November 2007



A team of researchers has hit the jackpot by correctly predicting the crystal structures of four organic molecules in a competition organised by the University of Cambridge.The crystalline structure of a material defines many of its properties, including solubility, hardness and colour. Accurate prediction could be a boon for the pharmaceutical industry and help researchers design new materials with unique properties.

Cambridge’s ‘crystal structure prediction challenge’, which has been running since 1999, requires teams to predict the crystal structures of four compounds from only the molecular structure and conditions of crystallisation. This year, seven of the 15 teams that took part were able to correctly predict at least some of the crystal structures using the latest computational techniques while one team got all four right using a new computer program called GRACE.

Read more here.

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Thecommercialchemist

In this week’s Chemistry World business news round-up, we cover big pharma’s latest moves into biotech, updated safety warnings on flu drugs Tamiflu and Relenza, and Google’s quest to make solar energy cheaper than coal.

Chemical Industry

Bayer China chair:
German chemicals firm Bayer has endowed a chair of sustainable development at Tongji University in Shanghai, China. Professor Du Qun will take up the position on 1 January 2008. The endowment totals $1 million over the first five years, and will support emerging environmental technologies.

Italian job:
Dow is to spend $20 million expanding its facilities at Correggio, Italy – and will make the plant its global R&D centre for polyurethane formulation and application technology. The company also plans to increase styrofoam production capacity at the site. Dow has also completed the acquisition of three epoxy systems formulators – GNS Technologies and Poly-Carb in the US, and UPPC in Germany.

Catalyst for growth:
UK catalyst and fine chemicals company Johnsson Matthey is to build two new plants to make diesel engine emission-control catalysts. The two plants, a £34 million facility in Macedonia and a £21 million plant in Pennsylvania, US, will serve the growing demand for catalysts as Europe and the US tighten vehicle emission regulations.

Flower power:
Following EC approval, UK chemicals company Ineos has formed a joint venture to expand production at its Baleycourt biodiesel facility in France, from 110,000 to 230,000 tonnes by 2008. Ineos, along with farming cooperative SICLAÉ and oil-seed crushing group C Thywissen, will invest over 70 million euros (£50 million) in the plant, which will convert around 400,000 tonnes of locally produced rapeseed into oil and then biodeisel.

Oilseed rape

Medical and Pharmaceuticals

Cross-Pacific and Transatlantic:
French pharmaceuticals firm Sanofi Aventis, and Astellas Pharma, Japan’s second-largest drug company, have become the latest drugmakers buying into biotech. Astellas has agreed to buy US biotech firm Agensys for up to $537 million. Agensys, which specialises in antibody technology, has at least seven potential cancer treatments in development. Meanwhile, Sanofi has boosted its stake in US biotech firm Regeneron from 3 to 19 per cent, at a cost of $400 million. The deal helps Sanofi improve its biologics pipeline – the French firm also paid $85 million, and promised up to $475 more, for the rights to jointly discover, develop and commercialise Regeneron’s collection of human therapeutic antibodies.

Cleaning produces impurities:
A report for the European medicines agency (EMEA) has concluded that a toxic impurity came to be in Roche‘s HIV drug Viracept because the Swiss firm failed to understand the manufacturing process. Ethyl mesilate, the offending impurity, was produced when the company used ethanol to clean a holding tank, and didn’t let the tank dry before adding methanesulfonic acid, a starting material of Viracept, investigators concluded.

Flu drug psychiatric warning:
An expert panel has endorsed a US Food and Drug Administration (FDA) proposal that flu drugs Tamiflu and Relenza have warnings about possible psychiatric side-effects. Roche‘s Tamiflu was being taken by five Japanese children who became delirious and died, and GSK‘s Relenza has also been linked with abnormal behaviour, the FDA noted – although whether the deaths and abnormal behaviour were caused by the drugs, or the flu virus, is yet to be established. Tamiflu made $257 million for Roche in the third quarter, 62 per cent down on last year. Relenza sales also fell 7 per cent in quarter three.

Indonesia IP:
Indonesia is considering exercising national laws to produce generic versions of three more HIV/AIDS drugs without permission from the patent holders. The three second-line anti-viral drugs, didanosine, lopinavir and tenofovir, are made and marketed by Bristol-Myers Squibb, Abbott and Gilead, respectively. The country has previously used its compulsory licensing laws to make three first line HIV/AIDS drugs.

More drug safety warnings:
An FDA expert panel has recommended strengthening the safety warnings on GSK‘s inhaled asthma drug Serevent, following reports of hospitalizations and deaths in children taking the drug. While sales of Serevent have fallen following safety concerns, GSK’s asthma blockbuster Advair ($6.8 billion worldwide sales in 2006) uses the same active ingredient, prompting suggestions that this treatment could also be caught up in the concerns.

New drug-coated heart stent:
An FDA external panel has recommended the regulator approve Abbott Laboratories drug-eluting heart stent Xience, despite a lack of information about long-term safety. The panel said the FDA should require a post-market study on longer term effects. Sales of drug-coated stents have fallen since concerns were raised that they could trigger potentially fatal blood clots years after being implanted.

Axcan buyout:
Texan private equity firm TPG Capital has agreed to buy Canada’s Axcan Pharma in a $1.3 billion cash deal. Axcan, who specialises in gastrointestinal treatments, posted fourth quarter earnings of $16.8 million – double its equivalent 2006 earnings – on the back of high prescription growth.

Caring for orphans:
The European Commission, the European Medicines Agency and the FDA have agreed a common application form for companies seeking to have a medicine classified an orphan drug – a drugs that treat rare diseases. The US and EU provide regulatory and financial incentives to encourage companies to develop orphan drugs, which are otherwise difficult to make profitable given the small numbers of patients. The regulators also discussed 28 further areas where administration could be simplified, with a view to reducing the costs.

Mining and Petrochemicals

Internationalist:
US chemicals giant Dow has signed a memorandum of intent with Russian gas exporter Gazprom and petrochemicals company Sibur on deep hydrocarbons refining. The companies will look into creating a joint venture to expande Dow’s petrochemical production facilities in Germany, and to develop natural gas processing of Valangin deposits in Yamalo-Nenets, an autonomous region in Siberia.

Energy

Googling for cheap energy:
Search engine giant Google has announced it will spend tens of millions of dollars to develop renewable energy sources that can produce electricity more cheaply than coal. The company is hiring engineers and energy experts to lead the R&D project, dubbed RE<C, which will initially focus on solar power. Google says it anticipates investing hundreds of millions of dollars into breakthrough technologies which generate positive returns.

Google solar panels

Big deal:
French nuclear energy giant Areva has secured a deal worth eight billion euros to build and fuel two new nuclear reactors in China. Areva’s EPR reactors, at 1600 MW capacity, are the most powerful of the third generation of nuclear power plants.

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06sgsscreen.jpgThis is the Springerville Solar Array in northeastern Arizona: it claims to be the most productive photovoltaic array in the Western hemisphere. It doesn’t always produce its maximum power output of 4.6MW, of course, because it isn’t sunny all the time. You can check out how much power it generates, day by day, at this site. But what the graphs there don’t tell you is that every 10 seconds or so, its electricity production jumps up and down by around 40%, thanks simply to the fast clouds scudding overhead.

Jeff Nelson, of Sandia Laboratories, brought this to our attention in a lecture today at MRS, Boston. His point? That the intermittency of solar and wind and the need to evolve grid infrastructure that can cope with this, is one of the greatest challenges facing renewable energy. So better batteries and energy storage and delivery systems can do as much to further solar’s cause as any amount of clever work with excitons and nano-structured surfaces.

At the MRS there was much talk of improving new types of solar cells – organic, dye-sensitised, nano, CIGS (copper indium gallium selenide), thin film cadmium telluride, and so on.  Indeed, CdTe films are moving successfully into larger-scale production right now. But Nelson pointed out that silicon (in various forms) takes up 94% of the current solar cell market. No-one is quite sure what secret fine-tuning is going on inside the laboratories of the big silicon solar panel producers. But silicon is successful; the key to beating it with other materials is going to lie in demonstrating robust, consistent manufacturing, not in improving efficiencies, Nelson said. 

On the plus side, Nelson dismissed cost as not an issue – he thinks concentrating solar arrays can easily provide electricity at 5 or 10 cents per kilowatt hour soon, and even photovoltaics will easily make it to 10 cents. That is cheaper than the 15-20 cents paid in Japan, Europe and California – which is why solar has taken off in those areas. The rest of the US, enjoying cheap fossil fuel electricity, has had little motivation to develop solar, which is why the US market share in this area has dropped to a mere 10%, Nelson said, while the rest of the world forges ahead.

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Gold nanoparticles are hot properties in medicine, especially as imaging probes and tumour destroyers. But many are worried that this nano gold-rush could damage innocent cells. Cells actively take in larger nanoparticles – especially coated ones – as food: they wrap around them, take them in, and then find that they can’t digest them. What happens then?

Tatsiana Mironava, of Stony Brook University, New York, addressed this question on Thursday morning at the Materials Research Society Fall conference in Boston, US. Her group are growing fibroblast (skin) cells in a nanoparticle-dotted culture medium, then taking the nanoparticles away and replacing them with the usual cell culture, to see if the dividing cells recover after a week or so.

Preliminary results are not encouraging. Cells given a temporary hit of small (13nm) particles carried on dividing afterwards; but those taking in large (45nm) particles grew much more slowly. Not only did the particles concentrate in the vacuole – giving the cell a swiss cheese appearance – but they also appeared to break up actin fibres (the thin filaments supporting a cell’s scaffolding, which also play a part in cell division). Even new divided cells had damaged actin fibres.

Scary stuff – especially as it was also suggested at the meeting that while cells are busy sucking in gold nanoparticles they may have less resources to lure in the pathogens that they’re meant to be destroying. Which doesn’t bode well for a strong immune system after nanoparticle therapy.

Preliminary studies like these should be helpful, filling a much-needed gap in our knowledge of nanoparticle toxicity. But at the moment they are adding up to much less than the sum of their parts. Because, as Rebecca Drezek, of Rice University, pointed out to me, there isn’t even consensus on how to do these studies. What are the right testing regimes? What concentrations of nanoparticles should we use, and which are meaningful? At the moment the field is a whirl of conflicting results. We badly need experimenters to establish useful protocols and follow common standards – and that is quite apart from separate calls for regulation of nano-technology.

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Museums have to be specially careful that their exhibits don’t degrade due to air pollutants or gases emitted from the materials used to make displays. Traditionally, they check this beforehand using a so-called ‘Oddy test’, where materials are stored for a month with silver films that tarnish if gases are emitted. Though useful, this test takes time and damage is hard to quantify.

Nanotechnology could improve that protection, as Rui Chen, of the Art Conservation Research Centre at Carnegie Mellon University, Pennsylvania, explained today at the Materials Research Society Fall meeting in Boston. He’s tested a film sensor made with silver nanoparticles, that react much more rapidly with pollutant gases than bulk silver.  Putting numbers on corrosion is now also possible, thanks to before-and-after UV-vis spectroscopy measuring the changing optical absorption of the nanoparticle film. All in the cause of fine art – the scientists done well. How expensive this new system would be was unclear, however.

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nanotubesWalking round the MRS expo, I was startled to find a stall advertising Cheap Tubes, Inc.; with the snappy catchphrase: We search the world for the highest quality, lowest cost carbon nanotubes so YOU don’t have to!!!

It was an incongruous sales pitch, but the company (who source their nanotubes from Asia, I was informed) do seem to offer low prices, through what could politely be described as a no-frills website. They promise nanotubes by the gram from $10 to $150, or by the tonne for a six-figure sum. Other nanotube suppliers are available, of course, and Cheap Tubes, Inc. graciously provide visitors with a comparison shop page, well worth checking out. ‘Don’t be fooled by those that sell high purity, low nanotube content CNTs,’ they warn.

The carbon nanotube market is burgeoning, as Chemistry World’s recent report explains – and driving down the price is crucial to make high-quality nanotechnology affordable. I hadn’t reckoned on entrants to the bidding war looking like this though.

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As you’ll have gathered from my previous blog post, I’m currently in Boston enjoying the Materials Research Society Fall conference. The MRS organisers have persuaded some students (one of them’s only 11!) into blogging about the sessions they attended, so you can find out more about what went on in various sessions at their joint official blog – check it out here

Nobel laureate Steven Chu, of Lawrence Berkeley National Laboratory, had a lot of useful suggestions for chemists and materials scientists at his plenary today (‘The World’s energy problem and what we can do about it’), some of which were new to me (you can read about many more in Chemistry World’s Energy issue). For example, that China and India will increasingly adopt coal-fired power stations is inevitable, he said. So we should try to improve the efficiency of those coal plants, via supercritical steam boilers which work at high temperatures (600 degrees). That requires better temperature-resistant metals. Another interesting materials challenge concerns the transmission of electricity from wind turbines. According to Chu, at long transmission distances (from wind turbines placed in remote deserts, to cities, for example), a high-voltage DC grid is more robust and cheaper than our current AC system. But for this efficiency-saving benefit we must first invent better electronic switches and diodes that convert the DC source back to AC. And we need better insulating materials for ultra-high DC voltage cables undersea or underground.

But Chu was preaching to the converted. He went on to wonder whether, after all, most people don’t really understand the urgency of climate change, despite the steady drumbeat of coverage in newspapers. For example, he pointed out, doubling the cost of electricity (via conversion to solar, say) is widely seen as a frightful measure. But since electricity costs are some 1-2% of one’s typical household bills, doubling them only amounts to another 1 or 2% on top – which is a small insurance to pay against possible catastrophe. The same argument applies to expensive electricity in businesses, Chu said – ‘ruin the economy? I don’t think so’. One of the reasons, he suggested, that electricity hasn’t yet got more expensive is that the public (and crucially, government) still haven’t yet understood how ruinous climate change could turn out to be.

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harry-kroto.jpgHarry Kroto, discoverer of the buckyball, 1996 Nobel laureate, and past RSC president, has just been awarded another honour here at the Materials Research Society Fall meeting in Boston, US –  the inaugural Fred Kavli distinguished lectureship in nanoscience. In his lecture Sir Harry, wearing a charismatic bright orange shirt, namechecked Galileo, Dante, Thomas Paine, Walt Whitman, Richard Feynman, Albert Einstein, John Cornforth, Carl Sagan, Abraham Lincoln, and Ian McKellen (with whom he was in a play at school). With a scattergun of inspirational quotes, he touched on the responsibilities of scientists as citizens; the devil of religious and moral certainty; the demise of the meccano set that inspired him as a child; the world’s obsession with celebrity; and, above and beyond all, the need for educating future generations about science.

Kroto discussed his amazing outreach work, including the Global Educational Outreach Initiative, which aims to provide a globally accessible cache of quality science and technology material for teachers to use in classrooms. He’s also founded the Vega Science Trust, which provides some very interesting science TV, including many Nobel Laureate interviews. There’s a danger that all these worthwhile educational initiatives may end up as lone voices drowned out in a profusion of sub-standard cool science YouTube videos, but if anyone can pull them together into something more coherent, Kroto may be the man.

For all his renaissance man quotes, Kroto seemed rather downbeat about the future of humanity (a question put to him at the end); ‘irrationalism is stalking the world,’ he said. But he’s kept his sense of humour, pointing out that the Mexican children enjoying balancing models of C60  on their heads (in a video shoot of one of his recent workshops) were the only ones who’d found a use for buckyballs so far…

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Lee Cronin of the University of Glasgow has won the Philip Leverhulme Prize for his work in nano-scale chemistry and molecular engineering. The prize recognises young UK academics who have made a substantial and internationally-recognised contribution to their field, and who are expected to continue to produce high-impact work in the

future.

Lee

The Cronin group works on a variety of nano-scale systems, from synthetic building blocks to DNA architectures, with a view to making molecules and materials with interesting properties, from magnetic and optical to porous structures. Many of Cronin’s nanoarchitectures are made via directed self-assembly.

Cronin says he plans to use the £70,000 prize to part-finance a student, and for study visits to nanotechnology groups in Japan and the USA.

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Thecommercialchemist

In this week’s Chemistry World business news round-up, we cover billion dollar deals in pharma and fine chemicals, the reopening of the last Cornish tin mine, and more potential ructions over GM crops in the EU.

Chemical Industry

Russian investments:
The Russian government has announced it will build six major new chemicals plants by 2015 – at a reported cost of $164 billion. The country is seeking to increase domestic production of value-added products, such as plastics, to supply growing industries such as car manufacture, said Energy and Industry Minister Viktor Khristenko, and to boost the chemical industry’s contribution to GDP from 1.7 to 3 per cent.

Merger moves closer:
US chemicals firm Lyondell Chemical Company shareholders have voted to approve the acquisition of the company by Dutch firm Basell for $48 (£23) per share. The EU has already cleared the deal. Once the $12 billion agreement completes, the new company will be known as LyondellBasell Industries.

Lonza’s bio focus:
Swiss-based pharmaceutical, healthcare and life science industry supplier Lonza has completed the sale of its Singapore isophthalic acid plant to Swedish speciality chemicals company Perstorp. Lonza says the $138 million sale is part of its strategy to focus on its life science operations.

Bioethanol plant opens:
The UK’s first bioethanol plant has opened in Wissington, Norfolk. The British Sugar-run plant will produce 55 000 tonnes of bioethanol from the 110 000 tonnes of sugar grown in the UK that is surplus to quota allowances and can’t be exported from the EU.

Medical and Pharmaceuticals

GSK’s mixed fortunes:
The UK’s GlaxoSmithKline has agreed to buy US pharmaceuticals firm Reliant for $1.65 billion – acquiring the US rights to heart disease drug Lovaza in the process. Reliant made $341 million in net sales in the first nine months of the year, $206 million of which came from Lovaza, with sales expected to grow. The company has also received a boost from clinical trials of its rotavirus vaccine Rotarix, which showed it was effective against the five most commonly circulating types of the gastroenteritis-causing bug. The disease kills over 600 000 children every year, primarily in the developing world.
Meanwhile, GSK’s former head of research Tachi Yamada has been summoned to appear before a US congressional body over alleged intimidation of a scientist who had criticised the company’s diabetes drug Avandia (pictured below). John Buse raised concerns that the drug heightened the risk of heart attack shortly after the drug launched in 1999. Last week the US Food and Drug Administration added a ‘black box’ warning to the drug, adding information about an increased risk of heart attack.

Avandia

First liver cancer therapy:
Nexavar has become the first FDA-approved drug to treat an inoperable form of liver cancer – the third largest cause of cancer-related deaths globally. The Bayer/Onyx Pharmaceutials drug is already approved for advanced kidney cancer.

Up in smoke?:
US government scientists are investigating whether Pfizer’s antismoking drug Chantix can trigger suicidal thoughts and agressive behaviour. Investigating the link between drug and behaviour will be complicated by the fact that nicotine withdrawal is already known to affect existing mental problems. The research follows reports received by the FDA.
In other Pfizer news, the company has won a US court ruling that may limit the number of lawsuits the firm faces over painkiller Celebrex. The judge ruled that plaintiffs have not proven that Celebrex taken at 200mg, the most common dose, causes heart attacks or strokes. However, the drug could also be prescribed at higher doses, and it is unclear how many of the 3000-plus plaintifs will be affected by the ruling.
Finally, Pfizer will pay $164 million to buy biopharma firm Coley Pharmaceutical. Coley specialises in vaccine adjuvants, and in a new class of drug candidates called toll-like receptor (TLR) therapeutics which stimulate or block the immune system.

Organon sale completes:
US drug firm Schering-Plough has completed its 11 billion euro (£7.5 billion) purchase of Organon BioSciences from Dutch firm Akzo Nobel – and has taken out full page newspaper adverts announcing completion of the deal. Akzo plans to use the cash in its acqisition of ICI.

Pain for Prexige:
Novartis’s painkiller Prexige has been suspended from sale in the UK, Germany and Austria by drug regulators, over safety concerns over links to liver damage. The European Medicines Agency has said it will review the drug’s safety data in December. The drug has already been withdrawn in Australia and Canada, and refused approval by the US FDA, due to safety fears. Like Merck’s infamous Vioxx, withdrawn in 2004, Prexige is a Cox 2 inhibitor.

Buying Biotech:
US biotechnology company Celgene has agreed to buy Pharmion for $2.9 billion in cash and stocks. Colorado, US-based Pharmion’s biggest drug is Vidaza, a blood cancer treatment which analysts have suggested has the potential to become a billion dollar product.

Mining and Petrochemicals

Cornish mine reopens
South Crofty Mine, the last working tin mine in Cornwall, UK, which had been decommissioned in 1998, is to restart production, thanks to increasing demand for the metal from China and the developing world. The 1998 closure had been thought to mark the end of 4000 years of tin mining in the area. The mine’s owners will invest £50 million to reopen in the mine, with production to start within 2 years.

Cornish tin mine

Government

Green business:
UK Business Secretary John Hutton has announced a new manufacturing strategy to examine how the Government can help British industry take advantage of opportunities presented by tackling climate change. Hutton called on UK manufacturers to respond positively to new opportunities created by emerging markets in the green economy, such as renewable energy and other low-carbon technology.

Agrochemicals

GM seed:
EU environmental officials have proposed a ban on GM corn seeds produced by DuPont, Dow and Syngenta, because they could harm butterflies and affect food chains and rivers, according to a preliminary report seen by the International Herald Tribune. The European Commission has neither accepted, nor rejected, an application for GM products to be grown in the EU, since 1998.

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