Back, ThomasMcMillan, Jacob Daniel Roy2022-11-032022-11-032022-11-01McMillan, 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.http://hdl.handle.net/1880/115402https://dx.doi.org/10.11575/PRISM/40383Glutathione 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.engUniversity 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.SeleniumSulfurGPx MimeticsAntioxidantsChemistry--Organicmaster thesis