New frontiers in the therapeutic application of gadolinium. This research involves the design and development of new anticancer agents that will dramatically expand the clinical efficacy of a promising treatment for highly aggressive tumours. The innovative nature of this research will also contribute to Australia's science knowledge base and provide excellent training in the area of drug discovery.
Group 13 Mixed Halide-Hydride and Rare Earth Complexes - New Selective Chiral Hydridic or Low Valent Reducing Agents. This project will make a landmark contribution to two areas of metallohydride chemistry. Both studies will utilise and develop metals that have traditionally been mined and exported from these shores while concurrently imported as value added products at vastly inflated cost. This research will identify knock-on applications in order to stem this financial bias. The new paths to ....Group 13 Mixed Halide-Hydride and Rare Earth Complexes - New Selective Chiral Hydridic or Low Valent Reducing Agents. This project will make a landmark contribution to two areas of metallohydride chemistry. Both studies will utilise and develop metals that have traditionally been mined and exported from these shores while concurrently imported as value added products at vastly inflated cost. This research will identify knock-on applications in order to stem this financial bias. The new paths to rare earth (= Ln) hydrides will have broad industrial appeal, particularly for new materials, where, like similar group 13 materials, they may be used in the deposition of Ln films or even as precursors to superconducting solids. It is anticipated industrial collaboration will ensue. Australia will be promoted as a developer and innovator of frontier technologies.Read moreRead less
Enhancing single-molecule magnets. This project aims to design, synthesise and investigate single-molecule magnets that can function at higher temperatures for use in quantum computing and molecular spintronics. Materials science increasingly benefit from molecular approaches, and lanthanoid-based single-molecule magnets could achieve otherwise inaccessible technological developments such as the development of molecular materials for quantum computing and molecular spintronics. Advances in funda ....Enhancing single-molecule magnets. This project aims to design, synthesise and investigate single-molecule magnets that can function at higher temperatures for use in quantum computing and molecular spintronics. Materials science increasingly benefit from molecular approaches, and lanthanoid-based single-molecule magnets could achieve otherwise inaccessible technological developments such as the development of molecular materials for quantum computing and molecular spintronics. Advances in fundamental chemistry are anticipated, and this project is expected to benefit Australia's participation in related high-end technology industries.Read moreRead less
Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collecti ....Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collection of structure restraints by nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectrometry, which are needed to generate accurate models of proteins and their complexes with other molecules. Major beneficial outcome will include an increase in the number of protein targets amenable to rational drug design and improved methods for generating new drug leads.Read moreRead less
Understanding biological nitrogen fixation: an investigation of multi-electron reduction catalysis at novel iron-sulfur clusters. A new class of iron-sulfur clusters held together by a central light atom will be prepared and their reactions thoroughly studied. These clusters are important because they will have the same structure as the iron-molybdenum cluster of the enzyme nitrogenase. This enzyme fixes atmospheric nitrogen as ammonia. It is the primary route of nitrogen entry into all living s ....Understanding biological nitrogen fixation: an investigation of multi-electron reduction catalysis at novel iron-sulfur clusters. A new class of iron-sulfur clusters held together by a central light atom will be prepared and their reactions thoroughly studied. These clusters are important because they will have the same structure as the iron-molybdenum cluster of the enzyme nitrogenase. This enzyme fixes atmospheric nitrogen as ammonia. It is the primary route of nitrogen entry into all living systems. Industrially ammonia is produced in an energy-demanding process on a vast scale. The studies will provide insights into how nitrogenase works and how to design new multi-electron reduction catalysts. The research may lead to new energy-efficient routes to ammonia and to other new alternative fuel sources. Such processes would transform Australian industry and how we live.Read moreRead less
DNA Nanoshuttles: A New Class of DNA-Binding Molecules. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. DNA-nanoshuttles are ring-shaped molecules that thread onto DNA and shuttle from one end to the other. This threading interaction is without precedent and hence DNA-nanoshuttles have significant potential applications in all areas of medicine, biotechnology and nanotechnology that in ....DNA Nanoshuttles: A New Class of DNA-Binding Molecules. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. DNA-nanoshuttles are ring-shaped molecules that thread onto DNA and shuttle from one end to the other. This threading interaction is without precedent and hence DNA-nanoshuttles have significant potential applications in all areas of medicine, biotechnology and nanotechnology that involve DNA interactions. This research may lead to the design of new diagnostics and applications that will benefit the Australian community, and will provide excellent training of researchers in skills required for employment in the biotechnology and pharmaceutical fields.Read moreRead less
Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. ....Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. Using the combined expertise of the applicants, it is proposed to stereospecifically synthesise dinuclear complexes and study their DNA binding. This will greatly assist in the development of drugs that can selectively target genes and altered DNA.Read moreRead less
Mechanistic Studies on Biologically Active Iron Chelators. The need for orally effective drugs as alternatives to invasive treatment regimens such as subcutaneous infusion is an ongoing concern in health care. This is particularly true in people suffering iron overload. In many cases this condition is present at birth and thus the administration of vital iron chelation therapy via the oral route is a much preferred option. We have unearthed a novel series of candidates for iron chelation therapy ....Mechanistic Studies on Biologically Active Iron Chelators. The need for orally effective drugs as alternatives to invasive treatment regimens such as subcutaneous infusion is an ongoing concern in health care. This is particularly true in people suffering iron overload. In many cases this condition is present at birth and thus the administration of vital iron chelation therapy via the oral route is a much preferred option. We have unearthed a novel series of candidates for iron chelation therapy (the pyridine-2-carboxaldehyde isonicotinoyl hydrazone [PCIH] analogues) which show oral activity. These chelators undergo some interesting iron catalysed oxidation chemistry and it is vital that the mechanism of this reaction be elucidated to determine whether it will be of biological significance upon administration of these compounds as iron chelators.Read moreRead less
Cation Ordering - A Strategy to Prepare Multiferroic Oxides. This project will produce new families of functional metal oxides with technologically relevant properties, especially multiferroic behavior. Such materials are highly sort-after in the rapidly emerging field of spintronics. Through comprehensive experimental studies of a number of such materials this project will enhance the ability of industry to develop new and improved materials.