Science Concentrates LAB SAFETY
Pyrophorics handling, made safer
C R E D I T: ORG . P ROC. R ES . D ES . ( S E T UP ) ; K EVA N S H O KAT ( P ROTE I N D I AG RAM )
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Simple equipment decreases the danger of transferring small volumes of chemicals prone to igniting When chemists want to transfer a small amount of a pyrophoric reagent, such as tert-butyl lithium, they typically use a needle and a syringe. But this protocol can be dangerous: One wrong move and the chemical could drip, or worse, squirt out of the needle and ignite. A fire caused by tert-butyl lithium resulted in UCLA research assistant Sheharbano Sangji’s fatal burns in 2009. Now, chemists at Aarhus University have devised a simple setup and protocol that can make small transfers safer. The setup consists of a sealed transfer vial made by fusing the tops of two crimp-neck vials, a three-dimensionally printed bottle cap that screws onto the bottle of the pyrophoric reagent and holds the transfer vial, and a metal clip that secures the system so that it’s “hands free.” To transfer the reagent once the setup is assembled, a chemist pushes a long needle through both crimp cap seals on the transfer vial (which is filled with inert gas) and then through the reagent bottle’s rubber seal. The chemist draws the required amount of reagent into the syringe and then withdraws the needle so that it is contained within the transfer vial. After removing the transfer vial from the 3-D-printed
bottle cap, the chemist places the transfer vial onto the reaction flask, pushes the needle through the transfer vial and through a septum on the reaction flask, and finally transfers the reagent (Org. Process. Res. Dev. 2018, DOI: 10.1021/acs.oprd.8b00151). Chemists Anders T. Lindhardt, Mogens Hinge, and Martin B. Johansen and glassblower Jens C. Kondrup devised the system in response to an undergraduate laboratory experiment that called for students to transfer tert-butyl lithium. Although senior scientists closely supervised the students while doing the transfer, Lindhardt says that safety was a major concern. So, after many iterations, they came up with this system, which was tested and evaluated by 60 undergraduates. Xiao-Feng Wu at Leibniz Institute for Catalysis points out that pyrophoric reagents like tert-butyl lithium are used on a daily basis in some research laboratories, even though their high air and moisture sensitivities can lead to serious accidents, particularly when used by chemists who are inexperienced at transferring such materials. “With this system, even high school students can enjoy the advantages of tert-butyl lithium,” he says.
The setup developed by Aarhus University scientists for transferring pyrophoric reagents. Debbie M. Decker, safety manager for the chemistry department at the University of California, Davis, thinks that the setup may be useful for transferring small amounts of pyrophoric reagents via syringe. “I think this is an important technique for undergraduates to learn in a teaching environment, rather than in the research environment,” she says. Teaching students the cannula technique, in which a double-tipped needle is used to transfer the reagent under pressure, may be more useful in a research setting, Decker adds. Lindhardt agrees that a cannula setup is better for transferring large volumes of tert-butyl lithium and similar reagents. He says the goal of this work was to make “something simple that people could construct themselves.” Although the chemists enlisted a glassblower to make the transfer vial, they published vial schematics online with the paper, along with specifications for 3-D printing the bottle cap and an instructional video.—BETHANY HALFORD
PHARMACEUTICALS
Drugging the undruggable Although genome sequencing has helped scientists reveal proteins wreaking havoc in our bodies, that doesn’t guarantee scientists can design drugs to fix them. Depending on whom you talk to, up to 85% of the human proteome is currently “undruggable.” These proteins—such as KRas, shown here in gray—lack easyto-find pockets where therapeutics, such as small molecules, can bind. But a wave of biotech companies, each one armed with new technology, has arrived to tackle the problem. In this month’s Stereo Chemistry podcast episode, industry and academic scientists explain why they think the business and scientific environment is ripe for finally overcoming the most elusive drug targets. Listen to the full episode at cenm.ag/undruggable.—LISA JARVIS JUNE 25, 2018 | CEN.ACS.ORG | C&EN
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