Stopping malignancy in its tracks

 

An unusual chemical compound isolated from a mud-dwelling fungus found in a soil sample collected in Daejeon, South Korea, could lead to a new family of antitumor drugs. Discovered by teams led by Jong Seog Ahn at the Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, and  Hiroyuki Osada at the RIKEN Advanced Science Institute, Wako, the compound prevents cancerous cells from forming mobile colonies—the point at which cancers become malignant and spread through the body. The teams began collaborating after Yukihiro Asami from RIKEN joined KRIBB.

The researchers spotted the compound while searching extracts of the fungus for candidate drug compounds using a recently developed screen called a 3D epithelial culture system. To date, this kind of biological assay has rarely been used to search for natural products with novel bioactivity, says Ahn. It was during the 3D screen, which they spiked with cancerous cells, that the researchers realized that a compound produced by the fungus was inhibiting the cancer cells from clumping together to form colonies (Fig. 1). This type of screen is difficult using a conventional two-dimensional cell culture. 

The researchers isolated the bioactive compound and named it fusarisetin A. They then investigated its structure using an array of chemical characterization techniques, including nuclear magnetic resonance (NMR) and x-ray crystallography. They showed that fusarisetin A was a previously undescribed compound. Being able to grow crystals of the compound for x-ray studies was a breakthrough, says Osada. “It is very important for exact structural elucidation to get crystal analysis,” he says.

Having established that fusarisetin A is a new compound, the researchers probed its bioactivity in more detail. They showed that it simply blocks colony formation rather than killing cancer cells. They then compared the compound to others known to inhibit this process, and showed that it works differently to other compounds capable of blocking clumping. This suggests to the researchers that it could offer a new way to treat tumors.

The team is already working to discover how fusarisetin A inhibits the clumping of cancerous cells by looking for its molecular target. “We have already got candidate target proteins,” Osada adds.

Fusarisetin A itself is not bioactive enough to become a drug. However, it may be possible to fine-tune the structure to improve its activity, from which new drugs could be developed. “If we can get higher biological activity derivatives [of fusarisetin A], it may be possible,” says Ahn.

More information: Jang, J.-H., et al. Fusarisetin A, an acinar morphogenesis inhibitor from a soil fungus, Fusarium sp. FN080326. Journal of the American Chemical Society 133, 6865–6867 (2011).

Provided by RIKEN (news : web)

Stanford team devises a better solar-powered water splitter (w/ video)

The process of splitting water into pure oxygen and clean-burning hydrogen fuel has long been the Holy Grail for clean-energy advocates as a method of large-scale energy storage, but the idea faces technical challenges. Stanford researchers may have solved one of the most important ones.

Solar energy is fine when the sun is shining. But what about at night or when it is cloudy? To be truly useful, sunshine must be converted to a form of energy that can be stored for use when the sun is hiding.

The notion of using sunshine to split water into oxygen and storable hydrogen fuel has been championed by clean-energy advocates for decades, but stubborn challenges have prevented adoption of an otherwise promising technology.

A team of Stanford researchers may have solved one of the most vexing scientific details blocking us from such a clean-energy future.

The team, led by materials science engineer Paul McIntyre and chemist Christopher Chidsey, has devised a robust silicon-based solar electrode that shows remarkable endurance in the highly corrosive environment inherent in the process of splitting water.

They revealed their progress in a recent paper published in the journal Nature Materials.

Conceptually, splitting water could not be simpler. Scientists have long known that applying a voltage across two electrodes submerged in water splits the water molecules into their component elements, oxygen and hydrogen.

From an environmental standpoint, the process is a dream: an electrochemical reaction whose only requirements are water and electricity and whose only byproducts are pure oxygen and hydrogen, a clean-burning fuel applicable in a promising new class of renewable energy applications. In fact, hydrogen is the cleanest burning chemical fuel known.

Practical challenges

"In theory, water splitting is a clean and efficient energy storage mechanism. Unfortunately, solving one problem creates another," said McIntyre, associate professor of materials science and engineering. "The most abundant solar electrodes we have today are made of silicon, a material that corrodes and fails almost immediately when exposed to oxygen, one of the byproducts of the reaction."

This video is not supported by your browser at this time.

An interdisciplinary group of Stanford researchers from the engineering and chemistry departments have developed a new way to protect silicon semiconductors during water-splitting reactions. Scientists say the breakthrough may hold the key to storing solar energy.

This particular problem has vexed researchers since at least the 1970s. Many had given up, but McIntyre and Chidsey have devised a clever solution. They coated their silicon electrodes with a protective, ultra-thin layer of titanium dioxide.

"Titanium dioxide is perfect for this application," explained McIntyre. "It is both transparent to light and it can be efficient for transferring electricity, all while protecting the silicon from corrosion."

Sunlight travels through the protective titanium dioxide into the photosensitive silicon, which produces a flow of electrons that travels through the electrochemical cell into the water, splitting the hydrogen from the oxygen. The hydrogen gas can be stored and then, when the sun is not shining, the process can be reversed, reuniting hydrogen and oxygen back into water to produce electricity.

Decades of dead ends

Other researchers had attempted to protect the electron-producing silicon electrodes. Some tried other materials, which failed for reasons of performance or durability. Some had even tried titanium dioxide, but those efforts also fell short. Their layers were either materially flawed, allowing oxygen to seep through and corrode the semiconductor, or too thick to be electrically conductive. 

Yi Wei Chen and Jonathan Prange, the lead doctoral students on the McIntyre-Chidsey team, discovered that the key to the titanium dioxide's protectiveness is achieving a very thin, yet high quality layer of material. They found that a layer just two nanometers thick was sufficient so long as it was free of the pinholes and cracks that doomed earlier titanium dioxide experiments.

With their electrodes successfully shielded from corrosion, the researchers revealed yet one more engineering ace in the hole, adding a third layer of ultra-thin iridium, a catalyst, atop the titanium dioxide. Iridium boosts the rate of the splitting reaction and improves performance of the system.

Broader applications

In side-by-side durability experiments, the researchers put their creation to the test. Control samples without the protective layer corroded and failed in less than a half-hour, while those with the titanium dioxide lasted the full duration of the test, eight hours without apparent corrosion or loss of efficiency.

The authors pointed out that their approach is general enough to work on other semiconductor substrates and to integrate other catalysts, allowing for fine-tuning of electrodes to maximize performance. Likewise, atomic layer deposition, the technique that allowed such fine and flawless layering, is in wide application in the semiconductor industry today. It should, therefore, lend itself to application on a large scale. Lastly, the results were achieved without exploring the use of other efficiency-enhancing techniques, such as surface texturing, which could further improve performance.

"We are excited about the possibilities of this technology," said McIntyre, "as much for the electrode itself, as for the process used to create it."

Their success might just push a promising technology one step closer to practical application and the world one step closer to a clean-energy future.

Provided by Stanford University (news : web)

Branch offices: New family of gold-based nanoparticles could serve as biomedical 'testbed'

 Gold nanoparticles are becoming the … well … gold standard for medical-use nanoparticles. A new paper by researchers from the National Institute of Standards and Technology (NIST) and the National Cancer Institute's Nanotechnology Characterization Laboratory (NCL) proposes not only a sort of gold nanoparticle "testbed" to explore how the tiny particles behave in biological systems, but also a paradigm for how to characterize nanoparticle formulations to determine just what you're working with.

Prospective uses of gold nanoparticles, says NIST chemist Vince Hackley, include high-precision drug-delivery systems and diagnostic image enhancers. Gold is nontoxic and can be fashioned into particles in a range of sizes and shapes. By itself, gold doesn't do much biologically, but it can be "functionalized" by attaching, for instance, protein-based drugs along with targeting molecules that cluster preferentially around cancer cells. The nanoparticles are generally coated as well, to prevent them from clumping together and to avoid rapid clearance by the body's immune system.

NCL's Anil Patri notes that the coating composition, density and stability have a profound impact on the nanomaterial safety, biocompatibility (how well the nanoparticles distribute in the body), and efficacy of the delivery system. "Understanding these parameters through thorough characterization would enable the research community to design and develop better nanomaterials," he says.

To facilitate such studies, the NIST/NCL team set out to create a nanoparticle testbed -- a uniform, controllable core-shell nanoparticle that could be made-to-order with precise shape and size, and to which could be attached nearly any potentially useful functionality. Researchers then could study how controlled variations fared in a biological system.

Their trial system is based on regularly shaped branching molecules called dendrons, a term derived from the Greek word for "tree." Dendron chemistry is fairly new, dating from the 1980s. They're excellent for this use, says NIST researcher Tae Joon Cho, because the individual dendrons are always the same size, unlike polymers, and can readily be modified to carry "payload" molecules. At the same time, the tip of the structure -- the "tree's" trunk -- is designed to bond easily to the surface of a gold nanoparticle.

The team made an exhaustive set of measurements so they could thoroughly describe their custom-made dendron-coated nanoparticles. "There aren't a lot of protocols around for characterizing these materials -- their physical and chemical properties, stability, et cetera," Hackley says, "so, one of the things that came out of the project is a basic series of measurement protocols that we can apply to any kind of gold-based nanoparticle."

Any single measurement technique, he says, is probably inadequate to describe a batch of nanoparticles, because it likely will be insensitive to some size ranges or confused by other factors -- particularly if the particles are in a biological fluid.

The new NIST/NCL paper provides the beginnings of a catalog of analysis techniques for getting a detailed lowdown on nanoparticles. These techniques include nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry, dynamic light scattering, ultra-violet/visible spectroscopy and X-ray photoelectron spectroscopy. The dendron-coated nanoparticles also were tested for stability under "biologically relevant" conditions of temperature, acidity and some recognized forms of chemical attack that would take place in the bloodstream. In vitro biological tests are pending.

The work was funded in part by the National Cancer Institute, National Institutes of Health.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by National Institute of Standards and Technology (NIST).

Journal Reference:

Tae Joon Cho, Rebecca A. Zangmeister, Robert I. MacCuspie, Anil K. Patri, Vincent A. Hackley. Newkome-Type Dendron-Stabilized Gold Nanoparticles: Synthesis, Reactivity, and Stability. Chemistry of Materials, 2011; 23 (10): 2665 DOI: 10.1021/cm200591h

Researchers devise biomaterial that could be used in the detection of toxins and pollutants

In research recently published in the leading international journal PNAS, Trinity researchers exploit the potential of a biomaterial to reveal the activity of important fat metabolising enzymes. The findings show that the biomaterial could possibly be used in the future detection of toxins, explosives, pollutants, and medicines.

Detection devices have superior sensitivity when the sensor itself can be packaged at high density.  Certain proteins that are found in the membranes of cells can act as sensors.  However, the density with which cellular membranes can be packed in a sensor of a defined volume can limit the application.  In this study, use was made of a particular form of matter, referred to as a liquid crystal or mesophase, that behaved as a densely packed mimic for cellular membranes.

Certain naturally occurring lipids or fats, when combined with water spontaneously form liquid crystals.  One of these lipids called monoolein is a product of fat digestion.  The liquid crystalline cubic phase that monoolein forms, when wet, has the lipid arranged as a bilayer just two molecules thick that is bathed on either side by water.  This hydrated bilayer resembles the membrane that surrounds the cells in living organisms. The cubic phase is particularly notable as a liquid crystal in the extraordinary density with which it packages the membrane and the enormous surface area that it has. Thus, for example, a mere thimbleful of the cubic phase has enough surface area to cover a football field.

The research conducted by Trinity’s Professor of Membrane Structural and Functional Biology, Martin Caffrey and Research Associate Dr  Dianfan Li in the School of Medicine and School of Biochemistry & Immunology used the cubic phase; but the cubic phase made from hydrated fat alone was useless.  It needed to have a membrane protein sensor incorporated into it and the protein needed to be active.  The test sensor used in the research was a membrane protein, referred to as DgkA.  DgkA is an enzyme that interconverts the fatty components of natural cellular membranes.  The enzyme was produced in E. coli bacteria, using recombinant DNA technology, as an inactive or dead ‘scrambled egg’ type of insoluble aggregate.   ‘Life’ was breathed back into the enzyme by dissolving the aggregated protein in a soapy solution and inserting it into the membrane of the cubic phase.  In this new and quite artificial environment the researchers showed that the protein had regained its original native enzyme activity and that it could behave as a model sensor.

The research sets the stage for the exploitation of this most extraordinary of biomaterials.  These include its use in high density, high sensitivity biosensors for the detection of biological molecules such as hormones, proteins, carbohydrates, and lipids, as well as toxins, explosives, pollutants, and drugs. 

Provided by Trinity College Dublin (news : web)

Inkjet printing could change the face of solar energy industry

Inkjet printers, a low-cost technology that in recent decades has revolutionized home and small office printing, may soon offer similar benefits for the future of solar energy.

Engineers at Oregon State University have discovered a way for the first time to create successful "CIGS" solar devices with inkjet printing, in work that reduces raw material waste by 90 percent and will significantly lower the cost of producing solar energy cells with some very promising compounds.

High performing, rapidly produced, ultra-low cost, thin film solar electronics should be possible, scientists said.

The findings have been published in Solar Energy Materials and Solar Cells, a professional journal, and a patent applied for on the discovery. Further research is needed to increase the efficiency of the cell, but the work could lead to a whole new generation of solar energy technology, researchers say.

"This is very promising and could be an important new technology to add to the solar energy field," said Chih-hung Chang, an OSU professor in the School of Chemical, Biological and Environmental Engineering. "Until now no one had been able to create working CIGS solar devices with inkjet technology."

Part of the advantage of this approach, Chang said, is a dramatic reduction in wasted material. Instead of depositing chemical compounds on a substrate with a more expensive vapor phase deposition -- wasting most of the material in the process -- inkjet technology could be used to create precise patterning with very low waste.

"Some of the materials we want to work with for the most advanced solar cells, such as indium, are relatively expensive," Chang said. "If that's what you're using you can't really afford to waste it, and the inkjet approach almost eliminates the waste."

One of the most promising compounds and the focus of the current study is called chalcopyrite, or "CIGS" for the copper, indium, gallium and selenium elements of which it's composed. CIGS has extraordinary solar efficiency -- a layer of chalcopyrite one or two microns thick has the ability to capture the energy from photons about as efficiently as a 50-micron-thick layer made with silicon.

In the new findings, researchers were able to create an ink that could print chalcopyrite onto substrates with an inkjet approach, with a power conversion efficiency of about 5 percent. The OSU researchers say that with continued research they should be able to achieve an efficiency of about 12 percent, which would make a commercially viable solar cell.

In related work, being done in collaboration with Greg Herman, an OSU associate professor of chemical engineering, the engineers are studying other compounds that might also be used with inkjet technology, and cost even less.

Some approaches to producing solar cells are time consuming, or require expensive vacuum systems or toxic chemicals. OSU experts are working to eliminate some of those roadblocks and create much less costly solar technology that is also more environmentally friendly. New jobs and industries in the Pacific Northwest could evolve from such initiatives, they say.

If costs can be reduced enough and other hurdles breached, it might even be possible to create solar cells that could be built directly into roofing materials, scientists say, opening a huge new potential for solar energy.

"In summary, a simple, fast, and direct-write, solution-based deposition process is developed for the fabrication of high quality CIGS solar cells," the researchers wrote in their conclusion. "Safe, cheap, and air-stable inks can be prepared easily by controlling the composition of low-cost metal salt precursors at a molecular level."

This work was supported by the Daegu Gyeongbuk Institute of Science and Technology, the U.S. Department of Energy and OSU's University Venture Development Fund, which helps donors receive tax benefits while sponsoring projects that will bring new technology, jobs and economic growth to Oregon.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Oregon State University.

Journal Reference:

Wei Wang, Yu-Wei Su, Chih-hung Chang. Inkjet printed chalcopyrite CuInxGa1-xSe2 thin film solar cells. Solar Energy Materials and Solar Cells, 2011; 95 (9): 2616 DOI: 10.1016/j.solmat.2011.05.011

New delivery system for Viagra ingredient

 

Scientists are reporting development and successful initial tests of a potential new delivery system for the biological signaling agent responsible for the effects of Viagra. It could be used to deliver the substance, called nitric oxide or NO, to treatment conditions ranging from heart disease to skin ulcers and other wounds that fail to heal, according to a report in the Journal of the American Chemical Society.

Joao Rocha and colleagues explain that NO acts as an important agent in the body for expanding blood vessels (its role in Viagra and related medicines for erectile dysfunction), preventing the formation of blood clots, aiding nerve signals, and repairing wounds. NO's multipurpose role makes it an exciting prospect for new drug development, but current NO delivery systems sometimes cause undesirable side effects. "Clearly, new materials and technologies are needed to store and target-deliver NO in biological amounts," the report notes.

The researchers developed a highly absorbent material that can carry varying amounts of NO. The material slowly releases NO at a rate that is useful for treating diseases, they conclude. More work must be done to calculate the "shelf life" of the material loaded with NO, Rocha and colleagues note, but they conclude: "This work is a first step toward assessing the real potential therapeutic applications of these materials."

More information: “Slow Release of NO by Microporous Titanosilicate ETS-4”, J. Am. Chem. Soc., 2011, 133 (16), pp 6396–6402
DOI: 10.1021/ja200663e

Abstract
A novel approach to designing nitric oxide (NO) storage and releasing microporous agents based on very stable, zeolite-type silicates possessing framework unsaturated transition-metal centers has been proposed. This idea has been illustrated with ETS-4 [Na9Si12Ti5O38(OH)·xH2O], a titanosilicate that displays excellent NO adsorption capacity and a slow releasing kinetics. The performance of these materials has been compared to the performance of titanosilicate ETS-10, [(Na,K)2Si5TiO13·xH2O], of benchmark zeolites mordenite and CaA, and of natural and pillared clays. DFT periodic calculations have shown that the presence of water in the pores of ETS-4 promotes the NO adsorption at the unsaturated (pentacoordinated) Ti4+ framework ions.

Provided by American Chemical Society (news : web)

Chemist develops biosensor that changes color when bacteria are present in water samples

A team of chemists led by Vincent M. Rotello of the University of Massachusetts Amherst has developed a fast, simple and low-cost field test for detecting bacteria in low concentrations in drinking water using a biosensor made of gold nanoparticles, an enzyme and dye. The biosensor can detect harmful bacteria in concentrations as low as 100 cells per milliliter. Their report appears in the current online edition of the Journal of the American Chemical Society.

The new test could have a significant impact in developing countries where public health workers, physicians and water quality specialists are most in need of a quick, sensitive way to detect pathogens such as bacteria in a water supply. The time it takes to culture samples and wait for relatively expensive lab results severely hampers efforts to save the estimated 300 million people affected by bacterial illness each year. Estimates are that more than 2 million children die annually from bacteria-related disease.

Currently, there are many methods, some quite sophisticated for detecting harmful bacteria such as the killer E. coli. These include culturing, nucleic acid probes and microarrays. But clinics and environmental managers in developing nations often don’t have access to them because of high cost or the need for skilled technicians to read the results.

To address this problem, the research team headed by Rotello with partners at the University of Puerto Rico and the Georgia Institute of Technology, developed a test strip suitable for field use that has a simple visual read out. This new uses enzyme-nanoparticle assemblies absorbed on paper strips. When the paper comes in contact with bacteria, the enzyme is activated and the strip turns from yellow to red, an easily observable change that takes place within 10 minutes.

Rotello also notes that very small amounts of the nanoparticles and enzyme are needed for the reaction, keeping the price of the test strips low. The team is now working to improve the sensitivity of the test strips to be able to detect even smaller amounts of bacteria.

The work is supported by the National Science Foundation through the UMass Amherst Center for Hierarchical Manufacturing.

Provided by University of Massachusetts Amherst (news : web)

Scientists discover dielectron charging of water nano-droplet

Scientists have discovered fundamental steps of charging of nano-sized water droplets and unveiled the long-sought-after mechanism of hydrogen emission from irradiated water. Working together at the Georgia Institute of Technology and Tel Aviv University, scientists have discovered when the number of water molecules in a cluster exceeds 83, two excess electrons may attach to it -- forming dielectrons -- making it a doubly negatively charged nano droplet. Furthermore, the scientists found experimental and theoretical evidence that in droplets composed of 105 molecules or more, the excess dielectrons participate in a water-splitting process resulting in the liberation of molecular hydrogen and formation of two solvated hydroxide anions.

The results appear in the June 30 issue of the Journal of Physical Chemistry A.

It has been known since the early 1980s that while single electrons may attach to small water clusters containing as few as two molecules, only much larger clusters may attach more than single electrons. Size-selected, multiple-electron, negatively-charged water clusters have not been observed -- until now.

Understanding the nature of excess electrons in water has captured the attention of scientists for more than half a century, and the hydrated electrons are known to appear as important reagents in charge-induced aqueous reactions and molecular biological processes. Moreover, since the discovery in the early 1960s that the exposure of water to ionizing radiation causes the emission of gaseous molecular hydrogen, scientists have been puzzled by the mechanism underlying this process. After all, the bonds in the water molecules that hold the hydrogen atoms to the oxygen atoms are very strong. The dielectron hydrogen-evolution (DEHE) reaction, which produces hydrogen gas and hydroxide anions, may play a role in radiation-induced reactions with oxidized DNA that have been shown to underlie mutagenesis, cancer and other diseases.

"The attachment of multiple electrons to water droplets is controlled by a fine balancing act between the forces that bind the electrons to the polar water molecules and the strong repulsion between the negatively charged electrons," said Uzi Landman, Regents' and Institute Professor of Physics, F.E. Callaway Chair and director of the Center for Computational Materials Science (CCMS) at Georgia Tech.

"Additionally, the binding of an electron to the cluster disturbs the equilibrium arrangements between the hydrogen-bonded water molecules and this too has to be counterbalanced by the attractive binding forces. To calculate the pattern and strength of single and two-electron charging of nano-size water droplets, we developed and employed first-principles quantum mechanical molecular dynamics simulations that go well beyond any ones that have been used in this field," he added.

Investigations on controlled size-selected clusters allow explorations of intrinsic properties of finite-sized material aggregates, as well as probing of the size-dependent evolution of materials properties from the molecular nano-scale to the condensed phase regime.

In the 1980s Landman, together with senior research scientists in the CCMS Robert Barnett, the late Charles Cleveland and Joshua Jortner, professor of chemistry at Tel Aviv University, discovered that there are two ways that single excess electrons can attach to water clusters -- one in which they bind to the surface of the water droplet, and the other where they localize in a cavity in the interior of the droplet, as in the case of bulk water. Subsequently, Landman, Barnett and graduate student Harri-Pekka Kaukonen reported in 1992 on theoretical investigations concerning the attachment of two excess electrons to water clusters. They predicted that such double charging would occur only for sufficiently large nano-droplets. They also commented on the possible hydrogen evolution reaction. No other work on dielectron charging of water droplets has followed since.

That is until recently, when Landman, now one of the world leaders in the area of cluster and nano science, and Barnett teamed up with Ori Chesnovsky, professor of chemistry, and research associate Rina Giniger at Tel Aviv University, in a joint project aimed at understanding the process of dielectron charging of water clusters and the mechanism of the ensuing reaction -- which has not been observed previously in experiments on water droplets. Using large-scale, state-of-the-art first-principles dynamic simulations, developed at the CCMS, with all valence and excess electrons treated quantum mechanically and equipped with a newly constructed high-resolution time-of-flight mass spectrometer, the researchers unveiled the intricate physical processes that govern the fundamental dielectron charging processes of microscopic water droplets and the detailed mechanism of the water-splitting reaction induced by double charging.

The mass spectrometric measurements, performed at Tel Aviv, revealed that singly charged clusters were formed in the size range of six to more than a couple of hundred water molecules. However, for clusters containing more than a critical size of 83 molecules, doubly charged clusters with two attached excess electrons were detected for the first time. Most significantly, for clusters with 105 or more water molecules, the mass spectra provided direct evidence for the loss of a single hydrogen molecule from the doubly charged clusters.

The theoretical analysis demonstrated two dominant attachment modes of dielectrons to water clusters. The first is a surface mode (SS'), where the two repelling electrons reside in antipodal sites on the surface of the cluster. The second is another attachment mode with both electrons occupying a wave function localized in a hydration cavity in the interior of the cluster -- the so-called II binding mode. While both dielectron attachment modes may be found for clusters with 105 molecules and larger ones, only the SS' mode is stable for doubly charged smaller clusters.

"Moreover, starting from the II, internal cavity attachment mode in a cluster composed of 105 water molecules, our quantum dynamical simulations showed that the concerted approach of two protons from two neighboring water molecules located on the first shell of the internal hydration cavity, leads, in association with the cavity-localized excess dielectron, to the formation of a hydrogen molecule. The two remnant hydroxide anions diffuse away via a sequence of proton shuttle processes, ultimately solvating near the surface region of the cluster, while the hydrogen molecule evaporates," said Landman.

"What's more, in addition to uncovering the microscopic reaction pathway, the mechanism which we discovered requires initial proximity of the two reacting water molecules and the excess dielectron. This can happen only for the II internal cavity attachment mode. Consequently, the theory predicts, in agreement with the experiments, that the reaction would be impeded in clusters with less than 105 molecules where the II mode is energetically highly improbable. Now, that's a nice consistency check on the theory," he added.

As for future plans, Landman remarked, "While I believe that our work sets methodological and conceptual benchmarks for studies in this area, there is a lot left to be done. For example, while our calculated values for the excess single electron detachment energies are found to be in quantitative agreement with photoelectron measurements in a broad range of water cluster sizes -- containing from 15 to 105 molecules -- providing a consistent interpretation of these measurements, we would like to obtain experimental data on excess dielectron detachment energies to compare with our predicted values," he said.

"Additionally, we would like to know more about the effects of preparation conditions on the properties of multiply charged water clusters. We also need to understand the temperature dependence of the dielectron attachment modes, the influence of metal impurities, and possibly get data from time-resolved measurements. The understanding that we gained in this experiment about charge-induced water splitting may guide our research into artificial photosynthetic systems, as well as the mechanisms of certain bio-molecular processes and perhaps some atmospheric phenomena."

"You know," he added. "We started working on excess electrons in water clusters quite early, in the 1980s -- close to 25 years ago. If we are to make future progress in this area, it will have to happen faster than that."

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Georgia Institute of Technology, via EurekAlert!, a service of AAAS.

Journal Reference:

Robert N. Barnett, Rina Giniger, Ori Cheshnovsky, Uzi Landman. Dielectron Attachment and Hydrogen Evolution Reaction in Water Clusters. The Journal of Physical Chemistry A, 2011; 110603091014098 DOI: 10.1021/jp201560n

Finding is a feather in the cap for researchers studying birds' big, powerful eyes

Say what you will about bird brains, but our feathered friends sure have us -- and all the other animals on the planet -- beat in the vision department, and that has a bit to do with how their brains develop.

Consider the in-flight feats of birds of prey: They must spot their dinner from long distances and dive-bomb those moving targets at lightning speed. And then there are the owls, which operate nimbly on even the darkest nights to secure supper in swift swoops. Some birds have ultraviolet sensitivity; others have infrared sensitivity. To boot, some birds can even see the Earth's magnetic field.

Much of the credit for avian visual acuity goes to the extraordinary retina, which grows out of the brain during development, making it an official component of the central nervous system. Indeed, the avian retina is far more complex in structure and composition than the human retina, and it contains many more photoreceptors -- rod- and cone-shaped cells that detect light and color, respectively.

While researchers over the years have come to better understand much about the avian retina, many nagging questions remain. For Thorsten Burmester's research team at the University of Hamburg, the question was this: How does such a productive retina sustain itself when the avian eye has very few capillaries to deliver oxygen to it? After all, it has to "breathe," so to speak.

"The visual process in the vertebrate eye requires high amounts of metabolic energy and thus oxygen," Burmester's group writes in this week's Journal of Biological Chemistry. "Oxygen supply of the avian retina is a challenging task because birds have large eyes, thick retinas and high metabolic rates, but neither deep retinal nor superficial capillaries."

To answer the question, Burmester's team took a closer look at a protein that they discovered exists in large quantities in photoreceptor cells of the avian eye -- and only of the avian eye. They named the protein globin E. (The "E" is short for "eye," of course.)

Burmester's team used a number of techniques to characterize globin E and found that it is responsible for storing and delivering oxygen to the retina.

The finding is intriguing for a number of reasons.

Firstly, it helps explain how birds evolved to have such large eyes, relative to their body mass, without a dense network of ocular capillaries for blood delivery. (Some owls, for instance, have bigger eyes than humans.)

"The exact origin of globin E is still somewhat a mystery," Burmester said. "It clearly evolved from some type of globin, but it has no obvious relative outside the birds."

The globins are all thought to share a common ancestor, and the most well-known members of the family are myoglobin and hemoglobin. Myoglobin is responsible for oxygen storage and release in heart and skeletal muscle fibers. Hemoglobin, meanwhile, transports oxygen from the lungs to other parts of the body in red blood cells.

Burmester explains: "Bird eyes have evolved to have a system not unlike those in our heart, which uses myoglobin to store and release oxygen to maintain respiration and energy-consumption during muscle contraction. In eyes, oxygen and energy are needed to generate neuronal signals."

Secondly, the finding puts to rest an earlier hypothesis that another molecule, neuroglobin, might be the oxygen-delivery vehicle for the avian eye. Neuroglobin is known to deliver oxygen to brain tissue, so it was only natural to suspect it. But it turns out that the messenger RNA fingerprint of globin E was 100-fold more prevalent than that of neuroglobin in Burmester's chicken retina samples, indicating that neuroglobin probably has another, yet-to-be defined function in the avian eye.

Lastly, globin E is another interesting illustration of the convergent evolution of "myoglobin-like" molecules. Among the organisms with proteins with similar functions are the soybean, which needs its leghemoglobin to deliver oxygen to the Rhizobium soil bacteria that colonize in root nodules, and the 2-foot-long sea worm Cerebratulus lacteus, which needs its mini-hemoglobin to keep its brain and neurons oxygenated when it burrows deep into the sea floor, where oxygen levels are low, in search of clams.

More information: The abstract for the paper, which was titled "Oxygen supply from the bird's eye perspective: Globin E is a respiratory protein in the chicken retina," is available at http://www.jbc.org … 34.abstract.

Provided by American Society for Biochemistry and Molecular Biology

Embracing superficial imperfections

Chemists normally work rigorously to exclude impurities from their reactions. This is especially true for scanning tunneling microscopy (STM) experiments that can produce atomic-scale images of surfaces. Using STM to investigate processes such as catalysis usually requires pristine substrates—any flaws or foreign particles in the surface can critically interfere with the test study. Preconceptions about interface defects and catalysis are about to change, however, thanks to recently published research led by Yousoo Kim and Maki Kawai at the RIKEN Advanced Science Institute in Wako, Japan.

Through a series of high-level computer simulations, the researchers found that the catalytic splitting of water molecules occurs faster on an ultrathin insulating film containing misplaced atoms than on a non-defective surface. Because water splitting reactions are one of the easiest ways to generate hydrogen fuel, this finding could be a boon to future fleets of hybrid vehicles.

Recently, Kim, Kawai, and colleagues discovered that depositing insulating magnesium oxide (MgO) onto a silver (Ag) substrate enabled extraordinary control over water dissociation reactions. By injecting electrons into the MgO/Ag surface with an STM tip, they were able to excite absorbed water molecules and cause them to sever hydrogen and hydroxide ions. Optimizing the MgO film thickness was a key part of this approach; only ultrathin layers could direct water splitting owing to its enhanced electronic interaction strength. 

This relationship between insulator thickness and chemical reactivity suggested to the researchers that the oxide–metal interface plays a crucial role in directing catalytic reactions. Engineering specific flaws into the ultrathin interface could be one way to heighten the electronic control over the water-splitting process. However, since artificially manipulating oxide atoms is a difficult experimental procedure, they used density functional theory simulations, based on quantum mechanics, to analyze the role of structural imperfections in MgO.

Surprisingly, the researchers found that three different types of defects—oxygen and magnesium impurities, as well as an oxygen vacancy—improved water adsorption and substantially lowered dissociation energy barriers compared to an ideal MgO film. Further analysis revealed that the oxide defects accumulate charges injected into the substrate (Fig. 1), creating an electronic environment that speeds up the catalytic water splitting. “In the presence of these defects, the film’s chemical reactivity can be greatly enhanced,” says Kim.

The next goal for the researchers is to find systematic techniques to control interface imperfections on these novel catalytic films—an objective best achieved by the team’s unique combined experimental–theoretical approach, notes Kim.

More information:

1. Jung, J., et al. Activation of ultrathin oxide films for chemical reaction by interface defects. Journal of the American Chemical Society 133, 6142–6145 (2011). 

2. Shin, H.-J., et al. State-selective dissociation of a single water molecule on an ultrathin MgO film. Nature Materials 9, 442–447 (2010).

3. Jung, J., et al. Controlling water dissociation on an ultrathin MgO film by tuning film thickness. Physical Review B 82, 085413 (2010).

Provided by RIKEN (news : web)

Bacterium engineered with DNA in which thymine is replaced by synthetic building block

ScienceDaily (June 29, 2011) — The genetic information of all living cells is stored in the DNA composed of the four canonical bases adenine (A), cytosine (C), guanine (G) and thymine (T). An international team of researchers has now succeeded in generating a bacterium possessing a DNA in which thymine is replaced by the synthetic building block 5-chlorouracil (c), a substance toxic for other organisms.

The project, coordinated by Rupert Mutzel (Institut für Biologie, Freie Universität Berlin) and Philippe Marliere (Heurisko USA Inc.), involved researchers of the French CEA (Commissariat a l'Energie Atomique et aux Energies Alternatives) and of the Katholieke Universiteit Leuven (Belgium). As described in the latest issue of Angewandte Chemie International Edition, the experimental work was based on a unique technology developed by Marliere and Mutzel enabling the directed evolution of organisms under strictly controlled conditions. Large populations of microbial cells are cultured for prolonged periods in the presence of a toxic chemical -- in this case, 5-chlorouracil -- at sublethal levels, thereby selecting for genetic variants capable of tolerating higher concentrations of the toxic substance.

In response to the appearance of such variants in the cell population the concentration of the toxic chemical in the growth medium is increased, thus keeping the selection pressure constant. This automated procedure of long term evolution was applied to adapt genetically engineered Escherichia coli bacteria unable to synthesize the natural nucleobase thymine to grow on increasing concentrations of 5-chlorouracil. After a culture period of about 1000 generations descendants of the original strain were obtained which used 5-chlorouracil as complete substitute for thymine. Subsequent genome analysis revealed numerous mutations in the DNA of the adapted bacteria. The contribution of these mutations to the adaptation of the cells towards the halogenated base will be the subject of follow-up studies.

Besides the obvious interest of this radical change in the chemistry of living systems for basic research the scientists consider the outcome of their work also to be of importance for "xenobiology," a branch of synthetic biology. This young area of the life sciences aims at the generation of new organisms not found in nature harboring metabolic traits optimized for alternative modes of energy production or for the synthesis of high value chemicals. Like GMOs, such organisms are seen as a potential threat for natural ecosystems when released from their laboratory confinements, either through direct competition with wild type organisms or through diffusion of their "synthetic" DNA.

Scientists have recognized that physical containment cannot in every single case prevent engineered live forms from reaching natural habitats, in the same way as radioactive isotopes can leak into the surroundings of a nuclear power plant. However, synthetic organisms like those evolved by Marliere and Mutzel and their collaborators which depend on the availability of substances for their proliferation not found in nature or which incorporate non-natural building blocks in their genetic material could neither compete nor exchange genetic messages with wild type organisms, but would die in the absence of the xenobiotic.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Freie Universitaet Berlin, via AlphaGalileo.

Journal Reference:

Philippe Marliere, Julien Patrouix, Volker Döring, Piet Herdewijn, Sabine Tricot, Stéphane Cruveiller, Madeleine Bouzon, Rupert Mutzel. Chemical Evolution of a Bacterium's Genome. Angewandte Chemie International Edition, 2011; DOI: 10.1002/anie.201100535

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

Chemists figure out how to synthesize compounds from resveratrol

 Researchers working at Columbia University in New York have succeeded in synthesizing several compounds from the stilbenoid, resveratrol, a chemical commonly found in the skin of grapes that has been shown to have a wide variety of medicinal benefits.

The team, led by Scott Snyder, devised a technique to get around the problem of individual plants making such minute quantities of the chemical that it has been virtually impossible until now to isolate and then put them to good use; they built compounds that are similar to the polyphenols normally produced by grapes, but different enough to allow the syntheses of differing chemicals contained within them.

The health benefits of resveratrol are wide and varied; some have suggested that it’s responsible for the relatively low levels of coronary disease in France, due to the resveratrol in red wine that is consumed widely in the country, this despite the fact that the French diet is known for inclusion of lots of fatty foods. Also, a recent study by a University of Florida team of researchers found evidence that resveratrol might make getting older a less traumatic experience.

Thus, the search to find ways to extract the chemical from grapes, or other resveratrol producing plants, so as to put it in a pill that people could take, has been underway for several years. Until now though, the going has been extremely slow due to the plants stubborn insistence on making just enough of the stuff to ward of diseases such as fungus.

Now however, Snyder and his colleagues Andreas Gollner and Maria Chiriac, have figured out a way to use a reagent (a chemical or substance added to something to produce a specific reaction) called bromodiethylsulfide bromopentachloroantimonate to cause a resveratrol dimer (a chemical structure consisting of two sub-units) to accept additional monomers (a molecule that binds to other molecules to form a polymer) to in effect, grow more resveratrol from its basic unit, allowing for the production of virtually any amount of the precious chemical.

Having resveratrol in pill form would offer the benefits of drinking red wine to consumers without the drawbacks, such as the ill effects of alcohol and the breakdown of tooth enamel that occurs with all citric based drinks that lead to dental problems.

More information: Regioselective reactions for programmable resveratrol oligomer synthesis, Nature 474, 461–466 (23 June 2011) doi:10.1038/nature10197

Abstract
Although much attention has been devoted to resveratrol, a unique polyphenol produced by plants and credited as potentially being responsible for the ‘French paradox’—the observation that French people have a relatively low incidence of coronary heart disease, even though their diet is high in saturated fats—the oligomers of resveratrol have been largely ignored despite their high biological activity. Challenges in achieving their isolation in sufficient quantity from natural sources, coupled with an inability to prepare them easily synthetically, are seen as the main obstacles. Here we report a programmable, controlled and potentially scalable synthesis of the resveratrol family via a three-stage design. The synthetic approach requires strategy- and reagent-guided chemical functionalizations to differentiate two distinct cores possessing multiple sites with the same or similar reactivity, ultimately leading to five higher-order natural products. This work demonstrates that challenging, positionally selective functionalizations of complex materials are possible where biosynthetic studies have indicated otherwise, it provides materials and tools with which to unlock the full biochemical potential of this family of natural products, and it affords an intellectual framework within which other oligomeric families could potentially be accessed.

 

New rapid test tells difference between bacterial and viral infections

 Scientists are reporting development and successful testing of a rapid and accurate test to tell the difference between bacterial and viral infections. Those common afflictions often have similar symptoms but vastly different treatments — antibiotics work for bacterial infections but not for viruses. The report appears in ACS' journal Analytical Chemistry.

Robert Marks, Daria Prilutsky, and colleagues cite the importance of determining the source of an infection in order to quickly start the right treatment. If left untreated until results of a throat culture, for instance, are in, bacterial infections can get worse. But needlessly giving antibiotics to patients with a viral infection could contribute to the growing problem of antibiotic-resistant bacteria. Since current diagnostic methods to sort out the two kinds of infection are time-consuming and may not be completely accurate, the researchers sought to develop a new test that would enable doctors to rapidly make the right diagnosis.

They found that the immune systems of patients with bacterial infections behaved differently than the immune systems of patients with viral infections, and developed a test based on those differences. "The method is time-saving, easy to perform and can be commercially available, thus, having predictive diagnostic value and could be implemented in various medical institutions as an adjunct to clinical decision making," say the researchers.

More information: “Differentiation between viral and bacterial acute infections using chemiluminescent signatures of circulating phagocytes” Anal. Chem., 2011, 83 (11), pp 4258–4265 DOI: 10.1021/ac200596f

Abstract
Oftentimes the etiological diagnostic differentiation between viral and bacterial infections is problematic, while clinical management decisions need to be made promptly upon admission. Thus, alternative rapid and sensitive diagnostic approaches need to be developed. Polymorphonuclear leukocytes (PMNs) or phagocytes act as major players in the defense response of the host during an episode of infection, and thereby undergo functional changes that differ according to the infections. PMNs functional activity can be characterized by quantification and localization of respiratory burst production and assessed by chemiluminescent (CL) byproduct reaction. We have assessed the functional states of PMNs of patients with acute infections in a luminol-amplified whole blood system using the component CL approach. In this study, blood was drawn from 69 patients with fever (>38 °C), and diagnosed as mainly viral or bacterial infections in origin. Data mining algorithms (C4.5, Support Vector Machines (SVM) and Nave Bayes) were used to induce classification models to distinguish between clinical groups. The model with the best predictive accuracy was induced using C4.5 algorithm, resulting in 94.7% accuracy on the training set and 88.9% accuracy on the testing set. The method demonstrated a high predictive diagnostic value and may assist the clinician one day in the distinction between viral and bacterial infections and the choice of proper medication.

Provided by American Chemical Society (news : web)

Subatomic quantum memory in diamond demonstrated

Physicists working at the University of California, Santa Barbara and the University of Konstanz in Germany have developed a breakthrough in the use of diamond in quantum physics, marking an important step toward quantum computing. The results are reported in this week's online edition of Nature Physics.

The physicists were able to coax the fragile quantum information contained within a single electron in diamond to move into an adjacent single nitrogen nucleus, and then back again using on-chip wiring.

"This ability is potentially useful to create an atomic-scale memory element in a quantum computer based on diamond, since the subatomic nuclear states are more isolated from destructive interactions with the outside world," said David Awschalom, senior author. Awschalom is director of UCSB's Center for Spintronics & Quantum Computation, professor of physics, electrical and computer engineering, and the Peter J. Clarke director of the California NanoSystems Institute.

Awschalom said the discovery shows the high-fidelity operation of a quantum mechanical gate at the atomic level, enabling the transfer of full quantum information to and from one electron spin and a single nuclear spin at room temperature. The process is scalable, and opens the door to new solid-state quantum device development.

Scientists have recently shown that it is possible to synthesize thousands of these single electron states with beams of nitrogen atoms, intentionally creating defects to trap the single electrons. "What makes this demonstration particularly exciting is that a nitrogen atom is a part of the defect itself, meaning that these sub-atomic memory elements automatically scale with the number of logical bits in the quantum computer," said lead author Greg Fuchs, a postdoctoral fellow at UCSB.

Rather than using logical elements like transistors to manipulate digital states like "0" or "1," a quantum computer needs logical elements capable of manipulating quantum states that may be "0" and "1" at the same time. Even at ambient temperature, these defects in diamond can do exactly that, and have recently become a leading candidate to form a quantum version of a transistor.

However, there are still major challenges to building a diamond-based quantum computer. One of these is finding a method to store quantum information in a scalable way. Unlike a conventional computer, where the memory and the processor are in two different physical locations, in this case they are integrated together, bit-for-bit.

"We knew that the nitrogen nuclear spin would be a good choice for a scalable quantum memory -- it was already there," said Fuchs. "The hard part was to transfer the state quickly, before it is lost to decoherence."

Awschalom explained: "A key breakthrough was to use a unique property of quantum physics -- that two quantum objects can, under special conditions, become mixed to form a new composite object." By mixing the quantum spin state of the electrons in the defect with the spin state of the nitrogen nucleus for a brief time -- less than 100 billionths of a second -- information that was originally encoded in the electrons is passed to the nucleus.

"The result is an extremely fast transfer of the quantum information to the long-lived nuclear spin, which could further enhance our capabilities to correct for errors during a quantum computation," said co-author Guido Burkard, a theoretical physicist at the University of Konstanz, who developed a model to understand the storage process.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of California - Santa Barbara, via EurekAlert!, a service of AAAS.

Journal Reference:

G. D. Fuchs, G. Burkard, P. V. Klimov, D. D. Awschalom. A quantum memory intrinsic to single nitrogen–vacancy centres in diamond. Nature Physics, 2011; DOI: 10.1038/nphys2026