In Chapter Two, the synthesis and coordination behaviour of the aryl-substituted N-picolyethylenediamines and N-bis(picolyl)ethylenediamines along with bis(2-picolyl)amine, tris(2-picolyl)amine in manganese(II), iron(II) cobalt(II) complexes are reported. The notable influence of steric effects upon the nuclearity and the binding mode is described. The flexibility of the N-picolyl-en systems when coordinated to iron or cobalt is observed by single crystal X-ray diffraction studies, paramagnetic 1H NMR spectroscopy and DFT calculations.;In Chapter Three, the reactions of the sterically variable aryl-substituted diethylenetriamines with CoCl2 to afford NNN-chelated complexes are reported. Notably, the analogues iron(II) complexes are not produced. The introduction of a picolyl donor affords the ligand set, N-picolyldiethylenetriamine, which is capable of coordinating to iron and cobalt in a pseudo-tetradentate fashion.;In Chapter Four, the N-aryl substituted NNN -iron(II) and -cobalt(II) complexes are activated by the addition of excess methylaluminoxane for the oligomerisation of ethylene. The activities are low-to-moderate at 1 bar ethylene pressure and the selectivity of the catalysts is dependent on the metal centre with the iron systems forming linear alpha-olefins while the cobalt systems give a mixture of linear and branched oligomers.;In Chapter Five, the versatile preparation of the novel NNO- ligand sets anisole-pyidine-imine, phenol-pyridine-imine and phenol-pyridine-amine and their coordination behaviour in aluminium(III), iron(II) and cobalt(II) complexes is described. Preliminary catalytic evaluation studies reveal moderate-to-high activities for the polymerisation of ethylene into moderate-to-high molecular weight polyethylene.

N-heterocyclic carbenes (NHCs) have emerged over the last two decades as an important class of ligands in transition metal complexes, main group chemistry and organocatalysis. NHCs are now common replacements for phosphines in transition metal chemistry.

The synthesis and coordination chemistry of monodentate phosphorus ligands that span a range of stereoelectronic effects is the topic of this thesis. It is shown that many Rh complexes of the type [Rh(L)2(olefin)]BF4 (L = ligand) exhibit restricted Rh-P bond rotation, which is slow enough to be observed on the NMR timescale. Variable temperature NMR studies of a range of Rh complexes of mono ph os ligands reveal similarities in the observed pattern, suggesting that the M-P restricted rotation is a more general phenomenon of the cis-ligated square planar complexes. OFT calculations and solid state analysis are employed to shed light on the structures of the Cl- and C2-symmetrical rotamers observed in the NMR spectra. The improvement of the separation of enantiomers of optically active 1,3,5,7- tetramethyl-4,6,8-trioxa-2-phospha-adamantane, CgPH is reported, allowing the recovery of the previously inaccessible a-CgPH. Optically active a-CgPH yields a highly selective catalyst in the asymmetric hydrogenation of various olefins, producing ee of up to 95%. Rh complexes of CgPH are extensively studied by NMR techniques and OFT calculations in order to understand the unexpectedly high enantioselectivity obtained with Rh-CgPH catalysts; it is proposed that the enantioselectivity arises from the presence of a Cl-symmetrical rotamer in solution. A series of 3,3' -dimethylphosphonite ligands of a type (binolate)PR (R = Me, iPr, Cy, tBu) are synthesised and their coordination chemistry is investigated. Most of the ligands upon reaction with [Rh(cod)2]BF 4 produce complexes of a type [Rh(L)2(cod)]BF4• The tBu-phosphonite does not follow this reactivity pattern, presumably due to the steric bulk of the ligand, making the incorporation of two ligands in the cis arrangement unfavourable. Of all the above mentioned ligands, the iPr- and Cy-phosphonite are the best catalysts for the hydrogenation of a- dehydroaminoacid derivative substrates, methyl-(Z)-a-acetamidocinnamate (up to 94%) and methyl-a-acetamidoacrylate (up to 97%), but they are less selective for dimethylitaconate (up to 75%). A series of ligands bearing extended aromatic systems are synthesised in order to probe the possibility of the backbone formation using pi-pi interactions in cis square planar complexes. Some circumstantial evidence for the interactions have been observed and the presence of the extended pi systems is shown not to be beneficial on the asymmetric hydrogenation outcome.

A series of alkyl phobane ligands PhobPR (R = nBu, iBu, sBu, sPn, ipn, CH2SiMe), menthyl, CH2C4H70) have been prepared by electrophilic Or nucleophilic routes as pure s- or a -isomers. Reaction of these ligands with [PtCI(NCIBu)2] or [PdCh(NCPh)2] gave square planar trans-[MCh(PhobPR)2] (M = Pt, Pd) complexes. Variable temperature 31p {H} NMR studies on the trans-[MC12(PhobPRh)2] complexes revealed restricted rotation about the M-P bond. The complexes generally existed in two forms: with R groups on opposite sides of the square plane (anti, C2h-symmelry) or on the same side (syn C2v-symmetry). Free energies of activation for the fluxional process of interconversion between the two rotamers were calculated ranging 8-17 kcal mol-1. The experimental hypotheses were supported by OFT calculations. Reaction of thc alkyl phobane ligands with ligands with [PtCb(COD)] gave square planar The cis-[Pt,CI2,(PhobPR)2] complexes displayed similar fluxionality to their analogous trans-{PtCI2(PhobPR)2] complexes showing anti (C2-symmetry) and syn (C3--symmetry) rotamers. Reaction of the alkyl phobane ligands with [Rh(diene2),] [BF4] (diene= nbd, COD) gave [Rh(diene)(PhobPR),][BF,l complexes. Steric effects were used to form pseudo-chelating ligands and this novel ligand design principle was applied to rhodium-catalysed asymmetric hydrogenation giving 40% enantioselectivity. Long chain B-branched tertiary phobane ligands were prepared by stoichiometric or catalysed routes as pure s- or a- isomers or as s/a mixtures. In order to gain an understanding of the B-effect, the platinum coordination chemistry was probed and the ligands were evaluated in cobalt-catalysed hydroformylation. The high molecular weight catalysts gave a higher percentage of the linear aldehyde product and a slightly lower paraffin make but also a lower rate of catalysis compared to low molecular weight PhobPR catalysts. C-centred and N-centred tripodal triphosphine ligands have been synthesised. The platinum and silver coordination chemistry was investigated generating some interesting results arising from the different bonding modes of tripodal ligands. The ligands have been tested in ruthenium-catalysed ester hydrogenation and palladium- and ruthenium-catalysed Il1cthoxycal'bonylation producing some promising initial results.

The work presented in this thesis encompasses two research areas; phosphaalkyne chemistry and gold(I) coordination complexes. In parts, the two topics overlap. Chapter 2 focuses on the synthesis, manipulation and coordination of phosphaalkyne substrates. A variety of phosphaalkynes are synthesised, but the majority of the work presented deals with the kinetically stabilised PCtBu. A modified synthesis of PCtBu is reported utilising an improved apparatus set up, allowing for safer preparation of large quantities of PCtBu. The synthesis of the unstable phosphaalkyne PCH is also reported along with attempts to obtain the first coordination complex. Investigation into the interaction between gold and tantalum metal centres with phosphaalkyne substrates has led to characterisation of the first gold(I)-phosphaalkyne complex and a series of tantalum-phosphaalkyne cations. The formation of main group frameworks is achieved from the thermal coupling of phosphaalkynes with pnictogen trihalides. This leads to a variety of P/Clhalogen cages and incorporation of arsenic was achieved resulting in a novel P/CIAs framework. In addition a unique spiro-PsC6 compound was crystallographically observed. Chapters 3 and 4 focus on the coordination chemistry of a trimer of PCtBu, 2,4,6- tritert-butyl-I,3 ,5-triphosphabenzene. The first crystallographically characterised examples of an r{triphosphabenzene are obtained along with a theoretical investigation into the aromaticity of the complexes. Reactivity towards pnictenium ions is also explored both computationally and experimentally. Unprecedented main group architectures are obtained when arsenic is incorporated into the framework, whereas phosphenium ions form novel 1,4-addition products. Chapters 5-6 move away I from phosphorus-carbon triple bonds and address the interaction of gold(I) cations with carbon-nitrogen multiple bonds. The gold(I) cations utilised in the previous chapters are applied towards complexation of Nheterocycles and azides. The work reports 11 novel complexes of a range of nitrogen containing substrates, from the simple pyridine and azide to nitrogen rich L Abstract heterocycles 2,4,6-triphenyl-l,3,5-triazine and hexachlorocyclotriphosphazene. An unusua~ bonding interaction is observed in bipyridine complexes where symmetric vs. asymmetric K2 complexation is dictated by the gold(I) ligand. The work in this thesis has resulted in several publications outlined below: Chapter 2 Townsend, N. S.; Russell, C. A, Phosphorus(III) Ligands in Homogeneous Catalysis: Design and Synthesis, First Ed. Chapter 11 Phosphaalkynes. John Wiley & Sons Ltd, Published 2012 . . Sanguramath, R. A; Townsend, N. S.; Lynam, 1. M., Russell, C. A, Eur. J Inorg. Chem., 2013, asap. Doi: 10.l002/ejic.201301089. Chapter 3 Townsend, N. S.; Green, M.; Russell, C. A, Organometallics, 2012, 31,2543. Chapter 4 Townsend, N. S.; Shadbolt, S. R.; Green, M.; Russell, C. A, Angew. Chem. Int. Ed., 2013, 52, 3481. ;' 11

Metal-Organic Frameworks (MOFs) represent a new type of multi functional porous materials. These materials can be obtained from the connection of metal centres or clusters and organic ligands in such way that extended ID, 2D or 3D structures can be isolated. The unlimited possibilities of connecting the different building blocks within these materials make possible the formation of networks with a range of pore sizes and applications in gas storage and separation, catalysis, molecular sensing and drug delivery. In this thesis, the synthesis and characterisation of adenine based and pyrene derived MOFs is presented. Based on the physical properties of these MOFs, we are demonstrating that they can potentially used for advanced applications in CO2 capture, C}--4 storage, C02/C}--4 separation, xylene separation, sensing and base pairing recognition. The first part of this thesis deals with the synthesis of novel adenine based MO F s. Within the isolated MOFs, adenine provides a wide range of binding modes for metal coordination and different protonated forms acting as a bridging or terminal ligand. The diverse functionality of small biologically relevant building blocks such as adenine can tune the chemistry of MOF type structures to permit increased chemical interactions with guest molecules (C02 and C}--4) for applications such as gas storage and separation. The second part describes the design of a tetracarboxylate ligand based on an optically active pyrene core, H4 TBAPy. The choice of the ligand for the construction of extended networks is important for the construction of fluorescent MOFs for sensing applications. The isolated MOFs show interesting properties for CO2 capture and CH4 storage and due to the specific size and shape of the channels and nature of the polyaromatic ligand used for the isolation of the frameworks, aromatic molecules were introduced for separation applications. The [mal part demonstrates the synthesis of a network based on Zn, adenine and }--4TBAPy. The Watson-Crick face of the nucleobase within this framework is located within the channels, responsible for the hydrogen bonding with thymine, the pair base of adenine. Thymine solution isotherms revealed that the 3D structure can adsorb thymine molecules and this is further confirmed with Infrared Spectroscopy and Thermogravimetric and Elemental Analyses. In conclusion, this thesis represents a small contribution to the extraordinary field of Metal-Organic Framework chemistry. The formation of novel materials with unprecedented network topologies and possible applications in gas storage, gas and liquid separation and molecular sensing is important in order to create novel materials with improved and advanced properties.

Experimental and theoretical techniques are employed to further our understanding of the chemistry of the poly(methimazolyl)borate ligands.Synthesis of RTm ligands from boronic acid and borane precursors is reported, including the formation of the novel ligand, p--fluoro-phenyltris(methimazolyl)borate.

This research thesis considers the design and synthesis of a range of thiourea bipyridyl complexes and their use as anion binding receptors. A range of isothiocyanate precursors were synthesised from a reaction employing carbon disulphide. These precursors were then coupled with 5-aminomethyl-2,2’-bipyridine to prepare a group of novel bipyridyl Iigands each containing at least one thiourea functionality. Three of the Iigands were successfully reacted with [Re(CO)5Br] to create three dinuclear rhenium{l} complexes. All of the Iigands were successfully reacted with [Ru(bpy)2Cl2] to yield eight new fully characterised ruthenium(II) complexes; with each ligand forming a mononuclear and a dinuclear complex respectively. Two of the ligands were also successfully attached to both a rhenium{l} and a ruthenium{II} centre resulting in two new heterometallic complexes. Anion binding investigations with the tetrabutylammonium salts of acetatel bromidel chloridel fluoridel perchloratel nitratel dihydrogenphosphate and hydrogensulfate were carried out. The Iigandsl anion binding potential was explored by lH NMR spectroscopic titrations. In general the Iigands show an affinity for both acetate and dihydrogenphosphatel with fluoride resulting in deprotonation

In this thesis we discuss the role played by computational methods in drug discovery and present studies chiefly using molecular simulation methodologies to characterise the binding of compounds that may serve as leads for antitumour agents against two separate proteins. We report flexible docking and QSAR studies on aplyronine A, and its analogues, a potent inhibitor of the actin protein system. Our findings delineate the mechanism by which the compounds bind to an actin monomer and highlight key features of the compounds that are fundamental for actin- depolymerisation, which instigates the necessary cytotoxic response. We show that the docking energy scores for the compounds are highly correlated with experimental depolymerisation data. The results are relevant for the design of a putative set of analogues and the development of efficacious actin-targeting cancer drugs. In a second study, we focus on the ETS domain of the Elk-l transcription factor, which is key to the protein's stability and a potential target for therapeutic compounds. The work presented identifies peptide binders of the ETS domain that may be used to inform the design of peptidomimetic compounds. Using MD simulations we show the domain undergoes conformational reorganisation at the α Iβ 1 loop. By taking frames from the MD trajectory of the loop region, we conducted virtual screening experiments for libraries of all possible di- and tri-peptides against each frame. The di- peptides showed no particular preference towards the binding site. However, several tri-peptides made specific interactions with key residues involved in Elk-l dimerisation. Further, we performed peptide-bound dynamics and relative binding free energy simulations to assess the stability of each complex, and to rank more accurately the best binding peptides identified from the docking calculations. We proposed a series of peptide binders for synthesis and experimental binding studies. The thesis ends with a brief discussion on some of the limitations to, and recent advancements in the field of computational modelling, particularly in the realm of atomistic simulations for computer-aided drug discovery.

This thesis details the design, synthesis and characterisation of metal-organic frameworks (MOFs), with particular interest in their gas storage properties. 23 novel MOFS were synthesised by solvothermal methods from transition and lanthanide metal cations and a range of pyridine-carboxylate ligands. Three new Cu MOFs, all based on a similar metal node were synthesised. One possessed a previously unreported topology and H2 storage that was comparable to similar Cu MOFs in the literature. Another possessed a very rare self-entangled topology and the third possessed a more common rutile topology; this series demonstrated how compounds based on similar building blocks can show structural diversity_ A series of isostructural lanthanide frameworks were synthesised. They exhibited N2. H2 and C02 storage with particularly high enthalpies of adsorption of CO2; these values were amongst some of the highest published in the literature. A range of MOFs based on the same ligand were synthesisd, they had different structures but possessed the same topology, once again showing how MOF structures can share features but ultimately be different from one another. This thesis demonstrates the structural diversity that can be achieved when using pyridine-carboxylate ligands in the synthesis of MOFs and the impact upon gas storage of the functional groups in the ligand.