New insights into the cohesive forces of crystal structures

 A study published in the journal Nature Chemistry, conducted by researchers from the University of Barcelona and the Hebrew University of Jerusalem, has shown that under certain conditions the interactions between carbon-hydrogen (CH) groups, commonly found in organic compounds, may be much stronger than previously thought.

The study focuses on the polyhedranes formed by carbon atoms surrounding hydrogen atoms, in particular their capacity to form stable crystal structures with melting temperatures of up to 400 oC. According to Santiago Alvarez, a professor with the Department of Inorganic Chemistry and researcher for the UB's Institute of Theoretical and Computational Chemistry, "In the study we have found that polyhedranes meet various chemical conditions that enable them to exhibit stronger hydrogen interactions than had been thought possible. In particular, we have seen that interaction is strongly favoured by the fact that the carbon atom holding the hydrogen is connected to a large skeleton structure containing more carbon atoms."

The team of researchers carried out a systematic computational study of homopolar hydrogen bonds (CH•••HC), the name given to the forces that bind polyhedrane structures. The results show that the flatter the surface of the polyhedrane, the stronger the intermolecular interactions in the structure, and the team also observed that the spherical form of the examples studied allows them to establish interactions with neighbouring molecules in multiple directions. "The combination of these factors explains the strong cohesive forces in polyhedranes, which require high temperatures to break the three-dimensional structure and form a liquid," explains Santiago Alvarez.

"These types of interactions are ubiquitous in the molecular chemistry of organic, organometallic and coordination compounds, and we believe that this widespread presence will require us to reconsider previous studies of aspects such as the relative stabilities of the different crystal structures in a single compound," says Alvarez. This is an important consideration in the design of synthetic compounds, particularly for the pharmaceutical industry, since each form of a single compound, or polymorph, exhibits different pharmacological properties and industrial patents cover only one of these polymorphs, making the identification of a new form a patentable discovery.

Story Source:

The above story is reprinted  from materials provided by Universidad de Barcelona, via AlphaGalileo.

Journal Reference:

Jorge Echeverría, Gabriel Aullón, David Danovich, Sason Shaik, Santiago Alvarez. Dihydrogen contacts in alkanes are subtle but not faint. Nature Chemistry, 2011; 3 (4): 323 DOI: 10.1038/NCHEM.1004

 

Quantum mapmakers complete first voyage through spin liquid

Scientists from Oxford University have mapped a state of matter called 'quantum spin liquid', whose existence was proposed in the 1970s but which has only been observed recently.

Until now there has been very limited information describing the physical characteristics of a quantum spin liquid state, but researchers from Oxford University's Department of Physics working with the Rutherford Appleton Laboratory have demonstrated the effect of temperature and magnetic field on this state of matter. The results are published in a Nature paper.

The scientists mapped quantum spin liquid by implanting muons -- sub-atomic particles which come from space but can also be produced in particle accelerators -- into the spin liquid in order to measure the microscopic magnetism. The experiments used the muon sources at ISIS in Oxfordshire and the Paul Scherrer Institute in Switzerland.

Professor Stephen Blundell of the Department of Physics explained: 'Muons are an excellent tool for this kind of study because they are a very sensitive probe of weak magnetism and fluctuating states, just as we have now found in mapping the spin liquid state.'

The quantum spin liquid state is found in 70 milligrams of tiny black crystals of an organic material cooled to just a couple of hundredths of a degree above absolute zero. Inside the material, magnetic atoms are arranged on triangular grids and behave as 'quantum spins'. The interactions between these spins make them liquid-like, so they never freeze into one configuration. This behaviour is completely different to that of more familiar magnets found in everyday life in which, at some particular temperature, the quantum spins become locked into a particular configuration.

Dr Tom Lancaster of the Department of Physics said: 'The organic material we have used is a really remarkable compound. This is because its interactions seem perfectly tuned to achieve this spin liquid state.'

Dr Francis Pratt of the Rutherford Appleton Laboratory said: 'Since the idea was proposed there have been over 800 papers published speculating on the properties of quantum spin liquids, but until now there has been very little experimental evidence to compare these ideas with.'

Story Source:

The above story is reprinted from materials provided by University of Oxford.

Journal Reference:

F. L. Pratt, P. J. Baker, S. J. Blundell, T. Lancaster, S. Ohira-Kawamura, C. Baines, Y. Shimizu, K. Kanoda, I. Watanabe, G. Saito. Magnetic and non-magnetic phases of a quantum spin liquid. Nature, 2011; 471 (7340): 612 DOI: 10.1038/nature09910

Next-generation computers: Advance in microchannel manufacturing opens new industry applications

Engineers at Oregon State University have invented a new way to use surface-mount adhesives in the production of low-temperature, microchannel heat exchangers -- an advance that will make this promising technology much less expensive for many commercial applications.

This type of technology will be needed, researchers say, in next-generation computers, lasers, consumer electronics, automobile cooling systems, fuel processors, miniature heat pumps and more.

New industries and jobs are possible. A patent has been applied for, the findings reported in the Journal of Manufacturing Processes, and the university is seeking a partner for further commercial development.

"Even though microchannel arrays have enormous potential for more efficient heat transfer and chemical reactions, high production costs have so far held back the broad, mainstream use of the technology," said Brian Paul, a professor in the OSU School of Mechanical, Industrial and Manufacturing Engineering.

"In certain applications, this new approach has reduced material costs by 50 percent," Paul said. "It could cut production bonding costs by more than 90 percent, compared to existing approaches to microchannel lamination. And the use of surface-mount adhesives is directly translatable to the electronics assembly industry, so there is less risk going to market.

"This type of manufacturing research could enable a microchannel revolution," he said.

Microchannels, the diameter of a human hair, can be patterned into the surface of a metal or plastic, and can be designed to speed up the heat exchange between fluids, or the mixing and separation of fluids during chemical reactions. The accelerated heat and mass transfer leads to smaller heat exchangers and chemical reactors and separators, such as a portable "home dialysis" system that evolved out of previous OSU research.

Cost and production issues, however, have until now constrained the wider industrial use of this technology. The new manufacturing technique developed at OSU should help change that.

"We have demonstrated the use of surface-mount adhesives to create microchannels on a wide variety of metals, including aluminum, which is very cheap," said Prawin Paulraj, an OSU doctoral candidate and lead author on the recent study. "Bonding aluminum is difficult with conventional techniques."

These very thin pieces of patterned metal -- akin to aluminum foil -- can be bonded one on top of another to increase the number of microchannels in a heat exchanger, and the amount of fluid that can be processed. Creation of laminated microchannel arrays in a wide variety of materials is possible, including aluminum, copper, titanium, stainless steel and other metals.

"In computers and electronics, the heat generated by the electrical circuit is a limiting factor in how small you can make it," Paulraj said. "Microchannel process technology provides an efficient way to cool computers and consumer electronics, and make them even smaller."

The adhesives are limited in temperature to about that of boiling water. The researchers say that possible uses might include radiators to cool an automobile engine or small, very efficient heat pumps for efficient air conditioning within buildings.

This research was conducted at the Microproducts Breakthrough Institute, a user facility of the Oregon Nanoscience and Microtechnologies Institute.

University officials are now seeking a commercial partner in private industry to continue development and marketing of the technology, according to Denis Sather, a licensing associate in the OSU Office for Commercialization and Corporate Development.

Story Source:

The above story is reprinted from materials provided by Oregon State University.

Journal Reference:

Prawin, Paulraj and Paul, Brian K. Metal Microchannel Lamination Using Surface Mount Adhesives for Low-Temperature Heat Exchangers. Journal of Manufacturing Processes, Mar 12, 2011 [link]

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Toward a solution to nerve agent exposure: Chemist uses supercomputers to test reagents for new treatments

Scientists are working to develop a new drug that will regenerate a critical enzyme in the human body that "ages" after a person is exposed to deadly chemical warfare agents.

Christopher Hadad, Ph.D., professor of chemistry at The Ohio State University (OSU), is leveraging Ohio Supercomputer Center (OSC) resources to help develop a more effective antidote to lethal chemicals called organophosphorus (OP) nerve agents.

"This project is a combination of synthetic and computational organic chemistry conducted through OSC at Ohio State, and biochemical studies conducted by colleagues at the U.S. Army Medical Research Institute of Chemical Defense at Aberdeen Proving Ground in Maryland," said Hadad.

OP nerve agents inhibit the ability of an enzyme called acetylcholinesterase (AChE) to turn off the messages being delivered by acetylcholine (ACh), a neurotransmitter, to activate various muscles, glands and organs throughout the body. After exposure to OP agents, AChE undergoes a series of reactions, culminating in an "aging" process that inactivates AChE from performing its critical biological function. Without the application of an effective antidote, neurosynaptic communication continues unabated, resulting in uncontrolled secretions from the mouth, eyes and nose, as well as severe muscle spasms, which, if untreated, result in death.

Conventional antidotes to OP nerve agents block the activity of the nerve agent by introducing oxime compounds, which have been the focus of a number of studies. These compounds attach to the phosphorus atom of the nerve agent, after the OP is bound to AChE, and then split it away from the AChE enzyme, allowing the AChE to engage with receptors and finally relax the tissues.

However, in some cases, the combined nerve agent/AChE molecule undergo a process called aging, in which groups of single-bonded carbon and hydrogen atoms called alkyl groups are removed from the molecule and a phosphonate residue is left behind in the AChE active site. Relatively unstudied in nerve agents, this process, called dealkylation, makes the nerve agent/AChE molecule unreceptive to oximes -- an unfortunate situation, considering that certain nerve agents (e.g., soman) can undergo aging within minutes of exposure to AChE.

Hadad's study is focused on the identification of compounds that would return an appropriate alkyl group to the aged nerve agent/AChE molecule, thus allowing treatment with oximes to provide for complete recovery. The project is investigating common OP nerve agents Tabun, VX, VR, Sarin, Soman, Cyclosarin and Paraoxon, all of which take on a similar molecular structure upon aging.

"Computational studies of the interaction of the alkylating compounds with AChE were used to provide insight for the design of selective reagents," Hadad explained. "Ligand-receptor docking, followed by molecular dynamics simulations of the interactions of alkylating compounds with aged OP-AChE, was carried out in conjunction with experimental studies to investigate the binding of alkylating compounds to AChE. These results were then used to suggest interactions that aided in the orientation of alkylating compounds for maximal efficacy."

Throughout the project, Hadad employed computational studies to guide the progress of each objective, as well as to rationalize the observed experimental results.

"Dr. Hadad's work on this project has made use of a range of the tools of electronic structure theory, molecular docking, molecular dynamics and hybrid quantum mechanical/molecular mechanical methods," said Ashok Krishnamurthy, interim co-executive director of OSC. "It was by design that OSC's flagship system, the Glenn IBM 1350 Opteron cluster, was developed to meet the needs of the bioscience research investigators, such as Dr. Hadad."

Hadad's investigations of nerve agent antidotes are funded by the Defense Threat Reduction Agency (W81XWH-10-2-0044) and supported by the award of an OSC Discovery Account.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Ohio Supercomputer Center.

Nano Fitness: Helping enzymes stay active and keep in shape

Proteins are critically important to life and the human body. They are also among the most complex molecules in nature, and there is much we still don't know or understand about them.

One key challenge is the stability of enzymes, a particular type of protein that speeds up, or catalyzes, chemical reactions. Taken out of their natural environment in the cell or body, enzymes can quickly lose their shape and denature. Everyday examples of enzymes denaturing include milk going sour, or eggs turning solid when boiled.

Rensselaer Polytechnic Institute Professor Marc-Olivier Coppens has developed a new technique for boosting the stability of enzymes, making them useful under a much broader range of conditions. Coppens confined lysozyme and other enzymes inside carefully engineered nanoscale holes, or nanopores. Instead of denaturing, these embedded enzymes mostly retained their 3-D structure and exhibited a significant increase in activity.

"Normally, when you put an enzyme on a surface, its activity goes down. But in this study, we discovered that when we put enzymes in nanopores -- a highly controlled environment -- the enzymatic activity goes up dramatically," said Coppens, a professor in the Department of Chemical and Biological Engineering at Rensselaer. "The enzymatic activity turns out to be very dependent on the local environment. This is very exciting."

Results of the study were published last month by the journal Physical Chemistry Chemical Physics.

Researchers at Rensselaer and elsewhere have made important discoveries by wrapping enzymes and other proteins around nanomaterials. While this immobilizes the enzyme and often results in high stability and novel properties, the enzyme's activity decreases as it loses its natural 3-D structure.

Coppens took a different approach, and inserted enzymes inside nanopores. Measuring only 3-4 nanometers (nm) in size, the enzyme lysozyme fits snugly into a nanoporous material with well-controlled pore size between 5 nm and 12 nm. Confined to this compact space, the enzymes have a much harder time unfolding or wiggling around, Coppens said.

The discovery raises many questions and opens up entirely new possibilities related to biology, chemistry, medicine, and nanoengineering, Coppens said. He envisions this technology could be adapted to better control nanoscale environments, as well as increase the activity and selectivity of different enzymes. Looking forward, Coppens and colleagues will employ molecular simulations, multiscale modeling methods, and physical experiments to better understand the fundamental mechanics of confining enzymes inside nanopores.

The study was co-authored by Lung-Ching Sang, a former Rensselaer graduate student in the Department of Chemical and Biological Engineering.

This research was supported by the National Science Foundation, via the Nanoscale Science and Engineering Center for Directed Assembly of Nanostructures at Rensselaer. The project was also supported by the International Center for Materials Nanoarchitectonics of the National Institute for Materials Science, Japan.

Story Source:

The above story is reprinted  from materials provided by Rensselaer Polytechnic Institute.

Journal Reference:

Lung-Ching Sang, Marc-Olivier Coppens. Effects of surface curvature and surface chemistry on the structure and activity of proteins adsorbed in nanopores. Physical Chemistry Chemical Physics, 2011; 13 (14): 6689 DOI: 10.1039/C0CP02273J

Nanopolymer shows promise for helping reduce cancer side effects

A Purdue University biochemist has demonstrated a process using nanotechnology to better assess whether cancer drugs hit their targets, which may help reduce drug side effects.

W. Andy Tao, an associate professor of biochemistry analytical chemistry, developed a nanopolymer that can be coated with drugs, enter cells and then removed to determine which proteins in the cells the drug has entered. Since they're water-soluble, Tao believes the nanopolymers also may be a better delivery system for drugs that do not dissolve in water effectively.

"Many cancer drugs are not very specific. They target many different proteins," said Tao, whose findings were published in the early online in the journal Agnewandte Chemie International Edition. "That can have a consequence -- what we call side effects."

In addition to the drug, the synthetic nanopolymer is equipped with a chemical group that is reactive to small beads. The beads retrieve the nanopolymer and any attached proteins after the drug has done its work. Tao uses mass spectrometry to determine which proteins are present and have been targeted by the drug.

Knowing which proteins are targeted would allow drug developers to test whether new drugs target only desired proteins or others as well. Eliminating unintended protein targets could reduce the often-serious side effects associated with cancer drugs.

Tao said there currently is no reliable way to test drugs for off-targeting. He said drugs are often designed to inhibit or activate the function of a biomolecule associated with cancer, but those drugs tend to fail in late-stage clinical tests.

Tao also believes his nanopolymers could better deliver drugs to their targets. Since they are nanosized and water soluble, the nanopolymers could gain access to cells more effectively than a standalone drug that is only minimally water-soluble.

Tao demonstrated the nanopolymer's abilities using human cancer cells and the cancer drug methotrexate. The nanopolymers were tracked using a fluorescent dye to show they were entering cells. Then, Tao broke the cells and retrieved the nanopolymers.

Tao has shown the nanopolymer's ability using a metabolic drug, which are small, low-cost drugs but are less target specific and have more side-effects. He now plans to do the same using drugs that are based on synthetic peptides, which are larger and more expensive but more specific and with fewer side effects.

The National Institutes of Health's National Center for Research Resources and a National Science Foundation Career Grant funded the research.

Story Source:

The above story is reprinted from materials provided by Purdue University. The original article was written by Brian Wallheimer.

Journal Reference:

Lianghai Hu, Anton Iliuk, Jacob Galan, Michael Hans, W. Andy Tao. Identification of Drug Targets In Vitro and in Living Cells by Soluble-Nanopolymer-Based Proteomics. Angewandte Chemie International Edition, 2011; DOI: 10.1002/anie.201006459

Electron microscopy: New type of genetic tag illuminates life in never-before-seen detail

By modifying a protein from a plant that is much favored by science, researchers at the University of California, San Diego School of Medicine and colleagues have created a new type of genetic tag visible under an electron microscope, illuminating life in never-before-seen detail.

Led by Nobel laureate Roger Tsien, PhD, Howard Hughes Medical Institute investigator and UCSD professor of pharmacology, chemistry and biochemistry, a team of scientists radically re-engineered a light-absorbing protein from the flowering cress plant Arabidopsis thaliana. When exposed to blue light, the altered protein produces abundant singlet oxygen, a form of molecular oxygen that can be made visible by electron microscopy (EM).

The findings are published in the online, open access journal PLoS Biology.

Tsien was co-winner of the 2008 Nobel Prize in chemistry for his role in helping develop and expand the use of green fluorescent protein (GFP), a protein from jellyfish that is now widely employed in light microscopy to peer inside living cells or whole animals and observe molecules interacting in real-time. Tsien said the development of the small, highly engineered Arabidopsis protein, dubbed "miniSOG," may elevate the abilities of electron microscopy in the same way that GFP and its relatives have made modern light microscopy in biological research much more powerful and useful.

"The big advantage of EM is that it has much higher spatial resolution than light microscopy. You can get up to a hundred-fold higher useful magnification from EM than from light microscopy," said Tsien. The result has been extraordinarily detailed, three-dimensional images of microscopic objects at resolutions measuring in the tens of nanometers, tiny enough to meticulously render the internal anatomy of individual cells. But current EM technologies do not distinguish or highlight individual proteins in these images. Although individual proteins can be tagged with GFP or other fluorescent proteins to aid localization by light microscopy, there has been no equivalent technology for the higher-resolution images provided by EM.

To create this ability, the scientists began with a protein from Arabidopsis that absorbs incoming blue light. It's normal function is to trigger biochemical signals that inform the plant how much sunlight it is receiving. "We rationally engineered the protein based on its atomic model so that it changes incoming blue light into a little bit of green fluorescence and a lot of singlet oxygen," said the paper's first author, Xiaokun Shu, now an assistant professor at UC San Francisco. Established methods were then used to convert singlet oxygen production into a tissue stain that the electron microscope can "see." The scientists tested the modified protein's utility as an EM marker by first using it to confirm the locations of several well-understood proteins in mammalian cells, nematodes and rodents, and then used miniSOG to successfully tag two neuronal proteins in mice whose locations had not been known.

Tsien is optimistic that miniSOG will grant new powers to electron microscopy, permitting scientists to pursue answers to questions previously impossible to ask. MiniSOG will especially be useful to scientists who investigate cellular and subcellular structures including neuronal circuits at nanometer resolution in multicellular organisms since previous methods have great difficulty in achieving both efficient labeling and good preservation of the structures under study. While EM can provide much higher useful magnification than light microscopy, EM will not replace light microscopy. "When we use miniSOG, we see the tagged proteins plus the landmarks that we are used to navigating by," said Tsien. "On the other hand, EM has the disadvantage that it gives a snapshot of cells before we killed them (to make the image), whereas light microscopy can show the dynamics in live cells. Each technique has different complementary strengths and weaknesses."

Co-authors of the paper include: Varda Lev-Ram, UCSD Department of Pharmacology; Thomas J. Deerinck, National Center for Microscopy and Imaging Research, Center for Research on Biological Systems, UCSD; Yingchuan Qi and Yishi Jin, Howard Hughes Medical Institute, UCSD and UCSD Division of Biological Science; Ericka B. Ramko and Michael W. Davidson, National High Magnetic Field Laboratory and Department of Biological Science, Florida State University; and Mark H. Ellisman, National Center for Microscopy and Imaging Research, Center for Research on Biological Systems, UCSD and UCSD Department of Neurosciences

Story Source:

The above story is reprinted  from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

Journal Reference:

Xiaokun Shu, Varda Lev-Ram, Thomas J. Deerinck, Yingchuan Qi, Ericka B. Ramko, Michael W. Davidson, Yishi Jin, Mark H. Ellisman, Roger Y. Tsien. A Genetically Encoded Tag for Correlated Light and Electron Microscopy of Intact Cells, Tissues, and Organisms. PLoS Biology, 2011; 9 (4): e1001041 DOI: 10.1371/journal.pbio.1001041