THE UNIVERSITY OF ADELAIDE
2016 CHEMISTRY HONOURS BOOKLET
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WELCOME This booklet contains information about doing Honours in Chemistry at the University of Adelaide. Honours is an additional year of full-time study at the end of your undergraduate degree: it is a prerequisite and stepping stone to a research higher degree, and an opportunity to specialise and increase your competitiveness if you are seeking a job. It is an exciting and challenging step towards your future career. The Honours Year provides you with the opportunity to undertake a significant research project in Chemistry, and is the first year of your research career. Regardless of your career aspirations, Honours is an opportunity for personal and professional development: it will develop your abilities in clear-thinking, criticism and communication, and test your imagination, self reliance and self-discipline. During the Honours year, you are required to undertake a research project under the direct supervision of a member of staff. The research you do will provide you with training in various research techniques, as well as give you the experience of using modern research instrumentation and techniques. At the end of the Honours year, you will write a thesis that details your research efforts. In addition, you will attend advanced lecture courses and seminars. Carrying out research is the defining feature of the Honours year and thus, selecting the project and your supervisor is an important decision. It is imperative that you talk to a wide range of prospective supervisors to discover what their research interests are. In addition, it is recommended that you talk to the current Honours students and the PhD students in Chemistry to find out more about Honours. Individual staff members are eager to discuss their work and will be pleased to give you more information on projects on offer for 2016. Note that most projects can be adapted to suit a student's own interests and strengths. In the following pages of this booklet, you will find:
further details of what the Honours year entails, and
general accounts of the research being carried out by each supervisor and their research group.
We look forward to seeing you doing Honours in Chemistry at the University of Adelaide in 2016.
A/Prof. Hugh Harris (Honours Coordinator)
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HONOURS IN CHEMISTRY What is Honours like? As an Honours student you become a member of the School and a valued colleague. You will spend most of your time as part of a research group sharing the goals, triumphs, disappointments and all of the other things that are part of the adventure of scientific research. For the first time, you become responsible for the outcome of your own scientific work. Honours students also partake in all aspects of the social life of the School. You will form friendships and professional associations that will last a lifetime. The Honours degree gives students a thorough training in scientific method and a detailed insight into the area of research that they pursue. The scientific approach to problem solving, maturity and self-discipline gained during the Honours year equips them for a wide variety of careers. Many of our students elect to continue in the research domain by enrolling in the School's PhD programs. However, the analytical and communication skills that our students acquire have led previous Honours graduates into a range of different fields. Aims The Honours course consists of a research project and coursework. The aims of the course are:
to provide advanced training in the principles of scientific research and in the current state of knowledge and techniques used in your chosen area of study, and
to develop the skills required for a successful career in scientific research or related activities.
Thus, students learn to search and understand literature relevant to their chosen discipline, to formulate and assess research proposals, to design, evaluate and present scientific experiments, and to develop written and verbal communication skills. Who is Eligible to do Honours? Anybody who has majored in Chemistry and performed to a satisfactory level in your third year subjects (a Credit or better in Level III Chemistry subjects is normally required). It is possible for someone who is close to a Credit average to enter the Honours year, but it is recommended that you discuss your options with the Honours Coordinator to determine your individual situation.
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The Honours Year Honours in 2016 will commence on the 1st of February. The first week will consist of various inductions, including sessions on occupational health and safety. There will be an additional intake of Honours students into Chemistry in second semester of 2016. It is anticipated that Mid-Year Honours will commence on 25th July 2016. During Honours, students are required to do the following:
undertake a major research project under the supervision of an academic staff member
write a thesis on the research
present an end of year seminar on the work carried out
undertake an oral examination, which will focus on the research carried out
attend lectures/workshops on a range of Chemistry topics
attend weekly research seminars Assessment The Honours grading system is not like the one used for undergraduate courses. It ranges from First Class (I) through Second Class Division A (2A), Second Class Division B (2B) and Third Class (3). The grade divisions are: Honours Class
Assessment Range > 80 79 - 70 69 - 60 59 - 50
First (I) 2A 2B 3
The greatest rewards in assessment are for originality, insight, clear thinking and technical competence. These things will come through hard work and dedication, and with the guidance of your supervisor. The Honours year consists of two distinct courses; a 9-unit coursework component in semester 1 and a 15unit project component that runs across both semesters. The percentage assessment weightings of each part of the Honours in Chemistry programme is as follows: Component Coursework (CHEM4010)
Maximum marks
Units
100
9
Research Project (CHEM4020) Thesis
70
Oral Examination
20
Seminar
10
5
15
Research Components The research components of the Honours Year add up to a total of 15 units, and thus, this aspect of the program is the most important part of the year. Selecting the project and your supervisor is an important decision. You are strongly encouraged to talk to a wide range of prospective supervisors to discover what their research interests are. In addition, it is recommended that you talk to the current Honours students and the PhD students in Chemistry to find out more about Honours.
The role of the supervisor Your research supervisor is someone with enough expertise in your field of interest to be able to advise you about techniques, literature and so on. Supervisors know from experience that student's inclinations and abilities differ, and they adjust their contribution accordingly. Your relationship with your supervisor is important. They should be someone you find easy to talk with and, most importantly, someone you feel you could work with and learn from.
Coursework The coursework component of the Honours year will be held in the first 8 weeks of Honours. It is expected that students will focus on the coursework for this entire period, with no research work to be undertaken during this time. There are normally five different parts of the coursework, with selected academics presenting a wide range of topics. It is expected that some choice among subjects will be available to students in 2016 from a larger number of courses; final details will be provided at a later date. The ways of assessing this work is quite varied, ranging from examinations, oral presentations and essays.
Employment and Demonstrating As an Honours student, you will be offered employment as a casual demonstrator in the First Year Laboratory classes. This is normally a 3 hr (plus marking) commitment per week during the teaching periods. At the time of printing, the standard rate for demonstrating/marking is $42.09 per hour. Further details will be provided at the start of Honours. It is not compulsory for students to demonstrate, but we have found over the years that Honours students find it to be a rewarding experience, and you are strongly encouraged to take part.
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The Application Process There are two steps to applying to join the Honours program, both have the same deadline – 30th October. Step 1 – all applicants must fill out the online form titled “Honours Expression of Interest’ It is found at: http://www.sciences.adelaide.edu.au/future-students/honours/form/ This form provides the Faculty of Sciences with all your information and allows them to keep you informed of the process. This form can be filled in at any time – the sooner the better! AND Step 2 – all applicants must submit the Chemistry Honours supervisor preference nomination form (attached at the back of this booklet) to the Chemistry Honours Coordinator (A/Prof. Harris). This form requires you to nominate your preferences for supervision, and will take precedence over information entered into the online form above. When deciding your preferences, you should ensure that you talk to a number of possible supervisors to obtain a clear idea of what their research interests are. Individual staff members are eager to discuss their work and will be pleased to give you more information on projects on offer for 2016. Note that most projects can be adapted to suit a student's own interests and strengths. Allocation of Supervisors Allocation of supervisors is carried out by the Honours Coordinator and ratified by the other Chemistry academics. Every effort will be made to accommodate your first preference of supervisor, but it should be remembered that allocations depend on space, resources and supervisor availability. Accordingly, it is essential that you include FOUR preferences of supervisor on your application form. Furthermore, it is possible for students to be jointly supervised by two academics, whereby the research project will involve work in an area of mutual interest to both academics. If you are interested in this type of joint research project, it would be helpful if you indicated this on the Chemistry Honours supervisor nomination form. You will be informed of the outcome of your application by letter in December (after examination results are confirmed). Allocation of supervisors will occur shortly afterwards and you will be informed about your supervisor by email from the Honours Coordinator. Mid-Year Enrolments Students who are considering starting in semester 2, 2016 are able to apply at the same time as the standard Honours Year, but allocation to a supervisor will be made towards the end of Semester 1, 2016. Late Applications Chemistry is happy to take late applications for Honours and will accept students up to and including the first week of the Honours year. Students are reminded that it may be difficult to assign them to the supervisor they prefer as initial allocations will be made in December. If you are considering a late application, you are strongly encouraged to contact the Honours coordinator so that we can discuss your options. 7
RESEARCH IN CHEMISTRY Research within the field of chemical sciences at the University of Adelaide has international recognition for excellence in the areas of laser & ion chemistry (one of the leading facilities in the southern hemisphere), medicinal & biological chemistry, organometallic chemistry, molecular recognition, and new materials. The research of the Chemistry Department is divided into four major areas. These areas demonstrate that chemical research is a multidisciplinary endeavour that overlaps with biology, physics, medicine, and material science. Energy and Environment Professor Andrew Abell, Professor Michael Bruce, Assoc. Prof. Christian Doonan, Assoc. Prof. Hugh Harris, Dr David Huang, Professor Stephen Lincoln, Prof. Greg Metha.
Fundamental research in the key areas of energy usage and demand and environmental chemistry. Aspects of green and environmental chemistry. Examples of projects include: •
Application of carbon dioxide as a primary reagent for the formation of useful organic molecules
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Hydrogen storage with metal-organic frameworks
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Nanocatalysis using metal clusters
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Speciation of heavy metal toxicants in environmental samples
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Computer simulation of charge transport in polymer solar cells
Functional Materials Professor Andrew Abell, Professor Michael Bruce, Assoc. Prof. Christian Doonan, Dr David Huang, Professor Stephen Lincoln
The design and construction of new molecules and molecular assemblies, which can be utilised in the generation of new materials, such as polymers, proteins, peptides, catalysts, molecular devices, sensors, and probes. Examples of projects include: •
General approaches to protein ligand design: new therapies and biological probes
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Applications of cyclodextrins to the design of molecular devices and smart materials
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Supramolecular chemistry and crystal engineering
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Complexes with carbon chains as models for molecular wires
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Theory of self-assembly of nanoscale functional materials
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Medicinal and Biological Chemistry Professor Andrew Abell, Dr Stephen Bell, Dr Jonathan George, Assoc. Prof. Hugh Harris, Assoc. Prof. Tak Kee, Professor Stephen Lincoln, Dr Tara Pukala, Professor Simon Pyke
Drug design and development, with an emphasis on the chemistry of proteins and peptides. Work is this area is related to identifying and synthesizing small novel molecules, and framing biological questions that such molecules might help answer by blocking or activating protein targets. Examples of projects include: •
Molecular chaperone proteins: their structure, function and interactions
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Enzyme mimics and molecular reactors
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Total synthesis of biologically active natural products
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Structural determination of proteins using mass spectrometry and NMR
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Structure-based drug design
Molecular Photoscience and Ion Chemistry Assoc. Prof. Tak Kee, Prof. Greg Metha, Dr. Tara Pukala
The application of light and mass spectrometry as central chemical research tools to gain insight into the chemical and physical properties of molecules. Computational chemistry using state-of-the-art high performance computers underpins these experimental studies. Examples of projects include: •
Application of mass spectrometry to the sequence determination of bioactive peptides
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Non-invasive chemical imaging of cardiac cells and tissues
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Investigation into gas phase metallic and bi-metallic clusters
Further details on each academic’s research programs are detailed in the following pages. Please read them and then make an appointment to speak to the people that you may be interested in working with.
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School of Chemistry and Physics Department of Chemistry Academic Staff Contact Details Head of Chemistry:
Professor Gregory Metha
Professor Andrew D. Abell Office
Badger Room G19
Tel
8313 5652
Email
[email protected] au
Dr Stephen G. Bell Office
Badger Room G22
Tel
8313 4822
Email
[email protected] au
Assoc. Prof. Christian J. Doonan Office
Badger Room 104
Tel
8313 5770
Email
[email protected] au
Dr Jonathan H. George Office
Badger Room 103
Tel
8313 5494
Email
[email protected] au
Assoc. Prof. Hugh H. Harris Office
Badger Room 231
Tel
8313 5060
Email
[email protected] au
Dr David M. Huang Office
Badger Room 232
Tel
8313 5580
Email
[email protected] au
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Assoc. Prof. Tak W. Kee Office
Badger Room 230
Tel
8313 35039
Email
[email protected] au
Prof. Gregory F. Metha Office
Badger Room 105a
Tel
8313 5943
Email
[email protected] au
Dr Tara L. Pukala Office
Badger Room 222
Tel
8313 5497
Email
[email protected]
Professor Simon M. Pyke Office
Badger Room 221
Tel
8313 5358
Email
[email protected]
Assoc. Prof. Christopher J. Sumby Office
Badger Room 105
Tel
8313 5358
Email
[email protected]
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In addition to the above academic staff, it is possible to carry out research with the researchers listed below. As they do not hold full-time positions in the Department of Chemistry, they are only able to supervise research projects in collaboration with one of the above academic staff members. It is also feasible to have other University of Adelaide academics cosupervise Honours projects in Chemistry, at the discretion of the Head of Department.
E. Professor Michael Bruce Office
Badger Room 234
Tel
8313 5939
Email
[email protected]
Assoc. Prof. Heike Ebendorff-Heidepriem – see pages 25 and 34. Office
The Braggs Room 183
Tel
8313 4380
Email
[email protected]
Prof. Peter Hoffman Office
Molecular Life Sciences Room 149
Tel
8313 4362
Email
[email protected]
E. Professor Richard Keene – see page 34. Office
Johnson Room G01a
Tel
8313 1025
Email
[email protected]
E. Professor Stephen F. Lincoln Office
Badger Room 233
Tel
8313 5559
Email
[email protected]
Dr Natalie Williamson – see page 32. Office
Badger Room 223
Tel
8313 5496
Email
[email protected]
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Professor Andrew Abell The function of peptides and proteins is defined by their linear sequence of amino acids and how this folds into a biologically active 3D shape or conformation. A detailed molecular understanding of these processes allows one to rationally design and synthesize small molecules that can bind to a peptide or protein of interest. Such molecules provide important biological probes for studying key metabolic events and also potential therapies for important human diseases. Skills and experiences gained: All the projects listed below involve organic synthesis and product characterisation by NMR and other spectroscopic techniques, with an opportunity to get involved in biology and computational chemistry to broaden your experience. You will work closely with senior members of our group and gain some exposure to industry and commercialisation of basic research. A general approach to the inhibition of cysteine proteases (with Prof David Callen, Head Breast Cancer Genetics Group; and our new start up, Calpain Therapeutics, see http://calpaintherapeutics.com/). Many therapeutics based on protease inhibitors are currently in late clinical trials, or are already available as drugs. However, inhibitors of the cysteine protease family are very much under represented, primarily because of flaws in their design: existing inhibitors are conformationally flexible and biologically unstable structures with a 'reactive warhead' that makes them un-drug like. We have recently computationally designed and prepared (using ring closing metathesis and click chemistry) potent cyclic inhibitors of cysteine proteases (see left) that over come these basic problems. The constituent cycle constrains the inhibitor cataract lens into a (below), resulting in improved biostability, an entropic advantage to inhibitor binding, and increased potency without the need for a 'reactive warhead'. We have shown that these inhibitors stop the progression of cataract in lens culture (left) and also in animal trials by inhibiting a cysteine protease and the study is entering a commercial phase. This project involves the inhibitor treated stereoselective synthesis of examples of these macrocyclic inhibitors and their assay against a range of proteases (including the proteasome) and an investigation into their potential to stop the growth of various cancer cell lines. See: Angew. Chem. Int. Edit. 2014, in press (DOI: 10.1002/anie.201404301).
The inhibition of Biotin Protein Ligase: new anti bacteria agents (with Prof Wallace, Dr Polyak and A/Prof Booker, MBS; and Prof Wilce, Monash). Antibiotic resistance is a significant threat to human health world-wide and new antibiotics are desperately required to control bacterial infections that are currently untreatable. Two million patients contract infections each year at a cost of $5 billion annually in extended stays and expensive drug regimens. Around 90,000 of these will die from hospital-acquired infections untreatable with current antibiotics. Biotin protein ligase (BPL) is an attractive target for the development of a new class of antibiotics. We have recently designed inhibitors of BPL from the pathogenic bacterium Staphylococcus aureus based on our recently solved x-ray structures of this enzyme (see opposite). These structures have been prepared and shown to be specific inhibitors of the Staphylococcus aureus BPL. We have recently identified BPL mutants for an in situ ‘Click’ synthetic approach to optimising these inhibitors using the enzyme as a template for selecting the optimum structure from a library of precursor acetylene and azides (see schematic). The project involves all aspects of this study.
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See: RSC Chemical Science, 2013, 4, 3533-3537.
Electron transfer in peptides and proteins (with Dr Jingxian Yu, Dr David Huang and Dr Denis Scanlon). The ability to transfer an electron from one biomolecule to another forms the basis of a number of key biological processes, including photosynthesis and respiration. Figure 2 This ‘flow of electrons’ is catalysed by oxidoreductases over surprisingly large redox probe molecular distances (10 Å or more) through the interaction of associated helical peptide redox partners. These oxidoreductases are rich in α-helices, the structures of which are defined by a characteristic network of hydrogen bonds. This, gold surface together with the fact that the rate of electron transfer decay across a hydrogen bond is approximately twice that of a covalent bond, suggests that these structures provide the molecular ‘shortcut’ necessary for electron transfer. This project involves the solid phase synthesis and characterisation of helical peptides for electron transfer studies, and/or a computational study on the associated mechanisms of electron transfer. (a)
S
S
S
(b)
electrode
donor
acceptor
See: J. Am. Chem. Soc. 2014, in press; and Chem. Commun. 2014, 50, 16521654
A biocompatible platform for metal ion sensing in cells (Centre for Nanoscale BioPhotonics, http://cnbp.wordpress.com/ with Dr Sabrina Heng and Dr Christopher McDevitt, MBS). Metal ions such as zinc and calcium are essential for proper cellular function and an imbalance in their distribution is a major contributor to aging and disease. These ions can be detected on complexation to a suitably designed ligand, with measurement of the resulting fluorescence. This allows for high sensitivity of detection at the single molecule level. However, many existing fluorophores that might be used in this context are not biocompatible, suffering from cellular toxicity and poor water-solubility. We have recently developed an approach to overcome these limitations whereby a zinc sensing fluorophore is incorporated into a biocompatible liposome. This then allows detection of zinc efflux from cells. The project now aims to develop this methodology for sensing other ions such as calcium. With our collaborators, this will provide the basis of a new generation of robust and sensitive biosensor for real life applications such as monitoring zinc and calcium during early embryonic development. See: ACS Macromolecules, 2013, 14, 3376−3379. Detecting calcium ions in biology (Centre for Nanoscale BioPhotonics, http://cnbp.wordpress.com/ with Dr Sabrina Heng and Profs Mark Hutchinson and Jeremy Thompson). We recently reported a glass microstructured optical fibre (MOF)-based sensor that selectively binds lithium ions, with an ability to be switched on and off on irradiation with light. Molecular switching is provided by a photoswitchable spiropyran that is attached to tiny air holes that run the length of the MOF. On exposure to UV light, the spiropyran ring ‘opens’ to chelate the metal ions (on state). Exposure to white light then expels the metal ion to revert the sensor molecule to its starting ‘off’ state (Off state), where it is ready to be used again. The sensor undergoes multiple cycles of on/off switching without the loss of sensitivity. This project involves the synthesis of spiropyran-based sensor molecules specific for calcium ions and their subsequent characterization in solution, in optical fibre, and in biological fluids such as in vitro fertilisation (IVF) media and mice serum. See: RSC Adv. 2013, 3, 8308–8317.
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Dr Stephen Bell P450 biocatalysis and enzyme structure-function studies The cytochrome P450 (CYP) superfamily of heme-thiolate monooxygenases, catalyse the partial oxidation of organic compounds using atmospheric oxygen (Eqn. 1 and Fig. 1). R–H + 2H+ + 2e– + O2 R–OH + H2O
(Eqn. 1)
The selective oxidation of a non-activated C–H bond in a complex organic molecule to the alcohol functionality is a challenging problem in chemical synthesis. With rising energy cost and increasing environmental awareness and concerns, a catalyst with the ability to oxidise a targeted C–H bond would allow multistep routes to be shortened and new ones developed. Bacterial CYP enzymes provide an alternative approach to C–H bond oxidation and have a range of biotechnological applications. In the laboratory we investigate the CYP complement of metabolically diverse microorganisms to discover functional Fig. 1. The active site of P450cam, showing systems with biocatalysis applications. We also study the electron the heme, the cysteine thiolate ligand transfer proteins of these enzymes, including flavin reductases (C357), the substrate (cam; camphor) and and a variety of iron-sulphur cluster ferredoxins in order to other active site residues. optimise CYP enzyme activity. Structural studies of all these proteins are undertaken with collaborators at the University of Adelaide. The structures provide important information on how the enzymes function and the protein-protein interactions which control electron transfer. In addition whole-cell oxidation systems are generated with a view to scale-up the monooxygenase activities using fermentation techniques.1 In the laboratory honours students employ a number of biochemical techniques including molecular biology (e.g. the polymerase chain reaction, gene cloning, rational and random mutagenesis), protein production using Escherichia coli and protein purification. The inorganic metal centres of the enzymes and the electron transfer proteins are analysed using UV/Vis and other spectroscopies. Organic chemistry techniques are used for the production, isolation and identification of hydroxylated organics from enzymatic turnovers and whole-cell reactions via HPLC, GC, GC-MS and NMR. Projects can therefore be designed to be compatible for those with an interest in chemical synthesis or in the biochemical aspects of the work. Evolution of CYP enzymes for fine chemical synthesis Novosphingobium aromaticivorans is a bacterium that can grow in environments that offer very low levels of nutrients. It has evolved to degrade polyaromatic hydrocarbons and several enzymes from this bacterium, are able to bind a wide range of compounds including polyaromatic hydrocarbons (PAHs), chlorinated aromatics, drug molecules such as warfarin and diclofenac and mono- and sesquiterpenoid molecules which are flavour and fragrance additives (Fig. 2).2 Projects are available solving the crystal structure of several of these CYP enzymes (in collaboration with Dr John Bruning in School of Biological Sciences) which will allows us to investigate their properties in more detail. The utilisation of a soluble bacterial CYP system for synthesis has many advantages over membrane bound mammalian or plant systems and the generation of efficient enzyme hydroxylation catalysts for the synthesis of medicinally important compounds such as oxygenated sesquiterpenes and drug metabolites and for the bioremediation of recalcitrant pollutants such as PAHs or chlorinated biphenyls are important chemical challenges. 15
Fig. 2. Selected substrates of CYP108D1.
The project will involve modifying the substrate range of the enzymes using rational and random protein mutagenesis techniques. The goal is to change the substrate binding preference of the enzyme and to identify the oxidation products (Fig. 3).3,4 A number of different substrate classes will be targeted including terpenoid compounds to generate flavour and fragrance compounds (e.g. pinene to verbenol and valencene to nootkatone), alkanes and halogenated aromatics for bioremediation (pentachlorobenzene to pentachlorophenol) (Fig. 3).3,4 Alternatively we can also alter the product selectivity by adding protecting groups to modify the substrate.
Fig. 3. The substrates and products of some natural P450 enzymes (in black) and of redesigned P450 variants (red). Understanding mechanism of action of bacterial P450 systems More often than not electron transfer is the rate-determining step in the CYP enzyme’s catalytic cycle. The electron transfer proteins of P450 enzymes can be difficult to identify and isolate. Enzymes from different bacteria are also highly specific for their natural ET partners. This project involves the isolation and reconstitution of novel electron transfer systems in order to obtain a better fundamental understanding of the critical factors involved and to improve productivity. To this end we are studying a diverse range of P450 enzyme and their electron transfer partners from different bacteria. These systems are involved in natural product synthesis and in the catabolic processes of pathogenic microbes and are therefore biotechnologically or medicinally important. This project involves extensive training in protein purification and characterisation techniques and biochemical assays. Opportunities to crystallise and solve the protein structures using X-ray crystallography are available. There are also projects available to investigate the chemical mechanisms by which cytochromes P450 catalyse novel oxidative transformations e.g. CC bond cleavage, C=C bond epoxidation and formation (dehydrogenation) and heteroatom oxidation and demethylation.5 Such reactions are critical in both biosynthetic and drug metabolic pathways and understanding their mechanism will allow us to predict and utilise their occurrence in drug metabolism, and inhibit them in key biosynthetic pathways to develop novel chemotherapeutics. Investigation of the metabolism of fatty acids by P450 enzymes (Joint Project with Prof. Simon Pyke) Branched-chain fatty acids are the major lipid constituent of the membranes of many bacteria and are hypothesised to increase the fluidity of the membrane. Modified fatty acids are building blocks for other complex molecules and P450 enzymes are known to oxidise fatty acids. This project aims to better understand the specific roles of methyl branched fatty acid. Branched fatty acids, of varying length, with methyl branching groups at different locations will be generated in enantiomerically pure forms using synthetic organic chemistry. These acids, and their non-branched analogues, will be tested as potential substrates for a range of bacterial P450 enzymes. 3 The oxidation products, which may be chiral, will be analysed and characterised. This project will provide a broad range of skills predominantly in organic synthetic chemistry as well as in biochemical assays and chemical analysis techniques. References [1] A cytochrome P450 class I electron transfer system from Novosphingobium aromaticivorans. Bell, S.G., et al. Appl Microbiol Biotechnol, 2010, 86 (1), 163-175. [2] Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: an aromatic hydrocarbon binding P450 enzyme. Bell, S.G., et al. Acta Crystallogr Sect D Biol Cryst, 2012, 68 (3), 277-291. [3] Evolved CYP102A1 (P450BM3) variants oxidise a range of non-natural substrates and offer new selectivity options. Whitehouse, C.J.C., Bell, S.G., et al. Chem. Commun., 2008, 28 (8), 966-968. [4] The heme monooxygenase cytochrome P450cam can be engineered to oxidize ethane to ethanol. Xu, F., Bell, S.G., Lednik, J., Insley, A., Rao, Z. and Wong, L.-L. Angew Chem Int Ed, 2005, 44 (26), 4029-4032. [5] Investigation of the substrate range of CYP199A4: modification of the partition between hydroxylation and desaturation activities by substrate and protein engineering Bell, S.G., et al. 2012 Chem Eur J 18 (52), 16677-16688.
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Assoc. Prof. Christian Doonan Chemistry of Porous Extended Networks Porous networks are of significant interest due their application in topical research areas such as catalysis and sustainable energy. The main focus of my research is developing new materials for the selective capture and activation of industrially and environmentally significant gas molecules such as (CH4, CO2 and H2) and the development of new and efficient hybrid catalytic systems. Students working in my laboratory will gain experience in organic, inorganic and materials synthesis as well Scheme 1. Representation of the synthesis of a typical MOF from metalas a variety of analytical and oxide (e.g. zinc oxide) and organic building blocks. spectroscopic techniques such as, ! synchrotron X-ray absorption spectroscopy, X-ray diffraction, porosity analysis and solid state NMR. Two classes of materials will be synthesized and studied Metal-organic frameworks (MOFs) and Network polymers. MOFs are a new class of highly porous (known to exceed 5000 m2g-1), crystalline materials that have immense potential for use in heterogeneous catalysis and the storage and production of energetically important materials such as H2 and CO2. A feature of MOFs is their simple synthesis from metal-oxide and rigid organic building blocks that form the joints and links, respectively, of an open network (Scheme 1). This modular synthetic approach facilitates the design and construction of materials with unique properties. Three honours projects will be offered that are at the cutting edge of MOF chemistry. 1. MOFs as hybrid catalytic systems (joint with Dr. C. J. Sumby.) This project is aimed at developing truly hybrid catalysts that integrate the advantages of both homogeneous (well defined and finetuneable active sites) and heterogeneous (stability and ease of separation from reaction products) systems. Although MOFs have been widely proposed as catalyst platforms only a limited number of examples exist in the literature and the majority of these are metal-based Lewis-acid catalysed reactions that occur at the metal-oxide joint. This project will involve synthesizing organic links that are catalytic supports for known homogeneous catalysts and subsequently incorporating them into a MOF structure. Examples of a recent catalytic MOF system from our group is shown below. 17
2.
MOF biocomposites.
Proteins and enzymes are known to catalyse a diverse range reactions. The conditions that these reactions that these performed at are governed by the stability of the protein, generally conducted under mild conditions. Utilising a new technique to encompass these proteins in highly stable metal organic frameworks (MOFs) conferring enhanced stability under a wide of conditions including the refluxing in various organic solvents, while maintaining permanent framework porosity.1 The project aims to apply this technique to a range of catalytic reactions under conditions that would typically diminish or inhibit the activity of protein. In particular the project would focus on the investigation of tandem catalysis, allowing for multistep synthesis to be conducted utilising a one-pot method which would ordinarily break down either the protein or secondary catalyst. 3.
Surface MOFs (SURMOFs)
Epitaxial growth has been used regularly in materials science to take advantage of the surface properties as well as the ability to control growth based on surface patterns and dimensions. A wide range of potential applications associated with MOFs, such as sensing, catalysis and gas separation; require greater control over the structural properties of MOF crystals. The first cases of epitaxial MOF growth are the SURMOFs that use self-assembled monolayers as substrates for the MOF to grow on.2 There is a relatively long list of useful MOFs grown in this way, as well as on rough surfaces3 but in these cases the MOF crystals have no correlation to others on the same surface; limiting their use in many applications. Recently the use of highly aligned nano-substrates as a base for MOF growth has given rise to a series of simple MOFs that are aligned on the millimetre scale. This alignment allows for an intrinsic relationship between the crystals on these surfaces and can be used, for example, in design of light driven technology that will benefit from the variation in polarisation present within the MOF-substrate material.
Suggested Reading H. Deng, C. J. Doonan, H. Furukawa, R. B. Ferreira, J. Towne, C. B. Knobler, B. Wang, O. M. Yaghi, Science, 2010, 327, 846-850; Bloch, W.; Burgun, A.; Coghlan, C.; Lee, R.; Coote, M.; Doonan, C. J.; Sumby, C. J.; Nature Chem. 2014, 6, 905-912; Liang, K.; Ricco, R.; Doherty, C. M.; Styles, M. J.; Bell, S.; Kirby, N.; Mudie, S.; Haylock, D.; Hill, A. J.; Doonan, C. J.; Falcaro, P. Nat Commun 2015, 6. 18
Dr Jonathan H. George Synthetic Organic Chemistry The total synthesis of complex natural products continues to be at the forefront of organic synthesis, both in terms of driving forward the development of new reaction methodology and in supplying biologically active substances for applications in medicinal chemistry and chemical biology. In particular, we are interested in applying a “biomimetic” approach to synthesis. Nature can assemble intricate molecules with apparent ease from a relatively few simple starting materials. Careful consideration of the biosynthetic origin of a complex natural product within the context of a total synthesis project can inspire new synthetic methodology and strategies, which may be of broad utility within the wider organic chemistry community. Furthermore, a biosyntheticallyinspired synthesis of a natural product should be concise and efficient, so that significant quantities of the target compound (and carefully designed analogues) can be obtained. This should allow additional explorations into the chemical biology of these molecules, including identification of specific biological targets and mechanism of action. 1. Synthesis of PI3K inhibitors and anti-cancer agents based on meroterpenoid natural products isolated from marine sponges The isolation of biologically active marine natural products is a traditional method used to identify drug candidates and lead compounds thereof. Often these natural products are isolated in minute quantities from rare or inaccessible sources, resulting in a supply problem which can only be solved by chemical synthesis. For example, (+)-liphagal is a tetracyclic meroterpenoid natural product isolated from a marine sponge which selectively inhibits the phosphoinositide-3-kinase (PI3K) signaling pathway and shows promising anti-cancer activity.1 We recently completed a synthesis of (+)-liphagal using a biosynthetically-inspired cascade reaction to form the unusual 6-7 ring system fused to a benzofuran.2 Further work in this project will include development of a new, more efficient end-game for the synthesis, as well as the design and biological testing of analogues.
The frondosins are a family of five meroterpenoids, also isolated from a rare marine sponge, which inhibit the binding of interleukin-8 (IL-8) to its receptor in the low micromolar range and hence show promise for the development of new anti-inflammatory and anti-cancer agents. Remarkably, several members of this family have also been shown to exhibit anti-HIV properties. This project will involve the development of a general synthesis of the frondosins via a biosynthetically-inspired ring expansion reaction. The project will allow exploration of the biosynthetic relationship between these compounds, and inspire the development of novel reactions of orthoquinone methides, a type of reactive intermediate which is of increasing utility in organic synthesis. The biological properties of these molecules could be further explored in collaboration with chemical biologists.
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2. Oxidative radical cyclizations in the synthesis of complex polycyclic polyprenylated acylphloroglucinols Perhaps the main goal of research in modern synthetic organic chemistry is to develop more efficient, less wasteful and “greener” methods for the synthesis of complex target molecules. One way we can do this is by developing “cascade” reaction processes, in which several bond-forming events may occur in the same reaction vessel. For example, we recently synthesised the polycyclic polyprenyalted acylphloroglucinol (PPAP) natural products, ialibinones A and B, via a cascade reaction which features two successive radical cyclizations and two separate single-electron oxidations to install the 6-5-5 ring system.3
PPAP natural products are isolated from a wide range of plant species, and many have been shown to exhibit potent biological activities.4 They are therefore highly attractive targets for synthesis. Future work in this area will be directed towards the synthesis of more complex PPAPs such as garcinol, which shows antibiotic activity against methicillin-resistant S. aureus (MRSA) comparable to that of vancomycin (the traditional “last resort” drug for treatment of severe bacterial infections). Furthermore, the intricate polycyclic molecular architecture of garibracteatone and its proposed biosynthetic pre-cursor nemorosonol could be potentially be constructed, again using an oxidative radical cyclization pathway. 3. A biomimetic approach to swerilactones A and B via a [4+2] heterodimerization strategy Plants used in traditional Chinese medicine have proven to be a rich source of biologically active and structurally intriguing natural products. For example, swerilactones A and B were recently isolated as part of an investigation into the active ingredients of the traditional Chinese herb Swertia mileensis, which is used to treat viral hepatitis.5 These natural products contain an unusual pentacyclic 6-6-6-6-6 ring system. We propose a biosynthesis of swerilactones A and B via a heterodimerisation of constitutionally isomeric 2H-pyran and dienal components. In order to investigate this hypothesis, we intend to conduct a biomimetic synthesis of the natural products. H
H
O O O
O
OH
O
O O
O
OH
O O
swerilactone A
swerilactone B
1. Marion, F.; Williams, D. E.; Patrick, B. O.; Hollander, I.; Mallon, R.; Kim, S. C.; Roll, D. M.; Feldberg, L.; Van Soest, R.; Andersen, R. J. Org. Lett. 2006, 8, 321. 2. George, J. H.; Baldwin, J. E.; Adlington, R. M. Org. Lett. 2010, 12, 2394. 3. George, J. H.; Hesse, M. D.; Baldwin, J. E.; Adlington, R. M. 2010, 12, 3532. 4. Ciochina, R.; Grossman, R. B. Chem. Rev. 2006, 106, 3963. 5. Geng, C.A.; Jiang, Z. Y.; Ma, Y. B.; Luo, J.; Zhang, X. M.; Wang, H. L.; Shen, Y.; Zuo, A. X.; Zhou, J.; Chen, J. J.Org. Lett. 2009, 11, 4120.
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Assoc. Prof. Hugh H Harris Bio-metals and metalloids. My current research interests cover a number of areas which come under the broad classification of bioinorganic chemistry, some of which are outlined below. X-ray absorption spectroscopy is a pivotal tool in this area, as it can provide element-specific structural information in tissue samples that are very close to the in vivo ideal. This information is also frequently combined with X-ray fluorescence imaging experiments that map the distributions of elements in a sample. As such, much of my research is conducted at synchrotron facilities in Japan and the USA, as well as Australia's own synchrotron in Melbourne, and opportunities for students to experience how science is carried out at these facilities should be available. Cellular models of protective dietary selenium species. Recent studies indicate that the dietary intake of various selenium compounds provides considerable protection against the development of cancer in both humans and laboratory animals. However the efficacy of different species varies significantly, with inorganic selenium being less effective than organoselenium compounds, whose properties in turn are affected by whether or not they become involved in the selenoprotein assimilatory pathway. Selenium status has also been linked to a number of other health conditions that widely affect humans, including various muscle diseases, Alzheimer’s Disease, and the amount of damage caused during heart attacks, presumably due to its presence at the active site in a number of enzymes with antioxidant properties. Smallmolecule selenium-based drugs, such as Ebselen, which mimics the behaviour of the antioxidant selenoenzymes, also offer promise in the treatment of stroke events. However, many selenium compounds are quite toxic at higher doses. Dietary selenium supplementation has the potential to provide significant health benefits, but the narrow safety window in terms of dose and the sensitivity of biological response to chemical form suggests that seeking a better understanding of Se metabolism in mammals would be a prudent course. Projects in this area will focus on determining the fate of different selenium compounds in cultured cells by employing a range of synchrotron-based X-ray techniques, including microprobe imaging of single cultured cells. The data collected using these techniques will be supported, and cellular responses to treatment with selenium understood, using results from a range of other techniques including tissue culture and associated biochemical and toxicological assays, ICP-MS and Se NMR. Our current goals include understanding recent results that show a spatial association of copper with selenium in both cultured cells treated with selenite and in various tissues from rats that have been fed diets supplemented with selenite at subtoxic levels. This work could involve assessing the toxicity of selenium compounds towards cultured cells that have access to variable levels of copper in growth media, or determining what cellular organelles and biomolecules are targeted
X-ray fluorescence elemental distribution maps of a single human cancer cell treated with selenite.
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by copper and selenium using various fractionation and hyphenated “metallomics” techniques such as HPLCICPAES/MS and MALDI-MS. Projects can be tailored to suit your interests. [1] Weekley CM, Aitken JB, Vogt S, Finney LA, Paterson DJ, De Jonge MD, Howard
DL, Witting PK, Musgrave IF and Harris HH. Metabolism of selenite in human lung cancer cells: X-ray absorption and fluorescence studies. J. Amer. Chem. Soc. 133, 18272-18279. 2011.
Mobilisation of selenium and other heavy elements in response to redox stress in female reproductive function – in collaboration with Prof. Ray Rodgers (Obstetrics and Gynaecology). This year we demonstrated for the first time that the nutritional trace element selenium was critical to female fertility in cows and humans. This discovery was driven by X-ray fluorescence imaging of bovine ovaries which showed dramatic localisation of selenium to the granulosa cells in the ovary just prior to ovulation. Some of these cells stick to the egg after ovulation and this project will involve XRF imaging of the so-called “cumulus-oocyte” complexes combined with the use of small molecule fluorescent probes for redox status, antioxidant response elements such as glutathione peroxidase, as well as different pools of copper.
Zn
Fe
Se
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[2] Ceko MJ, Hummitzsch K, Hatzirodos N, Bonner WM, Aitken JB, Russell DL, Lane M, Rodgers RJ and Harris HH. X-ray fluorescence imaging and other analyses identify selenium and GPX1 as important in female reproductive function. Metallomics. 7, 71-82, 2015.
Determining modes of action of ruthenium-based anticancer drugs. Cisplatin, (cis-diamminedichloroplatinum(II)) is the most widely used drug in clinical cancer chemotherapy. Unlike most cancer drug candidates currently under clinical trial, cisplatin undergoes significant chemical transformation in the body before exerting its anticancer activity (i.e. it is a prodrug). Despite its success, however, cisplatin displays a range of serious side effects and many cancers develop resistance after initial treatment. Several classes of ruthenium complexes are now being trialled as cancer drugs with the hope of avoiding the shortcomings of cisplatin. While the biological chemistry of cisplatin is well understood (chloro ligands are lost once inside cancer cells, binds DNA leading to apoptosis) the same cannot be said for any of the ruthenium-based drugs. This project aims to extend our group’s work on determining the biotransformations of the ruthenium complexes, and their cellular targets, by tagging various ligands with either X-ray visible iodine or with optically fluorescent labels. The project would involve some coordination chemistry followed by synchrotron cell imaging and confocal microscopy. [3] Aitken JB, Antony S, Weekley CM, Lai B, Spiccia L and Harris HH. Distinct cellular fates for KP1019 and NAMI-A determined by Xray fluorescence imaging of single cells. Metallomics, 4, 1051-1056, 2012. [4] Antony S, Aitken JB, Vogt S, Lai B, Brown T, Spiccia L, Harris HH. X-ray fluorescence imaging of single human cancer cells reveals that the N-heterocyclic ligands of iodinated analogues of ruthenium anticancer drugs remain coordinated after cellular uptake. J. Biol. Inorg. Chem. 18, 845-853, 2013.
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Dr David Huang Theoretical and Computational Nanoscience My research uses theory and computation to study condensed phase phenomena on the molecular and nano scales. I am especially interested in devising new ways to control the properties of soft matter for applications in renewable energy, novel functional materials, and drug design. Students in my research group learn a variety of theoretical and computational techniques, including statistical mechanics, quantum mechanics, fluid dynamics, and computer simulation methods. The projects listed below illustrate a few potential directions for Honours research; projects can also be tailored to suit your interests. Kinetics and thermodynamics of DNA nanotechnology (with Prof Amanda Ellis, Flinders University) DNA nanotechnology uses the exquisite control of DNA base-pairing to direct the selfassembly or disassembly of functional materials and to guide nanoscale functional processes. One novel application of DNA nanotechnology is targeted disease diagnosis and drug delivery, using the recognition between a disease-related DNA or RNA sequence to trigger the release of a therapeutic agent. Most DNA nanotechnology is based on a process called toehold-mediated strand displacement (illustrated on the right), in which a single complementary DNA or RNA strand invades double-stranded DNA containing an overhang (toehold). Many aspects of the mechanism, kinetics, and thermodynamics of this process are still not well understood, such as the sequence dependence of strand displacement, e.g. due to a single-base mutation, and the effect of four-way branch migration, due to a partially double-stranded displacing sequence (which can offer greater control than three-way migration). This project aims to develop a theoretical model of the thermodynamics and kinetics of the strand displacement process that can account for effects such as sequence dependence and four-way branch migration and to use this model to optimize discrimination between target and non-target sequences for disease diagnosis and drug delivery. Self-assembly and destabilisation of unusual DNA structures (with Dr Tara Pukala) Many variations from the well-known Watson–Crick duplex DNA structure, such as triplexes formed from three DNA strands, play key roles in cellular processes. DNA triplexes are also associated with a number of debilitating neurological diseases, including muscular dystrophy, Friedreich’s ataxia, and Huntington’s disease. But approaches to investigate biologically important DNA triplexes under physiologically relevant conditions and knowledge of structural features that mediate triplex stabilisation for design of potential drugs are currently inadequate. The project will take a multi-scale computational approach to address challenges associated with resolving both the sequence specificity of DNA triplex formation and the long sequences associated with neurological disorders. The aim is to clarify the thermodynamics and mechanism of DNA triplex stability and disruption by drug molecules, in order to design better drugs for treating Friedreich’s ataxia and related diseases. The project can focus on either (1) atom-level prediction of triplex DNA and DNAligand interactions by molecular simulations or (2) development of a genome-level statistical mechanical model of triplex DNA. Interplay of structural and electronic properties in organic electronics Organic electronic devices, such as polymer solar cells, show promise as cheap and flexible alternatives to conventional silicon-based electronics. But organic devices are generally much less efficient than their inorganic counterparts. The microstructure of organic semiconductor films, which often consist of phaseseparated electron donoracceptor mixtures, has a substantial impact on device performance. But the microstructure is difficult to control and its impact on 23
electronic properties is still poorly understood. For example, the generation of free charges in many donoracceptor systems has been found to be more efficient than predicted by simple models of Coulomb binding at a structureless interface, but the origin of this enhanced efficiency, possibly driven by interfacial energetic disorder or energy gradients induced by structural inhomogeneity, is not currently known. Furthermore, the impact of electronic effects on microstructure and phase behavior, which could potentially be exploited to control the microstructure, has barely been explored. The project will investigate these issues using quantum mechanics, statistical mechanics, and/or classical molecular simulations. Molecular surface effects in membrane-based energy conversion processes The free energy of mixing of fresh and salt water mix where rivers meet the sea can be harvested by interposing a nanoporous membrane between the fresh and salt water streams. This can be achieved by using the osmotic pressure across the membrane to drive a turbine or by exploiting the net transfer of ionic charge across a charged membrane to drive an electric current in an external circuit. Conversely, energy can be expended to remove salt from seawater to produce fresh water in the process of desalination using a membrane. The efficiency and rate of these energy-conversion processes are sensitive to nano-scale ion and water fluxes across the membrane, which in turn depend on molecular- and nano-scale properties of the membrane surface and pores. This project aims to develop a general theoretical understanding of how parameters such as the pore size, pore asymmetry, surface charge density, and salt concentration affect these energy-conversion processes and to use this understanding to optimize energy conversion. Depending on the student's interests, the project can take different approaches to study nano-scale effects on membrane-based energy conversion: it can be mostly computational, using molecular simulations of flows in nanotubes, or mostly theoretical, using continuum fluid dynamic and statistical mechanical theories. Chemical and physical processes in porous frameworks (with A/Profs Christian Doonan and Chris Sumby) Metal-organic frameworks (MOFs) are extended materials consisting of metal ions or clusters coordinated to organic ligands. They can be highly porous, possessing huge internal surface areas with properties that can be finely tuned by modifying the metal node or organic ligands for applications in gas separations and chemical catalysis. The research group of Christian Doonan and Chris Sumby has recently synthesized a novel MOF containing an ordered 3D array of binding sites to which metal complexes can be post-synthetically attached. Thus, using single-crystal x-ray diffraction, the MOF can act as a platform for studying reactions and reaction intermediates in metal-based catalysis and gas separations at a molecular level. This provides a new and unique opportunity to test theoretical and computational methods for studying such processes and to answer fundamental theoretical questions about mechanistic differences between homogeneous and heterogeneous catalysis: e.g. how the constraints of the 3D structure of the MOF affect reactivity compared with the analogous discrete metal complex in solution. This project will use quantum chemical calculations of framework materials and discrete molecular complexes to investigate these issues. Suggested Reading Protected DNA strand displacement for enhanced single nucleotide discrimination in double-stranded DNA. Khodakov, D.A. et al. Sci. Rep. 2015, 5, 8721. On the biophysics and kinetics of toehold-mediated DNA strand displacement. Srinivas, N. et al. Nucl. Acids Res. 2013, 41, 1064110658. Structure of triplex DNA in the gas phase. Arcella, A. et al. J. Am. Chem. Soc. 2012, 134, 65966606. Molecular-level details of morphology-dependent exciton migration in poly(3-hexylthiophene) nanostructures. Tapping, P.C. et al. J. Phys. Chem. C 2015, 119, 70477059. Coarse-grained simulations of the solution-phase self-assembly of poly(3-hexylthiophene) nanostructures. Schwarz, K.N. et al. Nanoscale 2013, 5, 20172027. Massive amplification of surface-induced transport at superhydrophobic surfaces. Huang, D.M. et al., Phys. Rev. Lett. 2008, 101, 064503. Capturing snapshots of post-synthetic metalation chemistry in metal-organic frameworks. Bloch, W.M. et al. Nat. Chem. 2014, 6, 906912. Molecular design of amorphous porous organic cages for enhanced gas storage. Evans, J.D. et al. J. Phys. Chem. C 2015, 119, 77467754.
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Assoc. Prof. Tak W. Kee Materials Chemistry, Physical Chemistry Characterisation of organic materials – conjugated polymers and graphene This is an exciting project in nanoscience that will lead to a better understanding of the applications of conjugated polymers and graphene for solar cells and optical sensors. Conjugated polymers have many desirable characteristics of functional materials including ease of processing and tunability of absorption wavelength. In particular, these polymers have absorption coefficients with values rivalling those of Fluorescence of conjugated polymers. naturally occurring pigments including chlorophyll, giving rise to their ability to serve as light harvesting systems. Graphene is a two-dimensional sheet of carbon that exhibits many interesting characteristics including electrical conductivity and optical luminescence. These properties have led to significant promise of this material to be used in sensors. Project aims. The central aims of this inter-disciplinary project are as follows. First, to use state-of-the-art femtosecond laser technology to investigate the (i) charge transfer phenomena and (ii) the nature of triplet excited states of conjugated polymer and other types of organic solar cells. In addition, we aim to investigate the spectroscopic properties of graphene in solution and in a glass matrix. Charge transfer of conjugated polymer. The ability of conjugated polymers to donate electrons to an electron acceptor is the basis of the photovoltaic effect of these materials. We collaborate with a research group at Monash University to use a state-of-the-art laser system in our laboratory (picture below) with a time resolution of 100 femtoseconds (femto = 10-15) to study efficient thin-film solar cells. We aim to unravel the important processes that enable these solar cells to have a high efficiency (~10%).
State-of-the-art femtosecond laser system for investigations on energy transfer phenomena of conjugated polymer NPs.
Triplet excited states as energy source. The emphasis in organic solar cell research thus far has been largely placed on harnessing energy from the singlet excited state. Recent work has shown that using conversion of a singlet excited state to a pair of triplet excited states may increase the theoretical limit for solar cell efficiency from ~32% to 45%. In this project, we will study the chemical and physical properties of the triplet states of a molecular crystal to uncover new methods of harnessing energy from these long-lived species. Surface functionalisation of tellurite glass with graphene for photonics applications. Tellurite glass has a wide range of applications for fabricating non-linear optical devices and fibre laser because of its high refractive index (i.e. larger than 2.00) and high solubility of rare earth ions. This glass is also an attractive host material for embedding graphene, which is of growing interest for non-linear optical properties including electro-optic switching and saturable absorption. This project builds on the successful demonstration of single photon emission from nanodiamond embedded in tellurite glass. The challenge for embedding graphene into tellurite glass is to ensure the survival of graphene combined with considerably well dispersion within the glass after the fabrication procedure. In this project, we will compare embedding of graphene into tellurite glass surface by glass annealing above 500°C with coating of graphene onto the tellurite glass surface using silanisation, which avoids high temperature treatment. The spectroscopic properties (Raman, absorption, fluorescence) of the two types of graphene functionalized glass samples will be analysed in terms of retaining and enhancing graphene properties. (see: M. R. Henderson et al., Adv Mater. 2011, 23, 2806). This project is in collaboration with Assoc. Prof. Heike Ebendorff-Heidepriem and Dr Herbert Foo. 25
Physical Chemistry, Materials Chemistry Multidimensional Optical Spectroscopy of Light Harvesting Systems This project will enable students to contribute to the research effort of setting up a brand new optical instrument, characterising the instrument and finally using it for data collection. The aim of this project is to understand the light harvesting process in a naturally occurring light-induced proton pump, i.e., bacteriorhodopsin. The knowledge will provide important design rules for future solar cells. Construction and characterisation of a 2D electronic spectrometer. Two-dimensional electronic spectroscopy (2DES) is the UV-visible analogue of 2D NMR. Similar to 2D NMR, which detects the coupling between nuclear spins, 2DES is sensitive to the coupling of chromophores, which are light absorbing units such as chlorophyll and carotenoids. Thus far, 2DES has been applied to the studies of energy migration in light harvesting complexes and semiconductor quantum dots. Several high impact studies have been reported in recent years. The first part of this project involves construction of a novel 2D electronic spectrometer, as shown in the figure below (left). A highly novel approach will be used to increase the rate of data acquisition and sensitivity of 2DES. Students will learn the skills involved in constructing an instrument including optical manipulation and computer programming. Examples of the 2D data are shown in the figure below (right).
Energy migration in bacteriorhodopsin and mechanism of photoconversion. Bacteriorhodopsin is the light-induced proton pump of microbes. It has been shown that the efficiency of its photochemical cycle, i.e., conversion of photon energy to mechanical work, is 67%. In this project, 2DES will be used to study monomers and trimers of bacteriorhodopsin. The effect of coupling of neighbouring bacteriorhodopsin units on its ability to enhance light absorption and energy conversion will be investigated. The knowledge we gain will lead to further understanding of the mechanism bacteriorhodopsin uses to achieve a high photoconversion efficiency, which in turn may lead to approaches for efficient photoconversion in a new form of solar cells. Bacteriorhodopsin.
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Prof. Gregory F. Metha Metal Nanoparticle & Cluster Laboratory Transition Metal Clusters for Nano-catalysis & Photo-catalysis The ability to expedite chemical reactions by addition of small particles of catalytic material reduces capital costs, improves chemical and energy efficiency, reduces environmental impact and allows more rapid product development. Currently, around 80% of all current industrial chemical processes rely on catalytic action. Generation of chemical feedstocks from generally available gases using metal-based catalysts is a vitally important component of the world's economy. Two examples are the Haber-Bosch (using an iron, and more recently ruthenium, catalyst for the production of ammonia from N2 and H2) and steam-reforming (H2 and CO production from methane and water using a nickel catalyst) processes. Metal-based catalysts are also critical in the development of emerging solar-driven photocatalytic systems, with platinum being one of the best catalysts for water-splitting to produce hydrogen. Given that many catalytic materials are expensive metals, it is well known and understood that its efficiency can be improved by reducing particle size, simply by increasing the active surface area for a given quantity of material. As particle size reduces to the nano-scale, the chemical properties of the metal begin to change. For example, gold, normally a very inert metal, becomes reactive at sizes of 10 nm and less. Furthermore, research in the last 5 years has revealed that the reactivity change becomes more marked as the size reduces below 1 nm. At these sizes, the particles contain less than ~50 atoms and are known as metal clusters. Due to their small size, clusters have a low density of states which produces size-dependent properties that do not scale with size. Furthermore, each atom within the cluster is not “locked” into place allowing clusters to be able to move readily between various structural minima. Due to the size dependent variation of each cluster's electronic structure, the interaction of a molecule with a specific sized Interaction of a molecule with a bulk metal surface (left) cluster is unique, yielding species with novel and a metal cluster, M3 (right). chemical and physical properties. Recently, researchers have shown that the variable reactivity of nano-sized metal particles can be exploited to enhance catalytic activity of metallic systems. Metal clusters deposited onto surfaces, containing as few as several atoms, have been shown to induce catalysed activity at significantly lower temperatures compared with bulk metallic surfaces. The study and understanding of the underlying principles of these effects will provide a revolutionary methodology for developing next generation ultra-efficient and cheaper catalysts. Research within the Metal Nanoparticle & Cluster Laboratory involves the experimental and theoretical study of the chemical and physical properties of metal clusters, their interactions with surfaces, and their chemical activity towards important molecules such as CO2 and H2O. The research is broadly separated into 3 projects. Catalytic Activity of Metal Clusters on Surfaces For any possible application of metal clusters as catalysts it is necessary to deposit them onto surfaces. Therefore, it is the geometric and electronic (valence) structure of clusters at the surface that determines their interactions, and consequent reactivity, with molecules. In collaboration with Flinders and Canterbury Universities, we are developing techniques to explore the geometric and electronic structure of size-specific gold clusters (Aun, n = 8, 9, 11 and 100) deposited onto titanium-oxide surfaces. The approach involves the direct comparison between the chemistries displayed by isolated and condensed clusters to disentangle the surface effects. Surface characterization will occur through a combination of X-ray Photoelectron Spectroscopy (XPS), Scanning Tunnelling Microscopy Au4 cluster bound to titania reacting with H2O molecules.
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(STM) and Metastable Induced Electron Spectroscopy (MIES). Combined, these techniques will provide information about the interaction between each size-specific cluster and the titania surface. In addition, we are exploring the photo-catalytic behaviour of these clusters following the excitation of electrons across the band-gap of titania with near-UV light. The project also involves visits to the Australian Synchrotron to use X-ray and far-IR spectroscopies to characterise the physical properties of the gold clusters on titania. Gas-Phase Models of Cluster-Surface Interactions The electronic and geometric structures are key pieces of information that are necessary to gain understanding of any cluster-surface interaction. For small cluster sizes where quantum effects dominate, the electronic structure can change significantly when a single metal atom is added or subtracted. Since the electronic structure is strongly linked to the geometric structure, changes in geometry can also be expected when the cluster size is altered. However, this information is extremely difficult to extract by only investigating clusters deposited on surfaces. By combining accurate laser-based photo-ionisation efficiency (PIE) spectroscopy with state-of-the-art computational methodology we are able to determine the local geometric and electronic structures of metal clusters bound to model metal-oxide “surface” clusters. Our current and emerging work is focused on Aun, Rhn and Ptn clusters bound to cerium-oxide and titanium-oxide clusters, which are all important surfaces for catalytic oxidation reactions. The change in ionisation energy of these "bi-clusters" yields quantitative information about the electronic charge transfer between the cluster and metal-oxide support. The theoretical calculations are directly compared against the experimental values to provide valuable benchmarking data to enable more complicated calculations on bulk (real life) metal-oxide surfaces. Transition Metal-Carbide Clusters The bulk surface properties of Group 4, 5 and 6 metal-carbides (NbC, TiC, WC etc.) are known to have catalytic properties similar to those of the platinum-group metals, which are the workhorses of modern-day industrial catalysis. However, the physical and chemical properties of transition metal-carbides (TMC) have not been explored when they are reduced to the sub-nano size regime. This project is aimed at investigating the physical and chemical properties of well-defined TMC clusters, consisting of only several metal atoms, which are expected to be highly dependent upon size and composition. Calculated structures of various Nb4Cn (n = 3-6) clusters.
To date, our lab has investigated the Group 5 metal-carbide clusters, NbnCm and TanCm (n = 3-5; m = 1-6) and found that the measured ionisation energies (via PIE spectroscopy) correlate extremely well with theoretically predicted values. For Nb4C4 and Ta4C4, the optimised geometry is a structure that consists of a distorted tetrahedron of metal atoms with a C atom bound to each of the 4 "faces" of a tetrahedron, resulting in a cube of dimension 222. The lowest energy structure of Nb4C3 can be considered as the cubic structure of Nb4C4 minus a C atom (i.e. C atoms on three faces of the Nb 4 tetrahedron). For the clusters Nb4C5 and Nb4C6, the experimental values correlate with structures containing one and two molecular C2 groups, respectively. The next stage of this work is to react these clusters with small key molecules such as CO and CO 2 and to elucidate the molecular geometries of the resultant complexes they form. The outcomes will be a significant advancement in our knowledge of the structure and reactivity of metal-carbide clusters and therefore, an understanding of molecular activation by TMC clusters. Furthermore, it will provide fundamental base knowledge of isolated metalcarbide cluster chemistry that will assist future cluster deposition (condensed phase) experiments that will necessarily be complicated by the effects of surface charge, morphology and defect sites.
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Dr. Tara Pukala Biomolecular Structure and Function Biological macromolecules such as proteins and DNA form the machinery that underlies all biological functions. The ability to ‘see’ the atomic detail of these assemblies, including their structures and interactions with other molecules, provides an opportunity to understand their biological activity. It also helps unravel processes which have gone astray to cause disease, and therefore find new treatments for a range of human illnesses. In recent years mass spectrometry (MS) has emerged as a powerful tool for structural biology, in many cases capable of exceeding other techniques in application and information content. This is due to the unique ability of MS to precisely identify molecules and binding interactions with physiological relevance, even for complex mixtures, or very large, dynamic species which elude other techniques. Research in my group is directed towards development of new approaches, primarily using MS, to obtain insight into the structure, function and interactions of macromolecules, with a focus on multi-molecular systems involved in disease. The honours projects outlined below are indicative of the type of research performed in the group, which can be adapted according to the interests and input of individual students (and may be carried out in collaboration with other supervisors where appropriate). These projects can provide students with skills and broad experience in biological MS and protein handling and purification, and complementary analytical methodologies such as ion mobility, NMR, UV-visible, and fluorescence spectroscopy, computational modelling and chemical synthesis. 1. Protein Misfolding and Aggregation: A broad range of debilitating human diseases is connected with the failure of a specific protein to adopt or remain in its functional conformation and instead aggregate to insoluble deposits. These disorders (such as Alzheimer’s and Parkinson’s Diseases) impose enormous social and economic burden on society. Mechanistic studies: A major goal in attempts to understand protein misfolding diseases is to define the structures of protein species intermediate between correctly folded and aggregated, and extract a kinetic description of the aggregation process. This remains difficult, due to the inability of current approaches to analyse unstable protein complexes with structurally diverse populations, and consequently MS is ideally suited to this application [1]. This project will use innovative MS methods to probe the aggregation pathway of disease related proteins. Importantly, it will also investigate the structural basis of inhibitors of the aggregation process in order to identify new approaches for therapeutic intervention. The research also includes a focus on critical protein-chaperone interactions, to provide unprecedented detail on the role of these assemblies in protein folding, and in particular formation of toxic species implicated in Alzheimer's Disease. Role of lipids in Aggregation Diseases: Increasing evidence suggest lipid membranes play a critical role in protein misfolding diseases, however, the underlying molecular basis for this remains elusive. For example, it is known that the lipid GM1 ganglioside, present in membrane domains known as lipid rafts, is essential for binding and trafficking α-synuclein, and accumulation of the toxic lipid glucosylsphingosine presents the highest genetic risk factor for Parkinsonian syndrome. This research takes a relatively new approach to study of misfolding diseases by investigating the role of lipid metabolism on development of protein aggregation and neurodegeneration. The project will utilise MS to provide detail of the structure, oligomerisation and molecular interactions of amyloid proteins with glucosylsphingosine and lipid vesicles to correlate lipid composition and binding interactions with neurodegeneration to identify new avenues to halt the progression of disease. 2. Analysis of Unusual DNA Structures (with Dr David Huang): Many variations from the well-known duplex DNA structure play key roles in a range of cellular processes. These structures, such as triplex DNA shown at right, are often formed by repetitive DNA stretches (such as tri-nucleotide repeats) that are genetically unstable, and are associated with numerous hereditary neurological diseases that include muscular dystrophy, Friedreich’s 29
ataxia and Huntington’s disease. MS in combination with computational modelling offers a unique approach to studying the formation, structural properties and binding interactions of DNA triplex structures. Aims of this research are to develop MS methodology to probe formation and structural properties of DNA triplexes associated with Friedrich’s ataxia and ligand binding interactions. Based on this research we expect to explore new leads for disruption of DNA triplex structures for treatment of Friedrich’s ataxia and related diseases. 3. Fundamental Developments in Mass Spectrometry for Structural Biology: Identification and detailed structural characterisation of protein complexes is vital for predicting protein functions and understanding the principles of cellular regulation. Many protein assemblies of interest are intractable by conventional structural biology methods (such as NMR spectroscopy and X-ray crystallography) and hence complementary low resolution approaches such as MS are increasingly sought to provide structural information. Design and synthesis of MS amenable protein cross-linking reagents: A common method for the detection of protein interactions is chemical cross-linking, in which a small reactive molecule forms intermolecular covalent bonds between amino acids at the binding interface. Restrictions of current cross-linking methods make it difficult to rapidly identify the exact site of linkage, thereby limiting the structural information available. This project involves design, synthesis and application of new MS cleavable cross-linking reagents which are readily identifiable in MS/MS experiments and can provide precise identification of binding interactions and atomic level structure information [2]. These novel reagents will be used for the first time to overcome limitations in the study of protein interactions, and probe structural properties of important protein assemblies not amenable to other methods. Ion mobility-MS of large protein assemblies: Much of our MS development centres on application of ion mobility-mass spectrometry (IM-MS), a relatively new hybrid analytical method which provides not only mass but shape information for an ion. IM-MS can potentially define protein identity, stoichiometry, size, structural arrangement and subunit interactions in a single experiment to derive low resolution structural models of interacting proteins [3]. This research aims to optimise successful detection and analysis of noncovalent protein complexes of a wide range of structures and binding interactions by IM-MS. In addition, aspects of this project can involve development of theoretical methods to generate model protein structures for comparison with experimentally derived measurements, to not only assist IMMS analysis, but have implications for protein structure prediction in general. The ultimate aim of this work is to utilise IM-MS methods in combination with other biophysical techniques (such as NMR, SAXS, microscopy) to support the emerging field of integrative structural biology where many pieces of data are combined to generate a complete picture of a protein assembly [4]. To highlight the ability of IM-MS to derive new structural data for challenging protein complexes, we are currently pursuing a project involving isolation of transcription factor complexes directly from cells. This project will produce protein interaction maps (using cross-linking), and incorporate IM-MS measurements to describe a structural model (using computational modelling) of interacting components of the transcription machinery in advance of X-ray structures, and form the basis for better understanding of their important role in transcription. Suggested Reading: [1] Williams, D; Pukala, T. Mass Spectrom. Rev. (2013) 32(3):169-187. [2] Calabrese,A; Good, N; Wang, T; He, J; Bowie, J; Pukala, T. J. Am. Soc. Mass Spectrom. (2012) 23(8):1364-1375. Pukala, T. Aust. J. Chem. (2011) 64(6):681-91. Pukala, T; Ruotolo, B; Zhou, M; Politis, A; Stefanescu, R; Leary, J; Robinson C. Structure (2009) 17(9):1235-43.
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Professor Simon Pyke Structure-Based Drug Design The pharmaceutical industry is being driven to dramatically improve the rate and cost effectiveness of new drug discovery – using the 3-dimensional structure of a protein as a template for drug design is likely to be an important component of such improved discovery methods. This project aims to capitalise on our initial success targeting shallow protein-protein interaction surfaces on the SH3 domain of Tec (an intracellular signaling protein).1 Tec is a widely expressed intracellular tyrosine kinase that is certainly involved in signaling pathways although its biological role has yet to be clearly defined. The structure of the SH3 domain of this protein has been determined by NMR methods and a range of small molecule ligands have been identified by titrating aliquots of the ligands into a solution of uniformly 15N-labeled protein and observation of the [1H,15N]-HSQC NMR spectrum at 600 MHz (Figure 1).
Figure 1. Binding of a small molecule ligand to the Tec SH3 domain using NMR Spectroscopy. (A) A region of overlaid NMR [1H,15N]HSQC spectra of 15N labelled Tec SH3 protein in the presence of increasing concentrations of a ligand. (B) Chemical shift mapping of backbone or side-chain (H-N) resonances where the δ 1H had changed by at least 0.1 ppm at or near saturation binding of the ligand. (C) Binding isotherm represented by normalized chemical shift changes for residues involved in binding of the ligand.
All of the ligands identified to date bind at the same site with moderate (Kd 4100 μM) to good (Kd 5 μM) affinity and with good specificity (there are in excess of 300 SH3 domains known in the human proteome). The larger aims of this project include (i) further optimisation of the identified ligands to improve their binding affinity and specificity; (ii) determination by NMR methods of the ligand/protein complex structure; (iii) development of a fluorescently labeled ligand that will be used as a tool in SH3 domain homology modeling studies. These projects will involve synthesis of a range of small molecules and investigation of their binding to the Tec SH3 domain by use of the NMR titration technique together with other NMR techniques designed to probe the structure of ligandprotein complexes.
Natural Products Chemistry Chemotaxonomy of Cassytha species The genus Cassytha is a green, leafless, vine-like hemiparasite in the Lauraceae family. Although the genus Cassytha (Lauraceae) is a widely distributed parasitic plant, it is found predominantly in Australasia, with 19 endemic species Australia-wide, the majority located in south-west Western Australia. The genus is relatively unexplored beyond basic species taxonomy and parasite ecology, with only four Australian species being studied phytochemically. Thus, a detailed study is necessary to accurately document the phylogenies of the genus. The key focus of this project will be to examine the variation in alkaloid chemistry between species and how the compounds present might relate to each other, aiding in clarifying taxonomy in the genus. This project will be carried out in conjunction with Dr John Conran (School of Biological Sciences). Investigation of the metabolism of fatty acids by P450 enzymes (with Dr Stephen Bell) 31
Branched-chain fatty acids are the major lipid constituent of the membranes of many bacteria and are hypothesised to increase the fluidity of the membrane. Modified fatty acids are building blocks for other complex molecules and P450 enzymes are known to oxidise fatty acids. In this project branched fatty acids, of varying length, with methyl branching groups at different locations will be generated in enantiomerically pure forms using synthetic organic chemistry. These acids, and their non-branched analogues, will be tested as potential substrates for a range of bacterial P450 enzymes.2 The oxidation products, which may be chiral, will be analysed and characterised.
Science Education (with Dr Natalie Williamson) (1) Enhancing the experiences of students in undergraduate laboratories Most researchers agree that the laboratory experience ranks as a significant factor that influences students’ attitudes to their science courses. Consequently, good laboratory programs should play a major role in influencing student learning and performance. The laboratory program can be pivotal in defining a student's experience in the sciences, and if done poorly, can be a major contributing factor in causing disengagement from the subject area. The challenge remains to provide students with laboratory activities that are relevant, engaging and offer effective learning opportunities. The Advancing Science by Enhancing Learning in the Laboratory (ASELL) project (www.asell.org) has developed over the last 10 years with the aim of improving the quality of learning in undergraduate laboratories and providing a means of evaluating the laboratory experience of students.3 Recent results have highlighted the importance of using appropriate technological interfaces in laboratory experiments to ensure that learning about the science in the experiment is not impeded by the interface deployed.4 This project will involve collecting and interpreting data on undergraduate laboratory activities using the ASELL survey instrument (ASLE). The findings of this work will be used to influence further development of the laboratory activities examined. (2) Investigating ‘motivators’ and ‘barriers’ that may contribute to student performance Why do some students struggle as undergraduates whereas others flourish? What attitudes (and other ‘baggage’) do students bring with them as they commence university studies and do these attitudes influence their academic performance? How do commencing students approach their learning and does this approach change according to context and progress? How does the academic background of a student influence their success and progress? Do students respond to assessment tasks in different ways? In order to investigate these and other related questions a range of approaches will be taken: to address the issue of ‘attitudes’, survey data using the validated ‘ASCIv2’5 instrument will be collected; to address the issue of ‘approaches to learning’, survey data using the validated ‘RSPQ-2-F’6 instrument will be collected; to address the issue of academic background, student data identified at entrance to university will be examined. In each of these cases, the survey data and academic background data will be correlated with student performance. As part of this analysis, gender will also be considered in relation to assessment performance as a number of studies report a small systematic gender bias towards males in some forms of assessment at a high school level, even though females tend to outperform males in overall subject achievement.7 1.
2.
3. 4. 5. 6. 7.
S. R. Inglis, C. Stojkoski, K. M. Branson, J. F. Cawthray, D. Fritz, E. Wiadrowski, S. M. Pyke, and G. W. Booker, J. Med. Chem., 2004, 47, 54055417; S. R. Inglis, R. K. Jones, D. Fritz, C. Stojkoski, G. W. Booker and S. M. Pyke, Org. Biomol. Chem., 2005, 3, 2543-2557; S. R. Inglis, R. K. Jones, G. W. Booker and S. M. Pyke, Bioorg. Med. Chem. Lett., 2006, 16, 387-390; J. A. Smith, R. K. Jones, G. W. Booker and S. M. Pyke, J. Org. Chem., 2008, 73, 8880-8892. C. J. C. Whitehouse, S. G. Bell, et al., Chem. Commun., 2008, 28(8), 966-968. S. M. Pyke, A. Yeung, S. H. Kable, M. D. Sharma, S. C. Barrie, M. A. Buntine, K. Burke da Silva and K. F. Lim, Internat. J. Innov. Sci. Maths. Educ., 2011, 19(2), 51-72; S. C. Barrie, R. B. Bucat, M. A. Buntine, K. Burke da Silva, G. T. Crisp, A. V. George, I. M. Jamie, S. H. Kable, K. F. Lim, S. M. Pyke, J. R. Read, M. D. Sharma and A. Yeung, Internat. J. Sci. Educ., 2015, 37(11), 1795-1814. S. Priest, N. M. Williamson, and S. M. Pyke, J. Chem. Educ., 2014, 91, 1787-1795. X. Xu, & J. E. Lewis, J. Chem. Educ., 2011, 88, 561-568; X. Xu, D. Southam & J. E. Lewis, Aust. J. Ed. Chem., 2012, 72, 32-36. J. B. Biggs, D. Kember & D. Y. P. Leung, D.Y.P., Br. J. Educ. Psychol., 2001, 71, 133-149 See for example: The ETS Gender Study: How Females and Males Perform in Educational Settings, N. Cole, 1997 (ETS Technical Report Princeton, NJ); Gender and fair assessment, W. Willingham, N. and Cole, 1997 (Erlbaum Associates, Mahwah, NJ); Sex differences in objective test performance, R. Murphy, Brit. J. Educ. Psychol., 1982, 52, 213-219; Sex-related performance differences on Constructed Response and Multiple-choice Sections of Advanced Placement Examinations, A. P. Schmitt, J. Mazzeo, and C. Bleistein, 1993 (Educational Testing Service, Princeton, NJ).
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Assoc. Prof. Chris Sumby Supramolecular Chemistry and Nanomaterials Our research activities revolve around the design, synthesis, and characterisation of discrete supramolecular systems, porous materials (see, for example Figure 1), and functionalised surfaces. The research ranges from the synthesis of unusual organic molecules for studying fundamental intermolecular forces in supramolecular chemistry, through to developing the chemistry of porous crystalline materials that can selectively separate CO2 from post-combustion flue streams in a coalfired power plant. The projects offered in my group will provide you with skills and experience in synthetic organic and inorganic chemistry, spectroscopic characterisation (typically NMR, IR, and UV-visible spectroscopy), and where appropriate, X-ray crystallography, powder X-ray diffraction and other techniques (TGA/DSC and gas adsorption). The research projects outlined below are an illustrative selection of those on offer.
Illustrative Research Projects
Figure 1. The structure of a metal-organic framework (MOF) synthesised in the group.
1. Metal-Organic Framework (MOF) Chemistry The projects offered in this space are concerned with the synthesis and characterisation of MOF materials (Figure 2). MOFs are porous crystalline materials that can be synthesised in a building block approach from organic links and metal ion or metal-oxide nodes. The materials are stable, have large surface areas and, due to the nature of the building block approach, can be readily reticulated and elaborated by the choice of metal salt and/or organic link. These materials have applications in gas storage; gas separations, e.g. Figure 2. The linker and node approach to MOFs. N2/CO2, for separating CO2 from flue gas; catalysis, e.g. homogeneous catalysts chemically integrated into the organic links; and sensing (see: S. Kitagawa, R. Kitaura, S.-i. Noro, Angew. Chem., Int. Ed. 2004, 43, 2334; J.D. Evans, C. J. Sumby, C. J. Doonan, Chem. Soc. Rev., 2014, 43, 5933). Some examples of projects are given below: (a) Understanding metal-based reactions crystallography in MOFs. MOF materials can act like a matrix to reveal unusual products or stabilise unstable intermediates. Using a MOF that is poised to allow post-synthetic metalations we have been able to examine the products of inorganic reactions within MOF crystals solely by single crystal X-ray diffraction. For example, we have examined the reaction products of three transformations involving catalytically-active rhodium(I) species (Figure 3; W. M. Bloch et al., Nat. Chem., 2014, 6, 906). (b) Synthesis of azolium-containing MOFs. Azoliums compounds are important precursors to organometallic N-heterocyclic carbene compounds. The aim of this project is to generate framework materials (e.g. Figure 1) that contain imidazolium derivatives as pendant donors or integrated into 33 Figure 3. Crystallography in MOFs - some recent results.
the organic link. We will functionalise these materials with catalytically active species or to use the charge to enhance the adsorption properties of the resulting materials (see: R. S. Crees et al., Inorg. Chem. 2010, 49, 1712; A. Burgun et al., Chem. Commun., 2014, 50, 11760). (c) Flexible MOFs. New links (ligands) that confer dynamic behaviour to a solid-state material can be advantageous for selective gas adsorption. Can we prepare new examples of flexible MOFs that build upon our previous work (see: W. M. Bloch, C. J. Sumby, Chem., Commun. 2012, 48, 2534; W. M. Bloch et al., J. Am. Chem. Soc., 2013, 135, 10441)? (d) Particle size effects in MOFs. The dynamic behaviour and chemical properties of MOF materials can be strongly influenced by the particle sizes of the material. To use MOF materials as additives in mixed-matrix membranes, MOFs of smaller particle sizes are required. How do different synthetic methods and processing steps affect the particle sizes (right) and properties of MOFs? (e) Controlled release from MOFs (in collaboration with Dr Chris McDevitt, SBS). MOFs are important hosts for molecular species. Can porous MOFs be prepared with antibiotic activity that stems from the material itself and a molecular antibiotic that is loaded into the pores of these materials (see: W. M. Bloch, C. J. Sumby, Chem., Commun., 2012, 48, 2534)? 2. Supramolecular Chemistry: Probing protein structure - can metallo-helicates be used as DNA mimics? (in collaboration with Emeritus Prof. Richard Keene, SPS) If small (~12-mer) DNA oligonucleotides are attached to the surface of Sepharose beads, they constitute a very efficient stationary phase for the affinity chromatographic separation of the stereoisomers of metal complexes. Of particular interest is their discrimination between the enantiomers of metallo-helicates (C.R.K. Glasson, Chem., Eur. J. 2008, 14, 10535). The project aims to (a) develop synthetic methods of helical complexes of ruthenium(II), (b) investigate their separation into enantiomers using the DNA affinity chromatography technique, and (c) if possible, crystallise one of the metal complex-oligonucleotide species and determine its X-ray crystal structure to assist elucidation of the mechanistic features of the discrimination. Ultimately - once the methods of routine separation of the enantiomeric forms of the metallo-helicates are established - it is intended to use these resolved double- and triple helicate species as models for DNA in the probing of the structure of proteins. 3. Monitoring wine fermentation progress through metabolite analysis using NMR spectroscopy (in collaboration with Dr Tommaso Liccioli, Dr David Jeffery, SAFW) During winemaking, important compositional changes occur during alcoholic and malolactic fermentation, when microorganisms (yeast and bacteria) consume substrates and generate a variety of metabolites. One approach to monitoring fermentation is to measure the concentration of key metabolites over time but traditional monitoring methods are usually imperfect. The proposed research project will focus on proving the validity of NMR technology to monitor wine fermentation progression, targeting key metabolites in fermenting grape must and juice. The ultimate goal is to investigate the feasibility of integrating compact NMR systems with an existing, semi-automatic fermentation system, allowing further automation and online monitoring of fermentation progress. 4. Surface Functionalisation of Optical Materials - MOFs @ MOF (in collaboration with Assoc. Prof. Heike Ebendorff-Heidepriem and Dr Herbert Foo, IPAS) In this project we will try to coat the interior surface of a microstructured optical fibre (MOF) with a metal-organic framework (also a MOF!). The aim of this work is to engineer some selectivity for the surface of the fibre that may, for example, facilitate the development of improved gas sensing fibres (see: H. T. C. Foo et al., J. Mater. Chem. C. 2013, 1, 6782). 34
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Nomination of Supervisor Preference -Honours Chemistry 2016 Please return to A/Prof. Hugh Harris – Badger Laboratories Room 231.
Student Name: You must list FOUR supervisors in order of preference AND a general preferred area of research, ie medicinal and biological chemistry, functional materials, energy and environment, or molecular photoscience & ion chemistry. The general area of research is to help guide the Honours committee in selecting you a project if you cannot receive one of your preferences. If you are interested in a joint project (ie. two Chemistry academics as supervisor), please indicate that in the Research area of preference section. My choice of supervisor(s) is as follows: Nominate FOUR supervisors in order of preference AND a research area of preference
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Research area of preference/Joint projects
If you have no preference, please strike out the numbers beside the names. 36
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