ISSN 0110-5566 Volume 74, No.3, July 2010

i Featuring: . The Banwell Symposium: From Small Rings to Big Things Fs Light Metals Research at the University of Auckland Antioxidant Plastics based upon Conducting Polymers The Mechanism of Mutation Initiated by One-Electron Oxidation On the Origin of the Dimeric Aplysinopsin Alkaloids Making Sense of N-Confused Porphyrins i

Published on behalf of the New Zealand Institute of Chemistry in January, April, July and October each year.

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Volume 74, No.3, July 2010

93 The Banwell Symposium: From Small Rings to Big Things Russell J. Hewitt and Robert A. Keyzers 96 Light Metals Research at the University of Auckland

J. Metson, P. Lavoie, L. Perander and R. Etzion 101 Antioxidant Plastics based upon Conducting Polymers Paul A. Kilmartin 106 The Mechanism of Mutation Initiated by One-Electron Oxidation Johannes Reynisson 109 On the Origin of the Dimeric Aplysinopsin Alkaloids Emily M. Boyd and Jonathan Sperry 113 Making Sense of N-Confused Porphyrins Anna Mtodzianowska and Penelope J. Brothers

86 NZIC July News 118 Chemistry in the News 115 Patent Proze 119 Conference Calendar 116 ChemScrapes 120 Grants and Awards 117. Dates of Note

Inside front cover NZ Scientific 105 1 NZ Drug Discovery and Development Meeting 119 Chemical Education Trust Inside back cover Pacifichem Back cover Science Directions 85 Chemistry in New Zealand July 2010

Hy & New Zealand Institute of Chemistry yeaa supporting chemical sciences YNi July News

Commentfrom the President and ICY 2011

One ofthe more enjoyable tasks of being Presidentis the impact on New Zealand. opportunity to visit the Branches. I completed the North We will then ask for the Island leg of my Presidential tour in May. I would like to membership to vote for and also the top ten (maybe twenty) thank the Branchesfor their generous hospitality a thankall those who spoke with me. I took the opportunity of these and then compile to discuss the details of Council’s plans for International narratives about the win- International Year of Year of Chemistry 2011 that will focus on three major ning molecules. This will projects. With these projects we hope to maximize media provideseconcontent for medianein CHEMISTRY and public exposure, actively involve the members of the releases, educational ma- 2 011 Institute and encourage young people to continue to study terial, and material for the Manawatu Branch committee is cur- chemistry. These aims broadly reflect the UNESCO and NZIC website. The details of this. TUPAC goals for International Year of Chemistry 2011. rently working on the So whatare these projects? Thethird majorproject is The Molecular Imaging Project. chemistry and the involvement Thefirst project is our launch event. This will take place The graphical nature of various forms inspired the Wel- at the AMN-S5conference (organized by the MacDiarmid of chemistry with art in the genesis of this idea, which Institute) in Wellington in early February. The AMN-5 or- lington Branch to suggest into the Molecular Imaging ganizing committee already has plans to incorporate TyC has subsequently developed we will seek submissionsthat use 2011 into their programme and our launch event com- Project. Forthis project imagesas inspiration. The Wel- bines the worlds of chemistry and fashion. At this point I chemistry and chemical driving this project and is now planning must give credit to Glenda Lewis, who Council has hired lington Branchis as our IYC 2011 consultant. Those of you who know how bestto activate the ideas. Glenda will be familiar with her work in science media So wehavethe basic framework for IYC 2011 in place. relations, especially with the RSNZ and the MacDiarmid I’mreally excited about the plans. Of course, the hard Institute. Glenda’s Chemistry and Fashionidea involves work now begins. The International Year of Chemistry is Jim Johnston’s Gold Merinotextiles, garments designed a rare opportunity to promote the benefits of chemistry by the Massey University School of Design and a show at to society and I amsurethat ourefforts this year will be the Michael Fowler Centre during AMN-S. I think this is justly rewarded in 2011. an ideathat will attract the attention of the media and the general public — the idealstart to LYC 2011. All the best, Mark Anthology. With Our second project is The Molecular Mark Waterland input from you, our members, a list of molecules, com- President pounds or materials will be compiled that have had an

NZIC NEWS plannedandparticipants went back to Dr Justin Hodgkiss (Wellington), and During April and May the Chemistry their schools armed with a set of four Prof Adam Abdul Gafoor (Overseas Education Grouprana series of eight DVDsofresources. Section). nationwide for secondary workshops ~ NZIC MEMBERSHIP schoolteachers. The workshopsenti- Student Members tled DIY-ICT were run by Peter Hol- MATTERS Mr Brendan D. Harvey and Miss lamby from the University of Cardiff MNZIC Jacqueline Knobloch (Auckland), and attracted 200 teacherparticipants. Mrs Zhen (Jenny) Jia, Mr Ron- The workshops got off to a bad start The Institute is pleased to welcome ald H. Marks and Mr David Mills in Auckland as Peter was grounded in the following as new members: (Canterbury), Mr Emad Mohamed the UKbythe Icelandic volcano dust Al-Imarah (Manawatu), Mr Alfred cloud. The Chemical Education group Dr Jack Flanagan and Mr Amir Azi Yiu Chau Tong, Miss Trudyanne is grateful to Jan Torrie for fronting (Auckland), Dr Gareth J. Rowlands Goeghegan, Mr Ryan E. Hill, Mr the Auckland and North Shore work- and Miss Yogomalar Gnanasegaram Horvath, Miss Isobel Max- shopsin Peter’s place. OncePeter ar- (Manawatu), Dr Robert D. Fagerlund Raphael well-Cameron, Mr Lindon W. K. rived the remaining workshopsran as (Otago), Miss Katherine Haines and

86

Chemistry in New Zealand July 2010

Moodie, Mr Gregory Rankin and School ofChemical and PhysicalSci- 24 h 35 min. Food Science MScstu- Mr Matthew C. Smart, (Otago), Ms encesat Victoria University where he dent Yi-Chern Lee was also winner Emma Aitken, Mt Mark Bartlett, Mr will establish a new research group of two Gold Medals for table tennis Hemi Cumming, Mr Alan Dopson, in Theoretical Chemistry. John Har- (men’s singles and doubles) at the re- Mr Xuyu (Johnny) Liu and Ying Tang rison recently returned from Stanford cent Uni Gamesheld in Invercargill. (Wellington) and Ms Julia Rinck University where he collaborated (Overseas Section). with 2010 Priestley Medalist, Rich- Recognition of the high standard and ardZare. They can be seen ina C&E increased output of PhD research News picture (2010, No./2, 17). Al work within the Department came at BRANCH NEWS Nielson is going on sabbatical leave the time of the May graduation cere- to Oxford. monies, when 20 eligible PhD theses AUCKLAND from 2009 were considered for the L H Briggs Memorial Prize. Amelia Al- The April NZIC Branch meeting University ofAuckland brett and Sarah Carley were jointly featured a talk given by Dr Duncan In Marchthe single crystal X-ray dif- awarded the prize for the best doc- McGillivray (Chemistry Department, fractometer moved from its location toral thesis presented in the Depart- Auckland) on Big Science: Research on the 4"floor to the new basement mentin the preceding year. PhD stu- at Large Experimental Facilities. laboratory, and the entire X-ray dif- dent Greg Hungis also deserving of Duncanoutlined research he has been fraction facility is now functional in congratulations for winning a highly undertaking at the synchrotron X-ray its new site across the hall from the commended prize at the Maurice source in Melbourne and the nuclear NMRsuite. The basement area is now Wilkins Centre poster competition facility in Sydney. He pointed out the very active with several instrumental held on the April 22", His poster was growing opportunities for New Zea- facilities now in the one place. entitled Synthesis ofthe Cyclic Anti- landers to undertake researchat these microbial Peptide/Xenematide. The centres. In May, Prof Ken Ghiggino Practice for the Chemistry. Olympiad second annual Chemistry Research (University of Melbourne) spokeat a camp wentinto full operation in April Showcase took place on 9 June, and Branch meeting on Mimicking Pho- with support provided by Drs David featured talks by Norizah Abdul tosynthesis and the development of Salter and Katrina Graaf, and further Rahman, Lauren Ferguson, Catrin materials for light-energy conversion laboratory staff. The Department has Guenther, Philip McGill, Elizabeth and the dynamicsoflight harvesting. hosted a visitor, Zswyoshi Shimada McKenzie, Claire Rye, Zoe Wilson from Waseda University. Visiting and 7sz Ying Yuen. Massey University-Albany overseas in April was HoD Prof Jim Metson, firstly to the National Uni- On the appointmentsfront, Dr Yacine Two research seminars were pre- versity of Singapore and then on to Hemar, a Senior Scientist at Food & sented at the Albany campus towards the University of Qatar and alumini- Nutrition Sciences of the CSIRO in the end of March. Dr Doreen Mol- um smelters in the Middle East. Jim Australia, is due to start work in the lenhauer (Freie Universitat Berlin) gave lectures to classes of engineer- Department as a new Associate Pro- spoke on Electronic Effects in Multi- ing undergraduates at the University fessor within the Food Science pro- valent Interactions — From Gold Pyr- of Qatar, but had somedelaysin trav- gramme. Yacine presented a seminar idine Complexes to Larger Systems, elling out of Dubaiat that time. More in the Department on Simple Physi- including the use of quantum-me- severe delays were experienced by cochemical Approaches to Complex chanical methods for describing the ProfDavid Williamson an annual re- Problems of Food Science, and out- interaction of pyridines with single search visit to Dublin. The effects of lined research that includes the ap- gold atoms through to gold nanopar- Eyjafjallajokull saw David stranded plication of novel processing tech- ticles. Prof Hans-Beat Buerg (Bern in Ireland for several days. For the nologies (High Hydrostatic Pressure, University) presented on The Dynam- benefit of the Department, the recent Pulsed Electric Field and Ultrasound) ics ofMolecules in Crystals, in which seminarthat Dr Johannes Reynisson, to the physicochemical properties of a diffractometeris effectively used as presented on Benchmarking in Drug proteins and polysaccharides. Con- an infrared spectrometer to provide Discovery, started with a group les- gratulations are also due to Prof Mar- dynamic information on chemical son on the correct pronunciation of garet Brimble as the winner of the systems. the Icelandic volcano responsible for Royal Society of Chemistry Natural Michael Wormit arrived in May to the travel delays, along with further Products Chemistry Award for her take up a von Humboldt two-year Fe- Icelandic family names — the break- outstanding contribution to the syn- odor-Lynenpostdoctoral. He is work- downof drugtargets into their class- thesis ofbiologically active natural ing on excited states of solid state es was equally interesting but easier products, their derivatives and ana- systems, an extension of his previous to pronounce! logues. research on the accurate description Ona more sporty theme, PhD student Further Departmental seminars in of excited states in molecules. Af- Marsilea Booth completed the 100 recent months have included Prof ter six years at Massey University’s km Oxfam Trail Walker Challenge in Peter Scott (Warrick University) on Centre for Theoretical Chemistry and April, supported by a team given the Stereogenic Metal Centres and the Physics, Matthias Lein leaves in Au- appropriate name of We just popped Mechanisms ofHydroamination; and gust to take up a new position at the outfor the paper. It was completed in Dr Alexander Tuerke (a six month 87 —

Chemistry in New Zealand July 2010

annealing device that optimizes the Department of Mac- HighSchool,respectively. visitor from the yield of the biologically active na- Technische romolecular Chemistry, tive states of target proteins. He was on the Synthesis of Canterbury Universitat Dresden) University working in Biology and Chemistry. Characterization of Silver Hy- (Ruhr- and Thecivil union of Jan Shaw and Da- Prof Wolfgang Schuhmann Particles for Ink Jet Printing of a semi- brid vid Zehms took place on the week- Universitit Bochum), gave Tracks, which had been as Conductive end of February 13"at their scenic nar Modified carbon nanotubes focus of his PhD studies in Ger- and biofuel the property in Teddington. A good time materials for biosensors Anotherresearch visitor to the Richard S. many. was had by all and the Department cells on March 15. Prof Electronics Research Centre College, Polymer wishes Ian and David a happy future Moog(Franklin & Marshall A/Prof Jin-Heong Yim 30" at Auckland, together. PA) gave a seminar on March University, Korea) (Kongju National entitled, Process orientated guided of research un- to Canterbury provided an overview RecentErskinevisitors inquiry learning (POGIL): A stu- group at the Nano- McKee derway with his have included Prof Vickie dent centered approach to instruc- Laboratory, in- who functional Polymer (Loughborough University) tion during his NZIC sponsored NZ silica and mid-June. cluding micelle-templated was here mid-April until visit, POGIL is an approach to in- catalysts, along in the appli- hydroformylation Her research interests struction in the sciences (and other forms of the and structural with highly transparent cation of coordination areas) that is based on research on PEDOT, and mi- from conducting polymer chemistry across areas ranging howstudents learn. Timothy J. Wal- ink-jet printing. to cropatterning using bioinorganic and supramolecular lington, Ford Motor Company, USA) werealso present- were aired in In March seminars solid state chemistry gave a seminar on Atmospheric sci- (UC-London) effects ed by Dr Helen Hailes her seminar Double template ence and sustainable mobility: an of Ketodi- on on Biocatalytic Synthesis — mechanism and manipulation industrial perspective in mid-April. using novel tran- (Bristol ~~ ols and Aminodiols May 17". Dr Paul Wyatt He described progress in reducing chiral conver- the De- sketolasesto effect the University) is also visiting the vehicle contribution to local air (IRL, Lower Fellow. He sions; Dr Shaun Hendy partment as an Erskine quality and stratospheric ozone is- and Multiscale Cambridge Hutt) on Atomistic completed his PhD at sues and the current challenge posed with a focus in asym- Materials Modelling, and has research interests by climate change. Prof Lee Sharp formed at surfac- He gave a on nanostructures metric organic chemistry. (Grinnell College, US) gave a semi- of switchable inno- es, and the wettability seminar on May 20", teaching nar on May6", in which he described Derek Reynolds to enrich surfaces; and Dr vations — using technology semiconductor materials as chemi- spoke on Compu- some of (Reytek Ltd. UK) the traditional, that detailed cal sensors and photocatalysts for Drug Discovery, have been tational Models for the practical changes that hydrogen production. His research of lipophilicity including andthe importantrole made in Bristol chemistry investigates the use of semiconduc- chemistry. full use of within medicinal online resourcesthat make tor materials for the development of e-learning. animated andinteractive phosphor-based chemical sensors, of cataysts for CANTERBURY Richard and the development Othervisitors have included of water to pro- in mid- from the photoelectrolysis The NZIC BBQ was held Johari James, a PhD candidate duce hydrogen using sunlight. Prof March for the 2™, 3and 4" year and Pharmacy at UiTM Malaysia whose Kenneth Ghiggino (University of postgraduate Christchurch Chemistry research interests revolve around Melbourne,) gave his RSC-RACI- students and NZIC membersat the drug discoveries for brain related NZIC lecture on May 24" entitled University Staff Club. It was a well diseases. Richard is working on the mimicking photosynthesis. He out- attended event. BACEI pathway which is involved lined the principles involved in de- in the production of B-amaloid, a veloping materials with appropriate protein in the development CPIT hallmark for photosynthetic mimics. His UC hosts properties of Alzheimer’s disease. gave an Enter- twenty six teams of Year Andrew Rudge, CEO In mid-May Murray Munro and John Blunt are seminarentitled Anthrax detec- 12 students from twenty schools Tony Cole (Bio- prise (Chemistry) and on May 17". Christchurch competed tors — the Veritude story around logical Sciences). Clément Roux, Christchurch Andrew was the 2004 MacDiarmid against each otherat the from France, is at UC originally of the Year and he Polytechnic Institute of Technology’s in Alison Young Scientist completing a post-doctorate Christchurch start-up Chemistry Competition. Sponsored centres described the Downard’s group. His work developed it saw students carry- companyVeritude that has by the Branch, on the preparation of smart switch- exercises 4 hand-held instrument capable of ing out a range of practical project funded by the able surfaces, a other bacterial chemical identification of detecting anthrax and including MacDiarmid Institute. Prof George compounds and creation spores. unknown H Lorimer, FRS, (Maryland, USA) of models of enantiomers. At the until early was with the Department Congratulations to Reuben Jane and end of the evening the top team was on March 1 June and gave a seminar James Bull who have successfully from Riccarton High School with an a entitled The GroELS nanomachine: defended their PhD theses. James impressive score of 197 out of 200. ma- biological simulated annealing has commenceda postdoctorate with In second andthird place were Mid- folding, chine for optimizing protein Peter Harland. Congratulations also School and Cashmere dleton Grange a biological example of a simulated

ee 88 Chemistry in New Zealand July 2010

to Sunita Chamyuang who defended chemistry to general media and to Betz-Stablein is working with Dr her PhD thesis in late March. Ellen bring to the attention of the public the Paul Plieger on making molecular Worthington and’ Daniel King won many positive impacts that chemis- nanomagnetic compounds, Mathew a competition for first-year students try has on everyday life. The second Price and Mohammeed Alsubei are run earlier this year and were each section ofhis talk dealt with his very working with Dr Shane Telfer on syn- presented with copies of the new intriguing research entitled Strongly thesizing novel zeolitic imidazolate first-year chemistry text Chemis- Absorbing n-n* and Metal-to-Ligand frameworks for potential applications wry’. Emily Parker attended the 2010 Charge-Transfer States in Novel Ru- for organocatalysts and MOF growth NZVCC NZ Womenin Leadership thenium Dipyrrin Complexes: Prob- on conductive surfaces, respectively. Programmein late June for women ing Ultrafast Dynamics with Reso- Nick Bentis working with Drs Shane academics who are, or aspire in the nance RamanSpectroscopy. Telfer and Mark Waterland on the future to be, leaders within the ter- self-assembly of metallodipyrrin tiary sector. Emily is also to be con- In Marchofthis year Dr Alan Lim- complexes, Nick Collins is work- gratulated on receiving the UC 2010 mer, noted soil scientist and wine ing with Drs Vyacheslav Filichev, Teaching Award. Deb Crittenden and maker, sold his Stonecroft winery Mark Waterland and A/ Prof. Kath- Peter Steel made it through to the in Hawke’s Bay. He started planting ryn Stowell on SERS dependence second round of the Marsden Fund. grapes in 1982 and was recognised and Oliver Mooney is working with Francine Smith has received $900 by the Queen for his development of Dr Mark Waterland on the structure funding from the RSNZ for travel the (now) highly regarded Gimblett and dynamicsof ionic liquids at in- assistance to attend the International Gravels region, seen as a wasteland at terfaces. Shane Chapmanis working Conference on Toxic Cyanobacteria that time. He wasthefirst in modern with Dr Gareth Newlandon triazole- in Istanbul in late August/early Sep- times to produce Syrah, now regarded based monophosphines for catalysis tember. Vladimir Golovko has gained as the hottest variety in Hawke’s Bay, and Jom Featonby is working with access to the Australian Synchrotron and his Chardonnay and Gewiirztra- Dr David Harding on chitosan sur- for the 2010-12 operations cycle. mineralso have top reputations. factants. Vladimir’s project is: XPS and NEX- An NZIC beer tasting evening took AFSstudy ofnovel catalysts — support place at The Brewer’s Apprentice on Landcare NZ immobilizedAuclusters. Congratula- March 9. Those in attendance were tions to Sam Drew who represents Dr Benny Theng attended the Nano- treated to a range of appetizers, a UC at the AINSE Winter School on Formulation 2010 conference in series of short lectures on brewing Applications of Nuclear Techniques Stockholm in June under funding ar- theory and, more importantly, were at ANSTO (Lucas Heights) in July. rangements from the EU 7" Frame- provided with a constant supply of Sam has received full funding to at- work Programme. The conference beer. tend the forum. focus was on research, develop- ment and applications of innova- Massey University - IFS MANAWATU tive formulation technologies where nanomaterials play an essential role. The April/May period saw a number Congratulations to Adrian Jull who Benny participated in a of seminars given to IFS. In April, has been elected to Fellowship of discussion on smart and functional A/Prof Scott MecIndoe (University Institute for his outstanding contribu- materials in formulations: coatings, of Victoria, Canada) gave a talk ti- tion to the profession of chemistry in films andtapes. In April we said fare- tled Mass spectrometry-led catalyst the field of chemical education. The well to Mike Horner who has moved discovery and Daryl Rowan (Plant President presented Adrian with his to Auckland. & Food Research) spoke at the Te Fellowship certificate. Adrian is a Manawa Museum about Finding previous winner of the Dennis Ho- Metabolic Markers of Inflammation. NZP gan Memorial Prize and has made On May20, as part of the 2010 RSC In March, NZP welcomed DrLoretta substantial contributions to chemical Australasian Lectureship we had Prof education both at secondary and ter- Croweinto the fold; Loretta complet- Kenneth Ghiggino (Melbourne) give tiary level. Adrian runs the Institute ed her PhDat the Georgia Institute of a talk about mimicking photosynthe- of Fundamental Sciences outreach Technology in 2006. Since then she sis by developing materials with ap- programme that involves visits to has had positions at Massey Univer- propriate properties which would be the campus by Year-10 and Year-12 sity, working with David Officer and able to mimic nature’s effective way students from Manawatu, Taranaki, Ashton Partridge, and then at Pre- of harvesting light energy. Hawkes Bay and Wairarapa. pared Foods Ltd. In May, Drs Selwyn Dr Simon Hall has replaced Dr Trev- Yorke, Ghislaine Cousins and Jenni- On May 19, we were honoured to fer Peat departed for extended stays or Kitson as Head of the Chemis- have Dr Mark Waterland give his try. Trevor has taken on a new role at Dextra in Reading (UK). Dextrais Presidential Address. The first part as teaching fellow. A new group of a carbohydrate and custom synthe- of the talk was about the NZIC plans sis company that was purchased by students have started postgraduate and aspirations for the /nternational NZP in September 2009. While in studies: Kelsey Mortensen is work- Year of Chemistry, 2011, which pro- ing with Dr Vyacheslav Filichev on Reading, Jennifer has been involved vides a rare opportunity to promote fluorescently silent probes, Kerry with the catalogue side of business.

89 Chemistry in New Zealand July 2010

to work with WAIKATO Catalogue have continued to grow postdoctoral fellowship (Trinity Col- in recent times due to the increasing Thorri Gunnlaugsson Faulkner University of Waikato demand from glycobiology. This has lege Dublin) and Stephen developmentof lan- led to strong sales of glycoconju- (Oxford) on The The Chemistry Department had a ion directed self-as- gates and oligosaccharides to univer- thanide-metal large number of students working of water-soluble sity and biotechnology organizations sembly formation over the past summer ondiverse re- triple strandedhelicates. world wide. dimetallic search projects, many of whom were recipients of summerresearch schol- Planning for the 2012 International arships. Recently, the University held OTAGO Symposium on Macrocyclic and Su- its inaugural Swnmer Scholarship annual dinner pramolecular Chemistry (ISMSC-12) The Branch held its (SSS) Symposium, at which is well underway — if you Student in May at the new Otago Polytech- in Dunedin presentation please reg- all students gave a brief restaurant, Technique. haven’t already doneso, nic training on their research work. It proved to from the Pharmacy ister your interest via the conference Thomas Rades be an enjoyable wayforstaff and fel- the guests website www.otago.ac.nz/ismse2012/ Department entertained low students to find out what it was lecture en- to ensure you are on the emailing list with a lively post-dinner they had all been up to. for further information. titled From Drugs to Medicine. prizes in Hunter’s The 2009 undergraduate Two PhD students in Keith Chemistry were awarded recently as University Chemistry Depart- group, Katherine Baer and Hugh follows: ment Doyle, received NZ Marine Sciences Society travel grants to attend the After 27 years in the Campbell Mi- 1 year prize (Orica Chemnet Prize) Ocean Sciences Meeting in Portland, croanalytical Laboratory and 32 in Connie Hui Jui Kueh and Erica Oregonin February. the Department, Marianne Dick Prentice retired in May. The Departmentis students from science A group of 2" year prize (NZIC-sponsored J. E. greatly appreciative of her efforts communication and from Kimberly Schroder the years as Allan Prize) [van and hard work through Hageman’s research group received the NZ chemical we are sure many of first runner-up place for their contri- 3" year (DOW Agrosciences spon- community are. bution to the Environmental Science sored prize) Sam Pachal and Technology journal’s video con- Barrie Peake has had two students test, How Does Chemistry Help YOU recently complete research in his Be Green? Their video is available group. Alfred Tong (PGCert: Direct for viewing at www.youtube.com/ UVphotolysis ofaspirin, diclofenac watch?v=8bsLYLm0pUc_ or pubs. and oseltamivir in aqueous solution) acs.org/page/esthag/video/contest- and Vida Rowhani (MSc: Environ- winners.himl mental aspects of the Cadbury Con- (Dunedin) opera- fectionery Limited Catherine Sansomis commissioning now started a PhD tions). Alfred has a new GC-MSin the Plant Extracts with Rhian- under joint supervision Research Unit. This will be used for investigat- non Braund (Pharmacy), work on flavours, in native and in- practices and the 2009 Undergraduate ing drug disposal troduced plants, and Plant & Food Waikato University pharmaceuticals in Prize-winners in Chemistry. L-R: Sam levels of selected Research’s workon insectattractants. Another of Barrie’s Pachal, Ivan Schroder, Erica Prentice and NZ waste waters. The unit includes automated solid- Cubillos [with Connie Kueh. PhD students, Victor phase micro-extraction (SPME) for Miles Lamare (Marine Sciences) and headspace analyses. Our congratulations go to Ho Ying David Burritt (Botany)], is complet- Yuen, a BSc (Tech.) student in ing his study of the seasonal depen- David Warren, David McMorran, Chemistry who won one of the three dence of mycosporine-like amino ac- and a number of students from poster prizes at the recent Waikato ids in a rangeofintertidal organisms the Department spent a Sunday Sustainable Bioeconomy Student around NZ.In February, Barrie gave a in March at Otago Museum’s The Poster Conference. Her work is on Trace metal signatures of Together doing chemistry seminar on Big Get beeswax/PEO as a material for con- cardboard at the Carter Holt Whaka- experiments, helping kids make trolled release drug delivery in ani- tane Mill and at SCION (Rotorua). slime and ice cream, and supervising mals. The research was conducted in people exploring the properties vis- the Department over the summer on a Grace Morgan (UC-Dublin) of non-Newtonian fluids in a very and Annie Powell smmerresearch scholarship. ited during March large container of custard. The event (Karlsruhe), a long standing collabo- attracted a large number of people, Joseph Lane presented a talk at the rator of Sally Brooker’s, visited for many of whomstopped to see what ACS Spring Meeting entitled Ex- a week in March. Jonathan Kitchen, was going on and to talk about plicit correlation and intermolecular a PhD student and then postdoctoral chemistry and science. interactions,and also visited Profs in Sally’s group, recently left to take Randy Snurr (Northwestern Univer- up a two-yearIrish Research Council 90

2010 Chemistry in New Zealand July

market Australasian pharmaceuticals for the treatment of cancer and the ESI-MS techniques to drugs opmentof go back to the (see: www.epichem.com.au/). non-po- her studies of Taxol include neutral compounds, 1970s. It is largely as a result BioCryst Phar- and MS-MSdata, Scott early US biotech company, lar solvents the National Cancer with his in- of her work that Inc. recently announced captivated the audience de- maceuticals became interested inits Phase 2 human methodology and its ap- Institute the initiation of a sight to new She spoke on Taxol, Tu- metal catalysed velopment. trial of the drug candidate plication to transition well clinical Cor- bulin and Tumors to an audience This is for patients suf- organic reactions. Dr Emiliano BCX4208. excess of 100, enthralled everyone, gout, a severe form of tés (Theoretical and Applied Physical fering from was interviewedfor the Kim Hill of millions of National University of then arthritis affecting tens Chemistry, that aired on May particu- was with us in radio programme people globally and whichis La Plata, Argentina) remember on 29. It was an occasion to in Maori and Pacific mid-April and described his work larly common go to Dr Peter Northcote co-devel- monolayers (SAMs) and thanks Island peoples. BCX4208, self-assembled for Biodiscovery) pu- methods that (SPCS and Centre oped by IRL,is a next generation and_nanofabrication this very distinguished (PNP) for many promising for attracting rine nucleoside phosphorylase are key elements to NZ. Thiols speaker and researcher which a recent study shows applicationsin this wide field. inhibitor, utility in diseases depen- are essential in manyof the so-called may have build IRL B-cells or uric acid. bottom-up methods proposedto dent on T-cells, to deter- devices and mate- The latest trial is designed a wide variety of April a new Bruker 500 MHz particularly During the effect of doselevels of oral- rials. On gold they are was installed on mine NMRspectrometer BCX4208 on uric because they represent an the ly administered attractive the Gracefield campusto augment organic, acid levels in the blood, the build-up easy path to link inorganic, provided by the exist- service already to the often painful biological materials to a stable of which can lead and ing 300 and 500 MHzinstruments. inert surface. They condition knownas gout. and chemically The two 500 MHz spectrometers as basic units in molecu- are regarded the workhorses for a user the era ended with the blocksin become March saw lar electronics, as building NMRservice Keith friendly, easy to use retirement of IRL glassblower sensing and biorecognition devices, synthetic or- on for over 30 very active Holden. Keith has been replaced molecular motors, and in actuators, ganic chemists. The deliberate choice basis by Grant Franklin, membranes. a part-time biomimetic phospholipid identical spectrometers Jeremy Wu re- thiol and of almost the VUWglassblower. The fundamental concepts of sample auto- Con- equipped with a 60 cently attendedthe International self-assembled monolayers on dithiol changer provides high throughput, On Nanoscience and Nano- were discussed as ference metallic surfaces for interchangeability of and presented molecu- redundancy technology (Sydney) well as examples related to duplication of of modules, and avoids a talk on template assisted growth electronics and nanofabrication new lar expensive probes. Moreover, the by anodic alumina. This Wyatt (Teaching nanowires methods. Dr Paul features Bruker’s state four-week BRAP- and spectrometer wasfollowed by a and Learning, Bristol University Probe which Tech- of the art liquids Smart sponsoredvisit to the Industrial Erskine Fellow) met with Canterbury two probes (Standard Mul- Institute in Taiwan, Innova- combines nology Research staff and spoke on Teaching probes) into En- tinuclear and Inverse where he workedin the Energy & - Using Technology to Enrich tions one, and provides the commonly laboratories. The IRL Ma- that included some vironment the Traditional 'C,*'P, °F as well as has established in used nuclei 'H, terials & Energy team the practical changes made nu- of more than 50 other NMRactive for fabricating thin ceramic University. He a process Chemistry at Bristol potentially accessible uniform, tune- in- clei, all ofthem templates with highly described how these influenced Other novel po- automatically on the fly. able nanoporous channels. These for the Bristol ChemLabS novations probes include a | mm MicroProbe alumina (PAA) templates that has on-line rous anodic Centre for Excellence microgram quantities of and thermally stable use of for studying are amorphous resources, which make full High Speed sample and a range of up to 800°C. and interactive e-learning animated Magic Angle Spinning Solids probes enrich the understanding students in is working with col- to that support IRL’s programmes Robert Holt the practical experience. The Hy- to devel- haveof Nanotechnology, Geopolymers, leaguesat IRL-Christchurch system does not replace Ce- for the Coal e-learning drogen Storage and Advanced op an oxygen generator hands-on practical experi- the real ramics. Research Laboratory lignite-biomass to take on ence but allows students gasifier. A wind-powered electrolyser a fas- have an- a more challenging experiments; IRL and EpichemPty Ltd. (based upon the IRL design) offers strategic alli- that cinating new innovation. nounced the launch of a scheme to generate future fuels clients with ance designed to provide are nearly carbon neutral and that May 26 saw the visit of the highly services re- continuous and seamless can potential exploit a major NZ distinguished Prof Susan B. Horwitz pro- from drug discovery to cGMP source, namely lignite. Pharmacology, Albert (Molecular duction. Both are viewed as provid- College of Medicine, New ser- is busy organising the Einstein ers of high quality products and Tim Kemmitt Associate Director, Thera- Institute Ad- York City; vicesin the area of organic chemistry, early 2011 MacDiarmid Albert Einstein Cancer Cen- skills and Nanotechnol- peutics, and possess complementary vanced Materials a continuing interest This will ter). She has had combineto better serve the ogy conference (AMN-5). new that will in natural products as a source of eS 97 Chemistry in New Zealand July 2010

be held in Wellington 7-11 February applications, althoughit is aimed pri- Neil Milestone has returned to NZ next (see wwwmacdiarmid.ac.nz/ marily at studying some fascinating after seven years at the University of amn-5/) for further details. His PhD chemistry. New MScstudent Rachael Sheffield where he was Director of student Kathryn Graham spent a Linklateris studying the factors con- the Immobilisation Science Labora- couple of months overseas, firstly at trolling the incorporation of Al dop- tory. Muchofhis workthere involved

the Pacific Northwest National Labo- ing in ZnO sol-gel films, controlling the use of cements for waste stabili- aunjea4 ratory (Washington State) to carry film texturing and alignment, and zation and in gaining an understand- out some synthesis and high field optimising conductivity. The project ing of the reactions that occur be- solid state NMRstudies of native and is aimed at making transparent con- tween cements and various types of deuterated versions of methyl am- ductive films for photovoltaic appli- wastes, including nuclear materials. monium borohydride containing all cations. Finally, Tim is completing He is now working with Carl Bigley "'B. The samplesare then to be trans- a joint NIWA/IRL/JamesCookUni at IRLs Cementing Systems research ferred to Oxford, whereshewill carry project to use photocatalysis for ma- unit investigating reactions used in out neutron beam experiments at the rine antifouling that is showing great geothermal applications for cement- Rutherford Appleton Laboratory to promise. This will renew his interest ing steamwells. examinevariousaspects of structural in photocatalysis after some years of and chemicalinterest. The project has low key involvement following his some relevance to hydrogen storage pioneering work in the 1990s.

The Banwell Symposium: From Small Rings to Big Things Russell J. Hewitt and Robert A. Keyzers School of Chemical & Physical Sciences, Victoria University,PO Box 600, Wellington 6140 (e-mail: rob. [email protected])

May 18, 2010 wasa particularly significant day in the annals of Victoria University of Wellington (VUW) and its division of chemistry. The day marked the graduation ceremonyat which Prof. Martin Banwell[Director ofthe Research School of Chemistry (RSC) at the Australian National University (ANU)], was awarded the degree of Doctorof Science, honoris causa by the University. Prof. Banwell has an outstanding researchrecordthat hasled to his recognition as one of the greatest organic chemists in the Southern Hemisphere, further exemplified by VUW judging him worthy of an honorary DScafter only 31 years since obtaining his PhD from the sameinstitution.

The significance of this ceremony was not only due to Fromleft: Professors Brian Halton and Martin Banwell, Drs Prof. Banwell’s award but also for the multiple genera- Russell Hewitt and Joanne Harvey. Photography by Woolf. tions of related chemists present. Emeritus Professor Bri- Big Things on May 20 Mayin his honour. This sympo- an Halton, Prof. Banwell’s VUW PhD supervisor was on- sium marked another noteworthy day, as the meeting was stage as was Dr. Joanne Harvey, a VUW graduate, now the first official function hosted by SCPSin the new Alan staff member and former ANU PhDstudent of Banwell’s. MacDiarmid Building, a multi-million dollar investment Finally, Mr. Russell Hewitt, a student of Dr. Harvey’s, had for Science and Engineering, named after VUW’s 2000 his PhD conferred at the same ceremony. Consequently, Nobel Laureate. The Banwell Symposium showcased the four generations of PhD researchers of the Halton Dy- excellent teaching and researchfacilities now available to nasty were on-stage at once, with two having doctoral de- the school. grees conferred in the same ceremony. Moreover,all four generations have made significant contributions to the The symposium itself was opened by fellow chemist and same area of chemistry, namely, the formation and practi- Dean of Science, Prof. David Bibby, who described Mar- cal application of fused cyclopropane ring systems. This tin Banwell as the ... most outstanding chemist of his gen- gathering of four generations of chemists, of which two eration in Australasia and it was obviousto all just how were awarded doctorates,is believed to be unprecedented muchofa pleasure this gave the Dean. The symposium in New Zealand chemicalhistory. included local speakers from VUW and Industrial Re- search Limited (IRL) with invited lectures from by Profs. In recognition of Prof. Banwell’s remarkable achieve- Peter Steel (Canterbury University) and Martin Banwell. ments and to celebrate his award of his Hon. DSc, the School of Chemical and Physical Sciences (SPCS) at The day’s event focused on organic chemistry in the VUW held a symposium entitled From Small Rings to broadest possible sense as a wide range of topics was 93

Chemistry in New Zealand July 2010

which mimic the transition state during an enzymatic transformation, rather than the actual substrate, which leads to permanent inhibition. Forodesine analogue, BCX-4208isin clinicaltrials to treat gout and is a potent inhibitor (K, = 16 pm) of Purine Nucleoside Phosphory- lase (PNP).

The Timmer/Stockergroup, on the other hand, have devel- of oped a protecting-group free strategy for the synthesis aza-sugars. This talk, Synthesis ofAza-Sugars contained their latest results towards a combined Vasella reductive amination/carbamate annulation strategy for the forma- tion of a variety of aza-sugars (see: This Journal, 2010, 74, 57). The seminaralso presented the latest attempts to of probethe probable mechanismat play in the formation these important drug leads, which may act as glycosidase inhibitors.

The newly graduated Dr. Russell Hewitt described part of ProfessorPeter Steel his PhD research, a fascinating introduction into the use of cyclopropanated carbohydrates. He focused on his cor- Steel began the presentations with an en- covered. Prof, rection of the ring-opening product of cyclopropanated lecture entitled The Power ofWeak Interactions thralling carbohydrate 3 as C-2 substituted 4 and not the seven- New Metallosupramolecular Assemblies, in Constructing membered oxepine 5. (Scheme 1) He also demonstrated syntheses of such assemblies from various in which the how the desired oxepine 5 can be formed from use of suit- to give a wide range of metals and ligands was shown able silversalts. geometrical structures. Peter spoke about the ability to metal Scheme 1 construct desired geometries by using different no ON NY centres coupled with ligands containing specific bind- base A by of! wee BnO” "| ing angles within flexible spacer groups as depicted eoee OBn Br obtained by coupling bisphenols a Br 1. Typically, these were BnO I 1H “See 4 He also described the specific to nitrogen heterocycles. n Ag@ a Bno“\_-0~ Nu use of m-m, Ag-Ag or Ag-alkene interactions in the con- 3 Nu BnO f~B struction of the different metal complexes. Peter first met Martin at Canterbury University when he (Martin) went Bnd 5 to Christchurch to record some 'C NMRspectra in their facility, the only one available at the time. Since then they Joanne Harvey then presented an insightful and detailed have had the opportunity to meet many times, with Ban- account of two natural product syntheses using gem-di- of well describing Steel as a magnificent host during his Er- halocyclopropanes. The first concerned the synthesis skine Fellowship - even though Peter was distracted from maritinamine6 during her doctoral studies, a target whose his duties when Bob Grubbs,also an Erskine Fellow, was similarity in its name to that of her supervisor was but advised of his receipt of the 2005 Nobel Prize in Chem- incidental. The second part described an attempt to syn- istry. thesize the fungal natural product (-)-TAN-2482B7. Al- 7, the Harvey team came P though unsuccessful in making Flexible oe h will com- spacer Cy tantalizingly close and are confident that they aa fT “Wo —@) H@H plete the total synthesis of this challenging target in the SLAP n=28 HO N N near future. 1 OHOH 9 OH AS H Me Another former Halton PhD student, Andy Kay of IRL, Meo. J) his team’s work to produce Nucy HoT ~~ gave fascinating discourse on ° that can be used in non-lin- HO new chromophoric molecules 6 7 ear optics. In particular, he described the photophysics of such materials and the fundamental results they have Twonatural products seminars were also presented, the a generated by optimizing right-hand side chromophores, first by recently appointed VUWacademic Rob Keyz- niche area of such research, which mayfind use in optical ers. He described postdoctoral work involving the isola- data transmission (see This Journal, 2010, 74, 72). tion and structural elucidation of the tetraprenyl alkaloid malonganenoneB,8. Keyzers then went on to discuss his Furneaux (IRL) and Mattie Timmer (VUW) of Both Richard group’s work focused upon the synthesis of analogues accounts of the syntheses of aza-sugars gave interesting 8 that are designed to explore novel H/D exchange within producedforthe treatment of specific dis- that have been the natural product. In an entertaining discussion, Dr. Pe- team, in collaboration with Schramm eases. Furneaux’s ter Northcote described in detail his group’s methodol- of Medicine, New York) have (Albert Einstein College ogy, historical and on-going, to use NMRspectroscopy developed drugs such as Forodesine (Immucillin-H) 2, 94

Chemistry in New Zealand July 2010

to guide the isolation ofnatural products. The workdates highlighted Martin’s inspiring and elegant synthetic ven- from the late 1990s and hasevolvedfrom simple 'd NMR tures incorporating the total synthesis of a very impres- spectral analysis 6f spongeextracts to comprehensive 2D- sive numberofnatural products, providing a magnificent NMR-based screening using sophisticated in-house soft- tourdeforce. ware for spectral manipulation. x E. coli x JM109 OH dboo (pDTG601) “OH Y y 11 12

«) Student posters were also presented throughout the day

9 10 that showcased the variety and quality of VUW research. Profs. Banwell and Steel awarded the Dean’s prize to Thefinal session of the day, purposefully chaired by Rus- MarkBartlett for his poster A Novel Palladium-Catalysed sell Hewitt, saw Halton himself providea ... hysterical/his- Allylic Alkylation Cascadeforthe Synthesis ofFuranopy- torical account... of Martin’s timein the laboratory during rones from his first year of doctoral research. his research days at VUW. Onepoint Brian noted was that Martin’s PhD researchto synthesize angular 9 andlinear The day concluded with drinks and a symposium dinner 10 bis-cycloproparenes was...singularly unsuccessful... in the staff club where SCPS Head Prof. John Spencer in its aim, yet produced some wonderful results. Martin’s presented Martin with a commemorative bound copy of great enthusiasm during this time was a sure indicator of the symposium programme. his future success; few PhD students submit and defend their thesis, and then depart for a postdoctoral fellowship within 30 months! Brian also highlighted the difficulties in ordering chemicals during that era - orders could only be put through once or twice a year. Today’s younger generation tend to purchase anythinglisted in the Aldrich catalogue if needed, whereasBrian stated if the chemical wasin the Aldrich Catalogue thenit could be made!. Mar- tin replied that was the curse of the Aldrich Catalogue. If it was in the catalogue you could makeit, andif it’s not there then you HAD to makeit!

Professor Martin Banwell

Martin Banwell has made enormous contributions to chemistry with over 260 papers, patents and book chap- ters that describe chemical methods and syntheses at the forefront ofmodern organic research.Asdirector ofANUs RSC,he heads the most prominent school of chemicalre- search in the southern hemisphere. He maintains one of Dr Russell Hewitt the more productive research groups in natural product synthesis and has supervised over 100 graduate students. Martin then providedthefinal seminarofthe day entitled He is an Honorary Fellow of the Royal Society of New Chemoenzymatic Methodsforthe Assembly ofBiological- Zealand, a fellow of the Australian Academy of Science ly Active Natural Products. Through use of an enzymatic and a Fellow of Royal Australian ChemicalInstitute. His asymmetric dihydroxylation process, Banwell has shown honorary doctorate exemplifies his impact as a research that the cis-1,2-dihydrocatechol products obtained, eg. chemist, and he remains an inspirational figure to younger 12 from 11, are versatile intermediates for the synthesis chemists. of various alkaloids. His group hasutilized the enantio- specific formation of the catechols in a numberoftotal syntheses of natural products including (-)-panepophen- anthrin. Moreover, Martin presented several insightful Strategies to take the single enantiomer of the catechol produced and use an enantiomeric switching technique to make natural products with each possible absolute configuration, a wonderful feat. Once again the seminar

95

Chemistry in New Zealand July 2010

Light Metals Research at the University of Auckland J. Metson, P. Lavoie, L. Peranderand R. Etzion 92019, Auckland 1142 Light Metals Research Centre, University of Auckland, Private Bag

Article (e-mail: [email protected])

by far the largest part of the research Introduction of the-industry, is undertaken, with projects also in areas such as titanium Light Metals Research Centre (LMRC) at the Uni- The processing, magnesium alloy development and surface founded in 2002 and followed versity of Auckland was treatment. sometwelveyears of research in aluminium,titanium and magnesium largely in Engineering led by Profs. Barry Technical consultancy and research contract services Welch and John Chen. Their activity expanded signifi- provided through the Centre are supported by research cantly through the 1990s with the involvement of Mar- in process fundamentals, aligned with experience in ma- garet Hyland and Jim Metson. Following Welch’s retire- terials science, process control, operations management ment, a cross-faculty research centre was formed under and scientific method-based process improvement. The the interim directorship of Jim Metsonand taken over by Centre also offers tailored industrial training courses and Mark Taylor when he joined the University in 2003. The postgraduate qualifications from the University. Long- Centre was established with the objective of providing term research in material science and engineering has world-leading expertise with a full suite of research and made the LMRCinto a world leaderin Alindustry, indus- development capabilities, and training and education for trial materials, and process development. For example, the global light metals sector. The Centreis located largely it has developed standard quality tests for electrode and within Chemistry, but the emphasis on external (and par- refractory materials where chemical and electrochemical ticularly international) contract research means activities corrosion can be tested. Coupled with advanced material are managed through Auckland Uniservices Ltd., wholly characterization methods, they give insights into complex ownedbythe University of Auckland. corrosion mechanismsandhelp in the design of materials with properties better suited to their operating environ- for alumina refining and Although both the Bayer process ment. the Hall-Heroult process for electrolytic reduction are morethan a century old, both face major challenges in an The LMRC hasalso been developing and commercial- increasingly energy- and carbon-constrained world. There izing its own technologies. An example is the Sidewall are ongoingissues in materials science, process control, Heat Exchanger (SHE), a compactandefficient air-driven energy recovery and reduced environmental impacts that heat exchangercapable ofproviding controlled cooling of are increasingly part of the industry’s viability and li- smelter cell sidewalls. The SHEsenable increased amper- cence to operate. Herein, the contributions of the Centre age to the reduction cell and the ability to accommodate in addressing twoparticular chemistry-themed challenges power modulation, while retaining other operational ben- encountered in the aluminium production chain are pre- efits, including a cooler operating cell and ultimately al- sented, Thefirst case study describes how advanced char- lowing waste heat recovery of 100-200 kW per cell. acterization techniques give insights on how calcination technologyaffects the phase transformation reactions and The Microstructure of Metallurgical Grade phase distribution in smelter-grade aluminas; the second Aluminas understanding of the corrosion mechanisms addresses the The Hall-Heroult process produces aluminium metal by of silicon carbide sidewall refractories,critical to the life electrolysis of alumina (AI,O,) dissolved in molten cryo- of the reduction cell. lite (Na,AIF,). For every tonne of primary metal, 1.92 of alumina are required. Thus, the tonnage of alu- Light Metals Research Centre tonnes mina produced rises at approximately twice the rate of around 30 research pro- The LMRCcurrently employs growth in metal production. Primary metal productionsits with some chemists and fessionals, mostly engineers at about 40 M tonsannually and typically shows ca. 3-4% postgraduate students. Some physicists, and hosts 12 year on year growth.' It is worth noting that secondary that include chemistry, math- 20 academics from fields (recycled) production has grown considerably faster than and multiple engineering ematics, industrial psychology, primary and,since around 2004, has exceededthe produc- operat- fields also contribute to the research programmes tion of primary metal. ing within the Centre. The LMRCis currently engaged in over 40 such projects with 20 industrial, 13 University Around 90 M tonnes of alumina are produced annually, and 7 Governmental agencypartners spanning 15 coun- 95% of whichis destined for aluminium smelting.** The tries. These projects range from fundamental research to balance is produced primarily for catalysis, refractories commercialization of industrial technologies, and cover andabrasives markets. The largestrefineries now produce the majorindustrial growth areas such as in China and the between 4 and 7 M tonnesofalumina annually. The dis- Middle East. Additionally, smelter innovations in older tribution of the scientific literature on alumina is almost plants are driven by the need to accommodate a changing the inverse of this and is dominated by applications in energy market. Aluminium smelting technology, includ- catalysis, and (increasingly) the synthesis alumina in a ing alumina production and the environmental impacts range of exotic morphologies extending to the nanoscale. 96

Chemistry in New Zealand July 2010

However, the microstructure and properties of metallurgi- cal or smelter grade aluminas (MGAs)are of considerable interest, primarily because of the relationship to alumina refinery operation and in their impacts on the smelting process.

Aluminais produced in the Bayer process by the diges- tion of bauxite, the precipitation of Gibbsite [Al(OH),] froma clarified sodium aluminate solution, and calcina- tion to produce the alumina.‘ Anelectron micrograph of a typical Bayerprocess alumina particle resulting from this process is shown in Fig. 1. The aggregated particle morphology and texture reflect the seeding strategy and precipitation conditions, typical for a Bayer plant, where agglomeration is a faster mechanismofparticle growth than the growth of individual crystals.

HV Mag| WD See3 | eTARPA Atte: AO faa) N Fig. 2. Charge contrast differences in gibbsite.

sc] 100 200 300 400 500 600 700 600 900 1000 1100 1200|*c T T T T T T T T T T Gibbsite| Chi Kappa Alpha

AKOH), 7-Al;O2 -Al:O2 eALOs

Boehmite Gamma| Gamma’ Delta Theta Alpha

AIOOH ALOs | y'AbO. | 5-AlLOs |0-AlO] _a-AlO:

Eta Theta Alpha n-AlzOx 0-AlO. o-AlOs

Rho

ALO;

L L L 1 L L L i | L _k | 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500 |K

HV /Spot|Det/ Mag) WD |_ Ee aiele senoe inal Fig. 3. Gibbsite calcination pathways (adapted from Wefers, et al. — see ref.9). Fig. 1. SEM imageofa typical Smelter Grade Aluminagrain.

Charge contrast in the Environmental Scanning Electron moist Gibbsite. However, contact times between particles Microscope (ESEM),or variable pressure SEM, has been and gases at temperatures of up to 1000 °C in the hot zone shownto be a useful toolin studying gibbsite and alumina maybeas short as a few seconds; thus, rapid heat transfer microstructure.*® Previously, the technique has been used into the particle is critical in achieving conversionto alu- to study Gibbsite growth characteristics as slight varia- mina. Transformation of gibbsite to the transition alumi- tions in structure owing to defects and impurities; these nas is pseudomorphic, with the original crystal habits, the result in a contrast difference observable in particle cross external dimensions and the morphologylargely retained, a sections.® More recent approaches have revealed further even though series of crystallographic phase changes internal andstructural features that can be related to crys- occur. As a consequence, significant porosity develops tal growth mechanisms. Compositional variations arise during the initial heating stages.’ fromthe cycling of growing crystals through precipitation Thepresenceofthis porosity and the tanks that have a varying Al:Na ratio as the Al is depleted dominanceoftransi- tion aluminas is key both to the use ofthe alumina as a by gibbsite precipitation. Fig. 2 shows a gibbsite cross mediumfor dry-scrubbingofcell gases,'° and in effective section where these growth ringsare visible through such charge contrast techniques. dissolution of the alumina in the electrolyte. Before feed- ing to the reduction cell, alumina is used as the primary Calcination transforms Gibbsite into a range of pre- medium for cell gas scrubbing. Specific surface areas be- dominantly transition aluminas (Fig. 3) with the pathway tween 70 and 80 m*/g typically are specified to accom- across this phase roadmap and makeupofthe final prod- modate scrubberneeds. uct, dependenton calciner technology.”* This technology X-ray diffraction-based structural phase analysis of the has progressively moved from rotary kilns to more en- MGAsis especially challenging owing to the presence ergy efficient gas suspension or circulating fluidized bed processes, in some cases with capacity in excess of 4,000 of these metastable, sub-crystalline, transition alumina phases. The gibbsite transformation pathways are often tonnes per day. Energy consumption is now typically be- (mis)represented by diagrams such low 3 MJ/kg in suchstationary calciners, within about as Fig. 3. The dis- tinction betweenthetransition 20% of the theoretical minimum for the calcination of a alumina phases, or forms, 97

Chemistry in New Zealand July 2010

occupan- spectrum has been usedto probe site defined as the diagram might imply. It is (XANES) is not as well It can be seen that resonances char- is more ordered than 6- cy in these materials. generally agreed’that 6-alumina the industrially acteristic of alpha alumina are present in which again is more ordered than the y-alumina alumina, Similarly, features related to aluminium exactly how the transformation into calcined samples. phase.'" However, coordination are also visible in the the subject of de- in tetrahedral oxygen the more ordered formsproceedis still tool for SGA, SGAs. Although useful as a fingerprinting formation of y-, y'-, and @-alumina can be bate.2"5 The of this data is challenging due to the transformation into the quantitative analysis seen as waypoints on the gradual the sample. complex multiple scattering interactions in fully orderedstate represented by a-alumina. collected at the Austra- —-- Gibbsite Atypical X-ray diffraction pattern =-- Boehmite from fluid bed (CFB)cal- --- Gas Suspensio Calcined MGA lian Synchrotron for an alumina ~~~ Rotary Kiln Calcined MGA, in wave- Circulating Fluidised Bed MGA] cination is shownin Fig. 4. For several reasons — provides ---- Alpha Alumina. length selection and intensity, the synchrotron these difficult a substantial advantage in data quality for approach samples. At the LMRC,the Rietveld refinement based on the has been developedto build an SGA model phase y-, Y'-, 0-, and a-phases, to allow a quantitative based analysis.'° The transition aluminas are modelled spinel struc- upon literature data for these defect cubic = tet- 5 varying occupancies of the octahedraland tures, with =S This approach still recognizes ee rahedral aluminium sites. 2 can never & that although such a quantitative phase analysis 2a because of the arbitrary boundaries 2 be absolutely correct = This has pro- between phases, it can be self-consistent. aluminas and, vided a valuable tool in the comparison of and in in particular, the impacts of calciner technologies understanding their behaviourin the smelter.

140000

120000 190000 B s0000 = 1590 1600 & sono ‘ of aluminas Fig. 5. Al K-edge XANESspectra froma selection 40000 the gibbsite starting typical of several calcination technologies, fully calcined o-alu- material, the oxyhydroxide boehmite, and seFal uyolgly daliol mina (bottom). Nenanaaan transfer into An interesting consequenceofthe rapid heat within grains boll OS particles is the phase differences observed 20 (7) beautifully il- in addition to that betweengrains. This is pattern of a CFB contrast ESEM imagesin Fig. 6, Fig. 4. Synchrotron X-ray powderdiffraction lustrated in the charge refinementresults; layer shows evidence calcined MGA sample andresulting Rietveld where the lighter coloured surface nature of the while the sloping backgroundis a result of the amorphous of almost complete conversion into a-alumina, mounting. structures. The quartz capillary used for sample the interior retains the transition alumina with the contrast in the im- scale of ordering phase assignments associated Thecentral problemin the short length diffraction have been confirmed with TEMelectron has prompted several more novel ap- ages in these materials samples.’ The structure seen in Fig. 6 analysis question. We studies on sectioned proachesto addressthis structural impacts on the dissolution field *’Al MASSS is expected to havesignificant have made considerable use of high reduction cell. behaviour of the alumina when fed to the Absorption Spectroscopy (XAS) and Atom- NMR,X-ray to have poor dissolution character- derived from neu- a-Alumina is known ic Pair Distribution Functions (PDF) reduction cell, istics and often sinks to the bottom of the data, in examining the structural relation- tron diffraction sludgelayer. Forthis reason, modern These methods allow an forminga persistent ships within these materials.'""’ have the a content below without MGAstypically are specified to examination of the local chemical environment Access to ca. 3%. the need for crystallographic long-range order. in the UK, and Synchrotron of modern cal- highfield SS NMRfacilities These results demonstrate that the speed and the USA has been morphology, and Neutron Facilities in Australia ciners, andthe variation of particle size and with clear centralto these studies. yields a non-equilibrium phase distribution, differences both between and within individual the soft x-ray line at the Aus- structural Fig. 5 illustrates data from mixture of phases presents absorption alumina grains. This complex tralian Synchrotron, where the near edge X-ray

98

Chemistry in New Zealand July 2010

SNBSC materials are formed by the high temperature ni- tridation of a green form containing SiC grains and a Si powderbinder(Eq.1). 3Si_,, + 2N 2@) = SiN,#4 (9) AH = -824.7 kJ/mol.... Eq. |

This leads to a composite material in whichthe SiC grains are supported in a Si,N, binder phase. However, notall SNBSC materials are created equal and this leads to un- predictable, and occasionally short, lifetimesin the cell.2° Microstructural analysis of SNBSC materials, before and after use, has been undertaken by X-ray diffraction, solid state Si MAS NMR,2! and SEM,to examine the degrada- tion of these materials in a variety of cell environments. Thesestudies identify, for example, significant variations in the a/B Si,N, ratio and porosity in the binder phase, both between manufacturers and as a function of location Omer Neate aoe ON Mtiad eeease ge oko relad within an individual refractory brick.2? Typically, higher porosity levels Fig. 6. Environmental SEM imageof the cross-sectionofa rela- and B Si,N, content are found in the in- tively small industrial alumina grain showingsignificant phase terior part of the brick where during manufacture, the differentiation across the section; phase distribution is influ- nitridation reaction occurs both later and at higher tem- enced bythe calcination conditions and calciner technology. peratures.*

SNBSCsamples weretested in a laboratory-scale alumin- significant challenges in understanding their structure, ium reduction cell. A testing rig with somenovelfeatures, particularly in relation to the performance as a raw mate- such as a rotating anode (Fig. 7), was developed to ex- rial for the smelting process. A holistic approach, where amine corrosion resistance of samples under electrolysis orderondifferent length scalesis probed, is necessary for conditions in molten cryolite at up to 1000 °C. Corrosion a more complete understanding of these materials. test results, supported by thermodynamic calculations, Sidewall Refractories identify the Si,N, binderas the reactive phase in these ma- terials, especially in the gas phase abovethe bathlevel. Aluminium smelters drive production increases through increasing the amperage of individual reduction cells as well as increasing the numberof reductioncells. The larg- est cells now operate at 500 kA while the largest smelters operate a 1000 or more reduction cells. The life of a cell, typically 5-7 years, is a critical parameter in economic viability, with costs approaching $0.3 M to rebuild the largest of the cells. Failure occurs usually through ero- sion of the graphitized or semi-graphitic carbon cathode, or through breachingofthe sidewall refractory.

The sidewall in a high amperagecell is typically con- }<——Inconel® can structed from cemented blocks of silicon nitride-bonded silicon carbide (SNBSC). This material shows the optimal combination of resistance to molten cryolite, mechanical SNBSC. Graphite crucible strength at operating temperature samples (ca. 1000 °C), and suf- ficient thermal conductivity to shed the required heat load COzbubbies through the sidewall. Thelatter pointis critical —— Anode 3 em gp [> as the re- Bath fractory is protected, not by its corrosion resistance, but Aluminium by maintaining a frozen layer of electrolyte at the hot face of the refractory. Corrosion resistance ofthis material, thus, is of considerable interest, as would be the develop- Fig. 7. Laboratory-scale corrosiontesting rig. mentof a material inert to molten cryolite. The develop- The phase distribution within the binder ment of such a material would aid in the move towards is also relevant, with high B Si,N, content showinga statistically an insulated cell, and, thus, the ability to reduce the cur- signifi- cant contribution to the corrosion rate in lab-scale rent energy loss through the sidewall as waste heat. To cor- rosion trials (Fig. 8). The crystal morphology putthis in context, current energy consumptionacrossthe of B Si,N, is suggested as the reason for the high reactivity industry is stalled at a best practice of ca. 13 kWh/kg Al, of these materials. This morphology, characterised almost:exactly twice the theoretical requirement. Given by elongated rod-like crystals with hexagonalcross section, the estimate that between 1 and 2% of the world’s electri- presents a higher surface area compared to a Si,N, cal poweris being used to make aluminium,the potential crystals contain- energy savings are enormous. ing mainly flat matte crystals. 99

Chemistry in New Zealand July 2010

Kia Wallwork (Australian Synchrotron), and Prof. Paul Monroe Corrosionvs. B SisNs content in SNBSC samples and the Electron Microscopy (University of New South Wales). The support of Australian Synchrotron, and the Australian Insti- 2 tute ofNuclear Science and Engineering, the companies Outotec Be 02 10.00 Aluminium, Hydro Aluminium, Rio Tinto Alcan, Alcoa World

8.00 Alumina, Noranda Aluminum, Trimet Aluminium AG, the (%) 6.00 LuoyangInstitute of Refractories Research, Simonsens Ltd and 4,00 the CSIRO Light Metals Flagship is acknowledged.

Corrosion 2.00 =

0.00 References 50.0 60.0 0.0 10.0 20.0 30.0 40.0 1. Internaional AluminiumInstitute;see: http://stats.world-aluminium. B SisNa (%) org/iai/stats_new/index.asp (accessed 13 May 2010). WorldAl.com; see: http://www.worldal.com/market/statistics/ (ac- corrosion N Fig. 8. Corrosion rate (% weight gain owing to the cessed 13 May 2010). products) as a function of B Si,N, content of SNBSC samples 3. International Aluminium Institute statistics. 2008; see: http://www. showsa highcorrelation. world-aluminium.org/?pg=statistics/ Den Hond R,; Hiralal, 1; Rijkeboer, A. In Alumina Yield in the proposed corrosion mechanism for SNBSC materi- 4. The BayerProcess Past, Present and Prospects. Light Metals 2007 (M. atmosphere is based, als in the aluminium reduction cell Sorlie, Ed.) Minerals, Metals & Materials Society, Warrendale, PA, therefore, on a combination of oxidation of the binder 2007, p.37-42. to his- followed by attack of corrosive gases, particularly HF, 5. Roach, G. I. D.; Cornell, J. B.; Griffin, B. J. Gibbsite growth technique. produce volatile SiF,. Thus, the binder phaseisinitially tory- revelations ofa newscanning electron microscope Light Metals, Warrendale, PA, 1998, p.153-158. passivated below the electrolyte level on the sidewall, Griffin, B. J.; Browne, J. R.; Lincoln,F. J. Microscopy where exposure to corrosive gasesis limited, but occurs 6. Baroni, T. C.; Microanal. 2000, 6, 49-58. more rapidly in the area of the sidewall above the elec- 7. Perander,L.; Klett, C.; Wijayaratne, H.;, Hyland, M., ef al. Jmpact The intrusion of electrolyte into the trolyte/air interface. ofCalciner Technologies on Smelter grade Alumina Microstructure refractory and capillary and vapour transport up the side- andProperties Proc 8" International Alumina Quality Workshop, wall is a key factor in accelerating this reaction. AQW Inc. 2008, 103-108. 8. Reh, L. Chem. Eng. Technol. 1995, 18, 75-89. these studies point to improved performance Eds.), Although 9. Oxides and Hydroxides ofAluminum (Wefers, K.; Misra, C., through better temperature control during nitridation, the Alcoa Technical Paper No. 19. 1987, Aluminum Company ofAmer- major gains in sidewall technology will arise from the ica: Pittsburgh, PA. 51(5), developmentofentirely new cryolite resistant materials 10. Gillespie, A. R.; Hyland, M. M.; Metson,J. B. J Metals 1999, which do not require a frozen ledge. We are currently 30-34. 1989, 37: 569-78. looking into such materials in a joint project with sev- 11. Jayaram,V..; Levi, C. G. Acta Metallurgica, 30, 247-55. eral Australian Universities and the Light Metals Flagship 12. Wilson, S. J.J. Solid State Chem. 1979, 34(3), programme of CSIRO. 13. Wilson, S. J.; McConnell, J.D. C.J. Solid State Chem. 1980, 315-22. Conclusions 14. Levin, L.; Brandon, D. J. Am. Ceramic Soc. 1998, 87,1995-2012. Wolverton, C.; Hass, K. C. Phys. Rev. B, 2001, 63(2), 24102/I- maturity of the technologies used in alumina 15. Despite the 24102/16. refining and aluminium smelting, a range ofmaterials sci- 16. Ashida, T,; Metson,J. B.; Hyland, M. M. NewApproaches to Phase constraints still ence, process control and performance Analysis of Smelter Grade Aluminas. Light Metals 2004 (A. Ta- limit improvements in energy consumption and the envi- bereaux, Ed.) The Metals Minerals and Materials Society, Warren- ronmental footprint ofthis industry. The Auckland Light dale, PA 2004. p.93-97. T. ef al., Phys. Metals Research Centre has been prominent in both the 17. Kato, Y.; Shimizu, K.-i.; Matsushita, N.; Yoshida, Chem. Phys. 2001, 3, 1925-1929. underpinningresearch and technical support of the indus- Chem. S. J. L. Chem. Mat. 2006, 18, try to address these challenges. 18. Paglia, G.; Bozin, E. S.; Billinge, 3242-3248. Groutso, T.; Hyland, M. M., ef al. Metallurgical aluminas, as opposed to those produced for 19. Perander, L. M.; Zujovic, Z. D.; Can J. Chem. 2007, 85, 889-897. the chemical industry, are poorly understood materials, 20. Skybakmoen, E.; Stoen, L. I; Kvello, J. H.; Darell O. Quality eval- particularly in the light of very rapid calcination process uationofnitride bondedsilicon carbide sidelining materials , Light MGAs. The structural typically used to produce modern Metals, TMS (The Metals Minerals and Materials Society Warren- analysisof these materials and understanding their perfor- dale, PA), 2005, p. 773-778 mancein the smelter continuesto be a challenge, although 21. Zujovic, Z. D.; Etzion, R.; Metson, J. B. Ind. Eng. Chem. Res. significant advances have been madeoverthe past decade. 2008, 47, 9913-9918. ofsili- Sidewall refractories are another area where reductioncell 22. Andersen, F. B.; Dérsam, G.; Stam, M.; Spreij, M. Wear bondedSiC bricksin aluminiumelectrolysis cells, Light design and the energy efficiency of the smelting process con nitride Metals Minerals and Materials Society, Warren- limitations. Although Metals, TMS (The is constrained by materials science dale, PA), 2004,p. 413-418. of SNBSCrefractories is now better under- the corrosion 23. Etzion, R.; Depree, N.; Metson,J. B. A study ofthe wear mechanism inert to molten stood, we are no closerto a viable sidewall ofsilicon nitride bondedsilicon carbide refractory materials, Light cryolite. Metals, TMS (The Metals Minerals and Materials, Warrendale, PA), 2008, p 955-959 Acknowledgements Weare grateful for the contributions of Prof. Mark Smith and the NMRgroup (University of Warwick), Drs. Bruce Cowie and 100

Chemistry in New Zealand July 2010

Antioxidant Plastics based upon Conducting Polymers Paul A. Kilmartin® Polymer Electronics Research Centre, Chemistry Department, University of Auckland, Private Bag 92019,

Auckland (e-mail: [email protected]) a}9134V

Introduction: Active Packaging tion of the plastic itself, and to prolong the shelf-life of The packaging industry increasingly is turning to polymer products coming in contact with the packaging. At the chemists and engineers to develop novel plastic materials same time the small molecule antioxidants might leach with added active functions. In addition to containing a out of the packaging material, which is not always desir- food product or pharmaceutical, the packaging then as- able. sists in prolonging the product’s shelf-life or improving Conducting Polymers convenience, e.g. through moisture or oxygen control. Further active agents can include ethylene scavengers and Plastics that conductelectricity is a concept that has be- antimicrobial compounds such as ascorbic acid. One of come very familiar to NZ chemists, particularly following the most widespread types of active packaging involves the 2000 Nobel Prize awarded to Alan MacDiarmid, Hide- the addition of oxygen scavengers. In the food industry, ki Shirakawa (Japan) and Alan Hegger (USA)for work on these scavengersare designed to lessen oxidative damage, conducting polymers. Polymers with good environmental such asrancidity in oils and fats, discolouration of meats, stability that are easy to prepare, e.g. polypyrrole (PPy), andloss of nutritive elements. To be effective, the scaven- polyaniline (PANI) and poly(3,4-ethylenedioxythio- gers needto be able to absorb large quantities of oxygen, phene) (PEDOT)(Chart 1), have attracted considerable be economically priced and preferably recyclable, and, research attention and are being considered in a diverse importantly, contain no toxic products that will come in range of applications such asplastic solar cells, actuators contact with the consumer. and in biosensing. In somecases, the high conductivity of the polymers in the doped state is important, while in One of the most effective means of removing oxygen others it is the ability of the polymers to be reversibly from within a package is the inclusion of small sachets oxidised and reduced, viz. to be redox-active, that is the containing powderediron. In other cases an active oxy- important consideration. Oxidized PPy has been found to gen scavenger is embedded in the packagingitself. The be a suitable material for in vitro nerve cell culture and active material then lowers the internal oxygen concen- for the controlled release of drugs.** An important con- tration by removing oxygen that would otherwise migrate sideration for in vivo applicationsis the toxicity for PPy, through the plastic. Examples include nylon MXD6as a which to date has been found to be low, pointing to good high gas barrier resin that is easy to recycle, and which biocompatibility.’ In further studies, PPy particles did not can be prepared as a single layer blend with a beverage induce a cytotoxic effect in experiments on mouse cells° plastic such as PET (polyethylene terephthalate) or as a and showed no evidence of systemic toxicity around the multilayer construction where the scavenger is included rat sciatic nerve.’ Biocompatability studies have been ex- within an inner layer. In some cases a cobalt catalyst is tended more recently to considercell proliferation on PPy added to improve the scavenging properties of the nylon. substrates.* Anotheralternative is to incorporate small molecule an- Chart 1. Structures of three common conducting polymers tioxidants, such as ascorbic acid or sulfites, or to employ an unsaturated organic polymer that can be oxidised and AAP\ NoN F\ NR Py thereby remove oxygen coming through the packaging. In NOUN ar trials on red winesstored in PETbottles with the inclusion polypyrrole of a polyester copolymer oxygen scavenger, the oxygen permeability was found to be decreased by more than 10- 4OHO fold.' Tests over 170 days showed that SO,, anthocyanin benzenoid quinoid ring rings polyaniline and flavanol retention was greatest in the PET contain- ers with the oxygen scavenger included. The containers ° o O° ° performed even better than: storage in glass and this is “\ 5 I\ 5 LN ascribed to the ability of the scavenger within the PET to Benty seyret \ remove oxygen already dissolvedin the wine. ° Vy Ly A further related concept in active packagingis the inclu- PEDOT sion of antioxidants with radical scavenging properties. Theserange fromtheclassic antioxidant vitamins, such as Antioxidants and Radical Scavenging Test a-tocopherol and f-carotene, through to the more stable Procedures synthetic antioxidants, such as butylated hydroxylanisole Dietary antioxidants such as vitamin C, vitamin E and (BHA)and butylated hyrdoxytoluene (BHT). Theseanti- polyphenols appear to offer protection against cardiovas- oxidants scavenge free radicals to lessen rancidification cular diseases and cancers.° They can also act as preserva- in oils and fats, and so they can be includedin the plastic tives in foods, and in the case of lipid-soluble antioxidants packaging, both to retard the oxidation and the degrada- can help limit the onset of rancidity, especially for foods 101

Chemistry in New Zealand July 2010

commercially available soluble conducting polymers rich in polyunsaturated fats. An excessive production of of assay over a 30 minute test period, and the free radicals is thoughtto be responsible for high levels of in the DPPH polymers were found to be very effective free oxidative damage, whereby species that contain unpaired conducting scavengers.'*!” By using electrochemical tests to electrons react with biomolecules to cause cellular injury radical the potential at which the DPPH radical is re- and death.!° The mechanismofaction of antioxidants can evaluate in a methanolic test solution, itself a weak oxidis- include chelation of pro-oxidative metals, oxygen scav- duced the high effectiveness ofthe conducting poly- enging and free radical termination.'' Antioxidants can ing agent, to the original aniline and pyrrole monomers then be defined as compoundspresent in foods orin the mers-relative understood. Likewise, the high scavenging ac- body in small amounts that prevent or inhibit reactions could be in the DPPHassay of certain groups of polyphenols, promoted by oxygen andradicals suchas peroxides. tivity namely those with morereadily oxidizeable catechol and re- Asthe ultimate effects of a good dietary supply of anti- galloyl groups, was also explained relative to the low oxidants in the body orthe inclusion of preservative an- sponse observed for polyphenols with more isolated phe- is This obser- tioxidants, such as SO, or ascorbic acid, in beverages nol groups that are moredifficult to oxidise. only realized overa time-frameofyears, more rapid anti- vation is importantin understanding differences obtained com- oxidant capacity tests have been developed for food and with the DPPHassay for food and beverage extracts Fo- biomedical studies. These rapid bench-top assays, many pared to measures of polyphenol content such as the of which provide a measureofthe free radical scaveng- lin-Ciocalteau assay.” ing ofthe antioxidant compoundspresent, have inevitable further investigations various spectroscopic measure- limitations but can be used to provide an indication of In were applied to solid conducting polymer samples, the potential, or capacity, for antioxidantactivity, e.g. of ments polyaniline, before and after exposure to a DPPH a glass of red wine. The main antioxidant capacity test mainly including EPR, XPS, and solid state NMR, procedures have been classified as either single electron test solution, both 8C and '"N NMRstudies. For this work and transfer (ET) assays or hydrogen atom transfer (HAT) using subsequent studies, the conducting polymer powders assays.’2 An example of an ET-based method, in which in prepared using ammoniumpersulfate as the oxidis- antioxidants reduce a supplied oxidantradical, is the 2,2’- were agentto effect the required chemical polymerisations. azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) ing various spectroscopic studies confirmedthat polyani- assay, based upon their reaction with the ferrylmyoglo- The line was oxidised in the course of the DPPHtest and that, bin radical, formed through activation of metmyoglobin it had acted as a reducing agent, while no evidence by hydrogen peroxide,or alternatively by the reaction of indeed, seen for additional chemical binding or trapping of ABTSwith potassium persulfate, to produce the coloured was within the polyaniline structure.”!** radical cation ABTS*." Antioxidants can quench the the DPPHradicals radical and thereby decolourise the reaction mix- ABTS* Solid conducting polymer samples created some difficul- which is monitored by a spectrophotometer at 753 ture, tics with standard DPPHtest protocols, where 1.5 mL of The ABTSassayis applicable to both lipophilic and nm. a 72 uM solution of coloured DPPH radicals (with anini- phases.'* A further ET methodis the a,a-di- hydrophilic tial absorbance maximumat 516 nm of around 0.65 units) (DPPH) assay, in which a more phenyl-B-picrylhydrazyl wastypically employed. Thefirst issue centered around a radical scavenger removes the purple coloured effective nearly complete removal of DPPH radicals within a cou- radical more rapidly and/or more completely.'*'° DPPH ple of minutes whenjust | mg of conducting polymer was of these assays have been widely applied to measure Both employed. This means that conducting polymer samples total antioxidant capacity of foods and beverages.'® the could not be differentiated using the existing methodol- example of an HAT-based assay is the oxygen radical An ogy. The final form of the DPPH assay now involves 20 capacity (ORAC), in which the antioxidants absorbance mLof a 255 iM solution of DPPHradicals and 1.0 mg a substrate compete for peroxyl radicals generated by and conducting polymer samples with controlled shaking dur- of azo compounds. A further approach the decomposition ing the reaction period.? Even though the initial absor- the effectiveness of antioxidants is to set up ac- to testing bance reading is around 2.6 units, final readings in the aging trials in which a beverage or food oil is celerated 0.5 to 1.0 rangeare typically obtained, allowing compari- for several weeks, and the browning of the bever- heated sons between conducting polymer samples to be made. or degradation of the oil with build-up of peroxides, age, Underthese conditions, the scavenging of DPPH radicals is monitored. : continues well beyond the 30 minutetest period typically for small molecule antioxidants in solution. Conducting Polymers as Free Radical employed Differences between soluble antioxidants and the solid Scavengers conducting polymers contribute to this effect, along with The role of polyanilines, alongside aromatic amines, in the wide range of oxidation potentials of the conducting stabilising rubber mixes has been demonstrated, whereby polymerstructural units (seen also in the broad oxidation polyaniline or poly(methoxyaniline) slowed down the curvestypical of cyclic voltammograms). The test proce- rate of oxidation of the rubber itself.'7 Our interest in dure has thus been extended to 24 hours of reaction time conducting polymers as antioxidants was stimulated by before the final readings are taken. a recognition of the similar oxidation potentials of sev- in the performance of the antioxidant eral polyphenol antioxidants, such as catechin and many Owingto variations is a current trend to apply a range of the commonconducting polymers, indicating a similar capacity assays, there to confirm experimental findings. The strength as reducing agents.'* This led us to test a number of test procedures 102

Chemistry in New Zealand July 2010

ABTSassay has thus been adapted for use with conduct-

ing polymer powdersin a 3 hourtest procedure.Like- 3.0 -@- Control wise, the ORAC “assay has been adapted for use with —O- PPy (as-prepared) conducting polymer-containing films.** With these test —¥- PPy (reduced) nm 25, procedures in place, it has been possible to assess the radical scavenging efficiency of different conducting 516 2.0 polymers. In their as-prepared, partially oxidised forms, at polypyrrole and polyaniline showed moreeffective radi- a cal scavenging than PEDOT,both on a massbasis, and in the number of monomerunits required to scavenge each

free radical (Table 1). Similar results were obtained us- Absorbance 0.5 ing both DPPH and ABTSassays,although the polymers

0.0 were able to scavenge more DPPH than ABTSradicals. QO 5 10 15 20 25 This trend was observed despite that fact that the ABTS Time (hr) radical is a stronger oxidizing agent than the DPPHradi- « cal, suggesting that further properties are at work in de- Fig. 1. Decline in the 516 nmabsorbance of a 225 iM metha- nolic solution of DPPH radicals with 1.0 mg of PPy powders termining the extent of radical scavenging than oxidation added. strength alone.** Table 1. Comparison of DPPH’ and ABTS”scavenging activity of the as-prepared conducting polymers, expressed as the ratio of the number of monomerunits required per free radical scay- enged.”

PPy PANI PEDOT

ABTS** 6:1 4:1 Fl

DPPH’ 3:1 ve 8:1

“Data taken fromref. 24 It was further established that pre-reduced forms of the conducting polymer powders, obtained by reduction with hydrazine, were even more effective free-radical scaven- gers than the as-prepared partially oxidised forms (Fig. Fig. 2. SEM imageofpolyaniline nanotubes from oxidation of 1), consistent with the expected redox interaction in- aniline by ammoniumpersulfate in the absenceofstrong acids volved.*”° The available surface area is also expected to (500 nm scale bar). be important in determining the extent of radical scaveng-

ing: PANI nanofibres of decreasing average diameter have been shownto exhibit a greater radical scavenging ability 3.0 —@- Control ~O- PEDOT in the DPPH assay.” The enhanced antioxidant activity a —¥— PANI(acid) nm ~e —d\— PANI(no acid) wasattributed to the increased surface area of the PANI nanofibres, a result obtained in a further study on PANI 516 nanofibres.** We have also found that PANI prepared at conventionally in the presence of a strong acid such as sulfuric acid, consisting of granular PANIparticles, was less effective than PANI prepared without added acid,

in which high surface area nanotubes are formed (Fig. Absorbance 2). This was seen in the DPPH assay (Fig. 3), and in the

ABTSassay.™ That said, the higher scavenging of DPPH 0 5 10 15. 20 25 radicals of the nanotube form may be related as much to Time (hr) the initial oxidation state of the PANI products, as to the surface area of the different polymer forms. Fig. 3. Decline in the 516 nm absorbance of a 225 1M methano- lic solution of DPPHradicals with 1.0 mg of PANI and PEDOT Conducting Polymer Blends powders added. Conducting polymers on their own are not immediately suitable as a plastic packaging materials, as they lack the Polyaniline has been blended with ethyl cellulose (EC) necessary mechanicalproperties. Forming blends between via dispersion in ethanol prior to casting and solvent re- conducting polymers and food-grade plastics is the next moval to produce PANI/EC films. The ORAC assay was step to consider, with the aim of retaining the mechanical readily applied to the films, and it was found that the properties of the packaging material and the radical scav- greater the size of the PANI/EC film present, the more enging activity of the conducting polymer. Blends be- effectively it competed with fluorescein for the peroxyl tween conducting polymers and both ethyl cellulose and radicals, leading to a longer delay in fluorescence decay polyethylene have been developed at the University of and correspondingly larger ORAC area (Fig. 4). Once Auckland and form thebasis of a provisional patent.*>”° again, films containing reduced PANI were more effec- 103

Chemistry in New Zealand July 2010

tive radical scavengers. In eachcase, the results indicated provided that high molecular weight conducting polymers that active conducting polymer wasavailable to the test are used and smaller oligomeric units are removed prior solution and wasnot completely blocked by the presence to blending. of ethyl cellulose, even thoughthefilms themselves had very low conductivity values. To extend the test proce- dures to a real food sample,fish oils were subject to accel- erated degradation at 60 °C in the presenceofair, leading to considerable oil oxidation and the build up of perox- ides. PANI/EC films were able to slow downthe rate of oxidation to a measureable extent, although the benefit was onlyslightly better with a film containing 20% PANI comparedto one prepared with 10% PANI(Fig. 5). 30 Polyethylene: Polyethylene with 12% PANI

25 Fig. 6. Photograph of two polyethylene pressed disks (11 cm diam.); that at right contains 12% PANIby weight. 20 Final Remarks 15 area Conducting polymers have been shownto be effective

ORAC 10 free radical scavengers,related to their ability to be oxi- dised in a similar potential range to small molecule anti- oxidants. Several conventional food science radical scav- enging, assays and accelerated storage procedures have

0 20 40 60 80 100 been adaptedto solid conducting polymersto evaluate the Area (mm’) of PANI/ECfilm effectivenessof different samples and preparations. At the same time, the applied test assays can be considered as a Fig. 4. ‘Response of PANI/ethyl cellulose films in the ORAC useful meansofassessing the available redox activity of antiradical assay. conducting polymers whenpresentin blendsor as surface coatings. This provides important information on surface

300 properties that can complement conductivity measure-

= ° —O- Control ments,in particular. BP 250+ Film with 10% PANI = LE Film with 20% PANI The prospects for active packaging involving conducting

iB 200 polymers remain very promising where the effects of a &—E solid antioxidant material can be used to extend product @ 150 shelf-life. The radical scavenging property of conducting =o polymersalso needsto be kept in mind whenvarious bio- > 100 ® medical applications are being developed, e.g. in nerve 2 regeneration, woundhealing andartificial muscles. This 23 50 o is because the scavenging of free radicals mayassist in a 0 0 2 4 6 8 10 loweringlevels of oxidativestress in the tissues and fluids in immediate contact with the conducting polymer. Time (days) Acknowledgements Fig.5. Accelerated stability test on a fish oil using PANI/ethyl Researchinto conducting polymersas antioxidants has involved cellulose films; 60 °C with exposureto the air (7 = 3). several projects over the past seven years. | am grateful to my collaborators Drs Allan Easteal and Jadranka Travas-Sejdic, Ethyl cellulose is an interesting cellulose derivative that and Profs. Graham Bowmaker and Ralph Cooney. The research can be used asa thin-film coating material, but the thermo- studies of Drs. Marija Gizdavic-Nikolaidis, Chyong Fang plastic polymer polyethylene (PE) is much more widely Hsu, Zoran Zujovic, Hui Peng and Lijuan Zhang, and Corrina applied, with an annual production of around 80 million Thompson, Richard Delgenes, Cedric Basle and Ashveen Nand tons world-wide. Blending of PANI and PE hasalso been haveled to the results described herein. achieved through compression moulding at 180 °C. With the inclusion of 12% PANI(Fig. 6), very good mechani- References cal properties of the PE were retained and effective radi- 1. Giovanelli, G.; Brenna, O. V. Eur, Food Res. Technol. 2007, 226, cal scavenging again established. Like the famous Ford 169-179. Model T motorcar, these films are currently available in 2. Kane-Maguire, L. A. P.; Wallace, G. G. Synth. Met. 2001, 119, 39- any colour, as long asit is black! Through the inclusion 42. of a polymeric antioxidant in the blend, rather than small 3. Pernaut, J.-M.; Reynolds, J. R. J. Phys. Chem. B 2000, 104, 4080- molecule antioxidants, the issue of the leaching of the 4090, antioxidant out into the packaged product is minimised, 4. Schmidt, C. E.; Shastri, V. R.; Vacanti, J. P.; Langer, R. Proc. Natl. Acad. Sci. USA 1997, 94, 8948-8953.

104 Chemistry in New Zealand July 2010

Jiang, X.; Marois,Y.; Traore, A.; Tessier, D., et al. Tissue Eng. 2002, 18. Gizdavic-Nikolaidis, M.; Travas-Sejdic, J.; Bowmaker, G. A.; 8, 635-47. Cooney, R.P., ef al. CurrAppl.Phys. 2004, 4, 347-350.

Ramanaviciene, A’;Kausaite, A.; Tautkus, S.; Ramanavicius, A. J. 19, Gizdavic-Nikolaidis, M.; Travas-Sejdic, J.; Bowmaker, G. A.; Pharm. Pharmacol. 2007, 59, 311-315. Cooney, R. P.; Kilmartin, P. A. Synth. Met. 2004, 140, 225-232.

Wang, X.; Gu, X.; Yuan, C.; Chen,S., ef al. J. Biomed. Mater: Res. 20. De Beer, D.; Harbertson,J. F.; Kilmartin, P. A.; Roginsky, V.; Bar- A 2004, 684, 411-422. sukova,T, ef al. Am. J. Enol. Vitic. 2004, 55, 389-400.

Gilmore, K. J.; Kita, M.; Han, Y.; Gelmi, A., eal. Biomaterials 21. Kilmartin, P. A.; Gizdavic-Nikolaidis, M.; Zujovic, Z.; Travas-Se- 2009, 30, 5292-5304. jdic,J., etal. Synth. Met. 2005, 153, 153-156.

Bachmeier, B.; Nerlich, A.; Iancu, C.; Cilli, M., et al. Cell. Physiol. 22. Zujovic, Z. D.; Gizdavic-Nikolaidis, M. R.; Kilmartin, P. A.; Idriss, Biochem. 2007, 19, 137-152. H., et al. Polymer 2006, 47, 1166-1171.

10. Mollaoglu, H.; Gokcimen, A.; Ozguner, F.; Oktem,F., ef al. Toxicol- 23. Hsu,C. F.; Zhang, L.; Peng, H.; Travas-Sejdic, J.; Kilmartin, P. A. ogy 2006, 227, 15-20. Synth, Met. 2008, 158, 946-952.

- Wong,S. P.; Leong, L. P.; Koh, J. H. W. Food Chem. 2006, 99, 775- 24. Hsu, C. F.; Peng, H.; Basle, C.; Travas-Sejdic, J.; Kilmartin, P. A. 783. Polym. Int. 2010,in press. . Huang, D.; Ou, B.; Prior, R. L. J. Agric. Food Chem. 2005, 53, 25. Hsu, C. F. Developmentof conducting polymer-based antioxidant 1841-1856. packaging materials PhD, Thesis, University ofAuckland, 2009.

. Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A., ef al. Free Radi- 26. Hsu, C. F.; Peng, H.; Zhang, L.; Travas-Sejdic, J.; Kilmartin, P. A. cal Biol. Med. 1999, 26, 1231-1237. e-J. Surf. Sci. Nanotech. 2009, 7, 269-272.

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105 Chemistry in New Zealand July 2010

The Mechanism of Mutation Initiated by One-Electron Oxidation Johannes Reynisson Department of Chemistry & Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland (e-mail: [email protected])

Introduction After departure of the proton from the N1-site, it becomes a hydrogen bondacceptorinstead of a hydrogen bond do- The aqueous redox chemistry of the nucleosides and nor. The question emerged as to whether this event leads nucleotides has beenextensively investigated for the last to a change in the pairing ability of the G moiety with 40 years using pulse radiolysis, laser photolysis, electron other bases.'° In fact, it is a common view that ligand hy- spin resonance, andother time resolved and steady state drophobicity gives affinity, whereas hydrogen bonding techniques.' More recently, theoreticalmethods have been gives specificity for interactions in biochemical systems.” employedin the study of redox damage of DNA.’ This in- Simulating one-electron oxidation and the consequent de- tensive interest in the components of DNAis understand- protonation of the central Nl-proton for G-C using den- able sinceit carries our genetic code and, if damaged, can sity functional theory (DFT),”! a new slipped configura- lead to mutations possibly resulting in cancer.?? Further- tion of the base pair was formed as depicted in Fig. 2."” more, oxidative damage of DNAis implicated in aging* This slipped configuration, G(-H)'-C, was later indepen- and drugresistance of bacteria.* It is now understood that dently derived by Bera ef a/. using a systematic search DNAdamageinitiated by ionising radiationelicits a com- for all possible hydrogen bonding configurations between plicated set of events engaging varioussignalling path- G(-H)'and C.” The predicted base pairing energy (BPE) waysin cells.° is —18.2 kcal/mol for G(-H)—C.'°It lies between the Deprotonation Alters Hydrogen Bonding BPE’s of the adenine-thymine base pair (A—T) at —13.0 kcal/mol and of G-C of -21.0 kcal/mol.**?* Capabilities S Interestingly, it has been found that when organic mol- i 6 rane> ecules are one-electron oxidized in the aqueous phase, a 7ai IH 7 NW NH rapid deprotonation occurs from hydrogen bond donors, NEAH”" Oxidation | undoubtedly driven by the massive solvation energy of Kell/ iyaw haya“O the proton (AG,, = —263.9 kcal/mol). ” Thus, the pK, of H 4 2 cytosine (C) is lowered from 12.15 to lie between 2 and BPE= -21.0 kcal/mol pa 408 Kealirios 4 when is one-electron oxidised.*!""' With respect to G-c Gt DNA,guanine (G) is its most easily oxidized compo- napa nent!? and when double stranded DNA’s m-stack loses an electron, the positive charge migrates to G-C rich areas in H N the double strand.'*'° The pK,ofG is loweredsignificant- ly from 9.4 to 3.9 at the nitrogen-1 atom (N1) as depicted in Fig, 1.10718

me) bond donor BPE = -18.2 kcal/mol

O° G(-H) -C

N i € Fig. 2. Deprotonation-induced structural change of the G-C 8

is unlikely since it takes place on the milli-to-micro sec- be —10.4 kcal/mol for G(—H)~T, which is comparable ondtime scale andit is in competition with further charge to the A-T base pairing energy (—13.0 kcal/mol).?475?%35 migration in the DNAhelix and/or with water addition to The relatively low energy can be explained in terms of C8 of G*. The rates of these processes are estimated as the non-planarity of the bases with respect to each other. 5x107/s and 6x10*/s, respectively, i.e. in the micro—nano- From the calculations, they appear to be ca. 25° out of second timescale.'*’* Furthermore, the BPE of G*—C is plane, measured attheir carbonyl groups O° (G) and O* increased to -40.9 kcal/mol compared to —21.0 kcal/mol (T). The distance between these oxygen atomsis 3.5 A,a of its parent pair inhibiting the frequency of the breath- proximity which leads to Coulombic repulsion and hence ing motionsofthe base pair.**°“° Second, when duplica- the non-planar conformation. The calculated hydrogen tion of DNAoccurs, the DNAstrand is untwisted and the bonding energy of G(-H)—Abasepair is -13.6 kcal/mol, hydrogen bonds between the bases are broken to allow as shownin Fig. 4. This binding is somewhat stronger the duplication of the strand. Third, the H-bonds may be than for the natural A-T pairing (—13.0 kcal/mol).7475945 broken during DNAtranscription to messenger RNA as this proceeds in a mannersimilar to the duplication of The hydrogen bond energy of G(-H)-G(see Fig. 4) is DNA.Also,it has been suggested that deprotonation oc- similar to that of G-C.*° This is not surprising because curs from the exocyclic amine group of C in G*—C,based three hydrogen bonds are present in both structures. A on pulse-radiolysis and kinetic isotope experiments.*!* second type of a G-G basepair is conceivable between The proposed deprotonation mechanism is shownin Fig. two G(-H)' moieties [G(—-H)—G(-H)’], as shownin Fig. 3. This reaction cascade can lead to the G(-H)—-Cslipped 4. Forthis, the hydrogen bond energy is —18.5 kcal/mol, configuration.** somewhat lower than for G( H)—G sinceit has oneless hydrogen bond. Pt(II) electrophile coordinates at N7 of G. Deprotonatedto the aqueous phase ra This acidifies the N1 proton, akin to what happens during the oxidation of G. With these Pt-G species, structures ey similar to G(—H)—G and G(-H)—G(-H)’ were observed Q ne “arib by 'H-NMRandX-raycrystallography,*” thus providing et experimental evidencefor their existence. ribs Fig. 3. Possible mechanism involving the exocyclic amine Oxidation During DNA Duplication moiety of C as proton donorofthe one-electron oxidized base Usingin situ photolysis electron paramagnetic resonance pair; the initial charge sits on G in the complementary strand; (EPR), Hildenbrand and Schulte-Frohlinde detected a spin-charge separation between G and C plays a crucialrole in long-lived radical (lifetime ~5 s) that was produced only the reaction cascade and the depicted deprotonationcan lead to from double stranded DNA whenionised with < 220 nm the formation of G(—H)—C -seeref. 34. light in an aqueoussolution at pH ~7.** This radical was assigned to G(-H)’. The rate of DNA duplication was Base Pairing of the Deprotonated Guanine measured to lie between 5 and 500 nucleotides per sec- Radical ond depending on thecell type, the species and other fac- A related question emerged as to whetherit is possible to tors.*°° Considering the long lifetime of G(-HYin double pair T, A and itself to G(-H)’. This wasinvestigated stranded DNA andthe rapid DNA duplication rate, the using the DFT method and the results are presented in scenario emerges that in case of one-electron oxidation Fig. 4." during mitosis-/-meiosis G(—H)’ is formed when the two strands unwind. As shownin Fig. 4, base pairs can form H NZNON with all of the nucleotides with binding energies similar o UN NH etl rT L >? to the classical A-T and G—C Watson-Crick base pairs. a rand* low N This means that G(—-H)’ doesnothavespecific affinity for GAH CAN t knNv oi No SN N7 H N° ON C, i.e, it is completely promiscuous whenit comesto base H H pairing. Therefore G(—H)' canpair with all of the nucleo- BPE = -10.4 kcal/mol BPE= -25.1 kcal/mol tides and lead to mispairing. A depiction of this scenario G(-H) -T G(-H)-G is presented graphically in Fig. 5.

The mechanism presented here is new andprovidesanal- ; . walt? Ms ‘ ternative to the scenario that mispairing of the DNA bases enra wy “ne is mostly caused by oxidative end products such as 7,8- dihydro-8-oxoguanine (8-OG). These products are closed BPE = -13.6okealine BPE = 48.5 kcal/mol shell, i.e, they are not radical species and, therefore, have G(-H)-A G(-H) - G(-HY muchlonger lifetimes than G(—H)’. Redox product 80G Fig. 4. The unnatural base pairs between G(—H)' and the other is one of many derived from DNAone-electron oxidation bases — see ref. 19 The substantial base pairing energy (BPE) and subsequentwateraddition to G.'”'*“! [t can form syn- for the non-classical complexes depicted leads to the conclusion anti base pairs® with all of the nucleotides and these have that G(—H)' does not have anyspecificity for C. base pairing energies of ~ —10 kcal/mol.’ The 80G—-A base pair is depicted in Fig. 6 as an example of syn-anti Armed with the knowledge of the G(—-H)-C base pair basepairs. with only two hydrogen bonds, G(—H)’ waspaired to T and structurally optimized. The BPE wascalculated to 107

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Chemistry in New Zealand July 2010

Steenken, S. Chem. Rev. 1989, 89, 503-520. Steenken, S. Free Rad, Res. Comms. 1992, 16, 349-379. J. Tissandier, M. D.; Cowen,K.A.; Feng, W. Y.; Gundlach,E., er al. Oxdative Chem. A 1998, 102, 77187-1794. Event Phys. |. Dean, J. A. Lange s Handbook of Chemistry, McGraw-Hill: New York, 1985. Migration to G-C pairs . Geimer, J.; Hildenbrand, K.; Naumov, S.; Beckert, D. Phys. Chem. + Chargedregion Chem. Phys. 2000, 2, 4199-4206. _ Steenken, S.; Jovanovic, S. V. J. Am. Chem. Soc. 1997, 119, 617- 618. |. Steenken, S. Biol. Chem. 1997, 378, 1293-1297. . Schuster, G. B. Ace. Chem. Res. 2000, 33, 253-260. . Giese, B. Ace. Chem. Res. 2000, 33, 631-636. . Giese, B.; Spichty, M. Chem. Phys. Chem. 2000, 1, 195-198. . Reynisson,J.; Steenken, S. Phys. Chem. Chem. Phys. 2002, 4, 527- $32. |. Candeias, L. P.; Steenken, S. J. Am. Chem, Soc. 1989, 111, 1094- 1099. . Reynisson, J.; Steenken, S. Phys. Chem. Chem. Phys. 2002, 4, Old New 5346-5352. Structure and Mechanism in Protein Science, W.H. unwind, each _ Fersht, A.R. Fig. 5. As the two strands of the double helix Freeman & Co.: NewYork, 1999. with the appropriate bases to form a new double helix. pairs up . Koch, W.; Holthausen, M. C. A Chemist's Guide to Density Func- are identical to each other and to the origi- Thetwo new helices tional Theory, Wiley-VCH: Weinheim, 1999. nal. This process is compromised by one-electron oxidation of Bera, P. P.; Schaefer, H. F. III. Proc. Nat. Acad. Sci, USA 2005, 102, from G* and the subsequent 22. the m-DNA stack, deprotonation 6698*6703. of G(-HYthat is promiscuousin regard to base pair- formation . This is the energy contained in the hydrogen bonds between the ing. bases. 24. Yanson, I. K.; Teplitsky, A. B.; Sukhodub, L. F. Biopolymers 1979, 18, 1149-1170. . Sukhodub, L. F. Chem. Rev. 1987, 87, 589-606. . Bouvier, B.; Grubmilller, H. Biophys. J. 2007, 93, 770-786. 489- . Priyakumar, U. D.; MeKerell, A. D. Jr. Chem. Rev. 2006, 106, 505. Res. 28. Lewis, F. D.; Letsinger, R. L.; Wasielewski, M. R. Acc. Chem. BPE = -10.8 kcal/mol 2001, 34, 150-170. 80G-A 29. Colson, A. O.; Besler, B.; Sevilla, M. D. J. Phys. Chem. 1992, 96, Fig. 6. The syn-anti base pair of 80G-A; BPE = Base Pairing 9787-9794. Energy. 30. Hutter, M.; Clark, T. J. Am. Chem. Soc. 1996, 118, 7574-7577. Si. Kobayashi, K.; Tagawa, S. J. Am. Chem. Soc. 2003, 125, 10213- Conclusions 10218. . Kobayashi, K.; Yamagami, R.; Tagawa,S. J. Phys. Chem. B 2008, In this review,an alternative mechanism for promiscuous 112, 10752-10757. base pairing during DNA duplication initiated by one- _ Anderson, R.F.; Shinde, $.S.; Maroz, A. J. Am. Chem. Sac. 2006, electron oxidation is proposed based on theoretical calcu- 128, 15966-15967. /2, in lations. Some experimental results that support the exis- _ Steenken, S.; Reynisson, J. Phys. Chem. Chem. Phys. 2010, tence of the non-classical base pairs discussed exists, i.e. press. Mejzlik, P.: Vondrasek, J. J. for the slipped G(-H)—C and the G(-H)-G base pairs. . Hobza, P.; Kabelic, M.; Sponer, J.; Comp. Chem. 1997, 18, 1136-1150. Further experimental and theoretical work is needed to and theoretically derived values of the base pair- the mechanism proposed. In particular, ex- . The experimental corroborate ing energy of G-C differ by ca.4 kcal/mol. This difference is most resolved resonance Ra- periments conducted with time likely due to the experimental setup, which is unable to discern manspectroscopy on model DNA. duplication systems are between classical Watson-Crick base pairs and non-classical ones pertinent. , —see ref.19 Chem. 3h. Schréder, G.; Lippert, B.; Sabat, M.; Lock, C. J. L. et al. J. References & Notes Soc. Dalton Trans. 1995, 3767-3775. D. Free Rad. Res. Com. 1990, 1. von Sonntag, C. Free-Radical-Induced DNA Damage and Its Re- 38. Hildenbrand, K.; Schulte-Frohlinde, pair. A Chemical Perspective, Springer-Verlag: Berlin Heidelberg, 11, 195-206. 2006. 39. Klemperer, N.; Zhang, D.; Skangalis, M.; O’Donnell, M. J. Biol. Chem.2000, 275, 26136-26143. 2. Cooke, M. S.; Evans, M. D.; Dizdaroglu, M.; Lunec,J. FASEB 2003, 17, 1195-1214. 40. Podust, V. N.; Podust, L. M.; Miiller, F.; Hiibscher, U. Biochemistry Arlt, V. M. Mutagenesis 2005, 20, 399-410. 1995, 34, 5003-5010. Merry, B. J. Aging Cell 2004,3, 7-12. 41. Burrows, C. J.; Muller, J. G. Chem. Rev. 1998, 98, 1109-1151. C.; Kadlubar, F. F.; Evans F. E. Chem. Res. Kohanski, M. A.; DePristo, M.A.; Collins,J. J. Mol. Cell 2010, 37, . Culp, S. J.; Bongsup,P. 311-320. Tox. 1989, 2, 416-422. S. J. Mol. Struc. (Theochem) 2005, 723, 6. Darzynkiewicz, Z.; Traganos, F.; Wlodkowic, D. Eur J. Pharm. 43. Reynisson, J.; Steenken, 2009, 625, 143-150. 29-36. 108

Chemistry in New Zealand July 2010

On the Origin of the Dimeric Aplysinopsin Alkaloids Emily M. Boyd and Jonathan Sperry*

Department of Chemistry, University of Auckland, 23 Symonds Street, Auckland (e-mail: [email protected])

Introduction was shownthat 1 existed as a mixture of double bond iso- The aplysinopsins comprise a group of compoundsisolat- mers (~ 9:1) ofwhich the major isomeris the (Z)-isomer.? ed from marine sources and are unusual in that they con- Theisolation report also confirmedthe structure of 1 by tain a series of dimers of unexplained biogenetic origin. synthesis. Condensation of indole-3-carbaldehyde with a These dimers have long been thought to arise from the creatinine derivative gave rise to 1 identical in every re- Diels-Alder cycloaddition between two monomers with spectto the natural material.! one acting as the diene and the other as the dienophile. Me oO However, recent findings have evoked a possible second a Nis 8 $Me biosynthetic pathway whereby the dimers are formed by \ I NS the rearrangement of a corresponding dimeric cyclobu- \ WW mg > NH tane aplysinopsin. A chronological history ofthis fasci- "6 1 4 @ nating classofalkaloidsis discussed herein.

Monomeric Aplysinopsins The years following Wells’ initial report saw the isolation of several more aplysinopsin-type secondary metabolites In 1977, Wells and co-workers isolated two novel tryp- (Table 1) and in the latter part of 1977, 1 was isolated tophan-based secondary metabolites from the sponges from the sponge Verongia spengelii.’ In 1980, an extract Thorecta sp. collected from the Australian Great Barrier of the sponge Dercitus sp. from Belize was also shown Reef.' These natural products were subsequently named to contain 1, along with minor amounts of 3 and 4 (Table aplysinopsin (1) and 3’-deimino-3’-oxoaplysinopsin (2) 1).3 In late 1980, analysis of the extracts of the Caribbean that occur as (£)- and (Z)-isomers (below andTable 1),.! It sponge Smenospongia aurea afforded the novel 6-bromo-

Table 1. The family of monomeric aplysinopsins Rt ° 7 E 2. x2 3 A (NEN 6 Vat wk \ De x er nn OO CORP N Ri’ Y HH (© @

No. Natural Product R' R Y E/Z ratio Ref. E/Z ratio

1 aplysinopsin Me Me H NH > 95:5 10

2 3’-deimino-3’-oxo- Me Me oO > 95:5 10 aplysinopsin

3 2’-de-N-methyl- H Me H NH = 595 10 aplysinopsin

4 6-bromo-2’-de-N- H Me Br NH <5:95 10 methylaplysinopsin

5 6-bromo-3’-deimino- H H Br oO 1:1 9 2’ 4’-bis(demethyl)-3- oxoaplysinopsin

6 N-methylaplysinopsin Me Me H NMe High E 5

7 6-bromoaplysinopsin Me Me Br NH 100% E 5

8 6-bromo-3’-deimino- Me Me Br oO 5:2: 9 3’-oxoaplysinopsin

9 3’-deimino-2’,4’- H H H oO <5:95 10 bis(de-methyl)-3’- oxoaplysinopsin

10 2’-demethyl-3°-N-methyl- H Me H NMe <5:95 10 aplysinopsin

i 6-bromo-2’-demethyl- H Me Br NMe <5:95 10 3°-N-methylaplysinopsin

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Chemistry in New Zealand July 2010

3°-deimino derivative 5* and, in 1981, the N-methyl 6 oss wasisolated from Aplysinopsis recticulata.’ Interestingly, various monomeric aplysinopsins have also been found in several scleractinian corals of the family Dendrophyl- acesI liidae. In 1982, the extracts of Tubastraea coccinea re- vealed the presence of3 and 4, as well as the new natural product 6-bromoaplysinopsin (7).° Aplysinopsins 1 and 7 15, R'= H syetencipeetogain A have been found in Astroides calycularis,’ and 1 also from 16,R'= OH cycloaplysinopsin B Tubastraea aurea.’ In 1988, two novel 3’-oxoaplysinop- sins were identified from two separate corals.” Thus, ex- tracts of Tubastraea sp. contained 2 and the novel oxoap- lysinopsin 8, with the extracts of Leptopsammia pruvoti containing both the bis(demethyl)-3’-oxoaplysinopsin 5 and the novel bis(demethyl)-3’-oxoaplysinopsin 9. A year later, two further analogues [2’-demethyl-3’-N-methyl- aplysinopsin (10) and its 6-bromo derivative (11)] were 12,X= ; R? = Br, R4= R°= Me tubastrindole A

isolated from Dendrophyllia sp. along with 3 and 4.'° In 13, = = R°= Me tubastrindole B a series of importantfindings, it was subsequently shown 14, X = NH; Y R= H; R¢= R®= Me tubastrindole C 47, X= NH; Y =0; = R?=H; R? = Br; R4= a= Me tubastrindole D that various aplysinopsins undergo a thermally-reversible 18, X= NH; Y= OR= OH; R?= R? =H; R4= R°= Me tubastrindole E photoisomerization.’ An instructive review regarding the R® = Br, R*= R® = Me tubastrindole F synthetic efforts towards this monomeric class of natural 20,X=0;Y== NH: R' = R2= R39 =H; R= R°= Me tubastrindole G productsis available." : = R° =H; R*=R®°= Me tubastrindole H = R® = Br; R*=R° = Me dictazoline A The Dimeric Aplysinopsins =H dictazoline B In 2000,the aplysinopsin story acquired a new dimension whenit was reported that an extract of the coral Tubas- traea faulkneri contained a dimer of 4. This dimer was identified from the extract using spectral and melting point analyses, but the only spectroscopic information re- ported was the molecular weight.'? It took a further three 24, cycloaplysinopsin C years before a fully characterized aplysinopsin dimer ap- peared. Fig. 1. Dimeric aplysinopsins and key nOecorrelations.

Thus, the first fully characterized dimeric aplysinopsins Dimeric Aplysinopsins: Diels-Alder were reported in 2003. Extracts of Tubastraea sp. contained Cycloadducts? the cyclohexenyl tubastrindoles A-C (12-14; Fig.1), along with aplysinopsin 1'° Around the sametime, extracts oftwo When considering the biosynthetic origin of the cyclo- corals afforded cycloaplysinopsin A (15), smaller amounts hexenyl aplysinopsin dimers,their structural similarity to of B (16) and the known monomers2 and 8.'* Interestingly, the monomeric aplysinopsinsis striking. Alas, in the vast detailed 2-D NMRstudies conducted by separate groups majority of cases, the dimeric aplysinopsin is co-isolated confirmed that the tubastrindoles A-C (12-14) and 15 and from the same host organism along with its respective 16 possess differentrelative stereochemistry (Fig. 1). Fur- monomer, suggesting that the monomeric aplysinopsins ther investigation of the extracts of Tubastraea aurea in are related to the dimers.'*!4 To investigate this possible 2008led to the discovery of five further tubastrindoles D-H relationship, Mancini and co-workersinstigated an inves- (17-21) that had the same relative stereochemistry as pre- tigation involving 2 and its dimeric partner, cycloaplysin- viously established 12-14.'° Thefirst dibrominated aplysin- opsin A (15), two natural products isolated from the same opsin dimers appeared whenanalysis of the extracts of the coral. This group showedthat subjecting synthetic 2 to sponge Smenospongia cerebriformis afforded dictazolines the exact conditions used during the extraction process A and B (22 and 23)'° along with the previously described did not result in the formation of 15. This suggests that tubastrindoles 12 and 13. Subsequently, dictazolines A and cycloaplysinopsin A (15) is not an artefactofthe isolation B were shownto have the samerelative stereochemistry procedure and is indeeda natural productin its own right as all the previously isolated tubastrindoles.'*'° In 2009 (Scheme1). the isolation of a novel aplysinopsin dimer took the total numberof distinct diastereomer classes to three whenit Me o-SS.0 was shownthat the extracts of the sponge Tubastraea sp. (collected in Yemen) yielded cycloaplysinopsin C (24). TWeS NMeruin, Diels-Alderey Detailed 2-D NMR studies confirmed that 24 possesses Now NMe \ sy) -—%— - isolation " . different relative stereochemistry from both the previously Me ° conditions" o“Ay’So (612 described cycloaplysinopsins 15 and 16 (Class I) and the 15, cycloaplysinopsin A Me tubastrindoles and dictazolines 12-14, and 17-23 (ClassII) (Fig. 1)."7 Scheme1. Diels-Alder cycloaddition with two moleculesof (E)-2.

110

Chemistry in New Zealand July 2010

The observations regarding the biogenesis of the dimeric Diastere- Cycloadduct Diene/ aplysinopsins present a fascinating possibility omer (representative Dienophile that they class example) may,in fact, be cycloadducts of their respective aplysin- Me opsin monomers. Diels-Alder cycloaddition is a credible Oxy pathway for this dimerization, whereby the monomeric = NMe aplysinopsinis acting both as the diene and the dienophile QA ran RoxNo. SNMe NH in the [4+2] process (Scheme 1).'>"4 After dimerization, No further modifications Me occur in somecases, i.e. oxidation 15, cycloaplysinopsin A at C8 in the case of 16, 18 and 24. Me WhatPromotes the Dimerization? °. N. SeNH It is well established that cycloaplysinopsin 15 is not \ \ ti formed when subjecting the corresponding monomer, 2, HodN” os “NMe Ce to the extraction conditions. This implies that an external MeN NH entity associated with the host organismis aiding the di- 13, tubastrindole B merization in some way. Cycloaplysinopsins A-B (15 and 16) both possessa slight excess Me of one enantiomer (~30% Oot ee), suggesting HO,Y=NH that, if a Diels-Alderase is responsible,it NMe [~ is enantio-defective,'4 However, Mancini and co-workers Coe Wea " '\ = concludedthat owing to the ongoing controversy over en- Beadve NH Nog sl NOSNH zymesthat catalyze concerted cycloaddition processes, it 24, cycloaplysinopsin is morelikely that the host organism (or associated sym- C NH biont) contains an adventitious Diels-Alder catalyst that Fig. 2. Three diastereomerclasses could arise from different cycloaddition pairs. aids the dimerization. Moreover, the chiral environment (steroids and other common metabolites) appears respon- aplysinopsin dimers took another twist. Williams and sible for the slight asymmetric induction." Presumably co-workers reported the isolation of the three new dic- this postulate can be applied to other dimeric aplysin- tazolines C-E (25-27), along with the structurally unique opsins, as Iwigawa and co-workers also concluded that dictazoles A and B, 28 and 29, respectively,'® from the because of the small optical rotation values seen in the same extract of S. cerebriformis that had earlier afforded tubastrindoles,it is highly likely that they exist as a mix- dictazolines A and B (22 and 23)'6 (Fig. 3). Interestingly, ture of both enantiomers.'* However, further investigation the authors did not report the isolation of any monomeric into this proposalis hindered bythe fact that manyofthe aplysinopsins. isolation reports do not disclose the enantiomeric excess of the dimeric aplysinopsins. Nonetheless, the Diels-Al- 5 ii der cycloaddition proposaloffers potential insightinto the N different Os ):NH R? relative stereochemistry observed in the various NR dimeric compounds.It is possible that both (£)- and (Z)- R? \ anny ‘ No_- ~NMe aplysinopsins are viable substrates for the cycloaddition Rost NH Ne NH process and,as the vast majority of the monomeric aply- Sinopsins essentially exist as a single regioisomer (Table 22, R°= R? = Br, R4=R®= Me: dictazoline A 1), it is conceivable dictazoline B that photoisomerization?is pivotal for =H; dictazoline C the Diels-Alder reaction to proceed in some cases, Ac- 26, R?= Br; Ri R® = Me; dictazoline D 27, R? = R? = R4*=H; R5 = Me: dictazoline cordingly, the dimers can be grouped into three classes E and used to rationalize the relative stereochemistry ob- ro Neo served: Class I: (£)-diene and (£)-dienophile 15 and 16; Nn vA es SNH Class II: (Z)-diene and (£)-dienophile 12-14 and 17-23; NMe(NH “OS Br. o . ClassIII (Z)-diene and (Z)-dienophile 24 eo SSNMe ~SNMe (Fig. 2). | os At T o= N NH we ONWAY As showninFig. 2, it is assumed that during the cyclo- H Me 2 H Me Nie addition process, the diene and the dienophile are orien- 28, dictazole A 29, dictazole B tated as depicted. This is based on the orientation being Fig. 3. Dictazolines A-E and dictazoles A and B. the most favourable from MM calculations for (E)-2 di- Using Baran’s pioneering biomimetic total synthesis of ene and (£)-2 dienophile to give 15.'‘ However,it is also ageliferin from the cyclobutane sceptrin as a guide,'° the conceivable that 15 may be constructed from an anti ap- authors suggested that the dictazoles are possible pre- proachofa (Z)-2 diene and an (£)-2 dienophile. Alas,it cursors to the corresponding dictazolines. Specifically, is equally feasible that the three distinct classes of diaste- dictazole A (28) can be converted to dictazoline C (25) reomers could arise through the dimerization of (£)- and via the vinyleyclobutane rearrangement, as outlined (Z)-regioisomersin both syn andanti orientations. in Scheme2.'* Circumstantial evidence supporting this pro- Dictazoles and the Vinylcyclobutane posed pathwayis the relative abundanceofthese isolated compounds; the cyclobutane Rearrangement derivative 28 is isolated in significantly higher quantities than the cyclohexenyl ana- In early 2010, the proposed biosynthetic origins of the logue 25. as 111

Chemistry in New Zealand July 2010

[2+2]

retro [2+2]

eyelobuiane dictazole A (28) dimer

Vinyleyelobutane| Rearrangement Monomeri Vinylcyclobutane aplysinopsins rearrangement

4 ‘SNH Os NSSNs ATe sits “NH Br AT c " Retro Br VP ny AOHO ‘“ye Diels-Alder NO Me \\ ne AANH2 Diels-Alder MeN NH cyclohexenyl ' dimer Scheme4. Possible biosynthetic cycle. a Ma Concluding Remarks \Sa set > = Nate Thefascinating history of the aplysinopsin natural prod- ucts, fromits inception with the isolation of aplysinopsin in 1977 up until the appearance ofthe dictazoles in early dictazoline C (25) 2010 has been summarized. Upon considering the bio- Scheme2. Vincylcyclobutane rearrangement synthetic origin of the cyclohexenyl aplysinopsin dimers, both the Diels-Alder cycloaddition and the vinylcyclobu- An attempt to effect this rearrangement by heating an tane rearrangementproposals appear equally feasible. An aqueous solution of pure dictazole A (28) to 200 °C ina examination of both compelling biosynthetic pathways microwavereactor led to fascinating results. A significant through chemical synthesis is in progress in our labora- amount of dictazoline C (25) was detected by LC-MS tory andtheresults will be reported in due course. along with three monomeric aplysinopsins, presumably arising from a retro-Diels-Alder reaction of 25 (Scheme References 3). Disappointingly, owing to a scarcity of natural materi- 1. Kazlauskas, R.; Murphy, P. T.; Quinn, R. J.; Wells, R. J. Tetrahedron al, no products could be characterized by NMRnorcould Lett, 1977, 18, 61-63. the sxpeniments be repeated.'® 2. Hollenbeak, K. H.; Schmitz, F. J. Lloydia 1977, 40, 479-481. 3. Djura, P.; Faulkner, D. J. J. Org. Chem. 1980, 45, 735-737. 4. Djura, P.; Stierle, D. B.; Sullivan, B.; Faulkner, D. J. e¢ al. J. Org. Chem. 1980, 45, 1435-1441. 5. Taylor, K. M.; Baird-Lambert, J. A.; Davis, P. A.; Spence,I. Fed. Proc. oAaOpe9NMeoe LH 1981, 40, 15-20; Baird-Lambert, J.; Davis, P. A.; Taylor, K. M. Clin. Exp. Pharmacol. Physiol. 1982, 9, 203-212. 6. Okuda, R. K.; Klein, D.; Kinnel, R. B.; Li, M.; Sheuer, P. J. Pure Appl. ateneinia c Chem. 1982, 54, 1907-1914. (25) 7. Fattorusso, E.; Lanzotti, V.; Magno,S.; Novellino, E. J. Nat. Prod. 1985, Retro Diels-Alder 48, 924-927. 8. Fusetani, N.; Asano, M.; Matsunaga,S.; Hashimoto, K. Comp. Biochem. R! Physiol., Part B: Biochem. Mol. Biol. 1986, 85, 845-846. = ee) 9. Guella, G.; Mancini, I.; Zibrowius, H.; Pietra, F. Helv. Chim. Acta 1988, rx 4 NMe 71, 173-782. nv Oo H 10. Guella, G.; Mancini, I.; Zibrowius, H.; Pietra, F. Helv. Chim. Acta 1989, 2,X=H,R!=Me 72, 1444-1450. 8,X=Br,R'=Me 11. Stanovnik, B.; Svete, J. Mini Rev. Med, Chem. 2005, 2, 211-224. unnatural, X = Br, R! =H 12. Koh, E. G. L.; Sweatman, H. J. Exp. Mar. Bio. Ecol. 2000, 251, 141- Scheme3. Retro Diels-Alder fragmentation of dictazoline C 160. 13. Iwagawa,T.; Miyazaki, M.; Okamura, H.; Nakatani, M. ef al. Tetrahe- Thefindings of Williams and co-workers have led to even dronLett. 2003, 44, 2533-2535. more unanswered questions. Could the monomeric aply- 14. Mancini, I; Guella, G.; Zibrowius, H.; Pietra, F. Tetrahedron 2003, 59, sinopsins undergo conversion to the corresponding cy- 8757-8762. clobutane dimer in a [2+2]-process? Does the proposed 15. Iwagawa,T.; Miyazaki, M.; Yokogawa, Y.; Okamura, H. ef al. Hetero- vinyleyclobutane rearrangementto the cyclohexenyl di- evcles 2008, 75, 2023-2028. mer render the Diels-Alder proposal obsolete, or is there 16. Dai, J.; Jiménez,J. 1.; Kelly, M.; Barnes, S.; Lorenzo,P.; Williams,P. J. Nat. Prod, 2008, 71, 1287-1290. a biosynthetic cycle involved that incorporates more than 17. Meyer, M.; Delberghe,F.; Liron, F.; Guillaume, M.; Valentin, A.; Guyot, one defined pathway (Scheme 4)? Theresults from testing M. Nat. Prod. Res. 2009, 23, 178-182. the viability of these propositions with labelling studies 18. Dai, J.; Jiménez,J.; Kelly, M.; Williams, P. G. J. Org. Chem. 2010, 75, and chemical syntheses are eagerly awaited. 2399-2402. 19. Baran, P. S.; O'Malley, D. P.; Zografos, A. L. Angew. Chem. Int, Ed. 2004, 43, 2674-2677.

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Chemistry in New Zealand July 2010

Making Sense of N-Confused Porphyrins Anna Mtodzianowska and Penelope J. Brothers Department of Chemistry, University of Auckland, Private Bag 92019, Auckland 1124 (e-mail: [email protected])

Porphyrins (1, Chart 1) are organic molecules that act as and Latos-Grazynskiet al.’ in Poland. They discoveredthat macrocyclic ligands and are comprisedoffour pyrrole rings N-confused porphyrin is produced in very low yield (4-7 connected by methine bridges. They are most familiarly %) as a by-product in the pyrrole/aldehyde condensation knownasthe red pigmentin hemoglobin where they serve reaction used to form regular porphyrin. An optimized syn- as oxygencarriers. In this role, the porphyrin coordinates an thetic route subsequently was published by Lindsey.* iron atom inthe central cavity in place of the two internal N-boundprotons, and O,is bound to a vacantposition on N-confused porphyrin canexistas two tautomers, depending the iron. In the laboratory, tetra-arylporphyrins (1, Chart 1) on the solvent (Chart 2). Tautomer 2a, observed in dichlo- can be easily prepared by a self-assembly reaction involv- romethane, has three inner protons, two NH and one CH. ing condensation of four equivalents each of pyrrole and The second tautomer2b, which occurs in N,N-dimethylfor- an aldehyde (ArCHO) with subsequentoxidation to the 18 mamide, has one CH and one NH protoninside the macro- n-electron aromatic macrocycle. Synthetic modifications cycle and one NH proton located outside. These tautomers of porphyrin ligands for a range of different applications are readily distinguished bytheir significantly different UV- in catalysis, medicine, and materials science are well-es- visible and NMRspectra, as well as from the colours of the tablished, and most elements from the periodic table can compoundin different solvents.5 From experimental obser- be inserted into the porphyrins to form an ever-expanding vation, tautomer 2a wasfound to be the moststable andthis range of coordination complexes. Most modifications of the was confirmed by DFTstudies.*” porphyrin itself are concerned with different substituents at the meso-positions (those occupied by an aryl ring in 1) or Chart 2. Tautomeric forms of N-confused porphyrin. at the B-pyrrolic positions (occupied by H in the five-mem- bered rings of 1). However, over the last decade, interest in the special properties of porphyrin ligands has extended beyond these simple modifications to a growing family of porphyrinoid molecules, which share the essential features of porphyrin, namely pyrrole building blocks and an unsat- 2b urated macrocylic framework. This extended family com- prises expanded, contracted and isomeric porphyrins.It is The proton NMRspectrum of N-confused porphyrin 2 the last of these, structural isomersofthe familiar porphyrin is very different from that of regular porphyrin 1 that has ring,that are described below with a focus, in particular, on idealized D,, symmetry and so a very simple spectrum in the isomer of regular porphyrin known as the N-confiused porphyrins 2 (Chart 1). which, for example, the resonance for the eight B-pyrrole protons appearsas a singlet. N-confused porphyrin has no Chart 1. Porphyrin (1) and N-confused porphyrin(2). symmetry (C,), so that a uniquesignal is observed for each B-pyrrole proton and the inner CH and NH protons.

Depending upon which tautomeris involved in metal co- ordination, N-confused porphyrin can bea dianionicortri- anionic ligand and can form different types of metal com- plexes. Thefirst group of complexes comprises compounds containing a covalent M-C(21) bond betweenthe metal and the inner [C(21)] carbon,in which the V-confused porphyrin In N-confused porphyrin 2 the connectivity, and hence ori- is a dianion based on tautomer 2b and bears an external NH. entation of oneofthe pyrroleringsis different from porphy- For example, these types of metal complexesare observed rin itself. Normally, each pyrrole is connected into the mac- for all three of the group 10 metals Ni(II) 3d, Pd(II) 3e and rocycle through positions 2 and 5, whereas in N-confused Pt(II) 3f as well as a range of other main group and transi- porphyrin one pyrrole ring is, instead, connected through tion metal ions 3a-n as shown in Chart 3.*!7 The second positions 2 and 4. This small change causes oneofthe ni- class of complexesalso contains a covalent M-C(21) bond, trogen atomsto be located on the periphery ofthe macro- but the external nitrogen on the ligandis not protonated, and cycle and a carbonatom to be locatedinside. This has a big the ligand coordinatesas a trianion in the tautomer2a form, influence on the ligand properties, not surprising as instead e.g. Ag(III) 4a, Cu(II) 4b, as well as 4a-g in Chart 3.%!®!722 of the four N-donor atomsthat occur in porphyrin 1, the The third and fourth group of metal complexes contain an N-confused porphyrin 2 has three N-donors and a carbon agostic bond between M and H-C(21), in which C(21) re- available to coordinate to a central element. tains its H substituent and the metal centre interacts with the Thefirst example of an N-confused porphyrin (5,10,15,20- C-H bond,occurring in the 2a dianionic forms 5a-d,°'53 or tetraaryl-2-aza-2 1-carbaporphyrin, 2) was published simul- the 2b trianionic forms 6a-c,”*”° (Chart 3). taneously by two research groups, Furuta ef al.' in Japan

Tis

Chemistry in New Zealand July 2010

Chart 3. Metal complexes of N-confused porphyrin. kinds, and the isomeric analoguesare also being explored for these applications. Materials science applicationsutilize their strong light-absorbing properties and the N-confused and N-fused porphyrins add further members with differ- ent symmetries and electronic excited states to this family of chromophores. Last but notleast, they are adding to our fundamental knowledge of the chemistry of the porphyrin 3a: M=Co(ll),X=py, 3h: M=Nillll), X =Br 4a: M = Agilll) 4b: Cu(lll) coreitself, which despite being familiar and widely utilized NH=NCH2COsEt 3: M= Nill, Mnilll), X = py ; M= Cuil) 3j: M= Nill), Moilll), now hasstructural isomers established as an integral part of M= Ni(l) 3k M=Ni(ll), X=Y=CN af its chemistry, along with many new metal complexes.*! Pail!) 3m: = Sn(IV), X= Cl : till) 3n: M= Sb(V), X= Br M=Mn(), X= By N= References Furuta, H.; Asano, T.; Ogawa,T. J. Am.Chem.Soc. 1994, 116, 767-768. o L. Chmielewski, P. J.; Latos-Grazynski, L.; Rachlewicz, K.; Glowiak, T. N Angew. Chem.Int. Ed. Engl. 1994, 33, 779-781. Ghosh, A. Angew. Chem.Int. Ed. 2004, 43, 1918-1933. Geier, G. R., III; Haynes, D. M.; Lindsey, J. S. Org. Lett. 1999, 1, 1455- Sa: M = Cu(ll), X= Cl 6a: M= Mn(ll), L = py 1458. 5b: M Fe(ll), X= Br 6b: M= Ybilll), L= = 5c: M=Fe(\l), X = S-p-Tol Furuta, H.; Ishizuka, T.; Osuka, A.; Dejima, H., efal. J. Am. Chem. Soc. M=Mn(ll), X= Br (n°-CsH)Co[P(=0)(OMe)a] 2001, 123, 6207-6208. Sd: 6c: M= Er(lll), L= (n°-CgHs)Co[P(=0)(OMe)a} Szterenberg, L.; Latos-Grazynski, L. Inorg. Chem. 1997, 36, 6287- 6291. The examples given above primarily involve transition Ghosh, A.; Wondimagegn,T.; Nilsen, H. J. J. Phys. Chem. B 1998, 102, 10459-10467. metals as well as two examples each oflanthanides Yb and Er,56 and the heavier main group elements Sn and Sb.'*!7"? Qu, W.; Ding, T.; Cetin, J.; Harvey,J. D., e al. J. Org. Chem. 2006, 71, 811-814. The smaller, lighter main group elements boron and phos- 9. Chmielewski, P. J.; Latos-Grazynski, L.; Schmidt, I. Inorg. Chem. 2000, phorusyield further unusualstructural types of porphyrin- 39, 5475-5482. like complexes. The reaction of PhBCl, with N-confused Maeda, H.; Osuka, A.; Ishikawa,Y.; Aritome, I., ef al. Org. Lett. 2003, 5, porphyrin yields twotypes of monoboron complexes, 7 and 1293-1296. 8. Both of them have N-fused rather than N-confused por- . Maeda, H.; Ishikawa, Y.; Matsuda, T.; Osuka, A.; Furuta, H. J. Am. phyrin skeletons.”’ The V-fused porphyrin skeleton features Chem. Soc. 2003, 125, 11822-11823. onepyrrole a-carbon, which has bondsto two pyrrole nitro- . Chmielewski, P. J.; Latos-Grazynski, L. Jnorg. Chem. 1997, 36, 840- gens. The addition of PCI, to N-confused porphyrin yields 845. phosphorus(V) complex 9, also containing the N-fused por- Furuta, H.; Kubo, N.; Maeda, H.; Ishizuka, T., e¢ al. Inorg. Chem. 2000, 39, 5424-5425. phyrin skeleton.”* Compounds 7-9 have subtle differences, . Furuta, H.; Youfu, K.; Maeda, H.; Osuka, A. Angew. Chem. Int. Ed. includingtheir charge, and the ligands occur as monoanion, 2003, 42, 2186-2188. dianion andtrianion, respectively. The ligand in complex 7 . Bohle, D. : Chen, W.-C.; Hung, C.-H. /norg. Chem. 2002, 41, 3334- is a true N-fused porphyrin, which is two oxidation levels 3336. higher than a porphyrin. The ligands in 8 and 9 are tauto- . Xie, Y.; Morimoto,T.; Furuta, H. Angew. Chem.Int. Ed. 2006, 45, 6907- mers, but are formally at the same oxidation level as por- 6910. phyrin, which meansthey are further examplesofstructural Liu, J.-C.; Ishizuka, T.; Osuka, A.; Furuta, H. Chem. Commun. 2003, 1908-1909. isomers of porphyrin and N-confused porphyrin. . Furuta, H.; Ogawa,T.; Uwatoko, Y.; Araki, K. Inorg. Chem. 1999, 38, 2676-2682. Chart 4. Boron(II1) and phosphorus(V) complexes. . Furuta, H.; Morimoto, T.; Osuka, A. Org. Lett. 2003, 5, 1427-1430. . Harvey, J. D.; Ziegler, C. J. Chem. Commun, 2003, 2890-2891. . Harvey, J. D.; Shaw, J. L.; Herrick, R. S.; Ziegler, C. J. Chem. Commun. 2005, 4663-4665. . Ogawa, T.; Furuta, H.; Takahashi, M.; Morino, A.; Uno, H. J. Organo- metallic Chem. 2000, 611, 551-557. Chen, W.-C.; Hung, C.-H./norg. Chem. 2001, 40, 5070-5071. . Harvey, J. D.; Ziegler, C. J. Chem. Commun. 2002, 1942-1943.

Whatis the outlook for these new membersofthe porphyrin . Zhu, X.; Wong, W.-K.; Lo, W.-K.; Wong, W.-Y. Chem. Commun. 2005, family? In fact, they are notall that new as they comprise 1022-1024. by-products from porphyrin syntheses, but the recent focus . Wong, W.-K.; Zhu, X.; Wong, W.-Y. Coord. Chem. Rev. 2007, 251, on their chemistry has opened up some new possibilities. 2386-2399. Firstly, the notion ofa porphyrin isomer capable of forming Mlodzianowska, A.; Latos-Grazynski, L.; Szterenberg, L.; Stepiefi, M. a trianionic ligand has proved useful for stabilizing com- Inorg. Chem. 2007, 46, 6950-6957. plexesof transition metals in higher oxidation states and . Miodzianowska, A.; Latos-Grazynski, L.; Szterenberg, L. Jnorg. Chem. 2008, 47, 6364-6374. also in unusual coordination geometries.”*” Examples of 29. Chmielewski, P. J.; Latos-Grazyniski, L. Coord. Chem. Rev. 2005, 249, less commonhigh oxidation states stabilized by coordina- 2510-2533. tion to N-confused porphyrin are the Ni(II) 3h-l, Ag(III) 30. Harvey,J. D.; Ziegler, C. J. Coord. Chem. Rev. 2003, 247, 1-19. 4a and Cu(II) 4b complexeslisted in Chart 3.!°!*'*!? Por- 31. Srinivasan, A.; Furuta, H. Ace. Chem. Res. 2005, 38, 10-20. phyrins and their expanded and contracted isomers are being widely used in supramolecular architectures ofall

114

Chemistry in New Zealand July 2010

Compulsory Licensing in a Nutshell Tim Stirrup and Katherine Hebditch

BaldwinsIntellectual Property, PO Box 5999, Wellesley St, Auckland (email: [email protected] or katherine. [email protected])

It would seem inconceivable that a government or com- In the face of a growing incidence of HIV/AIDS,Thai- petitor could ride roughshod over your hard-earned patent land granted a compulsory licence for the anti-retroviral rights. Surely the right to exclusively exploit your inven- (ARV)Efavirenz in 2006. It is estimated that this decision tion is enshrined in law and international agreements? enabled the Thai government to save US$23 million per In exceptional circumstances this is exactly what can year over 5 years.! happen, and every major patent system in the world has provisions for the governmentor a court to intervene and Soonafter, Brazil followed suit by issuing a compulsory grant a competitor the right to use the invention without licence for the import of a generic version of Efavirenz the patentee’s permission. These are known as compul- fromIndia and in early 2010 Brazil started producing the sory licences and although the patent owner should still drug locally. The Brazilian decision cameafter rejecting receive royalty payments,they arestill a serious issue for Merck’s offer to lower the price from US$1.57 per dose patentees. While there may be a perception that the use of to US$1.10 per dose. Instead Brazil demanded a cost of compulsory licensing is the domain of left wing govern- US$0.65 per dose, which was the offer made to Thailand. ments sporting anti-capitalist, anti-imperialist ideologies Indian generics were available at US$0.43 so the decision this is not necessarily the case. to grant a compulsory licence was made andresulted in an estimated US$30 million saving to the Brazilian govern- Howarethey granted? mentin 2007.7 World Trade Organisation (WTO) agreements dictate that compulsory licences may be granted where an invention The repercussions of grant is not being made available to the market in a country Although the issuing government may save millions on on reasonable terms, or not being made availableatall. healthcare costs, the grant of a compulsory licence is of- Alternatively, they may be granted in cases of national ten an actionoflast resort which must be weighed against emergency orsituations of extremeurgency. the potential repercussions from trading partners and other countries. These repercussions can take the form Pharmaceuticals are most commonlyassociated with com- of increased trade barriers and diplomatic pressure from pulsory licensing provisions and have been the subject of governments and the pharmaceutical industry. Following a number of major cases in which negotiations over the the Thai decision to grant a compulsory licence the USA price of patented pharmaceuticals have broken down and apparently retaliated by adding Thailand to its Priority led to a compulsory licence being granted. Watch List and increasing import tariffs for a number of However, although many developing countries may have Thai exports to the USA.> public health emergenciesthat could justify the grant of a Retaliatory measures can seem hypocritical in the face compulsory licence, thereality is that they often lack the of similar actions being taken by those same governments. capability to manufacture high grade pharmaceuticals. In For example soon after the Anthrax scare in 2001 the recognition of this fact, the WTO declared in 2003 that threat of a compulsory licence being granted compulsory licences may be legitimately granted in de- in both Can- ada and the USA wasenoughto persuade veloped countries to respondto public health emergencies Bayerto reduce the price of the antibiotic Ciprofloxacin from $1.77 in designated countries, with a particular emphasis on the per tablet least developed countries of the world. to $0.95 and resulted in a saving to the US govern- mentofat least US$82 million.* Public health emergencies The USAhasalso granted whatare, effectively, compul- While a compulsory licence has never been granted in sory licences in numerousrulings. Since June 2006, the New Zealand, the emergency/urgencyprovisions were put courts have issued decisions that have benefitted Micro- into practice in Canada in 2006. In this case, the Canadian soft’ (on DRM technology patents), Toyota® (patent on governmentlicensed the company Biolyse to produce and automatic transmission system), and Direct TV’ (set-top export a generic version of the drug Tamiflu (usedto treat boxes) among others. In these cases, the courts have al- avian influenza or bird flu). The action was taken by the lowed continued infringementof the patent in return for governmentonthe premise that Roche (the patent owner) court-ordered royalty paymentsto the patentee. could not produce enough of the drug to meet potential demandin Canadaorin the least developed countries in Compulsorylicensing as a negotiating tool the eventofa bird flu epidemic. However, these decisions Althoughthe actual instances of compulsory licensing are are rarely taken solely on the basis of a lack of supply of a few and far between, the real powerof the compulsory treatmentfor a potential public health crisis. Political and licensing provisionslies in their use as a negotiating tool financial interests are often also very muchto the fore. to drive down prices and promote competition. The use of this tool has been used to provide huge numbers of HIV/ 115

Chemistry in New Zealand July 2010

AIDSsufferers with treatment that they might otherwise If you have any queries regarding intellectual property re- have been unable to afford. lated matters (including patents, trademarks, copyright or licensing), please contact us: [email protected] The benefits to public health of using compulsory licens- or [email protected] ing as a negotiation tool must be weighed against the negative effects that would occur if compulsory licensing References were to be abused and become commonplace. Sucha cul- 1 Projected Cost savings of medicines in Thailand in 2007-2012. ture of disrespect for intellectual property would be a se- Ministry of Public Health and the National

vere impedimentto the development of domestic research Licenga compulsoria do efavirenz no Brasil em 2007: contextu- is) and development and result in severe trading sanctions alizagao. Rodrigues, W.C.V., Soler, O. (2009) Pan Am J. Public from developed nations. Health 2009 26(6), 558. 3. Use of Compulsory Licenses; Selected National Experiences. The grant of compulsory licences in any country is an Braun, J., IP Law and Policy Research Unit, University of Cape area of patent law that provokes intense debate. On the Town. one handis the need for patent owners to be able to dic- 4 US takes a ‘hypocritical’ stance on Cipro. (Anthrax)(Ciprofloxacin) tate the terms on whichtheir inventions are used so they , Buttler, R. Chem. Ind. 2001, November5. can recoup the costs of research and development. On the 5 24 Technologies, Inc. v. Microsoft Corp., 434 F. Supp.2d 437, 440 other hand is the need for governments to reduce costs (E.D. Tex. 2006). and provide access to patented technologies that may be 6 Paice LLC v. Toyota Motor Corp., 2006 WL 2385139, at * 5 (E.D. the difference betweenlife and death. As the complexity Tex. Aug. 16, 2006). and diversity of medicines continues to increase, as well 7 Finisar Corp. v. DirecTV Group,Inc., 2006 U.S.Dist. LEXIS 76380 as the prevalence of diseases such as HIV/AIDS,it ap- (E.D. Tex. July 7, 2006). pears that compulsory licensing will continue to be used to influence the termsof international trade for the fore- seeable future.

Katherine Hebditch and Tim Stirrup of Baldwins Intellectual Property in Aucklandspecialise in chemistry and biotechnology patents. Katherine obtained her PhD in organic chemistry from the University of Manches- ter in the UK in 2004. She is currently working towards registration as a patent attorney. Tim obtained his PhD in molecular biology from the University ofSouthampton in the UK in 2007. Heis also working towards registration as a patent attorney.

- Everything wasfine... then it suddenly wentall pear-shaped. Brendan Burkett

116 Chemistry in New Zealand July 2010

Dates of Note

July 28 is the sixth anniversary of the death of Nobel ministrator whose work around 1920 (with David Pye) Laureate and DNAstructure giant Francis Crick. Distin- ultimately led to the octane anti-knocking guished crystallographer rating system. Dorothy Hodgkin, born in 1910, Sir Hans AdolfKrebs (of Krebs cycle fame) was born on died on 29 July 1994. Jean Antoine Claude Chaptal was Aug 25 in 1900. Aug 26"is the 23" the French anniversary of Georg chemist who wrotethefirst book on industrial Wittig’s death while the 27" marks 135 years since the chemistry and coined nitrogenas the name for the gas; he discovery of gallium by PE. Lecogq de died on 30 July Boisbaudran from 1832. Stephanie Louise Kwolek, the Pol- a 52 kg mineral sample taken fromthe Pierrefitte mine in ish-American chemist who invented poly-paraphenylene France. E.M. Purcell, the American terephtalamide physicist who shared — Kevlar, was born on July 31, 1923. The (with Bloch) the NobelPrize for Physics in 1952 for his day also marks the 210" anniversary of the birth ofFried- independent discovery (1946) of rich W6hler; nuclear magnetic reso- he died on Sept 23, 1882. nance inliquids and in solids, was born on Aug 30, 1912. Sir Ernest Rutherford was born on Otto Heinrich Warburg was a Germanbiochemist award- 30 Aug 1871 and died ed on Oct 19, 1937. Sir George Porter, the the NobelPrize for Physiology or Medicine in 1931 for distinguished English photochemist and Director his research on cellular respiration, the process by which of the RoyalInstitu- substances tion, died 7 years ago on Aug 31. directly supplied to cells (or stored in them) are broken downinto simpler components while using The little known Phoebus Levene oxygen. was a Russian-born August | marks the 40" anniversary of his death. American chemist and pioneerin the study of nucleic ac- The French chemist Joseph-Achille Le Bel was the first ids. In 1909, he foundthat the carbohydrate presentin nu- to presenta theory on therelationship between molecules cleic acid from yeastis ribose and, in 1929, he identified and how they absorborreflectlight. The 80" anniversary the carbohydrate in the nucleic acid from the thymus of of his death is on August 6. Viktor Meyer, whose appara- an animal.It is also a pentose sugar but lacks one oxygen tus continuesto be used to measure vapour densities, died atom of ribose and was, therefore, on 8 August 1897. called deoxyribose; they were namedribonucleic and deoxyribonucleic acids (RNA and DNA). Later discoveries showed John Ulric Nef, the Swiss-American chemist demon- them to be strated key elements in the maintenanceoflife. that carbon can have a valence of two as well as He died 70 years a valence ago on Sept6. Military explosives expert and offour thereby advancing the understanding of chemist Sir Frederick Abel died on the same day in theoretical organic chemistry. He provideda basis for the 1902. modern system of chemical notation and has a reaction Sir John Warcup Cornforth, named the Australian chemist who after him. He died 95 years ago on Aug 14. Bio- shared the 1975 Nobel Prize for Chemistry (with Prelog) chemist Sune K. Bergstrém who shared the 1982 Nobel for his work on the stereochemistry of enzyme-catalyzed Prize for Physiology or Medicine died 6 years ago on Aug reactions, will celebrate his 15. 93" birthday on Sept 7. The Aug 16, 1957 saw the death of Irving Langmuir, the same day marksthe 25" anniversary of the death of Rod- American physical chemist whose studies of molecular neyPorter, the British biochemist films on who (with Edelman) solid andliquid surfaces opened new fields in was awarded the 1972 Nobel Prize in Physiology or colloid research and biochemistry and won him the No- Medicine for discoveries concerning the chemicalstruc- bel Prize for Chemistry in 1932; Langmuir-Blodgett films ture of antibodies. On Sept 8, 1980 Willard needlittle introduction Frank Libby, these days. The same day marks the American chemist whoestablished carbon-14 (radio- the 7 years since Element 110, Darmstadtium wasoffi- carbon) dating and was awarded cially named. the 1960 Nobel Prize in Chemistry, died, as did polymer pioneer Hermann Lothar Staudinger in 1965. Meyerindependently discovered the Periodic Law of Dmitry Mendeleyevat about the same time in 1869. John Kidd was the English chemist and physician who He was born on Aug 19, 180 years ago. Johan Gottlieb obtained naphthalene in 1819 and gaveit its name.In ad- Gahn was born on the same day 265 years ago (1745). dition to teaching chemistry at Oxford, he was elected He was a Swedish mineralogist and crystallographer, who (1803) as the first Aidrichian professor of chemistry, he improved smelting methods at the copper mine in Falun, later taught mineralogy and and geology. His geology stu- discovered both manganese and selenium. This same dents included William Conybeare, William Buckland day is the 16" anniversary of Linus Pauling’s death and and Charles Daubeny. Holding a medical degree, he also the 245" since Axel Fredrik Cronstedt died (1765). He taught anatomy (from 1816) and medicine (from 1822). was another Swedish chemist and metallurgist and the He wrote a pamphlet on the role of science in educa- first to isolate nickel (1751) and noticeits slight magnetic tion. He was born on properties. Sept 10, 1775 and died on Sept 17, A (new) chemicalclassification of minerals he 1851. made wastranslated into several languages. Sept 25, 2010 marks the 25% anniversary of the death of Aug 23 is the 77" birthday of Robert F. Curl, who with William Cumming Rose. He was an American biochemist Smalley and Kroto discovered Coos the first fullerene, in whoresearchedthe role of aminoacids in nutrition, deter- 1985. On the same day 125 years ago, Sir Henry Tizard mining which wereessential, was and calculated the minimum born. He wasthe English chemist, inventor and ad- daily requirementfor each of them. Having found that the ee 117 eee Chemistry in New Zealand July 2010

milk protein, casein, was essential in a healthy rat’s diet, discovering the potent toxic effects on insects of DDT, he discovered (1936) the threonine in the casein was an died 45 years ago on Oct 12. Nobel’sfirst patent for the essential amino ‘acid. Over several years he established productionofnitroglycerine was issued on Oct14, 1863 in the primary importance of nine more amino acids, namely Sweden. Konrad Emil Bloch, the German-born American lysine, tryptophan, histidine, phenylalanine, leucine, iso- biochemist who shared the 1964 NobelPrize for Physiol- leucine, methionine, valine, and arginine. ogy or Medicine (with Lynen)for discoveries concerning the natural synthesis of cholesterol and fatty acids, died Frenchman Bernard Courtois died on Sept 28, 1838. The ten years ago on Oct 15, the same day as Herbert Henry ChemNews son of a saltpeter manufacturer from Dijon, he grew inter- Dow in 1930,the pioneer of US chemical industry. ested in chemistry, was apprenticed to a pharmacist and becamethefirst to isolate pure morphine from opiumin On October 16, 2006, researchers from JINR and Law- 1804. He also discovered the element iodine. This same rence Livermore National Laboratory of California, USA, day marked the death of Louis Pasteur in 1895. The last working at the JINR in Dubna, announcedthat they had day of Septemberis the 67" birthday of Johann Deisen- indirectly detected a total of three (possibly four) nuclei hofer (the German biochemist who shared the 1988 No- of ununoctium-294 (one or two in 2002 and two more in bel Prize in Chemistry with Michel and Huberfor protein 2005), the heaviest elementyet. It was produced via colli- structure) and the 71* ofJean-Marie Lehn,often a visitor sionsof californium-249 atoms and calcium-48 ions. The to NZ and Otagoin particular. same day in 1846 saw the first demonstration of ether an- esthetic by dentist Dr William Thomas Green Morton. New Zealander Maurice Wilkins died 6 years ago on Oct 5. He shared the 1962 NobelPrize for Physiology or The German-Swiss chemist who discovered and named Medicine (with Watson and Crick) for their X-ray diffrac- ozone (1840) and was the first to describe guncotton(ni- tion studies of deoxyribonucleic acid (DNA). Sir Harry trocellulose), William Cookworthy, died on Oct 17, 1780. Kroto, MacDiarmid Board Member and 1996 Chemistry Lewis Frederick Urry, the Canadian-American chemical Nobel Laureate, has his 71* birthday on Oct 7. The day engineer whoinvented the alkaline and lithium batteries, also marks the 125" anniversary of Neils Henrik David died on Oct 19, six years ago. On the sameday in 1875 Sir Bohr’s birth; his fame was with quantum theory. Charles Wheatstone died; he popularized the Wheatstone bridge. Paul Hermann Miiller, the Swiss chemist who received the Nobel Prize for Physiology or Medicine in 1948 for

£1 million prize for the first 100% chemical free product!

The UK Cosmetic, Toiletry and Perfumery association Dr Richard Pike the Chief Executive of the RSCstates: (CTPA)is an association of manufacturers of cosmetic, Ifproducts are marketed as ‘chemical-free’ as though toiletry and perfumery products. It was founded in 1945 thats not only possible, but actually desirable, its no and launched a new additionto its website (http://www.the- wonder some consumers might feel concerned about factsabout.co.uk/) entitled Facts about Chemicals in Feb- the safety of chemicals. To raise awareness of how im- ruary of this year, in conjunction with the Royal Society possible ‘chemical-free’ is as a claim, I’m challenging of Chemistry (RSC). The aim of the Facts about Chemi- anyone to place in my hand a product I considerto be cals site is to answer consumerand media questions about chemical-free. The truth, as any right-minded person chemicals in cosmetic andpersonalcare products. will say, is that everything we eat, drink, drive, play with andlive in is made ofchemicals — both natural and syn- We have all heard media claims that you can buy house- thetic chemicals are essentialfor life as we knowit. hold cleaning products, shampoos and foods that claim to be chemicalfree or do not containany nasty chemicals. As This is the second time this challenge has been issued by we knowthereis no such thing as a ‘chemical free’ product the RSC asit tried to re-claim the word chemicalin Octo- as it is impossible to achieve. The CTPA,therefore, works ber 2008. This followed claims from a popularfertilizer with the manufacturers ofcosmetic and personalcare prod- manufacturer who advertised that its product contained no ucts to encourage them notto use these terms when adver- chemicals whatsoever. tising their products to consumers. In relation to the launch of the new website page Dr Pike In February of this year the RSC announcedit would give said: It will help to reduce some ofthe confusion about a prize of £1 million pounds to anyone who could create chemicals so that people can make better-informed deci- what the RSC would consider to be a 100% chemical free sions andchoicesin theirdaily lives. Any measures indus- product. try can take to promote a more science-based understand- ing ofchemicals, andthe very positive role they playin our everydaylives, can only be a goodthing. Anthea Lees

118

Chemistry in New Zealand July 2010

Conferences a o 60" Anniversary Conference on Coordination Chemis- chemistry, Biogeochemistry, Clean technologies and >, try (60CCCO), 27-30 September 2010, Osaka, Japan green chemistry, Ecotoxicology, Biomarkers. © Deadline for abstract submission: July 23" 2010 http://sabotin.ung.si/~emec11/ oO http://www. sakutai.jp/index.eng.html = Biocatalysis Conference, 10-13 December 2010, a Polymer Chemistry Conference 2010, 18-21 Novem- Puerto Morelos, Mexico, North America © n ber 2010, Puerto Morelos, Mexico, North America This conference will cover recent developments in bio- This conference will focus on polymer chemistry and ma- catalysis in both academia and industry including topics terials science applied to biological problems of current such as enzymediscovery, directed evolution of enzymes, relevance. scale-up of biocatalytic processes, novel screening meth- ods, metagenomics, pathway engineering and other ar- http://www.zingconferences.com/index.cfm?page=confere eas of related research. nce&intConferencelD=66&type=conference http://www.zingconferences.com/index.cfm?page=confere MM 2010 molecular modelling for life and material nce&intConferencelD=69&type=conference sciences, Melbourne, 28 November - 1 December 2010, Australia 5 International Conference on Advanced Materials and Nanotechnology - AMN-5, 7-11 February 2011, This meeting will focus on the latest developments in mo- Wellington, New Zealand lecular modelling in both the life sciences and materials sciences, particularly in the areas of drug development, The biennial conference offers a broad interdisciplinary nanotechnology, biophysical modelling and methods and overview of advanced materials and nanotechnology, and algorithms. Provides an exciting forum to discuss new and exciting advancesin the field http://mm2010.org/ Abstracts can be submitted from 1 July 2010 to 31 August Organic Synthesis: A Toolkit for the Industrial Chem- 2010. ist, 1-3 December 2010, Barcelona, Spain http://www.confer.co.nz/amn-5/ This 3-day course, written and presented by highly ex- perienced chemists from the pharmaceutical and fine 5* International Congress of Chemistry and Envi- chemical industry, provides a modular overview of the ronment (ICCE 2011), May 27-29 2011, Kuching, most important tools available for the organic chemist Sarawak, MALAYSIA working in industry. http://www.chemistry-conferences.com/2011/05/27%20- http://www.scientificupdate.co.uk/training/scheduled- %2029%20Conference%20of%20Chemistry%20and%20Environ courses/details/92-organic-synthetic.html ment%20(Kuching%20-%20MY).htm www.accc3.org 11 European Meeting on Environmental Chemistry, 8-11 December 2010, PortorozZ, Slovenia 2012 International Symposium on Macrocyclic and Conference topics are: Emerging contaminants, Atmo- Supramolecular Chemistry (ISMSC-2012), 29 Janu- spheric chemistry, Water treatment and waste manage- ary - 2 February 2012, University of Otago, Dune- ment, Analytical methods for environmental science, din, New Zealand Soil chemistry, Pollutant chemistry, Aquatic and marine Register interest via: www.otago.ac.nz/ismsc2012/ CHEMICAL EDUCATION TRUST

Applications are invited from secondary school teachers (via the Head of Science) for grants from the NZIC Chemical Education Trust to promotethe teaching of chemistryin their school. For the 2010 distribution, grants ofaround $500 are envisaged, but greater or lesser amounts can be applied for. Closing datefor applications: 1 August 2010 Applications must includefull details ofthe item(s) for whichfunding is requested together with an up-to-date quotation, email contact andfullpostal address. Send yourapplication to: Professor Andrew. Brodie, NZIC Chemical Education Trust, Institute of FundamentalSciences, Massey University, Private Bag 11-222, Palmerston North 4442. Fax: 06 350 5682; e-mail: [email protected]

Applications that arrive after the closing date or do notincludefull details, as listed above, will not be considered. 119

——————EEElll—NB Chemistry in New Zealand July 2010

Grants and Scholarships

The Prime Minister’s Science Prizes Foundation of Research, Science and Technology The Prime Minister’s Science Prizes recognise the impact This has a number of on-demand schemes that provides Grants of science on New Zealanders’ lives. They are an oppor- funding to enable businesses to develop new research tunity for the people of New Zealand to celebrate the and developmentprojects. There are a numberofdiffer- contribution of our current scientists and to encourage ent options available. those of the future. The Prizes will highlight the signifi- The following website has a table with how often these canceofscience bytelling the story of our successes and on-demand schemesare considered for funding and fur- achievements. ther details about the various schemes. 1. The Prime Minister’s MacDiarmid Emerging Scientist http://www.frst.govt.nz/investframe/process/ondemand Prize: $200,000 2. The Prime Minister’s Science Teacher: $150,000 New Zealand Trade and Enterprise International Growth Fund 3. The Prime Minister’s Future Scientist Prize: $150,000 The fund is targeted at businesses New Zealand Trade and Enterprise (NZTE) is working closely with on a plan to 4. The Prime Minister’s Science Media Communication help them develop and grow. These are businesses that Prize: $100,000 NZTE has assessed as being mostlikely to contribute to Deadline: 27 August, 2010. New Zealand’s long-term growth, including through suc- cess internationally in the short to medium term. Busi- The 2010 Future Scientist Prize will be awarded to the nesses that receive funding need to at least match the Supreme Awardrecipient from the Royal Society of New level of investment that NZTE makes through the fund. Zealand’s ‘Realise the Dream’ competition. Judging for All investments from the fund are at NZTE’s discretion the Prime Minister’s MacDiarmid Emerging Scientist Prize and there is no guarantee a business will get financial is currently underway. support? http://www.pmscienceprizes.org.nz/news/100519_ http:www.nzte. govt.nz/find-funding-assistance/Pages/In- 2010_prize_round_announced.html ternational-Growth-Fund. aspx For further information please contact: Rebecca Goffin, Royal Society of New Zealand, The New Zealand Trade and Enterprise Capital raising Prime Minister’s Prizes Project Manager. Email: Rebecca. advice and assistance Goffin@royalsociety. org.nz This service provides assistance to any business or entre- preneur who needsto raise funds to expand, diversify or Primary Science Teacher Fellowships commercialise a new concept. A six-month fellowship designed to create potential sci- For further details see the website: ence curriculum leaders in the primary sector. This is done through placement for six months in a scientific http://www. nzte. govt.nz/find-funding-assistance/capital- organisation learning how science is applied outside of raising-advice-and-assistance/pages/capital-raising-advice- schools, intensive curriculum support and leadership and-assistance.aspx training. This is a fellowship which aims to create poten- tial curriculum leaders in Science for the primary sector. Rutherford PhD scholarships at Cambridge Univer- If you have been teaching for three or more years, have sity an interest in up-skilling in science, and are keen to un- These scholarships are for applicants undertaking full- dertakea leadership role in your school in Science educa- time study towards a PhD at Cambridge University in pure tion, this may be the fellowship for you. or applied science. The Rutherford Scholars receive an Deadline: 17 September 2010 for Fellowships beginning allowance of approximately £10,500 for up to three years term 1 2011 as well as university and college fees and one return air- fare between New Zealand and the United Kingdom. http://www.royalsociety. org.nz/Site/teachersstudents/ Funding_for_teachers/teacher_fellowships/primary- Closing date for applications is 30 July 2010 science.aspx For further details see the website: Conventions and Incentives New Zealand Confer- http://www. royalsociety.org/Site/rutherford/ guidelines. ence Assistance Programme aspx This programmeis to provide assistance for bidding to host an international conference in New Zealand. This can include discounted airfares to travel to present a bid, help to write bid documents and accompanying mar- keting material, as well as other assistance. For further details see the website: http://www.conventionsnz.com/cap.aspx

120 and synchrotron radiation: What’s the connection?

Oneofthe world’s most famousrace horses ‘Phar Lap’ was duced from this analysis showed the presence of low con- born in New Zealand (in Seadown near Timaru) andhislife centrations of arsenic throughout the hair. However in the and infamous death in 1932 have been widely tabulated. subcutaneous region (area just below the skin) an intense Hedied after winning the world’s richest race of that time, band (which occurred at the same location in each hair) the Agua Caliente Handicap in Mexico, in what werethen, was observed, which suggested a sudden increase and then considered to be, very suspicious circumstances. Rumours quick decay following ingestion and subsequent excretion of foul play at the time, including arsenic poisoning, were of arsenic. To look at the chemical environmentof the ar- reported but the actual cause of death was never fully es- senic, X-ray absorption near edge spectroscopy (XANES) tablished. Following his death, his mounted hide was dis- wasperformed on the same samples along the arsenic rich played at the Melbourne Museum;his skeleton wassent to region. Two arsenic species were observed: an As "thiol the MuseumofNew Zealand Te Papa Tongarewawhile his complex andarsenate. The results obtained suggested that heart is displayed at the National Museum of Australia in arsenic may have been ingested in the form of a complex Canberra. such as arsenic glutathione. It was also noted that the in- gested arsenic did not undergo significant photoreduction A paperrecently published in Angew. Chem.Int. Ed. (2010, but, that arsenic associated with the taxidermy process was 49, 4237-4240) by Ivan Kempson and DermotHenry, looks degraded fromarsenateto arsenite. at a possible theory behind the death of this famoushorse. Researchers took a numberofhairs from Phar Lap’s hide This research provides evidence for the differences be- and analysed them for arsenic poisoning. If Phar Lap was tween any arsenic which had entered the haircells via the indeed poisoned,then any recordof this poisoning could be blood and arsenic which hadinfused into the hair cells by recorded along the length ofthe strands of his hair. It should the taxidermy process when the body of Phar Lab was pre- howeverbe noted that arsenic was also used to preserve served.at the museum. The real reason behind Phar Lap’s Phar Lap’s hide after his death. It is, therefore, important death may never be knownbut it is known that horsesat that the arsenic usedin the preservation of the hide should that time were subjected to ointments and tonics which be distinguishable from any arsenic which may have been contained arsenic and strychnine which leads to the pos- ingested by the horse while he wasalive. sibility of his death being due to an accidental overdose.

Hairs, which were knownto be actively growing at his On 25" November 2009, a life sized bronze statue of Phar death, were chosen from his hide and were analysed us- Lap was unveiled at Phar Lap raceway in Timaru to recog- ing a synchrotron X-ray-fluorescence microprobe (XRF). nize this outstanding thoroughbred. The XRFs technique was usedto longitudinally map four of the hairs for elemental analysis and the arsenic map pro- Anthea Lees

Promoting Scientific Exchange in

tot. the Pacific Basin for a Healthy and Sustainable Future 15 - 20 December 2010 Conference Update

The conferencewill be held at the Hawaiian Convention Center and the beachfront Hilton, Sheraton, Royal Hawaiian; and Westin Moana Surfriderhotels.

The abstract submission phase has closed, program schedule been published and acceptancenotices will be posted in the next few weeks. There have been over 13,000 abstracts submitted for the conference.

Entries for the student poster competition will be pre judged and the 200 selectedfinalists will be informed in Oct/Nov 2010.

Booking for accommodation is now open. Registration for the conference will open in June 2010.

For moredetails see: http://www.pacifichem.org/

For informal information and general background please contact the NZIC representative on the organiz- ing committee: Prof Rob Smith, Chemistry Department, University of Otago, Dunedin - 03 4797924; [email protected]

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