Mycobacterial Cholesterol Degradation: A Unique Metabolic Weakness? This project aims to understand the use of the steroid cholesterol as a source of essential metabolic building blocks by bacteria. Cholesterol utilisation is a key feature of many bacterial pathogens which have evolved to survive in niche environments. By understanding the initial step in cholesterol degradation and the bioinorganic and bioorganic chemistry of the metalloenzymes that catalyse it, this work aims to develop strate ....Mycobacterial Cholesterol Degradation: A Unique Metabolic Weakness? This project aims to understand the use of the steroid cholesterol as a source of essential metabolic building blocks by bacteria. Cholesterol utilisation is a key feature of many bacterial pathogens which have evolved to survive in niche environments. By understanding the initial step in cholesterol degradation and the bioinorganic and bioorganic chemistry of the metalloenzymes that catalyse it, this work aims to develop strategies to block this activity. This will turn a key strength of these bacteria into a potent weakness and will generate the proof of principle and knowledge required for the future development of effective strategies to combat pathogenic bacteria.Read moreRead less
Challenging targets in rare earth metal-organic chemistry. This project aims to prepare highly reactive rare earth organometallic and metal-organic compounds, especially from the free metals, and to determine their structures and reactivity. Abundant rare earth resources position Australia to be a major supplier of these strategic elements. The challenging target systems include coordination stabilised novel ligands, pseudo-Grignard reagents LnR(X) including the rare fluorides, complexes primed ....Challenging targets in rare earth metal-organic chemistry. This project aims to prepare highly reactive rare earth organometallic and metal-organic compounds, especially from the free metals, and to determine their structures and reactivity. Abundant rare earth resources position Australia to be a major supplier of these strategic elements. The challenging target systems include coordination stabilised novel ligands, pseudo-Grignard reagents LnR(X) including the rare fluorides, complexes primed for carbon-fluorine activation, and intermediates from use of lanthanoid reagents in organic synthesis. The project will provide a knowledge base and expertise for the utilisation of Australia's abundant rare earths and will transform the current behaviour of the elements. It builds the expertise and knowledge needed to underpin Australian rare earth processing and develops the breakthrough science needed for new applications in fine chemical manufacturing, catalysis and recycling.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
Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelati ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelation. They have discovered and characterised new chelators that show marked anticancer activity, and act by a new mechanism that overcomes problems of resistance. In this project they will pursue a course that will lead to a greater understanding of how these compounds work with the outcome that new effective anticancer drugs may emerge.Read moreRead less
Development of New Materials Based on Multinuclear Ruthenium Complexes. The program aims to design new materials for use in applications such as catalysis and light-activated devices (including light harvesting or solar energy conversion), for the detection and analysis of specific small molecules and anions of particular interest, and to provide an insight to the operation of biological systems such as metal-containing enzymes. The particular molecules will also be investigated for the developm ....Development of New Materials Based on Multinuclear Ruthenium Complexes. The program aims to design new materials for use in applications such as catalysis and light-activated devices (including light harvesting or solar energy conversion), for the detection and analysis of specific small molecules and anions of particular interest, and to provide an insight to the operation of biological systems such as metal-containing enzymes. The particular molecules will also be investigated for the development of a new type of therapeutic agent for the treatment of a range of diseases, with a particular interest in this work on a drug for the treatment of HIV-AIDS. Read moreRead less
Advancing the chemistry of topical rare earth metals. Abundant rare earth resources positions Australia to be a major supplier of these strategic elements and overcome the shortage created by the Chinese monopoly and export restrictions. This project will build the expertise and knowledge needed to underpin Australian rare earth processing and develop the breakthrough science needed for new applications.
Electrochemically Driven Molybdoenzyme Catalysis. Enzymes that catalyse oxidation and reduction reactions need to exchange electrons with their substrate and this supply of electrons needs to be sustained. Artificially reconstituted systems can be developed where the enzyme is coupled with an electrode and the current (electrons) exchanged during the reaction are measured directly. In this project we will reveal whether some unusual and unexplained electrochemical phenomena seen before are relat ....Electrochemically Driven Molybdoenzyme Catalysis. Enzymes that catalyse oxidation and reduction reactions need to exchange electrons with their substrate and this supply of electrons needs to be sustained. Artificially reconstituted systems can be developed where the enzyme is coupled with an electrode and the current (electrons) exchanged during the reaction are measured directly. In this project we will reveal whether some unusual and unexplained electrochemical phenomena seen before are related to the properties of the enzymes themselves or the ways in which their experiments have been conducted.Read moreRead less
Pioneering stable copper carbanions for new C-C bond forming paradigms. The stabilisation of highly reactive carbanions underpins advances in chemical synthesis of new compounds including polymers, agrichemicals and pharmaceuticals. This project aims to deliver an innovative chemical reactivity platform, underpinned by copper carbanion complexes accessed via synthetic electrochemistry. Carbanions are essential components of carbon-carbon bond forming reactions but their high reactivity can be pr ....Pioneering stable copper carbanions for new C-C bond forming paradigms. The stabilisation of highly reactive carbanions underpins advances in chemical synthesis of new compounds including polymers, agrichemicals and pharmaceuticals. This project aims to deliver an innovative chemical reactivity platform, underpinned by copper carbanion complexes accessed via synthetic electrochemistry. Carbanions are essential components of carbon-carbon bond forming reactions but their high reactivity can be problematic. Expected outcomes of this project are an understanding of why these novel copper compounds are stable and how they can be utilised as synthetic reagents. This should provide significant benefits in unlocking the synthetic potential of a new class of chemical compound that has until now remained unexplored.Read moreRead less
Probing polynuclear platinum biomolecule interactions. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration with the inventor of these new drugs puts Australian research at t ....Probing polynuclear platinum biomolecule interactions. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration with the inventor of these new drugs puts Australian research at the forefront of the clinical development. There is the potential for the generation of new IP from new strategies in the design of improved anticancer drugs. The project builds strong international links and provides international training for Australian PhD students. Read moreRead less
The fate of copper in atom transfer radical reactions. Copper (Cu) complexes of poly-amine ligands have emerged as extremely active homogeneous catalysts in atom transfer radical reactions, forming organic radicals from alkyl halide precursors, and they are now employed extensively in polymer and organic chemistry. The catalyst cycles between its Cu(I) and Cu(II) oxidation states reversibly yet both forms are susceptible to side reactions, particularly with solvents which can lead to loss of cat ....The fate of copper in atom transfer radical reactions. Copper (Cu) complexes of poly-amine ligands have emerged as extremely active homogeneous catalysts in atom transfer radical reactions, forming organic radicals from alkyl halide precursors, and they are now employed extensively in polymer and organic chemistry. The catalyst cycles between its Cu(I) and Cu(II) oxidation states reversibly yet both forms are susceptible to side reactions, particularly with solvents which can lead to loss of catalytic activity. This project aims to apply a multifaceted approach to interrogate the catalysts in both their Cu(I) and Cu(II) oxidation states and identify for the first time the pathways that lead to undesirable side reactions and provide new ways of optimising catalyst performance.Read moreRead less