Monday, February 28, 2011

Producing clean water in an emergency

Disasters such as floods, tsunamis, and earthquakes often result in the spread of diseases like gastroenteritis, giardiasis and even cholera because of an immediate shortage of clean drinking water. Now, chemistry researchers at McGill University have taken a key step towards making a cheap, portable, paper-based filter coated with silver nanoparticles to be used in these emergency settings.

"Silver has been used to clean water for a very long time. The Greeks and Romans kept their water in silver jugs," says Prof. Derek Gray, from McGill's Department of Chemistry. But though silver is used to get rid of bacteria in a variety of settings, from bandages to antibacterial socks, no one has used it systematically to clean water before. "It's because it seems too simple," affirms Gray.

Prof. Gray's team, which included graduate student Theresa Dankovich, coated thick (0.5mm) hand-sized sheets of an absorbent porous paper with silver nanoparticles and then poured live bacteria through it. "Viewed in an electron microscope, the paper looks as though there are silver polka dots all over," says Dankovich, "and the neat thing is that the silver nanoparticles stay on the paper even when the contaminated water goes through." The results were definitive. Even when the paper contains a small quantity of silver (5.9 mg of silver per dry gram of paper), the filter is able to kill nearly all the bacteria and produce water that meets the standards set by the American Environmental Protection Agency (EPA).

The filter is not envisaged as a routine water purification system, but as a way of providing rapid small-scale assistance in emergency settings. "It works well in the lab," says Gray, "now we need to improve it and test it in the field."

The research was funded by the National Sciences and Engineering Council of Canada (NSERC) and the work is part of the NSERC Sentinel Bioactive Paper Network.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by McGill University.

Journal Reference:

Theresa A. Dankovich, Derek G. Gray. Bactericidal Paper Impregnated with Silver Nanoparticles for Point-of-Use Water Treatment. Environmental Science & Technology, 2011; : 110211114613010 DOI: 10.1021/es103302t

Metallic molecules to nanotubes: Ruthenium complexes dissolve nanotubes, add functionality

A lab at Rice University has stepped forward with an efficient method to disperse nanotubes in a way that preserves their unique properties -- and adds more.

The new technique allows inorganic metal complexes with different functionalities to remain in close contact with single-walled carbon nanotubes while keeping them separated in a solution.

That separation is critical to manufacturers who want to spin fiber from nanotubes, or mix them into composite materials for strength or to take advantage of their electrical properties. For starters, the ability to functionalize the nanotubes at the same time may advance imaging sensors, catalysis and solar-activated hydrogen fuel cells.

Better yet, a batch of nanotubes can apparently stay dispersed in water for weeks on end.

Keeping carbon nanotubes from clumping in aqueous solutions and combining them with molecules that add novel abilities have been flies in the ointment for scientists exploring the use of these highly versatile materials.

They've tried attaching organic molecules to the nanotubes' surfaces to add functionality as well as solubility. But while these techniques can separate nanotubes from one another, they take a toll on the nanotubes' electronic, thermal and mechanical properties.

Angel Marti, a Rice assistant professor of chemistry and bioengineering and a Norman Hackerman-Welch Young Investigator, and his students reported this month in the Royal Society of Chemistry journal Chemical Communications that ruthenium polypyridyl complexes are highly effective at dispersing nanotubes in water efficiently and for long periods. Ruthenium is a rare metallic element.

One key is having just the right molecule for the job. Marti and his team created ruthenium complexes by combining the element with ligands, stable molecules that bind to metal ions. The resulting molecular complex is part hydrophobic (the ligands) and part hydrophilic (the ruthenium). The ligands strongly bind to nanotubes while the attached ruthenium molecules interact with water to maintain the tubes in solution and keep them apart from one another.

Another key turned out to be moderation.

Originally, Marti said, he and co-authors Disha Jain and Avishek Saha weren't out to solve a problem that has boggled chemists for decades, but their willingness to "do something crazy" paid off big-time. Jain is a former postdoctoral researcher in Marti's lab, and Saha is a graduate student.

The researchers were eyeing ruthenium complexes as part of a study to track amyloid deposits associated with Alzheimer's disease. "We started to wonder what would happen if we modified the metal complex so it could bind to a nanotube," Marti said. "That would provide solubility, individualization, dispersion and functionality."

It did, but not at first. "Avishek put this together with purified single-walled carbon nanotubes (created via Rice's HiPco process) and sonicated. Absolutely nothing happened. The nanotubes didn't get into solution -- they just clumped at the bottom.

"That was very weird, but that's how science works -- some things you think are good ideas never work."

Saha removed the liquid and left the clumped nanotubes at the bottom of the centrifuge tube. "So I said, 'Well, why don't you do something crazy. Just add water to that, and with the little bit of ruthenium that might remain there, try to do the reaction.' He did that, and the solution turned black."

A low concentration of ruthenium did the trick. "We found out that 0.05 percent of the ruthenium complex is the optimum concentration to dissolve nanotubes," Marti said. Further experimentation showed that simple ruthenium complexes alone did not work. The molecule requires its hydrophobic ligand tail, which seeks to minimize its exposure to water by binding with nanotubes. "That's the same thing nanotubes want to do, so it's a favorable relationship," he said.

Marti also found the nanotubes' natural fluorescence unaffected by the ruthenium complexes. "Even though they've been purified, which can introduce defects, they still exhibit very good fluorescence," he said.

He said that certain ruthenium complexes have the ability to stay in an excited state for a long time -- about 600 nanoseconds, or 100 times longer than normal organic molecules. "It means the probability that it will transfer an electron is high. That's convenient for energy transfer applications, which are important for imaging," he said.

That nanotubes stay suspended for a long time should catch the eye of manufacturers who use them in bulk. "They should stay separated for weeks without problems," Marti said. "We have solutions that have been sitting for months without any signs of crashing."

The Welch Foundation supported the research.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Rice University.

Journal Reference:

Disha Jain, Avishek Saha, Angel A. Mart. Non-covalent ruthenium polypyridyl complexes–carbon nanotubes composites: an alternative for functional dissolution of carbon nanotubes in solution. Chemical Communications, 2011; 47 (8): 2246 DOI: 10.1039/C0CC05295G

Structure, dynamics of a chemical signal that triggers metastatic cancer revealed

 By Warren Froelich  Molecular Dynamics simulation shows that oxygen molecules reach the active site of Lysine Specific Demethylase 1 although substrate peptides (black, H3 histone tail & orange, SNAIL1 protein) are bound Credit: Riccardo Baron et al., UC San Diego

In cancer and other pathological diseases, researchers are discovering that packaging is important: specifically, how DNA – about two meters long when unwound and stretched – coils up and compacts neatly inside the nucleus of a cell.

What they’ve learned is that molecular signals that control the packaging of DNA are critical to the activation and silencing of genes in the human body – a process generally described as epigenetics.

Now, a team of researchers from UC San Diego and the University of Pavia in Italy, with the help of high-performance computers housed at the San Diego Supercomputer Center (SDSC), have captured the chemical structure of one such signal – in static crystal form and in motion – which is at the heart of a variety of morphological events including the rapid movement of cells during embryonic development, wound healing, and .

The results offer a potentially new path to combat by blocking the activity of this epigenetic signal, which, among other things, has been shown to silence a gene responsible for cell-to-cell adhesion, a “molecular glue,” thus allowing cancer cells to spread.

“Our study opens the understanding of the molecular interaction and dynamics to be targeted to develop epigenetic drugs which hopefully will lead in the future to potent drugs against cancer,” said J. Andrew McCammon, Joseph Mayer Chair of Theoretical Chemistry and Professor of Pharmacology at UC San Diego and a Howard Hughes Medical Institute Investigator.

Historically, cancer researchers have generally focused on genetic mutations, specific changes in DNA which alter the function of the proteins they encode; studies ultimately have yielded several targeted drugs based on this approach. But treatments for many forms of cancer remain limited, prompting the search for other novel approaches. In particular, some have turned to epigenetics and processes that activate or silence genes by altering the physical structure of DNA -- how it’s packaged -- leaving its message or sequence intact.

“The full potential of epigenetic therapy is far from being exploited,” said Riccardo Baron, a postdoctoral researcher in McCammon’s lab and first author of the study, published in the February issue of the journal Structure. “Very little has been done in terms of pharmacological manipulation and studies such as this are a start down that road. Computer applications in chemistry hold great promises for designing new experiments and future drug development.”

Briefly, to compact an otherwise lengthy strand of DNA neatly inside the nucleus, cells rely on proteins called histones. DNA tightly loops around histones to form nucleosomes, the so-called “beads- on-a-string” that coil up to make up chromatin, the basic unit of chromosomes. Here, the DNA remains sequestered until it’s silenced or activated by enzymes responsible for gene expression.

One such enzyme coming under increasing scrutiny lately is lysine-specific demethylase 1, or LSD1 (no relation to the hallucinogen). Specifically, in 2004 researchers at Harvard University and University of Pavia found that LSD1 – particularly when bound to another protein called CoREST – removes one or more methyl groups from the amino acid lysine on histone H3, in a region that protrudes from the globular core known as the N-terminal tail. The result: closes up shop, shutting down gene expression.

In a study published last year by a team at the University of Kentucky, it was discovered that the LSD1-CoRest complex worked in tandem with an enzyme called SNAIL1 to silence the activity of a gene responsible for E-cadherin, considered a type of “molecular glue” that keeps cells together. When this gene is repressed, cancer cells are allowed to spread – a hallmark of metastasis.

SNAIL1, a master regulator of the epithelial-mesenchymal transition (EMT) process that’s at the heart of many morphological events, has been found in high quantities in the sera of patients with several cancers, including breast and certain forms of leukemia.

Based partly on this work, the UCSD-University of Pavia team sought to find out precisely how and where the enzyme complex bound to and interacted with SNAIL1, and why LSD1-CoREST is selectively drawn to, and recruited by, SNAIL1 in the first place.

Their research included analysis of the crystal structure of the LSD1-CoREST complex bound to SNAIL1 as determined from X-ray diffraction experiments. This snapshot demonstrated that the LSD1-CoRest complex tightly binds to a region of the SNAIL1 molecule that closely resembles the N-terminal tail of histone effectively mimicking the active site on this histone. The structure has been made publicly available in the Protein Data Bank.

“What this shows is how LSD1 recognizes and discriminates specific proteins in a crowded cell environment, and why the LSD1 complex is drawn to SNAIL 1,” said Andrea Mattevi, a researcher from the Department of Genetics and Microbiology at the University of Pavia, and the study’s principal investigator.

Though insightful, X-ray structures offer only a static view of molecular activity at a given moment. To learn more about the interaction of the enzyme complex and its target over time, scientists work with molecular dynamics software that simulate how proteins wiggle, weave and gyrate over time. Such is the complexity of the calculations needed for these simulations that researchers often turn to supercomputers.

“Experiments captured a key molecular-level photograph of this process from which computer simulations were initiated providing a movie on the nanosecond timescale,” added Baron. “For example, molecular films like these allow us to predict the routes of individual oxygen molecules to the reactive site of LSD1.”

Of particular note, the UCSD-University of Pavia researchers examined picosecond-by-picosecond movement of the LSD1-CoREST complex as it binds to SNAIL1, and changes – at the atomic level -- resulting from this activity. The “movies” show that oxygen can continue to reach the enzyme’s active site even when it’s bound to the histone tail, allowing the enzyme to perform its de-methylating task without needing to detach from its target.

“Overall, these observations and data are of crucial importance to understand which of these processes is the most promising target for future drugs,” said Mattevi. “Potent drugs could be developed targeting both the binding cleft of LSD1, as well as the active site access by oxygen molecules.”

Mattevi’s group in Pavia recently demonstrated that inhibitors to LSD1, and a close relative known as LSD2, strongly increased the potency of a chemotherapeutic agent called retinoic acid in the treatment of acute promyelocytic leukemia. Further, they recently discovered that known antidepressant drug inhibitors of enzymes with similar active sites (monoamine oxidase A and B) are promising candidates to develop highly specific inhibitors of LSD1 and LSD2.

Baron added he is in the process of establishing an independent research group focused on epigenetic drug discovery and design of LSD1 and LSD2 inhibitors using computational methodologies developed by the McCammon lab.

Swimming microbes monitor water quality

 By Peter Gwynne  Scott Gallager works on the swimming behavioral spectrophotometer to analyze the safety of a water sample. Credit: Tom Kleindinst Copyright Woods Hole Oceanographic Institution (WHOI)

Miners used to rely on canaries to alert them to dangerous build-ups of gases. Now much smaller animals -- the smallest of all -- can warn of toxins in water supplies.

Single-celled creatures called provide the warning when they change the way they swim. If efforts to develop the patent-pending technology succeed, the "swimming behavioral spectrophotometer", or SBS, could be coming to a water supply near you.

The SBS, said inventor Scott Gallager, an associate scientist at the Woods Hole Oceanographic Institution in Mass., can potentially "monitor all the drinking water in the world."

To facilitate that goal, local start-up company Petrel Biosensors, Inc., has licensed the technology.

"Once we have financing, it will take between 12-15 months to get to a commercial product," said CEO Robert Curtis.

Visible only through a microscope, protozoa are covered in hair-like projections called cilia. In clean water, cilia propel the protozoa forward by working together like the oars of a rowing team. Pollutants in water can interfere with the movement of calcium through the microbes' bodies to the cilia. That alters their owners' swimming styles. The protozoa might spiral out of control or careen erratically around their tanks.

Different pollutants impact the swimming styles in identifiable ways. And various types of protozoa react to specific pollutants and other toxins in different ways. By using just a few types of protozoa in the SBS, scientists can trace a wide range of impurities, including pesticides, , and biological warfare agents.

Between 50-250 protozoa are placed in the water to be tested, in a chamber about the size of a container for emergency gasoline. A camera records their movements for any time between 10 seconds and a minute.

The camera then feeds the images to software that evaluates about 50 characteristics of the microbes' swimming. The software determines the purity of the water sample by comparing the characteristics with those of protozoa in distilled water.

The SBS uses a colored light system to reveal the water's quality. Green indicates that the water is safe, yellow calls for further testing, and red indicates danger, meaning, don't drink the water.

Gallager and his colleague Wade McGillis, now at Columbia University's Lamont-Doherty Earth Observatory in Palisades, N.Y., developed the SBS with a grant from the Defense Department.

"The technology is very quick; it monitors in real time," said Curtis. "It's got a great ability to detect a broad range of contaminants."

The SBS remains in a pilot stage. Eventually, Curtis expects to miniaturize the device and that each test will cost $1-2, in contrast to the $50-250 per test for existing methods. He also claimed the test will reduce the response time and the number of false positives and negatives.

One reason for the high cost of current methods is that they are very labor-intensive, said Andrew Gottlieb, executive director of the Cape Cod Water Protection Collaborative.

"So anything that can give us a line on less expensive water quality monitoring is good," Gottlieb said.

Initially, Petrel Biosensors plans to use the technology to test discharges of industrial waste water and runoff from storm drains. "Then we'll target municipal drinking water and military installations," Curtis said.

Another potential application: rapid testing of that engineers use in hydraulic fracturing of rocks in the search for oil and gas.


Sleeping Trojan horse to aid imaging of diseased cells

February 17, 2011 A unique strategy developed by researchers at Cardiff University is opening up new possibilities for improving medical imaging.

Medical imaging often requires getting unnatural materials such as metal ions into , a process which is a major challenge across a range of biomedical disciplines. One technique currently used is called the 'Trojan Horse' in which the drug or imaging agent is attached to something naturally taken up by cells.

The Cardiff team, made of researchers from the Schools of Chemistry and Biosciences, has taken the technique one step further with the development of a 'sleeping Trojan horse'. The first example of its kind, this is delivery system resolves some of the current difficulties involved in transporting metal ions into cells.

It is not itself taken up by cells so does not interfere with natural functions until it is 'woken' by the addition of the metal ions. This minimises the unwanted uptake and need for time-consuming purification associated with the common 'Trojan Horse' technique.

The research was led by Dr Mike Coogan, Senior Lecturer in Synthetic Chemistry, along with the paper's first author, Flora Thorp-Greenwood.

Dr Coogan said: "The sleeping process happens rapidly, and the vessel is capable of carrying metals which have positron-emitting isotopes, so it has potential for use in bimodal fluorescence and PET imaging. Combined agents for these types of imaging are known but rare, so this is a significant development in the field.

"There is also additional potential for use in as the metal-bearing form not only enters cells but also localises in the nucleolus. In principle, the concept could also be used to improve delivery of a huge range of drugs and imaging agents into cells or the body."

The study A 'Sleeping Trojan Horse' which transports into cells, localises in nucleoli, and has potential for bimodal fluorescence/PET imaging is published in the advanced article section of Chemical Communications. Published by the Royal Society of Chemistry, this is the leading weekly journal for the publication of important developments in the chemical sciences.

Provided by Cardiff University (news : web)

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The hidden danger of oxygen


Birch pollen with allergenic potential. The colouring of the fluorescence microscopic picture shows the difference in the chemical composition of the pollen which can contain allergy-triggering protein in the cell and on its surface. Credit: Manabu Shiraiwa/MPI for Chemistry

( -- New findings from German researchers at the Max Planck Institute for Chemistry and the Paul Scherrer Institute in Switzerland help to explain how toxic and allergy-causing substances in our air are formed. The scientists have for the first time detected long lived reactive oxygen intermediates on the surface of aerosol particles. These forms of oxygen survive here for more than 100 seconds and in that time react with other air pollutants such as nitrogen oxides. Chemically speaking, the dust particles are oxidized and nitrated. This is what makes soot particles more toxic and increases the potential of pollen to cause allergies.

Although scientists have suspected for years that these intermediate forms exist, it was believed that they disappeared within a fraction of a second, and therefore had little impact on chemical processes in the atmosphere. The intermediate forms of oxygen develop when reacts with particulate matter such as soot, polycyclic or pollen proteins.

"Not only does our research resolve earlier contradictions between theoretical calculations and measurements, it also shows that intermediates are also responsible for many atmospheric and physiological reactions," said Manabu Shiraiwa, lead author of the study.

Ulrich Pöschl, head of the aerosol research group at the Max Planck Institute in Mainz, goes one step further: "We suspect that the increase in allergies in industrialized countries is linked to these reactions. The more ozone and that are emitted by industry and traffic, the more frequently organic molecules such as birch pollen proteins are being nitrated and this is what irritates our immune system.” Pöschl and his colleagues have obtained evidence that these nitrated proteins can indeed cause more severe allergic reactions than the native form. If this hypothesis is confirmed, human health would be at even greater risk from combustion-related emissions than previously thought.

The reactive oxygen intermediates may also explain some of the direct adverse health effects of diesel soot and tobacco smoke particles. The polycyclic aromatic hydrocarbons found on the surface of these particles again readily react with ozone and form long-lived reactive oxygen intermediates. If the particles are inhaled, they interact directly with physiological processes in the human lung and other organs.

The scientists assume also that the oxygen intermediates may have an indirect effect on our climate. Presumably they are involved in the formation and growth of fine organic particles from volatile organic compounds emitted from both natural and manufactured sources such as vegetation and industrial activities. These particles scatter sunlight and influence the formation of clouds and precipitation, thus affecting the Earth’s energy balance and the hydrological cycle.

To quantify the atmospheric abundance and climatic effects of intermediates, the Mainz-based Max Planck researchers will perform further kinetic experiments and extensive, numerical simulations. In collaboration with biomedical partners, they are also investigating the physiological effects of nitrated proteins formed by the oxygen intermediates reacting with .

More information: Manabu Shiraiwa, et al. The role of long-lived reactive oxygen intermediates in the reaction of ozone with aerosol particles. Nature Chemistry, 20. Februar 2011; doi: 10.1038/NCHEM.988

Provided by Max-Planck-Gesellschaft (news : web)

Manipulating molecules for a new breed of electronics

ScienceDaily (Feb. 21, 2011) — In research recently appearing in the journal Nature Nanotechnology, Nongjian "NJ" Tao, a researcher at the Biodesign Institute at Arizona State University, has demonstrated a clever way of controlling electrical conductance of a single molecule, by exploiting the molecule's mechanical properties.

Such control may eventually play a role in the design of ultra-tiny electrical gadgets, created to perform myriad useful tasks, from biological and chemical sensing to improving telecommunications and computer memory.

Tao leads a research team used to dealing with the challenges entailed in creating electrical devices of this size, where quirky effects of the quantum world often dominate device behavior. As Tao explains, one such issue is defining and controlling the electrical conductance of a single molecule, attached to a pair of gold electrodes.

"Some molecules have unusual electromechanical properties, which are unlike silicon-based materials. A molecule can also recognize other molecules via specific interactions." These unique properties can offer tremendous functional flexibility to designers of nanoscale devices.

In the current research, Tao examines the electromechanical properties of single molecules sandwiched between conducting electrodes. When a voltage is applied, a resulting flow of current can be measured. A particular type of molecule, known as pentaphenylene, was used and its electrical conductance examined.

Tao's group was able to vary the conductance by as much as an order of magnitude, simply by changing the orientation of the molecule with respect to the electrode surfaces. Specifically, the molecule's tilt angle was altered, with conductance rising as the distance separating the electrodes decreased, and reaching a maximum when the molecule was poised between the electrodes at 90 degrees.

The reason for the dramatic fluctuation in conductance has to do with the so-called pi orbitals of the electrons making up the molecules, and their interaction with electron orbitals in the attached electrodes. As Tao notes, pi orbitals may be thought of as electron clouds, protruding perpendicularly from either side of the plane of the molecule. When the tilt angle of a molecule trapped between two electrodes is altered, these pi orbitals can come in contact and blend with electron orbitals contained in the gold electrode -- a process known as lateral coupling. This lateral coupling of orbitals has the effect of increasing conductance.

In the case of the pentaphenylene molecule, the lateral coupling effect was pronounced, with conductance levels increasing up to 10 times as the lateral coupling of orbitals came into greater play. In contrast, the tetraphenyl molecule used as a control for the experiments did not exhibit lateral coupling and conductance values remained constant, regardless of the tilt angle applied to the molecule. Tao says that molecules can now be designed to either exploit or minimize lateral coupling effects of orbitals, thereby permitting the fine-tuning of conductance properties, based on an application's specific requirements.

A further self-check on the conductance results was carried out using a modulation method. Here, the molecule's position was jiggled in 3 spatial directions and the conductance values observed. Only when these rapid perturbations specifically changed the tilt angle of the molecule relative to the electrode were conductance values altered, indicating that lateral coupling of electron orbitals was indeed responsible for the effect. Tao also suggests that this modulation technique may be broadly applied as a new method for evaluating conductance changes in molecular-scale systems.

The research was supported by the Department of Energy -- Basic Energy Science program.

In addition to directing the Biodesign Institute's Center for Bioelectronics and Biosensors, Tao is a professor in the School of Electrical, Computer, and Energy Engineering, at ASU's Ira A. Fulton Schools of Engineering, and an affiliated professor of chemistry and biochemistry, physics and material engineering.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Arizona State University. The original article was written by Richard Harth, Science Writer at The Biodesign Institute.

Journal Reference:

Ismael Diez-Perez, Joshua Hihath, Thomas Hines, Zhong-Sheng Wang, Gang Zhou, Klaus Müllen & Nongjian Tao. Controlling single-molecule conductance through lateral coupling of ? orbitals. Nature Nanotechnology, 20 February 2011 DOI: 10.1038/nnano.2011.20

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.