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.

Dramatic rate-enhancement of oxygen atom transfer by an iron(iv)-oxo species by equatorial ligand field perturbations.

Nonheme iron dioxygenases are efficient enzymes with relevance for human health that regio- and stereospecifically transfer an oxygen atom to substrates. How they perform this task with such selectivity remains unknown, but may have to do with substrate binding, positioning and oxidant approach. To understand substrate approach on a catalytic reaction centre, we investigated the structure and reactivity of a biomimetic oxidant with ligand features that affect the interactions between oxidant and substrate. Thus, we report here the synthesis and characterization of an iron(iv)-oxo complex with pentadentate nonheme ligand, where structurally induced perturbations in the equatorial ligand field affect the spectroscopy and reactivity of the complex. We tested the activity of the complex with respect to oxygen atom transfer to and hydrogen atom abstraction from substrates. This oxidant shows improved reaction rates toward heteroatom oxidation with respect to the nonsubstituted ligand complex by ∼104 fold. The origin of the enhanced reactivity is explained with a series of density functional theory studies that show an enhanced electron affinity of the oxidant through equatorial ligand perturbations.