Autumn 2008

Mutant proteins and cancer drugs Towards the $1000 genome The possibilities of metal structures What’s next for the CCDC? As I see it...

virtual screening, we try to filter out those mol - Colin Groom, the Cambridge Crystallographic Data Centre’s new ecules that can’t possibly bind and identify the director, talks to Sarah Houlton about the centre and its future ones that might. What uses does it have outside What’s the CCDC all about? information about molecular recognition than pharma? It was set up in 1965 from the chemistry any other database, and the recognition that goes While it is primarily used in pharma, it also has department, and became independent in 1989 on between a small molecule and a crystal is very potential in crystalline materials. These are used as a not-for-profit company. This gives us a nice similar to that between a small molecule and a in many applications and we would like to stable structure as a self-sustaining research protein in the body. This allows us to derive com - extend the database into this field. It’s also institution, where we’re not driven by max - putational descriptions of those interactions, being used by material scientists who are trying imising profit but by doing good science. Our which companies not only use to optimise the fit to understand crystal growth – this also has activities fall into three strands, and the main between the molecule and the protein, but also pharma applications where scientists are trying one is the structural database, which now con - between a molecule and a lattice of other mole - to find the best crystal form to use in a drug tains more than 450,000 small molecule crystal cules in the materials science area. product. As well as organic molecules, the data - structures. It’s used by well over a thousand In terms of molecular docking software, base contains metal organic compounds, for institutions and companies around the world, although some companies have gone down the example, and these are of interest to material including 100 or so commercial organizations. route of screening millions of compounds scientists in areas such as catalysis, gas storage It’s not just a repository – it also contains con - against a target protein, this can only be done and carbon capture. There’s a huge range of textual data and software that helps scientists with compounds that already exist. With virtual possibilities for the database – and we’re begin - make proper use of the crystal structures. screening, we can look at compounds that ning to make people in those scientific commu - The second strand is other software, devel - might exist but don’t, opening up a whole new nities aware of what the database can offer oped primarily in the pharma area. The most area of science. them. We don’t yet know all its possible uses – well known is Gold, a ligand docking program. It also reduces the need for physical testing – we’re hoping that people in other fields will be It is heavily used by industry, but also in acade - a company may have millions of compounds in able to tell us as they know their science better mia, and we’re continuing to develop it so that their libraries but for a complex system they than we possibly could. it allows much better virtual screening for can only realistically test several thousand. We active compounds. And the third strand is the can direct them towards the most appropriate So what does the future hold for research we do in the broad area of molecular ones to test. There are two issues here – one is CCDC? interactions. identifying whether a compound has the The primary thing, of course, is to ensure the potential to bind to a protein, and the other database stays up-to-date, and available for sci - Why is the database important? defining the most probable binding mode. And entists to use. And the secondary one, which is I think it has become an essential tool for com - these are really quite different problems, as in also essential, is to make sure it is used for the panies in developing new pharmaceuticals, the latter you have to look very closely at the best scientific good. We do our own research reflected in the fact that all the major pharma geometry of the ligand and the energetics of with the database and collaborate with others, companies use our database. It contains more interaction between it and the protein. With and we want to encourage users to get as much benefit as possible from the database. So we will He’d been sponsored by the RAF at school continue to develop new tools to help scientists m and for his degree, but realised that science in their research, and the revenue we generate o was for him and he stayed on to do a PhD

o from providing the database allows us to r with Sandy Giddes. ‘It was expensive as I had develop these tools. G

to pay the RAF back!’ he says. n

i Career: After a postdoc in Leeds with Simon l Is the idea is that it will remain self-

o Philips, Tony North and John Findlay, he went sustaining? C to New Zealand for a second postdoc at Absolutely. I think it is the most stable model Massey University – the outdoor lifestyle was for the centre, as we are not reliant on applying a definite draw! Pfizer came calling in 1994 as V for grants every few years, which would leave

C they were setting up a protein crystallography the research community uncertain about the group, so he returned to the UK and the future of the database. Ultimately, someone has company’s Sandwich site, also spending a year to pay, and I guess the taxpayer could pay for it helping set up a new research site in through the research councils, but this way, Cambridge, US. In 2002, he moved to with the funding coming from the current Celltech to lead the computational group in users, it is much more predictable. Cambridge. He took up his new role at CCDC in October. So you’re looking forward to the Interests: Much of his time is taken up with future, then? his family and other animals – his wife rescues Absolutely. This is a fantastic place, and after 15 Born: Telford, Shropshire, when it was sick creatures and there are chickens running years in industry it’s great to come somewhere still a collection of little villages and round the garden. He’s also a frustrated that’s a mixture of academia, biotech and indus - before it became a New Town climber – Cambridge is far too flat for his try, full of people who are really motivated by Status: His wife, Kerrie, was a molecular liking, so he likes to travel to less flat places as what they do. It’s a great blend of academia with biologist, and now works for various often as possible. commercial reality. I also think the structure and charities. They have two children – Did you know? He’s also a big footy fan – ethos of the organisation encourages people to Thomas, who’s 12, and 11-year-old Ellen. supporting both Telford United and Leeds work with us – we’re a charity and we exist to Education: After the local comprehensive United. And his choice of university was made do great science. People like that and want to and sixth form college, he went to Leeds on the strength of its proximity to Elland work with us. Industry doesn’t just see us as a University to study biotechnology – one of Road… ‘I had a big club and a local club profit-driven software company – they see us as the first universities to offer the subject as when I was a kid. The way things are going, a research organisation with a great scientific a degree course. Telford will soon be the big club!’ pedigree which can help them with their own science. And that’s really refreshing.

2 Chem@Cam Autumn 2008 Reluctant reactions Letters

Not just old girls! scheme, for which I am increasingly grateful! Dear Editor Yours sincerely Your article ‘The class of 1946 remi - Reg Lewis nisces’ prompted by Mary Ashworth’s 93 Buryfield Road, Solihull, letter and photograph produced letters W Midlands B91 2DQ from four other ‘old girl’ students. This letter is just to prove that at least one ‘old boy’ student still survives, Wonder and delight thought Jennifer Turner’s letter suggests that Peter Gray also survives. Dear Editor I enjoy Chem@Cam , because it keeps I was recently made aware of the article me up-to-date on what the chemistry in the Autumn 2007 edition of department is doing, but I do not pre - Chem@Cam about pictures from the tend to understand the more advanced 1950s, which included a rather fine one work – when we were students there of my father, Sandy Ashmore. were only 92 known elements. I partic - Ah, that picture of RGW Norrish. ularly enjoy the Puzzle Corner, and was One of my friends at Emmanuel lucky enough to win a prize a couple of recounts still how he came across him years ago. One of your puzzle setters, in November 1968 (or so) flat on his Keith Parsons, is a former colleague of back in the garden, saying to himself mine at Bakelite. ‘I’ve got a *@&*ing Nobel prize’ in After graduating, I decided to go into tones of wonder and delight! And I the chemical industry. The plastics recall watching him at the Nobel prize industry was then fashionable, and ceremony with three Swedish student Bakelite was in Birmingham, my home caps stacked on his head, in a decidedly town. I had been away from home for jovial mood. A fierce man, but really seven years – four evacuated and three kind underneath and with a great years at Cambridge. So I used my appetite for life. chemistry to develop new and, hope - Yours sincerely fully, improved thermosetting plastics, Fred Ashmore and was successful in so far [email protected] as having half-a-dozen patents in my name. I stayed with Bakelite for 40 years! Class of 49, anyone? It was an intellectually rewarding job in as much as we first did the labo - Dear Editor ratory work then, if we developed I was very interested to see the photo - head of the biochemistry department at something promising, we did the pilot graph of the Part II year of 1946. Can the Rowett Research Institute near plant work. If it was still promising, anyone provide a similar photograph Aberdeen when I was working there. we did the works trials, then the cus - of the 1948–49 year, of which I was Alan Sharpe, who appears in the tomer trials, then we had to make sure a member? 1946 group, was one of my demonstra - it was profitable. It is noteworthy that the 1946 group tors in 1949. We did all the entrepreneurial work, contained nine girls and 21 men, Yours sincerely without the risk and without the whereas there was only one girl in my Tony Care rewards – apart from a reasonable salary year of 50 students. She later became Mrs Mill Farm, Manorowen, Fishguard and a good inflation-linked pension Ron Smith, and her husband was the SA65 9PT

Cover This newsletter is published three times a year by the Chemistry Department. Opinions are not necessarily those of the editor, the department, or the university. Editor-in-Chief: Steve Ley Editor: Sarah Houlton Photographers: John Holman, Nathan Pitt, Caroline Hancox Contents Editorial Board: News 4 Brian Crysell, Bill Jones, Jonathan Goodman, Research 7 Rosemary Ley, Jeremy Sanders This issue’s cover star is Francis Address: Alumni 11 Pope, an atmospheric chemist Chem@Cam, Department of Chemistry, in Tony Cox’s group University of Cambridge, Lensfield Road Chat lines 12 Cambridge CB2 1EW Photograph: Phone: 01223 763865 Puzzle corner 15 John Holman and Nathan Pitt email: [email protected] website: www.ch.cam.ac.uk

Chem@Cam Autumn 2008 3 News

Matt wins Novartis award A new computing regime Matt Gaunt is one of this year’s winners of the Novartis Early A virtual private network, or VPN, is Career Awards in organic chemsitry. Two awards are made currently being piloted. When con - every year – one to a scientist working in Europe, and the nected to the VPN, it means that a com - other to one based in north America. puter will behave as if it were physically Recipients will have started their independent research in the department. ‘People will be able careers within the previous 10 years, and work in the areas of to access their data as if they were in the organic or bioorganic chemistry in the broadest sense. lab,’ he says. ‘This has a number of ben - Matt was recognised for his significant contributions to pal - efits, such as being able to work at home ladium-catalysed C–H bond functionalisations and the devel - behind a firewall, access journals, and opment of new enantioselective organocatalytic reactions, get at data when away at a conference. It including their use in the synthesis of architecturally complex should also help remote collaboration. molecules. Another project he’s working on is ‘It was an enormous surprise when I heard I’d won, but I the possibility of implementing an elec - was absolutely delighted!’ Matt says. The award is a substantial tronic lab notebook. ‘This would give unrestricted research grant, which will provide a fantastic huge benefits. For example, spectra contribution to support his chemistry efforts. ‘The award is in could be indexed with chemistry infor - dollars, and as sterling slides against the dollar, it is getting mation for the first time. Today, they are even more valuable!’ he says. filed on the computer with name and The department has a new computing date, but no chemistry information. Matt was and IT manager, Tim Dickens. He has a With an electronic lab notebook, they rewarded for PhD in chemistry from the University of could be linked to reaction conditions his C-H bond Kent, worked as a postdoc in the chem - and yield in a searchable way.’ It would functionalisations ical crystallography department in also be possible to integrate safety and new chiral Oxford, and then spent 24 at Glaxo (and assessments properly, and offer oppor - organocatalytic reactions its subsequent incarnations), first in tunities to manage the location and computer graphics and then in IT infra - ordering of chemicals within the structure and service management. He department. started work here in Lensfield Road in ‘I’m really enjoying it here – it’s a great September, and has already begun to place to work and there are fantastic implement a number of changes. opportunities,’ Tim says. ‘And I’m amazed The first of these is a centralised ‘trou - by the diversity of equipment – that’s one ble ticket’ system to manage every of the biggest challenges. For example, request for IT help. ‘We get about 300 when we were setting up the VPN, we requests for computer support a month,’ had to make it work on three different he says. ‘The new system is much more versions of Windows, three versions of proactive, and makes sure nothing gets Linux and two Mac systems. Issues are lost – we’re now tracking everything.’ still crawling out of the woodwork.’

There have been a number of changes to the academic staff recently. Markus Kalberer is the new lecturer in physical chemistry. He joins us from the Paul Scherrer Institute and ETH in Gone, but not forgotten! Zürich. Also new to the staff is Justin Benesch, who has been working with Carol Robinson for a while and is now a Royal Society University Research Fellow. Meanwhile, we are sad to see two leave us. Stuart Mackenzie has moved to a lectureship at Oxford, and Royal Society URF Martin Smith has also taken up a lecturing post at Oxford. We wish them both well for their future careers.

Sanders. He was back in Cambridge in Nobel chemistry 2003 as our Todd Professor. ‘Roger decided it was important to Roger Tsien: know the concentration of calcium in

honoured t t cells, and he had an entirely novel idea i P

for his work n

on green about how to measure it,’ Jeremy says. a h t

fluorescent ‘His idea was to design a molecule that a N

:

protein could get into cells and change its fluo - o t o

rescence when it bound to calcium ions. h It was a brilliant conception, combining P chemistry and biology.’ He may have returned to his native Andy (in the centre He spent his time in chemistry mak - Australia a few years ago, but Andrew with the purple ing the compound, and then returned to Holmes is far from forgotten here in tie) with a few physiology to prove that the idea actu - Cambridge. Andy turned 65 recently, familiar faces back One of the winners of this year’s chem - ally worked. ‘His original compound and numerous of his former students for the day istry Nobel prize, Roger Tsien, has links and its descendants have transformed and collaborators gave talks on subjects to the department. The University of our understanding of how ion concen - ranging from natural product synthesis California San Diego scientist has a trations control cell biology. He has con - to materials chemistry to a packed audi - Cambridge PhD in physiology, but spent tinued to work in this area, and is an ence one Friday in September. And the much of his time working here in inspiration to everyone who reads his day concluded in suitable style with a chemistry, supervised by Jeremy work or hears him speak,’ says Jeremy. dinner at Clare College.

4 Chem@Cam Autumn 2008 www.ch.cam.ac.uk t t i P

n Plans well under way for a h t a N

: o t o the Chemistry Olympiad h P Plans are well under way for next sum - The best students will be presented mer’s Chemistry Olympiad, which is with medals at a ceremony in the chapel being held in the UK for the first time – at Kings, followed by a dinner in a mar - here in Cambridge to coincide with the quee on the backs at Kings. Social events 800th anniversary of the university. will include the chance to sight-see in ‘The Olympiad is a really big deal inter - London followed dinner at the Natural nationally,’ says teaching fellow Pete History Museum while they’re waiting Wothers, who is chairman of the event – for the results. Current students from and who took part in the event himself the department will also be involved in The latest addition to the department’s collection of NMR back when he was at school. ‘In some helping the visitors. spectrometers is an Avance III from Bruker. The 400MHz has a countries, students who do well get schol - The Olympiad’s Cambridge coordina - QNP cryoprobe which will give better sensitivity for 31 P and 19 F arships to go to university, and even tor, Emma Powney, is currently focusing than our existing machines, as well as for conventional 1H and excused from military service. Those who on raising sponsorship for the event. 13 C spectra. And, according to Brian Crysell, it’s also our first take part are the star chemists of the future.’ Sponsors already include the Goldsmiths ultrashield plus magnet where the 5 gauss line (the ‘safe’ level) is Being held between 18 and 27 July, stu - Company, the Salters Institute and the within the footprint of the magnet itself, rather than outside it dents from 70 countries all over the world Royal Society of Chemistry, plus the will take part. Each country can send up to Oxford and Cambridge University four students and two mentors, and the Presses, Cambridge Assessment and the competition itself consists of a five-hour Department of Innovation, Universities It’s 50 years in written exam, and a five-hour practical and Skills. Any further offers of sponsor - test. They will be staying at Trinity, St John’s ship would be gratefully received; Emma and St Catharine’s colleges. can be contacted at [email protected] Lensfield Road Pete accepts the official Olympiad Amazingly, it’s now half a century since Flag at the 2008 event in Budapest the chemistry department moved out of Pembroke Street and onto its current site here in Lensfield Road. To coincide with the 50th anniver - sary of the official opening by Princess Margaret in November, a small exhibi - tion of departmental memorabilia was held in the Todd-Hamied room. This included the silver salver presented by the building’s architects on the occasion of the opening, and a signed photo - graph of Princess Margaret, which used to take pride of place on the walls of the old library. balances, hotplates, a machine for The exhibition also featured some of determining melting points, a timer, More awards for Steve the memorabilia electrician Roger Ward and even a centrifuge. Steve Ley’s international medal collec - has ‘rescued’ over the years from vari - They may seem hugely out-of-date tion continues to grow. In 2008, he was ous skips. These gave a fascinating now, but in reality some are only 20 or awarded four more, including one from insight into lab equipment of the past 30 years old. It will be interesting to see , for different aspects of his science. for those too young to remember the what future generations of chemists The Hans Herlo/Inhoffen Medal days before everything was electronic make of the current state-of-the-art from the Helmholtz Zentrum für and computers were taken for granted. equipment we use today when they are Infectionsforschung in Germany was Among Roger’s ‘haul’ were various rescued from skips! made for his contribution to natural products chemistry, while he was given the Prous Institute/Overton and Meyer Award for new technologies in drug discovery by the European Federation of Medicinal Chemistry. He also received the Royal Society of Chemistry’s High Throughput Drug Discovery Methodologies award. And the Indian prize is the U.R. Ghatak Endowment Lecture and Gold Medal from the Indian Association for the Cultivation of Science. He’s off to Kolkata in January to give the lecture. To find out more about the exciting Roger shows off his research that’s going on in Steve’s impressive collection group, go to leygroup.ch.cam.ac.uk and of lab memorabilia leyitc.ch.cam.ac.uk

Chem@Cam Autumn 2008 5 News

Several Cambridge chemistry groups have had ready for photosynthesis to start the cycle again. such as cyclohexane. Guest molecules could be their science highlighted on journal covers Unlike present biofuels, the whole plant would liberated through the addition of a chemical sig - recently. First off is a joint effort from Steve be used, not just the part susceptible to fermen - nal – a triamine – which destroyed the cage, or Jenkins and postdoc Oliver Inderwaldi on Chem tation. The image also includes schemes of the cage could be ‘unlocked’ in reversible fashion Soc Rev . The special issue in honour of Nobel some key reaction steps described in the review. by lowering the pH. prize winner Gerhard Ertl was an invited review The Angewandte cover originates from And Dave Spring’s work featured on the cover of theoretical work on the synthesis and comp - Jonathan Nitschke’s group. A pair of commer - of Org. & Biomol. Chem . The molecule is bustion of small alkanes. cially available diamine and formyl–pyridine azithromycin, which has clinically beneficial The image features a hypothetical carbon sub components were observed to come together effects at sub-inhibitory concentrations against cycle in which putrefaction of biomass creates with iron(II) ions in water to form a hollow Pseudomonas aeruginosa infections. These effects methane, which is then converted to liquid fuel tetrahedral cage moleule. Its crystal structure are, in part, the result of inhibition of bacterial via partial alkane combustion and subsequent revealed the presence of an internal cavity 140Å 3 biofilm formation. The 96-well plate at the back alkane synthesis; combustion of the liquid fuel in volume, allowing the cage to serve as an excel - is a biofilm assay showing that the molecule emits CO 2 and water into the atmosphere, lent host for a small lipophilic guest molecule inhibits biofilm formation in P. aeruginosa . Daan’s grant success Gifted & Talented kids come to Cambridge

The chemistry department is pioneering Talented Partnership with local schools a scheme whereby high-achieving sixth and colleges. It’s being coordinated by formers can take part in master classes. Joanna Taylor in the university admis - About a hundred 16 and 17 year old sions office, who believes it’s a fantastic Year 12 students who are considering chance for sixth-formers to step outside studying chemistry at university are the curriculum. spending four-and-a-half hours of their ‘The classes offer a unique opportu - Saturday afternoons for 10 weeks here nity to develop and deepen knowledge in Lensfield Road – four before and understanding of this area of sci - Christmas, and six after it. ence in a university environment,’ she The idea is to introduce them to says. ‘But the classes aren’t designed aspects of chemistry that are beyond simply as revision-type sessions based what they will experience at school, and on the A-level chemistry syllabus with help them to understand what they are the aim of improving A-level grades. The already learning. Topics that will be cov - subject matter in some cases goes Head of theoretical Daan Frenkel has ered over the 10 weeks include the syn - beyond the syllabus.’ been awarded an Advanced Grant by the of medicines, analytical chemistry One of the tasks they’ve already been European Research Council. These are and green chemistry. set involves drawing the structures of large personal grants for senior ‘It’s going well,’ says teaching fellow isomers of organic molecules. ‘I set researchers, and Daan has been given Pete Wothers. ‘So far, we’ve had sessions them a challenge to come up with as 1.8m over five years. on NMR, a talk on X-ray crystallography many isomers for C 5H8O as they could, ‘My proposal focused on the devel - from John Davies, and they’ve been with a prize for the one who found the opment of numerical tools to predict working on problems with a group of most,’ Pete says. good strategies for inducing the sponta - 10 student demonstrators.’ He hopes ‘I rather recklessly added that if they neous assembly of complex structures they’ll go back to their schools fired up could beat me, I’d give them £20. I’ve with nano- or micro-scale building to take part in the Chemistry Olympiad managed to draw more than 300, blocks,’ Daan says. ‘The grants are highly selection process. including enantiomers and exotic things desirable, and there was stiff competi - The master classes are organised by like chiral allenes, so I’ll be pretty tion – the success rate in my field was Excellence East, the regional hub that impressed if any of them do manage to just 4%.’ links the Eastern Region Gifted and beat my tally!’

6 Chem@Cam Autumn 2008 Research

Filling a whole issue of Nature is a long way from a few doodlings on the back of a beermat. But that’s exactly what’s Towards the $1000 genome happened for Shankar Balasubramanian and Dave Klenerman – their idea of a A chat over a pint in the Panton Arms led to a faster, cheaper way of way to sequence genomes quickly and cheaply has now been used to sequence sequencing DNA for Shankar Balasubramanian and Dave Klenerman the first Asian and African human genomes, as reported in three articles in the 6 November issue of the journal. One summer afternoon back in 1997, Shankar, Dave and postdocs Colin Barnes and Mark Osbourne were bouncing ideas around over a pint or three in the Panton Arms. Back then, DNA was sequenced by separating it on a gel or by capillary electrophoresis, but it is synthesised attached to a solid sup - port. What if a piece of DNA could be pinned to a surface and the natural monomers that DNA polymerases use t t could be engineered so they were i P

colour-coded for the different bases? It n a h t

might be possible to read off the a N colours to determine the sequence. : o t o

A little post-pub cogitation later, they h realised they might be on to something. P Inspired by the DNA microarrays that seems obvious. But at the time, it was Shankar and Dave thinks that the focus on chemistry has were becoming popular for genetic this realisation that allowed them to back in the Panton provided an important edge. ‘Beautiful analysis, there was a realisation that if move forward and develop a massively Arms, where the systems and elegant hardware are all lots of DNA samples could be pinned parallel automated high-throughput story began very well, but without chemistry it can’t onto the same surface, many sequences system. They filed a foundation patent, work. We invested a lot of effort in could be read in parallel, dramatically and the company was born in June developing the chemistry we needed speeding up the process. A few prelimi - 1998 under the name Solexa. Initially, it from scratch, which turned out to be nary calculations later – they’d moved on sponsored a couple of postdocs in the essential in terms of competitive advan - to the back of an envelope by now – and university to prove the concept before tage,’ he says. they figured that it might be possible to the formal spin-out company was The Genome Analyser was only sequence a billion bases on a 1cm 2 chip. established in Chesterford Research Park launched in January 2007, and within a They decided that the only way this in 2001. ‘We raised money, and it grew couple of months papers were appear - was ever going to become a reality would and grew,’ Shankar says. ing in journals using the technology. be to spin out a company to do it. ‘You Several hundred machines are now in can only go so far with a single postdoc!’ CHEMICAL CHALLENGES use. And it’s now not only being used Shankar says. ‘The Wellcome Trust were While they faced many engineering for genome sequencing – users are interested, but we realised that one post - challenges, Shankar believes the chem - finding a variety of other applications doc for three years wouldn’t be enough. istry was pivotal. ‘We had to engineer such as RNA sequencing and mapping So we approached venture capital com - polymerase enzymes that would toler - transcription factors onto their binding pany Abingworth in November 1997. ate the structural changes to the DNA sites within the genome. ‘These are all Our ideas were very ambitious – if not a monomers that contained the colour things we’d never thought of!’ he says. little unrealistic – but they were very markers,’ he says. ‘But another impor - ‘If you put a new tool into the hands of interested in having a 10,000-fold tant development that affected the cost scientists, they’ll do creative, and often improvement in speed, capacity and cost.’ and usability of the instrument was crazy things with it.’ The due diligence process threw up finding a technology to amplify the Solexa itself was acquired by US com - some further challenges they’d not fragments – reproducing each one to pany Illumina in Jan 2007, and Illumina thought of, such as how to prepare the give several hundred copies to UK (formerly Solexa UK) now employs samples. ‘You can’t go spotting a million strengthen the fluorescent colour signal 140 people and is moving into a new different samples on the surface – you’d and making it easier to image. building near Cambridge in 2009. Both have to prepare each one separately!’ he ‘And, of course, it generates a lot of Dave and Shankar are delighted with its says. ‘Provoked by a due diligence chal - sequence data which need to be success. ‘It wouldn’t have been possible lenge, I recall a “lightbulb” moment processed and then put back together to without the huge number of talented one Sunday afternoon – if you frag - give the longer strands of DNA in the people within the company,’ Dave says. mented the DNA from a genome and genome. So it started with chemistry, ‘There are 100 authors on our Nature could somehow immobilise the frag - but it needed biochemists, geneticists, paper, and the input of all of them was ments randomly on a surface in a way bioinformaticians, hardware and soft - essential, from the science itself to devel - that they remained in separate spots and ware engineers, and even fluidics oping the robust machine that is now didn’t cluster together, then when you experts to deliver a system that works.’ being used in labs around the world.’ imaged the surface you would see each Their original aim was to deliver a ‘It’s been an amazing journey,’ one as a single molecule. That way you system that could sequence a genome Shankar concludes. ‘I’ve learnt many could create maybe 10 million different for $1000 in a day. They’re not quite things from the process, and perhaps samples that can be sequenced sepa - there yet – but Shankar believes it’s now the most important is to be ambitious. rately on one surface in a single step.’ only a couple of years away. There are Anything is possible, as long as you In retrospect, he says, that probably several competing systems, but he have the right team of people behind it.’

Chem@Cam Autumn 2008 7 Research Reactivating protein mutants

Alan Fersht has spent his career working with proteins, trying to understand how they fold, what makes them stable, and how they interact with molecules. Recently, he’s been looking at a protein which can cause cancer when it goes wrong

Alan with his p53 inactive simply make it less stable, recently awarded and start melting at body temperature Royal Society Royal or below.’ Medal and the Since then, the group has been devel - GN Lewis Medal oping strategies to reactivate p53 from Berkeley mutants. The first tack was to design peptide molecules that could bind to p53 and stabilise it. ‘We showed these peptides would stabilise p53 in a test tube, and in collaboration with Swedish colleagues that they could reactivate the p53 mutants that had become desta - bilised in cancer cells,’ he says. ‘One of our major goals now is to make small molecules that could become therapeu - tics by reactivating p53. Ideally, one t t i would like to get molecules that would P

n activate all mutants of p53, but it’s not a h t

a an easy target.’ N

: They have now found that one o t o

h mutant has a mutation at the ‘wrong’ P end of the protein molecule, far away The main focus of ’s chem - If the cell’s DNA has become dam - from its active end, which causes a deep istry is protein engineering – under - aged, it activates the genes controlling cleft to form at the bottom of the pro - standing protein stability, how proteins pathways that repair the damage. If it tein structure, and it should be easier to fold and how enzyme catalysis works. can’t repair the damage, it activates find drug molecules that fit into it. ‘It takes an enormous amount of effort genes that stop the cell cycle. But that’s ‘We solved the structure of this just trying to understand the interactions not enough – it has to go one stage fur - mutant just over a year ago, and we are within proteins, and with the molecules ther and kill the cancer, so it activates now looking for small molecules that they interact with,’ he says. ‘Over the genes that are involved in programmed bind in this cleft,’ he says. ‘We have years, we have learnt a lot about proteins cell death, or apoptosis – the body’s identified a class of molecules that will by putting mutations into them, and way of killing cells that are past their bind there, and which stabilise the p53 now know a lot about the strengths of useful life. protein – and we have preliminary the interactions and what contributes to ‘When p53 and all its pathways biological data in cancer cells that protein stability. And for the past 15 years are active, cancer cells are killed,’ he show it does work.’ or so, we’ve been looking at mutations says. ‘But in about half of all Alan is convinced that they will that cause disease.’ human cancers, p53 is inactivated find a drug that works by binding Perhaps the most important of these by mutation. That’s bad news – to this cleft. ‘Although this mutant diseases is cancer, where the cell lifecy - not only does it mean that the probably occurs in only 1% of can - cle becomes uncontrolled. ‘Two types of cancerous cells can proliferate, cers, this still represents something proteins are involved – oncogenes but in addition treatments such like 70,000 new cases a year. And it’s which start the cell proliferation as radiotherapy and old-fash - relatively easy and cheap to sequence process, and at the other end there are ioned chemotherapy that work by acti - p53, so this could be done routinely tumour suppressors which stop the cell vating p53 are rendered ineffective.’ in cancer patients to see if a drug from proliferating. Mutations must hap - Alan became interested in p53 that acts there is likely to work.’ pen in both of these types to cause can - because it was inactivated by muta - They have already discovered cer,’ Alan explains. tion, and about 12 years ago discovered their first lead compounds, but these ‘The protein suppressor p53 is one of that about a third of the mutations that The core domain do not yet bind tightly enough to p53 the most important proteins in the cell, inactivate p53 do so simply by destabil - of a mutant of to make a successful drug. ‘It’s pretty being implicated in processes from fer - ising the protein structure. ‘We discov - p53, with the clear from our structural work where tility to ageing. It is present in low lev - ered that normal p53 in a cell melts at molecule they we need to build onto the molecule to els in cells, and if there are any stresses 44°C, only just above body tempera - designed filling a make it bind to the protein more effec - in the cell that could lead to cancer, it ture. It then starts denaturing very rap - cavity induced by tively,’ he says. ‘I’m sure we’re going to becomes activated.’ idly. Many of the mutations that make the mutation get down from micromolar binding to

8 Chem@Cam Autumn 2008 www.ch.cam.ac.uk – a new way to cure cancer? x o c n a H

e n i l o r a C

: o t o h P

nanomolar or even picomolar very these in the past, thinking perhaps that A team effort: ing,’ he explains. ‘So the only way to do quickly. We’ve set up a reasonably high- something had gone wrong with the Alan surrounded it is to carry out experiments in solu - throughput drug screening operation in protein, but we’ve now realised that by his talented tion, combining high field NMR to look our labs, and I’m very optimistic that maybe 40% of structures in the human group of scientists at the folded regions and find it’s going to work.’ proteome are disordered, like the dena - domain–domain interactions, and other Alan’s group is also working on the tured states of proteins. And tumour techniques such as small angle X-ray structural determination of biological suppressor p53 is typical of this – it is a scattering. This method languished for a macromolecules. ‘It’s now 50 years complex protein with some domains very long time, but with modern soft - since the first protein structure was that are beautifully folded, and others ware you can carry out scattering solved, but we’re used to proteins being which are disordered.’ experiments in a synchrotron and start beautifully folded molecules, with Solving the structures of these intrin - reconstructing the molecules.’ alpha helices, beta sheets and having a sically disordered regions remains Last year, they succeeded in solving regular structure,’ he says. ‘But in recent something of a challenge. ‘You can’t the structure of the full length of p53 in years, it has been discovered that many crystallise them and find the structure solution using a combination of these important proteins have disordered by X-ray crystallography, because the methods. ‘This is probably the first of regions in them. People had ignored disorder prevents them from crystallis - these types of structures to be solved like this – I’m very pleased and it has opened up a whole new area of Born: London Brenner put his head around the door, and Max research,’ Alan says. ‘We’re now trying Status: Married to Marilyn, a history graduate Perutz and Aaron Klug were both around too,’ to build up the structures of various he says. He moved to Imperial College in 1979 t who’s now retired, but does a huge amount of other structures of complex proteins in h charity work and is chairman of a local fine arts to hold the Royal Society Wolfson chair formerly solution using these techniques. s r society. Daughter Naomi is a consultant held by Dorothy Hodgkin, and in 1988 moved ‘These proteins tend to be involved in e back to Cambridge as Professor F oncologist and radiotherapist and is married to controlling the cell cycle and cell sig - of Organic Chemistry. n a surgeon – they have two children (Joe 6 and nalling, some of which work in con - a

l Ruby 4). Son Phil lives in Boston in the US, and Interests: A former junior chess champion and junction with p53. It’s now routine to

A is an expert in outsourcing. president of the Cambridge university chess determine the structures of protein Education: He went to the local grammar club, he’s recently rekindled his interest in crystals, and the challenge now is to school in Walthamstow. ‘No-one ever got an chess and has started collecting chess sets in look at those which you can’t crystallise V between the large amount of travelling he – it’s not simple and makes for fascinat - C exhibition or scholarship to Oxbridge from there, but in those days there were state scholarships. I does for work. His grandchildren also take up a ing academic research.’ managed to get one of these and Caius offered lot of his time. He is delighted that his group remains at the forefront of protein me a place to study natural sciences. He stayed Did you know? Last year, Alan spent a month on for a PhD with Tony Kirby. structure determination. ‘We’re moving of evenings writing a small book on chess sets forward very quickly – we had to as we Career: In 1968, he spent a postdoc year with as an exercise in desk-top publishing. He found needed the structures to solve the other physical organic chemist Bill Jenks at Brandeis an academic publisher in Dorset, uploaded a problems we were looking at, such as University in the US. He returned to the 100Mb file to their website, and they printed it p53,’ he says. ‘We are now looking at Laboratory of Molecular Biology in Cambridge in out on high-quality art paper. He’s already sold the complexes between p53 and various 1969 to work on the mechanisms of protein enough copies of the book to cover his costs. ‘I other proteins which interact with it – activity. ‘Those were heady days – you’d see wrote one less review that year – and a book there are some very interesting ques - Francis Crick in the canteen at lunchtime, Sydney on chess pieces instead!’ tions about how it works that we are hoping to answer.’

Chem@Cam Autumn 2008 9 Research

he says. ‘By making the phosphine lig - Metals and molecules ands bigger, you can tune the size of the channel opening. You could then take a mixture of, say, alkenes, and only those that can fit inside the pores will react. Simon Humphrey’s work on metals may lead to new ways of This raises the potential of applications storing and separating gases, and novel metal catalysts in simultaneous separation and catalysis.’ Another idea is to make biologically inspired versions of the same materials, molecules are about the same size; it also for example by using dipeptides as the completely separates mixtures of nitro - ligands. ‘Because they are naturally chi - gen, oxygen, carbon dioxide and hydro - ral, it might mean the frameworks could gen in a single pass through the material, be used to carry out chiral separations,’ or carbon dioxide from methane at he says. ‘They are harder to put together room temperature. We think the elec - because the peptides are “floppy”, but tronics at the pore mouth have an effect, work elsewhere shows that although the and it may be that some molecules bind separation isn’t great yet, if you can tai - more strongly than others.’ lor the channel correctly you can get The next step is to use more exotic some selective absorption in the channel organic molecules as the linkers, with that could allow the separation of com - extra functionality built in to allow the pletely racemic mixtures. frameworks to induce ‘smart’ guest- ‘Our idea is to use easy-to-make responsive behaviour. ‘I’m looking at dipeptides and tripeptides to give us phosphine ligands, where polar groups more complex systems. It’s too difficult on the phosphines can lead to the for - to make chiral phosphine ligands that mation of two separate but interlinked would coordinate into the framework, x o

c frames which are trapped together but so we are focusing on biological mole - n a still able to move,’ he says. cules that will bond quite strongly to a H e n ‘Effectively, this induces a “breathing” metal through carboxylate groups. But i l o r mode where the frameworks are weakly they are still a challenge to make.’ a C

: held close together to open the pores, His second focus is on metal o t o and spontaneously spring apart to close nanoparticles. In collaboration with h P them. As a result, argon gas may be Richard Lambert here in Cambridge Simon Humphrey’s work is focused on absorbed at one temperature, for exam - and Don Tilley in Berkeley, he is making two rather different aspects of inorganic ple, and the frameworks move apart to rhodium, palladium, platinum and gold chemistry – porous coordination poly - trap the argon inside; you nanoparticles using a mers and metal nanoparticles. PCPs Right: Structure can even apply a vacuum synthetic method that of a porous consist of metal ions linked together coordination and the argon won’t come allows control over the into lattices by organic molecules, with material based on out until the temperature is kinetics of nanoparticle each metal bonded to a fixed number of triphenylphosphine raised. This makes it possi - nucleation and growth. ligand molecules. For example, an octa - oxide and zinc ble to store a gas like argon The precursor is added hedral metal which likes to join to six hydroxide that doesn’t strongly adsorb using a pump, and by ligands would give a box girder-type networks. The two to surfaces as it relies on a controlling the rate of lattice structure. interpenetrated physical trapping effect.’ addition, they can con - ‘Early examples were targeted at appli - networks are He’s also looking at trol the shape and size cations such as hydrogen gas storage, but shown in green attaching catalytic metals to of the nanoparticles. and orange I’m interested in more niche markets as the phosphines. ‘You could ‘We can make core I’m not sure that the extremely stringent imagine taking a well known catalyst like shell nanoparticles, where one metal sits requirements for their applications in Wilkinson’s catalyst and turning it into a inside another,’ he says. ‘They can be put hydrogen storage that are being laid completely heterogeneous array. Even onto inert supports like silica and used down by the US department of energy though it is a solid catalyst, it still has sin - for solution or gas phase catalysis, and will ever be reached,’ Simon says. gle active sites, just like in the homoge - we’re also looking at different metals in ‘However, they are also very good at sep - nous catalyst. You can also change the epoxidation reactions. They can also be arating different types of molecules. shape of the pore mouth, which allows heated up so the metals mix, giving We’ve made a material that can separate you to change the site selectivity of the bimetallic nanoparticles, or even inverted nitrogen and oxygen – even though the catalyst – you can’t do this in solution,’ so the outside layer moves to the centre.’

y Born: Wisbech, where his father has a farm Career: Simon moved back to the Californian Did you know? Simon likes to go to Las e r and he spent most of his summers growing sunshine for a postdoc with Profs. T Don Tilley Vegas a couple of times a year to play poker, h

p up driving tractors. and Gabor A. Somorjai at Berkeley, before and claims a successful trip is one where

m Status: His girlfriend is a biophysicist. ‘I returning here in 2006 where he’s now a he wins enough to pay for his flight and u always said you should never date someone Research Fellow at St John’s College. hotel, and maybe make a small profit. ‘I have H from your own subject,’ he says. ‘I failed!’ Interests: He spends his summers playing a habit of playing very well against the n

o Education: He went to the local school his cricket, and squash and football in the winter, tourists who are only there to lose money,

m but claims he’s only really any good at cricket. and then getting too cocky when playing

i parents and grandparents had attended, in a

S small village, Gorefield, in north Cambridge- Playing for the chemistry department this against the one guy who is sitting behind a shire. He studied chemistry at UEA, spending summer he managed to take 4 for 5 off five mound of chips. Playing two kings when he time studying in Santa Barbara. He came to overs, and three of the runs were wides! He’s has two aces is a good way to lose your V Cambridge in 2002 for a PhD with Paul Wood. also a Peterborough United fan. money all at once!’ C

10 Chem@Cam Autumn 2008 Chat lines

And finally… we got the lot! A plea from the editor... In the process of the hard disk failure that caused It’s taken a while, but it now looks like we’ve identified so many problems with the last issue, all the submis - all of the faces in Mary Ashworth’s 1946 photo sions we’d been sent for the alumni page also went AWOL. So if you’ve sent in something to the maga - zine and it’s not been used, it means it’s vanished in a puff of expired silicon, and it would be fantastic if you could send it to us again. And, of course, any other contributions are extremely welcome!

At last – we have a full set of names. Unless you can identify any errors?! Back row: Olga Rutherford, E.C. Webb, J. Sawyer, V.M. Clark, Heather Platt, W. Rosenfelder, Helen Frenkel, W. Burne, Mary Ashworth; Middle row: Akbar Imam, Costi Edeleanu, Alec Sutton, A.J. Poynton, Reg Lewis, J. Cave-Brown- Cave, H.M. Kimberley, Fred Webber, Alan Sharpe, Peter Gray, A. Wild, D. Goodison; Front row: Susan Neuberger, Joan Banus, B. Whittaker, Leslie Hunt, A. Hutchinson, Ernie Elborn, Audrey Free, Jennifer Turner, Shirley Wickham-Jones.

Dear Editor spends forever elaborating his apparatus Dear Editor On the middle row, eighth from the left, and consequently fails to use it to get The few 1946 blanks can be filled in as is Fred Webber, a senior lab assistant results of any value. Some of the struc - follows: Back row second from left is working in the top floor lab of the phys - tures were a sight to behold. physical chemistry technician E.C. Webb. ical chemistry department in Free I found your reminiscences very Fourth left on the middle row is School Lane when I was there in 1952 evocative of the inhabitants of the lab in A.J. Poynton, and eighth left is glass - as a senior research student supervised my time. We all used to meet for tea in blower and physical chemistry techni - by Professor Norrish. the Perse Room – George Porter, cian Fred Webber. Fred was a clever and very knowl - Maurice Sugden, the Prof and so on. Yours sincerely edgeable chap who had great skills as a Your sincerely Peter Gray glassblower, self-taught. He had great Geoff Drinkwater 2 Fendon Close, Cambridge patience with the type of student who [email protected] CB1 7RU The Corporate Associates Scheme Arecor Thanks to the generosity of the depart - networking events at the department; Illumina ment’s Corporate Associates, we have I Access to emerging Cambridge Astex Therapeutics been able to benefit the education and research via conferences, special brief - Johnson Matthey Catalysts Astra Zeneca environment for students and staff. For ings and various publications; Kodak European Research example, the Associates pay for univer - I Access to the department library Asynt sity-wide access to SciFinder Scholar and photocopying/printing facilities; Lectus Therapeutics Biotica Technology and ChemOffice. They also make signifi - I Regular communications about cant contributions to the library for upcoming events and colloquia; Maruzen International Boehringer Ingelheim Pharma journal subscriptions. Moreover, they I Subscriptions to department publi - Merck Sharp & Dohme BP provide exam prizes, faculty teaching cations, including Chem@Cam; awards and summer studentships, and I Priority notification of and free Novartis BP Institute have recently funded the refurbishment access to departmental research lectures; Pfizer Bristol-Myers Squibb of a state-of-the-art meeting room with I Ability to hold ‘Welcome Stalls’ in teleconferencing and display facilities. the department entrance hall; Proctor & Gamble Cambridge BioTechnology Corporate Associate membership not I Preferential conference rates; I Roche Cambridge Medical Innovations only provides essential support for the Free access to the teaching lectures department, but also provides numer - held within the department; Shell Global Solutions CambridgeSoft ous benefits to help members work with I The full services of the Corporate us and achieve their business objectives. Relations team to facilitate interaction Sigma-Aldrich Chemical Computing Group Members enjoy many benefits through with students, staff, and other parts of Cornelius Specialties their enhanced partnership with the the University of Cambridge to help Society of department, such as: achieve your corporate objectives. Chemical Industry Dr Reddy’s Custom Pharmaceutical I Visibility within the department; If your organisation would be inter - Services I A dedicated meeting room and ested in joining the Corporate Associates Takeda Cambridge GlaxoSmithKline office for members to use while visiting Scheme, then please email Jane Snaith at Unilever the department; [email protected], or call Heptares I Invitations to recognition days and 01223 336537. Uniqsis

Chem@Cam Autumn 2008 11 Chat lines A happy day in Dublin Four-wheel drive!

Dudley Williams and is now a postdoc with Carol Robinson, and Susan Fowler, a former PhD student with Jane Clarke, who was also a postdoc with Chris Dobson, and now works for MedImmune on Granta Park in Cambridge. The romance started seven years ago when they were both doing their PhDs. They bumped into each other at a mutual friend’s birthday party Sam Barton – another Cambridge chemist, who was in Joe Spencer’s group. The happy couple tied the knot in Susan’s home town of Dublin, with plenty of current and former Cambridge chemists in attendance. They then escaped to Italy for a romantic honey - When Nick Handy retired a couple of moon in Venice and Florence, with short years ago, he and his wife Carol left stopovers in Bologna and Pisa. Cambridge and moved up to the Lake ‘The day flew past so quickly it’s all a District. Their new abode is a farm that bit of a blur!’ Alan claims. ‘We were very has been in Carol’s family for some Chem@Cam reckons no issue is complete lucky as the weather was absolutely glo - time, in the beautiful countryside near without a good wedding. This time, it fea - rious – bright sunshine and clear blue Bassenthwaite Lake. In the summer. tures two Cambridge chemists – Alan skies – which is really surprising for John Pyle popped in to visit, and reports Sandercock, who did his PhD with Dublin, especially this summer!’ that they are loving the country lifestyle. And Nick has gone one better than the normal Cambridge bike – scooting around on the bright red four- Farewell to three wheel drive vehicle pictured above!

Three members of the assistant staff have moved on: physical sector secretary Anita Hudson (left), cleaner Barbara Partridge (above), and Katie Dryden-Holt, who worked for Steve Ley. We wish all three of them good luck for the future!

Comings A sad goodbye to Gladys and Roy & goings Sad news reaches us of the death of two New Staff long-serving former members of the Anita Klosowska Rachael Jefferies assistant staff. Gladys Fenning (left) Robert Baron started in 1962 as a cleaner in the Daniel Fisher department of physical chemistry, and Glen MacElroy Andrew Milner stayed for around 20 years before mov - Peter Hartley ing to the Assistants Sports & Social Noah Maheya Club. She retired in 1999 at the grand Leaving old age of 87. She was widowed in Henneli Greyling 1958, and later married Jack Fenning, Gabriela Ridlova Rolandas Kvarinskas one time chief storekeeper in chemistry. Katie Dryden-Holt Roy Denston (right) came to the lab Retired in 1967 as an electrician in the mainte - Barbara Partridge nance department and stayed until he John Flanagan retired in 1993.

12 Chem@Cam Autumn 2008 www.ch.cam.ac.uk What, no Sports Day rain?

What better to do on a lovely sunny day (well, a non-rainy one, anyway!) than escape from the lab for a spot of cricket, football, croquet and even boules? Caroline Hancox’s exercise was limited to her shutter finger to take these photos of Sports Day action!

Chem@Cam Autumn 2008 13 Chat lines The hills are alive…

The annual organic sector postgrad symposium and welcome party in October was once again sponsored by Pfizer. This year’s theme for the party was ‘musicals’, which gave plenty of opportunity for some rather imaginative costumes!

Above right: Cats Sam Cheung and Patricia Garcia Dominguez; right and below: nun Shankar Balasubramanian, and Alessandra Polaro and Sebastian Muller from the Sound of Music

Above: Stars of the Wizard of Oz, Mike Cooke, Ben Haffmayer, Falco Magnus-Meyer and Jochen Brandt; left: Four members of the Gaunt group forgot their costumes; below: Georg Blaser, Fredrik Andersson, Leegyan Kwa, Zoë Waller in Chicago style, Kid from Fame Beth Ashbridge, and Keith McLuckie as a random soldier

Danny Allman failed to dress up, but instead he pinched James Shearman’s hat; apparently he’s the star of An Officer and a Gentleman, The Musical. No, neither have we…

14 Puzzle corner

The return of ChemDoku! Ir Ru Pd And now… back by popular demand… current spot rates are to be believed, the it’s ChemDoku! most expensive option would appear to Pd Au And this time, the credit crunch has be rhodium. got us thinking where might be a safer All you have to do is to arrange the Ag Ir place to invest our hard-earned loose chemical symbols of the nine different change than the bank. precious metals in the grid so that each Pd Os Ru Ag Under the bed is probably not the appears once – and once only – in each worst idea right now, but we went look - horizontal row, vertical column and 3x3 ing at precious metals instead. And if the square. Easy! Ag Pt Ru Pt Re Os Chemical crossword Rh Au

We thought it was about time for but could be SPaNISH as that’s six. Re Os another crossword, and as if by magic, Graham reports that his team of crack Graham Quartly has sent us one. crossword testers failed to get two of the Rh Pt Ru As ever, each square has to be filled answers – both of the number 6s – but with the symbol for a chemical element he claims one is in the dictionary and in such a way that the resulting words fit the other is a common Spanish word. £20 prizes are on offer for both puzzles. Send entries the clues. For example, ‘European lan - As ever, a £20 prize will go to the first by email to [email protected] or by snail mail to guage’ requiring six elements couldn’t correct solution randomly picked out of Chem@Cam, Department of Chemistry, University of be SPaNiSH as it’s only five elements, whichever receptacle comes to hand. Cambridge, Lensfield Road, Cambridge CB2 1EW

12345

67 8 Last issue’s winners 9 10 11 12 Molecular weights Ah, the joy of open-ended questions... This one got a few 13 14 15 16 brain cells working overtime! The highest allowable (assum - ing my sums and checking are correct – apologies if my caf - 17 18 19 feine-addled brain has failed in this task) answer sent in was 149, which could be achieved with three different molecules. 20 21 22 Richard Brown suggested CH 3BrClF, Ian Potts BrClFSiCH 3 (which he admits is possible neither particularly common nor 23 24 25 26 stable), and CHClBrCO 2H from Roger Duffett (who also sug - gested a rather unlikely helium clathrate with inexplicable 27 28 29 atoms of helium, beryllium, oxygen, aluminium, bromine and americium which has – or so he claims! – been discov - 30 31 32 33 ered on Mars…). The prize goes to Richard Brown. And a special mention to Annette Quartly who managed to 34 35 36 get 530 (from CH 2F.GeClAt 2, which she claims is easily con -

37 38 structable with ball-and-stick models!), and 418 for the sub - stituted ethane C 2HAtBrClFI (which is only dubiously stable because of the short half-life of astatine). Her highest allow - able total was 142 for chloromethylphosphonic acid which, Across 26. Domestic animal 6. Salsa move from apparently, costs £2/g (or did in her geriatric Sigma cata - 2. Cake or stone? 27. Ancient tribe the 70s logue, anyway). 4. Relaxed, informal? 28. Spy fatale 7. Sword 6. Swaying of water 30. Get better 12. Misgiving Compound elements 14. Acoustic tracker The next four numbers are 50, 54, 83 and 85 – being the 8. Spanish town in 33. Restriction to move - atomic numbers of elements that can be written out in ele - Africa ment 16. Face down mental symbols, for example BiSmUTh. 9. Physical unit 34. Timepieces 18. Offspring This one had most readers stumped! And the prize goes to 10. Annoy 36. Not out! 20. Caution Andy Lynch (with help from Rose Lynch who’s really the Cambridge chemist), whose brain was clearly exercised to the 11. Central 37. Future past 22. Instinctive and bloody limits by it. Well done for getting there in the end!. 13. Girl’s name 38. Single 23. Lose resolution The setter’s husband also got the answer – and says he was 15. Island tree 25. Support very frustrated it took him so long to work it out as he’d 17. Celestial bodies Down 26. Gun already made lists of elements that can be spelt like this for crossword-creating purposes! 19. Blanket 1. With more knowledge 28. Stroke We also had an imaginative but wrong answer from Richard 20. Small bird 2. Pronoun 29. Possesses Brown (who found place names loosely close to the atomic 21. Sheepish 3. Part of body 31. Stes up or triggers numbers in the question, and added the US towns of Silver, Tin City, Gold and Lead as the extra elements), and a marvel - 23. Equal 4. Earth shattering 32. Firm hold on sin lously surreal one involving the 12 Days of Christmas from 24. Element 5. Rough 35. Girl’s name Roger Duffett.

Chem@Cam Autumn 2008 15 Do you think we’ll find inspiration down the pub?

Chem@Cam is written, edited and produced

by S ARAH H OULTON

Printed by Callimedia, Colchester