Молекулярные машины: от основ к применению

Molecular scale artificial or biological device

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 (AMM) 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. AMMs have diversified rapidly over the past few decades and their design principles, properties, and characterization methods have been outlined better. A major starting point for the design of AMMs is to exploit the existing modes of motion in molecules, 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 (such as materials research, homogenous catalysis and surface chemistry).

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. Molecular machines differ from other stimuli responsive compounds that can produce motion (such as cis trans isomers) in their relatively larger amplitude of movement (potentially due to chemical reactions) and the presence of a clear external stimulus to regulate the movements (as compared to random thermal motion). 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 (also referred to as "nanomachines"). Biological machines are considered to be nanoscale devices (such as molecular proteins) 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.

Over the past few decades, AMMs have diversified rapidly and their design principles, have been outlined more clearly. A major starting point for the design of AMMs is to exploit the existing modes of motion in molecules. 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 (typically irradiation with a suitable wavelength), 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 (primarily catenanes). While this type of rotation can not be accessed beyond the molecule itself (because the rings are confined within one another), 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. 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 (blue) between two possible binding sites (red) along the dumbbell like rotaxane axis (purple). d) Rotation of interlocked rings (depicted as blue and red rectangles) 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. 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 (such as redox responsive viologens). Eventually, several different forms of energy (electric, magnetic, optical and so on) have become the primary energy sources used to power AMMs, even producing autonomous systems such as light driven motors.

The most complex macromolecular machines are found within cells, often in the form of multi protein complexes. Important examples of biological machines include motor proteins such as myosin, which is responsible for muscle contraction, kinesin, which moves cargo inside cells away from the nucleus along microtubules, and dynein, which moves cargo inside cells towards the nucleus and produces the axonemal beating of motile cilia and flagella. "[I]n effect, the [motile cilium] is a nanomachine composed of perhaps over 600 proteins in molecular complexes, many of which also function independently as nanomachines  Flexible linkers allow the mobile protein domains connected by them to recruit their binding partners and induce long range allostery via protein domain dynamics." Other biological machines are responsible for energy production, for example ATP synthase which harnesses energy from proton gradients across membranes to drive a turbine like motion used to synthesise ATP, the energy currency of a cell. Still other machines are responsible for gene expression, including DNA polymerases for replicating DNA, RNA polymerases for producing mRNA, the spliceosome for removing introns, and the ribosome for synthesising proteins. These machines and their nanoscale dynamics are far more complex than any molecular machines that have yet been artificially constructed. Biological machines have potential applications in nanomedicine. For example, they could be used to identify and destroy cancer cells. Molecular nanotechnology is a speculative subfield of nanotechnology regarding the possibility of engineering molecular assemblers, biological machines which could re order matter at a molecular or atomic scale. Nanomedicine would make use of these nanorobots, introduced into the body, to repair or detect damages and infections, but these are considered to be far beyond current capabilities.

The construction of more complex molecular machines is an active area of theoretical and experimental research. Though a diverse variety of AMMs are known today, experimental studies of these molecules are inhibited by the lack of methods to construct these molecules. In this context, theoretical modeling has emerged as a pivotal tool to understand the self assembly or disassembly processes in these systems. A wide range of applications have been demonstrated for AMMs, including those integrated into polymeric, liquid crystal, and crystalline systems for varied functions. Homogenous catalysis is a prominent example, especially in areas like asymmetric synthesis, utilizing noncovalent interactions and biomimetic allosteric catalysis. AMMs have been pivotal in the design of several stimuli responsive smart materials, such as 2D and 3D self assembled materials and nanoparticle based systems, for versatile applications ranging from 3D printing to drug delivery. AMMs are gradually moving from the conventional solution phase chemistry to surfaces and interfaces. For instance, AMM immobilized surfaces (AMMISs) are a novel class of functional materials consisting of AMMs attached to inorganic surfaces forming features like self assembled monolayers; this gives rise to tunable properties such as fluorescence, aggregation and drug release activity. Most of these applications remain at the proof of concept level, and need major modifications to be adapted to the industrial scale. Challenges in streamlining macroscale applications include autonomous operation, the complexity of the machines, stability in the synthesis of the machines and the working conditions.