Abstract
The hydrogen bonds (H-bonds) are at the origin of the secondary and tertiary structures of enzymes (proteins), but also of the double helix structure of the DNA. The nucleobases are the main active frameworks which are at the origin of H-bond formation in genetic material: Cytosine (C), Guanine (G), Adenine (A), Thymine (T) (and Uracil for RNA)). The co-assembly of complementary nucleobases is favored over other possible combinations (A-T > A-A, AG or AC in the case of adenine for example). In a biomimetic approach, some groups have investigated the synthesis of polymers containing nucleobases. However, the nucleobase-containing polymers presented so far in the literature are insoluble in water, which limits their potential use in biological sciences. However, the systems previously obtained in the literature from nucleobase-containing copolymers form supramolecular self-assemblies. Their morphology is adaptable and is mainly influenced by the architecture of the starting copolymers (the degree of polymerization, the number of nucleobases in the polymer), and thus, by the hydrophilic/hydrophobic balance of the system. Overall, the examples of the literature have shown that these morphologies result from equilibria between supramolecular interactions (hydrogen bonds, van der Waals forces, π-π interactions) and are influenced by the structural parameters of the polymers. These studies provided a proof of concept on the self-assembly of nucleobase-containing copolymers, but did not specifically investigate the parameters that influence these co-assemblies, nor their limitations. The knowledge of the type of supramolecular interactions that are at the origin of the resulting self-assemblies (i.e. complementary hydrogen bonds or hydrophobic interactions) is of significant importance in order to modulate the dynamics of self-assembly (to obtain reversible or irreversible self-assemblies), as well as to control the kinetics of H-bond association. Nevertheless, the investigation of the kinetics or dynamics of H-bond association has never been explored before in the case of self-assembled nucleobase-containing copolymers. As a perspective, the control of the kinetics of association/dissociation of hydrogen bonds can be a valuable tool in applications such as delivery systems of active substances and/or genetic material. The first axis of this thesis included the development of water-soluble nucleobase containing copolymers, the investigation of the properties of resulting co-assemblies at physiological conditions, as well as the in-vitro evaluation of biocompatibility of these polymers. The second objective of this project was to investigate the properties of supramolecular co-assemblies of nucleobase-containing polymers under pH changes, in order to design supramolecular systems with tuneable kinetics of H-bond association. Finally, the aim of this project was to find a potential applicability of nucleobase containing copolymers in biology. To this, we investigated the complexation via hydrogen bonds between nucleobase-containing polymers and different types of genetic material in order to design a future platform for mRNA artificial vectors.