Interplay Between Steric and Electronic Effects: A Joint Spectroscopy and Computational Study of Nonheme Iron(IV)‐Oxo Complexes

Iron is an essential element in nonheme enzymes that plays a crucial role in many vital oxidative transformations and metabolic reactions in the human body. Many of those reactions are regio‐ and stereospecific and it is believed that the selectivity is guided by second‐coordination sphere effects in the protein. Here, results are shown of a few engineered biomimetic ligand frameworks based on the N4Py (N,N‐bis(2‐pyridylmethyl)‐N‐bis(2‐pyridyl)methylamine) scaffold and the second‐coordination sphere effects are studied. For the first time, selective substitutions in the ligand framework have been shown to tune the catalytic properties of the iron(IV)‐oxo complexes by regulating the steric and electronic factors. In particular, a better positioning of the oxidant and substrate in the rate‐determining transition state lowers the reaction barriers. Therefore, an optimum balance between steric and electronic factors mediates the ideal positioning of oxidant and substrate in the rate‐determining transition state that affects the reactivity of high‐valent reaction intermediates. It takes two: A combined spectroscopy and computational study on engineered iron(IV)‐oxo complexes identified a second‐coordination sphere effect that enables better positioning of the iron(IV)‐oxo and higher reactivity.