New synthetic strategies to small cyclic peptides. This project aims to invent new synthetic strategies that enable chemical manipulation of small cyclic peptides, a promising class of biologically active molecules with high metabolic stability. Combining theory and practice, this project will develop novel acyl transfer reactions that will allow traceless, site-selective, ring expansion and contraction of small cyclic peptides. This project will result in new synthetic methodology that will sim ....New synthetic strategies to small cyclic peptides. This project aims to invent new synthetic strategies that enable chemical manipulation of small cyclic peptides, a promising class of biologically active molecules with high metabolic stability. Combining theory and practice, this project will develop novel acyl transfer reactions that will allow traceless, site-selective, ring expansion and contraction of small cyclic peptides. This project will result in new synthetic methodology that will simplify the synthesis of an important class of small drug-like molecules. This will provide significant benefits, such as a breakthrough in the synthetic approach to small cyclic peptides, which will strengthen Australia’s international standing in peptide research and provide new strategies for translation to the growing biotechnology industry.Read moreRead less
Discovering new organic chemistry using an inorganic touch. This project aims to discover new organic chemistry by treating carbon like a metal atom. Advances in fundamental organic chemistry have been important in developing products, including medicines, plastics and television display technology. Much research activity relies on applying existing organic chemistry, but inventing genuinely new organic chemistry is more difficult. By viewing carbon as a metal, this project will try to solve imp ....Discovering new organic chemistry using an inorganic touch. This project aims to discover new organic chemistry by treating carbon like a metal atom. Advances in fundamental organic chemistry have been important in developing products, including medicines, plastics and television display technology. Much research activity relies on applying existing organic chemistry, but inventing genuinely new organic chemistry is more difficult. By viewing carbon as a metal, this project will try to solve important problems in organic chemistry that have been unresolved for decades, and synthesise valuable chemicals normally generated using expensive precious metal catalysts.Read moreRead less
Atmospheric Free-Radicals: Exploring the Role of Nitrate Radicals in the Oxidative Damage of Bio-Surfaces. This project falls within the National Research Priority 2 (Promoting and Maintaining Good Health) as identified by the ARC, specifically Priority Goal 2 (Ageing well, ageing productively) and Priority Goal 3 (Preventive healthcare). The study will lead to a better understanding of environmental factors influencing health and welfare of Australians every age and will provide unique opport ....Atmospheric Free-Radicals: Exploring the Role of Nitrate Radicals in the Oxidative Damage of Bio-Surfaces. This project falls within the National Research Priority 2 (Promoting and Maintaining Good Health) as identified by the ARC, specifically Priority Goal 2 (Ageing well, ageing productively) and Priority Goal 3 (Preventive healthcare). The study will lead to a better understanding of environmental factors influencing health and welfare of Australians every age and will provide unique opportunities for students to be trained in cutting-edge basic research. Knowledge and fundamental understanding of the damage of bio-surfaces caused by atmospheric free-radical oxidants and their potential role in ageing processes will help to develop novel medical strategies, which substantially contribute to the quality of Australian sciences.Read moreRead less
Gas Phase Studies to Catalyze a Better Understanding of Metal Reactivity. The proposed research will increase knowledge of fundamental questions related to the mechanisms of catalysis and metal ion reactivity. The insights gained will be an important addition to the knowledge base of our culture, both nationally and in the wider international context. We note that research into the behaviour and design of catalysts is a burgeoning field which reflects the great importance of this area in the int ....Gas Phase Studies to Catalyze a Better Understanding of Metal Reactivity. The proposed research will increase knowledge of fundamental questions related to the mechanisms of catalysis and metal ion reactivity. The insights gained will be an important addition to the knowledge base of our culture, both nationally and in the wider international context. We note that research into the behaviour and design of catalysts is a burgeoning field which reflects the great importance of this area in the international scientific community. Our proposal will add to fundamental knowledge and may also result in practical applications. More importantly, we will train and equip talented young people with a spectrum of skills which will make them well placed to meet the demand for highly skilled professional scientists.Read moreRead less
Novel Synthetic Receptors for Recognition and Transport of Biologically Important Anions. Anion receptors are not currently tailored for the ‘real world’ biological environments (for example, physiological saline and membranes) in which anions perform their many critical roles. The project will design and synthesise a range of molecular receptors based on large, rigid, precisely functionalisable scaffolds, tailored specifically to complement both the shape, size and charge of target anions as we ....Novel Synthetic Receptors for Recognition and Transport of Biologically Important Anions. Anion receptors are not currently tailored for the ‘real world’ biological environments (for example, physiological saline and membranes) in which anions perform their many critical roles. The project will design and synthesise a range of molecular receptors based on large, rigid, precisely functionalisable scaffolds, tailored specifically to complement both the shape, size and charge of target anions as well as their native environment. The project will investigate the ability of these receptors to strongly bind their target anions with high selectivity in both aqueous systems and in membrane environments. This will lead to the development of innovative synthetic receptors that recognise and/or transport biological anions for use in biomedical applications.Read moreRead less
Structures and Properties of beta-R3M (M = Si, Ge, Sn)- and beta-Chalcogenyl-substituted Carbenium Ions. The benefits of this work are many-fold. The scientific knowledge gained will be invaluable to all scientists working in organic chemistry; mechanistic chemists who will learn from the science, and synthetic organic chemists who can utilise the results when planning strategies for the synthesis of complex drugs. Another major benefit of this research is in the training of young scientists. Th ....Structures and Properties of beta-R3M (M = Si, Ge, Sn)- and beta-Chalcogenyl-substituted Carbenium Ions. The benefits of this work are many-fold. The scientific knowledge gained will be invaluable to all scientists working in organic chemistry; mechanistic chemists who will learn from the science, and synthetic organic chemists who can utilise the results when planning strategies for the synthesis of complex drugs. Another major benefit of this research is in the training of young scientists. The students who work on this proposal gain invaluable experience in many areas of chemistry, ranging from synthetic chemistry to structural chemistry and theoretical chemistry. They will also gain experience in important physical techniques from NMR spectroscopy to X-ray crystallography.Read moreRead less
Formation, structure and chemistry of non-covalent complexes of biomolecules via mass spectrometry. The studies proposed address fundamental issues which are essential to developments in biotechnology and related industries and of implication for human health and disease, with special attention to mechanisms of Deoxyribonucleic acid (DNA) damage, for example through Ultraviolet (UV) A and B. This has a special resonance for our sunburnt nation. The work, using world class Australian Research Cou ....Formation, structure and chemistry of non-covalent complexes of biomolecules via mass spectrometry. The studies proposed address fundamental issues which are essential to developments in biotechnology and related industries and of implication for human health and disease, with special attention to mechanisms of Deoxyribonucleic acid (DNA) damage, for example through Ultraviolet (UV) A and B. This has a special resonance for our sunburnt nation. The work, using world class Australian Research Council funded instrumentation, will carry out breakthrough science, exploiting and enhancing existing national strength in biological science with a strong interdisciplinary element. This project will also maintain and enhance Australia's international research profile through its novelty and new overseas collaborations. The project will equip talented young scientists with a spectrum of skills.Read moreRead less
Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of ex ....Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of exposure. Structure determination of biomolecules is at the heart of identifying, diagnosing and potentially developing treatments for diseases, and thus another important reason for studying these interactions is the potential to develop new mass spectrometry based analytical methods.Read moreRead less
Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unch ....Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unchartered area! We will examine the fundamental chemistry (unimolecular and bimolecular reactions) of these systems and build upon some exciting preliminary results which suggest potential applications (e.g. as a proteomics tool to sequence and distinguish between leucine and isoleucine residues in peptides).Read moreRead less
Environmental polymer degradation. This project will use the powerful combination of mass spectrometry and computational chemistry to tease out key aspects of polymer degradation mechanisms under environmental conditions. Society increasingly relies on manufactured polymers but polymer lifespan and fossil fuel reserves are limited. Design principles are needed to guide the synthesis of durable polymers for applications from paints to protective coatings in photovoltaic cells. This project will e ....Environmental polymer degradation. This project will use the powerful combination of mass spectrometry and computational chemistry to tease out key aspects of polymer degradation mechanisms under environmental conditions. Society increasingly relies on manufactured polymers but polymer lifespan and fossil fuel reserves are limited. Design principles are needed to guide the synthesis of durable polymers for applications from paints to protective coatings in photovoltaic cells. This project will establish appropriate guidelines and provide the scientific foundation for the synthesis of robust, long-lasting polymers, or polymers that decompose without damaging the environment. This will deliver significant economic and environmental benefits to an industry sector that contributes about 12 per cent of total Australian manufacturing.Read moreRead less