The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

The miniaturization of components used in the construction of working devices is being pursued currently by the large-downward (top-down) fabrication. This approach, however, which obliges solid-state physicists and electronic engineers to manipulate progressively smaller and smaller pieces of matter, has its intrinsic limitations. An alternative approach is a small-upward (bottom-up) one, starting from the smallest compositions of matter that have distinct shapes and unique properties-namely molecules. In the context of this particular challenge, chemists have been extending the concept of a macroscopic machine to the molecular level. A molecular-level machine can be defined as an assembly of a distinct number of molecular components that are designed to perform machinelike movements (output) as a result of an appropriate external stimulation (input). In common with their macroscopic counterparts, a molecular machine is characterized by 1) the kind of energy input supplied to make it work, 2) the nature of the movements of its component parts, 3) the way in which its operation can be monitored and controlled, 4) the ability to make it repeat its operation in a cyclic fashion, 5) the timescale needed to complete a full cycle of movements, and 6) the purpose of its operation. Undoubtedly, the best energy inputs to make molecular machines work are photons or electrons. Indeed, with appropriately chosen photochemically and electrochemically driven reactions, it is possible to design and synthesize molecular machines that do work. Moreover, the dramatic increase in our fundamental understanding of self-assembly and self-organizational processes in chemical synthesis has aided and abetted the construction of artificial molecular machines through the development of new methods of noncovalent synthesis and the emergence of supramolecular assistance to covalent synthesis as a uniquely powerful synthetic tool. The aim of this review is to present a unified view of the field of molecular machines by focusing on past achievements, present limitations, and future perspectives. After analyzing a few important examples of natural molecular machines, the most significant developments in the field of artificial molecular machines are highlighted. The systems reviewed include 1) chemical rotors, 2) photochemically and electrochemically induced molecular (conformational) rearrangements, and 3) chemically, photochemically, and electrochemically controllable (co-conformational) motions in interlocked molecules (catenanes and rotaxanes), as well as in coordination and supramolecular complexes, including pseudorotaxanes. Artificial molecular machines based on biomolecules and interfacing artificial molecular machines with surfaces and solid supports are amongst some of the cutting-edge topics featured in this review. The extension of the concept of a machine to the molecular level is of interest not only for the sake of basic research, but also for the growth of nanoscience and the subsequent development of nanotechnology.

Artificial Molecular Machines.

The widespread use of molecular machines in biology has long suggested that great rewards could come from bridging the gap between synthetic molecular systems and the machines of the macroscopic world. In the last two decades, it has proved possible to design synthetic molecular systems with architectures where triggered large amplitude positional changes of submolecular components occur. Perhaps the best way to appreciate the technological potential of controlled molecular-level motion is to recognize that nanomotors and molecular-level machines lie at the heart of every significant biological process. Over billions of years of evolution, nature has not repeatedly chosen this solution for performing complex tasks without good reason. When mankind learns how to build artificial structures that can control and exploit molecular level motion and interface their effects directly with other molecular-level substructures and the outside world, it will potentially impact on every aspect of functional molecule and materials design. An improved understanding of physics and biology will surely follow.

The first steps on the long path to the invention of artificial molecular machines were arguably taken in 1827 when the Scottish botanist Robert Brown observed the haphazard motion of tiny particles under his microscope.1,2 The explanation for Brownian motion, that it is caused by bombardment of the particles by molecules as a consequence of the kinetic theory of matter, was later provided by Einstein, followed by experimental verification by Perrin.3,4 The random thermal motion of molecules and its implications for the laws of thermodynamics in turn inspired Gedankenexperiments (“thought experiments”) that explored the interplay (and apparent paradoxes) of Brownian motion and the Second Law of Thermodynamics. Richard Feynman’s famous 1959 lecture “There’s plenty of room at the bottom” outlined some of the promise that manmade molecular machines might hold.5,6 However, Feynman’s talk came at a time before chemists had the necessary synthetic and analytical tools to make molecular machines. While interest among synthetic chemists began to grow in the 1970s and 1980s, progress accelerated in the 1990s, particularly with the invention of methods to make mechanically interlocked molecular systems (catenanes and rotaxanes) and control and switch the relative positions of their components.7−24

Here, we review triggered large-amplitude motions in molecular structures and the changes in properties these can produce. We concentrate on conformational and configurational changes in wholly covalently bonded molecules and on catenanes and rotaxanes in which switching is brought about by various stimuli (light, electrochemistry, pH, heat, solvent polarity, cation or anion binding, allosteric effects, temperature, reversible covalent bond formation, etc.). Finally, we discuss the latest generations of sophisticated synthetic molecular machine systems in which the controlled motion of subcomponents is used to perform complex tasks, paving the way to applications and the realization of a new era of “molecular nanotechnology”.

1.1. The Language Used To Describe Molecular Machines
Terminology needs to be properly and appropriately defined and these meanings used consistently to effectively convey scientific concepts. Nowhere is the need for accurate scientific language more apparent than in the field of molecular machines. Much of the terminology used to describe molecular-level machines has its origins in observations made by biologists and physicists, and their findings and descriptions have often been misinterpreted and misunderstood by chemists. In 2007 we formalized definitions of some common terms used in the field (e.g., “machine”, “switch”, “motor”, “ratchet”, etc.) so that chemists could use them in a manner consistent with the meanings understood by biologists and physicists who study molecular-level machines.14

The word “machine” implies a mechanical movement that accomplishes a useful task. This Review concentrates on systems where a stimulus triggers the controlled, relatively large amplitude (or directional) motion of one molecular or submolecular component relative to another that can potentially result in a net task being performed. Molecular machines can be further categorized into various classes such as “motors” and “switches” whose behavior differs significantly.14 For example, in a rotaxane-based “switch”, the change in position of a macrocycle on the thread of the rotaxane influences the system only as a function of state. Returning the components of a molecular switch to their original position undoes any work done, and so a switch cannot be used repetitively and progressively to do work. A “motor”, on the other hand, influences a system as a function of trajectory, meaning that when the components of a molecular motor return to their original positions, for example, after a 360° directional rotation, any work that has been done is not undone unless the motor is subsequently rotated by 360° in the reverse direction. This difference in behavior is significant; no “switch-based” molecular machine can be used to progressively perform work in the way that biological motors can, such as those from the kinesin, myosin, and dynein superfamilies, unless the switch is part of a larger ratchet mechanism.14

Artificial Molecular Machines

A solid state, electronically addressable, bistable [2]catenane-based molecular switching device was fabricated from a single monolayer of the [2]catenane, anchored with phospholipid counterions, and sandwiched between an n-type polycrystalline silicon bottom electrode and a metallic top electrode. The device exhibits hysteretic (bistable) current/voltage characteristics. The switch is opened at +2 volts, closed at −2 volts, and read at ∼0.1 volt and may be recycled many times under ambient conditions. A mechanochemical mechanism for the action of the switch is presented and shown to be consistent with temperature-dependent measurements of the device operation.

https://science.sciencemag.org/content/sci/289/5482/1172.full.pdf

A [2]Catenane-Based Solid State Electronically Reconfigurable Switch

Artificial Molecular Rotors

Analogues of mechanical devices that operate on the molecular level, such as shuttles, brakes, ratchets, turnstiles and unidirectional spinning motors, are current targets of both synthetic chemistry and nanotechnology. These structures are designed to restrict the degrees of freedom of submolecular components such that they can only move with respect to each other in a predetermined manner, ideally under the influence of some external stimuli. Alternating-current (a.c.) electric fields are commonly used to probe electronic structure, but can also change the orientation of molecules (a phenomenon exploited in liquid crystal displays), or interact with large-scale molecular motions, such as the backbone fluctuations of semi-rigid polymers. Here we show that modest a.c. fields can be used to monitor and influence the relative motion within certain rotaxanes, molecules comprising a ring that rotates around a linear 'thread' carrying bulky 'stoppers' at each end. We observe strong birefringence at frequencies that correspond to the rate at which the molecular ring pirouettes about the thread, with the frequency of maximum birefringence, and by inference also the rate of ring pirouetting giving rise to it, changing as the electric field strength is varied. Computer simulations and nuclear magnetic resonance spectroscopy show the ring rotation to be the only dynamic process occurring on a timescale corresponding to the frequency of maximum birefringence, thus confirming that mechanical motion within the rotaxanes can be addressed, and to some extent controlled, by oscillating electric fields.

Influencing intramolecular motion with an alternating electric field

Linear and Unanticipated Second‐Order Nonlinear Optical Properties of Benzylic Amide [2]Catenane Thin Films: Evidence of Partial Rotation of the Interlocked Molecular Rings in the Solid State

Rotaxanes: novel photonic molecules

New polythiophene derivatives containing azo dye side group were prepared via copolymerization of 3-alkylthiophenes and Disperse Red 1 substituted thiophenes. The presence of chromophore groups in the polymers was confirmed by NMR and FTIR spectroscopies as well as by elemental analysis. The obtained soluble polymers were processed into thin films by spin coating technique and their nonlinear optical properties were studied by the optical second harmonic generation technique and by quadratic electro-optic Kerr effect. The second order nonlinear optical coefficients are : dsp = 6.8 pm/V and dpp = 28.3 pm/V at 1064 nm fundamental wavelength. The quadratic electro-optic Kerr coefficient is about three times larger for the unfunctionalized polymer than for unfoncionalized.

Azo Chromophore Functionalized Polythiophenes. Synthesis and Nonlinear Optical Properties

Benzylic amide catenanes are a class of synthetically-accessible interlocked molecular rings which can rotate one through the other depending on the nature of the local environment. The rings contain four phenyl units each and interlocking also affords their packing in novel, highly interacting ways that may lead to unexpected properties thus opening up the possibility of developing new materials. Third harmonic generation in benzylic amide catenane solutions was measured at a wavelength of γ = 1064 nm, with the fundamental and the harmonic wavelengths in the region of transparency of the material. The thoroughly non resonant value of the hyperpolarisability γ(-3ω; ω, ω, ω) was found to be (6.5 ± 0.7) × 10−35 esu with a negligible imaginary part, in agreement with the value of (6.8 ± 0.9) × 10−35 esu calculated from a bond-additivity model of hyperpolarisability. The static second order hyperpolarisability predicted by a Molecular Orbital model was about a factor four less than the experimental v...

Torsten Gase

Papers

Influencing intramolecular motion with an alternating electric field

Linear and Unanticipated Second‐Order Nonlinear Optical Properties of Benzylic Amide [2]Catenane Thin Films: Evidence of Partial Rotation of the Interlocked Molecular Rings in the Solid State

Rotaxanes: novel photonic molecules

Azo Chromophore Functionalized Polythiophenes. Synthesis and Nonlinear Optical Properties

Nonlinear Optical Properties of Benzylic Amide [2] Catenanes: A Novel Versatile Photonic Material