SYNTHESIS AND PREPARATION OF METAL COMPLEXES AS G4 BINDERS
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Authors
Hoeve, Celena
Date
Type
thesis
Language
eng
Keyword
G4 binders , Synthesis , Metal complexes
Alternative Title
Abstract
G4s are a higher order architecture which can form in guanine-rich areas of DNA and RNA. These structures have been found to be relevant in medical conditions such as cancer, neurological disorders, and viral and parasitic infections. Because of the role of G4s in these conditions, G4 binders have gained relevance as potential therapeutic tools. The goal of the binders is to provide G4 stabilization, thus interfering with the mechanisms of these medical conditions. A platinum complex based on the pyridyl-triazolopyridine diad was previously identified in our group which showed promise as a G4 binding platform. This thesis focuses on the synthesis of novel G4 binders based on that parent platinum complex.
Chapter 2 explores the initial synthetic steps toward a potentially G4-binding macrocyclic metal complex. The goal of this macrocyclic binder is to provide increased binding affinity compared to the parent complex through increased conjugation and increased surface area. The macrocyclic structure is based on the imidazo[1,5-a]pyridine moiety. The coupling of imidazo[1,5-a]pyridine groups through C-H activation is discussed, as well as efforts made toward functionalization with aldehyde and amine groups in preparation for assembly into a macrocycle.
Chapter 3 outlines the preparation of a new family of three platinum complexes bearing alcohol tags of different lengths. The two primary steps discussed are reduction of alkynes to give the final alcohol-tagged ligands, and the use of these ligands in the preparation of platinum complexes. Through the alcohol tags, this new family of complexes offers the opportunity for derivatization into a variety of G4-binding conjugates.
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Attribution-NonCommercial-NoDerivs 3.0 United States
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivs 3.0 United States