Enzymatic activation of dioxygen at mononuclear and binuclear copper sites
Abstract/Contents
- Abstract
- The activation of dioxygen at copper sites in metalloenzymes is essential for the biosynthesis of a number of natural products including neurotransmitters and melanin. In biological systems, these reactions occur at either a mononuclear or binuclear copper site. Central to the function of these enzymes is the geometric and electronic structure of the copper dioxygen species that is formed. For a number of copper enzymes, dioxygen is activated at a single reduce copper to form a mono-nuclear copper(II) superoxo species that is activated for H-atom abstraction. Due to challenges isolating this intermediate in the enzymatic systems, these studies will focus on the characterization of synthetic copper(II) superoxo and copper(II) hydroperoxo species. Results presented here indicate that the triplet ground state of the end-on copper(II) superoxide is activated for H-atom abstraction as well as proton coupled electron transfer. In contrast, the copper(II) hydroperoxo specie is not activate for this reaction but rather decays via homolytic Cu--O bond cleavage. In contrast to these mononuclear systems, dioxygen is activated by two electrons at a binuclear copper site to form a side-on (μ-η2∶η2) copper(II) peroxide intermediate in enzyme systems including Tyrosinase (Ty). Two other Cu2O2 core isomers have been observed in synthetic systems, the binuclear end-on (μ-1,2) peroxo and the binuclear copper(III) bis-μ-oxo structure. Previous studies on these synthetic systems have shown that the side-on peroxo core can be in equilibrium with the bis-μ-oxo isomer and that both are able to perform the biomimetic hydroxylation of phenolate. The studies reported here build upon this synthetic chemistry by characterizing a new end-on peroxo/bis-μ-oxo equilibrium. The observation of this interconversion suggests that the electrophilic reactivity (phenol oxygenation and sulfoxidation) observed for complexes that form end-on peroxo species results from an accessible bis-μ-oxo isomer that is responsible for the electrophilic reactivity. In addition, the coupled binuclear copper enzyme family is extended to include a new, fourth class of enzymes, the hydroxyanilinases. These enzymes have the same side-on peroxo active site and have similar reactivity to Ty while also possessing the unique ability to convert o-aminophenols to nitrosophenols. These studies provide insight into the function of mononuclear and binuclear copper enzymes and the dioxygen intermediates that make up their catalytic cycle.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Ginsbach, Jake W |
|---|---|
| Associated with | Stanford University, Department of Chemistry. |
| Primary advisor | Solomon, Edward I |
| Thesis advisor | Solomon, Edward I |
| Thesis advisor | Martinez, Todd J. (Todd Joseph), 1968- |
| Thesis advisor | Stack, T. (T. Daniel P.), 1959- |
| Advisor | Martinez, Todd J. (Todd Joseph), 1968- |
| Advisor | Stack, T. (T. Daniel P.), 1959- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jake W. Ginsbach. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Jake William Ginsbach
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...