Science Concentrates

Nanocluster catalyst lives longer

Chinese chemists report a rhodium nanocluster catalyst that demonstrates "unprecedented" lifetime and activity in benzene hydrogenation under forcing conditions (J. Am. Chem. Soc. 2005, 127, 9694). The rhodium nanoclusters, which tend to coalesce into bulk metal on their own, are stabilized by the novel combination of a pyrrolidone-substituted, ionic-liquidlike copolymer (shown) dissolved in an imidazolium ionic liquid. The total turnovers for the catalyst--a measure of catalytic lifetime--exceeded 20,000 over five runs, which is more than five times the previous record for benzene hydrogenation by a nanocluster catalyst. Yuan Kou and coworkers at Peking University suggest that the high stability and activity of the rhodium catalyst are due to the combined stabilizing influences of the ionic liquid and the pyrrolidone-substituted copolymer. The stabilized rhodium nanoclusters, each roughly 3 nm across, were synthesized by hydrogenation of a mixture of RhCl₃3H₂O and the copolymer dissolved in the ionic liquid.

Brain-based pain relief

A mechanism by which the brain suppresses pain after severe injury suggests a new target for pain-relieving drugs. According to a new study by an international team, intense stress activates the release of cannabinoid compounds in the brain (Nature 2005, 435, 1108). Because binding of these compounds to their receptors in the brain initially blocks the pain caused by injuries sustained under extreme stress, the pain is not immediately felt. The team has identified 2-arachidonoyl glycerol and anandamide as pain-relieving compounds rapidly formed under severe stress. The researchers have shown that the pain relief due to these compounds is enhanced when the enzymes that deactivate them--monoacylglycerol lipase (MGL) and fatty acid amide hydrolase, respectively--are inhibited. A small molecule (shown) designed by the group of Daniele Piomelli at the University of California, Irvine, to selectively inhibit MGL dramatically increases pain relief in rats. The study identifies MGL "as a previously unrecognized therapeutic target," the researchers say.

Catalyst caught on tape

Chemists regard tape made of DuPont's Teflon as an indispensable sealer for lab equipment, but according to researchers in Germany, Teflon tape may be just as useful inside a reaction flask. John A. Gladysz and Long V. Dinh of the University of Erlangen-Nuremberg have discovered that Teflon tape is surprisingly effective at introducing and recovering homogeneous fluorous catalysts from a reaction mixture (Angew. Chem. Int. Ed. 2005, 44, 4095). Thermomorphic fluorous catalysts dissolve in organic solvents only at elevated temperatures, so chemists usually have to heat their reaction mixtures to get the catalyst into solution and then cool and decant the mixture to recover the catalyst. Gladysz and Dinh found that if they added Teflon tape to a ketone hydrosilylation reaction featuring a fluorous rhodium catalyst, the reaction could proceed with much less catalyst. Upon cooling, the catalyst clung to the tape so that the chemists could fish it out of the mixture. The researchers speculate that their findings could lead to industrial-scale reactors or reactor components that use Teflon to release and recapture certain fluorous catalysts.

Enzyme mimic raises questions

A model complex that mimics the active site of tyrosinase hydroxylates phenol substrates by a mechanism different from the one the enzyme is thought to use, according to a new study (Science 2005, 308, 1890). Liviu M. Mirica, Daniel Stack, and coworkers at Stanford University say their findings raise the possibility that tyrosinase may use an alternative mechanism, too. Tyrosinase--which plays a key role in melanin formation--relies on a pair of copper ions to activate O₂, which then hydroxylates a CH group of a phenol. The CuO₂Cu active species has long been assumed to contain an intact O₂ molecule, with each oxygen atom bound to both Cu(II) ions. In the model complex, however, hydroxylation is performed by a bis(oxo)dicopper(III) species (shown, R = tert-butyl) formed when the substrate (red) binds. The O-O bond has already been broken in this species, which was detected spectroscopically at -120 C and confirmed computationally. It remains to be seen whether tyrosinase uses such a species, Stack notes.

Small molecule fights anthrax

The antibiotic Cipro is effective against pulmonary anthrax only if it's administered at the early stages of infection. At later stages, the antibiotic can kill the anthrax bacteria but has no effect on the lethal toxin released by the bacteria. Now, a team led by Maurizio Pellecchia of the Burnham Institute, La Jolla, Calif., has developed a series of small molecules that inhibit the Bacillus anthracis lethal factor metalloproteinase--one of the components responsible for pulmonary anthrax' onset and progression (Proc. Natl. Acad. Sci. USA, published online, www.pnas.org/cgi/doi/10.1073/pnas.0502733102). Pellecchia and colleagues used library screening to identify a compound that inhibits the lethal factor. They then employed their medicinal chemistry know-how to tweak the small molecule, culminating in a series of derivatives that inhibit the lethal factor at nanomolar concentrations. In experiments with mice, a combination of Cipro and the compound shown protected 40% of mice against anthrax infection, whereas Cipro alone protected only 20%.