Probing the Mechanism for 2,4′-Dihydroxyacetophenone Dioxygenase Using Biomimetic Iron Complexes

Abstract

In this study, we report the synthesis and characterization of [Fe­(T1Et4iPrIP)­(2-OH-AP)­(OTf)]­(OTf) (2), [Fe­(T1Et4iPrIP)­(2-O-AP)]­(OTf) (3), and [Fe­(T1Et4iPrIP)­(DMF)3]­(OTf)3 (4) (T1Et4iPrIP = tris­(1-ethyl-4-isopropyl-imidazolyl)­phosphine; 2-OH-AP = 2-hydroxyacetophenone, and 2-O-AP– = monodeprotonated 2-hydroxyacetophenone). Both 2 and 3 serve as model complexes for the enzyme–substrate adduct for the nonheme enzyme 2,4′-dihydroacetophenone (DHAP) dioxygenase or DAD, while 4 serves as a model for the ferric form of DAD. Complexes 2–4 have been characterized by X-ray crystallography which reveals T1Et4iPrIP to bind iron in a tridentate fashion. Complex 2 additionally contains a bidentate 2-OH-AP ligand and a monodentate triflate ligand yielding distorted octahedral geometry, while 3 possesses a bidentate 2-O-AP– ligand and exhibits distorted trigonal bipyramidal geometry (τ = 0.56). Complex 4 displays distorted octahedral geometry with 3 DMF ligands completing the ligand set. The UV–vis spectrum of 2 matches more closely to the DAD-substrate spectrum than 3, and therefore, it is believed that the substrate for DAD is bound in the protonated form. TD-DFT studies indicate that visible absorption bands for 2 and 3 are due to MLCT bands. Complexes 2 and 3 are capable of oxidizing the coordinated substrate mimics in a stoichiometric and catalytic fashion in the presence of O2. Complex 4 does not convert 2-OH-AP to products under the same catalytic conditions; however, it becomes anaerobically reduced in the presence of 2 equiv 2-OH-AP to 2.