Synthetic H-bonding information oligomers

The nucleic acids contain chemical information in the form of a sequence of bases. This information content is expressed through sequence selective duplex formation and template directed synthesis. To date, the only programmable artificial information molecules that can truly rival the nucleic acids, in terms of their function, are structurally very similar to the nucleic acids. This thesis describes a synthetic approach to duplex forming hydrogen bonding oligomers that contain information in the form of a sequence of H-bond donor and acceptor groups, in the pursuit of a programmable material that is orthogonal to the nucleic acids. Chapter 1 is a literature review of natural and synthetic information molecules and their applications in nanotechnology, including an overview of the structurally reengineered versions of the nucleic acids, foldamers, template polymerisation and synthetic duplexes. The review highlights the absence of totally synthetic information oligomers, that are orthogonal to the nucleic acids, and Chapter 2 sets out the aims of this thesis, which is to address this gap. Chapter 3 describes the synthesis of oligomers equipped with phenol H-bond donors and phosphine oxide H-bond acceptors. Through cooperative H-bond formation, these oligomers form double stranded complexes, which were characterised by NMR titrations and thermal denaturation experiments. For each additional H-bond there is an order of magnitude increase in association constant. In Chapter 4 it is demonstrated that the modular design for the oligomers in Chapter 3 represents a general strategy to synthetic information oligomers. Two new classes of H-bond acceptor oligomer were synthesised, bearing pyridine and pyridine N-oxide groups. Both these systems also exhibit cooperative duplex formation with H-bond donor oligomers, which were characterised by NMR titration. Chapter 5 examines the ability of mixed sequence 3-mers formed of H-bond donors (phenol) and H-bond acceptors (pyridine N-oxide) to form duplexes in a sequence selective manner. All 8 combinations of donor and acceptor were synthesised, and NMR titrations were used to measure the association constants for each pairwise combination of oligomers. Sequence matched duplexes generally have the highest association constants, but there are some anomalies.