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Molecular machines – Tiny but significant


A thousand times thinner than a strand of hair, but with an impact as big as the microchip.

The Nobel Prize in Chemistry 2016 was awarded to three scientists, Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa, for the design and synthesis of molecular machines. Molecular machines have been defined as “an assembly of a distinct number of molecular components that are designed to perform machine-like movements, i.e. producing quasi-mechanical movements (output) as a result of an appropriate external stimulation (input)”. Molecular machines are also often referred to as molecular motors, and can be either synthetic or natural molecules that convert chemical energy into mechanical motion and forces. They require a supply of energy for their operation and they are so small that you need an electron microscope to see them. In fact, all life is powered by tiny biological machines. The most fundamental processes of life, such as translating genetic code to make proteins, require the use of molecular machines 10 000 times smaller than a human hair and functioning only on chemical energy.

Catenane, Rotaxane and a molecular motor

The first step towards a molecular machine was taken in 1983, when Jean-Pierre Sauvage succeeded in linking two molecules in a chain (a so-called catenane), hence creating several parts that can move relative to each other – a requirement for a machine. He used copper ions to develop molecular complexes and photochemistry to create active complexes that capture energy contained in solar rays to drive chemical reactions. Sauvage and his colleagues used this experiment to construct a ring-shaped and a crescent-shaped molecule so that they could be welded to the copper ion using the cohesive force that kept the molecules intact. Then they removed the copper ion, which had solved its purpose of providing a base to construct these chains.

Eight years later J. Fraser Stoddart was able to create a ring of molecules that moved along an axle in a controlled way when heat was added (a so-called rotaxane). He built an open ring that lacked electrons and a long axle that had electron-rich structures in two places. When the two molecules met in a solution, electron-poor was attracted to electron-rich and the ring threaded on to the axle. In the next step he closed the opening in the ring so that it remained on the molecular axle. When he added heat the ring jumped forwards and backwards, and a few years later Stoddart could completely control the movement. He had created the first “molecular shuttle”, according to Nature.

In 1999 Bernard L. Feringa was able to build the first molecular motor, consisting of two small rotor blades and two flat chemical structures joined with a double bond between two carbon atoms. A methyl group was attached to each rotor blade, forcing the molecule to keep rotating in the same direction. When exposed to a pulse of ultraviolet light one rotor blade jumped 180 degrees around the central double bond, then the ratchet moved into position and with the next light pulse the rotor blade jumped another 180 degrees, and so it continued.

Feringa’s research group has since optimized the design of the motor, making it rotate at a speed of 12 million revs per second and creating a four-wheel drive nanocar.

The first steps into a new world

But the magnitude of these discoveries is yet to come, according to the scientists themselves and the Nobel Prize committee. “Just like the molecules of life, Sauvage’s, Stoddart’s and Feringa’s artificial molecular systems perform a controlled task. Chemistry has thus taken the first steps into a new world. In terms of development, the molecular motor is about the same stage as the electric motor was in the 1830s, when researchers proudly displayed various spinning cranks and wheels in their laboratories without having any idea that they would lead to washing machines, fans and food processors,” stated the Royal Swedish Academy of Science in their press release, and in his first interview after the announcement of the Nobel Prize, Feringa said he felt like the Wright brothers. “When they flew for the first time, over 100 years ago, people asked why they needed a flying machine. Now we have a Boeing 747 and an Airbus. [With this technology] we will be able to build materials that will change, adapt or even store energy. There is endless opportunity.”

Since their discoveries the three scientists have constructed several molecular machines, including a molecular lift that can raise itself 0.7 nanometers above a surface (2004), an artificial muscle (2005), an elastic structure that is reminiscent of the filaments in a human muscle (2000) and a rotaxane-based computer chip with a 20 kB memory. However, the greatness of their discoveries is yet to come, and to quote Stoddart, “We’re on a very early part of a very steep learning curve. Chemistry is a fundamental science and it needs some space in which to develop the fundamentals. It’s going to be a slow process and it may take decades to develop the field to a stage where it’s applied to whatever the technology of the day is, but then suddenly it will take off, and people will see what all that fundamental development can lead to.”

Tiny robots injected in your veins

In the field of life science molecular machines will hopefully be able to deliver drugs within the body directly to cancer cells or a specific area of the tissue to medicate, and hence reduce, the damage treatment like chemotherapy does to a patient’s healthy cells. In a recent report by Scientific American, nanorobots that can be sent through blood vessels and nanomaterials that can monitor vital organ health may soon revolutionize healthcare. “Like tiny robots injected in your blood veins targeting the cancer cells,” suggested Feringa to the Nobel Media after the announcement.

Recent advances in the field include micro/nanoscale machines for biomedical applications like drug delivery, diagnostics, nanosurgery and biopsies of hard-to-reach tumors. In 2013 Dave Leigh at the University of Manchester was able to develop a molecular robot that can grasp and connect amino acids. Last year Nature reported that researchers have exploited the light-activated mechanism to develop some 100 drug-like compounds that switch on or off in response to light (Borowiak et al., Cell 2015, Jul). In 2014 US scientists reported that lab-made molecules whose parts come together when exposed to light might be used to treat macular degeneration or retinitis pigmentosa, like a photoswitchable molecule (Tochitsky et al., Neuron 2014, Feb)

Researchers have also shown that molecular machines could lead to the design of a molecular computer, placed inside the body to detect a disease before any symptoms are exhibited (Xing Jiang, University of California, Oct 4 2016).

It is unknown today what the killer application (as Stoddart put it) will be, but without a doubt scientists believe that these tiny machines could have a huge impact on our future and revolutionize medicine and our quality of life.