Abstract
This thesis consists of four chapters.
Chapter 1 introduces bacteria and the growing problem of antibacterial resistance. Mechanically interlocked molecules (MIAs) and the many subtypes are then presented, with a particular focus on rotaxanes and catenanes. The origin, design and synthesis of these interlocked architectures are closely examined. The potential applications for these types of supramolecules are also explored, with a particular focus on catalysis and biology. Crown ether containing compounds are then examined, and their applications in biology are discussed, in particular their ability to incorporate different cations into their central cavity. The aims of this project are then laid out, first to synthesize and characterise a family of [2]catenanes and [2]rotaxanes, and then to test the antibacterial activity of these compounds.
Chapter 2 discusses the origins of rotaxanes, as well as the different approaches which can be used to synthesize these MIAs. With a particular focus on the template approach, using either metal atoms or hydrogen bonding. The synthetic approach to [2]rotaxane formation designed by the Leigh group is then discussed, as they developed a family of [2]rotaxanes using a 1o amine, a crown ether, and an electrophile in a one pot reaction. Building on this approach used by the Leigh group, our own approach to [2]rotaxanes is then explored, starting with the first generation of [2]rotaxanes, which followed closely to the work by the Leigh group. The synthesis of the second generation of [2]rotaxanes is then investigated, using electrophiles with additional methylene groups, which produced more interesting MIAs, but in more modest yields. Additionally, attempts to synthesize [3]rotaxanes were described, using double headed electrophiles and two equivalents of nucleophile and crown ether, the results proved unsuccessful however, and no amounts of [3]rotaxane were seen, with only trace amounts of [2]rotaxane observed via HR-ESIMS.
Chapter 3 details different metal ion templated approaches to synthesizing catenanes. First the ring closing metathesis (RCM) approach used by Leigh and coworkers, and then the imine condensation pathway used by Au-Yeung and coworkers. Catenation attempts are then described using the palladium trimer first designed by Nitschke and coworkers. The focus then shifts to the synthesis of the tridentate ligands and the subsequent attempts made to form [2]catenanes using the ligands and a preformed macrocycle. The synthetic pathway used by Au-Yeung and coworkers is then followed, forming copper(I) complexes which were confirmed by single crystal x-ray crystallography. Attempts where then investigated to form [2]catenanes from these complexes but were ultimately proven unsuccessful.
Chapter 4 discusses the potential future directions of this research, including the synthesis of a third generation of [2]rotaxanes as well as potential improvements to the synthesis of [3]rotaxanes. The formation of metal complex containing rotaxanes is also mentioned, along with the future directions for the attempts made for the synthesis of a family of [2]catenanes. The potential biological results are discussed, and the work performed in this research is concluded.