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.
Development of metal probes for the selective recognition of DNA. Transition metal complexes with large aromatic ligands have recently been shown to bind DNA by intercalation. However, controversy continues over their base sequence and groove selectivity. We will synthesise a range of chiral metal complexes and screen these against combinatorial oligonucleotide libraries to determine their base sequence selectivity. The information obtained will help us design better intercalators that can be us ....Development of metal probes for the selective recognition of DNA. Transition metal complexes with large aromatic ligands have recently been shown to bind DNA by intercalation. However, controversy continues over their base sequence and groove selectivity. We will synthesise a range of chiral metal complexes and screen these against combinatorial oligonucleotide libraries to determine their base sequence selectivity. The information obtained will help us design better intercalators that can be used as sensitive molecular probes and may find application as antitumour drugs. Binding interaction between the complex and DNA will be studied by NMR spectroscopy.Read moreRead less
Control of the Enantiomeric Self-Resolution Process. The availability of enantiopure molecules is crucial in chemistry and medicine. Enantiomeric self-resolution on crystallisation provides pure left- and right-handed molecules from 1:1 mixtures of the two. It is the simplest and cheapest means of obtaining enantiopure molecules, but its occurrence in any given case cannot normally be
predicted. The understanding and control of the self-resolution process gained through this project will repre ....Control of the Enantiomeric Self-Resolution Process. The availability of enantiopure molecules is crucial in chemistry and medicine. Enantiomeric self-resolution on crystallisation provides pure left- and right-handed molecules from 1:1 mixtures of the two. It is the simplest and cheapest means of obtaining enantiopure molecules, but its occurrence in any given case cannot normally be
predicted. The understanding and control of the self-resolution process gained through this project will represent a major breakthrough in organic and pharmaceutical chemistry. This technological advance will make pure handed molecules available readily and cheaply, thereby allowing chemical, pharmaceutical and biological developments to be made by Australian industry.
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The roles of metal ions in glucose metabolism and the treatment of diabetes. Metal supplements, such as chromium and vanadium are consumed widely for their purported fat reduction and anti-diabetic activities. However, much is still to be learnt about the efficacy and safety of such metal ions when they are taken in supplements and whether they have an essential role in the prevention of diabetes or, in some instances, are a risk factor for cancer. The research will provide an understanding of ....The roles of metal ions in glucose metabolism and the treatment of diabetes. Metal supplements, such as chromium and vanadium are consumed widely for their purported fat reduction and anti-diabetic activities. However, much is still to be learnt about the efficacy and safety of such metal ions when they are taken in supplements and whether they have an essential role in the prevention of diabetes or, in some instances, are a risk factor for cancer. The research will provide an understanding of how these metal complexes exert their anti-diabetic effects and how they can be made safer and/or more efficacious for the treatment of type 2 diabetes, which is a rapidly expanding epidemic in developed countries. Read moreRead less
Design and Mechanistic Studies of Metal-Based Anti-Diabetic Drugs. Metal supplements, such as chromium and vanadium, are consumed widely for their purported fat reduction and anti-diabetic activities. However, much is still to be learnt about the efficacy and safety of such metal ions and whether they have an essential role in the prevention of diabetes or, in some instances, are a risk factor for cancer. The research will provide a fundamental understanding of how these metal complexes exert th ....Design and Mechanistic Studies of Metal-Based Anti-Diabetic Drugs. Metal supplements, such as chromium and vanadium, are consumed widely for their purported fat reduction and anti-diabetic activities. However, much is still to be learnt about the efficacy and safety of such metal ions and whether they have an essential role in the prevention of diabetes or, in some instances, are a risk factor for cancer. The research will provide a fundamental understanding of how these metal complexes exert their anti-diabetic effects and how they can be made safer and/or more efficacious for the treatment of type 2 diabetes, which is a rapidly expanding epidemic in developed countries. Read moreRead less
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