Glutamic and aspartic acids are considered to be potent excitatory amino acid neurotransmitters of vertebrates. Receptors for these amino acids may be sub-divided into three types: (i) Quisqualate/glutamate, (ii) N-methyl-D-aspartate (NMDA) and (iii) Kainate type. The aim of this project has been to develop specific mimetics which act only at one defined site. In particular, attention has been focused on the two former sub-groups. It has been shown that 2-amino-5-phosphonopentanoic (APP) and 2-amino7-phosphonoheptanoic (APH) acids are very potent NMDA antagonists and anticonvulsants and in order to further the pharmacological study of this class of compound, efficient synthetic routes have been developed which afford the compounds in high overall yields. APB(2-amino-4-phosphono-butanoic acid), APP and APH can now be obtained in 10-50 g quantities which has permitted the evaluation of these compounds in a variety of animal models of epilepsy closely related to those in man. A study focused on photically stimulated seizures in the baboon has shown APP and APH to be particularly effective. This model is thought to be one of the closest to human seizures. Quinolinic acid (Quin), an endogenous excitant and neurotoxin, may be classified as an NMDA type compound. The aim of this project has been to develop analogues of Quin, some of which may well be specific antagonists of NMDA. The higher homologue (1) of Quin has been s3rnthesised and has very recently been shown to be at least twelve times more potent than Quin as a neurotoxin. A series of homologues are to be synthesised, the synthesis of homologue (2) is now being completed. The peptide derivative (3) and its phosphonate analogue (4) have recently been synthesised and experiments are now in progress to determine their potency. Tricholomic acid (TA)(5), an amino acid extracted from Tricholoma muscarium, has been suggested to be a very potent neuroexcitant of the quisqualate/glutamate sub-division by some Japanese workers. However, studies on this compound and the development of putative mimetics have been hindered by the lack of any reasonable synthetic route to TA. Such a route has now been devised and TA has been synthesised.

A number of 1-aminoalkanephosphonic acid derivatives incorporating physiologically Iabile groupings (ester, amide e.g. peptide, carbamate and tosyl) were prepared as a development from earlier studies in which certain phosphonic acid derivatives were shown to have previously unrecognised activity as fungicides. Such derivatisation might aid the translocation of the active phosphonic acid to the site of action. Compounds were screened for in vivo fungicidal activity against Drechslera teres. Drechslera graminae. Drechslera avenae. Prythium ultlmum. Rhizoctonia solani. Fusarium culmorum. Pyricularia oryzae, Puccinia recondita. Erysiphe zraminis[?] and Septoria nodorum. Results showed that all the phosphonopeptides prepared had moderate to good antifungal activity, with the L-alanine di- and tripeptides of l-aminopropanephosphonic acid having superior activity to the commercial fungicide imazalil when tested against D. teres and D. avenae. The proton, carbon-13 and phosphorus-31 nmr spectroscopy of the compounds prepared was examined in detail with carbon-13 proving particularly useful. The carbon-phosphorus coupling constants varied along the alkyl chain in the phosphonopeptides with JPC=145-148 Hz, JPCC=0 Hz , JPCCC=12-14 Hz and JPCNC=4-6 Hz. The use of Fast Atom Bombardment mass spectrometry has proven to be successful for the characterisation of aminophosphonic acid derivatives, especially phosphonopeptides, with the MH ion normally being the base peek. Phosphonopeptides give characteristic fragmentation patterns due to the sequential loss of [alpha]-lactam units arising from the amino acid chain. A number of routes to the preparation of l-aminoalkanephosphonic acids were investigated, in particular those routes utilizing 1-ozo-alkanephosphonates, and a detailed study into the hydrogenation of dialkyl l-hydroxyiminoalkanephosphonates using Raney Nickel and, more successfully, palladiua-on-carbon catalysts was undertaken. Preliminary attempts were made to prepare phosphonopeptides via the previously unexamined route of solid phase synthesis and some of the difficulties involved with this method are discussed.

This thesis describes apparatus and techniques for making ultrasonic measurements in fluids and applications of them to measurements of ultrasonic parameters in colloidal dispersions. A brief description of the properties and uses of ultrasound propagation in dispersions is followed by an extensive review of theories which relate the particulate properties of the dispersions to the measurable ultrasonic parameters, velocity (c) and attenuation (a [alpha]). Measurement principles are outlined related to the design of near-field measurement methods and the development of three techniques is described. These are shown 10 give results which are both highly self-consistent and in excellent agreement with a far-field method. Measurements of a[alpha] and c for model dispersions of glass spheres in Newtonian Iiquids are shown to be in good agreement with the relevant theory when particle polydispersity is taken into account. For structured fluids as the continuous phase, the a[alpha] and c data for suspensions of spheres are used to obtain the continuous phase viscosity (n). The a[alpha] data agree approximately with the macroscopic viscosity, but the velocity data requires the introduction of a shear elastic term and the revision of theory in order to obtain agreement. Attenuation as a function of barite concentration in Newtonian liquids was investigated and the ultrasonic particle radius was found to be systematically larger than expected. This is attributed to particle rugosity. Measurements of a[alpha] and c using non-gelling aqueous kaolinite suspensions are shown to agree well with theory when the eccentricity and the interactions of particles are taken into account. For gelling aqueous bentonite suspensions, a[alpha] and c were found to be time-dependent over a period of several days following initial dispersion. The observed increases in both a[alpha] and c are interpreted in terms of a growth in gel fraction and shear modulus, respectively. The effect of shear flow on a[alpha] and c was investigated for the above dispersions. Changes were barely resolvable but consistent with shear-degradation of structure within the fluid.

Some aspects of the corrosion fatigue crack initiation in EN1 type mild steel have been studied. Results of the electrochemical investigations show that the application of both static and compressive stresses enhance anodic dissolution. Application of cyclic stress assists the breakdown of the surface film resulting in localised attack, Metallographic studies indicate that a sulphur enriched band of ferrite exists around the non-metallic inclusions and corrosion occurs in this contaminated band with and without applied stress. Cyclic stress enhances the formation and coalescence of micropits at and around the inclusions leading to the nucléation of cracks. Preferential attack also occurs at the ferrite - pearlite interfaces, at slip band - matrix interfaces, and at grain boundaries. All these modes of attack can lead to crack nucleation. It has also been found that non-metallic inclusions can act as sites for hydrogen blisters; this may assist the nucléation of cracks.

The reaction between N,N,N‘,N'-tetramethylphosphoric triamide (TMPT) and chloral has been shown to give chloroform, dimethylformamide, (Me2N)2P(0)NHCH(CCl,)NMe2 and polymeric phosphorus containing compounds. A possible mechanism for the formation of these products is given.

N-(o-aminophenyl)-iminotriphenylphosphorane (I) has been synthesised and its physical and chemical properties studied in depth, especially in its nucleophilic reactions.

Synthetic routes have been developed for the ready preparation of a range of novel polyphosphorus ligands containing up to seven potential donor atoms.

The ruthenium(II) complexes Ru(nqo)2 (nqoH = 1,2-naphthoqulnona 1-oxima, or 2-oxima) were prepared by the interaction of the sodium salts of the 112-naphthoquinone mono-oximes with hydrated ruthenium(III) chloride in aqueous tetrahydrofuran.

The synthesis of mono and dinucleating ligands and their copper complexes are described. Three types of dinacleating tetraimine macrocycles have been prepared from 4,7-diaza-2,3;8,9-dibenzodecane-l,10-dione by condensation with the appropriate polyamine; I, large-ring octa-aza macrocycles e.g. the 28—membered ring compound 5,6,7,8,15,16,23,24,25,26,33,34— dodecahydrotetrabenzo(e,m,s,a’) (1,4,11,15,18,22,25) octaaza- cyclooctacosine and related 30- and 36- membered ring compounds; II, the "fused" bis(tetra-azamacrocycle) 5,6,7,8,22,23,24,25-octahydrotetrabenzo (f,f’1,1’) benzo (1,2-b:4,5-b’)- bis(1,4,8,)tetraazacyclotetradecine; III, the "Linked" bis(tetra-azamacrocycle) 5,6,7,8,24,25,26,27-octahydrotetrabenzo (f,f’,1,1)diphenyl(3,4-b:3’,4’-b’)bis(l,4,8,11)tetraazacyclotetradecine. For the type I and III ligands reduction of the imine linkages yielded the related octa-amines. The preparation of copper complexes is described. For many of the neutral copper complexes (formed by deprotonation of anilino nitrogen atoms) a novel synthetic route had to be used to overcome problems associated with the very low solubility of both ligand and complex.

This thesis is concerned with internal redox reactions of metal complexes and the application of such reactions in the selective filtration of tobacco smoke. The reactions of Fe(II), Fe(III) and Cu(II) quinoneoximic complexes and of some other complexes of these metals with Lewis bases (e.g. Ph3P and py) have been investigated. From the results obtained and from a critical consideration of analogous reactions reported in the literature the behaviour of metal chelates towards Lewis bases has been assessed. It has been established that the reaction between a metal chelate and a Lewis base may lead to: (i) Adduct formation, (ii) condensation and (iii) to an internal redox reaction, M(chel)n LB[over arrow] M(chel)n-1(LB)x + chel* The latter is favoured when the metal in M(chel)n has a stable lower oxidation state, by Lewis bases capable of E[eta]—bonding and by chelating ligands exerting a strong ligand field. The type of behaviour shown by chel* has been considered. The dissociated radical may: (i) Abstract a hydrogen atom to give the protonated ligand, (ii) dimerise, (iii) undergo coupling or degradation. A detailed investigation of the reactions of Fe(l-nqo)3 and Fe(2-nqo)3 with Ph3P (including kinetic studies) showed that these complexes undergo internal redox reactions to give iron(II) complexes and products arising from the deoxygenation of the nqo* radical. Mechanisms for these resctions have been proposed. The behaviour of quinoneoximic complexes of iron towards the Lewis base CO has been examined both directly and indirectly by studying the behaviour of nqoH towards Fe(CO)5 or Fe(CO)5/PhNH2. Fe(CO)5 and 1-nqoH or 2-nqoH afforded complexes of the type Fe(nqo)2, without formation of CO adducts or deoxygenation products. In the presence of PhNH2 complexes of type Fe(nqo)2 and Fe(nqo-A)2 resulted, where nqo-A is a species arising from the coupling of the nqo ligand with PhNH2. Both systems also afforded various organic products. On the basis of Mossbauer and other techniques oligomeric structures have been suggested for the complexes Fe(nqo)2 and Fe(nqo-A)2. Whereas CO did not react with Fe(nqo)2 or Fe(nqo)2.2py, it reacted with Fe(nqo)3, possibly via an internal redox process. For Fe(2-nqo)3 products arising from a deoxygenated ligand and a complex tentatively formulated as the nitrene species, Fe(2-nq)2, were isolated. The reactivity of the Fe(nqo), complexes towards CO has been successfully utilised in the selective filtration of tobacco smoke. Both Fe(1-nqo)3, and Fe(2-nqo)3 were shown to be capable of significantly reducing the level of CO in tobacco smoke under smoking conditions when supported on suitable filters. Reduction of the levels of other Lewis bases in tobacco smoke, e.g. nicotine and furfural, was observed. The complexes Fe(nqo)2, Fe(nqo)2.2py and Fe(nqo)3 reacted readily with NO to give complicated mixtures, but their effectiveness in removing NO from tobacco smoke has not been unambiguously established.