Science Concentrates NEUROSCIENCE
Brain waves clear Alzheimer’s plaques Triggering certain patterns of brain activity could spur immune cells to remove amyloidOur brains can get quite rhythmical as groups of neurons fire together in oscillating patterns during various activities, such as processing sensory information or encoding memories. A study suggests that one of these rhythmical patterns, called gamma waves, can stimulate the brain’s immune cells to clear out amyloid-β (Aβ), the peptide that forms plaques in the brains of people with Alzheimer’s disease (Nature 2016, DOI: 10.1038/nature20587). The researchers, led by Li-Huei Tsai of Massachusetts Institute of Technology, think their results hint at a noninvasive therapy for the neurodegenerative disorder. “The implications are significant,” says Michal Schwartz of the Weizmann Institute of Science, who was not involved in the work. And, she says, if the effects of gamma waves also improve cognition in Alzheimer’s models, “it’s unbelievable.” Gamma waves—patterns of brain activity with frequencies between 30 and 90 Hz—
rons with light beamed into the brain, is invasive. To demonstrate a noninvasive way to trigger gamma waves, the team placed the animals in a dark chamber and then flashed a light-emitting diode at 40 Hz.
are often disrupted in many neurological disorders, including Alzheimer’s. The MIT team wanted to understand the conAmyloid-𝝻 Microglia nection between these oscillations and the disease. The scientists Gamma stimulation used optogenetics to generate gamma waves at 40 Hz in the brains of mice engineered to overproduce Aβ and found that the rhythmical activity When stimulated by gamma waves, microglia take up amyloidsignificantly refrom their surroundings. duced levels of the peptide. When the scientists studied these This flickering generated gamma waves in animals’ brains further, they found evithe visual cortex of the animals’ brains and dence that immune cells called microglia reduced the amount of amyloid plaques had cleared the peptide. in that brain region after a week of treatBut optogenetics, which activates neument.—MICHAEL TORRICE
REAGENTS
Researchers create new reagents for a fluorinated version of azide-alkyne click chemistry With the help of new fluorinating reagents, a team led by Zsófia E. Blastik and Petr Beier of the Czech Academy of Sciences has devised a versatile fluorinated version of copper-catalyzed click chemistry. The approach overcomes some previous difficulties with preparing suitable fluorinated reagents for click reactions and opens the door to broader use of click chemistry, which has become invaluable to chemical biology and materials science. The new chemistry hinges on the ability to make azidoperfluoroalkanes. Azidotri-
CF3CF2H
n-Butyllithium
CF3Si(CH3)3 CsF C3F7Si(CH3)3 C8H17Si(CH3)3
8
fluoromethane (CF3N3) has been known for some time, but its best reported synthesis starting from CF3I requires cumbersome handling of toxic and corrosive CF3NO, N2H4, and Cl2 gases—an approach that has limited CF3N3’s applications. Beier’s group alternatively attempted using electrophilic CF3I with sodium azide (NaN3) as a nucleophile, but the reaction didn’t work. Instead, the team found that CF3N3 and its previously unknown longer chain analogs can be prepared more conveniently from CF3Si(CH3)3 and related
CH3C6H4SO2N3
RF
–
or
CF3(CF2)3SO2N3
C&EN | CEN.ACS.ORG | DECEMBER 12/19, 2016
RF–N3 Fluorinated azide
R Copper catalyst
N N
N RF
R
Triazoles
nucleophiles and sulfonyl azide electrophiles. In effect, the researchers flipped the polarity of the reaction’s constituents (Angew. Chem. Int. Ed. 2016, DOI: 10.1002/ anie.201609715). The reported azidoperfluoroalkanes undergo copper-catalyzed azide-alkyne cycloadditions, also known as click reactions, leading to N-perfluoroalkyl triazoles as underexplored building blocks, Beier says. “In fact, azidoperfluoroalkanes are more reactive in the click reaction with alkynes than nonfluorinated alkyl azides.” “A reminder emerging out of this paper by Beier and colleagues is that, if you want to build a bond by a polar mechanism, there are always two options,” says Andrei K. Yudin of the University of Toronto, who focuses on the chemistry of heterocyclic compounds. “It is a good idea to reverse the polarity of components if one path is problematic. As a result, they have developed an efficient entry into azidoperfluoroalkanes.”—STEVE RITTER
CREDIT: NAT U RE (MICROGLIA)
Fluorinated azides click to make triazoles
