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

Ferroelectric Metal–Organic Frameworks

Molecular piezoelectrics are highly desirable for their easy and environment-friendly processing, light weight, low processing temperature, and mechanical flexibility. However, although 136 years have passed since the discovery in 1880 of the piezoelectric effect, molecular piezoelectrics with a piezoelectric coefficient d33 comparable with piezoceramics such as barium titanate (BTO; ~190 picocoulombs per newton) have not been found. We show that trimethylchloromethyl ammonium trichloromanganese(II), an organic-inorganic perovskite ferroelectric crystal processed from aqueous solution, has a large d33 of 185 picocoulombs per newton and a high phase-transition temperature of 406 kelvin (K) (16 K above that of BTO). This makes it a competitive candidate for medical, micromechanical, and biomechanical applications.

http://science.sciencemag.org/content/sci/357/6348/306.full.pdf

An organic-inorganic perovskite ferroelectric with large piezoelectric response

The development of molecular materials whose physical properties can be controlled by external stimuli - such as light, electric field, temperature, and pressure - has recently attracted much attention owing to their potential applications in molecular devices. There are a number of ways to alter the physical properties of crystalline materials. These include the modulation of the spin and redox states of the crystal's components, or the incorporation within the crystalline lattice of tunable molecules that exhibit stimuli-induced changes in their molecular structure. A switching behaviour can also be induced by changing the molecular orientation of the crystal's components, even in cases where the overall molecular structure is not affected. Controlling intermolecular interactions within a molecular material is also an effective tool to modulate its physical properties. This Review discusses recent advances in the development of such stimuli-responsive, switchable crystalline compounds - referred to here as dynamic molecular crystals - and suggests how different approaches can serve to prepare functional materials.

Dynamic molecular crystals with switchable physical properties

Inorganic perovskite ferroelectrics are widely used in nonvolatile memory elements, capacitors, and sensors because of their excellent ferroelectric and other properties. Organic ferroelectrics are desirable for their mechanical flexibility, low weight, environmentally friendly processing, and low processing temperatures. Although almost a century has passed since the first ferroelectric, Rochelle salt, was discovered, examples of highly desirable organic perovskite ferroelectrics are lacking. We found a family of metal-free organic perovskite ferroelectrics with the characteristic three-dimensional structure, among which MDABCO ( N -methyl- N9 -diazabicyclo[2.2.2]octonium)–ammonium triiodide has a spontaneous polarization of 22 microcoulombs per square centimeter [close to that of barium titanate (BTO)], a high phase transition temperature of 448 kelvins (above that of BTO), and eight possible polarization directions. These attributes make it attractive for use in flexible devices, soft robotics, biomedical devices, and other applications.

http://science.sciencemag.org/content/sci/361/6398/151.full.pdf

Metal-free three-dimensional perovskite ferroelectrics

Molecular rotation has attracted much attention with respect to the development of artificial molecular motors, in an attempt to mimic the intelligent and useful functions of biological molecular motors. Random motion of molecular rotators—for example the 180∘ flip-flop motion of a rotatory unit—causes a rotation of the local structure. Here, we show that such motion is controllable using an external electric field and demonstrate how such molecular rotators can be used as polarization rotation units in ferroelectric molecules. In particular, m-fluoroanilinium forms a hydrogen-bonding assembly with dibenzo[18]crown-6, which was introduced as the counter cation of [Ni(dmit)2]− anions (dmit2−=2-thioxo-1,3-dithiole-4,5-dithiolate). The supramolecular rotator of m-fluoroanilinium exhibited dipole rotation by the application of an electric field, and the crystal showed a ferroelectric transition at 348 K. These findings will open up new strategies for ferroelectric molecules where a chemically designed dipole unit enables control of the nature of the ferroelectric transition temperature. Molecular rotors have seen considerable interest as functional molecules on surfaces or for applications as memory devices. However, it is now shown that molecular rotation may also be used to induce ferroelectricity in a molecule.

Ferroelectricity and polarity control in solid-state flip-flop supramolecular rotators.

Supramolecular rotators of hydrogen-bonding assemblies between anilinium (Ph-NH3+) or adamantylammonium (AD-NH3+) and dibenzo[18]crown-6 (DB[18]crown-6) or meso-dicyclohexano[18]crown-6 (DCH[18]crown-6) were introduced into [Ni(dmit)2] salts (dmit2− is 2-thioxo-1,3-dithiole-4,5-dithiolate). The ammonium moieties of Ph−NH3+ and AD−NH3+ cations were interacted through N−H+∼O hydrogen bonding with the six oxygen atoms of crown ethers, forming 1:1 supramolecular rotator−stator structures. X-ray crystal-structure analyses revealed a jackknife-shaped conformation of DB[18]crown-6, in which two benzene rings were twisted along the same direction, in (Ph−NH3+)(DB[18]crown-6)[Ni(dmit)2]− (1) and (AD−NH3+)(DB[18]crown-6)[Ni(dmit)2]− (3), whereas the conformational flexibility of two dicyclohexyl rings was observed in (Ph−NH3+)(DCH[18]crown-6)[Ni(dmit)2]− (2) and (AD−NH3+)(DCH[18]crown-6)[Ni(dmit)2]− (4). Sufficient space for the molecular rotation of the adamantyl group was achieved in the crystals of salts 3 and 4...

Solid-state molecular rotators of anilinium and adamantylammonium in [Ni(dmit)2](-) salts with diverse magnetic properties.

The supramolecular (HOPD(+))(DB[18]crown-6) cation, in which HOPD(+) and DB[18]crown-6 are o-aminoanilinium and dibenzo[18]crown-6, respectively, was introduced into [Ni(dmit)(2)](-) salts (dmit(2-) = 2-thioxo-1,3-dithiole-4,5-dithiolate). Conformational polymorphs were observed as tetragonal (HOPD(+))(DB[18]crown-6)[Ni(dmit)(2)](-) (1) and monoclinic (HOPD(+))(DB[18]crown-6)[Ni(dmit)(2)](-) (2). The ammonium group of HOPD(+) in salts 1 and 2 formed the N-H(+)O hydrogen bonds at the bottom and upper positions of V-shaped DB[18]crown-6, respectively, thereby producing a different supramolecular conformation. The [Ni(dmit)(2)](-) anion arrangements in salts 1 and 2 were 4(1)-helical pi stacking and a two-dimensional layer, respectively, depending on the conformation of the supramolecular cations. The magnetic behavior of salts 1 and 2 obeyed the Curie-Weiss law at room temperature with S = 1/2 spin on the [Ni(dmit)(2)](-) anion. However, the g value and line width in the electron resonance spectra of salt 1 showed a magnetic anomaly at 28 K, which was owing to antiferromagnetic ordering in the 4(1)-helical [Ni(dmit)(2)](-) pi stack. Large temperature- and frequency-dependent dielectric responses were observed for salt 2 at temperatures above 200 K, whereas no particular dielectric responses were observed in salt 1. The molecular motion of HOPD(+) within the cationic layer of salt 2 contributed to the dielectric response, and this was supported by ab initio calculations showing the potential-energy curve for pendulum motion and by the large thermal parameters in the X-ray crystal structure analysis. The fixed (HOPD(+))(DB[18]crown-6) arrangement in the crystal of salt 1 was consistent with the small dielectric response. The steric hindrance of the o-amino group of HOPD(+) in the supramolecular cation structure yielded the conformational polymorph with different dielectric and magnetic properties.

Hiroyuki Koshinaka

Papers

Ferroelectricity and polarity control in solid-state flip-flop supramolecular rotators.

Solid-state molecular rotators of anilinium and adamantylammonium in [Ni(dmit)2](-) salts with diverse magnetic properties.

Conformational polymorph of o-aminoanilinium(dibenzo[18]crown-6) supramolecules in [Ni(dmit)2]- salts.