Kiss of death for cancer cells

31 October 2010

Scientists have deciphered the surprising structure of the perforin pore, which delivers the 'kiss of death' to virus-infected cells and cancer cells in the body.

The perforin pore delivers the 'kiss of death' to virus-infected cells and cancer cells in the body
© Helen Saibil (Birkbeck College)

When the immune system has identified a target cell in the bloodstream that is either cancerous or virus-infected, it activates killer cells which execute it by lethal injection.

Upon close contact with the target, the killer cells release the protein perforin into a narrow space between the cells, which will then punch holes in the membrane of the target cell, through which destructive enzymes enter the cell. Now, researchers in Australia and the UK have elucidated the structure of perforin both in the water-soluble state and in the membrane pore.

'The first major step in understanding perforin came from the discovery that it is related to a family of bacterial toxins, including pneumolysin, which we had previously studied,' reminisces researcher Helen Saibil of Birkbeck College London, UK. 'We went on to obtain an electron microscopy map of perforin pores, and we could see some similarities to pneumolysin pores but we couldn't interpret the structure in detail.'

Each pore is made up of 19-24 molecules of the protein, creating an entrance between 130 and 200 Angstroms in width. The variable composition of the pore rules out structure analysis by crystallography, while its size makes it unsuitable for NMR.

The breakthrough came when the Australian researchers at Monash University in Australia determined the structure of the form the molecule adopts in solution, before it inserts into the membrane, applying x-ray crystallography to a mutant version that lacks the ability to associate into pores.

When they tried to match up the crystal structure to the less detailed images of the pore obtained by electron microscopy, the researchers were in for a surprise. 'We were initially puzzled to find that the molecule seemed to fit into our pore structure in an inside-out orientation compared to pneumolysin pores,' Saibil says. However, labelling experiments confirmed that mammalian cells use the pore 'the wrong way round' compared to the bacterial system.

'Remarkably, the same basic pore forming machine, used both by the immune system for defence and by bacteria for attack, works in opposite orientations in these two systems,' Saibil concludes.

'This is a wonderful extension of the breakthrough work of 2007,' says Hagan Bayley of the University of Oxford, UK, referring to the discovery of the similarity between perforin and bacterial pores. 'The weapons used by our immune cells and by pathogenic bacteria have a common origin, but now it seems they swing their swords in different ways.'

Michael Gross



Further questions over Deepwater Horizon cement mix

29 October 2010

An independent investigation into the Deepwater Horizon oil spill has reinforced concerns over the suitability the cement used in the well construction. Laboratory tests and analysis of data provided to BP by cement contractor Halliburton indicate that the cement may have been faulty, but also that tests to confirm the integrity of the cement were misinterpreted or not conducted.

As reported by Chemistry World in September, an internal analysis by BP highlighted possible problems with the cementing of the well as a contributing factor to the explosion and subsequent oil spill at the oil rig in April. The National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling, established by the US government in May this year, has now released its own independent assessment of the cementing process.

The debate hinges on Halliburton's use of nitrogen gas and other additives to make a cement foam that would flow to the bottom of the well and remain stable as it cured. The commission's interpretation of the information provided to it is that 'the cement may have been pumped without any laboratory results indicating the foam would be stable'.

Eleven workers were killed in the explosion on the Deepwater Horizon oil rig in April
© U.S. Coast Guard

Independent laboratory tests performed by cement specialists at US firm Chevron were 'unable to generate stable foam cement from materials provided by Halliburton and available design information'. The commission points out that the cement and additives supplied by Halliburton were not from the same batches as those used on the rig, but were 'in all other ways identical in composition'.

In its preliminary response, Halliburton states the materials from the rig are subject to a Federal Court preservation order, but will soon be released to the Marine Board of Investigation for analysis. The company also asserts that tests on off-the-shelf materials rather than the 'unique blend of cement and additives that existed on the rig' could lead to 'significant differences' in test results.

The commission's assessment concludes by pointing out that 'cementing wells is a complex endeavour and cementing failures are not uncommon even in the best of circumstances.' It also points out that the oil industry has developed tests and techniques to identify and remedy cementing failures, but that personnel at BP and/or rig owner Transocean 'misinterpreted or chose not to conduct such tests.'

Halliburton's response echoes this conclusion, saying that the company believes that 'had BP conducted a cement bond log test, or had BP and others properly interpreted a negative-pressure test, these tests would have revealed any problems with Halliburton's cement.'

Phillip Broadwith


Smuggling key factor in China's rare earth actions

29 October 2010

Widespread smuggling of rare earth materials and rapidly increasing domestic demands are key factors in China's recent moves to drastically reduce exports of the sought after elements.

In July, China, currently in control of almost the entire global rare earths market, announced a reduction of up to 72 per cent in its exports for the second half of 2010 compared to the same period last year. Despite its position as the world's major producer of rare earth elements, as the materials bleed out from the country, China has attempted to acquire other mines around the globe to maintain its control of the growing global market.

According to a report published by the Institute for the Analysis of Global Security (IAGS), a non-profit think tank in the US, China controls around 97 per cent of the global rare earth elements market and almost 60 per cent of all known global rare earth resources, which are needed to produce trillions of dollars worth of high-tech electronic goods including everything from smart phones to hybrid cars to wind turbines.

Smuggling supplies

Last year China's state-owned news agency Xinhua reported that as much as 20,000 tonnes or one-third of the total volume of rare earth elements leaving China in 2008 had been smuggled out of the country as a result of high prices in the legitimate market. Earlier this year, Xinhua reported the arrest of seven suspects implicated in smuggling over 4000 tonnes of rare earth metals and compounds worth around Yuan109 million (£10.3 million).

Smuggling is detrimental to the Chinese rare earth industry because it keeps prices low and depletes resources more quickly, causing supply problems for Chinese companies. Recently the country has been taking steps to gain more control over the industry by clamping down on illegal mining and smuggling, and reducing export quotas.

'Even today, the Chinese rare earth industry has a large number of unofficial, sometimes even unknown, entities,' says Jack Lifton, a senior fellow at IAGS. 'This is the first time that China is trying to organise the industry because they want an accurate picture of how much [rare earth] they have and how much they produce.'

China controls the majority of the rare earths market, causing supply concerns for other regions

Domestic demand

Roderick Eggert, director of the economics and business division at the Colorado School of Mines, US say China's actions to reduce export quotas is understandable: 'The demand of Chinese manufacturers for rare earths has increased and China is merely acting like a private company would [to protect its interests].'

A 2008 report by consultancy firm Industrial Minerals Company of Australia, suggested that China's domestic consumption would become equal to its domestic production of rare earth elements by 2012. Reviewing the projections in light of the economic slow down extended this timeframe to 2014. With a rapidly growing economy, satisfying domestic demand of rare earth elements has become a priority for China.

Global acquisitions

In 2005, Xu Guangxian, a renowned Chinese rare earth chemist, called for protective measures in the Chinese rare earth industry, saying that resources at some sites were in 'urgent need of protection and rational utilisation'.

In the same year, China National Offshore Oil Corporation tried unsuccessfully to acquire Unocal, an oil company based in California, US for $18.5 billion (£11.6 billion). At the time, Unocal's subsidiary Molycorp Minerals owned the only rare earth mine in the US. If the bid had been successful, the Chinese firm would have gained access to the biggest rare earth mine outside of China. Molycorp closed the mine in 2002, but now plans to restart production in 2012.

In early 2009, rare earths firm Lynas Corporation made plans to open a mining site at Mount Weld in southwest Australia. By May 2009, China Non-Ferrous Metal Mining Company had tried to acquire 51 per cent stake in Lynas but were unsuccessful due to intervention by the Australian government. 'In Australia, the Chinese did just not want a large stake in a mine, but they also wanted control. The Australians did not want this to happen,' says Lifton.

Last year Jiangsu Eastern China Non-Ferrous Metals completed the acquisition of a 25 per cent stake in Arafura Resources, another rare earth developer in Australia. Arafura's operations in Australia are scheduled to start in 2013, with the company predicting annual production from its Whyalla site near Adelaide of 20,000 tonnes of rare earths - around 10 per cent of the world's supply.

China is now also actively trying to develop mines in unregulated markets such as in West Africa, says Lifton.

Akshat Rathi


Sex hormone in cancer warfare

29 October 2010

Inactive platinum complexes can be transformed into exciting anticancer compounds by coupling them with testosterone using a quick and simple method, claim UK scientists. This could pave the way for new target specific anticancer drugs.

Platinum compounds cisplatin, carboplatin and oxaliplatin are commonly used to treat cancer. But these drugs can only treat a limited number of tumours and some types of cancer are now showing resistance. The drugs are also highly toxic and cause unwanted side effects. Drugs that target the site of disease without harming healthy tissue are better and have been explored by using the sex hormone oestrogen attached to a Pt compound. These target oestrogen receptors which are over-expressed in most breast cancer tumours.

Now, Carlos Sanchez-Cano, Michael Hannon and colleagues at the University of Birmingham,UK, have used testosterone to create a metallodrug that targets the androgen receptor, the predominant sex-steroid receptor over-expressed in all prostate tumours as well as many breast and ovarian tumours.

Testosterone delivers the platinum warheads resulting in interesting effects on the activity and properties of the drug

By attaching steroidal testosterone to inactive platinum compounds, the team show that targeted drugs have enhanced cell uptake and anticancer activity levels compared to non-steroidal cisplatin. Further investigation on a small library of testosterone-coupled platinum complexes shows that testosterone serves not only as a delivery agent for the compounds but modifies the types of DNA binding formed. The testosterone-based complexes cause the DNA helix to undergo significant unwinding and bending.

'To date, nobody has used testosterone for targeting,' says Sanchez-Cano. 'We have shown that drug delivery agents are not only the mere transporters of warheads; instead, they can have an interesting effect on the activity and properties of the carried drug,' he adds.

Terry Jenkins, a medicinal chemist at the University of Greenwich, UK, comments: 'This design strategy has great significance as the approach offers prospects for a worthwhile increase in drug activity together with a reduced burden for patients through toxic side-effects resulting from inefficient, untargeted delivery.'

The team are now exploring the effects of linking different metallic units to steroidal molecules. 'More work needs to be carried out to fully understand the mode of action these compounds have once inside the cell and to see how they would work in more complicated systems presenting target and non-target cells at the same time, to see the real potential of this kind of strategy,' concludes Sanchez-Cano.

Carl Saxton


Hope on the Horizon for ecological recovery

29 October 2010

Hope may be in sight for the Deepwater Horizon clean up operation as Spanish researchers show the rapid recovery of wild mussel populations following a similarly disastrous oil spill.

In November 2002, the tanker Prestige split in two, disgorging over 60 000 tonnes of oil into the Atlantic Ocean. The Galician coastline, Europe's largest producer of mussels, was one of the worst affected areas. Miren Cajaraville led a team at the University of the Basque Country, Leioa, to assess the impact of the spill on the reproductive capabilities of wild mussel populations.

Mussels are commonly used as a gauge of marine pollution levels as they are inactive and do not move to feed, so accumulate high levels of contaminants from their environment. Cajaraville monitored the levels of a protein that control the development of sex cells in females along with other indicators of abnormality, such as premature cell death and abnormal reproductive organ development to determine the effect of the oil-contaminated waters on the mussels.

Mussels are commonly used as a gauge of marine pollution

Shortly after the spill a number of deviations from the norm were observed, says Cajaraville, including a significant reduction in the size of the reproductive organs. But, as the small organs still contained mature sex cells, it is uncertain in this case whether size really does matter.

Gordon Watson, an expert on reproduction in marine invertebrates from the University of Portsmouth in the UK highlights the complexity involved in 'teasing apart the impact of oil from any underlying influences, including other pollutants already present.' But Cajaraville says that the data shows a very clear effect caused by the oil spill: 'Our conclusion is that there are transient effects one year after the oil spill, and it seems that the mussels were able to cope and adapt.'

This could be good news for similar invertebrate species affected by oil leaked from the Deepwater Horizon rig in the Gulf of Mexico. Mike Moore, an environmental pathologist at Plymouth Marine Laboratory in the UK comments that the method developed by Cajarville's group could be 'readily transferred to monitoring the current oil disaster,' and adds that he wouldn't be surprised to see further work using these methods to monitor the recovery of other invertebrates affected by the Deepwater Horizon spill.

Fran Burgoyne


Hybrid electrolyte for better batteries

28 October 2010

Safer, more durable batteries are the aim of a US team that has made a new, hybrid nanoparticle-ionic liquid electrolyte.

Batteries containing lithium metal as the ion source can store the highest known density of energy, but the most commonly used electrolytes (the ion-conducting medium within the battery) do not work well in these batteries as they are unstable in typical operating conditions and may break down disastrously.

This problem has stimulated research into other electrolytes, made of polymers or ionic liquids (ILs). While polymer electrolytes generally have low conductivity at room temperature, ILs are salts in a liquid state and thus have good conductivity and stability under the battery operating conditions. They are, however, unable to prevent the formation of lithium networks called dendrites, which degrade battery performance.

A team led by Lynden Archer at Cornell University, New York has now developed a new family of solventless electrolytes made of hard zirconium oxide nanostructures linked to softer IL species, using a simple one-pot procedure. The electrolytes, which are a gel-like fluid at room temperature, are temperature- and redox-stable which makes them suitable for use in batteries, they transport lithium ions well and they also prevent the growth of dendrites.

Tethering ionic liquids to hard inorganic ZrO2 nanostructures to make a new class of electrolytes (IL-NIM = nanoscale ionic material)
© Angew. Chem. Int. Ed.

Archer is motivated by making batteries for everyday use, such as for electric vehicles, and says the technology has a nice connection to making very high energy-density rechargeable batteries. 'Because the components are joined by ionic bonds they can't vaporise easily. From the point of view of safe, explosion-proof secondary batteries, this is in all respects ideal,' he adds.

Michel Armand, an expert in lithium batteries at University of Picardie in Amiens, France, is less certain. 'It is a very clever material design but it must be tested at currents 100-1000 times higher to show it is suitable for practical operation,' he says.

Archer believes that tethering the cation part of the IL maximises the lithium ions' contribution to the conductance of the battery. However Armand points out that the anion part of the IL could be mobile, and extended battery use could result in depletion of the salt from one side of the battery. He suggests that the design could easily be modified to tether the anion also, thereby preventing movement of all but the lithium ions, and potentially making a better battery.

Carol Stanier


Nanowire fuel cell for biological power

28 October 2010

Scientists in China and the US have developed a miniature fuel cell that can produce electricity from biological fluids such as blood. The cell could, the researchers suggest, be an autonomous source of power for devices implanted in living tissues, such as medical biosensors.

Jing Zhu, of Tsinghua University in Beijing, and colleagues constructed the fuel cell by coupling two redox enzymes via a nanowire of a polymer composite capable of conducting single protons. Glucose oxidase is tethered to one end of the 200-800nm diameter wire by carbon nanotubes, which improve its stability, while laccase is attached to the other end of the wire. Each end of the wire sits on a gold electrode.

At the anode the glucose, an almost ubiquitous solute in biological fluids, is oxidised, generating protons and electrons. The protons are siphoned away down the nanowire while the electrons are directed around an external circuit to provide an electrical current. At the cathode the protons and electrons are combined with dissolved oxygen to generate water, catalysed by the laccase enzyme. The researchers were able to generate electricity from the fuel cell in human blood and the juice of a watermelon.

The nanowire based biofuel cell could be fuelled by biological fluids such as blood or glucose. When immersed into a biofuel solution, two chemical reactions occur in the anode and cathode regions, creating a corresponding chemical potential drop along the nanowire, which drives the flow of protons in the wire and electrons through the external load
© Adv. Mater.

'The nanowire-based fuel cell generates an output power as high as 0.5-3microwatts, and it has been integrated with a set of nanowire based sensors for performing self-powered sensing,' says Zhu. 'It shows the feasibility of building self-powered nanodevices for biological sciences, environmental monitoring, defence technology and even personal electronics.' Zhu adds that different pairs of enzymes could be used depending on the local environment in which the fuel cell is to operate.

Peter Harrop, chairman of the company IDTechEx which carries out research and analysis on energy harvesting technologies, says, 'This is an interesting initial study of a new approach to energy harvesting in the human body and the power generated appears to be suitable for nanodevices.' Harrop adds, however, 'Whether it becomes a commercial prospect depends on adequate life, reliability and cost being demonstrated in further work.' Nowadays, says Harrop, there is huge interest in implanted medical devices including for drug delivery, sensing vital signs, defibrillation, heart pacemakers and so on. 'This device may suit the low power end, notably sensors, but there are alternative approaches,' he adds.

Simon Hadlington



Single molecule magnets line up

27 October 2010

Italian researchers claim that they've bound a single molecule magnet (SMM) to a gold surface, whilst retaining the magnet's properties. The results could help in the development of molecular scale 'spintronics' - electronic devices based on electron spin.

SMMs are metal-organic clusters that display purely individual magnetic properties, with each molecule able to be individually magnetised. This has led to a lot of interest in using SMMs for data storage, and potentially quantum computing, but the magnetisation of the individual molecules is dictated by its orientation - something that has been difficult to control.

Now, Roberta Sessoli from the University of Florence, Italy and colleagues have found a way to encourage SMMs to adopt a preferential orientation in a monolayer on a gold surface.

Sessoli's SMM contains a disc-like cluster of four iron atoms arranged like a propeller, with one central iron atom surrounded by the other three. These three arms of the propeller are bonded to stocky ligands while the central atom has two longer organic arms attached. One of these long arms binds to the gold surface, and the steric interactions from the stockier ligands orientate the molecule axis, and hence the magnetisation axis, of the molecule.

The team synthesized molecular magnets that adopt a preferred orientation in a monolayer on a gold surface
© Nature

Sessoli's team has shown that these SMMs have 'magnetic memory' - a key feature for data storage applications - by changing the magnetic field around the molecules and showing how the molecules become magnetised. The key step in the process is that the cluster shows quantum tunnelling effects, as particles tunnel from one spin state to another, which has potential in data storage applications making use of the discrete levels of magnetisation.

Sessoli admits this is very much a proof of principle work: 'What we're now hoping is for people to come forward and collaborate with us on the next step.'

Wolfgang Wernsdorfer, who works on molecular spintronics at the Néel Institute in Grenoble, France, agrees that the results are very promising, and hopes that they will motivate further studies. In particular, he is impressed that Sessoli's work appears to have overcome the problem of SMMs losing their magnetic properties when coupled to metal surfaces. Wernsdorfer hopes that theorists will now look at the influence of metal surfaces on nanomagnets. 'The important question is whether the memory effect on a metal surface is true,' he says.

Ultimately, Wernsdorfer agrees that this is an important research area, both for spintronics and to test other ideas using quantum physics. 'I am convinced that "quantum functions" will be important in future devices,' he says, and he sees SMMs as the ideal test molecules for that investigation.

Laura Howes


Pepper plant provides drug hope

27 October 2010

Researchers have found potential new treatments for the tropical disease leishmaniasis, by isolating compounds from a pepper plant used by Peru's native Chayahuitas people as an anti inflammatory.

Leishmaniasis, a disease transmitted through the bite of an infected sand fly, affects two million people each year with a further 350 million thought to be at risk worldwide. The most common form, cutaneous leishmaniasis, results in sores on the skin while the more dangerous visceral leishmaniasis can attack internal organs and ultimately cause death.

Despite the millions of people affected, the disease is mainly present in the developing world and there are few treatments available. 'Current drugs are based on antimony compounds,' says author Nicolas Fabre of the Institute for Research and Development and the University of Toulouse in France. 'But these present renal and cardiac toxicity. Other drugs such as Amphotericin B, also cause a lot of adverse effects. On top of that these treatments are very expensive and unfortunately this disease affects poor countries.'

The team found three caffeic acid esters that could help in the development of new drugs to treat leishmaniasis
© Journal of Natural Products
Hunting for new drug leads, Fabre, with colleague Michel Sauvain and their teams in France and Peru, turned to natural remedies used by the Chayahuitas, a native Peruvian group strongly exposed to leishmaniasis. One of plants the team analysed was the pepper plant, Piper sanguineispicum, whose leaves are used by the Chayahuitas as an anti-inflammatory.

Fabre and Sauvain isolated a number of new compounds from the leaves and tested their ability to kill the disease in vitro. Among these they found three new caffeic acid esters which all demonstrated good activity towards the infecting form of the disease, while showing only moderate toxicity against living cells.

'The most interesting result is the selectivity of the activity,' says Fabre. 'The antileishmanial value is nothing if compounds are toxic to cells.' However he is quick to exercise caution: 'It is worth noting that these results are very preliminary and in vivo investigations are needed to confirm the interest of these esters.'

Felipe Otálvaro, a professor of natural product synthesis at the University of Antioquia, Colombia, believes the group's findings have good potential. 'The three compounds have more or less similar activities to Amphotericin which is really hard to achieve,' he says. 'While it needs more experimentation in vivo, these assays give hope that you're getting close to a leading compound and it's especially nice because the structures are not complicated.'

Manisha Lalloo



Waterproof cotton that can go through the wash

26 October 2010

Chinese researchers have made cotton fabric that is completely impervious to water and can be put through the laundry without losing its superhydrophobic properties, overcoming a key obstacle in the commercialisation of these highly waterproof materials.

The waterproof cotton was made by grafting a super-hydrophobic polymer onto bundles of cotton fibres. This polymer prevents water from adhering to the cotton surface, and since water has a high surface tension, the droplets form into spheres and simply roll off. In this process, any dirt or other surface materials are also collected and removed - an effect that can be observed in nature on leaves of the Lotus plant, which are kept clean and dry by nano-sized crystals of wax.

Superhydrophobic fabrics have been made before, but their waterproofing effect tends to fade with washing, and they can be uncomfortable to wear if they prevent air flow through the fabric. Now, researchers at the Chinese Academy of Sciences in Shanghai, China, have developed a much more durable and comfortable solution.

Left: SEM image of the pristine cotton fabric (insert: the interaction of water with the cotton fabric). Right: SEM image of the superhydrophobic cotton fabric
© Advanced Materials

'Our superhydrophobic cotton looks almost the same as normal cotton fabric,' says Jingye Li, who worked on the project. 'The small air holes between the cotton bundles are retained, which make it breathable and comfortable to wear, and it feels smoother than cotton because of the superhydrophobic nature of the fabric.'

Li's team tested the durability of the fabric with different detergents and included 50 stainless steel balls in the washes to simulate repeated laundering. After undergoing an equivalent of 250 domestic washes at 40°C, the fabric still maintained its superhydrophobic properties.

The material retained its superhydrophobicity after the equivalent of 250 domestic laundry washes
© Advanced Materials

The secret to the durability, Li explains, is how the hydrophobic polymer is attached to the cotton. Rather than simply coating the fabric, the cotton is first irradiated with gamma rays, which forms covalent bonds between the surface and the polymer which cannot easily be separated.

'Few superhydrophobic surfaces are abrasion resistant as the high roughness required makes them fragile, so it is impressive for a textile to survive this many washing cycles,' says Neil Shirtcliffe, a superhydrophobic materials expert at Nottingham Trent University, UK. 'The results are very promising, but are still some way from a finished product.'

Lewis Brindley



Playing games with enzymes

25 October 2010

It might not be Deep Blue, the chess-playing supercomputer, but US researchers have shown that a solution of biological molecules can be taught to play any strategy of a simple board game against a human opponent and never lose. The programmable biomolecular 'automaton' demonstrates how molecules can behave in a way that extends beyond their 'hard-wired' chemical function, says Milan Stojanovic of Columbia University, New York, who lead the research team.

The simple game of tit-for-tat is played on a set of four squares, numbered 1,2,3 and 4. The human player nominates any square, the automaton chooses a free square, the human player chooses one of the two remaining squares and the automaton the last remaining square; the automaton wins by having the same number of squares as the human player at the end.

The automaton consists of 16 enzymes whose substrates are oligonucleotides. Four of the enzymes act on one of four specific oligonucleotides, the 'input' oligonucleotides. The remaining 12 enzymes act on pairs of the four inputs. When an enzyme meets its appropriate inputs the reaction produces fluorescence.

The solution of enzymes is divided into four wells - the playing board as it were. The human player selects a square on the board by adding the corresponding input oligonucleotide to all wells: input molecule 1 indicates that the player is choosing square 1, input 2 square 2 and so on.

Winning tit-for-tat. The second player (automaton) marks a fresh quadrant after each of the human player's moves. The human's new moves are represented by a blue filled circle and previous moves by a black filled circle. The automaton's new moves are represented by a red open circle and previous moves by a black open circle.
© Nature Nanotechnology

Initially all the enzymes are deactivated but each can be selectively activated by the programmer by the addition of a 'training oligonucleotide'. If the programmer wants to activate an enzyme to be responsive to a human move to square 1 then he/she has somehow to tell the automaton 'when input 1 is chosen, you respond with well 2'. To do this, the enzyme responsive to input 1 is activated only in well number 2, but not in the other three wells, by adding the corresponding training oligonucleotide. For the second move the programmer says 'If the human next chooses square 3 [by adding input 3 oligonucleotide to all the wells], you respond in well 4', choosing to activate in well 4 the enzyme responsive to the presence of both oligonucleotides 1 and 3.

In this way, through a 'training session' all possible permutations can be covered so that the automaton is programmed to respond to any combination of moves. The total number of possible strategies dictating how to respond to the human move is 34, or 81.

Stojanovic says that the idea of the work is not to make a computer that can compete with silicon, but rather to explore how biological molecules can be programmable, multifunctional and adaptable.

Experts in the field are impressed by the work. Erik Winfree of the California Institute of Technology in the US woks on molecular programming and says, 'It's the first serious attempt to construct an artificial chemical system that learns from examples and I'm sure it will stimulate a lot of productive controversy and inspire a whole line of research.'

Tom Ran who works on biomolecular computers at the Weizmann Institute of Science in Israel comments that by introducing the concept of 'reconfigurability' into molecular computing the research 'brings closer the goal of a multipurpose reprogrammable molecular computer.'

Simon Hadlington


Dual purpose dyes offer new imaging options

25 October 2010

US researchers have developed a new series of combined fluorescent and chemiluminescent dye compounds that can be stored at low temperatures and then activated to release near infrared light when warmed to body temperature. The work could offer safer, more sensitive alternatives for imaging biological systems.

Many imaging techniques used in disease diagnostics and drug development in animal models use radioactive tracer molecules to track and image particular compounds, tissues and metabolic processes. However, radiotracer molecules can damage DNA and their quick decay means that they must be prepared immediately before use and cannot be easily stored.

More recent optical molecular imaging approaches use luminescent compounds such as luciferase enzymes instead, which decay by emitting harmless visible light. The problem is that the emitted light scatters and gets absorbed by molecules and cells, which limits tissue penetration and affects image clarity.

Now, Bradley Smith and colleagues at the University of Notre Dame, Indiana, US, have created a class of compounds that could overcome these problems. Called squaraine rotaxane endoperoxides (SREPs), the compounds comprise highly sensitive dye molecules called squaraines that are placed inside a macrocyclic shell. When irradiated with red light, the squaraine rotaxane oxidises to contain a thermally unstable 9,10-anthracene endoperoxide group. This structure stores light energy as a chemical bond at low temperature and when warmed, releases the energy as near infrared light.

Fluorescent imaging typically requires that a given sample is illuminated, which results in unwanted background light. Importantly, SREPs can provide a chemiluminescent as well as fluorescent signal. 'When it is chemiluminescent we don't need to illuminate the sample, so there is no background irradiation. In this regard, we can see things deeper and in higher contrast because we can eliminate this bothersome background signal,' explains Smith. 'On the other hand, it still functions as a fluorescent dye, giving the end user two options when they want to look at tissue after it is removed from the body.'

The molecules provide both a fluorescent and chemiluminescent signal, as illustrated in this animal model
© Nature Chemistry

Eva Sevick-Muraca, director of the Center for Molecular Imaging at the University of Texas Health Science Center in Houston, US, is enthusiastic about the work. 'Given that commercial small animal systems are unable to sufficiently filter the backscattered excitation light from weak fluorescence signals, the development of red and near-infrared chemiluminescence offers a new opportunity for more sensitive optical molecular imaging,' she says.

Smith points out that being able to store SREPs indefinitely at low temperatures (below -20°C) means they can be prepared on a relatively large scale, transported and stored easily until needed - a considerable advantage over traditional radiotracers.

'If adequate photon count rates can be collected through tissues, chemiluminescence SREPs may challenge the use of near-infrared excitable (>780 nm) fluorophores currently under development and in use within our device and drug clinical studies,' says Sevick-Muraca.

James Urquhart



UK carbon capture a one horse race

22 October 2010

On the same day UK ministers revealed a £1 billion fund for the development of carbon capture and storage (CCS), power company E.ON UK announced it is pulling out of the government's national CCS competition, leaving just one company in the race. In 2007 the government announced a competition to build one of the world's first commercial scale CCS demonstration plants in a bid to strengthen the UK's position as a world leader in cleaner fossil fuel technology. Before E.ON's departure from the race, energy firms BP and Peel Power had already pulled out of the competition in 2008 and 2009 respectively.

ScottishPower's CCS pilot plant at Longannet is the last contender in the national competition
© ScottishPower/Aker

The current economic climate has made E.ON's plans to build a new coal-fired power plant at Kingsnorth uneconomical 'for the foreseeable future,' meaning the company will not have a facility on which to develop the CCS technology, E.ON chief executive Paul Golby said. The company also said it could not keep up with competition timescales and thus was left with no option but to withdraw from the race.

'As a group we still believe that carbon capture and storage is a vital technology in the fight against climate change and will now be concentrating our efforts on our Maasvlakte project in the Netherlands for future generation of CCS projects,' Golby said in a statement.

As part of the government's comprehensive spending review, chancellor George Osborne on Wednesday announced a fund of up to £1 billion for CCS demonstration projects. Scottish Power, the only firm now left in the government's CCS contest, welcomed E.ON's decision and said it was 'committed to the CCS project at our Longannet plant and are on schedule with our engineering and design work.'

The Department of Energy and Climate Change told Chemistry World that 'Although Scottish Power is the only company eligible for the £1 billion, it does not guarantee the company will satisfy all of the conditions to secure the money. We need to ensure that the taxpayers are getting their value for money.'

The government also announced that it is committed to launching three more such competitions before the end of the year and will begin a consultation to decide whether the money will come from a CCS levy on consumer bills or government funds.

Ayrshire Power, which was part of the Peel Power consortium that entered the first competition only to pull out last year, is keen to enter the new competitions. The firm is currently developing CCS technology for a planned multi-fuel plant at Hunterston power station in Ayrshire, Scotland.

Akshat Rathi


Nanoparticles make leaves glow

22 October 2010

Can street lights be replaced by trees? Taiwanese scientists believe that they can using gold nanoparticles to induce luminescence in leaves.

Light emitting diodes (LEDs) are used in street and bicycle lights as they have a higher efficiency than traditional light bulbs but even more environmentally-friendly LED's are desirable. Now Yen Hsun Su and coworkers at Academia Sinica and the National Cheng Kung University in Taipei and Tainan have tackled this problem by synthesising gold nanoparticles shaped like sea urchins and diffusing them into plant leaves to create bio-LEDs.

Chlorophyll shows bioluminescence upon high wavelength (400 nm) ultra violet excitation. In contrast, the gold nanoparticles are excited at shorter wavelengths and emit at 400 nm. By implanting the nanoparticles into Bacopa caroliniana plants, Su was able to induce the chlorophyll in the leaves to produce a red emission. In addition, the nanoparticles are able to suppress emission blinking - a known problem for gold nanoparticles -as they have a strong surface plasmon resonance which localises light on the nanoscale.

Gold nanoparticles in the leaves induce bioluminescence

'The bio-LED could be used to make roadside trees luminescent at night. This will save energy and absorb CO2 as the bio-LED luminescence will cause the chloroplast to conduct photosynthesis,' says Su.

'The way the researchers introduce these gold nano-sea urchins in live plants utilising the 400 nm photoluminescence of gold to obtain the bioluminescence of chlorophyll is impressive,' comments Krishanu Ray, an expert in nanotechnology and fluorescence at the University of Maryland in the US. 'Proper optimisation and tuning could potentially result in stronger bioluminescence,' he adds.

The researchers agree that bioluminescence efficiency needs to be improved and are also looking to apply the same strategy to other plant biomolecules.

Yuandi Li


Where on Earth has our water come from?

22 October 2010

Evidence that water came to Earth during its formation from cosmic dust, rather than following later in asteroids, has been shown by a group of international scientists.

The origin of the abundant levels of water on Earth has long been debated with the main differences in the theories being the nature of the material that carries the water, and whether the water came during or after planet formation.

Now, Nora de Leeuw at University College London, UK, and colleagues have used molecular-level calculations to prove that dissociative chemisorption of water onto the surface of olivine rich minerals, such as forsterite, is highly exothermic. And so when these mineral dust particles came together during Earth formation, gas-solid interactions could have resulted in water being adsorbed onto the surface of the dust particles. This means that water could have been part of the Earth from the very beginning.

Water could have been adsorbed onto minerals that created the Earth

'Our calculations indicate that it is viable for water to become adsorbed at the surfaces of dust particles in the interstellar medium, where planets are formed. The water is thus trapped and becomes incorporated into the Earth,' says de Leeuw.

De Leeuw's work challenges the common assumption made by astronomers that the Earth's water originated from bodies in the asteroid belt. 'The work will be of tremendous interest to those modelling the geology and habitability of extrasolar terrestrial planets,' comments Philip Armitage, an expert in astrophysical and planetary sciences at the University of Colorado, Boulder, US.

Rebecca Brodie


Extended elements: new periodic table

22 October 2010

An extended periodic table with 54 predicted elements has been mapped out by a chemist in Finland.

The periodic table of the elements was proposed in 1869 by Dimitri Mendeleev. The value of his scheme for organising the elements was proven by the prediction of the existence and properties of then unknown elements including gallium (first isolated in 1875).

Now Pekka Pyykkö at the University of Helsinki has used a highly accurate computational model to predict electronic structures and therefore the periodic table positions of elements up to proton number 172 - far beyond the limit of elements that scientists can currently synthesise.

The proposed new periodic table for elements

The extra 54 super heavy elements predicted by Pyykkö may exist under extreme conditions with very short lifetimes owing to radioactive decay, but have not yet been synthesised.

Pyykkö says that the value of the work is in showing 'how the rules of quantum mechanics and relativity function in determining chemical properties.' He gives the example of the potentially record-high oxidation states his work predicts.

An expert in electronic structure theory, Peter Schwerdtfeger at Massey University in Auckland, New Zealand, comments: 'chemistry is unthinkable without the periodic table of elements. Pyykkö has used relativistic calculations to go beyond the known elements into unknown territory.'

But he adds that the work in this area is the subject of debate amongst experts who disagree on the placement of certain elements. For atoms with very high nuclear charges, the nucleus could capture an orbiting electron and emit a neutrino causing the proton number to decrease by one.

The debate may only be settled once all the elements have been synthesised but Pyykkö does not expect this to happen anytime soon. 'It is hard to say how far experimentalists will get during this century, maybe close to 130, if not more. Although the experimental results may never appear, the basic physics of the problem are sound,' he concludes.

James Hodge



Studies probe key flu protein

21 October 2010

New details about the structure of an influenza protein that is a key drug target have been revealed in separate studies by groups in the US. The two studies provide insights into the workings of the protein machinery that the virus needs to infect cells.

In the cell, the flu virus is taken up in compartments called endosomes, but in order to infect, it has to force its genetic information inside. The M2 protein, which straddles the outer membrane of the virus, is a pH-activated trigger for this process. At around pH 6, a pore in the tetrameric protein conducts hydrogen ions from the cell to the inside of the virus.

The M2 protein is a key target in anti-flu drug development

Both studies, published back-to-back in Science, use solid-state nuclear magnetic resonance to probe the fine structure of the M2 channel protein and propose mechanisms for proton transfer - in each, histidine residues in the pore play a central role. While Mei Hong's team at Iowa State University focused on a short segment of the protein containing the crucial histidines,1 Huan-Xiang Zhou at Florida State University and colleagues looked at a larger portion, but used simulations to propose a more detailed mechanism for proton transfer.2

Zhou and Hong grant that there are 'no major disagreements' between their studies, which broadly suggest a shuttling model driven by rapid protonation and deprotonation of histidines, relaying hydrogen ions to the interior of the virus. But according to Zhou, Hong's proposed mechanism omits a core component of the proton shunting machinery - a tryptophan residue.

'They basically say the proton is handed to histidine and then gets released to the other side,' says Zhou. 'I think the tryptophan is actually a very integral part of this mechanism and I think not having the involvement of a tryptophan is too simplistic.' In Zhou's model, the proton is transferred from water to histidine, through a tryptophan to another water molecule.

Hong admits that simulations can provide greater detail than her team's more experimental approach, but she 'wouldn't necessarily agree' with the finer points of Zhou's work. 'I would say that the direct experimental result is more trustworthy,' she says. 'But there's more we can study by looking at the interaction of tryptophan with histidine and that will be the future.'

Jason Schnell, who studies the flu protein at the University of Oxford, UK, says M2 is a particularly difficult protein to work with and applauds both groups' efforts, although he liked different aspects of each paper. 'I felt like they should have got together and found an ideal system to work in,' he says. 'I like the construct that the Florida group used but I like the experiments that the Iowa group used.' He does, however, point out that the lipid bilayers used by both groups as synthetic mimics for the viral membrane don't yet offer the same resolution as previous studies carried out in detergents, including crystallographic studies.

The new studies support the idea that interfering with the histidine components of the shuttling mechanism might produce a more effective anti-flu drug - the aim is to achieve this for mutant strains that are resistant to old flu drugs. Zhou's team is already screening for compounds based directly on its mechanism.

Hayley Birch


Dancing facets reveal nanowire kinetics

21 October 2010

In certain circumstances, sapphire nanowires grow by executing an unexpectedly frenetic dance, where oxygen atoms change between partners in vapour, liquid and solid phases. That dance has now been captured by Sang Ho Oh of Pohang University of Science and Technology (Postech) in Korea. 'Our observations are the first of nanowire growth mechanisms at atomic scale in real time,' Oh told Chemistry World.

To get such detailed images, Oh produced sapphire nanowires using a vapour-liquid-solid (VLS) nanowire growth technique directly on a transmission electron microscope's 'hot stage'. The stage contained a thin alpha-Al2O3 sapphire single crystal in an almost-complete vacuum, except for 10-6 Pa of oxygen. Heating the crystal above 660°C while irradiating it with a focused electron beam formed aluminium droplets, the final dance partner needed to begin nanowire growth.

VLS growth is common in nanowire production, and several groups have already observed it directly, Oh notes. 'The problem was resolution,' he says. 'They can see nanowires grow under the liquid phase, but nothing more about how material is transported, and whether the interface between three phases - the triple junction - would be stationary or dynamic.'

A sapphire nanowire's oscillatory growth, adding material to a facet, until that facet disappears, when the added material dissolves in order to form a new atomic layer on top of the nanowire
© Science/AAAS

Oh did observe the triple junction, and in certain circumstances recorded a two-steps forward, one-step back, oscillating growth. Here, liquid aluminium continuously transports oxygen from the vapour phase to feed the wire surface's facets. Sapphire adds to these facets until they effectively disappear, as their neighbouring facets meet. Then, some of the recently-added material dissolves and moves to form atomic layers on top of the nanowire. This reveals the previously-disappeared facets again, restarting the dance.

Understanding these oscillations could help future nanowire applications, such as computer memory, Oh suggests. 'To control nanowire growth kinetics, to change orientation and control diameter or length, or dope impurities into nanowires, we have to know the atomic scale growth mechanism,' he says. 'Maybe these observations can give clues to nanowire growers, because before this they didn't even know this kind of oscillation could exist.'

Takeshi Kasama, of the Center for Electron Nanoscopy at the Technical University of Denmark, who has also worked on characterising nanomaterials, calls the work 'a piece in the puzzle of understanding VLS nanowire growth.'

'The paper contains some interesting new dynamic observations and high quality images recorded at high temperature, which can eventually lead to a better understanding of a complicated process,' he adds.

Andy Extance


Mining soil DNA for molecular decorators

21 October 2010

US Researchers have harnessed enzymes hidden in the genomes of soil bacteria to modify a natural antibiotic molecule in ways that would be difficult or impossible by traditional synthesis. The technique could be applicable to other families of molecules, providing easy access to a huge variety of complex molecules.

Synthesising novel derivatives of known drugs is a widely used method to find new drug candidates and overcome problems such as antibiotic resistance. The team, led by Sean Brady at the Rockefeller University in New York, chose a family called glycopeptides to test out their idea.

Glycopeptides are defensive antibiotics produced by a range of bacteria and have a cyclic peptide core with sugars and sulfate groups attached at a variety of different positions. 'We chose glycopeptides as model compounds because there are many known derivatives out there,' says Brady. 'We wanted to show that by can make derivatives that have never been made previously.'

Enzymes (rings) found in eDNA libraries can modify glycopeptides cores (top) in new ways
© J. Am. Chem. Soc.

The team extracted DNA in bulk from soil samples and generated large libraries containing up to 15 billion unique DNA fragments. They then searched this environmental DNA (eDNA) megalibrary for sequences corresponding to the proteins involved in making glycopeptides.

Their aim was to find the enzymes that attach sulfate decorations to the glycopeptide core. 'By systematically going through an environmental sample of DNA we were able to find additional glycopeptide-producing biosynthetic gene clusters from organisms in soil. Once identified, we could then use the functionalisation ability of these tailoring enzymes to make a library of modified glycopeptides', says Brady. The search turned up six unknown tailoring enzymes, which the team used to generate 15 new unnatural glycopeptides with sulfate groups attached at specific positions.

'It's easier to not to have to build the core structure again and just go and harness from the environment the enzymes that we know are going to be different in each pathway and yet selective towards the core structure', adds Brady.

In recent years researchers have sequenced complete genomes of many useful natural product-producing organisms. 'We and others were quick to recognise that there were a lot of structurally novel natural products with potentially interesting and useful bioactivity yet to be discovered in such organisms, even very well-studied ones', says Greg Challis from the University of Warwick, UK, who works on natural product biosynthesis and genome mining approaches to new natural product discovery.

Challis adds that the prevailing view in the pharmaceutical industry 10 years ago was that there was little structural novelty left to be discovered in the reservoir of bioactive natural products. 'Genome sequencing has shown us that this is not true,' he says. 'Brady's paper provides a nice example of how the structural variation in a well known class of clinically important drugs can be significantly expanded by tapping into the soil metagenome'.

Future work in Brady's lab will focus on applying this technique to other families of molecules with a common, functionalised core. 'But we want to look at rarer families', said Brady.

Akshat Rathi



Science budget frozen in spending review

20 October 2010

The UK's science budget will suffer a 10 per cent cut in real terms over the next four years and higher education has been hit hard in the government's public spending review announced today.

After recent fears that the science budget could be cut by up to 25 per cent, a tide of cautious relief has spread through the UK's scientific community as chancellor George Osborne announced this afternoon that science spending will be frozen at £4.6 billion a year through to 2014/15.

In practice, this will mean will mean real terms cuts of 10 per cent, a better outcome than most had feared. Further efficiency savings of £324 million will be made within the science budget, although details of how were not given.

The UK government has announced deep cuts in its spending review

'A flat cash settlement is the best one could have hoped for, but it is a real terms cut from a starting level of spending that's already not high by international standards,' says Richard Jones, pro-vice chancellor for research and innovation at Sheffield University, UK. 'But that ring fence is really important because it means you can plan for the future.'

Science funding is covered by the Department of Business, Innovation and Skills (BIS), whose budget will be cut by 7.1 per cent each year through to 2014/15. With the science budget protected, higher education funding (also covered by BIS) is taking a significant hit - a 40 per cent reduction from £7.1 billion to £4.2 billion by 2014/15. Higher and further education funding combined will be reformed to deliver around 65 per cent of resource savings in the department as a whole.

Osborne today said that universities were 'the jewel in our economic crown' but that funding mechanisms needed to be overhauled. Significant increases to university tuition fees were proposed last week in the Browne review and an official response to the recommendations is due in the coming weeks, but the cuts to teaching budgets announced today mean departments will be heavily reliant on attracting students willing to pay higher rates for the courses they offer.

'One would hope that quality of teaching and the student experience will have a positive impact and the students will still come and will pay the higher fees,' says Geoff Cloke of the University of Sussex's chemistry department. 'But the cuts are likely to have a serious impact on recruitment and retention of post-graduate students who are the engine for the generation of new science and technology. Universities might be "the jewel in our economic crown" - but it seems like the students are going to be expected to pay for the diamonds.'

Jones emphasises that although the science budget is ring fenced, university research is carried out in science departments that have a 'mixed economy', relying on funds from teaching and science budgets. 'The very large cuts in teaching budgets that we're anticipating are going to be very destabilising, and we don't know how that's going to affect science departments,' he says.

'There's a big question about how many universities with chemistry departments believe they can recruit students at the sort of level that they would need to charge fees that would replace the loss of public funding,' says Paul Cottrell, national head of public policy at the Universities and College Union. 'Some departments or institutions are just not going to be able to survive in that market place.'

He adds: 'We didn't think that the government would essentially go for wholesale privatisation of higher education which is essentially the plan,' he says. 'We're very worried about the whole picture that being presented as the future of higher education.'

Further details on departmental savings are expected in the coming weeks.

Anna Lewcock


Enzymes - a new ingredient for marine paint?

20 October 2010

Cross-linked enzyme aggregates have great potential in marine antifouling paints claim Danish scientists.

Paints with antifouling activity are used in the marine industry to prevent undesirable accumulation of microorganisms, plants and animals on ship surfaces below the waterline. Previously tributyltin self-polishing copolymer (TBT-SPC) paints have been used however they were banned in January 2008 due to environmental regulations.

The main alternatives are copper-based paints but these also cause concern for the environment. Consequently it non-toxic alternatives are desirable which is where enzymes can have a niche explains Stepan Shipovskov at Aarhus University, Denmark.

Enzymes can interact directly with microorganisms on the ships surface but organic solvents, such as xylene, are the main base of paints and can inactivate the enzymes. Shipovskov and co-workers tested cross-linked enzyme aggregates (CLEAs) of proteases in artificial sea water and found that they are tolerant to xylene and have great stability in dried paint. Shipovskov explains that 'a stabilisation effect occurs due to the covalent linking between enzyme molecules which prevents enzyme inactivation in organic solvents'.

Environmentally friendly paints for boats use enzymes instead of metals

Additionally, activity of the enzymes becomes 9 times higher when it is immersed in artificial sea water, says Shipovskov. The level of paint hydration continuously increases in seawater leading to an increased amount of molecules leaching from the paint surface, and the cross-linking in the enzyme increases the efficiency of the catalyst, he explains.

Peter Halling at the University of Strathclyde, UK, who researches the use of enzymes in industrial processes, comments: 'CLEA's are a well known method to stabilise enzymes and [this work] is an interesting application and worth researching further.'

Shipovskov now plans to text how long the paints remail active for, 'the technological requirement for antifouling paints is for them to remain active for at least 1 year for private yachts and 6 years for commercial vessels. Therefore, it is crucial to obtain an adequate antifouling effect in addition to the required lifetime,' he says.

Nicola Wise


Tumour detection takes an ultrasonic leap

20 October 2010

Hollow silica nanoparticles filled with gas behave as efficient contrast agents for use in ultrasound imaging. This could improve detection of tumours in breast cancer patients, claim US scientists.

Ultrasound imaging is a safe, fast and non-invasive technique used for medical diagnosis. However, one shortcoming is the inferior image contrast compared to more sophisticated magnetic resonance imaging (MRI). To improve this, radiologists use microbubble contrast agents to enhance the reflection of ultrasonic waves and therefore improve the quality of the ultrasound image, or radioactive seeds that are injected into the patient before surgery to visualise the entire tumour. However, the contrast particles - normally comprised of a soft protein outer shell and a gas core - can be unstable due to their high sensitivity to changes in pressure, while the radioactive seeds have to be painfully injected into the patient and only last a few hours.

Now, a team led by William Trogler at the Univeristy of Califonia, San Diego have developed a stable, hard shell, hollow particle which, when filled with gas, produces a ultrasound signal and can be safely and painlessly injected into breast tissue to locate tumours. The gas-filled microbubbles adhere to human breast tissue for days and have a longer imaging lifetime than their soft counterparts, explains Trogler. So if used in early stage breast cancer patients, they could help surgeons better visualise the tumours and remove it all in one procedure.

Breast cancer tumours imaged using hollow silica nanoparticles

Elizabeth Shaughnessy, a specialist in breast diseases at the University of Cincinnati in the US agrees. 'The injection of these silica hollow spheres with gas-filled contrast provides a less toxic alternative, [to radioactive seeds] that won't degrade within a short time period.' She adds that the work is 'highly innovative and will have great appeal to surgeons, radiologists and patients, as well as operating staff.'

It is still early days but next Trogler and his team hope to move to animal models, toxicology studies and eventually clinical trials. Methods are also being developed to make biodegradable gas filled silica micro and nanoshells that would broaden the possible imaging applications.

Philippa Ross



A silver bullet for DNA separation

19 October 2010

A simple and greener way to separate DNA using branched silver microparticles is revealed by scientists in China.

Separation techniques are required for a multitude of applications from disease diagnosis to environmental monitoring. Many materials are used to separate complex chemical mixtures with more recent interest focussing on magnetic nanoparticles as they can be easily recovered.

However, preparation of magnetic nanoparticles requires a large amount of organic reagents and energy and it can be difficult to get the right dimensions. Now Erkang Wang and co-workers at the Changhun Institute of Applied Chemistry have developed crystalline silver particles, know as dendrites, as an alternative to magnetic nanoparticles for DNA separation. 'The development of a facile, economical and simple strategy to synthesize a new monodisperse, easily-modified substitute for magnetic nanoparticles with controlled size is a great challenge' explains Wang.

Nanoparticles can be used to detect DNA then be easily separated using gravity

Wang used the silver microdendrites to analyse human T-lymphotropic virus types I (HTLV-I), which is associated to adult T cell lymphoma/leukemia. The silver micro-dendrites were firstly modified with a probe to target the DNA and a second fluorophore labelled probe was used to enable detection with a confocal laser scanning microscope. The separation uses gravity thus eliminating the need for magnetic separation and simplifying the process.

'If the described approach would extend the toolbox of nanoparticle-based bioanalytical techniques by providing another, alternative separation technique without the requirements of either magnetic particles nor centrifuges it would be a welcome addition to the field,' comments Wolfgang Fritzsche, an expert in nanobiophotonics at the Institute of Photonic Technology in Jena, Germany.

'Many other chemicals such as proteins, organic pollutants and even heavy metal ions could be detected using this technique,' adds Wang and adds that the next challenge is to develop this technique for real sample analysis.

Leanne Marle



Red mud could prompt chemical rule review

18 October 2010

The alumina waste sludge accident in Hungary shows that the the European Union needs to be more effective in its enforcement of legislation on waste containing dangerous chemicals, according to environmental lawyers.

Nine people were killed and over a hundred injured after a dyke around an alumina waste pond belonging to MAL Magyar Alumínium near Ajka burst on 4 October. Around 600,000-700,000m3 of highly alkaline red mud spread across 1000ha into nearby villages and rivers, eventually running into the Danube.

'It is not so much that there needs to be changes to legislation but that the existing rules should be more rigorously enforced,' says Vito Buonsante, an environmental lawyer at the legal pressure group ClientEarth in Brussels.

The sludge from a bauxite conversion process had a pH of 13-13.5 - the same as bleach
© Flickr/Hornyák Dániel

In 1982, the EU brought into force the so-called Seveso directive (82/501/EEC) aimed at the prevention and control of accidents in the chemical industry. This was replaced by Seveso II in 1996.

'It is not exactly clear which directive - whether Seveso II and the recently approved mining waste directive or other EU legislation - has been applied to this waste pond,' Buonsante continues. 'But whatever the EU legislation, it would have required close monitoring and supervision of the waste, which clearly did not happen. The lesson to be learned from this incident is that EU regulations on dangerous chemicals waste are not being implemented effectively, particularly in the eastern European countries.'

This is a view echoed by the World Wildlife Fund (WWF), which says aerial photographs taken in June show a leakage through the dyke around the waste pond. 'The regulatory monitoring and control of these waste sites needs to be tightened up,' says Gábor Figeczky, acting director of WWF Hungary.

In the aftermath of the disaster, the chemical industry is now bracing itself for a tightening up of the Seveso II directive and other EU legislation covering potentially hazardous production sites. 'It is now likely that when [the Registration, Evaluation, Authorisation & Restriction of Chemicals regulation] is reviewed in 2012 its extension to cover waste will be considered,' says Steve Elliott, chief executive of the UK Chemical Industries Association.

The accident is also considered to be test for the 2004 European liability directive (ELD). This has been incorporated into Hungary's national legislation, alongside a plan for it to be mandatory for companies to set aside funds for remedying environmental damage in the event of accidents.

'The ELD was specifically drawn up to prevent these kinds of accidents because companies would take action to ensure they didn't happen due to high liabilities,' says Sandy Luk, another ClientEarth lawyer.

Sean Milmo



Twist and shine

17 October 2010

An international team researchers has developed flexible sheets of tiny light emitting diodes (LEDs) that could be implanted under the skin like glowing tattoos and used in a range of biomedical applications.

John Rogers at the University of Illinois at Urbana-Champaign, US, worked with researchers in the US, Korea, China and Singapore to build on his previous work on flexible circuits and ultra-thin LEDs.

To make the new LEDs, the team worked with arrays 100 x 100um in size and just 2.5um thick, several times smaller than any similar commercially available devices. The researchers printed the circuits onto a rigid glass substrate before transferring them to poly(dimethylsiloxane) (PDMS), a low cost, flexible biocompatible polymer.

Arrays of LEDS on a flexible PDMS substrate can be twisted and still fuction effectively
© Nature Materials

Most recent research on flexible LED circuits has focused on organic LEDs (OLEDs) but Rogers argues that his approach has benefits for biomedical applications. 'I wouldn't necessarily characterise this approach as better [than OLEDs],' he says, 'OLEDs are extremely sensitive to oxygen or water, but we encapsulate our device in a thin layer of silicon rubber. The brightness, lifetime and the ability to make them in a waterproof form distinguishes our devices.' To demonstrate the array's ability to function in these environments, Rogers and his team integrated the miniature LEDs into the fingertip of a vinyl glove and immersed it in soapy water, and implanted an LED array beneath the skin in an animal model.

The hope is that these new devices will find a variety of applications, including as suture threads or implantable patches that could perform spectroscopy to characterise bodily tissue, or be used in sophisticated diagnostics and to monitor wound healing. The arrays could also be used in photodynamic drug therapy, to control the delivery of drugs that are triggered by light in a more precise way.

The LED arrays were implanted under the skin of an animal model (left) and integrated into the fingertip of a vinyl glove
© Nature Materials

'We're used to thinking of electronic devices as distinct from things we wear or put over our wounds to heal them' says Michael Strano, of the chemical engineering department at Massachusetts Institute of Technology, Cambridge, US. 'Nobody knows what's going to come from a lot of this work, but it's going to have an enormous impact.'

Rogers has recently launched a spin out company, to work on commercialising some of his devices, a goal he sees as 'incredibly appealing'. 'We try to choose problems in science where the solutions can have an impact on society through commercialised products,' he says. 'I want to see this stuff have impact - it's the end goal that's serving as a motivation.'

Laura Howes


Polymerisation reveals hidden fingerprints

15 October 2010

Fingerprints leave their mark on surfaces that remain even if they are washed off allowing them to be detected using disulphur dinitride, claim UK scientists.

Fingerprint analysis of crime scenes has become a powerful weapon in the forensic scientist's arsenal. The ridges present on the tips of the fingers are unique to a person. By comparison of impressions left in materials - typically flat, regular surfaces, such as glass - to a sample taken from a suspect it is possible to identify the owner of the fingerprints.

But there are occasions where fingerprints are not easily viewable or are fragmented. Here, latent fingerprinting - where obscured fingerprints are enhanced - can be used to identify an individual. In 2008, Paul Kelly and co-workers at Loughborough University noticed that the strained four-membered ring system S2N2 quickly polymerises to (SN)x in the presence of fingerprints. Detecting this polymer produces a visual image of the fingerprint.

It could be possible to identify fingerprints that have been washed from surfaces

Now they have shown that this polymerisation still occurs when the chemicals in the fingerprint that were thought to trigger it are 'washed off' the surface, which could occur by simple wiping or an explosive blast. The polymerisation is triggered by an effect brought about by interaction of the chemicals with the surface before they are removed.

'As long as the print has been on the surface long enough to bring this about before washing off - and this only has to be hours or less - this signature will be present and we can image it,' explains Kelly. He goes on to say that the key to this process is that it is 'based on the interaction of S2N2 vapour with the surface'. The crucial point is that a vapour can reach areas of a surface that are not accessible to solids and liquids, such as the crumpled remains of an explosive device, he adds.

John Plater, an expert in the enhancement of latent fingerprints at the University of Aberdeen in the UK sees promise in the system: 'developing latent fingerprints on metal surfaces is difficult and a vapour phase method may offer added sensitivity to existing methods.'

Kelly is keen to stress that this research is still in its infancy and the team is working on further research to develop the method so that it could be used in forensics.

Jon Watson


Making fuels from biomass waste

15 October 2010

Jet and diesel fuel can be produced in a simple economic process using waste products of wood processing and pulp mills, claim US scientists.

World decline in fossil fuel resources, rising oil prices, and an increased awareness in environmental impact has made the search for alternative renewable fuel sources extremely important. Sustainable production of fuels has been attempted using non-food biomass (composed of cellulose, hemicellulose, and lignin) and vegetable oils. But these methods only make light alkanes that are not suitable for use as jet and diesel fuel due to their high volatility, so jet and diesel fuels are currently still reliant on petroleum-based crude oils.

In the search for alkanes more suited for transport fuels, George Huber at the University of Massachusetts in Amherst and colleagues have shown that waste feedstocks from biomass power plants or composite wood manufacturing facilities can be turned into jet fuel in an integrated and economical process.

4 step process produces heavy alkanes suitable for diesel

Huber treats a hemicellulose extract from hardwood trees, a common by-product from the wood manufacturing industry, in a four-step process that includes acid hydrolysis and xylose dehydrogenation, aldol condensation, low temperature hydrogenation, and high temperature hydrodeoxygenation. High yields of 76 per cent are obtained and the cost works out to between $2.06/gal and $4.39/gal, depending on initial xylose concentration, refinery size and overall yield.

'Our society will always have a critical need to produce renewable liquid transportations fuels that can run heavy machinery like jet or diesel engines. It is imperative that we develop inexpensive routes to produce these liquid fuels from our renewable resources,' comments Huber. Though in its beginning stages, Huber hopes it can be developed to a commercial level.

David Shonnard, director of the Sustainable Futures Institute at Michigan Technological University in the US comments, 'this is a significant step forward in achieving sustainable transportation. The economic analysis is also particularly important and the sensitivity analyses highlight promising pathways for improvement.'

Rebecca Brodie


France and Spain commit funds to research

14 October 2010

The 'knowledge economy' has been declared a priority for the governments of both France and Spain, as they announce extra funds for higher education and research in their 2011 budgets.

France's ministry for higher education and research has pledged to spend 15.2 billion (£13.4 billion) on research, 412 million up on 2010, while the Spanish ministry for science and innovation's budget has increased by 63 million for 2011 to 5.4 billion.

Marja Makarow, chief executive of the European Science Foundation, says the move by the countries to increase rather than decrease R&D investment under the current financial conditions was 'a wise decision'.

Makarow cites Finland as an example of a country that invested in education and research during a stark financial downturn in the 1990s, transforming it from a resource-based economy to a knowledge economy. 'Today, Finland's total R&D investment is second highest in the world, 4 per cent of GDP,' she notes.

France and Spain have both made modest increases to their research budgets

The budget was welcomed by French researcher Julien Mozziconacci, who models nanomachinery at the University of Pierre and Marie Curie in Paris, but he says researchers' attitudes in the country may have to change. Mozziconacci explained that one of the ambitions of French President Nicolas Sarkozy is that institutions and universities in the country achieve better international rankings. 'The plan is to bring together several institutions to create centres of excellent research, and to give more money to people who publish more papers in better journals,' he says.

'It's good that they push people to publish because I think in France there is great potential for us to have a better ranking than we have,' Mozziconacci told Chemistry World. 'We do good science and have good scientists - we just don't bother so much about publishing because our careers don't depend on it.'

Both France and Spain also intend to support industry-based research. France's research tax credit system will continue, and will increase by €145 million. The system covers all R&D expenses for firms operating in the country and is seen as one of the best in Europe. Spain's state innovation strategy, which involves direct investment in scientific infrastructure and allows R&D costs to be tax deductable, will continue at its current level of 3.2 million.

France was one of the first countries in the eurozone to emerge from recession, with the French national statistics office reporting growth of 0.1 per cent in the second quarter of 2009. However, despite the national budget pledging to reduce France's deficit from 8 per cent in 2010 to 6 per cent in 2011, overall public spending by the French government is set to rise only in line with inflation.

Spain's economy, by contrast, only excited recession after the first quarter of 2010 according to the Bank of Spain, and the country's unemployment rates - over 20 per cent according to the Spanish National Statistics Institute - are twice those of France. The Spanish government's budget commits the country to reducing its large deficit of 11 per cent of GDP in 2010 to 6 per cent in 2011, as well as investing in R&D innovation and education. After presenting the budget to parliament in September, the Spanish finance minister, Elena Salgado, described it as 'the most austere' of recent years, with a 16 per cent cut in spending by ministries.

Laura Howes



14 October 2010

A new family of cobalt-gadolinium cage compounds are highly efficient for low temperature cooling, say European scientists.

Liquid helium is currently used to achieve very low temperatures in a large amount of technology, such as super-conducting magnets that are needed for magnetic resonance imaging scanners. But the world supply of helium is falling, making it more expensive. An alternative method for low temperature cooling is to use demagnetisation of magnetic materials.

Now Richard Winpenny at the University of Manchester and colleagues have synthesised a new family of cobalt-gadolinium cage compounds, creating heterometallic molecular squares that show potential for the creation of magnetic coolants. Winpenny explains that magnetic coolants work because demagnetisation increases the entropy of the material, and this increase in entropy comes from taking heat out of the surroundings.

Cobalt-gadolinium molecular squares act as super coolants

Juergen Schnack at the University of Bielefeld, Germany, an expert in the area of magnetic molecules, comments: 'most interesting for me is the ability to synthesise such structures in such a great variety as demonstrated by the different grids of this work. This justifies our hopes that compounds with desired properties, for instance a large magnetocaloric effect - where compounds show a large change in temperature with a change in the magnetic field - are achievable.'

The highly anisotropic cobalt(II) ions in these compounds would be expected to have an adverse effect on the magnetocaloric effect, according to the scientists, but anti-ferromagnetic exchange between the octahedral cobalt ions appears to cancel out their contribution.

'We have a fairly precise understanding of what is needed for a good magnetic coolant,' says Winpenny. 'What is surprising is that cobalt(II) complexes shouldn't meet those requirements, and yet the complexes we've studied look interesting. Therefore I think we are going to find a few more surprises along the way and maybe we will need better theory as we proceed.'

Rachel Cooper


Aerosol theory solidifies

13 October 2010

An international team of researchers has found that atmospheric aerosol particles long thought to be liquid can in fact be amorphous solids.1 The discovery could have implications for understanding the formation of such particles and could improve atmospheric models and climate predictions.

Secondary organic aerosol (SOA) particles form in the atmosphere by the oxidation of predominantly plant-derived volatile organic compounds (VOCs) and influence the Earth's climate by scattering solar radiation and acting as cloud-forming nuclei. Knowing their physical phase state is fundamental in understanding how the particles form, which in turn affects how atmospheric models are produced. Although previous reports have hinted that SOA particles might exist as solids2,3, this new study is the first to provide direct evidence, prompting a need to revise existing models.

The team took terpenoid samples emitted from Scots pine seedlings to confirm the theory

'Initially when we saw the experimental data we thought something must be wrong with our apparatus,' says Annele Virtanen at Tampere University of Technology in Finland, who carried out the research with international colleagues. 'It was only after many additional experiments and very careful tests that we convinced ourselves that the only explanation was that the particles had to be solids.'

The team first captured SOA particles in a plant chamber that contained Scots pine seedlings. The plants emit terpenoids - naturally occurring (VOCs) - and react with hydroxyl (OH) radicals and ozone (O3) to form SOA particles. Using an electrical low-pressure impactor, the team forced the particles to collide with metal substrates. If in a liquid state, the particles would be seen to stick to the surface, but the team observed the particles bounce off.

By comparing the bounce of the SOA particles to that of other aerosol particles with known liquid, crystalline or solid phase states, the team concluded that the SOA particles must exist as amorphous solids. Electron microscopy further verified the results by revealing the shape and phase state of the particles.

The researchers also headed to a boreal forest in Finland to take aerosol measurements and conducted similar impactor experiments. While the bounce factor of these atmospheric SOA particles was found to be lower than that of the plant chamber SOA particles, it was significantly larger than that of liquid particles (the team used dioctyl sebacate) and slightly larger than crystalline (NH4)2SO4 particles.

'The belief that the organic component of atmospheric aerosol particles is liquid is widespread in the atmospheric science community,' says Paul Ziemann, at the University of California, Riverside, US. 'It is amazing that Virtanen and coworkers were able to so convincingly disprove this important premise, and that they did so from rather simple but elegant measurements on particles formed in forests, arguably the most important type of particle present in the atmosphere.'

George Marston, an atmospheric chemistry expert at the University of Reading, UK, thinks the work is 'very interesting.' He points out that internal aerosol material will have a longer lifetime in the solid phase than the liquid phase owing to diffusion limits for the transport of reactants into the particles. 'Thus the ageing of aerosols in the atmosphere will be strongly affected, and the processing of aerosol particles to act as cloud condensation nuclei is strongly affected; this has obvious implications for the role of SOA in climate.'

The discovery doesn't mean that current climate models are totally wrong, however. 'The biggest scientific uncertainties in climate model predictions are related to the magnitude of the cooling effects of aerosols,' explains Virtanen. 'We believe that predictions will become less uncertain when the details regarding the particle phase and chemistry have been implemented to the models, but these new predictions will most probably remain within the error bars of the current predictions.'

James Urquhart