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Author
Title COMPUTATIONAL MODEL OF THE CATALYTIC CYCLE OF ORGANOSELENIUM ANTIOXIDANTS
URL
Publication Date
Degree PhD
Discipline/Department Department of Chemistry
Degree Level doctoral
University/Publisher Dalhousie University
Abstract The chemistry of the enzyme glutathione peroxidase and synthetic organoselenium enzyme mimics has been a significant research interest for more than three decades. In this work, the results of a computational study employing modern electronic structure methods to model the reactions of a synthetic glutathione peroxidase mimic are presented. The ability of nine density-functional theory methods and thirteen basis sets to predict both molecular geometries and bond dissociation energies in organoselenium compounds is examined. This is used to determine the best methodology to employ for the study of glutathione peroxidase mimics. The key reactions in the catalytic mechanism of the organoselenium antioxidant N,N-dimethyl-benzylamine-2-selenol are the focus of the remainder of the document. This is a three-step mechanism which includes many of the organic forms adopted by selenium compounds, including selenol, oxoacids, and selenylsulfides. In the first step of the cycle, the well-studied reduction of hydrogen peroxide by a selenol and a diselenide is modelled. The second step modelled is a substitution reaction at the selenium centre of a selenenic acid with a thiol. The final step discussed is the reduction of the selenium centre in a selenylsulfide, regenerating the selenol and forming a disulfide species. Each mechanism is evaluated by discussing both molecular geometries and reaction energetics. To close the document, the peroxide reduction reaction is revisited to determine the effects of substitution on the phenyl ring of the synthetic antioxidant. This serves as a preliminary attempt to improve the antioxidant efficiency of this compound. In addition to a discussion of the changes in reaction energetics predicted, the topology of the electron density is studied using the quantum theory of atoms in molecules to better understand how the distribution of electron density is affected by substituents.
Subjects/Keywords Computational Chemistry; Organoselenium; Glutathione Peroxidase; Glutathione Peroxidase Mimic
Contributors James W. Gauld (external-examiner); Mark Stradiotto (graduate-coordinator); Axel D. Becke (thesis-reader); D. Jean Burnell (thesis-reader); Donald F. Weaver (thesis-reader); Russell J. Boyd (thesis-supervisor); Not Applicable (ethics-approval); Yes (manuscripts); Yes (copyright-release)
Language en
Country of Publication ca
Format application/pdf
Record ID handle:10222/15141
Other Identifiers TC-NSHD-15141
Repository canada
Date Indexed 2017-01-03
Grantor Dalhousie University

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…who were my first teachers and have been the inspiration to achieve all I have done. Finally, the Killam Trusts, Nova Scotia Health Research Foundation, Natural Sciences and Engineering Research Council of Canada, and Dalhousie University are thanked…

…for their generous financial support during my time at Dalhousie University. Additionally, thanks are given to ACEnet for the use of their computing facilities, without which I would have been unable to complete the work presented herein. xviii…

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