On the functions of palladium (II) cages
This thesis consists of four chapters. Chapter 1 provides an overview of metallosupramolecular chemistry, detailing the three main approaches to self-assembled metallosupramolecular architectures: the ligand direct approach, the symmetry interaction approach, and the weak link approach. The various applications of these systems are discussed with regards to their molecular recognition properties. A series of [Pd2(L)4]4+ cages designed and produced by the Crowley group is introduced and their achievements and failings of binding the inorganic anticancer drug cisplatin are outlined. The necessity to address the failings of these systems is the foundation for one of the aims of this project. The other goals of this project are centred around structurally similar, but functionally different [Pd2(L)4]4+ cages. These are investigated as molecular reaction vessels and their potential to enhance the rate of [4+2] Diels Alder cycloaddition reactions are studied. Chapter 2 describes the global struggle against cancer, and how inorganic drug molecules such as cisplatin are used to combat the fatal disease. Advances in the use of metallosupramolecular architectures as drug delivery vectors are discussed, in particular [Pd2(L)4]4+ cage systems. Work building on the cages first developed by the Crowley group is detailed. Terminal coordinating pyridine groups have been substituted for quinoline and isoquinoline units in the new cages. The quinoline system no longer has the ability to bind cisplatin due to a twisting caused by steric clashes of the quinoline units. As these units are situated over the external faces of the palladium(II) metal ions, they provide protection from biological nucleophiles and therefore increase the kinetic robustness of the cage. This is reflected in the increased, sub-micromolar anticancer activity, the highest activity of any [Pd2(L)4]4+ system to date. However, like cisplatin, the system displayed very little discrimination between cancerous cells and healthy tissue. Chapter 3 introduces a new [Pd2(L)4]4+ cage system whereby the central pyridine ring is replaced with a rotationally flexible, redox active ferrocene moiety. X-ray crystallography confirmed the structure of both the BF4- salt and the PF6- salt. The coordination chemistry of an alteration of the ferrocene-based ligand, whereby a 3-pyridyl donor is replaced by a 4-pyridyl donor, is also studied. Again, a single architecture was generated (and confirmed through X-ray crystallography), in this case a [Pd3(L)6]6+ prism. The exploration of the host-guest properties of both systems revealed them to interact strongly with the toluenesulfonate anion. While the cages retained the redox properties of ferrocene, the ferrocene units in each ligand did not interact with each other, and the electrochemical signals were unperturbed upon the introduction of the guest. Chapter 4 details the history and current state of artificial enzymes, with particular emphasis on metallosupramolecular structures and more specifically, how [Pd2(L)4]4+ cages accelerate the rate of bimolecular [4+2] Diels Alder cycloaddition reactions. The work presented in this chapter is a continuation of a project started by the Lusby group in which the original [Pd2(L)4]4+ cage developed by Crowley was shown to not only accelerate the cycloaddition, but also alter the chemo- and regio-selectivity of the products. Electronic alterations to the cage have been explored in this section with regard to the catalytic activity. The new cages maintained their hosting abilities however altering the electronics only seemed to diminish the catalytic behaviour of the system when compared to the parent cage.
Advisor: Crowley, James; McMorran, David; Giles, Gregory
Degree Name: Doctor of Philosophy
Degree Discipline: Chemistry
Publisher: University of Otago
Keywords: palladium; host-guest chemistry; biological chemistry; metallosupramolecular chemistry; catalysis; redox; anti-cancer
Research Type: Thesis