-bonded and the O-bonded sulfinato complexes, namely, Na-2[Fe-III(PyP{SO2}(2))(CN) ] (4) and (Et4N)(2)[Fe-III(PyP{SO2}(2))(CN)] (5), afford green solutions in water and other solvents. The iron(II) complex (Et4N)(2)[Fe-II(PyPS)] (3) has also been isolated and structurally characterized.