SCIENCE & TECHNOLOGY CONCENTRATES
TRIFLUOROMETHYLATION MEETS FLOW CHEMISTRY When chemists want to tweak the properties of an aromatic or heteroaromatic molecule, they often gussy it up with a trifluoromethyl group. The CF3 substituent is known to alter solubility and improve the activity of drugs. There are several ways to append CF3 groups to the rings, but no existing process is without its flaws. Some produce a variety of regioisomers. Others require reagents that are tricky to work with. Seeking to provide chemists with a simple and scalable trifluoromethylation method, MIT chemists Stephen L. Buchwald and Mao Chen combined their expertise in trifluoromethylation with their know-how in flow chemistry, where reactions are run via a continuous stream instead of in a batch. They’ve come up with a process that can make trifluoromethylated aromatics and heteroaromatics in a matter of minutes (Angew. Chem. Int. Ed. 2013, DOI: 10.1002/ anie.201306094). The copper-mediated cross-coupling reaction uses aryl iodides as starting materials and inexpensive and easy-to-handle potassium trifluoroacetate as a CF3 source.—BH
GROWTH HORMONE’S KNACK FOR REGENERATING Steroids given to cattle to promote growth can wind up in water supplies, where they may act as potent endocrine disruptors in wildlife. But some of the metabolized compounds, such as those stemming from trenbolone OH Light acetate, are believed to degrade too H quickly to be a problem. Not so H 2O fast, says a group led by David H OH M. Cwiertny of the University of O Iowa and Edward P. Kolodziej 17α-Trenbolone H of the University of Nevada, Reno. In both laboratory and H H2O field experiments, they find Dark O OH2+ OH that compounds such as 17αand 17β-trenbolone degrade H Dark via light-induced hydroxylation during the day but convert back H+ H O to the parent compound in the dark (Science 2013, DOI: 10.1126/ science.1243192). The driving force behind the regeneration reaction may be to restore a conjugated trienone system in the steroid framework. Similar regeneration occurs for steroids used for oral contraception and, illegally, for bodybuilding, the researchers report. The results suggest that regeneration of steroidal contaminants should be part of environmental risk-assessment models.—JK
ACS NANO
SMARTPHONE SNAPS NANOPARTICLE PICS
Nano 2013, DOI: 10.1021/nn4037706). The device, designed by Aydogan Ozcan of UCLA and colleagues, consists of a laser By attaching a small, inexpensive gadget to diode to excite fluorescent dyes and a the back of a smartphone, scientists have compact system of lenses and filters that created a sensitive handheld fluorescence remove background noise created by the microscope. The attachment allows the laser light. The team used the microscope phone’s camera to take pictures of fluoto detect human cytomegalovirus parrescently labeled nanoparticles and virus ticles, which are between 150 and 300 nm particles, making the phone a potentially in diameter, and polystyrene beads, which useful portable diagnostic tool for health at about 100 nm in diameter were the care workers in developing countries (ACS smallest objects that could be detected. According to Ozcan, the mini microscope is the first portable, cell-phone-based imaging system sensitive enough to resolve individual nanoparticles and viruses. Ozcan started a company called Holomic to commercialize the device, and his SAY CHEESE With a device attached to a smartphone (left), group has created researchers took pictures of fluorescent nanoparticles (center) smartphone apps for and compared them with scanning electron microscope images. data analysis.—JNC CEN.ACS.ORG
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SEPTEMBER 30, 2013
FRICTION MEASURED A FEW ATOMS AT A TIME Frictional forces between surfaces sliding across each other are behind the wear and tear on things such as car engines, computer hard drives, and shoe soles. The study of these forces, called tribology, helps scientists and engineers develop longerlasting products that require less energy to operate. Physicist A. Jay Weymouth of the University of Regensburg, in Germany, and colleagues have now pushed tribology to the atomic level for the first time. The team prepared a silicon crystal in which the orientation of silicon surface dimers in one region is perpendicular to that of an adjacent region. By using a specially equipped atomic force microscope, the team measured the drag caused by sliding the AFM tip across the different regions. They found that friction depends strongly on the orientation of the dimer bonds with respect to the sliding direction (Phys. Rev. Lett. 2013, DOI: 10.1103/physrevlett.111.126103). The technique provides an opportunity to compare quantum mechanical friction simulations, which are currently limited
OH
by computing power to a few atoms, with laboratory measurements that could not be made at the atomic scale until now.—MJ
PROC. NATL. ACAD. SCI.USA
SCIENCE & TECHNOLOGY CONCENTRATES
extracellular domain. They detected this site by developing a light-activated labeling reagent, o-propofol diazirine, with similar biological activity as propofol. They allowed the label to attach to the channel and then determined attachment points with mass spectrometry. The team plans to test whether mutations to the proposed binding site affect propofol activity in animals.—CD
LACTONES BLOCK WASTE DISPOSAL IN TB BACTERIA
EARWAX TELLS A WHALE OF A STORY The earwax of some whales builds up in layers continuously over their lifetimes. This phenomenon has been used to age the animals, much like tree rings. Sascha Usenko and Stephen J. Trumble of Baylor University have taken this tracking method a step further by tracing the concentrations of pollutants and hormones trapped in a blue whale’s earwax plug over time (Proc. Natl. Acad. Sci. USA 2013, DOI: 10.1073/pnas.1311418110). For Trumble, one of the most interesting findings is that testosterone spiked at
around nine years of age, indicating the onset of sexual maturity, and the stress hormone cortisol spiked shortly thereafter. “Being a male, you can sort of say, ‘That makes sense,’ ” he says. “You’re roughing it up with the big guys out there and trying to mate; you can understand a spike in the stress hormone.” Going forward, the team will study earwax plugs in museum collections as well as from sources such as the ship collision that felled this blue whale. The team anticipates that the technique will fundamentally transform assessment of human impact on whales and their ecosystems.—CB
Each new layer of a whale’s earwax plug wraps around the previous one, as shown in this diagram (top) and image (bottom); changes in color caused by migration and diet patterns allow six-month monitoring precision.
ANSWERING CURIOSITY QUESTIONS ON MARS
SHINING LIGHT ON HOW PROPOFOL KNOCKS YOU OUT The intravenous drug propofol is one of the most common anesthetics used in surgery. It’s popular because it rarely causes nausea and is fast-acting, but it can cause unwanted side effects such as low blood pressure and breathing problems. Researchers seek a next-generation propofol derivative that induces unconsciousness without any side effects, but they lack exact information about how the drug works. Now, one group of scientists say they’ve uncovered propofol’s binding site at its most important protein target, an ion channel called the GABAA receptor (Nat. Chem. Biol. 2013, DOI: 10.1038/ nchembio.1340). Prior studies pointed to a propofol-binding site between subunits of the ion channel, but much of the evidence was indirect. Nicholas P. Franks of Imperial College London, Alex S. Evers of Washington University School of Medicine, in St. Louis, and colleagues report that the site is instead at the interface between the membrane-spanning part of the channel and its CEN.ACS.ORG
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NASA/JPL-CALTECH/MALIN SPACE SCIENCE SYSTEMS
Despite an arsenal of antibiotics, tuberculosis still kills more than 1 million people annually as it continually evolves resistance to the latest drugs. Now, researchers have identified a set of cyclic ester compounds known as β-lactones that show promise against Mycobacterium tuberculosis by targeting an enzyme it needs to survive but that current drugs don’t attack (ACS Chem. Biol. 2013, DOI: 10.1021/cb400577b). Corey L. Compton and Jason K. Sello of Brown University and colleagues tested 14 β-lactones on a nonpathogenic close relative of M. tuberculosis; four of them curbed bacterial growth. The team’s additional study on the two most potent compounds showed O that they also inhibited O the growth of M. tuberculosis. The researchers deduced through β-Lactone enzymatic assays that peptidase inhibitor the new β-lactones probably work by reacting with ClpP, a TB enzyme that degrades and eliminates damaged or unneeded bacterial proteins. The most effective compound (shown) had potency similar to streptomycin, an antibiotic used to treat TB. The researchers believe the β-lactone’s potency stems from an aromatic benzyl group attached to the compound’s α-carbon. Although the β-lactone hasn’t been tested in animals, the researchers say the findings show ClpP’s viability as a target for developing drugs.—PK
SEPTEMBER 30, 2013
NASA’s Curiosity rover has spent the past year studying several geochemically complex areas on the surface of Mars. Curiosity carries the most sophisticated suite of analytical instruments ever deployed to an extraterrestrial destination. The rover drilled into rocks, ground up samples, and processed the samples in ovens and in mass and X-ray spectrometers. International teams of dozens of scientists have now had a chance to analyze the data and assemble a collection of reports detailing the findings (Science 2013, DOI: 10.1126/science.1244258). Curiosity had previously hinted that ancient Mars had a watery, moderate pH environment that would have been hospitable to organisms (C&EN, March 18, page 7). The myriad new results include detection of alkaline and fractionated magma, which were never The Mars before seen on Mars but are rover profoundly similar to Earth’s Curiosity scoops igneous rocks. Heated samsamples ples of Mars’s crust released of dirt volatile compounds such as from the carbon dioxide, sulfur dioxmartian ide, water, and oxygen, which surface in scientists suggest could have this mosaic of images been incorporated from the taken by planet’s atmosphere. The one of the data from this examination, rover’s the scientists say, give an cameras. unprecedented understanding of the nature of Earth’s planetary neighbor.— EKW
