Graduation Year
2023
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Chemistry
Major Professor
Xiaodong Shi, Ph.D.
Committee Member
Jianfeng Cai, Ph.D.
Committee Member
Kirpal Bisht, Ph.D.
Committee Member
Libin Ye, Ph.D.
Keywords
Cesium, G-quadruplex, Ionophores, IsoG-pentaplex
Abstract
This dissertation is primarily divided into three parts: 1) Anion, solvent-mediated, tunable self-assemblies of isoguanosine (isoG). 2) Post-assembly modification of the non-covalent isoG-pentaplex for Cesium extraction. 3) Supramolecular asymmetric amine catalysis.
The structural conformational design of the isoG decamer was employed for systematic investigations involving various substituted groups at the C8 position of purine and ribose. A series of isoG analogs with C8-phenyl substitutions were synthesized and utilized for Cesium coordination. The proximity between purine and ribose structures limited pentaplex formation for C8-phenyl substituted isoG derivatives. Based on this observation, a deoxy isoG derivative with a modified ribose was employed to assemble with the Cesium cation. Critical solvent (CDCl3 and CD3CN) and anion (BPh4-, BARF-, and PF6-) investigated, leading to the controllable formation of various stable isoG pentaplexes. Finally, the X-ray crystal structure of [isoG20Cs3]3+(BARF-)3 was successfully determined, representing the first example of multiple-layer deoxy isoG binding with the Cesium cation, providing robust evidence for the existence of this novel isoG ionophore beyond the two-layer sandwich self-assembly.
Based on the studies of isoG derivatives' self-assembly, the self-assembled isoguanosine pentaplexes were found to be excellent Cesium-selective ionophores, even in the presence of excess alkali cations. Furthermore, the tunable isoG-pentaplex served as an excellent template for macrocyclization within layers. Post-assembly modification of a cation-templated isoG complex was achieved by subsequent formation of a Cesium cation ionophore. Reversible olefin metathesis was employed to cross-link subunits within the isoG pentaplex. Various isoG derivatives with varying chain lengths of the linkers were tested. The resulting covalently tethered isoG oligomer could effectively extract Cesium cations from an aqueous source into an organic receiving phase. The oligomer could be recycled and exhibited higher extractant efficiency compared to the corresponding free monomer. These results clearly demonstrate the efficacy of covalently tethered molecular self-assembly for constructing highly selective ionophores.
The self-assembly of secondary amine-guanosine provides a highly efficient approach to access a macroscopic reaction environment through a simple process, which can be applied in organocatalytic processes via the "accumulation effect." Two activation modes, enamine/iminium, can be applied in this system. The asymmetric aldol reaction was initially performed to evaluate the new G-amine catalyst, which showed improved reactivity and stereoselectivity.
In conclusion, the formation of stable G8-octamer and isoG-decamer with a concise and well-defined bottom-to-bottom stacking mode provides a novel supramolecular platform. A unique molecular scaffold was developed as a template for achieving macromolecule synthesis, and its application in catalysis demonstrated good regio- and stereoselectivity. The incorporation of this new system into material and biological applications is expected and is currently being investigated in our laboratory.
Scholar Commons Citation
Liu, Mengjia, "Supramolecular Architectures Generated by Self-assembly of Guanosine and Isoguanosine Derivatives" (2023). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/9983
