Concentrates Chemistry news from the week
▸ Highlights Liposome system mimics GPCRs to deliver drugs Aluminum gets 3-D printed without cracking Copper nanoparticle catalyst could recycle CO2 New insight into Alzheimer’s genetic risk factor Firms turn to garbage to make ethanol Trio of Boston biotech firms unveiled NSF: U.S. business spending on R&D was up in 2015 EU controls said to be leading to safer substitutes
4 5 7 9 10 11 15 15
MOLECULAR MACHINES
Molecular machine builds set of chiral molecules
C R E D I T: NAT UR E
System’s ‘arm’ swivels back and forth to add pieces stereoselectively Molecular machines, large molecules with moving parts that can carry out various useful tasks, were honored last year with the Nobel Prize in Chemistry. Researchers would like these tiny machines to someday synthesize other molecules, similar to the way ribosomes make proteins, because the machines might work more efficiently than conventional stepwise, solution-based syntheses in the lab and create products not easily accessible in other ways. David A. Leigh of the University of Manchester and coworkers made molecular-machine-based synthesis a reality when they developed a large molecule that picks up amino acids and assembles them into tripeptides (Science 2013, DOI: 10.1126/ science.1229753). Now, they’ve taken the concept to another level by designing a programmable molecular machine that creates four different products by adding thiol and alkene substituents asymmetrically to an , -unsaturated aldehyde substrate (Nature 2017, DOI: 10.1038/nature23677). The machine reactions’ stereoselectivities are similar to, but in some cases lower than, those of corresponding catalytic reactions in solution, Leigh says. The , -unsaturated aldehyde is attached to an “arm” in the molecular machine. An acyl hydrazone in the machine changes conformation in response to pH changes, causing the arm to rotate between two orientations. These motions position the substrate above one of two silyl prolinol activation sites that mediate reactions with opposite chirality—R for one site, S for the other. So arm position controls reaction chirality.
microorganisms use to create peptide natural products and which scientists can engineer to make analogs. Snapper and Boston College’s T. Ross Kelly also write in The substrate forms a reactive iminium a Nature commentary associated with the intermediate with an activation site, and new report that molecular machines “offer the intermediate reacts with the thiol for an alternative strategy” to other automated the first addition. Then the substrate, with synthesis techniques, like the reactor sysits added sulfide, forms a reactive enamine with an activation site, and the alkene adds tem Martin D. Burke and coworkers at the University of Illinois, Urbana-Champaign, to that intermediate. If the arm is rotated between sites midsynthesis by adding acid, designed to make organic small molecules (Science 2015, DOI: 10.1126/science.aaa5414 the steps have opposite chirality, and the diastereomer products have R,S or S,R con- and C&EN, March 16, 2015, page 3). But it figuration. If the arm is stationary between is too early to tell whether molecular machines “will offer advantages” over these steps, both additions occur with the same other techniques, they note. chirality, and the product is R,R or S,S. Molecular-machine synthesizers “might Marc L. Snapper of Boston College tells C&EN that Leigh’s machine is reminiscent indeed never find favour,” and the new system may be “more contrived than ingeof biological molecular assemblers such as nious,” Kelly and Snapper write. However, nonribosomal peptide synthetases, which “Those who dismiss the concept of molecO ular assemblers should heed the lesson of O O Lord Kelvin’s infamous 1895 pronouncement O that ‘heavier-than-air H flying machines are O N impossible.’ ”—STU O H N N BORMAN N
HN (CH3CH2)3SiO Ph Ph = phenyl
(S)
N N N
N N N
Ph Substrate
NH (R)
OSi(CH2CH3)3 Ph
Ph Arm
Rotary switch
Molecular structure and model of the new molecular machine. S
Chiral activating sites
R
SEPTEMBER 25, 2017 | CEN.ACS.ORG | C&EN
3
