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Resistance to tetracycline (Tc), an inhibitor of protein synthesis, decreases its effectiveness for the treatment of bacterial infections. Tc resistance (TcR) can be mediated by the ribosomal protection protein, Tet(O), which was first reported in Campylobacter jejuni, a cause of bacterial diarrhea worldwide. Tet(O) confers TcR by mediating Tc release from 70S ribosomes, thus restoring protein synthesis. Tet(O) is widely distributed in a variety of bacterial genera, restraining the clinical use of Tc. This thesis is the first investigation into the role of the conserved set of amino acid residues, YSPVST, occupying positions 507-512 at the tip of domain IV of Tet(O). Impaired Tc release from 70S ribosomes observed with Tet(O)mutants lacking one or more of these conserved residues suggests residues at positions 509-512 play a role in Tet(O)-mediated TcR. This study provides insight into the molecular mechanism of TcR, which is essential for the development of novel therapeutics.

In the present study, the corrosion behaviour of several magnesia-chrome (MC) and magnesia-alumina spinel (MA) bricks against fayalite type slags was investigated and the role of the spinel phases was highlighted . The experimental results revealed that the corrosion resistance of the MC bricks was superior to the MA bricks against KIVCET slags in static and dynamic conditions . As a result of the interaction between MgO from MC bricks and the slag, a modified forsterite phase (Mg, Fe, Zn, Ca)₂SiO₄ was formed, which destroyed the precipitated complex spinel bonds at the grain boundaries of periclase and magnesia-chromia spinel . Furthermore, both MgO and MgO-MgAl₂O₄ spinel in the MA brick dissolved into the slag, which resulted in modified forsterite phases of (Mg, Fe, Zn, Ca)₂SiO₄ and (Mg, Fe, Zn)(Fe, Al)₂O₄ complex spinels, respectively. In addition, the accretion formation in the KIVCET furnace was investigated through solubility experiments of Cr₂0₃ in the KIVCET slag with various amounts of lead, which revealed that the net contribution of Cr₂0₃ to the spinel formation is the highest in the barren (no Pb) slag, followed by high-lead (11% Pb) and it is the lowest for the low-lead (6% Pb) slag. The amount of spinel solid solution increased consistently with increasing Cr₂0₃ dissolved and the PbO existent in the slag. From examinations of several used bricks from the tuyere area of a Peirce Smith nickel converter, it was found that the corrosion is due to the interaction of the partially oxidized matte penetrating deep into the brick and the magnesia grains forming (Mg, Fe, Ni, Co) xOy spinels . Analyses of brick samples used in the KIVCET Electric Furnace roof identified deep reaching sulphation, which weakened the bonding phase between coarse magnesia grains. In the Bottom Blown Oxygen Converter, a highly aggressive lead and bismuth oxide rich slag penetrated deep into the brick, which destroyed the grain boundaries, causing the refractory to be easily eroded at the refractory-slag interface. Our studies concluded that the spinel phases, either as magnesium chromate, magnesium aluminate or complex spinel [(Mg, Fe)(Cr, Al, Fe)₂O₄], enhanced the corrosion resistance of a basic refractory to fayalite type slags from the non-ferrous smelting and converting furnaces.

The primary aim of this thesis was to synthesize a new class of peptide mimics derived from N-acylisatins and to investigate various methodologies for their synthesis. N-Acetylisatin 15 and its derivatives 39 and 40 were found to undergo facile nucleophilic ring-opening with amino acid esters yielding a range of 2-acetamidophenylglyoxylamide derivatives in moderate to good yields. This type of reaction was also found to work for di- and tripeptide methyl ester hydrochlorides leading to a range of N-glyoxylamide peptide mimics. The methodology of the reaction conditions was further extended to N,N′-oxalyl bisisatins 17 and 134, and 1,3,5-tris(2,3-dioxoindoline-1-carbonyl)benzene 168 substrates and their reaction with amino acid esters gave a new range of C,C′-linked-bis-glyoxylamide peptide mimics and C,C′,C′′-linked tris-glyoxylamide peptide mimics respectively. Meanwhile, reactions of N-acylisatins with 1,10-diaminodecane 155 and tris(2-aminoethyl)amine 167 gave the corresponding bis and tris-glyoxylamides. In the event of introducing amino acids at the N-1 position of isatin 9, a range of NH protecting groups for the synthesis of N-protected amino acid acyl isatins 193 were examined. It was found that the phthalamido group, e.g. phthaloylglycine 197, was the best protecting group for the introduction of a glycine unit at the N-1 position of isatin 9. Additionally, a viable and interesting alternative approach utilizing N-succinyl acylisatin 158 as the starting material was also demonstrated. In continuation of our interest in the peptidomimetic approach, a new class of cyclic peptide mimics using Grubbs?? ring-closing metathesis approach was also successfully synthesized. A range of bis-O-allyl substrates 237, 240, 242 and 246 were prepared from reaction of the corresponding N-acylisatins with L-valine allyl ester hydrochloride 236 and 1,10- diaminodecane 155 respectively. High conversion yields of the target macrocyclic systems 238, 241 and 243 were observed when the bis-Oallyl substrates were irradiated with Hoveyda-Grubb catalyst in a microwave reactor. These latter studies will provide a synthetically versatile platform for the future design of potential new drugs candidates against Gram-positive bacterial infections