Nobel Prize winner’s unfinished symphony

 When Robert Burns Woodward passed away in 1979 he left 699 pages of handwritten notes. Because R.B. Woodward was a Nobel Laureate (Chemistry, 1965) his family had carefully preserved his notes for posterity. A paper published in Elsevier's Tetrahedron summarizes the process of an extensive study uncovering the hidden treasures in these notes.

The notes were meticulously drawn sketches outlining Woodward's ideas on organic superconductors. Woodward's family felt these notes could provide valuable insights to other chemists. With the help of Prof Robert Williams from the Colorado State University, two suitable researchers -- Michael P. Cava and M.V. Lakshmikantham from the University of Alabama -- were appointed to study these notes extensively. The result of this long study is presented in the paper to be published in Tetrahedron, including original scans of Woodward's work. 

Cava and Lakshmikantham had no easy task. Although the family had numbered the pages and later digitally scanned them, the notes were written on various types of paper and at various times as the ideas occurred. Cava and Lakshmikantham took some of the main compounds from Woodward's notes, redrawing them using modern techniques, also searching for any later available literature on the same compounds.

A superconductor allows electricity to flow without resistance. Although the first superconductor had been described in 1911, Woodward developed his ideas when superconductors were still at an experimental stage and the only superconductors known operated at very low temperatures, meaning their practical use was limited. Woodward felt confident he could develop an organic superconductor which would operate at room temperature: his notes set out his ideas for suitable compounds.

Chemical Engineering and News, a weekly journal of the American Chemical Society, describes in more detail the work that went into producing this paper (Volume 89, number 22, pp.46-49).

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Elsevier, via AlphaGalileo.

Journal Reference:

Michael P. Cava, M.V. Lakshmikantham, Roald Hoffmann, Robert M. Williams. R. B. Woodward’s unfinished symphony: designing organic superconductors (1975–79). Tetrahedron, 2011; DOI: 10.1016/j.tet.2011.05.004

Researchers uncover new catalysis site

 Mention catalyst and most people will think of the catalytic converter, an emissions control device in the exhaust system of automobiles that reduces pollution.

But catalysts are used for a broad variety of purposes, including the conversion of petroleum and renewable resources into fuel, as well as the production of plastics, fertilizers, paints, solvents, pharmaceuticals and more. About 20 percent of the gross domestic product in the United States depends upon catalysts to facilitate the chemical reactions needed to create products for everyday life.

Catalysts are materials that activate desired chemical reactions without themselves becoming altered in the process. This allows the catalysts to be used continuously because they do not readily deteriorate and are not consumed in the chemical reactions they inspire.

Chemists long ago discovered and refined many catalysts and continue to do so, though the details of the mechanisms by which they work often are not understood.

A new collaborative study at the University of Virginia details for the first time a new type of catalytic site where oxidation catalysis occurs, shedding new light on the inner workings of the process. The study, conducted by John Yates, a professor of chemistry in the College and Graduate School of Arts & Sciences, and Matthew Neurock, a professor of chemical engineering in the School of Engineering and Applied Science, is published in the journal Science.

Yates said the discovery has implications for understanding catalysis with a potentially wide range of materials, since oxidation catalysis is critical to a number of technological applications.

"We have both experimental tools, such as spectrometers, and theoretical tools, such as computational chemistry, that now allow us to study catalysis at the atomic level," he said. "We can focus in and find that sweet spot more efficiently than ever. What we've found with this discovery could be broadly useful for designing catalysts for all kinds of catalytic reactions."

Using a titanium dioxide substrate holding nanometer-size gold particles, U.Va. chemists and chemical engineers found a special site that serves as a catalyst at the perimeter of the gold and titanium dioxide substrate.

"The site is special because it involves the bonding of an oxygen molecule to a gold atom and to an adjacent titanium atom in the support," Yates said. "Neither the gold nor the titanium dioxide exhibits this catalytic activity when studied alone."

Using spectroscopic measurements combined with theory, the Yates and Neurock team were able to follow specific molecular transformations and determine precisely where they occurred on the catalyst.

The experimental and theoretical work, guided by Yates and Neurock, was carried out by Isabel Green, a U.Va. Ph.D. candidate in chemistry, and Wenjie Tang, a research associate in chemical engineering. They demonstrated that the significant catalytic activity occurred on unique sites formed at the perimeter region between the gold particles and their titania support.

"We call it a dual catalytic site because two dissimilar atoms are involved," Yates said.

They saw that an oxygen molecule binds chemically to both a gold atom at the edge of the gold cluster and a nearby titanium atom on the titania support and reacts with an adsorbed carbon monoxide molecule to form carbon dioxide. Using spectroscopy they could follow the consumption of carbon monoxide at the dual site.

"This particular site is specific for causing the activation of the oxygen molecule to produce an oxidation reaction on the surface of the catalyst," Yates said. "It's a new class of reactive site not identified before."

The work was funded by the U.S. Department of Energy's Office of Basic Energy Sciences.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by University of Virginia. The original article was written by Fariss Samarrai.

Journal Reference:

Isabel Xiaoye Green, Wenjie Tang, Matthew Neurock, John T. Yates, Jr. Spectroscopic Observation of Dual Catalytic Sites During Oxidation of CO on a Au/TiO2 Catalyst. Science, 2011; 333 (6043): 736-739 DOI: 10.1126/science.1207272

Light unlocks fragrance in laboratory

In Anna Gudmundsdottir's laboratory at the University of Cincinnati, dedicated researchers endeavor to tame the extremely reactive chemicals known as radicals.

Highly reactive radicals are atoms, molecules or ions frantically trying to become something else. Their lifetimes are measured in fractions of seconds and typically occur in the middle of a chain of chemical reactions. They are also known as reactive intermediates. Much of Gudmundsdottir's work has focused on a family of radicals known as triplet nitrenes.

"Triplet nitrenes are reactive intermediates with high spin," Gudmundsdottir said. "You have a nitrogen molecule that has two unpaired electrons on it. We discovered they were actually very stable for intermediates. They live for milliseconds and that's when we got into this idea can we make them stable enough for various investigations."

The potential uses of relatively stable radicals have excited interest from industry. The high spin Gudmundsdottir describes suggests that triplet nitrenes, for example, might be ideal candidates for creating organic magnets that are lighter, more flexible and energy-intensive than conventional metal or ceramic magnets. Gudmundsdottir's research suggests that radicals, including triplet nitrenes, may show a pathway to materials with many magnetic, electrical and optical properties.

"I talk a lot about radicals," Gudmundsdottir said. "Nitrenes are radicals. We study the excited state of the precursors to the nitrenes. We are looking at how you use the excited state of molecules to form specific radicals."

One line of inquiry, presented by Gudmundsdottir to a recent Gordon Research Conference, described how her team used radicals to create a specific trap for a fragrance, which is then slowly released when exposed to light.

"The question was, can you actually tether a fragrance to something so that it will release slowly?" Gudmundsdottir said. "It turned out that a precursor similar to the ones we used to form the nitrenes could be used it as a photoremovable protecting group."

The "photoprotectant" acts as a sort of cap, containing the fragrance until the cap is pried off by a photon of light. For this particular purpose, Gudmundsdottir said it was important to design a photoprotectant "cap" that was somewhat difficult to pry off. For household products, such as a scented cleaning fluid, consumers want fragrance to be released slowly over a long period of time. That requires what is known as a low "quantum yield." In other words, how much fragrance gets released by how many photons.

The difficulty, Gudmundsdottir said, is that different applications need different rates of release. For medical uses, doctors might want a higher quantum yield, by which a little bit of light releases a lot of medicine.

"There are all kinds of applications for photoreactions," she said, "from household goods, perfumes, sun-protection, drug delivery and a variety of biologically reactive molecules. So we just decided, OK, we are very fundamental chemists, we'll design different systems and see if we can manipulate the rate of release."

Gudmundsdottir's research group studies the release mechanism, locates where there are limitations, and tries to determine what controls the rate. They also consider environmental factors, including how the delivery systems react with oxygen.

"We do very fundamental work to get the knowledge here before can take it into specific directions," she said. "If we don't understand it, we can't design where to take it next."

Much of this understanding develops from watching how radicals form and decay. Gudmundsdottir's group uses a laser flash photolysis system to fire a laser into a sample and to track the spectrum of radiated light as the radicals decay.

"What I like about transient spectroscopy is actually seeing the intermediates we work with on nanosecond, microsecond and millisecond timescales," she said.

The team also uses computer modeling, but the chemical operations of these short-lived and rapidly reacting chemicals are difficult to model, so Gudmundsdottir has tapped into the resources of the Ohio Supercomputer Center.

"Calculating excited states takes up quite a bit of computer resources and that's why we use the supercomputer," she said. "That's a really nice resource to have available. I can sit anywhere or my students can sit anywhere and we can do the calculations to model reactions."

Gudmundsdottir said the questions raised by applications leads to helpful fundamental questions that can be tackled through basic research.

"Going forward, we probably want to do more applied study with our photo protective groups, to collaborate with someone to see them in some other applications," she said. "I'm interested in how they act inside cells."

Gudmundsdottir's team has received research support from the National Science Foundation, the American Chemical Society-Petroleum Research Fund, UC's University Research Council, Ohio Supercomputer Center and the English Speaking Union.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of Cincinnati. The original article was written by Greg Hand.

DNA building blocks can be made in space, NASA evidence suggests

NASA-funded researchers have evidence that some building blocks of DNA, the molecule that carries the genetic instructions for life, found in meteorites were likely created in space. The research gives support to the theory that a "kit" of ready-made parts created in space and delivered to Earth by meteorite and comet impacts assisted the origin of life.

"People have been discovering components of DNA in meteorites since the 1960's, but researchers were unsure whether they were really created in space or if instead they came from contamination by terrestrial life," said Dr. Michael Callahan of NASA's Goddard Space Flight Center, Greenbelt, Md. "For the first time, we have three lines of evidence that together give us confidence these DNA building blocks actually were created in space." Callahan is lead author of a paper on the discovery appearing in Proceedings of the National Academy of Sciences of the United States of America.

The discovery adds to a growing body of evidence that the chemistry inside asteroids and comets is capable of making building blocks of essential biological molecules. For example, previously, these scientists at the Goddard Astrobiology Analytical Laboratory have found amino acids in samples of comet Wild 2 from NASA's Stardust mission, and in various carbon-rich meteorites. Amino acids are used to make proteins, the workhorse molecules of life, used in everything from structures like hair to enzymes, the catalysts that speed up or regulate chemical reactions.

In the new work, the Goddard team ground up samples of twelve carbon-rich meteorites, nine of which were recovered from Antarctica. They extracted each sample with a solution of formic acid and ran them through a liquid chromatograph, an instrument that separates a mixture of compounds. They further analyzed the samples with a mass spectrometer, which helps determine the chemical structure of compounds.

The team found adenine and guanine, which are components of DNA called nucleobases, as well as hypoxanthine and xanthine. DNA resembles a spiral ladder; adenine and guanine connect with two other nucleobases to form the rungs of the ladder. They are part of the code that tells the cellular machinery which proteins to make. Hypoxanthine and xanthine are not found in DNA, but are used in other biological processes.

Also, in two of the meteorites, the team discovered for the first time trace amounts of three molecules related to nucleobases: purine, 2,6-diaminopurine, and 6,8-diaminopurine; the latter two almost never used in biology. These compounds have the same core molecule as nucleobases but with a structure added or removed.

It's these nucleobase-related molecules, called nucleobase analogs, which provide the first piece of evidence that the compounds in the meteorites came from space and not terrestrial contamination. "You would not expect to see these nucleobase analogs if contamination from terrestrial life was the source, because they're not used in biology, aside from one report of 2,6-diaminopurine occurring in a virus (cyanophage S-2L)," said Callahan. "However, if asteroids are behaving like chemical 'factories' cranking out prebiotic material, you would expect them to produce many variants of nucleobases, not just the biological ones, due to the wide variety of ingredients and conditions in each asteroid."

The second piece of evidence involved research to further rule out the possibility of terrestrial contamination as a source of these molecules. The team also analyzed an eight-kilogram (21.4-pound) sample of ice from Antarctica, where most of the meteorites in the study were found, with the same methods used on the meteorites. The amounts of the two nucleobases, plus hypoxanthine and xanthine, found in the ice were much lower -- parts per trillion -- than in the meteorites, where they were generally present at several parts per billion. More significantly, none of the nucleobase analogs were detected in the ice sample. One of the meteorites with nucleobase analog molecules fell in Australia, and the team also analyzed a soil sample collected near the fall site. As with the ice sample, the soil sample had none of the nucleobase analog molecules present in the meteorite.

Thirdly, the team found these nucleobases -- both the biological and non-biological ones -- were produced in a completely non-biological reaction. "In the lab, an identical suite of nucleobases and nucleobase analogs were generated in non-biological chemical reactions containing hydrogen cyanide, ammonia, and water. This provides a plausible mechanism for their synthesis in the asteroid parent bodies, and supports the notion that they are extraterrestrial," says Callahan.

"In fact, there seems to be a 'goldilocks' class of meteorite, the so-called CM2 meteorites, where conditions are just right to make more of these molecules," adds Callahan.

The team includes Callahan and Drs. Jennifer C. Stern, Daniel P. Glavin, and Jason P. Dworkin of NASA Goddard's Astrobiology Analytical Laboratory; Ms. Karen E. Smith and Dr. Christopher H. House of Pennsylvania State University, University Park, Pa.; Dr. H. James Cleaves II of the Carnegie Institution of Washington, Washington, DC; and Dr. Josef Ruzicka of Thermo Fisher Scientific, Somerset, N.J. The research was funded by the NASA Astrobiology Institute, the Goddard Center for Astrobiology, the NASA Astrobiology: Exobiology and Evolutionary Biology Program, and the NASA Postdoctoral Program.

Story Source:

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

Researchers use neutrons to spy on the elusive hydronium ion: Unprecedented proof of ion's role in enzymatic process

A Los Alamos National Laboratory research team has harnessed neutrons to view for the first time the critical role that an elusive molecule plays in certain biological reactions. The effort could aid in treatment of peptic ulcers or acid reflux disease, or allow for more efficient conversion of woody waste into transportation fuels.

In a paper appearing in Angewandte Chemie International Edition, Los Alamos researchers join an international team in describing the role played by the elusive hydronium ion in the transfer of protons during enzyme-catalyzed reactions.

Prior to this research, no one has ever directly witnessed the role of the hydronium ion, a water molecule bound to an additional hydrogen ion, in macromolecular catalysts -- the catalytic mechanisms of enzymes.

Researchers took an interest in an enzyme that has the potential to allow conversion of sugars in woody biomass into alcohol, a potential alternative fuel, because the enzyme loses its effectiveness when the pH value of the milieu is lowered -- a common occurrence in the interior of industrial yeast cells fermenting alcohol. As it turns out, this biochemical reaction also has ramifications for the activation of proton pumps in the stomach, which produces excess acid in those afflicted by gastric diseases.

The scientists sought to figure out the mechanism behind these reactions. Neutrons from the Los Alamos Neutron Science Center provided a possible tool for unveiling the secret agent at the heart of the chemistry.

Hydronium ions had not been seen before by researchers who attempted to use X-rays to understand the chemical mechanism of enzymes. This is because tiny hydrogen atoms are essentially invisible under X-rays. To help make things visible, the researchers substituted hydrogen in their enzyme samples with deuterium, an isotope of hydrogen that behaves chemically identical to its nonisotopic counterpart. Deuterium yields a clear signal when bombarded with neutrons. Therefore, neutrons provided a perfect method for uncloaking the elusive hydronium ions, which appeared as a pyramid-shaped mass in the enzyme's active site where the chemical reaction occurs.

The researchers discovered a crucial change as the system they were studying fell into the acidic range of the pH scale (below 6). The hydronium ion that could be seen facilitating the binding of a metal ion cofactor crucial to the conversion of the sugar molecule into its fermentable form suddenly became dehydrated -- think of water, H2O, being removed from hydronium, H3O+. The space occupied by the relatively large hydronium ion collapsed into a tiny volume occupied by the remaining proton (a positively charged hydrogen ion, H+). This spatial change in the molecular structure prevented the sugar from being attacked by the enzyme.

The observed phenomenon provided an answer about why pH plays such an important role in the process and renders the enzyme inactive under acidic conditions. More important, it definitively illustrated that the hydronium ion plays a key role in the transport of protons in these types of biochemical systems.

"This is something that has never been seen before," said Los Alamos researcher Andrey Kovalevsky, principal author of the paper. "This proves that hydronium is the active chemical agent in our studies of the catalytic mechanism of enzymes."

The research has broad implications for the possible role of hydronium ions in other biological systems. In addition to acid reflux disease, the research may help provide a better understanding of metabolic transfer of energy in living cells or living organisms.

Other members of the Los Alamos research team include Suzanne Fisher, Marat Mustyakimov, Thomas Yoshida, and Paul Langan (currently at Oak Ridge National Laboratory).

Other institutions involved in the effort are the University of Toledo, Ohio; the Institut Laue Langevin, Grenoble, France; Keele University, Staffordshire, England; and the ISIS facility Oxfordshire, England.

Los Alamos funding for the research came, in part, from the Laboratory's Directed Research and Development Program (LDRD) and the U.S. Department of Energy's Office of Biological and Environmental Research (DOE-OBER). Funding was also provided through the National Institutes of Health.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by DOE/Los Alamos National Laboratory.

Journal Reference:

Andrey Y. Kovalevsky, B. L. Hanson, S. A. Mason, T. Yoshida, S. Z. Fisher, M. Mustyakimov, V. T. Forsyth, M. P. Blakeley, D. A. Keen, Paul Langan. Identification of the Elusive Hydronium Ion Exchanging Roles with a Proton in an Enzyme at Lower pH Values. Angewandte Chemie International Edition, 2011; 50 (33): 7520 DOI: 10.1002/anie.201101753