summer studentship projects 2012-13...the project will aim at profiling fscs in the fermentation...

SUMMER STUDENTSHIP PROJECTS 2012-13

Section Page

Food and Wine Science 1-2

Inorganic and Green Chemistry 3-10

Organic and Medicinal Chemistry 11-23

Physical and Materials Chemistry 24-25

Structural and Computational Chemistry 26-27

Food and Wine Science

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1. Sulfur compounds profiling in selected yeast strain fermentations

Supervisor: Bruno Fedrizzi, Room 301.422 ext. 88473 email [email protected]

Fermentative sulfur compounds (FSCs) are pivotal species in defining, tuning and spoiling wine

quality. Their contribution to the overall wine bouquet is controversial and it seems to have both

negative and positive implications1. As the name suggests these molecules are generated from the

yeast metabolism, putatively from amino acids or amino acidic precursors. Nowadays, the most

important sulfur compounds can be quantified at the School of Chemical Sciences2; this information

could be successfully combined with the yeast genetic knowledge generated at the School of

Biological Sciences in order to further our understanding on the formation of these species.

Image adapted from Ljungdahl and Daignan-Fornier3

The project will aim at profiling FSCs in the fermentation trials carried out at SBS with particular

yeast strains for which the genetic analyses are currently undergoing. Gas chromatography coupled

to mass spectrometry will be applied to detect and quantify these molecules. Furthermore the

student shall develop an analytical method to analyse the main amino acids present in grape and

wine via HPLC-DAD and analyse the same sample set.

1. B. Fedrizzi, F. Magno, D. Badocco, G. Nicolini, G. Versini, J. Agric. Food Chem. 2007, 55. 10880-

10887, DOI: 10.1021/jf072145w; M. Ugliano, B. Fedrizzi, T. Siebert, B. Travis, F. Magno, G. Versini, P.

A. Henschke, J. Agric. Food Chem. 2009, 57. 4948-4955, DOI: 10.1021/jf8037693.

2. N. Dang Dung, L. Nicolau, S. I. Dykes, P. A. Kilmartin, Am. J. Enol. Vitic. 2010, 61. DOI:

10.5344/ajev.2010.10020; B. Fedrizzi, F. Magno, S. Moser, G. Nicolini, G. Versini, Rapid Commun.

Mass Spectrom. 2007, 21. 707-714, DOI: 10.1002/rcm.2893.

3. P. O. Ljungdahl, B. Daignan-Fornier, Genetics 2012, 190. DOI: 10.1534/genetics.111.133306.

mailto:[email protected]

Food and Wine Science

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2. Characterisation of milk antioxidants using cyclic voltammetry. Supervisor: A/Prof Paul Kilmartin, Room 301-529B, ext 88324, [email protected]

The antioxidants present in beverages can be quantified and information provided about their

reducing strength using the electrochemical technique of cyclic voltammetry. This technique has

been developed at the University of Auckland to profile wines, fruit juices, teas and coffees. In this

project, the voltammetry procedure will be applied to the antioxidants present in both the aqueous

and lipid fractions of milk. An examination of the most appropriate organic solvent for the extraction

of lipid soluble antioxidants will be made, along with the electrode conditions needed to make a

reliable quantification. Comparisons will be made with standard Food Science antioxidant assays,

and a selection of milks, including those fortified with antioxidant vitamins, will be surveyed.

1) P.A. Kilmartin, H. Zou and A.L. Waterhouse, “Correlation of wine phenolic composition vs.

cyclic voltammetry response”, American Journal of Enology and Viticulture 53 (2002): 294-302.

2) P.A. Kilmartin and C.F. Hsu, “Characterisation of polyphenols in green, oolong, and black teas,

and in coffee, using cyclic voltammetry”, Food Chemistry 82 (2003): 501-512.

3) O. Makhotkina and P.A. Kilmartin, “Uncovering the influence of antioxidants on polyphenol

oxidation in wines using an electrochemical method: cyclic voltammetry”, Journal of

Electroanalytical Chemistry 633 (2009) 165-174.

4) O. Makhotkina and P.A. Kilmartin, “The phenolic composition of Sauvignon blanc juice

profiled by cyclic voltammetry”, Electrochimica Acta (2012) in press.


Inorganic and Green Chemistry

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3. Towards new molecular materials: exploring macrocycles for supramolecular chemistry

Supervisor: Professor Penny Brothers, Room 301-627B, ext 88281, [email protected]

Like a bathroom wall, a tiled plane is covered with no gaps or

overlaps. This is easy to achieve using regular tiles like

triangles, squares or hexagons but impossible using only

shapes with 5-fold symmetry. In the 1960s Roger Penrose

approached this intriguing mathematical problem by using

tiles of more than one shape, either rhombic or pentagonal,

and the resulting patterns are called Penrose tilings. Similar

tilings have been observed in ancient Islamic architecture.

Penrose tiling on a surface has never been achieved using

molecules and we are interested in exploring this using 5-fold symmetric macrocycles as the

pentagonal tiles. Examples are shown below. These molecules have in common 5-fold symmetry

and functional groups (X) which can be designed to provide supramolecular links which will be

essential to holding the tiles together in the correct pattern. The first step required to investigate

using these molecules for Penrose tiling will be to synthesise them containing appropriate functional

groups (X) which can be used for the intermolecular links. An example would be carboxylate groups

(–COOH) which can interact through hydrogen bonding. The synthesis of these molecules will be the

target of the project.

(a) (b) (c)

The project will provide experience in a range of organic and inorganic synthesis techniques carried

out in a research setting, and the techniques used to purify and characterise the resulting

compounds, including crystallisation, chromatography, NMR, IR and UV-vis spectrometry and the

preparation of crystals for X-ray crystallography. This project will be co-supervised by Dr David

Ware.

(a) Naumann, C. et al., Chem.-Eur. J. 2001, 7, 1637-1645. (b) Guieu, S. et al., Chem. Commun. 2011, 47, 1169-1171; Qin, B. et al., Org. Lett. 2008, 10, 5127-

5130. (c) Böhmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713-745.



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4. Cucurbiturils: “pumpkins” for supramolecular chemistry


Cucurbiturils are large macrocyclic molecules prepared by the condensation of glycouril with

formaldehyde. They form symmetrical, cylindrical rings incorporating different numbers of glycouril

monomers, with 5, 6, 7, 8, and 10 repeat units. They are named cucurbit[n]urils or CB[n] where n is

the number of monomers incorporated in the macrocycle. The name comes from the Latin name for

the pumpkin family, cucurbitaceae, because the molecules look somewhat like pumpkins.1

Cucurbiturils are widely used in supramolecular chemistry because the cavities have excellent

molecular recognition properties. More recently, it has been discovered that they can be

functionalised on the outside by replacing the C-H groups in the glycouril monomer by a range of

functional groups, which opens up the possibility of achieving supramolecular chemistry interactions

on the outsides of the cavities, and in particular controlling the interactions between cucurbituril

rings.

This is a new project in our laboratory which will begin by investigating published methods for the

synthesis of cucurbit[n]urils in order to understand how molecules with different values of n are

prepared. We will then investigate the synthesis of functionalised cucurbit[n]urils and look at how

ring-ring interactions might be controlled, for example using coordination chemistry techniques and

metal ions as the linkers.



compounds will include crystallisation, chromatography, NMR, IR and UV-vis spectrometry and the


Ware.

1. http://upload.wikimedia.org/wikipedia/en/d/d8/Models_of_cucurbiturils.jpg


http://upload.wikimedia.org/wikipedia/en/d/d8/Models_of_cucurbiturils.jpg


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5. Towards new molecular materials: applications of fluorescent boron complexes


BODIPYs are fluorescent dyes based on a boron dipyrrin molecule. They are widely used as laser

dyes and as fluorescent markers in biomedical applications. Our research group has experience in

the preparation of boron porphyrins and corroles, which can be considered to contain two BODIPY

units linked into a macrocycle.

BODIPY boron

porphyrin

Boronic acid complexes are complexes have potential as sugar sensors, through formation of B-O-C

bonds linking the boron and sugar groups. The boron must also have a signalling group attached

which is turned on (or off) when the sugar is attached. The use of fluorescent BODIPY derivatives as

the signalling group is a new idea. Although researchers have appended BODIPYs to sugar sensors

they have not directly investigated the interaction of a sugar with a BODIPTY derivative.

boronic acid sugar boronic acid-sugar complex:

activates “signal” on boron

This project will involve synthesis of molecules related to BODIPY and to porphyrins and

investigation of their chemistry with boron. The aim will be to develop new compounds which can

be examined for their fluorescent properties and interactions with sugars, or small diol molecules

used as models for sugars.





Ware.



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6. Towards new molecular materials: white light emitting polymers


White light emitting polymers are useful, in photovoltaics and in memory devices. In lighting

applications they are useful as white light LEDs, for LCD and TV backlighting and solid state large area

lighting. White light can be emitted by using a mixture of emitting materials of different colours, e.g.

blue, red, green, and orange. These emitters need to be either incorporated into a polymer

backbone or grafted into a polymer support.

Lanthanide complexes with suitable ligands are known to be strongly emissive, for example as

shown in the acac/bipy derivative shown below. The europium (Eu) complex fluoresces red while

the terbium (Tb) complex is green.

The project will involve preparing several simple lanthanide complexes that are known to be

emissive. The complexes will then be functionalized so that they can be attached to a polymer

backbone. Preparation of simple acrylate polymers will also be investigated.




preparation of crystals for X-ray crystallography. This project will be co-supervised by Dr Jianyong Jin

and Dr David Ware.

http://www.gelightingsolutions.com/Indoor/id-

456789e/Lumination_LED_Luminaires_-_Troffer



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7. Carbon monoxide binding from CO releasing molecules (CORMs) to metalloproteins

Supervisor: A/Prof. Christian Hartinger, Room 301-631B, ext 88220, [email protected] http://hartinger.wordpress.fos.auckland.ac.nz/

Carbon monoxide is an important gasotransmitter endogenously produced in higher organisms, including humans, with vasodilatory as well as cytoprotective activity. Since carbon monoxide as a gas is difficult to apply to patients and highly toxic when overdosed, there is a growing interest in the use of metal carbonyl complexes (CO releasing molecules, CORMs) as solid storage forms for CO, from which it can be released by either hydrolytic or photolytic processes. However, the speciation of CORMs under physiological conditions and the transfer kinetics of carbon monoxide from metal-carbonyl complexes to metalloprotein targets are largely unexplored. In addition, only a very small number of cellular target structures of CO have so far been identified and characterised at a molecular level. Thus, in this project the CO releasing properties of CORMs in presence of the protein myoglobin will be studied by UV-vis spectroscopy, liquid chromatography (LC) and mass spectrometric (MS) methods. This will allow discerning whether the metal-coligand fragments generated by the CO release will also bind to metalloproteins. This approach will eventually allow us to identify relevant biological targets of carbon monoxide signalling at a molecular level. Such a bottom-up approach will complement current, systemic investigations and thus significantly aid to the understanding of the biological activity of CO as a gasotransmitter and its potential therapeutic use in human medicine. The student will learn to apply modern separation, spectroscopic and mass spectrometric techniques in biological inorganic chemistry and how to analyse and interpret the data with regard to the biological action of CORMs. Furthermore, the methods developed can be applied in studies on the protein binding of anticancer-active metal complexes.

8. Ru-Arene Anticancer Chemotherapeutics: Delivery to the Tumour by Macromolecular Carriers

– “Drug targeting”

Supervisor: A/Prof. Christian Hartinger, Room 301-631B, ext 88220, [email protected] http://hartinger.wordpress.fos.auckland.ac.nz/

Metal-based anticancer agents are frequently used in the chemotherapy of tumourigenic diseases.

Their major drawbacks are severe adverse effects and resistance of tumours to the drug. In order to

overcome these problems, more selective accumulation of the drug compound in the tumour is

envisaged by developing drug targeting approaches. One option to achieve this goal is the coupling

of a cytotoxic moiety to a macromolecular carrier and exploiting the enhanced permeability and

retention (EPR) effect. The EPR effect allows macromolecules to enter and accumulate in tumour

tissue and therefore provides a means to locate the drug component in the area where it should

exert its tumour-inhibiting potency without affecting healthy tissue.


http://hartinger.wordpress.fos.auckland.ac.nz/


http://hartinger.wordpress.fos.auckland.ac.nz/


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Within this project a series of

organometallic compounds based on the

Ru-arene scaffold will be synthesised with

ligands based on functionalised pyridones

(see Figure). The pyridone moiety will carry

a maleimide group which reacts very

selectively with the thiol residue of cysteine.

The most abundant human serum protein,

i.e., human serum albumin (HSA), has a

single free thiol group (Cys34) that is aimed

to be selectively modified by maleimide-functionalised molecules. The reaction with biological thiols

will be followed by NMR spectroscopy as well as by separation methods and mass spectrometry.

The recruited student will gain experience in both organic and inorganic synthesis. The prepared

compounds will be purified using different techniques and characterised with state-of-the-art

analytical methods (NMR, IR and UV/vis spectroscopy, electrospray ionisation mass spectrometry

and if crystals can be obtained by X-ray diffraction analysis). Furthermore, the student will be

introduced to the drug development process and especially the hot topic of drug targeting.

9. Metallabenzenes

Supervisor: A/Prof. L. J. Wright (http://www.che.auckland.ac.nz/staffsites/WrightJ/index.html)

Room 301-627A, ext 88257; [email protected]

Metallabenzenes are compounds in which one of the CH groups of

benzene has been formally replaced by a transition metal with its ancillary

ligands. The first example of a metallabenzene, an osmabenzene, was

synthesised at the University Auckland. We are interested in exploring the

syntheses, reactivity and bonding of this intriguing new class of

compounds and have an active research programme in this area.

Although these compounds are interesting in their own right, information

gained about them may also have relevance to materials such as metal-

substituted carbon nano-tubes and conducting polymers. Summer

Scholarship projects will involve either investigation of the reactivity of a

new amino-substituted metallabenzene that we have recently prepared

(isolated in the ammonium form, see Figure) or investigation of routes to

new functionalised metallabenzenes that will serve as precursors for new

materials. The projects will enable experience to be gained in a broad

range of areas including synthesis, spectroscopy (especially NMR, IR,

ESMS), and X-ray crystallography.

http://www.che.auckland.ac.nz/staffsites/WrightJ/index.html



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10. New ligands for Metal Catalysts



Catalysis is widely recognised as one of the key areas in contemporary chemical endeavour. The

lower temperatures, higher selectivity, and in some cases chiral induction observed for transition

metal catalysed reactions are all features that are consistent with Green Chemistry principles. The

ancillary ligands attached to a metal catalyst play a crucial role in determining the properties and

stability of the catalytic system. Over the last 15 years there has been rapidly accelerating interest in

the development of new types of ligands that are applicable to a wide range of catalytic systems. N-

heterocyclic carbenes (NHCs) provide an example of one ligand

class that has recently attracted a very large amount of

international research effort. The overall aim of this project is to

develop new classes of ligands for metal catalysts that are

related to NHCs but have superior properties. One such class of

ligands are the pyridinium amidates (see Figure for a Pd

derivative). Appropriate metal complexes of these ligands will

be synthesised and the catalytic activities of the resulting complexes tested. Target catalytic

reactions initially will be olefin metathesis and C-C bond forming reactions. Two Summer

Scholarship projects are available in this area. One involves the synthesis and study of new carbon-

donor ligands and the other involves the synthesis and study of new nitrogen-donor ligands. In both

cases simple synthetic routes to the target ligands are available. Both projects will enable

experience to be gained in a broad range of areas including synthesis, spectroscopy (especially NMR,

IR, ESMS), analysis and X-ray crystallography.

11. Catalysts for Green Oxidations



Oxidation chemistry plays a central role in many key processes including fine chemical and

commodity chemical manufacture, bleaching, waste remediation and disinfection. The use of the

environmentally benign oxidants oxygen and hydrogen peroxide in these processes is very attractive,

but these oxidants usually react very slowly under ambient conditions. To make efficient use of

these oxidants appropriate oxidation catalysts are needed. In a joint Green Chemistry programme

with Carnegie Mellon University in the USA and Scion Ltd. at

Rotorua, we have developed a series of iron complexes that

efficiently catalyse hydrogen peroxide oxidations under

ambient conditions. One example of these compounds is

shown in the Figure. The Summer Scholarship project involves

the synthesis and study of an important new analogue of this

macrocyclic iron complex which we anticipate will have the

important properties of longer lifetime under operating






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conditions and the ability to activate hydrogen peroxide at neutral pH. The project will enable

experience to be gained in a broad range of areas including synthesis, spectroscopy (especially NMR,

IR, UV-vis, ESMS), and analysis.

12. pH-Triggered CO-Releasing Molecules with Targeted Pharmacological Activity

Supervisors: A/Prof.L. J. Wright and A/Prof. Christian Hartinger

[email protected], ex 88257, or [email protected], ex 83220

It has recently been established that carbon monoxide (CO) plays a key role as a gaseous messenger

in the human body. At very low concentrations CO has been shown to elicit protection and

beneficial outcomes against inflammation, apoptosis (including cancer cells), cell proliferation, and

hypertension. Accordingly, there is rapidly growing interest in the potential therapeutic applications

of CO. Since administration of CO gas through inhalation is not feasible because of its lack of

selectivity and high general toxicity when overdosed, there is a strong research drive to develop

water soluble transition metal (TM) compounds that can bind CO and release it inside the body in a

controlled way. Current CO-releasing

molecules (CORMs) of this type release CO

either by hydrolytic or photolytic processes.

There is a clear need for the development of

more sophisticated “triggers” for CO release

from CORMs that are activated by selective

tissue types. We are currently developing

special ligands for metal carbonyl complexes

that will respond to pH changes and trigger CO loss from the metal when they encounter slightly

acidic regions such as those found in solid tumours or in the heart after cardiac arrest. The project

will involve the synthesis of selected examples of these trigger ligands, the formation of metal

carbonyl complexes of these ligands and the study of CO release from these as a function of pH. The

project will enable experience to be gained in a broad range of areas including synthesis,

spectroscopy and analysis (especially using NMR, IR, UV-vis, ESMS and HPLC).

Organic and Medicinal Chemistry

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13. Synthesis of Ophiocerol, a novel anti-fungal macrocylic neolignan

Supervisor: Dr David Barker, Room 301-727B, ext 89703, [email protected]

Lignan natural products are one of the largest plant derived natural product families and many

members of the family have been found to bebiological active. They exhibit a wide range of activites

inclduing cytotoxicity, hepatoprotective, acting as α- or β-blocking agents useful in antidepression or

antihypertension therapy. Others exhibit antihyperglycemic properties and act as inhibitors of 5-

lipoxygenase.

Ophiocerol was recently isolated in minute amounts from the freshwater fungus Ophioceras

dolichostomum YMF1.00988. Ophiocerol was found to exhibit antifungal activity against several

plant pathogens but limited biological work was able to be carried out before the total isolated

sample was exhausted. The

carbon skeleton of ophiocerol is

unique and represents the first

naturally occurring example of a

novel dibenzo-1,6-

dioxacyclodecane ring carbon

framework. Also the absolute

stereochemistry of ophiocerol has

not been determined. This project

will aim to synthesize ophiocerol to determine its absolute stereochemistry and to provide more

material to allow a complete investigation of its biological properties.

14. Synthesis of the Lepadin family of bioactive alkaloids (with Prof. Margaret Brimble)


The Lepadin family of alkaloids are a family of cis-decahydroquinoline isolated from a number of

different marine sources (eg. Clavelina lepadiformis and Aplidium tabascum) (eg. Lepadins B and E

below). The lepadins possess a range of biological activities ranging from cytotoxicity, inhibitions of

kinases and antimalarial properties. This project will attempt to synthesis the key

decahydroquinoline using a one-pot multi-component reaction. This will efficiently construct the key

decahydroquinoline framework in a single step and allowing the synthesis of a number of natural

lepdadins and synthetic analogues.

Lepadin B

O

O

CO2Me

Br

NH2

Ph

N

CO2Me

O

Ph

NH

H

H

OH

O

O

HO

OH

OH

HO

Ophiocerol

O

HO

HO

OH

OH

HO

OMs

OP2

OP1

MgX

O

MeO

OH




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15. Synthesis of Novel Indole-2-caboxamide inhibitors of PLC- (with Dr. Jóhannes Reynisson)


Phospholipase C- (PLC-) is a promising biological target for anticancer drug therapy with

compounds binding to PLC- showing marked growth inhibition of haematological tumour cells. Biological screening has determined that compound with the thieno[2,3-b]pyridine ring system such as CCT196686 (compound 1 below) are potent compounds in both the biochemical and cell-based assays.

This project will involve the synthesise a number of analogues of CCT196686 to further probe the

ability of compounds of this structural type to inhibit PLC-. The student involved in this project will

also evaluate the compounds for their ability to bind to PLC- using advanced molecular modelling techniques, whilst their cytotoxicity against cancer cells with be measured at the National Cancer Institute.

N S O

HN

O NH2

Cl

CCT196686

Docking of CCT196686 to PLC

16. Synthesis of 1,1,-diaryl-butanol lignans via an unusual 1,4-diaryl rearrangement


The family Schisandraceae, consisting of Schisandra and Kadsura genera, is medicinally important. Many plants of this family are commonly used in Traditional Chinese Medicine for their diverse beneficial bioactivities. Many lignans from these plants possess anti-HIVantitumor, cytotoxic, antioxidant and antihepatotoxic effects. Recently discovered were the lignans Kadangustin J and K which have an uncommon 1,1-diaryl-butanol structure. We have recently synthesised kadangustin J using an unexpected aryl rearrangement and the aim of this project to further investigate the reaction and synthesise both natural 1,1-diaryl butanol lignans and their analogues.

TBDMSO

ArAr

OH

Ar

Ar

Oarylrearrangement

HO OMe

OMe

OMe

OMe

Kadangustin J

HO

X

Y

diarylbutanol

lignan analogues




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17. Synthesis of the Human Telomerase Inhibitors the Rubromycins as Anticancer Agents

Supervisor: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected] An important goal in devising novel treatments for cancer is the identification of targets that are uniquely and vitally important to cancer cells but not essential or even present in normal cells. Attacking this critical target would afford the desired selectivity by killing the cancer cells while leaving normal cells unaffected. Existing cancer therapies have generally not fulfilled this goal because the targets of most therapeutic agents are not unique to cancer cells. Telomeres are the natural ends of linear chromosomes, essential for maintenance of stable chromosomes and are important for maintenance of the cell cycle clock. Tumour cells typically have shortened telomeres that are maintained by the highly specialized telomerase enzyme. Elevated telomerase levels are found in almost all human cancers and levels frequently correlate with disease progression. The rubromycins are a unique class of antibiotics produced from a strain of Streptomyces that inhibit human telomerase. The novel aryl spiroketal ring system present in the rubromycins has been suggested to be the main structural feature responsible for the observed telomerase inhibition. This project therefore focuses on the synthesis of more potent and selective inhibitors of human telomerase based on β-and γ-rubromycin as lead structures, to find a malignant- cell-selective toxic molecule that will not harm normal cells. 18. Synthesis of Anti-Helicobacter Pylori Agents as Anti-ulcer Agents

Supervisor: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected] Recent studies have shown that the microaerophilic spiral-shaped Gram negative bacterium Helicobacter pylori that is present in the mucus layer of the stomach is a major cause of gastric and duodenal ulcers, and stomach cancer which can result from untreated ulcers. The natural product CJ-12,954 produced by Phanerochaete velutina, exhibits potent activity against Helicobacter pylori and is a lead compound for the treatment of ulcers. This project focuses on the first synthesis of CJ-12,954 and analogues thereof, in order to provide novel anti-ulcer agents. Compounds prepared will be evaluated for anti-Helicobacter Pylori activity by Prof John Fraser in the Faculty of medicine and Health Sciences. 19. Synthesis of Shellfish Toxins as Pharmacological Probes for the Treatment of Cardiovascular

and Neurodegenerative Diseases

Supervisor: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected]

The production of shellfish toxins (also known as phycotoxins) is associated with dinoflagellate blooms (“red tide” phenomenon) that can result in massive kills of fish and marine animals. During algal blooms the level of toxins within healthy shellfish can reach a level that is harmful to humans causing symptoms ranging from diarrhoea to extreme cardiovascular and neurotoxic effects at

O O

O

OH

O

CO2MeHOO

O

MeO

OH

-rubromycin

OMe

MeO

O

O

O O MeCJ-12,954





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exposures as low as a few parts per billion. One of our research programmes is directed towards the synthesis of the complex shellfish toxins the spirolides and the pectenotoxins. The chemical synthesis of these toxins and partial structures of these molecules provides compounds for the development of pharmacological probes for the activation of type L calcium channels. Blockage of L-type calcium channels by drugs is exploited as a therapeutic principle to treat cardiovascular disorders such as hypertension and angina pectoris. 20. Synthesis of Pyranonaphthoquinone Antibiotics as Anticancer Agents and Agents to Treat the

Common Cold (with Dr Jonathan Sperry and The Scripps Research Institute) Supervisors: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected] The pyranonaphthoquinone family of antibiotics exhibit inhibitory activity against a variety of pathogenic fungi, yeast and Gram-positive bacteria. They also act as bioreductive DNA alkylating agents via quinone methide intermediates thereby resulting in cross-linking of DNA strands which is, in turn, interfere with the cell replication process. This concept of bioreductive alkylation offers an exciting mechanism of drug action for the development of new anticancer agents that target hypoxic cancer cells which exist in very low oxygen conditions and are difficult to treat using standard therapies. One pyranonaphthoquinone antibiotic, thysanone, is a potent inhibitor of human rhinovirus 3C protease and is a promising lead for development of a therapeutic agent to cure of the common cold. 21. Synthesis of Acortatarins Isolated From Traditional Chinese Medicine to Provide a Drug

Discovery Platform Against Diabetic Nephropathy Supervisor: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected] Diabetic nephropathy (DN) is a major complication of diabetes and a leading cause of end-stage renal disease worldwide. Evidence has shown that the overproduction of reactive oxygen species (ROS) in renal cells plays an important role in the development and progression of DN. Therefore, inhibition of renal oxidative stress could have an important impact on the intervention of DN. Acortatarin A was isolated from the rhizome of Acorus tatarinowii Schott (Araceae) which has been widely used as a traditional Chinese medicine for treating central nervous system disorders. Acortatarin A was shown to inhibit ROS production in high-glucose-stimulated mesangial cells in a dose and time dependent manner. The bioactivity and its scarcity from its natural source make acortatarin A an interesting target for synthetic studies. This current project will focus on synthesising a range of analogues to access this important new spiromorpholine template of acortatarins for drug discovery platform directed towards the intervention of DN.

H

Me

O O

R3

Me

HO

O

OO

Me

Me

HO

MeMe

N

Spirolide A




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22. Synthesis of Peptide Components for Use in Human Vaccines (with Prof Rod Dunbar, School of Biological Sciences)

Supervisor: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected] The immune system often recognises tumour cells and infectious agents from the unique peptides found on their surfaces associated bound to MHC (major histocompatibility complex) molecules. Synthetic peptides of similar structure can be used as vaccines to stimulate the immune system. In the present project, new components for human vaccines will be synthesized and tested in vitro for biological activity on human cells. Vaccines based on synthetic peptides present a practical solution to many of the problems encountered with other forms of vaccines aimed at stimulating “cytotoxic T lymphocytes” or CTL. Simple peptide vaccines, often comprising only the 9-10 amino acid peptide recognised by CTL, have proven weakly stimulatory in humans, but there is a great need for improvement in potency and stability of peptide vaccines. The current project aims to build more complex vaccine constructs that incorporate multiple small peptides recognised by CTL together with additional sequences to target the vaccine correctly to immune cells and improve immune recognition. These more complex vaccine components are more likely to exhibit greatly improved potency against disease. 23. Synthesis of Antimicrobial Peptides and Peptide Mimics (with Dr Amanda Heapy in the Institute

for Innovation in Biotechnology)

Supervisor: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected] The synthesis of natural product peptides containing unnatural amino acids, depsipeptides, cyclic peptides and natural proteins that exhibit potent antimicrobial activity, is one theme in our peptide chemistry laboratory. Analogues of the natural peptides are then synthesised to either simplify or stabilise the molecule with the aim of producing a more potent analogue. The ability to combine contemporary organic reactions such as cross-metathesis, “peptide stapling,” click chemistry, thiol-ene chemistry and the preparation of unnatural amino-acid building blocks with modern solid phase synthesis methods provides a powerful peptidomimetic platform to combat the problem of increasing resistance to existing antibiotics. Analogues of natural products that are antimicrobial peptides will be prepared and evaluated for their antimicrobial activity. 24. Synthesis of AGE Peptides as Agents to Study Metabolic Disorders (with Prof. Garth Cooper,

Maurice Wilkins Centre for Molecular Biodiscovery) Supervisor: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected] Advanced glycation end-products (AGEs) are unnatural amino acid derivatives that form in the reaction of sugars with lysine and arginine side-chain residues in proteins. AGEs have been implicated in the pathogenesis of diabetes mellitus and AGEs were shown to bind transition group metals. However, the underlying molecular mechanisms that link these processes remain unclear. Collagen is the most abundant protein in vertebrates and its long-lived nature makes it susceptible to glycation. The aim of this project is to prepare chemical probes in which AGEs are incorporated





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into collagen model peptides (CMPs) to study the interaction between peptide bound AGEs and transition metal ions and the factors affecting the structure of collagen. 25. Synthesis of Preptin Analogues for the Treatment of Diabetes and Osteoporosis (with Prof.

Garth Cooper and Prof Jill Cornish, Maurice Wilkins Centre for Molecular Biodiscovery, (with Dr Amanda Heapy in Institute for Innovation in Biotechnology)

Supervisor: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected] Preptin is a peptide hormone originally isolated from the secretory granules of cultured pancreatic islet cells. It was shown to be co-secreted with insulin and enhance glucose-induced secretion of insulin in rat islet cells. It is of considerable interest as this may comprise another means of controlling the elevated blood glucose seen in the diabetic state. The aim of this project is to engineer the native preptin peptide to improve its metabolic stability, improve peptide activity, enhance membrane permeability and enhance receptor selectivity. Cyclic preptin analogues will be prepared using Ring Closing Metathesis technology to provide robust, chemically inert and constrained “carba” bridge structures with improved pharmacological effects. Recently, the importance of nutritional hormones in maintaining skeletal health has also been recognized. This is reflected in the lower prevalence of osteoporosis in those with obesity. Preptin is known to exhibit to have effects on bone cells in vitro and in vivo and is anabolic to osteoblasts ence analogues of preptin will also be tested for their ability to act as agonists for osteoblast formation. 26. Structure aided design of broad range inhibitors of hrv 3c protease

(In collaboration with Prof. J.Fraser and the Scripps Research Institute, USA) (with Dr Jonathan

Sperry)

Supervisor: Distinguished Professor Margaret Brimble Room 301- 731B, Phone number: 9238259, Email: [email protected]

Human rhinoviruses (HRVs) are the major cause of the common cold in the Western world and

currently only symptomatic treatment is available to medicate rhinoviral infections. In addition to

being attributed to the common cold, HRV infections are associated with

acute and chronic bronchitis. The enzymatic activity of HRV 3C protease

is required to produce mature viral proteins and functional viral

enzymes essential for completion of viral replication. We have an

ongoing interest in the design and synthesis of inhibitors of 3C-protease

that are subsequently tested for bioactivity at the Faculty of Medical and

Health Sciences at the University of Auckland. Particularly promising

analogues will be sent to the Scripps Research Institute, USA for crystallisation studies with purified

3C-protease enzyme in order to gauge the exact site of binding to aid in our understanding of 3C-

protease inhibition.




17

27. The Number of Small Organic Compounds in Clinical use. How many are there?

Supervisor: Dr Jóhannes Reynisson, Room: 301-433, ext 83746, [email protected] Using the physicochemical properties of known drugs in clinical use is utilised for designing new

drugs. [1, 2] The number of small organic molecules used in clinical settings is not the same in each

country and depends on the relevant regulatory agencies, i.e., it is known that the European Medical

Agency has allowed more drugs to reach the clinic compared to its US counterpart, the Food and

Drug Administration (FDA). An estimate of 1250 small molecules was recently published giving an

idea how many compounds there are in in clinical use. [3] In this project a comparison between the

numbers of drugs in different countries will be made. Furthermore, which drugs are universal and

which are specific to some regions. Finally, an analysis on the impact on therapeutic areas and

administration will be conducted.

1. Mirza, R. Desai, J. Reynisson, Eur. J. Med. Chem., 44 (2009) 5006-5011. 2. P. Axerio-Cilies, I.P. Castañeda, A. Mirza, J. Reynisson, Eur. J. Med. Chem., 44 (2009)

1128-1134. 3. J.P. Overington, B. Al-Lazikani, A.L. Hopkins, How many drug targets are there?, Nature

Rev. Drug. Dis. 5 (2006) 993-996. 4.

28. Exploiting bioactive natural products

Supervisor: A/Prof Brent Copp, Room 301- 729B, ext 88284 [email protected] Natural products continue to be the dominant inspiration for the development of new

pharmaceuticals, with recent analysis showing that 60% of anticancer and anti-infective new drug

registrations are of natural origin. My research group is interested in the discovery of new natural

products with potential applications against human diseases including inflammation, cancer and

neglected diseases such as tuberculosis, leishmania and malaria. We not only target the isolation of

biologically active natural products but we also undertake their synthesis or the synthesis of related

compounds to allow exploration of structure-activity relationships.

Very few of these natural products we discover will ever be of use as pharmaceuticals themselves

due to undesirable pharmacokinetic or toxicity problems. Such natural products can still be of use to

further understand biological processes, acting as probes or tools for biological chemistry studies.

We have identified two families of marine sponge natural products, discorhabdin C and

halenaquinone that exhibit potent biological activities by forming irreversible complexes with

cellular enzymes or receptors. We are interested in determining the protein targets of these natural

products – such studies can often identify new targets for drug discovery or uncover new

biochemical pathways in cells. To identify protein targets, we will make use of the Huisgen alkyne-

azide cycloaddition reaction, whereby an azide-functionalised natural product is allowed to react

with cellular protein targets, followed by subsequent reaction with a fluorescently labelled alkyne

probe. The resultant complex yields proteins that are fluorescently labelled, allowing for their

identification by proteomic analysis.




18

The aim of this summer project is to prepare a range of novel fluorescently labelled alkyne probes

that can be used for copper-free Huisgen labelling of live cells that will allow us to determine not

only the protein targets of bioactive natural products, but also their intracellular location.

29. Sustainable Organic Synthesis with Biomass-Derived Building Blocks

Supervisor: Dr Jonathan Sperry, Room 301- 731A, ext 88269 [email protected]

In response to the increasingly urgent issue of sustainability, lignocellulosic biomass has attracted

attention as a renewable and carbon-neutral energy source.1 For example, the acidic hydrolysis of

cellulose affords predominantly 5-(hydroxymethyl)-furfural (HMF), which we envisage can be used

as a starting material in a variety of chemical syntheses. This project will involve the investigation of

biomass-derived carbon building blocks such as HMF in the synthesis of industrially important

materials and complex organic molecules under green chemistry conditions.

1. Rinaldi, R.; Schuth, F.; ChemSusChem 2009, 2, 1096.

30. Synthetic Studies Towards the Anti-Cancer Natural Product Aspidophylline A


Cancer affects people of all ages and accounts for 13% of all human deaths worldwide. There is an

obvious demand for new anti-cancer agents due to multiple drug resistance (MDR) which can quickly

render current treatments useless. MDR is considered to be

the major obstacle to successful cancer chemotherapy.1,2

Aspidophylline A is a structurally unique pentacyclic alkaloid

that has been recently isolated from the Malayan Kopsia

singapurensis.3 Importantly, aspidophylline was found to

reverse resistance in drug-resistant KB cells, making it a promising lead compound for the treatment

of cancers displaying MDR. The miniscule amounts available from the natural source means a

chemical synthesis of aspidophylline A is essential for further biological evaluation. This summer

project will consider the total synthesis of aspidophylline A, with initial attention aimed at

developing an efficient synthesis of the bridged furoindoline moiety using a novel cyclization

strategy.

1. Kessel, D.; Botterill, V.; Wodinsky, I. Cancer Res. 1968, 938. 2. Biedler, J. L.; Riehm H. Cancer Res. 1970, 1174. 3. Subramaniam, G.; Hiraku, O.; Hayashi, M.; Koyano, T.; Komiyama, K.; Kam, T.-S. J. Nat.

Prod. 2007, 1783.




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31. Synthesis of Brousonetine using a C-H Functionalization Strategy


Carbon-hydrogen (C-H) bonds are among the least reactive in organic chemistry and C-H

functionalization is a reaction that selectively cleaves and/or modifies these otherwise inert C-H

bonds. Considering the high abundance of C-H bonds in organic molecules, their direct, selective

conversion to a C-C, C-O or C-N bond (amongst others) is a powerful

generic way to add valuable complexity to a compound without

resorting to functional group transformations and opens up several

new directions for organic synthesis in the 21st century.1 The natural

product brousonetine, a bis-hydroxyquinoline butyrolactone isolated

nearly 30 years ago2 has never been synthesized. This project will aim to carry out the first chemical

synthesis and structure confirmation of this alkaloid using an iterative C-H functionalization strategy.

1. For useful reviews, see: (a) Labinger, J. A.; Bercaw, J. E. Nature, 2002, 417, 507. (b)

Gutekunst, W. R.; Baran, P. S. Chem. Rev. 2011, 40, 1976. (c) Wencel-Delord, J.; Dröge, T.;

Liu, F.; Glorius, F. Chem. Soc. Rev., 2011, 40, 4740.

2. Gunatilaka, A. A. L.; Surendrakumar, S.; Thomson,, R. H. Phytochemistry. 1984, 23, 929.

32. Synthesis of Natural Sunscreens


The ongoing health concerns associated with the use of sunscreen cosmetics necessitates research

into viable alternatives.1 Several natural products are known to act as natural suncreens, protecting

the host organism from the harmful effects of solar radiation.2 One fascinating example are the

hipposudoric and norhipposudoric acids, two compounds secreted by hippos that have recently

shown to protect the animal from the effects of UV-A radiation.3 The bright colour of these

compounds has also provided an explanation for the ‘blood sweat’ seen on the skin of these animals.

This project will be concerned with the total synthesis and stability investigations of the

hipposudoric and norhipposudoric acids (and analogues).4

1. (a) Hayden, C. G. J.; Roberts, M. S.; Benson, H. A. E. Lancet 1997, 350, 863. (b) Cross, S. E.;

Jiang, R.; Benson, H. A. E.; Roberts, M. S. J. Invest. Dermatol. 2001, 117, 147. (c) Kunisue,

T.; Chen, Z.; Louis, G. B.; Rajeshwari, S.; Hediger, M.; Sun, L.; Kannan, K. Environ. Sci.

Technol. 2012, 46, 4624.


http://www.sciencedirect.com/science?_ob=RedirectURL&_method=outwardLink&_partnerName=27983&_origin=article&_zone=art_page&_linkType=scopusAuthorDocuments&_targetURL=http%3A%2F%2Fwww.scopus.com%2Fscopus%2Finward%2Fauthor.url%3FpartnerID%3D10%26rel%3D3.0.0%26sortField%3Dcited%26sortOrder%3Dasc%26author%3DGunatilaka,%2520A.A.Leslie%26authorID%3D7006219520%26md5%3Dbda57dc7034b1eec813d062ba0d9599f&_acct=C000011498&_version=1&_userid=140507&md5=18eabcda2357c3a3181c3034af5c7b11

http://www.sciencedirect.com/science?_ob=RedirectURL&_method=outwardLink&_partnerName=27983&_origin=article&_zone=art_page&_linkType=scopusAuthorDocuments&_targetURL=http%3A%2F%2Fwww.scopus.com%2Fscopus%2Finward%2Fauthor.url%3FpartnerID%3D10%26rel%3D3.0.0%26sortField%3Dcited%26sortOrder%3Dasc%26author%3DSurendrakumar,%2520Sivagnanasundram%26authorID%3D11139773500%26md5%3D526592335210fe5e606a5c2fd7de8261&_acct=C000011498&_version=1&_userid=140507&md5=37d0387ee4fb97ef3769520991fe8658

http://www.sciencedirect.com/science?_ob=RedirectURL&_method=outwardLink&_partnerName=27983&_origin=article&_zone=art_page&_linkType=scopusAuthorDocuments&_targetURL=http%3A%2F%2Fwww.scopus.com%2Fscopus%2Finward%2Fauthor.url%3FpartnerID%3D10%26rel%3D3.0.0%26sortField%3Dcited%26sortOrder%3Dasc%26author%3DThomson,%2520Ronald%2520H.%26authorID%3D11140698700%26md5%3Dc66e69c111baf70610350d4c38462586&_acct=C000011498&_version=1&_userid=140507&md5=48854a10c5974e22f70fe0a151e9241a

http://en.wikipedia.org/wiki/Tetrahedron_Letters



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2. (a) Cockell, C. S.; Knowland. J. Biol. Rev. 1999, 74, 311. (b) Siezen, R. J. Microb. Biotech.

2011, 4, 1; (c) Balskus, E. P.; Case, R. J.; Walsh, C. T. FEMS Micobiol. Ecol. 2011, 77, 322. (d)

Gao, Q.; Garcia-Pinchel, F. Nat. Rev. Microbiol. 2011, 9, 791.

3. Saikawa, Y.; Hashimoto, K.; Nakata, M.; Yoshihara, M.; Kiyoshi Nagai, K.; Ida, M.; Komiya, I. Nature. 2004, 429, 363.

4. For previous work on natural sunscreens in our laboratory, see: (a) Wang, C.; Sperry, J. Synlett

2012, 1824. (b) Wang, C.; J. Sperry, J. Org. Lett, 2011, 13, 6444.

33. Synthesis of Thysanone Analogues as Inhibitors of HRV 3C Protease (with Professor M. A.

Brimble)


Human rhinoviruses (HRVs) are the major cause of the common cold in the Western world and

currently only symptomatic treatment is available to medicate rhinoviral infections. In addition to

being attributed to the common cold, HRV infections are associated with acute and chronic

bronchitis.1 It is estimated the total economic impact of cold-related work loss exceeds $20 billion

annually in the United States alone and the quest to discover efficacious therapeutic agents of HRV

infections continues to be of major pharmaceutical interest.1,2

The project will involve the design and synthesis of

analogues of the selective 3C-protease inhibitor

natural product thysanone3,4 which will be

subsequently tested for improved bioactivity using

our in house developed assay.5 Potent analogues will be sent to the Scripps Research Institute, USA

for crystallisation studies with the target enzyme and to the University of Alberta for NMR studies in

order to gauge the exact site of binding to aid in our understanding of 3C-protease inhibition by the

thysanone class of compounds.

1. Couch, R. B. in Fields Virology 713. Raven Publishers, Philadelphia, 1996 2. Binford, S. L. et al. Antimicrob. Agents Chemother. 2005, 619. 3 Singh, S. B. C.; Ball, R. G.; Smith, J. L.; Dombrowski, A.W.; Goetz, M. A. Tetrahedron Lett.

1991, 5279 4. (a) Sperry, J.; Yuen, T. Y.; Brimble, M. A. Synthesis 2009, 2561. 5. Schünemann, K.; Connelly, S.; Kowalczyk, R.; Sperry, J.; Wilson, I. A.; Fraser J. D.; Brimble,

M, A. Bioorg. Med. Chem. Lett. 2012, 5018

34. Hybrid Antimicrobial Peptides Targeting Bacterial Biofilms

Supervisor: Dr. Viji Sarojini, Room 301-727A, Ext: 83387, [email protected]

Combat Antimicrobial Resistance’ was the theme of the World Health Day 2011, underpinning the

global need to develop novel drugs against multidrug resistant (MDR) microbes. Human pathogens

such as P. aeruginosa and M. tuberculosis form MDR biofilms

which evade treatment by host defence mechanisms and

antibiotics. Antimicrobial Peptides (AMPs) that form part of

innate immunity in all forms of life are attractive


http://www.ncbi.nlm.nih.gov/pubmed?term=Sch%C3%BCnemann%20K%5BAuthor%5D&cauthor=true&cauthor_uid=22763202

http://www.ncbi.nlm.nih.gov/pubmed?term=Connelly%20S%5BAuthor%5D&cauthor=true&cauthor_uid=22763202

http://www.ncbi.nlm.nih.gov/pubmed?term=Kowalczyk%20R%5BAuthor%5D&cauthor=true&cauthor_uid=22763202

http://www.ncbi.nlm.nih.gov/pubmed?term=Sperry%20J%5BAuthor%5D&cauthor=true&cauthor_uid=22763202

http://www.ncbi.nlm.nih.gov/pubmed?term=Wilson%20IA%5BAuthor%5D&cauthor=true&cauthor_uid=22763202

http://www.ncbi.nlm.nih.gov/pubmed?term=Fraser%20JD%5BAuthor%5D&cauthor=true&cauthor_uid=22763202

http://www.ncbi.nlm.nih.gov/pubmed?term=Brimble%20MA%5BAuthor%5D&cauthor=true&cauthor_uid=22763202

http://www.ncbi.nlm.nih.gov/pubmed?term=Brimble%20MA%5BAuthor%5D&cauthor=true&cauthor_uid=22763202

http://www.ncbi.nlm.nih.gov/pubmed/22763202



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alternatives to conventional antibiotics to combat antimicrobial resistance. Our screening program in

the past couple of years has been successful in identifying short peptides and small molecules with anti-

biofilm activity. In this project we aim to create synergy between short antimicrobial peptides and

organic scaffolds to generate novel hybrid peptides with efficacy against P. aeruginosa and M.

tuberculosis biofilms. Design and synthesis of the peptide hybrids, in vitro screening against P.

aeruginosa and M. tuberculosis and NMR studies on promising candidates will be carried out. This

project will involve collaboration with researchers at the School of Biological Sciences and FMHS.

35. Cell Penetrating Peptide Nanoparticles


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 A/Prof Jadranka Travas-

Sejdic.

36. De novo Designed Models of Protein β-sheets


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 misfunction

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




22

into higher order structures will be investigated using multi-dimensional NMR and circular

dichroism.

37. Synthetic Peptides for Preserving Texture in Frozen Foods


Considerable international interest is focused on understanding the antifreeze properties exhibited

naturally by certain organisms, because of their potential applications in cryoprotection. These are

attributed to antifreeze proteins (AFPs) that 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.

38. Studies towards Cyclic Antimicrobial Peptides against Food-Borne Pathogens


Development of effective therapeutics to treat multidrug-resistant (MDR) Gram-negative bacteria is

a challenge. Cationic antimicrobial peptides (CAPs) are promising therapeutics to address the

challenge of bacterial resistance. However, susceptibility to proteolytic

degradation in vivo, high production costs and toxicity to eukaryotic cells

remain unresolved problems and warrant the development of novel CAPs

with improved activity profiles. Introduction of conformational constrains

such as head-to-tail cyclization, conjugation to aliphatic chains as well as the

use of sterically hindered amino acids are used to enhance the selectivity of

CAPs towards bacterial pathogens. In this project, linear, cyclic and lipid-

conjugated versions of short cationic antimicrobial peptides will be developed

for anti-bacterial screening particularly against E. coli O157:H7 and Listeria monocytogens, the food-

borne pathogens of major public health concern. We aim to generate the minimum inhibitory

concentration (MIC) and minimum bactericidal concentration (MBC) of the peptides against these

pathogens to identify lead candidates for further investigations.




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39. Synthetic Studies towards Biocompatible Adhesive Proteins


Medical adhesives form an important component of the surgical toolbox and provide an interesting

area for research and development. Their applications range from attaching skin grafts onto burn

patients, bacterial inhibition in combination with known antibiotics and synergistic treatments for

diabetes. Naturally occurring adhesive proteins, particularly those produced by marine mussels and

barnacles, have attracted the attention of scientists due to their incredible adhesive strength and

biocompatibility. However, inadequate supply of naturally occurring adhesive proteins has

hampered research efforts directed towards understanding their unique properties. Synthetic

peptide analogues provide a viable alternative to these rare natural bioadhesive proteins. Mefp-5 is

the most recently discovered adhesive protein from marine mussles. Extensive post-translational

modifications in Mefp-5 are thought to provide stronger binding forces making it potentially a better

substitute to existing medical adhesives. The aim of this project is to chemically synthesise relevant

fragments of Mefp-5 and study their adhesive properties to various surfaces like medically relevant

metals, Teflon and other plastic under different temperatures and moisture conditions. The peptides

will be synthesized by Solid Phase Peptide Synthesis (SPPS) and purified by High Performance Liquid

Chromatography (HPLC). Evaluation of the adhesive property of the peptide analogues to various

surfaces will be explored in collaboration with the Faculty of Engineering, UoA.


Physical and Materials Chemistry

24

40. Conducting Polymers

Supervisor: A/Prof Paul Kilmartin, Room 301-529B, ext 88324, [email protected]

Conducting polymers are of considerable interest as plastics that conduct electricity. Their discovery by researchers including the New Zealander Alan MacDiarmid led to the award of the Nobel Prize in Chemistry in 2000. At the University of Auckland we have demonstrated that conducting polymers such as polyaniline are very efficient at scavenging free radicals and in this sense act as solid antioxidant materials. Polyanilines have also been blended with conventional plastics such as polyethylene, to obtain mechanical robust films with effective antioxidant properties [1-4]. In this project a range of polyethylenes, from low density through to high density, will be compared for their compatibility for blending with granular polyaniline, including retention of useful mechanical properties, and maximizing blend antioxidant effects. Important considerations such as leaching from the blends and oxygen permeability will also be tested.

ESEM micrograph of a cryo-fractured cross-sectional surface of low density polyethylene with the inclusion of 15% polyaniline [4]

http://www.hybridpolymers.auckland.ac.nz/uoa/home

www.perc.auckland.ac.nz

1. A.V. Nand, S. Ray, A J. Easteal, G.I.N. Waterhouse, M. Gizdavic-Nikolaidis, R.P. Cooney, J. Travas-Sejdic and P.A. Kilmartin, “Factors affecting the radical scavenging activity of polyaniline”, Synthetic Metals 161 (2011) 1232-1237.

2. A.V. Nand, S. Ray, J. Travas-Sejdic and P.A. Kilmartin, “Characterization of polyethylene terephthalate/polyaniline blends as potential antioxidant materials”, Materials Chemistry and Physics 134 (2012) 443-450

3. C.F. Hsu and P.A. Kilmartin, “Antioxidant capacity of robust polyaniline-ethyl cellulose films”, Reactive and Functional Polymers (2012) in press.

4. A.V. Nand, S. Ray, J. Travas-Sejdic and P.A. Kilmartin, “Characterization of antioxidant low density polyethylene/ polyaniline blends prepared via extrusion”, Materials Chemistry and Physics (2012) in press.

41. Switchable Smart Surfaces Based on Conducting Polymer Brushes

Supervisors: Assoc. Prof. Jadranka Travas-Sejdic and Dr. Jenny Malmstrom Room 301-527B, ext 88272, [email protected] Smart surfaces with reversible switchable properties (such as wettability, charge and confomation) are of great interest for applications in materials science, sensors and biology.

In this project we are developing smart switchable surfaces based on polyelectrolyte brushes grafted from conducting polymers that will be able to reversibly switch from an extended to a collapsed


http://www.hybridpolymers.auckland.ac.nz/uoa/home

http://www.perc.auckland.ac.nz/

mailto:%[email protected]

Physical and Materials Chemistry

25

state upon application of an electrical stimuli. This change is expected to lead to differences in protein and cell adhesion to the interfaces. The project involves synthesis of functionalized monomers of conducting polymers, electropolymerization of the conductive polymer backbone and subsequent surface initiated growth of polymer brushes from the conducting polymer via controlled radical polymerization processes. Work will be undertaken to vary the grafting density and length of the grafted brushes and material produced will be used to study the effect of these parameters on switching of cell adhesion. The project will suit a summer student with a background in materials science and organic synthesis.

42. Calculations of ionisation potentials and spin-charge distribution for novel conducting polymer monomers

Supervisors: Assoc. Prof. Jadranka Travas-Sejdic and Dr Jóhannes Reynisson Room 301-527B, ext 88272, [email protected]

We work on design of novel conducting polymers with various functional, stimuli-responsive and electric properties for applications including electronics, microfluidics, self-cleaning surfaces and biomedical applications.

In this collaborative project between Dr Jóhannes Reynisson and A/Prof. Jadranka Travas-Sejdic we will model monomers of conducting polymers of various structures and functional groups and side chains, in solvents and without solvents, in order to calculate their electronic structure. This will be done by means of Density functional theory (DFT) predictions. In particular, the electron affinities (EA) and ionisation potentials (IP) will be calculated and the charge - spin distributions of the radical ions will be analysed using the Mulliken and natural bond order theory (NBO). The calculated structure will guide future design of novel conducting polymer materials.

43. Extending the pH-stat approach: from polyaniline to nanocomposites

Supervisors: Dr Zoran Zujovic and Assoc. Prof. Jadranka Travas-Sejdic Room 301-527B, ext 88272, [email protected], [email protected]

The conducting polymer (CP) polyaniline (PANI), a leading material in a field of organic conductors for nanotechnology, has been used in a number of our studies. Interest in nanostructured CPs stems from their potential applications in sophisticated micro- and nano-electronic circuit components. It is well established that the physical and chemical properties of nanomaterials are highly dependent on their morphology. Apart from other reaction conditions, such are concentrations, temperature, type of acid and/or surfactant the structural and morphological homogeneity of PANI nanostructures dramatically depends on the pH, which changes during the falling- pH reaction. Therefore, there is a need for an approach where all reaction parameters can be kept under control yielding a product with uniform morphological and structural characteristics, leading to improved chemical and physical properties.

The morphology and structure of the self-assembled PANI nanostructures will be controlled by the pH-stat approach to nanocomposites and by introducing different templates (for instance ZnO, TiO2,

WO3, noble metal particles, etc.) during the PANI polymerization. In this way we will selectively produce and characterize various nanocomposites of improved purity and defined morphology. These can be used in plastic electronic devices such as chemical and biosensors, photo-sensitive devices such as solar cells, LED screens, digital camera detectors, etc.




Structural and Computational Chemistry

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44. Computational Investigations On Transition Metal Chelate Complexes

Supervisor: Dr Tilo Söhnel, Room 436, ext. 89722, email: [email protected]

Polyamines like triethylenetetramine (TETA) have a wide range of biological activities, which makes them interesting applicants especially in human biology. Cardiac disease is by far the most common cause of death amongst diabetic patients. It was shown that treatment with TETA, a selective Cu(II) chelator, can lead to profound improvements in the structure and function of the diabetic heart. Two metabolites of TETA, N1-monoacetyltriethylenetetramine (MAT) and the N1,N10-diacetyltriethylenetetramine (DAT) that also show Cu(II) chelating properties were identified. TETA and its metabolites are ambivalent and multidentate ligands, which can form a variety of open chain, macrocyclic and three-dimensional architectures. To understand Cu(II) complexation by TETA, as well as to obtain more information about the selectivity and binding of other metals, computational calculations at the DFT level of theory will be performed. The program Gaussian09 will be used to run these calculations with different basis sets and DFT functionals.

Me2+

45. The Chemical Transport and Characterisation of the Solid Solution of Cu2V2O7 and Co2V2O7.

Supervisor: Dr Tilo Söhnel; Room 436, ext. 89722, email: [email protected]

This project is in the field of solid-state materials and deals with the preparation and characterisation of vanadium-compounds with mixed transition metal content. Vanadium oxides show a large variety of crystal structures where the main building blocks are various extended units of vanadium–oxygen polyhedra, from low-dimensional (chains, sheets) to more complex three- dimensional blocks. These vanadium oxides show an impressive variety of functional properties whose origin is closely related to the structural and electronic peculiarities of the compounds. Therefore, they are widely used as advanced materials like phosphors, optical switches, chemical sensors, catalysts, in solid-state batteries.

The goal is to prepare solid solutions of Cu2V2O7 and Co2V2O7 to study the influence of doping on electric and magnetic properties on single crystals. These compounds are known to show different and complex magnetic arrangements and dielectric behavior at low temperatures. For the preparation a number of different methods will be applied, ranging from classical high-temperature sintering to chemical transport reactions for the preparation of single crystals. Especially chemical transport reactions have been proven to be a very successful technique for the preparation of highly pure single crystals in many different systems, which is essential for the study of the physical properties.


Structural and Computational Chemistry

27

46. Photocatalytic Production of Hydrogen from Biofuels over Au/TiO2 Catalysts

Supervisor: Dr. Geoff Waterhouse, Room 301-441, ext. 87212, [email protected]

Hydrogen-powered fuel cells, electrochemical devices that combine hydrogen (H2) and oxygen (O2) to produce electricity, water and heat, are increasingly being used for commercial, industrial and residential power generation because of their high energy efficiency and their extremely low level of greenhouse gas emissions. The need to find simple and inexpensive methods for hydrogen production, storage and distribution are major obstacles to the widespread implementation of fuel cell technologies for automotive and stationary power applications. The photocatalytic decomposition of biofuels, such as ethanol, glycerol or formic acid are promising future technologies for H2 generation. Our recent research has demonstrated that Au/TiO2 photocatalysts, comprising gold nanoparticles of diameter 1-5 nm dispersed on high surface area TiO2 supports, are highly efficient for H2 production from biofuels under UV irradiation.

Figure 1 – Photocatalytic H2 production from ethanol over a 1.5 wt% Au/TiO2 catalyst

As an extension of this exciting research, I am offering 2 summer student projects aimed at the development of novel and improved Au/TiO2 catalysts for biofuel photodecomposition. These projects support the development of a sustainable hydrogen-based energy economy, and will offer the successful applicants training in a wide range of modern synthetic and nanomaterial characterisation techniques.

References:

1. NADEEM, A.M., WATERHOUSE, G.I.N., IDRISS, H. The reactions of ethanol on TiO2 and

Au/TiO2 anatase catalysts. Catalysis Today, 182 (1), p16-24, 2012.

2. WATERHOUSE, G.I.N; MURDOCH, M; LLORCA, J; IDRISS, H. Ethanol photoreaction to

hydrogen over Au/TiO2 catalysts. Investigating the synergistic effect of nanoparticles,

International Journal of Nanotechnology, 9 (1-2), p113-120, 2012.

3. SCOTT, M; NADEEM, M.A; WATERHOUSE, G.I.N; IDRISS, H. Hydrogen Production from

Ethanol. Comparing Thermal Catalytic Reactions to Photo-catalytic Reactions. MRS

Proceedings, 2011, 1326: MRSS11-1326-F07-07. DOI:10.1557/opl.2011.1118.

4. WANG, X.D; WATERHOUSE, G.I.N; MITCHELL, D.R.G; PRINCE, K.R; CARUSO, R.

5. Noble Metal Modified Porous Titania Networks and Their Application as Photocatalysts,

ChemCatChem, 3 (11), 1763-1771, 2011.

MURDOCH, M; WATERHOUSE, G.I.N; NADEEM, M.A; METSON, J.B; KEANE, M.A; HOWE, R.F;

LLORCA, J; IDRISS, H. The effect of gold loading and particle size on photocatalytic hydrogen

production from ethanol over Au/TiO2 nanoparticles. Nature Chemistry, 3 (6), p489-492,

2011.

0.0E+00

5.0E-04

1.0E-03

1.5E-03

2.0E-03

2.5E-03

3.0E-03

3.5E-03

4.0E-03

4.5E-03

0 20 40 60 80 100 120 140

MO

L o

f H

2

time (min)

Binding Energy (eV)

Inte

nsi

ty (

arb

itra

ry u

nit

s)

Au/TiO2

Au metal

X 0.025

Au4f3/2 Au4f5/2

S.O.S. =3.7 eV

83.6 eV84.0 eV
