Chemists transform acids into bases: Research offers vast family of new catalysts for use in drug discovery, biotechnology

Chemists at the University of California, Riverside have accomplished in the lab what until now was considered impossible: transform a family of compounds which are acids into bases.

As our chemistry lab sessions have taught us, acids are substances that taste sour and react with metals and bases (bases are the chemical opposite of acids). For example, compounds of the element boron are acidic while nitrogen and phosphorus compounds are basic.

The research, reported in the July 29 issue of Science, makes possible a vast array of chemical reactions -- such as those used in the pharmaceutical and biotechnology industries, manufacturing new materials, and research academic institutions.

"The result is totally counterintuitive," said Guy Bertrand, a distinguished professor of chemistry, who led the research. "When I presented preliminary results from this research at a conference recently, the audience was incredulous, saying this was simply unachievable. But we have achieved it. We have transformed boron compounds into nitrogen-like compounds. In other words, we have made acids behave like bases."

Bertrand's lab at UC Riverside specializes on catalysts. A catalyst is a substance -- usually a metal to which ions or compounds are bound -- that facilitates or allows a chemical reaction, but is neither consumed nor altered by the reaction itself. Crucial to the reaction's success, a catalyst is like the car engine enabling an uphill drive. While only about 30 metals are used to form catalysts, the binding ions or molecules, called ligands, can number in the millions, allowing for numerous catalysts. Currently, the majority of these ligands are nitrogen- or phosphorus-based.

"The trouble with using phosphorus-based catalysts is that phosphorus is toxic and it can contaminate the end products," Bertrand said. "Our work shows that it is now possible to replace phosphorus ligands in catalysts with boron ligands. And boron is not toxic. Catalysis research has advanced in small, incremental steps since the first catalytic reaction took place in 1902 in France. Our work is a quantum leap in catalysis research because a vast family of new catalysts can now be added to the mix. What kind of reactions these new boron-based catalysts are capable of facilitating is as yet unknown. What is known, though, is that they are potentially numerous."

Bertrand explained that acids cannot be used as ligands to form a catalyst. Instead, bases must be used. While all boron compounds are acids, his lab has succeeded in making these compounds behave like bases. His lab achieved the result by modifying the number of electrons in boron, with no change to the atom's nucleus.

"It's almost like changing one atom into another atom," Bertrand said.

His research group stumbled upon the idea during one of its regular brainstorming meetings.

"I encourage my students and postdoctoral researchers to think outside the box and not be inhibited or intimidated about sharing ideas with the group," he said. "The smaller these brainstorming groups are, the freer the participants feel about bringing new and unconventional ideas to the table, I have found. About 90 percent of the time, the ideas are ultimately not useful. But then, about 10 percent of the time we have something to work with."

The research was supported by grants to Bertrand from the National Science Foundation and the U.S. Department of Energy.

An internationally renowned scientist, Bertrand came to UCR in 2001 from France's national research agency, the Centre National de la Recherche Scientifique (CNRS). He is the director of the UCR-CNRS Joint Research Chemistry Laboratory.

A recipient of numerous awards and honors, most recently he won the 2009-2010 Sir Ronald Nyholm Prize for his seminal research on the chemistry of phosphorus-phosphorus bonds and the chemistry of stable carbenes and their complexes.

He is a recipient of the Japanese Society for Promotion of Science Award, the Humboldt Award, the International Council on Main Group Chemistry Award, and the Grand Prix Le Bel of the French Chemical Society. He is a fellow of the American Association for the Advancement of Sciences, and a member of the French Academy of Sciences, the European Academy of Sciences, Academia Europea, and Academies des Technologies.

He has authored more than 300 scholarly papers and holds 35 patents.

Bertrand was joined in the research by Rei Kinjo and Bruno Donnadieu of UCR; and Mehmet Ali Celik and Gernot Frenking of Philipps-Universitat Marburg, Germany.

UCR's Office of Technology Commercialization has filed a provisional patent application on the boron-based ligands developed in Bertrand's lab.

Story Source:

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

Journal Reference:

R. Kinjo, B. Donnadieu, M. A. Celik, G. Frenking, G. Bertrand. Synthesis and Characterization of a Neutral Tricoordinate Organoboron Isoelectronic with Amines. Science, 2011; 333 (6042): 610 DOI: 10.1126/science.1207573

Emulating nature for better engineering

UK researchers describe a novel approach to making porous materials, solid foams, more like their counterparts in the natural world, including bone and wood in the new issue of the International Journal of Design Engineering.

According to Carmen Torres-Sanchez of the Department of Mechanical Engineering, at Heriot-Watt University, Edinburgh and Jonathan Corney of the Department of Design, Manufacture and Engineering Management, at the University of Strathclyde, Glasgow in the natural world, the graduated distribution of porosity has evolved so that nature might transfer forces and minimise stresses to avoid whole structure failure. For instance, a crack in the branch of a tree will not lead to the felling of the tree in the same way that a broken ankle will not lead to collapse of the whole leg. "Porosity gradation is an important functionality of the original structure that evolution has developed in a trial and error fashion," the team explains.

It is not just tree trunks and bones that have evolved graduated porosity, beehives, marine sponges, seashells, teeth, feathers and countless other examples display this characteristic. Researchers would like to be able to emulate the way in which nature has evolved solutions to the perennial issues facing engineers. In so doing, they will be able to develop structures that use the least amount of material to gain the lowest density structure and so the maximum strength-to-weight ratio.

"Many engineering applications, such as thermal, acoustics, mechanical, structural and tissue engineering, require porosity tailored structures," the team says. If materials scientists could develop porous materials that closely mimic nature's structural marvels, then countless engineering problems including bridge building and construction in earthquake zones, improved vehicle and aircraft efficiency and even longer-lasting more biocompatible medical prosthetics might be possible.

Unfortunately, current manufacturing methods for making porous materials cannot mass-produce graduated foams. The collaborators in Scotland, however, have turned to low power-low frequency ultrasonic irradiation that can "excite" molten polymers as they begin to foam and once solidify effectively trap within their porous structure different porosity distributions throughout the solid matrix. This approach allowed the team to generate polymeric foams with porosity gradients closely resembling natural cellular structures, such as bones and wood. The technology opens up new opportunities in the design and manufacture of bio-mimetic materials that can solve challenging technological problems, the team adds.

The researchers anticipate that using more sophisticated ultrasound energy sources as well as chemical coupling agents in the molten starting material will allow them to fine tune the formation of pores in the material. This is an area of current interest because it would facilitate the design of novel texture distributions or replicate more closely nature porous materials, the team concludes.

Story Source:

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

Journal Reference:

C. Torres Sanchez, J.R. Corney. A novel manufacturing strategy for bio-inspired cellular structures. International Journal of Design Engineering, 2011; 4 (1): 5 DOI: 10.1504/IJDE.2011.041406

Nano sensor detects minute traces of plastic explosives: Scientists enable inexpensive, reliable checks for explosives

 Working in collaboration with the RhineMain Polytechnic, materials scientists at the TU Darmstadt have developed an extremely sensitive explosives sensor that is capable of detecting even slight traces of the high-explosive chemical compound pentaerythritol tetranitrate (PETN). Terrorists had employed PETN in several attacks on commercial aircraft.

To date, the high-explosive chemical compound PETN could be detected exclusively by means of wipe tests and an ion-mobility spectrometer. However, since conducting such tests involves considerable time and effort, it is employed at airports for spot-checking only. Airport scanners and dogs trained to sniff out explosives have a hard time detecting PETN, since PETN is only slightly volatile and therefore liberates only small numbers of molecules into the ambient air. PETN is also a high explosive. Just a few grams are enough to totally destroy a medium-sized passenger car. Thanks to those properties, PETN has recently been frequently employed by terrorists. PETN was found in the package bombs that were intended to blow up cargo planes late last year and was also employed by the "underpants bomber" in his attempted attack on a passenger plane in December 2009.

Scientists at the TU-Darmstadt have recently developed a nanosensor capable of detecting a single PETN-molecule among ten billion air molecules. Explaining the new type of explosive detector's operation, Dipl.-Ing. Mario Boehme stated that, "If a PETN-molecule enters the sensor's nanotube, the nitro groups characteristic of PETN adhere to its surface and change its electrical conductivity, and that change may be detected by electronic instrumentation."

Checking for explosives without spending more time in the process

In order to detect PETN using the new sensor, all that is necessary is conducting ambient air across the sensor. Boehme added that, "One possibility would be equipping the conventional metal detectors and X-ray machines employed at airport security checkpoints with the new sensor and a device for inducting air." That approach would allow discreetly checking all passengers and their luggage for explosives without spending more time in the process. He went on to state that, "However, another possibility would be utilizing a hand-held device similar to a table vacuum cleaner that would allow checking individual passengers." Since the sensors are extremely small and inexpensive to manufacture, he can also envision employing them at sports events or in other types of security checks. He and his research associates are currently seeking industrial collaboration partners.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Technische Universität Darmstadt.

Computational chemistry shows the way to safer biofuels

 Replacing gasoline and diesel with plant-based bio fuels is crucial to curb climate change. But there are several ways to transform crops to fuel, and some of the methods result in bio fuels that are harmful to health as well as nature.

Now a study from the University of Copenhagen shows that it is possible to predict just how toxic the fuel will become without producing a single drop. This promises cheaper, faster and above all safer development of alternatives to fossil fuel.

Solvejg Jorgensen is a computational chemist at the Department of Chemistry in Copenhagen. Accounts of her new computational prediction tool are published in acclaimed scientific periodical The Journal of Physical Chemistry A.

Among other things the calculations of the computer chemist show that bio fuels produced by the wrong synthesis path will decompose to compounds such as health hazardous smog, carcinogenic particles and toxic formaldehyde. Previously an assessment of the environmental impact of a given method of production could not be carried out until the fuel had actually been made. Now Jorgensen has shown that various production methods can be tested on the computer. This will almost certainly result in cheaper and safer development of bio fuels.

"There is an almost infinite number of different ways to get to these fuels. We can show the least hazardous avenues to follow and we can do that with a series of calculations that take only days," explains Jorgensen.

Chemically bio fuel is composed of extremely large molecules. As they degrade during combustion and afterwards in the atmosphere they peel of several different compounds. This was no big surprise. That some compounds are more toxic than others did not come as a revelation either but Jorgensen was astonished to learn from her calculations that there is a huge difference in toxicity depending on how the molecules were assembled during production. She was also more than a little pleased that she could calculate very precisely the degradation mechanisms for a bio fuel molecule and do it fast.

"In order to find the best production method a chemist might have to test thousands of different types of synthesis. They just can't wait for a method that takes months to predict the degradation mechanisms," explains Jorgensen who continues: "On the other hand: For a chemist who might spend as much as a year trying to get the synthesis right it would be a disaster if their method leads to a toxic result."

It seems an obvious mission to develop a computational tool that could save thousands of hours in the lab. But Solvejg Jorgensen wasn't really all that interested in bio fuels. What she really wanted to do was to improve existing theoretical models for the degradation of large molecules in the atmosphere.

To this end she needed some physical analysis to compare to her calculations. Colleagues at the Department of Chemistry had just completed the analysis of two bio fuels. One of these would do nicely. But Jorgensen made a mistake. And instead of adding just another piece to a huge puzzle she had laid the foundation for a brand new method.

"I accidentally based my calculations on the wrong molecule, so I had to start over with the right one. This meant I had two different calculations to compare. These should have been almost identical but they were worlds apart. That's when I knew I was on to something important," says Solvejg Jorgensen, who has utilised her intimate knowledge of the theoretical tool density functional theory and the considerable computing power of the University of Copenhagen.

The article is published in The Journal of Physical Chemistry A with the title: Atmospheric Chemistry of Two Biodiesel Model Compounds: Methyl Propionate and Ethyl Acetate.

Story Source:

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

Journal Reference:

Vibeke F. Andersen, Tesfaye A. Berhanu, Elna J. K. Nilsson, Solvejg Jorgensen, Ole John Nielsen, Timothy J. Wallington, Matthew S. Johnson. Atmospheric Chemistry of Two Biodiesel Model Compounds: Methyl Propionate and Ethyl Acetate. The Journal of Physical Chemistry A, 2011; : 110728091620061 DOI: 10.1021/jp204819d

Researchers graft olfactory receptors onto nanotubes

Penn researchers have helped develop a nanotech device that combines carbon nanotubes with olfactory receptor proteins, the cell components in the nose that detect odors.

Because olfactory receptors belong to a larger class of proteins that are involved in passing signals through the cell membrane, these devices could have applications beyond odor sensing, such as pharmaceutical research.

The research was led by professor A. T. Charlie Johnson, postdoctoral fellow Brett R. Goldsmith and graduate student Mitchell T. Lerner of the Department of Physics and Astronomy in the School of Arts and Sciences, along with assistant professor Bohdana M. Discher and postdoctoral fellow Joseph J. Mitala Jr. of the Department of Biophysics and Biochemistry at Penn's Perelman School of Medicine. They collaborated with researchers from the Monell Chemical Senses Center, the University of Miami, the University of Illinois, Princeton University and two private companies, Nanosense Inc. and Evolved Machines Inc.

Their work was published in the journal ACS Nano.

The Penn team worked with olfactory receptors derived from mice, but all olfactory receptors are part of a class of proteins known as G Protein Coupled Receptors, or GPCRs. These receptors sit on the outer membrane of cells, where certain chemicals in the environment can bind to them. The binding action is the first step in a chemical cascade that leads to a cellular response; in the case of an olfactory receptor, this cascade leads to the perception of a smell.

The Penn team succeeded in building an interface between this complicated protein and a carbon nanotube transistor, allowing them to convert the chemical signals the receptor normally produces to electrical signals, which could be incorporated in any number of tools and gadgets.

"Our nanotech devices are read-out elements; they eavesdrop on what the olfactory receptors are doing, specifically what molecules are bound to them," Johnson said.

As the particular GPCR the team worked with was an olfactory receptor, the test case for their nanotube device was to function as sensor for airborne chemicals.

"If there's something in the atmosphere that wants to bind to this molecule, the signal we get through the nanotube is about what fraction of the time is something bound or not. That means we can get a contiguous read out that's indicative of the concentration of the molecule in the air," Johnson said.

While one could imagine scaling up these nanotube devices into a synthetic nose -- making one for each of the approximately 350 olfactory GPCRs in a human nose, or the 1,000 found in a dog's -- Johnson thinks that medical applications are much closer to being realized.

"GPCRs are common drug targets," he said. "Since they are known to be very important in cell-environment interactions, they're very important in respect to disease pathology. In that respect, we now have a pathway into interrogating what those GPCRs actually respond to. You can imagine building a chip with many of these devices, each with different GPCRs, and exposing them all at once to various drugs to see which is effective at triggering a response."

Figuring out what kinds of drugs bind most effectively to GPCRs is important because pathogens often attack through those receptors as well. The better a harmless chemical attaches to a relevant GPCR, the better it is at blocking the disease.

The Penn team also made a technical advancement in stabilizing GPCRs for future research.

"In the past, if you take a protein out of a cell and put it onto a device, it might last for a day. But here, we embedded it in a nanoscale artificial cell membrane, which is called a nanodisc," Johnson said. "When we did that, they lasted for two and half months, instead of a day."

Increasing the lifespans of such devices could be beneficial to two scientific fields with increasing overlap, as the as evidenced by the large, interdisciplinary research team involved in the study.

"The big picture is integrating nanotechnology with biology, " Johnson said. "These complicated molecular machines are the prime method of communication between the interior of the cell and the exterior, and now we're incorporating their functionality with our nanotech devices."

In addition to Johnson, Goldsmith, Lerner, Discher and Mitala, the research was conducted by Jesusa Josue and Joseph G. Brand of Monell; Alan Gelperin of Monell and Princeton; Ana Castro and Charles W. Luetje of the University of Miami; Timothy H. Bayburt and Stephen G. Sligar of the University of Illinois, Urbana; Samuel M. Khamis of Adamant Technologies, Ryan A. Jones of Nanosense Inc.; and Paul A. Rhodes of Nanosense Inc. and Evolved Machines Inc.

The research was supported by the Defense Advanced Research Projects Agency's RealNose project, Penn's Nano/Bio Interface Center, the National Science Foundation and the Department of Defense.

Story Source:

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

Journal Reference:

Brett R. Goldsmith, Joseph J. Mitala, Jesusa Josue, Ana Castro, Mitchell B. Lerner, Timothy H. Bayburt, Samuel M. Khamis, Ryan A. Jones, Joseph G. Brand, Stephen G. Sligar, Charles W. Luetje, Alan Gelperin, Paul A. Rhodes, Bohdana M. Discher, A. T. Charlie Johnson. Biomimetic Chemical Sensors Using Nanoelectronic Readout of Olfactory Receptor Proteins. ACS Nano, 2011; 5 (7): 5408 DOI: 10.1021/nn200489j

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