MICROBIOME
▸ Caterpillar gut bacteria makes an antibiotic
CREDIT: MAX PLANCK INSTITUTE FOR CHEMICAL ECOLOGY (LEAFWORM & ANTIBIOTIC); CARSTEN STREB (TWO STRUCTURES); NANO LETT. (TETRODOTOXIN)
Mounting evidence suggests that beneficial gut bacteria can help fight pathogens—just ask anyone who’s successfully tackled a Clostridium difficile infection thanks to a fecal transplant from a healthy donor. However, researchers haven’t had much luck identifying specific species of microbes doing the heroic defense work and the specific molecular weapons they use. That luck could be
Bacteria in the cotton leafworm gut produce the antibiotic mundticin, a peptide that helps protect the insect from virulent pathogens. changing, thanks to a research team led by Wilhelm Boland of the Max Planck Institute for Chemical Ecology and Yongqi Shao of Zhejiang University (Cell Chem. Biol. 2017, DOI: 10.1016/j.chembiol.2016.11.015). The researchers were studying the cotton leafworm, Spodoptera littoralis, a nefarious destroyer of crops in temperate regions worldwide, when they noticed that shortly after caterpillars hatched and started to eat their guts filled with harmful pathogens, including virulent Enterococcus species that can digest the insect from the inside out. The team discovered that with time these bad bacteria were eliminated by an antimicrobial peptide called mundticin produced by another Enterococcus bacterium, E. mundtii. Mundticin is currently being studied as a potential food preservative. The findings support the idea that antimicrobial peptides made by insect gut bacteria might be a source of new antimicrobial food additives or coatings for food contact surfaces, and it lends credence to the hope some researchers have that new antibiotics for humans might be lurking in gut microbiomes of a variety of creatures.—SARAH EVERTS
IONIC LIQUIDS
New composite material provides triple-pure water Scientists have developed an all-in-one water-decontamination material—a powder made from a polyoxometalate-based ionic liquid adsorbed onto a porous silica support. The composite material does the job traditionally tackled by a combination of filtration materials: It removes organics, kills microorganisms, and captures heavy metals (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/
A tetraalkylammonium cation (left) and polyoxotungstate anion (right) form an ionic liquid that is the basis of a composite material that rids water of most types of contaminants. anie.201611072). The material’s developers, led by Carsten Streb of the University of Ulm and Scott G. Mitchell of the University of Zaragoza, hope it could be a start to developing easily transportable water-purification systems for remote areas with limited or contaminated water. Streb’s lab has specialized in polyoxometalate-based ionic liquids. In this case, the researchers created a supported ionic liquid phase, or SILP, using an ionic liquid made with polyoxotungstate anions and tetraalkylammonium cations adsorbed onto silica. In lab experiments, they demonstrated the multitasking abilities of the resulting free-flowing powder. The polyoxotungstate anion binds heavy-metal ions, including nickel and lead, with the silica support further trapping radioactive uranyl ions. In addition, the composite material is lipophilic and so adsorbs organic compounds, such as trityl dyes. And the tetraalkylammonium cations are antimicrobial and thus inhibit harmful bacteria, such as Escherichia coli.—ELIZABETH WILSON
DRUG DELIVERY
▸ On-demand pain relief, triggered by light Seeking more effective pain management, researchers have designed injectable liposomes—cell-like sacs made of phospholipids—that can repeatedly release small bursts of local anesthetic when zapped for just one minute with near-infrared light (Nano Lett. 2017, DOI: 10.1021/acs.nano lett.6b03588). The on-demand system could one day offer physicians or patients better control in delivering a local anesthetic than current approaches. Daniel S. Kohane of
Gold nanorods (green) on the surface of a liposome heat up when exposed to nearinfrared light. The heat frees phosphocholine molecules (yellow) in the particle’s membrane, releasing a burst of the pain blocking drug tetrodotoxin (purple).
Harvard Medical School and his colleagues filled liposomes with the nerve blocker tetrodotoxin and decorated the outer surface of the lipid membrane with gold nanorods. The nanorods absorb near-infrared light and generate heat, causing the membrane to expand and leak some of its payload. The team also included a phosphocholine derivative in the liposome’s membrane that can break free when heated by the nanorods, creating additional pores for tetrodotoxin to escape. As the membrane cools, it tightens again and the cycle can be repeated. Rats injected in the foot with the loaded liposomes experienced no pain when poked for the first two hours. The effect wore off completely after six hours. The researchers also used the lipo-
Near-infrared light
JANUARY 23, 2017 | CEN.ACS.ORG | C&EN
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Science Concentrates PROCESS CHEMISTRY somes to repeatedly block the sciatic nerve in one leg of test animals, which caused them to lose sensation in that leg during the treatment.—PRACHI PATEL, special to C&EN
Fluorine flow chemistry yields flucytosine
NEUROSCIENCE
In Africa, about one-third of the roughly 2 million HIV/AIDS-related deaths each year stem from the fungal infection cryptococcal meningitis. The first-line treatment for this disease and other HIV/AIDS-related fungal infections is a combination of flucytosine and New continuous-flow process: amphotericin B. Although these two drugs are on the O O World Health Organization’s N NH 10% F2 in N2, HCOOH N NH List of Essential Medicines, uneven global pricing and H2 N H2 N distribution has left flucyF tosine largely unavailable to Cytosine Flucytosine Africans who need it—flucy-
Researchers have uncovered a molecular pathway in neurons that shines new light on how the biggest genetic risk factor for Alzheimer’s disease may contribute to the disorder. Thomas C. Südhof and colleagues of Stanford University Medical School describe a clear link between apolipoprotein E activity and the production of amyloid-β, the peptide that forms the characteristic plaques that develop in the brains of people with the disease (Cell 2017, DOI: 10.1016/j. cell.2016.12.044). The gene that codes for apolipoprotein E comes in three forms, each with different probabilities for developing Alzheimer’s: People with ApoE2 have a lower risk, those with ApoE3 have an average risk, and people with ApoE4 have a greatly increased risk. By using neurons derived from human embryonic stem cells to eliminate noise from other cells and molecules found in the brain, the researchers found that ApoE proteins bind receptors on the neuron surface and activate an “unusual” signaling pathway. The final step of the pathway turns on transcription of the amyloid-β precursor gene, with ApoE4 proteins causing the highest amyloid-β levels and ApoE2 proteins the lowest, “paralleling their relative effects on Alzheimer’s disease risk,” Südhof says. Jungsu Kim of the Mayo Clinic calls the details of the unexpected pathway “exciting,” adding that it “may provide a new therapeutic target” for Alzheimer’s.—RYAN CROSS
MATERIALS
▸ Covalent organic frameworks form processable colloids Covalent organic frameworks (COFs) are crystalline porous polymers with features that include having a pore size that can be tailored by choosing suitable building blocks. Researchers are examining COFs and other types of framework compounds for use as selective membranes, catalyst
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C&EN | CEN.ACS.ORG | JANUARY 23, 2017
tosine is relatively expensive Direct fluorination of cytosine could ease to make and there’s little gethe availability of flucytosine, an essential neric competition to reduce antifungal drug for people with HIV/AIDS. cost. Answering a call from the infectious diseases community, a team led by Graham Sandford of Durham University, working in collaboration with scientists at Sanofi Aventis and the nonprofit group MEPI within the EU’s Innovative Medicines Initiative Chem21 network, has developed a streamlined method for making flucytosine that could improve its global availability (Org. Process Res. Dev. 2017, DOI: 10.1021/acs. oprd.6b00420). Flucytosine is currently manufactured in a four-step process starting from uracil, which includes fluorination, chlorination, amination, and hydrolysis steps. Taking advantage of the Durham group’s expertise in selective fluorinations using flow reactors, the team developed a pilot-scale continuous-flow process to convert cytosine directly into flucytosine at a rate of 60 g per hour. Besides improving access to flucytosine to combat fungal infections, the researchers believe the new process could benefit flucytosine’s use as an intermediate in the synthesis of anticancer and HIV drugs.—STEVE RITTER
supports, and other applications. But COFs tend to form tough-to-process insoluble microcrystalline powders, thwarting those efforts. Help may now be on the way thanks to a study reporting a method to prepare COFs as stable colloidal suspensions by inhibiting the usual irreversible crystallite aggregation and precipitation (ACS Cent. Sci. 2017, DOI: 10.1021/ acscentsci.6b00331). A team led by William R. Dichtel of Northwestern University and Nathan C. Gianneschi of the
University of California, San Diego, studied a boronate ester-linked hydroxytriphenylene material known as COF-5. On the basis of X-ray scattering, liquid-cell microscopy, and other analytical methods, the team determined that nitrile solvents impede crystallite aggregation yet do not inhibit framework polymerization. They found that adding even a small amount of acetonitrile to the dioxane-mesitylene solvent used to synthesize COF-5 prevents precipitation, yielding instead a colloidal suspension that remains stable for weeks. The team used those suspensions to cast high-quality free-standing transparent films, a key step toward applications.—MITCH
JACOBY COF-5, a framework compound, typically forms an unprocessable powder (left vial). Adding acetonitrile gradually yields an easy-toprocess colloidal suspension (right vial).
CREDIT: ACS CENTRAL SCI. (SUSPENSION)
▸ Genetic risks for Alzheimer’s explained
