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School of Chemical Sciences
5th Annual Research Showcase
12th June 2013
Programme & Book of Abstracts
2
Organising Committee
Dr Jianyong Jin (Chair)
Dr David Barker
Mr Hugo Fong
Dr Mandy Herbst‐Johnstone
Ms Min‐Young Lee
Dr Vijayalekshmi Sarojini
Dr Peter Swedlund
School of Chemical Sciences The University of Auckland Private Bag 92019 Auckland 1142 New Zealand
Phone 64-9-373-7599
Fax 64-9-373-7422
3
Programme
Page
Organising Committee 2
Acknowledgements 4
Programmes
Lecture Programme 10
List of Presentations 11
List of Posters 12
Lecture Abstracts 14
Poster Abstracts 21
Advertisements (Platinum and Gold Sponsors) 86
4
We gratefully thank our sponsors:
Platinum Sponsors
5
Platinum Sponsors
6
Gold Sponsors
7
Gold Sponsors
8
Silver Sponsors
9
Bronze Sponsors
10
Programme
Morning Session
9:00 – 9:10 Welcome
9:10 – 9:40 Two minute talks
9:40 – 10:00 Lian Kho
10:00 – 10:20 Shu Ki Lam
10:20 – 10:40 Fan Li
10:40 – 11:10 Morning Tea
11:10 – 11:40 Two minute talks
11:40 – 12:00 Lisa Pilkington
12:00 – 12:20 Tanya Rutan
12:20 – 12:40 Teresa To
12:40 – 12:50 Morning wrap-up
12:50 – 1:30 Lunch
Afternoon session
1:30 – 3:00 Poster Session
3:00 – 3:30 Afternoon Tea
3:30 – 4:30 Keynote lecture by Dr Lance Gravatt
4:30 – 5:00 Prize giving; closing
5:00 – 6:30 Wine tasting / Mixer
11
List of Presentations Page
1. Keynote lecture: Dr Lance Gravatt 14 Kiwi Chemical Sciences: A Backwater or the Headwater of the Pacific?
2. Lian Kho 15 Time resolved spectroscopy for solar energy harvesting complexes
3. Shu Ki Lam 16
Physico-chemical properties of transglutaminased milks at high pH
4. Fan Li 17 Synthetic studies towards chromanone-based natural products
5. Lisa Pilkington 18 Studies towards the asymmetric synthesis of 1,4-benzodioxane lignans
6. Tanya Rutan 19
Characterization of the aroma of Central Otago Pinot noir wines 7. Teresa To 20
Electrodeposited polyaniline on aluminium for antifouling
12
List of Posters Poster
Number Poster Title Page
1 Dynamic analysis of angiogenesis in transgenic zebrafish embryos using a 3D multilayer chip-based technology
21
2 Performance Evaluation of M/TiO2 (M = Au, Pd, Pt or combinations thereof) for Hydrogen Production form Ethanol
22
3 Effect of shear, protein and oil concentration on model processed cheese 23
4 Synthetic Studies Towards the Telomerase Inhibitors the Griseorhodins 24
5 Conducting Polymers for Label Free, Electrochemical, Real-time detection of PCR 25
6 Synthetic Studies Towards Pestalospirane A & B 26
7 Synthetic studies towards homodimeric indole-based natural products 27
8 Sequencing and stutter: characterising a forensic DNA locus 28
9 Synthesis of Mukanadin B and Analogues as Possible Neuroprotective Agents 29
10 Synthetic studies towards yuremamine 30
11 Adhesion Improvement Of Poly(Dimetylsiloxane) Surface By Grafting Of Polymer Brush 31
12 Total Synthesis of Danshenspiroketallactone 32
13 Synthesis and Structure Activity Relationship Studies of Novel Cyclic Lipopeptide, Battacin 33
14 Development of a catalyst for polyurethane high solids two-component (2k) coating systems and investigation of the catalytic mechanism using experimental and computational methods
34
15 Total Synthesis of Antibiotic Nitropyrrole Natural Product, Heronapyrrole C 35
16 Synthetic Studies Towards Lamellarin K 36
17 Interfacial Structure and Reactivity: H4SiO4 polymerization on different oxide surfaces 37
18 Effect of Combined High Hydrostatic Pressure and Dense Phase CO2 on Enzyme Activity in Feijoa puree
38
19 Synthetic studies towards Cephalosporolides H and I 39
20 Application of non-targeted high resolution mass spectrometry to monitoring tea fermentation level and origin
40
21 Regulation of kiwifruit softening by differential cell wall modifications 41
22 Ultrasound inactivation of bacteria at different growth phases
and application in skim milk
42
23 Convergent Synthesis of Acortatarin A: a 2-Formylpyrrole Spiroketal Natural Product 43
24 Switch-on DNA Sensor Based on Water Soluble Photoluminescent polymers 44
25 Switchable surfaces based on brushes grafted from conducting PEDOT 45
26 New efficient macrocyclic tetraamidate iron catalysts for oxidations with hydrogen peroxide 46
27 Vaccine design for lectin targets 47
28 Impact of Pectin Fine Structure on Their Interactions with β-Lactoglobulin Nanofibrils 48
29 Phenolic composition and antioxidant activities of different extracts from Actinidia macrosperma
49
30 Synthetic Studies Towards Phorbaketal A and Alotaketal A 50
31 Synthetic Studies towards the Virgatolides 51
32 Developing Novel Macrocyclic Tetraamidate Iron Complexes as Green Oxidation Catalysts for Industrial Applications
52
13
33 Design and Synthesis of Novel Rodenticides 53
34 Theoretical DFT-D Investigation of Supramolecular Porphyrin-Fullerene Interactions 54
35 Semiconductor Photocatalysts for H2 Production from Biofuels 55
36 Purification and Characterisation of Phosphorylated Lactose Milk Protein Conjugates 56
37 Interaction between Advanced Glycation End-Products and Transition Group Metals 57
38 Analysis of Beverage Antioxidants using a PEDOT-Based Sensor 58
39 Biomimetic Synthesis of Thiaplidiaquinone A and B 59
40 Total synthesis of Chaetoquadrins 60
41 Oxidative stress alters the membrane-binding interaction of plant annexin Gh1 61
42 In-Situ Synchrotron Corrosion Studies of CO2 Corrosion of Carbon Steel 62
43 Proteomics to Determine the Age of Human Bruises 63
44 A new synthetic approach to white light emitting polymers 64
45 The impact of vegetative clone on rotundone concentration throughout ripening and at commercial harvest in New Zealand Vitis vinifera L. Syrah for wine production
65
46 Boron Corrole Complexes 66
47 Cobalt(III) complexes as potential anticancer drugs 67
48 The forbidden crystal: Penrose tiling with molecules 68
49 Synthetic Studies Towards the Griseusin Family of Anticancer Agents 69
50 Electrospinning for encapsulation in food applications 70
51 Synthetic Studies Towards a Novel Family of Bioactive Cyclic Peptides, Psychrophilins A-D
71
52 A multiplex analysis of RNA expression during injury healing in human dermal injuries for injury age estimation
72
53 The Synthesis of Antimicrobial Marine Natural Products: Plicatamide and Analogues 73
54 Antibacteria Activity of Mushrooms: A Comparative Study on Paper Disk Diffusion and Mirodilution Methods
74
55 Studies towards the interaction of HRV 3C protease with (–)-thysanone 75
56 Organic-Inorganic Hybrid Polymer Composites 76
57 Conducting polymer substrates for electrochemically-mediated ATRP 77
58 Blueberries and probiotics, perfect recipes for a healthy heart 78
59 Illuminating the past: linking ultrafast photodynamics to hundred year photostability in hydroxyanthraquinones
79
60 Evaluation of electrodeposited polyaniline on marine grade aluminium for antifouling properties
80
61 Total Synthesis of the Initially Reported and Revised Structures of the Neuroprotective Agent Palmyrolide A
81
62 Structure-antimalarial activity relationship studies of the New Zealand marine natural products didemnidine B and orthidine F
82
63 Total Syntheses of (+)-Terreusinone and Schischkiniin 83
64 Novel Glycopolymer with Polyaniline backbone and pendant Mannose attached through a 1,3-dipolar cycloaddition
84
65 Electrospinning of Nanofibrous Polyaniline and Poly-ɛ-Caprolactone with Potential Application in Tissue Engineering
85
14
Keynote Lecture
Kiwi Chemical Sciences: A Backwater or the Headwater of the Pacific?
Lance Gravatt graduated from the University of Auckland in 1979 and after obtaining a teaching certificate worked as a science and chemistry teacher before returning to the University to undertake postgraduate study. Graduating firstly with an MSc and then in 1987 with a PhD in Chemistry, winning the L.H. Briggs Memorial Prize for the best PhD thesis in Chemistry in the process. He then took up a post-doctoral position at the University of Oxford before returning to New Zealand, working at the Cancer Research Laboratories at the Auckland Medical School. After this, Lance began working in the pharmaceutical industry working for companies such as Roche Products NZ, Bristol-Myers Squibb NZ and Astra NZ. From 2002-2011 he worked as Managing Director/Company President for AstraZeneca Limited New Zealand and since then has become the Chairman of Te Arai Biofarma, a 100% privately owned New Zealand Company working in the importation and distribution of both human and animal healthcare products, specialising in vaccines, biological and specialty products.
Dr Lance Gravatt
15
Lecture 1
Time resolved spectroscopy for solar energy harvesting complexes
Julie Kho Ali Hosseini, Peter Boyd, and Cather Simpson
Porphyrin-fullerene assemblies have been discovered over decades ago as potential artificial photosynthetic mimics due to their unique characteristics exhibiting photoinduced multistep electron transfer1. A new class of calix[4]arene-linked bisporphyrin (“jaws” porphyrin) has been constructed to bind with fullerenes (C60 and C70) with high affinity2. Understanding of the photochemistry of these self-assembly complexes, in particular the charge-separated state lifetime is the focus of this study. For this purpose, state-of-the-art near-IR transient absorption spectroscopy (TrA) has been utilized to measure the excited state lifetime of fulleride C60
- and C70-. The initial study of the bisporphyrin-fullerene dyad in two
different solvents, toluene and cyclohexane – showed that a higher binding constant of C60 to porphyrin in cylcohexane led to faster charge combination (lifetime of 560ps and 430ps in toluene and cyclohexane respectively). Experimental results also demonstrated enhanced lifetime (2.5 ns) when a tert-butyl pyridine group is coordinated to the bisporphyrin complex due to solvation effects. Interestingly, the ferrocene pyridine coordinated triad complex did not show evidence of secondary electron transfer, thus exhibiting a lifetime of 1.5 ns. On the other hand, C70 complexes which possessed even higher binding constant exhibit lifetimes of 360ps and 1200ps for the dyad and triad respectively.
Figure: Calix[4]arene-linked bisporpyrin-fullerene constructs (left). An example of nIR transient absorption spectrum obtained from the experiment showing decay of C60
- signal. References 1. (a) Kuciauskas, D.; Lin, S.; Seely, G. R.; Moore, A. L.; Moore, T. A.; Gust, D.; Drovetskaya, T.; Reed, C. A.; Boyd, P. D.
W., Energy and Photoinduced Electron Transfer in Porphyrin−Fullerene Dyads. The Journal of Physical Chemistry 1996, 100 (39), 15926-15932; (b) Imahori, H., Porphyrin-fullerene linked systems as artificial photosynthetic mimics. Organic & Biomolecular Chemistry 2004, 2 (10), 1425-1433.
2. Hosseini, A.; Taylor, S.; Accorsi, G.; Armaroli, N.; Reed, C. A.; Boyd, P. D. W., Calix[4]arene-Linked Bisporphyrin Hosts for Fullerenes: Binding Strength, Solvation Effects, and Porphyrin−Fullerene Charge Transfer Bands. J. Am. Chem. Soc. 2006, 128 (49), 15903-15913.
16
Lecture 2
Physico-chemical properties of transglutaminased milks at high pH
Elisa Lam Yacine Hemar, Peter Swedlund, Don Otter
Milk is a complex biological fluid comprising of water, milk fats, and solids-non-fats including carbohydrates, proteins, minerals, organic acids and miscellaneous, distributed between the aqueous phase and casein micelles (see figure). Native casein micelles at pH ~6.70 comprise of ~94% total caseins and ~6% inorganic components present as colloidal calcium phosphate (CCP). These native casein micelles are stabilised predominantly by electrostatic and hydrophobic interactions and the CCPs. However, during alkalinisation, the physico-chemical properties of casein micelles are affected. When the pH of the milk system is increased to the alkaline range (pH 8.00 to 10.00), three major chemical reactions occur: alteration in the ionisation state of proteins, alteration in kosmotropic ionic content (Ca2+
and HPO42-) in the aqueous phase of milks, and changes in ion equilibria between the aqueous phase and
casein micelles. All of these reactions lead to the disruption of casein micelles. To prevent the disruption of casein micelles during alkalinisation, transglutaminase (TGase) was added to crosslink peptide-bound glutamine and lysine residues on caseins in the micelles. Hence, this work aims to investigate the changes in physico-chemical properties of casein micelles in milks induced by alkalinisation, and compare these properties with those treated with TGase.
Figure 1. Cryo- transmission electron micrograph of casein micelle.
17
Lecture 3
Synthetic Studies towards Chromanone-based Natural Products
Freda F. Li Daniel P. Furkert, Margaret A. Brimble
Chromanones, especially those containing the 2-butyrolactone substituted chromanone core (1), are privileged natural products that display a wide variety of biological activities (Figure 1).1-2 These natural products have been also recently identified as potential lead compounds for inhibition of the histone deacetylase (HDAC) enzyme, which has been targeted as a treatment option for various cancers and neurological diseases.3-4 Although 2-butyrolactone substituted chromanones are themselves important pharmocophores, there is no available general and efficient synthetic method for accessing molecules of this class in a stereoselective manner.5-6 Our current work is focused on a development of practical and flexible stereoselective methods to synthesise these enantiopure 2-butyrolactone substituted chromanones.
OH
O
O
O
O
H
OMe
O
O
OHOOMe
OO
OH
gonytolide A
OH
O
O
O
OH
OMe
O
OH
HO O
O
O
OH
microdiplodiasone gonytolide C
Figure 1: Chromanone-based natural products. The initial approach to the chromanone-lactone structure core (1) hinges on carbon-carbon bond formation through the intermolecular conjugate addition of a furan-based nucleophile (e.g., 2 or 3) to a chromenone substrate (Scheme 1). Both conventional catalysis using chiral Cu(II)-complexes and the more recently developed Rh-catalysed asymmetric conjugate addition of furan-based boron nucleophiles (3) were investigated. In parallel, an alternative strategy to synthesise the core structure that involves carbon-heteroatom bond formation through intramolecular conjugate addition reaction of 4 is also currently under investigation (Scheme 1).
OH
O
O
O
O
O
O
O
O
O OTMS O ORR2B
+or
chromenone
chromanone-butyrolactone core
furan-based nucleophile
inter intra1
2 3
4
Scheme 1: Strategies for the synthesis of chromanone-butyrolactone core 1. References 1. Kikuchi, H.; Isobe, M.; Sekiya, M.; Abe, Y.; Hoshikawa, T.; Ueda, K.; Kurata, S.; Katou, Y.; Oshima, Y. Org Lett. 2011, 13
(17), 4624-4627. 2. Siddiqui, I. N.; Zahoor, A.; Hussain, H.; Ahmed, I.; Ahmad, V. U.; Padula, D.; Draeger, S.; Schulz, B.; Meier, K.; Steinert,
M.; Kurtan, T.; Florke, U.; Pescitelli, G.; Krohn, K. J Nat Prod. 2011, 74 (3), 365-373. 3. Kazantsev, A. G.; Thompson, L. M. Nature reviews. Drug discovery. 2008, 7 (10), 854-68. 4. Remiszewski, S. W. Curr Med Chem. 2003, 10 (22), 2393-2402. 5. Qin, T. A.; Johnson, R. P.; Porco, J. A. J Am Chem Soc. 2011, 133 (6), 1714-1717. 6. Stubbing, L. A.; Li, F. F.; Furkert, D. P.; Caprio, V. E.; Brimble, M. A. Tetrahedron 2012, 68 (34), 6948-6956.
18
Lecture 4
Studies Towards the Asymmetric Synthesis of 1,4-Benzodioxane Lignans
Lisa I. Pilkington David Barker
1,4-Benzodioxane neolignans are a significant subgroup within the lignan class that exhibit a diverse range of pharmaceutical properties, including cytotoxic and hepaprotective activities.1,2 1,4-Benzodioxanes have also demonstrated activities that indicate the potential for use in an antihyperintensive, antidepressant and antihyperglycemic pharmacological capacity.3
Our current work has been focussed on the development of a flexible, enantioselective method to produce 1,4-benzodioxanes (1,4-benzodioxane moiety highlighted in red in the figure below) and its application to the synthesis of a number of naturally occurring compounds, with members of the rodgersinnine (e.g. cis-rodgersinine B 1), eusiderin (e.g. eusiderin A 2) and isoamericanin (e.g. isoamericanin A 3) families our primary targets. The synthetic route produces both cis and trans isomers and also facillitates variation in the sidechains and the substitution on the appended aromatic ring to produce a range of natural products and their analogues.
O
O
HO OH
O
O
MeO
OMe
MeO
O
O
HO
OH
OMe
OH
O
1 2
3
7
8
We will present the first asymmetric synthesis of six members and several analogues of the eusiderin family, as well as results of CD experiments on the compounds and the resultant implications in the confirmation of the stereochemistry of the natural products.4 We will also present results of anti-HCV testing of some of these eusiderin products, revealing interesting anti-viral activities that provide the basis for further investigation.
References 1. Jing, X.-B.; Wang, L.; Han, Y.; Shi, Y.-C.; Liu, Y.-H.; Sun, J., J. Chin. Chem. Soc. 2004, 51, 1001-1004. 2. Sefkow, M., Synthesis. 2003, 17, 2595-2625. 3. Jing, X. B.; Gu, W. X.; Bie, P. Y.; Ren, X. F.; Pan, X. F., Chin. Chem. Lett. 2000, 11, 875-878. 4. Pilkington, L. I.; Barker, D., J. Org. Chem. 2012, 77, 8156-8166.
19
Lecture 5
Characterization of the aroma of Central Otago Pinot noir wines through chemical composition, aroma extract dilution analysis and sensory reconstitution studies
Tanya Rutan Mandy Herbst-Johnstone, Benedicte Pineau and Paul Kilmartin
The aroma of two representative Pinot noir wines from Central Otago has been elucidated over two consecutive vintages. Fifty one compounds were quantified via GC/MS following liquid-liquid and solid phase microextractions of which 22 odorants were present at levels above perception threshold. The most important odorants were β-damascenone, ethyl octanoate, ethyl hexanoate, ethyl isovalerate, isovaleric acid, and 3-mercapto-hexan-1-ol with odour activity values ranging from 17 to 95. Forty two odorants were identified in the Aroma Extract Dilution Analysis study with over 20 having flavor dilution factors > 81, the highest being phenylethyl alcohol (rose), ethyl isobutyrate (strawberry), β-damascenone (floral), isovaleric acid (cheese), ethyl isovalerate (fruity), ethyl cinnamate (cinnamon), guaiacol (smoky). Aroma models were prepared by deodorizing two Pinot noir wines with LiChrolut EN resin followed by reconstitution. Control models for each wine were made by adding back compounds to the deodorized matrix at their original concentrations. Five other models for each wine were prepared in the same manner but with the omission of one major aroma family and the models were presented to a trained panel. When compared to the fully reconstituted model, the omission treatments altered certain sensory descriptors; although, overall, no profound differences were observed or were often too subtle to be clearly defined.
20
Lecture 6
Evaluation of electrodeposited polyaniline on marine grade aluminium for antifouling properties
Teresa To1
Simon Swift1,2, Paul Kilmartin1 1Hybrid Polymers Research Group, School of Chemical Sciences 2Molecular Medicine and Pathology, School of Medical Sciences
Antifouling coatings are generally defined as those that can prevent the settling of microorganisms on a surface through the controlled release of toxic agents. There is considerable interest in the development of coatings that are non-toxic to the environment, but also prevent unwanted microbial-based fouling. Many conducting polymers have been studied for different applications, with polyaniline the first to show antifouling properties1. The objective of the research is develop an optimum polyaniline coating on aluminium alloys that does not release toxic chemicals, but at the same time provides a useful antifouling property.
Polyaniline films were synthesized electrochemically from 0.5 M oxalic acid solution containing 0.1 M aniline, under potentiostatic control. Coated and control marine grade aluminium were challenged by immersion in growing cultures of Escherichia coli ATCC 25922 lux and E. coli 536 lux under controlled conditions to simulate the marine environment in an accelerated fashion. This novel testing method allowed a non-destructive evaluation of bacterial growth on different surfaces, using selected coatings, with bioluminescence from bacteria colonizing the aluminium coupons imaged using an IVIS kinetic at 24 hourly intervals over a 2 weeks period (Figure 1). Only live bacteria bioluminesce and so signal (seen as a pseudocolour image in figure 1) reflects areas of the coupon colonized by bacteria. Polyaniline-coating of marine grade aluminium delays colonization indicating a lower rate of fouling.
Figure 1: Bioluminescence images overlaying a photograph of coated and control samples. A commercially available antifouling coating and an electrochemically synthesized polyaniline on marine grade aluminium are compared with bare marine grade aluminium and glass controls. The images are taken after 4 days of exposure to the bacteria. References: 1. Wang, X. H.; Li, J.; Zhang, J. Y.; Sun, Z. C.; Yu, L.; Jing, X. B.; Wang, F. S.; Sun, Z. X.; Ye, Z. J., Polyaniline as marine antifouling and corrosion-prevention agent. Synthetic Metals 1999, 102 (1–3), 1377-1380.
21
Poster 1 Dynamic analysis of angiogenesis in transgenic zebrafish embryos using a 3D multilayer chip-based
technology
Jin Akagi Feng Zhu, Chris J. Hall, Khashayar Khoshmanesh, Kourosh Kalantar-Zadeh,
Arnan Mitchell, Kathryn E. Crosier, Philip S. Crosier, Donald Wlodkowic
Zebrafish (Danio rerio) models of human diseases have recently emerged as innovative experimental systems in drug discovery and molecular pathology. None of the currently available technologies, however, allow for automated immobilisation and treatment of large numbers of spatially encoded embryos during real-time developmental analysis. This work describes the proof-of-concept design and validation of an integrated 3D microfluidic chip-based system fabricated directly in the poly(methyl methacrylate) thermoplastic using infrared laser micromachining. At its core, the device utilises an array of 3D micro-mechanical traps to actively capture and immobilise single embryos using a low-pressure suction. It also features built-in piezoelectric pumps, embryo trapping suction manifold, drug delivery manifold and optically transparent indium tin oxide (ITO) heating element to provide optimal temperature during embryo development. Furthermore, we present design of the proof-of-concept off-chip electronic interface equipped with robotic servo actuator driven stage, innovative servomotor-actuated pinch valves and miniaturised fluorescent USB microscope. Our results show that the device has 100% embryo trapping efficiency while supporting embryo development for up to 72 hours in a confined microfluidic environment. We also present data that this microfluidic system can be readily applied to kinetic analysis of a panel of investigational anti-angiogenic agents in transgenic zebrafish Tg(fli1a:EGFP) line.
Wlodkowic, D.; Khoshmanesh, K.; Akagi, J.; Williams, D. E.; Cooper, J. M. Cytometry Part A 2011, 79(10), 799-813 Wheeler, G. N.; Brandli, A. W. Dev. Dyn. 2009, 238(6), 1287-1308 Zon, L.I; Peterson, R. T. Drug Discov. 2005, 4(1), 35-44 Chakraborty, C.; Hsu, C. H.; Wen, Z. H.; Lin, C. S. Curr. Drug Metab. 2009, 10(2), 116-124 Kidd K. R.; Weinstein B. M. Br. J. Pharmacol. 2003, 140(4), 585-594 Lawson, N. D.; Weinstein, B. M. Dev. Biol. 2002, 248(2), 307-318 Akagi, J.; Khoshmanesh, K.; Evans, B.; Hall, C. J.; Crosier, K. E.; Cooper, J. K.; Crosier, P. S.; Wlodkowic, D. PLoS One 2012, e36630
22
Poster 2 Performance Evaluation of M/TiO2 (M = Au, Pd, Pt or combinations thereof) for
Hydrogen Production form Ethanol
Zakiya H.N. Al-Azri Geoffrey I.N. Waterhouse and James B. Metson
The establishment of a hydrogen energy economy depends critically on the development and implementation of cheap, efficient and environmentally friendly H2 production technologies. This study systematically compares the activity of a series of M/TiO2 photocatalysts (M = Au, Pd, Pt or combinations thereof) for H2 production from ethanol-water mixtures (80 vol.% CH3CH2OH, 20 vol.% H2O) under UV irradiation. Various M/TiO2 (M= Au, Pd and Pt) photocatalysts with metal loadings of 0-4 wt.% were synthesized by the deposition-precipitation method using a commercial TiO2, Evonik P25 as the support. The present work and other studies have shown that the photocatalytic activity of M/TiO2 photocatalysts for H2 production from ethanol depend on three factors: i) the metal loading on the TiO2 support, ii) the oxidation state of the noble metal, iii) the metal nanoparticle size 1-4. Results show that Pt/TiO2 photocatalysts exhibited the highest activity and stability for H2 production, with the optimum loading being 0.5 wt.% (H2 production rate of ~ 500 µmol h-1 g-1); and that at 2 wt.% nominal loading of Au/TiO2 or Pd/TiO2 photocatalysts gave almost similar H2 production rate of ~ 400 µmol h-1 g-1. For all the photocatalysts, supported metal nanoparticles of diameter < 5 nm were observed by TEM, with the presence of zero valent metal essential to efficient H2 production. Photogenerated holes in the valence band of TiO2 oxidise ethanol to acetaldehyde, whilst the supported metal nanoparticles act as sinks for electrons photoexcited in TiO2, thereby inhibiting electron-hole pair recombination and providing the surface active sites for H2 production 3 (Figure 1). Bimetallic Au-Pd/TiO2, Au-Pt/TiO2 and Pd-Pt/TiO2 photocatalysts were also prepared, and demonstrated comparable activities to the M/TiO2 photocatalysts for H2 production from ethanol when compared at the same total metal loading.
Figure 1. (Left) TEM image of 2 wt.% Pt/TiO2. The Pt nanoparticles are of size 1-3 nm and highly dispersed over the TiO2 support. (Right) The photo-catalytic process of ethanol to hydrogen on M/TiO2 catalyst (M = Au, Pd or Pt). Open circle: hole; close circle: electron, copyright from ref 3. References 1. Waterhouse, G.; Murdoch, M.; Llorca, J.; Idriss, H. Int. J. of Nanotechnology. 2012, 9, 113-120. 2. Murdoch, M.; Waterhouse, G.; Nadeem, M.; Metson, J.; Keane, M.; Howe, R.; Llorca, J.; Idriss, H. Nat. Chem. 2011, 3, 489-492. 3. Yang, Y. Z.; Chang, C. H.; Idriss, H. Appl. Catal. B. 2006, 67, 217-222. 4. Sakthivel, S.; Shankar, M. V.; Palanichamy, M.; Arabindoo, B.; Bahnemann, D. W.; Murugesan, V. Water Res. 2004, 38 , 3001-3008.
M: 2H+ +2e- → 2H(adsorbed) → H2(g)
CH3CH2OH → CH3CHO + 2H+
Surface trap Band gap of TiO2
Eg
= 3.2 eV
Conduction band
Valence band
Energy
2 wt.% Pt/TiO2
Pt nanoparticles
23
Poster 3 Effect of shear, protein and oil concentration on model processed cheese
Anis Arzami Sylvie Marchesseau and Yacine Hemar
The impact of shear, different protein concentrations and different oil concentrations on the rheological properties, fat particle size, meltability and microstructure of a model processed cheese spread system were investigated. The model processed cheese was made of sunflower oil, calcium caseinate (protein) and trisodium citrate (TSC) (2%). G* values increased with the increase in the processing shear up to certain extent, then decreased slightly. The size of the fat particles become smaller as the speeds increased up to a maximum level. As the protein concentration and oil concentration increased, the cross-over of G’ (elastic modulus) and G” (viscous modulus) shifted to lower frequencies indicating that the processed cheese becomes more elastic. Fat particle size of processed cheese samples decreased as the protein concentration increased from 2.5% up to 20% of protein. When 25% and 30% of oil were used to the manufacture of processed cheese, the value of G*, shear stress and melting percentage slightly decreased compared to processed cheese made with 20% of oil. This study demonstrated that it is possible to taylor the rheological and melting properties of the processed cheese by manipulating the different compositional parameters.
References: Cunha, C. R.; Viotto, W. H. Casein Peptization, Functional Properties, and Sensory Acceptance of Processed Cheese Spreads Made with Different Emulsifying Salts. J. Food Sci. 2010, 75(1), C113-C120. Dimitreli, G.; Thomareis, A. S. Effect of Chemical Composition on the Linear Viscoelastic Properties of Spreadable-type Processed Cheese. J. Food Eng. 2008, 84(3), 368-374. Lee, S. K.; Anema, S.; Klostermeyer, H. The Influence of Moisture Content on the Rheological Properties of Processed Cheese Spreads. Int. J. Food Sci. Technol. 2004, 39(7), 763-771. McClements, D. J. Food Emulsions: Principles, Practices, and Techniques, 2nd ed.; Taylor & Francis: United Kingdom, 2004; pp 132-134. Mizuno, R.; Lucey, J. A. Effects of Two Types of Emulsifying Salts on the Functionality of Nonfat Pasta Filata Cheese. J. Dairy Sci. 2005, 88(10), 3411-3425. Purna, S. K. G.; Pollard, A.; Metzger, L. E. Effect of Formulation and Manufacturing Parameters on Process Cheese Food Functionality - I. Trisodium Citrate. J. Dairy Sci. 2006, 89(7), 2386-2396. Shirashoji, N.; Jaeggi, J. J.; Lucey, J. A. Effect of Trisodium Citrate Concentration and Cooking Time on the Physicochemical Properties of Pasteurized Process Cheese. J. Dairy Sci. 2006, 89(1), 15-28. Trivedi, D.; Bennett, R. J.; Hemar, Y.; Reid, D. C. W.; Lee, S. K.; Illingworth, D. Effect of Different Starches on Rheological and Microstructural Properties of (I) Model Processed Cheese. Int. J. Food Sci. Technol. 2008, 43(12), 2191-2196.
24
Poster 4 Synthetic Studies Towards the Telomerase Inhibitors the Griseorhodins
Darcy J. Atkinson Jonathan Sperry, Daniel P. Furkert, Margaret A. Brimble.
Telomerase is an enzyme found in 85% of cancerous tumours that aids in prolific reproduction and growth of cancer cells. Inhibition of telomerase shows potential as a new effective cancer therapy1
The griseorhodins are a structurally related family of compounds closely related to the telomerase inhibitors the rubromycins. They were isolated from different strains of Streptomyces and possess potent cytotoxic activity and telomerase inhibition with IC50 values between 6 and 12 µM.2
The griseorhodins contain naphthazarin and isocoumarin ring systems linked through a 5,6-spiroketal core. To date there are four total syntheses of the rubromycins and total synthesis of the griseorhodins is yet to be reported.3 Late stage spiroketalisation in the synthesis towards the rubromycins has proven problematic due to the electronic properties of the isocoumarin fragment. Adjustment of the electronic properties through functional group manipulation and its effects on late stage spiroketalisation will be investigated in the synthesis of these complex natural products.
O O
OO
HOOHO
MeO
O OH OH O
O O
OO
HOOHO
MeO
O OH OHOH R1
Griseorhodin A Griseorhodin C R1 = OHGriseorhodin G R1 = H
MeO
OMe
OMe
OMe
OMe
O OH
OMe
O
O
OH
O O
O
MeO
OMe
OMe
OMe
OMe
MeOO
Acid catalysedspiroketalisation
Fig. 1: Key spiroketalisation step.
References: 1. Hiyama, E.; Hiyama, K. Cytotechnology 2004, 45, 61-74. 2. Ueno, T.; Takahashi, H.; Oda, M.; Mizunuma, M.; Yokoyama, A.; Goto, Y.; Mizushina, Y.; Sakaguchi, K.; Hayashi, H.
Biochem. 2000, 39, 5995-6002. 3. (a) Rathwell, D. C. K.; Yang, S. H.; Tsang, K. Y.; Brimble, M. A. Angew. Chem. Int. Ed. 2009, 48, 7996-8000; (b)
Akai, S.; Kakiguchi, K.; Nakamura, Y.; Kuriwaki, I.; Dohi, T.; Harada, S.; Kubo, O.; Morita, N.; Kita, Y. Angew. Chem. Int. Ed. 2007, 46 (39), 7458-7461; (c) Siu, T.; Qin, D. H.; Danishefsky, S. J. Angew. Chem. Int. Ed. 2001, 40, 4713-4716. (d) Wu, K. L.; Mercado, E. V.; Pettus. T. R. R. J. Am. Chem. Soc. 2011, 133, 6114-6117
25
Poster 5 Conducting Polymers for Label Free, Electrochemical, Real-time detection of PCR
Nihan Aydemir, Hazel McArdle, Selina Patel, Clive Evans, David Williams, Jadranka Travas
Sejdic Described in here is a novel method for label free, electrochemical, real time detection of the polymerize chain reaction (PCR) by using conducting polymers (CPs). Performing a semi-solid state PCR, amplification of a 648 base pair region of the mitochondrial cytochrome c oxidase (COI or cox1) gene was successively performed. In situ electrochemical impedance spectroscopy (EIS) was carried out for real time electronic read-out. First, pyrrolle (Py) and 3-pyrrolylacrylic acid (PAA) were electrochemically co-polymerized onto glassy carbon (GC) electrode to use as transducer and sensing element. Then, tethered forward primer, carrying an amine group, covalently attached on to CP surface. Electrode was immersed into the PCR master mix containing [Fe(CN)6]3−/4−redox couple and in situ EIS measurements were carried out at the end of each cycle, specifically at extension temperature of 72 oC ( Figure 1 A). Duplication of DNA during the extension resulted in increase in the interfacial charge transfer resistance of CP (Figure 1B). The main advantages of this method are: 1) label- and intercalator- free measurement, avoiding any chemical contamination of DNA, 2) real time electrical read out, providing not only detection but also quantification from the very first cycle, 3) introducing CPs as sensitive and cost effective media for solid state PCR.
Figure 1: (A) Working mechanism of electrochemical, real time, in situ and label free detection of DNA amplification. (B) Nyquist diagrams obtained during a PCR reaction. Radius of semi circle, representing the charge transfer resistance of polymer, allows the detection from the very first cycle and keeps increasing as the following cycles.
26
Poster 6 Synthetic Studies Towards Pestalospirane A & B
Sandhya Badrinarayanan Dr. Daniel P. Furket, Dr. Jonathan Sperry, Prof. Margaret A. Brimble
The two natural products pestalospiranes A (1) and B (2) are epimers at C-3ꞌ, and were isolated in 2011 by Kesting et al, from Pestalotiopsis virgatula culture derived from the plant Terminalia chebula.1 The dispiro metabolites 1 and 2 are derivatives of benzo-[c]oxepin (3), a rare heterocyclic motif that is only observed in a small number of natural products.1 The unique molecular architecture of pestalospiranes A and B (1 and 2) makes them attractive synthetic targets. Extracts isolated from Pestalotiopsis virgatula were limited and pharmacological testing has therefore not been possible. As a result the total synthesis of pestalospiranes A (1) and B (2) is necessary to uncover any biological activity of the compound.1 Our synthetic strategy is to synthesise the spiroketal core by employing a novel double oxidative radical cyclization in order to construct the 7-membered rings. Herein we report synthetic studies towards the synthesis of pestalospiranes A (1) and B (2).
(R)(S)
O(R)
(S)
OMe
MeOO
OH
OH
(R)(S)
O(R)
(R)
OMe
Me
O
O
OH
OH
1 2
O
benzo-[c]oxepin(3)
= C-3'
References: (1) Kesting, J. R.; Olsen, L.; Staerk, D.; Tejesvi, M. V.; Kini, K. R.; Prakash, H. S.; Jaroszewski, J. W. J. Nat. Prod. 2011, 74, 2206.
27
Poster 7 Synthetic studies towards homodimeric indole-based natural products
Emily Boyd
Dr Jonathan Sperry This project aims to develop the first total synthesis of two natural indole alkaloids using a combination of biomimetic and synthetic techniques.
Dendridine A is a structurally unique C2-symmetrical bisindole alkaloid isolated in 2005 from the marine sponge Dictyodendrilla species.1 The sterically congested 4,4'-bisindole bond is unique to natural products, and dendridine A is one of only two types of alkaloids ever isolated to possess this heterocyclic ring system. Dendridine A exhibits both antibacterial and antifungal activity. The monomeric subunit of dendridine A (hemi-dendridine A) has been synthesised2 and subjected to a variety of conditions in an attempt to elicit the key phenolic coupling. Bidirectional approaches have also been explored. Aspergilazine A is the only indole-based compound known that is dimerized at N1-C6. It was isolated in 2012 from a strain of marine-derived fungus Aspergillus taichungensis and exhibits weak inhibitory activity against the influenza virus H1N1.
3 The synthesis of aspergilazine A will be attempted via copper-mediated N-arylation of the monomeric subunit with its brominated derivative. Model studies suggest that this will occur regioselectively, reducing the need for protecting groups. The subunits are tryptophan-derived diketopiperazines, which can be readily assembled from natural amino acids.
HN
H2NNH
NH2
OH
Br
OH
Br NH
HN
NO
OH
N
NHN
O
OH
aspergilazine A
dendridine A
NH
HN
N
O
OBr
H
NH
NHN
O
OH
+
OH
OH
Br
HN
H2N
NH
NH2
BrNAc
2 NH
NHAc
OH
Br
+
44' 1' 6
2
Bidirectional Phenolic coupling N1-arylation
References: 1. Tsuda, M.; Takahashi, Y.; Fromont, J.; Mikami, Y.; Kobayashi, J. i. J. Nat. Prod. 2005, 68 (8), 1277-1278. 2. Boyd, E. M.; Sperry, J. Tetrahedron Lett. 2012, 53, 3623-3626. 3. Cai, S.; Kong, X.; Wang, W.; Zhou, H.; Zhu, T.; Li, D.; Gu, Q. Tetrahedron Lett. 2012, 53 (21), 2615-2617.
28
Poster 8 Sequencing and stutter: characterising a forensic DNA locus
Jo-Anne Bright
Professor James Curran and Dr John Buckleton
The forensic analysis of DNA is most often undertaken by the amplification of short tandem repeats (STR) by the polymerase chain reaction (PCR). DNA amplification can result in the target allele and a by-product called stutter. Stutter is the miscopy of the target allele and is typically one repeat smaller1. Stutter is traditionally described as a ratio of stutter and allele height; stutter ratio (SR). The challenge to DNA profile interpretation is most serious whenever stutter products are of a similar height to the minor allelic peaks in a mixed DNA profile. An accurate assignment of peaks and the prediction of their height is important when objectively interpreting forensic DNA profiles. The longest uninterrupted stretch (LUS) of tandem repeats within the allele has previously been shown to be a good predictor of stutter ratio2. LUS is determined by sequencing a range of observed alleles at a locus.
The locus D6S1043 is a relatively new locus to appear in commercial forensic DNA testing kits. To date however, there has been no comprehensive report of sequencing of this locus. In this work, we sequence the locus D6S1043 to determine LUS and investigate LUS as an explanatory variable for SR at this locus. References 1. Walsh, P. S.; Fildes, N. J.; Reynolds, R., Sequence analysis and characterization of stutter products at the tetranucleotide repeat locus vWA. Nucleic Acids Res 1996, 24, 2807-2812. 2. (a) Brookes, C.; Bright, J.-A.; Harbison, S.; Buckleton, J., Characterising stutter in forensic STR multiplexes. Forensic Science International: Genetics 2012, 6 (1), 58-63; (b) Bright, J.-A.; Taylor, D.; Curran, J. M.; Buckleton, J. S., Developing allelic and stutter peak height models for a continuous method of DNA interpretation. Forensic Science International: Genetics 2013, 7 (2), 296-304.
29
NH
HN NH
HN
O
Br O
O(3)
NH
HN NH
HN
O
Br O
O
OH
(1)
9
(2)
NH
HN NH
HN
O
Br NH
O
OMe
9
Poster 9 Synthesis of Mukanadin B and Analogues as Possible Neuroprotective Agents
Michelle Brothers Dr. David Barker
Glutamate is an important amino-acid that acts as an excitatory neurotransmitter in the central nervous system (CNS),1 demonstrating effects described as being both beneficial and detrimental. The beneficial effects can be seen by its regulation of neuronal function, growth, and differentiation. However, due to glutamate being an excitatory amino acid it has effects that could be injurious to brain tissue. These effects result from large amounts of glutamate or aspartate being released into the extracellular space, leading to hyperactivation of glutamate receptors.2 This hyperactivation, termed ‘excitotoxicity’, has been seen in patients with ischemia, hypoglycaemia, epileptic seizures, and in neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.3-5 For this reason, glutamate antagonists may prove to be neuroprotective through their actions of inhibiting the hyperactivation of glutamic receptors which occurs in the presence of excessive glutamate.
Recently members of the mukanadin family, 9-hydroxy mukanadin B (1) and 9-methoxy mukanadin A (2), were found to possess potent glutamate antagonism.2 We therefore present our progress towards the synthesis of mukanadin B (3), mukanadin B pyrrole analogues and C-9-substituted mukanadin B derivatives in order to determine what effect different substitutions have on glutamate antagonism and general bioactivity.
References
(1) Arai, Y.; Mizuguchi, M.; Takashima, S. Anat. Embryol. (Berl.) 1997, 195. (2) Aiello, A.; D'Esposito, M.; Fattorusso, E.; Menna, M.; Muller, W. E. G.; Perovic-Ottstadt, S.; Schroder, H. C. Bioorg. Med. Chem. 2006, 14, 17-24. (3) Harkany, T.; Abraham, I.; Timmerman, W.; Laskay, G.; Toth, B.; Sasvari, M.; Konya, C.; Sebens, J. B.; Korf, J.;
Nyakas, C.; Zarandi, M.; Soos, K.; Penke, B.; Luiten, P. G. Eur. J. Neurosci. 2000, 12. (4) Aarts, M. M.; Tymianski, M. Curr. Mol. Med. 2004, 137. (5) Larsen, G. A.; Berg-Johnsen, J.; Moe, M. C.; Vinje, M. L. Neurochem. Res. 2004, 1931. (6) Uemoto, H.; Tsuda, M.; Kobayashi, J. J. Nat. Prod. 1999, 62, 1581-1583.
Figure 2. Elephant ear sponge from the genus Agelas. Mukanadins A-C were isolated from the Agelas nakamurai sea sponge.6
Figure 1. 9-Hydroxy mukanadin B (1), 9-methoxy mukanadin A (2) and mukanadin B (3).
30
Poster 10 Synthetic studies towards yuremamine
Matthew Calvert
Dr. Jonathan Sperry Yuremamine was isolated in 2005 from the Brazilian shrub Mimosa tenuiflora.1 This brightly coloured alkaloid is thought to be responsible for the psychoactive effects of traditional beverages made from this plant. It has been suggested that intramolecular H-bonding (shown below) protects the dimethyl tryptamine side chain from the effects of monoamine oxidase, thereby enabling oral bioavailability. Our approach to yuremamine is based around sp3 arylation chemistry.2 C-H activation is a highly topical area of research in organic synthesis and the use of this methodology in the total synthesis of a complex natural product would demonstrate the advantages of such reactions in terms of atom, step and redox economy.3 Synthetic studies towards the tricyclic indole core A and subsequent C-H activation will be discussed.
N
OH
O OH
HO
HOOH
NH
N
N
HN
O
N
I
I
OHHO
HO
OH
HO
sp3 arylation
A
Yuremamine, with proposed intramolecular hydrogen bonding interaction, and sp3 arylation substrate References: 1. Vepsalainen, J. J.; Auriola, S.; Tukiainen, M.; Ropponen, N.; Callaway, J., Planta Med. 2005, 71, 1053-1057. 2. Zaitsev, V. G.; Shabashov, D.; Daugulis, O., J. Am. Chem. Soc. 2005, 127, 13154-13155. 3. Newhouse, T.; Baran, P. S.; Hoffmann, R. W., Chem. Soc. Rev. 2009, 38, 3010-3021.
31
Poster 11 Adhesion Improvement Of Poly(Dimetylsiloxane) Surface By Grafting Of Polymer
Brush
Omer Javed Chaudharya Jadranka Travas-Sejdica,d, Emilio Caliusb, John Kennedyc
aPolymer Electronics Research Centre, School of Chemical Sciences, University of Auckland, New Zealand bIndustrial Research Limited, Auckland, New Zealand cNational Isotope Centre, GNS Science, Lower Hutt, New Zealand dMacDiarmid Institute of Advanced Materials and Nanotechnology, New Zealand Biomimetic polymer-brush modified surfaces can offer a large number of attachment points to surfaces and this could result in improvement in adhesion1. ATRP is a convenient tool for producing well-defined biomimetic dry adhesive surfaces: the ease of polymerization procedure, ability to process large surface areas, a large choice of monomers and control over polymerization allow production of modified surfaces on large scale with properties tailored to target applications2. To study the effect of polymer brushes on adhesion, Atom Transfer Radical Polymerization (ATRP) was used to graft polymer brushes on a poly(dimethylsiloxane) (PDMS) surface. Poly(butylacrylate) chains were chosen as grafts. PDMS samples with grafted poly(butylacrylate) chains were obtained with varying degree of polymerization. Growth of polymer brushes was verified by ATR-FTIR spectroscopy. Ellipsometric measurements were made on Silicon wafer modified with poly(butylacrylate) using same surface immobilized initiator and under similar conditions. To establish relationship between polymer brush thickness and the adhesion strength, all samples were tested for pull off adhesion. In general, polymer-brush modified samples showed an increase in adhesion compared to unmodified samples. In modified PDMS samples, adhesion strength increased generally with polymer brush thickness. Such modification of biomimetic structure by polymer chains can offer a low-cost solution for improvement of adhesion in such systems, by avoiding use of expensive nano-fabrication techniques.
Figure 1. schematic diagram showing the behaviour of polymer brush during attachment and detachment. References 1. Sitti, M.; Cusick, B.; Aksak, B.; Nese, A.; Lee, H. I.; Dong, H.; Kowalewski, T.; Matyjaszewski, K., Dangling chain elastomers as repeatable fibrillar adhesives. ACS Applied Materials and Interfaces 2009, 1 (10), 2277-2287. 2. Matyjaszewski, K., Atom Transfer Radical Polymerization (ATRP): Current status and future perspectives. Macromolecules 2012, 45 (10), 4015-4039.
i. iv.iii.ii.
F’F
32
Poster 12 Total Synthesis of Danshenspiroketallactone
Daniel Chorley
Jack Li-Yang Chen, Daniel P. Furkert, Jonathan Sperry, Margaret A. Brimble Danshen, the traditional Chinese medicine consisting of dried roots of Chinese sage, Salvia miltiorrhiza has been used for hundreds of years to treat renal failure, heart disease, and strokes.1 In an ongoing project aimed at identifying compounds responsible for the therapeutic effect in traditional Chinese medicines, combined with our continued interest in the synthesis of benzannulated spiroketal natural products,2 we decided to initiate a synthesis of danshenspiroketallactone. Described herein is the first synthesis of the monobenzannulated 5,5-spiroketals danshenspiroketallactone and epi-danshenspiroketallactone, two components of Danshen.3 Key features of the synthesis include a directed metallation–lactonisation sequence to install the isobenzofuranone moiety and an oxidative radical cyclisation to afford the monobenzannulated 5,5-spiroketal.4
CH3
O
O
(R)(R)
O
CH3
OO
(R)
(S)
O
Danshenspiroketallactone epi-danshenspiroketallactone
References: 1. Kong, D. Y.; Liu, X. J.; Teng, M. K.; Rao, Z. H. Yao Xue Xue Bao 1985, 20 (10), 747-51. 2. (a) Rathwell, D. C. K.; Yang, S.-H.; Tsang, K. Y.; Brimble, M. A. Angew. Chem. Int. Ed. 2009, 48, 7996. (b) Wilson, Z. E.; Brimble, M. A. Org. Biomol. Chem. 2010, 8, 1284. (c) Yuen, T.-Y.; Yang, S.-H.; Brimble, M. A. Angew. Chem. Int. Ed. 2011, 50, 8350. (d) McLeod, M. C.; Wilson, Z.
E.; Brimble, M. A. Org. Lett. 2011, 13, 5382. 3. Asari, F.; Kusumi, T.; Zheng, G. Z.; Cen, Y. Z.; Kakisawa, H. Chem Lett 1990, (10), 1885-1888. 4. Chorley, D. F.; Chen, J. L. Y.; Furkert, D. P.; Sperry, J.; Brimble, M. A. Synlett 2012, 23 (1), 128-130.
33
Poster 13 Synthesis and Structure Activity Relationship Studies of Novel Cyclic Lipopeptide,
Battacin
Gayan Heruka De Zoysa Vijayalekshmi Sarojini
Battacin (Octapeptin B5) is a novel cyclic lipopeptide isolated from Paenibacillus tianmuensis soil isolate.1 Battacin exhibits broad spectrum antibacterial activity against numerous Gram negative pathogens such as hospital strains of E.coli and P.aeruginosa. Battacin has a similar structure to Polymyxin B, the last line of defence against antibiotic resistant Gram negative bacteria. However Battacin has a lower acute toxicity than Polymyxin B. Therefore Battacin could be a better and safer alternative to combat multi drug resistant Gram negative bacteria. Currently there is no information on the synthesis or structure activity relationship studies (SARs) of Battacin reported in the literature. Our studies towards the synthesis of Battacin and its analogues to will be presented in this poster.
References: 1. Qian, C.D.; Wu, X.C.; Teng, Y.; Zhao, W.P.; Li, O.; Fang, S.G.; Huang, Z. H.; Gao, H.C. Antimicrob Agents Chemother. 2012, 56, 1458-65.
HN
O
NH2
NH
O
HN
O
NH2
HN
ONHO
HN
ONH2
NH
O
NH2
NH
O
O
NH
OH
Battacin
34
Poster 14 Development of a catalyst for polyurethane high solids two-component (2k) coating
systems and investigation of the catalytic mechanism using experimental and computational methods
Ransi Devendra
Tilo Söhnel and Neil Edmonds,
Aliphatic polyurethanes are widely used in the coatings industry due their superior colour retention [1]. They are products formed by a reaction between an aliphatic polyisocyanate and a polyol in the presence of a catalyst [2]. Although organotin catalysts are preferred by industry, solvent based two-component (2k) polyurethane coatings systems containing these catalysts have pot-life and tack-free time limitations. In the present work an alternative catalyst based on a titanium chelate was developed and its catalytic function investigated using experimental and computational methods [3]. Based on this evidence a mechanism has been proposed for the titanium chelate catalysis of the reaction between aliphatic isocyanate and alcohol. Computational results are further supported with data from statistical experimental design (Fig. 1and 2), FTIR and NMR.
The catalyst developed has commercial potential in the existing two-component (2k) high solids polyurethane systems to give improved pot life and shorter tack-free time.
Design-Expert® Software(viscosity ratio)^-1
Shapiro-Wilk testW-value = 0.888p-value = 0.349A: chelating agentB: organotinC: titanium chelate
Positive Effects Negative Effects
Half-Normal Plot
Hal
f-N
orm
al %
Pro
babi
lity
|Standardized Effect|
0.00 0.06 0.13 0.19 0.25
010
20
30
50
70
80
90
95
A
B
C
AC
Fig. 1. Half normal plot for viscosity ratio after 30 minutes. A: Chelating agent, B: Organotin, C: Titanium chelate and AC: interaction between chelating agent titanium chelate [4].
Design-Expert® SoftwareLn(tack free time)
Shapiro-Wilk testW-value = 0.788p-value = 0.065A: chelating agentB: organotinC: titanium chelate
Positive Effects Negative Effects
Half-Normal Plot
Hal
f-N
orm
al %
Pro
babi
lity
|Standardized Effect|
0.00 0.16 0.32 0.48 0.64
0
10
20
30
50
70
80
90
95
B
C
Fig. 2. Half normal plot for the tack free time for draw-down. B: Organotin and C: Titanium chelate [4].
References: [1] M. Bock, Polyurethane for Coatings, Vincentz Verlag, Postfach 6247, 30062 Hannover, Germany (2001), 11-17. [2] Szycher, M. Szycher’s handbook of polyurethanes CRC Press: New York (1999) 10-1-20. [3] R.Devendra, N.R. Edmonds, T. Söhnel , J. Mol. Catal. A: Chemical, 366 (2013) 126-139. [4] Design Expert V8 – www.statease.com
35
Poster 15 Total Synthesis of Antibiotic Nitropyrrole Natural Product, Heronapyrrole C
Xiaobo Ding
Daniel P. Furkert, Margaret A. Brimble Heronapyrrole C was isolated from beach sand off Heron Island, Australia. It displayed promising activity against the Gram-positive bacteria but no cytotoxicity toward mammalian cell lines. Heronapyrrole belongs to the exceptionally rare family of nitropyrrole natural products. The structure of heronapyrrole C includes a 2-nitropyrrole, two tetrahydrofuran rings and five chiral centres. It is one of the first documented natural products bearing a 2-nitropyrrole functionality.1 We investigated two different strategies to synthesise heronapyrrole C. While the strategy based on a palladium catalysed coupling reaction (strategy 1) was to date proven unsuccessful, an alternative strategy hinging on Julia olefination, followed by oxidative cyclization, afforded N- protected heronapyrrole C, which could be deprotected to afford the final product.
NH
O
O
OH
Me
Me
Me MeHO
O2N
H
NO2N
OH
OH
PG
R
+
NO2N
PG
Br
OH
O
OH
H
Me
+
OTESO
OTES
S NN
NN
PhO
O
Heronapyrrole C
strategy 1 strategy 2
R = BF3KBPinSnBu3
H
H
NO2N
PG
CHO
NO2N
PG
References: 1. Raju, R.; Piggott, A. M.; Barrientos, D. L. X.; Khalil, Z.; Capon, R. J. Org. Lett. 2010, 12, 5158–5161.
36
Poster 16 Synthetic Studies Towards Lamellarin K
Nora Dittrich
Dr David Barker Lamellarins are a family of polycyclic alkaloids whose first member was isolated in 1985 by Faulkner et al.1 The lamellarin class has since expanded to include over 30 compounds, whose diverse biological activities show promise in the treatment of a number of disease states. In particular their anti-tumour activity and ability to reverse multidrug resistance has made them interesting synthetic targets for a number of research groups including ours.1,2 Our synthetic approach towards lamellarin K hinges on a Paal-Knorr cyclization step to install the central pyrrole ring. Studies by Amarnath et al. indicate that pyrrole formation is favoured for diketones with 2,3-syn aligned substituents.3
N
HO
MeO
MeO
HO MeO
O
O
OMeOH
A
BC
DE
F
O
N
O OP2
OP1
MeO
OMe
OP1
A F
acyl Claisen- derived amide Lamellarin K
Figure 1: Proposed synthesis of lamellarin K from the acyl Claisen-derived amide.
We will report on the use of an acyl Claisen rearrangement to prepare amides and hence the corresponding diketones with this key syn relationship between rings A and F (Figure 1). Our convergent approach allows for the synthesis of other members of the lamellarin family, most of who differ in their substitution around rings A, E and the non-fused aromatic ring F. References:
1) Andersen, R. J.; Faulkner, D. J.; Cun-heng, H.; Van Duyne, G. D.; Clardy, J. J. Am. Chem. Soc. 1985, 107, 5492- 5495. 2) Ishibashi, F.; Tanabe, S.; Oda, T.; Iwao, M.; J. Nat. Prod. 2002, 65, 500-504. 3) Amarnath, V.; Anthony, D. C.; Amarnath, K.; Valentine, W. M.; Wetterau, L. M.; Graham, D. G. J. Org. Chem. 1991, 56, 6924-6931.
37
Poster 17 Interfacial Structure and Reactivity: H4SiO4 polymerization on different oxide surfaces
Rossuriati Dol Hamid
Peter Swedlund and Gordon Miskelly The spatial arrangement of adsorption sites at the metal oxide/water interface can promote specific lateral interactions between adsorbed species. For example, silicic acid (H4SiO4) condensation produces numerous and diverse products in solution whereas the adsorption of H4SiO4 monomers on the surfaces of some iron oxides leads to the formation of a particular oligomeric species1. In this work we use in situ ATR-IR to compare interfacial H4SiO4 oligomerization on two oxide surfaces;
1. the disordered and high curvature surface of ≈ 2 nm diameter particles of ferrihydrite 2. the ordered arrangement of FeO6 octahedra on crystalline faces of goethite (-FeOOH)
The in situ ATR-IR spectra collected as goethite or ferrihydrite react with H4SiO4 over time are shown below. The spectra have three components at ≈ 950, 1020 and 1100 cm-1 representing monomeric sorbed H4SiO4, a linear trimer and a three dimensional polymer respectively2. On the disordered ferrihydrite there is a gradual progression from a monomeric to trimeric silicates on the surface as the surface coverage increases. In contrast on goethite monomers are present with polymers and the intermediate trimers are not significant3. The structural interpretation of this is presented below.
1. Swedlund, P. J.; Dol Hamid, R.; Miskelly, G. M., Journal of Colloid and Interface Science 2010, 352, 149–157. 2. Dol Hamid, R.; Swedlund, P. J.; Song, Y. T.; Miskelly, G. M., Langmuir 2011, 27, 12930-12937. 3. Song, Y.; Swedlund, P. J.; Zou, C.; Dol Hamid, R., Chemical Geology 2013, In press; accepted March 22 2013.
750850950105011501250
Wavenumber (cm‐1)
Ferrihydrite
increasing coverage
750850950105011501250Wavenumber (cm‐1)
Goethite
increasing coverage
Fe O FeOSi SiOSi Si
The small particle size of ferrihydrite means there is a large number of sorption sites and a high probability of adjacent sites allowing linear oligomerization. However the high surface curvature prevents higher degrees of polymerization.
110, the main face, sorption sites too distant to allow for any polymerization.
110
110
021
021, a minor main face, sorption sites close and allow for 3D polymerization
021
38
Poster 18 Effect of Combined High Hydrostatic Pressure and Dense Phase CO2 on Enzyme Activity
in Feijoa puree Trang Duong
Carmen Ortuño, Murat Balaban, Conrad Perera
High hydrostatic pressure(HHP) and dense-phase CO2(DPCD) processes have been separately studied as non-thermal technologies to inactivate undesirable enzymes in food. However, some enzymes are highly pressure resistant and can be functionally enhanced after HHP or DPCD treatments1. The combining of DPCD with HHP could improve the enzyme inactivation2,3. This research aimed to treat feijoa puree with a simultaneous HHP and DPCD process and to investigate its effects on the activity of pectin-methylesterase (PME), peroxidase (POD) and polyphenol-oxidase (PPO) enzymes. The samples were treated with HHP only (HHP), or HHP+carbonated (HHPcarb),or HHP+carbonated with added 8.5mL CO2/g sample (HHPcarb+CO2) at 300, 450 and 600MPa, 5min. HHP increased the residual enzyme activity (REA) of POD in HHP sample at 300MPa to 140±5%, but decreased to 60±9% and 22±13% at 450MPa and 600MPa, respectively. The addition of CO2 affected the REA of POD in samples at all tested pressures. The REA of PME significantly decreased in HHPcarb+CO2 samples from 73±14 % at 300MPa to 53±3 % at 600MPa. In general, PPO inactivation increased with the increasing of pressure, and amounts of added CO2. The addition of CO2 enhances enzyme inactivation with HHP. The effects of different treatment times, and pressures need to be investigated. References
1. Balaban, M. O., Effects of DPCD on enzymes. In Dense Phase Carbon Dioxide: Food and Pharmaceutical Applications, Balaban, M. O.; Ferrentino, G., Eds. Blackwell Publishing Professional: 2012; Vol. 1, pp 113-134.
2. Park, S.-J.; Lee, J.-I.; Park, J., Effects of a combined process of high pressure carbon-dioxide and high hydrostatic pressure on the quality of carrot juice. Journal of Food Science 2002, 65 (5), 1827-1834.
3. Corwin, H.; Shellhammer, T. H., Combined carbon dioxide and high pressure inactivation of pectin methylesterase, polyphenol oxidase, Lactobacillus plantarum and Escherichia coli. Journal of Food Science 2002, 67 (2), 697.
39
Poster 19 Synthetic studies towards Cephalosporolides H and I
Orla C. Finch,
Daniel P. Furkert, and Margaret A. Brimble
Cephalosporolides H (1) and I (2) are natural products that have been isolated from marine-derived fungus Penicillium sp. in 2007 by Li et al.1 Preliminary biological testing has revealed that both cephalosporolides (1) and (2) inhibit xanthine oxidase and 3α-hydroxysteroid dehydrogenase.2,3 Xanthine oxidase inhibitors are currently in use for the treatment of gout 3 and in studies as a possible treatment for heart failure.4
O
O
OO
H
H
R = C6H13 Cephalosporolide H (1)
R = (CH2)2CO2H Cephalosporolide I (2)
OBnO
O
O
OH
O
BnO
O
OBn
O
BnO
O
OBn+
3 4
5 6
R
Our synthetic approach hinges on a hindered cross methathesis reaction between 5 and 6 to form alkene 4. Sharpless dihydroxylation of 4 will lead to the lactone 3 which should undergo oxidative radical cyclisation to afford the tricyclic core of cephalosporolides H (1) and I (2). Functionalisation of the remaining hydroxy group will furnishes the desired products 1 and 2.
References
1 Li, X., Yao, Y., Zheng, Y., Sattler, I., Lin, W., Arch. Pharm. Res. 2007, 30, 812-815. 2 Degtiar, W., Kushlinsky, N., Biochem. 2001, 66, 256-266. 3 Pacher, P., Nivorozhkin, A., Szabó, C., Pharmacol. Rev. 2006, 58, 87-114. 4 Kittleson, M., Hare, J., Eur. Heart J., 2005, 26, 1458-1460
40
Poster 20 Application of non-targeted high resolution mass spectrometry to monitoring tea
fermentation level and origin
Karl Fraser Yacine Hemar, Siew-Young Quek, Don Otter, Geoff Lane, Scott Harrison
Tea is a beverage made from the leaf and bud of Camellia sinensis and is the second most consumed beverage in the world (Cabrera et al., 2006). It can be broadly classified according to its production method as either unfermented (green tea), semi-fermented (oolong tea), or fully fermented (black tea) and tea produced from particular regions of the world (e.g. Darjeeling region in India) can command a higher price due to perceived quality/health attributes. Eighty eight tea samples consisting of three different tea types (above) from 13 different countries/regions were collected and extracted with a hot water infusion for 5 minutes and analysed using high resolution UHPLC-MS. Eluting components were extracted and aligned from the LC-MS data and the resulting peak area matrix data was normalised and analysed with multivariate statistics. Both tea type and country of origin (figure 1) could be resolved using multivariate techniques, and the key components responsible for these observed differentiations have been further characterised. This non-targeted UHPLC-MS approach combined with multivariate statistics can be a useful tool for determining potential markers of tea type and provenance. Figure 1: Principle component analysis of green teas from China and Sri Lanka
Cabrera, C.; Artacho, R.; Gimenez, R., Beneficial effects of green tea - a review. J. Am. Coll. Nutr. 2006, 25 (2), 79-99.
41
Poster 21 Regulation of kiwifruit softening by differential cell wall modifications
Christina Fullerton
Roswitha Schröder, Ian Hallett, Robert Schaffer, Ross Atkinson, Conrad Perera, Bronwen Smith
Fruit softening has been shown to be the result of differential enzyme activity, determining how fast the fruit cell wall is deconstructed. In many fruit species softening is controlled, at least in part, by the ripening hormone ethylene. Kiwifruit (Actinidia spp.) is unusual because the fruit ripens to eating softness seemingly independent of ethylene. Within Actinidia there are closely related genotypes that show large differences in the rate of softening. We compared three genotypes with different softening rates to investigate the biochemical, structural and molecular basis of fruit softening with a view to identifying key softening regulators. Compositional analysis of cell walls during softening showed differences in monosaccharide composition between genotypes at the same fruit firmness, indicating that the rate of softening may not just be a matter of increased enzyme activity, but that there are differences in the cell wall composition from early in fruit development. Differences in the activities of key cell wall enzymes, such as xyloglucan endotransglycosylase, suggest that the softening rate is influenced by the modification of specific cell wall polysaccharides. Cell wall swelling also occurred to a different extent amongst the three kiwifruit genotypes. Further work will focus on the solubilisation and degradation of pectin and xyloglucan.
42
Poster 22 Ultrasound inactivation of bacteria at different growth phases
and application in skim milk
Shengpu Gao Yacine Hemar and Gillian Lewis
Ultrasonic treatment is considered as a novel method to inactivate bacteria in food system without causing the loss of nutrient and flavours. The aims of this study were to determine the effects of both low-frequency and high-frequency ultrasound treatment to bacteria at different growth phases, and to understand the mechanism of bacterial inactivation by ultrasonication, as well as the application of ultrasound inactivation in skim milk. Enterobacter aerogenes, Bacillus subtilis and Staphylococcus epidermidis were ultrasonicated at 20 kHz and 850 kHz under controlled temperature. Ultrasound cavitation resulted in lethal damage to some bacteria, by causing breakage of the bacterial cells into irregular, smaller fragments, which was observed by TEM and by measuring bacterial particle size distribution. Quantitatively, the results showed that the logarithm of survival ratio of the bacteria decreased linearly with the increase in the ultrasound power and ultrasound time, and that bacteria, especially E.aerogenes were more sensitive to ultrasonication in the exponential growth phase than in the stationary growth phase. The study also showed that gram-positive bacterial cells with capsules were more resistant to ultrasound treatment. In addition, it was found that E.aerogenes was more sensitive to ultrasound in water than in milks at different protein concentrations. This is mainly due to the effect of viscosity on cavitation1. This work also showed that ultrasonication had no significant influence on the milk proteins and on the structure of and the size of casein micelles. Reference: 1. Mason, T. J.; Lorimer, J. P., General Principles. In Applied Sonochemistry:Uses of Power Ultrasound in Chemistry and Processing, Wiley-VCH Verlag GmbH & Co. KGaA: 2003; pp 25-74.
43
Poster 23 Convergent Synthesis of Acortatarin A: a 2-Formylpyrrole Spiroketal Natural Product
Huimin Geng Margaret A. Brimble
Diabetic nephropathy (DN) is a major complication of diabetes and the leading cause of end-stage renal disease worldwide. Increasing evidence shows that high-glucose-induced overproduction of reactive oxygen species in renal cells plays an important role in the progression of DN, hence molecules that inhibit renal oxidative stress could have an important impact on the intervention of DN. Acortatarins A (1) and B (2) were isolated in 2010 by Cheng et al.1 from the rhizome of Acorus tatarinowii, commonly used for the treatment of central nervous system disorders. The acortatarins exhibited antioxidant activity in high-glucose-induced mesangial cells. The unusual pyrrole-fused morpholine motif is a pharmacophore present in the inhibitors of several enzymes, including phosphoinositide 3-kinase related kinases,2 TNF-R converting enzyme,3 matrix metalloproteinases, and tumor necrosis factor.4
N
OO
HO
HO
OHC
acortatarin A (1)
N
OO
HO
HO
OHC
OH
acortatarin B (2)
Our synthetic strategy aimed at accessing the spiroketal core of acortatarin A (1) through an acid-mediated cyclisation of 3. Ketone 3 was obtained from a Maillard-type connection5 of amino alcohol 4 and dihydropyranone 5. This approach provides a convergent route to acortatarin A and also provides a facile route to access a variety of other bioactive 2-formylpyrrole containing natural products.6
N
OO
HO
HO
OHC
N
OO
O
CHO
OTBS
TBDPSO
NH2
OO
OH
TBDPSO
O
O
HO
OTBS1 3
4
5
References
1. Tong, X. G.; Zhou, L. L.; Wang, Y. H.; Xia, C. F.; Wang, Y.; Liang, M.; Hou, F. F.; Cheng, Y. X., Org. Lett. 2010, 12, 1844-1847. 2. Verheijen, J. C.; Zask, A., Drug Future 2007, 32, 537-547. 3. Levin, J. I.; Chen, J. M.; Laakso, L. M.; Du, M.; Du, X.; Venkatesan, A. M.; Sandanayaka, V.; Zask, A.; Xu, J.; Xu, W.; Zhang, Y.; Skotnicki, J. S., Bioorg. Med. Chem. Lett. 2005, 15, 4345-4349. 4. Almstead, N. G.; Bradley, R. S.; Pikul, S.; De, B.; Natchus, M. G.; Taiwo, Y. O.; Gu, F.; Williams, L. E.; Hynd, B. A.; Janusz, M. J.; Dunaway, C. M.; Mieling, G. E., J. Med. Chem. 1999, 42, 4547-4562. 5. Ledl, F.; Schleicher, E. Angew. Chem. Int. Ed. 1990, 29, 565-706. 6. Geng H.; Chen, J. L-Y; Furkert, D. P.; Jiang. S.; Brimble, M. A.; Synlett. 2012, 855-858.
44
Poster 24 Switch-on DNA Sensor Based on Water Soluble Photoluminescent polymers
Anupama Rao Gulur Srinivas
David Barker, Jadranka Travas-Sejdic
There has been an enormous demand for commercial label-free DNA sensors in a diverse range of fields including pre-emptive medicine, diagnostics, environmental monitoring, and food industry. Addressing the need for sensitive, selective and facile DNA sensors, we demonstrate a novel optical DNA sensor with “switch-on” readout with novel water-soluble photoluminescent conjugated polymers (CPs) (Figure 1A). The sensor design utilizes sandwich hybridization between CP bound captureprobe (PPV-MagSi-CapODN) coated onto magnetic beads, target oligonucleotides (ODN) and the signalling probes (SP1). Hybridization with target ODNs was monitored by Fluorescence Resonance Energy Transfer (FRET) from the donor CP to acceptor dye-labelled SP1– a more robust system with lower detection limits to detect DNA. The selectivity with target, non-complementary and mis-matched DNA (Figure 1B), sensitivity and detection limit will be presented. Additionally, the application of the sensor in a “real” sample containing bovine serum albumin (BSA) will be presented. This work follows on from our previous research, involving an optical sensor based on a switch-on/switch-off anionic PPV [1] and interactions of a cationic PPV with DNA [2]. Furthermore, our DNA sensor has the manifold advantages of easy handling, facile, low-cost at the proof-of-design stage, and therefore has great potential for conversion into a microfluidic device.
Figure 1: (A) Schematic representation of the novel FRET based optical DNA sensor and (B) selectivity of the DNA sensor. References: 1. Gulur Srinivas, A.R.; Peng, H.; Barker, D.; Travas-Sejdic, J., Biosensors & Bioelectronics 2012, 35 , 498-502. 2. Peng, H.; Soeller, C.; Travas-Sejdic, J., Chemical Communications 2006, (35), 3735-3737.
A B
45
Poster 25 Switchable surfaces based on brushes grafted from conducting PEDOT
Alissa Hackett
Jenny Malmström, Lisa Strover, Yiwen Pei, Duncan McGillivray, Jadranka Travas-Sedjic Surfaces with readily-modulated properties show great promise in a range of applications, including microfluidic devices, self-cleaning surfaces, and biomedical devices. Recently, switching behaviour has been demonstrated in polymer brushes grafted from conducting polymer (CP) backbones.1-2 The CP can be electrochemically switched between the oxidised (conducting) and reduced (insulating) states, causing changes in brush morphology. In this way, an applied potential may be used to modulate the physical properties of the material. We report on the synthesis and characterisation of a novel surface based on insulating polymer brushes grafted from a conducting poly(3,4-ethylenedioxythiophene) (PEDOT) backbone that has been modified to include ATRP-initiating sites. A range of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) brushes were grafted from the backbone by AGET ATRP. These brushes are known to exhibit thermoresponsive behaviour, which is sensitive to salt concentration. We aim to induce brush collapse by controlling the ion concentration at the CP-brush interface by application of an electric potential. These brushes have potential in cell culture applications, as substrates that can reversibly control cell adhesion.
Figure 1. Proposed salt-induced collapse of polymer brushes, caused by electrochemical oxidation of the conducting polymer backbone.
References: 1. Strover, L.; Roux, C.; Malmström, J.; Pei, Y.; Williams, D. E.; Travas-Sejdic, J. Synthetic Metals 2012, 162 (3-4), 381-390. 2. Pei, Y.; Travas-Sedjic, J.; Williams, D. E. Langmuir 2012, 28 (37), 13241-13248.
46
Poster 26 New efficient macrocyclic tetraamidate iron catalysts for oxidations with hydrogen
peroxide
Brendan D. Harvey Terrence J. Collins, Laura G. Raymond, Trevor R. Stuthridge, L. James Wright
The widespread utilisation of hydrogen peroxide as a greener alternative to the potentially environmentally harmful chlorine- and metal-based oxidants commonly used in industrial oxidation processes is limited by its slow rates of oxidation with most organic substrates. Catalysts have the potential to significantly increase both the rates and selectivities of these oxidation reactions with hydrogen peroxide. One such catalyst which has recently been designed and synthesised, FeB*, is depicted in Figure 1. FeB* is a macrocyclic tetraamidate iron complex developed by T. J. Collins et al. which efficiently catalyses the oxidation of a wide variety of substrates with hydrogen peroxide in both aqueous and non-aqueous systems at sub-micromolar catalyst concentrations. [1] FeB* is composed of non-toxic elements and breaks down into environmentally benign products at the end of its useful lifetime. In the presence of hydrogen peroxide, FeB* undergoes intramolecular oxidation at a rate which is faster than ideal. This oxidation occurs at the dimethyl malonamide group at the ligand “tail” position. [2] We have developed a new macrocyclic tetraamidate complex, FeBJ (Figure 2), in which the weak dimethyl malonamide group at the “tail” position has been substituted with an oxalamide group. The catalytic properties of FeBJ vary substantially from those found for FeB*. While FeBJ catalyses the oxidation of organic substrates with hydrogen peroxide at slower rates than does FeB*, it is considerably more resistant towards self-oxidation. FeBJ is also far more stable towards acid-induced demetallation and displays optimal catalytic performance under less strongly basic conditions. Functionalisation of the aromatic ring of FeBJ with various substituents has led to a suite of related catalysts with different catalytic properties. A mechanism of dye oxidation catalysed by the substituted FeBJ catalysts has also been postulated, in agreement with kinetic data.
References: [1] N. Chahbane, D.-L. Popescu, D. A. Mitchell, A. Chanda, D. Lenoir, A. D. Ryabov, K.-W. Schramm, T. J. Collins, Green Chem. 2007, 9, 49-57. [2] T. J. Collins, Acc. Chem. Res. 2002, 35, 782-790.
47
Poster 27
Vaccine design for lectin targets
Paul Laurence Haseler
Margaret Brimble and Rod Dunbar.
Macrophage Galactose-type Lectin (MGL) is commonly found on the surface of Monocyte derived Dendritic Cells (MoDC). MGL is a homo-trimeric cluster complex protein that has three galactose binding domains, and is involved in the internalisation of glycosilated antigens into MoDC. Through the process of cross-presentation these antigens are presented to T cells, triggering an immune response. The aim of this project is to selectively target the interstitial N-Acetyl Galactose (GalNAc) binding sites of the MGL complex with a range of synthetic ligands. The ultimate goal is internalization of a vaccine by the MGL receptor, leading to the process of cross-presentation which will trigger an immune response.
The initial work focused on an efficient synthesis of the carbohydrate residue GalNAc, and the construction of mini-dendrimer scaffolds using solid phase peptide synthesis. These two components were united through “click” chemistry to give glycosylated mini dendrimers. The current focus is the selective targeting of MoDC using the library of compounds synthesised, through the use of cell binding and thermal melt assays. The result of these binding studies guides the optimisation for the synthesis of mini dendrimers, to increase the selectivity and strength of the binding to MGL.
O
OH
HO
OH
AcHNO
N
NN
AcHN
HN
O
HN
O
NHAc
O
HO
HO
OH
AcHNO
N
NN
OHN
NH
HN
O
O
NH
O
HOOC
HN
NHAc
N
NN
O
O
HO
HO
OH
AcHN
O
O
O
HO
OH
O
Fig 1. An example of a mini dendrimer glycosylated using “click” Chemistry
48
Poster 28 Impact of Pectin Fine Structure on Their Interactions with β-Lactoglobulin Nanofibrils
C. A. Hettiarachchi
Laurence D. Melton, Martin A. K. Williams, Juliet A. Gerrard, Simon M. Loveday and Duncan
McGillivray
-Lactoglobulin fibrils were interacted with structurally different pectins (P1, P2 and P3) to understand their behaviour in the presence of anionic polysaccharides. Morphology of the composites formed in selected -lactoglobulin fibrils-pectin systems was assessed in detail by different microscopic techniques and the images suggested that the interactions are highly specific to the type of pectin. Further evidence for the structural dissimilarities of the composites was obtained by small angle X-ray scattering and studying the accessibility of chemical probes to the specific moieties of the fibril surface. Results showed that the specificity of fibrils-pectin interactions was mainly governed by the electrostatic potential, which can be manipulated by the use of different pectins or by altering the pH and the ionic strength of the medium. One of the pectins was capable of laterally binding -lactoglobulin nanofibrils into well aligned ‘ribbons’ and this systems was extensively studied to understand the types of interactions involved and to find out the reactions cites of pectin that cause such an association. The results suggested that a few charged-blocks present in this particular pectin were driving the ribbon formation. The knowledge gained on the pectin fine structure and its impact on the physicochemical nature of the resulting composites will enable to produce biomaterials tailor-made to suit the required properties.
References
Sperber, B. L. H. M.; Cohen Stuart, M. A.; Schols, H. A.; Voragen, A. G. J.; Norde, W. Biomacromolecules 2009, 10, 3246−3252.
Tolstoguzov, V. B. Food Hydrocolloids 2003, 17, 1−23.
P1 P2 P3
P3
P3
49
Poster 29 Phenolic composition and antioxidant activities of different extracts from Actinidia
macrosperma
Sujeewa Hettihewa1
Yacine Hemar1, Christian Hartinger2 and H.P. Vasantha Rupasinghe3
1Food Science Programme, School of Chemical Sciences, The University of Auckland, New Zealand, 2School of Chemical Sciences, The University of Auckland, Zealand, 3Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Canada
Actinidia macrosperma, endemic to eastern China, is a wild Kiwifruit which has been extensively employed in Chinese traditional medicine. Total phenolic content (TFC), total flavonoid content (TFC) and antioxidant activity of the extracts from the fruit of A. macrosperma were determined by UV-visible spectroscopy. The extracts were prepared employing different solvent systems, namely 70% acetone, 80% methanol, 80% ethanol, 100% methanol, and 100% water, as well as extraction techniques namely, steeping, shaking, sonicating and blending. Total phenolic content values ranged from 321.61 ± 18.68 to 823.08 ± 14.39 mg gallic acid equivalent / 100 g dry weight of fruit. The total flavonoid contents of the extracts varied from 14.24 ± 6.00 to 170.70 ± 3.11 mg catechin equivalent / 100 g of dry weight of the fruit. DPPH values ranged from 2.02 ± 0.09 to 5.0 7± 0.09 mM Trolox equivalent / 100 g dry weight of the fruit and FRAP varied from 1.75 ± 0.08 to 8.25 ± 0.04 mM Fe (II) equivalent / 100 g dry weight of the fruit. The aqueous 70 % acetone extract indicated the highest values of TPF, TPC, and antioxidant activities. This work shows the possibility to isolate chemical compounds from A. macrosperma for scavenging and antioxidant activities. Further work is needed to elucidate the structural properties of these compounds.
References Jayaprakasha, G.K.; Singh, R.P.; and Sakariah, K.K. Antioxidant activity of grape seed (Vitis vinifera) extracts on peroxidation
models in vitro. Food Chem. 2001, 73(3), 285-290. Latocha, P.; Krupa, T. Antioxidant activity and chemical difference in fruit of different Actinidia sp. International Journal of
Food Sciences and Nutrition. 2010. 61(4), 381-394.
50
Poster 30 Synthetic Studies Towards Phorbaketal A and Alotaketal A
J. G. Hubert
D. P. Furkert, M. A. Brimble Phorbaketal A and alotaketal A are closely related natural products which contain a unique spiro-sesterterpenoid core structure.1,2 While both are of marine sponge origin, they are derived from distinct species; phorbaketal A from Phorbas sp. isolated off the coast of South Korea and alotaketal A from Hamigera sp. collected from Milne Bay, Papua New Guinea. Biological testing of these novel compounds has unveiled a broad range of biological activity.1,2 Phorbaketal A possesses moderate cytotoxicity against a range of cancer cell lines, as well as exhibiting osteoblast and mast cell differentiation activity and inhibition of fatty acid synthesis in the liver.1,3,4 Additionally, alotaketal A has been shown to activate the cAMP signalling pathway at nanomolar concentrations.2 The interesting biological profile of these compounds along with their complex polyunsaturated structures has prompted our research group to pursue synthetic investigations for their construction. Herein we report studies towards the enantioselective syntheses of phorbaketal A and alotaketal A.
References 1 Rho, J.-R.; Hwang, B. S.; Sim, C. J.; Joung, S.; Lee, H.-Y.; Kim, H.-J. Org. Lett. 2009, 11, 5590-5593. 2 Forestieri, R.; Merchant, C. E.; De Voogd, N. J.; Matainaho, T.; Kieffer, T. J.; Andersen, R. J. Org. Lett. 2009, 11, 5166-5169. 3 Kang, H. J. R., J. R; Hong, J. H; Park S. B; Shin, C. S; Lee, J. H; Hong, J. Y.; Kim, J. A; Oh, S. M. South Korea, 2010; Vol. WO 2010/050783 A2. 4 Byun, M. R.; Kim, A. R.; Hwang, J.-H.; Sung, M. K.; Lee, Y. K.; Hwang, B. S.; Rho, J.-R.; Hwang, E. S.; Hong, J.-H. FEBS Letters 2012, 586, 1086-1092.
51
Poster 31 Synthetic Studies towards the Virgatolides
Paul Hume
Margaret Brimble and Daniel Furkert Benzannulated spiroacetals are a structural element found in several naturally occurring molecules. Within the class of benzannulated spiroketal containing natural products, those possessing a 6,6-spiroacetal functionality are rare.1 Virgatolides A-C2 are a recently discovered family of compounds containing a benzannulated 6,6-spiroacetal moiety. The compounds were isolated in 2011 from Pestalotiopsis virgatula, a fungal endophyte inhabiting the leaves of Dracontomelon duperreanum, a plant traditionally used by the Chinese for its medicinal properties.3 Preliminary biological testing revealed virgatolides A-C to each have comparable cytotoxicity against HeLa (cancerous cervical epithelium) cells, with respective IC50 values of 19.0, 22.5 and 20.6 µM.2,3
The relatively unknown biological relevance of the virgatolides coupled with their novel molecular architecture has prompted us to investigate their total synthesis. Our synthetic strategy relies on a common initial synthetic sequence for all three compounds, followed by late stage divergence in order to allow construction of each member of the family.
Refernces 1 Sperry, J.; Wilson, Z. E.; Rathwell, D.; Brimble, M. A. Nat. Prod. Rep. 2010, 27, 1117-1137. 2 Li, J.; Li, L.; Si, Y.; Jiang, X.; Guo, L.; Che, Y. Org. Lett. 2011, 13, 2670-2673.
3 Yang, X.; Zhang, J.; Luo, D. Nat. Prod. Rep. 2012, 29, 622-641.
52
Poster 32 Developing Novel Macrocyclic Tetraamidate Iron Complexes as Green Oxidation Catalysts
for Industrial Applications N. Ismail,a T. J. Collins,b B. D. Harvey,a L. G. Raymond,a T. R. Stuthridge,c, N. Singhald, L. J.
Wrighta aSchool of Chemical Sciences, University of Auckland, Auckland, NZ
bDepartment of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA cScion Ltd., Rotorua, NZ
dDepartment of Civil & Environmental Engineering, University of Auckland, NZ
The replacement of chlorine-based oxidants with the more environmentally benign oxidant, hydrogen peroxide is still limited due to the slow rate at which hydrogen peroxide oxidises organic compounds. This problem can be overcome through the development of suitable catalysts that lower the kinetic barriers to these reactions. One such catalyst is the macrocyclic tetraamide iron complex FeB* Figure 1 [1]. Among the attractive features of this catalyst are: its relatively simple preparation, its high water solubility and its very high activity. The FeB*/H2O2 oxidation system therefore provides a “greener” alternative to chlorine-based oxidants, where the formation of unwanted organocholorines is often problematic [2]. Unfortunately, the dimethylmalonamide section of FeB* is susceptible to oxidative decomposition. This led to the design of the new iron complex FeBJ, Figure 2 [1] in which this section is replaced with an oxalamide group. This new group modifies the ligand N-donor properties and reduces the macrocyclic ring size. These changes in turn significantly alter the properties of the catalyst. In comparison to FeB*, the rate of oxidation of organic substrates catalysed by FeBJ is slower but the new catalyst is more stable. Furthermore, the free ligand, H4B
J, can easily undergo functionalization at the aromatic ring. The resulting family of new iron complexes that has been prepared has been shown to catalyse the oxidation of organic contaminants such as phenol and EE2 by H2O2 and these results will be discuss further.
References [1] T. J. Collins, Acc. Chem. Res. 2002, 35, 782-790. [2] C. P. Horwitz, T. J. Collins, J. Spatz, H. J. Smith, L. J. Wright, T. R. Stuthridge, K. G. Wingate, K. McGrounther, Iron-
TAML Catalysts in the pulp and paper industry, ACS Symposium Series, (2006) 921 (Feedstocks for the Future). Edited by J. J Bozell and M. K. Patel, pp. 156-169.
53
Poster 33
Design and Synthesis of Novel Rodenticides
Morgan Jay-Smith Margaret Brimble, David Rennison
Rats (Rattus spp.) are among the world’s most invasive pest animals and cause global economic, environmental and epidemiological damage.1 Current market rodenticides have little to no species selectivity leading to secondary toxicity in non-pest animals. The development of improved technologies to control these detrimental pests is highly desirable. Our approach hinges on the modifications of a known rat specific toxin, norbormide, and concurrent design and synthesis of a novel class of toxins, carbon monoxide releasing molecules (CORMs). Norbormide is toxic to rats at levels of 5 mg/kg (p.o.), however it has not had commercial success due to its low palatability, resulting in bait shyness.2 Prodrugs of norbormide at the dicarboximide nitrogen are expected to delay the toxic effect and mask palatability issues, so as to allow ingestion of a lethal dose. Our second research focus is the synthesis of CORMs – compounds which release CO (a known poison) under physiological conditions. To date, these compounds have only been developed for therapeutic applications.3 We present here our progress towards the development of novel norbormide- and CORM-based rodenticides.
Figure 1: Norbormide prodrugs
R4
R1
R2
R3O
R4
R1
R2
R3
CO +
R6
R5
R6
R5
Figure 2: Carbon monoxide releasing molecule scaffold
References: 1. Brockie, R. E.; Loope, L. L.; Usher, M. B.; Hamann, O., Biological invasions of island nature reserves. Biol. Conserv. 1988, 44, 9-36. 2. Rennison, D.; Laita, O.; Bova, S.; Cavalli, M.; Hopkins, B.; Linthicum, D. S.; Brimble, M. A., Design and Synthesis of Prodrugs of the Rat Selective Toxicant Norbormide. Bioorg. Med. Chem. 2012, 20 (13), 3997-4011. 3. Motterlini, R.; Mann, B. E.; Foresti, R., Therapeutic applications of carbon monoxide-releasing molecules. Expert Opin. Invest. Drugs 2005, 14 (11), 1305-1318.
54
Poster 34 Theoretical DFT-D Investigation of Supramolecular Porphyrin-Fullerene Interactions
Leonie Jones
Associate Professor Peter D.W. Boyd
Porphyrins and fullerenes are spontaneously attracted to each other by van der Waals interactions between the planar π-surface of a porphyrin and the curved π-surface of a fullerene.1 The supramolecular interaction between porphyrins and fullerenes is a primary structure-defining element which can be used to construct porphyrin-fullerene cocrystallates and supramolecular host-guest complexes.1 The close association of porphyrins and fullerenes has been observed in a large number of porphyrin-fullerene supramolecular complexes. In contrast to the large amount of experimental studies, theoretical investigations of non-covalent supramolecular porphyrin-fullerene interactions are quite rare, and the effect of porphyrin substituents on these supramolecular interactions have not yet been reported. Here we present a systematic density functional (DFT-D)2-5 study of the effect of porphyrin substituents on supramolecular porphyrin-fullerene interactions. We have examined this by investigating porphyrin-fullerene complexes in the order: Porphine > DPP > TPP > D3tbutylPP > T3tbutylPP which, across the series, gives rise to increased C-H···fullerene interactions. Historically, theoretical investigations of porphyrin-fullerene interactions have proved to be difficult due to the long-range non-local nature of dispersion interactions.6 We conducted our theoretical investigation using different functionals which have been designed to overcome the difficulties associated with modeling dispersive intermolecular interactions. References: 1 Boyd, P.D.W.; Reed, C.A. Acc. Chem. Res. 2005, 38, 235 2 Grimme, S. J. Comp. Chem. 2004, 25, 1463 3 Grimme, S. J. Comp. Chem. 2006, 27, 1787 4 Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys. 2010, 132, 4104 5 Grimme, S.; Ehrlich, S.; Goerigk, L. J. Comp. Chem. 2011, 32, 1456 .6 Liao, M.-S.; Watts, J.D.; Huang, M.-J. J. Phys. Chem. B. 2007, 111, 4374
HN
N
NH
N
HN
N
NH
N
55
Poster 35 Semiconductor Photocatalysts for H2 Production from Biofuels
Vedran Jovic Geoff Waterhouse and Tilo Sӧhnel
Hydrogen powered fuel cells are expected to play a key role in both automotive and stationary
power applications of the future due to their high energy efficiency and negligible greenhouse gas emissions. Current H2 production technologies are based on methane reforming, an energy intensive process with a large carbon footprint. Alternative H2 production methods which are environmentally friendly are becoming essential. Photocatalysis is regarded as potentially a key process for the generation of H2 based energy carriers from biomass. As a result, a great deal of attention has been dedicated to the development of novel AuTiO2 catalysts for the photo conversion of biomass to clean H2 based energy carriers. This may be achieved through the photo-oxidation of ethanol (a renewable biofuel) and the water gas-shift reaction, yielding H2 and CO2.
1 P25, a benchmark material due to its efficiency in a wide range of reactions, is a mixed phase commercial TiO2 photocatalyst, composed of approximately 80% Anatase and 20% Rutile. During irradiation, electrons from the conduction band of Rutile migrate across the interfacial junction and are trapped as Ti3+ sites within the Anatase lattice or exist as free electrons within the conduction band.2 Owing to the indirect nature of the Anatase band gap, charge recombination is greatly suppressed. However, the synergistic effect in P25 and its direct influence on H2 generation in Au-P25 is yet to be fully understood. In this work, a systematic study of H2 production from ethanol/water, over a series of novel Au-P25 (Au = 0.5-10 Wt. %) materials, is presented. By deconstructing Degussa P25 into its component phases, interfacial sites between individual Anatase and Rutile crystallites have been identified as catalytic hotspots for photocatalytic H2 production.
1. Nadeem, M.A.; Murdoch, M.; Waterhouse, G.I.N. J. Photochem. Photobiol. A. 2010, 216, 250-255. 2. Hurum, D.C.; Agrios, A.G.; Crist, S.E.; Gray, K.A.; Rajh, T.; Thurnauer, M.C. J. Electron. Spectrosc. 2006, 150, 155-
163.
0.0
wt.%
Au
0.5
wt.%
Au
1.0
wt.%
Au
2.0
wt.%
Au
3.0
wt.%
Au
4.0
wt.%
Au
5.0
wt.%
Au
6.0
wt.%
Au
8.0
wt.%
Au
10.0
wt.%
Au
WG
C R
efe
renc
e
Rat
e of
H2 P
rodu
ctio
n (µ
mol
g-1h-1
)
0
100
200
300
400
500Au/P25
WG
C
P2
5
Ana
tase
Rut
ile
3 w
t.% A
u/P
25
3 w
t.%
Au/
Ana
tase
3 w
t.% A
u/R
utile
3%
Au/
A+A
u/R
Mix
Rat
e of
H2 P
rodu
ctio
n (µ
mol
g-1h-1
)
0
100
200
300
400
500 Rate of H
2 Production (µ
molm
catal -2h-1)
0
2
4
6
8
10
56
Poster 36 Purification and Characterisation of Phosphorylated Lactose Milk Protein Conjugates
Norliza Julmohammad
Yacine Hemar, Gordon Miskelly and Don Otter The main aim of this work is the preparation and characterisation of phosphorylated lactose using two methods. In the first method, regiospecific modification of lactose is being attempted. Lactose was first reacted with 2,2-dimethoxypropane and the products were purified on a silica gel column [1]. The presence of 2,3:5,6:3',4'-tri-O- isopropylidenelactose dimethyl acetal was confirmed by TLC, FTIR, ESI-MS and NMR. This compound will be reacted with sodium hexametaphosphate, to phosphorylate the unprotected -OH groups, followed by a deprotection step to give the phosphorylated lactose. The second method is based on the reaction of lactose and sodium at pH 5.5 [5]. The phosphorylated lactose is then purified on an anion resin column. Fractions collected were monitored with reducing sugar test (PAHBAH assay), total phosphorus test, and 31P NMR [2]. The phosphorylated samples were further analysed by 1D NMR (1H, 13C, 31P and DEPT-135), 2D NMR (COSY, HMBC, and HSQC) and LC-MS. After further purification to obtain specific lactose-6’-phosphate, conjugation of the phosphorylated lactose to milk proteins through their lysine residues (Figure 1). It is expected that these conjugates will enhance the milk protein functionalities, such as stability under heating and better digestive properties.
O OO
OH
HO
PO
O
O
HO
OHOH
HO
HN
O
O
NH
Figure 1: Phosphorylated Lactose Milk Protein Conjugates References [1] Barili, P. L.; Catelani, G.; Andrea, F. D.; Rensis, F. D.; Falcini, P., Improved preparation of 2,3:5, 6:3', 4' - tri- O- isopropylidenelactose dimethyl acetal and its 6'-O-(1-methoxy-1-methylethyl) derivative. Carbohydrate Research 1997, 298, 75-84. [2] Breg, J.; Romijn, D.; van Halbeek, H.; Vliegenthart, J. F. G.; Visser, R. A.; Haasnoot, C. A. G., Characterisation of four lactose monophosphates by application of 31P-, 13C-, and 1H-NMR spectroscopy. Carbohydrate Research 1988, 174, 23-36. [3] Catelani, G.; D'Andrea, F.; Puccioni, L., Selective deprotection of 2',6'-di-O-benzyl-2,3:5,6:3',4'-tri-O-isopropylidenelactose dimethyl acetal. Carbohydrate Research 2000, 324, 204-209. [4] Lever, M., Colorimetric and Fluorometric Carbohydrate Determination with p-Hydroxybenzoic Acid Hydrazide. Biochemical Medicine 1973, 7, 274-281. [5] Tarelli, E.; Wheeler, S. F., The preparation of sucrose monophosphates from dried mixtures of sucrose and sodium phosphate. Carbohydrate Research 1995, 269, 359-368.
57
Poster 37 Interaction between Advanced Glycation End-Products and Transition Group Metals
Meder Kamalov
Tom Woods, Garth Cooper, Margaret A. Brimble Advanced glycation end-products (AGEs) are unnatural amino acid derivatives that form in the reaction of sugars with side-chain residues of various amino acids in proteins. AGEs have been implicated in the pathogenesis of diabetes mellitus. It is known that prolonged hyperglycemia can lead to an increase in the formation and accumulation of AGEs and this increase has been linked to diabetic organ damage.1 Additionally, it has been shown that abnormal metabolism of Zn, Cu and Fe can also lead to diabetic organ damage2 and in other studies AGEs were shown to bind transition group metals.3 However, the underlying molecular mechanisms that link these processes remain unclear. The aim of this project was to develop chemical probes with which to investigate such mechanisms. Collagen is the most abundant protein in vertebrates and its long-lived nature makes it susceptible to glycation. Various collagen model peptides (CMPs) have previously been prepared comprising of 21-30 residues4 to study the factors affecting the structure of collagen. Therefore, we propose that AGEs incorporated into CMPs will function as useful probes for studying the interaction between peptide bound AGEs and transition metal ions. To date, we have prepared peptide-ready Fmoc-protected AGEs carboxymethyllysine (CML) derivative X and carboxyethyllysine (CEL) derivative Y and incorporated them in CMP (Fig. 1). The stability constants of AGE complexes with several metal ions will be determined both in free and peptide bound environments via potentiometric titration measurements. This should help to elucidate the relationship between individual AGEs, the host proteins and metal ions and enable development of novel therapeutic strategies for diabetic patients.
OH
NHFmoc
O
N
SO2
O
O
NO2
R
N NHN N
HN
HN N N
HNH
O O O
OH
3 3O O O O O
OH
OH
O
NHHO
O R
Lysinei -v
SPPS
X: R=H
Y: R=CH3
Figure 1. Synthesis of CMP with carboxymethyllysine (CML) (R = H) and carboxyethyllysine (CEL) (R = CH3). Reagents and conditions: (i) 9-BBN dimer, MeOH, reflux, 1h; (ii) NsCl, 10% K2CO3, 1,4-dioxane, overnight; (iii) Ethyl bromoacetate (for CML) and ethyl bromopropionate (for CEL), K2CO3, CH3CN (for CML) or DMF (for CEL); (iv) 4M HCl in 1,4-dioxane, 90 min; (v) Fmoc-OSu, 1,4-dioxane, 10% Na2CO3, overnight. References (1) Singh, R., et al. Diabetologia 44, 129-146 (2001). (2) Zheng, W, et al. Hemoglobin 32, 135-145 (2008) (3) Saxena, A.K. et al. Biochem. and Biophys. Res. Comm. 260, 332-338 (1999) (4) Persikov, A.V., et al. Biopolymers 55, 436-450 (2000).
58
Poster 38 Analysis of Beverage Antioxidants using a PEDOT-Based Sensor
Hande Karaosmanoglu1, Jadranka Travas-Sejdic1, Paul Kilmartin1
1School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland
Antioxidants are important both in terms of human health and food quality. The currently used antioxidant determination techniques have various disadvantages such as long time requirements, low sensitivity, interfering agents etc. Recently, there has been an increase in research using cyclic voltammetry (CV). In addition to glassy carbon electrodes (GCE)1, conducting polymers such as polypyrrole2, poly(3,4-ethylene dioxithiophene) (PEDOT)3 and polythiophene4 have been used to improve sensitivity and specificity. In this study, electrochemically polymerized PEDOT-covered 1 mm diameter GCEs were used for rapid and selective antioxidant analyses of tea and coffee samples. After identifying and quantifying the antioxidant content of samples by HPLC, the major compounds were tested using the electrochemical sensor. The CVs of green tea and coffee resembled that of epigallocatechin gallate and chlorogenic acid, respectively, which are the main phenolic compounds present in these beverages. Moreover, the integral of the current vs. time to 500 mV (Q500) from the voltammogram was used as a measure of the total antioxidant content. Spectrophotometric assays were also performed to evaluate the total phenolic content (TPC) and antioxidant activity of the samples. When the data were compared with Q500 values, good correlation values were obtained (Figure 1). The findings showed that the electrochemical sensor is easy to handle and gives rapid results.
Figure 1: Comparison of the TPC values obtained by CV with Folin-Ciocalteu (FC) (A), ABTS (B) and DPPH (C) methods.
References 1. Kilmartin, P. A.; Hsu, C. F., Characterisation of polyphenols in green, oolong, and black teas, and in coffee, using cyclic
voltammetry. Food Chem 2003, 82 (4), 501-512. 2. Rodríguez-Méndez, M. L.; Apetrei, C.; de Saja, J. A., Evaluation of the polyphenolic content of extra virgin olive oils
using an array of voltammetric sensors. Electrochim Acta 2008, 53 (20), 5867-5872. 3. Türke, A.; Fischer, W. J.; Beaumont, N.; Kilmartin, P. A., Electrochemistry of sulfur dioxide, polyphenols and ascorbic
acid at poly(3,4-ethylenedioxythiophene) modified electrodes. Electrochim Acta 2012, 60 (0), 184-192. 4. Lupu, S.; Mucci, A.; Pigani, L.; Seeber, R.; Zanardi, C., Polythiophene Derivative Conducting Polymer Modified
Electrodes and Microelectrodes for Determination of Ascorbic Acid. Effect of Possible Interferents. Electroanal 2002, 14 (7-8), 519-525.
A B
C
59
Poster 39 Biomimetic Synthesis of Thiaplidiaquinone A and B
Iman Khalila Jacquie Harperb, David Barkera and Brent Coppa
aThe School of Chemical Sciences, University of Auckland, New Zealand bMalaghan Institute of Medical Research, P.O. Box 7060, Wellington, New Zealand
Ascidians (known as sea-squirts) of the genus Aplidium are known as a rich source of prenylated quinone and hydroquinone natural products. These secondary metabolites are typically bioactive and typically contain complex structural scaffolds.1
Studies on a Mediterranean ascidian, Aplidium conicum, have previously led to the isolation of two bioactive natural products, thiaplidiaquinone A and B.2 Due to our interest in the benzo[c]chromene subunit, we devised a biomimetic synthesis starting from a monomeric geranyl benzoquinone using a 5-step reaction sequence where one of the key steps is a base-mediated dimerisation.
We herein report the synthesis of thiaplidiaquinone A and B and the consequent synthesis of dioxothiazino regioisomers of the natural products.3 Biological evaluation of the two natural products and their regioisomers using a cell viability assay identified that the orientation of the dioxothiazine ring increases the antiproliferative potency of the compounds and more interestingly that the position of the diprenyl chain on the aromatic ring dictates whether cell death occurs via an apoptotic or necrotic pathway. These results have proven the importance of the synthesis of not only the natural products but also their regioisomers and have paved the way for a more extensive SAR study on this series of unusual natural products.
1. Zubia, E.; Ortega, M. J.; Salva, J., Natural products chemistry in marine ascidians of the genus Aplidium. Mini-Reviews in Organic Chemistry 2005, 2, 389-399.
2. Aiello, A.; Fattorusso, E.; Luciano, P.; Macho, A.; Menna, M.; Muñoz, E., Antitumor Effects of Two Novel Naturally Occurring Terpene Quinones Isolated from the Mediterranean Ascidian Aplidium conicum. J. Med. Chem. 2005, 48, 3410-3416.
3. Khalil, I. M.; Barker, D.; Copp, B. R., Biomimetic Synthesis of Thiaplidiaquinones A and B. J. Nat. Prod. 2012, 75, 2256-2260.
A B C D A B C D
A B C D A B C D
Iso‐Thiaplidiaquinone B
% Cell death
% Cell death
A : Untreated, B : Necrosis, C : Apoptosis, D : Dead
Thiaplidiaquinone BThiaplidiaquinone A
Iso‐Thiaplidiaquinone A
60
Poster 40 Total synthesis of Chaetoquadrins
U Bin Kim
Dan Furkert, Margaret Brimble Various chromone natural products have been isolated from the Ascomycete Chaetomium quadrangulatum. Many of these compounds, including chaetoquadrins A, G, I, K, have exhibited inhibitory activity against mouse liver monoamine oxidase.1,2 In our endeavour to synthesise the spiroketal chaetoquadrin A we have established methodology that enables rapid access to non-spiroketal chromone natural products including chaetoquadrin G, I and K. Chromone 1 and spiroketal 2 have also been successfully synthesised (figure 1). The synthesis of these chromones started from the known natural product noreguenin (3) and our synthetic strategy featured an aromatic Claisen rearrangement and an aldol reaction as key functionalization steps. The synthesis of these natural products and closely related chromones will be presented.
O
O
Me OH
OH
noreugenin (3)
O
OH
O
O
O
O
chaetoquadrin G
O
OH
O
O
O
O
chaetoquadrin I
O
OH
O
O
O
O
chaetoquadrin Gisomer (1)
Claisen-aldolMethodology
O
O
O
O
O
deoxy-chaetoquadrin A (2)
O
O
O
O
O
OH
chaetoquadrin A
O
OH
O
O O
OH
chaetoquadrin K
Figure 1. Synthesis of natural and unnatural products from chromone noreugenin 3. References: 1. Fujimoto, H.; Nozawa, M.; Okuyama, E.; Ishibashi, M. Chem. Pharm. Bull. 2002, 50, 330-336. 2. Fujimoto, H.; Nozawa, M.; Okuyama, E.; Ishibashi, M. Chem. Pharm. Bull. 2003, 51, 247-251.
61
Poster 41 Oxidative stress alters the membrane-binding interaction of plant annexin Gh1
Jacqueline J. Knobloch
Andrew R. J. Nelson, Andreas Hofmann, Vanessa Lake, Anthony P. Duff, Duncan J. McGillivray
Oxidative stress, caused by an imbalance between the production and removal of oxidising species, has been linked to neurodegenerative and cardiovascular diseases.1 Annexins, a ubiquitous group of membrane binding proteins found in plants, animals and fungi, are thought to be involved in the cell’s physiological response following oxidative stress.2 Recently, an annexin has been shown to self-assemble into two-dimensional arrays sealing defects in the cellular membrane, promoting membrane repair.3 Various plant annexins also display peroxidase activity and it has been speculated that they could therefore recognise and recycle peroxidated lipids in the membrane.4
The membrane binding interaction of a cotton (Gossypium hirsutum) derived annexin, annexin Gh1, was studied on oxidised and non-oxidised biomimetic phospholipid membranes.5 Oxidative stress was mimicked either in vitro using iron(II) and ascorbate to initiate phospholipid oxidation or by employing membranes containing a synthetic “oxidised” phospholipid. Neutron and x-ray reflectometry showed annexin Gh1 formed thick, non-crystalline layers on non-oxidised membranes with a concurrent disruption of the membrane structure. Thinner annexin Gh1 layers were observed on oxidised membranes, with less disruption to the membrane structure.
References 1. Halliwell, B.; Gutteridge, J. M., Free Radicals in Biology and Medicine. 4th ed.; Oxford University Press: Oxford, 2007. 2. Gidrol, X.; Sabelli, P. A.; Fern, Y. S.; Kush, A. K., Annexin-like protein from Arabidopsis thaliana rescues Delta oxyR mutant of Escherichia coli from H2O2 stress. Proc. Natl. Acad. Sci. U. S. A. 1996, 93 (20), 11268-11273. 3. Bouter, A.; Gounou, C.; Berat, R.; Tan, S.; Gallois, B.; Granier, T.; d'Estaintot, B. L.; Poeschl, E.; Brachvogel, B.; Brisson, A. R., Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair. Nature Communications 2011, 2. 4. Konopka-Postupolska, D.; Hofmann, A.; Clark, G., Structure, function and membrane interactions of plant annexins: an update. Plant Science 2011. 5. Hofmann, A.; Delmer, D. P.; Wlodawer, A., The crystal structure of annexin Gh1 from Gossypium hirsutum reveals an unusual S3 cluster. Implications for cellulose synthase complex formation and oxidative stress response. Eur. J. Biochem. 2003, 270 (12), 2557-2564.
62
Poster 42 In-Situ Synchrotron Corrosion Studies of CO2 Corrosion of Carbon Steel
Monika Ko
Bridget Ingham, Nicholas Laycock, David E. Williams Corrosion of pipeline steel in CO2 containing environment is a significant problem in the oil and gas industry1. The corrosion rate typically increases with temperature up to a certain point, and then decreases at higher temperatures due to the formation of protective corrosion product on the steel surface2. Under certain conditions, FeCO3 forms a strongly adherent and tightly packed crystalline scale that protects the underlying steel from further corrosion. The goal set in this work was to gain an improved understanding for the reasons behind different growth habits in scales formed in CO2 containing environment, particularly in relation to those that turn out to be highly protective. In-situ synchrotron technique was used to characterise the surface layer on carbon steel in CO2 saturated solutions at 80°C while the corrosion was accelerated through anodic polarisation under potentiostatic control. Figure 1 shows the relationship between the formation and growth of FeCO3
in relation to the current density as a function of time. There is a clear peak in the current transient which coincides with the formation of FeCO3 and then rapidly decreased as the current decreases, indicating the growth of a protective layer. The effect of changing solution composition, steel composition and microstructure are investigated.
Figure 1: Results for 0.5 M NaCl brine at pH 6.3 and an applied potential of -500 mV, at 80C. References: 1. Kermani, M.B. and Morshed, A. Corrosion, 2003, 59, 659-683. 2. De Waard, C and Lotz, U. Prediction of CO2 Corrosion of Carbon Steel, proceeding of NACE Corrosion, NACE International, 1993, Paper 69.
63
Poster 43 Proteomics to Determine the Age of Human Bruises
Marie Lecomte
Dr. Joanne Simons, Dr. Janine Cooney, Ms. Sue Vintiner, Dr. Douglas Elliot
Evidence of physical abuse is often left on victims, with bruising being the most common symptom. Bruises are also the most frequent injury resulting from sports and everyday accidents, leading to abusive injuries sometimes being misinterpreted as accidental ones. Despite its prevalence, bruising remains a much neglected field of study with most of our knowledge to date deriving from post-mortem human investigations and animal studies, which have a limited application to real-world situations involving living individuals. Bruise biomarkers, as signs of physical abuse, could provide vital evidence in legal cases concerning suspected abuse. This would be particularly valuable in cases involving vulnerable individuals, such as children, elderly people or victims of domestic violence, who may be unable to provide an accurate account of the circumstances or timing of an assault. In this study, proteomic techniques such as 2-D gel electrophoresis and LCMS will be used to identify biomarkers specific to bruises present in the interstitial fluid of living individuals. The work completed to date to identify candidate biomarkers using these techniques will be discussed, along with the potential applications of this project to the forensic science field.
64
Poster 44 A new synthetic approach to white light emitting polymers
Katie Lin
Jianyong Jin, Penelope Brothers, David Ware We present a novel method for synthesising a white light emitting polymer for applications such as solid-state area lighting and screen display backlighting, as polymers have a processability and cost advantage over the current solid state inorganic materials employed for these purposes. A single polymer system is described, wherein red and green emitters are covalently bonded to a functionalised blue-emitting polymer backbone (see Figure 1) via a Diels-Alder cycloaddition reaction. The red and green emitters will be complexes of lanthanide ions, europium(III) and terbium(III), respectively. Lanthanides were chosen because the emissions bands are very narrow (on the order of 10 nm), the wavelengths are ion-specific and are not affected by the coordination sphere of the metal ion. The blue-emitting backbone will contain carbazole and anthracene groups, the latter of which will be used for reaction with a maleimide group present on one of the ligands of the metal complexes. The advantage of this concept is that post-functionalisation allows the concentration of the emitters to be precisely controlled, which is key to obtaining optimum output colour purity.
Blue-emitting polymer backbone
Red and green emitters
Figure 1 Schematic representation of proposed polymer system.
65
Poster 45 The impact of vegetative clone on rotundone concentration throughout ripening and at
commercial harvest in New Zealand Vitis vinifera L. Syrah for wine production
Gerard A. Logan1 Tracey E. Siebert2, Mark Solomon2, Glen L. Creasy3†, Richard Smart4†,
Muraleedharan G. Nair5†, Paul A. Kilmartin1† 1 Wine Science Postgraduate Programme, School of Chemical Sciences, The University of Auckland, New Zealand 2 The Australian Wine Research Institute, Urrbrae, Australia 3 Centre for Viticulture and Oenology, Lincoln University, New Zealand 4 Smart Viticulture, Tasmania, Australia and United Kingdom 5 Bioactive Natural Products and Phytoceuticals Laboratory, Michigan State University, East Lansing, Michigan, United States of America. † Ph.D. Supervisory Committee, Chair: Assoc. Prof. Paul A. Kilmartin. New Zealand Syrah is becoming increasingly popular as a high quality and in some cases iconic wine, largely due to an elevated, pungent black pepper aroma that contributes to the profile of the wine. Rotundone is an oxygenated bicyclic sesquiterpene recently identified as the black pepper aroma compound in grapes, wine and other plants. Currently little is known about the impact of selecting different vegetative clones of Syrah on the concentration of rotundone in fruit for winemaking, despite a myriad of anecdotes. Thus our approach was to determine if vegetative clonal selection impacts on the final concentration of rotundone in the fruit at harvest. Vines were spur-pruned unilateral cordon Syrah, planted on 3309 Couderc rootstock in alluvial gravel soils during 1999 and trained onto a single canopy Vertical Shoot Positioned trellis (VSP). Three commonly used vegetative clones of Syrah were chosen for the initial work at the beginning of the annual growing cycle each year. We selected Vitis vinifera L. Syrah clones ‘Chave’, ‘Dijon 470’ and ‘Mass Select (MS)’. All vineyard management inputs were applied uniformly to the vines throughout the growing season. Replicated samples of ~300 g fruit were taken at three intervals between veraison and harvest from all areas and were immediately frozen with liquid nitrogen. The samples were stored at -20°C until being flown to the Australian Wine Research Institute in Adelaide on dry ice. Results showed that these selected vegetative clones of Syrah impacted upon the concentration of rotundone in Syrah fruit. Further it was shown that rotundone concentration increased at different rates among the clones. Fruit of the clone ‘Dijon 470’ had higher concentrations of rotundone at harvest than fruit from the ‘Chave’ or ‘MS’ clones. These results indicate that common clone selection practices in the field for quality wine production impact rotundone concentration, and may be used to manage rotundone levels as desired in finished wines. Acknowledgements Wine Science Postgraduate Programme, The University of Auckland School of Chemical Sciences, The University of Auckland, New Zealand Craggy Range Vineyards Ltd, Hawke’s Bay, New Zealand Romeo Bragato Trust Postgraduate Viticulture Research Scholarship Andrew Hull, Craggy Range Vineyards Ltd, Hawke’s Bay, New Zealand
66
Poster 46 Boron Corrole Complexes
Stefanie Maslek
David C. Ware and Penny J. Brothers
Corroles are related to the heme-like molecules porphyrins. Boron porphyrin complexes have been investigated much in the last two decades, whereas the analogous corrole complexes are relatively unexplored. The smaller bonding cavity, due to missing a methyne carbon, makes the corrole an interesting, unsymmetrical trianionic ligand for boron.1 Reaction of corrole with a boron halide resulted in mono- or diboron complexes, depending on the reagent stoichiometry. Despite the small ring size, two boron atoms are easier coordinated, giving unusual boron chemistry. The boron coordination showed an out-of-plane cisoid arrangement;2 however the coordination geometry of the mono boron complex is not completely solved, results indicate an out-of-plane dipyrromethene coordination. Reaction of the free-base corrole with aryl boron yielded in the metastable B-H-B boron hydride complex. The hydride complex undergoes a spontaneous reductive coupling to form a B-B corrole complex. Reactivity studies were conducted concerning the further oxidation to B-O-B and its heterolytic activation towards small molecules. UV/vis absorbance and fluorescence emission spectra were recorded, using the higher energy Soret band as an indicator for the boron coordination. The relative strong fluorescence, due to the similar structure of corrole to BODIPY dyes, gives these complexes a possible application in fluorescent labelling and its activation of small molecules makes it interesting as a sugar sensor.3
Figure 1: Flow chart of accomplished reactions.
References: 1 Brothers, P. J., Boron Complexes of Pyrrolyl Ligands. Inorg. Chem. 2011, 50, 12374-12386. 2. Albrett, A. Synthesis of Boron Corrole Complexes. University of Auckland, 2009. 3. Brothers, P. J., Boron complexes of porphyrins and related polypyrrole ligands: unexpected chemistry for both boron
and the porphyrin. Chem.Commun. 2008, 2090-2102.
67
Poster 47 Cobalt(III) complexes as potential anticancer drugs
Meet V. Mistry
Penelope J. Brothers, David C. Ware The therapeutic methods for cancer treatment involve surgery, radiotherapy, and chemotherapy. These methods are often used in combination to achieve better results, because of their individual limitations on their own. The presence of hypoxia in solid tumours is recognised as a limiting factor in the success of both radiotherapy and chemotherapy treatments, but also as a consistent tumour-specific condition it could be exploited for the selective activation of prodrugs.1 The objective of the project is to exploite tumour hypoxia as a condition for prodrug activation. The project describe design and synthesis of cobalt(III) complex, that contain tetradentate N-propargylcyclen and 8-hydroxyquinoline (8-HQ) ligands. This octahedral complex is then coupled with tetraphenylporphrin (TPP) via triazole bridge using Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The presence of 8-hydroxyquinoline in complex will serve as a model for a potent cytotoxic analogue4 and TPP is expected to provide tumour selectivity to prodrugs.2 The second objective of this project is to Synthesise dipeptide and tripeptide analogues of Bortezomib (boronic dipeptide), a proteasome inhibitor.3 The synthesis of cobalt(III) complex containing dipeptide and tripeptide analogue as tridentate ligands will be investigated.
CoN
N
N
NHH
H
+2
NNN
N
NH N
HN
Ph
Ph
Ph
NO
Cytotoxin modeleffector
Tumour localising agent
Trigger
N
NH N
HNH2N
References: [1] Brown J. M.; Wilson W. R.; Nat. Rev. Cancer, 2004, 4, 437-447. [2] Zanelli G. D, Kaelin A. C.; Br J Radiol. 1981 54(641), 403-407. [3] Bachovchin W. W.; Journal of Medicinal Chemistry 2011, 54, 4365-4377. [4] Chang J.Y-C.; Brothers P. J.; Denny W.A.; Ware D.C. Dalton Trans., 2010, 39, 11535-11550.
68
Poster 48 The forbidden crystal: Penrose tiling with molecules
Seong Joo Nam
Geoffrey I. N. Waterhouse, David C. Ware, Penelope J. Brothers Since the first discovery of quasicrystals by mathematicians in the 1960s, quasicrystalline patterns which possess unusual symmetric orders have become an issue among mathematicians. Observation of 5-fold crystal symmetry in metal alloys in 19841 has attracted other scientists. Penrose tiling is the simplest quasicrystal comprised of only pentagon motifs. Although quasicrystals have been observed in alloys and soft matter states (polymers, colloids), no one has yet successfully generated molecular quasicrystals. We are working on this challenge by using molecules with 5-fold symmetry as molecular ‘tiles’ to create 2-dimensional molecular Penrose tilings. Alignment of the tiles is the key to creating the quasicrystalline pattern. Possible candidates as tiles which must be synthetically accessible are croconate2 and its derivatives, macrocycles such as campestarene3 and supramolecules such as cucurbit[5]uril.4 The techniques of coordination and supramolecular chemistry will direct the ordering of the tiles. After deposition of the synthesised tiles on substrates, surface imaging (STM and AFM) and analytical techniques (XPS, LEED, GI-SAXS) will be used to investigate the resulting films.
References: 1. Levine, D.; Steinhardt, P. J. Phys. Rev. Lett. 1984, 53, 2477–2480. 2. West, R.; Niu, H. Y. J. Am. Chem. Soc. 1963, 85, 2586-2588. 3. Guieu, S.; Crane, A. K.; MacLachlan, M. J. Chem. Commun. 2011, 47, 1169-1171. 4. Kim, K.; Selvapalam, N.; Ko, Y. H.; Park, K. M.; Kim, D.; Kim, J. Chem. Soc. Rev. 2007, 36, 267-279.
69
Poster 49 Synthetic Studies Towards the Griseusin Family of Anticancer Agents
Briar Naysmith
Margaret Brimble, Jon Sperry
The griseusins are members of the pyranonaphthoquinone family of antibiotics.[1]1 The first members of the family to be isolated were griseusins A and B (Figure 1) by Tsuji et al. in 1976.[2] Since then, fifteen more natural products have been isolated.[3] The griseusins exhibit activity against fungi and Gram positive bacteria. More importantly, they have been found to exhibit strong cytotoxicity against leukaemia, lung, melanoma, breast and renal cancer cell lines.[4] This is consistent with the proposal that pyranonaphthoquinone antibiotics act as bioreductive alkylating agents by selectively inhibiting serine-threonine kinase AKT.[5]
Figure 1: Selected natural griseusins An efficient method to construct the pyranonaphthoquinone skeleton of griseusin B in enantiopure form will be presented, in which the key step involves use of a Hauser phthalide annulation strategy (Figure 2).[6]
Figure 2: Proposed Hauser phthalide annulation strategy to griseusin B deacetate References [1] J. Sperry, P. Bachu and M. A. Brimble, Nat. Prod. Rep. 2008, 25, 376-400. [2] N. Tsuji, M. Kobayashi, Y. Wakisaka, Y. Kawamura, M. Mayama and K. Matsumoto, J. Antibiot. 1976, 29, 7-9. [3] Z.-G. Ding, J.-Y. Zhao, M.-G. Li, R. Huang, Q.-M. Li, X.-L. Cui, H.-J. Zhu and M.-L. Wen, Journal of Natural Products 2012, 75, 1994-1998. [4] J. He, E. Roemer, C. Lange, X. Huang, A. Maier, G. Kelter, Y. Jiang, L.-H. Xu, K.-D. Menzel, S. Grabley, H.-H. Fiebig, C.-L. Jiang and I. Sattler, J. Med. Chem. 2007, 50, 5168-5175. [5] E. J. Salaski, G. Krishnamurthy, W.-D. Ding, K. Yu, S. S. Insaf, C. Eid, J. Shim, J. I. Levin, K. Tabei, L. Toral-Barza, W.-G. Zhang, L. A. McDonald, E. Honores, C. Hanna, A. Yamashita, B. Johnson, Z. Li, L. Laakso, D. Powell and T. S. Mansour, J. Med. Chem. 2009, 52, 2181-2184. [6] B. J. Naysmith and M. A. Brimble, Org. Lett. 2013.
70
Poster 50 Electrospinning for encapsulation in food applications
Yun Ping Neo
Conrad Perera, Jianyong Jin
Electrospinning is a technology which involves the application of electric power to spin polymers into fibers with different range of diameters. The fiber mats so produced usually exhibit high porosity and large-surface-area to volume ratios that have a great advantage of enhancing the interaction with their surrounding media. In this study, gallic acid was used as the model functional ingredient to study the performance of gallic acid loaded zein fibers using electrospinning as an encapsulation technique. The aim of this work was to better understand the use of electrospinning as a one-step preparation technique to obtain gallic acid loaded sub-micron structured zein fibers. The prepared gallic acid-zein fibers were evaluated for various physicochemical characterizations including morphology of electrospun fibers; distribution of gallic acid in the electrospun fibers and thermal stability. The interaction between gallic acid and zein and radical scavenging properties of gallic acid after electrospinning were explored to gain more fundamental understanding on this system. The fabricated product may display good potential in rendering the increased health concerns caused by synthetic plastics and contributes towards the development of nanostructured bioactive packaging materials. Hence, evidence for the efficacy and effectiveness of gallic acid loaded zein electrospun fiber mat for food contact applications were determined by evaluating its release performance, mechanism of action, cytotoxicity and antimicrobial abilities.
References Kriegel, C., Arrechi, A., Kit, K., Mc Clements, D. J., & Weiss, J. Fabrication, functionalization, and application of electrospun biopolymer nanofibers. Critical Reviews in Food Science and Nutrition 2008, 48, 775–797.
Li., Y., Lim, L. T., & Kakuda, Y. Electrospun zein fibers as carriers to stabilize (-)-epigallocatechin gallate. Journal of Food Science 2009, 74 (3), 233-240.
71
Poster 51 Synthetic Studies Towards a Novel Family of Bioactive Cyclic Peptides,
Psychrophilins A-D
Ngen Tack Yain (Sarah)
Daniel P. Furkert, Jonathan Sperry, Margaret A. Brimble
In 2004, a previously unknown family of structurally related nitrated cyclic peptides, psychrophilins A-D, were isolated from psychrotolerant fungi Penicillium ribeum1 and Penicillium algidum.2 Psychrophilin D exhibits moderate anticancer activity against the P388 murine leukaemia cell line,3 whilst the biological activities of psychrophilins A-C are yet to be investigated. To date, there are no known syntheses for any of these compounds. The psychrophilins contain an unprecedented nitro-tryptophan moiety and are the only natural cyclic peptides known to possess a nitro (NO2) group.1 Although it is not uncommon to find nitro groups in naturally occurring linear peptides, it is very rare to find this group alpha to the amide bond. Our proposed syntheses of the psychrophilins will not only provide more material for detailed biological evaluation, but will also allow for construction of analogues based on this scaffold. Herein we report synthetic studies towards the synthesis of psychrophilin C.
N
N
HNO
O
O NO2
N
HN
HNO
O
R1
O NO2
Psychrophilin A Psychrophilin B R1 = CH(CH3)2Psychrophilin C R1 = CH3
Psychrophilin D R1 = CH2CH(CH3)2
(s)
(s)
(s)
(s)
References
1. Dalsgaard P. W., Larsen T. O., Frydenvang K., Christophersen C., J. Nat. Prod., 2004, 878-881. 2. Dalsgaard P. W., Blunt J. W., Munro M. H., Larsen T. O. Christophersen C., J. Nat. Prod., 2004, 1950-1952. 3. Dalsgaard P. W., Larsen T. O., Christophersen C., J. Antibiot., 2005, 141-144.
72
Poster 52 A multiplex analysis of RNA expression during injury healing in human dermal injuries
for injury age estimation
Sai Palagummi Douglas Elliot, Rachel Fleming, SallyAnn Harbison
The determination of the timing of a human dermal injury is important in forensic work. It helps answer questions such as, the timing of the injury and incident, the order of infliction of the injuries, the survival time after injury and, the relation of the injury to the incident, that are important to the reconstruction of a crime.1 In spite of its indisputable importance there currently exists no method to accurately estimate human dermal injury age.1, 2
Normal healing begins the moment the cell is injured. Immediately after injury, a time-course cascade of pathways to repair the cell is initiated. The repair process is complex and is broadly divided into three phases: inflammation, proliferation and maturation.3, 4 Within each phase, a methodical and temporal series of healing events occur, which are brought about by timely changes in the expression of genes involved in injury healing.5 In this study, we developed a RNA based multiplex assay that identifies some of these genes and used it to analyse their expression through the time course of the injury healing process to determine their usefulness in the estimation of human dermal injury age. We analysed samples from human dermal injuries, collected at specific time points during the healing process, with our multiplex and were able to obtain expression patterns for our selected target genes. The expression patterns observed for some of the selected target genes suggest that they have potential to estimate human dermal injury age, especially during the early stages (days) of injury healing. References 1. Bauer, M. Forensic Sci Int- Gen. 2007, 1, 69-74. 2. Takamiya, M.; Biwasaka, H.; Saigusa, K.; Nakayashiki, N.; Aoki, Y. Leg Med. 2009, 11, 186-190. 3. Takamiya, M.; Saigusa, K.; Kumagai, R.; Nakayashiki, N.; Aoki, Y. Int J Leg Med. 2005, 119, 16-21. 4. Bai, R.; Wan, L.; Shi, M. Forensic Sci Int. 2008, 175, 193-197. 5. Kagawa, S.; Matsuo, A.; Yagi, Y.; Ikematsu, K.; Tsuda, R.; Nakasono, I. Leg Med. 2009, 11, 70-75.
73
Poster 53 The Synthesis of Antimicrobial Marine Natural Products: Plicatamide and Analogues
Michael Pullar
A/P Brent Copp and Dr. Viji Sarojini Plicatamide is an antimicrobial octapeptide, isolated in 2000 from the marine tunicate Styela plicata.1 It contains an unusual trans-enamide moiety, resulting from the decarboxylation of the C-terminal DOPA residue. Plicatamide has been shown to permeate the cell membranes of bacteria, causing a fatal influx of potassium into the cell. This mechanism renders it effective against a wide range of bacteria, including methicillin resistant Staphylococcus aureus.2 As plicatamide kills upon contact with the bacterial cell, it is an ideal substrate for use in the creation of biofilm resistant materials. If tethered onto polymers it would create a hostile surface, preventing the growth of bacteria. Any such materials would have potential uses in the production of things such as antifouling paints and surgical equipment. Solid phase peptide synthesis can be used to produce the bulk of the peptide chain, while the enamide section will be synthesised separately. The enamide moiety can be accessed through an oxidative decarboxylation reaction of the C-terminal peptide bond,3,4 or via a ruthenium catalysed addition of an alkyne onto a primary amide.5 The desired analogues of plicatamide will be formed by replacing various amino acids with their unnatural enantiomers, as well as by replacing the DOPA group with similar substrates such as tyrosine and phenylalanine.
H2N
O
HN
O
NH
N
NH
O
HN
O
NH
N
NH
O
HN
O
NH
N
NH
O
HN
OH
OH
Structure of Plicatamide
1. Tincu, J.A,; Craig, A.G.; Taylor, S.W. Biochem. Bioph. Res. Co. 2000, 270, 421-424. 2. Tincu, J.A.; Menzel, L.P.; Azimov, R.; Sands, J.; Hong, T.; Waring, A.J.; Taylor, S.W.; Lehrer, R.I. J. Biol. Chem. 2003,
278(15), 13546-13553. 3. Wang, X.; Porco, J.A. J. Org. Chem. 2001, 66, 8215-8221. 4. Min, G.K.; Hernandez, D.; Lindhardt, A.T.; Skrydstrup, T. Org. Lett. 2010, 12(21), 4716-4719. 5. Gooßen, L.J.; Rauhaus, J.E.; Deng, G. Agnew. Chem., Int. Ed. 2011, 117, 4110-4113.
74
Poster 54
Antibacteria Activity of Mushrooms: A Comparative Study on Paper Disk Diffusion and Mirodilution Methods
Lu (Ray) Ren
Yacine Hemar, Conrad Perera, and Gillian Lewis
Infectious diseases are a long standing issue and considered as constant threats to human health. Numerous antimicrobial agents have been developed to treat pathogenic microorganisms, which has also raised another public health concern due to the global antimicrobial resistance of those drugs. Thus, new antimicrobial agents are highly required and searched from various biological sources. Mushrooms generate vast amount of functional metabolites against bacteria and fungi in surrounding environment for their survival purpose. In this paper, the antibacterial activity of the polysaccharides isolated from mushrooms was determined utilizing both paper disk diffusion and microdilution methods. Eight mushroom species, including five New Zealand wild ones, and five bacteria strains were applied to produce the comparative outcomes between the two methods. The extract from C. sinensis demonstrated the inhibition against B. subtilis and S. epidermidis with the minimum inhibitory concentration (MIC) values of 938 and 469 μg/mL respectively. P. australis extract had the same MIC of 469 μg/mL against S. epidermidis. Comparatively, microdilution methodology was more efficient and accurate than disk diffusion method to monitor the antimicrobial activity of high molecular weight polysaccharides having a high viscosity. The former method is more suited since false negative results caused by the restrained mobility of the polysaccharides, as seen in the latter method, can be avoided.
Figure 1. Inhibition zones of antibiotics on an agar detected in disk diffusion method (left), the mixtures of bacteria and extract solutions in a 96-well plate used in microdilution method (right).
75
Poster 55 Studies towards the interaction of HRV 3C protease with (–)-thysanone
Katrin Schünemanna,
Daniel P. Furkert, Stephen Connellyc, Jonathan Sperrya, Margaret A. Brimblea, John Fraserb, Ian A. Wilsonc,d
aDepartment of Chemistry, The University of Auckland bDepartment of Molecular Medicine and Pathology, The University of Auckland
cDepartment of Molecular Biology and dThe Scaggs Institute of Chemical Biology, The Scripps Research Institute, USA
More than 500 million cases of common colds occur each year in America alone, costing society an estimated US$40 billion.[1] The major cause for this common disease is the human rhinovirus (HRV), and currently only symptomatic treatment is available to medicate these infections.[2] The RNA genome of HRV encodes 12 different structural and non-structural proteins/enzymes which are expressed intracellularly as one polyprotein that undergoes subsequent proteolytic processing.[3,4] In HRV, these cleavages are mainly governed by two virally encoded cysteine proteases designated 2A and 3C.[3,4] The action of HRV 3C protease is required to produce mature viral proteins and functional viral enzymes essential for completion of viral replication.[2-9] (–)-Thysanone 1 exhibits potent inhibition of HRV 3C protease (IC50 13 μg/mL)[10] and it is a promising lead for development of novel chemo-therapeutic agents for control of the common cold. In this current study, we synthesised (–)-thysanone 1 and a series of analogues with varied stereochemistry, heteroatom position and substitution pattern. Furthermore, we developed a novel fluorescence based assay to test compounds quantitatively for activity against HRV 3C protease for determination of structure-activity relationships. Mechanistic studies towards the mode of interaction of HRV 3C protease with (–)-thysanone 1 and its analogues were also performed. This information will be used to design improved inhibitors for HRV 3C protease for treatment of the common cold. References 1. Fendrick, A. M.; Monto, A. S.; Nightengale, B.; Sarnes, M. Arch. Intern. Med. 2003, 163, 487–494 2. Couch, R. B. Fields Virology 1996, 713-34. 3. Porter, A. G. J. Virol. 1993, 67, 6917-21. 4. Palmenberg, A. C. Annu. Rev. Microbiol. 1990, 44, 603-23. 5. Hellen, C. U.; Wimmer, E. Virology 1992, 187, 391-7. 6. Krausslich, H. G.; Nicklin, M. J.; Lee, C. K.; Wimmer, E. Biochimie 1988, 70, 119-30. 7. Nicklin, M. J.; Krausslich, H. G.; Toyoda, H.; Dunn, J. J.; Wimmer, E. Proc. Natl. Acad. Sci. USA 1987, 84, 4002-6. 8. Stanway, G. J. Gen. Virol. 1990, 71, 2483-501. 9. Toyoda, H.; Nicklin, M. J. H.; Murray, M. G.; Anderson, C. W.; Dunn, J. J.; Studier, F. W.; Wimmer, E. A. Cell 1986, 45, 761-70. 10. Singh, S. B. C.; Cordingley, M. G.; Ball, R. G.; Smith, J. L.; Dombrowski, A. W.; Goetz, M. A. Tetrahedron Lett. 1991, 32, 5279-82.
76
Poster 56 Organic-Inorganic Hybrid Polymer Composites
Manatchanok Sitthiracha
Paul Kilmartin and Neil Edmonds Epoxy resins have been used extensively for coatings, adhesives, and reinforced composites. In this study, hybrid materials comprised of inorganic glasses and organic polymers were proposed to replace the neat organic matrices generally used in reinforced composites to improve mechanical and thermal properties of polymer matrices. Epoxy functionalized silane, 3-glycidoxy propyl trimethoxysilane (GPTMS), was employed to synthesize organic-inorganic hybrid materials (OIHMs) via a sol-gel process. The oxirane ring in GPTMS was crosslinked by an aliphatic amine curing agent, diethylene triamine (DETA). Amine functionalized silane, n-(2-aminoethyl)-3-aminopropyltrimethoxysilane (APTMS), was also used as a curing agent to produce a high inorganic content OIHM. Another curing system for epoxy was hexahydrophthalic anhydride (HHPA), which was reacted with an oxirane ring in an esterification reaction. OIHMs derived from di-functional organosilanes, (3-glycidoxypropyl)methyl dimethoxysilane (GPDMS) were also synthesized to compare the mechanical properties with OIHMs derived from GPTMS. The hydrolysis, condensation, epoxy ring opening reactions, and the optimal reaction conditions were investigated. In addition, OIHMs derived from methacrylyl functional silanes, i.e. methacryloxypropyl trimethoxysilane (MAPTMS) and 3-methacryloxypropylmethyl dimethoxysilane (MAPDMS), were also studied. The selected OIHMs were then used as polymer matrices to produce fiberglass and basalt fiber reinforced composites. Zeolite was added into OIHM matrices to function as water absorbents and reinforcing fillers.
77
Poster 57 Conducting polymer substrates for electrochemically-mediated ATRP
Lisa Strover, Jenny Malmström, Olivia Laita, David E. Williams, Margaret Brimble, Jadranka
Travas-Sejdic
Copper-catalysed atom-transfer radical polymerisation (ATRP) is one of the most ubiquitous controlled radical polymerisation methods. The redox-activity of ATRP catalysts (which is proportional to polymerisation rate) has led to electrochemical screening of ATRP catalysts.1 This early work facilitated the development of electrochemically-mediated ATRP (eATRP); that is, ATRP where the ratio of Cu(I) to Cu(II), and therefore the rate of polymerisation, is moderated by applied potential.2 Advantages of eATRP include low copper concentrations, in-situ catalyst removal, and the flexibility to turn polymerisation on and off whilst retaining excellent end-functionality. A recent development is surface-initiated eATRP (SI-eATRP), where polymers are grafted directly from an initiator-functionalised substrate to form a polymer brush.3 We are currently investigating the use of conducting polymer (CP) films as substrates for SI-eATRP. These surfaces are ideal for the application as they can be grown directly onto conductive substrates to provide a robust layer of ATRP initiator. Furthermore, properties of the substrate polymer can impart functionality to the polymer brush. In our current work, a new macroinitiatior for electrochemically-active molecular brushes: poly(2-(2,5-di(pyrrol-2-yl) thiophene-3-yl)ethyl 2-bromopropanoate)) (PPyThon), is used as a substrate for SI-eATRP. This technique allows for excellent control over brush composition and grafting density so that surface properties can be readily tailored.
Figure 1. Scheme of PPyThon-based molecular brush, comprising conductive PPyThon backbone and grafted sidechains, on Au-coated substrate.
References 1. Qiu, J. et al. Macromolecular Chemistry and Physics. 2000, 201, 1625-1631. 2. Bonometti, V. Journal of Electroanalytical Chemistry. 2009, 633, 99-105; Bortolamei, N. et al. Angew. Chemie. 2011, 50, 11391-11394; Magenau, A. et al. Science. 2011, 332, 81-84. 3. Li, B. et al. Angew. Chemie. 2012, 124, 5182-5185.
78
Poster 58 Blueberries and probiotics, perfect recipes for a healthy heart
Winai Suthanthangjai, Kevin Davies, Anthony Phillips, Juliet Ansell and
Paul A. Kilmartin
Blueberries are one of the most anthocyanin-rich fruits, containing more than 25 forms of anthocyanins. This high anthocyanin content may contribute to the health benefits of blueberries against cardiovascular diseases and cancers1. However, intact anthocyanins are unlikely to act as local antioxidants2. This study has investigated the biotransformation of blueberry anthocyanins into metabolites by Lactobacillus plantarum at pH 3.4, 4.2, 5.9 & 7.0 and incubated anaerobically at 37oC for up to 24 h. Samples were centrifuged and the supernatants were analysed using semi-preparative liquid chromatography. The metabolites were identified using high performance liquid chromatography-mass spectrometry. Anthocyanin glycosides were found to almost completely hydrolyse at pH 4.2 and 5.9 after 24 h of incubation. The anthocyanins were quite stable at pH 3.4 but were highly unstable at neutral pH and almost disappeared after 8 h at pH 7.0. The primary metabolites are phenolic acids (Fig. 1) which showed a greater antioxidant capacity than the anthocyanins themselves as the antiradical power was found to increase in the order, malvidin-3-glucoside < syringic acid < protocatechuic acid < gallic acid. Thus, the metabolites of blueberry anthocyanins may be mainly responsible for the antioxidant activity of blueberries against chronic diseases, which then contribute to a healthy heart.
Figure 1. Bioconversion of blueberry anthocyanins by Lactobacillus plantarum. References Routray, W., Orsat V. Compr Rev Food Sci F. 2011, 10 (6), 303-320. Yang, M., Koo, S. I., Song, W.O., Chun, O. K. Current Medicinal Chemistry. 2011, 18 (2), 291-300.
79
Poster 59 Illuminating the past: linking ultrafast photodynamics to hundred year photostability in
hydroxyanthraquinones
Sarah Thompson Charles Rohde, Erin Griffey and Cather Simpson
Alizarin (1,2-dihydroxyanthraquinone) and Purpurin (1,2,4-trihydroxyanthraquinone) are the principal colour bearing components of madder, a colourant that has been extracted from the roots of Rubia tinctorum and used for a little over 4000 years as a dye and artists’ pigment.1 In that time, madder has been recognised as notoriously vulnerable to light,2 but the underlying mechanism of this vulnerability has remained a matter of speculation. Logic dictates that the more time a molecule spends in a (photo)excited state, the more likely it is to undergo processes that do not return it safely to the original ground state. The TrA studies presented here, conducted in the Photon Factory, represent the first femtosecond time-resolved spectroscopic studies of alizarin and purpurin. In combination with long-term photodegradation studies, they demonstrate for the first time a link between the ultrafast lifetimes of photoexcited alizarin and purpurin, and their macroscopic photostability. They indicate that even very small differences in anthraquinone structure and solvent proticity can have a significant impact upon the photodegradation of pigment molecules, and reflect the reported superior macroscopic photostability of alizarin compared to purpurin.3
References 1. Saunders, D.; Kirby, J. Nat. Gall. Tech. Bull. 1994, 15, 79-97. 2. Casadio, F.; Leona, M.; Lombardi, J. R.; Van Duyne, R. Acc. Chem. Res. 2010, 43, 782-791. 3. Clementi, C.; Nowik, W.; Romani, A.; Cibin, F.; Favaro, G. Anal. Chim. Acta. 2007, 596, 46-54.
80
Poster 60 Evaluation of electrodeposited polyaniline on marine grade aluminium for antifouling
properties
Teresa To1 Simon Swift1,2, Paul Kilmartin1
1Hybrid Polymers Research Group, School of Chemical Sciences 2Molecular Medicine and Pathology, School of Medical Sciences
Antifouling coatings are generally defined as those that can prevent the settling of microorganisms on a surface through the controlled release of toxic agents. There is considerable interest in the development of coatings that are non-toxic to the environment, but also prevent unwanted microbial-based fouling. Many conducting polymers have been studied for different applications, with polyaniline the first to show antifouling properties1. The objective of the research is develop an optimum polyaniline coating on aluminium alloys that does not release toxic chemicals, but at the same time provides a useful antifouling property.
Polyaniline films were synthesized electrochemically from 0.5 M oxalic acid solution containing 0.1 M aniline, under potentiostatic control. Coated and control marine grade aluminium were challenged by immersion in growing cultures of Escherichia coli ATCC 25922 lux and E. coli 536 lux under controlled conditions to simulate the marine environment in an accelerated fashion. This novel testing method allowed a non-destructive evaluation of bacterial growth on different surfaces, using selected coatings, with bioluminescence from bacteria colonizing the aluminium coupons imaged using an IVIS kinetic at 24 hourly intervals over a 2 weeks period (Figure 1). Only live bacteria bioluminesce and so signal (seen as a pseudocolour image in figure 1) reflects areas of the coupon colonized by bacteria. Polyaniline-coating of marine grade aluminium delays colonization indicating a lower rate of fouling.
Figure 1: Bioluminescence images overlaying a photograph of coated and control samples. A commercially available antifouling coating and an electrochemically synthesized polyaniline on marine grade aluminium are compared with bare marine grade aluminium and glass controls. The images are taken after 4 days of exposure to the bacteria. 1. Wang, X. H.; Li, J.; Zhang, J. Y.; Sun, Z. C.; Yu, L.; Jing, X. B.; Wang, F. S.; Sun, Z. X.; Ye, Z. J., Polyaniline as marine antifouling and corrosion-prevention agent. Synthetic Metals 1999, 102 (1–3), 1377-1380.
81
Poster 61 Total Synthesis of the Initially Reported and Revised Structures
of the Neuroprotective Agent Palmyrolide A
Andrew Wadsworth
Daniel P. Furkert, Jonathan Sperry, Maragret A. Brimble
The total syntheses of the initially reported1 and revised2 structures of the neuroprotective agent palmyrolide A have been reported following our research efforts3. The key macrocyclization step was achieved using a unique sequential ring closing metathesis/olefin isomerization reaction. This synthetic work also serves to confirm the recent structural revision of this unusual natural product, by delivering a number of stereochemical analogues.
N(R)
O(R)(R)
O
O
Palmyrolide A
sequentialRCM-olefin
isomerization N
O
O
O
HO
O
MeHN
O
OH
EtOP
O
OMe
O
2
R R
R
References
(1) Pereira, A. R.; Cao, Z.; Engene, N.; Soria-Mercado, I. E.; Murray, T. F.; Gerwick, W. H. Org. Lett. 2010, 12, 4490-4493. (2) (a) Tello-Aburto, R.; Johnson, E. M.; Valdez, C. K.; Maio, W. A. Org. Lett. 2012, 14, 2150-2153. (b) Tello-Aburto, R.;
Newar, T. D.; Maio, W. A. J. Org. Chem. 2012, 77, 6271-6289. (3) Wadsworth, A. D.; Furkert, D. P.; Sperry, J.; Brimble, A. M. Org. Lett. 2012, 14, 5374-5377.
82
Poster 62 Structure-antimalarial activity relationship studies of the New Zealand marine natural
products didemnidine B and orthidine F
Jiayi Wanga Marcel Kaiserb,c and Brent R. Coppa
a School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand b Swiss Tropical and Public Health Institute, Socinstrasse 57, PO Box, CH-4002 Basel, Switzerland
c The University of Basel, CH-4003 Basel, Switzerland
Parasitic protozoal infection leading to neglected tropical diseases is a cause of suffering for an estimated one billion people worldwide.1 While drugs exist for these diseases, they have undesirable side-effects or are showing reduced efficacy from growing prevalence of drug resistant strains.1 Polyamines are well recognized as a biologically active scaffold exhibiting anti-protozoal activities.2 Evaluation against neglected disease parasite targets indicated the natural product didemnidine B (1) as a mildly active compound towards the malaria parasite Plasmodium falciparum, however with notable cytotoxicity.3 The same protozoal screening programme identified the ascidian metabolite orthidine F (2) as being a non-toxic, moderate growth inhibitor of malaria.4 With the aim of discovering new classes of antimalarial agents, we have synthesised novel compounds that contain structural features of both natural product templates, and evaluated all compounds against drug resistant strains of P. falciparum. Thus, analogues bearing variously substituted indole moieties with different polyamine chain lengths were synthesized and characterised. The results of in vitro evaluation against P. falciparum will be reported.
HN
BrO
HN
O
H2N
NH3
HO
O NH
O
NH2
H2N
HN
O
O
OH
didemnidine B (1)
orthidine F (2)
References: 1. Watts, K. R.; Tenney, K.; Crews, P. Curr. Opin. Biotechnol. 2010, 21, 808-818. 2. Bi, X.; Lopez, C.; Bacchi, C. J.; Rattendi, D.; Wooster, P. M. Bioorg. Med. Chem. Lett. 2006, 16, 3229-3232. 3. Finlayson, R.; Pearce, A. N.; Page, M. J.; Kaiser, M.; Bourguet-Kondracki, M. L.; Harper, J. L.; Webb, V. L.; Copp, B. R. J. Nat. Prod. 2011, 74, 888-892. 4. Liew, L. P. P.; Kaiser, M.; Copp, B. R. Bioorg. Med. Chem. Lett. 2013, 23, 452-454.
83
Poster 63 Total Syntheses of (+)-Terreusinone and Schischkiniin
Christy Wang
Jonathan Sperry We have accomplished two separate total syntheses of (+)-terreusinone, a potent UV-A protecting natural product. Path A is noteworthy for the use of a novel one-pot Larock indolization–Sonogashira coupling reaction.1 Path B features a copper- and amine-free double Sonogashira reaction with an electron rich dibromide.2 The resulting intermediates from both pathways undergo gold (I) catalyzed hydroamination followed by oxidation to deliver (+)-terreusinone, confirming the gross structure and absolute configuration of this natural dipyrrolobenzoquinone.3,4
OMe
H2N Br
NO2Br
one-potLarock
+ Sonogashira
OMe
NH2
OTIPSHNTIPSO
Au(I) hydroaminationthen [O]
O
NH
OH
HNHO
O
OMe
H2N Br
NH2Br
doubleSonogashira
OMe
NH2
OTIPSH2N
TIPSODouble
Au(I) hydroaminationthen [O]
Path A
Path B
(+)-TerreusinoneOTIPS
OTIPS
Schischkiniin is a structurally unique cytotoxic bis-indole alkaloid isolated from seeds of the thistle Centaurea schischkini, and is a rare example of a natural product that contains the 1,1'-bisindole moiety.
The first general synthetic approach to 1,1'-bisindoles was successfully developed, whereby various diallylated hydrazobenzenes undergo two simultaneous Mori-Ban cyclizations with minimal cleavage of the N-N bond.5 Application of this methodology towards the total synthesis of schischkiniin is currently in progress.
N NI I
R R
SimultaneousMori-Ban
ambient temp.base f ree
N NR R
1
1'
N N1 1'
NH
HN
HN
NH
O O
H
H
H
Hschischkiniin
6 examples
References 1. Wang, C.; Sperry, J. Org. Lett. 2011, 13, 6444. 2. Wang, C.; Sperry, J. Synlett 2012, 23, 1824. 3. Wang, C.; Sperry, J. Tetrahedron 2013, accepted 5th April 2013. 4. Wang, C.; Sperry, J. J. Org. Chem. 2012, 77, 2587. 5. Wang, C.; Sperry, J. Chem. Commun. 2013, Advance Article DOI: 10.1039/C2CC37241J
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Poster 64 Novel Glycopolymer with Polyaniline backbone and pendant Mannose attached through a
1,3-dipolar cycloaddition
Christopher Wilcox
Jianyong Jin, Hayley Charville, Simon Swift, Margaret Brimble, Ralph Cooney
Glycopolymers are polymers containing carbohydrate functionality and are of particular interest due to their recognition properties.1 Herein is reported the attempted synthesis of a polyaniline glycopolymer that was functionalized pre-polymerization with a Mannose group through a Huisgen 1, 3 dipolar cycloaddition also known as a copper azide alkyne click reaction.2 Compound (1) is capable of taking place in a click reaction with functionalized aniline (2). These were reacted together to form the functionalized monomer (3). Polymerization of the monomer was then attempted using general aniline polymerization conditions resulting in a brown powder (4). Finally the Mannose group on the polymer was deprotected resulting in the final product (5). The monomers and polymers were characterized using a variety of techniques including FTIR, GPC, UV-Vis, NMR and cyclic voltammetry. The final product will also be tested for its ability to interact with carbohydrate binding lectins and bacteria with the ability to recognize Mannose. For this Concanavalin A will be used as it is a Mannose specific lectin that is extensively used in model studies of glycopolymers to show their binding selectivity.3
OAcO
AcO
OAc
O
OAc
N3
O
AcOAcO
OAc
O
OAc
N
NH2
CuSO4•5H2O (5 mol%)Sodium ascorbate (10 mol%)
N
N
H2N
Oxidant Deprotection
O
AcOAcO
OAc
O
OAc
N
N
N
NH
O
HOHO
OH
O
OH
N
N
N
NH
1. Slavin, S.; Burns, J.; Haddleton, D.; Gibson, M.; Becer, R., Synthesis of glycopolymers via click reactions. European Polymer Journal 2011, 47, 435-446. 2. Rostovtsev, V.; Green, L.; Fokin, V.; Sharpless, B., A Stepwise huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective "Ligation" of Azides and Terminal Alkynes. Angewandte Chemie International Edition 2002, 41 (14), 2596-2599. 3. (a) Papp, I.; Dernedde, J.; Enders, S.; Riese, S.; Shiao, T.; Roy, R.; Haag, R., Multivalent Presentation of Mannose on Hyperbranched Polyglycerol and their Interaction with Concanavalin A Lectin. ChemBioChem 2011, 12, 1075-1083; (b) Ting , S.; Chen, G.; Stenzel, M., Synthesis of glycopolymers and their multivalent recognitions with lectins. Polymer Chemistry 2010, 1, 1392-1412.
(1)
(2)
(3) (4) (5)
85
Poster 65 Electrospinning of Nanofibrous Polyaniline and Poly-ɛ-Caprolactone with Potential
Application in Tissue Engineering
James Chun-Cheng Wu Marija Gizdavic-Nikolaidis, Sudip Ray, Simon Swift, Jianyong Jin, Ralph Cooney
Nanofibrous polyaniline (PANI), prepared by rapid-mixing of aniline with ammonium persulfate in a hydrochloric acid medium, has advantage of solution-processability.1,2 In this study, ultrafine fibres composed of poly-ɛ-caprolactone (PCL) and PANI were obtained by electrospinning of PANI particulates dispersed in a mixed-solvent of chloroform and methanol, diameter ranging from 144 to 155nm. Addition of PANI in PCL resulted in improvements of several physical properties as compared to pristine PCL fibre-scaffolds. Incorporation of 20wt% of PANI in PCL fibre-scaffolds resulted in enhanced conductivity by 4 orders of magnitude. The PCL/PANI fibre-scaffolds showed significant enhancement in free-radical scavenging capacity (using 2,2-diphenyl-1-picrylhydrazyl, DPPH*) when compared to PCL/PANI films, and almost comparable to free-standing PANI. The cell attachment, proliferation and biocompatibility of L929 fibroblast cells on PCL/PANI fibre-scaffolds were assessed, and results were comparable to tissue-culture plates (TCP), a known industry standard (Figure 1), in agreement with previous published report for PANI/gelatine blend fibres.3 The antimicrobial properties of PCL/PANI fibre-scaffolds was found to be active against Staphylococcus aureus ATCC 6838 and Escherichia coli ATCC 25922; with knockdown rate > 99.9%. The electrospun fibres of PCL/nfPANI produced from this work exhibit potential usefulness in wound dressings and tissue engineering applications.
Figure 1. Fluorescence microscopy of L929 fibroblast cells after 4 days of proliferation on various
substrates: (a) glass cover slips (control); (b) neat PCL fiber-scaffolds; (c) PCL/PANI fiber-scaffolds.
1. Li, D.; Huang, J.; Kaner, R. B. Acc. Chem. Res. 2009, 42 (1), 135-145. 2. Borriello, A.; Guarino, V.; Schiavo, L.; Alvarez-Perez, M. A.; Ambrosio, L. J. Mat. Sci.: Mat. Med. 2011, 22 (4), 1053-1062. 3. Li, M.; Guo, Y.; Wei, Y.; MacDiarmid, A. D.; Lelkes, P. I. Biomaterials 2006, 27, 2705-2715.
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