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February 2002
Vol. 11, No. 2
pp 14, 16, 18.
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SciTech Briefs

odor-free thiols
Odor-free thiols
Getting the Stink Out

Of all the bad luck, to work with thiols! Certainly, they are a synthetically versatile chemical group, essential reagents in making everything from coatings to pharmaceuticals to catalysts. But, frankly, as many chemists know all too well, thiols wouldn’t be the compounds of choice to use right before a romantic evening on the town; they often have an unbearable and persistent stench. Working with thiol reagents can be a very unpleasant experience, and that’s not to mention how much worse it can be for those carrying out large-scale, industrial processes with these foul-smelling substances.

With all of this in mind, Manabu Node and colleagues from Kyoto Pharmaceutical University in Japan recently decided to explore the use of odorless substitute compounds for the very commonly used reagents ethanethiol and benzyl mercaptan. The team synthesized a range of compounds based on the structures of these compounds and ranked them on a 0–5 odor index (5 being the most disagreeable and 0 being odorless), based on the perceptions of two human test subjects (Tetrahedron Lett. 2001, 42 (52), 9207–9210). Generally, the longer the carbon chain length of the thiol, the less odor perceived. Specifically, the compounds 1-dodecanethiol and p-heptylphenylmethanethiol both received scores of zeros.

All right, so they don’t smell, but do they do anything? Node’s group demonstrated that the compounds could be great substitutes in at least two types of important thiol-mediated reactions. 1-Dodecanethiol was able to take the place of ethanethiol in the dealkylation of several aliphatic and aromatic ethers, typically showing yields of around 95%. In addition, p-heptylphenylmethanethiol was used instead of benzyl mercaptan in the Michael addition of a thiol to an alpha,beta-unsaturated ketone, obtaining a 95% yield.

Thus, the use of these odorless thiols could greatly improve the physical environment in which many synthetic researchers work, and maybe even spark up their social lives.

David Filmore


Crossing the Optical Channel
Experimental setup for the optical channel
Experimental setup for the optical channel
ANAL. CHEM. 2001, 73 (24), 5791–5795
When light strikes the surface of a particle, the light is reflected and refracted. This changes the momentum of the light and induces radiation pressure. Thus, in processes such as laser trapping, researchers use laser light to move small particles such as cells. But laser trapping uses intense radiation that can damage cells and typically only measures one cell at a time. To address these problems, another technique, called optical chromatography, which is gentler on the cells, was developed in the mid-1990s by Totaro Imasaka and colleagues at Japan’s Kyushu University (Hakozaki, Fukuoka).

In optical chromatography, the radiation force is countered by the opposing flow of medium through a capillary, and a given particle will drift to a position where the influence of the two forces is equal. Because different-sized particles will experience different forces, they will occupy different equilibrium positions. By changing either the laser intensity or the medium flow rate, the particles can be selectively passed through the focal point of a charge-coupled-device camera. The researchers first used this technology in an immunoassay in which they examined the dimerization of antibody-coated beads in the presence of antigen (Anal. Chem. 1997, 69, 2711–2715).

Recently, the same research group used a variation of optical chromatography, the optical channel, to measure the elasticity of the membrane of red blood cells (Anal Chem. 2001, 73 (24), 5791–5795). Elasticity, which varies with age, is a product of the viscosity of the cell’s cytoplasm, the proteins located within the membrane, and the ratio of surface area to volume, and is often used in the diagnosis of diseases such as sickle cell and immune hemolytic anemia.

Imasaka’s group watched red blood cells as they deformed in the medium stream of an optical channel, which mimics the conditions in a blood vessel; the greater the degree of deformation, the greater the elasticity. The researchers found that cell elasticity as measured by their optical channel was on par with that measured by other techniques. Because the cells are exposed to less energy than they would be by laser trapping, they remain viable and can be tested for other properties such as chemical content. Thus, the optical channel provides a useful tool for the correlation of cell function with chemical composition.

Randall C. Willis


illustration of nanotubeCleaner Hydrogen and Nanotubes to Boot
Hydrotreating diesel fuel is a common method for cleaning up gasoline, particularly for removing some of the sulfur content. Hydrogen also plays a key role in the workings of advanced fuel cells. Hydrogen has traditionally been produced for these purposes by reforming or partial oxidation of methane to produce hydrogen and carbon monoxide as well as carbon dioxide. Because of concern over CO and CO2 emissions, and an increasing demand for hydrogen, finding a catalytic process for hydrogen production from hydrocarbons has become an important goal.

Researchers at the University of Kentucky have recently made some interesting headway in this effort. They have reported the use of binary catalysts, of the type Fe-M (M = Pd, Mo, or Ni; 4.5 wt% Fe, 0.5% M, on alumina support), for the catalytic decomposition of methane (Energy and Fuels 2001, 15 (6), 1528–1534). At temperatures between 700 and 800 °C, all of the catalysts achieved peak activity, resulting in a product gas that was 85-90% hydrogen (by volume). This is about 400 °C below the temperatures required for thermal decomposition of methane.

This method provides a great alternative for use in fuel cells, since the CO from conventional hydrogen production reactions can poison fuel cell catalysts. The binary catalytic decomposition, on the other hand, is basically free of CO.

However, the most fascinating aspect of this new catalyst is the carbon product that is formed. When the process was carried out in the 700–800 °C range, the carbon deposits were identified, via electron micrographs, as multiwalled nanotubes. This is significant for two reasons. First, the nanotubes seem to allow the catalyst to remain active, whereas other carbon deposits, like amorphous carbon and carbon fibers, tend to block activity. Second, carbon nanotubes are being widely investigated for many different industrial applications, and therefore, both major products of this reaction could be valuable in their own right.

Michael Felton


chemical structures
4-Methy-3-(1-pyrrolidinyl)-2(5H)-furanone (2) exhibited a significantly lower “cooling” flavor threshold than the ever-popular menthol (1).
Enamines of the (Cool) State
Why do things taste or feel cool? Menthol, a terpene, is frequently used as an additive in gums, mints, medicines, and cigarettes to impart the familiar coolness or “freshness” effect. Significantly, such cooling agents are also used in cosmetics to create the same feelings on the skin. As neither evaporation nor blood vessel dilation are involved with the effect, there is no actual change in temperature occurring, only a perceived one. But what parts of the body are doing the perceiving and what aspects of chemical structure are responsible for inducing the feeling? “Cooling” active compounds are found in a wide variety of structural types, from methyl esters to phosphine oxides to sulfonamides. But they all appear to act through a common mechanism—a direct effect on cellular receptors.

Animals have specific receptors for perceiving cold. Compounds such as menthol appear to bind in a lock-and-key fashion to these receptors, depolarizing them, and hence interfering with calcium mobility across cell membranes. The lack of calcium efflux from the cold receptor-containing cells triggers nervous discharge (signifying cold to the brain) in the presence of mentholated products.

Researchers at the Deutsche Forshungstalt für Lebensmittelchemie (Garching, Germany) have previously identified novel-class natural “cooling” compounds, 3-methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one and 5-methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one, using taste bioassays of roasted glucose/L-proline mixtures and dark malt, as well as mass spectrometry and nuclear magnetic resonance analysis (J. Ag. Food Chem. 2001, 49 (3), 1336–1344).

More recently, the scientists carried out structure–activity studies on synthesized versions of these cyclic alpha-keto enamines to probe the molecular features required to exhibit strong cooling activity (J. Ag. Food Chem. 2001, 49 (11), 5383–5390). The studies showed that the structures could be modified and the effective cooling threshold greatly increased by the insertion of an oxygen atom into the 2-cyclopenten-1-one ring. One resultant compound, 4-methy-3-(1-pyrrolidinyl)-2(5H)-furanone, proved active at oral threshold concentrations of 0.02-0.06 mmol/L, 35-fold below the determined value for menthol. Because these compounds are odorless and tasteless, the researchers concluded that “there is no physiological link between cooling activity and mint-like odors.” Thus, enamines may be of use for evoking certain cooling effects in nonmint products such as drinking water, confectionaries, citrus beverages, hair shampoos, and body lotions.

Mark Lesney


A Few Reviews
The mass of published research these days has arguably become overwhelming for many scientists. But there is nothing like a good old fashioned review of the literature to pull things together and provide something approximating a comprehensive picture of happenings in topics of current research. Informative reviews are constantly being published, and below several recent ones are briefly discussed.

In the December 2001 issue of Chemical Reviews, polymer chemistry is the focus, along with progress in the highly complex endeavor of synthetically mimicking biological structures and functions. One review (p 4013–4038), from Japanese scientists, looks at macromolecule compounds with helical structures, which are fundamental shapes of biomolecules, that have been synthesized—everything from polymethacrylates to polyaldehydes to polymer metallic complexes. Another paper (p 4039–4070), from the University of Nijmegen (The Netherlands), discusses work that has been accomplished in copying the action of protein formation from amino acids, for example for the construction of macromolecular architectures with defined three-dimensional structures using programmed organization of small molecules.

In Chemistry of Materials, an interesting review is included from a German chemist on organometallic chemistry being carried out on periodic mesoporous silica surfaces (2001, 13, 4419–4438). Such endeavors offer a unique approach to constructing nano composite material.

On the natural products front, Tom Mabry from the University of Texas, Austin, has written a first-person account of his 40 years of research with betalains (red-violet pigments), flavonoids, antiviral proteins, and neurotoxic amino acids. It appears in the Journal of Natural Products (2001, 64, 1596–1604). And in a more focused effort, researchers in India have summarized the available information on the chemistry and biochemistry of (-)-hydroxycitric acid [(-)-HCA] from the Garcina genus of trees and shrubs. This compound has been used, it is claimed, to enhance weight loss, protect the heart, correct lipid abnormalities, and increase endurance (J. Ag. Food Chem. 2002, 50, 10–22).

Finally, an environmental chemistry review (Environ. Sci. Tech. 2001, 35 (24), 4697–4702) was published on endocrine-disrupting chemicals that are left behind after conventional sewage sludge treatment—including their metabolic fate, health effects, removal techniques, and so on.

David Filmore


SciTech Briefs || Business Bits

Business Bits

CAS provides almost a century of access. Chemical Abstracts Service (CAS) has expanded its online literature database to include bibliographic and abstract information from 3.8 million more records, including journal papers, patents, books, and more, dating back to 1907. Previously, the searchable database only extended back to 1967 (CAS press release).

Ecstasy test approved. American Bio Medica Corp. (Kinderhook, NY) has received 510(k) clearance, needed for medical device marketing, from the Food and Drug Administration for its on-site test for the illegal designer drug 3,4-methylenedioxymethamphetamine (Ecstasy). Rapid One Ecstasy is a one-step immunoassay capable of detecting the drug in urine at concentrations of 1000 ng/ml (Business Wire).

Polymer Laboratories to develop Symyx methods. Symyx Technologies, Inc. (Santa Clara, CA) has licensed Polymer Laboratories (Shropshire, UK) to develop and commercialize its proprietary high-performance liquid chromatography and flow injection techniques for high-throughput polymer analysis, such as molecular weight measurements (Symyx Technologies press release).

“Nano” company receives funding. A professor at Stanford University, Hongjie Dai, has founded and received initial funding for Molecular Nanosystems, Inc. (Palo Alto, CA), a company that aims to pursue applications of carbon nanotubes in biotechnology, chemistry, and electronics. The company produced its first batch of nanotubes in December 2001 (Business Wire).

Pharsight, Roche link. Roche Bioscience (Palo Alto, CA) and Pharsight (Mountain View, CA) will collaborate to bring together Roche’s genomics discovery program with Pharsight’s software, modeling, and simulation technologies for clinical drug development. The companies hope to spur research into individually tailored drugs (GenomeWeb).


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