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Science Concentrates SYNTHESIS

Chemical manufacturing for the masses 3-D-printed reactors create complex small molecules

CHEMICAL COMMUNICATION

How some crabs avoid being eaten Waterways are a mess of molecules, presenting a massive challenge for researchers trying to understand how marine life communicates chemically. But with an assist from analytical chemistry, researchers from Georgia Institute of Technology have now solved an underwater mystery: what chemical cues mud crabs use to avoid predatory blue crabs (Proc. Natl. Acad. Sci. USA 2018, DOI: 10.1073/pnas.1713901115). To see how the team did it, watch the video at cenm.ag/crabs.—KERRI

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C&EN | CEN.ACS.ORG | JANUARY 22, 2018

3-D-printed reactor used to make baclofen (white powder in glass dish). “What I find particularly tempting are the fast iteration cycles made possible by the combination of computer-controlled design and 3-D printing.” Ameloot notes that while Cronin has shown a nice synthesis of an active pharmaceutical ingredient (API), it’s not the same as making a formulated drug, which includes nonactive substances that tune a drug’s release. Cronin says he doesn’t intend for digitized chemical synthesis to replace largescale API manufacturing. However, he notes, it could be used for small, bespoke applications, for people to perform chemical synthesis uniformly, and to crowdsource validation, regulation, and quality control. “This is going to enable us to standardize chemical synthesis.”—BETHANY HALFORD

C R E D I T: P H I LI P J. K I TS O N A N D LE ROY C RO N I N ( R EACTO R ) ; C& E N ( S C R E E N SH OT )

synthesize the muscle relaxant baclofen. Constructing complex chemicals could This particular reactor performs three reone day be as easy as building an Ikea actions, two liquid-liquid extractions, and bookshelf, if a synthesis approach dea set of evaporations and filtrations, ultiveloped by chemists at the University of mately producing baclofen hydrochloride Glasgow catches on. Instead of relying on as a white powder. The entire process can a hex key as the central tool in the assembe described through a platform-indepenbly process, molecule makers would use a dent code so that anyone could print the three-dimensional printer. Leroy Cronin reactor and duplicate the synthesis (Sciand colleagues report a chemical manuence 2018, DOI: 10.1126/science.aao3466). facturing process that uses customized, “We wanted to come up with a way of 3-D-printed, sealed reactors that users ensuring if you put chemicals in a reacload with chemicals according to simple tor system that they would process the instructions. same way each time, giving you a complex “The aim is to make a molecule with reaction procedure without very little expertise just folO anything going wrong,” Cronin lowing the instruction manual,” Cronin explains. He thinks OH says. The concept is to take the complex orchestration this digitized chemistry techof reactants, substrates, and nology will allow nonchemists, techniques performed by labosuch as biologists and medical NH2 Cl ratory chemists and put those professionals, to synthesize in the design of a reactor that molecules with short shelf Baclofen could be used by anyone. lives when and where they’re “That’s a better use of the chemist’s needed. It would also create a method for time,” Cronin says. “Organic chemists are reproducibly synthesizing a compound. creative individuals that are highly skilled. “Once you’ve digitized the process to do Why should they be enslaved to make the the synthesis, it can be resurrected forevsame molecule again and again?” er,” he says. “The concept of digitizing chemistry As a proof of concept, Cronin’s team is appealing,” comments Rob Ameloot, designed a 3-D-printed polypropylene an expert in 3-D printing at KU Leuven. reactor with multiple compartments to