PROCESS CHEMISTRY
CREDIT: H. KRISP/WIKIMEDIA COMMONS (SNAKE); ANGEW. CHEM. INT. ED. (DDT)
▸ Continuous crystallization of carbamazepine As continuous manufacturing makes inroads in drug production, the process of continuous crystallization—in which active pharmaceutical ingredients are purified via solidification from a liquid phase—has proven to be a major roadblock. Looking to understand the risks involved with such systems and how they might be mitigated, scientists led by Celia N. Cruz at the U.S. Food & Drug Administration’s Office of Pharmaceutical Quality designed and built a lab-scale continuous crystallization platform for the anticonvulsant compound N carbamazepine (Org. Process Res. Dev. 2017, O NH2 DOI: 10.1021/acs. oprd.7b00130). CarCarbamazepine bamazepine has four crystalline polymorphs, making it a good model compound for troubleshooting. The continuous crystallization system uses an automated, two-stage mixed-suspension and mixed-product removal platform and integrates two process analytical technology tools, Raman microscopy and focused-beam reflectance microscopy, to monitor the crystallization process in real time. The researchers were able to use the analytical tools to address two major problems with continuous crystallization— clogging and particle settling. They plan to optimize the system further to evaluate more advanced strategies for controlling continuous crystallization processes.—
NATURAL PRODUCTS
Green mamba venom could treat kidney disorder A green mamba bite results in dizziness, nausea, difficulty breathing, irregular heartbeats, convulsions, and sometimes death. But the snake’s deadly venom contains a small peptide that could one day save lives. Researchers led by Christiane Mendre of the University of Montpellier, Ralph Witzgall of the University of Regensburg, Nicolas Gilles of Paris-Saclay University, and colleagues plucked a peptide out of the venom that might help people with polycystic kidney disease (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/ pnas.1620454114). These individuals develop water-filled cysts on their kidneys that interfere with the organ’s function and can eventually be fatal. Treatment for the disease currently involves so-called vaptan drugs that interfere with a protein called the type 2 vasopressin receptor. But the drugs are toxic to another organ—the liver. The team of researchers noticed that a 57-residue peptide in the green mamba venom called mambaquaretin-1 also targets the receptor but is more selective than existing drugs. “With high selectivity and without toxic metabolic by-products associated with its peptidic nature, mambaquaretin-1 could become the preferential treatment for these disorders,” they note.—SARAH EVERTS
BETHANY HALFORD
MATERIALS
▸ New crystal structure of DDT identified A newly identified crystal structure of DDT suggests that reformulating the compound to boost its insecticidal properties may be possible (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201703028). The advance could lead to ways of using DDT more efficiently and in smaller quantities, thereby reducing its broader environmental effects. DDT was developed in the 1940s as an insecticide, and many countries still use it for malaria control. But it
Crystalline DDT shows spherulites of form I (orange) in fields of form II (gray). The orange color of form I arises from its interaction with polarized light. is also a persistent organic pollutant that is banned elsewhere because of its toxicity to other species. Since DDT’s discovery,
scientists have believed that it had only one crystal structure, dubbed form I. Inspired by a stock micrograph that suggested helical twisting of DDT crystals, a team led by Bart Kahr and Michael D. Ward of New York University has now experimentally characterized a second crystal structure, form II. Computational analysis points to two more possibilities. DDT adsorbs on insects’ hydrophobic footpads when walking on crystals, a first step toward insecticide uptake. So the researchers hypothesized that different crystal structures could influence adsorption. Experiments with Drosophila melanogaster fruit flies indicated that form II is a more potent insecticide than form I, at least for that species.—JYLLIAN
KEMSLEY JUNE 26, 2017 | CEN.ACS.ORG | C&EN
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