Development of Chemical Tools for Delivery of Hydrogen Selenide to Biological Environments
| dc.contributor.advisor | Pluth, Michael | |
| dc.contributor.author | Newton, Turner | |
| dc.date.accessioned | 2022-10-26T15:28:38Z | |
| dc.date.available | 2022-10-26T15:28:38Z | |
| dc.date.issued | 2022-10-26 | |
| dc.description.abstract | Hydrogen selenide (H2Se) is the central species in the selenium metabolic cycle, sitting at the crossroads of protein-synthetic and excretory pathways. Despite its importance in biology and potential for therapeutic applications, this species has received limited attention from researchers in the past. Commonly used methods for studying H2Se in biology are confined to solutions of H2Se/HSe– prepared through hydrolysis of selenide salts or reduction of elemental selenium, but significant drawbacks are presented with these techniques that prevent comprehensive investigation. It is necessary for researchers to develop tools that will facilitate investigations into the roles and fates of H2Se in biology, and inspiration can be taken from the closely related field of research on hydrogen sulfide (H2S), the third gasotransmitter. The research presented in this dissertation is aimed at adapting previously established strategies for studying H2S in biology to the heavier chalcogenide H2Se.Fully understanding the motivations behind H2Se research requires a familiarity with the necessity of selenium in the mammalian diet, specifically its inclusion in the family of selenoproteins, which play key roles in the maintenance of redox status and thyroid hormone modulation among many others. This material is covered in Chapter I along with more detailed analysis of the challenges currently facing H2Se research. The development of the first well-characterized H2Se donor, modeled after the most widely-studied H2S donor, is covered in Chapter II and sets the stage for future research in this area. Chapter III details an expansion upon the technology discussed in the previous chapter with efforts to produce H2Se donors with tunable hydrolysis rates. Additionally, experiments on the viability of these compounds in biology are discussed in Chapter III through performing cell permeability and antioxidant capacity experiments in HeLa cells. Current work is detailed in Chapter IV, revealing the use of selenocarbamates as H2Se donors with the goal of developing donors with diverse triggering mechanisms and amine-based payloads that facilitate investigations into the chemical and biological behavior of H2Se. Finally, Chapter V summarizes this work, the current state of the field, and provides avenues for further advancement of H2Se donor technology. This dissertation includes previously published and unpublished co-authored materials. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1794/27757 | |
| dc.language.iso | en_US | |
| dc.publisher | University of Oregon | |
| dc.rights | All Rights Reserved. | |
| dc.title | Development of Chemical Tools for Delivery of Hydrogen Selenide to Biological Environments | |
| 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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