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.

A solid-state dynamic supramolecular structure consisting of (anilinium)([18]crown-6) was arranged as the cation in a salt of [Ni(dmit)2]- (dmit = 2-thioxo-1,3-dithiole-4,5-dithiolate). With the ammonium moiety of anilinium located within the cavity of [18]crown-6, a hydrogen-bonded supramolecular structure is formed, with an orthogonal arrangement between the pi plane of anilinium and the mean O6 plane of [18]crown-6. In this supramolecular cation, both anilinium and [18]crown-6 act as dynamic units with different rotational modes in the solid state. The uniform stacks of cations form an antiparallel arrangement, thus producing a layer structure. Sufficient space for the 180 degree flip-flop motion of the phenyl ring and the rotation of [18]crown-6 was observed in the cation layer. Thermally activated 180 degree flip-flop motions, with a frequency of 6 MHz at room temperature and an activation energy of 31 kJ mol(-1), were confirmed by temperature-dependent 2H NMR spectra of ([D5]anilinium)-([18]crown-6)[Ni(dmit)2]. A double-minimum potential for the molecular rotation of anilinium, with a barrier of approximately 40 kJ mol(-1), was indicated by ab initio calculations. The wide-line 1H NMR spectra indicated a thermally activated rotation of [18]crown-6 at temperatures above 250 K. Therefore, multiple molecular motions of the 180 degree flip-flop motion of the phenyl ring and the rotation of [18]crown-6 occur simultaneously in the solid state. The temperature-dependent dielectric constants revealed that the molecular motion of [18]crown-6, other than the flip-flop motion, dominates the dielectric response in the measured temperature and frequency range.

Multirotations of (anilinium)([18]crown-6) supramolecular cation structure in magnetic salt of [Ni(dmit)2]-.

Adamantylammonium (ADNH3+) was complexed with [18]crown-6, forming a supramolecular cation of (ADNH3+)([18]crown6), which was introduced into a [Ni(dmit)2]- salt as a supramolecular rotor. The cation layers were alternately arranged with [Ni(dmit)2]- layers in the crystal, in which the molecular rotation of (ADNH3+)([18]crown-6) was confirmed from the temperature-dependent solid-state 1H NMR.

Supramolecular Rotor: Adamantylammonium([18]crown-6) in [Ni(dmit)2]- Salt

Supramolecular cations of HOPD+([18]crown-6) and HMPD+([18]crown-6) were introduced into [Ni(dmit)2]− salts (HOPD+: o-aminoanilinium, HMPD+: m-aminoanilinium, and dmit2−: 2-thioxo-1,3-dithiole-4,5-dithiolate). Alternate layers of cations and anions were observed in the two new salts of (HOPD+)([18]crown-6)[Ni(dmit)2]− (1) and (HMPD+)([18]crown-6)[Ni(dmit)2]− (2). From X-ray crystal structural analyses, solid state 1H nuclear magnetic resonance (NMR) spectra, and dielectric constants, the thermal rotations of [18]crown-6 in both of the (HOPD+)([18]crown-6) and (HMPD+)([18]crown-6) supramolecules occurred at temperatures above ∼200 K based on the orientational disorder in the crystal structures. The two-fold flip-flop motions of HOPD+ and HMPD+ cations in salts 1 and 2 were suppressed, due to the relatively large potential energy barriers. The [Ni(dmit)2]− anion formed π-dimer arrangements in both salts, with a layer structure by lateral sulfur–sulfur interatomic contacts. Although the simple dimer model reproduced the magnetic properties of salt 1, the ladder arrangement of the π-dimer in salt 2 yielded the magnetic behavior of a spin-ladder with a spin-gap of 92.5 K. The temperature dependent magnetic susceptibility of salt 2 was well reproduced by the magnetic anisotropy of J1/J2≈ 8 between the ladder-leg (J1: intra-dimer interaction) and ladder-rung (J2: inter-dimer interaction). The [18]crown-6 supramolecular rotator of (HMPD+)([18]crown-6) was coexistent with the spin-ladder chain of [Ni(dmit)2]− anions in salt 2.

Daisuke Sato

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.

Multirotations of (anilinium)([18]crown-6) supramolecular cation structure in magnetic salt of [Ni(dmit)2]-.

Supramolecular Rotor: Adamantylammonium([18]crown-6) in [Ni(dmit)2]- Salt

[18]Crown-6 rotator in spin-ladder compound of m-aminoanilinium([18]crown-6)[Ni(dmit)2]-.