Serendipitous Synthesis of Sulfur and Selenium-Containing Macrocycles and Their Application as GPx Mimetics

McMillan, Jacob Daniel Roy

Serendipitous Synthesis of Sulfur and Selenium-Containing Macrocycles and Their Application as GPx Mimetics

dc.contributor.advisor	Back, Thomas
dc.contributor.author	McMillan, Jacob Daniel Roy
dc.contributor.committeemember	Ling, Chang-Chun
dc.contributor.committeemember	Derksen, Darren
dc.contributor.committeemember	Sutherland, Todd
dc.date	2023-02
dc.date.accessioned	2022-11-03T15:41:16Z
dc.date.available	2022-11-03T15:41:16Z
dc.date.issued	2022-11-01
dc.description.abstract	Glutathione peroxidase, or GPx, is a selenocysteine based enzyme whose role is to prevent oxidative stress in mammalian cells by catalytically reducing harmful hydrogen peroxide and hydroperoxides, to water or their corresponding alcohols, respectively. This process simultaneously results in the oxidation of glutathione, a naturally abundant thiol, to glutathione disulfide. While GPx generally works well at preventing oxidative stress, there are certain circumstances where GPx can become overwhelmed, such as during reperfusion after a heart attack or stroke, that can result in excessive oxidative stress. Therefore, there is interest in the development of small molecule selenium compounds that could act as mimetics of GPx and aid it in the reduction of harmful peroxides. Spirodioxyselenuranes have been reported to be particularly effective GPx mimetics and analogues that contain heteroatoms other than oxygen are also of interest. During attempts to prepare spirodithiaselenuranes, which would be a novel class of compounds, a series of macrocyclic dimers containing both selenide and disulfide moieties was obtained instead. Chapter two describes attempts toward the synthesis of spirodithiaselenuranes and the characterization of the isolated macrocyclic species. Based on these results, the remainder of chapter two describes the synthesis of a range of these macrocyclic dimers. Chapter three focuses on the application of these dimers as GPx mimetics and the assays used to measure their activity. During this study a surprising induction period in the catalysis was observed which was determined to be due to autocatalysis by the oxidized macrocycle.	en_US
dc.identifier.citation	McMillan, J. D. R. (2022). Serendipitous synthesis of sulfur and selenium-containing macrocycles and their application as GPx mimetics (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.	en_US
dc.identifier.uri	http://hdl.handle.net/1880/115402
dc.identifier.uri	https://dx.doi.org/10.11575/PRISM/40383
dc.language.iso	eng	en_US
dc.publisher.faculty	Science	en_US
dc.publisher.institution	University of Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.	en_US
dc.subject	Selenium	en_US
dc.subject	Sulfur	en_US
dc.subject	GPx Mimetics	en_US
dc.subject	Antioxidants	en_US
dc.subject.classification	Chemistry--Organic	en_US
dc.title	Serendipitous Synthesis of Sulfur and Selenium-Containing Macrocycles and Their Application as GPx Mimetics	en_US
dc.type	master thesis	en_US
thesis.degree.discipline	Chemistry	en_US
thesis.degree.grantor	University of Calgary	en_US
thesis.degree.name	Master of Science (MSc)	en_US
ucalgary.item.requestcopy	true	en_US