The theory of nuclear quadrupole resonance and quadrupolar relaxation is reviewed, and the chemical interpretation of n.q.r. data is discussed. The super-regenerative oscillator system as employed in the Decca spectrometer for the detection of n.q.r. is described. Details of the measurement of relaxation times using a pulsed r.f. spectrometer are also given. In a study of hydrogen-bonded anions containing conveniently situated chlorine atoms a combination of the relative value of the 35C1 n.q.r. frequency and the magnitude of its shift on deuterium substitution is used to distinguish between centrosymmetric and asymmetric hydrogen bonds. The effect is clearly observed in the n.q.r. spectra of eight salts of the hydrogen or deuterium dichloride ion, and in four series of hydrogen di-chlorocarboxylate anions. For caesium and tetramethylammonium hydrogen dichlorides the direction of the n.q.r. frequency shift suggests that the asymmetry of the bond in the anion is increased on deuteriation. The very small deuteriation shift observed for the symmetrically hydrogen- bonded anion in tetraethylammonium hydrogen dichloride and caesium chloride, 1/3 hydronium hydrogen dichloride, is consistent with a single broad minimum potential function. The assignment to a torsional mode of a line at 85 cm- l in the neutron inelastic scattering spectrum of the latter salt is consistent with the observed temperature dependence of the 35 Cl n.q.r. frequency. The temperature dependences of the 35Cl spin-lattice relaxation time in caesium and tetramethylammonium hydrogen dichlorides are not sensitive to deuteriation. It is proposed that below 250 K in the former salt and 300 K in the latter, relaxation occurs by field gradient fluctuations due to lattice vibrations, and that above these temperatures the severe decrease in TI with temperature may be explained by diffusion of hydrogen chloride molecules throughout the lattice. The 35C1 T1 temperature dependence of the symmetrically bonded hydrogen dichloride ion in the hydronium dichloride salt is however sensitive to deuteriation, and this is consistent with a relaxation mechanism arising from field gradient fluctuations due to reorientation of the hydronium ions. Activation energies for this motion are estimated to be 8.1 k cals/mole for H30 +and 10.5 k cals/mole for D30 + • The n.q.r. spectra of acid salts of mono, di, and trichloroacetic acids and ortho-, meta- and para-chlorobenzoic acids are discussed with relevance to the particular hydrogen bond structure of the anion. In a series of complexes of general formula trans-L2 0sC14 , the measurement of the 35 C1 n.q.r. frequency provides the following order of cis-influence of ligands: C1 <AsEt3 < PEt2Ph < PEt3 A phase transition in trans-(PEt3)20sC14 is indicated near 100 K. It is suggested that intramolecular non-bonding interactions for the earlier members of the series of complexes trans-LiMC14 and K 2 MC1 6 may have a Significant effect on the magnitude of the chlorine n.q.r. frequency and its temperature coefficient. The chlorine n.q.r. frequencies of some 3-chloroacetylacetonato-complexes are shown to vary considerably with the polarity or charge of the complex, and to depend very little on the central element. The differences can be explained in terms of linear intramolecular electric field shifts, the signs and magnitudes of which correlate with experimental values of the Stark coefficient. The n.q.r. spectra of a series of six addition compounds of phosphorus pentachloride favour the ionic structure containing the tetrachloro-phosphonium ion in each case. Values for the libration frequency of the PC1 4 + ion are predicted.

Evidence is presented in this thesis for the possible involvement of a novel olefinic π-complex of cobalt (III) in the solvolysis of β -acetoxyalkylcobaloximes. The enzymatic reactions catalysed by coenzyme B12 are described in the introduction. Evidence obtained from an extensive study of these reactions, and reported in literature, is discussed in terms of various mechanisms for coenzyme B₁₂ action. The similarity between biacetyldioxime complexes of cobalt and the B₁₂ coenzymes is described and, on the basis of studies on the former (reported in Chapters II and III), the suggested intermediary of an olefinic π-complex of cobalt(III) in some of the enzymatic reactions can be supported. The hydrolysis, ethanolysis and deuteromethanolysis of β-acetoxyalkylcobaloximes are discussed in Chapter II. The evidence obtained, and results of studies on cobaloximes reported in literature, are interpreted in terms of a scheme which requires the involvement of the intermediate mentioned above. However, two possible alternatives to this complex are also considered The similarity of these solvolyses with the acid catalysed deoxymercuration reactions and solvolyses of substituted ferrocenes is pointed out. Chapter III deals with the solvolyses of chiral and specifically labelled cobaloximes and also of cobaloximes with different trans-ligands. The results of these experiments are shown to be in favour of the πcomplex as the key intermediate in these solvolyses.

Synthetic double-stranded ribopolynucleotides are inducers of interferon, a protein which increases the resistance of cells to virus attack. This work describes the synthesis of poly (halogenated ribocytidylic acids) and their complex formation with both riboinosinic acid and deoxyriboinosinic acid. The RNA/RNA hybrids are potent interferon inducers with high thermal and nucleolytic stability, the DNA/RNA hybrids are, however, completely inactive . as inducers of interferon. The synthesis and physical properties of poly (5-hydroxycytidylic . acid) are discussed. In basic solution this polymer undergoes a conformational change and can also bind magnesium ions in an unusual manner. The polymer does not hybridise with polyinosinic acid.

Modified cytidylic and adenylic acids have been synthesised and studied as possible inducers of interferon when hybridised with the appropriate polynucleotides. The report in this thesis describes: a) The synthesis and characterisation of poly (5-fluorocytidylic acid) to complete the series of 5-halo substituted cytidylic acids. Poly(I). poly(fl⁵C) was interferon inducing. b) The synthesis and characterisation of poly (5-dimethylaminocytidylic acid) in which a substituent other than the halogens was inserted into the 5-postion of cytidine. The polymer formed a 1:1 hybrid with poly(I) and the hybrid was a good inducer of interferon. c) The synthesis and characterisation of poly (8-oxyadenylic acid) which was one of the first 8-substituted homopolymers of adenosine.

This thesis describes new nitro-chemistry in studies related to a possible synthesis of Vitamin B12 as proposed by J. W. Cornforth. Some of the Vitamin B12 intermediates possess special nuclear magnetic resonance properties when examined as their nitronate anions. Some synthetic studies of fluorinated compounds as potential substrates for glyceroldehydrase, an enzyme requiring 5' -deoxyadenosyl cobalamin (Coenzyme B12 ), are also described .. The Introduction discusses the chemical synthesis of corrins, together with some of the prominences of the Eschenmoser-Woodward synthesis of Vitamin B12. A brief account of the possible synthesis of Vitamin B12 proposed by Cornforth is also given. The chemistry of the related B12 coenzymes is summarised in a section on the enzymatic reactions requiring a 5' -deoxyadenosyl cobalamin as a cofactor, The current proposals for the mechanism of action of glyceroldehydrase and dioldehydrase are also compared. The Cornforth approach to Vitamin B12 was to utilise the reaction of an anion with a germinal bromonitro or dinitro compound in order to join precursors of ring A and ring D. Chapters I and II describe the synthesis of suitable precursors and models for these radical-anion coupling reactions, and attempts to realise an intermolecular coupling of ring A and ring D intermediates. The synthesis of 4-carboxamidodiethylmalonyl-3-methyl-3-(2', 2' -brornonitroethyljcyclo-hexanone ethylene ketal and 4-(2',2' -dinitro)n -butoxycarbonyl-3-(2' -nirroethyl )- 3-methyl ccyclohexanone are described together with attempts to use these intermediates for intramolecular coupling purposes. In chapter I, the attempted coupling of hindered geminal halogenonitroso compounds with nitronate anions is also described. Attempts to incorporate an intramolecular Michael addition into the synthesis, for the linking of ring A and ring D precursors are the subject of chapter III. The synthesis of amide derivatives of Hagemann's ester (4-ethoxycarbonyl-3-methyl cyclohex-2-enone ) containing a nitro-enamide residue as the 4-substituent,to examine this scheme was unsuccessful. The corresponding hydrazide analogues, for example, 3-methyl cyclohex-3-ene-1-one ethylene ketal 4-carboxylic acid 3'-nitrobutylidene hydrazide, are more readily accessible and some reactions are described. In chapter IV, interesting long range deshielding effects are noted in the 1H n, m. r. spectra of the nitronate anions derived from 4-alkoxycarbonyl-3- methyl-3-(2 '-nitroethyl) cyclohexanones, ring A precursors for coupling studies. The deshielding effect associated with the nitronate anion is a useful probe in conformational analysis, and shows the axial conformer of 2-substituted cyclo- hexane nitronate anions to be preferred. Also the 13C n. m, r. spectra of several nitronate anions show large solvent dependent chemical shift difference which correlate with differing electronic distibution in the anions in solvents of different protonating ability. Chapter V is an account of the synthesis of potential substrates and inhibitors for the enzyme glyceroldehydrase. 3,3, 3-Trifluoro-1, 2-propanediol is a substrate for the enzyme and is converted to 3,3, 3-trifluoropropionaldehyde isolable as its 2, 4-dinitrophenyl hydrazone. Attempts to synthesise authentic 3,3, 3-trifluoro- propionaldehyde and the effects of the CF3 group are also discussed. The reaction between 3,3, 3-trifluoro-1, 2-propanediol and glyceroldehydrase is readily monitored by 19F n. m. r. allowing an examination of reaction intermediates. The synthesis of several bromopropanols and some preliminary investigations as to their reactions with glyceroldehydrase are also noted.

Electrospray (ESI-MS) and cryospray mass spectrometry (CSI-MS) techniques were developed to analyse and investigate the self-assembly, reactivity and structure of supramolecular architectures. Using ESI-MS, the complexation reactions of the ligand cis,trans-1,3,5-tris(pyridine-2-carboxaldimino)cyclohexane (ttop) with divalent first row transition metal salts to form complexes with nuclearities 1,2 and 4 were followed. In-situ mass spectrometry was also utilised to show the stepwise formation of the ligand-metal complexes. Mass spectrometry has been used to identify the reactive species in the catalytic oxidation of conventionally hard to activate C-H and C=C moieties. The identity of the reactive species under catalytic conditions has been postulated as Fe(V)=O but direct observation of this species has not been possible before. Using cryospray mass spectrometry, the Fe(V)=O reactive intermediate within the synthetic [FeV(O)(OH)(PyMe2tacn)]+ (PyMe2tacn = 1-(2’-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane) complex at -40 ºC and its reaction with an olefin was observed. Oxygen atom transfer from H2O2 / H2O was followed through Fe(V)=O to the products with isotopic labelling, and the reactivity was probed as a function of temperature. Mass spectrometry has been used as both a qualitative and quantitative tool to deduce the stoichiometry of an anion receptor and the corresponding anion. Job plots of mass spectrometry data have been compared to the conventional 1H NMR job plot data to give corresponding results therefore providing evidence of the use of mass spectrometry as a quantitative and qualitative analytical tool. Mass spectrometry has been used to follow the formation of heterometallic complexes and provide evidence of their building block in solution. The formation of the complexes has been followed using time-resolved mass spectrometry experiments and the building blocks analysed.

Oxidative stress is implicated in the ageing process and age-related diseases. A dual sensor spin trap i was used with electron paramagnetic resonance (EPR) spectroscopy to detect and distinguish between oxygen-centred radicals, carbon centred radicals and redox active metal ions, all of which contribute to oxidative stress. A novel mitochondria-targeted nitrone spin trap MitoSpin vi has been prepared for the detection and amelioration of oxidative stress. The synthesis utilises a novel Parham-type cyclization of aryl bromide iv to afford the isoindolone core vI in good yield. MitoSpin vi accumulates in mitochondria in the presence of a membrane potential and affords a unique EPR signal and electrospray ionisation mass spectrometry (ESI-MS) detectable oxidation product on reaction with hydroxyl radicals. A hydrogen peroxide-sensitive, mitochondria-targeted probe vii has been prepared. It utilises the reactivity of the boronate moiety with hydrogen peroxide to afford an oxidation product. This process is easy to detect by ESI-MS. Mitochondrial moderators were synthesised, which are designed to react with to release an uncoupler (proton trans locator). If released in vivo the uncoupler would lower the mitochondrial membrane potential inhibiting further ROS production.

Multireference Configuration Interaction (MRCI) is widely and successfully used for the accurate computation of molecular energies and properties when chemical bonds are broken, and in other cases of quasi-degeneracy. However, it suffers from a lack of extensivity, which introduces significant errors for large molecules. Currently feasible Multireference Coupled Cluster (MRCC) approaches, which address the extensivity issue, are complicated and expensive. In this work we investigate simple approximations to MRCC, generalising the single-reference linked pair functional theories to the multi-reference case. We show how to develop a simple extension to MRCI that gives approximate extensivity, retains orbital invariance and acts as an approximation to a multireference variational Coupled Cluster theory.

Two organic systems have been selected for the study ofnonstatistical dynamic effects using a combination of computational and lab based techniques. Chapters one and two provide an introduction to nonstatistical dynamics and computational methodology respectively. The computational element of this work focuses on the thermal rearrangements of spiropentane, and is presented in chapters three and four. The rearrangement involves two singlet biradical intermediates, and the suitability of the rearrangement to the study of nonstatistical dynamics is explored. While evidence of nonstatistical effects has been found in previous experimental work on the system, the study presented here involves molecular dynamics simulations to uncover further details about the nature and mechanism of the rearrangements. The work also involved an evaluation of the use of various density functional methods for studying the system and a benchmarking exercise to choose a suitable computational methodology for the dynamics. The results of two sets of simulations are presented, and evidence of nonstatistical effects from both is discussed. Chapters five and six concern the synthesis of a novel peroxide that was designed specifically for this work, which undergoes thermal dissociation to form a radical pair. The properties of the molecule are discussed, and various attempts at its synthesis are described. An explanation of how the compound could be used for lab-based nonstatistical dynamics studies is also presented, involving an isotopic labelling study. Unfortunately, while several synthetic routes were proposed, the synthesis was ultimately unsuccessful and so could not be used to search for nonstatistical dynamic effects.

I The research presented in this thesis describes the direct synthesis of hydrogen peroxide from H2 and O2 using supported gold-palladium based catalysts. The direct synthesis process offers a green and sustainable approach compared to the anthraquinone autoxidation (AO) process, which is currently used on an industrial scale to produce >95% H2O2 worldwide. The work presented in this thesis is an attempt to examine the direct synthesis process in terms of determining optimum catalyst compositions for potential scale-up in the near-future. The primary aim of this investigation is centred on catalyst design and characterisation. The first part of this work is a catalyst optimisation study for 2.5 wt% Au-2.5 wt% Pd/TiO2, and involved changing the amount of water used in the catalyst preparation, in this case wet impregnation. It was found that the addition of small amounts of water resulted in approximately 100% enhancement in activity for TiO2-supported catalysts but not for carbonsupported Au-Pd catalysts. The rate of Au/Pd uptake was contrasted and it was determined that the isoelectric point of the support was highly influential. While the activity can be enhanced for TiO2-supported catalysts, both catalyst nanostructure and stability were detrimentally affected by the addition of water during the impregnation step. The second part of this work is focussed on understanding the precise nature of the acid pre-treatment effect, where treatment of a carbon support in dilute nitric acid prior to the impregnation of Au and Pd precursors can result in the complete switching-off of sequential H2O2 hydrogenation activity over the catalyst. Characterisation and heat treatment studies gave an improved understanding of the relationship between Au/Pd and the carbon support. The next part of the study addresses the use of a colloidal immobilisation method to pre-fabricate Au-Pd ‘designer’ nanoparticles onto supports and is accompanied by extensive advanced aberration corrected electron microscopy studies. The effect of acid pre-treating silica based supports is then considered for catalysts prepared by wet-impregnation, specifically the fact that acid pre-treatment of silica is required to induce synergy between Au and Pd metals for the direct synthesis of hydrogen peroxide. The final part of this work considers the effect of introducing a third metal into the catalyst design, specifically the addition of Pt to Au/Pd compositions. An extensive catalyst screening study is undertaken for Au-Pd-Pt/CeO2 catalysts.