chemistryFor the full biographies of confirmed speakers to the RACI 2014 National Congress please...

ALSO IN THIS ISSUE: Mapping the metabolome • Nobel Prize 2013 Part II • Unearthing chemical furphies

chemistryin AustraliaMarch 2014

The longroad of drugdiscovery

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Key DatesCall for Abstracts Opens 2 December 2013

Registration Opens 2 December 2013

Abstract Submission Deadline 9 May 2014

Notification of Acceptance of Abstract June 2014

Early Bird Registration Closes 1 August 2014

Accommodation Booking Deadline 30 September 2014

Congress Dates 7-12 December 2014

Participating Divisions

Scientific Program Themes

• Analytical & Environmental Chemistry Division

• Biomolecular Chemistry Division

• Carbon Division

• Chemical Education Division

• Colloid and Surface Chemistry Division

• Electrochemistry Division

• Industrial Chemistry Division

• Inorganic Chemistry Division

• Materials Chemistry Division

• Organic Chemistry Division

• Physical Chemistry Division

• Polymer Chemistry Division

• Radiochemistry Division

• Health, Safety & Environment Division

• Synthetic Chemistry

• Fundamental Interactions in Chemistry

• Advanced Materials

• Chemical Health and Safety

• Chemistry in Health

• Chemical Analysis and Sensing

• Community Engagement

Contact UsRACI2014 Congress Secretariat ICMS AustralasiaGPO Box 3270, Sydney NSW 2001Ph: +61 2 9254 5000 • Fax: +61 2 9251 [email protected]

Confirmed PlenarySpeakers

Associate Professor Alán Aspuru-Guzik, Harvard University

Professor Phil Baran, The Scripps Research Institute

Dr Stacie Canan, Global Health Division, Celgene Corporation

Professor Makoto Fujita, The University of Tokyo, Japan

Professor Hubert Girault,Ecole Polytechnique Fédéralede Lausanne

Professor KatharinaLandfester, Max Planck Institute

Professor David Leigh,University of Manchester

Professor Daniel Nocera,Harvard University

Professor Greg Scholes,University of Toronto

For the full biographies of confirmed speakers to the RACI 2014 National Congress please visit theCongress website at www.racicongress.com

views & reviews4 Guest editorial6 Your say33 Books34 Chemical furphies36 Energy38 Technology & innovation39 Grapevine40 Postdoc diary41 Letter from Melbourne

March 2014

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raci.org.au/chemaust

cover story

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news & research7 News12 Research42 Cryptic chemistry42 Events

members5 From the President28 RACI news29 New Fellows31 Obituary

16 Getting to know big molecules. 2013 Nobel Prize in Chemistry II Modelling enzyme-driven reactions is now possible thanks to a confluence of ideas: those of a Nobel trioand those of earlier chemistry pioneers.

22 ‘Omics’ on the brainFor a relatively new kid on the block, metabolomics has a lot to offer neuroscience research.

Q&A: Clinical trialsThe 0.01% of novel drug compounds that make it to market havesatisfied requirements well beyond those of clinical studies.

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Key DatesCall for Abstracts Opens 2 December 2013

Registration Opens 2 December 2013

Abstract Submission Deadline 9 May 2014

Notification of Acceptance of Abstract June 2014

Early Bird Registration Closes 1 August 2014

Accommodation Booking Deadline 30 September 2014

Congress Dates 7-12 December 2014

Participating Divisions

Scientific Program Themes

• Analytical & Environmental Chemistry Division

• Biomolecular Chemistry Division

• Carbon Division

• Chemical Education Division

• Colloid and Surface Chemistry Division

• Electrochemistry Division

• Industrial Chemistry Division

• Inorganic Chemistry Division

• Materials Chemistry Division

• Organic Chemistry Division

• Physical Chemistry Division

• Polymer Chemistry Division

• Radiochemistry Division

• Health, Safety & Environment Division

• Synthetic Chemistry

• Fundamental Interactions in Chemistry

• Advanced Materials

• Chemical Health and Safety

• Chemistry in Health

• Chemical Analysis and Sensing

• Community Engagement

Contact UsRACI2014 Congress Secretariat ICMS AustralasiaGPO Box 3270, Sydney NSW 2001Ph: +61 2 9254 5000 • Fax: +61 2 9251 [email protected]

Confirmed PlenarySpeakers

Associate Professor Alán Aspuru-Guzik, Harvard University

Professor Phil Baran, The Scripps Research Institute

Dr Stacie Canan, Global Health Division, Celgene Corporation

Professor Makoto Fujita, The University of Tokyo, Japan

Professor Hubert Girault,Ecole Polytechnique Fédéralede Lausanne

Professor KatharinaLandfester, Max Planck Institute

Professor David Leigh,University of Manchester

Professor Daniel Nocera,Harvard University

Professor Greg Scholes,University of Toronto

For the full biographies of confirmed speakers to the RACI 2014 National Congress please visit theCongress website at www.racicongress.com

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EDITOR Sally WoollettPh (03) 5623 [email protected]

PRODUCTION EDITORCatherine Greenwood

ADVERTISING SALES Gypsy Media & Marketing Services Marc Wilson, ph 0419 107 [email protected]

PRODUCTIONControl Publications Pty Ltd Ph/fax (03) 9500 0015/0255 [email protected]

BOOK REVIEWSHelmut Hügel [email protected]

GENERAL ENQUIRIESRobyn TaylorRACI National Office, 21 Vale StreetNorth Melbourne VIC 3051 Ph/fax (03) 9328 2033/[email protected]

PRESIDENT Mark Buntine FRACI CChem

MANAGEMENT COMMITTEESam Adeloju (Chair) [email protected] Anesbury, Anna-Maria Arabia, Helmut Hügel, Alan Jones, Amanda Saunders, Colin Scholes, Curt Wentrup

CONTRIBUTIONSContributors’ views are not necessarily endorsed by the RACI, and noresponsibility is accepted for accuracy of contributions. Visit the website’sresource centre for more information about submissions.

© 2013 The Royal Australian Chemical Institute Inc.Content must not be reproduced wholly or in part withoutwritten permission. Further details on the website.

ISSN 0314-4240 e-ISSN 1839-2539

www.raci.org.au/chemaust

guest editorial

Chemistry in Australia4 | March 2014

On 11 October 2013, the Norwegian Nobel Committeeannounced that the Nobel Peace Prize would be awarded to theOrganization for the Prohibition of Chemical Weapons (OPCW)for its extensive efforts to eliminate chemical weapons.

This is a great and important recognition for an organisationthat works so diligently to make the world a safer place. I amhumbled to relay IUPAC’s heartfelt congratulations to our OPCWcolleagues for this fantastic and well-deserved recognition fortheir tireless work to free the world of chemical weapons. Inrecent years, IUPAC has been privileged to work with OPCW,both in contributing technical expertise to the reviewconferences of the Chemical Weapons Convention (CWC) and indeveloping educational resources on the multiple uses ofchemicals. As recently as the July–Aug 2013 issue of ChemistryInternational, Leiv K. Sydnes contributed a feature outliningIUPAC’s involvement with OPCW over the last 12 years. Thatfeature was triggered by the recent IUPAC Technical Report (inthe April 2013 Pure and Applied Chemistry) titled ‘Impact ofScientific Developments on the Chemical Weapons Convention’(http://dx.doi.org/10.1351/PAC-REP-12-11-18), released inadvance of the Third Review Conference of the CWC held lastApril.

In 2004, the president of IUPAC and the director general ofthe OPCW agreed on a joint project on chemistry education,outreach and the professional conduct of chemists; see IUPACproject 2004-048-1-020. As an outcome of this project, theneed for peer-reviewed educational materials was clearlyidentified. In response, a set of web-based materials to be usedby educators and students has been created and publishedonline at www.iupac.org/multiple-uses-of-chemicals orhttp://multiple.kcvs.ca. The approach was to start with thebeneficial uses of chemicals, give examples of the misuse andabuse of chemicals, and then provide basic information aboutthe Chemical Weapons Convention, ending with the need forand examples of existing codes of conduct.

The Nobel recognition to OPCW contributes to validatingIUPAC’s mission ‘to advance the worldwide aspects of thechemical sciences and to contribute to the application ofchemistry in the service of Humankind’. Today, I feel proud ofbeing a chemist and helping IUPAC members to take part inthese Union activities!

Fabienne Meyers [email protected] is editor of IUPAC’s magazine ChemistryInternational, in which this editorial was first published (Nov–Dec 2013).Reproduced with permission. A follow-up feature related to OPCW will appear in afuture issue.

A heartfelt congratulations to OPCW

During World War I, chemical weapons were used to aconsiderable degree. The Geneva Convention of 1925prohibited the use, but not the production or storage, ofchemical weapons. During World War II, chemical means wereemployed in Hitler’s mass exterminations. Chemical weaponshave subsequently been put to use on numerous occasions byboth states and terrorists. In 1992–93 a convention wasdrawn up prohibiting also the production and storage of suchweapons. It came into force in 1997. Since then the OPCWhas, through inspections, destruction and by other means,sought the implementation of the convention. 189 stateshave acceded to the convention to date.

The conventions and the work of the OPCW have definedthe use of chemical weapons as a taboo under international

law. Recent events in Syria, where chemical weapons haveagain been put to use, have underlined the need to enhancethe efforts to do away with such weapons. Some states arestill not members of the OPCW. Certain states have notobserved the deadline, which was April 2012, for destroyingtheir chemical weapons. This applies especially to the USAand Russia.

Disarmament figures prominently in Alfred Nobel’s will. TheNorwegian Nobel Committee has through numerous prizesunderlined the need to do away with nuclear weapons. Bymeans of the present award to the OPCW, the Committee isseeking to contribute to the elimination of chemical weapons.

nobelprize.org

from the raci

Chemistry in Australia 5|March 2014

As I write this column, I have just returned to work followingan extended summer break. It was relaxing and reinvigoratingto not think about chemistry, work or the RACI for the betterpart of six weeks. I made a promise to myself not to look atemails while I was on leave. It wasn’t until the Friday before Ireturned to work that I took a peek at my inbox to see whatawaited me after the Australia Day celebrations. This has beenthe first time in quite a few years that I’ve taken such acomprehensive break away from my professional life, and I feelrefreshed and energised for the tasks ahead. I hope thatmembers feel similarly refreshed from the hustle and bustle of2013.

In December this year the RACI will be holding a NationalCongress in Adelaide. I encourage all members to seriouslyconsider participating in the Congress. The exciting list ofplenary speakers covers a diverse range of the subdisciplineareas of the chemical sciences. I think that there is somethingfor everybody in the technical program. For those interested inpresenting their work at the Congress the abstract submissiondeadline is 9 May – only a couple of months away! Other keydates and related information can be found at the Congresswebsite at www.racicongress.com.

An ongoing challenge for the RACI, as for many societies, isto attract and then retain new members, particularly younger orrecently graduated chemists just beginning their careers.Growing the number of these members is a strategicallyimportant renewal objective as the overall RACI membershipdemographic gets steadily older. Much on the subject ofattracting new members has been written and talked about overthe years. However, it seems to me that retention of newmembers is a more pressing issue. We are not particularly goodat keeping younger chemists who do sign up, and we must dobetter.

One issue that we must confront is how to recognise andreward the loyalty of this cohort as they progress through theirstudies. At the moment undergraduate and Honours studentmembers pay a subsidised annual membership fee of $25. Oncethese students graduate, if they move on to postgraduatestudies they are eligible for the concessional member rate of$115 per year. If they move into the workforce, these membersface an increase in membership to $230 per year!

Feedback from many young and/or recently graduatedcurrent and former members has consistently indicated that thesudden increase in membership fees is too steep and that thereis a perception of lower value for money flowing from thehigher fee structure. To date the RACI has tended to focus on avariety of communication strategies to demonstrate the benefitsand value of membership. However, in the world of marketing‘perception is reality’ – it is evidently inadequate to merely tellthese members, who face a significant membership fee increase,that being an RACI member is ‘good value for money’. The

challenge remains to develop a membership fee structure that isboth financially sustainable and removes disincentives for thosemoving through the early career membership grades. (As anaside, the non-concessional MRACI CChem annual membershipfee in 2003 was $236, compared to $260 currently. Thisrepresents a significant reduction in membership fees in realterms over the past decade.)

One approach being explored by the RACI Board involvessoftening the rate of increase in membership fees for those whohave been longer-standing RACI members. For instance, agraduating PhD student who has been an RACI member for fouror more years could have a multi-year transition from theconcessional member rate to the full member annualsubscription fee. Similarly, a graduating Honours student whohas been an RACI member for two or more years could have amulti-year progression to the concessional or standardmembership fee, as appropriate. Another option that has beensuggested is to provide longer-standing RACI student memberswith larger discounts to attend RACI conferences. Carefulfinancial modelling is currently being undertaken to explore theimpact of these measures and detailed proposals will bedeveloped for consideration by the Branches and Divisionsbefore any decisions are made by the Board later in the year. Iencourage all readers of this column, particularly youngerand/or recently graduated RACI members, to provide feedbackto the options canvassed here and to make other suggestionsfor the Board’s consideration. Feedback can be provided [email protected].

From the President

Mark Buntine FRACI CChem ([email protected]) is RACIPresident.

Australia Day 2014 HonoursThe late Dr Trevor Appleton was awarded the Medal(OAM) of the Order of Australia in the General Division inthis year's Australia Day Honours, for service toeducation through the teaching and promotion ofchemistry. A Distinguished Fellow, Trevor's longstandinginvolvement with the RACI included his extensive work atboth Branch and Group level in Queensland, includingthree decades as coordinator of the National TitrationCompetition. Trevor passed away in June 2013 (seeFebruary issue, p. 26).

The RACI is very pleased at such deservedrecognition of Trevor's contributions to chemistry, andcongratulates all RACI members who have receivedhonours this year.

your say

6 | March 2014Chemistry in Australia

The changing PhDReading ‘The changing PhD: demand and supply’ (December2013/January 2014 issue, p. 16), I was prompted to considerthe entire Group of Eight discussion paper. I felt compelled toascertain to what extent, if any, the paper differentiated outand analysed PhDs by field, particularly of course chemistry.Alas, a quick word search of the paper’s 60-odd pages revealedjust one lonely reference to ‘chemistry’. For ‘science’, a moreencouraging 49 instances occurred. Here are a few otherinteresting observations about PhDs from the paper:• On PhD employment trends:

– The scarcity of fine detail concerning what becomes ofAustralia’s PhD awardees – science or otherwise – islargely due to a lack of any recent longitudinal datathat will allow an assessment to be made of the longerterm career prospects of doctoral students. The limitednational data that does exist showed that in 2006 abouta third of people in Australia having doctorates workedas university and vocational education teachers androughly the same proportion in higher education in2008. Expanding the PhD data set over time,differentiating and analysing by specialty would be ofvalue to the demand and supply debate.

– Almost 80% of people who attain PhDs in science in theUK will eventually find careers outside science. Thepaper goes on to suggest there’s no reason to suspectthe situation is any different with respect to the socialsciences, humanities or creative arts. Or indeed that thetrend is any different in other developed countries.Consequently if most PhD graduates work in positionsthat don’t tap into their specialised disciplinaryknowledge, it may not always be fair to assume thatPhD education is concerned with creating ‘stewards ofthe discipline’ as postulated by The Carnegie Foundationfor the Advancement of Teaching.

• On the welfare and professional standing of the PhD student:that research students function as part of a Ponzi (‘pyramid’)scheme that supports ‘the interests of universities byensuring a continuing supply of creative, well educated,cheap (and easily disposable) labour able to supply aconstant stream of new ideas to those tenured academics

who were lucky enough to enter the system first.’ For more,dip into economist Paula Stephan’s How economics shapesscience.

• On the relative private versus public investment in PhDs byresearch: within the OECD, around 70% of all research isperformed by business, a figure not dissimilar to that in theAustralian market.

• On possible improvements: – Introduce or enhance a PhD by research’s coursework

component. International experience demonstrates thatincorporating coursework to develop ‘transferable skills’markedly increases timely thesis submission. Courseworktypically includes business-oriented topics such asproject management, communication skills and financialmanagement.

– Extend the study period (e.g. two year Masters degreeprior to three year PhD) to ensure that students can beintroduced to and acquire transferable skills.

– Expand and enhance student placements in industry andgovernment research settings throughout their PhDtraining.

Damien Blackwell MRACI CChem

Another Soviet man of scienceIn a previous letter to the editor (August 2013, p. 5) I outlinedthe life and work of N.N. Semenov. The letter explained howSemenov’s work was built upon initially by combustion expertsin Europe and then Australia and New Zealand. In the autumnof 2006, a conference was held in Yerevan, Armenia, to markthe 75th birthday of Alexander Merzhanov, sole survivor ofthose who had worked directly with Semenov. Merzhanov diedon 31 July 2013, so there ended all direct continuity withSemenov, although the scientific succession continues.

The reluctance of successive Australian governments to grantvisas to scientists from the Soviet Union was in my opinion toAustralia’s disadvantage at a time when it was expanding itsscientific research base. Such reluctance continued at least untilthe 1980s. At the 7th National Convention of the RACI inCanberra in 1982, Professor Andy Cole of the University ofWestern Australia announced that a scientist from the SovietUnion had been refused permission to enter Australia and that arequest for reconsideration by Professor Cole on behalf of theRACI had been to no avail.

I know of at least one ‘elder statesman’ on the Australiancombustion scene who probably had dealings with Merzhanov atsome time (having met Semenov in Hungary in the earlyeighties). If he reads this, I would be interested for hisresponse.

Clifford Jones FRACI CChem

news

March 2014

An Australian scientist has joinedinternational colleagues to accuratelydate Martian rocks using a speciallydesigned instrument on board NASA’sCuriosity rover.

The remarkable finding is part of aseries of ground-breaking discoveriesmade by University of Queensland’sSchool of Earth Sciences Head ProfessorPaulo Vasconcelos and other members ofthe Curiosity rover team, published in sixpapers in Science.

The team adapted specialisedgeochronological techniques used onEarth to determine the age and exposurehistory of rocks.

Vasconcelos said the significance froma geological perspective was that themore recent the exposure, the more likelythat an area could potentially be hostingsigns of life.

‘We can now use geochronology toguide where to look for signs of life enroute to Mt Sharp, the ultimate goal ofthe Curiosity mission on Mars.’

The Martian rock – nicknamed‘Cumberland’ – was studied directly froma modified instrument aboard the

Curiosity rover.‘We used a noble gas dating

technique – the K-Ar dating method – todetermine the age of the rock on Mars,’Vasconcelos said.

‘We then used the concentrations ofthree noble gas isotopes 3He, 21Ne, and36Ar produced by cosmic rays at theMartian surface to determine how longthe sample had been exposed on thesurface of Mars.’

Analyses of data unveiled that theestimated age of the Cumberland rockwas 3.86–4.56 billion years, and that ithad been exposed to the Martian surfacefor 60–100 million years.

‘Sixty to 100 million years of exposurefor the sample is very recent for thatsite, suggesting that active geologicalprocesses have removed the shieldinglayers above the rock in the recent past,’Vasconcelos said.

In a collaborative effort arising froma successful 2005 Australian ResearchCouncil grant, Vasconcelos and ProfessorKen Farley of Caltech (USA) hadcombined methodologies forsimultaneously dating rocks and

measuring their exposureages while working onseveral Australian andBrazilian sites.

‘To measure noble gasisotopes forgeochronology on Earth,we had used large high-resolution sector massspectrometers,’Vasconcelos said.

‘To make the samemeasurements on Marsas we did on Earth, wehad to adapt and use aminiaturised quadrupolemass spectrometer –that was a bigchallenge.’UNIVERSITY OFQUEENSLAND

Rock-dating technique could point tosigns of life in space

Drilling at the Martian rocky outcrop of Yellowknife Bay, Gale Crater. Image credit: NASA/Jet Propulsion Laboratory, Mars Science Laboratory Mission.

MEPinstrumentsThe right chemistry.

M962 Adv_MEP_NIRSystMasterlab_275x76_20131111.indd 1 12/11/2013 11:33

news


Radioactivity muddles the alphabetof DNACurtin University researchers have shown natural radioactivitywithin DNA can alter chemical compounds, providing a newpathway for genetic mutation.

The research, recently published in Biochimica et BiophysicaActa-General Subjects (doi.org/10.1016/j.bbagen.2013.10.003),for the first time looked at natural radioactivity within humanDNA on the atomic-scale.

While radioactivity occurs naturally in our bodies as well asin every living organism across the planet, it was never beforethought to affect our DNA in such a direct way.

Using high-performance computers, the research team fromCurtin and Los Alamos National Laboratory were able to showradioactivity could alter molecular structures that encodegenetic information, creating new molecules that do not belongto the four-letter alphabet of DNA.

Professor Nigel Marks from Curtin’s Discipline of Physics andAstronomy and Curtin’s Nanochemistry Research Institute saidthe new molecules may well generate mutations by confusingthe replication mechanisms in DNA.

‘This work takes an entirely new direction on research intonatural radioactivity in biology and raises important questionsabout genetic mutation,’ Marks said.

‘We have discovered a subtle process that could easily beoverlooked by the standard cell repair mechanisms in the body,potentially creating a new pathway for mutations to occur.’

Marks said the work was both exciting and unexpected,emerging as a spin-off from an Australian Research Councilfunded project on nuclear waste.

‘As part of the project between Curtin and Los Alamos, wedeveloped a suite of computational tools to examine deliberateradioactivity in crystalline solids, only to later realise that thesame methods could be applied to natural radioactivity inmolecules,’ he said.

‘This direction was an unplanned outcome of our researchprogram – just the way blue skies research should be.’

The natural radioactivity in focus involved the decay ofcarbon-14 to nitrogen-14 – one of the most abundant forms ofradioactive decay occurring in biological systems. Over a humanlifetime, around 50 billion carbon-14 decays occur within ourDNA.

‘While it is still not obvious how DNA replication is affectedby the presence of chemical compounds that are different tothe four-letter alphabet of DNA, it is quite remarkable toconsider that carbon-14 could be a source of genetic mutationthat would be impossible to avoid due to the universalpresence of radiocarbon in the environment, Marks said. CURTIN UNIVERSITY


Laundering money – literally – couldsave billions

A new money-cleaning technique can remove years of oil build-up, as shown.American Chemical Society

A dollar note gets around, passing from hand to hand, fallingon streets and footpaths, eventually getting so grimy that abank machine flags it and sends it to the shredder. Rather thandestroying it, scientists have developed a new way to cleanpaper money to prolong its life. The research, which appears inIndustrial & Engineering Chemistry Research (doi.org/10.1021/ie403307y), could save billions and minimise the environmentalimpact of banknote disposal.

Nabil M. Lawandy and Andrei Smuk point out that replacingold currency is a growing problem. When notes become toodirty, central banks take them out of circulation and replacethem with crisp new notes. As a result, the world’s treasuriesprint nearly 150 billion new banknotes every year at a costapproaching $11 billion. And about 150 000 tonnes of old notesbecome destined for shredding and disposal. The main culpritfor this costly turnover is human sebum, the oily, waxysubstance the body produces to protect skin – also the bane ofacne-prone teenagers. Over a note’s lifetime of about 3–15 years depending, on the denomination, sebumaccumulates on its surface, reacts with oxygen in the air andturns a yellowish hue. To delay a banknote’s retirement,Lawandy’s team decided to see whether they could just clean it,removing the accumulated sebum.

They turned to supercritical CO2, which acts like both a gasand a liquid and is commonly used in other cleaningapplications. When they tested it on banknotes from around theworld, they found that it effectively removed oxidised sebumand motor oil while leaving intact security features such asholograms and phosphorescent inks.AMERICAN CHEMICAL SOCIETY

Science at the heart of budgetsustainabilityAustralia’s investment in science is moving backwards and willdrive the nation’s best and brightest towards greateropportunities offshore, the Australian Academy of Science haswarned in a submission to the National Commission of Audit.

The nation is not investing nearly enough in science, saidAustralian Academy of Science Secretary for Science Policy,Professor Les Field.

‘Australia is going backwards while other governmentsaround the world have recognised that investing in science isessential to increasing resilience, productivity andcompetitiveness, and is fundamental to ensuring futureprosperity,’ Field said.

‘Strategic support for Australian research and for science,technology, engineering and mathematics education is essentialto achieving the goals set for the National Commission of Audit,such as ensuring long-term budget sustainability.

‘Our best hope for creating a strong economy and addressinglooming issues for society is through investing in science andinnovation so that we have the tools in place to tackletomorrow’s problems.’

Field said the Academy welcomed the Prime Minister’s recentpledge to continue to support science to the fullest extentpossible.

But with the Australian Research Council Future Fellowshipscheme set to expire this year along with other key programs,Field said that it is urgent that Australia puts in place a long-term and stable plan for science.

‘Our very best and brightest researchers will have limitedopportunities to do research in Australia, and are increasinglylikely to seek careers offshore.’

Minister for Education Christopher Pyne recently describedARC research as the ‘lifeblood’ of many of the most significantresearch endeavours in the country, and its Future Fellowshipscheme as enabling researchers to make a crucial contributionto solving major problems.

‘We must find a replacement for this successful program andstop the potential brain-drain before it builds up a head ofsteam,’ Field said.

Previous long-term funding schemes for major nationalresearch infrastructure have also come to an end, leavingfacilities underutilised, underfunded, under-resourced and atrisk of closure. These facilities were granted brief reprieve in thelast budget with short-term funding.

‘Stop-gap funding is in an inefficient way to fund researchinfrastructure. We need to find a long-term sustainable plan toproperly operate and maintain Australia’s major researchfacilities,’ Field said.

The Academy’s submission to the National Commission ofAudit is available at www.science.org.au/reports/documents/NationalCommissionOfAudit.pdf.AUSTRALIAN ACADEMY OF SCIENCE

Theoretical physicist Ana Maria Rey usesthe computer, as well as pencil andpaper, to develop mathematical modelsthat describe the behaviour of ultra-coldatoms. The idea is to use these systemsto learn more about condensed matterphysics and quantum mechanics with thegoal of inspiring new materials, precisionmeasurements and quantum information.

Using ultra-cold atoms, ‘we aim todevelop synthetic materials that do notexist in nature, but which can help usunderstand materials that do exist innature,’ said Rey, a research assistantprofessor in the University of ColoradoBoulder’s Department of Physics and afellow at JILA, a joint institute of theuniversity and the National Institute ofStandards and Technology.

‘Electrons in solids can exhibit richbehaviour, complex behaviour, that we do

not understand,’ she added. ‘Thisbehaviour comes from interactions ofmany electrons. When the electrons inthe solids interact and see otherelectrons, the laws of quantum mechanicsgovern how they behave. This is verycomplicated behaviour. This behaviour isso complex that even a classicalcomputer cannot solve it.’

Rey and her colleagues create artificialmaterials by trapping atoms with light.In order to do this, ‘we have to makethem very cold,’ she explained. ‘We thenuse lasers to try to mimic the potentialthat electrons feel in real solids.’

Ultimately, her research could lead tonew materials for more effectivesuperconductors, as well as new magneticbehaviour that could speed up computerdevelopment. One of the eventual goals,for example, is to develop new materials

that superconduct at room temperature,rather than only in extreme cold.

‘This will help everything, becausenowadays you have to cool the materialsdown, which is very expensive,’ she said.‘If we don’t have to cool them down,everything that uses superconductivitycan be made much less expensively.’

She also is developing acomprehensive theoretical framework foran optical-lattice quantum computerbased on alkaline earth metals, and shealready has proposed solutions forproblems associated with storing,addressing and transporting qubits,which are the quantum equivalent oftraditional computing bits.

Among other things, she is attemptingto resolve long-standing obstacles tolarge-scale entanglement between atoms,which quantum computers require both

news


Research models behaviour of ultra-cold atoms andpolar molecules

Ana Maria Rey of the Universityof Colorado Boulder, received aMacArthur Fellowship in 2013.Casey Cass

How zinc starveslethal bacteria tostop infection


for communication and calculations.‘We want to use atoms trapped in

light to create a quantum computer,’she said. ‘The internal levels of theatom are the qubits of thecomputer. For example, we areproposing atoms in the secondcolumn of the periodic table –alkaline earth elements, such asstrontium – which have largenumber of degrees of freedom toimprove computation capabilities.’

Such research potentially couldproduce smaller and fastercomputers with capabilities thatclassical computers do not nowhave. ‘A classical computer has todo its computations one at a time,but with quantum mechanics, allthe computations are done inparallel,’ she says.

Finally, she also is working onadvances in developing an opticalatomic clock.

‘Atoms are a tool that allows usto measure time in a very preciseway,’ she said. ‘The energy levels ofan atom are like the ticking of aclock. The higher the energyseparation between levels, the moreticks you have and the more preciseyour clock.

‘The atomic clock measures time,and to measure time better, weneed more atoms,’ she said. ‘Themore atoms we have, the higher thesignal-to-noise ratio, meaning thatin principle, the clock is moreprecise.’

One persistent problem, however,is that atoms collide, ‘and that isbad for the clock,’ she added. ‘WhatI have done is try to understand theorigins of these collisions, and tryto control them in order to improvethe clock.’MARLENE CIMONS, NATIONAL SCIENCE FOUNDATION

Australian researchers have found thatzinc can ‘starve’ one of the world’s mostdeadly bacteria by preventing its uptakeof an essential metal.

The finding, by infectious diseaseresearchers at the Universities ofAdelaide and Queensland, opens theway for further work to designantibacterial agents in the fight againstStreptococcus pneumoniae.

Streptococcus pneumoniae isresponsible for more than one milliondeaths a year, killing children, theelderly and other vulnerable people bycausing pneumonia, meningitis andother serious infectious diseases.

The researchers describe in NatureChemical Biology (doi.org/10.1038/nchembio.1382) how zinc ‘jams shut’ aprotein transporter in the bacteria sothat it cannot take up manganese,which Streptococcus pneumoniae needsto be able to invade and cause diseasein humans.

‘It’s long been known that zinc playsan important role in the body’s abilityto protect against bacterial infection,but this is the first time anyone hasbeen able to show how zinc actuallyblocks an essential pathway, causingthe bacteria to starve,’ says projectleader Dr Christopher McDevitt,Research Fellow in the University ofAdelaide’s Research Centre forInfectious Diseases.

‘This work spans fields from

chemistry and biochemistry tomicrobiology and immunology to see, atan atomic level of detail, how thistransport protein is responsible forkeeping the bacteria alive byscavenging one essential metal(manganese), but at the same time alsomakes the bacteria vulnerable to beingkilled by another metal (zinc),’ siadProfessor Bostjan Kobe, Professor ofStructural Biology at the University ofQueensland.

The study reveals that the bacterialtransporter (PsaBCA) uses a ‘spring-hammer’ mechanism to bind the metals.The difference in size between themanganese and zinc causes thetransporter to bind them in differentways.

The smaller size of zinc means thatwhen it binds to the transporter, themechanism closes too tightly aroundthe zinc, causing an essential spring inthe protein to unwind too far, jammingit shut and blocking the transporterfrom being able to take up manganese.

‘Without manganese, these bacteriacan easily be cleared by the immunesystem,’ said McDevitt. ‘For the firsttime, we understand how these types oftransporters function. With this newinformation we can start to design thenext generation of antibacterial agentsto target and block these essentialtransporters.’UNIVERSITY OF ADELAIDE

iStockphoto/Linde1

research


Mesoporous carbonaceous spheresThe interest in the design and controlled fabrication ofmonodisperse porous carbonaceous nanospheres emanates fromtheir tremendous potential applications in energy conversionand storage, catalysis and nanomedicine. In collaboration withProfessors Max Lu (University of Queensland), Dongyuan Zhao(Fudan University) and Shi Zhang Qiao (University of Adelaide),Dr Jian Liu and colleagues from the Department of ChemicalEngineering, Curtin University, have presented important workon the fabrication of mesoporous carbon nanospheres andhollow nanospheres with high surface area (Liu J., Yang T.,Wang D.W., Lu G.Q., Zhao D. Qiao S.Z. Nature Comm. 2013, 4,2798). The innovative, facile and efficient soft-templatesynthesis reported is low-cost, suitable for industrial productionand can controllably provide spheres of various size. The carbonnanospheres are promising candidates for high rate performancelithium–sulfur batteries with excellent cycling stability, andmay have other applications in energy storage and conversion,as electrode materials, in photonics, separation science, watertreatment and drug delivery.

Mannosidases are glycosidehydrolases that catalyse thehydrolysis of a diverse range ofpolysaccharides andglycoconjugates, with applicationsin the pharmaceutical, detergent,food, biofuels, and oil and gasindustries. Using a combination ofcomputational chemistry, inhibitordesign and synthesis, and X-raycrystallography of inhibitor/enzymecomplexes, research groups from theUniversities of Melbourne, York,Newcastle and Barcelona haveshown that that so-calledmannoimidazole-type inhibitors areenergetically poised to reportfaithfully on mannosidasetransition-state conformation(Williams R.J., Iglesias-FernándezJ., Stepper J., Jackson A., Thompson A.J., Lowe E.L., WhiteJ.M., Gilbert H.J., Rovira C., Davies G.D., Williams S.J. Angew.Chem. Int. Ed. 2014, doi: 10.1002/anie.201308334)). By usingthe newly synthesised mannobiose-derived mannimidazole(ManMIm), direct evidence was provided for the conformationalitinerary used by poorly characterized mannosidases from twosequence-unrelated families (GH26 and GH113). In particular,this work provides direct evidence in support of a boat-shaped

transition state. On the other hand, isofagomine-type inhibitorswere shown to be poor mimics of transition-state conformation,owing to the high energy barriers that must be crossed toattain mechanistically relevant conformations. However, themannobiose-derived isofagomine (ManIFG) allowed theacquisition of a ternary complex spanning the active site,delivering valuable insight into active-site residues involved insubstrate recognition.

Ship-shape inhibitors

Transition state mimicking binary complex: Active site spanning ternary complex:


There is an emergence of drug-resistantmicroorganisms, mostly due to the over-use of antimicrobial drugs. Newantimicrobials are needed; particularly,new classes of antimicrobials. Researchconducted by teams at the University ofNew South Wales, James Cook University,University of Technology Sydney,University of Adelaide, and the AustralianArmy Malaria Institute, has indicatedthat inert dinuclear ruthenium(II)complexes have significant potential as anew class of antimicrobial agent. The

ruthenium complexes are highly activeagainst most bacterial strains – includingthose resistant to current drugs – butexhibit low toxicity to healthy eukaryoticcells. Recently, the mechanism of theantimicrobial activity of the rutheniumcomplexes has been proposed (Li F.,Harry E.J., Bottomley A.L., Edstein M.D.,Birrell G.W., Woodward C.E., Keene F.R.,Collins J.G. Chem. Sci., 2014, 5, 685–93). In vivo wide-field fluorescencemicroscopy studies with E. colidemonstrated that the ruthenium

complexes target RNA over DNA. RNAtargeting could be an advantage for newantimicrobial drugs due to differencesbetween bacteria and eukaryotic cells.Furthermore, the ruthenium complexescondensed ribosomes (the site of proteinsynthesis) when they existed aspolysomes (a number of ribosomesattached to mRNA). The condensation ofpolysomes would halt protein production,and thereby inhibit bacterial growth.

RNA-targeting Ru antimicrobials

Researchers at the University of Sydney, led by AssociateProfessor Richard Payne, have reported the first peptideligation–desulfurisation protocol at N-terminal tryptophanresidues for the construction of homogeneous peptide andprotein targets (Malins L.R., Cergol K.M., Payne R.J. Chem. Sci.2014, 5, 260–6). The ligation technology involves thechemoselective condensation of a peptide bearing an N-terminal 2'-mercaptotryptophan residue with a peptide bearinga C-terminal peptide thioester functionality. Following theligation of the two peptide fragments, removal of the 2'-thiolligation auxiliary via reductive desulfurisation afforded nativepeptide products in excellent yields. Unlike the majority ofligation–desulfurisation protocols, which rely on challenging

multistep syntheses of preformed thiolated amino acids, thistechnique utilises an efficient, late-stage sulfenylation reactionto rapidly install the crucial thiol auxiliary at the 2-position ofthe tryptophan indole ring within completely unprotectedpeptides or on resin-bound peptide fragments. The overallutility of the methodology was further demonstrated throughthe synthesis of a glycopeptide fragment of the N-terminalextracellular domain of the chemokine receptor CXCR1. Inaddition to providing a powerful approach to ligation–desulfurisation at tryptophan, the operational simplicity of thismethod may also facilitate the site-selective modification andlabelling of large peptides and proteins for use in a variety ofbiological studies.

Giving Trp a try – just thiolate then ligate


Researchers headed by Associate Professor Bayden Wood,Centre for Biospectroscopy, School of Chemistry at MonashUniversity, and the Henryk Niewodniczanski Institute of NuclearPhysics in Poland, have recently characterised the site of DNAdouble strand breaks (DSBs) in plasmid DNA by using tip-enhanced Raman scattering (TERS) (Lipiec E., Sekine R., BieleckiJ., Kwiatek W.M., Wood B.R. Angew. Chem. Int. Ed. 2014, 53,169–72). DSBs are a type of DNA damage that can result fromexposure of cells to UV radiation, leading to genetic defects andapoptosis; however, the terminal structure and mechanisms ofthese breaks at the molecular level are not well understood.TERS combines the high spatial resolution of atomic forcemicroscopy and the high sensitivity of surface-enhanced Ramanscattering, enabling the investigation of molecular structure atthe nanoscale. Using this approach, the researchers observedthree types of spectroscopic features, assigned to P–O–H andmethyl/methylene deformation modes at the origin of the DSB.On the basis of these observations, it was hypothesised that thelesion occurs at the 3¢- and 5¢- bonds of deoxyribose units.

Importantly, this study demonstrates the unique capabilities ofTERS as an independent modality to characterise DSBs,providing a new approach to study DNA damage in response toradiation exposure.

Stereospecific ring polymerA novel stereospecific ring polymer, referred to as cyclicsyndiotactic poly(methyl methacrylate) (st-PMMA), wasprepared through a collaborative effort between the PolymerScience Group, headed by Professor Greg Qiao at theUniversity of Melbourne, and the Kamigaito research groupat Nagoya University, Japan (Ren J.M., Satoh K., Goh T.K.,Blencowe A., Nagai K., Ishitake K., Christofferson A.J.,Yiapanis G., Yarovsky I., Kamigaito M., Qiao G.G. Angew.Chem. Int. Ed. 2014, 53, 459–64.). Complete with controlledstereochemistry and cyclic topology, this polymer is capableof forming an unprecedented polypseudorotaxane ormolecular necklace-type supramolecular assembly with thecomplementary linear isotactic poly(methyl methacrylate)(it-PMMA). In conjugation with molecular modellingconducted by the Yarovsky research group at RMITUniversity, the experimental characterisations of the uniquesupramolecular assembly by X-ray diffraction, differentialscanning calorimetry and dynamic light scattering providedstrong evidence for the polypseudorotaxane-typeconfiguration of the stereocomplex. Compared to theconventional triple-helix stereocomplex obtained from thelinear st-/it-PMMA pair, the polypseudorotaxanestereocomplex exhibits different physical propertiesincluding a unique crystallisation mode, crystallite structureand melting behaviour. This study revealed that the topologyof polymer components does not affect their stereocomplexhelix formation capability, but rather the microstructure andproperties of the resultant supramolecular assemblies.

Defining DNA damage

research


Gerhard Raabe et al. (RWTH Aachen University) report ab initio calculations on theexperimentally known pyridine–borabenzene donor–acceptor (D–A) complex (C5H5N–BC5H5), in which a dihedral angle of approximately 40° is found between the two rings,and the formation of the complex is exothermic by a sizeable 50 kcal/mol. The D–Abond is best described as a highly polarised single bond with a barrier to rotation ofapproximately 3 kcal/mol. The graphic shows the complex before and after chargetransfer from N to B. The compound absorbs in the visible at approximately 600 nm,and the wavelength of this HOMO–LUMO transition is highly solvent dependent.

C5H5B C5H5N

Toby Bell and coworkers (Monash University) highlight super-resolution imagingwith direct stochastic optical reconstruction microscopy (dSTORM), a technique capableof achieving spatial resolutions well below the diffraction limit of light. ‘Super-resolution’ microscopy is finding wide use, particularly in the biochemical sciences,routinely generating fluorescence images with resolutions of the order of tens ofnanometres. The dSTORM is founded on the detection of fluorescence emissions fromsingle molecules. A highly functional and versatile dSTORM set-up built from ‘off-the-shelf’ components (see diagram) at quite a modest budget is described with sometypical super-resolution images of microtubules and actin filaments within cells.

Widespread implementation ofmodular super-resolution isexpected in coming years.

Vittorio Pace (University of Vienna) describes the synthetic usefulness ofmonohalomethyllithium carbenoids as methylene transfer agents in academe andindustry alike. These species are formed on treatment of a dihalomethane (ICH2Cl,ICH2Br, CH2Br2, CH2I2) with alkyllithiums at –78°C. Remarkably, they allow the directincorporation of a reactive halomethylenefragment into an electrophile, thereby avoidingadditional steps usually needed when employingdiazoketones or b-oxo dimethylsulfoxoniumylides as methylene equivalents. Thenucleophilicity of the lithium species accountsfor exclusive 1,2-addition to a,b-unsaturatedcompounds, contrasting the 1,4-additionobserved with sulfur ylides.

Aust J Chem

Curt Wentrup FAA, FRACI CChem ([email protected]),http://uq.edu.au/uqresearchers/researcher/wentrupc.html?uv_category=pub

Schematic diagram of the dSTORMmicroscope. The two lenses andsteering mirror are translatable toallow switching from conventional toquasi-total internal reflectionfluorescence illumination. Theobjective and sample are decoupledfrom the microscope body by a nose-piece stage.

Compiled by Matthew Piggott MRACI CChem([email protected]). This section showcasesthe very best research carried out primarily inAustralia. RACI members whose recent work has beenpublished in high impact journals (e.g. Nature, J. Am.Chem. Soc., Angew. Chem. Int. Ed.) are encouraged tocontribute general summaries, of no more than 200words, and an image to Matthew.

Three-fingers pick ASIC’s pocketBioactive venom peptides are invaluable aspharmacological tools. The mambalgins, anovel class of peptides from black mambavenom, have attracted great interestbecause of their potent analgesic action,mediated through acid-sensing ion channel(ASIC) inhibition. Mambalgins are relativelylarge (~6 kDa) and share little sequencehomology with other snake toxins or othertoxins targeting ASICs. Researchers from theInstitute for Molecular Bioscience(University of Queensland) have reported thechemical synthesis, first 3D structuredetermination and ASIC binding site formambalgin 2 (Schroeder C.I., Rash L.D.,Vila-Farr X., Rosengren K.J., Mobli M., KingG.F., Alewood P.F., Craik D.J., Durek T.Angew. Chem. Int Ed. 2014, 53, 1017-20).The 57-residue peptide was readilysynthesised by native chemical ligation ofthree smaller fragments, and its solutionstructure was determined by 2D NMRspectroscopy. The 3D structure revealed athree-finger toxin fold that is commonamong functionally unrelated snake toxins.Electrophysiology studies of mambalgin-2revealed that it binds to a-helix 5 onASIC1a. This region borders the acidicpocket that functions as the putativeproton-sensing site, and overlaps with thebinding site of the structurally unrelatedspider toxin PcTx1. The combination oftechniques used in this investigation willfacilitate rapid structure–activity studies anddevelopment of this promising analgesicpeptide.

Modelling enzyme-driven reactions isnow possible thanksto a confluence ofideas: those of aNobel trio and thoseof earlier chemistrypioneers.

The development of molecularmechanics, from thepioneering ideas of TerrellHill to the work of Michael

Levitt on protein folding, was the focusof part I of this 2013 Nobel Prize inChemistry series (February issue).The Nobel recipients, Martin Karplus(Université de Strasbourg/HarvardUniversity), Arieh Warshel (Universityof Southern California) and MichaelLevitt (Stanford University), wererecognised for developing multiscalemodels of enzyme reactions bymarrying classical and quantummechanics. This part concentrates onKarplus, Warshel and the quantummechanical aspects of describing

chemical reactions, and the integrationof molecular mechanics and quantummechanics used today to model allsorts of enzyme-catalysed reactions.

A key figure in the 2013 Nobel Prizein Chemistry has gone generallyunrecognised. He is Shneior Lifson,who worked at the Weizmann Institutefrom 1949 until his death in 2001. Hewas the focal point of a nearcongruence of the three Nobellaureates in 1968–9. Arieh Warshel wasa PhD student of Lifson’s (1967–9),during which time Michael Levitt cameto Lifson’s lab to work on the consistentforce field before starting his PhD withKendrew at the MRC in 1968. Withinsix months, Martin Karplus arrived for


BY PETER KARUSO

Getting to know big molecules2013 Nobel Prize in Chemistry II

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a six-month sabbatical in Lifson’s lab,where he met, and later recruited,Warshel as a postdoc. It was Warshel’sbackground in the consistent force fieldand molecular mechanics that allowedhim to combine the quantum mechanicsapproaches of Karplus and marry thesetwo competing approaches into what wetoday call quantum mechanics/molecular mechanics.

Martin Karplus was bornon 15 March 1930 to aJewish family in Vienna.His family fled a few days

after the Anschluss (13 March 1938) toavoid the Nazi occupation of Austria, toZurich in Switzerland and then LaBaule in Brittany, France, beforeemigrating to the US. The family settledin Newton, Massachusetts (nearBoston), where Martin’s older brother(Bob) was given a chemistry set. Theusual smells and explosions fascinatedMartin and he pleaded for a chemistryset as well but was given, instead, aBausch and Lomb microscope. Thiswas the beginning of his fascinationwith the natural world, despite a familyassumption that, following in the stepsof both grandfathers, he wouldeventually become a physician.

The Karplus brothers attendedNewton High School, with Bobexcelling in all the sciences. Martin,despite a particularly unpleasantchemistry teacher, also did well inscience and won the WestinghouseScience Talent Award, despitediscouragement from theaforementioned teacher. He publishedhis first paper at the age of 16 in theBulletin of the Massachusetts AudubonSociety (1946) on the lives of alcidbirds, based on his Westinghousescience project. Graduating top of hishigh school class in 1947, he enteredHarvard University in the same year ona full scholarship, intending to studybiology. Concluding rapidly that a firmgrasp of physics and chemistry isessential to understand biology (amessage that much of the rest of theworld is only now beginning to

understand), he enrolled in Harvard’sProgram in Chemistry & Physics.

After earning his BA in 1950, Martindecided to do his PhD on the westcoast. Bob was, at this time, doing aPhD at Princeton in physics, workingfor Oppenheimer, who advised Martinto go for Caltech, which he describedas a ‘shining light in a sea of darkness’,initially joining Max Delbrück’s groupin biology, where he proposed to workon the theory of vision (how retinalisomerisation leads to nerveimpulses). Unable to continue withDelbrück (who was notoriously criticalduring student seminars) and losinghis subsequent supervisor, JohnKirkwood in the chemistrydepartment, to Yale, Karplus acceptedLinus Pauling’s offer of supervision.Karplus graduated in 1953, at the ageof 23, after trying to develop a methodto predict the structure of hydrogendifluoride (FHF–) using ab initiomethods. According to Pauling,Karplus ‘was [his] most brilliantstudent’ but did not manage to get asingle publication from his PhD,primarily because William Moffitt(Harvard) had scooped him in 1954,publishing a similar method that wasmore general and more elegant thanthat of Karplus.

Despite this apparent poor trackrecord, Karplus obtained an NSFPostdoctoral Fellowship to OxfordUniversity (1953–5), where he workedwith British theoretical chemist CharlesCoulson (incidentally William Moffitt’sDPhil supervisor). His first item ofbusiness, when he arrived at Oxford,was to get his paperwork signed off byCoulson and the second was a longholiday in Paris. He admits he spentmore time thinking about researchthan actually doing any during hispostdoctoral years, but travelledextensively throughout Europe,including Yugoslavia, landing him onan FBI list of possible ‘communists’.

When it came time to leave Oxfordand find a job, he applied for achemistry instructor’s position at theUniversity of Illinois. Linus Pauling

wrote a letter of support and Karpluswas offered the job without any papers,no interview and without waiting for areference from Coulson. The latter wasfortunate, because Coulson hadwritten that, although he had no doubtabout Karplus’ intellectual abilities, hehad done very little work on problemshe had suggested.

Karplus’ first paper in chemistryappeared in 1956, in the Journal ofChemical Physics, 25, 605–6, a workexamining the electronic chargedistribution in the hydrogen molecule.It marked the beginning of Karplus’influence on our thinking about thequantum chemical make-up ofmolecules. What was particularlyinteresting about Illinois in the early1950s was the presence of CharlesSlichter (Physics) and HerbertGutowsky (Chemistry), who weredoing pioneering work on applyingnuclear magnetic resonance tochemical problems. While at Illinois,Karplus developed the Karplusequation (J. Chem. Phys. 1959, 30, 11–15), which describes the size of thecoupling constant between two atomsbased on their dihedral angle. Thiswas developed using valence bondtheory, which he was introduced to byPauling (who thought every problem inchemistry can be solved by valencebond theory). The paper had animmediate impact: E.J. Corey used themethod to help determine thestructure of new natural products in thesame year and the paper now has over2800 citations.

However, the Midwest was no placefor a Europhile like Karplus. During anNSF-funded teaching program at TuftsUniversity, in the toilets, Karplus wasasked by Ben Dailey from ColumbiaUniversity (in New York City) to


According toPauling, Karplus‘was [his] mostbrilliant student’...

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consider relocating to Columbia. Just afew weeks later, he took a position asan Adjunct Associate Professor at theIBM Watson Laboratory, the firstcorporate pure science researchlaboratory that had magnificentequipment, unlimited time on state-of-the-art computers (IBM 650), access toColumbia University postdocs and noteaching.

Despite these obvious attractions, in1963 he moved to the ChemistryDepartment at Columbia – an optionhe negotiated when accepting the jobat Watson, which was just as wellbecause the Watson lab closed downin 1970. In 1965, Karplus decided itwas time to move again. By this time,

he was famous in the chemistrycommunity; when word got out that hewas looking for a ‘new challenge’many universities contacted him. Hisfinal choice was between Berkeley(where his brother Bob was a fullprofessor of physics) and Harvard.After spending a sabbatical year atHarvard, he decided to move there in1969. Besides, the fine weather andhippie lifestyle in San Francisco wouldhave been too much of a distractionfrom his work.

Soon after he arrived at Harvard, hetook six months’ leave (sabbatical) andwent to the Weizmann Institute(Shneior Lifson) in Israel where he metArieh Warshel, Lifson’s only PhD

student. Michael Levitt had recently leftto start his PhD at the MRC. With timeto read and think and to discuss hisideas with Lifson and other visitors toLifson’s lab such as Chris Anfinsen(Nobel Prize, 1972), Karplus came upwith ideas about how to applytheoretical chemistry to biology. Backat Harvard, Karplus returned to hisoriginal PhD proposal: investigatingthe visual pigment (retinal) from atheoretical perspective. A postdoc(Barry Honig) did calculations thatused semi-empirical quantummechanics for the p-electrons (doublebonds) and simple pairwise non-bonded energy function (molecularmechanics) for the sigma bondframework of the molecule. By splittingthe calculation up into a region ofclassical mechanics (the backbone ofthe molecule) and a region of quantummechanics (the p-system), it made thecalculations tractable. The modellingpredicted the 11-trans,12-s-cis-retinalto be the most stable isomer and theresults were sent to Nature forpublication. The paper wasimmediately rejected by the editor(John Maddox) because there was noevidence the predictions were correct.At the time, there was no structure ofretinal or rhodopsin, but after a longconversation, Maddox (who was also a


Martin Karplus receiving his Nobel Prize at theStockholm Concert Hall, 10 December 2013Copyright © Nobel Media AB 2013. Photo: Alexander Mahmoud

theoretician) reluctantly accepted thepaper (Honig, Karplus Nature, 1971,228, 558). The paper, unfortunately,has received fewer than two citations ayear since then; nonetheless, it is alandmark in the background to themost recent Nobel Prize in Chemistryas probably the earliest example ofquantum and molecular mechanicscombined.

The intersection of broad thinkersaround Shneior Lifson at the Weizmannin the late 1960s led to Arieh Warshel’sdecision to join Karplus’ group as apostdoc in 1970. He brought with himthe consistent force field molecularmechanics program that he andMichael Levitt had written in Israel, andin Karplus’ lab, Warshel combined theconsistent force field with higher levelquantum mechanical calculations topredict the vibrational spectrum o,different retinal isomers (Karplus andWarshel J. Am. Chem. Soc. 1974, 96,5677). However, there was no real wayto translate this to macromoleculessuch as proteins.

Bruce Gelin (just returned toKarplus' lab from Vietnam after beingdrafted mid-PhD) was given the task ofbuilding a package that could simulateproteins and find the minimum energystructure. They started with theconsistent force field but completely

recoded it to deal withmacromolecules. After it was finished,they had to come up with a name:HARMM (HARvard MacromolecularMechanics) was the first idea, butchanged it to CHARMM by adding‘Chemistry’ at the front. This was thefirst molecular mechanics packagethat could handle structures the size ofproteins, and it is still used widelytoday.

Richard Feynman famously said that‘everything that living things do can beunderstood in terms of the jigglingsand wigglings of atoms’ (The FeynmanLectures in Physics, 1963) so the nextinnovation of CHARMM was to addmolecular dynamics (solving Newton’sequation for motion). This was codedby Andy McCammon (another PhDstudent in Karplus' lab) and BruceGelin and spectacularly used for thefirst time to simulate the dynamics of asmall protein (McCammon, Gelin,Karplus Nature, 1977, 267, 585). Thevision of another giant in the field(Peter Kollman, University of California,San Fransisco) led to the firstapplication of molecular modelling tobiomedical problems such as drugdesign. Peter Kollman was absolutelydevoted to science, and his enthusiasmwas contagious. He had no trace ofego and was an inspiring group leader

but was taken by cancer suddenly andfar too soon. He developed the AMBERset of programs, which is still one ofthe most widely used and citedmolecular modelling programs, andopened the doors to practicalpharmaceutical applications ofcomputational chemistry.

Arieh Warshel was born 20November 1940 in kibbutzSde Nahum, Israel. In thekibbutz he was

discouraged from going to university,but his burning desire to learn aboutscience drew him to the Technion inHaifa after completing his militaryservice. In 1965, Warshel was awardedthe Technion Award – Best Third-YearStudent in Chemistry. He graduatedsumma cum laude, continuing on to hisMasters and PhD at the Technion.During his Masters, he attended anintimidating quantum mechanics classin the physics department andunderstood very little but didunderstand the implications of theasymptotic quantum mechanical wavefunctions. He naïvely remarked that hewould one day develop an asymptoticwave function for enzymes. He had noclue about how enzymes worked oreven what they looked like or how awave function could explain their


Arieh Warshel in his office at University ofSouthern California DornsifeMax S. Gerber

action. He enrolled in a PhD withShneior Lifson, not for any scientificreason but only because Lifson grewup on a kibbutz three kilometres fromhis own. He was Lifson’s only student atthe time, but a congruence of greatminds, including Martin Karplus,Michael Levitt and Chris Anfinsen inLifson’s lab, in 1969 sent Warshel ontoa trajectory that resulted in a NobelPrize.

After his postdoc in Karplus’ lab,and armed with a deeperunderstanding of quantum mechanics,Warshel returned to the WeizmannInstitute and joined forces with MichaelLevitt, who had just finished his PhD atCambridge, to further developcomputational methods. He realisedthat molecular mechanics andmolecular dynamics can never explainthe action of enzymes because theycannot say anything about a reactioncoordinate or the structure/energy of atransition state. For this, quantummechanics was needed. He first triedjust dropping a quantum mechanicspackage into the consistent force fieldbut it did not work because there wasno driving force to break bonds. Whatwas needed was a line of code thatsays it is all right to be charged. Withthis came the emergence of the firstquantum mechanics/molecular

mechanics simulation of an enzymemechanism.

Levitt and Warshel published arevolutionary paper in 1976 (J. Mol.Biol. 1976, 103, 227) on themechanism of lysozyme that wasgeneral and scalable to molecules ofany size. The method considered theentire enzyme–substrate complextogether with the surrounding waterand evaluated all the quantummechanical and classical energyfactors of the reaction pathway,including the quantum mechanicalenergies associated with bondcleavage and charge redistribution ofthe substrate and the molecularmechanical energies of steric andelectrostatic interactions between thesubstrate and the enzyme. In addition,the electrostatic polarisation of theenzyme atoms and the orientation ofthe dipoles of the surrounding watermolecules was simulated by amicroscopic dielectric model. Thequantum mechanics–molecularmechanics interface can beconsidered like an asymptotic wavefunction for an enzyme’s action.

Warshel and Levitt both left Israelbecause Warshel was surprisinglydenied tenure at the WeizmannInstitute. Levitt returned to Cambridgeand eventually moved to Stanford.

Warshel became an assistant professorat University of Southern CaliforniaDornsife in 1976, where he hasdevoted his academic life tounderstanding how enzymes work,based on their structure anddynamics.

The crucial achievement of thethree Nobel laureates was to marryclassical and quantum mechanics inorder to model the fast reactionmechanism at the centre of an enzymeand the large-scale slow movements ofthe rest of the enzyme andsurrounding solvent. This was madepossible by the classical mechanicalexpertise of Shneior Lifson and thestimulating environment at theWeizmann in the late 1960s, thequantum mechanical expertise ofMartin Karplus and the desire of allthree laureates to apply their work tobiological systems. Biomolecularmodelling is now an important part ofboth academic and industrial labs andhas a range of applications, includingrefinement of X-ray and NMR structure,simulation of protein folding andunfolding, drug design and liganddocking, study of enzyme reactions,function of ion channels, GCPRs(Nobel Prize 2012) and the modellingof transport through membranes. In thefuture, when computational facilitiesallow, it will be used to model the life ofan entire cell, not just individualcomponents, and reveal intricacies thatwe cannot even imagine at this time.

The field of computationalchemistry has always beencontroversial and struggled behindexperiment: if computations agreedwith experiment, they wereconsidered uninformative and if theypredicted new properties, they wereconsidered unverifiable andunpublishable. The broad vision of thethree laureates of computationalmodelling as a reliable substitute forexperiments is becoming a reality.

Peter Karuso FRACI CChem([email protected]) is the Professor ofChemistry at Macquarie University, Sydney.


It is a central dogma of biochemistry that enzymes stabilise the transition state of a reaction so theenzyme–substrate complex resembles a reaction transition state. In quantum mechanics/molecularmechanics (QM/MM) an enzyme’s active site is treated using QM (red) while the bulk of the enzyme istreated using MM (gold). A transition between QM and MM is required and finally the solvent istreated using some sort of boundary (blue) because only a finite number of atoms can be included inany calculation. The total energy of the system is thus given by: ET ≈ EQM + EMM + EQM/MM + Eboundary

Adrian Mulholland, University of Bristol

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In 2007, Dr David Wishart’s team atthe University of Alberta finishedtheir first draft of the humanmetabolome. The latest draft

(version 3.0) of this chemicalcounterpart of the human genome,with details of more than 40 000metabolites, is an extremely valuableresource for the young but rapidlydeveloping field of metabolomics.

The thousands of naturallyoccurring metabolites involved in andcreated by the body’s everydayprocesses are the focus ofmetabolomics. In the same way that anorganism’s genome comprises itscomplete genetic content, a

metabolome is that organism’s fullcomplement of metabolites, such asamino acids, carbohydrates, fats andsugars. Physiology, health status andenvironment are closely linked to themetabolome, so metabolomics is auseful way to study their interactions.

Existing as a distinct field sincearound the mid-1990s, metabolomicsblends analytical and biologicalchemistry with chemometrics(especially multivariate statistics andsophisticated pattern recognitiontechniques). Although the concept ofmetabolic analysis is not new,metabolomics is made distinct by itsglobal approach: the attempt to


BY OLIVER A.H. JONES

‘Omics’on the brain

For a relatively newkid on the block,metabolomics has alot to offerneuroscienceresearch.

iStockphoto/Lonely_

simultaneously detect and quantify asmany metabolites as possible. Analysisfor particular metabolite groups mayalso be part of the approach.Metabolomics as a whole is a powerfulplatform to investigate a range ofimportant phenomena. It has beensuccessfully applied to (among others)biomarker discovery and metabolicphenotyping of body tissues (includingliver, kidney, muscle and brain) forvarious disorders, in both human andanimal models of disease. Its versatilityhas seen it successfully utilised infields such as cancer research, clinicalpharmacology and toxicology, drugtoxicity gene function, microbiology,nutrition and neuroscience.

Worldwide, diagnosis of Parkinson’sand Alzheimer’s disease, as well asschizophrenia and depression, amongothers, is on the rise. This isparticularly true of developedcountries with ageing populations.Patients are usually only diagnosedafter significant neuronal damage,largely irreversible, and pathogenicageing mechanisms can furthercomplicate diagnosis and treatment.Most therapies slow diseaseprogression but can’t reverseneurological damage. In recent years,researchers have demonstrated thatmetabolomics can help to addresssome of these issues.

Metabolomics could, for example,lead to faster, more effective and morereliable testing for the diagnoses ofboth neurodegenerative diseases andneurological disorders. NMR-basedmetabolomics is especially useful forthis because it can allow for the non-invasive assessment of metaboliteconcentrations directly in vivo.Metabolomics could also lead to thediscovery and use of metabolicbiomarkers, which could assist withdisease diagnosis, and/or be used inmonitoring the treatment of thepatients. In theory, such biomarkerscould mean that patients could betreated before symptoms appear,reducing the overall neuronaldamage.

Determining useful biomarkers ofbrain disease requires at least someanalysis of affected tissue and/orbiofluids, and a number of challengesare associated with using humantissue, even post-mortem, but withcare and consideration these issuescan be overcome. • Brain tissue is one of the most

metabolically active tissues in thebody. Tissue samples must befrozen rapidly after collection so themetabolites do not degrade.

• It can be difficult to distinguish non-pathological differences – causedby sample collection method, age,gender, genetic background,lifestyle and combinations of these– between control and diseasedsamples. Human patients are likelyto be taking medications (e.g.dopamine agonists and/or levodopa

therapy for Parkinson’s disease) thatmay contribute more to observeddifferences between control anddisease than the underlyingdisease.

• The use of biofluids in braindisorder diagnosis is especiallydifficult because the blood–brainbarrier membrane, whichencapsulates the central nervoussystem, selectively restricts themovement of some metabolites.(However, there have been somereports of the use of blood plasmametabolites and/or proteins asmarkers for neurological disorders). Because of the procedural and

ethical difficulties of using humantissue, animal models are often usedfor the study of neurological diseases.Such samples have many advantages:they can be treated in a uniform way,


Metabolites and analytical approachesAn important feature of metabolites is that, well, there a lot of them – researchersin Canada recently detected 2651 compounds in urine alone. Also, metabolitesexhibit a large dynamic range in concentration, mass and polarity. Thus, no singleanalytical approach can detect and analyse all metabolites in an organism ortissue; multiple analytical techniques and sample preparation strategies arenecessary, but huge gains are being made in this area all the time.

NMR-based analysis is a backbone of metabolomics: it is relatively quick andcheap on a per-sample basis and it is also non-destructive and almost a universaldetector. Although it does, at present, have limited sensitivity compared to massspectrometry based methods the recent development dynamic nuclear polarisation(DNP)-based NMR holds great promise.

GC-MS is often seen as the gold standard in metabolomics. It offers very highchromatographic resolution and increased sensitivity compared with NMR.Searchable libraries of molecular fragmentation patterns also facilitate metaboliteidentification. However, because samples must be in the gas phase for analysis,only volatile, thermally stable compounds can be analysed directly. Nearly allbiological compounds therefore require chemical derivatisation prior to analysis,significantly increasing the sample preparation time. In addition, some largeand/or very polar metabolites cannot be analysed using this method. There hastherefore been a push therefore for LC-MS based methods for lipid based studies.Interpretation of LC-MS based metabolomics data can be quite demanding, butthere is considerable potential in the technique, especially because derivatisationis not required. This sounds bad but both techniques provide huge amounts ofuseful information, as the Wishart team have shown.

Other techniques such as capillary electrophoresis mass spectrometry (CE-MS)are also gaining increasing respect in a variety of bioanalytical applications,including metabolomics.

have the same genetic backgroundand are free from any medications.Several transgenic animal models,from yeast and fruit flies to mice andlarge animal models, are a valuablecomplement to standard smallmammal studies in such casesbecause they have a longer life span(allowing for prolonged temporalstudies) and a larger brain size(allowing easier examination ofvariation within organs). In all cases,metabolite profiles prepared fromintact tissue, tissue extracts andbiofluids have proven to be highlydiscriminatory for neurologicaldisorders. For example, metabolicdeficits in mouse models ofHuntington’s disease and sheepmodels of Batten disease have beencharacterised and suggest aredistribution of neural osmolytes andan alteration in glutamate–glutaminecycling.

Last year was a good year for brainresearch, with both the US and the EUlaunching large research programs. InJanuary 2013, the EuropeanCommission announced plans tospend approximately €1 billion(AU$1.5 billion) over the next 10 yearson the Human Brain Project. In the US,the BRAIN (Brain Research throughAdvancing InnovativeNeurotechnologies) Initiative wasproposed Administration in April and

carries a price tag of US$110 million(AU$120.5 million) in 2014 alone.

Australia is also very well servedwith knowledge in both metabolomicsand neuroscience. For example,Neuroscience Research Australia(NeuRA) (a research institute based inSydney) is a world leader in brain andnervous system research. Brainscience was also the theme of lastyear’s Australian Academy of ScienceTheo Murphy High Flyers Think Tankin Melbourne, in which I took part.Metabolomics Australia has nodesaround the country and offers high-throughput metabolomics services toall life science researchers. RMITUniversity, the University of Melbourneand Metabolomics Australia recentlylaunched the Australia and NewZealand Metabolomics Network, aninterest group for researchers inAustralia, New Zealand and the greaterAustralasian region. This has beenvery successful and the group recentlysigned an agreement with theinternational Metabolomics Society toincrease collaboration.

All of this indicates a great deal offuture potential for metabolomics inneuroscience (and indeed many otherfields). Especially useful will be itsability to monitor subtle changes in aspecific region of the brain, possiblyleading to strategies for targetedtreatment. The integrated analysis of

metabolomics with other ‘omics’ willbe important in providing moresensitive ways to detect changesrelated to disease as well as todiscover novel biomarkers. Newer andmore advanced methods for theacquisition, interpretation andintegration of all omics-based data willbe crucial for establishing validatedand predictive metabolomic modelsfor a wide range of sciences.

Oliver Jones MRACI CChem is a lecturer in AnalyticalChemistry at RMIT University’s School of AppliedSciences. He first came across metabolomics as apostdoc at the University of Cambridge. He continuesto work in the field and is currently the vicepresident of the Australian and New ZealandMetabolomics Network (www.anzmn.com.au).


Sample collection

Sample preparationand metabolite extraction

Chemicalanalysis, e.g. by NMR,GC–MS

Data analysis (multivariate)

Database creation andmanagement

Generation of models for disease prediction

Simplified workflow of ametabolomics experiment

Last year was agood year for brainresearch, with boththe US and the EUlaunching largeresearchprograms.

What is a clinical trial?

A clinical trial is ‘an experimentconducted in humans in order toassess the effects, efficacy and/orsafety of a medicine, medical device,or procedure/intervention’(Therapeutic Goods Administration,Access to unapproved therapeuticgoods, 2004).

How do the phases ofclinical trials differ?

A clinical trial program for a noveldrug compound will usually progressthrough three phases before anapplication for registration andmarketing (see diagram, p.26).

Phase 1 participants (usuallyhealthy male volunteers) are enrolledin cohorts (usually of three) andadministered the compound at aparticular dose. After that dose hasbeen shown to be safe, another cohortof three volunteers will be enrolled at ahigher dose and so on, untilunacceptable toxicities are observedand dose-escalation is terminated. Afurther group of volunteers may then

be enrolled at the last dose shownsafe, to bolster the safety dataset.

No direct measures of the drug’sdisease-modifying activity can betaken because the trial subjects arenot suffering the disease for which thecompound is intended; however,biomarker data, which may indicatesubsequent drug action, can becollected.

In some clinical settings, mostnotably oncology, Phase 1 studies maybe conducted in patients with thecondition of interest. In contrast tohealthy volunteer studies, measures ofdrug efficacy (for example, tumourshrinkage) can be made along withthe usual safety assessments, and forthis reason combined Phase 1/Phase 2studies, which provide both safety andearly efficacy data, are common.

The clinical characteristics ofpatients enrolled in Phase 2 and thenPhase 3 will dictate what subsequentpatient group the drug can bemarketed for and what information thedrug label may contain. Phase 3studies also often compare a new drugof interest with other marketed agents(or a placebo if no other standard of

care exists) to allow claims ofsuperiority over currently availabletherapies, thereby increasing marketshare.

How are clinical trialsregulated?

Clinical trials in Australia are regulatedby the Therapeutic GoodsAdministration (TGA) under theauspices of the Therapeutic GoodsAct. The Act envisages twomechanisms by which clinical trialscan be approved in this country,namely the Clinical Trials Exemption(CTX) and Clinical Trials Notification(CTN) schemes.

The CTX scheme requiressubmission of a substantial dossiercontaining chemistry, pharmacology,toxicology and clinical information,including the clinical trial protocol, tothe TGA. TGA experts are thenrequired to review the submissionwithin 30 or 50 days and issue anapproval to proceed with the clinicaltrial or, more likely, a series of queriesand clarifications. The CTX schememost closely resembles the


Q&A: Clinical trialsBY GREGG SMITH

The 0.01% of novel drug compounds that make it to market havesatisfied requirements well beyond those of clinical studies.

investigational new drug (IND) approval arrangementsin the US (and the CTA scheme in the UK) where centralregulatory approval is required prior to thecommencement of a clinical study.

In parallel with the TGA review, the sponsor submitsthe clinical trial protocol, investigator brochure,informed consent documentation and supporting non-clinical information to one or more human researchethics committees responsible for the clinical trials sitesof interest. Along with TGA approval, ethics committeeconsent is required before a clinical study cancommence.

Given the relative complexity (and cost) of a TGAsubmission, by far the most commonly utilised of the twoschemes is the CTN.

Unlike the CTX, the CTN only requires ethicscommittee approval to undertake a clinical study.Members of the Human Research Ethics Committee(HREC) are therefore responsible for the review of thenon-clinical dossier and clinical trials documents.

Once approved by the relevant ethics committee(s), acompleted ‘Notification of intent to supply unapprovedtherapeutic goods’ (which includes consents from theprincipal investigator, HREC, the study institution and thesponsor) must be submitted by the sponsor company tothe TGA, prior to study commencement. A new CTN isalso required when additional investigational sites areadded to the same trial.

Although the TGA is only ‘notified’ of the conduct of aclinical trial under the CTN scheme, the regulatorretains the right to enquire into a clinical study at anytime and may halt the study should safety concerns orother circumstances require.

Which non-clinical study data arerequired in the regulatorydossier?Data from a diverse range of non-clinical studiessupports the clinical trial application. Although notprescribed by regulation, a significant body of non-clinical biology, pharmacology and efficacy data wouldusually be included in a compound dossier. This data isdesigned to support claims around the mechanism ofaction of the compound as well as its potency, selectivityand other biological attributes.

A suite of toxicology data is also included. Unlikeefficacy studies, guidance for the scope and nature oftoxicology studies is provided by regulatory agencies.For a standard first-in-human Phase 1 study, data fromsingle and repeat-dose toxicity studies in two preclinicalspecies, genetic toxicology and safety pharmacologystudies designed to determine cardiovascular safety(among others) would be undertaken. These studies


1Phase 20–80 participants

2Phase Few hundredparticipants

• Is first dedicated setting to determine activity of new drugin patients

• Drug typically adminsistered at dose selected in Phase 1and may be compared to a placebo

• Drug may be administered in combination with anapproved therapy and its activity compared to theapproved therapy alone

• Collects and assess safety data as a prelude to largerPhase 3 studies

3Phase Many hundredsto thousands ofparticipants

• Data collection for registration and marketing, monitoringof adverse events

4Phase

• After approval of new drug, post-marketing surveillancestudies are frequently undertaken to better define safetyand efficacy in general use

• Most often conducted in young, healthy (usually male)subjects in specialist centres, where participants areintensively monitored for untoward clinical events

• Determines safety, tolerability and pharmacokinetics,dose-limiting toxicities and recommended dose forsubsequent phases

iStockphoto/yganko

iStockphoto/yganko

iStockphoto/yganko

iStockphoto/yganko

would also be supported by formulation analysis and plasmabioanalysis to confirm drug exposure and pharmacokinetics.

CMC (chemistry, manufacturing and controls) informationwould also be available. At an early stage of clinicaldevelopment, this CMC data would include data to supportthe identity, purity and preliminary stability of the drugsubstance under investigation and the formulation in whichthe drug is administered to human subjects.

Which clinical documents areneeded?

Under Good Clinical Practice (GCP) arrangements, theapproved clinical trial protocol is the pivotal documentdirecting the conduct of the clinical study. Other thanemergency medical therapy, all study procedures andanalyses must be detailed in the trial protocol and conductedin accordance with it. Failure to adhere to the protocolrequirements (either intentionally or in error) can be aserious violation of GCP that may endanger trial participantsand impugn the clinical trial itself.

The voluntary provision of informed consent by trialparticipants before their participation in any clinical trial is acentral feature of good clinical practice. To this end, thepatient informed consent form, which provides trialparticipants with a brief background to the study and detailspossible trial outcomes and risks, is a vital feature of the study,which is also approved by the trial ethics committee.

Finally, the investigator brochure is a clear and concisesummary of the drug dataset prepared by the sponsor toassist medical staff working in the trial. Key features of thebiology, pharmacology, toxicology and clinical experiencewith the compound must be included to facilitate the safety oftrial participants.

How many new drugs actually reachthe market each year?

The business of drug development is inordinately expensiveand risky. Total investment required from discovery to marketlaunch has been estimated well in excess of $1.5 billion.

Despite this investment, it is estimated that only one in10 000 preclinical compounds survive the drug developmentprocess and reach the market. Furthermore, 19 of 20compounds that have successfully reached Phase 1 clinicaltrial will ultimately fail prior to approval.

In 2011, only 30 new drugs were approved by the Foodand Drug Administration (FDA) in the US, with 24 of thesebeing new chemical entities and six being biological agents,such as antibody therapies. A similar number of new drugswas approved by the FDA in 2012, with 35 new agents in total,of which approximately half were new chemical entities.

Gregg Smith is Director of Smith Pharmaceutical Consulting, a strategic clinical andnon-clinical development consultancy provider for the biotechnology industry.


raci.org.au/resourcecentre/chemaust

Your member magazineand other great reads View the latest issue or archives ofChemistry in Australia, and access otherpublications such as tce, magazine ofthe Institution of Chemical Engineers.

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A pioneer of research in organicelectronics, Professor AndrewHolmes MRACI CChem, has beenelected as the next President ofthe Australian Academy of Science.He will assume the role after theAcademy’s next Annual GeneralMeeting in May 2014. Thepresidency alternates between thephysical and biological sciencesand the term lasts for four years.

Holmes is a Laureate Professorof Chemistry at the University ofMelbourne’s Bio21 Institute, aCSIRO Fellow and a DistinguishedResearch Fellow in the Department

of Chemistry at Imperial College London.The current President of the Australian Academy of Science,

Professor Suzanne Cory, said the Academy will benefit greatlyfrom Holmes’ international reputation and experience.

‘Professor Holmes will lead our Academy with greatdistinction, energy and integrity,’ she said.

‘As Foreign Secretary, he has worked tirelessly on behalf ofthe Academy and its programs, with the deep conviction thatAustralia’s future prosperity depends on strong research andeducation in science and mathematics and in further developinginternational science linkages.’

Holmes graduated in chemistry from the University ofMelbourne and pursued PhD studies at University CollegeLondon. He then moved to Cambridge University, where he hadan illustrious career, becoming Professor of Organic and PolymerChemistry and Director of the Melville Laboratory for PolymerSynthesis.

In the1990s, Holmes achieved international prominencewhen, in collaboration with Cambridge physicists in England,the team developed a new class of light-emitting polymers.These polymers transformed technology for televisions andcomputers with lightweight, super-thin, flexible video screensbright enough to be viewed even in direct sunlight.

He returned to Melbourne in 2004 as a Federation Fellow toestablish a laboratory at the then newly established Bio21Institute. He was instrumental in forming the Victorian OrganicSolar Cell Consortium.

Holmes has been accorded many honours. In 2000, he waselected a Fellow of the Royal Society and awarded itsprestigious Royal Medal in 2012. He was elected a Fellow of theAustralian Academy of Science in 2006 and appointed a Memberof the Order of Australia in the 2004 Australia Day Honours list. AUSTRALIAN ACADEMY OF SCIENCE

RACI Fellows receive 2013 NSWScience & Engineering AwardThe 2013 NSW Science & Engineering Awards were held at NSWGovernment House on 1 November 2013. The event was hosted byHer Excellency, Professor Marie Bashir AC CVO, Governor of NewSouth Wales, who is also Patron of the Awards. The Master ofCeremonies was NSW Chief Scientist and Engineer, Professor MaryO’Kane, and the evening was quite splendid, as one might expect.

It was also very pleasing that of the nine awards given on thenight, four were awarded to Fellows of the RACI. Indeed, thewinner of the most coveted award, NSW Scientist of the Year, wasamongst these, and another went to our current Hon Gen Sec.

The RACI Fellow awardees were:• Laureate Professor Graeme Jameson, Chemical Engineer and

Director of the Centre for Multiphase Processes a theUniversity of Newcastle – 2013 NSW Scientist of the Year

• Professor Martina Stenzel, Co-Director and ARC Future Fellowat the Centre for Advanced Macromolecular Design at theUniversity of New South Wales – Excellence in Engineeringand Information and Communications Technologies

• Scientia Professor Justin Gooding, ARC AustralianProfessorial Fellow at the University of New South Wales –Emerging Research

• Professor Thomas Maschmeyer, ARC Future Fellow at theSchool of Chemistry at the University of Sydney – RenewableEnergy Innovation

Roger Read FRACI CChem

28 March 2014

raci news

RACI member elected President ofAustralian Academy of Science

RACI National Awards2014: dates for your diaryOne of the most important duties of the RACI is therecognition and promotion of the contributions andachievements of our members.

There are a range of prestigious awards covering a broadrange of areas from school education to applied researchthat are aimed at the full range of members from PostGraduate Students through to Distinguished Fellows.

These awards are open to all members of the RACI whomeet the specific award requirements. Some can be appliedfor while others require nomination by third parties.

Multiple candidates for each award will enable the juriststo select the most deserving recipients and thus the Boardappeals to members to review the available awards andensure all appropriate candidates are proposed.

The awards will be listed at www.raci.org.au/awards inMarch, together with the criteria requirements and proposalmethods. Any other information can be requested by emailfrom [email protected] or by phoning (03) 9328 2033.

The opening date for submissions is 1 April 2014 and thedeadline is 5 pm EST on 30 June 2014.

The presentation of the awards will be at a special dinnerto be held at the end of the year.


new fellows

Professor Amanda Ellis iscurrently an Australian ResearchCouncil Future Fellow (2014–17),Chair of the RACI PolymerDivision and an academic atFlinders University in Adelaide.Originally from New Zealand, sheobtained a New ZealandCertificate in Chemistry in 1990and worked in industry for AjaxLtd and Pentex Allcolour – asubsidiary of ICI. After leavingNZ, Ellis completed a BSc(Applied Chemistry (Hons)) andthen a PhD (Applied Chemistry)

at the University of Technology, Sydney, graduating in 2003.Supervised by Professor Mick Wilson, she investigated theinfluence of organic inputs (humic acids and carbohydrates)into the Bayer process.

Ellis started postdoctoral research at Rensselaer Polytechnic(starting her career in nanotechnology), and then went to NewMexico State University. During this time, she was instrumentalin the use and development of Raman spectroscopy toinvestigate carbon nanotubes for molecular electronics,discovering a new mode of molecular vibration. Importantly,modification of this mode led to easier attachment of polymerto nanotubes and a full US patent related to reversible additionfragmentation chain transfer (RAFT) polymerisations. Herinnovative research also resulted in two international patentson nanotube–organic photoelectric conversion devices andnanocomposite for enhanced rectification.

In 2004, Ellis returned to NZ upon receiving a New ZealandFoundation of Science and Technology Fellowship (one of 16) toundertake research with Distinguished Scientist ProfessorJeffery Tallon in the area of microfluidic design and fabricationand submitting two provisional patent applications.

In late 2006, Ellis commenced as a lecturer in ateaching/research position at Flinders University. Since then,she has pioneered the successful integration of polymer science,nanotechnology and microfluidics with fundamental biologicalsystems. She was awarded the Vice Chancellors Early CareerResearcher Award in 2010. Most recently, she has developed aparadigm shift in DNA analysis, using toehold-mediated DNAstrand displacement reactions linked with polymer-basedsystems for genotyping and the analysis of forensically relevantgenes.

Ellis has been instrumental in the establishment of theFlinders Centre for Nanoscale Science and Technology and theClean Technology Degree at Flinders. She is a strong advocate ofbroad collaborative research and networking key expertise tosolve important fundamental scientific problems. She believes itis of upmost importance to inspire, motivate and mentor thenext generation of scientists.

Associate Professor PaulFrancis received a BSc(Hons)in 1999 and a PhD inanalytical chemistry in 2003from Deakin University. Hecurrently holds an AustralianResearch Council FutureFellowship, administered byDeakin University, with LaTrobe University (Australia)and the University ofManchester (UK) as ‘hostinstitutions’. His fellowshipprogram of research is focusedon the development of highlysensitive luminescence-based detection systems for applicationsin areas such as clinical diagnostics and illicit drug screening.

Although fascinated by science and mathematics from anearly age, Francis credits a fortuitous meeting and discussionwith Professor Neil Barnett at Deakin University in 1994 withsparking his interest in a career in the field of chemistry. Yearslater, Francis would collaborate with Barnett on an extensiveand on-going series of investigations into the fundamentalchemistry and spectroscopy of chemiluminescence (chemicalreactions that produce light).

Francis’s other research interests include the assessment ofbiomarkers of oxidative stress, new approaches to point-of-caretesting using mobile-phone-based sensors, and the developmentof novel reagents for photoredox catalysis. He has over 100publications and has been recognised by such honours as aVictoria Young Tall Poppy Science Award (The AustralianInstitute of Policy and Science), and the RACI Robert CattrallMedal. He has been an active member of the RACI and iscurrently the Secretary of the Analytical and EnvironmentalChemistry Division.

new fellows obituary

Growing up in the 1940s inwestern Adelaide where there wasa factory on every second corner,John Mason continually badgeredfactory workers with the usualhow’ and ‘why’. Inadequateanswers led to much libraryreading, and it soon becameapparent that chemical processeswere the least understood. Froman early age, he decided that hewanted to answer such queries ina clearly understandable manner.

Following secondaryeducation at Adelaide TechnicalHigh School, Mason worked as a

laboratory assistant in Pope Products Ltd, a typically diverselocal industry making domestic white goods, irrigationequipment, industrial electric motors, television sets andgardening equipment. The job included chemical analyses andinvolvement in process control of the operations in thefactories. Evening studies at the SA School of Mines andIndustries (later to become SA Institute of Technology and thenthe University of South Australia) led to a Certificate inAnalytical Chemistry and later an Industrial MetallurgyCertificate. He developed a strong interest in the science ofcorrosion and its prevention. After a short spell at PhillipsElectrical Ltd, Mason became an analyst at GM-Holden Ltd.

Holden encouraged him to undertake part time study for aBSc (Chemistry) at the University of Adelaide. Graduating in theearly 1980s, Mason joined the RACI and became involved in SABranch Committee and the local Industrial Chemistry Group,chairing that group for a short time. During the late 1980s, hebecame heavily committed to upgrading Holden paint finishquality to compete in international markets. This included theplanning, engineering and commissioning of a moderndedicated factory, leading to his becoming Area Manager ofVehicle Painting Operations, responsible for the successfuloperation of not only the chemical processes, but plant,equipment, financial and people management of the operation –a demanding role from which he retired in late 1999.

Mason then re-energised his life in RACI, becoming Convenorof the SA Retired Chemists Group, representing that group onthe SA Branch Committee since 2002. Retirement allows time toenjoy SA Branch events – especially the yearly Murder Mysteryand Science Alive. He stays fit by cycling and enjoys his closefamily life.

He has never regretted taking his formal education nofurther, considering that he was too busy improving hisunderstanding of work-related sciences and building aworldwide network in his many interest fields. He advises youngchemists to never quit learning, and always build friendshipswith others sharing their science, something that RACI can ablyfacilitate.

Professor Roland DeMarco received the RACIBloom-Guttmann award forthe best paper by a youngauthor under 30 years ofage, and was awarded the2008 RACI Lloyd SmytheMedal for excellence inresearch in analyticalchemistry.

From 1990 to 1992, DeMarco worked as a researchscientist at CSIRO Mineralsin Melbourne, undertakingresearch on lead–acidbatteries. He spent three years between 1992 and 1995 workingas a lecturer in physical and analytical chemistry at theUniversity of Tasmania. In 1995, he joined Curtin University ofTechnology, served as its chemistry department head from 2001to 2007, and was promoted to professor in 2006. From July2007 to December 2009, he served as Dean of Research in theFaculty of Science and Engineering at Curtin University,presiding over 300 teaching/research and research staff in afaculty comprising comprehensive activities across a diverserange of disciplines, leading to his subsequent appointment asAssociate Deputy Vice-Chancellor (Research Strategy) at CurtinUniversity in 2010. In January 2011, De Marco took up theposition of Pro Vice-Chancellor (Research) at the University ofthe Sunshine Coast.

De Marco also leads a small research team of students andstaff undertaking research in the field of electrochemicalsurface and interface analysis and electrochemical sensors, hasprocured over $8 million in competitive research funding andhas published over 100 refereed publications in the field. Hestill makes time to work in the laboratory with his researchteam, and he engages in his love of synchrotron and neutronscience by participating in cutting-edge experiments onrelevant beamlines at the Australian Synchrotron and ANSTO inpartnership with his graduate students, postdoctoral staff andcollaborators. He relishes the challenges and rewards of thesecomplex and difficult experiments, and the more difficult theexperiment, the greater is his propensity for the work.

De Marco is a family man, and is devoted to his wifeCatherine Anne and his children Sebastian Thomas and EmilyCaitlin.


new fellows obituary

Dr Renate Griffith was bornRenate Keller and grew up inGermany, and studied chemistry atthe Johannes GutenbergUniversität in Mainz, where shealso undertook her studiestowards her Diplom and PhD inpolymer chemistry. Griffith andher husband of nearly 30 years,David Griffith FRACI CChem, metand married in Germany. Griffithmoved to Australia with herhusband in 1986, on hisappointment to the University ofWollongong. Over the years and

with a long interruption due to raising their two, nowgrown-up children, Griffith has developed a career as anacademic with positions first at the University ofWollongong, then at the University of Newcastle, and nowat the University of New South Wales, where she is anassociate professor in pharmacology in the School ofMedical Sciences.

Griffith has successfully supervised or co-supervised 12PhD students and a large number of Honours students. Sheenjoys undergraduate teaching, in particular herinvolvement in the new Medicinal Chemistry degree at theUniversity of NSW. Her research interests are in computer-aided drug design and span several collaborative projects,often with chemists at the University of NSW. A long-standing project concerns the discovery of novel smallmolecules to modulate adrenergic receptors; other projectsare in the areas of novel antibacterial and anticanceragents. She has published 57 papers in peer-reviewedjournals, several in highly ranked journals in differentdisciplines. A recent highlight was an invitation to speakat a Gordon Conference on DNA topoisomerases in August2014.

Griffith’s ‘home’ in RACI at first was in the OrganicDivision, but then quickly changed to ‘MEDAG’, as it wasthen known. She has been involved in the organisation of anumber of conferences of that Division, starting withMEDAG’98 in Wollongong, and has been a long-standingcommittee member, and saw the name of the Divisionchanged from Medicinal and Agricultural to BiomolecularChemistry. As Division Chair ,she instigated the most recent(hopefully the last) name change to the current name ofMedicinal Chemistry and Chemical Biology. As immediatepast-chair, Renate is currently taking a brief ‘holiday’ fromthe Division, but is still involved in the next NationalCongress program organisation.


Fred Sanger, 1918–2013A remarkable manFred Sanger, who died onTuesday 19 November 2013,aged 95, was the quiet giant ofgenomics, the father of an areaof science that we will explorefor decades to come.

His achievements rankalongside those of FrancisCrick, James Watson, RosalindFranklin and Maurice Wilkins indiscovering the structure ofDNA. In research marked bytwo Nobel Prizes, he developed methods that allow us todetermine the order of the building blocks of DNA and ofproteins. This technique allowed the languages of life to beread.

Because of Sanger's work, we have been able to interpretthose languages and to use that knowledge for good.

‘Fred was an inspiration to many, for his brilliant work, forhis quiet determination and for his modesty. He refused mostinvitations for interviews, but often helped schools andstudents,’ said Professor Sir Mike Stratton, Director of theWellcome Trust Sanger Institute.

‘Fred won two Nobel Prizes. His work for his second Prize, amethod to decode DNA, has transformed our understanding oflife on Earth and is the foundation of developments inhealthcare from understanding inherited disease to developingnew cancer treatment.

‘It was an honour for this Institute when Fred acceded tofounding Director John Sulston’s request that we be namedafter him. Fred’s only stipulation was that “It had better begood”.

That typically Fred response is our inspiration and willcontinue to be so.’

Sanger developed methods that allow us understand theblueprint of life. His findings spurred research that, today,brings benefits to patients around the world.

Without his method to understand the structure of proteins,we would not have efficient treatments such as insulin.Without his method to decode our genetic material, DNA, wewould not have the treatments for breast cancer, melanomaand infectious disease that have been developed in recentyears.

Our programs to develop vaccines for malaria are builtentirely on understanding DNA sequence, on Sanger's methodsand their descendants. Or, as he would say, carefullyacknowledging his co-authors, on the method of Sanger,(Steve) Nicklen and (Alan) Coulson.WELLCOME TRUST SANGER INSTITUTE

Find out how to accessdecision-makers in:

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Molecularfluorescence,principles andapplicationsValeur B., Berberan-Santos M.N., Wiley-VCH,2nd edition, 2013, soft cover, 569 pp., ISBN9783527328468, $140

Molecular fluorescence is a usefulchemical phenomenon that is familiarto any undergraduate chemistrystudent, and its versatility has found

application in a wide range of fields. As a result, there havebeen numerous books written on the topic, such as J.R.Lakowicz’s seminal Principles of fluorescence. So, in reviewingthe updated Molecular fluorescence by Valeur and Berberan-Santos, the real question becomes, is there need for anotherfluorescence book, given that the fundamental properties andtechniques have been essentially the same for decades. If yourapplication is fluorescence chemical sensing and applyingfluorescence to biology and medicine, then the answer is yes.The coverage of these topics is what sets this book apart fromothers on fluorescence. The fluorescence chemical sensingchapter is especially insightful and thorough, with all majorareas covered, such as pH, molecular recognition, ions, gasesand other chemical environmental indicators. The application offluorescence in biology and medicine is where the majority ofrecent advancements in fluorescence have been made, and theauthors do this field justice with a strong coverage offluorescence labelling.

Most of the text is devoted to fluorescence theory andtechniques, and the discussion is thorough with good examples,though not that original when compared with otherfluorescence texts – there are only so many ways to describeground and excited states. One of the most interesting parts ofthe book for me was the very end, where fluorescenceapplications in forensics, counterfeit detection and art werediscussed. These were applications that showed the trueversatility of fluorescence spectroscopy, and hopefully they willbe elaborated upon in future editions.

Colin Scholes MRACI CChem

Chromatography –basic principles,sample preparationsand related methodsLundanes E., Reubsaet L., Greibrokk T., Wiley-VCH, 2014, soft cover, 200 pp. approx., $62.95,ISBN 139783527336203

I was impressed by this book andgreatly enjoyed reading it. The authorshave successfully ‘captured’chromatography in 200 pages, and thatbrevity is remarkable.

The text is clear, concise and to the point. There areexcellent Info Boxes interspaced throughout the chapters,which elaborate on the main text. There is good coverage of theprinciples of chromatography and different forms ofchromatography, with the exception of paper chromatography,which the authors have omitted deliberately because of itsclaimed lack of current applicability. Readers may notnecessarily agree.

Related methods, in particular electrophoresis, are discussed,as is relevant and informed speculation about the futureprospects of various techniques. Illustrative, clear examples ofresults obtainable with the techniques are appropriatelyinterspersed throughout the book. There is good referencing atthe end of each chapter to the appropriate review literatureand/or original source materials.

Sample preparation techniques are reviewed in an excellentchapter, which ought to be compulsory reading for all aspiringanalysts.

Inevitably, brevity comes at some cost. The narrative of thedevelopment of chromatography, the human and social context,is not covered. While that is a positive for brevity, and ideal ifyou are just looking for the ‘hard core’ of the field, if you areinterested in the context of science, the people and thecircumstances driving the discovery and development ofchromatography, then you will not find it here. The detailbehind development of formulas and equations is alsofrequently omitted. However, the Info Boxes and the chapterreferences guide you to where you can find it. If you just wantthe ‘answer’, it is there: if you want the detail, you are directedappropriately.

This book is an excellent introduction to chromatography fornon-specialists. It very efficiently and effectively encapsulateschromatography. Within the limitations outlined in the previousparagraph, it would be a first-rate choice as a textbook for anundergraduate course in chromatography: brief, reasonablycomprehensive, well written with clear guidance to furthersources, and reasonably priced.

R. John Casey FRACI CChem

books


John Wiley & Sons books are now available to RACI members at a 25%discount. Log in to the members area of the RACI website, register onthe Wiley Landing Page, in the Members Benefits area, search andbuy. Your 25% discount will be applied to your purchase at the end ofthe process.

If you want to scare people these days, announce chemicalnames in a sombre voice. The pervasive public mistrust ofchemicals rings true to many chemists, no matter their sectoror field of chemistry.

Public ignorance about how chemicals are linked to everyaspect of our lives is understandable. But what about a basicappreciation of the innumerable positive contributions – soap,pharmaceuticals, materials and food preservation, to name justa few – of chemistry to society? Unfortunately, the negativeassociations – related to the environment and to people – faroutweigh positive awareness. Chemicals are more readilythought of as harmful than good.

Some segments of the media are partly to blame. Bad newsdoes sell! According to consumer psychologist Adam Ferrier, ‘wewere born with a disposition to focus on the negative’ (RetailWorld, 20 September 2013). All it takes is one media story withan angle that generates fear or outrage – babies, pregnancy orcancer usually does the trick – for the message to go viralonline. Some activist groups also exploit this innate negativebias, employing scare tactics to advance their agenda. Add tothis a general decline in scientific literacy, and perhaps even acultural legacy of literature, film and television – think theiconic ‘mad scientist’, usually a chemist – and the presentsynonomy of ‘chemistry’ and 'harm' becomes easier tounderstand.

The formulated chemical products industry is not immune tothe effects of chemophobia. Many messages about the safety ofproducts such as household cleaners and personal care productsstate concerns for which there is little scientific basis. Whetherit’s claims that lipsticks contain dangerous levels of lead or thatphthalates increase the risk of premature birth, these urbanmyths continue to lurk online, waiting to again be fanned intoflame.

Smartphone apps that scan and rate cosmetic products are arecent example of what the industry has to face. Alarmingly,one such app ‘red flags’ all petrochemical ingredients andfragrances, as well as all of the usual suspects – certainingredients such as parabens for which the body of evidencepoints to safety, but which nevertheless are targeted again andagain.

Recognising that rational debate about the safety of ourindustry’s products is often hijacked by a range of myths andmisconceptions, Accord, the industry body for hygiene, cosmeticand specialty chemical products, developedwww.furphies.org.au.

The aim of furphies.org.au is to address unfounded publicalarm by helping put safety myths about everyday products intoproper perspective. The website covers issues relating tocosmetics and personal care products, household cleaningproducts, specific chemical ingredients, and chemical categoriessuch as nanomaterials and preservatives.

For each topic, the myth is identified and the evidenceexamined. Evidence includes research publications and reviews;opinions of expert bodies such as the European Commission’sScientific Committee on Consumer Safety and the US CosmeticIngredient Review Expert Panel; and positions taken byAustralian and overseas regulatory agencies and healthorganisations, such as the American Council on Science andHealth and the International Agency for Research on Cancer. Foreach issue, ‘the bottom line’ summary shows where the weightof evidence lies.

The Furphies website also aims to tackle a number of generalmisconceptions arising from poor scientific literacy. Essential inteaching the value of evidence, the ability to question claimsand how to draw evidence-based conclusions, scientific literacyis key to making informed decisions about issues of health andwellbeing in daily life. With the Office of the Chief Scientist’s2012 Health of Australian Science report describing decliningparticipation rates in secondary and tertiary sciences (see box),including chemistry, there is little wonder that Australia’sscientific literacy has been identified as slipping.

Poor scientific literacy opens the door to a host ofmisconceptions: ‘natural’ substances being perceived as


Fact versus furphyUnfounded fear about chemicalsand everyday chemical productsprompted the start of Accord’sconsumer information website.

chemical furphies

iStockphoto/gcoghill


inherently safer than man-made substances; hazard beingconfused with risk; a nonsense concept such as ‘chemical free’as a desirable product attribute! The Furphies website addressesthese and more issues relating to scientific literacy. And theseare clearly messages that have an audience – website statisticsreveal ‘what are chemicals’ to be the most common searchphrase for all traffic to the site.

Why do these misconceptions matter? As Trevor Butterworthfrom the Statistical Assessment Service, George MasonUniversity, US, puts it, ‘if we fear everything, we’re not going totake the genuine risks to our health seriously’. Among the manyreal health and safety risks that do deserve our attention areinfectious disease and illness spread through poor hygiene, andthe serious skin damage caused by UV radiation. Both of thesecan be mitigated through judicious use of everyday productssuch as handwashes and sunscreens.

Speaking at a recent Accord conference, AustralianGovernment Chief Medical Officer Chris Baggoley said thatunfounded safety fears about chemicals can ‘… misdirectimportant efforts to protect and improve public health. Furphieshelps put chemical risks into perspective in a balanced andevidence based way. As a result it plays a valuable role infurthering the public health agenda.’

Negative public perceptions have still broader implications.The European Chemical Industry Council identifies publicopinion as ‘a powerful “driver” of the chemical industry’sbusiness environment’. Because this same public forms theconstituency of politicians, public opinion is ‘a strong catalystfor regulatory initiatives in the political arena’.

Safety is the number one priority for the formulatedchemical products industry and Accord supports an effectiveregulatory framework that is proportionate to risk. Butoverregulation has broadly negative impacts, ranging fromlimited access to new ingredients, decreased efficiency and highoperating costs, which can in turn stifle innovation andmanufacturing in Australia. Flow-on impacts for consumersinclude increased costs or lack of access to the latest, mostinnovative products widely available overseas. It wasn’t untilearly 2013, following long-awaited regulatory changes, thatAustralian consumers could access SPF50+ sunscreen, a product

available overseas for several years. Of course the image of a fundamental science is also at

stake. If chemistry is perceived as an undesirable career choice,Australia’s proud record of world-class research output,innovation and collaboration could be at risk in the longerterm.

Accord hopes that Furphies will bring some balance to theperception of safety issues relating to chemicals and everydaychemical products. We encourage anyone who is interested inpromoting more balanced thinking about chemicals andeveryday chemical products to spread the word aboutfurphies.org.au.

Jennifer Semple MRACI CChem is Education and Sustainability Manager at Accord.This is the first in a series of articles relating to chemical furphies.

The aim of furphies.org.au is toaddress unfounded publicalarm by helping put safetymyths about everyday productsinto proper perspective.

Declining science, decliningscience literacy• In 1992, 90% of year 12 students in Australia studied

science; in 2010 this had fallen to 50%.• In 1992, nearly 23% of year 12 students in Australia

studied chemistry; in 2010 this had fallen to just over17%.

• Internationally, Australian secondary students rankabove the OECD average for scientific literacy but haveslipped from third in 2000 to sixth in 2009.

Office of the Chief Scientist, 2012, Health of Australian Science. AustralianGovernment, Canberra

Online indexesThe latest Chemistry in Australia indexes are now online.Browse or search our archived back issues from 2003onwards.

To view the latest indexes, visit www.raci.org.au/resourcecentre/further-information/indexes.

iStockphoto/Onur Döngel

energy

My observation of and bewilderment at theworkings of nature never cease. The more questionsI have asked (of my father, myself and mymentors), the more the true complexity of systemshas been revealed. When I was ten, during a familytrip through North Dakota, a tyre blew on our 1974Mercury Brougham. I eagerly got out of the car tohelp my dad and was utterly shocked by how hotthe tyre felt. When I asked about it, my dadshrugged it off and said ‘friction’, but that momentand many like it have stuck.

That first experience taught me that at leasttwo forms of energy are produced when we ignitepetrol. Of course, I learned later on that manyenergies are released during energetic events, andthat those energies could potentially be harvestedand put to work. I eventually found out thatcertain materials, such as piezoelectric crystals, can respond tothermal, physical, electrical and magnetic distortions, and, ifproperly induced, can produce electric current.

Piezoelectric crystals are part of a broad class of crystals,which includes both pyroelectrics and ferroelectrics. Allferroelectrics are piezoelectric, although the converse is notnecessarily true. Piezoelectrics exhibit a temporary electricmoment when applied mechanical force deforms the substance,and, conversely, exhibit a distortion in dimension when anelectric field is applied. The process is reversible and produces anet, non-zero potential (the useable work part). All three typeshave a common theme: the atoms that make up their unit cells(the basic counting unit in crystallography) either exhibit orcan be induced to exhibit some sort of cooperative asymmetry.This asymmetry results primarily from two sources: geometricskew and dissimilar metals.

Arguably, the most common type of piezoelectric crystal isthe mineral type perovskite. The most general molecular formulafor perovskites is ABO3, where A and B are the vertex andcentral metals (see diagram), respectively, with three oxygenatoms – the red balls at the vertices. Convince yourself of thisformula by doing a little mental slicing of the spheres that liealong the geometric axes of the cuboidal object shown,followed by some arithmetic.

Charge compensation has to be maintained, but the twometals A and B are always different: they have aliovalentoxidation states, different coordination shells and dissimilarionic radii (piezoelectrics are predominantly ionic, with verylittle covalent character). These factors contribute to the unit-cell distortion these crystals demonstrate.

Of course, this diagram belies the complex electron densitiesof these ions. Coulombics win out, so the unit cell can exist ina lowest energy state, but these factors contribute to thespatial stress found in these materials (more about this below).Ultimately, the asymmetry results in a non-zero dipole moment

within the unit cell. It is this non-zero dipole moment that canpermit current production. When the cell is subjected to someexternal stress, the ability of the unit cell to polarise anddepolarise, relative to its inherent dielectric value, is how low-level AC current is ultimately generated.

Mentally connect the eight teal balls in the diagram andyou’ll see that it is a cube. Quite often, unit cells ofpiezoelectric crystals do not have 90° crystallographic axes.This means that the axes, made up of the atoms that constitutethe octahedra of the unit cell (the vertices of the cube,depicted in teal) are slightly canted, relative to each direction.As a result, these unit cells are classified in rhombohedral ortetragonal space groups. Furthermore, the octahedra themselvescan be canted, relative to their six nearest neighbours.

Upon closer inspection, you will see that the metals thatoccupy the ‘A’ position are surrounded by six oxygen atoms each(the red balls). The axial and off-axial movements of these MO6

octahedra are critical to how piezoelectrics produce current.*By now you may have guessed (if you didn’t know) how

piezoelectrics work: the pre-canted MO6 octahedra are skewedusually because of a combination of bulky cations in the A andB positions and the tendency towards a lowest-energy state forthe unit cell. So, in some fashion, these crystals can be stressedsuch that they are depolarised.

If you recall your electricity and magnetism or your physicalchemistry course(s) (ugh, really? Do I have to?) the definitionfor current (I) is actually ∂V/∂t, since the change inpolarisation represents a synonymous change in voltage, perunit time. Shown here is a nice polarisation/electric field curve


Piezoelectrics: chemistry and innovations

*For more information on these systems, read Goodenough J.B. and Zhou J.S. (J.Mater. Chem. 2007, 17, 2394–405), and the excellent book by Bonin K. andKresin V. (Electric-dipole polarizabilities of atoms, molecules and clusters, WorldScientific, 1997).

Generic perovskite

(light black), combined with displacement (thick black) on aform of very popular piezoelectric material, lead-zirconatetitanate (PZT).

Piezoelectrics need to fall into this ‘sweet spot’: somehysteresis has to occur, but not too much (or the processbecomes irreversible) and not too little (ferroelectric behaviourwith little net, non-zero dipole moment). One final note on thediagram: you’ll note at the bottom that the x-axis reads ‘appliedvoltage’. Well, the beautiful reversibility of piezoelectrics comesinto play here: piezoelectrics can either produce inducedpolarisation by displacement or become displaced by an appliedvoltage.

Your common doorbell, elevator tones and children’s toysvery often have piezoelectrics at their core. Find a toy or an olddoorbell set-up, locate the crystal, get out your multimeter andstart tinkering!

March 2014 | 37Chemistry in Australia

Piezoelectrics at work A number of businesses around the world are trying toexploit the piezoelectric effect. Although the energy-scale issue is a troubling one, researchers are going bothsmall and large to harvest energy from mechanicaldisplacement.• In Israel, Innowattech (www.innowattech.com) has

implemented piezoelectric crystals in a number ofapplications, including construction and insertion ofpiezoelectric pads in roadways and railway ties.

• IDTechEx (www.idtechex.com) is an excellent resourceto read up on the technologies and the companiestrying to produce commercial success frompiezoelectric science.

• Researchers at MIT have developed a nice method ofharvesting usable energy from both vibrational andthermal sources within the same crystal(http://ieeexplore.ieee.org/xpl/articleDetails.jsp?reload=true&arnumber=6225400).

• In a clever departure from straight-up engineeringthemes, Dutch company Sustainable Dance Clubprovides supplemental power from dance floors(www.sustainabledanceclub.com). The city ofToulouse, France, has joined the party by using thiscompany’s technology to power local streetlights.

• My colleagues John Palumbo, Robert Miller and I havepatented a spray-on crystal system withaccompanying electrically collimating crystallinesubstrate. With about 100 mW/cm2, we believe we cantake advantage of the large surface area (about110 kilometres of Long Island Expressway I-495),combined with high vehicle volume here in New YorkCity (about 8000 cars per hour for 15 hours a day) inan all-weather application.

Dr Stephen Boyd is currently CEO of Havelide Systems, Inc., anenergy IP company in New York. He has degrees in solid-statechemistry, international finance/political science. He is particularlyinterested in molten salts and in piezoelectrics as energy sources,with several patents filed. He has no affiliation with any of thecompanies listed.

Dutch company Energy Floor’s Sustainable Dance Floor converts the kineticenergy of dance into electricity, which powers LED lights in the floor. Theelectricity can also be fed back into the grid.

Change in polarisation versus applied voltage with displacement for lead-zirconate titanate. Adapted from Iijima T., Ito S., Matsuda H., Dugnani R.,Chang F.-K. Mater. Trans. 2004, 45(2), 233–5.

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technology & innovation

The first industrial revolution was driven by the introduction ofwater and steam power, which allowed manufacturing machines toreplace human labour. The second industrial revolution was a20th-century phenomenon initially in the West, heralded byassembly-line production but still using relatively low-skilledlabour. The third industrial revolution was a result of theintroduction of electronics, modern optical technology,communications technology and the internet, leading to thelargely automated production of ‘high-tech’ products in factories.

There is now talk of a fourth industrial revolution. InGermany, they have started the Industry 4.0 project whichpromotes the ‘Smart Factory’. The key characteristics of a SmartFactory are adaptability and resource efficiency as well as theintegration of customers and business partners in business andvalue processes. What this means in English is that (a) therewill be virtually no people in the factories, (b) customers willbe able to order products via the internet and the products willbe automatically manufactured and delivered without humanintervention, and (c) factories will be highly configurable, i.e.able to automatically switch between product variationswithout requiring either human intervention or downtime. Thislast point is important since it allows the massive technical andfinancial input into Smart Factories to be amortised over moreproducts, thus maximising the utilisation of factories, therebyallowing the investment in the first place.

Today, Germany is a leader in manufactured products andmanufacturing equipment. It makes a lot of sense for Germanyto invest today’s profits from its manufacturing sector into amore efficient next-generation of manufacturing technologies.Ultimately, their goal is to reduce the cost of manufacturedgoods as well to enable new and more complex products to bemade.

However, the Germans do have competition and it is notnecessarily the Chinese; it is from ‘distributed manufacturing’(let’s call it Industry 5.0 or the fifth industrial revolution) that isdeveloping concurrently. An example is the 3D printer. Over time,I expect many more manufacturing technologies to be developedthat disintermediate (bypass) the ‘factory’. True, raw materials maystill be made in (chemical) factories, but then higher-levelfabrication will be done at the end-user site, cutting out Industry4.0 entirely. Apart from 3D printing for plastic and metalcomponents, we already have printers for printed circuit boards,and a quick glance at Kickstarter highlights many other ideas indevelopment. There is also a focus on the development of low-cost robots, allowing the fabrication of complex products from 3Dprinted components at the end-user site. One goal of thedistributed manufacturing movement is machines that self-replicate without human intervention!

You may ask whether making products in your home or officeis cost-effective. A factory-based manufacturing process isgenerally far more efficient and adds less cost to the incomingraw materials in the process of making the end product.

However, as soon as product leaves a factory, transport costsand distribution and retail margins get stacked on top and thecost-benefits start getting frittered away. In addition, thecompetition, distributed manufacturing, pays a much lowerpremium for intellectual property, i.e. by one means or another,patent and design rights are less enforceable when the productsare made by the end user. Finally, when you make your ownproduct, you get instant gratification and the potential for ahigher degree of customisation. Where near-equivalent costscan be achieved, I suspect that Industry 5.0 will ultimatelybeat Industry 4.0.

Industry 5.0 may ultimately challenge most currentmanufacturing processes but the tougher challenges will be inthe capital-intense processes (e.g. LCD manufacturing), ‘wet’manufacturing processes and the chemical manufacturingprocesses. Large-scale homogenous products with wetmanufacturing steps, e.g. gypsum wallboard, may be the last tofall. However, taking this example further, eventually the wholeconcept of building a house may be re-thought. Here inAustralia building materials now represent only around a thirdto a half of the finished cost of a house – labour and servicesrepresenting the rest. This represents a large opportunity foronsite or offsite automated fabrication. This may mean there isan opportunity to abandon traditional building materials, evenif the replacements are more expensive on an area or weightbasis, simply because the end-cost of the house may be lower.

One of the largest mid-term opportunities for the chemicalindustries will be the development and supply of the chemicalinputs for distributed manufacturing tools. Obvious examplesare the polymers and metals used in 3D printing, noting thatincumbent suppliers in these areas are already in place.However, new and more complex requirements for the chemicalinputs into distributed manufacturing will emerge as distributedmanufacturing expands in scope and complexity. Ultimately, wecan also expect distributed synthesis of chemicals to emerge,where standard inputs such as ethene and catalysts are used tomake more complex chemicals at the point of use and asrequired by, say, 3D printers.

What role does Australia play in all this? Historically we area user and adapter of imported technologies rather than adeveloper of new technologies. That is, our greatest skill is inthe services around the use and customization of newtechnologies. However I would note that chemistry will be verycentral to distributed manufacturing in the fifth IndustrialRevolution and this does represent an interesting opportunityfor our sophisticated (but somewhat intellectually under-utilised) chemistry R&D capability.


The fifth industrial revolution

Ian A. Maxwell ([email protected]) is a serial (andsometimes parallel) entrepreneur, venture capitalist and AdjunctProfessor in Electrical and Computer Engineering at RMITUniversity, who started out his career as a physical polymerchemist.

Over the last 10 years or so, there has been an increasingtendency to add tannins to red wine. There are two classes oftannins that may be used, each having different chemistry. Grape-derived tannins are based on the flavan-3-ol units (+)-catechinand (–)-epicatechin and are sometimes described as condensedtannins or non-hydrolysable tannins.

The other main class is the hydrolysable tannins. These arebased on gallic acid or ellagic acid and give gallo-tannins andellagi-tannins. Hydrolysable tannins are characterised by having acarbohydrate molecule (usually D-glucose) at the centre, clearlydifferentiating them from condensed tannins. The glucosehydroxyl groups are partly or totally esterified with gallic acid orellagic acid. Hydrolysable tannins are hydrolysed in acidic or basicconditions to yield the free phenolic acids and the carbohydrate.These tannins can be extracted from oak used in winemaking oradded when sourced from oak or another plant species. Ashydrolysable tannins are not derived from the fermentation, theyare sometimes referred to as exogenous tannins.

Oenotannin is the term now used to describe the full group ofcompounds that may be added to wine. The purpose of theaddition may be to improve the body or phenolic weight of a wineas well as to stabilise the colour and inhibit laccase activity inbotrytis-affected grapes. There is now considerable interest in thehealth or anti-oxidant properties of these compounds.

A wide range of oenotannins is available commercially.Commercial-in-confidence issues tends to limit the amount ofspecific information available regarding their chemicalcomposition. Grape-derived tannins are sourced for the skins,seeds and stalks of processed grapes. Oak, chestnut, gallnut,myrobalan (red) fruits and quebracho wood are sources of gallo-and ellagi-tannins. There is a useful review of oenotannins byVersari and co-authors in the Australian Journal of Grape and WineResearch (2013, 19, 1–10).

The addition of oenotannins to enhance the body of a wine isa response to a market sector that seeks wines high in tanninwithout an astringent or aggressive sensory response. Tanninextraction from grape skins and seeds during wine processing is aslow process, taking up to three to six weeks for some wine styles.An alternative is to take the wine off skins and seeds after a fewdays of fermentation, thereby freeing up tank space for the nextfermentation, and then adding oenotannins to adjust tanninlevels to suit a specific market sector.

Generally, work showing the advantage of oenotannin additionhas been carried out by company marketing and consumerprofiling. However, major sensory studies on Shiraz at theAustralian Wine Research Institute (Mango Parker et al. Aust. J.Grape Wine Res. 2007, 13, 30–7) and on Monastrell at theUniversidad de Murcia in Spain (Ana Bautista-Ortín et al. Int. J.Food Sci. Tech. 2005, 40, 867–78) found that oenotanninadditions had only a minor impact on perceived astringency. TheSpanish study showed that gallo-tannin additions resulted inwines with higher astringency, dryness and bitter sensorycharacteristics. My observations agree with the Spanish study.

Stabilising red wine colour through the use of oenotannins hasbeen the subject of speculation for some time. Anthocyanins arewater soluble, and so their extraction from the skins commencesbefore ethanol extraction of other phenolic compounds. Theinteraction between, say, flavan-3-ols and anthocyanins helpscolour stability. So, the argument goes that if oenotannins areadded early in the life of the wine, this may be advantageous inhelping stabilise wine colour. But the studies described above onShiraz and Monastrell found little influence of oenotanninadditions on wine colour.

Where improvements in colour have been reported, the studiestend to be observational and not mechanistic. However, StefanChassaing and colleagues from Bordeaux have attempted toexplore the mechanism (Eur. J. Org. Chem. 2010, 1, 55–63) byperforming a spectral and NMR study on 1-deoxyvescalagin-(1β→8)-oenin, an anthocyanin-ellagitannin pigment. Theobserved bathochromic shift in the visible spectrum of thepigment with respect to the free oenotannin was interpreted interms of intramolecular p-stacking between the two parts of thepigment. While still somewhat speculative, the study highlightsthe advantages of fundamental chemistry in explaining thecomplex reactions in the wine matrix.

A few years ago, my colleague Paul Bowyer suggested thatoenotannins are radical scavengers and may contribute to the poolof supposed health-promoting compounds in wine. This argumenthas now been extended to determine the anti-oxidant capacity ofoenotannins so that winemakers could use this information aspart of decision-making when selecting which oenotannin to add.In a study soon to be published, researchers at the University ofPorto have examined the anti-oxidant capacity of 20 commercialoenotannins by six different methods. Each assay provideddifferent information, so all would be needed as a guide towinemakers. And the amount to be ingested before there is anyimpact on the human system remains an unknown. Much moreneeds to be done before health benefits can be claimed.

grapevine


Oenological tannins in winemaking

Geoffrey R. Scollary FRACI CChem ([email protected])was the foundation professor of oenology at Charles SturtUniversity and foundation director of the National Wine andGrape Industry Centre. He continues his wine research at theUniversity of Melbourne and Charles Sturt University.

postdoc diary


Graduation dayIt should have been an amazing moment. My entireacademic career had been leading up to this. Theexperiments had been concluded, the round-bottomflasks put away. The thesis had been written, proof-read and submitted. The referees’ comments had beenreceived and read, a sigh of relief sighed, the thesisamended and re-submitted. I had done all that wasexpected of me. Now it was up to the appropriaterubberstamping to occur before I could proudly beginto call myself Dr John.

So when the email came, there should have beenwhooping and leaping with joy. So what happened?Why was there no celebration on 21 January 2013?Why was there no round at the pub and throwing ofhats in the air?

Well, let me tell you what happened that day. That was theday my son was born. The inconsiderate little tyke chose tooutshine me on my day of glory. Now, I know that being ahealthy bouncing boy is an achievement worth noting. However,he’d only been working towards this goal for eight months andsome change while I had been slogging away in a smelly fume-hood for the best part of four years.

But these are things my boy didn’t understand. As far as hewas concerned, this was the crowning achievement of his shortlife and he wasn’t going to let his dad’s little degree-gettingmoment steal his thunder. And the worst thing was, he seemedto have the vindication and support of all whom I thoughtwould be firmly in my camp; my wife and parents and siblings,even my lab mates and supervisors were somehow moreenthralled with his achievement than the kudos that lay withinmy inbox. Et tu Brutuses?

However, I bore them no ill will for not celebrating myglorious triumph. You see, I too was there cheering my son onas he began consuming Earthly oxygen and treating theuniverse to the sound of his wailing. I too was ignoring mypoor inbox and celebrating the little fella’s smallestachievements.

And so, ironically, on the very day that was to mark an endto my studies, the real lessons began. It is hard to put intowords what a transformative change parenthood is. I went, in

the space of a year, from being an individual terrified of awailing illogical mini-human to one who can confidentlycomfort him and understand what his grunts and groans mean.

After years of handling fear-inducing substances such astriphosgene and hydrofluoric acid and working with reactionvessels at elevated temperatures and pressures, I still found itan order of magnitude more terrifying to hold a screamingchild. I used to consider the fact that, as a point of pride, I hadminimal physical damage as a result of my career choice. Now, Iam even more proud of the fact that I have successfullyhandled a wriggly boy for over a year without impartingphysical damage to him. Going to work never used to be anordeal (well, almost never), but now I look for every excuse togo in a little later and play with him in the morning. Similarly,working late has never been as torturous as it is now andtravelling for a conference has never been less attractive.

My greatest experiment began the day I graduated. Andsince then, I’m happy to report that the initial results are verypromising indeed. I don’t begrudge him stealing my thunder. Heis welcome to it. But as soon as he is old enough to understandthese things, I plan to exact my revenge. You see, one day we’regoing to stop celebrating his birthdays and instead celebratedad’s graduation day. And then everyone will wear funky hatsand throw them in the air.

John is looking forward to regaling his son with tales of triphosgene andhydrofluoric acid.

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… ironically, on the very daythat was to mark an end tomy studies, the real lessonsbegan. It is hard to put intowords what a transformativechange parenthood is.

Chemistry information crops up in unexpected places, such asThe diary of a vice-chancellor, edited a few years ago byUniversity of Melbourne historian Ron Ridley. Raymond Priestleywas Melbourne’s first full-time, paid Vice-Chancellor, who servedbriefly before resigning over conflict with the Chancellor, whohad ceded many of the powers possessed by his predecessors.Priestley recounts in his diary a lunch in March 1935 at theLyceum Club where he was accompanied by his wife, Phyllis,and met a number of chemists. The hosts were Sir David Rivett,professor of chemistry at Melbourne (1924–7) but then head ofCSIR, and his wife, who was the daughter of Alfred Deakin.Among the ‘other guests were Sir David and Lady Masson,formerly ornaments of the University world when Sir David wasProfessor of Chemistry and Lady Masson the leader of Universitysociety and its chief link with the outside world’. Lady Massonhad organised ‘social evenings once a week at the Universitywhich lasted until the War and then faded out’.

In May 1937, Priestley records that he lunched with Hartung(1928–53 professor of chemistry) and Norman Taylor, a seniormanager of Imperial Chemical Industries of Australia and NewZealand (ICIANZ). Lord McGowan, ICI director, had visitedAustralia shortly before and recommended that the companycooperate with the university on a research program. Acommittee to organise this had been set up, and Hartung hadsuggested a grant for research maintenance in the Chemistryschool, including a stipend for a senior officer (AssistantDirector of Research under the professor), laboratoryattendants, equipment, and maintenance allowances forpostgraduate students. Taylor (1885–1960) was a Fellow of theInstitute of Chemistry (of Great Britain and Northern Ireland,later the Royal Institute of Chemistry) and of the AustralianChemical Institute, in whose records he is described asSuperintendant of Factories and later Managing Director ofICIANZ. He graduated BSc from Manchester University in 1907,studied for three years at Zurich Polytechnic and joined theexplosive manufacturer Nobels in 1911, working at Ardeer,Scotland. He remained in explosives with the British SouthAfrica Company and Nobels Australia (Deer Park), where hestarted the Leathercloth Pty Ltd subsidiary. Mimicking theformation of ICI UK from Nobels, Brunner Mond, United Alkaliand British Dyestuffs, ICIANZ was formed in 1927 and Taylorwas absorbed by the new company, which he later headed.

Taylor presided over substantial expansion of Australia’schemical industry, when synthetic ammonia was produced in the1930s, and during the war years the famous sulphamerazineproject and the construction of the Albion explosives factory. Asa young man, Taylor played county hockey and international icehockey, the latter no doubt an activity of his Swiss days, but I

think the company kept him too busy for such frivolity inAustralia. Others enjoyed light-hearted moments on his watch,however, like the employees’ sports meeting held at Frankstonin March 1938. As well as running races and relays for marriedand single men, there was bowling at the wicket, a tug of war,men’s and women’s egg-and-spoon races, and a mixed Siameserace. Taylor retired in 1947 and lived out his days in Longford,Tasmania.

In May 1938, Priestley chaired a meeting in a private homewhere the first of a new series of Women’s College lectures waspresented. No students or professors were present, but severalwives of teaching staff were and also Lady Masson. She tookhim to task about the nude picture in the university gallery –Bernard Hall’s Despair – which he thought privately to be a finepicture but one that had already offended other people.‘Dowagers such as … Lady Masson obviously expected tocontinue to exercise influence at the highest levels’, heobserved.

Later that month, the foundation stone of the new ChemistryBuilding was laid, an occasion made more joyous by thepremier’s gift of £75 000 for the building program and a further£5000 for maintenance. ‘Several hundred students attended andapplauded in the right places … (and) … Hartung wound thewhole show up excellently with a fine speech.’

In June, Priestley and Medley (soon to be his successor as V-C) went to Chemistry for morning tea, where Hartung assuredthem that ‘Anderson, the new import from England, is a greatsuccess’. Chatting with him revealed that he was keen on skiing,squash and mountaineering. Examination of the plans convincedPriestley that before long, Melbourne ‘would have the finestchemistry building in the southern hemisphere’. On that visit,Hartung told the story of the gift to the department by Felton,Grimwade and Company of 17 620 bottles, and the company’srequest that ‘F.G. and Coy’ be engraved on the backs of thebottles. Hartung replied that he would be delighted, since theengravings would imply that the company would replace anybreakages so as to maintain the collection. The companyrepresentative ‘said that Hartung was wasted as a professor’,and offered him a job on their sales staff.

I remember the vast stock of bottles kept under the SeniorTheatre in chemistry, but I thought it had been compiled duringthe war years when glass was short and reuse of bottles wasencouraged. Maybe that was true, but perhaps the remnants ofthe Felton Grimwade collection were there, too.

letter from melbourne


Ian D. Rae FRACI CChem ([email protected]) is a veterancolumnist, having begun his Letters in 1984. When he is notcompiling columns, he writes on the history of chemistry anddispenses advice on chemical hazards and pollution.

Trials of a vice-chancellor


cryptic chemistry

Across1 Additional advance. (7)5 Friends find Science a lot of pressure. (7)10 Advantage in lithium-drifted germanium

crystal application. (4)11 Give an edge to drudgery. (5)12 Dragging pine. (4)13 Shape air return in unending gentle

turbulence. (8)14 Seldom depend on gas. (6)15 Coming to drawback. (6)17 Representing cobalt in the finish. (8)18 Phosphorus piece, a little one. (8)21 Exudations about errors. (6)23 See 24 Across.24 & 23 Across Clear objective attained less

time with feeding frenzy. (8,6)26 Tender for an element in the same

place? (4)27 & 28 Across For how long have you believed

that there are only six elements needed?(5,4)

28 See 27 Across.29 Difficult to hold on to National Security

Agency record. (7)30 Woke agitated. (7)

Down

2 Subordinate shot for experience. (7)3 The metal θ. (5)4 Intended to be busy. (7)6 Radical change when the terminal –OH

groups of a sugar are replaced by –COOHgroups. (7)

7 Rich lodes mined for salts. (9)8 Emollient coming up in studies of

chloranil on aluminium catalysts. (7)9 Deepened tint with final bloom changes

determined by temporal changes. (4-9)16 Perform in new side making from 89 to

103. (9)19 A broken leg support deals with the

unknown. (7)20 Assigns places to mixed up scalers. (7)21 Echo brood. (7)22 R-N: annoying bug about neon. (7)25 Three elements of more recent origin. (5)

Graham Mulroney FRACI CChem is Emeritus Professor of Industry Education at RMIT University.Solution available online.

HazMat 201414–15 May 2014, Melbourne, Vic.www.fpaa.com.au/events/hazmat.aspxEarly Bird discount to 14 March

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Shechtman International Symposium29 June – 4 July 2014, Cancun, Mexicowww.flogen.org/ShechtmanSymposium

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RACI National Congress7–12 December 2014, Adelaide, SAwww.raci.org.au/events-awards/raci-national-congress-2014Call for abstracts opens 2 December 2013Registration opens 2 December 2013Abstract submission closes 9 May 2014Acceptance of abstracts June 2014Early Bird registration closes 1 August 2014

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WORLD WAR I CENTENARY SERIES:Researchers are turning to everything fromcommon plastics to nanotechnology to tryand save lives on the battlefield.

Breath analysis is an important tool inmedical diagnostics, say researchers atAustria’s BREATH RESEARCH INSTITUTE.

DAVE SAMMUT sifts through a range of R&Dgrants and incentives.

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Coming up

Prep H at Mentone Girls is ecstatic afterwinning the Art and Science of CrystalGrowing competition for the prep to year 2 age category. Students donnedtheir lab coats and protective glasses,and joined Head of Science, Mrs HelenSilvester, in the senior science labs towork on their project over a period ofthree months.

The students were involved in themixing and stirring of chemicals,recording observations regarding rate ofgrowth and measuring the size and shapeof the crystals. They also experimentedusing the effects of light and shade,

colour and other techniques to producean artwork featuring the crystal anddemonstrating the principles ofdiffraction, reflection and dispersionusing light.

Entries were judged on how well thescientific observations were set out, thequality of the artwork produced and theirexplanation of how their imagedemonstrates the principles of diffraction,dispersion or reflection as judged by anexpert panel. Their entry was on display atScienceworks over the summer holidaysand each student receives a family pass tovisit during this period.

The competition is run by the RACIVictorian Branch, in conjunction withNational Chemistry Week and is open toprep to year 8 students from across thestate.

Prep H teacher, Ms Nicole Hardman,jumped at the opportunity to be a part ofthis fantastic initiative, engaging studentswith science from a young age. Aligningwith the school’s comprehensive STEMprogram, initiatives such as these developa passion for science at the crucial earlyages and inspire a curiosity in the studentsfor the world around them. MENTONE GIRLS


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Preps championed for their chemistry of crystals

One of the Mentone Girls’ Grammar preps growing crystals in their school science lab.

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