Autumn 2009

New materials for better batteries Novel catalysts in the car industry Electron correlation: a solution Using fragments to probe biology As I see it...

Martyn Twigg started life in academia, but has spent most of his career in the chemical industry. He tells Sarah Houlton how he ended up there, and the importance of catalysts in the motor industry

How did you come to work in industry? What do the autocatalysts do? ishing. It is rewarding that chemists together with After a junior faculty position at the University of In a petrol engine, partially oxidised hydrocarbons engineers are able to produce things like this that Toronto, I came to Cambridge to work with Jack such as aldehydes and carbon monoxide are pro - have such a major benefit to society. Lewis and Brian Johnson – the only kineticist work - duced, as well as the expected combustion prod - ing in a preparative group! It was one of the most ucts water, carbon dioxide, and nitrogen. Because What’s the next challenge for catalysts in exciting times of my life – working almost every the temperature is so high at the flame front, oxy - the car industry? day until midnight, and it was a very stimulating gen and nitrogen combine through a complex This is already being addressed. The composition environment with eminent visitors from all over the series of free radical reactions to form nitric oxide. of diesel exhaust is very different from petrol world, many of whom I am still in contact with. This is a fascinating molecule – at room tempera - engines that operate around the stiochiometric One of my colleagues was an ICI employee, vis - ture it is thermodynamically unstable, it is a free point with no excess oxygen. Diesel engines also iting the lab for six months, and he invited me to radical, and it should fall apart, but it does not! contain CO, hydrocarbons and NOx, but because visit ICI’s corporate laboratory in Runcorn to see Instead, its only facile reaction is oxidation to of the higher thermodynamic efficiency of the what they did there. When I first arrived, I was nitrogen dioxide and because this is a third order diesel engine, its exhaust temperature is consider - introduced to one of their senior people who told process (second order in NO) at low nitric oxide ably lower. As if this was not a significant challenge me there were ‘no jobs’. I reassured him I was not concentrations the homogeneous oxidation in air itself, diesel engines run lean, so excess oxygen is after a job – to which his response was that there is extremely slow. present, making it impossible to reduce the NOx. were no short-term contracts either! I went on to However, in combination with hydrocarbons We have developed two solutions. One is to trap meet several of scientists, including one senior and sunlight, NO 2 is more readily formed, and and store NOx as nitrate so it does not enter the researcher whom I interrogated about what they photolytically this can form oxygen atoms that environment through the tailpipe, and then peri - actually made. He pulled a jar of little polythene react with oxygen to form ozone. This is a lachry - odically enrich the exhaust gas to reduce the beads out of his desk drawer, and I must have mator – and in particularly sunny locations like stored nitrate to nitrogen. While this is effective, asked some good questions as later on I was inter - Los Angeles, Tokyo and even Rome, other photo - there is an alternative strategy – selective catalytic cepted and offered a job. So I ended up in indus - chemical reactions can lead to very potent lachry - reduction using ammonia as the reductant. Since it try very much by accident! mators like peroxyacetylnitrate . This can make you is not practical to store the necessary ammonia on cry at levels of parts per trillion. These secondary the vehicle, an aqueous solution of urea is used, So what did you do at ICI? pollutants are only formed if the primary pollu - that readily decomposes to give the desired I started off, bizarrely, managing the accounts of a tants are present, and as legislation has brought ammonia. The urea tank needs to be refilled at research group of more than 100 people who these levels down, catalyst technology has devel - service intervals, but this is straightforward, and were spending huge amounts of money develop - oped to meet the increasingly stringent demands. we are well on the way to making a success of this ing an organometallic catalysed ethylene poly - Today, tailpipe emissions have been lowered to lev - approach – already there are several tens of thou - merisation process for low-density polythene. But els that can be below those present in the natural sands of cars on the roads in Europe using this I still had time to work on several of my chemical environment, so this is really a tremendous success new technology! hobbies such as phthalocyanines and low-spin story of what can be achieved at the chem- iron(II) complexes. I also got involved with the istry/engineering interface. CV Martyn Twigg development of phosphate non-misting glasses. After a couple of years I moved to the agricul - What about diesel engines? tural division in Billingham, where I first became One of our big success stories at Johnson Matthey Born: Wolverhampton involved with heterogeneous catalysis, with involves particulates – soot from diesel engines – Status: He and his wife responsibility for developing and manufacturing and while modifications to engines have reduced Sarah have a six-year-old catalysts for producing hydrogen, ammonia, the levels that are produced, the particulate matter daughter, Isabella methanol and so on. It was very exciting as it was remains very worrying in terms of health effects. Education: Studied a completely new field for me, and there were sev - Initially, very expensive multicomponent filter sys - ‘special chemistry’ at eral significant successes. After 12 years, I moved tems were used, comprising one or more usually Hull. His PhD was in to the US to manage a research group investigating two oxidation catalysts, a large ceramic soot filter kinetics and reaction new polymerisation routes to PVC with facilities and a small tank of fuel additive that mediated the mechanisms of inorganic in America, England and Italy, and an office in periodic combustion of retained soot in the filter. complexes at the Univer - Brussels. I did an enormous amount of travelling! They were heavy and both material and energy sity of Kent at Canterbury. In 1992, I was headhunted by Johnson Matthey as intensive to produce, and they also consumed a technology director in the automotive catalyst busi - considerable amount of energy in use. Career: He spent two years at the University of ness, a very important area for the company that was Recently we introduced a new filter design that Toronto as an NRC Fellow, before returning to the being severely pressed by the competition who, can remove the particulates from diesel exhaust, as UK and Cambridge on a personal ‘Bring-Back basically, had better technology. The challenge was to well as control gaseous tailpipe emissions. The Fellowship’ with Jack Lewis and Brian Johnson. improve the commercial situation by enhancing the new single units are only six-inch long so they can After two years he moved to ICI, and then to technical performance of our catalysts. be mounted directly in the engine compartment, Johnson Matthey, where he is now chief scientist. preventing heat loss and thus adding to overall Interests: Applications of chemistry, including Why are catalysts used in the car industry? efficiency. Periodically, perhaps every 1000 km pyrotechnics. He is a Class A licensed radio Catalysts have been fitted in cars sold in the US depending on driving conditions, the temperature amateur, and in the past was a member of the since 1975 to control tailpipe exhaust emissions in the filter is increased to above 600°C to initiate British Rocketry Association of hydrocarbons, carbon monoxide and nitrogen combustion of the retained particulate in the filter. Did you know? He did not study any science at oxides (NOx), but it was not until the early 1990s This is done by putting additional fuel through school, and owes his chemical career to his that it became mandatory to fit them in Europe. I the engine, which is oxidised over catalyst at the mother’s decision to arrange for him to sit came into the industry just as the European mar - front of the filter. The particulate oxidation is a entrance exams at a college of further education ket started, and we focused on the development of very exothermic process that is carefully con - to do science O-levels. His chemical interest was fundamental chemistry required to make better trolled to prevent a meltdown! The car does this ignited by an exceptional chemistry teacher called catalysts. One of the key features is durability – computer-controlled process automatically, and Ivan Nutter who, Martyn says, lived up to his these hi-tech products must meet minimum per - the emissions generated during this process are name. In the evenings he and several other formance criteria and effectively last the life of the controlled as well. This design has won several students stayed in the laboratory to do all sorts of car. The better the catalyst technology the less awards, most notably two Queen’s Awards this fascinating experiments – he remembers amount of costly platinum, palladium or rhodium summer – one for innovation and one for interna - preparing a series of mixed salts, while other that is required, so making it overall more cost- tional trade. The uptake has been very rapid, and experiments involved materials such as mercury effective. We pushed the scientific boundaries very already more than four million of them have been and benzene. As this was taking place, Nutter hard, and did many things we were not supposed made and exported to mainland Europe, and the carefully crafted crossbows, which he fired down to do, we just got on with it and developed new quantity of particulates that have already been pre - the central isle of the lab to targets that appeared advanced world beating products! vented from going into the atmosphere is aston - after the end of the normal working day!

2 Chem@Cam Autumn 2009 Reluctant reactions Letters

Pictorial delight also provides the source for many of the images, as does Paradise Lost and the Dear Editor, Bible.This issue’s is Don Quixote again, I have for some time been meaning to with an image of the Don in his library. write and say how much I enjoy Chem@Cam – not least the pictures on the back. I have one request, though; Corrosive atmosphere might we be told (perhaps on an inside page somewhere) the picture’s original Dear Editor, subject? I guess that the latest one shows Seeing the article about fire extinguish - Don Quixote, but do not know the occa - ing reminded me that one of the regular sion – or what would happen if he held housekeeping jobs in 287 (1967-70) his pose a few seconds longer!. was to go around making sure the pins I did my PhD in Organic Chemistry could be removed from the extinguish - from 1954 to 57, working under Dr ers – when I first arrived there, all of Kenner (as he then was) but never get - them (being brass) were firmly cor - ting as far as being involved in his main roded in place and required superhu - field of interest. I remember little of that man strength or a pair of pliers to time, but can say that I moved to loosen them. I hope the atmosphere is Lensfield Road about half way through less corrosive now. it, being placed in a small basement lab - Yours faithfully oratory quite near the front entrance. Peter B Baker Another occupant was an Australian 9 Kenilworth Road, London, W5 5PB named Brian Milligan (generally called ‘Spike’ for some reason); his habit was to come into the lab of a morning, look Welsh confusion at the results of his latest chromato - graphic run or whatever, and declaim Dear Editor, ‘It’s a cruel, cruel, world!’ I was interested to see the picture of the Of myself, it was once said that I was physical chemistry department of 1960 always to be seen in the lab, but never in the summer Chem@Cam . As an actually doing anything – which sounds undergraduate doing practicals I was football supporters were killed and hun - about right. Somewhere there is a group often observed – and chatted to in Welsh dreds injured in a cup match between photo with Professor Todd in the centre, – by someone I assumed was the lab Bolton and Stoke City. in which I may be identified as the one technician with long sideburns and usu - Huw Idris Jones (1965-1968) grinning inanely while everyone else ally dressed in a blue pin striped suit. [email protected] looks properly serious! Imagine my surprise when I was Yours sincerely, introduced to him after the Sunday Chris Tylor Welsh service in Wesley Chapel to find Footy correction 3 Meadow Close, St Austell, Cornwall out he was Professor Moelwyn Hughes, PL25 3UD the son of an eminent bard and preacher Dear Editor, John Gruffydd Moelwyn Hughes, who I noticed that two names got omitted in The pictures on the back page are all taken wrote the famous Welsh hymn ‘Pwy a’m the list of footballers in the last from Cassell’s Dore Gallery, an ageing col - dwg i’r ddinas gadarn’. Chem@Cam . lection of tomes containing a 250 engrav - His brother, a lawyer, Rowy Moelwyn The names omitted were John ings by French illustrator Gustav Doré. Hughes was Labour MP for Carmarthen (‘Bones’) Connors and David Rand. Many – like the last issue’s – are indeed and headed the inquiry into the Best wishes scenes from Don Quixote. Dante’s Inferno Burnden Park disaster in 1946 when 33 Ian Smith

Cover This newsletter is published three times a year by the University of Cambridge Chemistry Department. Opinions are not necessarily those of the editor, the department, or the university. Editor-in-Chief: Steve Ley Editor: Sarah Houlton Photographers: Nathan Pitt, Caroline Hancox Editorial Board: Contents Brian Crysell, Bill Jones, News 4 Jonathan Goodman, Rosemary Ley, Jeremy Sanders Research 7 Anthoulla Papageorgiou from Address: Alumni 11 Richard Lambert’s group operating Chem@Cam, Department of Chemistry, a scanning tunnelling microscope, University of Cambridge, Lensfield Road Chat lines 13 which is used to study surfaces Cambridge CB2 1EW Phone: 01223 763865 Puzzle corner 15 Photograph: email: [email protected] Nathan Pitt and Caroline Hancox website: www.ch.cam.ac.uk

Chem@Cam Autumn 2009 3 News

model enzymes’, written with Florian A trio of tomes hit the shelves Hollfelder from biochemistry, is about catalytic efficiency – how to measure, Ian, Tony and understand and create it using the tools Stuart: still writing and thinking of organic chemistry and away in the molecular biology. ‘By a happy coinci - department. dence, the cover picture of the ribo - ‘Visitors interested some is a gift from Ada Yonath, whose in discussing their Nobel prize was announced the day the chemistry are book was published,’ Tony says. always welcome to Stuart’s latest book is a new edition of visit us!’ Tony says the Workbook that accompanies d r

a ‘Organic synthesis: the disconnection n r e approach’. These have been completely B y

r rewritten, in collaboration with former a M

Cambridge student Paul Wyatt, who’s : o t now director of undergraduate teaching o h

P at Bristol. This workbook completes a mammoth four-volume set of organic The three retired(ish) professors who ‘There was always a problem – com - chemistry teaching books that have inhabit M21 have been busy. Ian putations showed the frontier orbitals appeared since 2007. Fleming, Tony Kirby and Stuart have do not make a significantly larger con - ‘The first edition of these books were been occupied with writing for years, tribution than the sum of all the other published in 1982,’ Stuart says. ‘They and in the past few weeks all three have orbital interactions,’ he says. ‘The diffi - were typed, and the structures done had books published. culty is that it often works as an expla - with stencils. The results looked more The fruit of Ian’s labours is the long- nation where nothing else is immedi - like an underground publication in awaited second, completely revised, edi - ately compelling.’ He hasn’t ditched Soviet Russia than a modern chemistry tion of his famous book on frontier them completely in the new book, but book. The new editions look very differ - orbitals, in the shape of ‘Molecular there’s a greater emphasis on the molec - ent.’ He’s now working on the second orbitals and organic chemical reactions’. ular orbital basis for understanding edition of the big textbook ‘Organic The original came out in 1976 and sur - organic chemistry. chemistry’ with Jonathan Clayden, and vived in print for more than 30 years. Tony Kirby’s ‘From enzyme models to aims to finish this in 2010. Eric the honorary RSC fellow

Eric (left) receiving his certificate from RSC president t

t Dave Garner i P

n a h t a N

: s o t o h P The Unilever Centre for Mol- ecular Science Informatics held a workshop to start off the new £3.2m funding from Unilever. ‘This is our core funding for the next five years,’ says centre director Bobby Glen, pictured right Congratulations to Eric Walters, who Walters Kundert Trust, with donations to at the workshop. ‘It includes was made an Honorary Fellow by the our Science Day activities, as well as funding for three lecturers, computer officer and Royal Society of Chemistry earlier this funding Next Generation Fellowships secretarial support, and year in recognition of his support for for promising young lecturers – he’s £1.5m is reserved for chemistry. Eric is also a long-time sup - currently supporting Jonathan Nitschke projects with Unilever.’ porter of the department through the and Oren Scherman.

Wiith theiir ANU hosts,, from the lleft:: Vance Lawrence,, Pete Wothers and Mark Hudson took this year’s Science Festival Mark, Pete, Mark Ellison, Geoff Salem and Paul Gugger Mark, Pete, Mark Ellison, Geoff Salem and Paul Gugger schools’ lecture, ‘Just add water’, all the way down under in August. As part of Australian National Science Week, Canberran schoolkids were treated to the action-packed chemistry show at the Australian National University. It was so popular they had to perform four times! ‘Some reactions didn’t behave the same way as they do over here,’ Pete says. ‘We couldn’t make cyclohexane ice cubes, and the silver nitrate and magnesium powders were more reactive. I spent several days with lots of black spots on my face from a rather frisky reaction!’ They’re now TV stars in Australia, too, as it was shown on the ABC channel. It went down so well they’re returning to Oz next year, also visiting Sydney, Melbourne and Tasmania

4 Chem@Cam Autumn 2009 www.ch.cam.ac.uk

Congratulations to Steve Jenkins, who’s Prizes for Steve, Ian and Oren been appointed to a university lectureship. Steve Steve Ley has added three more medals include several which are promising works in surface to his collection. The Tetrahedron Prize anticancer agents that are in short sup - science, and one for Creativity in Organic Chemistry was ply from their natural sources, especially of his hobbies is presented at the ACS meeting in Boston those of marine origin. creating computer- in August, and the citation mentioned Oren was one of the three Harrison- generated images the wide range of chemistry he’s been Meldola Memorial Prize winners. These of chemical subjects. They make involved in over the years, including are given for the ‘most meritorious and great journal synthetic organic methodology, chemi - promising original investigations in covers, and here’s cal technology and complex natural chemistry and published results of those his latest offering. It product synthesis. investigations,’ and Oren won for his accompanies an He also received the Heinrich work on supramolecular polymers, in invited review in Proceedings of the Wieland prize for his ‘extraordinary sci - particular in aqueous environments. ‘I Royal Society A entific achievements in the fields of syn - was delighted to win the prize,’ Oren about aromatic thesis, structural analysis and biological says. ‘The work wouldn’t have been pos - adsorption on characterization of natural products’. sible without the hard work of my tal - metals via first- The prize is endowed by Boehringer ented group, and it was really nice to be principles density Ingelheim, and was presented at a cere - in such good company with the other functional theory mony in Munich in October. ‘I’ve had a prize winners.’ very good year, and am very proud that On the funding front, Oren has been our work is being supported and recog - awarded a prestigious starting grant nised in this way,’ Steve says. from the European Research Council. The third prize, the RSC’s Perkin Prize There were 10 times as many applicants for Organic Chemistry, was given at the as grants, so this is something of an RSC’s awards ceremony in November. achievement! The grants are designed to Two other Cambridge chemists were support scientists who are in the early also given awards at the event – Ian stages of their independent research Paterson and Oren Scherman. careers, and Oren has been given a grant Ian was one of three winners of the of €1.7m to support his work on aque - Tilden Prize for advances in chemistry. ous supramolecular polymers and pep - He won for his ‘outstanding achieve - tide conjugates in reversible systems. ments in the total synthesis of complex I Congratulations also go to Dave natural products’. Over the years, Ian King, who’s been appointed Chancellor has introduced general methods for of Liverpool University. Dave was pro - The university’s 800th anniversary celebrations are drawing to a close, and one of the recent events was a celebration for alumni stereocontrolled synthesis, which have fessor of physical chemistry in and donors in New York. The Empire State Building was even lit up enabled the total synthesis of a large Liverpool in the 1970s and 1980s, in Cambridge blue for the occasion. Guests included such luminaries number of biologically important before he came to Cambridge chemistry as Stephen Fry, Sir David Frost… and Jeremy Sanders (above)! polyketides within his group. These in 1988. The Corporate Associates Scheme Arecor Thanks to the generosity of the depart - networking events at the department; Heptares 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 - IDBS Astra Zeneca Astra Zeneca environment for students and staff. For ings and various publications; Illumina Cambridge – MedImmune example, the Associates pay for univer - I Access to the department library sity-wide access to SciFinder Scholar and photocopying/printing facilities; Johnson Matthey Catalysts Asynt and ChemOffice. They also make signifi - I Regular communications about cant contributions to the library for upcoming events and colloquia; Maruzen International Biotica Technology journal subscriptions. Moreover, they I Subscriptions to department publi - Boehringer Ingelheim Pharma provide exam prizes, faculty teaching cations, including Chem@Cam; Merck Sharp & Dohme awards and summer studentships, and I Priority notification of and free Novartis BP have recently funded the refurbishment access to departmental research lectures; BP Institute of a state-of-the-art meeting room with I Ability to hold ‘Welcome Stalls’ in Pfizer teleconferencing and display facilities. the department entrance hall; Bristol-Myers Squibb Corporate Associate membership not I Preferential conference rates; Proctor & Gamble Cambridge BioTechnology only provides essential support for the I Free access to the teaching lectures department, but also provides numer - held within the department; Roche Cambridge Medical Innovations ous benefits to help members work with I The full services of the Corporate Royal Society of Chemistry CambridgeSoft us and achieve their business objectives. Relations team to facilitate interaction Members enjoy many benefits through with students, staff, and other parts of Sigma-Aldrich Chemical Computing Group their enhanced partnership with the the University of Cambridge to help department, such as: achieve your corporate objectives. Society of Chemical Industry Cornelius Specialties I Visibility within the department; If your organisation would be inter - Takeda Cambridge Dr Reddy’s Custom Pharmaceutical I A dedicated meeting room and ested in joining the Corporate Associates Services office for members to use while visiting Scheme, then please email Jane Snaith at Unilever the department; [email protected], or call GlaxoSmithKline I Invitations to recognition days and 01223 336537. Uniqsis

Chem@Cam Autumn 2009 5 News The lab book enters the 21st century extended to the whole world,’ Tim says. The traditional lab notebook is great for recording results, but not This isn’t as insane as it might sound very good for searching them. The electronic version changes all that – there’s a big drive in the US to make all experimental data publicly available, particularly when the research was paid for by a public body like the NIH, and that’s bound to spread. It will certainly make producing papers and theses more straightforward as all the data are in one place. The ELN will make it easy to pull out all the data on the experiments and compounds from the database and drop them into a publishable format. Brian says many researchers currently store their data in Excel spreadsheets and write-up their experiments in Word documents; this raises the question of what advantage the ELN has over this approach. ‘It’s a good question,’ he says. ‘But ELNs have so much more functionality, quite apart from the searchability of the x o database. The ELN holds the whole con - c n a Bhavinita Patel text of an experiment in one location. H

e from Bill Jones’ n And the ELN has capabilities to make the i l o r group is one of the content more active; the viewer soft - a C

: pioneering souls ware, for example, allows you to rotate o t o taking part in the chemical structures on screen, and with h P ELN pilot project an NMR spectrum you can take a small The department is in the throes of a reagents given the stoichiometry. The subsection and expand it to get a clearer pioneering project that will make it the ELN collects the health and safety data, view of the peaks.’ All this is done within first UK chemistry department to displays the risk factors, and records the the same software environment, with - implement an electronic lab notebook emergency procedures. out having to jump between different system, or ELN. Based on a commercial ELNs have been used in the pharma - packages, making life much simpler and system from IDBS, it will enable ceutical industry for some time. easier for the chemist. chemists to manage their data more However, it’s much more of a challenge In the future, Tim envisages hi-tech effectively. The first 20 or so chemists developing a system for an academic gadgets being used in the lab to input are already using it, and their feedback chemistry department as the science is and view data, such as devices that proj - will be crucial in designing the final so much more diverse. It also has to ect virtual keyboards onto surfaces, and shape of the notebook. work seamlessly on Macs, PCs, and even even data projectors within a fume Linux machines. This is being addressed hood. ‘The technology is moving very DATA MINING by using a terminal server – the data are fast,’ he says. ‘Devices like these only The amount of data that experiments kept on a central server, and the ‘front take up a very small amount of space, generate these days can be huge, yet end’ which interfaces with that server and so they can be activated wherever there is currently no efficient way for can be on any type of computer. they are needed.’ our chemists to archive their spectra in ‘It’s a neat way of doing things,’ a searchable way that also captures explains Brian Brooks, who imple - CHEMICAL INVENTORY information about the experiment mented the lab notebook system at It also offers the potential for further itself. ‘Today, NMR spectra, for example, GlaxoSmithKline, and is helping the improvements in the future – such as an are filed away under date and scientist, implementation process here in chem - end to those ‘has anybody got this but there’s no chemical information istry. ‘You can log into your lab note - chemical’ email that clutter up inboxes there,’ explains Tim Dickens, the depart - book area on any linked machine – on a regular basis. ‘Implementing a ment’s IT manager. whether in the lab, a write-up area or chemical inventory would make us ‘If you want to find a spectrum run even the library. It also logs straight into much more efficient,’ Tim says. ‘It by someone who has left, you have to the same session, so you don’t have to would require cooperation from a lot of dig out notebooks, papers or the thesis start again. We’re really pleased with the different groups, and also data such has of the person who did the research from way it works.’ how old chemicals with a finite shelf- around when you think the experiment There’s also the issue of who has life are would have to be included. might have been done. If that person did access to the data. The ELN has three ‘I think we will look back in a few a lot of reactions, that means a lot of files ‘audience’ areas; one which is years’ time and wonder how we ever to wade through. Being able to link the restricted, one which allows their own managed to do science without the ELN,’ spectra to the experimental results is research group to see the experiments, Tim says. ‘I also think it will become something of a sea change.’ and one which the whole department increasingly important as we form larger The system is really straightforward can see. The scientist decides who they groups and partnerships, and people to use. For a synthetic reaction, the wish to be able to see their experiment, work in a more collaborative fashion in chemist draws the reaction scheme and then creates their experiment in the different locations. Being able to share using ChemDraw, and the lab notebook appropriate area. ‘At some point in the data electronically in a seamless fashion will automatically calculate quantities of future, we foresee this might be like this is the way forward.’

6 Chem@Cam Autumn 2009 Research Small is beautiful It’s important to know how drugs bind to their active sites if better ones are to be designed. Alessio Ciulli’s using fragments to explore them

Drug molecules work by binding to active sites within the body, often at some form of protein such as an enzyme. In recent years, huge advances in chemical techniques such as X-ray crystallography and NMR spectroscopy

have made it possible to determine the x o c structures of many of these proteins. n a H While this is a great starting point for e n i finding a new drug, it’s not always l o r a

immediately obvious exactly where the C

: o drug needs to bind to the protein to t o h

work, or at how many points. One P method that can help probe these active sites uses fragments – small molecules ‘TB is a particularly nasty infection as fragment bind, what are the key interac - that interact weakly with the protein. the bacterium becomes latent, and com - tions, and what can we learn from it?’ he While these in themselves won’t make pletely changes its metabolism,’ Alessio says. ‘We want to find out what the good drugs, they can provide optimal says. ‘What’s really needed is a chemical hotspots for binding are, and then how to starting points for finding a molecule validation of new targets. Fragments are go about designing a molecule that works that binds more effectively to the protein potentially fantastic tools to probe the effectively there, or taking them forward and has the desired therapeutic effect. druggability of targets, and to show into new chemical tools.’ Alessio Ciulli is using fragments like whether inhibiting it will actually have a In collaboration with Chris Abell and this to try and gain new insights into physiological effect in living cells.’ graduate student Alvin Hung, he has biology. ‘During my PhD, I started recently published a direct comparison working on enzymes from Mycobac - INTELLECTUAL CHALLENGE between two different ways of doing terium tuberculosis , the bug which During his JRF, he was involved in vari - this – starting with a small fragment and causes TB, with the hope of finding new ous collaborative projects with scientists making it larger by adding further func - compounds that might be useful in in other fields, and has carried these on tionality so it fills the binding site better, treating the disease, or at least find a into his independent research career. and taking two fragments that bind starting point for a medicinal chemistry ‘This brings many different expertises weakly to different parts of the protein programme,’ he says. ‘TB is a tremen - together, such as protein chemistry, and linking them together. ‘We came up dous health burden, especially in the molecular biology, structural biology, with two very similar molecules in this developing world, and the newest drug biophysical screening and, ultimately, way, which differ very slightly at the that’s currently used was discovered 50 medicinal chemistry,’ he explains. ‘It ends, but while one binds like the two years ago! So there’s a great need for would be impossible for a single person initial fragments, as you would expect, new targets and new drugs.’ to work on all these different disciplines, the other binds differently. Yet the core Many people have been looking for so working together is essential.’ structure is very similar!’ potential targets within M. tuberculosis Because these fragments are such small A new collaboration is taking the idea using genetics, but while genetics can molecules and bind so weakly, the real into another area – sugars. ‘Barbara tell you if that target is essential in its intellectual challenge lies in telling the Imperiali at MIT has a long standing lifecycle, it can’t tell you whether difference between a specific, weak inter - interest in the biosynthesis of highly inhibiting it will prove lethal to the bac - action between the molecule and the pro - modified sugars in Gram negative bac - terium, so you need to try it and see. tein and a non-specific one. ‘ Why does a teria, which are crucial to both their pathogenesis and their virulence,’ he Born: Florence, Italy returned to Cambridge and chemistry this

i says. ‘Most of the enzymes responsible l summer as a BBSRC David Phillips fellow. l Status: His girlfriend, Stefania Lanni, was brave for the biosynthesis of these modified u i enough to follow him to Cambridge when he Interests: Skiing, road cycling, tennis, playing sugars are unique to these bacteria, and C started his PhD, despite speaking no English. She the guitar, and he’s learning to play bridge. we hope my fragment screening expert - o i is now office manager at the acute neonatal Did you know? Alessio first came to Britain as ise will enable us to discover how we s transport service unit at Addenbrookes. s a 16 year-old English language student. On a can target sugar binding sites. e l Education: He studied chemistry at the day trip to London, he and a friend headed to ‘There have been very few drugs that

A University of Florence, and his first experience Wimbledon with the dream of watching the target sugar sites, the exception being of Cambridge was as an undergraduate ladies’ final, despite not having a ticket for the neuraminidase inhibitors like Erasmus exchange student a decade ago. He Centre Court. They were foiled by a security Tamiflu. The general consensus is that V returned to Cambridge in 2002 for a PhD with guard, but he relented at the end of the match the binding site has to be flat and polar C Chris Abell on a Gates scholarship. and they took photos of Jana Novotna crying in nature. This makes them difficult to Career: After three years as a JRF at Homerton on the Duchess of Kent’s shoulder after target, and this excites me as my ulti - and mastering protein X-ray crystallography throwing away a win. ‘Since then, I’ve had a mate goal is to see if fragments can with Tom Blundell, he spent five months as an day out of the lab at Wimbledon every teach us how to design molecules that HFSP fellow with Craig Crews at Yale. He summer!’ he says. work against binding sites traditionally considered undruggable.’

Chem@Cam Autumn 2009 7 Science Designing new materials for energ

to the whole street when it was plugged Clare Grey’s chemistry is focused on helping identify novel materials into the mains! Fuel is a very efficient for making better and more effective batteries to store energy way of transporting power. The strategy is to design cars that would allow peo - ple to drive short distances regularly before charging up overnight, but that A sustainable energy supply for the would combine a back-up source of future will require reliable renewable power generation to allow occasional sources of power – and a mixture of long trips – the plug-in hybrid.’ sources. Yet wind turbines only produce The main issues, she says, are cost, energy when it’s windy, and solar panels materials, resources, capacity, power when the sun is shining. Neither is it and safety. ‘I would argue that if you easy to store the electricity that’s pro - want to make progress in this field, you duced for the times when none is being have to understand how some of these generated. Transporting it is another processes work, and then use this issue – it’s all very well building huge knowledge to design and improve the wind farms in isolated areas or installing materials we have now, and come up miles and miles of solar panels in the with better ones.’ Sahara desert, but if the energy can’t be One of the main focuses of Clare’s distributed to where it’s needed then it’s research is using NMR to understand a fairly pointless exercise. what’s happening to the lithium ions as It can’t simply be stored on the grid a battery is charged and discharged. as that’s merely a series of intercon - ‘Lithium is a good nucleus for NMR, nected wires. Too much of the electric - and it’s intimately involved in the whole ity is lost on transmission down those process,’ she explains. ‘We’ve been wires to make very long-distance distri - doing experiments ex situ by taking the bution viable, and it’s expensive and battery apart, and also in situ , which logistically difficult to run the cables. means we can watch what is happening Electricity distribution can be made to the lithium ions in a working battery more efficient by increasing the voltage in real time.’ and using superconductors, but even It’s not just the big picture of energy There is a number of reasons why this has practical problems. The bottom generation and transportation that is an this is useful. ‘Even a simple material line is a wholesale move away from fos - issue – at a smaller scale, the batteries like lithium cobalt oxide is a layered sil fuels to renewable energy sources that are used in mobile phones and lap - material, and when all the lithium ions will require the ability to store electric - tops are far from ideal. The standard lap - are pulled out the layers shear, making it ity, and transport it from where it’s pro - top and mobile phone battery was very difficult for the lithiums to get duced to where it’s needed. developed by Sony in 1990 using back in again,’ she says. ‘So in practice, New and better materials will pro - chemistry from John Goodenough’s lab only about half of the lithiums are vide the key to solving some of these at Oxford, Clare says. removed as the battery is charged to problems, and Clare Grey’s chemistry is ‘He came up with the chemistry for ensure it retains its structure, resulting aimed at helping to find them. ‘I’m an the cathode, a material containing layers in 50% dead-weight. If the layers could inorganic chemist, but my work bridges of metal, oxide and lithium ions. When inorganic and physical chemistry, mate - it’s charged, the metal ions are oxidized, Born: Born: Middlesbrough, where her dad worked 3+ 4+ y rials science and chemical engineering,’ for example from Co to Co . At the e for ICI. She moved to the Netherlands at the age of 2, she says. ‘I’m very interested in how same time, the lithium ions are pulled r Belgium at the age of 7, and then at 14 went to G local structure of the materials used in out of the structure, and then travel school in St Albans. e batteries and fuel cells – devices through a non-aqueous electrolyte to r Education: a chemistry degree at Oxford led to a a required to store and convert energy the anode, where they are then inserted l DPhil there on the solid state chemistry and NMR C efficiently – affect their performance in in between the carbon layers of the spectroscopy of paramagnetic materials with Tony specific applications.’ graphite anode. The opposite process Cheetham, who’s now Goldsmiths' Professor of occurs as the battery is discharged.’ Materials in Cambridge ELECTRIC VEHICLES The ideal battery material will use V Electric cars are one example where reversible chemistry that can go back C Career: After a brief stint as a junior research fellow at better batteries are critical. Current and forth thousands of times without Balliol, she moved to the University of Nijmegen in the technology is limited to hybrid electric degrading, will have large differences in Netherlands as a Royal Society research fellow, before vehicles such as the Toyota Prius, where the electrochemical couples between heading to Du Pont’s central research labs in the US. the combustion engine is supplemented the two materials to give high voltages Two years later she moved to Stony Brook University in by a battery system that stores the and thus high energy, and also be light New York as an assistant professor, being made a full kinetic energy lost on braking. New bat - and thus give a high capacity on a professor in 2001. She moved to Cambridge in July as teries are required to power the next weight basis. Current materials fall short Geoffrey Moorhouse-Gibson professor of chemistry. generation of electric vehicles, which of these ideals. Status: Husband Daniel Raleigh is an academic are plugged into the mains to recharge ‘It takes a long time to charge a lap - biophysicist, working on protein folding and them. ‘This doesn’t solve the problem of top, and for a car, consumers want to be amyloid formation where the energy comes from as a bat - able to charge it in 20 minutes,’ she Interests: Cross country skiing, hiking, playing the cello tery merely stores it,’ Clare says. ‘But explains. ‘But that’s not even a problem DId you know? Clare plays an18th century Czech combustion engines are massively inef - with the battery – it would probably cello that she found abandoned in an antique shop ficient, whereas electric motors can, in require cables half a foot thick and and rescued. It cost her the princely sum of £50! principle, be almost 100% efficient.’ would probably short-circuit the power

8 Chem@Cam Autumn 2009 www.ch.cam.ac.uk y storage How to run an NMR of a functioning battery It may seem unlikely, but it is indeed possible to run an NMR spectrum of a battery in real time as it be stabilised somehow, the operating charges and discharges. In a solid state NMR machine, the sample is put inside a chamber about 1cm power of the battery could be doubled.’ by 0.5cm in size. Normally, a battery would be encased in metal, but this makes it difficult for the One project she’s carrying out, in association with GM, involves looking at radio waves to pass through. Instead, it is sealed inside a plastic bag with an aluminium coating that the problems involved with inserting prevents oxygen and moisture from entering the system. These bags are exactly the same material as lithium ions into the graphite anode. ‘In those ground coffee is sold in to prevent the coffee from deteriorating in quality. principle, carbon has a large capacity, The battery is inserted in the bags, with leads protruding from the edges, the air sucked out, and then but if the battery is charged too fast, the it is heat sealed shut using a crimper, over the wires. The leads are then connected to the power kinetics of the lithiums entering source and placed in the NMR machine, and the battery can be charged and discharged while a between its layers become challenging. lithium spectrum is being run. ‘You can watch the whole battery, with the lithium ions going in and Instead of going inside the layers, out, and the NMR peaks grow and diminish as it cycles,’ Clare says. ‘It’s also possible to see what’s lithium plates and forms lithium den - happening to the electrolyte, for example in a silicon-based battery, it slowly forms a coating which drites, which eventually cause short-cir - ultimately stops the battery from working.’ cuits,’ she says. ‘We’re using in situ NMR to watch the dendrites forming to try It also shows the formation of lithium dendrites very clearly. ‘That’s why you can’t use pure lithium and work out what conditions they form metal as the anode – as you cycle backwards an forwards, instead of lithium plating on the surface it under, and then find a way to get rid of grows fibrous lithium dendrite structures,’ she says. ‘These grow and grow as the battery is cycled them. That would be impractical to do if backwards and forwards, and they are incredibly strong. Even though lithium is quite a soft metal, you had to take the battery apart.’ they can force their way through strong polymer membrane separators.’ She believes understanding what is happening is essential if new and better know the structure, we can’t even begin so why not use something that’s more materials are going to be discovered. to think about how to improve its per - abundant? ‘As the ions have to move ‘Although some discoveries appear to formance.’ through the solid, that is very limiting,’ be a result of trial and error, most Part of the problem is that it’s disor - she explains. ‘An alternative for a tiny inventions are underpinned by an dered, so techniques that look at long- ions is magnesium, whose ions are 2+, understanding of what’s going on,’ she range order such as diffraction are less and people are working on magnesium says. ‘Few inventions happen in a vac - useful. ‘We can study the lithium and batteries, but while only a little is lost in uum, and most require an enabling silicon NMR spectra, and use this to voltage, a lot is lost on rate perform - technology to inspire them. For exam - help us solve the structure, and with ance, because of the need to pull the the ple, lithium iron phosphate is a promis - diffraction experiments we should be doubly charged magnesium ions out of ing new cathode material, again able to determine a complete picture of the structure. Sodium is also a possibil - invented by Goodenough, but it was a the material. When we know what the ity, but it’s pretty reactive! Some buses very poor electronic conductor, mean - material changes to, then maybe we use a high temperature sodium battery ing that although the lithium ions could will be able to synthesise that structure based on ionic liquid electrolytes, be extracted, the electrons could not be from the beginning, or perhaps keep which operate at 300°C but there are extracted, and you need to be able to do the original structure by doping it safety concerns.’ both at the same time. appropriately to add stabilising ions.’ Then there are different metals. While CHEAP MATERIALS INCREMENTAL ADVANCES lithium iron phosphate works very She’s now collaborating with a group in ‘Someone else thought that coating the well, if the iron is replaced by man - Spain on an EU-funded project on material with a fine layer of carbon ganese, it doesn’t work well at all. sodium batteries. ‘While they may well would decrease the distance the elec - ‘Manganese would be good as it oper - not be viable for widespread transporta - trons would have to tunnel from the ates at a higher voltage, and would give tion uses as yet, they could have appli - carbon coating through to the material extra energy density and increase the cations in the home – though probably to the iron ions inside. Then someone battery’s power,’ Clare says. ‘But why not in laptops that could be taken on else showed that using nanoparticles doesn’t it work? Is it the crystal struc - aeroplanes!’ she says. ‘But a combina - could also reduce tunnelling lengths ture, or is a completely different reac - tion of sodium with other cheap mate - and showed that this resulted in very tion going on? We want to understand rials like iron silicates and phosphates high charging and discharging rates. how things like this work to give us the might offer alternative batteries. I’m This material has challenged conven - basis for designing different systems interested in how their structure tional wisdom, as insulators did not that might be more effective.’ impacts performance – we explore how make good cathode materials! But now Another issue is the lithium itself – to improve performance by systemati - there is a strategy that might make them there’s only a finite resource of lithium, cally varying structure.’ work, through incremental advances.’ She’s just had a grant funded with Peter Bruce at St Andrews as part of the Supergen consortium for batteries, looking at iron silicate batteries. ‘Silicon is the most abundant element after oxy - gen in the earth’s crust, and iron silicate batteries could be very cheap,’ she says. ‘The material itself doesn’t work well, but now we know we can try put - ting on a carbon coating. It then turns out that when the battery is cycled, the structure changes, so now we have to work out what changes. Can we sta - bilise this new structure? If we don’t

Chem@Cam Autumn 2009 9 Research

abstract lattice. He wondered whether it could be possible to devise simple rules Quantum complication to a game of life that, as it evolves, spontaneously leads to the ground state electronic wave function. The electron correlation problem has confounded theoreticians for And it turned out that it could. ‘There’s decades. A new method devised by Ali Alavi may provide a solution an incredibly simple set of rules that enable you to do this – and which are very easy to programme,’ he said. ‘Once Ali with some of I’d worked the idea out, I had it pro - his group: James grammed within three hours. The rules, Shepherd, George essentially, are that there are two types of Booth, Ali Alavi what we call “walkers” on the lattice, and Alex Thom positive and negative. They can do one of three things at each step. They can spawn progeny, which can be either positive or negative depending on the sign of the parent and the sign of the connection to it; they die in a random fashion, with a probability that is proportional to their energy; and if two walkers of the oppo - site sign find themselves next to each t t i other, they will annihilate each other.’ P

n That simple computer simulation has a h t

a allowed the solution to many electron N

: problems to be calculated. ‘We can use it o t o

h to solve the 10 electron system very P quickly and remarkably accurately on a Anyone who’s studied for a degree in number of uncorrelated wavefunctions desktop PC,’ he says. ‘It’s also about an chemistry will be familiar with the needed to account for electron correla - order of magnitude more accurate than Schrödinger equation. Dating back to tion grows at an exponential rate. ‘Each the simplified system. My group has been the 1920s, it is central to quantum extra electron adds a factor of 10 to the having an incredible amount of fun with mechanics, but for a molecule it con - number of terms, so by the time you this, and I’ve been amazed at the amount tains terms that arise from the fact that reach about 20 electrons even a huge of interest it’s generated in the quantum electrons repel each other, and this supercomputer cannot cope,’ he says. ‘The mechanics community. It’s pretty abstract greatly complicates solving the equa - biggest system that people seem to be as you can’t really think of the points in a tion. In practice, headway can be made able to solve using this brute force straightforward lattice, and it took me a only by making approximations known approach appears to involve 10 electrons, very long time to piece together these as self-consistent fields, which simplify such as the nitrogen molecule (with a abstract notions into a form that allowed matters by assuming each electron ‘sees’ frozen core). But if you want to look at, game of life algorithms to be set out. But an average field of all other electrons, say, a magnetic cluster of iron atoms, even once the basic simplicity became clear, rather than each one individually. if Moore’s Law [that computing power the rest followed quite quickly. It’s still The electrons are assumed to move in doubles every two years] holds, that will early days, but I believe the technique is an uncorrelated fashion, and the wave - still be out of reach in 100 years.’ incredibly promising.’ function solved in this way is said to be He has been working on the problem Born: Iran

uncorrelated. In some simple systems for the past 20 years, but last year i

this works well, but in more complex achieved a breakthrough, with the v Education: He was sent to school in the UK at the a ones such as bond-breaking transition inspiration to look at the problem in a l age of 13, and came to Cambridge as an undergraduate, A

states and transition metal molecules, different way. ‘In the 1970s, the staying on for a PhD with Ruth Lynden Bell. i this simplification is just not good Cambridge mathematician John Horton l

A Career: After a two-year postdoc in Amsterdam, he enough. However, computers are not Conway came up with something called returned to Cambridge as a JRF at Trinity in 1993. He powerful enough to cope if sufficient the game of life,’ he explains. ‘This is a took up a lectureship at Queen’s University in Belfast correlation between the electrons is set of simple rules for entities that live

V in 1995, and five years later returned to Cambridge as included – in essence, the correlation is on a lattice, and how they live or die or C a lecturer. He’s now a reader. built up from a vast array of uncorre - prosper.’ Basically, every cell at the cor - lated wavefuntions. ner of a square lattice is adjacent to Status: He’s married to Sanam, a former high-flyer at Ali Alavi is working on a method that eight others. Conway’s rules are that any Vodafone who’s currently a full-time mum to their will allow accurate solutions to the elec - live cell with fewer than two or more two-and-a-half year old son, Cyrus tron correlation problem to be achieved than three live neighbours will die Interests: Rowing in the fellows’ boat at Trinity, skiing without massive computing power. ‘The because of under- or overpopulation. If and being bossed around by Cyrus problem goes back to the very early days it’s next to two or three, it lives on to Did you know? He first met Sanam when he was 14 of quantum mechanics, and despite the the next generation, and if a dead cell and she was about 8 or 9, as their fathers were both vast increases in computer power over has exactly three live neighbours, it Iranian diplomats based in India. They stayed friends the years, it essentially remains unsolved becomes live. ever since. In 2005 Ali was invited to speak at a as it’s exponentially hard. It might be Ali realised that these simple-sound - conference in Sicily and fancied staying on for a possible to solve individual cases, but ing rules, which lead to staggering lev - holiday, but thought it would be more fun with a the general solution looks impossibly els of complexity, could be applied to friend. On a whim, he asked Sanam if she fancied out of reach,’ he says. ‘It doesn’t help that the electron correlation problem, if the going with him. ‘That whim gained me a wife – we the problem is not really understood at a array of uncorrelated wavefunctions married a year later!’ he says. ‘Sometimes whimsical fundamental level, either.’ used to construct the correlated wave - decisions can alter the course of your life.’ The root of the problem is that the function are viewed as an enormous

10 Chem@Cam Autumn 2009 History Further memories of the 1960s mentioned in the earlier reminiscences, Norman Sheppard adds his own reminiscences some of whom returned after 1945. to our collection of 50th anniversary memories Christoper Longuet-Higgins suc - ceeded John Lennard-Jones as professor of theoretical chemistry after the latter I was very interested in the reminis- core of the molecule, and small chemi- left to become first vice chancellor of cences in connection with the opening cal shifts led to distorted splitting pat- the new Keele University. of the Lensfield laboratories. Here are terns, but even so…! Lennard-Jones was, I believe, the pio- some of mine. I joined the University It suddenly came to me (a Gestalt neer of molecular orbital theory in the Chemical Laboratory as an ADR in spec- switch) that the assumption of an alter- 1930s and he developed it after the war, troscopy, at the same time as the start of native isomeric structure would allow with his research students John Pople the move. I had previously held research me to fully understand the spectra. It and George Hall, to show that it and fellowships in the department of colloid involved a change from aliphatic cyclic Linus Pauling’s hybridised orbitals were science, and had for several years groups based on CH3 -CH< units com- equivalent approximate treatments obtained and interpreted infrared spec- pared with the preferred –CH2 -CH2 - based on different starting assumptions. tra for the organic chemists. groups. What was I to do? If I told Yusuf It was the long-term effect of the My teaching duties in the laboratory straight away, I would completely upset ‘weird’ quantum theory, developed by were to give the research students lec- his, doubtless already carefully prepared, the physicists in the 1920s, that led to tures on the spectroscopic methods of research talk. So I decided to give my the bringing together of physics and determining molecular structures, to additional evidence – for what it was chemistry and the revolutionary, gener- supervise and develop the spectroscopic worth (though I was convinced) – at the ation separating, transition from the instrumentation, and to run a ‘clinic’ to end of his presentation. I did so as Ian ‘preparation and properties’ teaching of help students interpret the spectra of described, and there was a pregnant chemistry in the 1950s to the mecha- their own samples. silence. Then Professor Todd said, ‘Well nistic or ‘curly arrow’ approach at the When I was appointed ADR, I told now, we thought that we had eliminated hands of Peter Sykes and Alan Sharpe. Professor Todd that in my judgment the that structure t hree years ago. Perhaps we One of the best chemistry lectures next spectroscopy for structure determi- had better repeat that experiment! that I heard as an undergraduate was nation, after IR, was likely to be nuclear I was never told the result of that from Dr Emeléus (as he then was) who magnetic resonance. Commer cial equip- repeated experiment, but the revised visited from Imperial College during ment from Varian Associates was just structure was rapidly published. After the war to help with inorganic teaching. coming on the market, and Professor that episode, I did not have to make so It was a revelation to learn of the elec- Todd applied for, and obtained, what in many of my occasional ‘five bob bets’ tronic structures of the elements based those days was a very large grant for the during my structure/spectrum clinics on the Paul exclusion principle in rela- purchase of a 40MHz spectrometer. when there seemed to be a serious clash tion to the periodic table. After the war, Ralph Elsey, a senior technician, and I got of chemical and spectroscopic evidence! Todd persuaded Emeléus to come to it to work and saw it through many tech- I never lost any of those bets. Cambridge as inorganic professor. nical updates. With a recently acquired They were exciting days with Crick very good group of NMR research stu- ARMY VOICE TRAINING The original and Watson doing work on DNA at the dents, we made contributions to the My first personal experience of the new 40MHz NMR same time in the Cavendish Laboratory molecular structure database, and I building was when I gave my first lec- machine, being – and the new Cavendish professor, developed appropriate lectures. ture in what I think was designed as a operated by Eric Neville Mott, looking for alternative NMR turned out to be a very useful seminar room in the front of the build- Liddell. How things accommodation for them as he consid- technique when applied to many struc- ing. The only problem was that a very have changed! ered this not to be real physics! tural problems, but it was very embar- noisy bulldozer was operating just out- rassing that I was not able successfully side – luckily I had been trained to use to interpret the spectra from the ery- my voice by a regimental sergeant- throaphins, Professor Todd’s main major during the war, and I survived. research interest, in terms of the struc- With respect to the building itself, ture proposed. I made this clear several Ralph Gilson should be remembered as times, but was told firmly that the the laboratory superintendent who came chemical arguments for the structure from Manchester with Professor Todd. He were very secure. was a vital figure in equipping the labo- This story, of course, relates to the ratory, and he also checked every detail of incident in a research seminar the building under construction. described by Ian Fleming in his remi- The staff members who came with niscences in the Spring 2009 Todd (they were inevitably christened Chem@Cam . I learned that Yusuf the Toddlers!) were, if I remember cor- Hamied was going to describe the rectly, Dennis Marrian (who went on to chemistry and announce the preferred radiotherapy), George Kenner, Alan structure at a research seminar. The Johnson, Basil Lythgoe and later night before this I returned to the Malcolm Clark. John Harley-Mason was embarrassing NMR interpretation prob- already in Cambridge at that time – as lem. There were complexities to the an undergraduate in 1940 I remember spectra because there was possible over- him demonstrating, in military uni- lapping of spectra from the different form, in the first year organic practical conformations of aliphatic groups that laboratory in Pembroke Street – and so occur on either side of the aromatic was Peter Maitland as well as the others

Chem@Cam Autumn 2009 11 Alumni

Back to the 60s While being every bit as spiky as Ian And to ‘Norrish’ himself as he was remembers, he nevertheless had one soft always known – I was never told what Dear Editor spot – he was a avid fan of the theatre the “R” stood for. I received one serious Ian Smith’s piece on Physical Chemistry organ and made occasional pilgrimages reprimand from him. in the Summer 2009 issue of to the Tower Ballroom in Blackpool to I was joined in B68 by a Russian Chem@Cam evoked many memories. hear Reginald Dixon (was it?). The exchange student Igor Larin (a notable Along with Ian and many others I magic word ‘Wurlitzer’ would effect a first in Anglo-Soviet relations). I was moved to Lensfield Road as an under - transformation in him. It wouldn’t save told by Norrish’s secretary to take care graduate. In 1960 as a research student you, though, from caustic derision if of Igor and to see that he didn’t get into with Morris Sugden I worked in the you lost a few grams of mercury from a any mischief. basement of the Physical Chemistry broken vapour pump. At the same time an ebullient Greek- wing (Room B68). Across from Ernie was the main American called Peter Rentzepis joined Ian’s photographs reminded me of machine shop – the territory of Bill the lab via Brooklyn. He was fascinated the great bond of friendship between Symonds and Charlie Oates and occa - by Igor and was very keen to introduce the research students and the ‘lab assis - sional apprentices. him to the American Way of Life. One tants’ without whose skills we would This pair of wizards of the lathe came, small aspect of this was the use of the have been lost. I was so pleased to see I think, from the great Cambridge phrase ‘Keep tight!’ as a substitute for their recent photos. Instrument Company. If one’s apparatus ‘Goodbye’ when taking leave of a friend. Fred Webber, Cyril Smith and Brian were more metal than glass they would Igor’s good but not excellent command Challis worked in the glass blowing make sure it worked. of English reduced this to ‘Kiptie’. room on the second floor and hand- The necessary levels of precision One day to my great dismay I received made most of the glassware used in the machining required a separate language a call to the prof’s office – the only time research labs. Cyril was an expert in of measurement. One thousandth of I ever went there. Norrish was stern. making very delicate glass Bourdon an inch (usually a ‘thou’) was a ‘fagpa - ‘Larin constantly says “Kiptie” to me gauges that involved collapsing one side per’. But this was regarded as verging on whenever I see him. I know it’s not of a microscopically thin glass bubble to the crude and a proper finish (to less Russian. What does it mean?’ he said. create the ‘spoon’. Cyril was also very than a thou) was described as ‘within a Cold terror hit me. ‘I believe it means adept at creating a viable cigarette from gnat’s doodle’. “Goodbye”, Sir – “Keep tight!” It’s three or four shreds of Cut Golden Bar Mike Springett in B67 completed the American,’ I replied. and a Rizla. basement team. He is the lad behind ‘Keep tight! Keep tight what?’ he Eric Smith also worked on the second Princess Margaret in the photo. He was a growled back. floor overlooking the main entrance. I trainee – very tall and deeply innocent. There was no way out. ‘Keep a tight suspect that many theses relied on his He would turn his hand to anything. arse,’ I said, ‘It’s American…’. ability to (creatively) develop and read He was asked by the staff of the under - ‘Don’t let it happen again, Green’ he the plates from a spectrograph. graduate lab to help them re-label some said with menace, and dismissed me In the basement Donald Oliver was in reagent bottles. As a result, they acquired back to B68. charge of the instrument and equip - about 50 bottles of ‘Ethly Alocohol’. Fortunately, when he had stopped ment store with help from George (?). I was deeply saddened when you laughing, Igor saved the day for me. Next door was Ernie Cox and his store. reported a few years ago that he had John Green He is beautifully recalled in the photo. died at an air show in the US. [email protected]

An expert in Pa and EtOH Oh mighty Chromic Having never previously returned to Dear Editor, Dear Editor the labs after completing my PhD in I was saddened to hear of Alfie Maddock’s Although I welcomed the contribution 1970, I was fortunate enough to revisit death. He was always so cheerful and from Peter Baker in the Spring 2009 room 287 in its final year before recon - enthusiastic. He was my tutor at St. issue to put my name in the limelight struction, and to my amazement my Catharine’s from 1962 to 1965, though I regarding the Chromic Frog made from bench looked just the same as in the am ashamed to say I did not keep in Kleenex, sadly I must put the record illustration! I shan’t mention the stories touch. Even at lowly undergraduate level straight. It was the invention of David about the lethal and the fire hose, or the we became aware that he was probably Baird (two benches from me towards solvent cupboard… the world authority on protactinium. the door), using Delsey paper tissues. I Happy memories. One evening at dinner at his house, he have included the evidence in the form Steve Quarrie gave us slivovitz, which we had never of a rendering of some of the occupants Kraljice Natalije 39, Belgrade, Serbia. previously encountered, and he had to at that time (circa 1968) on the black - explain that it was plum brandy. So, an board at the end of room 287. expert on ethanolic drinks also. On David Baird, for some unexplained another occasion, a group of children reason, had a habit of kneeling in front charged through the house, and we asked of his chromic acid bowl. He is appar - if they were his, to which he replied that ently saying ‘Oh mighty Chromic, he thought some of them were! deliver to me this day my Delsey frog.’ I, He summed me up accurately in ref - on the other hand, am being quizzed by erences for chemistry teaching jobs as my supervisor, John Harley-Mason, who not being of the highest academic stan - used to tell me what I was doing, and dard (I got a third) but perfectly capable then I would confirm this: ‘You’re just of becoming a competent teacher (I running an alumina column, are you, eventually made head of chemistry). A Quarrie?’ to which the characteristic very good and caring man. reply was ‘Yes Sir [those were the days!], Yours sincerely, I’m just running an alumina column.’ Ian C Potts. The unfortunate soul between the [email protected] squeeze bottles is Peter Cann.

12 Chem@Cam Autumn 2009 Chat lines

Head of photo- graphy John A trio of future chemists Holman retired in the summer after more than 20 years in the department. So the photo- graphy team could enjoy his party properly, junior assistant substitute Julius (right) and photographer Tilly and Jasper Sarah Houlton was (below). One, two, handed the three, aaaaaaah! camera… Pictured We’ve got triple baby joy to report this from the left: Caroline Hancox, issue. First up is young Julius Noam John, Vicky Spring Scherman, son of Oren and his architect and Nathan Pitt partner Sandra Leythaeuser. Julius was born on 10 September and weighed in at 2.8kg (that’s 6lb 2oz in UK baby- units). Oren reports that he’s very impa - tient – just like his father. ‘I now sleep A German wedding even less than I did before!’ he says. ‘But bar overlooking Bremen on the Friday it’s worth it – he’s lovely, smiley and night. About 80 guests attended from giggly, and never fails to let us know five countries, and about half of them when he wants something!’ had a Cambridge connection from their Meanwhile, it was two for the price times as PhD students, postdocs and of one for Keith McLuckie from Shankar working life here. Balasubramanian’s group and his wife The wedding/blessing ceremony Rebecca, in the shape of twins Matilda itself took place in the St Petri Dom, or Grace and Jasper Gabriel. Tilly and cathedral, in Bremen on 19 September. Jasper made their appearance six weeks The wedding cake was served at an early on 24 August, weighing 5lb 4oz afternoon reception in the garden of the and 5lb 15oz respectively. theatre next door. Nadine claims this ‘They’re now smiling on demand – satisfied the German tradition of eating and also starting to demand quite a lot, large quantities of cake at teatime! too!’ Keith says. Tilly is older by a whole ‘The afternoon was full of surprises minute, and already knows she’s big sis - This issue’s wedding congratulations go planned by the guests,’ she says. ‘It ter – mum Rebecca reports that she likes to Matt Gaunt and Nadine Bremeyer. The started with the release of white doves, to stamp her authority over her brother happy couple met in Cambridge when then Matt carried me through a heart by leaning over and pulling Jasper’s they were both working in Steve Ley’s after cutting it out from a sheet with dummy out when he isn’t looking. group, and got engaged in Paris last blunt scissors, and red balloons – almost December, their six-year anniversary. 99! – flying up to the sky.’ The September wedding was planned The evening reception was in for Nadine’s native Germany, and as Germany’s oldest wine cellar, which is Matt speaks no German, Nadine reports part of the town hall. ‘We managed to that he managed to get out of most of survive the speeches, games and first the organising for the event. ‘In fact, as dance without too much embarrassment he speaks no German, we also had to – and the dancing lasted until 4am,’ she have a civil wedding in Cambridge,’ she says. ‘The weather was wonderful all says. ‘We’d have needed an official trans - weekend, giving us and the guests plenty lator if we were going to be legally mar - of time to visit several beer gardens!’ ried in Germany!’ They had a short honeymoon in The wedding weekend began with a Sardinia and Venice, and are now busy ‘Polterabend’ party in a rooftop rerrace planning a big celebration holiday.

Melville Lab secretary Catherine Jordan turned 60 recently, and her desk was invaded by celebratory balloons and streamers. We suspect they might x have made typing o c n a touch difficult! a Comings & goings H New staff Noah Maheya e n i Sara Collins Ernesto Prist l o r Trevor Groves Retired a C

: Leavers John Bullman o t Christina Akosile Alan Parsons o h Chris Amey Barry Wilson P

Chem@Cam Autumn 2009 13 Chat lines Playing in the rain

The weather wasn’t kind to this year’s sports day, but that didn’t stop the fun and games – or the barbecue! Nathan Pitt wielded the camera

Left: Bill Jones shelters from the rain

Chris Chalk (left) and Matt Bushen (above) get some exercise; Caroline Hancox, Catherine Jordan and Jane Snaith contemplate the barbecue (below right)

14 Chem@Cam Autumn 2009 Puzzle corner Last issue’s winners Elementary recognition ChemDoku This puzzle comes from regular contrib - once only, spell out the name of a well- Last issue’s ChemDoku garnered its usual excellent response. utor Graham Quartly, who professes known scientist and a brief (albeit Correct solutions came from Alison Griffin, Danny Levin (who himself ‘really pleased’ with it. As well as slightly cryptic) description of why they says he’s now in California, where he’s the president of con - chemistry, he says, it involves logic are famous. Spaces between the words tract pharma development company Noracpharma, still using (chess), English and general knowledge have been suppressed! We’d also like you the skills learned at Lensfield Road, albeit now having to forfeit about scientists. By tracing out a path of to tell us why this scientist has been in the letters U and S to comply with US spelling), Ian Potts, knight moves visiting all 25 squares the news recently. Godfrey Chinchen, Annette Quartly, Robin Cork (who says he’s from the completely unknown 1949 class), Mike Barlow, Tim O’Donoghue, David Wilson, Helen Stokes, A.J. Wilkinson, John N La Re Ni Er Turnbull, Jim Dunn, John Billingsley, Diana Sandford, R.N. Lewis, Jennifer Trusted and Rachel Holland. And the lucky win - ner is... Godfrey Chinchen. Congratulations! V Er OU S MS T Y E H CI R

YCITMRHSE Co Ar Cu K Ti REHISCYTM IMCEHTRYS POTh NS ERSCYI MHT

HTYSRMI EC YICo Lu In

SI MRTYECH Scrappage selections TYRHCESMI Here’s a logic-type puzzle from Keith not the Cheetah model. Parsons. Motivated by the car scrappage 3. The all-electric green car manufac - scheme, Alan and his sister Dorothy per - tured by Toylex was bought by one of CHEMIS TRY suaded three of their friends that all five the ladies. should trade in their old cars for new 4. Colin’s black Sprint model was models. Each chose a different combina - manufactured by Nissaud, who do not Naphthalene resistance tion of manufacturer, model, colour and make hydrogen-powered engines. Unsurprisingly, David Wilson’s naphthalene resistance prob - engine type. From the information pro - 5. Brenda bought a white Gazelle lem garnered far fewer entries. However, several brave souls vided, list the combination each chose. model, which does not have a hybrid got their heads around it, and entries were received from 1. One of the men bought a red Flier engine. Richard Moss, Annette Quartly, Paul Stickland, Ian Potts and model, manufactured by Jagro. 6. Morsko manufacture only petrol Richard Brown. The prize for the first randomly chosen cor - 2. Edward bought a grey diesel engine cars, and their range does not rect answer goes to Paul Stickland. And the solutions? engine car made by Vaumaz, which was include the Racer model. a) 1 →3, 2 →4 and 2 →9 have the same resistance as each other. Each pair is linked by a shorter path of one single and one double bond, and by a longer path of two single bonds And a bonus ChemDoku… and one double bond and the combined resistance between nodes 9 and 10. Similarly, 1 →9 and 2 →3 have the same Because it’s nearly Christmas (though it’s Fe U Mo resistance as each other. In this case the short path is one sin - probably been and gle bond, and the long path is 2 single bonds, 2 double bonds gone by the time this V Cu Ni Ba and the path from 9 →10. magazine emerges 2→4, 2 →9 and 2 →3 drop out as duplicates, leaving fifteen from the postal unique values from the original list of eighteen. system), here’s an Mo b) By symmetry, the cases where there is no current are extra puzzle in the 1→8 and 2 →7. shape of another ChemDoku. Well, lots U Fe Pt c) If there is just one case where the current flows 10 →9, of readers seem to then it must arise from a connection involving the node near - like them! This time, est to 9, as 9 will then be at the lowest potential. 1 →8 is we’ve gone green, in Mo Pt U already accounted for in (b) so the answer must be 2 →8. honour of the Copen- If anyone wants a copy of David’s complete calculations and hagen summit. We’ve Ba Ni Cl explanations, drop us an email and we’ll forward it on to you! got green chlorine, seven metals which have at least one Cl green chloride, plus £20 prizes are on offer for each puzzle. Send entries a further one that’s by email to [email protected] or by snail mail to white but makes Ba Ni Mo Fe Chem@Cam, Department of Chemistry, University of green fireworks. Cambridge, Lensfield Road, Cambridge, CB2 1EW Solutions in green ink very acceptable! U Fe Pt

Chem@Cam Autumn 2009 15 Once I’ve got an electronic lab notebook, I won’t have all this trouble finding my data!

Chem@Cam is written, edited and produced

by S ARAH H OULTON

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