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 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

The standard model for photoinduced cis-trans isomerization about carbon double bonds is framed in terms of two electronic states and a one-dimensional reaction coordinate. We review recent work that suggests that a minimal picture of the reaction mechanism requires the consideration of at least two molecular coordinates and three electronic states. In this chapter, we emphasize the role of conical intersections and charge transfer in the photoisomerization mechanism.

Isomerization through conical intersections.

Digital information processing in molecular systems.

In der Natur spielen gesteuerte Bewegungen auf molekularer Ebene bei vielen Prozessen eine Schlusselrolle. Das Schliesen der Lucke zwischen der aktuellen Generation synthetischer Verbindungen, bei denen hauptsachlich elektronische und chemische Effekte genutzt werden, und makroskopischen Maschinen, deren Funktionsfahigkeit auf der synchronisierten Bewegung von Maschinenteilen beruht, ware ein groser Erfolg. Dieses Forschungsgebiet wird derzeit intensiv bearbeitet und wachst auserordentlich schnell. Die ersten Uberlegungen zu molekularen Maschinen reichen allerdings weiter zuruck in die Vergangenheit, in eine Zeit, in der die Konzepte vom statistischen Verhalten der Materie und die Gesetze der Thermodynamik formuliert wurden. Wir umreisen hier die Erfolgsgeschichte der Bandigung molekularer Bewegungen, der Beherrschung der grundlegenden Prinzipien, an denen sich das Design zu orientieren hat, und der Fortschritte bei der Anwendung synthetischer Systeme, die durch mechanische Bewegung Aufgaben verrichten konnen. Ferner werden wir auf einige ungeloste Probleme eingehen.

Synthetische molekulare Motoren und mechanische Maschinen

The promise of new architectures and more cost-effective miniaturization has prompted interest in molecular and biomolecular electronics. Bioelectronics offers valuable near-term potential, because evolution and natural selection have optimized many biological molecules to perform tasks that are required for device applications. The light-transducing protein bacteriorhodopsin provides not only an efficient photonic material, but also a versatile template for device creation and optimization via both chemical modification and genetic engineering. We examine here the use of this protein as the active component in holographic associative memories as well as branched-photocycle three-dimensional optical memories. The associative memory is based on a Fourier transform optical loop and utilizes the real-time holographic properties of the protein thin films. The three-dimensional memory utilizes an unusual branching reaction that creates a long-lived photoproduct. By using a sequential multiphoton process, paral...

Biomolecular Electronics: Protein-Based Associative Processors and Volumetric Memories

Optimization of bacteriorhodopsin for bioelectronic devices.

Volumetric optical memory based on bacteriorhodopsin

The resolution of scanning surface potential microscopy (SSPM) is mainly limited by non-local electrostatic interactions due to the finite probe size. Here we present high resolution surface potential imaging with ultrasharp and high aspect ratio carbon nanotube (CNT) atomic force microscopy (AFM) probes fabricated via dielectrophoresis. Enhancement of surface potential contrast by several factors is reported for integrated circuit structures and purple membrane fragments for these CNT AFM probes as compared to conventional probes. In particular, ultrahigh lateral resolution (∼2 nm) surface potential images of self-assembled bacteriorhodopsin proteins are reported at ambient conditions, with the implication of label-free protein detection by SSPM techniques.

https://iopscience.iop.org/article/10.1088/0957-4484/19/23/235704/pdf

Ultrasharp and high aspect ratio carbon nanotube atomic force microscopy probes for enhanced surface potential imaging.

The nature of the chromophore binding site of light-adapted bacteriorhodopsin is analyzed by using all-valence electron MNDO and MNDO-PSDCI molecular orbital theory to interpret previously reported linear and nonlinear optical spectroscopic measurements. A total of 45 binding site models are investigated. The binding site is simulated by including the chromophore, the lysine residue (LYS216), the following nearby amino acids (ARG82, ASP85, ASP115, ASP212, THR90, TRP86, TRP138, TRP182, TYR57, TYR83, and TYR185) and zero, one, or two divalent cations. We conclude that the unique two-photon properties of the chromophore are due in part to the electrostatic field associated with a Ca2+ ion near to the chromophore. Four amino acids and three water molecules contribute significantly to the assigned chromophore adjacent calcium binding site (ASP85, ASP212, TYR57 and TYR185), and two conformational minima are predicted. The higher energy conformation has the calcium ion stabilized primarily by ASP85 and the chromophore imine proton by ASP212. The lower energy conformation has the calcium ion stabilized primarily by ASP212 and the imine proton by ASP85. The latter configuration is more stable due to strong hydrogen bonding between TYR185 and ASP212 coupled with electrostatic stabilization of the divalent cation by TYR57. Although both tyrosine residues are predicted to exhibit some “unprotonated” character, models involving full deprotonation of either TYR57 or TYR185 do not fit the spectroscopic data. We conclude that the cation binding site identified in this study is the second high affinity binding site for calcium, and that the chromophore binding site is, to a first approximation, positively charged. The chromophore “1B” and “1A” states, despite extensive mixing, exhibit significantly different configurational character. The lowest-lying “1B” state is dominated by single excitations (> 80% for all models studied) whereas the second-excited “1A” state is dominated by double excitations (> 70% for all models studied with extensive participation by spin-coupled triplet-triplet excitations). © 1995 John Wiley & Sons, Inc.

Jeffrey A. Stuart

Papers

Biomolecular Electronics: Protein-Based Associative Processors and Volumetric Memories

Optimization of bacteriorhodopsin for bioelectronic devices.

Volumetric optical memory based on bacteriorhodopsin

Ultrasharp and high aspect ratio carbon nanotube atomic force microscopy probes for enhanced surface potential imaging.

The active site of bacteriorhodopsin. Two‐photon spectroscopic evidence for a positively charged chromophore binding site mediated by calcium