The work described within this thesis focuses on the syntheses of neolignans derived from dimerisation and trimerisation of 4-allyphenol. The syntheses of magnolol and honokiol, while not the first of their kind, complement the current literature by providing synthetic alternatives as well as being the most efficient to date. The synthesis of dunnianol is currently the on ly reported synthesis of the natural product to date. The synthesis of 4'-O-methyl honokiol is currently the most efficient synthesis and again provides a novel method of constructing the widely used biaryl motif. The work towards syntheses of fargenin and fargenones A and B is the first of its kind and represents substantial progress towards a first synthesis of any of the members of the natural product family. This is also the case for magnolignan F, another natural product awaiting a first reported synthesis. While the synthesis of magnaldehyde D described within this thesis is yet to be reported, it is the f irst of its kind and emphasises the lack of current literature knowledge in this area of natural products. This thesis aims to provide an insight into the largely un-explored realm of neolignan natural product synthesis.

C3d, a proteolytic fragment of complement component 3, is a ligand for complement receptor 2 (CR2) expressed by B cells. When antigen (Ag) coated with C3d cross-links CR2 and Ag specific B cell receptor, the threshold for B cell activation is lowered resulting in an enhanced response to Ag. This made C3d a prime adjuvant candidate but after many years of research this has failed to materialise. This project examines the ability of multimeric C3d to enhance the immune response to a target antigen utilising C4b-binding protein (C4BP) to provide a multimeric arrayed scaffold of human (h) C3d fused to Ag. Analysis of an extended hC3d-Hen Egg Lysozyme (HEL)-hC4BP array revealed HEL mis-folding compromised its functionality and secretion. Therefore, a new multimeric hC3d-Tetanus Toxin C Fragment (TICF)-hC4BP and appropriate multimeric controls were developed. These were successfully expressed and purified from mammalian cell cultures. Immunoassays confirmed recombinant proteins self-formed into large multimeric structures and individual domains were in the correct conformation. Initial studies demonstrated that multimeric hC3d-TTCF array could bind to both h & mouse (m)CR2. Wild type mice were immunised with proteins but antibody response to the multimeric hC3d- TTCF were poor. Thorough analysis of construct binding to a range of mouse and human B cells revealed that whilst hC3d could specifically interact with hCR2 it did not bind mCR2. Immunisation of hCR2+ mice with the multimeric hC3d- TTCF was found to be equally poor and studies with hCR2+.C3-1- mice suggested that mouse C3 could compete with hC3d binding to hCR2 in vivo. These results have established no discernible interactions of mCR2 with recombinant hC3d and have added to existing concerns regarding the limitations of using multimeric C3d as an adjuvant. Indeed, the results indicate that multimeric arrayed C3d-Ag is inhibitory with respect to immune response that may provide future therapeutic applications.

This thesis describes the development of a new approach to the discovery of novel bioactive small molecules in which diversity-oriented synthesis techniques are integrated with structure-based ligand design. The approach was applied to the design, synthesis and evaluation of analogues of platensimycin, a potent natural product antibiotic known to target the fatty acid biosynthesis pathway enzyme FabF. The design of analogues was achieved by the creation of a virtual library of fragments that formed part of molecules which could be synthesised using diversity oriented methods developed within the Nelson group. These fragments could then be appended in silica to the headgroup taken from platensimycin to generate new molecular scaffolds. These molecules could be subsequently decorated in silica with a range of functional groups to further improve their predicted binding affinity. The synthesis of analogues was accomplished using fluorous-tagged specialised building blocks, containing the platensimycin headgroup. Skeletal information for molecular scaffolds was pre-encoded by appending simple building blocks, to yield metathesis substrates, which could be reprogrammed by ring closing metathesis, accessing a range of heterocyclic scaffolds. Further functionalisation of the heteroatoms in the resulting products allowed all the analogues to by prepared using a common synthetic route. Finally, the ligands were assessed using an NMR-based biophysical assay which had not been used previously to test FabF inhibitors. This assay allowed a critical evaluation of the approach by comparison of predicted and observed K; values.

New metal complex derivatives of tppz containing cationic "diquat" sites have been synthesized and characterized. Their interaction with DNA has also been explored .. Water-soluble organic cationic derivatives of the dppz ligand with a variety of functional groups and number of aromatic rings in the phenazine region have also been synthesised and characterized. These systems were synthesized with the aim of modulating the energy of the internal charge transfer excited state of the parent cation. The interactions of the new organic diquaterary salts of dppz with ON A have been studied. Metal complexes containing dppz ligands that are the free base analogues of the cationic systems have also been synthesized and their interaction with DNA has also been investigated.

The content of this thesis is concerned with two distinctly independent areas of research: (i) the synthesis and coordination chemistry of new multidentate ligands and investigate their emission properties; (ii) the synthesis and study of new poly(pyrazol-1-yl)borate and Pt(II) based ligands and their lanthanide complexes.

The synthesis and characterization of d- and f-block metal ions with aminopolycarboxylic acid derivatives of the iminodiacetic acid ligand family is described.

A number of bipyridyl compounds containing amide functionalities have been prepared as bridging bipyridyl ligands in coordination networks.  The bridging ability and hydrogen bond donor-acceptor functionality of these compounds in coordination networks has been explored by their inclusion in crystallisation experiments containing a single salt from a variety of <i>d</i> block metal salts, with ethanol and water as the solvent.  The crystal structures of the coordination network polymers of [Cd L₂ (H₂O)₂]_2/∞2NO₃ (L = <i>N,N’-bis</i>(3-pyridylmethyl)urea), [Cu L₂ (NO₃)₂]_2/∞^. 2H₂O ^.2EtOH (L = <i>N,N’-bis</i>(3-pyridylmethyl)urea), [Cd L₂ (NO₃) (H₂O)]_1/∞^. NO₃ ^. H₂O (L = <i>N,N’-bis</i>(4-pyridylmethyl)urea), [Cu L₂ (NO₃) (H₂O)]_1/∞^. NO₃ ^. H₂O (L = <i>N,N’-bis</i>(4-pyridylmethyl)urea), [Cd₃ L₄ (H₂O)₈ (H₂O)₈ (SO₄)₂]_1/∞^. 4H₂O ^. SO₄ (L = <i>N,N’-bis</i>(4-pyridylmethyl)urea), [Cu L (OAc)₂]_1/∞(L = <i>N,N’-bis</i>(4-pyridylmethyl)urea), [Cu₂ L₂ (NO₃)₄ (BIPY)₂ (H₂O)₃/_1/∞^. H₂O (L = <i>N,N’-bis</i>(4-pyridylmethyl)isophthalamide), (BIPY = 2,2’-bipyridine) and [Cu L₂ 2(H₂O)]_1/∞^. 2(H₂O) ^. 2(CIO₄)₂ (L = <i>N,N’-bis</i>(3-pyridylmethyl)succinamide) are described. Wittig reaction conditions, followed by hydrogenation are used for the preparation of a number of saturated bipyridyl compounds possessing an additional aromatic functionality.  The bridging ability of these ligands has been explored by their inclusion in crystallisation experiments containing a single salt from a variety of <i>d</i> block metal salts, with ethanol and water as the solvent.  The crystal structures of the coordination polymers of [Cd L₂ (NO₃)₂]_2/∞(L = 1,2-<i>bis</i>[2-(3-pyridyl)ethyl]benzene), [Cd L₂ (H₂O)₂ (CIO₄)₂]_2/∞(L = 1,2-<i>bis</i>[2-(3-pyridyl)ethyl]benzene), [Cu_1.5L₂ (NO₃) (H₂O)₂]_2/∞^. 2(NO₃) ^. 2.7(H₂O) (L = 3,5-<i>bis</i>[2-(4-pyridyl)ethyl]pyridine) and [Cd₂ L₅ (H₂O)₄]_1/∞^. L ^. 2H₂O ^. 2EtOH ^. 4CIO₄ (L = 1,4-<i>bis</i>[2-(4-pyridyl)ethyl]benzene) are described.

No description available.

This work is separated into two distinct sections. The first section deals with the analysis by variable temperature single crystal X-ray diffraction of crystalline molecular materials with novel physical properties. The second section details the electron density analysis of selected crystalline compounds using high resolution, low temperature single crystal X-ray diffraction. Chapter 1 provides introduction to X-ray diffraction outlining the theory this work is based on. Chapter 2 introduces the molecular material studies based on materials containing the bis(ethylenedithio)-tetrathiaftilvalene molecule. The aim of these studies was to achieve a greater understanding of the materials and the changes they undergo when exposed to variations in temperature whilst in the crystalline state. These structural changes observed are very minor but have dramatic effects on the electrical properties of the materials studied. It became apparent that the only way to form a full understanding of these materials was to be able to 'see' the electronic configuration of the materials, not just their gross structure. The field of electron density analysis by X- ray diffraction is now a well documented area. Chapter 4 provides an introduction to the field of electron density analysis. Diffraction experiments were conducted on systems of different complexity to investigate this field and these results are reported in Chapter 5. No electron density analyses have been conducted on the molecular materials studied in Chapter 3 as yet, due to the lack of crystals of suitable quality. It was also noted that to fully categorise the nature of the physical changes occurring in these structures that a diffractometer capable of analysing these samples throughout the temperature range of their physical phenomena was needed. An outline for the development of such a diffractometer is detailed in Chapter 6, 'future works'.

The content of this thesis is concerned with two distinctly independent areas of research: (i) the synthesis and study of new poly(pyrazol-1-yl)borate ligands and their metal complexes; (ii) crystallographic and photophysical studies of new d-f hybrid complexes. Chapter One is divided into three parts: Part one gives a general introduction to poly(pyrazol-1-yl)borate chemistry along with a concise and up-to-date review of those ligands containing substituents in the C3 position of the pyrazolyl ring; part two provides a brief introduction into the physical properties of lanthanide(III) metal ions, as well as describing the practical applications of their individual spectroscopic properties; and part three contains a brief review on the structural chemistry of cyanide-bridged coordination polymers. Chapter Two describes the syntheses of four new scorpionates: dihydrobis[3-(4-pyridyl)pyrazol-1-yl]borate (Bp4py); dihydro-bis[3-(3-pyridyl)pyrazol-1- yl]borate (Bp3py); hydro-tris[3-(4-pyridyl)pyrazol-1-yl]borate (Tp4py) and hydrotris[3-(3-pyridyl)pyrazol-1-yl]borate (Tp3py). A series of X-ray crystallographic studies reveals a range of mononuclear, dinuclear and polymeric coordination complexes with various metal ions. Chapter Three describes a range of structural and photophysical studies on lanthanide(III) complexes of poly(pyrazol-1-yl)borate ligands. New mixed-ligand lanthanide(III) complexes with various combinations of the anionic ligands Tp2py , Bp2py and dibenzoylmethane (dbm) were prepared and structurally characterised. Photophysical studies on the isostructual series [Ln(Bp2py)(dbm)2] (Ln = Pr, Nd, Er, Yb) show characteristic near-IR luminescence from the lanthanide ion. Near-IR luminescence was also demonstrated from the complexes [Ln(Bp2py) 2(NO3)] and [Ln(Tp2py)(NO3) 2] (Ln = Pr, Er), upon suitable excitation of the ligand chromophores. Chapter Four describes the structural and photophysical properties of new cyanide-bridged d-f coordination polymers. Structural and photophysical studies are presented for a series of Ru-Ln complexes based on the [Ru(bipy)(CN)4] 2- donor unit connected to a Ln(III) energy-acceptor via cyanide bridges (where bipy is 2,2’- bipyridine and Ln = Pr, Nd, Er, Yb). Structural and photophysical studies were also performed on [Cr(CN)6][Ln(DMF)4(H2 O)2] complexes, in which the lanthanide ion (Ln = Nd, Yb) acts as the energy acceptor from the hexacyanochromate chromophore. The structures of [Cr(CN)6][Ln(H2 O)2] (Ln = Gd, Yb) and K2[Ru(phen)(CN)4] (where phen = 1,10-phenanthroline) are also presented. Chapter Five gives a brief review of the field of X-Ray Crystallography with analysis of the history and theory of the technique, as well as an overview of its practical aspects used in this work. A few crystal structures solved by the author, and independent of the topics in this thesis, are also reported.