Abstract
This thesis consists of five chapters.
Chapter 1 discusses supramolecular chemistry and the three main approaches towards the self-assembly of metallosupramolecular architectures. These include the symmetry interaction, ligand directed and weak link approach. The host-guest chemistry of cavity containing supramolecular architectures are discussed as well as their potential applications as reaction vessels and catalysts, for drug delivery, molecular storage and sequestering of environmental pollutants. This is followed by an introduction into stimuli responsive cages that can switch on and off host-guest interactions by the addition/elimination of external stimuli. Next, the importance of heterometallic architectures and the three main synthetic approaches, metal/ligand geometry and chelation directed, subcomponent self-assembly and post-assembly modification, have been detailed. Finally, the aim of this project, that is to synthesise heterometallic Pd(II)/Pt(II) architectures for the purpose of creating stimuli responsive cages have been introduced.
Chapter 2 focusses largely on quadruply stranded Pd2L4 architectures, ease of synthesis and their host-guest chemistry as well as the difficulties that arise from making Pt(II) analogues due to Pt(II)’s higher degree of inertness. In this chapter, a range of different techniques were trialed towards the synthesis of heterometallic Pd(II)/Pt(II) structures. However, synthetic success was limited to the selective coordination of Pt(II) to a single binding site on a bis-monodentate ligand. Eventually, the most feasible approach towards the synthesis of these architectures was determined to be sub-component self assembly using mild conditions. With this approach, three new heterometallic [PdPtL4]4+ cages were synthesised through imine or hydrazone condensation reactions between a preformed [Pt(3-pyridylcarboxyaldehyde)4](BF4)2 complex and amine or hydrazide containing ligand components as well as the addition of naked Pd(II) metal ions. The ability of these cages to switch off host-guest chemistry was confirmed by the addition of the competitive ligand 4-dimethylaminopyridine (DMAP). The addition of DMAP reacted with only the labile metal end, and resulted in a [Pd(DMAP)4](BF4)2 complex and a partially disassembled cage. The addition of p-toluenesulfonic acid (TsOH) facilitated the reformation of the cages. This switching of the cages was also shown to controllably release and re-bind guest molecules.
Chapter 3 discusses the global issue that is the disease cancer and the revolutionary Pt(II) based drugs that have saved countless lives since their
v
discovery. In this chapter, the potential of supramolecular architectures as cytoxic agents and anticancer drug delivery systems have been discussed. The successfully synthesised heterometallic architectures were tested for their guest binding abilites using a selection of anticancer and antimicrobial molecules and other drug analogues. Additionally, the stability of these cages in water and when combined with selected guest molecules was examined. The cytotoxic activity of these cages along with selected host-guest mixtures was also studied.
Chapter 4 delves into the recent advances towards the synthesis of multicavity supramolecular architectures. The methods used to make the original heterometallic structures have been adapted to synthesise linearly extended double and triple cavity heterometallic architectures. The synthesis of these architectures, along with their host-guest chemistry, segregated guest binding and stimuli responsive switching have been discussed in this chapter. This chapter concludes by exploring new directions towards the synthesis of other heterometallic multicavity architectures including a heptacavity laterally extended molecule.
Chapter 5, the last chapter of this thesis, describes the synthesis of a different type of supramolecular architecture, metallohelices. Metallohelices have shown potential as cytotoxic agents due to their structural similarities to molecules ubiquitously found in nature. This chapter describes the synthesis of two new triple stranded Fe2L3 helicates, a study on their host-guest interactions and examination of their cytotoxic activity. Methods towards the synthesis of a new family of heterometallic M1M2L3 architectures have been proposed.