Chemists devise chemical reaction that holds promise for new drug development

A team of researchers at the California Institute of Technology (Caltech) has devised a new method for making complex molecules. The reaction they have come up with should enable chemists to synthesize new varieties of a whole subclass of organic compounds called nitrogen-containing heterocycles, thus opening up new avenues for the development of novel pharmaceuticals and natural products ranging from chemotherapeutic compounds to bioactive plant materials such as morphine.

The team -- led by Brian Stoltz, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry, and Doug Behenna, a scientific researcher -- used a suite of specialized robotic tools in the Caltech Center for Catalysis and Chemical Synthesis to find the optimal conditions and an appropriate catalyst to drive this particular type of reaction, known as an alkylation, because it adds an alkyl group (a group of carbon and hydrogen atoms) to the compound. The researchers describe the reaction in a recent advance online publication of a paper in Nature Chemistry.

"We think it's going to be a highly enabling reaction, not only for preparing complex natural products, but also for making pharmaceutical substances that include components that were previously very challenging to make," Stoltz says. "This has suddenly made them quite easy to make, and it should allow medicinal chemists to access levels of complexity they couldn't previously access."

The reaction creates compounds called heterocycles, which involve cyclic groups of carbon and nitrogen atoms. Such nitrogen-containing heterocycles are found in many natural products and pharmaceuticals, as well as in many synthetic polymers. In addition, the reaction manages to form carbon-carbon bonds at sites where some of the carbon atoms are essentially hidden, or blocked, by larger nearby components.

"Making carbon-carbon bonds is hard, but that's what we need to make the complicated structures we're after," Stoltz says. "We're taking that up another notch by making carbon-carbon bonds in really challenging scenarios. We're making carbon centers that have four other carbon groups around them, and that's very hard to do."

The vast majority of pharmaceuticals being made today do not include such congested carbon centers, Stoltz says -- not so much because they would not be effective compounds, but because they have been so difficult to make. "But now," he says, "we've made it very easy to make those very hindered centers, even in compounds that contain nitrogen. And that should give pharmaceutical companies new possibilities that they previously couldn't consider."

Perhaps the most important feature of the reaction is that it yields almost 100 percent of just one version of its product. This is significant because many organic compounds exist in two distinct versions, or enantiomers, each having the same chemical formula and bond structure as the other, but with functional groups in opposite positions in space, making them mirror images of each other. One version can be thought of as right-handed, the other as left-handed.

The problem is that there is often a lock-and-key interaction between our bodies and the compounds that act upon them -- only one of the two possible hands of a compound can "shake hands" and fit appropriately. In fact, one version will often have a beneficial effect on the body while the other will have a completely different and sometimes detrimental effect. Therefore, it is important to be able to selectively produce the compound with the desired handedness. For this reason, the FDA has increasingly required that the molecules in a particular drug be present in just one form.

"So not only are we making tricky carbon-carbon bonds, we're also making them such that the resulting products have a particular, desired handedness," Stoltz says. "This was the culmination of six years of work. There was essentially no way to make these compounds before, so to all of a sudden be able to do it and with perfect selectivity… that's pretty awesome."

In addition to Stoltz and Behenna, other authors on the paper, "Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams," include Yiyang Liu, Jimin Kim, David White, and Scott Virgil of Caltech, and Taiga Yurino, who visited the Stoltz lab on a fellowship supported by the Japan Society for the Promotion of Science. The work was supported by the King Abdullah University of Science and Technology, the NIH-NIGMS, the Gordon and Betty Moore Foundation, Amgen, Abbott, and Boehringer Ingelheim.

Story Source:

The above story is reprinted from materials provided by California Institute of Technology. The original article was written by Kimm Fesenmaier.

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Journal Reference:

Douglas C. Behenna, Yiyang Liu, Taiga Yurino, Jimin Kim, David E. White, Scott C. Virgil, Brian M. Stoltz. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams. Nature Chemistry, 2011; DOI: 10.1038/nchem.1222

Bucky balls for next-generation spintronics devices

The beauty of an electron's spin is that it responds very rapidly to small magnetic fields. Such external magnetic fields can be used to reverse the direction of spin. In this way, information can be carried by a flow of electrons. For instance, electrons with a left-hand spin could represent a "1," and those with a right-hand spin, a "0." It takes less time to flip the spin direction than it does to switch a current on or off. Accordingly, spintronics could potentially be very fast and extremely compact.

Organic materials

However, this would require a material that combines the characteristics of a semiconductor (such as silicon, the most widely used material in the chip industry) with magnetic properties. Research in this area (including work by Michel de Jong) has already delivered results. However, finding materials with this combination of properties is far from simple. For this reason, Michel de Jong is now hunting for an alternative. He is focusing on semiconductors consisting of carbohydrate chains, in other words, organic materials. "Such materials are already being used in the displays of the latest smart phones. Indeed, they are very much the 'in' thing. I expect it will ultimately be possible to make very cheap electronics from these materials, leading to a wide range of new applications. For instance, if supermarkets want to tag their products with pricing information, then the electronics involved will have to cost next to nothing."

Buckyballs

De Jong has been experimenting with buckyballs (spherical C60 molecules held together by weak bonds) sandwiched between two magnetic materials. "The great advantage of these molecules is that they have very little effect on electron spin. This enables them to store spin information for much longer periods of time than silicon." Depending on the orientation of the magnetic field in the upper and lower layers of magnetic material, electrons with the same direction of spin are either allowed through or held back, as if a valve were being opened or closed. This would make it possible to create sensitive magnetic sensors, for example. The "sandwich" might also form the basis for new electronic components that make use of spin.

"If we are to make truly effective components, we will need a detailed understanding of events at the interface between the magnetic and organic materials. However, this will require improvements in the quality of such interfaces. The current techniques for applying metallic layers to organic layers do not produce good interconnections. The organic material contains cavities that can fill with metal. This results in unpredictable behaviour. Over the next five years we will be seeking to improve the manufacturing process. This will help us to understand what exactly happens at the interface."

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The above story is reprinted from materials provided by University of Twente, via AlphaGalileo.

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The perfect liquid -- now even more perfect

How liquid can a fluid be? This is a question particle physicists at the Vienna University of Technology have been working on. The "most perfect liquid" is nothing like water, but the extremely hot quark-gluon-plasma which is produced in heavy-ion collisions at the Large Hadron Collider at CERN. New theoretical results at Vienna UT show that this quark-gluon plasma could be even less viscous than was deemed possible by previous theories.

The results were published in Physical Review Letters and highlighted as an "editors' selection."

Liquids and their Viscosity

Highly viscous liquids (such as honey) are thick and have strong internal friction, quantum liquids, such as super fluid helium can exhibit extremely low viscosity. In 2004, theorists claimed that quantum theory provided a lower bound for viscosity of fluids. Applying methods from string theory, the lowest possible ratio of viscosity to the entropy density was predicted to be h/4? (with the Planck-constant h). Even super fluid helium is far above this threshold. In 2005, measurements showed that quark-gluon-plasma exhibits a viscosity just barely above this limit. However, this record for low viscosity can still be broken, claims Dominik Steineder from the Institute for Theoretical Physics at Vienna UT. He obtained this remarkable result working as a PhD-student with Professor Anton Rebhan.

Black Holes and Particle Collisions

The viscosity of a quark-gluon plasma cannot be calculated directly. Its behavior is so complicated that very sophisticated tricks have to be applied, says Anton Rebhan: "Using string theory, the quantum field theory of quark-gluon plasma can be related to the physics of black holes in higher dimensions. So we are solving equations from string theory and then transfer the results to the physics of the quark-gluon plasma." The previously established lower bound for viscosity was calculated in a very similar way. However, in these calculations the plasma was modeled to be symmetric and isotropic. "In fact, a plasma produced by a collision in a particle accelerator is not isotropic at the beginning," says Anton Rebhan. The particles are accelerated and collided along one specific direction -- so the resulting plasma shows different properties, depending on the direction from which one looks at it.

Breaking the Limits

The physicists at Vienna UT found a way to include this anisotropy in their equations -- and surprisingly the limit for the viscosity can be broken in this new model. "The viscosity depends on several other physical parameters, but it can be lower than the number previously considered to be the absolute lower bound," Dominik Steineder explains. The on-going quark-gluon-experiments at CERN will provide opportunities for testing the new theoretical predictions.

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The above story is reprinted from materials provided by Vienna University of Technology, TU Vienna, via AlphaGalileo.

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Journal Reference:

Anton Rebhan, Dominik Steineder. Violation of the Holographic Viscosity Bound in a Strongly Coupled Anisotropic Plasma. Physical Review Letters, 2012; 108 (2) DOI: 10.1103/PhysRevLett.108.021601

Easier testing for diabetics? Biochip measures glucose in saliva, not blood

Engineers at Brown University have designed a biological device that can measure glucose concentrations in human saliva. The technique could eliminate the need for diabetics to draw blood to check their glucose levels. The biochip uses plasmonic interferometers and could be used to measure a range of biological and environmental substances. 

For the 26 million Americans with diabetes, drawing blood is the most prevalent way to check glucose levels. It is invasive and at least minimally painful. Researchers at Brown University are working on a new sensor that can check blood sugar levels by measuring glucose concentrations in saliva instead.

The technique takes advantage of a convergence of nanotechnology and surface plasmonics, which explores the interaction of electrons and photons (light). The engineers at Brown etched thousands of plasmonic interferometers onto a fingernail-size biochip and measured the concentration of glucose molecules in water on the chip. Their results showed that the specially designed biochip could detect glucose levels similar to the levels found in human saliva. Glucose in human saliva is typically about 100 times less concentrated than in the blood.

"This is proof of concept that plasmonic interferometers can be used to detect molecules in low concentrations, using a footprint that is ten times smaller than a human hair," said Domenico Pacifici, assistant professor of engineering and lead author of the paper published in Nano Letters, a journal of the American Chemical Society.

The technique can be used to detect other chemicals or substances, from anthrax to biological compounds, Pacifici said, "and to detect them all at once, in parallel, using the same chip."

To create the sensor, the researchers carved a slit about 100 nanometers wide and etched two 200 nanometer-wide grooves on either side of the slit. The slit captures incoming photons and confines them. The grooves, meanwhile, scatter the incoming photons, which interact with the free electrons bounding around on the sensor's metal surface. Those free electron-photon interactions create a surface plasmon polariton, a special wave with a wavelength that is narrower than a photon in free space. These surface plasmon waves move along the sensor's surface until they encounter the photons in the slit, much like two ocean waves coming from different directions and colliding with each other. This "interference" between the two waves determines maxima and minima in the light intensity transmitted through the slit. The presence of an analyte (the chemical being measured) on the sensor surface generates a change in the relative phase difference between the two surface plasmon waves, which in turns causes a change in light intensity, measured by the researchers in real time.

"The slit is acting as a mixer for the three beams -- the incident light and the surface plasmon waves," Pacifici said.

The engineers learned they could vary the phase shift for an interferometer by changing the distance between the grooves and the slit, meaning they could tune the interference generated by the waves. The researchers could tune the thousands of interferometers to establish baselines, which could then be used to accurately measure concentrations of glucose in water as low as 0.36 milligrams per deciliter.

"It could be possible to use these biochips to carry out the screening of multiple biomarkers for individual patients, all at once and in parallel, with unprecedented sensitivity," Pacifici said.

The engineers next plan to build sensors tailored for glucose and for other substances to further test the devices. "The proposed approach will enable very high throughput detection of environmentally and biologically relevant analytes in an extremely compact design. We can do it with a sensitivity that rivals modern technologies," Pacifici said.

Tayhas Palmore, professor of engineering, is a contributing author on the paper. Graduate students Jing Feng (engineering) and Vince Siu (biology), who designed the microfluidic channels and carried out the experiments, are listed as the first two authors on the paper. Other authors include Brown engineering graduate student Steve Rhieu and undergraduates Vihang Mehta, Alec Roelke.

Results are published in Nano Letters. The National Science Foundation and Brown (through a Richard B. Salomon Faculty Research Award) funded the research.

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The above story is reprinted from materials provided by Brown University.

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Journal Reference:

Jing Feng, Vince S. Siu, Alec Roelke, Vihang Mehta, Steve Y. Rhieu, G. Tayhas R. Palmore, Domenico Pacifici. Nanoscale Plasmonic Interferometers for Multispectral, High-Throughput Biochemical Sensing. Nano Letters, 2012; 120109130837001 DOI: 10.1021/nl203325s

Nanoparticles refined for more accurate delivery of cancer drugs

A new class of nanoparticles, synthesized by a UC Davis research team to prevent premature drug release, holds promise for greater accuracy and effectiveness in delivering cancer drugs to tumors. The work is published in the current issue of Angewandte Chemie, a leading international chemistry journal.

In their paper, featured on the inside back cover of the journal, Kit Lam, professor and chair of the Department of Biochemistry and Molecular Medicine, and his team report on the synthesis of a novel class of micelles called dual-responsive boronate cross-linked micelles (BCMs) , which produce physicochemical changes in response to specific triggers.

A micelle is an aggregate of surfactant molecules dispersed in water-based liquid such as saline. Micelles are nano-sized, measuring about 25-50 nanometers (one nanometer is one billionth of a meter), and can function as nanocarriers for drug delivery.

BCMs are a unique type of micelle, which releases the payload quickly when triggered by the acidic micro-environment of the tumor or when exposed to an intravenously administered chemical compound such as mannitol, an FDA-approved sugar compound often used as a diuretic agent, which interferes with the cross-linked micelles.

"This use of reversibly cross-linked targeting micellar nanocarriers to deliver anti-cancer drugs helps prevent premature drug release during circulation and ensures delivery of high concentrations of drugs to the tumor site," said first author Yuanpei Li, a postdoctoral fellow in Lam's laboratory who created the novel nanoparticle with Lam. "It holds great promise for a significant improvement in cancer therapy."

Stimuli-responsive nanoparticles are gaining considerable attention in the field of drug delivery due to their ability to transform in response to specific triggers. Among these nanoparticles, stimuli-responsive cross-linked micelles (SCMs) represent a versatile nanocarrier system for tumor-targeting drug delivery.

Too often, nanoparticles release drugs prematurely and miss their target. SCMs can better retain the encapsulated drug and minimize its premature release while circulating in the blood pool. The introduction of environmentally sensitive cross-linkers makes these micelles responsive to the local environment of the tumor. In these instances, the payload drug is released primarily in the cancerous tissue.

The dual-responsive boronate cross-linked micelles that Lam's team has developed represent an even smarter second generation of SCMs able to respond to multiple stimuli as tools for accomplishing the multi-stage delivery of drugs to the complex in vivo tumor micro-environment. These BCMs deliver drugs based on the self-assembly of boronic acid-containing polymers and catechol-containing polymers, both of which make these micelles unusually sensitive to changes in the pH of the environment. The team has optimized the stability of the resulting boronate cross-linked micelles as well as their stimuli-response to acidic pH and mannitol.

This novel nano-carrier platform shows great promise for drug delivery that minimizes premature drug release and can release the drug on demand within the acidic tumor micro-environment or in the acidic cellular compartments when taken in by the target tumor cells. It also can be induced to release the drug through the intravenous administration of mannitol.

The study was funded by grants from the National Institutes of Health and a Department of Defense Breast Cancer Research Program Postdoctoral Award. Other authors are Wenwu Xiao, Kai Xiao, Lorenzo Berti, Harry P. Tseng, and Gabriel Fung of UC Davis; and Juntao Luo of SUNY Upstate Medical University, Syracuse, New York.

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The above story is reprinted from materials provided by University of California - Davis Health System.

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Journal Reference:

Yuanpei Li, Wenwu Xiao, Kai Xiao, Lorenzo Berti, Juntao Luo, Harry P. Tseng, Gabriel Fung, Kit S. Lam. Well-Defined, Reversible Boronate Crosslinked Nanocarriers for Targeted Drug Delivery in Response to Acidic pH Values and cis-Diols. Angewandte Chemie International Edition, 2012; DOI: 10.1002/anie.201107144

Computer simulations revealing how methane and hydrogen pack into gas hydrates could enlighten alternative fuel production and carbon dioxide storage

For some time, researchers have explored flammable ice for low-carbon or alternative fuel or as a place to store carbon dioxide. Now, a computer analysis of the ice and gas compound, known as a gas hydrate, reveals key details of its structure. The results show that hydrates can hold hydrogen at an optimal capacity of 5 weight-percent, a value that meets the goal of a U.S. Department of Energy standard and makes gas hydrates practical and affordable.

The analysis is the first time researchers have accurately quantified the molecular-scale interactions between the gases -- either hydrogen or methane, aka natural gas -- and the water molecules that form cages around them. A team of researchers from the Department of Energy's Pacific Northwest National Laboratory published the results in Chemical Physics Letters online December 22, 2011.

The results could also provide insight into the process of replacing methane with carbon dioxide in the naturally abundant "water-based reservoirs," according to the lead author, PNNL chemist Sotiris Xantheas.

"Current thinking is that you need large amounts of energy to push the methane out, which destroys the scaffold in the process," said Xantheas. "But the computer modeling shows that there is an alternative low energy pathway. All you need to do is break a single hydrogen bond between water molecules forming the cage -- the methane comes out, and then the hydrate reseals itself."

Cagey Ice

Gas hydrates -- especially methane hydrates, which store natural gas -- look like ice but actually hold burnable fuel. Naturally found deep in the ocean, water and gas interweave in the hydrates, but little is known about their chemical structure and processes occurring at the molecular level. They have been known to cause problems for the petroleum industry because they tend to clog pipes and can explode. A methane hydrate produced the bubble of methane gas that contributed to 2010's Gulf of Mexico oil spill.

In previous work, Xantheas and colleagues used computer algorithms and models to examine the water-based, ice-like scaffold that holds the gas. Water molecules form individual cages made with 20 or 24 molecules. Multiple cages join together in large lattices. But those scaffolds were empty in the earlier analysis.

To find out how fuels can be accommodated inside the water cages, Xantheas and PNNL colleague Soohaeng Yoo Willow built computer models of the cages with either hydrogen gas -- in which two hydrogen atoms are bound together -- or methane gas, a small molecule made with one carbon and four hydrogen atoms.

In the hydrogen hydrates, which could potentially be used as materials for hydrogen fuel storage, a small hollow cage made from 20 water molecules could hold up to a maximum of five hydrogen molecules and a larger cage made from 24 water molecules could hold up to seven.

The maximum storage capacity equates to about 10 weight-percent, or the percentage of hydrogen by mass in the chunks of ice, although packing hydrogen in that tight puts undue strain on the system. The Department of Energy's goal for hydrogen storage -- to make the fuel practical -- is above 5.5 weight-percent.

Experimentally, hydrogen storage researchers typically measure much less storage capacities. The computer model showed them why: The hydrogen molecules tended to leak out of the cages, reducing the amount of hydrogen that could be stored.

The researchers found that adding a methane molecule to the larger cages in the pure hydrogen hydrate, however, prevented the hydrogen gas from leaking out. The computer model showed the researchers that they could store the hydrogen at high pressure and practical temperatures, and release it by reducing the pressure, which melts it.

Water Gates

Understanding how the gas interacts and moves through the cages can help chemists or engineers store gas and remove it at will. Willow and Xantheas' computer simulations showed that hydrogen molecules could migrate through the cages by passing between the figurative bars of the water cages. However, the cages also had gates: Sometimes a low-energy bond between two water molecules broke, causing a water molecule to swing open and let the hydrogen molecule drift out. The "gate" closed right after the molecule passed through to reform the lattice.

With methane hydrates, some fuel producers want to remove the gas safely to use it. Others see the emptied cages as potential storage sites for carbon dioxide, which could theoretically keep it out of the atmosphere and ocean, where it warms the earth and acidifies the sea. So, Willow and Xantheas tested how methane could migrate through the cages.

The water cages were only big enough to comfortably hold one methane molecule, so the chemists stuffed two methanes inside and watched what happened. Quickly, one of the water molecules forming the cage swung open like a gate, allowing one methane molecule to escape. The gate then slammed shut as the remaining methane scooted into the middle of the cage.

"This process is important because it can happen with natural gas. It shows how methane can move in the natural world," said Xantheas. "We hope this analysis will help with the technical issues that need to be addressed with gas hydrate research and development."

Xantheas said performing computer simulations with carbon dioxide instead of methane might help determine whether it's chemically feasible to store carbon dioxide in hydrates.

This work was supported by the Department of Energy Office of Science (BES). Computer resources used were at the National Energy Research Scientific Computing Center at DOE's Lawrence Berkeley National Laboratory in Berkeley, Calif.

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The above story is reprinted from materials provided by Pacific Northwest National Laboratory.

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Journal Reference:

Soohaeng Yoo Willow, Sotiris S. Xantheas. Enhancement of hydrogen storage capacity in hydrate lattices. Chemical Physics Letters, 2011; DOI: 10.1016/j.cplett.2011.12.036

Solar alchemy: Photocatalysts to clean water and recover chemicals

 Polluted water can be easily cleaned and treated to extract valuable chemicals, e.g., used in drug manufacturing. No factories or plants are needed, the sun and a "magic" powder are enough. The nearly alchemic transformation is accomplished due to photocatalysts studied by researchers from the Institute of Physical Chemistry of the Polish Academy of Sciences in Warsaw.

In many places of the world water is highly polluted by organic chemicals from industrial wastes. The experiments carried out at the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) in Warsaw prove that the biomass can be successfully transformed into useful chemicals and fuel. Due to appropriately selected photocatalysts, the transformation of polluted water into clean one and chemicals does not require specialized plants and takes place under conditions that are commonly met in nature.

Catalyst is a substance that participates in the chemical reaction, speeds its course and fully recovers after the reaction is completed. In typical catalytic processes the catalysts are activated at high temperatures, typically of several hundreds degrees centigrade, often at a significantly increased pressure.

"Photocatalysts studied by us differ in many respects from traditional catalysts. They are activated by light, and the temperature has no significant effect here," says Dr Juan Carlos Colmenares from the IPC PAS. The reactions with participation of photocatalysts occur at good exposure to sun rays, at temperature about 30 degrees centigrade and at normal atmospheric pressure -- so at conditions occurring naturally all year round in many equatorial countries.

The photocatalysts studied at the IPC PAS are solids based on titanium dioxide, TiO2. The catalysed reaction occurs in a liquid containing organic pollutants. After the reaction is completed, the catalyst can be isolated almost without losses and used again.

"My work resembles somewhat alchemy," jokes Colmenares. "I take a 'magic' powder, pour it into polluted water, stir and expose to the sun. After several hours, I get clean water plus chemicals that can be used to make useful things, for instance drugs."

The research on photochemical degradation of pollutants has been carried out in the world already in the late 1960's. By intensive UV irradiation chemical compounds with simple structures have been obtained at that time.

The research pursued at the IPC PAS aims at such a selection of photocatalysts and reaction conditions that the reaction can occur without using specialized equipment, and the degradation of biomass stops at a precisely defined stage. With titania-based photocatalysis the researchers managed to produce carboxylic acids used, e.g., in pharmaceutical and food industries. It is also possible to prepare a photocatalyst so as to have the reaction completed and yielding substances with the simplest structure, such as hydrogen or carbon dioxide. The latter compound is undesirable and would require disposal, hydrogen, however, has excellent prospects as the fuel of the future.

"In laboratory conditions, the reactions of the biomass with participation of photocatalysts are promising already now. In this year we are going to attempt the first tests in the pilot biochemical photoreactors at the University of Cordoba, Spain. The reactions will occur there in liquids with volumes measured in tens of litres," says Colmenares while making clear that still many tests and studies are to be carried out before the new technology gets disseminated.

The co-authors of the paper published in the Bioresource Technology journal, describing application of photocatalysts to glucose degradation and to production of valuable chemicals are Agnieszka Magdziarz and Dr Anna Bielejewska, who passed away late last year. The research has been financed from an international Marie Skłodowska-Curie reintegration grant under the 7th Framework Programme of the European Union.

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The above story is reprinted from materials provided by Institute of Physical Chemistry of the Polish Academy of Sciences, via AlphaGalileo.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Juan C. Colmenares, Agnieszka Magdziarz, Anna Bielejewska. High-value chemicals obtained from selective photo-oxidation of glucose in the presence of nanostructured titanium photocatalysts. Bioresource Technology, 2011; 102 (24): 11254 DOI: 10.1016/j.biortech.2011.09.101

T-rays technology could help develop Star Trek-style hand-held medical scanners

 Scientists have developed a new way to create Terahertz waves (T-rays) that may one day lead to biomedical detective devices similar to the 'tricorder' scanner used in Star Trek

Scientists have developed a new way to create electromagnetic Terahertz (THz) waves or T-rays -- the technology behind full-body security scanners. The researchers behind the study, published recently in the journal Nature Photonics, say their new stronger and more efficient continuous wave T-rays could be used to make better medical scanning gadgets and may one day lead to innovations similar to the 'tricorder' scanner used in Star Trek.

In the study, researchers from the Institute of Materials Research and Engineering (IMRE), a research institute of the Agency for Science, Technology and Research (A*STAR) in Singapore, and Imperial College London in the UK have made T-rays into a much stronger directional beam than was previously thought possible, and have done so at room-temperature conditions. This is a breakthrough that should allow future T-ray systems to be smaller, more portable, easier to operate, and much cheaper than current devices.

The scientists say that the T-ray scanner and detector could provide part of the functionality of a Star Trek-like medical 'tricorder' -- a portable sensing, computing and data communications device -- since the waves are capable of detecting biological phenomena such as increased blood flow around tumorous growths. Future scanners could also perform fast wireless data communication to transfer a high volume of information on the measurements it makes.

T-rays are waves in the far infrared part of the electromagnetic spectrum that have a wavelength hundreds of times longer than those that make up visible light. Such waves are already in use in airport security scanners, prototype medical scanning devices and in spectroscopy systems for materials analysis. T-rays can sense molecules such as those present in cancerous tumours and living DNA, since every molecule has its unique signature in the THz range. They can also be used to detect explosives or drugs, for gas pollution monitoring or non-destructive testing of semiconductor integrated circuit chips.

Current T-ray imaging devices are very expensive and operate at only a low output power, since creating the waves consumes large amounts of energy and needs to take place at very low temperatures.

In the new technique, the researchers demonstrated that it is possible to produce a strong beam of T-rays by shining light of differing wavelengths on a pair of electrodes -- two pointed strips of metal separated by a 100 nanometre gap on top of a semiconductor wafer. The structure of the tip-to-tip nano-sized gap electrode greatly enhances the THz field and acts like a nano-antenna to amplify the wave generated. In this method, THz waves are produced by an interaction between the electromagnetic waves of the light pulses and a powerful current passing between the semiconductor electrodes. The scientists are able to tune the wavelength of the T-rays to create a beam that is useable in the scanning technology.

Lead author Dr Jing Hua Teng, from A*STAR's IMRE, said: "The secret behind the innovation lies in the new nano-antenna that we had developed and integrated into the semiconductor chip." Arrays of these nano-antennas create much stronger THz fields that generate a power output that is 100 times higher than the power output of commonly used THz sources that have conventional interdigitated antenna structures. A stronger T-ray source renders the T-ray imaging devices more power and higher resolution.

Research co-author Stefan Maier, a visiting scientist at A*STAR's IMRE and Professor in the Department of Physics at Imperial College London, said: "T-rays promise to revolutionise medical scanning to make it faster and more convenient, potentially relieving patients from the inconvenience of complicated diagnostic procedures and the stress of waiting for accurate results. Thanks to modern nanotechnology and nanofabrication, we have made a real breakthrough in the generation of T-rays that takes us a step closer to these new scanning devices. With the introduction of a gap of only 0.1 micrometers into the electrodes, we have been able to make amplified waves at the key wavelength of 1000 micrometers that can be used in such real world applications."

The research was led by scientists from A*STAR's IMRE and Imperial College London, and involved partners from A*STAR Institute for Infocomm Research (I2R) and the National University of Singapore. The research is funded under A*STAR's Metamaterials Programme and the THz Programme, as well as the Leverhume Trust and the Engineering and Physical Sciences Research Council (EPSRC) in the UK.

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The above story is reprinted from materials provided by Imperial College London.

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Journal Reference:

H. Tanoto, J. H. Teng, Q. Y. Wu, M. Sun, Z. N. Chen, S. A. Maier, B. Wang, C. C. Chum, G. Y. Si, A. J. Danner, S. J. Chua. Greatly enhanced continuous-wave terahertz emission by nano-electrodes in a photoconductive photomixer. Nature Photonics, 2012; DOI: 10.1038/nphoton.2011.322

Breast cancer cells targeted, then burned, by gold-filled silicon wafers

 By shining infrared light on specially designed, gold-filled silicon wafers, scientists at The Methodist Hospital Research Institute have successfully targeted and burned breast cancer cells. If the technology is shown to work in human clinical trials, it could provide patients a non-invasive alternative to surgical ablation, and could be used in conjunction with traditional cancer treatments, such as chemotherapy, to make those treatments more effective.

The research is presented in the first issue of the new Advanced Healthcare Materials, a Wiley journal.

"Hollow gold nanoparticles can generate heat if they are hit with a near-infrared laser," said Research Institute Assistant Member Haifa Shen, M.D., Ph.D., the report's lead author. "Multiple investigators have tried to use gold nanoparticles for cancer treatment, but the efficiency has not been very good -- they'd need a lot of gold nanoparticles to treat a tumor."

Instead, Shen and his colleagues turned to a technology developed by the study's principal investigator, Mauro Ferrari, Ph.D., The Methodist Hospital Research Institute (TMHRI) president and CEO, to amplify the gold particles' response to infrared light.

"We developed a system based on Dr. Ferrari's multi-stage vector technology platform to treat cancers with heat," Shen said. "We found that heat generation was much more efficient when we loaded gold nanoparticles into porous silicon, the carrier of the multistage vectors."

Shen and his team found that in the presence of 808 nanometer light, the gold-filled silicon particles heated up a surrounding solution by about 20 deg C (35 deg F) in seven minutes. Water particles immediately around the particles were presumed to have been hotter. And experiments showed that tumor cell growth was lowest in the presence of gold-loaded silicon nanoparticles in three types of breast cancer cells -- MDA-MB-231 and SK-BR-3 (human), and 4T1 (mouse).

The silicon wafers the scientists are using are the result of painstaking work by Ferrari's group to design nanoparticles that preferentially bind to breast cancer cells, rather than, say, healthy liver or immune system cells. The shape and size of the silicon particles, as well as their surface chemistry, are all crucial, Ferrari's group found. Too big or the wrong shape, and the silicon nanoparticles bind to multiple cell types -- or none at all. Polyamine structures are attached to the wafers to improve their attraction to cancer cell surfaces and their solubility. The wafers are about one micrometer in diameter (one-thousandth of a millimeter). By contrast, the typical breast cancer cell is about 10 to 12 times that size.

Shen says the gold particles, too, must be designed with a specific use in mind, albeit for indirect reasons.

"The hollow gold particles we load into the porous silicon must be the right size and have the correct-sized space inside them to interact with the infrared light we are using," he said. "But the wavelength of infrared we use will have to change depending on where the tumor is. If it's close to the skin, we can use shorter wavelengths. Deeper inside the body, we have to use longer wavelengths of infrared to penetrate the tissue. The hollow space of the gold particles must be modified in response to that."

Both silicon and gold have low toxicity profiles in the human body, and are popular materials in current investigations using medical nanotechnology. Silicon is steadily broken down by physiological processes into an acid that is removed through the kidneys. And gold is chemically inert.

And infrared -- the type of light used by TV remote controls and garage door openers -- is also far less dangerous than light with shorter wavelengths, such as ultraviolet, which can cause DNA damage, and x-rays.

Understanding why hollow gold particles heat up in the presence of certain wavelengths of infrared is complex enough to require some background in physical chemistry. But the upshot is that the energy of certain wavelengths of light is largely absorbed by the particles, and that energy is released as vibrational (heat) energy. Absorption is influenced both by the diameter of the space within the hollow gold particles, and by the properties of gold itself.

Shen says he'd like to know whether the silicon-gold nanotechnology can be used to wipe out whole tumors, rather than just cancerous cells.

"We are planning pre-clinical studies to study the technology's impact on whole tissues, breast cancer cells and possibly pancreatic cancer cells," Shen said. "We would also like to see whether this approach makes chemotherapy more effective, meaning you could use less drugs to achieve the same degree of success in treating tumors. These investigations are next."

Coauthors of the Advanced Healthcare Materials paper were Jian You, whose contributions were equal to Shen's, Guodong Zhang, Arturas Ziemys, Qingpo Li, Litao Bai, Xiaoyong Deng, Donald R. Erm, Xuewu Liu, Chun Li, and Mauro Ferrari. The research was supported with grants to Ferrari from the Department of Defense and the National Institutes of Health.

Story Source:

The above story is reprinted from materials provided by Methodist Hospital, Houston.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Haifa Shen, Jian You, Guodong Zhang, Arturas Ziemys, Qingpo Li, Litao Bai, Xiaoyong Deng, Donald R. Erm, Xuewu Liu, Chun Li, Mauro Ferrari. Cooperative, Nanoparticle-Enabled Thermal Therapy of Breast Cancer. Advanced Healthcare Materials, 2012; 1 (1): 84 DOI: 10.1002/adhm.201100005

Flaky graphene makes reliable chemical sensors

Scientists from the University of Illinois at Urbana-Champaign and the company Dioxide Materials have demonstrated that randomly stacked graphene flakes can make an effective chemical sensor.

The researchers created the one-atom-thick carbon lattice flakes by placing bulk graphite in a solution and bombarding it with ultrasonic waves that broke off thin sheets. The researchers then filtered the solution to produce a graphene film, composed of a haphazard arrangement of stacked flakes, that they used as the top layer of a chemical sensor. When the graphene was exposed to test chemicals that altered the surface chemistry of the film, the subsequent movement of electrons through the film produced an electrical signal that flagged the presence of the chemical.

The researchers experimented by adjusting the volume of the filtered solution to make thicker or thinner films. They found that thin films of randomly stacked graphene could more reliably detect trace amounts of test chemicals than previously designed sensors made from carbon nanotubes or graphene crystals.

The results are accepted for publication in the AIP's journal Applied Physics Letters.

The researchers theorize that the improved sensitivity is due to the fact that defects in the carbon-lattice structure near the edge of the graphene flakes allow electrons to easily "hop" through the film.

Story Source:

The above story is reprinted from materials provided by American Institute of Physics.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Amin Salehi-Khojin, David Estrada, Kevin Y. Lin, Ke Ran, Richard T. Haasch, Jian-Min Zuo, Eric Pop, Richard I. Masel. Chemical sensors based on randomly stacked graphene flakes. Applied Physics Letters, 2012; 100 (3): 033111 DOI: 10.1063/1.3676276

Products of biotechnological origin using vegetable and fruit by-products generated by the industry

Through the TRANSBIO project, Tecnalia will be implementing biotechnological solutions, like fermention and enzymatic processes to obtain new, high-value products of biotechnological origin in the form of new materials offering the potential to replace current plastics, foodstuffs and enzymes for applications in detergents using the materials not taken advantage of in the fruit and vegetable processing industry. This way, the global sustainability of the biomass production and processing industry will be improved, and the competitiveness of the European biotechnology industry will be enhanced through new applications.

As a result of these processes, new and more sustainable plastic materials will be obtained to be used in food packaging application, enzymes for producing detergents, and other biotechnological products for application in foodstuff.

In parallel, and in order to achieve the total use of the by-products employed in the project, those that may not be suited for use in biotechnological processes and the waste materials coming from fermentation processes will be tested to assess their use as raw material for the production of biogas.

The consortium participating in the TRANSBIO project comprises various partners from the ambit of industry and the academic sector with experience in complementary fields. The combination of these synergies allows all the links in the value chain to be taken into consideration, from the reprocessing of by-products, fermentation, and right up to the processing of the final product.

Tecnalia is coordinating this international consortium that has 16 partners from nine countries and two continents (Latin America and Europe) to look into the potential of new biotechnological solutions for obtaining bioproducts that, in practice, will signify the cutting of the environmental impact of food-producing activities.

Provided by Elhuyar Fundazioa

Active compounds against Alzheimer's disease

Researchers recently identified a series of synthetic compounds (inhibitors) that interfere with the self-assembly of the amyloid beta peptide in vitro; they influence both early stages and the transition to the characteristic amyloid fibrils. On a theoretical level, these compounds thus satisfy an initial condition for the development of an Alzheimer drug.

Peptide's disorder determines interaction

In order to understand the interactions between the amyloid beta peptide and active compounds at a structural level, Marino Convertino, Andreas Vitalis, and Amedeo Caflisch from the University of Zurich's Department of Biochemistry simulated these interactions on the computer. In doing so, they focused on a fragment of the peptide that is thought to control both interactions with inhibitors and progression of disease. Based on these simulations, the biochemists were able to identify a hierarchy of interaction patterns between the peptide and various active compounds. To their surprise, they discovered that the disordered structure of the peptide controls the interactions.

"The peptide's disorder and flexibility enable it to adapt to many basic structural frameworks," explains Andreas Vitalis. Often it is only subparts of the molecules that mediate interactions on the compound side. However, even minimal changes to a compound may induce measurable changes to the peptide-compound interactions. "Design of active compounds that influence the amyloid beta peptide structurally in a specific manner will only be possible with the aid of high-resolution methods that are limited to one or a few molecules," concludes Vitalis. In the next step, the researchers from the University of Zurich want to identify new classes of active substances with controllable properties that interact with the amyloid beta peptide.

More information: Journal of Biological Chemistry. October 3, 2011. doi: 10.1074/jbc.M111.285957

Provided by University of Zurich

Helping hydrogen move back home

"The hardest part is getting the hydrogen back onto the storage material," said Dr. Tom Autrey, a chemist at PNNL who was involved with the study. "You can't just pump it back in. So, we needed to develop a chemical process where we can do it cost effectively."

It's all about cost and safety. Many processes developed in a laboratory can't be inexpensively and safely done when taken beyond the laboratory. Chemical hydrogen storage systems that could one day power cars and trucks can be recharged, but the devil is in the details. Current processes require molten sodium, which has safety concerns and cost issues at large scales. In early work, PNNL scientists demonstrated that rhodium complexes could be used, but rhodium is far too expensive. Their recent discovery shows that complexes of cobalt and nickel, abundant and inexpensive metals, could recharge an amine borane-based hydrogen storage system.

The researchers began by studying the underlying mechanics of the reactions. "We took a rational approach—mindful of the chemistry and how it impacts the refueling process," said PNNL chemist Dr. Michael Mock, who led the study.

"We can't just pressurize the spent fuel with hydrogen. You have to work with Mother Nature and use a chemical process to put the hydrogen back," said Autrey.

So, the team performed extensive electronic structure calculations using the NWChem software, previously developed in part at PNNL, to predict the reactivity of a large number of potential reaction schemes. "The calculations let us screen targets fast," said Dr. Don Camaioni, who led the theoretical portion of the research. "We quickly learned what influenced reactivity and what didn't."

With the properties determined, the researchers focused on the synthesis of a select number of cobalt and nickel complexes, benefiting from the use of resources in EMSL. They then analyzed the effectiveness of these complexes in activating hydrogen for transfer to targets molecules identified by computation. The experimental work confirmed that the cobalt and nickel complexes managed the job at reasonable temperatures and pressures.

"There is a lot of balancing required to match the energetics of all the different steps in the hydrogen refueling process," said Autrey. "This is a very good step forward."

This work is part broader of efforts at PNNL to answer the fundamental questions around molecular catalysis. For example, Mock is taking on a larger challenge in the Center for Molecular Electrocatalysis, a DOE Energy Frontier Research Center at PNNL. He will soon be solving fundamental questions around the complex multi-electron reduction that takes nitrogen gas to ammonia for fertilizer. Camaioni and Autrey are using the insight gained from these studies to investigate the potential of using non-metal complexes to catalytically activate hydrogen for energy storage applications.

More information: MT Mock, et al. 2011. "Synthesis and Hydride Transfer Reactions of Cobalt and Nickel Hydride Complexes to BX3 Compounds." Inorganic Chemistry 50(23): 11914-11928. DOI: 10.1021/ic200857x

Provided by Pacific Northwest National Laboratory (news : web)

New information on the waste-disposal units of living cells

"Using electron microscopy and a revolutionary new system for protein expression, we have determined at a subnanometer scale the complete architecture, including the relative positions of all its protein components, of the proteasome regulatory particle," says biophysicist Eva Nogales, the research team's co-principal investigator. "This provides a structural basis for the ability of the proteasome to recognize and degrade unwanted proteins and thereby regulate the amount of any one type of protein that is present in the cell."

Says the team's other co-principal investigator and corresponding author, biochemist Andreas Martin, "While the biochemical function of many of the proteasome components have been determined, and some subnanometer structures have been identified, it was unclear before now which component goes where and which components interact with one another. Now we have a much better understanding as to how the proteasome machinery works to control cellular processes and this opens the possibility of manipulating proteasome activity for the treatment of cancer and other diseases."

Nogales, who holds appointments with Berkeley Lab, UC Berkeley, and the Howard Hughes Medical Institute, and Martin, who holds appointments with UC Berkeley and the QB3 Institute, are the senior authors of a paper describing this work in the journal Nature. The paper is titled "Complete subunit architecture of the proteasome regulatory particle." Other co-authors were Gabriel Lander, Eric Estrin, Mary Matyskiela and Charlene Bashore.

At any given moment, a human cell typically contains about 100,000 different proteins, with certain proteins being manufactured and others being discarded as needed for the cell's continued prosperity. Unwanted proteins are tagged with a "kiss-of-death" label in the form of a polypeptide called "ubiquitin." A protein marked with ubiquitin is delivered to any one of the some 30,000 proteasomes in the cell – barrel-shaped complexes which act as waste disposal units that rapidly break-down or degrade the protein. The 2004 Nobel Prize in chemistry was awarded to a trio of scientists who first described the proteasome process, but a lack of structural information has limited the scientific understanding of the mechanics behind this process.

Nogales, an expert on electron microscopy and image analysis, and Martin, who developed the new protein expression system used in this work, combined the expertise of their respective research groups to study the proteasome regulatory particle in yeast. The particle features 19 sub-units that are organized into two sub-complexes, a "lid" and a "base." The lid contains the regulatory elements that identify the ubiquitin tag marking a protein for destruction, and the base features a hexameric ring that pulls the tagged protein inside the chamber of the proteasome barrel where it is degraded.

"The lid consists of nine non-ATPase proteins including ubiquitin receptors that accept properly tagged proteins but prevent a protein not marked for degradation from engaging with the proteasome," Nogales says. "Since degradation is irreversible, it is critical that only ubiquitin-tagged proteins engage the proteasome. Interestingly, the ubiquitin tag has to be removed before the protein can be translocated into the proteasome's destruction chamber, so the lid also contains de-ubiquitination enzymes that remove the tags after the protein has engaged with the proteasome."

The proteasome regulatory particle's base contains six distinct AAA+ ATPases that form the hetero-hexameric ring, which serves as the molecular motor of the proteasome.

"We predict that the ATPases use the energy of ATP binding and hydrolysis to exert a pulling force on engaged proteins, unfolding and translocating them through a narrow central pore and into the degradation chamber," Martin says. "The steps in the proteasome process – from protein recognition to de-ubiquitination and degradation have to be very highly coordinated in time and space. Locating all of these components and identifying their relative orientations has been very telling about how the processes are coordinated with each other."

Nogales credits the protein expression system developed by Martin and his research group, in which proteins are expressed and assembled in bacteria, as being critical to the success of this research.

"Until now researchers had to work with purified protein complexes from the cell, which could not be manipulated or modified in any way," she says. "Andy Martin's new heterologous expression system allows for the manipulation and dissection of protein functions. For our studies it was crucial to generate lid sub-complexes that had one marker at a time in each of the subunits so that we could determine the position of each protein within the lid. With this new system we generated truncations, deletions and fusion constructs that were used to localize individual subunits and delineate their boundaries within the lid."

Provided by Lawrence Berkeley National Laboratory (news : web)

12 new flavonoids discovered in Kew tree

Analysis and identification

Geoffrey Kite analysed an extract of the leaves of C. kentukea and found several of the flavonoids known from S. japonicum, but the overall mixture of flavonoids in C. kentukea was much more complicated, consisting of more than 50 compounds. Emily Rowe, a student from the University of Bath who was working at Kew for a year as part of her degree course, was given the task of trying to separate some of the flavonoids from the mixture so that their structures could be determined. She obtained 13 examples, whose structures were elucidated using a technique called nuclear magnetic resonance spectroscopy (NMR) by Nigel Veitch, who realised that 12 of them were new to science. The structures of these compounds were reported recently in the scientific journal Phytochemistry.

With this knowledge, Geoffrey Kite was able to suggest probable structures for another 39 of the flavonoids in the leaf extract using a technique called liquid chromatography-mass spectrometry. Many of these are probably new to science as well, but it was not possible to prove this without first purifying them and determining their structures by NMR.

Cladrastis kentukea at Kew

Cladrastis kentukea is a medium-sized tree endemic to eastern North America. The hard, close-grained wood is clear yellow when first cut and was used by early American pioneers to make gunstocks and furniture. Although it is not common in the wild, the species is widely grown for its ornamental value. There are several specimens of C. kentukea growing at Kew together with two other Cladrastis species, C. sinensis and C. platycarpa. Most can be found in the ‘legume dell’ near to the Pavilion Restaurant. One specimen of C. sinensis is growing in the corner of the outside seating area of the restaurant, where visitors can enjoy a meal in the shade of a new scientific discovery, since this species also contains many of the new flavonoids.

More information: Kite, G. C., et al.(2011). Acylated flavonol tri- and tetraglycosides in the flavonoid metabolome of Cladrastis kentukea (Leguminosae). Phytochemistry 72: 372-384.

Provided by Royal Botanic Gardens, Kew

Why coffee drinking reduces the risk of Type 2 diabetes

Ling Zheng, Kun Huang and colleagues explain that previous studies show that coffee drinkers are at a lower risk for developing Type 2 diabetes, which accounts for 90-95 percent of diabetes cases in the world. Those studies show that people who drink four or more cups of coffee daily have a 50 percent lower risk of Type 2 diabetes. And every additional cup of coffee brings another decrease in risk of almost 7 percent. Scientists have implicated the misfolding of a substance called human islet amyloid polypeptide (hIAPP) in causing Type 2 diabetes, and some are seeking ways to block that process. Zheng and Huang decided to see if coffee's beneficial effects might be due to substances that block hIAPP.

Indeed, they identified two categories of compounds in coffee that significantly inhibited hIAPP. They suggest that this effect explains why coffee drinkers show a lower risk for developing diabetes. "A beneficial effect may thus be expected for a regular coffee drinker," the researchers conclude.

More information: Coffee Components Inhibit Amyloid Formation of Human Islet Amyloid Polypeptide in Vitro: Possible Link between Coffee Consumption and Diabetes Mellitus, J. Agric. Food Chem., 2011, 59 (24), pp 13147–13155. DOI: 10.1021/jf201702h

Abstract
Global epidemic studies have suggested that coffee consumption is reversely correlated with the incidence of type 2 diabetes mellitus (T2DM), a metabolic disease. The misfolding of human islet amyloid polypeptide (hIAPP) is regarded as one of the causative factors of T2DM. Coffee extracts have three major active components: caffeine, caffeic acid (CA), and chlorogenic acid (CGA). In this study, the effects of these major coffee components, as well as dihydrocaffeic acid (DHCA) (a major metabolite of CGA and CA), on the amyloidogenicity of hIAPP were investigated by thioflavin-T based fluorescence emission, transmission electronic microscopy, circular dichroism, light-induced cross-linking, dynamic light scattering, and MTT-based cell viability assays. The results suggest that all components show varied inhibitory effects on the formation of toxic hIAPP amyloids, in which CA shows the highest potency in delaying the conformational transition of the hIAPP molecule with the most prolonged lag time, whereas caffeine shows the lowest potency. At a 5-fold excess molar ratio of compound to hIAPP, all coffee-derived compounds affect the secondary structures of incubated hIAPP as suggested by the circular dichroism spectra and CDPro deconvolution analysis. Further photoinduced cross-linking based oligomerization and dynamic light scattering studies suggested CA and CGA significantly suppressed the formation of hIAPP oligomers, whereas caffeine showed no significant effect on oligomerization. Cell protection effects were also observed for all three compounds, with the protection efficiency being greatest for CA and least for CGA. These findings suggest that the beneficial effects of coffee consumption on T2DM may be partly due to the ability of the major coffee components and metabolites to inhibit the toxic aggregation of hIAPP.

Provided by American Chemical Society (news : web)

Chemical engineers boost petrochemical output from biomass by 40 percent

"We think that today we can be economically competitive with crude oil production," says research team leader George Huber, an associate professor of chemical engineering at UMass Amherst and one of the country's leading experts on catalytic pyrolysis.

Huber says his research team can take wood, grasses or other renewable biomass and create five of the six petrochemicals that serve as the building blocks for the chemical industry. They are benzene, toluene, and xylene, which are aromatics, and ethylene and propylene, which are olefins. Methanol is the only one of those six key petrochemicals not produced in that same single-step reaction.

"The ultimate significance of our research is that products of our green process can be used to make virtually all the petrochemical materials you can find. In addition, some of them can be blended into gasoline, diesel or jet fuel," says Huber.

The new process was outlined in a paper published in the Dec. 23, 2011 edition of the German Chemical Society's journal Angewandte Chemie. It was written by Huber, Wei Fan, assistant professor of chemical engineering, and graduate students Yu-Ting Cheng, Jungho Jae and Jian Shi.

"The whole name of the game is yield," says Huber. "The question is what amount of aromatics and olefins can be made from a given amount of biomass. Our paper demonstrates that with this new gallium-zeolite catalyst we can increase the yield of those products by 40 percent. This gets us much closer to the goal of catalytic fast pyrolysis being economically viable. And we can do it all in a renewable way."

The new production process has the potential to reduce or eliminate industry's reliance on fossil fuels to make industrial chemicals worth an estimated $400 billion annually, Huber says. The team's catalytic fast pyrolysis technology has been licensed to New York City's Anellotech, Inc., co-founded by Huber, which is scaling up the process to industrial size for introduction into the petrochemical industry.

In this single-step catalytic fast pyrolysis process, either wood, agricultural wastes, fast growing energy crops or other non-food biomass is fed into a fluidized-bed reactor, where this feedstock pyrolysizes, or decomposes due to heating, to form vapors. These biomass vapors then enter the team's new gallium-zeolite (Ga-ZSM-5) catalyst, inside the same reactor, which converts vapors into the aromatics and olefins. The economic advantages of the new process are that the reaction chemistry occurs in one single reactor, the process uses an inexpensive catalyst and that aromatics and olefins are produced that can be used easily in the existing petrochemical infrastructure.

Olefins and aromatics are the building blocks for a wide range of materials. Olefins are used in plastics, resins, fibers, elastomers, lubricants, synthetic rubber, gels and other industrial chemicals. Aromatics are used for making dyes, polyurethanes, plastics, synthetic fibers and more.

Provided by University of Massachusetts at Amherst

Backing out of the nanotunnel: New method for nucleic acid analysis

In the world of biomolecules such as proteins and the hereditary nucleic acids DNA and RNA, three-dimensional structure determines function. Analysis of the passage of such molecules through nanopores offers a relatively new, but highly promising, technique for obtaining information about their spatial conformations. However, interactions between the test molecules and the proteins used as pores have so far hindered quantitative analysis of the behavior of even simply structured molecules within nanopores. This problem must be solved before the technique can be routinely used for structure determination. In a project carried out under the auspices of the Cluster of Excellence "Nanosystems Initiative Munich" (NIM), researchers led by LMU physicist Professor Ulrich Gerland and Professor Friedrich Simmel (Technical University of Munich) have developed a new method that depends on the analysis of reverse translocation through asymmetric pores, which minimizes the interference caused by interactions with the pore material itself. This approach has enabled the team to construct a theoretical model that allows them to predict the translocation dynamics of nucleic acids that differ in their nucleotide sequences.

The nucleic acids RNA and DNA both belong to the class of molecules known chemically as polynucleotides. Both are made up of strings of four basic types of building blocks called nucleotides, which fall into two complementary pairs. In their single-stranded forms, DNA and RNA can fold into what are called secondary structures, as complementary nucleotides in the sequence pair up, forcing the intervening segments to form loops. If the single-stranded loop is very short, the secondary structure is referred to as a hairpin. As in the case of proteins, the secondary structures of nucleic acids influence their biochemical functions. The elucidation of the secondary structure of nucleic acid sequences is therefore of great interest.

"Nanopores are increasingly being employed to investigate the secondary structures of RNA and DNA," Gerland points out. "Passage through narrow nanopores causes the sequence to unfold, and the dynamics of translocation provide insights into the structural features of the molecules, without the need to modify them by adding a fluorescent label. The technique is relatively new, and its potential has not yet been fully explored."

In the new study, he and his collaborators used a new experimental procedure, which allowed them to quantitatively describe the passage of simply structured polynucleotide sequences through nanopores, and develop a theoretical model that accounts for their findings. This level of understanding has not been achieved previously, because complicating factors such as interactions between the protein nanopore and the polynucleotide have had a significant influence on the measurements and made it difficult to predict the behavior of the test molecules.

Thanks to a clever change in experimental design, the impact of these factors has now been minimized. The trick is to perform the measurements on molecules as they translocate through the pore in reverse. First, the polynucleotide of interest is forced through the conical orifice from one side under the influence of an electrical potential. This causes its secondary structure to unfold and, as it emerges, the molecule refolds. An anchor at the end of the polynucleotide chain prevents it from passing completely through the pore onto the other side. For the return journey the potential is reversed, so that the process of unfolding now begins at the narrow end of the pore, and at this point the analysis is initiated.

"In contrast to the situation during forward translocation, no significant interactions appear to take place during the reverse trip," says Simmel.

On the basis of their experimental measurements, the researchers went on to construct a theoretical model that enabled them to predict the translocation dynamics of various hairpin structures with the aid of thermodynamic calculations of so-called "free-energy landscapes".

"This model could in the future provide the foundation of a procedure for the elucidation of the secondary structures of complex polynucleotides," says Gerland.

More information: "Quantitative Analysis of the Nanopore Translocation Dynamics of Simple Structured Polynucleotides" S. Schink, S. Renner, K. Alim, V. Arnaut, F.C. Simmel, U. Gerland Biophysical Journal Vol. 102, January 2012, pp 1-11. doi: 10.1016/j.bpj.2011.11.4011

Provided by Ludwig-Maximilians-Universitat Munchen

Infrared detector unmasks cocaine addicts

If a police patrol stops a suspicious driver these days, he has to blow into the famous tube for an alcohol test. If the driver is suspected of having consumed illegal substances like cocaine, however, the officer has to order a complicated and expensive lab test to obtain quantitative results. A new approach could now make the process easier: a team of ETH-Zurich researchers headed by physics professor Markus Sigrist is currently developing a device to detect cocaine in saliva. “Our work is the basis for a compact device that law enforcement authorities can use ‘in the field’,” says Sigrist. This basis for rapid drug detection has just been presented in an article published in the journal Drug Testing and Analysis.

A few micrograms suffice

With the aid of so-called ATR infrared spectroscopy, the researchers have succeeded in detecting cocaine and a variety of its metabolic products in saliva reliably and currently up to a threshold of fewer than ten micrograms of cocaine per millilitre. Compared to the standard methods at toxicology labs, which can trace the drugs up to a threshold of one to five nanograms per millilitre, this limit of detection is still too high. However, the samples have to be prepared painstakingly and the apparatus is not transportable. The ATR-IR method is different: it is non-invasive and the saliva can be obtained easily and with little preparation. Moreover, the detection levels reached using ATR-IR spectroscopy are already accurate enough to take consumers of illegal drugs into custody directly after consumption. If someone smokes cocaine, for instance, up to 500 micrograms per millilitre are still present in the saliva a short time later.

Careful not to mix up cocaine and caffeine

The first important step for the ETH-Zurich physicists was to find out which wavelengths cocaine and its metabolic products absorb, so they examined the spectra that are characteristic and distinctive of these substances.

The physicists also had to determine the spectra of other substances present in the saliva. to make sure they do not overlap within the spectrum of cocaine. Consequently, they examined caffeine, extenders used to cut cocaine, mouthwash, painkillers, and energy and soft drinks. The researchers especially focused on alcohol. The result of this detective work was that the cocaine spectrum leaves behind distinct traces. The substance and its metabolic products absorb within a wavelength range of 5.55 to 5.84 micrometers. However, because water in the saliva absorbs the infrared light strongly, the researchers first extract the cocaine with a water-repellent solvent that then evaporates on the test apparatus.

More accurate detectors, better light

Meanwhile, Markus Sigrist and his team are in the process of refining and simplifying the procedure. For instance, they have also begun measuring cocaine directly in the liquid phase after extraction into the solvent. The physics professor also wants to reduce the detection threshold dramatically. He believes it is possible to detect amounts of twenty nanograms per millilitre of liquid using the infrared spectroscopy method. Apart from more sensitive IR detectors that are ten times more sensitive, the researchers therefore also require a new light source: a so-called “quantum cascade laser”, which can generate infrared light within a narrow spectral band around a central wavelength of between four and fifteen micrometers. “This range is interesting for spectroscopy,” says Sigrist. The initial experiments with this light source have been positive. It might also be possible to extend the drug test for the detection of other narcotics, such as heroin.

However, Markus Sigrist and his team will not be developing a market-ready, compact device, for instance, for law enforcement officers,: “We provide the basis and a sensor platform for such a device. It is up to an industrial partner to realize it,” says the ETH-Zurich professor.

The detection of cocaine in saliva using infrared is a sub-project of IrSens conducted within the scope of the nationwide Swiss research initiative nano-tera. Besides Sigrist’s team, the research group headed by ETH-Zurich professor Jérôme Faist which developed the quantum cascade laser and other teams, including detector specialists from the University of Neuchâtel, are also involved in the sub-project.

Infrared spectroscopy

The measurement method is based on ATR infrared spectroscopy (IR-ATR). ATR stands for “attenuated total reflection”. This measurement technique was developed in 1960 and is used to examine the surfaces of opaque substances such as varnish or polymer foil. However, it can also be used to analyse liquid samples.

In IR-ATR, an infrared beam of light is directed into a crystal at a particular angle. The beam is reflected on both surfaces and thus crosses the entire crystal along a zigzag path before exiting it. The substances to be analysed are then applied to the upper surface of the crystal in an thin layer. The absorbed wavelengths are absent when the beam of light exits the crystal, which the researchers can measure.

More information: Hans KMC, Müller S & Sigrist MW. Infrared attenuated total reflection (IR-ATR) spectroscopy for detecting drugs in human saliva. Drug Testing and Analysis (2011), published online, doi: 10.1002/dta.346

Provided by ETH Zurich

Outlook for an industry that touches 96 percent of all manufactured goods

C&EN points to positive developments for some chemical manufacturers, like Boeing ramping up production of its Dreamliner planes, a boon for makers of high-tech glues and carbon fiber. The article explains U.S. chemical firms will be more competitive globally due to low prices of natural gas and other raw materials and good opportunities for exports. Petrochemical producers are looking past 2012, according to the article, and several companies plan to build new manufacturing plants to take advantage of the growing supply of natural gas in the U.S.

At the same time, the pharmaceutical industry is facing the challenge of expiring patents on some of its most popular drugs, which will allow generic manufacturers to grab profits from big-name companies like AstraZeneca. The story also predicts slowing growth in Asia will hurt a number of chemical industries, especially makers of paint and other construction materials. For chemical makers, the article says, "2012 is likely to be a year to endure rather than enjoy."

More information: World Chemical Outlook - http://cen.acs.org/articles/90/i2/World-Chemical-Outlook.html

Provided by American Chemical Society (news : web)

Strengthening metal alloys would provide energy, environment conservation benefit

The results of the work promise to help engineers and scientists better understand how to enhance the performance of new light-weight materials used in a wide variety of technological applications. The light-weight materials can be particularly effective in helping to improve the energy efficiency of motor vehicles and reduce their polluting emissions.

Solanki recently joined ASU as an assistant professor in the School for Engineering of Matter, Transport and Energy, one of the university’s Ira A. Fulton Schools of Engineering. He combines expertise in solid mechanics and material science to study the microstructural properties of materials and predict their behavior under various conditions.

The Minerals, Metals & Materials Society (TMS) has awarded Solanki and two co-authors its 2011 Light Metals Magnesium Best Paper award for the report detailing their research on light-weight metal alloys.

He has been aided by Mehul Bhatia, who is pursuing a doctoral degree in mechanical engineering at ASU, and Amitava Moitra, a former postdoctoral fellow at Mississippi State University who worked there with Solanki. Bhatia and Moitra are the winning paper’s other co-authors. 

Titled “Effect of Substituted Aluminum in Magnesium Tension Twin,” the paper addresses a major challenge in development of new alloys. It involves finding ideal concentrations of new solutes that can be added to base metals to optimize their performance. Solutes are substances that dissolve into another substance in solutions.

The solute additions are critical to enhance the deformation and failure modes of materials, which occurs both when alloys are manufactured and when they are subjected to complex loading such as in a crash impact, Solanki explains.

Understanding how the metal alloy will respond in such circumstances provides information needed to make effective adjustments in the ratio of the solute to the base metal in a solution. That ratio is important in affecting the mechanical properties of an alloy to produce an optimal performance.

In the award-winning paper, Solanki’s research team demonstrates use of a nanoscale simulation technique to reveal how an aluminum substitution in pure magnesium affects its deformation and its behavior when the material fails.

“Our research provides a fundamental understanding of the role of solutes on deformation and fracture modes of metal alloys,” Solanki says. “This will guide the science of designing structural materials with enhanced properties and performance capabilities.”

He is working with magnesium and magnesium alloys because they are particularly light-weight materials that also offer the advantage of being highly recyclable.

“With the world’s energy needs increasing, energy efficiency and conservation become more important. More effective light-weight structural materials that help reduce the energy consumption needed for transportation will contribute to meeting that goal,” Solanki says.

Prior to coming to ASU, Solanki was an associate director at the Center for Advanced Vehicular Systems at Mississippi State University, where he earned a doctorate degree in 2008.

He has published more than 50 peer-reviewed journal and conference papers and he serves on the editorial board of the Journal of Surfaces and Interfaces in Materials. His paper “Finite element analysis of plasticity-induced fatigue crack closure: an overview,” published in Engineering Fracture Mechanics, was one of the most highly cited papers from 2002-05.

Solanki won the 2008 Henry O. Fuch Award from the Society of Automotive Engineers International for outstanding achievements in fatigue and fracture mechanics.

Solanki and Bhatia will be presented their best paper award from the Minerals, Metals & Materials Society at the organization’s annual meeting in March in Orlando, Fla.

Provided by Arizona State University (news : web)

Twist-and-glow molecules aid rapid gas detection

Now, Takashi Uemura of Kyoto University and colleagues at several other Japanese institutes, including the RIKEN SPring-8 Center, have created a gas sensor that works rapidly, emits a clear fluorescent signal, and detects different gases. Most importantly, the new sensor can distinguish between gases with similar chemical and physical properties.

Uemura and colleagues’ sensor contains so-called ‘flexible porous coordination polymers’ coupled with fluorescent reporter molecules that change structure, and therefore emit signals, according to different gases present in the air. 

“We thought that the incorporation of functional polymers into flexible porous coordination matrices would show unique dynamic properties,” says Uemura. He and his colleagues therefore inserted a fluorescent reporter molecule into the coordination polymer, whereupon the whole combined structure twisted out of shape.

In this normal and twisted state, the fluorescent light from the reporter is quite dim and green. Once gas molecules are introduced, the structure begins to return to its original shape, and the fluorescence returns, brightening as the gas pressure intensifies. For example, the fluorescence changes from green to blue when the molecule adsorbs carbon dioxide.

By this method, the sensor allows regular monitoring of both the type of gas and its concentration in the air. Crucially, the fluorescent response begins within seconds upon interaction with the gas and is complete within minutes, allowing emergency responders to make decisions quickly (Fig. 1).

In addition to these attributes, this is the first such detection system shown to work for gases with almost identical physical properties, the team notes. “Physical properties, such as size, shape, and boiling points, are very similar between carbon dioxide and acetylene, for example, so it is difficult to distinguish between them,” explains Uemura. “Our material has carboxylate sites in the pore, and these sites can bind to acetylene more strongly than carbon dioxide.

“This unique cooperative change of host and guest could allow us to design new advanced materials,” he adds. By investigating different flexible host structures and other ‘guest’ reporter molecules, the researchers believe they could create gas detection systems for a variety of different gases and other applications in the future.

More information: Nature Materials 10, 787–793 (2011) doi:10.1038/nmat3104

Provided by RIKEN (news : web)

Twenty-year protein mystery solved with surprising results

In spite of more than 20 years of research efforts, the enzymatic function of the CRYM protein has remained elusive. Previous research has shown that CRYM functions both as an important structural protein and a binder of thyroid hormones, but PhD student Andre Hallen suspected something more.

"CRYM was first discovered in the ocular lens of marsupials, that is, in Skippy's eye! Since then, we've seen it in lamb brains, in other tissues and learnt how it can be observed and mutated in mammals like humans. Now we can see more of its full potential in human health and nutrition," Hallen explains.

In a study published in the Journal of Neurochemistry, Hallen conclusively demonstrated an enzyme function for CRYM, and identified how this enzymatic activity reveals a new role for thyroid hormones in regulating mammalian amino acid metabolism.

It also recognises a possible reciprocal role of enzyme activity in regulating bioavailability of intracellular T3, with further research pathways for how this regulatory role might open up new treatment options for a range of neurological and psychiatric conditions.

Hallen lead a team of scientists on this study, including three months working in North America with Dr Arthur Cooper, a world authority on neurochemistry and amino acid chemistry.

His research has also sparked the interest of international scientists, including Patrick W Reed and Robert J Bloch of the University of Maryland, who profiled Hallen's work in their article ‘Crystallin-Gazing: Unveiling Enzymatic Activity'.

In 2012, Hallen will continue his research into this area, further exploring the role of diet in influencing hormone function, and the effects of these changes on the CRYM protein, its related mutations and conditions.

Provided by Macquarie University

Algae for your fuel tank: New process for producing biodiesel from microalgae oil

Plant oils from sources such as soybean and rapeseed are promising starting materials for the production of biofuels. Microalgae are an interesting alternative to these conventional oil-containing crops. Microalgae are individual cells or short chains of cells from algae freely moving through water. They occur in nearly any pool of water and can readily be cultivated. "They have a number of advantages over oil-containing agricultural products," explains Lercher. "They grow significantly faster than land-based biomass, have a high triglyceride content, and, unlike the terrestrial cultivation of oilseed plants, their use for fuel production does not compete with food production."

Previously known methods for refining oil from microalgae suffer from various disadvantages. The resulting fuel either has too high an oxygen content and poor flow at low temperatures, or a sulfur-containing catalyst may contaminate the product. However, other catalysts are still not efficient enough. The Munich scientists now propose a new process, for which they have developed a novel catalyst: nickel on a porous support made of zeolite HBeta. They have used this to achieve the conversion of raw, untreated algae oil under mild conditions (260 °C, 40 bar hydrogen pressure). Says Lercher: "The products are diesel-range saturated hydrocarbons that are suitable for use as high-grade fuels for vehicles."

The oil produced by the microalgae is mainly composed of neutral lipids, such as mono-, di-, and triglycerides with unsaturated C18 fatty acids as the primary component (88 %). After an eight-hour reaction, the researchers obtain 78 % liquid alkanes with octadecane (C18) as the primary component. The main gas-phase side products are propane and methane.

Analysis of the reaction mechanism shows that this is a cascade reaction. First the double bonds of the unsaturated fatty acid chains of the triglycerides are saturated by hydrogen. Then, the now saturated fatty acids take up hydrogen and are split from their glycerin component, which reacts to form propane. In the final step, the acid groups in the fatty acids are reduced stepwise to the corresponding alkane.

More information: Towards Quantitative Conversion of Microalgae Oil to Diesel-Range Alkanes with Bifunctional Catalysts, B. Peng, Y. Yao, C. Zhao und J.A. Lercher, Angewandte Chemie, 2011. doi:10.1002/ange.201106243

Provided by Technische Universitaet Muenchen

New chemical reaction holds promise for drug development

The team -- led by Brian Stoltz, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry, and Doug Behenna, a scientific researcher -- used a suite of specialized robotic tools in the Caltech Center for Catalysis and Chemical Synthesis to find the optimal conditions and an appropriate catalyst to drive this particular type of reaction, known as an alkylation, because it adds an alkyl group (a group of carbon and hydrogen atoms) to the compound. The researchers describe the reaction in a recent advance online publication of a paper in Nature Chemistry.

"We think it's going to be a highly enabling reaction, not only for preparing complex natural products, but also for making pharmaceutical substances that include components that were previously very challenging to make," Stoltz says. "This has suddenly made them quite easy to make, and it should allow medicinal chemists to access levels of complexity they couldn't previously access."

The reaction creates compounds called heterocycles, which involve cyclic groups of carbon and nitrogen atoms. Such nitrogen-containing heterocycles are found in many natural products and pharmaceuticals, as well as in many synthetic polymers. In addition, the reaction manages to form carbon-carbon bonds at sites where some of the carbon atoms are essentially hidden, or blocked, by larger nearby components.

"Making carbon-carbon bonds is hard, but that's what we need to make the complicated structures we're after," Stoltz says. "We're taking that up another notch by making carbon-carbon bonds in really challenging scenarios. We're making carbon centers that have four other carbon groups around them, and that's very hard to do."

The vast majority of pharmaceuticals being made today do not include such congested carbon centers, Stoltz says—not so much because they would not be effective compounds, but because they have been so difficult to make. "But now," he says, "we've made it very easy to make those very hindered centers, even in compounds that contain nitrogen. And that should give pharmaceutical companies new possibilities that they previously couldn't consider."

Perhaps the most important feature of the reaction is that it yields almost 100 percent of just one version of its product. This is significant because many organic compounds exist in two distinct versions, or enantiomers, each having the same chemical formula and bond structure as the other, but with functional groups in opposite positions in space, making them mirror images of each other. One version can be thought of as right-handed, the other as left-handed.

The problem is that there is often a lock-and-key interaction between our bodies and the compounds that act upon them—only one of the two possible hands of a compound can "shake hands" and fit appropriately. In fact, one version will often have a beneficial effect on the body while the other will have a completely different and sometimes detrimental effect. Therefore, it is important to be able to selectively produce the compound with the desired handedness. For this reason, the FDA has increasingly required that the molecules in a particular drug be present in just one form.

"So not only are we making tricky carbon-carbon bonds, we're also making them such that the resulting products have a particular, desired handedness," Stoltz says. "This was the culmination of six years of work. There was essentially no way to make these compounds before, so to all of a sudden be able to do it and with perfect selectivity… that's pretty awesome."

More information: "Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams," Nature Chemistry.

Provided by California Institute of Technology (news : web)