SCIENCE & TECHNOLOGY CONCENTRATES
The forgetful marijuana user is a common comedy trope, but the memory-impairing effects of pot’s most psychoactive ingredient, ∆9-tetrahydrocannabinol (THC), are serious impediments to medical uses for cannabis. Those effects result from THC stimulating increased production of COX-2, the same enzyme that is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, say Chu Chen and colleagues at Louisiana State University (Cell 2013, DOI: 10.1016/j.cell.2013.10.042). The team observed that THC induced a doseand time-dependent increase in COX-2 in mice, so they tested the behavioral effects of giving HO mice THC H along with a COX-2 inhibitor. Mice O given both substances H did not suffer the im9 Δ -Tetrahydrocannabinol pairment of working memory and fear conditioning that the THC-only mice experienced, nor did they display the same degree of lethargy. THC has been shown to help the mouse brain clear Alzheimer’s-associated amyloid-β plaques; the team showed that this ability is not reduced by COX-2 inhibition. The results could broaden medical applications of THC and inform future studies on the biochemical mechanisms of cannabinoid activity.—CB
SHUTTERSTOCK
STAR FRUIT’S CHEMICAL CURSE Most folks sampling a tropical treat called star fruit can expect a tart, citrusy burst in their mouths. But people with kidney disease can also expect hiccups, confusion, a feeling of intoxication, seizures, vomiting, and sometimes even death. That’s because star fruit contains a toxin called caramboxin that healthy kidneys can easily metabolize but diseased ones cannot, reports a team of researchers led by Norberto Garcia-Cairasco and Norberto P. Lopes of the University of São
SILICON NANOPILLARS COMMIT BACTERICIDE Nanostructures present both in nature (on dragonfly wings) and in the lab (on a synthetic silicon mimic) kill bacteria, suggesting new approaches to antibacterial surfaces for biomedical and industrial applications, reports a group led by Elena P. Ivanova of Swinburne University of Technology, in Australia (Nat. Commun. 2013, DOI: 10.1038/ncomms3838). Dragonfly wing surfaces are patterned with lipids that form vertical pillars a few hundred nanometers tall and less than 90 nm in diameter. Socalled black silicon—named for its light absorption properties—has similarly sized pillars, made up of largely amorphous silicon. When Ivanova and colleagues incubated either material with suspensions of Pseudomonas aeruginosa, Staphylococcus aureus, or Bacterial cells rupture when they land on black Bacillus subtilis, as well as with B. silicon nanopillars, shown in an SEM image. subtilis spores, they found that the surfaces killed the cells and spores. In prior work with cicada wing surfaces, which also have bactericidal nanopillars, Ivanova and colleagues showed that when P. aeruginosa cells adsorb onto nanopillar surfaces, parts of the cell walls located between individual pillars stretch, leading to cell rupture. The authors note that black silicon is readily made using standard semiconductor etching techniques.—JK
Paulo, in Brazil (Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201305382). Researchers have tried previously to identify the toxic component of this fruit, initially focusing erroneously on oxalate. Lopes and Garcia-Cairasco’s team isolated and solved the structure of caramboxin, showing that the phenylalanine-like molecule can reproduce the toxic symptoms in animal models by acting on important ion channel receptors for the neuO rotransmitter gluNH2 HO tamate. They also discovered that CH3O over time, isolated OH caramboxin stored at room temperaOH O ture forms a closed Caramboxin ring structure that is no longer toxic. The team proposes that caramboxin and its inactive analog could be useful tools to study neurotransmitter receptors.—SE CEN.ACS.ORG
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METAL DUO MAKES β-ARYL KETONES The carbons immediately adjacent to a carbonyl group are usually straightforward places to form new carbon-carbon bonds. Just use a strong base, or a carefully designed catalyst, and that α-carbon is good to go. The next carbon over, the β-carbon, is not so amenable to change, however. Traditionally, β-substituted carbonyls require multiple steps to prepare. Because that β-motif is common in insecticides and drug candidates, chemists are keen to simplify the process. They’ve developed a handful of β-functionalization reactions, but none is generally applicable yet. Now, graduate student Zhongxing Huang and assistant professor Guangbin Dong of the University of Texas, Austin, have added to the toolbox with a reaction that inserts aromatic rings at the β-position of simple ketones (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja410389a). The palladium-catalyzed process uses readily available aryl iodides and bromides as the substrates. A silver salt regenerates the active catalyst. Dong cautions that the
NAT. COMMUN.
STONER MEMORY LOSS EXPLAINED
O
O + PhI
H N
Pd catalyst, Ag salt
Ph Ph
NH
too low, according to a new analysis of what’s actuPh Ph Ph Ph ally in the air (Proc. Serotonin reuptake Natl. Acad. Sci. USA inhibitors 2013, DOI: 10.1073/ pnas.1314392110). Emissions inventories by agencies such as EPA are done with a “bottom up” approach that calculates emissions based on estimates of the amount of methane typically released from sources such as livestock and natural gas extraction. In the new work, a team led by Scot M. Miller and Steven C. Wofsy of Harvard University analyzed methane measurements made at ground level, on towers, and from aircraft in various locations across the U.S. in 2007 and 2008. They then used air transport models to track back from the measurement location to emission points. They found that methane emissions are generally 50% higher than EPA estimates, with livestock across the entire U.S. and fossil-fuel extraction in the South Central region as primary targets of underestimation.—JK +
Ph
Ph = phenyl
A new β-arylation makes an intermediate used to synthesize serotonin reuptake inhibitors.
reaction is still in its infancy. He’d like to figure out the reaction mechanism and replace the silver reagent with something less expensive. UT Austin is pursuing a provisional patent on the chemistry.—CD
PROTEIN STRUCTURE FROM SCRATCH
MAX PLANCK SOCIETY
Free-electron lasers (FELs), which produce extremely intense, ultrashort X-ray pulses, have previously been used to determine structures of microscale protein crystals. But so far, all of the crystal structures solved this way have required the addition of data from already known and related structures. Now, researchers have used only FEL data to solve a known structure, lysozyme, at 2.1-Å resolution (Nature 2013, DOI: 10.1038/ nature12773). Ilme Schlichting and Thomas R. M. Barends of the Max Planck Institute for Medical Research, in Heidelberg, Germany, and coworkers there and at SLAC National Accelerator Laboratory acquired diffraction images from a gadolinium derivative of lysozyme. They used the heavy atoms to align the images. The researchers collected more than 2.4 million images to obtain 60,000 images with usable data. The method is ready to move on to unknown protein structures, Barends says. “I would trust it just as much as any crystal structure determined using another X-ray source.” The method is particularly suited to proteins that are difficult to crystallize or are extremely sensitive to radiation damage.—CHA
U.S. METHANE EMISSIONS HIGHER THAN ESTIMATED Estimates of how much methane is emitted to the atmosphere from the U.S. are
SLOW AND STEADY MAKES PERFECT CRYSTALS It’s not hard to be a perfectionist if you have all the time in the world to do a job right. Guided by that thinking, Northwestern University’s Evelyn Auyeung, Monica OlveA rendering of lysozyme. ra de la Cruz, Chad A. Mirkin, and coworkers have shown that metal nanoparticles tagged with strands of DNA can be coaxed into assembling nearly perfect crystals with predictable geometries simply by cooling the system from a little above to a little below its melting point over the course of several days (Nature 2013, DOI: 10.1038/nature12739). That finding may lead to custom-designed crystals for photonics, electronics, and catalysis applications. Atoms form crystals by way of fairly well understood processes. Not so for molecules and large particles. Previous attempts to use DNA base-pair recognition to form nanoparticle crystals led to ill-formed crystals or ones with unexpected geometries that varied with nanoparticle size. In contrast, the slowCEN.ACS.ORG
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SCIENCE & TECHNOLOGY CONCENTRATES
cooling method leads to micrometer-sized faceted crystals with a rhombic dodecahedron shape (shown, with inset rendering of DNA-tagged nanoparticles) regardless of nanoparticle size. That outcome is the thermodynamically favored and theoretically predicted one, the team notes.—MJ
CHEMISTS RING IN WITH NEW HETEROCYCLES Cyclic organic groups containing nitrogen, oxygen, and sulfur in the ring with carbon are essential in many pharmaceuticals. Although myriad variations of these heterocycles are known, chemists are always on the lookout for practical synthetic routes to new or rare versions. Two research teams have just come up N S with such strategies. Béatrice QuicletSire and Samir Z. Dihydro-1,2-thiazine Zard of École PolyO technique, in France, report an expedient N route to six-memH bered sulfur-nitro1,4-Oxazine gen ring compounds called dihydro-1,2-thiazines (Org. Lett. 2013, DOI: 10.1021/ol402973q). Only the parent compound (shown) has been prepared before. Building on their previous work on xanthate [ROC(=S)SR´] chemistry, the researchers coupled xanthates with olefins to form intermediates that undergo a ringclosing process to form substituted and fused-ring examples. Separately, R. Alan Aitken and coworkers at the University of St. Andrews, in Scotland, developed a method to prepare the six-membered oxygennitrogen heterocycle 1,4-oxazine (Chem. Commun. 2013, DOI: 10.1039/c3cc47801g). Substituted and fused-ring 1,4-oxazines are known, but this is the first reported synthesis and characterization of the parent compound (shown). The researchers prepared the unstable compound by flash vacuum pyrolysis of a substituted 1,4-oxazine.—SR
