Graduation Year

2019

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

Xiaodong Michael Shi, Ph.D.

Committee Member

Jianfeng Cai, Ph.D.

Committee Member

Shengqian Ma, Ph.D.

Committee Member

Kirpal Bisht, Ph.D.

Committee Member

Ruisheng Liu, Ph.D.

Keywords

Self-assembly, G-octamer, Stability, Fluorescence

Abstract

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.

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