Since its advent in the 1960s, through the pioneering work of Lehn, Cram, and Pederson – the field of supramolecular Chemistry has burgeoned and seen an array of applications across the chemical and materials sciences. From Metal-organic frameworks which exhibit notable chemical separation behaviours, to molecular receptors, and the compounds which form Organic Light Emitting Diodes used by millions daily, there are countless examples of the continuous advancements from the field. One such recent interdisciplinary area gaining traction in recent years, is the application of supramolecular chemistry concepts, and molecular design to the field of medicinal chemistry. For example, there have been a plethora of reports of anion transporters, molecules which can form association complexes with negatively charged ions and transport them across membranes. These anion transporters have shown utility in the development of therapeutics for Cystic Fibrosis, as anticancer therapeutics, and more recently as antimicrobial agents. Whilst the anticancer properties of anion transporters have been explored extensively, and mechanistically characterised, there has been little effort made to further refine the antimicrobial capacity of agents such as these. Furthermore, while several reports of antimicrobial anionophores have been made – very little mechanistic underpinning has been carried out. This Thesis, titled “Supramolecular tools to combat antimicrobial resistance” aims to establish several classes of anionophores, and chemical tools to further delve into the mechanistic subtleties of medicinally relevant supramolecular motifs. Chapter 1 of this thesis provides a historical perspective on the supramolecular chemistry of anion transport, paying particular attention to the medicinal relevance of anion transporting motifs. In addition, there is a discussion of concepts employed by medicinal chemists when designing antibiotics, aided through a discussion of historically relevant examples, and the emergence of antimicrobial resistance. Following this, some of the chemical biology techniques utilised throughout the course of this work are introduced and discussed from a technical viewpoint. Chapter 2 discusses the synthesis, supramolecular profiling, and mechanistic underpinning of a series of four potent “squindole” antimicrobials. These compounds, which can effectively bind, and transport Cl- across Large Unilamellar Vesicles (LUV’s), exhibit potent antimicrobial activity, which was discerned to be as a result of a disruption of chloride homeostasis. Chapter 3 follows on from the previous chapter, where we aimed to synthesise sophisticated bioconjugates of the most active lead compound, from chapter 2. Aided by the use of “click” chemistry, we made significant progress towards the development of natural product derived ion-pair receptors, for investigation as antimicrobials. Whilst we could not arrive at a set of synthetic conditions which afforded target compounds, we have made significant progress in this regard, and developed a series of biorthogonal anion receptor motifs. In addition, through conjugation of lead compounds to siderophores, we were able to expand the spectrum of activity to encompass Gramnegative pathogens. Chapter 4 takes a traditional “lead-refinement” approach to the development of heterocyclic antimicrobial anionophores. Through scaffold hopping approaches, from lead compounds of Chapter 2, we afforded three distinct heterocyclic subfamilies, each of which exhibits antimicrobial effect against MRSA – to varying degrees. Using conventional supramolecular approaches, in addition to cutting edge Chemical Biology techniques, we studied, and verified an analogous mechanism of action to previous leads, which is aided by the propensity for covalent modification of thiols in solution, which may rationalise the observed antimicrobial effect. Chapter 5 introduces a series of 13 structurally simplistic anion receptors, which show varying anion binding propensities, but potent anion transport in-cellulo. This anion transport behaviour manifests in potent antimicrobial activity against a range of pathogens (both Gram-positive, and -negative), which we discerned to be linked to both anion transport, and a disruption of membrane integrity. In addition, we successfully synthesised a “caged anionophore” and carried out preliminary dissection of the spatiotemporal control of anion transport in-cellulo. Chapter 6 consists of a thesis summary which details the main findings for this project, and potential future directions for each chapter. Chapter 7 includes the general experimental procedures, synthetic methodology and compound characterisation, and biological procedures for the work detailed in previous chapters. This is complimented and followed by literature references and an appendix which is comprised of spectroscopic and ancillary data which validates the work discussed in this thesis.