Chemical Sciences

Bioorganometallic Anticancer Chemotherapeutics: Preparation of Metal Complexes with Bioactive Ligands

Supervisor

Prof. Christian Hartinger

Discipline

Chemical Sciences

Project code: SCI030

The coordination of bioactive ligand systems to metal centres results in multimodal anticancer agents, i.e., anticancer drugs that have more than one of mode action. This design strategy is a promising route to overcome major limitations of current cancer chemotherapeutics. We will develop in this project new complexes between organometallic moieties and bioactive ligand systems and study their anticancer activity.

Design of Multimodal Organometallic Anticancer Agents

Supervisor

Prof. Christian Hartinger

Discipline

Chemical Sciences

Project code: SCI031

In the past decade the design of targeted anticancer agents was among the most prolific research areas. However, more recently it has become apparent that the combination of more than one pharmacophore in a single molecule can result in anticancer agents with advantageous properties. In this project, we will work on the preparation of a new compound class to be tested on its tumour-inhibiting properties.

Design and Applications of Organometallic Complexes for Catalysis

Supervisor

Prof. Christian Hartinger

Discipline

Chemical Sciences

Project code: SCI032

The production of everyday products, such as pharmaceuticals, fertilisers and functional materials, is reliant on efficient chemical transformations to yield high amounts of the desired products at low cost. In this project, we will use different ruthenium complexes and study their catalytic activity in important chemical transformations with relevance to industry.

Bioanalytical Mode-of-Action Studies of Metal-based Anticancer Agents

Supervisor

Prof. Christian Hartinger

Discipline

Chemical Sciences

Project code: SCI033

Understanding the mode of action of anticancer agents at the molecular level is key to develop the next generation anticancer drugs. In this project, we will investigate the biomolecule interaction of metallodrugs using advanced bioanalytical methods to characterize reaction products and/or binding kinetics. These studies are important to select compounds for further preclinical development.

Supramolecular structures and their use for targeted delivery of anticancer agents

Supervisor

Prof. Christian Hartinger

Discipline

Chemical Sciences

Project code: SCI034

Stimulus responsive supramolecular structure may provide a means to deliver anticancer agents selectively to the tumour and the stimulus can be used to release an anticancer drug from the structure. In this project, we will prepare ditopic ligands that will be coordinated to metal centres to form such supramolecular structures. The supramolecules will be characterised and their ability to host and release anticancer drugs will be assessed.

Towards new bioerodible materials

Supervisor

Erin Leitao

Discipline

Chemical Sciences

Project code: SCI035

Inorganic P-N polymers such as polyphosphazenes show promise as bioerodible materials (artificial bone, drug delivery, etc.) but are formed using toxic reagents and/or harsh reaction conditions. Phosphoramidate compounds have recently been shown to be accessible via catalytic routes. Expansion of the catalysis along with other potential routes towards the first examples of polyphosphoramidates will be explored along with the corresponding characterization using NMR spectroscopy and mass spectrometry.

Understanding the mechanism of copper-catalysed cross-coupling with main-group substrates

Supervisor

Erin Leitao

Discipline

Chemical Sciences

Project code: SCI036

Copper-catalysed oxidative cross-coupling has been gaining much momentum in the past 5 years for the formation of main group-main group bonds (e.g. P-N, P-O, P-P, P-S, N=N, P-C etc.). Although the process is attractive in terms of its potential impact and widely-applied, very little is known about the mechanism of catalysis. For example both Cu(I) and Cu(II) salts have been shown to be efficient catalysts for this transformation but presumably form the same active catalyst. Mechanistic studies, model reactions and attempted synthesis of a new active copper catalyst will be pursued in order to gain clues as to how the catalysis works. The project will involve inorganic synthesis, characterization and mechanistic studies using NMR spectroscopy and GC-MS.

Catalytic routes to robust polytetrels

Supervisor

Erin Leitao

Discipline

Chemical Sciences

Project code: SCI037

Polytetrels, polymers containing exclusively Si, Ge, or Sn, in the backbone, are very attractive for applications in electronics due to their semi-conducting ability. One of the current issues to access these polymers is that the bonds formed are weaker than the carbon analogues. Attempts to re-inforce the bonds and improve the catalysis will be explored. Inorganic synthesis including characterization using NMR spectroscopy and mass spectrometry will be learned.

Production and characterisation of putative mycobacterial Fe(II) and 2-oxoglutarate-dependent dioxygenases

Supervisor

Dr Ivanhoe Leung

Discipline

Chemical Sciences

Project code: SCI038

The non-haem Fe(II) and 2-oxoglutarate (2OG)-dependent dioxygenases (hereafter 2OG oxygenase) belong to a family of structurally related enzymes that are ubiquitous in plants, micro-organisms and animals. 2OG oxygenases catalyse oxidation reactions by incorporating a single oxygen atom from molecular oxygen into their substrates. This is always coupled with 2OG oxidation into succinate and carbon dioxide

In humans, 2OG oxygenases are involved in a wide range of important biological functions, from biosyntheses (e.g. collagen biosynthesis and carnitine biosynthesis) to oxygen sensing to epigenetic regulations (e.g. nucleic acid demethylation). 2OG oxygenases are also found to play important functional roles in microorganisms and plants.

Mycobacterium tuberculosis is the bacteria that causes tuberculosis, a disease that still affects about 1 in 3 people in the world. Whilst existing treatments against M. tuberculosis is largely effective, there is an increasing concern about multi-drug resistant M. tuberculosis. The identification of new drug targets is important to combat this problem.

Interestingly, giving the importance of 2OG oxygenases in animals and humans, mycobacterial 2OG oxygenases have been poorly-characterised to date. A complete biochemical and functional characterisation of mycobacterial 2OG oxygenases would enable new drug targets to be identified and hence allow new tuberculosis treatments to be developed.

You will be part of a wider team that aims to identify and characterise mycobacterial 2OG oxygenases. You will apply bioinformatics tools (e.g. BLAST) to identify potential mycobacterial 2OG oxygenases, use molecular biology techniques to produce mycobacterial 2OG oxygenases, and, if time allows, characterise the purified recombinant proteins using different biophysical techniques such as fluorescence spectroscopy.

There is no formal prerequisites to this summer scholarship, although an understanding of basic molecular biology and an enthusiasm in enzymology will be helpful. The work will be highly relevant to CHEM 350 and CHEM 390 in Stage 3. Training and supervision in molecular biology and enzymology will be given throughout the summer period. Please contact me by email if you require any more information.

References:
M. S. Islam, T. M. Leissing, R. Chowdhury, R. J. Hopkinson and C. J. Schofield, 2-Oxoglutarate-dependent oxygenases. Annu. Rev. Biochem., 2018, DOI: /10.1146/annurev-biochem-061516-044724

Research group website:
http://leungresearchgroup.wordpress.fos.auckland.ac.nz/

Recombinant protein expression and purification

Supervisor

Dr Ivanhoe Leung

Discipline

Chemical Sciences

Project code: SCI039

Our research group is interested in the applications of biophysical techniques to study proteins and enzymes that are important for (1) human health and disease, and (2) New Zealand’s agricultural industry.

A key step for any biophysical studies of proteins and enzymes involves the production and purification of recombinant proteins. In this project, you will be responsible for molecular cloning, conduct protein expression trials, optimise protein purification procedure and use biophysical tools including mass spectrometry and nuclear magnetic resonance spectroscopy to characterise the recombinant protein that you made.

There is no formal prerequisites to this summer scholarship, although an understanding of basic molecular biology and an enthusiasm in enzymology will be helpful. The work will be highly relevant to CHEM 350 and CHEM 390 in Stage 3. Training and supervision in molecular biology and enzymology will be given throughout the summer period. Please contact me by email if you require any more information.

Example of recent work from my group (including contribution from summer student):
Huang, R.; Ayine-Tora, D. M.; Muhammad Rosdi, M. N.; Li, Y.; Reynisson, J.; Leung, I. K. H. Virtual screening and biophysical studies lead to HSP90 inhibitors. Bioorg. Med. Chem. Lett. 2017, 27, 277–281.

Research group website:
http://leungresearchgroup.wordpress.fos.auckland.ac.nz/

Mechanistic and mutagenesis studies of grape (Vitis vinifera) polyphenol oxidase

Supervisor

Dr Ivanhoe Leung

Discipline

Chemical Sciences

Project code: SCI040

Polyphenol oxidases (PPOs) are type 3 di-copper enzymes that are widely found in both prokaryotes and eukaryotes. There are two main types of PPOs, including tyrosinase and catechol oxidase. Tyrosinase catalyses the oxidation of both monophenols and ortho-diphenols, whilst catechol oxidase only catalyses the oxidation of ortho-diphenols.

A number of structural and mechanistic studies were conducted in the last decade in order to understand the substrate selectivity of tyrosinase and catechol oxidase. Two proposals have emerged: One suggests the presence of a bulky ‘blocker’ residue above CuA may restrict PPO’s monophenolase activity, whilst the other suggests that the amino acid residues that govern the entry of the substrate(s) to the active site are more important for selectivity. To date, the differences in substrate selectivity between these two closely related enzymes are still not fully understood.

By using grape (Vitis vinifera) PPO as a model system, we hope to understand the structural and mechanistic basis of PPO substrate selectivity. This summer scholarship will form an integral part of this project, which will include the design and production of mutant PPO, and in vitro kinetic characterisation of different substrates using biophysical techniques.

There is no formal prerequisites to this summer scholarship, although an understanding of basic molecular biology and an enthusiasm in enzymology will be helpful. The work will be highly relevant to CHEM 350 and CHEM 390 in Stage 3. Training and supervision in molecular biology and enzymology will be given throughout the summer period. Please contact me by email if you require any more information.

References:
1. M. Goldfeder, M. Kanteev, S. Isaschar-Ovdat, N. Adir, A. Fishman, Determination of tyrosinase substrate-binding modes reveals mechanistic differences between type-3 copper proteins, Nat. Commun. 2014, 5, 4505.
2. Bijelic, M. Pretzler, C. Molitor, F. Zekiri, A. Rompel, The structure of a plant tyrosinase from walnut leaves reveals the importance of “substrate-guiding residues” for enzymatic specificity, Angew. Chem. Int. Ed. 2015, 54, 14677–14680.
3. E. Solem, F. Tuczek, H. Decker, Tyrosinase versus catechol oxidase: one asparagine makes the difference, Angew. Chem. Int. Ed. 2016, 55, 2884–2888.
4. Li, Y.; Zafar, A.; Kilmartin, P. A.; Reynisson, J.; Leung, I. K. H. Development and application of an NMR-based assay for polyphenol oxidases. ChemistrySelect 2017, 2, 10435–10441.

Research group website:
http://leungresearchgroup.wordpress.fos.auckland.ac.nz/

Metallabenzenes as building blocks for new materials

Supervisor

Prof. L. James Wright

Discipline

Chemical Sciences

Project code: SCI041

Metallabenzenes are compounds in which one of the CH groups of benzene has been formally replaced by a transition metal with its ancillary ligands. We are interested in exploring the syntheses, reactivity and bonding of this intriguing new class of compounds. The summer Scholarship project will involve the investigation of routes to functionalised metallabenzenes that will serve as precursors for the fabrication of new materials.

Water purification by catalytic oxidation of pollutants

Supervisor

Prof. L. James Wright

Discipline

Chemical Sciences

Project code: SCI042

The use of the environmentally benign oxidant hydrogen peroxide for water purification is very attractive, but appropriate oxidation catalysts are required. The Summer Scholarship project involves studies of newly discovered iron catalysts (Fe-TAMLs) that are incorporated into a new solid state technology we have developed for the oxidative destruction of dilute organic pollutants in water. Decontamination of the water occurs without contamination of the water with hydrogen peroxide, catalyst or base.

CO-Releasing Molecules with Targeted Pharmacological Activity

Supervisor

Prof. L. James Wright jointly with Prof C. Hartinger

Discipline

Chemical Sciences

Project code: SCI043

CO plays a key role as a gaseous messenger in the human body. At very low concentrations CO has been shown to act as an intercellular messenger that elicits beneficial outcomes against inflammation, apoptosis and oxygen reperfusion damage. There is a strong drive to develop water soluble transition metal (TM) compounds that can release CO inside the body selectively to target tissues. This project involves the synthesis of special ligands that will give CORMs this important tissue selectivity.

Water and lipophilic solubility of thienopyridines anticancer compounds as calculated using density functional theory (DFT).

Supervisor

Dr Jóhannes Reynisson, A/Prof David Barker

Discipline

Chemical Sciences

Project code: SCI044

The thienopyridines is a novel class of highly potent anticancer compounds. Limited aqueous solubility is the main issue hampering their further development. In this project quantum chemical calculations will be used to derive the solubility profile of these compounds and correlated with their anticancer potency.

The physicochemical properties of genotoxic compounds as compared to known drugs

Supervisor

Dr Jóhannes Reynisson
Dr Chris Seal
A/Prof Duncan

McGillivray

Discipline

Chemical Sciences

Project code: SCI045

In this project a compound collection with molecules known to be mutagenic / genotoxic, i.e. Ames and Comet positive, will be collected. The physicochemical parameters of these will be derived and compared to those of known drugs. The aim is to establish whether a unique property profile exists for DNA damaging agents as compared to clinically used drugs.

Molecular modelling of Heat shock protein 90 (HSP90) inhibitors to the binding pocket of the enzyme. An evaluation study.

Supervisor

Dr Jóhannes Reynisson

Discipline

Chemical Sciences

Project code: SCI046

Molecular modelling is a very useful tool in drug design. In order to test the robustness of the scoring functions used in docking a host of known inhibitors of the anticancer target HSP90 will be benchmarked against their experimental counterparts.

New Chemical Technologies for the Depolymerisation of Lignin

Supervisor

Associate Professor Jonathan Sperry

Discipline

Chemical Sciences

Project code: SCI047

Biomass is the only renewable carbon feedstock that could potentially replace fossil fuels. The efficient conversion of biomass into fine chemicals is one of the great scientific challenges of the 21st century. This project will investigate new chemical technologies for the production of fine chemicals from lignin, an abundant biopolymer present in wood biomass.

Pre-requisites: Interest in Green Chemistry

Chemical Synthesis using Biomass-Derived Building Blocks

Supervisor

Associate Professor Jonathan Sperry

Discipline

Chemical Sciences

Project code: SCI048

The global chemistry community must reduce its reliance on fossil fuels and employ molecules derived from biorenewable sources in the production of society enhancing chemicals. This project will investigate the synthesis of fine chemicals from building blocks derived from renewable biomass (cellulose and chitin).

Pre-requisites: CHEM 330 or equivalent; interest in Green Chemistry

Novel Synthetic Methods for Indole Construction

Supervisor

Associate Professor Jonathan Sperry

Discipline

Chemical Sciences

Project code: SCI049

The indole ring system represents one of the most abundant and important heterocycles in nature, with over 600 natural products possessing this ring system. Additionally, drugs containing the indole heterocycle account for nearly US$8 billion in sales annually. In keeping with their importance, the development of new routes towards indoles is a central theme and ongoing challenge in contemporary organic synthesis. This project aims to develop a novel indole synthesis using some intriguing transition metal chemistry recently reported by our research group.

Pre-requisites: CHEM 330 or equivalent

Mechanochemical synthesis

Supervisor

Associate Professor Jonathan Sperry

Discipline

Chemical Sciences

Project code: SCI050

Solvent waste from the chemical industry is an enormous financial and environmental burden. One potential solution to this issue is to synthesise valuable compounds in the solid state using mechanochemistry, an unexplored technique in chemical synthesis. In this project, the mechanochemical synthesis of medicinally important heterocycles and pharmaceutical motifs will be developed, with the aim to eliminate solvent from these processes.

Pre-requisites: Interest in Green Chemistry

Natural Indole-Inspired Therapeutics for Multidrug-Resistant Infections and Psychiatric Disease

Supervisor

Associate Professor Jonathan Sperry

Discipline

Chemical Sciences

Project code: SCI051

Natural products (secondary metabolites) contain a level of structural and chemical diversity that is unsurpassed by man-made libraries. Natural products are not vital for the growth or reproduction of the host organism, but serve as defence molecules that aid long-term survival prospects. Natural products are produced by organisms after millions of years of evolution, having undergone several rounds of ‘natural optimisation’ to interact efficiently with biological macromolecules. As such, natural products are inherently biologically active and constitute the greatest source of drugs; from the 1940s to the end of 2014, around half of all small molecule drug approvals can be classified as a natural product, derived from a natural product or a natural product mimic. This project will examine the synthesis of indole alkaloids that are unattainable from the natural source, and their subsequent biological evaluation.

Pre-requisites: Interest in medicinal chemistry, completed CHEM330

Characterisation of beverage antioxidants using cyclic voltammetry

Supervisor

Prof Paul Kilmartin

Discipline

Chemical Sciences

Project code: SCI052

In this project, the electrochemical procedure of cyclic voltammetry will be applied to the antioxidants present in a series of alcoholic beverages, including beer and fortified drinks. Comparisons will be made with standard Food Science antioxidant assays, and a wide range of beverages of different strengths will be surveyed.

Antioxidant packaging produced using biodegradable polymers

Supervisor

Prof Paul Kilmartin

Discipline

Chemical Sciences

Project code: SCI053

In this project, the target plastic will be biodegradable polylactic acid (PLA), with the inclusion of active natural tannin and/or essential oil containing additives. The mechanical performance of the films will be checked, and their application for active packaging evaluated through a range of antioxidant test procedures combined with leaching studies.

Wine chemical features linked to minerality in wines and the potential role of yeast

Supervisor

Dr Rebecca Deed

Discipline

Chemical Sciences

Project code: SCI054

To investigate the role of the wine yeast, Saccharomyces cerevisiae, on wine minerality by examining yeast-derived flavour neutrality, production of succinic acid during stress, volatile sulfur compounds (VSCs), and interaction with wine phenolics. The student undertaking this project will be involved in routine handling yeast, small-scale fermentation, analytical techniques such as HS-SPME GC/MS and LC/MS, and sensory evaluation.

Total Synthesis of Bioactive Natural Products from Traditional Chinese Medicine

Supervisor

Distinguished Professor Margaret Brimble
Dr Dan Furkert

Discipline

Chemical Sciences

Project code: SCI055

Our group has a strong interest in the total synthesis of complex and bioactive molecules, in both their asymmetric synthesis and potential applications in medicinal chemistry. Annotinolides A-C were isolated in 2016 from the moss Lycopodium annotinum Linn. (above left) in Shaanxi, China, and showed inhibitory activity against aggregation of αβ peptides, important in the progression of Alzheimer’s disease. This is the first time lycopodium alkaloids have shown this type of biological activity, showing the relevance of traditional Chinese medicinal knowledge and making them high priority targets for synthesis. Our group is currently focusing on identification of strategies for construction of advanced intermediates containing the polycyclic scaffold of annotinolide C. Once effective ways to assemble these substructures on useful scales have been identified, with control of stereochemistry, the final goal is the asymmetric total synthesis of the natural product, annotinolide C.

New students will have a great opportunity in the exciting challenge of natural product synthesis, and gain an insight into the tactics and techniques of synthetic organic chemistry. Research areas will include developing synthetic routes towards natural product intermediates, methods to functionalise and couple these with other substructures, and investigating biological mechanisms through structure-activity relationships of derivatives against Alzheimer’s disease.

Asymmetric Synthesis of Spiroketals and Polyketides

Supervisor

Distinguished Professor Margaret Brimble
Dr Dan Furkert

Discipline

Chemical Sciences

Project code: SCI056

Synthesis of spiroketals and spiroketal-containing natural products is a longstanding interest of our group. These molecular scaffolds, consisting of two (or sometimes even three) rings joined at a quaternary carbon with two bonds to oxygen, are privileged scaffolds found in a wide range of natural products that demonstrate promising bioactivity against a variety of pathologies. Some examples of our current and previous targets are shown below (spiroketals highlighted in blue boxes).

This research area offers a great opportunity to apply your organic chemistry background to the synthesis of complex molecules, building on our group’s particular expertise in spiroketal natural products. Projects will based on stereoselective multistep organic synthesis, aiming to successfully prepare structures found in recently-isolated natural products that can then be investigated for their activity in biological systems. New students will learn a wide variety of classic and state-of-the-art chemistry techniques for asymmetric synthesis including transition metal catalysis, C-H activation, pericyclic reactions, aldol and organometallic reactions.

New Chemical Reactions: Discovery and Mechanistic Studies

Supervisor

Distinguished Professor Margaret Brimble
Dr Dan Furkert

Discipline

Chemical Sciences

Project code: SCI057

The discovery and development of new reactions offers opportunities to improve synthetic access to important materials, to readily and selectively access previously challenging structures and improve our fundamental understanding of chemical processes. New reactions recently uncovered by our group include an epoxide opening that proceeds only in the presence of a cobalt catalyst, to give products homologated by two carbon atoms (below left), and an unexpected [3+2] cycloaddition of in situ generated vinyl azide (below right), a little-used reagent with an intriguing history dating back to original work conducted in 1910.

We are currently pursuing the possibilities opened up by these new reactivity patterns. Exploration of the mechanistic basis for the observed results through both experiment, real-time data collection and computer calculation (e.g. transition state TS1 above) will enable allow optimization and wider application for rapid synthesis of previously inaccessible synthetic intermediates and functional groups. We also aim to assess the potential of rarely-reported vinyl azide itself in organic synthesis. This project offers an unusual and fast-moving chance for new students to discover new areas of chemistry, while expanding your organic synthesis and lateral thinking skills.

Drug Discovery: Towards New Clinical Agents to Address Antimicrobial Resistance

Supervisor

Distinguished Professor Margaret Brimble
Dr Dan Furkert

Discipline

Chemical Sciences

Project code: SCI058

Growing incidence of antimicrobial resistance to clinically used antibiotic drugs is an immediate global health concern, as recently highlighted by the World Health Organisation (WHO), US and NZ governments. Academia and small biotech firms have an important role to play in generating novel compounds to address this resistance problem due to the low numbers of new pharma drug candidates currently entering the industrial development pipeline.

Our group is involved in several projects in medicinal chemistry, combining our skills in organic synthesis with the expertise of our collaborators in computer modelling, X-ray crystallogyraphy, enzyme reaction mechanisms, microbiology and pharmacology, to develop lead compounds against human pathogenic bacteria (above).

0Our current work includes synthetic routes towards the rare aminoacid enduracididine (3rd from left) a component of teixobactin, an antimicrobial peptide recently isolated from soil bacteria with potent activity against MRSA and vancomycin-resistant Enterococci (VRE) and C. difficile. We are also pursuing the rational design of inhibitors of enzymes in the mitochondrial electron transport chain (ETC) in bacteria with the aim of identifying selective antibacterial agents against M. tuberculosis (Mtb) and other pathogen species dependent upon similar enzymes for ATP production.

Synthesis of Pentaminomycin A, an Anti-melanogenic Agent

Supervisor

Distinguished Professor Margaret Brimble
Dr Iman Kavianinia
Dr Paul Harris

Discipline

Chemical Sciences

Project code: SCI059

Melanogenesis is the process of melanin production that serves to protect skin against the damaging effects of ultraviolet radiation exposure. However, overproduction and accumulation of melanin in skin can lead to various dermatological disorders. Over the past years, the search for safe and effective anti-melanogenic agents has received considerable attention for medicinal and cosmetic applications. The initial rate-limiting steps of melanin biosynthesis are catalysed by tyrosinase, which is therefore an attractive target for the development of anti-melanogenic agents.
Pentaminomycin A, a naturally occurring hydroxyarginine-containing cyclic peptide derived from the cultures of Streptomyces sp. RK88-1441, has recently been shown to exhibit anti-melanogenesis activity by suppressing the expression of melanogenic enzymes including tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2), with no observed cytotoxicity. This research project aims to establish a comprehensive structure-activity relationship of pentaminomycin A in order to obtain analogues with improved anti-melanogenic properties. Solid-phase peptide synthesis (SPPS) techniques will be used in combination with standard organic synthesis techniques.

Synthesis of New Generation Lipopeptide-based Antibiotics

Supervisor

Distinguished Professor Margaret Brimble
Dr Paul Harris

Discipline

Chemical Sciences

Project code: SCI060

Antibiotic resistance has been recognised by the WHO as one of the greatest threats to humanity and infectious diseases rank as the second most common cause of death worldwide. This is further compounded by the observation that development of new structural classes of antibiotics has all but ceased in the past 40 years.
An emerging subset of peptide based antibiotics include cyclic peptides containing a lipid or fatty acid e.g. daptomycin. They have been shown to be clinically relevant and are used as the “last line of defence” against otherwise untreatable bacterial infections. The challenge remains, however, to efficiently produce new antibiotics based on a cyclic peptide scaffold incorporating the crucial lipid motif.
Using our newly devised method of installing a lipid onto a peptide (a thiol-ene reaction), this project aims to exploit and develop this chemistry to generate a chemical library of peptide based antibiotics, which will undergo biological testing against the most antibiotic resistant strains of bacteria. Successful candidates will be using organic synthesis techniques and modern methods of solid phase peptide synthesis.
http://brimble.chem.auckland.ac.nz/research-3/

Chemical Synthesis of a Conotoxin Derived from the Venom of Cone Snails

Supervisor

Distinguished Professor Margaret Brimble
Dr Paul Harris

Discipline

Chemical Sciences

Project code: SCI061

Cone snails have evolved a venomous harpoon able to paralyse prey with an arsenal of toxic compounds, such as conotoxins, which show great promise in the treatment of conditions such as pain and neuromuscular disorders. κA-conotoxins are a major component of the venom of several species of fish-hunting cone snail, but as a class of compounds have been less well studied due to their molecular complexity and post-translational modifications.

CcTx is a 30 residue glycopeptide that contains an intricate serine-linked pentasaccharide, 3 intramolecular disulphide bonds, several hydroxylated proline residues and a C-terminal alpha helix spanning residues 23Ser-27Thr. The unique pentasaccharide moiety, which contains several rare and unnatural L-sugars, probably plays a key role in its bioactivity.

This project will embark on a total synthesis of CcTx using glycosylation and peptide chemistry to assemble the fully functional molecule from individual amino acids. Candidates will become well versed in modern methods of glycopeptide chemistry.

http://brimble.chem.auckland.ac.nz/research-3/

The Impact of AGEs in Alzheimer’s Disease

Supervisor

Distinguished Professor Margaret Brimble
Dr Iman Kavaninia
A/Prof Nigel Birch

Discipline

Chemical Sciences

Project code: SCI062

Alzheimer’s disease (AD) is a complex neurodegenerative disorder that results in progressive cognitive impairment, loss of memory and changes in behaviour. In 2011, 34 million people worldwide were diagnosed with AD, and it is estimated that this figure will triple by 2050 due to an increasing ageing population. Despite vast research spanning more than a century, current treatments for AD are still limited to modest symptomatic relief and the precise causes of AD remain largely unknown.

Recently, new evidence has suggested that beta-amyloid (A-beta) peptides (a hallmark of AD) that have been irreversibly modified by sugar derivatives known as advanced glycation end products (AGEs) are more pathogenic than A-beta itself. However, the A-beta-AGE peptides used in these studies were prepared by the non-specific incubation of A-beta in glucose; this results in the formation of a complex mixture of A-beta-AGE peptides. Thus, the precise impact of individual AGEs on the biophysical properties of A-beta remains to be evaluated.

This project aims to prepare a small library of A-beta-AGE peptides, which will then undergo biological testing by Associate Professor Nigel Birch (SBS) and Professor Michael Dragunow (FMHS). Successful candidates will employ organic synthesis techniques to prepare AGE building blocks followed by incorporation of the AGE building blocks into the A-beta peptide using solid phase peptide synthesis.

http://brimble.chem.auckland.ac.nz/research-3/
 

TLR2 Activation: Modulating the Activity of Lipopeptide Constructs as Adjuvants for Vaccines

Supervisor

Professor Margaret Brimble
Dr Geoff Williams
Prof Rod Dunbar

Discipline

Chemical Sciences

Project code: SCI063

Toll-like receptor 2 (TLR2) is a highly conserved membrane pattern recognition receptor that has evolved to recognize Lipoprotein motifs expressed by foreign pathogens. On binding of an agonist motif the receptor is activated and, after internalisation of the foreign agent, then modulates the production of signalling factors that up-regulate an effective immune response to that pathogen.
It has been shown that activation of TLR2 can be attained with S-(2,3-bispalmitoyloxypropyl)cysteine-based (Pam2-Cys and Pam-1-Cys) lipid motifs present in the cell wall of Gram-positive bacteria. Thus, by creating a construct in which this lipid is linked to a suitable peptide epitope, the TLR2 receptor can be recruited into producing a highly targeted immune response that can then be directed against cancerous cells within a host.


The linker portion of the lipid-peptide construct epitope has conventionally been Ser-Lys-Lys-Lys-Lys but it is still not clear to what extent TLR2 activation is governed by this sequence. The project aims to investigate this question by exchanging the key Serine residue by other amino acids – both natural and unnatural – to evaluate the effect on receptor activation and through this to better modulate the immunogenic response.

The relative activity of the library of analogues thus generated will be evaluated in the HEK-blue™ cell assay.

The skills necessary to carry this project out will include organic synthesis and modern solid-phase peptide synthesis and purification.
 

Synthesis of Pseudoxylallemycins, Antimicrobial Cyclic Tetrapeptides

Supervisor

Distinguished Professor Margaret Brimble
Dr Alan Cameron

Discipline

Chemical Sciences

Project code: SCI064

Multidrug antibiotic resistance poses an increasingly urgent threat to human health. Amongst antibiotic resistant species, Gram-negative bacteria in particular have become resistant to almost all available treatments. Whilst a number of antibiotics are currently being developed to target Gram-positive infections, only few are in progress for Gram-negative infections.
Recently, a family of four cyclic tetrapeptides, namely pseudoxylallemycins A-D, isolated from the termite-associated fungus Pseudoxylaria sp. X802 were found to exhibit Gram-negative antimicrobial activity (MICs of 12.5-25.0 μg/mL), cytotoxicity (HeLa cells, CC50 10.3-49.5 μg/mL) and antiproliferative activity (HUVEC cells, GI50 4.3-33.8 μg/mL; K-562 cells, GI50 4.2-42.8 μg/mL).
Pseudoxylallemycins B-D contain unique allene moieties (highlighted in blue), which rarely occur in natural products. Using a combination of organic and peptide chemistry, this project aims to synthesise the natural products pseudoxylallemycins A-D and structurally related analogues, which will then be evaluated for antimicrobial activity in collaboration with Professor Greg Cook (University of Otago).
http://brimble.chem.auckland.ac.nz/research-3/
 

Antibody-Drug Conjugates (ADCs)

Supervisor

Distinguished Professor Margaret Brimble
Dr Iman Kavianinia
Dr. Louise Stubbing

Discipline

Chemical Sciences

Project code: SCI065

Antibody-drug conjugates (ADCs) are a clinically proven class of medicines used in the treatment of various cancers. Utilisation of the exquisite selectivity of antibody targeting to cancer epitopes coupled to delivery of highly potent small molecules is revolutionising modern oncology. Given the modular nature of the ADC design concept, the future potential of this field is truly vast, and will rely on the discovery of i) new antibody-antigen couples, ii) novel linker chemistries and iii) the discovery of highly potent cytotoxins for conjugation.

Critically, the availability of suitably potent, stable cytotoxic agents is considered rate-limiting for progress in this field. Cytotoxic peptide natural products provide a rich source of anticancer agents that can be readily appended to antibodies using amino acid-based conjugation technology.

This research project provides a unique opportunity to develop a novel class of cytotoxin with optimal properties for use in ADCs. The student undertaking this project will be involved in modern solid-phase peptide synthesis, HPLC purification and compound characterisation using related spectroscopic techniques.
 

Divergent Peptide Cyclisation with a Minimalist Linker

Supervisor

Distinguished Professor Margaret Brimble
Dr Iman Kavianinia
Dr Paul Harris

Discipline

Chemical Sciences

Project code: SCI066

Cyclic peptides and depsipeptides are abundant in nature and possess a wide range of interesting biological activities, making them highly valuable molecules for drug development. Cyclisation of linear peptides can enhance both receptor binding, by reducing conformational freedom, and peptide stability towards physiochemical stress and enzymatic digestion.

Recently our research group reported the facile synthesis of N-vinylamides 1–3 via an unexpected and novel vinyl azide-enolate [3+2] cycloaddition. In this project we will exploit the bifunctional nature of compounds 1–3 for use in peptide cyclisation. The vinyl amide functionality can be used via a thiol-ene reaction to attach the linker to the sidechain of a cysteine residue. The α,β-unsaturated Michael acceptor can then be used to cyclise the peptide using recently reported decarboxylative macrocyclisation via photoredox catalysis.

The student working in this project will be trained in organic synthesis, purification, compound characterisation (NMR, MS, IR, etc) as well as solid-phase peptide synthesis. Students with interests in both organic and peptide chemistry are encouraged to apply.
 

Development of a bacterial cell membrane analogue using the Langmuir trough

Supervisor

A/Prof Duncan McGillivray
A/Prof Jane Allison
Dr Chris Seal

Discipline

Chemical Sciences

Project code: SCI067

Lipoteichoic acid is a major constituent of the cell wall of Gram positive bacteria that is known to be bound by anti-microbial peptides such as polymyxins, a current last resort antibiotic. However, little is known about its effect on the cell membrane and its interaction with other components, such as membrane proteins. You will help us to develop a synthetic outer membrane system to investigate these effects as well as provide quantitative experimental data to calibrate molecular dynamics simulations. This will be done using the Langmuir trough, which offers a robust method for generating a monolayer by physically compressing a suspended layer of molecules – in this case, membrane lipids

Exploring the molecular interaction of nanoplastics and proteins

Supervisor

A/Prof Duncan McGillivray
Dr Chris Seal

Discipline

Chemical Sciences

Project code: SCI068

There is no question that the quantity of waste plastic, particularly in marine environments, is a rapidly growing international concern. Photo-oxidation, biodegradation, and physical weathering of these plastics can reduce their size to below 100 nm (i.e., nanoplastics).
The toxic actions of nanoplastics have been demonstrated by many researchers and it is thought that the origin of these adverse effects arises from dysfunctioning of biological molecules which results from this interaction.
Nanoplastics in living organisms encountering proteins and cell membranes (collectively biological macromolecules), modify the chemical nature of both the nanoparticles and the proteins. However, there is little literature discussing the molecular interaction between nanoplastics and biological macromolecules.
This project aims to improve understanding of this problem by using physicochemical characterisation (spectroscopy and light scattering) of a model system (polystyrene nanoparticles and a model protein and cell membrane).
 

Atmospheric pressure plasma reactions for surface functionalization

Supervisor

A/Prof Duncan McGillivray
Dr Chris Seal

Discipline

Chemical Sciences

Project code: SCI069

Surface functionalisation using atmospheric pressure plasma (plasma enhanced chemical vapour deposition) is a process that is becoming more commonly integrated into current manufacturing processes. Unlike vacuum plasmas, the ability to generate a plasma at atmospheric pressures provides a relatively low cost, easy to use process with rapid deposition rates.
The use of these plasmas allows for a surface to be both physically and chemically modified that in turn creates desirable surface properties.
The aim of this project will be to create functional surfaces using atmospheric plasma modification and to characterise these surfaces using techniques such as Xray-photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and in-situ ellipsometry measurements
 

Chemical changes in fingermarks

Supervisor

Associate Professor Gordon Miskelly

Discipline

Chemical Sciences

Project code: SCI070

Once fingermarks are deposited on a surface they can start to be altered. Processes that may occur include the evaporation of volatile components including water, penetration of components into the underlying substrate, and oxidation by gases such as ozone. This project will investigate some of these chemical changes and the impact they have on fingermark enhancement.  

The effect of drying methods on the physicochemical properties of microcapsules containing fish oil and carotenoids

Supervisor

A/P Siew Young Quek

Discipline

Chemical Sciences

Project code: SCI071

The physicochemical properties of microcapsules containing fish oil and carotenoids prepared by different drying methods will be investigated. Fish oil (with high content of EPA and DHA) and carotenoids (β-carotene and lutein) will be firstly emulsified with whey protein isolate and OSA starch. The emulsions are then dried by mono-disperse droplet spray drying (MDSD), spray drying (SD), and freeze drying (FD) to produce 20% oil powders. The objective is to determine the key factors to influence powder stability, and to further understand the difference of the MDSD method with a comparison to SD and FD methods. The physicochemical properties of microcapsules will be determined by analysis on their moisture content, density, solubility, microencapsulation efficiency, glass transition temperature, and morphology.

Applicant is expected to have experience working in lab environment and is able to follow lab safety procedures well. Applicant should be interest on the topic and is committed to learn relevant research skill.
 

New Enzymes for Water Treatment

Supervisor

Dr Viji Sarojini
Prof James Wright

Discipline

Chemical Sciences

Project code: SCI072

In developing as well as in industrialized nations, a growing number of contaminants are entering the aqueous environment from human activity. Organic herbicides/pesticides for controlling weeds, insects and fungi in agriculture comprise the largest group of xenobiotic compounds deliberately introduced into the environment. These compounds, and their metabolites end up in drinking water at concentrations exceeding the 0.1µg/L threshold of pesticide residues in drinking water. This translates into an immediate need for effective, low-cost, robust water treatment methods to remediate waters without further stressing the environment or endangering human health. This project aims to undertake the basic research to develop biodegradable peptide-based scavenger enzymes for water remediation applications. The summer student working in this project will be trained in Molecular Modelling, Solid Phase Peptide Synthesis, HPLC purification and residue scavenging techniques relevant to the project.

Anti-Biofilm Peptides for Water Disinfection

Supervisor

Dr Viji Sarojini
Prof James Wright

Discipline

Chemical Sciences

Project code: SCI073

Billions of people lack access to safe drinking water and millions die annually from diseases transmitted through the consumption of unsafe water. Waterborne infectious agents causing such diseases include bacteria, fungi, protozoa and viruses. Viruses are of particular concern and account for half of the emerging pathogens in recent times. The main water disinfectant used worldwide, free chlorine, is ineffective in controlling certain waterborne pathogens, particularly Mycobacterium avium, ubiquitous in biofilms found in water distribution systems. Growing of biofilms within ageing water distribution systems is a significant challenge facing infrastructure providers across the world. Using our previous experience in developing antimicrobial peptides for biofilm control, this project aims to develop antimicrobial peptides with potency and selectivity towards Mycobacterium avium biofilms found in water distribution systems. The summer student working in this project will be trained in Solid Phase Peptide Synthesis, HPLC purification and microbiology techniques relevant to the project.

Antifreeze Peptides for Preserving Texture in Frozen Foods

Supervisor

Viji Sarojini

Discipline

Chemical Sciences

Project code: SCI074

Antifreeze proteins (AFPs) enable organisms like polar fish to survive the freezing temperatures of their natural habitat. As well as being cryoprotective, AFPs have the ability to influence the size, morphology and aggregation of ice crystals which can be used in food technology, where the growth of ice crystals in frozen foods is of primary concern. AFPs expressed in yeast have been used in the ice-cream industry for creating a smooth texture and preserving ice crystal size distribution until consumption. However, infusing large protein molecules into fruits and vegetables is not a viable option and there are no analogous commercial products in the frozen fruit and berry industries. In this project we aim to develop tailor-made analogues of natural AFPs for fundamental mechanistic studies as well as potential applications in the frozen food industry. Ice crystal morphology studies and texture analysis of frozen fruits using the synthetic peptides will be done in collaboration with the Food Science group at UoA. This interdisciplinary project applies cutting edge peptide research to the needs of the frozen fruit industry which plays a major role in New Zealand’s economy. The summer student working in this project will be trained in Solid Phase Peptide Synthesis, HPLC purification and food science techniques relevant to the project

Lipopeptides with Broad Spectrum Antimicrobial and Antibiofilm Activities

Supervisor

Dr Viji Sarojini

Discipline

Chemical Sciences

Project code: SCI075

According to the World Health Organisation, the rapid emergence of multidrug resistant ‘superbug’ bacteria has created an urgent need to develop novel classes of antimicrobial agents. Unfortunately, over the last 30 years, no major types of antibiotics have been developed. Cationic antimicrobial peptides (CAPs) are promising therapeutics to address the challenge of bacterial resistance. The near success of MSI-78 (pexiganan acetate) and MX-226 or CPI-226 (Omiganan) in reaching the clinic, provide us with the enthusiasm to overcome the current roadblocks of CAPs (e.g. proteoclytic susceptibility) to achieve clinical implementation of AMPs. To this end, we have developed several linear and cyclic lipopeptides with nonprotein amino acids which have shown low micromolar activity against bacterial pathogens and the ability to lyse bacterial membranes. This project will develop stereoisomers of our potent lipopeptides through chemical synthesis and investigate their potency and mechanism of action. The summer student working in this project will be trained in Synthetic Organic Chemistry, Solid Phase Peptide Synthesis, HPLC purification and spectroscopic techniques such as NMR and Circular Dichroism.  

Cell Penetrating Peptide Nanoparticles for Drug Delivery

Supervisor

Dr Viji Sarojini 
Prof Jadranka Travas-Sejdic

Discipline

Chemical Sciences

Project code: SCI076

Increase in the number of new therapeutics that fails to reach the clinic due to poor delivery has made novel drug delivery systems an important consideration in therapeutic development. Cell penetrating peptides (CPP) are promising tools for delivering biologically active molecules like oligonucleotides and proteins into cells. The carrier-biomolecule (cargo) interactions are dictated by the sequence of the CPP. Mechanism of cellular drug internalization by CPPs is not well understood. This project aims to develop short synthetic peptides derived from the trans-activating regulatory protein (TAT) of the human immunodeficiency virus (HIV) which is the first known CPP ever. The TAT sequence will be synthesized by Solid Phase Peptide synthesis and conjugated to short oligonucleotide chains. It is expected that the peptide-oligonucleotide complex will form stable nanoparticles facilitating the entry of the drug into the cell through the plasma membrane. Morphological features of the CPP-oligonucleotide complex will be investigated by scanning electron microscopy (SEM) and light scattering measurements in collaboration with Prof Jadranka Travas-Sejdic. This project also involves collaboration with the Auckland Cancer Society Research Centre. The summer student working in this project will be trained in Solid Phase Peptide Synthesis, HPLC purification and spectroscopic techniques such as NMR and Circular Dichroism and nanoparticle synthesis and analyses.

Antimicrobial Peptides against Food Spoiling Psychrophiles

Supervisor

Dr Viji Sarojini
A/P Siew-Young Quek

Discipline

Chemical Sciences

Project code: SCI077

Psychrophilic bacteria are cold-adapted organisms, found widely over the earth’s surface due to the vast number of habitats in which they can grow. Psychrophilic bacteria have also been found to grow in refrigerators, which is of great concern to the food industry. In particular, meat products have been found to be affected and spoiled by psychrophilic growth. An important psychrophile is the species Clostridium estertheticum, which has been found to cause blown pack meat spoilage in chilled vacuum-packed meat products. As New Zealand has a prominent meat industry, in particular of beef and lamb exports, targeting psychrophilic species such as C. estertheticum would be economically beneficial. This project will explore the potential of naturally produced antimicrobial peptides of the ice fish Chionodraco hamatus to inhibit the growth of Clostridium estertheticum in meat products. Promising peptide analogues will be used in combination with food packaging technologies in collaboration with A/P Quek, Director of the Food Science Programme. The summer student working in this project will be trained in Solid Phase Peptide Synthesis, HPLC purification, anti-bacterial and anti-biofilm assays, microscopy techniques as well as spectroscopic techniques such as NMR and Circular Dichroism.

De novo Designed Models of Protein β-sheets

Supervisor

Dr Viji Sarojini
Prof Juliet Gerrard

Discipline

Chemical Sciences

Project code: SCI078

The remarkable biological functions exhibited by proteins depend on the ability of the flexible peptide chains to fold into well-ordered and compact structures that originate with distinct secondary structural elements like alpha-helices and beta-sheets discovered by Linus Pauling half a century ago. Thus, the de novo design of protein secondary structures is an important step towards understanding the biological functions of proteins in living cells. Amongst the protein secondary structural elements, beta-sheets (aggregates of beta hairpins) are particularly interesting, since they ensure not only protein function but also mis-function as in the case of amyloid plaque formation in Alzheimer’s disease. This project aims to understand the factors that modulate the formation and stability of beta-sheets which are not well understood. Survey of the various peptidic and non-peptidic structures that promote chain reversals in proteins will be followed by the incorporation of selected structures in short synthetic peptides by Solid Phase Peptide Synthesis techniques. The ability of the peptides to fold into the desired beta-hairpin fold as well as its propensity to aggregate into higher order structures will be investigated using multi-dimensional NMR and circular dichroism (CD) The summer student working in this project will be trained in Synthetic Organic Chemistry, Solid Phase Peptide Synthesis, HPLC, NMR and CD

Synthesis of Antimicrobial Cyclic Tetrapeptides

Supervisor

Dr Viji Sarojini
Dr Heru De Zoysa

Discipline

Chemical Sciences

Project code: SCI079

Cyclic tetrapeptides (CTPs) are an important class of natural products that exhibit a wide spectrum of biological activities and are therefore attractive candidates in the development of pharmaceuticals. They generally contain turn-inducing non-protein amino acids such as alpha-amino-isobutyric acid (Aib), D amino acids and beta amino acids such as 2-aminobenzoic acid (Abz). CTPs are important models to study beta-turns. Their constrained structure provides the necessary stability against degrading proteases and also help to enhance target selectivity. This project explores the synthetic methodology and biological activity analyses of naturally occurring and designed cyclic tetrapeptides incorporating the novel D-Phe-2-Abz turn recently reported from the group. A combination of Organic Chemistry and Fmoc-Solid Phase Peptide Synthesis will be used to achieve the synthesis of novel cyclic tetrapeptides with biological activities, particularly antimicrobial activity. Secondary structure of the synthetic CTPs will be investigated using multi-dimensional NMR and circular dichroism (CD). The summer student working in this project will be trained in Synthetic Organic Chemistry, Solid Phase Peptide Synthesis, HPLC, NMR, CD and bioassays relevant to the project.

UV-crosslinkable, Highly Elastomeric Conducting Polymers

Supervisor

Jadranka Travas-Sejdic
Paul Baek

Discipline

Chemical Sciences

Project code: SCI080

The rapidly growing field of stretchable bioelectronics includes examples of wearable and implantable devices and sensors for biomedical applications. Such growth demands scalable production of bioelectronics, which calls for exciting new development in low-cost, solution processable, biomimetic polymers with electrical properties. In this work, we report molecular engineering of conjugated polymers to impart biomimetic properties such as elasticity, self-healing and softness - properties that are not inherent in conjugated polymers – for aforementioned applications.

The student involved in this project will partake in characterising the novel conducting polymer materials and fabrication of stretchable electrodes using a wide range of techniques: UV-Vis, NMR, FTIR, AFM, SEM, and much more. This project will present a great opportunity to understand the process of research as well as a wide range of characterisation techniques used in research.
 

Surfaces for Dynamic Microfluidics

Supervisor

Geoff Willmott

Discipline

Chemical Sciences

Project code: SCI081

Experimental projects are available in which surfaces are chemically altered in order to control their interactions with adjacent, moving fluids. High-speed photography is an important tool for characterizing the fluid flows. Examples of surfaces to functionalize include (i) spherical beads, which may be asymmetrically coated to create ‘Janus’ microparticles that self-assemble into interesting structures, (ii) capillary tubes, which are relevant to development of microfluidic devices, and (iii) substrates used on a quartz crystal microbalance. Suitable for chemistry students with good quantitative skills.

Synthesis of biologically active lignan natural products

Supervisor

A/Prof David Barker

Discipline

Chemical Sciences

Project code: SCI082

Lignans are a class of compound which has become the a target of particular interest to researchers, owing to their numerous biological activities including anti-cancer and cytotoxic properties and have also shown an array of pharmacological activities, including antifungal, antibacterial, antioxidant and anti-proliferative properties. In this project we will explore our recently developed methods to prepare a range of classes of lignan natural products using a common, easily made intermediate. This compound can be converted to both THF lignans and also aryl-tetralin lignans, both classes have highly bioactive members including clinically used drug. The student undertaking this project will be involved in organic synthesis, purification and compound characterisation (NMR, MS, IR, etc). They should have a reasonable knowledge of synthetic chemistry.  

Understanding the biogenesis of H2S in yeast and its role cell signaling

Supervisor

A/Prof David Barker
Dr Bruno Fedrizzi

Discipline

Chemical Sciences

Project code: SCI083

There is growing recognition that H2S is a “gasotransmitter’’ that plays critical roles in cellular signalling and hormonal regulation. In humans, H2S has come under intense recent scrutiny because of its importance in cardiovascular diseases, cellular energetics and apoptosis. Since gaseous transmitters diffuse rapidly and with fine temporal control, understanding their modes and sites of synthesis is critical to understanding their biology. Several enzymes produce H2S, but their roles and relative importance in H2S signalling are not yet clear. In this project students will work on the synthesis of novel H2S donors. These molecules are synthetic complexes that break down under cellular conditions to product H2S and are required to study the effect of H2S in the inter-species signaling. The student undertaking this project will be involved in organic synthesis, purification and compound characterisation (NMR, MS, IR, etc) and also complex analytical techniques such as GCMS and LCMS and they should have a reasonable knowledge of synthetic and/or analytical chemistry.

Synthesis of novel polymeric materials as surface active antimicrobial agents

Supervisor

A/Prof David Barker
Prof Brent Copp

Discipline

Chemical Sciences

Project code: SCI084

Due to the increase in bacterial resistance there is a need to develop new antibacterial agents, in particular in a hospital and medical environment. In this project we will synthesize novel antimicrobial polymers which not only kill bacteria upon contact but allow visualisation of the bacterial killing. The polymers will be designed so they can be used in a either a solution to be applied where desired or could be attached permanently to a surface to give an antibacterial surface. This project is conducted in collaboration with Prof Brent Copp. The student undertaking this project will be involved in organic synthesis, purification and compound characterisation (NMR, MS, IR, etc). They should have a reasonable knowledge of synthetic chemistry.

Lighting up sugars – fluorescent probes for mono-saccharides

Supervisor

Prof Penny Brothers
Dr David Ware

Discipline

Chemical Sciences

Project code: SCI085

We have developed a method of attaching a fluorescent label directly to glucose. This allows for highly targeted, sensitive, fluorescent labelling of sugars which could be applied to the detection of specific sugar disease markers on cell surfaces, the labelling of saccharide capsules coating pathogenic bacteria, and the determination of polysaccharide fine structure in biology and materials science. The project will involve exploring the chemistry of the fluorescent BODIPY molecule and its chemistry with sugars, focussing on monosaccharides.

Activities: chemical synthesis and spectroscopy
Skills: Stage 2 or 3 organic or inorganic chemistry
 

New dyes for electron and energy transfer

Supervisor

Prof Penny Brothers
Dr David Ware

Discipline

Chemical Sciences

Project code: SCI086

Many systems for light harvesting use a sensitiser dye which absorbs light energy and then either transfer the energy to a metal catalyst (e.g. hydrogen production from water) or transfer an electron to a semiconductor (e.g. dye sensitised solar cells). The key to an efficient process is a good connection between the sensitiser and the acceptor. We have been investigating the use of highly fluorescent BODIPY dyes as sensitisers and have developed new chemistry for introducing linking groups directly to the BODIPY boron. This project will investigate the synthesis of BODIPY pyrazole complexes and their use as sensitisers.
Activities: chemical synthesis and spectroscopy
Skills: Stage 2 or 3 organic or inorganic chemistry
 

Modular fluorescent tags: clickable BODIPYs

Supervisor

Prof Penny Brothers
Dr David Ware
Dr Dan Furkert

Discipline

Chemical Sciences

Project code: SCI087

BODIPY dyes are widely used as fluorescent tags for key sites in biomolecules. Typically, a BODIPY is synthesised with a specially designed tether attached to a receptor target, which in turn recognises the biomolecule receptor (Figure A). A new BODIPY is designed for each receptor target, and they are sold for over $100 per mg. We have designed a scheme whereby “clickable” azide or alkyne functional groups are appended to BODIPY. When paired up with the complementary alkyne or azide-functionalised receptor target, this will create modular BODIPY/receptor target combinations which can be tailored to particular receptors (Figure B). We have already prepared prototype clickable BODIPYs (Figure C). This project will further develop these and investigate click reactions to suitable targets.

Activities: chemical synthesis and spectroscopy
Skills: Stage 2 or 3 organic or inorganic chemistry
 

Porphyrin compounds for new functional materials

Supervisor

Prof Penny Brothers
Dr David Ware
Dr Tilo Soehnel

Discipline

Chemical Sciences

Project code: SCI088

Porphyrins are the pigment which gives heme its red colour. These planar, electron-rich molecules are good absorbers of light and are highly polarisable. In this project they are investigated for their ability to act as building blocks in new functional electronic materials. This project will explore the synthesis of a range of porphyrins designed for these applications and the preparation of solid state materials containing porphyrins intercalated to oxide materials.

Activities: chemical synthesis, surface chemistry, spectroscopy, solid state synthesis
Skills: Stage 2 or 3 chemistry
 

Cobalt complexes for catalytic hydrogen production

Supervisor

Prof Penny Brothers
Dr David Ware
Dr Geoff Waterhouse

Discipline

Chemical Sciences

Project code: SCI089

The efficient production of hydrogen from sustainable sources is an important goal in the search for new fuels. We have recently developed a cobalt-BODIPY dye complex which can be used for the photocatalytic production of hydrogen from water. This kind of technology is directed towards the use of sunlight to drive hydrogen production.

Activities: chemical synthesis, laser spectroscopy, electrochemistry
Skills: Stage 2 or 3 chemistry