Phenylacetylene oligomers as synthetic information molecules

Nucleic acids store genetic information in the sequence of nucleobases. Through duplex formation and template directed synthesis, the information stored in nucleic acids determines their three-dimensional structure and function. Nucleic acids are essential molecules for biological processes and have been used in nanotechnology. Modified nucleic acids have been synthesised that still form duplexes and can be tolerated by enzymes, suggesting that it is possible to construct a synthetic system comparable to nucleic acids, orthogonal to nucleic acids. This thesis describes the synthesis of a new class of synthetic information molecule, characterisation of the duplex forming properties, and attempts at templated oligomerisation reactions. The new synthetic information molecule is based on the phenylacetylene oligomer framework developed by Moore and co-workers. Recognition was achieved via a base-pair that is made from a single point high affinity H-bond, with phenol as the H-bond donor (D) and phosphine oxide as the H-bond acceptor (A). The Sonogashira coupling was used to construct the phenylacetylene oligomer backbone. The AA, DD and AD 2-mers were synthesised and complementary 2-mers showed cooperative duplex formation. No intramolecular H-bonding due to folding was observed in the AD mixed 2-mer. Longer oligomers were synthesised using a method of oligomerisation and chromatographic separation by reverse-phase preparatory HPLC. Homo-oligomers up to the 7-mer were isolated and binding studies between complementary all donor, all acceptor homo-oligomers showed increasing duplex stability with each additional recognition unit in the oligomer chain. Oligomers containing both acceptor and donor recognition modules in the same chain were synthesised and NMR dilution studies were used to investigate their ability to fold. Preliminary experiments were carried out to evaluate the ability of these information molecules to template oligomerisation reactions, but when reactions were carried out at concentrations low enough for a significant template effect, no coupling reactions were observed.