Binding of Hydrogen Sulfide to biologically relevant scaffolds: Metal systems and non-covalent binding
| dc.contributor.advisor | Pluth, Michael | |
| dc.contributor.author | Hartle, Matthew | |
| dc.date.accessioned | 2017-05-01T15:26:29Z | |
| dc.date.available | 2017-05-01T15:26:29Z | |
| dc.date.issued | 2017-05-01 | |
| dc.description.abstract | Hydrogen Sulfide (H2S) is an important biologically produced gasotransmitter along with carbon monoxide (CO) and nitric oxide (NO). Unlike CO and NO, the bioinorganic chemistry of H2S reactivity with biologically relevant metal centers remains underinvestigated. To address this gap, several model bio(in)organic complexes were used to understand the ligation and reaction chemistry of H2S, including phthalocyanine, protoporphyrin IX, tetraphenyl porphyrin, and a pyridine diimine zinc complex. In addition to being a reactive gasotransmitter, the hydrosulfide anion (HS–) has been found to be an important biological anion. Studies with readily available cobalt and zinc phthalocyanines in organic solution illustrated the importance of protonation state in the ligation and redox chemistry of H2S and highlighted the need for an organic-soluble source of HS–. To address this need, we developed a simple method to prepare tetrabutylammonium hydrosulfide (NBu4SH). Using NBu4SH, we expanded the knowledge of H2S reaction chemistry to encompass a significantly larger set of biologically relevant metals beyond iron using the protoporphyrin IX scaffold, revealing three principle reaction pathways: binding, no response, or reduction and binding. Iron in biology is of particular importance given its role in oxygen transport in hemoglobin. The swamp-dwelling bivalve L. Pectinata hemoglobin 1 (Hb1) transports H2S, via ligation to heme, to symbiotic bacteria. The stabilization of H2S in Hb1 is believed to be from one of the following: a protected pocket, hydrogen bonding with a proximal glutamate residue, or a complex combination of these or other factors. By using Collman's "Picket-Fence" porphyrin to isolate the protected pocket model, we determined that a protected pocket alone as insufficient to account for H2S stabilization on Hb1. This realization led to an examination of hydrogen bonding in the secondary coordination sphere of a zinc complex. Finally, we explored the role of HS– as a biologically relevant anion using a bis(ethynylaniline) supramolecular receptor. We determined that rather than covalently modifying the receptor molecule, HS– was bound in the pocket, similar to bacterial anion transport channel. This dissertation includes previously published co-authored material. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1794/22278 | |
| dc.language.iso | en_US | |
| dc.publisher | University of Oregon | |
| dc.rights | Creative Commons BY-SA 4.0-US | |
| dc.subject | Binding | en_US |
| dc.subject | Hydrogen Sulfide | en_US |
| dc.subject | Phthalocyanine | en_US |
| dc.subject | Porphyrin | en_US |
| dc.subject | Supramolecular | en_US |
| dc.title | Binding of Hydrogen Sulfide to biologically relevant scaffolds: Metal systems and non-covalent binding | |
| dc.type | Electronic Thesis or Dissertation | |
| thesis.degree.discipline | Department of Chemistry and Biochemistry | |
| thesis.degree.grantor | University of Oregon | |
| thesis.degree.level | doctoral | |
| thesis.degree.name | Ph.D. |
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