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
