Construction of DNA-based Photonic Wire Assemblies by Programmable Polyamides

A key problem in nanotechnology is the integration of individual components into larger networks capable of more complex processes. DNA based photonic wires are a promising solution as they have been shown to transmit light energy over 10 nm distances, but are limited by their problematic assembly and reliance on fluorophore labelled DNA. This thesis describes efforts to construct an improved photonic wire using functionalised DNA binding small molecules as proof of principle for a ‘mix and match’ approach to nanotechnology which delivers individual components to a specific site on DNA. Polyamides have been shown to bind to DNA with very high affinity and specificity which together with their modular nature makes them an ideal ‘delivery system’. To combine this with the versatility and efficiency of copper catalysed click chemistry, novel internally functionalised alkyne polyamides were synthesised using both solution and solid phase chemistry. A general route to produce these internally modified polyamides was developed and the synthesis of the standard polyamide building blocks was improved. Test click reactions on alkyne polyamide fragments showed up to 92% conversion, but the same reactions failed on the full length polyamides and previously reported modification methods were used to create a fluorophore labelled polyamide. A coumarin based fluorophore was selected to allow direct substitution into proven photonic wires, but when the DNA binding affinity of this polyamide was tested, it was found that only weak binding was observed with 1.5 equivalents of polyamide. Upon construction, the improved photonic wire transported energy over a distance of 6 nm with an overall efficiency of 9% which was attributed to the poor DNA affinity. This poor performance makes it difficult to assess the general potential for this ‘mix and match’ approach, but the non-applicability of click chemistry and improvements in the synthesis will inform future designs.