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UBC Theses and Dissertations

Template-assembled synthetic G-quartets (TASQS) Nikan, Mehran

Abstract

Fabrication of functional supramolecular structures requires a certain degree of control which may not be achieved by relying solely on noncovalent interactions. The current study aims to investigate the effect of a rigid cavitand template on morphology, function and stability of lipophilic G-quadruplexes. The first Chapter of this thesis introduces different aspects of G quadruplex chemistry and explains how these structures are particularly suited for the creation of supramolecular architectures. The second Chapter of this thesis presents the synthesis and self-assembly of a new class of supramolecular architectures composed of four guanosines attached to a rigid cavitand template. These structures, named template-assembled synthetic G-quartets (TASQs), were synthesized via the “click” reaction and manifest an ordered topology dictated by the template. The lipophilic TASQs were found to self-associate spontaneously to form a singular basket-like structure in chloroform. Moreover, it was found that TASQs form cation-free G-quartets which exhibit remarkable stability under this condition. The third Chapter of this thesis describes the preparation, characterization and solution study of the cation-bound complexes TASQNa⁺, TASQK⁺, TASQCs⁺, and TASQSr²⁺. Cations play a major role in controlling the morphology and stability of G-quadruplexes. The analysis of the cation-specific structures of TASQs reveals the formation of a monomeric G quartet for Na⁺ and Sr²⁺,a dimeric system for Cs⁺ and a mixture of monomers and dimers for K⁺. The factors governing the formation of these structures were evaluated, the selectivities of TASQs for cations were determined, and the cation-dependent structural transformations were studied. The fourth Chapter describes the efforts towards synthesizing a hydrophilic TASQ via the “click” reaction. The following steps have been taken: 1) a water-soluble cavitand has been successfully synthesized and characterized, which can potentially serve as a hydrophilic template, and 2) two oligonucleotides have been appropriately functionalized and preliminary coupling reactions were attempted. The next phases of this research along with potential future directions are discussed in Chapter five.

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