Templated synthesis of synthetic oligomers

Bolgar, Peter 

Thumbnail Image
Change log

Considerable progress has been made in the Hunter group towards the development of sequence oligomers equipped with H-bond donor and acceptor recognition units, which are able to assemble into duplexes by H-bonding between sequence-complementary oligomers. This thesis describes a new class of melamine oligomers composed of alternating triazine and piperazine units, which are equipped with phenol and phosphine oxide recognition groups. The order of the recognition groups defines the sequence of the oligomers. Complete sequence library of 1-mers, 2-mers and 3-mers, along with the homo 4-mers were synthesised by sequential temperature-controlled nucleophilic aromatic substitutions between cyanuric chloride and secondary amines. Complementary homo-oligomers undergo cooperative duplex formation, and hetero 3-mers form sequence-selective duplexes. H-bond templated synthesis of a similar melamine oligomer was attempted in toluene, but the template was inefficient at promoting the formation of sequence-complementary oligomers. The central H-bonding recognition unit of the melamine 3-mers was replaced by benzaldehyde or aniline side chains, giving oligomers that could assemble by imine formation as well as H- bonding. The 3-mer bearing two phosphine oxides and a benzaldehyde was converted to an imine with excess aniline, and then subjected to transimination in CDCl3 with the 3-mer bearing two phenols and an aniline. Transimination reached equilibrium at 70% conversion. The product duplex never fully assembled, indicating geometric incompatibility between the chosen H-bonding and dynamic covalent base pairs. Previously, a family of oligotriazoles equipped with phenol and benzoic acid recognition units was developed in the Hunter group, and shown to be capable of sequence information transfer by covalent templated synthesis of new oligomers. However, there are limitations associated with the choice of triazole backbone used in these systems. Here a novel strategy was developed for the rapid discovery of diazide and dialkyne building blocks for the synthesis of alternative backbones. Supramolecular scaffolds were created by mixing bidentate ligands and a metalloporphyrin appended with a dialkyne. The scaffolds were trapped by copper-catalysed azide alkyne cycloaddition with different diazides. The longest bidentate ligands gave the highest yield of linear triazole oligomers with any of the diazides used. No diazide gave the linear triazole oligomer as the major product with the dialkyne studied. A different backbone made by ring opening metathesis polymerisation was also investigated. An attempt was made for the synthesis of new oligomers from norbornenes functionalised with phenol and benzoic acid recognition units. Metathesis polymerisation gave a mixture of stereoisomers, and the monomers did not undergo successful base pair formation and cleavage cycle, making this system unsuitable for further studies.

Hunter, Christopher A
supramolecular chemistry, self-assembly, hydrogen-bonding, oligomers, templating, triazine chemistry, porphyrin complexes, organic chemistry
Doctor of Philosophy (PhD)
Awarding Institution
University of Cambridge