The first example of a nitrile hydratase model complex that reversibly binds nitriles

Area of Science:

• Bioinorganic Chemistry
• Enzyme Mechanisms
• Organometallic Chemistry

Background:

• Nitrile hydratase (NHase) catalyzes nitrile to amide conversion, but its mechanism remains unclear.
• A proposed mechanism involves nucleophilic attack by water on an iron-bound nitrile.
• Understanding NHase's active site is crucial for elucidating its catalytic function.

Purpose of the Study:

• To synthesize and characterize an iron(III) complex mimicking the NHase active site environment.
• To investigate the binding of nitriles and other ligands to the model complex.
• To elucidate the mechanistic aspects of nitrile hydration by studying ligand binding and exchange kinetics.

Main Methods:

• Synthesis of a five-coordinate iron(III) complex, [Fe(III)(S(2)(Me2)N(3)(Et,Pr))](+).
• X-ray absorption spectroscopy (XAS) to study complex formation.
• Variable-temperature electronic absorption spectroscopy and 13C NMR line-broadening analysis for thermodynamic and kinetic studies.

Main Results:

• The model complex reversibly binds nitriles, alcohols, amines, and thiocyanate.
• XAS confirmed the formation of six-coordinate complexes upon reaction with methanol and acetonitrile.
• Competitive binding studies showed nitriles preferentially bind over alcohols, suggesting they can displace water from the iron site.
• Thermodynamic and kinetic parameters for nitrile and pyridine binding/exchange were determined, revealing significant lability of the iron(III) center.

Conclusions:

• This study provides the first evidence that iron(III) in an NHase-like environment can form stable nitrile complexes.
• The observed ligand exchange rates indicate that low-spin iron(III) in this environment is more labile than anticipated.
• Minor ligand-induced distortions in the iron coordination sphere significantly impact metal complex reactivity.