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

Abstract

Iron is an essential elementi nn onheme enzymes that plays ac rucial role in many vital oxidative transformations and metabolic reactions in the human body.M any of those reactions are regio-ands tereospecific 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, selectives ubstitutions 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,abetter positioning of the oxidant and substrate in the rate-determining transition state lowers the reactionb arriers. Therefore, an optimum balance between steric and electronic factors mediates the ideal positioning of oxidanta nd substrate in the rate-determining transition state that affects the reactivity of high-valent reaction intermediates.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.

Selective Hydrogen Atom Abstraction from Dihydroflavonol by a Nonheme Iron Center Is the Key Step in the Enzymatic Flavonol Synthesis and Avoids Byproducts

“…[64][65][66][67][68][69][70][89][90][91][92][93] By contrast, with iron in octahedral coordination environment typically a triplet spin ground state is found with the quintet spin well higher in energy. [94][95][96][97] The optimized geometry of the reactant structures also highlights key interactions of the substrate with the protein that lock it into position. Thus, the phenol group of the substrate forms hydrogen bonding interactions with the alcohol groups of Ser 236 and Thr 239 .…”

Bioengineering of Cytochrome P450 OleTJE: How Does Substrate Positioning Affect the Product Distributions?

“…All calculations were done for the doublet and quartet spin states. These methods have previously been applied for the studies of enzymatic reaction mechanisms and shown to reproduce experimental rate constants, regioselectivities and kinetic isotope effects well [96][97][98][99][100][101].…”

Hydrogen-atom and oxygen-atom transfer reactivities of iron(iv)-oxo complexes of quinoline-substituted pentadentate ligands

“…Although the quinoline entity is a relatively strong donor, the weakened equatorial field that is a consequence of the steric effect results in higher HAT and OAT rates relative to other iron complexes containing ligands of the N4Py framework. 27 Considering the established high reactivity of 7 and the steric nature of its origin, and the ability of its precursor 3 to function as a ( pre)catalyst for alkane and alkene oxidation, we…”