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Guanosine self-assembly is a powerful tool for constructing nanostructures and materials with intriguing properties. Guanosine’s nucleobase has a hydrogen bond donor and acceptor face that in the presence of an appropriate templating cation can self-assemble to form larger G-quadruplex structures. Through the addition of a nonpolar solubilizing group on the 2, 3, or 5 position of guanosine’s ribose sugar, the G-quadruplex may be formed in organic solvents. Not surprisingly, any modification made to the guanine nucleobase can have a substantial effect on the self-assembly of the G-quadruplex core. These alterations can significantly alter or destroy the ability of the guanine base to form larger H-bond structures. For this reason, a major target for the synthetic modification of the G-quadruplex is the ribose sugar. Modifications to the sugar can be used to add new functionality or groups capable of modulating the G-quadruplexes stability and structure.

The 5-position is easily esterified and is an ideal target for incorporating new functionality to the G-quadruplex, not not much was known about how esterification of the 5-position of guanosine impacted self-assembly. In this thesis, a series of 5-modified aryl esters of guanosine were synthesized G 21-G 25, comprising either activating or de-activating substituents on the aromatic rings, to systematically investigate how the addition of an ester to the 5- position of guanosine affects the self-assembly G-quadruplex. The identity of the 5-aryl ester was found to have a direct impact on the molecularity (how many Gs are in each assembly) and stability of the G-quadruplexes. The information gained from these experiments was applied to rationally design a new G-quadruplex capable of templating a [2+2] photocycloaddition reaction.

With an increased knowledge of how modifications to the 5-position affect the structural integrity of the G-quadruplex, we applied this information to rationally design a new G-quadruplex system capable of templating a [2+2] photocycloaddition reaction. To achieve this goal a series of 5-cinnamate esters G 26-G 29 were synthesized and studied. Each derivative G 26- G 29 when self-assembled into a G-quadruplex an photoirradiated underwent a photocycloadditon reaction ins high yields with good stereoselectivity. These same compounds when disassembled only underwent trans-cis photoisomerization. Highlighting the need for the G-quadruplex self-assembly.