Molecular machine
Molecular machines are a class of molecules typically described as an assembly of a discrete number of molecular components intended to produce mechanical movements in response to specific stimuli, mimicking macromolecular devices such as switches and motors. Naturally occurring or biological molecular machines are responsible for vital living processes such as DNA replication and ATP synthesis. Kinesins and ribosomes are examples of molecular machines, and they often take the form of multi-protein complexes. For the last several decades, scientists have attempted, with varying degrees of success, to miniaturize machines found in the macroscopic world.
The first example of an artificial molecular machine was reported in 1994, featuring a rotaxane with a ring and two different possible binding sites. In 2016 the Nobel Prize in Chemistry was awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart, and Bernard L. Feringa for the design and synthesis of molecular machines. A major point is to exploit existing motion in proteins, such as rotation about single bonds or cis-trans isomerization. Different AMMs are produced by introducing various functionalities, such as the introduction of bistability to create switches. A broad range of AMMs has been designed, featuring different properties and applications; some of these include molecular motors, switches, and logic gates. A wide range of applications have been demonstrated for AMMs, including those integrated into polymeric, liquid crystal, and crystalline systems for varied functions.
Terminology
Several definitions describe a "molecular machine" as a class of molecules typically described as an assembly of a discrete number of molecular components intended to produce mechanical movements in response to specific stimuli. The expression is often more generally applied to molecules that simply mimic functions that occur at the macroscopic level. A few prime requirements for a molecule to be considered a "molecular machine" are: the presence of moving parts, the ability to consume energy, and the ability to perform a task. Molecular machines differ from other stimuli-responsive compounds that can produce motion in their relatively larger amplitude of movement and the presence of a clear external stimulus to regulate the movements. Piezoelectric, magnetostrictive, and other materials that produce a movement due to external stimuli on a macro-scale are generally not included, since despite the molecular origin of the motion the effects are not useable on the molecular scale.This definition generally applies to synthetic molecular machines, which have historically gained inspiration from the naturally occurring biological molecular machines. Biological machines are considered to be nanoscale devices in a living system that convert various forms of energy to mechanical work in order to drive crucial biological processes such as intracellular transport, muscle contractions, ATP generation and cell division.
History
Biological molecular machines have been known and studied for decades given their vital role in sustaining life, and have served as inspiration for synthetically designed systems with similar useful functionality. The advent of conformational analysis, or the study of conformers to analyze complex chemical structures, in the 1950s gave rise to the idea of understanding and controlling relative motion within molecular components for further applications. This led to the design of "proto-molecular machines" featuring conformational changes such as cog-wheeling of the aromatic rings in triptycenes. By 1980, scientists could achieve desired conformations using external stimuli and utilize this for different applications. A major example is the design of a photoresponsive crown ether containing an azobenzene unit, which could switch between cis and trans isomers on exposure to light and hence tune the cation-binding properties of the ether. In his seminal 1959 lecture There's Plenty of Room at the Bottom, Richard Feynman alluded to the idea and applications of molecular devices designed artificially by manipulating matter at the atomic level. This was further substantiated by Eric Drexler during the 1970s, who developed ideas based on molecular nanotechnology such as nanoscale "assemblers", though their feasibility was disputed.File:Molecular shuttle first report.png|thumb|center|upright=3.0|alt=The first example of an artificial molecular machine. The positively charged ring is initially positioned over the benzidine unit, but shifts to the biphenol unit when the benzidine gets protonated as a result of electrochemical oxidation or lowering of the pH.|The first example of an artificial molecular machine. The positively charged ring is initially positioned over the benzidine unit, but shifts to the biphenol unit when the benzidine gets protonated as a result of electrochemical oxidation or lowering of the pH.
Though these events served as inspiration for the field, the actual breakthrough in practical approaches to synthesize artificial molecular machines took place in 1991 with the invention of a "molecular shuttle" by Sir Fraser Stoddart. Building upon the assembly of mechanically linked molecules such as catenanes and rotaxanes as developed by Jean-Pierre Sauvage in the early 1980s, this shuttle features a rotaxane with a ring that can move across an "axle" between two ends or possible binding sites. This design realized the well-defined motion of a molecular unit across the length of the molecule for the first time. In 1994, an improved design allowed control over the motion of the ring by pH variation or electrochemical methods, making it the first example of an AMM. Here the two binding sites are a benzidine and a biphenol unit; the cationic ring typically prefers staying over the benzidine ring, but moves over to the biphenol group when the benzidine gets protonated at low pH or if it gets electrochemically oxidized. In 1998, a study could capture the rotary motion of a decacyclene molecule on a copper-base metallic surface using a scanning tunneling microscope. Over the following decade, a broad variety of AMMs responding to various stimuli were invented for different applications. In 2016, the Nobel Prize in Chemistry was awarded to Sauvage, Stoddart, and Bernard L. Feringa for the design and synthesis of molecular machines.
Artificial molecular machines
Over the past few decades, AMMs have diversified rapidly and their design principles, properties, and characterization methods have been outlined more clearly. A major starting point for the design of AMMs is to exploit the existing modes of motion in molecules. For instance, single bonds can be visualized as axes of rotation, as can be metallocene complexes. Bending or V-like shapes can be achieved by incorporating double bonds, that can undergo cis-trans isomerization in response to certain stimuli, as seen in numerous designs consisting of stilbene and azobenzene units. Similarly, ring-opening and -closing reactions such as those seen for spiropyran and diarylethene can also produce curved shapes. Another common mode of movement is the circumrotation of rings relative to one another as observed in mechanically interlocked molecules. While this type of rotation can not be accessed beyond the molecule itself, rotaxanes can overcome this as the rings can undergo translational movements along a dumbbell-like axis. Another line of AMMs consists of biomolecules such as DNA and proteins as part of their design, making use of phenomena like protein folding and unfolding.File:Molecular machine principle 1.png|thumb|center|upright=2.0|alt=Some common types of motion seen in some simple components of artificial molecular machines. a) Rotation around single bonds and in sandwich-like metallocenes. b) Bending due to cis-trans isomerization. c) Translational motion of a ring along the dumbbell-like rotaxane axis. d) Rotation of interlocked rings in a catenane|Some common types of motion seen in some simple components of artificial molecular machines. a) Rotation around single bonds and in sandwich-like metallocenes. b) Bending due to cis-trans isomerization. c) Translational motion of a ring between two possible binding sites along the dumbbell-like rotaxane axis Rotation of interlocked rings in a catenane.
AMM designs have diversified significantly since the early days of the field. A major route is the introduction of bistability to produce molecular switches, featuring two distinct configurations for the molecule to convert between. This has been perceived as a step forward from the original molecular shuttle which consisted of two identical sites for the ring to move between without any preference, in a manner analogous to the ring flip in an unsubstituted cyclohexane. If these two sites are different from each other in terms of features like electron density, this can give rise to weak or strong recognition sites as in biological systems — such AMMs have found applications in catalysis and drug delivery. This switching behavior has been further optimized to acquire useful work that gets lost when a typical switch returns to its original state.
Inspired by the use of kinetic control to produce work in natural processes, molecular motors are designed to have a continuous energy influx to keep them away from equilibrium to deliver work.
Various energy sources are employed to drive molecular machines today, but this was not the case during the early years of AMM development. Though the movements in AMMs were regulated relative to the random thermal motion generally seen in molecules, they could not be controlled or manipulated as desired. This led to the addition of stimuli-responsive moieties in AMM design, so that externally applied non-thermal sources of energy could drive molecular motion and hence allow control over the properties. Chemical energy was an attractive option at the beginning, given the broad array of reversible chemical reactions to switch molecules between different states. However, this comes with the issue of practically regulating the delivery of the chemical fuel and the removal of waste generated to maintain the efficiency of the machine as in biological systems. Though some AMMs have found ways to circumvent this, more recently waste-free reactions such based on electron transfers or isomerization have gained attention. Eventually, several different forms of energy have become the primary energy sources used to power AMMs, even producing autonomous systems such as light-driven motors.