Researchers at the University of Groningen have shown how infrared photons picked up by a dye molecule can be used to power another molecule acting as a motor. [Image: Nong Hoang, University of Groningen]
Tiny molecular motors powered by light could be used in everything from new kinds of functional material to the pinpoint administration of drugs. But until now the light in question has been at ultraviolet wavelengths, which is not well suited to in vivo applications.
New research carried out by scientists in the Netherlands shows how such motors can instead be operated using infrared light (Sci. Adv., doi: 10.1126/sciadv.abb6165). If these devices can be made practical, they could be ideal for medicine—given the ability of infrared waves to penetrate deeply into tissue while generally leaving it unharmed.
From ultraviolet to infrared
Ben Feringa of the University of Groningen won a share of the 2016 Nobel prize in chemistry for work he carried out 17 years earlier showing for the first time it was possible to build a molecular motor that rotated continually in the same direction. He did so using a molecule consisting of two rotors that were made from planes of atoms and connected to one another by a double carbon bond.
The idea was to turn one rotor relative to the other 180 degrees at a time, while using a ratchet-like mechanism facilitated by the addition of methyl groups to ensure no backward slippage. Each complete cycle of the motor consists of four steps, with ultraviolet light being applied on the first and third steps to stimulate chemical reactions that in turn generate the rotation. Overcoming the tension that occurs after each rotation, and which would normally see the structures forced back to their starting positions, is achieved through a spontaneous process known as thermal helix inversion that involves one rotor sliding past the other.
Attempts to power such motors with less energetic light have not borne fruit until now. The energy of one ultraviolet photon can, in principle, be supplied by having the motor molecule absorb two infrared photons at the same time. But such direct two-photon absorption turned out to be very inefficient, with chemically unaltered motors only rotating when exposed to light of such high intensity that it could start to damage cells if used for medical purposes.
An antenna system
In the latest work, Feringa and colleagues in Groningen instead use a second molecule acting as an “antenna” to absorb two near-infrared photons and then pass the energy on resonantly to the motor molecule, which is attached via a covalent bond. Among the biggest challenges of this arrangement, according to group member Lukas Pfeifer, now at the Swiss École Polytechnique Fédérale in Lausanne, Switzerland, was matching the energy levels of the two molecules as well as linking them without disrupting the motor's rotation.
The researchers found they could implement such a system using an antenna made from a dye molecule known as AF-343. They showed that after being excited by twin near-infrared photons, AF-343 could transfer energy to the motor molecule by emitting virtual photons in the near field. This breaks one half of the motor’s double carbon bond, causing one of the two rotors to rotate through 180 degrees. That structure then either falls back down to its ground state or else enters a metastable state at an intermediate energy level. In the former case it returns to its starting configuration, while in the latter a certain amount of heat input allows it to undergo thermal helix inversion before dropping down to the ground state—with its rotation intact.
The dye transfers energy to the motor molecule with an efficiency of 90%, which Feringa and co-workers say allows them to limit the intensity of near-infrared light to several orders of magnitude below the threshold at which tissue damage occurs. They add that this resonant transfer, by avoiding the need to emit and reabsorb up-converted photons, also minimizes the chance of photons being absorbed by other light-sensitive molecules in the body.
Feringa sees the technology as potentially benefiting a variety of medical treatments where precision is important. One is chemotherapy, where the ability to activate medication only once the chemicals involved have reached the tumor would allow other cells to remain unharmed. Similarly, the targeting of specific bacteria causing infection, as opposed to other kinds of bacteria, could limit the problem of antibiotic resistance.
The new motor is not yet a finished product, however. One limitation in particular is speed. While other steps in the rotation process, including the energy transfer from dye to motor molecules, require just trillionths of a second, thermal helix inversion takes about an hour to occur. But Pfeifer is confident that the kind of technical innovations intended to reduce repulsion between the two rotors, which they have used to speed up the operation of ultraviolet motors, can also be employed in the new antenna-based design.