Molecular assembling arm swivels back and forth to add pieces stereoselectively.
Credit: Kassem et al. 2017/Nature
Move over human chemists, there are now molecule-sized robot arms that do chemical synthesis with high selectivity and efficiency, and take no vacation. A team of researchers led by chemist David A. Leigh from of the University of Manchester has created a programmable molecular machine that synthesized four different products chiral molecules.
The world was awed by the nanoscaled machines in 2016, when the Nobel Prize was awarded to three prominent scientists for the design and construct of the so-called molecular machines that are a thousand times thinner than a hair strand: Jean-Pierre Sauvage gathered molecules around a copper ion and takes the first step towards building a molecular motor. J. Fraser Stoddart threaded a molecular ring onto a molecular axle called rotaxanes; His group used various version of rotaxanes to construct numerous molecular machines including a lift and an artificial muscle; Bernard L. Feringa built the first molecular motors. The ground-breaking work of these three pioneers have led to a toolbox of chemical structures that are used by researchers around the world to build increasingly advanced creations.
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This is not the first time the group attempted to build a sophisticated molecule-assembling mechanism. Back in 2013, Leigh and coworkers made developed a protein- and RNA-based molecule that can pick up amino acids and assembles them into tripeptides, which behaves like a ribosome. This time they built a molecular machine that can tackle chiral compounds. In the field of organic chemistry, chiral molecules commonly comprise a carbon atom attached to four different substituents. The substituents can be either atoms or groups of atoms, but each must differ from the other three for the carbon atom to be a chiral center (stereocenter). Their new machine, like a robot arm in factories, can move a substrate between different activating sites, and be programmed to produce diastereoisomers by adding thiol and alkene to α,β-unsaturated aldehyde substrate. According to Leigh, when compared to the catalytic reactions that aim to produce the same product, the chiral molecule assembling machine operates with the same if no less stereo-selectivity.
Commenting on the Leigh group’s work (which was published in Nature), renowned scientists Marc L. Snapper and T. Ross Kelly of Boston College thought that the molecular machines offer an alternative strategy to other synthesis techniques like automated reactor with yet-to-be-seen advantages. Nonetheless, “those who dismiss the concept of molecular assemblers should heed the lesson of Lord Kelvin’s infamous 1895 pronouncement that ‘heavier-than-air flying machines are impossible.’ We look forward to seeing what other impossibilities take flight in the future,” wrote Snapper and Kelly.
The Nobel Prize in Chemistry: Molecular Machines, Explained - Speaking of Chemistry. Credit: ACS