Catalysts for less: Slashing costs of metal alloys needed to jump-start crucial chemical processes

 When you hear the word hydrogenation, you might think of Crisco or margarine -- plant oils made thicker and more stable by adding hydrogen atoms. In fact, hydrogenation is a key process in a large number of industries, such as oil refining, where it is used to turn crude oil into gasoline.

Hydrogenation happens thanks to the presence of a catalyst -- usually a metal, such as nickel or palladium, or an alloy -- which allows the hydrogen atoms to bind with other molecules. Typically, metal alloys are mixtures of cheap common metals, such as nickel, and expensive precious metals, such as platinum or palladium. However, it is hard to produce alloys that are selective hydrogenation catalysts, which are able to attach the hydrogen atoms to specific sites on a molecule.

Now scientists at Tufts have found a way to create a selective hydrogenation catalyst by scattering single atoms of palladium onto a copper base. This catalyst requires less of the expensive metal, and the process is greener, too, offering potentially significant economic and environmental benefits.

The team reported its discovery in a paper published on March 9 in the journal Science.

Led by Charles Sykes, an associate professor of chemistry in the School of Arts and Sciences, the group of researchers heated up very small amounts of palladium to almost 1,000 degrees Celsius, or about 1,830 degrees Fahrenheit. At that temperature, the metal evaporated like a gas, so that single atoms were released. These atoms, less than half a nanometer wide, embedded themselves into a copper metal surface about three inches away.

Using a scanning tunneling microscope, which can capture pictures of objects at the atomic level, the researchers verified that single palladium atoms had indeed embedded themselves at scattered intervals in the copper. In a conventional metal catalyst, by contrast, palladium is used in clumps 5 to 10 nanometers wide. This is significantly less economical, since it requires much greater quantities of palladium, which costs more than $650 an ounce. It is less environmentally friendly as well, because of the energy that must be used to extract the additional necessary palladium from raw ore.

The new catalyst also behaves differently, says Georgios Kyriakou, a research assistant professor in chemistry and first author of the report. He helped determine that the single atom alloy was more effective in catalyzing hydrogenation than denser mixtures of palladium and copper.

"In the face of precious metals scarcity and exorbitant prices, these systems are promising in the search for sustainable global solutions," says Maria Flytzani-Stephanopoulos, the Robert and Marcy Haber Endowed Professor in Energy Sustainability in the School of Engineering, whose lab is studying the effectiveness of the single-atom process. She and Sykes are continuing to collaborate on advancing their research, funded by the National Science Foundation, the U.S. Department of Energy and Tufts Collaborates, a grant program administered by the Office of the Provost.

Flytzani-Stephanopoulos and her group in the School of Engineering are now looking into other approaches to achieve hydrogenation with different metal pairs. She says that eventually single-atom alloy catalysts could be used as low-cost alternatives for hydrogenation and dehydrogenation. That could be a boon for the production of agricultural chemicals, foods and pharmaceuticals.

Story Source:

The above story is reprinted from materials provided by Tufts University. The original article was written by Taylor McNeil.

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

Journal Reference:

G. Kyriakou, M. B. Boucher, A. D. Jewell, E. A. Lewis, T. J. Lawton, A. E. Baber, H. L. Tierney, M. Flytzani-Stephanopoulos, E. C. H. Sykes. Isolated Metal Atom Geometries as a Strategy for Selective Heterogeneous Hydrogenations. Science, 2012; 335 (6073): 1209 DOI: 10.1126/Science.1215864

Pharmacists crucial in plan for terrorist chemical weapons

Chemical weapons act on their victims through a number of mechanisms. They include nerve agents, chemicals that cause blistering (vesicants), choking agents, incapacitating agents, riot control agents, blood agents, and toxic industrial chemicals. With their knowledge of chemistry, microbiology, pharmacology, toxicology, and therapeutics, pharmacists are a valuable asset to health care facilities and government agencies planning for the unthinkable – a terrorist attack with chemical weapons.

In his article, clinical pharmacist and forensic pharmacologist Peter D. Anderson details the clinical effects chemical weapons, and their treatment. Nerve agents work by blocking the actions of acetyl cholinesterase (the chemistry involved is similar to how many pesticides kill). These toxins include sarin, tabun, VX, cyclosarin, and soman. Vesicants like sulfur mustard and lewisite produce blisters and damage the upper airways. Choking agents, which cause fluid to build up in the lungs (pulmonary edema), include phosgene and chlorine gas.

Incapacitating agents are temporary and "non-lethal," and include fentanyl and adamsite. Mace and pepper spray are familiar riot control methods. Blood agents include cyanide, which works by blocking oxidative phosphorylation in the body. Toxic industrial chemicals such as formaldehyde, hydrofluoric acid, and ammonia also merit consideration as terrorist weapons.

"Potential chemical weapons are in no way limited to the traditional agents that we think of as chemical weapons," Anderson explains.

The good news is that there are potential antidotes to these chemical agents, which can save lives if they are used quickly and correctly. Pharmacists need to work in their hospitals to prepare emergency plans, and with the pharmacy and therapeutic committees to stock for a potential chemical accident or terrorist attack. In the US, for example, The Centers for Disease Control and Prevention (CDC) maintains a Strategic National Stockpile of pharmaceuticals, medical equipment and supplies that can be sent in an emergency to any US state within 12 hours.

The threat from chemical agents may appear to be a symptom of our modern society, but the idea has been around since antiquity. Solon of Athens is said to have used hellebore roots (a purgative) to contaminate the water supply in the Pleistrus River during the Siege of Cirrha as long ago as 590 BC. Modern chemical warfare during World War I included the release by German soldiers of 150 tons of chlorine gas near Ypres, Belgium, and phosgene and nitrogen mustard also played a role in the conflict. Choking agents, vesicants, blood agents, and nerve gas joined the range of chemical weapons available by World War II. Even though conflicting nations produced these in large quantities, no major chemical weapon events occurred during World War II.

The Chemical Weapons Convention was finalized in 1993, prohibiting development, production, stockpiling, and use of chemical weapons. The treaty also mandated weapons destruction. 130 countries signed the convention (excluding Iraq and North Korea).

Although the article is about chemical weapons, Anderson emphasizes that pharmacists can also be a resource for biological, radiological and nuclear attacks as well as natural disasters.

More information: Emergency Management of Chemical Weapons Injuries by Peter D. Anderson is published in the Journal of Pharmacy Practice. The article is free to access here: http://jpp.sagepub … ull.pdf+html

Provided by SAGE Publications

Physicists uncover new data on adenine, a crucial building block of life

Early Earth's atmosphere provided little shielding for ultraviolet light from space, so many prebiotic molecules, bombarded by it and light of other wavelengths, had a hard time surviving at all. But some molecules became photostable-able to withstand the assault and thrive as building blocks of life.

Five of the many molecules that survived the bombardment from UV light were the nucleic acid bases adenine, cytosine, guanine, thymine and uracil. Now, in just published research, a University of Georgia physicist and a collaborator in Germany have shown that one of these building blocks of DNA and RNA, adenine, has an unexpectedly variable range of ionization energies along its reaction pathways.

This means that understanding experimental data on how adenine survives exposure to UV light is much more complicated than previously thought. It also has far-reaching implications for spectroscopic measurements of heterocyclic compounds-those with atoms of at least two different elements in their rings.

"Photoprotection relies on the conversion of potentially harmful UV radiation into heat and has to operate on ultrafast time scales to compete over pathways that lead to the destruction of the biomolecule," said Susanne Ullrich, assistant professor in physics in the UGA department of physics and astronomy, part of the Franklin College of Arts and Sciences. "Disentangling these pathways and their time scales is challenging and requires a very close collaboration between experimentalists and theorists."

The research is in the online journal Physical Chemistry Chemical Physics. Co-author of the paper is Mario Barbatti, a theorist at the Max-Planck Institute in Mulheim, Germany.

The quantum-chemical calculations create for the first time a new baseline on how time-resolved spectroscopic techniques based on photoionization can be most reliably used to study this class of molecules.

"Photostable organic molecules participated in the complex molecular evolution that led to the formation of life," said Ullrich. "Because of the significance of nucleic acid bases as the genetic coding material, the photophysics of nucleobases has received considerable theoretical and experimental attention. This new work can help clarify inconsistencies researchers have always found in studying photoionization and photoelectron spectra of adenine."

Ullrich and her team used a technique called time-resolved photoionization with femtosecond (a quadrillionth of a second) resolution to unravel the mechanisms that protect adenine against UV damage. For the spectroscopic measurements, they employ a state-of-the-art femtosecond laser and custom-built photoelectron and photoion spectrometer.

Adenine is vaporized and transported into the spectrometer in a supersonic jet expansion. A pump pulse excites the sample of molecules, and finally a probe pulse is used to examine the sample after an adjustable delay time.

This examination is based on the process of photoionization that removes an electron from the molecule. The kinetic energy of the released photoelectron is measured in the spectrometer and provides the spectroscopic information needed to establish the photoprotection mechanism of adenine. Interpretation, however, heavily relies on the knowledge of ionization potentials (IP) along the relaxation pathways. (Ionization potential is the energy needed to remove an electron from the molecule.)

There has been a longstanding divergence between theoretical and experimental results when it comes to studying the IP of adenine and understanding on which surface adenine "relaxes" after it is excited with UV light. Understanding it more clearly could give new insights into how this important building block of life has continued to exist with stability in a world with millions of genetic threats.

"To our surprise, we found there were significant variations in the ionization energy between two different regions on this pathway," said Barbatti. "Due to the general character of the three pathways we studied, we believe the IPs computed along them can be used as a general guide for helping with setup and analysis for further experiments, not only with adenine but other related compounds."

Before this work, little has been known about the behavior of ionization potentials along the main reaction pathways for gaseous adenine in an excited state. Calling that a "knowledge gap," Barbatti and Ullrich say the new findings have "implications for experimental setup and data interpretation."

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of Georgia. The original article was written by Philip Williams.

Journal Reference:

Mario Barbatti, Susanne Ullrich. Ionization potentials of adenine along the internal conversion pathways. Physical Chemistry Chemical Physics, 2011; DOI: 10.1039/C1CP21350D

Dynamics of crucial protein 'switch' revealed

Researchers at the University of Texas Medical Branch at Galveston and the University of California-San Diego School of Medicine have published a study that offers a new understanding of a protein critical to physiological processes involved in major diseases such as diabetes and cancer. This work could help scientists design drugs to battle these disorders.

The article was deemed a "Paper of the Week" by and will be on the cover of the Journal of Biological Chemistry. It is scheduled for publication May 20 and now available online.

"This study applied a powerful protein structural analysis approach to investigate how a chemical signal called cAMP turns on one of its protein switches, Epac2," said principal investigator Xiaodong Cheng, professor in the Department of Pharmacology and Toxicology and member of the Sealy Center for Structural Biology and Molecular Biophysics at UTMB.

The cAMP molecule controls many physiological processes, ranging from learning and memory in the brain and contractility and relaxation in the heart to insulin secretion in the pancreas. cAMP exerts its action in cells by binding to and switching on specific receptor proteins, which, when activated by cAMP, turn on additional signaling pathways.

Errors in cell signaling are responsible for diseases such as diabetes, cancer and heart failure. Understanding cAMP-mediated cell signaling, in which Epac2 is a major player, likely will facilitate the development of new therapeutic strategies specifically targeting the cAMP-Epac2 signaling components, according to the researchers.

The project involved an ongoing collaboration between Cheng's research group at UTMB, experts in the study of cAMP signaling, and UCSD professor of medicine Virgil Woods Jr. and colleagues at UCSD, pioneers in the development and application of hydrogen/deuterium exchange mass spectrometry (DXMS) technology. Compared with other protein-analysis techniques, DXMS is especially good at studying the structural motion of proteins.

Using this novel approach, the investigators were able to reveal, in fine detail, that cAMP interacts with its two known binding sites on Epac2 in a sequential fashion and that binding of cAMP changes the shape of the protein in a very specific way – switching on its activity by exposing further signaling interaction sites on Epac2.

"DXMS analysis has proved to be an amazingly powerful approach, alone or in combination with other techniques, in figuring out how proteins work as molecular machines, changing their shapes – or morphing – in the normal course of their function," said Woods. "This will be of great use in the identification and development of therapeutic drugs that target these protein motions."

Provided by University of Texas Medical Branch at Galveston (news : web)

Study suggests enzyme crucial to DNA replication may provide potent anti-cancer drug target

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During DNA replication of the lagging strand, numerous Okazaki fragments must be joined. The newer fragment ends in a short flap call the 3? overhang, while the previous fragment leaves a long 5? flap after its primer is removed. The junction opens when the template strand is bent 100 degrees. FEN1 grasps the DNA at the bend, threads the flap through an archway, and trims the flap to match the overhang.

(PhysOrg.com) -- An enzyme essential for DNA replication and repair in humans works in a way that might be exploited as anti-cancer therapy, say researchers at The Scripps Research Institute and Lawrence Berkeley National Laboratory.

The research, published in the April 15, 2011 issue of the journal Cell, focused on a member of a group of enzymes called flap endonucleases, which are essential to the life of a cell. The findings show new, clearly defined crystal structures of the enzyme FEN1 in action—demonstrating it functions in a way opposite to accepted dogma.

"This work represents a seminal advance in the understanding of FEN1," said team leader John Tainer, professor and member of the Skaggs Institute for Chemical Biology at Scripps Research and senior scientist at Lawrence Berkeley National Lab. "The research produced very accurate structures showing DNA before and after being cut by FEN1 activity, providing a basis for understanding a whole superfamily of enzymes that must cut specific DNA structures in order for DNA to be replicated and repaired."

This superfamily includes important targets for the development of new cancer interventions, Tainer added. Many cancers show high levels of FEN1 expression, which in some cases is correlated to tumor aggression. For these cases, FEN1-specific inhibitors may have chemotherapeutic potential.

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Much of the FEN1 structure was solved by Sakurai et al, but how FEN1 works was not apparent in the DNA-free structure. The presence of DNA appears to induce the transition from disorder to order; FEN1 positions the 5? flap and the 3? overhang mainly by grasping the double-strand portions of DNA on either side of the 100-degree bend.

"A better understanding of FEN1 structure and function may have long-term positive benefits to human health," noted co-author Andy Arvai, a scientific associate at Scripps Research.

Working rapidly with exquisite precision

In order for DNA to replicate, it has to unwind its double helix, which is formed out of two strands of amino acids coiled together. This unwinding is done by a replication fork whereby the two strands are separated. These strands, which form two branching prongs of the replication fork, serves as a template for production of a new complementary strand.

That task is fairly straightforward on what is known as the "leading" of the two strands. The replication fork moves along from the so-called 3' (three prime) end to the 5' (five prime) end, and DNA polymerase synthesizes a 5' to 3' complementary strand.

But because the two strands are anti-parallel, meaning they are oriented in opposite directions, the work of DNA polymerase, which can only work in the 5' to 3' direction, is more difficult on the so-called lagging strand. This strand needs to be replicated in pieces, which are known as Okazaki fragments, located near the replication fork. These fragments include a "primer," a strand of RNA that serves as a starting point for DNA synthesis.

This is where FEN1 comes in—it removes that RNA primer on the 5' flap, which occurs every 100 base pairs or so on the lagging strand, said Tainer. It's an enormous job that has to be done rapidly and accurately in order to glue the ends of replicated DNA on the lagging strand together to eventually provide an intact chromosome. "To replicate one DNA double helix in one cell you have to cut off a 5' flap so that you don't have one base pair too many or one base pair too few, and you have to do this accurately with 50 million Okazaki primers in each cell cycle," Tainer said. "It has always been a mystery as to how FEN1 can precisely cut this flap so efficiently and so rapidly. It's an amazing, efficient molecular machine for precisely cutting DNA."

To determine what FEN1 looked like in action, Arvai led the difficult but ultimately successful effort to grow crystals of the human FEN1 protein bound to DNA. The team then used X-ray crystallography to determine the atomic structure of the complex. Using Lawrence Berkeley National Laboratory's Advanced Light Source beamline, called SIBYLS, the scientists solved three different crystal structures.

The end result was a highly detailed and accurate model showing the structures of DNA before and after being cut by FEN1.

Earlier crystal structures suggested that FEN1 first grabs onto the flap of the 5' single stranded DNA, slides down to the joint where DNA is duplicated, and cuts and patches the primer there. But the new study found that, in fact, FEN1 binds, bends, frays, and then cuts the DNA.

"It binds duplex DNA, bends it into a single-stranded DNA right at the flap, flips out two base pairs, and cuts between them," said Tainer. "This gives FEN1 very precise control—a sophistication we had not expected."

Clues to cancer control

Researchers know that mutations in FEN1 can predispose humans to cancer growth because errors in flap removal can create unstable DNA that promotes cell growth and division. And studies in mice have shown that when one of two inherited FEN1 genes are knocked out, the mice are predisposed to cancer development if their DNA is damaged.

While other DNA repair systems can help compensate for FEN1 mistakes, or for missing FEN1 activity, "you need a lot of FEN1 for DNA repair and replication to work properly," Tainer said.

This suggests that, in tumors already missing one set of repair proteins, selectively inhibiting the function of FEN1 in rapidly replicating cells may prove to be an effective anti-cancer therapy. "The Achilles heel of cancer cells is defective DNA repair pathways," said Tainer, "because that makes them more sensitive to traditional therapies, such as chemotherapy and radiation. If cancer can't repair the damage these therapies do to tumors, they will die."

This is the paradox of DNA repair: while a defect in DNA repair can cause cancer, knocking out a number of backup repair systems may make tumors vulnerable to anti-cancer therapies.

"My hope is that our finding of how FEN1 works mechanistically might provide a foundation for a next-generation cancer drug," said Tainer. "We need to cut as many lifelines as possible in cancer cells in order to provide an effective treatment."

More information: "Human Flap Endonuclease Structures, DNA Double-Base Flipping, and a Unified Understanding of the FEN1 Superfamily," by Susan E. Tsutakawa et al. Cell.

Provided by The Scripps Research Institute (news : web)