A hint of blackcurrant: Olfactory properties and gas-phase structures of Cassyrane stereoisomers

Upon testing different fragrances in a perfumery, the so-called top note, consisting of the most volatile odorants, is what characterizes a scent. These odorants determine the first and often most decisive impression of a perfume. Blackcurrant, or cassis, scent is one of the most sophisticated and elegant fruity top notes, and is fashionable since “DKNY Be Delicious”. A team from the RWTH in Aachen (Germany) and Givaudan Schweiz AG has now taken a close look at the blackcurrant odorant Cassyrane. As the scientists led by Wolfgang Stahl and Philip Kraft report in the journal Angewandte Chemie, there are specific structural features that key the cassis scent.

In addition to their two classic scents, ”Cassis Base 345B” and ”Corps Cassis”, in April 2010 Givaudan introduced a new captive ingredient Cassyrane; this substance imparts a natural, juicy cassis odor with aspects of cassis sorbet upon the top note of a perfume. Cassyrane consists of different so-called isomeric molecules that are of identical atomic composition, but have different spatial arrangements.

When four different atoms are bound to a carbon atom, there are two different ways for these to be arranged relative to each other in space. These two possible structures are mirror images of each other. Natural substances often have several such chiral centers. In scents, each of the possible combinations, known as stereoisomers, can have a different odor that can also be more or less intense. Cassyrane has two chiral centers, which gives it four possible stereoisomers.

Because the cassis odor of the other cassis scents distinctly depends on the configurations of the molecules, the researchers wanted to investigate the scent properties of the individual Cassyrane stereoisomers. They also examined the stereoisomers of the dihydro derivative, a compound of nearly identical structure that also smells of cassis but is missing the double bond found in the Cassyrane molecule.

It was first necessary to synthesize pure forms of each stereoisomer by means of clever procedures. It turns out that not all of the isomers smell of cassis. In both compounds, an R configuration at carbon number 5 elicits a character reminiscent of Provencal herbs like rosemary, while isomers with the 5S configuration had the fruity odor of cassis. The stereocenter at carbon number 2 has a strong influence on the intensity of the odor.

A molecule is a flexible structure; its atomic groups can twist and bend in various ways relative to each other. The researchers wished to determine which of these spatial structures is preferentially adopted by each of these stereoisomers in the gas phase. They were able to achieve this by examining the molecular rotations by means of microwave spectroscopy and combining these results with quantum chemical calculations. When the calculated structures were overlaid with those of the stereoisomers in the classical scents the result was clear: a very specific configuration does seem to be important for the cassis character of the scents.

More information: Philip Kraft, Cassis Odor through Microwave Eyes: Olfactory Properties and Gas-Phase Structures of all the Cassyrane Stereoisomers and its Dihydro Derivatives, Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/ … ie.201100937

Provided by Wiley (news : web)

Droplets for detecting tumoral DNA

It will perhaps be possible, in the near future, to detect cancer by a simple blood or urine test. In fact, biologists from CNRS, Inserm, Paris Descartes and Strasbourg universities have developed a technique capable of detecting minute traces of tumoral DNA present in the biological fluids of patients suffering from cancer. The method consists in carrying out ultra-sensitive molecular analyses in microscopic droplets. Successfully tested on genes involved in various cancers, including cancer of the colon and leukemia, it has the potential of becoming a powerful tool for oncologists, both in making a diagnosis and in prescribing a treatment. A clinical study is already envisaged to evaluate this technique. The work is published on the website of the journal Lab on a chip.

When tumoral cells die, they spill their contents into the extracellular medium. These contents, in particular the DNA of cells, are then found in the biological fluids of the patient: blood, lymph, urine, etc. Since the development of most cancers involves genetic factors, a simple blood or urine test could in theory reveal the presence of tumoral DNA and thus cancer as soon as the first cancerous cells die, in other words at a very early stage.

Despite this great promise, there is a snag which explains why physicians cannot yet track down cancers in biological fluids: tumoral DNA is only present in trace amounts in these fluids. In blood, for example, it represents less than 0.01% of the total DNA found in diluted form. However, conventional DNA analysis methods are not sensitive enough to detect such small amounts. Hence the interest of the technique developed by researchers from CNRS, Inserm, the Université de Strasbourg and the Université Paris Descartes, in collaboration with a German team from the Max Planck Institute (Göttingen) and an American company (Raindance Technologies). The considerable advantage of this technique is that it makes it possible to detect DNA thresholds 20,000 times lower than was previously the case in clinics.

How does it work? A first step consists in distributing the DNA extracted from a biological sample into millions of droplets, which are sufficiently small to contain only a single target gene each. Then, this DNA is amplified by means of modern molecular multiplication methods. Simultaneously, fluorescent molecules specific to each gene interact with the DNA. This key phase provides a sort of gene color code. The droplets are then guided, one by one, into microscopic grooves where they are analyzed by laser: the color of the fluorescent molecules then indicates which gene is present in the droplet. If the droplet emits red fluorescence, for example, the DNA is healthy. If it is green, it is tumoral. If the droplet does not emit any fluorescence, it does not contain the targeted gene. A simple count of the colored spots then makes it possible to determine the tumoral DNA concentration.

The researchers have successfully applied their method to an oncogene (a gene that has the potential of causing cancer) known as KRAS (associated with leukemia and various cancers, such as cancer of the colon, pancreas and lung). The DNA bearing this gene was derived from laboratory cell lines. This new analytical method now needs to be tested in a therapeutic context. A clinical study is already scheduled. If it is a success, physicians will have an efficient “anticancer weapon”, not just for detecting the presence of tumors but also for proposing treatments. The aggressiveness of the cancer, its responsiveness to existing treatments and its risk of recurrence following local treatment: all this information is partly contained in the tumoral DNA. By deciphering it with the microdroplet technology, oncologists could benefit from a powerful diagnostic tool to help predict the evolution of the disease and determine a therapeutic strategy.

More information: Quantitative and sensitive detection of rare mutations using droplet-based microfluidics. Pekin, D., et al., Lab on a chip, published on-line on 19 May 2011, DOI:10.1039/C1LC20128J

Provided by CNRS (news : web)

A better way to see molecular structures

Enlarge

John Waugh in his laboratory in 1984. Credit: Calvin Campbell

In laboratories at MIT and around the world, scientists are deciphering the molecular structures of proteins involved in Alzheimer’s and Parkinson’s diseases, diabetes, and many other disorders. Much of that research would not be possible without the pioneering nuclear magnetic resonance (NMR) work of John Waugh, MIT Institute Professor Emeritus.

When Waugh first came to MIT, in 1953, NMR was already a valuable tool for the study of molecular structure — but only for liquid samples. In the 1960s Waugh developed a way to use it to study solids, making it useful for analyzing things that don’t dissolve in water, including proteins, nucleic acids (such as DNA) and some drugs. That technique eventually played a role in many of the past half-century’s discoveries in chemistry, physics, biology and materials science; it is now one of science’s most widely used tools.

“He basically started this whole business,” says Robert Griffin, professor of chemistry, director of MIT’s Francis Bitter Magnet Laboratory and a former postdoc of Waugh’s. “None of what goes on in a few hundred labs around the world would be going on without his seminal contribution.”

Earlier this month, for his work on NMR, Waugh was named the 2011 recipient of the Welch Award — given for contributions to basic research that benefits humankind — which carries a $300,000 prize.

‘One of those magic moments’

Waugh became interested in nuclear magnetic resonance at a graduate student at the California Institute of Technology (Caltech). At that time, around 1949, NMR was still very new. “It was a physicists’ plaything,” recalls Waugh, who recently turned 82.

He joined the lab of Caltech chemistry professor Don Yost, whose specialty was “getting interested in some new phenomenon and then learning about it by conning a student into doing work on it. That’s what happened to me. I became the nuclear magnetic resonance student,” Waugh says. He read up on NMR in physics journals and built his own system with a borrowed magnet and “all sorts of World War II surplus electronics.”

After finishing his PhD, Waugh spent another year as a research associate at Caltech and then accepted a job as a chemistry instructor at MIT. He taught freshman chemistry, but had no space to do his own research.

“The way things are now, they hire a young person and expect him or her to do research, and they provide money and lab space. They didn’t do that in those days,” Waugh recalls. “I had no lab, and no money. When I asked about this I was told, ‘Well, you’ve got a fume hood in your office, you can do research there.’”

Luckily for Waugh, physicist Francis Bitter, for whom MIT’s magnet lab is now named, took an interest in his career. Bitter let him borrow a magnet, found him a small lab in the basement of Building 6 and got him a membership in the Research Laboratory of Electronics — the successor to the wartime Radiation Lab.

Once settled in his new lab, Waugh set out to overcome the limitation of NMR structural studies to the liquid state. “I remember trying to figure out how to do that for a long time. I drove myself nuts trying to think of how to do it,” Waugh says.

One day in the late 1960s, while eating breakfast, he suddenly realized that it could be done by applying a very special sequence of sharp, intense pulses of radiofrequency power. “It was one of those magic moments,” he recalls. Waugh then demonstrated and developed the technique along with his student Lee Huber and postdoc Ulrich Haeberlen. Fundamental contributions

Enthusiasm for the new technique, dubbed WAHUHA in honor of its discoverers, spread all the way to Washington University in St. Louis, where Griffin was then a grad student. “Everybody knew about John Waugh and all the exciting things that were happening at MIT. So I started trying to come here,” he says.

Griffin joined Waugh’s lab as a postdoc in 1970, and worked on ways to improve the sensitivity of NMR. He stayed on at MIT and in 1992 became director of the Francis Bitter Magnet Lab, where he now oversees 100 researchers in six labs. Much of the Magnet Lab’s research focuses on biological pursuits, such as determining the structure of proteins — for example, the amyloid proteins found in the brains of Alzheimer’s patients.

“NMR spectroscopy, thanks to Dr. Waugh’s insights, continues to profoundly influence the way we do science today,” says James Kinsey, chair of the scientific advisory board for the Welch Foundation, which will present Waugh with the Welch Award this fall. “His contributions have been absolutely fundamental to many past and current additions to our scientific understanding.”

As for Waugh, he says he never anticipated the wide impact his work has turned out to have.

“I think that’s the way most [scientists] are,” he says. “You start off doing some limited kind of stuff that makes use of any particular talents or knowledge you happen to have. You don’t think of it as being something that’s going to revolutionize the world. It’s just something interesting to do, and might be fun. That’s what motivates most of us, when you start off.”
This story is republished courtesy of MIT News (http://web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and teaching.

Provided by Massachusetts Institute of Technology (news : web)

Related to the famous Maya blue: Indigo compounds give Mayan art their yellow color

For the Maya, blue was the color of the gods. For ritual purposes, art objects, and murals, they used Maya blue, a pigment without equal with regard to boldness, beauty, and durability. Maya blue is made of indigo embedded in a special clay mineral called palygorskite.

A team led by Antonio Doménech at the University of Valencia (Spain) has now discovered that some Mayan yellow pigments are based on similar components. As the scientists report in the journal Angewandte Chemie, the Maya appear to have developed a preparative technique that was not limited to Maya blue and anticipated modern syntheses of organic–inorganic hybrid materials.

Maya blue is so fascinating because it has a special brightness and a singular color that can range from a bright turquoise to a dark greenish blue. Does the color stem from a unique organic component, a unique linking of the molecules, or a unique production process? Doménech and his team tested these hypotheses. They surmise that the hue is determined by the ratio of indigo to dehydroindigo, the oxidized form. This ratio depends on how long the Maya heated their formulation. This would allow for the formation of different variations of the addition compound formed by the indigo compounds and the mineral. The researchers further conjecture that the Maya were also able to produce yellow and green pigments from indigo-based pigments.

By means of various spectroscopic and microscopic methods, as well as voltammetry -- a special electrochemical process that allows for the identification of pigments in micro- and nanoscale samples from works of art—the scientists examined a series of yellow samples from Mayan murals from different archaeological sites in the Yucatán (Mexico). The results confirm that a whole series of yellow pigments from Mayan mural paintings are made of indigoids bound to palygorskite. The researchers also found ochre.

Doménech and his co-workers think it very likely that the preparation of such “Maya yellow” pigments was an intermediate step in the preparation of indigo and Maya blue. Leaves and branches from indigo plants were probably soaked in a suspension of slaked lime in water and the coarse material filtered out. A portion of the yellow suspension could then be removed and added to palygorskite to make Maya yellow. The remaining suspension would then be stirred intensely and ventilated until it took on a blue color. It was then filtered and dried to obtain indigo for use as a dye. It could also be ground together with palygorskite and heated to produce Maya blue.

More information: Antonio Doménech, From Maya Blue to "Maya Yellow": A Connection between Ancient Nanostructured Materials from the Voltammetry of Microparticles, Angewandte Chemie International Edition, http://dx.doi.org/ … ie.201100921

Provided by Wiley (news : web)