New field of chemistry has potential for making drugs inside patients -- and more

The traditional way of making medicines from ingredients mixed together in a factory may be joined by a new approach in which doctors administer the ingredients for a medicine separately to patients, and the ingredients combine to produce the medicine inside patients' bodies.

That's one promise from an emerging new field of chemistry, according to the scientist who founded it barely a decade ago. Carolyn Bertozzi, Ph.D., spoke on the topic -- bioorthogonal chemistry -- in San Diego on March 27 in delivering the latest Kavli Foundation Innovations in Chemistry Lecture at the 243rd National Meeting & Exposition of the American Chemical Society (ACS).

Bertozzi explained that the techniques of bioorthogonal chemistry may fundamentally change the nature of drug development and diagnosis of disease, so that the active ingredients for medicines and substances to image diseased tissue are produced inside patients.

"Suppose a drug doesn't reach diseased tissue in concentrations high enough to work," Bertozzi said, citing one example of the potential of the new chemistry. "Maybe it is an oral drug that doesn't get absorbed very well into the blood through the stomach. You can imagine a scenario in which doctors administer two parts of the molecule that makes up the drug. The two units reach diseased tissue in large amounts or get absorbed through the stomach just fine. Then they recombine, producing the actual drug in the patient's body. Bioorthogonal chemistry is chemistry for life…literally!"

Bertozzi explained that bioorthogonal chemistry opens the door to creating new proteins, fats and sugars directly inside living cells without harming them. The field emerged from her frustration in the late 1990s with the lack of tools available to see sugars on the surfaces of living cells. Chains of these sugars, called glycans, sit on the surfaces of cells in the body and control the doorways through which different molecules enter. When a disease-causing virus enters and infects a cell, for instance, proteins on the virus's surface attach to certain glycans.

"To do that, we had to come up with a chemical reaction that would be really selective, only targeting the sugar of interest and the fluorescent probes that we delivered to it," said Bertozzi. The chemicals also couldn't stick to other biomolecules that the researchers didn't want to see.

That turned out to be a tall order, indeed. "We pulled all of our big textbooks off the shelves and flipped through them to see if there was something out there that fit our criteria," she said. Those criteria were essentially the conditions inside a living cell or living organism such as a mouse -- a reaction that could occur in water at pH 7 and at 98.6 degrees Fahrenheit. The reaction also couldn't interfere with all the other biomolecules in a cell or organism that keep it alive.

"It was a pretty restrictive set of conditions that a traditionally trained organic chemist like me never had to work within," she explained. That's because these types of reactions are usually performed in very clean, dry test tubes and flasks under conditions that the chemist can control. A living cell or organism, with all its water, proteins, fats, sugars and metabolites is very messy and uncontrollable by comparison.

Bertozzi and her team at the University of California, Berkeley, went on to develop a slew of reactions that can add fluorescent labels to biomolecules.

Now, the field is exploding, with her group and others reporting new bioorthogonal chemical reactions every year that help researchers see sugars, fats, proteins, and even DNA and RNA, that can't be seen using conventional methods. Researchers currently use the reactions not only to see where a biomolecule is within a living cell or organism, but also to determine when a biomolecule is made and what it binds to. Researchers also are using the methods to add things besides labels, like drugs, to various biomolecules. Some of the chemicals used for the reactions are currently available separately or in kits.

Several of Bertozzi's reactions are patented, and some are licensed to companies, including Redwood Bioscience, a company she co-founded with David Rabuka, Ph.D. The company is focused on bringing this technology to the clinic.

The scientists acknowledged funding from the National Institutes of Health and the Howard Hughes Medical Institute.

Story Source:

The above story is reprinted from materials provided by American Chemical Society (ACS), via Newswise.

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

Lab mimics Jupiter's Trojan asteroids inside a single atom

 Rice University physicists have gone to extremes to prove that Isaac Newton's classical laws of motion can apply in the atomic world: They've built an accurate model of part of the solar system inside a single atom of potassium.

In a new paper published this week in Physical Review Letters, Rice's team and collaborators at the Oak Ridge National Laboratory and the Vienna University of Technology showed they could cause an electron in an atom to orbit the nucleus in precisely the same way that Jupiter's Trojan asteroids orbit the sun.

The findings uphold a prediction made in 1920 by famed Danish physicist Niels Bohr about the relationship between the then-new science of quantum mechanics and Newton's tried-and-true laws of motion.

"Bohr predicted that quantum mechanical descriptions of the physical world would, for systems of sufficient size, match the classical descriptions provided by Newtonian mechanics," said lead researcher Barry Dunning, Rice's Sam and Helen Worden Professor of Physics and chair of the Department of Physics and Astronomy. "Bohr also described the conditions under which this correspondence could be observed. In particular, he said it should be seen in atoms with very high principal quantum numbers, which are exactly what we study in our laboratory."

Bohr was a pioneer of quantum physics. His 1913 atomic model, which is still widely invoked today, postulated a small nucleus surrounded by electrons moving in well-defined orbits and shells. The word "quantum" in quantum mechanics derives from the fact that these orbits can have only certain well-defined energies. Jumps between these orbits lead to absorption or emission of specific amounts of energy termed quanta. As an electron gains energy, its quantum number increases, and it jumps to higher orbits that circle ever farther from the nucleus.

In the new experiments, Rice graduate students Brendan Wyker and Shuzhen Ye began by using an ultraviolet laser to create a Rydberg atom. Rydberg atoms contain a highly excited electron with a very large quantum number. In the Rice experiments, potassium atoms with quantum numbers between 300 and 600 were studied.

"In such excited states, the potassium atoms become hundreds of thousands of times larger than normal and approach the size of a period at the end of a sentence," Dunning said. "Thus, they are good candidates to test Bohr's prediction."

He said comparing the classical and quantum descriptions of the electron orbits is complicated, in part because electrons exist as both particles and waves. To "locate" an electron, physicists calculate the likelihood of finding the electron at different locations at a given time. These predictions are combined to create a "wave function" that describes all the places where the electron might be found. Normally, an electron's wave function looks like a diffuse cloud that surrounds the atomic nucleus, because the electron might be found on any side of the nucleus at a given time.

Dunning and co-workers previously used a tailored sequence of electric field pulses to collapse the wave function of an electron in a Rydberg atom; this limited where it might be found to a localized, comma-shaped area called a "wave packet." This localized wave packet orbited the nucleus of the atom much like a planet orbits the sun. But the effect lasted only for a brief period.

"We wanted to see if we could develop a way to use radio frequency waves to capture this localized electron and make it orbit the nucleus indefinitely without spreading out," Ye said.

They succeeded by applying a radio frequency field that rotated around the nucleus itself. This field ensnared the localized electron and forced it to rotate in lockstep around the nucleus.

A further electric field pulse was used to measure the final result by taking a snapshot of the wave packet and destroying the delicate Rydberg atom in the process. After the experiment had been run tens of thousands of times, all the snapshots were combined to show that Bohr's prediction was correct: The classical and quantum descriptions of the orbiting electron wave packets matched. In fact, the classical description of the wave packet trapped by the rotating field parallels the classical physics that explains the behavior of Jupiter's Trojan asteroids.

Jupiter's 4,000-plus Trojan asteroids -- so called because each is named for a hero of the Trojan wars -- have the same orbit as Jupiter and are contained in comma-shaped clouds that look remarkably similar to the localized wave packets created in the Rice experiments. And just as the wave packet in the atom is trapped by the combined electric field from the nucleus and the rotating wave, the Trojans are trapped by the combined gravitational field of the sun and orbiting Jupiter.

The researchers are now working on their next experiment: They're attempting to localize two electrons and have them orbit the nucleus like two planets in different orbits.

"The level of control that we're able to achieve in these atoms would have been unthinkable just a few years ago and has potential applications in, for example, quantum computing and in controlling chemical reactions using ultrafast lasers," Dunning said.

The research was funded by the National Science Foundation, the Robert A. Welch Foundation, the Austrian Science Fund and the Department of Energy. Paper co-authors include S. Yoshida of the Vienna University of Technology; C.O. Reinhold of Oak Ridge National Laboratory and the University of Tennessee; and J. Burgdörfer of Vienna University of Technology and the University of Tennessee.

Story Source:

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

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

Journal Reference:

B. Wyker, S. Ye, F. Dunning, S. Yoshida, C. Reinhold, J. Burgdörfer. Creating and Transporting Trojan Wave Packets. Physical Review Letters, 2012; 108 (4) DOI: 10.1103/PhysRevLett.108.043001

New material synthesized: Graphene nanoribbons inside of carbon nanotubes

Physicists from Umea University (Sweden) and Finland have found an efficient way to synthesize graphene nanoribbons directly inside of single-walled carbon nanotubes.

The result was recently published in the journal Nano Letters.

Graphene, a one atom thin flake of plain carbon, has a wide range of unusual and highly interesting properties. As a conductor of electricity it performs as well as copper. As a conductor of heat it outperforms all other known materials. There are possibilities to achieve strong variations of the graphene properties by making graphene in the form of belts with various widths, so called nanoribbons. These nanoribbons are now the real focus of attention in physics and an extremely promising material for electronics, solar cells and many other things. However, it is has not been easy to make such ribbons.

Associate professor Alexandr Talyzin and his research group at the Department of Physics, Umea University, have together with colleagues from Professor Esko Kauppinen´s group, Aalto University in Finland, discovered a way to use the hollow space inside carbon nanotubes as a one-dimensional chemical reactor to make encapsulated graphene. An intriguing property of this space is that chemical reactions occur differently here compared to under bulk three-dimensional conditions.

"We used coronene and perylene, which are large organic molecules, as building blocks to produce long and narrow graphene nanoribbons inside the tubes. The idea of using these molecules as building blocks for graphene synthesis was based on our previous study," says Talyzin.

This study revealed that coronene molecules can react with each other at certain conditions to form dimers, trimers and longer molecules in a bulk powder form. The result suggested that coronene molecules can possibly be used for synthesis of graphene but need to be somehow aligned in one plane for the required reaction. The inner space of single-walled carbon nanotubes seemed to be an ideal place to force molecules into the edge-to-edge geometry required for the polymerization reaction.

In the new study, the researchers show that this is possible. When the first samples were observed by electron microscopy by Ilya Anoshkin at Aalto University, exciting results were revealed: all nanotubes were filled inside with graphene nanoribbons.

"The success of the experiments also depended a lot on the choice of nanotubes. Nanotubes of suitable diameter and in high quality were provided by our co-authors from Aalto University," says Talyzin.

Later the researchers found that the shape of encapsulated graphene nanoribbons can be modified by using different kinds of aromatic hydrocarbons. The properties of nanoribbons are very different depending on their shape and width. For example, nanoribbons can be either metallic or semiconducting depending on their width and type. Interestingly, carbon nanotubes can also be metallic, semiconducting (depending on their diameter) or insulating when chemically modified.

"This creates an enormous potential for a wide range of applications. We can prepare hybrids that combine graphene and nanotubes in all possible combinations in the future," says Talyzin.

For example, metallic nanoribbons inside insulating nanotubes are very thin insulated wires. They might be used directly inside carbon nanotubes to produce light thus making nano-lamps. Semiconducting nanoribbons can possibly be used for transistors or solar cell applications and metallic-metallic combination is in fact a new kind of coaxial nano-cable, macroscopic cables of this kind are used e.g. for transmitting radio signals.

The new method of hybrid synthesis is very simple, easily scalable and allows obtaining almost 100 percent filling of tubes with nanoribbons. The theoretical simulations, performed by Arkady Krasheninnikov in Finland, also show that the graphene nanoribbons keep their unique properties inside the nanotubes while protected from the environment by encapsulation and aligned within bundles of single-walled nanotubes.

"The new material seems very promising, but we have a lot of inter-disciplinary work ahead of us in the field of physics and chemistry. To synthesize the material is just a beginning. Now we want to learn its electric, magnetic and chemical properties and how to use the hybrids for practical applications," says Talyzin.

Story Source:

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

Journal Reference:

Alexandr V. Talyzin, Ilya V. Anoshkin, Arkady V. Krasheninnikov, Risto M. Nieminen, Albert G. Nasibulin, Hua Jiang, Esko I. Kauppinen. Synthesis of Graphene Nanoribbons Encapsulated in Single-Walled Carbon Nanotubes. Nano Letters, 2011; 110902093500003 DOI: 10.1021/nl2024678

Breakthrough in Photoemission Spectroscopy Allows Electronic Investigations Inside Crystals

The physical properties of solid substances are based on electronic states inside the materials. Now, an international team of researchers with the involvement of Jülich scientists has succeeded in studying these states in previously unimagined depths. The results have been published as an advance online publication by Nature Materials. In the "News and Views" commentary, the method is predicted to have a considerable potential for materials research.

For their measurements, the researchers from Germany, the USA, and Japan used the established method of angle-resolved photoemission spectroscopy. However, they used with a light source that was 100-times stronger than usual. This type of light is produced at a mere handful of scientific facilities throughout the world, in Germany, for instance, at the PETRA III storage ring in Hamburg. The team used SPring-8 in Japan, which is currently the world's most powerful synchrotron radiation facility in the hard X-ray range.

Photoemission spectroscopy has been used since the 1970s and is based on the photoelectric effect first theoretically described by Albert Einstein in 1905. Scientists use the method to irradiate samples with light, which causes electrons to become detached from the material. The distribution of angles and energy from the escaping electrons reveals information on the electronic states of the sample, for instance, the position and movement of electrons, band structures, or magnetic properties.

However, this had previously only been achieved for the first approximately five to ten atomic layers at the surfaces. From deeper layers, too few electrons reached the detectors of the measuring instruments. The scientists have now succeeded in achieving a view inside tungsten and arsenide over ten times deeper thanks to the especially brilliant light with high energies of up to six kiloelectron volts, an improved electron spectrometer, and cleverly selected sample material.

The participating scientists at SPring-8 adjusted the light source to allow a maximum number of photons to reach the sample on the smallest possible area. Experimental physicists from Jülich, Erlangen, Mainz, and Berkeley, optimized the spectrometer used and studied sample materials with low lattice vibrations in order to obtain the most detailed results possible. Theoretical physicists from Munich and Davis developed models that can be used to interpret the measurement results.

 

New method for imaging molecules inside cells

Using a new sample holder, researchers at the University of Gothenburg have further developed a new method for imaging individual cells. This makes it possible to produce snapshots that not only show the outline of the cell's contours but also the various molecules inside or on the surface of the cell, and exactly where they are located, something which is impossible with a normal microscope.

Individual human cells are small, just one or two hundredths of a millimeter in diameter. As such, special measuring equipment is needed to distinguish the various parts inside the cell. Researchers generally use a microscope that magnifies the cell and shows its contours outline, but does not provide any information on the molecules inside the cell and on its surface.

"The new sample holder is filled with holds cells in solution," says Ingela Lanekoff, one of the researchers who developed the new method at the University of Gothenburg's Department of Chemistry. "We then rapidly freeze the sample down to -196°C, which enables us to get a snapshot of where the various molecules are at the moment of freezing. Using this technique we can produce images that show not only the outline of the cell's contours, but also the molecules that are there, and where they are located."

Important to measure chemical processes in the body

So why do the researchers want to know which molecules are to be found in a single cell? Because the cell is the smallest living component there is, and the chemical processes that take place here play a major role in how the cell functions in our body. For example, our brain has special cells that can communicate with each other through chemical signals. This vital communication has been shown to be dependent on the molecules in the cell's membrane.

Imaging the molecules in the membrane of single individual cells's membrane enables researchers to measure changes. Together with previous results, Lanekoff's findings show that the rate of communication in the studied cells studied is affected by a change of less than one per cent in the quantities abundance of a specific molecule in the membrane. This would suggest that communication between the cells in the brain is heavily dependent on the chemical composition of the membrane of each individual cell,. This could be an important part of the puzzle which could go some way towards explaining the mechanisms behind learning and memory.

The thesis, Analysis of phospholipids in cellular membranes with LC and imaging mass spectrometry, has been successfully defended at the University of Gothenburg. Supervisors: Andrew Ewing and Roger Karlsson. Download the thesis at: hdl.handle.net/2077/25279

Story Source:

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