Tuesday, November 8, 2011

Chiral metal surfaces may help to manufacture pharmaceuticals; Novel approach could be used in pharmaceutical drug synthesis

New research shows how metal surfaces that lack mirror symmetry could provide a novel approach towards manufacturing pharmaceuticals.

These 'intrinsically chiral' metal surfaces offer potential new ways to control chiral chemistry, pointing to the intriguing possibility of using heterogeneous catalysis in drug synthesis. Such surfaces could also become the basis of new biosensor technologies.

A chiral object, such as your hand, is one that cannot be superposed on its mirror image. Chirality is fundamental in biochemistry. The building blocks of life -- amino acids and sugars -- are chiral molecules: their molecular structures can exist in either "left-handed" or "right-handed" forms (or "enantiomers").

A living organism may respond differently to the two enantiomers of a chiral substance. This is crucially important in the case of pharmaceutical drugs, where the therapeutic effect is often tied strongly to just one enantiomer of the drug molecule. Controlling chirality is therefore vital in pharmaceutical synthesis.

Research into controlling chiral synthesis focuses mainly on using homogeneous catalysts, where the catalyst is in the same phase as the reactants and products, such as a liquid added to a liquid-phase reaction. However, this poses significant practical challenges in recovering the valuable catalyst material from the mixture. To avoid this problem, an attractive alternative would be heterogeneous catalysis over a solid surface -- the type of catalysis used in catalytic converters in car exhaust systems, as well as in industrial Haber-Bosch synthesis of ammonia and Fischer-Tropsch synthesis of synthetic fuel, for example. The question then is how to achieve enantiomer-specific effects at a surface.

To help answer this question, scientists at the University of Cambridge have been probing the spontaneous self-organization of a simple chiral amino acid, alanine, into regular molecular arrays on copper single-crystal surfaces. Thanks to a powerful scanning tunnelling microscope, capable of resolving individual atoms and molecules, their work is revealing the various manifestations of chirality that occur, giving important clues to how they arise, and how they might be controlled and exploited.

Dr Stephen Driver, of the Department of Chemistry at the University of Cambridge, who led the experimental work, said: "We set out to investigate two distinct scenarios. In one scenario, the surface is non-chiral, so any chirality that we see can only arise from the chirality of the alanine molecule. In the other scenario, we move to a surface that is intrinsically chiral. Now the question becomes: do the two enantiomers of alanine behave differently on this chiral surface?"

On the non-chiral surface, the researchers found that alanine can self-organise into either of two patterns. In one of these, the self-organisation is driven by hydrogen bonding between the molecules, while the chiral centre has no discernable impact on the regular array. In the other structure, a network of long-range chiral boundaries punctuates the array, and the boundary chirality switches with molecular chirality.

Driver explained: "The implication is that the chiral centre is having a direct influence on the packing of two alanine neighbours at the boundary, and that the chirality of this pair propagates to the next pair and the next and so on, so that the chiral boundary is built up over a long range."

The chiral surface is created simply by choosing a surface orientation that lies away from any of the bulk mirror symmetry planes of the metal crystal. When the researchers added alanine, they found that the surface changes its local orientation, forming nanometre-scale facets. The two enantiomers of alanine self-organise into different chiral patterns: a strong, enantiomer-specific structural effect. This "proof of principle" could potentially be exploited in chiral recognition, in chiral synthesis (forming a chiral product from non-chiral reactants), and in chiral separations.

Driver added: "It looks like alanine can shape a comfortable, chiral bonding site for itself. The copper surface has the flexibility to adapt itself to the shape of the alanine molecule, and this shape is different for the two different molecular enantiomers."

The results imply that certain surface orientations will form stable, ordered structures with one molecular enantiomer but not the other: exactly the right conditions to promote chiral chemical effects.

Professor Sir David King, former Chief Scientific Advisor to the UK Government and current Director of the Smith School of Enterprise and the Environment at Oxford, brought together the team carrying out this research. "These results are very exciting," said King. "Tailoring the right surface to the right molecule should lead to strong enantiospecific effects. We see a real basis here for a breakthrough technology in the pharmaceuticals sector. It's something that pharma companies should be taking a close interest in."

The Cambridge team's findings are published in Topics in Catalysis.

Story Source:

The above story is reprinted from materials provided by University of Cambridge. The original story is licensed under a Creative Commons license.

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

Journal Reference:

Marian L. Clegg, Leonardo Morales de la Garza, Sofia Karakatsani, David A. King, Stephen M. Driver. Chirality in Amino Acid Overlayers on Cu Surfaces. Topics in Catalysis, 2011; DOI: 10.1007/s11244-011-9758-y

Gallium nitride is non-toxic, biocompatible; holds promise for implants, research finds

 Researchers from North Carolina State University and Purdue University have shown that the semiconductor material gallium nitride (GaN) is non-toxic and is compatible with human cells -- opening the door to the material's use in a variety of biomedical implant technologies.

GaN is currently used in a host of technologies, from LED lighting to optic sensors, but it is not in widespread use in biomedical implants. However, the new findings from NC State and Purdue mean that GaN holds promise for an array of implantable technologies -- from electrodes used in neurostimulation therapies for Alzheimer's to transistors used to monitor blood chemistry.

"The first finding is that GaN, unlike other semiconductor materials that have been considered for biomedical implants, is not toxic. That minimizes risk to both the environment and to patients," says Dr. Albena Ivanisevic, who co-authored a paper describing the research. Ivanisevic is an associate professor of materials science and engineering at NC State and associate professor of the joint biomedical engineering program at NC State and the University of North Carolina at Chapel Hill.

Researchers used a mass spectrometry technique to see how much gallium is released from GaN when the material is exposed to various environments that mimic conditions in the human body. This is important because gallium oxides are toxic. But the researchers found that GaN is very stable in these environments -- releasing such a tiny amount of gallium that it is non-toxic.

The researchers also wanted to determine GaN's potential biocompatibility. To do this they bonded peptides -- the building blocks that make up proteins -- to the GaN material. Researchers then placed peptide-coated GaN and uncoated GaN into cell cultures to see how the material and the cells interacted.

Researchers found that the peptide-coated GaN bonded more effectively with the cells. Specifically, more cells bonded to the material and those cells spread over a larger area.

"This matters because we want materials that give us some control over cell behavior," Ivanisevic says. "For example, being able to make cells adhere to a material or to avoid it.

"One problem facing many biomedical implants, such as sensors, is that they can become coated with biological material in the body. We've shown that we can coat GaN with peptides that attract and bond with cells. That suggests that we may also be able to coat GaN with peptides that would help prevent cell growth -- and keep the implant 'clean.' Our next step will be to explore the use of such 'anti-fouling' peptides with GaN."

The paper, "Gallium Nitride is Biocompatible and Non-Toxic Before and After Functionalization with Peptides," is forthcoming from Acta Biomaterialia and was co-authored by Ph.D. students Scott A. Jewett and Matthew S. Makowski; undergraduate Benjamin Andrews; and Michael J. Manfra -- all of Purdue. The research was funded by the National Science Foundation.

NC State's Department of Materials Science and Engineering, and joint Department of Biomedical Engineering, are part of the university's College of Engineering.

Story Source:

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

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

Journal Reference:

Scott A. Jewett, Matthew S. Makowski, Benjamin Andrews, Albena Ivanisevic, Michael J. Manfra. Gallium Nitride is Biocompatible and Non-Toxic Before and After Functionalization with Peptides. Acta Biomaterialia, 2011; DOI: 10.1016/j.actbio.2011.09.038

Discovering oil at micro level

“The process starts with a tiny chip of rock from a core sample where oil has become trapped,” said Mitra. “That slice of rock is scanned by a Focused Ion Beam-Scanning Electron Microscopy machine, which produces a 3-D copy of the porous rock.” The replica is made of a thin layer of silicon and quartz at Nanofab, the U of A’s micro/nanofabrication facility.

The researchers call the finished product a “reservoir on a chip”, or ROC.

“The hugely expensive process of recovering oil in the field is recreated right in our laboratory,” said Mitra. He explains that researchers soak the ROC in oil and then water, which is under pressure, is forced into the chip to see how much oil can be pushed through the microscopic channels and recovered.

“ROC replicas can be made from core samples from oil-trapping rock anywhere in the world,” said Mitra. “Oil exploration companies will be able to use ROC technology to determine what concentration of water and chemicals they’ll need to pump into layers of or to maximize oil recovery.”

The research findings were published at the cover article in the journal Lab Chip, a publication of the Royal Society of Chemistry.

Provided by University of Alberta (news : web)

Chemists find new dimension to rules for reactions

Theoretical chemists at Emory University have solved an important mystery about the rates of chemical reactions and the so-called Polanyi rules.

The findings, published in the journal Science, reveal why a reaction involving methane does not conform to the known rules, a problem that has baffled physical chemists in recent years.

"We showed that a pre-reactive, long-range force can align the reaction of a chorine atom with methane, or natural gas, in a way that actually inhibits the reaction," says Joel Bowman, a professor of theoretical chemistry at Emory and the Cherry L. Emerson Center for Computational Chemistry. "We believe that the theoretical work that we did has extended and modified the Polanyi rules."

Bowman published the results with Gabor Czako, a post-doctoral fellow in theoretical chemistry who performed most of the complex computational and mathematical analyses that uncovered the results.

Long-range, their findings could play a role in the development of cleaner, more efficient fuels.

Understanding the dynamics of chemical reactions is key to driving reactions efficiently, whether in a laboratory experiment or in an industrial application. In 1986, John Polanyi shared the Nobel Prize in chemistry, in part by providing general rules for how different forms of energy affect the rates of reactions.

"The Polanyi rules tell you the best way to deposit energy in a simple molecule to make a chemical reaction occur," Bowman says. "It's a bit like knowing in advance how to invest $1,000 to maximize the return on investment."

Polanyi developed the framework based on studies of simple reactions of chlorine and fluorine atoms with hydrogen gas. As technology has advanced in recent years, some chemists began testing the Polanyi rules for more complicated reactions, and the rules appeared to break down. Most notably, sophisticated molecular beam experiments by Kopin Liu at the Institute of Atomic and Molecular Sciences in Taiwan showed that the reaction of halogen atoms with methane did not conform to the rules.

"Suddenly, the rules appeared to have changed, and no one could explain why," Bowman says. "We decided to roll up our sleeves and attack the problem theoretically."

Bowman and Czako drew from the computational power of the Emerson Center, specialized software and analytical techniques. They first created theoretical-computational simulations of the experiments done by Liu and others, and then described the results mathematically.

"Our calculations showed essentially an exact agreement with the experimental results," Bowman says. "When theory and experiment agree you're happy, but you still want to know why."

Determining why the reactions did not conform to the Polanyi rules was another complicated task, involving quantum mechanics and forces that govern the reaction down to the atomic level.

"As theoreticians, we're able to zoom in and look at the results of our calculations in a way that's virtually impossible in an experiment," Bowman says.

They identified a subtle interplay between the Polanyi rules and a pre-reactive long-range force of methane with chlorine. If you follow the Polanyi rules, this long-range force, or steric control, will misalign the reactants, preventing them from docking correctly and inhibiting a reaction. But if you apportion the energy in the opposite way to the rules, the misalignment is wiped out and the reaction occurs.

"This long-range force was playing a bigger role than was previously realized," Bowman says. "It can actually trump the Polanyi rules, at least in the reactions that Liu and we looked at. The Polanyi rules are certainly not all wrong, they just appear to be too simple to apply to more complex reactions."

The research was funded by the National Science Foundation and the U.S. Department of Energy.

The reactive properties of natural gas are of particular interest since it is an important fuel. Bowman and Czako are now applying their techniques to study the combustion of methane and oxygen, which produces carbon dioxide. "It's important to understand the dynamics of this reaction, because it might lead to more efficient ways to produce fuel, and a reduction in the levels of pollution emitted," Bowman says.

Story Source:

The above story is reprinted from materials provided by Emory University. The original article was written by Carol Clark.

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

Journal Reference:

G. Czako, J. M. Bowman. Dynamics of the Reaction of Methane with Chlorine Atom on an Accurate Potential Energy Surface. Science, 2011; 334 (6054): 343 DOI: 10.1126/science.1208514

New protein structure expands nature's repertoire of biomolecules

The artificial protein made by the Bristol team – which they have named CC-Hex – has 6 polypeptide chains that the team designed from first principles; that is, whilst the chains take inspiration from biology they are not based on or related to any one particular natural protein.  Each chain folds into a helix, and these assemble to form a bundle (see top image).

This is interesting because nature appears not to have used this structure, or at least natural analogues of CC-Hex have not yet been observed.  Moreover, the structure is intriguing as the helices come together to form a ring that defines a central channel (see middle and bottom images).

 The protein has a central channel with defined chemistry that can be altered and controlled

This central channel provides the basis for engineering new proteins such as ion channels, which may be used as components of sensor and purification devices, and catalysts, which could pave the way to new industrial enzymes

The team, led by Professor Dek Woolfson and Professor Leo Brady, has also shown that the chemistry inside the channel can be altered using further design, chemical synthesis and X-ray crystallography.

Despite quite radical changes to the internal chemistry, the is robust to these alterations.  This is exciting because it is precisely how many natural proteins function: they alter chemistry within defined and highly controlled cavities within protein structures.  With this in mind, the team believes that CC-Hex represents an exciting opportunity to design new proteins, including enzymes and ion channels, from scratch.

Professor Dek Woolfson said of the discovery: “This is an exciting time for our labs.  Not only have we found a part of protein space that nature seems to have neglected, but we believe that the new structure will allow us to engineer functions much more rationally and confidently than has been possible before.”

More information: ‘A de novo peptide hexamer with a mutable channel’ by NR Zaccai, B Chi, AR Thomson, AL Boyle, GJ Bartlett, M Bruning, N Linden, RB Sessions, PJ Booth, RL Brady, and DN Woolfson in Nat. Chem. Biol. DOI: 10.1038/NChemBio.692

Provided by University of Bristol (news : web)