Spontaneous small molecule migration via reversible Michael reactions
Small molecule walkers developed to date take advantage of the reversibility of dynamic covalent bond formation to transport molecular fragments along molecular tracks using both diffusion processes and ratchet mechanisms. However, external intervention (the addition of chemical reagents and/or irradiation with light) is required to mediate each step taken by the walker unit in systems reported so far. In this Thesis, the first synthetic small molecule able to walk back-and-forth upon an oligoethylenimine track without external intervention via intramolecular Michael and retro- Michael reactions is described. The 1D random walk is highly processive and exchange takes place between adjacent amine groups in a stepwise fashion. The walker is used to perform a simple task: quenching of the fluorescence of an anthracene group situated at one end of the track as a result of the walking progress. In the presence of excess of base, the molecule preferentially ‘walks’ towards the favoured final foothold of tracks of increasing length and it is possible to monitor the population of all or a few positional isomers over time. In each case the molar fraction of walkers reaching the final foothold is determined quantitatively by 1H NMR. Control over the rate of exchange is achieved by varying the amount of base added. The dynamic migration of a small molecule upon the track is a diffusion process limited to one dimension and as such can in principle be described using the one dimensional random walk. Chapter I identifies a set of fundamental walker characteristics and includes an overview of the DNA-based and small molecule transporting systems published to date. Chapter II describes the inspiration for this work and model studies which lay the groundwork for the research presented in this thesis. The initial track architecture and optimisation of reaction conditions are demonstrated using a simple model compound which then led to the development and a detailed investigation of a first synthetic small molecule able to walk upon an oligoethylenimine track without external intervention. Chapter III presents a modified synthetic route towards the desired walker-track architectures and a comprehensive investigation of the dynamic properties of a series of tracks of increasing length upon which the walker migrates in a unidirectional fashion. The Outlook contains closing remarks about the scope and significance of the presented work as well as ideas for the design of novel small-molecule walkers, some of which are well under way in the laboratory. Chapter II (with the exception of model studies included at the beginning of the chapter) is presented in the form of article that has recently been published. No attempt has been made to re-write this work out of context other than merging content of the article with the supplementary information published together with the article. Chapter II is reproduced in the Appendix in its published format.