In this thesis, we document a comprehensive study of the cation-directed self-assembly of three guanosine derivatives: i) guanosine 5'-monophosphate (5'-GMP), ii) guanosine 5'-thiomonophosphate (5'-GSMP), and iii) 2',3',5'-O-triacetylguanosine (TAG). We discovered that, under the neutral pH condition, Na2(5'-GMP) molecules self-assemble into a right-handed helix structure consisting of alternating all-C2'endo and all-C3'endo planar G-quartets stacking on top of each other with a 30° twist. This self-assembled supramolecular structure uses multiple non-covalent forces (e.g., hydrogen-bond, phosphate-hydroxyl, pi-pi (base-base) stacking, ion-carbonyl, and ion-phosphate) to align individual monomers in a way that resembles RNA and DNA sequences in which covalent bonds are used to link monomers. Na+ ions are located in the channel and surface sites of the G-quadruplex. In contrast, under acidic pH conditions, Na2(5'-GMP) molecules self-assemble into a continuous right-handed helix where guanine bases are hydrogen-bonded in a lock-washer fashion with only C3'-endo monomers. Na+ ions are absent in the channel site due to smaller channel radius and lesser repulsions between phosphate groups (-1 vs. -2 charge under neutral pH) contribute to the stronger stacking mechanism. In Na2(5'-GSMP), a longer phosphate bond compared with Na2(5'-GMP) allows stronger P-O-…Na+…-O-P interactions to occur, thus enhancing self-assembly. Solid-state NMR, FT-IR, powder x-ray diffraction, model building, and calculation showed that Na2(5'-GSMP) forms the same self-assembled structure as Na2(5'-GMP) but with significantly greater tendency. This study proves that single-bond modification can enhance stacking in G self-assemblies, and shows direct evidence that Na+ ions reside at the surface (phosphate) sites. Lastly, using lipophilic TAG, we were able to show for the first time that trivalent lanthanide metal ions can facilitate G-quartet formation. A new mode of metal ion binding in G-quartet structures (i.e., a triple-decker G dodecamer containing a single metal ion in the central G-quartet) is reported. We also report the first 1H and 43Ca NMR characterization of Ca-templated G-quartet formation in a [TAG8-Ca]2+ octamer. / Thesis (Ph.D, Chemistry) -- Queen's University, 2012-06-27 16:53:43.359
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/7295 |
| Date | 27 June 2012 |
| Creators | Kwan, Irene Ching Man |
| Contributors | Queen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.)) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | 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. |
| Relation | Canadian theses |
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