The Synthesis and Study of Functionalised Catenanes and Rotaxanes for Supramolecular Chemistry Applications

Barlow, Sean and Evans, Nicholas (2024) The Synthesis and Study of Functionalised Catenanes and Rotaxanes for Supramolecular Chemistry Applications. PhD thesis, Lancaster University.

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Abstract

A key pillar of supramolecular chemistry is located in the field of mechanically interlocked molecules. Interlocked systems, such as rotaxanes and catenanes, offer bespoke and desirable properties due to the architecture arising from the mechanical bond. This thesis explores the design, synthesis, and properties of such systems for a host of supramolecular chemistry applications. Chapter 1 provides an introduction into the field of mechanically interlocked molecules, exploring routes to their synthesis through directed self-assembly. A review of the main properties and applications such systems possess are also discussed and the potential routes of further investigation are considered. Chapter 2 begins with the development of a rapid hydrogen bond templated synthesis towards novel [2]catenanes and [2]rotaxanes, with several high yielding catenane substrates being subsequently isolated. Their characterisation is then discussed. Further investigations into the improved templated synthesis of single amide-containing [2]rotaxanes is then explored by incorporating PNO and thioamide motifs. In the final part of the chapter, the application of rapidly synthesised PNO-[2]catenane which demonstrated moderate binding selectivity towards lithium cations is detailed. Chapter 3 explores the hydrogen bond templated synthesis developed in Chapter 2 for the synthesis of exotic interlocked architectures. In the first instance, the successful synthesis of two handcuff [2]rotaxanes are discussed and their characterisation is detailed. Following on from this, efforts to incorporate 1,3-substituted cubanes as a structural isostere in interlocked architecture is explored. This led to the isolation and characterisation of the first examples of cubane containing interlocked molecules. Chapter 4 describes the synthesis and study of Raman-active [2]rotaxanes with the intent of applying them for in vivo applications. An overview of the synthesis describing the means of incorporating specific Raman-active functional groups (tags) is presented and, following this, four potential [2]rotaxane candidates were successful prepared and characterised. Initial Raman spectroscopy studies, which showed detection of the expected tag signals, and fluorescence interference arising from the most promising rotaxane candidate are then presented. Chapter 5 details efforts towards the successive ring expansion of [2]catenanes through the SuRE and CARE methodologies. Investigations utilising the novel [2]catenanes synthesised from Chapter 2 were first explored, however, acylation attempts under the literature and modified conditions were sadly unsuccessful. In the second half, the synthesis and attempted ring expansion of a novel single amide containing [2]catenane is presented. Following a moderate redesign, isolation of the [2]catenane was achieved in high yield, however, follow-up ring expansion studies were unsuccessful due to failed acylation attempts. Chapter 6 focus on the synthesis of hydrogen bond and chloride anion templated mechanically chiral interlocked systems. Initially, investigations focused on the separation of the enantiomers via separation of the corresponding diastereomeric salts or via chiral-HPLC for both the hydrogen bond and chloride anion templated [2]catenanes system. Whilst their synthesis and characterisation in a racemic form was successful, subsequent attempts to separate the enantiomers came to no avail. With minimal success, investigation turned towards the synthesis and separation of the enantiomers of a chloride anion templated mechanically chiral [2]rotaxane. In this instance, synthesis of the [2]rotaxane and subsequent separation of its enantiomers via chiral-HPLC was successful and has opened a new avenue of investigation into this style of rotaxane architecture. Chapter 7 provides a discussion of the overall conclusions from this thesis with reflection on the outlook and contextualisation of the research. This highlighted the importance and application of the rapid hydrogen bonded templated methodologies and designs developed in this thesis. Further work and future avenues of investigation are also suggested. Chapter 8 provides the synthetic procedures and characterisation details for the compounds listed in this thesis broken down by chapter. Bibliography contains all the citations referenced in this thesis. Appendix reports the supplementary experimental information for titration protocols and X-ray crystal structure data.