Design and Synthesis of Information-bearing Oligomers for Sequence-directed Dynamic Covalent Self-assembly

Abstract

A long-standing challenge in the field of self-assembly is creating nanostructures that rival the complexity and stability of their biological counterparts. DNA, with its double helix structure, has been extensively used to construct complex, multi-dimensional assemblies through the self-assembly instructions encoded in its sequences. However, the inherent weakness of hydrogen bonds in DNA renders these structures fragile and susceptible to thermal and mechanical degradation. Dynamic covalent self-assembly has been employed to address these deficiencies, particularly using sequence-specific peptoids to create chemically and thermomechanically robust nanostructures. This approach leverages reversible amine/aldehyde reactions to generate imine linkages, offering a more stable alternative to the hydrogen bonding in DNA. This dissertation investigates the strategic equilibrium shifting of dynamic covalent interactions to construct sequence-selective molecular architectures with advanced functionalization. Initially, we examined the impact of a Lewis acidic catalyst, scandium triflate (Sc(OTf)3), on the equilibrium of imine formation, a well-documented dynamic covalent interaction. High concentrations of scandium triflate facilitated the dissociation of oligomeric strands embedded with amine- and aldehyde-pendant groups. The removal of excess scandium triflate through liquid-liquid extraction shifted the equilibrium, promoting the formation of imines between complementary strands. Further annealing of the assembly solutions at 70 °C allowed for rearrangement and error-correction of misaligned or mismatched sequences, resulting in the formation of information-bearing ladders, providing a novel method for information storage and retrieval by abiotic polymers. Furthermore, we explored the self-assembly of these ladder polymers using the thermally reversible Diels-Alder cycloaddition reaction, which requires external stimulation to overcome or eliminate kinetic trapping. Employing furan-protected maleimide and furfurylamine residues, we synthesized sequence-defined strands containing both reactants, preventing premature hybridization. These strands self-assembled in a temperature-controlled process, directed by their informational content, to form unique ladder polymers, demonstrating a dynamic method for controlled molecular construction. Finally, we designed and synthesized ethynyl phenyl halide monomers tailored for the creation of a new class of sequence-specific oligo(1,4-phenylene ethynylene) featuring pendant dynamic covalent side groups, such as aldehydes and amines, as well as solvophilic units with triethylene glycol side chains to enhance solubility. This design facilitates the incorporation of π-conjugated systems into the polymer backbone and enhances shape persistence, which is crucial for future scaffolding applications. A proof-of-concept hybridization experiment with these monomers demonstrated their potential in constructing molecular ladders, setting a solid foundation for further advancements in the development of functional materials.