This thesis describes studies, which have been realised towards the total syntheses of two natural products (–)-FR901483 (1) and (+)-TAN1251B (3), which are thought to be biosynthetically related. The introduction summarises the isolation and biological activities of both natural products. It then focuses on previous methods used to overcome the key challenges in their syntheses: formation of their related tricyclic cores and the quaternary stereocentre next to nitrogen. Our initial retrosynthetic analysis is presented, which proposes the formation of both targets from a common intermediate. 1,5-CH insertion of an alkylidene carbene would allow formation of this common intermediate, containing the challenging quaternary stereocentre adjacent to nitrogen, in a stereoselective fashion. A brief review of work employing this methodology, which has been described within the Hayes group towards these natural products follows. The results and discussion begins with the synthesis of the common intermediate. From here, work towards the formation of the tricyclic core of (–)-FR901483 (1) is presented. The initially proposed route of closing the final ring of the tricyclic core via a regioselective intramolecular aldol cyclisation was found to be unsuccessful. A revised route involving an intramolecular peptide coupling as the key ring closing step gives our first tricyclic derivative of (–)-FR901483 (1). Formation of a related tricycle is subsequently achieved via a palladium-catalysed alkenylation reaction. The unsuccessful attempts at elaboration of this structure are then discussed. Finally, the progress made in a revised route towards the formation of a key intermediate in Fukuyama’s synthesis of (–)-FR901483 (1) is depicted. The progress made towards the target, and possible work for the future is then reviewed. In the final part of the results and discussion, efforts made towards the synthesis of (+)-TAN1251B (3) are presented. The successful installation of the key hydroxyl group alpha to the ketone in a stereoselective manner via treatment of a silyl enol ether derived from the common intermediate with DMDO is reported. From here, formation of the tricyclic core is achieved using an intramolecular peptide coupling. Further elaboration allows installation of the side-chain and results in the carbon skeleton required for the total synthesis of (+)-TAN1251B (3). A summary of this work and the future steps required to complete the synthesis are then presented. The thesis concludes with an experimental section, which gives detailed procedures and full characterisation data for the novel compounds discussed in the results and discussion part.

One potentially attractive approach to cancer therapy is to recruit the body’s own immune system to reject solid tumours. The enzyme indoleamine 2,3-dioxygenase (IDO) has been shown to play a major role in supressing immune response, and there is now growing evidence to support the hypothesis that inhibition of IDO produces significant anticancer effects. The development of chemotherapeutic agents for cancer based on the inhibition of indoleamine 2,3-dioxygenase is the purpose of this present work. Chapter I contains an overview of indoleamine 2,3-dioxygenase, describing its structure, activation cycle, catalytic mechanism and inhibitors. Chapter II is divided in two parts. Initially the efforts towards the synthesis of a simple analogue, containing the isobenzofuranquinone moiety of annulins A and C are described. The aim was to verify which part of the molecule was important for IDO inhibiton. Four main approaches to the analogue are described. Next, investigations into the total synthesis of annulins A and C are discussed. These led to the synthesis of the naphthoquinone core of both natural products by performing a Diels Alder reaction. Attempts to introduce the furan ring proved challenging, and different approaches to this problem are described in this Chapter. In Chapter III, the synthetic approaches towards annulin B are discussed. The possibility to access this natural product via Diels Alder reaction, prompted us to investigate the synthesis of the required dienophile – a chroman-3-one substrate. We succeeded in constructing this highly advanced intermediate using two different strategies, namely a Dieckmann condensation and an intramolecular O-H insertion reaction. Finally, the synthesis and biological evaluation of a narrow range of benzofuranquinones with varying substituents are presented in Chapter IV. Their synthesis was based on the structure of the benzofuran ACH488, previously identified as a good IDO inhibitor. The experimental details of the above work are described in Chapter V.

The work presented in the thesis attempted to gain in-depth understanding of the effect that the microwave energy has on various facets of the ring-opening polymerisation of cyclic esters with a view to synthesising novel bio-degradable homopolymers, branched structures and copolymers. Chapter 1 introduces the various synthetic polymer procedures and lists possible final product architectures. The main technique that is used throughout this thesis, ring-opening polymerisation, is discussed in great detail. The various targeted linear aliphatic polyesters are introduced. Finally, the fundamental theory behind microwave dielectric heating is discussed. Chapter 2 outlines the various characterisation techniques that are used to analyse the various synthesised materials throughout the work in this thesis. The polymerisation techniques used, particularly using the microwave reactor, is also discussed. In Chapter 3, the effect that microwave heating has upon the homopolymerisation of poly(ε-caprolactone) is investigated. Detailed analysis of the dielectric properties of the reagents and accurate temperature monitoring is applied at various stages of the reaction mechanism to compare and contrast the effect of microwave and conventional heating. Chapter 4 describes the impact that microwave energy has upon the copolymerisation reactions when a second cyclic ester is introduced, D/L-lactide. Various procedures are utilised in an attempt to synthesise bio-degradable block copolymers with interesting mechanical properties and degradation rates. The dielectric properties of the reagents and their polymer structures are used to rationalise any experimental observations. The work presented in Chapter 5 investigates the synthesis of branched polymers using a di-lactone branching agent, composed to two joined ε-CL units. Various analytical techniques are employed to guarantee successful branching. The effect of microwave energy is scrutinised, with a view to creating faster rates of reaction and altering the final product structure using direct dielectric heating. Finally, Chapter 6 provides the overall conclusions obtained from the work presented in this thesis, before providing possible routes of subsequent study for further research into this area.

This thesis comprises six chapters. Chapter 1 introduces the background to the project. In this chapter, issues of energy problems, the advantages of H2 and materials and methods for storage are introduced and then the subject is focused on porous metal-organic frameworks (MOFs), a new class of porous materials which are good candidates as on-board storage materials combining with the fuel cell technology. Three topics are discussed about porous materials, (i) metal nodes as secondary building units (SBUs) to prepare porous MOFs, (ii) the strategy in design and synthesis for hydrogen storage in MOFs, (iii) review of gas storage by H2, CH4 and CO2 in MOFs. Chapters 2 to 6 are the results and discussions from my work. They are separated based on different metal cation system. Chapter 2 describes materials prepared from Mg(II) cations and bi- or tricarboxylate ligands. H2L1, H2L2 were purchased from commercial suppliers and three carboxylate ligands were synthesized. All have been employed in the preparation of MOFs to give five Mg(II) framework materials: {Mg3(L1)3(DMA)4}∞ 1, [Mg3(L2)3(DMF)4]∞ 2, [Mg3(L3)3(DMF)4]∞ 3, {[Mg3(L4)2(DMA)4]•(DMA)4}∞ 4, {[Mg3(L5)2(DMA)4]•(DMA)4}∞ 5. The structures of these compounds obtained from single crystal X-ray diffraction and porosity in network are discussed. H2 adsorption measurement is carried out on {[Mg3(L5)2(DMA)4]•(DMA)4}∞ 5, which gives a uptake of 2.06 wt% at 20 bar at 77 K. Chapter 3 describes materials prepared from Ni(II) cations and tetracarboxylate ligands. {[Ni2(L6)(H2O)4]•(DMF)3(EtOH)(H2O)5}∞ 6, {[Ni2(L7)(H2O)5]•(DMF)2(EtOH)2(H2O)6}∞ 7, {[Ni2(L8)(H2O)5]•(DMF)3(EtOH)2(H2O)7}∞ 8 are afforded. Analyses of structure, thermal stability and porosity of the compounds are discussed. Chapter 4 describes MOF materials prepared from Cu(II) cation and tri- or tetracarboxylate ligands. {[Cu2(L12)(H2O)2]•(DMF)3(C2H5OH)3(H2O)5}∞ 13, {[Cu2(L13)(H2O)2]•(DMF)3(C2H5OH)4(H2O)7}∞ 14, {[Cu3(L14)2(H2O)3]•(DMF)2(C4H8O2)4(H2O)5}∞ 15, {[Cu3(L14)2(H2O)3]•(DMF)1.5(DMSO)3(H2O)6}∞ 16, {[Cu2(L15)(H2O)2]•(DMF)(C4H8O2)2(H2O)5}∞ 17, {[Cu2(L16)(H2O)2]•(DMF)(C4H8O2)1.5(H2O)4}∞ 18, {[Cu2(L17)(H2O)2]•(DMF)0.5(C4H8O2)(H2O)3}∞ 19 are affored. Analyses of structure, thermal stability and porosity of the compounds are discussed. Gas adsorption measurements (N2, Ar, H2, CH4 and CO2) are carried out on porous materials. Chapter 5 describes a new (4,8)-connected polyhedral framework with mixed pores was synthesised based on Cu(II) cation and a tetrabranched octacarboxylate ligand {[Cu4L18(H2O)4]•10DMF•C4H8O2•8H2O}∞ 20. Analyses of structure, thermal stability and porosity of the compounds are discussed. Gas adsorption measurements (N2, Ar, H2, CH4 and CO2) are carried out this compound, which gives a hydrogen uptake of 2.5 wt% at 1 bar and 6 wt% at 20 bar at 77 K. Chapter 6 summarizes the crystal structure and gas adsorption of the MOF materials obtained in each chapter.

Consistent assignment of vibrational motions across substituted benzene derivatives is a long-standing desire amongst spectroscopists. In this thesis, the S1 electronic states of monohalosubstituted benzene molecules and their deuterated isotopologues are investigated, using resonance enhanced multiphoton ionisation spectroscopy. The observed vibrational bands are assigned using the Mi nomenclature proposed by Gardner and Wright where ring localised vibrations having the same atomic motion are given the same label, allowing straightforward comparisons of vibrational motions across monosubstituted benzene molecules to be achieved. Detailed investigation showed that it would not be possible to apply the same Mi nomenclature labels to the para disubstutited benzene derivatives owing to the different vibrational motions of mono- and disubstituted benzene molecules. As a consequence a new nomenclature, Di, for labelling the vibrational motions of para disubstituted benzene molecules is proposed in this work. The Di labelling scheme is based on the vibrations of the para difluorobenzene molecule. S0 state vibrations of symmetric and asymmetric para dihalobenzene species, para fluorotoluene and para xylene are studied in detail, showing that the ring localised vibrational motions of para disubstituted benzene species are being described by the same label.

This thesis describes the synthesis of diphenolate and dithiophenolate complexes of ZnII, NiII and CuII that derive inspiration from the natures of the active sites of the nickel-containing superoxide dismutase (NiSOD) and the copper-containing galactose oxidase (GO). Chapter One introduces the roles of transition metals in biology. The structures of the active sites of NiSOD and GO are described, together with a discussion of the proposed mechanisms of their action. A brief review of the coordination chemistry relevant to the chemistry of the actives sites of NiSOD and GO is presented and the aims of the research described in this thesis are set out. Chapter Two describes the syntheses and structural characterisations of a series of pentacoordinate ZnII, NiII and CuII diphenolate complexes MRLoNMe (M= Zn, Ni, Cu; R = Cl, Br, Nap, Ph, PhMe, PhOMe, tBu/Br, tBu/Ph, tBu/PhMe, tBu/PhOMe; page xiii) that differ in the natures of the substituents at the 3- and 5-positions of the phenolate rings within the ligand backbone. X-ray crystallographic studies on the ZnII, NiII and CuII complexes, and room temperature and frozen solution EPR spectroscopic experiments on the CuII complexes provide insight into the influence of the 3- and 5- substitution on the coordination geometries. The changes in substitution at the 3 position of the phenolate rings in MRLoNMe (M= Zn, Ni, Cu; R = tBu/Ph, tBu/PhMe, tBu/PhOMe) have significantly less influence on the geometry about the metal centre when compared to complexes that have substitutions that vary at the 3 and 5 positions in MRLoNMe (M= Zn, Ni, Cu; R = Ph, PhMe, PhOMe). DFT calculations provide a qualitative description of the electronic structures of these complexes, suggesting an increase in the metal character within the HOMOs for the NiII complexes relative to those of their ZnII and CuII counterparts. Chapter Three describes the electrochemical characterisations of the complexes synthesised in Chapter Two [MRLoNMe (M= Zn, Ni, Cu; R = Cl, Br, Nap, Ph, PhMe, PhOMe, tBu/Br, tBu/Ph, tBu/PhMe, tBu/PhOMe)]. Cyclic voltammetry demonstrates that MRLoNMe (M= Zn, Cu; R = Cl, Br, Nap, tBu/Br) possess oxidation processes that are not reversible. MRLoNMe (M= Ni; R = Cl, Br, Nap, tBu/Br) possess a reversible oxidation process assigned to the NiIII/NiII redox couple. MRLoNMe (M= Zn, Ni, Cu; R = Ph, PhMe, PhOMe, tBu/Ph, tBu/PhMe, tBu/PhOMe) display multiple oxidation processes, some of which demonstrate electrochemical reversibility, particularly when M = Ni or Cu. UV/Vis and EPR spectroscopic studies on the oxidised species [MRLoNMe]+ (M= Zn, Ni, Cu; R = Ph, PhMe, PhOMe, tBu/Ph, tBu/PhMe, tBu/PhOMe), supported by DFT calculations, suggest that the first oxidation process is significantly more metal based when M = Ni than for M = Cu or Zn and for the generation of [NiRLoNMe]+ is associated with the formation of formal NiIII species. The UV/vis and EPR spectroscopic results also suggest that [NiPhOMeLoNMe]+ exhibits temperature-dependent NiIII-phenolate  NiII-phenoxyl redox tautomerism. The variation of the aromatic substituents systematically decreases the redox potential in the order R = Ph > PhMe > PhOMe, consistent with the relative electron donor properties of each group. Chapter Four examines complexes that incorporate an aromatic, N-donor group pendant to the ligand background. These complexes serve as analogues of the active site of NiSOD. The dithiophenolate and diphenolate complexes NitBuLSPy, NitBuLSPyOMe, NitBuLOPy, NitBuLOPyOMe, and NitBuLOPh are prepared and characterised to examine the effect of different N-donor groups as potential axial donors to the metal centre on the redox properties of each complex. Advanced pulsed ESSEM and HYSCORE EPR spectroscopic studies probe the weak superhyperfine couplings involving the 14N imine donors in [NitBuLSPy]+, and benchmark the spin densities associated with these donors calculated by DFT. These spectroscopically validated DFT calculations show how the distribution of spin density varies between complexes incorporating an N-donor pendant to the ligand backbone and those that do not. Thus, those incorporating an additional N-donor possess spin density that is considerably more localised at the formal NiIII centre than those that do not. Chapter Five discusses the key conclusions of the research described in this thesis and compares and contrasts the chemistry exhibited by ZnII, NiII and CuII diphenolate and dithiophenolate complexes. The structural and electrochemical differences observed upon the introduction of alternative diphenolate substituents in MRLoNMe (M= Zn, Ni, Cu; R = Cl, Br, Nap, Ph, PhMe, PhOMe, tBu/Br, tBu/Ph, tBu/PhMe, tBu/PhOMe) are summarised, together with the importance of the geometric structure of NitBuLSPy in controlling the redox chemistry of this centre. Finally, implications for the chemistry of the active sites of GO and NiSOD are discussed.

The study of metal-ligand multiple bonding offers insight into the electronic structure and bond of metal systems. Until recently, for uranium, such systems were limited to uranyl, and terminal chalcogenide, imide and carbene complexes. In 2012, this was extended to nitrides with the first preparation of a uranium–nitride (U≡N) species isolable under standard conditions, namely [U(TrenTIPS)(N)][Na(12C4)2] (52), which is prepared by the two-electron reduction of sodium azide with a trivalent uranium(III) precursor [U(TrenTIPS)] (15), and the subsequent sequestration and encapsulation of the loosely bound sodium cations. In order to then fully explore the bonding within this newly isolated fragment, alternative routes to prepare uranium–nitrides were investigated, in order to both expand the family of known uranium–nitrides, as well as remove the synthetic bottleneck that occurs due to issues in scale-up. The reduction of the pre-installed azide ligand of [U(TrenTIPS)(N3)] (13) with one-electron external reductants, namely the alkali powders or metals (lithium and sodium, rubidium and caesium) and potassium graphite, affords the dinuclear uranium(V)–nitride species of the form [{U(TrenTIPS)(µ-N)(µ-M)}2] (M = Li, Na, K, Rb, Cs; 51, 106 – 109). Analogously to the preparation of the first terminal uranium–nitride system, encapsulation of the cation affords separated ion pair species of the form [U(TrenTIPS)(N)][M(crown)2] (M = Na, K, Rb, Cs; 52, 114 – 117), or if a slightly larger co-ligand is utilised, capped uranium–nitrides of the form [U(TrenTIPS){(µ-N)(µ-M)(crown)}] (M = Li, Na, K, Rb, Cs; 53, 111 – 113, 118, 119). Oxidation of the separated ion pair nitrides affords the neutral uranium(VI)–nitride, [U(TrenTIPS)(N)] (54). Attempts to prepare dinuclear uranium–nitrides by the reduction of 13 with benzyl potassium (KCH2Ph) afforded instead the cyclometallated species [U{CH2CH(Me)Si(iPr)2NCH2CH2N(CH2CH2NSiiPr3)2}] (110). Unexpectedly, in an inversion of the anticipated reactivity trend, attempts to prepare a thorium congener of 110 did not initially form a cyclometallated species, with the reaction of [Th(TrenTIPS)(I)] (123) and KCH2Ph affording [Th(TrenTIPS)(CH2Ph)] (124); and cyclometallation was thermolytically induced. Computational calculations indicate that this is due to the stabilisation of the σ bond metathesis transition state in the uranium case. A combination of experimental and computational studies allows for the determination of the electronic structure of the families of uranium(V)–nitrides, by considering all the spectroscopic data available for the dinuclear, terminal separated ion pair and capped species in conjunction with ab initio calculations. This approach then leads to a description of the ground and excited states of Tren–uranium(V) nitrides, where [{U(TrenTIPS)(µ-N)(µ-K)}2] (107) and [U(TrenTIPS){(µ N)(µ Na)(15C5)}] (53) exhibit a jz ≈ ±5/2 ground state doublet, with a jz ≈ ±3/2 first excited state doublet, in contrast to all other nitrides studied, where the reverse is the case. The excited states can be derived from spectroscopic data (EPR and UV-vis-NIR), which corroborate these findings. A series of investigations into the small molecule activation chemistry of uranium–nitrides were instigated. The reaction of Tren–uranium(VI) or uranium(V)–nitrides (54, with carbon monoxide resulted in two-electron reductive carbonylation to afford the corresponding uranium(IV)– and uranium(III)–isocyanates, [U(TrenTIPS)(NCO)] (135), [U(TrenTIPS)(NCO)][K(Bn 15C5)2] (136), [U(TrenTIPS){(µ NCO)(µ K)(18C6)}] (137). Reduction of 135 with potassium graphite afforded complete nitrogen atom transfer to eliminate KOCN and generate 15. In the presence of crown, the uranium–nitrogen bond is retained and 136 or 137 can be isolated. A synthetic cycle for the conversion of NaN3 to NaOCN was investigated employing the UIII-UV redox couple by the reaction of 15, NaN3 and CO in pyridine, where one turnover was observed. DFT calculations were used to model these reactions, and they provided evidence for nucleophilic behaviour and explained the difference in the rates of reaction. The reaction of heteroallenes (CE2, E = O, S) with Tren–uranium nitrides was also investigated. It was found that terminal uranium–nitrides react with CO2 to afford uranium–oxo–isocyanates, with retention of uranium oxidation state. In the case of uranium(V), [U(TrenTIPS)(O)(NCO)][K(Bn-15C5)2] (138) is stable, though for uranium(VI), [U(TrenTIPS)(O)(NCO)] (139), a cyanate radical is extruded, which decomposes via diisooxocyan to afford N2 and CO, preparing [U(TrenTIPS)(O)] (122). With CS2, uranium(V)–nitrides undergo overall disproportionation to afford uranium(IV)–trithiocarbonates [U(TrenTIPS)(κ2-CS3)][K(Bn-15C5)2] (140) and [{U(TrenTIPS)(µ-κ2:κ1-CS3)(µ-K)(Bn2-18C6)}2(µ-C6H6)] (141), and uranium(VI)–nitride (54), alongside the formation of [K(crown)n][SCN]. The reaction of 54, which cannot engage in disproportionation chemistry, with CS2 prepares a uranium(IV)–isothiocyanate, [U(TrenTIPS)(NCS)] (142), by the elimination of sulfur, which can be scavenged by triphenylphosphine. Calculations reproduced experimental outcomes, and show that while uranium(V)–nitrides (115) engage in outer sphere type reactivity, uranium(VI)–nitrides (54) instead react via inner sphere mechanisms.

Rylene diimides have attracted much attention for use in optoelectronic devices, with excellent absorption and emission profiles, as well as a tendency to form n-type semiconductors. The absorption and emission properties of rylene diimides can be varied through functionalisation at the imide nitrogens and by substitution to the aromatic core but the effects of alterations to the imide oxygen atoms are less well understood. A series of thionated naphthalene diimides (NDIs), in which the imide oxygen atoms have been replaced with sulfur has been synthesised in a single reaction using Lawesson’s reagent. Electrochemical measurements of the series reveal that the electron affinity increases significantly with sulfur substitution, making the singly and doubly reduced states of the NDI much more accessible. This work is expanded further with the production of asymmetric NDI and naphthalic imide systems. Phenothiazine is employed as an electron donor and thionated derivatives of NDIs and naphthalic imides are implemented as the electron acceptors. Photoinduced charge separation was observed for these dyads using a combination of picosecond time-resolved transient absorbance spectroscopy and infrared spectroscopy, finding that thionation increases the charge separated lifetime of the species by a factor of ten; producing radical pairs with lifetimes greater than 2 ns, sufficient for charge extraction in organic electronic devices. Perylene diimides (PDIs) are related to NDIs, but with a larger aromatic core. Despite an enhancement of desirable properties relative to NDIs, the practicality of PDIs can be limited by low solubility and demanding syntheses. As the field of supramolecular chemistry expands, the synthesis of more sophisticated molecular arrays has become necessary to build improved nanotechnological components. Herein, the effectiveness of a bulky aromatic solubilising group for PDIs is examined crystallographically and used to synthesise a range of soluble N,N’-asymmetrically disubstituted PDI compounds. The applications of this new solubilising group were demonstrated in the production of a multichromophoric PDI dimer; in the assessment of binding affinity of a hydrogen-bonding PDI to the nucleobase adenine and finally in the synthesis of a charge transfer complex, again utilising phenothiazine as an electron donor. This charge transfer complex was also thionated, providing a unique perylene monoimide monothiomide with an experimentally determined band gap of approximately 1 eV.

The main goal of this thesis was to design new small molecule DPP derivatives, which could have a multitude of potential applications in areas such as organic electronics and sensors. Based on literature precedent, four factors were chosen to manipulate in the design of novel DPP systems: the electron richness of the aryl unit, π - π stacking, chirality and hydrogen bonding. The influence of these modifications to the DPP system on the optical, electronic and structural properties was then investigated to screen materials for potential applications in the aforementioned areas and to gain greater understanding for future molecular design in terms of structure-property relationships.

Intramolecular vibrational redistribution (IVR) has long been investigated in para-fluorotoluene (pFT), with many comparisons made to para-difluorobenzene (pDFB). These comparisons have shown an increased IVR rate for pFT compared to pDFB at similar internal energies, and there are two factors which could influence this - the addition of the methyl group and the lowering of the symmetry of the molecule. This thesis looks to separate these two effects by introducing a comparison of pFT to para-chlorofluorobenzene, as well as an additional comparison of para-xylene (pXyl) to pDFB. Resonance-enhanced multiphoton ionisation (REMPI) spectra of these four molecules are presented, with zero-electron-kinetic-energy (ZEKE) photoelectron spectra recorded via many intermediate levels up to ~00+1200 cm-1 for both pFT and pXyl. These ZEKE spectra allow the assignment of many torsional, vibrational and vibration-torsion levels in these two molecules, with pXyl treated with the appropriate G72 molecular symmetry group for the first time. Several reassignments, as well as many new assignments, are presented for pFT and pXyl. Use of the REMPI and ZEKE techniques allows for the probing of any couplings between levels in the S1 state, as well as providing ground state cation information, and this is supplemented by comparison of REMPI activity between the four para-disubstituted benzene molecules. Proposed couplings, which appear to become more widespread at higher internal energies, are supported by density of states calculations, and a discussion of the influence of both the methyl group and the molecular symmetry on the couplings is presented.