Science Concentrates MATERIALS
▸ Growing polymers with mechanical force To date, most examples of polymer mechanochemistry—in which mechanical force initiates a chemical reaction—have involved breaking covalent bonds. But chemists working in this field would also like to use mechanical force to build bonds, just as the body uses mechanical force to restructure and reinforce bone. Taking a step in this direction, chemists at the University of California, Irvine, have developed a mechanically controlled radical polymerization process (Nat. Chem. 2016, DOI: 10.1038/nchem.2633). Aaron P. Esser-Kahn, Hemakesh Mohapatra, and Maya Kleiman used ultrasound to agitate piezoelectric BaTiO3 nanoparticles, generating a potential that then reduced a copper(II) complex. The reduced copper(I) complex then reacted with an atom-transfer radical polymerization initiator, ethyl α-bromoisobutyrate, to stimulate polymerization of n-butyl acrylate monomer. The longer the team used ultrasound, the longer the polymer chains grew. Now the chemists are gearing up to use environmental vibrations to spur polymerization reactions.—BETHANY
A hydrogen-bonded pair of bisulfate anions (yellow = S, red = O, white = H) nestles between stacked cyanostars (blue), as shown in these side (left) and top (right) views.
INORGANIC CHEMISTRY
Anion dimer captured Opposite charges attract and like charges repel, Coulomb’s law says. But anions can pair up and stabilize each other, according to research led by Amar H. Flood of Indiana University, Bloomington (Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201608118). Although indirect evidence had previously pointed to the existence of dihydrogen phosphate dimers, direct evidence was lacking. Combining macrocyclic cyanostars and bisulfate, HSO4–, Flood and coworkers expected to create a complex with one bisulfate anion sandwiched in the center of two cyanostars, as already documented for perchlorate. Instead, they observed a 2:2:2 complex incorporating a pair of bisulfate anions hydrogen-bonded to each other, nestled in the centers of two stacked cyanostars and capped by tetrabutylammonium cations. The anion dimer is stabilized by hydrogen-bonding interactions to the cyanostar’s cyanostilbene-based C–H groups. The complex persists in both crystalline form and in solution, as documented by X-ray crystallography and 1H NMR. The system could point to new ways to recognize and sequester ions, the researchers say.—JYLLIAN KEMSLEY
HALFORD
▸ Cyclic peptides with heterocycles are cell membrane-permeable Peptides, including cyclic peptides, generally don’t cross cell membranes easily, a property that has limited their use in medicine. Researchers have now boosted the drug potential of cyclic peptides by incorporating a heterocycle into their rings. Andrei Yudin and coworkers at the University of Toronto adapted an existing reaction to convert linear peptides into the heterocycle-containing peptidomimetics (Nat. Chem. 2016, DOI: 10.1038/nchem.2636). The one-step
R HN
CO2H
–C
+
N N PPh3
O
H2N H
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C&EN | CEN.ACS.ORG | OCTOBER 31, 2016
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This reaction converts linear peptides (left) to cyclic peptidomimetics with an oxadiazole ring and an amine. R is a variable group; Ph is phenyl.
rocyclization accessible to the chemistry community,” Yudin says.—STU BORMAN
MICROSCOPY
▸ Superresolution methods reveal new picture of the endoplasmic reticulum With emerging superresolution microscopy techniques, biologists can get more detailed pictures of structures they thought they already understood. The most recent biological structure to yield its secrets is the endoplasmic reticulum. The ER, which stretches from the nuclear envelope to the edges of a cell, is home to many biological processes, including protein and lipid synthesis. In conventional microscopy images, the peripheral portions of the ER appear to include flat membrane sheets. But that picture is wrong, according to a new study led by Jennifer Lippincott-Schwartz of Howard Huges Medical Institute’s Janelia Research Campus and
CREDIT: AMAR H. FLOOD/INDIANA UNIVERSITY, BLOOMINGTON
DRUG DISCOVERY
reaction of a linear peptide with a variable aldehyde and (N-isocyanimino)triphenylphosphorane doesn’t require peptide preactivation, as most current peptide cyclization reactions do. Yudin and coworkers demonstrated the reaction by constructing 15-, 18-, 21-, and 24-membered peptidomimetic macrocycles, each containing 1,3,4-oxadiazole and an amine. The high cell-membrane permeability of many of the macrocycles and their conformationally rigid structures are both important prerequisites for bioavailability and therapeutic use. The researchers’ ultimate goal is to develop the peptidomimetics as inhibitors of intracellular protein-protein interactions. The phosphorane reagent “is being commercialized by Sigma-Aldrich, which will make this mac-
NEUROSCIENCE
Transplanted neurons integrate into brain circuits When neurons die, they cannot be repaired—but perhaps they can be replaced. The idea of transplanting cells into injured brains has shown promise in the clinic. For example, some of the symptoms of Parkinson’s disease patients were alleviated after they received transplants of fetal brain cells to peripheral regions of the brain. But researchers did not know whether transplanted neurons can truly be integrated into preexisting circuits and participate in neural pathways. Now, a team led Mark Hübener of the Max Planck Institute of Neurobiology and Magdalena Götz of the Institute of Stem Cell Research at Munich’s Helmholtz Center have shown that embryonic neurons transplanted into the injured visual cortex of adult mice establish connections with other Embryonic neurons (red) cells in the brain such that their transplanted into the brains of neurological responses “become adult mice connect with host indistinguishable from those of neurons (black) to rebuild neural host neurons” (Nature 2016, DOI: circuits lost in an injury. 10.1038/nature20113). If the work in mice holds true in humans, this finding could lay a path toward healing brain injuries. An important next step is identifying chemical guidance cues that allow foreign cells to pass as native.—SARAH EVERTS
CREDIT: SOFIA GRADE (BRAIN IMAGE); MOL. PHARMACEUTICS (SCHEME); SCIENCE (ENDOPLASMIC RETICULUM)
Superresolution microscopy shows that the peripheral endoplasmic reticulum is an array of small tubes. This image was acquired by a method called grazing incidence structured illumination microscopy.
Craig Blackstone of NIH (Science 2016, DOI: 10.1126/ science.aaf3928). To probe the ER in multiple types of cells, the team used four superresolution optical microscopy methods, which provide images at a resolution that exceeds conventional microscopy limits, as well as focused ion beam scanning electron microscopy. With these methods, the researchers observed that the peripheral ER is actually made of a dense matrix of tubes instead of flat membrane sheets. They acquired images fast enough to observe the tiny tubes undergoing rapid movement and interconversion between tight and loose arrays. The tube organization may allow the ER to rapidly change its conformation as necessary to perform its many functions, the researchers speculate.—CELIA ARNAUD
DRUG DELIVERY
▸ Injectable, lightactivated gel releases insulin Patients with type 1 diabetes rely on daily insulin injections to help regulate their blood glucose. Now, researchers have devised a potentially less invasive way to deliver the drug: an insulin-carrying gel that can be placed under the skin and activated by light to release the hormone when needed (Mol. Pharmaceutics 2016, DOI: 10.1021/
N O N H Polymer bead
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acs.molpharmaceut.6b00633). To make the material, Simon H. Friedman of the University of Missouri, Kansas City, and colleagues linked human insulin molecules to a commercially available gel—a copolymer made of polystyrene and polyethylene glycol—using a linker molecule containing a light-sensitive chemical bond. When exposed to 365-nm-wavelength light, this bond breaks, Insulin (blue) is releasing the linked to a polymer insulin. To test bead (green) via a the material, molecule containing a the researchers
light-sensitive bond. Shining ultraviolet light on the material cleaves the bond, releasing the insulin. O
N N O
O
O
H N
O
injected 10-µm-diameter beads of the gel under the skin of diabetic rats and attached a coin-sized light-emitting device over the area. The researchers switched on the light for two minutes, then monitored the animals’ blood glucose and insulin levels. Insulin release began a few minutes after light exposure, peaked at 25 minutes, and then plateaued. The researchers found that blood glucose levels dropped in response to insulin and that they could reactivate the gel 65 minutes later to release a second dose of the hormone.—JYOTI
MADHUSOODANAN, special to C&EN
Bond cleaved by light O O O Insulin OH NO2
UV light
O
O Insulin
OH
HO
O
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