Modeling the active sites of diiron and dicopper metalloproteins with napthyridine-, phthalazine-, and diethynylbenzene-based ligands

Abstract

Chapter 1. Bio-Inspired Reactions of Diiron Centers with Dioxygen A variety of biological systems employ carboxylate-bridged diiron centers to achieve substrate oxidation using dioxygen, and numerous small molecule model compounds have been synthesized in order to mimic this chemistry in the absence of a protein scaffold. In this introductory chapter, a brief overview is presented of ligand systems that have been used to prepare diiron complexes, and the subsequent oxidation chemistry of these systems is outlined. Chapter 2. Carboxylate, Phosphodiester, and Hydroxide-Bridged Diiron(II) Complexes with a Sterically Hindered Phthalazine Ligand The synthesis and crystallographic characterization of a series of diiron(II) complexes with a sterically hindered bridging phthalazine ligand are presented. The compounds [Fe₂(Ph₄bdptz)([mu]-O₂CR)₂]²⁺ (R = CH₃ (3); C₂H₅ (4); CH₂Ph (5); t-C₄H₉ (6)), [Fe₂(Ph₄bdptz)([mu]-O₂P(OPh)₂)₂]²⁺ (7), and [Fe₂(Ph₄bdptz) ([mu]-OH)(MeCN)₂]³⁺ (8) were prepared as small molecule models of the catalytic sites in non-heme carboxylate-bridged diiron enzymes. The phenyl rings of Ph4bdptz form a hydrophobic size-constrained pocket in which additional ligands can be accommodated, and they block the possible formation of tetranuclear species. As the steric bulk of the ancillary ligands is increased, the carboxylates shift from a syn, anti to a syn, syn coordination mode, and the Mossbauer spectra of the diiron(II) compounds clearly reflect the symmetry of the iron coordination environment. The oxidation chemistry of the diiron(II) compounds is presented.

(cont.) Chapter 3. Modeling Features of the Non-Heme Diiron Cores in O0-Activating Enzymes through the Synthesis, Characterization, and Oxidation of 1,8-Naphthyridine-Based Complexes Multidentate naphthyridine-based ligands were used to prepare a series of diiron(II) complexes. The compounds [Fe₂(BPMAN)([mu]-O₂CPh)₂](OTf)₂ (1), [Fe₂(BPMAN)([mu]-OR) ([mu]-0₂CAr[superscript]Tol)] (OTf)2 (R = H (2); CH₃ (3)), [Fe₂(BBAN)([mu]-0₂CAr[superscript]Tol)₃]-(OTf) (4), and [Fe₂(BEAN) ([mu]-O₂CAr[superscript]Tol)₃](OTf) (5) were prepared as models of the active sites of non-heme diiron enzymes. The rigorously enforced dinuclear core allows the reactivity of the diiron unit to be evaluated. Upon oxidation of these compounds, there is evidence for the formation of a ([mu]-oxo)diiron(III) unit, a mixed-valent ([mu]-oxo)Fe(II)Fe(III) species, and oxidative N-dealkylation. The electrochemical properties of the compounds were correlated with the observed dioxygen reactivity, and Mossbauer spectroscopic properties of the diiron(II) complexes were also investigated. Chapter 4. Modeling the Syn Disposition of Nitrogen Donors at the Active Sites of Carboxylate-Bridged Diiron Enzymes. Enforcing Dinuclearity and Kinetic Stability with a 1,2-Diethynylbenzene-Based Ligand The syn coordination of histidine residues at the active sites of several carboxylate-rich non-heme diiron enzymes has not been effectively reproduced with small molecule model compounds. In this study, ligands derived from 1,8- naphthyridine, phthalazine, and 1,2-diethynylbenzene were employed to mimic this geometric feature ...