Doctor of Philosophy (Ph.D.)
Degree Granting Department
Xiaodong Michael Shi, Ph.D.
Jianfeng Cai, Ph.D.
Shengqian Ma, Ph.D.
Kirpal Bisht, Ph.D.
Ruisheng Liu, Ph.D.
Self-assembly, G-octamer, Stability, Fluorescence
This dissertation mainly contains three parts: 1) The construction of well-defined G8-octamers through the monomer conformational design. 2) The construction of cross-layer interactions in the G8-octamer for enhanced stability in H-bond competitive solvents. 3) Design and synthesis of 8-triazole guanosine with photoluminescent properties.
Through the structural conformational design, we have developed a new class of guanosine derivatives with modification on guanine (8-aryl) and ribose (2’,3’-isopropylidene). This unique design has led to the formation of the first discrete G8-octamer with structure characterized by NMR, MS and single crystal X-ray diffraction. The selectivity between monovalent (K+) and divalent cat-ions (Ba2+ and Sr2+) for both G8-octamer and G16-hexadecamer have been investigated. NMR titration experiments revealed interesting reversal binding ability for the two systems. Excellent K+ selectivity (over 100-fold Ba2+) was achieved in our newly developed G8-octamer system using guanosine derivative 1b. Energetic dissociation profiles were determined, revealing the crucial contributions of entropy in the thermodynamic stability of G8 system. This exceptional binding ability toward K+ was further examined by competition experiments with 18-crown-6, demonstrating the potential of this G8 system as a new potassium receptor.
Through the analysis of cross-layer interactions, further modification on the 8-aryl moiety was performed to incorporate cross-layer H-bond and covalent linkage respectively. An acetyl phenyl substituted guanosine derivative and a covalently tethered 8-aryl guanosine dimer were designed and prepared for supramolecular assembly. The expected G8-octamer was confirmed by X-ray, MS and NMR with significantly improved stability in MeOH and 1:1 DMSO/CDCl3 mixture. To the best of our knowledge, this is the first example of discrete G-quadruplexes formed from small molecules with enhanced stability in protic solvent (MeOH) and polar aprotic solvent (DMSO).
Based on the conformation of self-assembled 8-aryl guanosine, an 8-phenyltrizole substituted guanosine derivatives was designed and synthesized, which demonstrated strong fluorescence emission in the UV-blue region. Its self-assembly properties were also investigated with X-ray crystal structure confirming the G8-octamer formation adopting a bottom to bottom manner. The photophysical properties before and after the self-assembly of triazole guanosine were also explored.
In summary, formation of the stable G8-octamer with concise and well-defined bottom-to-bottom stacking mode provides a novel supramolecular platform. Incorporation of this new system into material and biological applications are expected and currently undergoing in our lab.
Scholar Commons Citation
He, Ying, "Construction of G-quadruplexes via Self-assembly: Enhanced Stability and Unique Properties" (2019). USF Tampa Graduate Theses and Dissertations.