Saturday, December 10, 2011

When will artificial molecular machines start working for us?

Northwestern University chemists recently teamed up with a University of Maine physicist to explore the question, "Can artificial deliver on their promise?" Their provocative analysis provides a roadmap outlining future challenges that must be met before full realization of the extraordinary promise of synthetic molecular machines can be achieved.

The tutorial review will be published Nov. 25 by the journal Chemical Society Reviews.

The senior authors are Sir Fraser Stoddart, Board of Trustees Professor of Chemistry, and Bartosz A. Grzybowski, the K. Burgess Professor of , both in Northwestern's Weinberg College of Arts and Sciences, and Dean Astumian, professor of physics at the University of Maine. (Grzybowski is also professor of chemical and in the McCormick School of Engineering and Applied Science.)

One might ask, what is the difference between a switch and a machine at the level of a molecule? It all comes down to the molecule doing work.

"A simplistic analogy of an artificial is the piston in a car engine while idling," explains Ali Coskun, lead author of the paper and a postdoctoral fellow in Stoddart's laboratory. "The piston continually switches between up and down, but the car doesn't go anywhere. Until the pistons are connected to a crankshaft that, in turn, makes the car's wheels turn, the switching of the pistons only wastes energy without doing useful work."

Astumian points out that this analogy only takes us part of the way to understanding molecular machines. "All nanometer-scale machines are subject to continual bombardment by the molecules in their environment giving rise to what is called 'thermal noise,'" he cautions. "Attempts to mimic macroscopic approaches to achieve precisely controlled machines by minimizing the effects of thermal noise have not been notably successful."

Scientists currently are focused on a chemical approach where thermal noise is exploited for constructive purposes. Thermal "activation" is almost certainly at the heart of the mechanisms by which biomolecular machines in our cells carry out the essential tasks of metabolism. "At the of single molecules, harnessing energy is as much about preventing unwanted, backward motion as it is about causing forward motion," Astumian says.

In order to fulfill their great promise, artificial molecular machines need to operate at all scales. A single molecular switch interfaced to its environment can do useful work only on its own tiny scale, perhaps by assembling small molecules into chemical products of great complexity. But what about performing tasks in the macroscopic world?

To achieve this goal, "there is a need to organize the molecular switches spatially and temporally, just as in nature," Stoddart explains. He suggests that "metal-organic frameworks may hold the key to this particular challenge on account of their robust yet highly integrated architectures."

What is really encouraging is the remarkable energy-conversion efficiency of artificial molecular machines to perform useful work that can be greater than 75 percent. This efficiency is quite spectacular when compared to the efficiency of typical car engines, which convert only 20 to 30 percent of the chemical energy of gasoline into mechanical work, or even of the most efficient diesel engines with efficiencies of 50 percent.

"The reason for this high efficiency is that chemical energy can be converted directly into mechanical work, without having to be first converted into heat," Grzybowski says. "The possible uses of artificial molecular machines raise expectations expressed in the fact that the first person to create a nanoscale robotic arm, which shows precise positional control of matter at the nanoscale, can claim Feynman's Grand Prize of $250,000."

More information: The title of the paper is "Great Expectations: Can Artificial Molecular Machines Deliver on Their Promise?" In addition to Stoddart, Grzybowski, Coskun and Astumian, the other co-author of the paper is Michal Banaszak from Adam Mickiewicz University, Poland.

Provided by Northwestern University (news : web)

New class of drugs for the reversible inhibition of proteasomes

The proteasome, a large protein complex, carries out a vitally important function in the cells of the body. Similar to a recycling plant, it decomposes unneeded proteins into short pieces and recycles them. In this way it controls a number of functions in the cell. It regulates cell growth and division, decomposes damaged proteins and also acts as a key partner of the immune system in and inflammatory reactions. Because it is involved in so many important mechanisms within the cell, the proteasome is also associated with many diseases such as cancer, mucoviscidosis and a whole series of neurodegenerative disorders such as Parkinson's or Alzheimer's disease.

Due to its significant role in the growth of , in recent years the proteasome has taken center stage in as a starting point for cancer medication. When it becomes inhibited, the growth of cancer cells slows down. , the first drug to apply this strategy, generates revenues of over one billion US dollars per year in the meantime. It is used against , a cancer disease of the bone marrow. Yet in spite of all its successes, the proteasome inhibitors currently in use often have severe disadvantages. As a result of their high reactivity they attack other proteins, too, thereby damaging not only cancer cells but also other healthy cells.

The search for alternatives conducted by a group of scientists headed by Professor Michael Groll, who holds the Chair of Biochemistry in the Department of Chemistry at the TU M√ľnchen, in collaboration with Professor Robert Huber, Director Emeritus at the Max-Plank Institute of Biochemistry and Dr. Stefan Hillebrand from Bayer CropScience, has now borne fruit: In a high throughput screening, the scientists examined a substance library of 200,000 potential agents in their quest to identify proteasome inhibitors – and they were successful. They identified a new structure with the so-called N-hydroxyurea motif, which reacts not only reversibly but above all specifically with the active nucleus of the proteasome. The structure inhibits the function of particular subunits of the protein complexes, which are catalytically active, and thus incapacitates the enzyme. Because of this property, the newly discovered hydroxyurea structures work more specifically than other proteasome inhibitors and are thus expected to lead to less severe adverse side effects.

The scientists were already familiar with the basic hydroxyurea structure, albeit in a completely different context. The substance in question is a derivative of the agent zileuton, which is used to treat asthma. Zileuton itself does not influence the proteasome, but its derivative, which had so far received little attention, does. "We have now found a completely new application for this previously known class of substances," explains Michael Groll. "This is of great advantage, because there are already clinical trials that give us first indications of how this class of substances behaves in the human body."

The initial structure originally discovered in the database inhibited the proteasome very specifically, but not terribly effectively. In order to modify the substance in such a way that it also works in lower concentrations – such as those required for medication – it was an important next step to understand how exactly the structure attacks the proteasome. To shed further light on this, the scientists conducted a crystal structure analysis. The outcome was that the hydroxyurea motif attacked the proteasome in a completely different manner than all other previously known inhibitors. It reacts via hitherto unknown binding pockets that may serve as starting points for the development of the new medication agents.

Starting from preliminary modeling studies, the researchers synthesized a series of different derivatives of the agent, which were then examined using X-ray crystallography and activity tests to optimize the effectiveness of the structure. The results showed that the proteasome inhibiting activity of the hydroxyurea derivatives depends on the two side chains attached to the basic structure.

Because the proteasome is contained in every cell and involved in numerous cellular functions the new inhibiting structure offers a whole range of applications, not only in the field of oncology. In the context of autoimmune diseases, an inhibition of the immunoproteasome, a derivative of the proteasome, might play an important role. In the case of autoimmune diseases, including some forms of rheumatism, the immune system attacks the body's own tissue. If the immunoproteasome is inhibited such over-reactions might be weakened. In future studies Professor Groll's team plans to improve the effectiveness of the hydroxyurea structure via experiments on cell cultures.

More information: New class of non-covalent proteasome inhibitors: the hydroxyureas, Nerea Gallastegui, Phillip Beck, Marcelino Arciniega, Robert Huber, Stefan Hillebrand and Michael Groll, Angewandte Chemie, DOI: 10.1002/anie.201106010 Link:

Provided by Technische Universitaet Muenchen

Nanoparticle electrode for batteries could make grid-scale power storage feasible

 Stanford researchers have used nanoparticles of a copper compound to develop a high-power battery electrode that is so inexpensive to make, so efficient and so durable that it could be used to build batteries big enough for economical large-scale energy storage on the electrical grid -- something researchers have sought for years.

The research offers a promising solution to the problem of sharp drop-offs in the output of wind and solar systems with minor changes in weather conditions.

The sun doesn't always shine and the breeze doesn't always blow and therein lie perhaps the biggest hurdles to making wind and solar power usable on a grand scale. If only there were an efficient, durable, high-power, rechargeable battery we could use to store large quantities of excess power generated on windy or sunny days until we needed it. And as long as we're fantasizing, let's imagine the battery is cheap to build, too.

Now Stanford researchers have developed part of that dream battery, a new electrode that employs crystalline nanoparticles of a copper compound.

In laboratory tests, the electrode survived 40,000 cycles of charging and discharging, after which it could still be charged to more than 80 percent of its original charge capacity. For comparison, the average lithium ion battery can handle about 400 charge/discharge cycles before it deteriorates too much to be of practical use.

"At a rate of several cycles per day, this electrode would have a good 30 years of useful life on the electrical grid," said Colin Wessells, a graduate student in materials science and engineering who is the lead author of a paper describing the research, published this week in Nature Communications.

"That is a breakthrough performance -- a battery that will keep running for tens of thousands of cycles and never fail," said Yi Cui, an associate professor of materials science and engineering, who is Wessell's adviser and a coauthor of the paper.

The electrode's durability derives from the atomic structure of the crystalline copper hexacyanoferrate used to make it. The crystals have an open framework that allows ions -- electrically charged particles whose movements en masse either charge or discharge a battery -- to easily go in and out without damaging the electrode. Most batteries fail because of accumulated damage to an electrode's crystal structure.

Because the ions can move so freely, the electrode's cycle of charging and discharging is extremely fast, which is important because the power you get out of a battery is proportional to how fast you can discharge the electrode.

To maximize the benefit of the open structure, the researchers needed to use the right size ions. Too big and the ions would tend to get stuck and could damage the crystal structure when they moved in and out of the electrode. Too small and they might end up sticking to one side of the open spaces between atoms, instead of easily passing through. The right-sized ion turned out to be hydrated potassium, a much better fit compared with other hydrated ions such as sodium and lithium.

"It fits perfectly -- really, really nicely," said Cui. "Potassium will just zoom in and zoom out, so you can have an extremely high-power battery."

The speed of the electrode is further enhanced because the particles of electrode material that Wessell synthesized are tiny even by nanoparticle standards -- a mere 100 atoms across.

Those modest dimensions mean the ions don't have to travel very far into the electrode to react with active sites in a particle to charge the electrode to its maximum capacity, or to get back out during discharge.

A lot of recent research on batteries, including other work done by Cui's research group, has focused on lithium ion batteries, which have a high energy density -- meaning they hold a lot of charge for their size. That makes them great for portable electronics such as laptop computers.

But energy density really doesn't matter as much when you're talking about storage on the power grid. You could have a battery as big as a house since it doesn't need to be portable. Cost is a greater concern.

Some of the components in lithium ion batteries are expensive and no one knows for certain that making the batteries on a scale for use in the power grid will ever be economical.

"We decided we needed to develop a 'new chemistry' if we were going to make low-cost batteries and battery electrodes for the power grid," Wessells said.

The researchers chose to use a water-based electrolyte, which Wessells described as "basically free compared to the cost of an organic electrolyte" such as is used in lithium ion batteries. They made the battery electric materials from readily available precursors such as iron, copper, carbon and nitrogen -- all of which are extremely inexpensive compared with lithium.

The sole significant limitation to the new electrode is that its chemical properties cause it to be usable only as a high voltage electrode. But every battery needs two electrodes -- a high voltage cathode and a low voltage anode -- in order to create the voltage difference that produces electricity. The researchers need to find another material to use for the anode before they can build an actual battery.

But Cui said they have already been investigating various materials for an anode and have some promising candidates.

Even though they haven't constructed a full battery yet, the performance of the new electrode is so superior to any other existing battery electrode that Robert Huggins, an emeritus professor of materials science and engineering who worked on the project, said the electrode "leads to a promising electrochemical solution to the extremely important problem of the large number of sharp drop-offs in the output of wind and solar systems" that result from events as simple and commonplace as a cloud passing over a solar farm.

Cui and Wessells noted that other electrode materials have been developed that show tremendous promise in laboratory testing but would be difficult to produce commercially. That should not be a problem with their electrode.

Wessells has been able to readily synthesize the electrode material in gram quantities in the lab. He said the process should easily be scaled up to commercial levels of production.

"We put chemicals in a flask and you get this electrode material. You can do that on any scale," he said.

"There are no technical challenges to producing this on a big-enough scale to actually build a real battery."

Story Source:

The above story is reprinted from materials provided by Stanford University. The original article was written by Louis Bergeron.

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

Journal Reference:

Colin D. Wessells, Robert A. Huggins, Yi Cui. Copper hexacyanoferrate battery electrodes with long cycle life and high power. Nature Communications, 2011; 2: 550 DOI: 10.1038/ncomms1563

Charge separation in a molecule consisting of two identical atoms: Size matters

Physicists from the University of Stuttgart show the first experimental proof of a molecule consisting of two identical atoms that exhibits a permanent electric dipole moment. This observation contradicts the classical opinion described in many physics and chemistry textbooks.

The work was recently published in the journal Science.

A dipolar molecule forms as a result of a charge separation between the negative charged electron cloud and the positive core, creating a permanent electric dipole moment. Usually this charge separation originates in different attraction of the cores of different elements onto the negative charged electrons. Due to symmetry reasons homonuclear molecules, consisting only of atoms of the same element, therefore could not possess dipole moments.

However, the dipolar molecules that were discovered by the group of Prof. Tilman Pfau at the 5th Institute of Physics at the University of Stuttgart do consist of two atoms of the element rubidium. The necessary asymmetry arises as a result of different electronically excited states of the two alike atoms. Generally this excitation will be exchanged between the atoms and the asymmetry will be lifted. Here this exchange is suppressed by the huge size of the molecule, which is about 1000 times larger than an oxygen molecule and reaches sizes of viruses. Therefore the probability to exchange the excitation between the two atoms is so small that it would statistically only happen once in the lifetime of the universe. Consequently, these homonuclear molecules possess a dipole moment. A permanent dipole moment additionally requires an orientation of the molecular axis. Due to their size the molecules rotate so slowly that the dipole moment does not average out from the viewpoint of an observer.

Physicists from the University of Stuttgart succeeded in experimentally detecting the dipole moment. They measured the energy shift of the molecule in an electric field by laser spectroscopy in an ultra cold atomic cloud. The same group caused worldwide a stir when they created these weakly bound Rydberg molecules for the first time in 2009. The molecules consist of two identical atoms whereof one is excited to a highly excited state, a so-called Rydberg state. The unusual binding mechanism relies on scattering of the highly excited Rydberg electron of the second atom. So far theoretical descriptions of this binding mechanism did not predict a dipole moment. However, the scattering of the Rydberg electron of the bound atom changes the probability distribution of the electron. This breaks the otherwise spherical symmetry and creates a dipole moment. In collaboration with theoretical physicists from the Max-Plank-Institute for the Physics of Complex Systems in Dresden and from the Harvard-Smithonian Center for Astrophysics in Cambridge, USA, a new theoretical treatment was developed that confirms the observation of a dipole moment.

The proof of a permanent dipole moment in a homonuclear molecule not only improves the understanding of polar molecules. Ultra cold polar molecules are also promising to study and control chemical reactions of single molecules.

Story Source:

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

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

Journal Reference:

W. Li, T. Pohl, J. M. Rost, S. T. Rittenhouse, H. R. Sadeghpour, J. Nipper, B. Butscher, J. B. Balewski, V. Bendkowsky, R. Low, T. Pfau. A Homonuclear Molecule with a Permanent Electric Dipole Moment. Science, 2011; 334 (6059): 1110 DOI: 10.1126/science.1211255

Human skin yields stem cell-like cells

These skin cells, called keratinocytes, form the outermost layer of skin and can be cultured from discarded skin tissues or biopsy specimens.

The findings, published in the Nov. 4 edition of the peer-reviewed , may be beneficial for individuals with limited sources of endogenous stem cells.

The gene known as ?Np63? is highly synthesized in regenerating cells of various tissues. The UCLA researchers found that introducing ?Np63? into skin keratinocytes makes them lose their skin-cell characteristics and de-differentiate to resemble mesenchymal stem cells (MSCs), undifferentiated cells that can self-renew and differentiate to yield specialized cells of various types.

MSCs may serve as an internal repair system by replenishing cells needed for tissue regeneration and homeostasis and are currently being investigated for a number of regenerative therapeutics.

The conversion of keratinocytes into mesenchymal-like cells involves a process known as epithelial-mesenchymal transition. This is the first study to show that the gene ?Np63? triggers this process in keratinocytes and that the transformed cells acquire multipotent stem cell characteristics.

Since the transformed by ?Np63? are induced to acquire the mesenchymal and stem cell characteristics, the research team named them "induced mesenchymal stem cells," or iMSCs. Specifically, the researchers demonstrated that iMSCs can be triggered to form bone-like tissues or become fat tissues in a laboratory setting.

Dr. Mo K. Kang, the Jack A. Weichman Chair of Endodontics at the UCLA School of Dentistry and a member of the research team, said the finding had great significance for human health.

"Since iMSCs may be obtained by taking a small punch-biopsy of skin tissues from patients, these cells are an easily accessible, patient-specific source of stem cells, which can be used for regenerative purposes," Kang said.

Stem cell-based therapies are currently being developed to treat degenerative conditions such as heart disease, diabetes, neuronal disorders and liver diseases. Many of these diseases are strongly associated with aging. Endogeneous MSCs found in various tissues, such as bone marrow, fat tissues and, in certain cases, dental tissues such as dental pulp, lose their regenerative potential during the aging process.

"It is possible that iMSCs retain their stem-cell characteristics even when derived from aged patients," Kang said. "In such cases, this new approach may be useful, especially for geriatric patients or individuals with limited therapeutic value of their endogenous stem cells."

"The UCLA School of Dentistry is very proud to be at the forefront of this research inquiry, which may facilitate future advances in regenerative dentistry and medicine," said Dr. No-Hee Park, dean of the UCLA School of Dentistry and one of the study's co-authors. "While the focus of this study was on the use of adult to regenerate dental tissue, including dental pulp and periodontal ligament, these findings could lead to further development of a variety of cell-based therapies."

Provided by University of California