Structural and oxidative reactivity studies of copper complexes with differing ligand environments: Toward understanding copper-protein (peptide) and enzyme chemistry

The study of suitably designed model compounds can lead to fundamental chemical insights into enzyme structure, spectroscopy, and reactivity. Structural and oxidative reactivity studies of copper(I) complexes with differing ligand environments to understand copper-protein (peptide) and enzyme chemistry are described in this dissertation.;In Chapter 1, we review copper proteins and copper model chemistry. The active site structures and catalytic mechanisms of the most well studied copper enzymes are described. The contributions to the understanding of enzyme function obtained from biomimetic studies using synthetic copper complexes are also highlighted.;In Chapter 2, model compounds for active-site Cu ions bound by contiguous His residues in certain oxygen-activating copper proteins, as well as the Alzheimer's disease associated Abeta-peptide are described. CuI complexes of modified His-His dipeptides possess linear, two-coordinate geometry and show limited-to-no reactivity with O2. Addition of a 3 rd ligand affords distorted T-shaped complexes and different reactivity, including CO binding and oxidation occurs rapidly upon exposure to dioxygen. On the other hand, copper(I) binds to Abeta-peptide fragments as a stable bis(histidine), two-coordinate, near-linear complex, even in the presence of potential additional ligands. Copper(I)-peptide complexes react with dioxygen to form H2O2, without the need for a 3 rd histidine ligand.;In Chapter 3, CuI and CuII complexes of His-Gly-His tripeptides are described. The CuI complex of delta-HGH shows a near-linear 2-coordinate geometry, formed via intermolecular binding and no redox activity, similar to findings for the CuIHisHis systems. On the other hand, the CuI complex of &egr;-HGH shows two His ligation but with some deviation from linearity while displaying different electrochemical and CO-binding behaviors and enhanced reactivity toward O2 and H2O2 compared to the delta-HGH system. In addition, oxidative nucleophilic reactions are described from hydroperoxo-copper(II) species with the &egr;-HGH ligand.;In Chapter 4, we describe the X-ray crystal structure of [{Cu(MeAN)} 2(O22-)]2+ (SbF6 - salt). The results indicate the presence of an unusually long O--O bond (O--O = 1.540(5) A). Solid-state EXAFS and rR spectroscopic studies on [{Cu(MeAN)}2(O22-)] 2+ indicate the exclusive formation of the mu-eta2:eta 2-peroxo-dicopper(II) isomer. The reversible nature of O2-binding is demonstrated via UV-Vis monitoring; the lack of reactivity of this peroxo complex is described.;In Chapter 5, the effect of thioether coordination in copper-O2 chemistry, demonstrated in complexes of tridentate N2S ligands, is described. Copper(I) complexes are synthesized and their redox properties, CO-binding, and O2-reactivity are investigated. Detailed spectroscopic and structural discussions (especially concerning S-donor coordination in Cu2/O2 adducts) are provided.