To examine inhibitor binding to an iron site resembling that of the metalloenzyme nitrile hydratase (NHase), a coordinatively unsaturated, five-coordinate Fe-III thiolate complex was synthesized, and its reactivity examined. Ferricinium hexafluorophosphate induced oxidation of gem-dimethyl-protected [(FeS2N3)-S-II-N-Me2(Pr,Pr)] affords the chiral, five-coordinate complex [(FeS2N3)-S-III-N-Me2(Pr,Pr)](+) (2) in reasonable yields. The magnetic properties and EPR of 2 an consistent with an S = 1/2 ground state. This unusual spin state, in conjunction with the low coordination number, of 2 result in unusually short Fe-S bonds (2.15(2) Angstrom). Ligand constraints distort the S-Fe-N angles in 2 and create an open (132.3(1)degrees) reactive site. Azide binds to this site to afford a model for the azide-inhibited form of NHase [(FeS2N3)-S-III-N-Me2(Pr,Pr)(N-3)] (3). In MeOH azide binds reversibly, whereas in MeCN it binds irreversibly. This demonstrates that the secondary coordination sphere (i.e., the solvent, or possibly a protein binding pocket) can have a dramatic influence on the substrate binding properties of a metal complex. A variable-temperature equilibrium study in MeOH afforded thermodynamic parameters (Delta H = -5.2 +/- 0.9 kcal/mol and Delta S = -12.4 +/- 0.4 eu) for the binding of this inhibitor. The electronic spectrum of 3 displays an intense band at 708 (1600) nm similar to that (710 (similar to 1200) nm) of the pH = 7.3 form of NHase, and other six-coordinate cis-dithiolate ligated Fem complexes synthesized by our group. EPR parameters for 3 (g = 2.23, 2.16, 1.99) are nearly identical to those of the azide-inhibited form of NHase (g = 2.23, 2.14, 1.99), suggesting that (1) the iron site of our model closely resembles that of the enzyme, and (2) azide binds directly to the metal ion in NHase. Reactivity is oxidation-state dependent, and the reduced analogue of 2, [(FeS2N3)-S-II(Pr,Pr)] (4), reversibly binds CO, but not azide, whereas oxidized 2 binds azide, but not CO.