LIGAND ARCHITECTURE EFFECTS UPON PRIMARY COPPER-DIOXYGEN ADDUCT CHEMISTRY

Copper;Oxygen;Superoxo;Cupric;phenol oxidation;C-H activation;thioether;ligand-copper;Mechanism;peptide chemistry;Chemistry

Lee, Jung Yoon CatherineKarlin, Kenneth D ;

Johns Hopkins University

关键词: Copper;    Oxygen;    Superoxo;    Cupric;    phenol oxidation;    C-H activation;    thioether;    ligand-copper;    Mechanism;    peptide chemistry;    Chemistry;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60581/LEE-DISSERTATION-2015.pdf?sequence=1&isAllowed=n

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

The investigation into the chemical/physical properties of synthetic copper complexes provide fundamental insights into the understanding of the enzyme chemistry overviewed in this dissertation.In Chapter 1, copper monooxygenases and oxidases involved in C–H/O–H bond oxidation are introduced, along with biological functions, coordination environment of their metal active sites and their proposed mechanisms. Recent investigations of various synthetic oxygen-derived copper intermediates, including their characteristics and reactivity, are described. Possible reaction mechanisms are also highlighted by comparison to aqueous O2-reduction chemistry. In Chapter 2, with the goal of understanding the mechanism of phenol oxidation by mononuclear cupric superoxo species, kinetic studies were performed with the reaction of a new copper(II) superoxo complex [(DMM-tmpa)CuII(O2•¬–)]+ and a series of para-substituted-2,6-di-tert-butylphenols (p-X-DTBP’s) affording 2,6-di-tert-butyl-1,4-benzoquinones (DTBQ’s). Significant deuterium kinetic isotope effects (KIE;;s) and a positive correlation of second-order-rate constants (k2’s) compared to rate constants for p-X-DTBP’s plus cumylperoxyl radical reactions indicate a mechanism involves rate-limiting hydrogen atom transfer (HAT). Product analyses, 18O-labeling experiments, and separate reactivity employing the 2,4,6-tri-tert-butylphenoxyl radical provide further mechanistic insights.Chapter 3 reports the first example of sulfur-ligated mononuclear superoxo species which mimics the putative CuII(O2•–) active species of the peptidylglycine-α-hydroxylating monooxygenase, PHM. This complex exhibits enhanced reactivity towards both O-H and C-H substrates in comparison to close analogues [(L)CuII(O2•–)]+, where L contains only nitrogen donor atoms. Cu-S(thioether) ligation with its weaker donor ability (relative to an N-donor) are demonstrated by comparisons to the chemistry of analogue compounds.Chapter 4 provides the coordination chemistry and reactivity study of primary CuI/O2 species featuring an intramolecular hydrogen bonding substituent, (XBA)CuII(O2●–) (XS). The stability of XS compounds are ascribed to internal H-bond, from the secondary coordination sphere, to the proximal superoxide ;;O’ atom. Direct evidence for hydrogen atom transfer from phenol substrates by XS complexes was obtained, and enhanced reactivity of copper(II) superoxo complexes possessing electron-withdrawing groups (i.e., X) compared with other CuII(O2●–) analogues was observed. This behavior is discussed and correlated to the H-bonding ability of the XBA ligands and the copper ion centered redox behavior for varying XS complexes. In Chapter 5, we describe an overview of the copper proteins with respect to their preference for tautomeric histidine binding sites (δNHis vs εNHis) and a unique histidine-chelated ligand environment. Newly designed copper-histidine complexes are introduced, which possess ligands mimicking the copper center of certain enzymes. Dioxygen-derived copper species are determined to be (trans-peroxo)CuII2 and(bis-μ-oxo)CuIII2 complexes based on spectroscopic studies.