Molecules, Motors, and Chemists: The Story of a Nobel Prize that Combines Ingenuity and Imagination

This year’s Nobel Prize in Chemistry was awarded to three outstanding scientists for revolutionizing the field of nanomachines. To put this in perspective, for a person to be on the same scale as one of these machines, they would have to shrink approximately one billion times, putting them on the same scale as atoms and molecules. The ingenuity, creativity and imagination of Drs. Sauvage, Stoddart, and Frenga is reflected in their work constructing precise molecular structures, including rotating molecular rings, nanomotors, and nanocars.

In 1984 Nobel Laureate Dr. Richard Feynman, while hosting a lecture on the creation of nanomachines and their potential, concluded his talk with a challenge to those attending: “Have a delightful time in redesigning all kinds of familiar machinery, to see if you can do it. And give it 25-30 years, there will be some practical use for this. What it is, I do not know.” Unbeknownst to Dr. Feynman, Dr. Jean-Pierre Sauvage had already taken the first steps towards that challenge.

Figure 1. Cantenads are two interlocking rings depicted here. The rings are held together by mechanical bonds and are not directly bonded together. Credit: “Catenane Crystal Structure Chem Comm page634 1991 commons” by M Stone is licensed under CC Attribution-Sharealike 3.0 Unported.

Figure 1. Cantenads are two interlocking rings depicted here. The rings are held together by mechanical bonds and are not directly bonded together. Credit: “Catenane Crystal Structure Chem Comm page634 1991 commons” by M Stone is licensed under CC Attribution-Sharealike 3.0 Unported.

It all began with a bond

In chemistry, covalent bonds are one type of connection holding molecules together. These bonds are found naturally and chemists have taken advantage of them to build complex molecular structures. Synthetic polymers such as plastics, medicines such as aspirin, and fuels such as octanes are all examples of molecules held together by covalent bonds. In recent years, the quest for more complex molecules has led chemists to begin building structures that are held together by mechanical bonds rather than just covalent bonds. In contrast to covalent bonds, these mechanical bonds hold together molecules without requiring that atoms directly bonded with each other, allowing for more independent and unrestricted movement of individual parts.

Building complex molecules held together by mechanical bonds is no simple feat. Initially, scientists encountered many difficulties in the production of these molecules, often resulting in minimal yields from highly complicated methods. However, in 1984, Dr. Sauvage published a paper describing the efficient fabrication of a new class of molecule, cantenads, which contain interlocking ring structuresIn Figure 1 the carbon atoms making up each ring are bonded together by covalent bonds, much like how a welder will fuse together spokes on a wheel, while the rings are interlocked and are held together by mechanical bonds, much like links on a chain.

Cantenads were constructed by utilizing a positively charged copper atom as a construction scaffold to hold the individual components in place as they were being assembled to form the final interlocking structures. The copper atom was then removed, leaving behind two freely interlocked rings [1]. Ten years later, Dr. Sauvage succeeded in creating the first interlocking structure in which one ring revolved around the other when energy was added to the molecule, signifying one of the first steps toward building a functional molecular machine [2].

Figure 2. Rotaxanes are a ring threaded onto an axle shown here. The caps at the end of the axle prevent the ring from falling off. Credits: Image compiled by Nisar A. Farhat. 

The invention of a molecular wheel, axle, and motion


It wasn't long before others began to use the principle of interlocking structures developed by Sauvage to build more complex nanomachines. In 1991, Dr. Fraser Stoddart used this method to develop one of the first "molecular switches," called a rotaxane depicted in Figure 2.

Dr. Stoddart's rotaxanes consisted of a negatively charged molecular ring (much like the rings used in cantenads) threaded onto an "axle" with positive charges at each end and held in place by two molecular "caps". When Dr. Stoddart applied heat to these rotaxanes, he discovered that the ring moved back and forth between the positive charges to which it is attracted and is prevented from falling off by the caps on each end of the axel [3], as shown in Figure 3. Three years after the initial creation of rotaxanes, Dr. Stoddart figured out how to control the back and forth movement of the ring structure, allowing him to create nanomachines such as molecular elevators and molecular switches.[4]

 

Figure 3. When heat is applied to the rotaxane the ring will move back and forth along the axle. Credits: Image compiled by Nisar A. Farhat.

 

Figure 4. The molecular disks are constructed to mechanically restrict their movement in one direction only. When energy is added the disks will rotate and flap over each other locking them in place and preventing them from reversing to their previous position. Only when energy is added in the form UV radiation or heat will the next movement occur, again locking the flat disks in the next position. This continued movement and locking continues until a full rotation is achieved. Credits: Image compiled by Nisar A. Farhat.

Motors, Cars, and Molecules

Combining the principles of constructing precise molecular complexes and controlling the motion of these interlocking structures was the first step towards building molecular machines. Missing however, was the ability to precisely control the direction of these movements. Machines perform key tasks through specific motion in controlled directions. If the pistons in your car suddenly decided to move differently, your car engine could no longer successfully burn the fuel required to turn your tires. Dr. Feringa faced a challenge: without application of an external force or influence, molecules move at random patterns and directions. His solution was ingeniously combining chemical and physical properties to mechanically restrict molecules to move in one direction. His work on molecular motors was published in 1999 and described the movement of a flat molecular blade moving in one direction after being fueled by ultraviolet (UV) radiation and heat [5]. Figure 4 depicts how the two molecular disks are assembled.

In 2011, Dr. Feringa created a molecular “car” consisting of four motors. [6]. Furthermore, in 2014 Feringa's team improved on the motor design allowing it to rotate at an astounding 12 million revolutions per second. [7].

Congratulations, Dr. Sauvage, Dr. Stoddart, and Dr. Feringa on winning the Nobel Prize and for accepting Dr. Feynman's challenge and making nanomachines a reality! Thanks to your curiosity and imagination nanomachines have a bright future ranging from aiding complex surgeries and improving drug delivery, to benefitting manufacturing of more robust and complex materials, to improving technology by making microchips even smaller.


Nisar Farhat
Co-Founder and CFO, Signal to Noise Magazine
PhD Candidate, Molecular and Medical Pharmacology, UCLA
 

References

[1] Buchecker-Dietrich, C. & Sauvage J.P. Templated Synthesis of Interlocked Macrocyclic Ligands: The Catenands. JACS 106, 3043-3045 (1984).

[2] Livoreil, A. Buchecker-Dietrich, C. & Sauvage J.P Electrochemically Triggered Swinging of a Catenate. JACS 116, 9399-9400 (1994).

[3] Anelli, P.L. Spencer, N. & Stoddart F. A Molecular Shuttle. JACS 113, 5131-5133 (1991).

[4] Bissell, R. A. Cordova, E. Kaifer, A. E. & Stoddart J.F. A chemically and electrochemically switchable molecular shuttle. Nature 369, 133-137 (1994)

[5] Koumura, N. Zijlstra, R.W.J. van Delden, R. A. N. Nobuyuki, H. & Feringa B.L. Light-driven monodirectional molecular rotor. Nature 401, 152-155 (1999)

[6] Kudernac, T. Ruangsupapichat, N. Parschau, M. Beatriz, M. Katsonis, N. Harutyunyan S. R. Ernst K.H. & Feringa B.L. Electrically driven directional motion of a four-wheeled molecule on a metal surface. Nature 479, 208-211 (2011)

[7] Hou, L. Zhang, X. Pijper, T.C. Browne, W.R. & Feringa, B.L. Reversible Photochemical Control of Singlet Oxygen Generation Using Diarylethene Photochromic Switches. JACS 136, 910-913 (2014)