MICROFLUIDICS
▸ Self-powered chip enables nucleic acid diagnostics The ability of doctors to use nucleic acid-based diagnostic tests in their offices rather than sending out blood samples to contract clinical labs will require simple, easy-to-use devices. Luke P. Lee and coworkers at the University of California, Berkeley, have developed a prototype—a disposable, inexpensive microfluidic device about the size of a microscope slide that only needs a drop of blood and even carries its own power supply (Sci. Adv. 2017, DOI: 10.1126/sciadv.1501645). The researchers pattern the reagents needed for nucleic acid amplification directly into microwells on the chip. When in operation,
CREDIT: TOBY HUDSON/WIKIMEDIA COMMONS (SPIDER); P NAS ( P E PT I DE ); SCI. ADV. (CHIP)
This nucleic acid testing chip is loaded with dyes so the channels and wells (red and green) and vacuum battery system (blue) can be seen. blood flows through the microfluidic channels, the blood cells are removed, and the plasma is partitioned into the microwells where nucleic acid amplification occurs upon heating in an oven or by reusable heat packs. Sequences of interest are detected by fluorescence readings. The chip is powered by a precharged vacuum battery, which pumps samples by pulling air through gas-permeable silicone and has a 2.5-hour lifetime. Lee and coworkers used the device to quantify HIV-1 RNA and Staphylococcus aureus DNA spiked into human blood at levels ranging from 10 to 200,000 copies per microliter. “Because nucleic-acid testing requires a number of different steps, it is important that a pointof-care device integrates all these steps together,” says Samuel K. Sia of Columbia University, who was not involved in the research. This work represents “a practical approach” for getting all the needed microfluidic innovations into one package, Sia says.—CELIA ARNAUD
BIOCHEMISTRY
Spider venom peptide helps protect the brain after a stroke The Australian funnel-web spider’s venom can be deadly to humans. But a small amount of one peptide in the arachnid’s poison arsenal has been found to protect the brain tissue of rodents after they’ve suffered a stroke. If the work holds true in humans, the venomous disulfide-rich peptide, called
A double-knotted peptide from this funnelweb spider can protect the brains of stroke victims via its interaction with ion channels (disulfide bonds shown in blue). Hi1a, could complement current treatments for stroke victims (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/ pnas.1614728114). In most strokes, blood supply to the brain is blocked, leading to a shortage of oxygen and glucose. Brain cells start to die quickly in regions closest to the blockage, but over the course of hours to days, tissue located farther away begins to perish. It’s this more-distant tissue that stroke drugs aim to salvage. However, these protective therapeutics—also derived from spider venom—must be delivered within four hours. The new peptide, discovered by Lachlan D. Rash and Glenn F. King of the University of Queensland and their colleagues, blocks an acid-sensing ion channel in neurons with beneficial effects even after eight hours. This ion channel is activated during a stroke because restricted blood flow to the brain lowers tissue pH levels. When these ion channels stay open, several biochemical pathways eventually trigger cell death in the brain. In rodent stroke victims, the venom peptide blocked this ion channel, thereby preventing the detrimental effects. The peptide also helped preserve neuronal architecture and restore neurological and motor function to the animals as they recovered.—SARAH EVERTS
FLUORINATION
▸ First direct catalytic difluoromethylations from ClCF2H
fluoroalkyl halides such as chlorodifluoromethane, ClCF2H, an inexpensive industrial chemical used for making fluorinated polymers. Xingang Zhang and coworkers at Shanghai Institute of Organic Chemistry wondered if they couldn’t simplify difluoromethylations further by using ClCF2H directly in a catalytic process. The researchers have found that they indeed can carry out palladium-catalyzed cou-
Researchers have traditionally prepared difluoromethylated compounds by the deoxyfluorination of F F CN CF2H aldehydes using harsh electrophilic fluoriO O nating reactions. More Rhodium Xantphos catalyst, recently, chemists have arylboronate, ClCF2H taken a milder approach O O by using preformed O O reagents to transfer a O 3 O 3 CF2H group to a target molecule. In this case, Cyhalofop herbicide the preformed reagent Borylation followed by difluoromethylation is often made from MARCH 27, 2017 | CEN.ACS.ORG | C&EN
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Science Concentrates GREEN CHEMISTRY
NEUROSCIENCE
▸ How zinc regulates storage and release of chemical messengers Neuroscientists think zinc is involved in learning and memory, but they don’t fully understand what it’s doing at the single-cell level. Using two electrochemical methods, Andrew G. Ewing and coworkers at Chalmers University of Technology and the University of Gothenburg have now shown that zinc regulates the storage of the messenger molecule catecholamine and the dynamics of its release from cells (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201700095). To measure the amount of catecholamine in cellular vesicles, the researchers insert nano-tip carbon-fiber electrodes directly into cells. The vesicles rupture on the electrodes and release all of their contents. The researchers also use single-cell amperometry to measure catecholamine as it is released from the cells. They found that cultured adrenal cells treated with zinc store less catecholamine than untreated cells. Even though the treated cells store less, they actually release the same amount of catecholamine as the untreated cells because they’re releasing nearly all of what they have taken in. That release also occurs much more slowly than the release from untreated cells. The electrochemical measurements suggest that zinc helps stabilize the opening between the vesicle and the cell membrane, thereby controlling the opening and closing process and the flow of catecholamine. “Our results provide the missing link between zinc and the regulation of neurotransmitter release processes, which might be important in memory formation and storage,” the researchers write.—CELIA ARNAUD
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C&EN | CEN.ACS.ORG | MARCH 27, 2017
Building a bigger and better solvent still Most labs have a small still for quickly purifying solvents. But for Stefan Böhmdorfer and his colleagues at the University of Natural Resources & Life Sciences in Austria, that wasn’t enough. The researchers carry out a lot of chromatography and realized they had much to gain by purifying and reusing their solvents, rather than paying someone to cart them away for recycling. The team had a hard time finding a commercially available still that could do everything they wanted, including handling between 2-L bench-scale and 30-L pilot-scale amounts, having fully solvent-resistant components, and offering precise control over separating solvent fractions. These So the researchers decided to build their own system. That’s homemade not a new idea, but the team spared no detail in designing its distillation system to handle solvents of all polarities and a wide range stills offer the of boiling points and to collect fractions automatically (Org. benefits of Process Res. Dev. 2017, DOI: 10.1021/acs.oprd.7b00007). The saving money researchers built two stills for 6-L batches inside a walk-in and preventing fume hood. The basic setup includes a 10-L round-bottom lab waste. flask, a 100-cm-long/30-mm-diameter packed column, a condenser, drying tubes, and collection vessels. Temperature sensors and electronically controlled valves enable the automated fraction collection and also serve as a safety feature to shut the system down if something starts to go wrong. The distilled solvents are typically of higher purity than the analytical-grade solvents the group was buying. “I am convinced that a lot of research groups are facing the same situation of having larger amounts of easily redistillable solvents and can decide to build their own device,” Böhmdorfer says.—STEVE RITTER
BIOCHEMISTRY
urally. The peptide is a shortened form of a protein called FOXO4. In senescent cells, FOXO4 binds another protein, called p53. This interaction prevents cell death. When delivered to mice, the team found that the peptide disrupts the normal FOXO4-p53 interaction and the cells are directed to die (Cell 2017, DOI: 10.1016/j.cell.2017.02.031). The researchers tested the treatment on As we age, our cells increasingly become elderly mice and found that these animals senescent: Instead of dying, these decrepit had thicker fur, healthier kidneys, and cells stop dividing and begin secreting were more active compared with controls. a cocktail of molecules that can cause Given that young, healthy problems for other cells. cells don’t produce much Scientists have long been FOXO4, de Keizer believes searching for chemical the peptide is unlikely to treatments that can clear have many side effects on away the problematic cells. normal cells. The team Now, a team of researchers hopes to test the peptide led by Peter L. J. de Keizer soon in humans. “With life at Erasmus University expectancy projected to Medical Center Rotterincrease in the foreseeable dam are reporting that a future, it is important cell-penetrating peptide to develop strategies to they prepared can make Elderly mice treated with extend and restore health senescent cells in mice antiaging peptides have span,” the researchers suicidal, allowing the anithicker fur (left) than their note.—SARAH EVERTS mals to remove them natuntreated cohorts (right).
▸ Peptide clears senescent cells, revitalizes aging mice
CREDIT: STEFAN BÖHMDORFER (STILL); PETER L. J. DE KEIZER (MICE)
pling reactions between ClCF2H and aryl and heteroaryl boronic acids and esters to create an array of aromatic difluoromethyl derivatives, providing new opportunities to develop bioactive compounds used as pharmaceuticals, agrochemicals (one example shown), and flavors and fragrances (Nat. Chem. 2017, DOI: 10.1038/ nchem.2746). Zhang says the catalytic process appears to proceed via a metal difluorocarbene intermediate, which could open the door to better knowledge of little-understood metal fluorocarbene reaction chemistry.—STEVE RITTER
