The Nature of the Mechanical Bond
761 pages defining a field, with a Nobel laureate.
A mechanical bond is not shared between atoms. It arises when molecular entities become entangled in space, so that they cannot be separated without breaking a chemical bond. Catenanes are rings threaded through rings; rotaxanes are rings trapped on an axle by stoppers too large to pass. Neither is held together by anything an atom would recognize as a bond, and both behave like molecules anyway.
The book is a comprehensive account of that idea: how to make mechanical bonds under kinetic and thermodynamic control, the topologies and architectures they permit, the strange new stereochemistry they create, and the switches and machines they make possible. It runs to 761 pages, more than 800 figures, schemes and tables, and citations to about 3,400 papers.
I wrote it with Fraser Stoddart, who received the Nobel Prize in Chemistry the year it appeared.
1. An Introduction to the Mechanical Bond
Mechanical bonds are omnipresent and all pervasive. They occupy every nook and cranny of human experience in both static and dynamic settings that range from being close to infinitesimally small to those which can be described as large by comparison. In the domain of the molecular world, the mechanical bond emerges as an additional expression of the nature of the chemical bond in all its manifestations. This emergent phenomenon takes place in the lower reaches of the nanometer length scale as a special architectural feature. It emerges just as soon as it becomes spatially possible to entangle the component parts of molecules, the sizes of which are governed in part by the subnanometer distances between their constituent atoms.
The production of chemical compounds composed of mechanically interlocked molecules (MIMs) by acts of templation, be they passive or active in their origins, are hand-me-downs from the science of (supramolecular) chemistry beyond the molecule, which affords molecular recognition free rein to exercise its special powers of organization in marshaling the component parts of the MIMs prior to their being transported back into the molecular world by the formation of chemical bonds. This relatively recent extension of bonding in molecules opens the door on a yet little explored field of chemistry – namely that of chemical topology, which leads to the concept of topological isomerism, where two or more molecular ensembles may contain the same atoms and chemical bonds, yet cannot be interconverted by any deformations that do not involve the breaking and making of chemical bonds.
Intersecting the fields of supramolecular chemistry and chemical topology is the discipline of mechanostereochemistry. Just as stereochemistry is the study of the relative spatial arrangements of atoms in molecules, mechanostereochemistry is the stereochemistry of molecules with mechanical bonds. Catenanes and rotaxanes are a subset of MIMs that possess mechanical bonds. A catenane is a molecule with two or more interlocking ring-shaped component parts. The simplest of catenanes with two interlocked rings is a topological isomer of the two rings separated from each other. A rotaxane comprises (a) ring(s) threaded by (a) dumbbell(s) possessing stoppers that are too bulky for the ring(s) to transgress. The simplest of the rotaxanes with one ring and one dumbbell is not a topological isomer of the ring and dumbbell separated from one another since expansion of the ring or compression of the stoppers (without the breaking of chemical bonds) can lead to the separation of the component parts by a process known as slippage.
A mechanical bond is an entanglement in space between two or more component parts, such that they cannot be separated without breaking or distorting chemical bonds between atoms. It follows that a mechanical bond is as strong as the weakest participating chemical bond. Hence, catenanes and rotaxanes are most appropriately described as molecules, or more precisely, as mechanomolecules. Since entanglements are possible in molecules – for example, knots – that lack component parts, not all MIMs possess mechanical bonds. While catenanes and knots fall under the aegis of chemical topology, rotaxanes are considered to be topologically trivial because their component parts may be separated by the continuous deformation of chemical bonds. It is this dichotomy that exists between catenanes and knots on the one hand and rotaxanes on the other that has led to the adoption of the term mechanical bond when describing catenanes and rotaxanes in preference to topological bonds, which are present in catenanes and knots, but not in rotaxanes. One of the endearing charms of chemistry is that it defies repeatedly attempts at clear-cut descriptions of phenomena under its guard. In this particular instance, the much higher promise of wider applicability on the part of rotaxanes makes the case for promoting the chemistry of the mechanical bond.
Although the mechanical bond has been exploited and revered in society, art and Nature from time immemorial, it has proved to be immensely challenging to introduce synthetically into molecules and hence chemistry. Nothing of much significance had been recorded in the scientific literature up until the 1960s. This decade and the succeeding one witnessed simultaneously the advent of a painstaking classical approach, under the guidance of covalent-directed synthesis alongside statistical forays based on little more than the chance events of the threading of large-sized rings by suitably long molecular chains. With the emergence of host-guest and supramolecular chemistry in the 1970s, however, the stage was set for molecular recognition to lead to the directed synthesis of mechanomolecules through the acts of templation with coordinative, followed by noncovalent, bonds of many different persuasions. The result has been an exponential growth these past 35 years in molecular nanotechnology, coupled to a paradigm shift in molecular structure and function. While mechanomolecules have found their way, both singly and collectively, into switches and motors, the molecules themselves have led to a renaissance in molecular aesthetics. Introducing mechanical bonds into molecules can only assist in garnering support for the growing initiative to widen aesthetic considerations in chemistry.
2. The Fundamentals of Making Mechanical Bonds
The advent of the mechanical bond has played a major role in orchestrating the dramatic growth in unnatural product synthesis during the past quarter of a century. Inventing strategies to make mechanically interlocked molecules (MIMs), such as rotaxanes and catenanes, has sparked the fertile imaginations, instigated the flow of creative juices, and challenged the practical ingenuity of synthetic chemists across the length and breadth of the discipline, uniting disparate factions in its wake. From strategizing to implementing synthetic protocols, making mechanical bonds relies heavily on synthetic chemists having, not only a command of the nature of the chemical bond in all its intricate manifestations, but also a fundamental knowledge and in-depth appreciation of molecular recognition as it is expressed at the levels of coordinative, noncovalent and electrostatic bonding. In essence, the mechanical bond has led to the redefining of chemical synthesis in its broadest sense.
While rotaxanes and catenanes are molecules, a common precursor is often a pseudorotaxane, that is essentially a complex in which, for example, a large-ring molecule, containing at least 20 atoms, and generally considerably more, is penetrated by a threadlike molecule. In the beginning, rotaxanes were obtained from pseudorotaxanes by a threading-followed-by-stoppering strategy or from a preformed dumbbell-shaped molecule by a ring-clipping approach. Subsequently, other approaches involving slippage of a ring onto a dumbbell or the swelling of stoppers or the shrinking of rings have been devised for the making of rotaxanes. Historically, the main focus was on the making of catenanes using a threading-followed-by-clipping strategy from preformed large-ring molecules. Subsequently, ring-capture and dumbbell-capture procedures have been invented to make catenanes and rotaxanes, respectively. The earliest of all approaches to the making of MIMs relied on (i) a statistical threading of rings by long linear molecules and (ii) a directed synthesis approach which relies on the formation of covalent bonds between rings and dumbbells that are cleaved subsequently following multiple (>20) reaction steps to afford component parts with little more than van der Waals interactions at best between the parts. The initial synthetic protocols, leading to the first generation of MIMs, were conducted under kinetic control for the most part and some were discovered serendipitously while others, such as the Möbius strip approach, await implementation.
In mechanostereochemistry, a template is an ion, a molecule or a radical that acts as a recognition platform for the assembly of another ion, molecule or radical such that both the original template and the assembled entity become the component parts of a MIM during transformations where ‘old’ molecules ‘disappear’ and ‘new’ molecules ‘appear.’ It was the rise of chemistry beyond the molecule – supramolecular chemistry – joining forces with molecular recognition and templation that transported MIMs from being esoteric curiosities to becoming one of the contemporary drivers of molecular nanotechnology and the nascent discipline of chemical topology. Aside from (i) the statistical threading and (ii) directed synthetic approaches, in addition to (iii) a much more recent and promising active template strategy for MIM production, by far the most successful methodology to date has been template-directed synthesis, which has evolved in a manner where usually one source of molecular recognition is dominant, yet never does that source act alone, more often it is in combination with other recognition motifs. A growing number of templates have lent their support to the making of MIMs, starting in the 1980s, while gaining momentum in the 1990s through into the 21st century. The frequency with which the range of templates have been used, as reflected by the number of reports relating to them in the literature, lends itself to the following identification of the top 10 recognition motifs – (i) solvophobic/hydrophobic, (ii) hydrogen-bonding, (iii) donor-acceptor, (iv) metallo-organic, (v) biomolecular, (vi) macrocyclic (hetero)arenes, (vii) anionic, (viii) radical pair, (ix) ion-pair and (x) alkali-metal ion. Hydrophobic templation is dominated by cyclodextrins, followed by cucurbiturils, while hydrogen-bonding comes with both neutral and charged variations. Donor-acceptor templates generally involve the stacking of aromatic rings, yet π–π interactions are usually foreshadowed energy-wise by the additional presence of stabilizing C–H⋅⋅⋅O hydrogen bonds. Metallo-organic templates, i.e., linear, square, tetrahedral, trigonal bipyramidal and octahedral, introduce rigidity and are ideal for defining geometries. A popular means of covalent capture, such as in the final steps of producing catenanes and rotaxanes in excellent yields with high atom efficiencies, is the use of the ubiquitous copper(I)-catalyzed azido-alkyne cycloaddition, also known as the click reaction. Employing this reaction, along with many other kinetically controlled reactions, has populated chemical laboratories with an enormously wide variety of MIMs, some of which can be easily rendered bistable so that, by appealing to acid-base or redox chemistry, molecular switches emerge as prototypes for the design and synthesis of artificial molecular machines. It could be argued that the mechanical bond has given unnatural product synthesis a new lease of life: much has been achieved in a short period of time, yet much remains to be accomplished by creative makers of molecules and materials.
3. Making Mechanical Bonds Under Thermodynamic Control
Making mechanical bonds employing concepts and protocols where finely balanced and environmentally sensitive equilibria in solution or in melts are in the order of minutes or hours or days or weeks or even months and patience is a virtue, has opened doors to the production of mechanically interlocked molecules (MIMs) that have so far remained out of reach using more conventional ‘billiard-ball’ chemistry—that is, the time-honored approach to chemical synthesis where, given reactant substrate molecules, ions or radicals, there is no going back: the desired products and undesired byproducts are what they are when the reaction is terminated. Replacing ‘one-way’ reactions under kinetic control with ‘two-way’, and ultimately ‘multiple-way’, processes under thermodynamic control not only engenders the need for out-of-the-box retrosynthetic analysis but it also calls for a mindset change on the part of synthetic chemists purveying their practice in the laboratory.
The concept of slippage offers a unique opportunity to synthesize rotaxanes without making or breaking any strong covalent or coordinative bonds and with one hundred percent atom efficiency: it can be looked upon as a physical synthesis as opposed to a chemical one. The conceptual framework wherein slippage lies relates to the logic of fuzzy sets that define the relationship between pseudorotaxanes (complexes) and rotaxanes (molecules). There is no fine dividing line between pseudorotaxanes and rotaxanes, where the former may be regarded (i) as being high in rotaxane character if its component parts exhibit slow exchange kinetics and high association constants and (ii) as being low in rotaxane character if it associates more weakly and exchanges more rapidly. Slippage is a manifestation of rotaxanes not sharing topological links along with their mechanical bonds and therefore being able to overcome either steric or electrostatic barriers that discourage them from dissociating. Since both slippage and deslipping are highly condition-dependent, with solvent and temperature playing decisive roles, finding stereoelectronic matches between stoppers—both neutral and charged—in addition to controlling the templation arising from molecular recognition between the dumbbells and the rings that is dictated by noncovalent bonding interactions, that are (i) hydrophobic, (ii) hydrogen-bonded, (iii) donor-acceptor, (iv) radical etc. in nature, is a chance event. If only computational chemistry could make the leap from providing rationalizations after the chance event to being predictive ahead of the practice, then the synthetic utility of slippage would be enhanced beyond being simply a hit or miss activity in the laboratory. The importance of gaining a good fundamental understanding of slippage and deslipping is taking on more urgency as the design and synthesis of molecular machines that work away from equilibrium gathers momentum.
Although kinetically controlled reactions account for the lion’s share of the production of chemical compounds, there are a relatively small, yet significant, number of reactions that proceed under thermodynamic control which means that at the same time as chemical bonds—covalent and coordinative ones for the most part—are being made, they are also being broken. This brand of chemistry in which combinatorial libraries of molecules are engaged in dynamic equilibrium processes involving reversible reactions is often referred to as dynamic covalent chemistry or DCC for short. Not only is the time it takes for reactions to reach equilibrium dependent on conditions such as solvent, temperature and concentration, but also the outcome of the reactions with special reference to the product composition can be swayed by the presence of templates and other additives. It is also not uncommon to be able to isolate products that are trapped in kinetic energy wells. The ability to be able to control the free energy landscape means that the thermodynamic parameters can often be amplified by the presence of a template or simply by a subtle change in solvent composition. Such was the case during the application of DCC to the synthesis of the first wholly synthetic molecular Borromean rings (BRs)—three rings linked in such a manner that should one be cleaved, the other two rings will fall apart. When the BR crystallization solvents were changed from methanol / diethyl ether to a 3:1 mixture of n-propyl ether and methanol / diethyl ether, a Solomon link, or doubly interlocked [2]catenane, crystallizes as a racemic mixture of topological enantiomers. A similar outcome can be achieved when the metal templates constitute a 1:1 mixture of zinc(II) and copper(II), whereas either metal template on its own affords only the Borromean rings! Aside from these two transition metal ions, (i) metal-ligand pairs that are kinetically labile under mild conditions, yet thermodynamically stable, have embraced much of the Periodic Table in the pursuit of MIMs, while the (ii) condensation and exchange of (coordinative) imine, hydrazone, and boronic ester bonds, along with (iii) the range of thermodynamically controllable olefin metathesis under the spell of the right catalysts, (iv) the redox reversibility associated with disulfide bond formation and cleavage, (v) reversible nucleophilic substitutions and additions, and (vi) reversible surface bonds, especially those involving the formation of self-assembled monolayers on gold, have all occupied pride of place in the promotion of DCC when it comes to producing MIMs with the greatest of ease. So far, a relatively small collection of reactions that are subject to equilibrium control has provided ready access to mechanically interlocked architectures and topologies, some of which can only be described as exotic in the extreme.
4. Molecular Topologies and Architectures with Mechanical Bonds
Classically, the structure of a chemical compound can be described by three C’s—its constitution, its configuration (relative and absolute), and its conformation. Introducing knotted and interlocked rings into the molecular potpourri leaves us confronted with also having to consider a molecule’s topology, whilst recognizing that the three C’s are obliged to come under serious scrutiny—given their classical roots and definitions—so much so that we find it convenient to advocate the use of the qualified descriptors—namely, co-constitution, co-configuration and co-conformation—to define the structures of mechanomolecules. In the realm of chemical topology, rotaxanes are positioned poles apart from catenanes—a dichotomy which has led us to refer in this Chapter to a catenane’s topology and a rotaxane’s architecture and, moreover, it is why this book as a whole cannot be an account of the nature of the topological bond, yet it can, catenanes willing, be a story about the nature of the mechanical bond.
Catenane topologies, be they based on prime links or composite ones, wherein mechanically interlocked rings displayed in linear, branched and radial (molecular necklaces) fashions, have been very much at the forefront—and ahead of rotaxanes at the outset—of the agendas of synthetic chemists targeting intellectually challenging unnatural products. Despite much effort and commitment, however, this community has still to uncover high molecular weight polycatenanes that can be produced on a commercial scale at the drop of a hat. They are a ‘holy grail’ in the field since there is every reason to believe that polycatenanes, with appropriate co-constitutions, will display unique thermal and viscoelastic properties, making them much sought after as plasticizers in everything from concrete to rocket fuel.
As time has progressed, catenanes have assumed ever more complex multi-annulated co-constitutions incorporating macrobi-, -tri-, -tetra-, and -pentacyclic component parts, not to mention covalently bridged ones known as pseudocatenanes. Hopf links have also intruded into the mesomolecular domain with cyclic oligo[2]catenanes, and main-chain / side-chain poly[2]catenanes. Lurking inside all this impressive array of complex co-constitutions are thousands of conventional polymer networks that become entangled in the solid state. These entangled networks emerge more commonly from the multi-annulated structures associated with cages and two- or three-dimensional polymer nets. Interpenetrated and polycatenated networks pervade the realm of coordination polymers, also known as metal-organic frameworks (MOFs) where more often than not the solid-state (super)structures tell us that the crystal is the (super)molecule and the (super)molecule is the crystal.
The sky is the limit when rotaxane architectures are brought into the picture. Simply limiting the component parts to dumbbells and rings alone opens up architectures involving (i) one dumbbell and many rings, (ii) one ring with many dumbbells (molecular sheafs), (iii) many rings and many dumbbells. While architectures finding their niche in categories (ii) and (iii) are not yet commonplace, coming out of category (i), main chain [n]rotaxane polymers are not only ubiquitous, they are also abundant. In particular, the promiscuous manner in which cyclodextrins (CDs) thread in aqueous solutions onto polymers—be they poly-ethers, -esters, -amides, -olefins, etc.—has been taken to the extremes for good reason. For example, the fact that CDs threaded onto π-conjugated polymers enhances their optical, electrical and luminescent properties drives research along in the direction of providing new electroluminescent display technologies, including light-emitting diodes (LEDs). Cucurbituril (CB) threaded polymers have commonly surfaced following either crystal growth of rotaxanated coordination polymers or from cucurbit[6]uril-promoted azide-alkyne cycloadditions (CB6AAC) where the introduction of CDs can lead to spectacular yields of high molecular weight polyrotaxanes by what has been dubbed cooperative capture synthesis. The hydrogen bonding between the CB and CD rings acts orthogonally and in concert with solvophobic templation to orchestrate high atom-efficient polymerizations. The theme of “the bigger, the better” when it comes to [n]rotaxanes carries over to the making of oligorotaxanes under thermodynamic control where strong hydrogen bonding conspires with stabilizing π–π interactions exercising positive cooperativity to produce disctrete mechanomolecules as large as a [20]rotaxane with dynamic covalent chemistry playing a helping hand with awesome aplomb. Not to be outdone, donor-acceptor templation between donating threads and accepting rings can produce foldamers, demonstrating that the mechanical bond can be deployed as a tool to install well-defined secondary structures into macromolecules.
Rotaxane architectures stretch far and wide embracing within their remit (Type 1) dendrimers with rotaxane cores, (Type II) dendrimers with (pseudo)rotaxane termini, and (Type III) dendrimers with rotaxane branches, not to mention covalently bridged rotaxanes, including [1]rotaxane (the molecular ouroboros), daisy chains, ladder rotaxanes, Bonnanes, handcuff rotaxanes, molecular bundles, slide-ring gels, rotacatenanes, ring-in-ring mechanomolecules, suitanes etc., etc., etc. The list will continue to grow at a rate of knots!
5. The Stereochemistry of the Mechanical Bond
In his monograph entitled “An Introduction to Stereochemistry” published in 1965, Kurt Mislow comments that “Stereochemistry is an old science (Louis Pasteur was its first practitioner) and terminology has not kept pace with the development of substantive matter.” In his treatment of this evolutionary science emphasizing the fundamentals of structural stereochemistry, new terminology and images were introduced quite freely. Half a century later a similar situation prevails. With the advent of the mechanical bond, there is a present and prescient need to invent precise language to describe the rapidly emerging aspects of mechanostereochemistry.
The conceptual basis for mechanostereochemistry – both static and dynamic – can be appreciated most readily by drawing analogies with the stereochemistry of compounds whose molecules possess only covalent bonds – for example, cyclohexane and its (monosubstituted) derivatives. Since compounds such as catenanes and rotaxanes contain mechanically interlocked entities, it is convenient to call these entities component parts. Thus, if stereoisomers are isomers possessing identical constitutions which differ in the arrangement of their atoms in space, then mechanostereoisomers are simply isomers that possess identical mechanically interlocked component parts but which differ in the arrangement of these parts in space. In common with the existence of static and dynamic stereoisomerism in covalent chemistry, we can contemplate both static and dynamic mechanostereoismerism, which recognizes the three-dimensional nature of the mechanical bond. As more often is the case than not in chemistry, the boundaries between static and dynamic mechanostereochemistry are not at all clearly defined. There are dynamic processes where interconversion occurs between different ‘static’ mechanostereoisomers and there are potentially ‘dynamic’ mechanostereoisomers that are prevented from undergoing isomerization by insurmountable energy barriers.
Whereas molecular structure can be defined at the level of a molecule’s constitution, configuration and conformation, when considering mechanomolecules, multiple molecular entities encompass the structural domain. They can be easily understood and explained by adding the prefix ‘co-‘ to denote co-constitution, co-configuration and co-conformation. While co-constitution and co-configuration describe the constitution and chirality, respectively, of a mechanomolecule, co-conformation describes the relative positions of the component parts affording spatial distinction between mechanostereoisomers, which can be interconverted by intramolecular movements involving translation, pirouetting, circumrotation and/or rocking under the jurisdiction of the mechanical bond. These intramolecular movements are generally characterized by very much larger amplitudes than are feasible under the constraints of the covalent bond: for example, a substituent X located on the chair conformation of a cyclohexane ring undergoing interconversion between an equatorial and an axial orientation. It is these relatively large amplitude motions between the component parts in non-degenerate bistable catenanes and, in particular, rotaxanes, which can be switched and actuated chemically, electrochemically and photochemically, that provide a fruitful platform for the furtherance of molecular nanotechnology.
The realm of static mechanostereochemistry is bristling with opportunities for stereochemically astute and enquiring minds. Molecules containing mechanical bonds and entanglements open up a veritable Pandora’s box for stereoisomerism as it relates to differences in (i) sequences and (ii) orientations of component parts in mechanically interlocked molecules, as well as (iii) the infinite possibilities for chirality to be expressed mechanically in planar, axial, helical and topological contexts. The fact that, for example, catenanes, knots, and extended networks occupy an exclusive domain between chemical topology and mechanostereochemistry has given rise to the discipline of topological stereochemistry from which mechanically interlocked molecules such as rotaxanes are excluded. Topological stereoisomers are molecules that are both homeomorphic and non-isotopic. When chirality is introduced into topological stereochemistry it transpires that molecules can display either enantiomerism or diastereoisomerism in both an unconditional and conditional sense. For example, while a doubly interlocked [2]catenane (Solomon knot) and a trefoil knot are unconditionally chiral, molecular Borromean rings and Hopf link [2]catenanes are conditionally chiral when their rings are constitutionally cyclodirectional.
Chemical topology and mechanostereochemistry can be regarded as emergent stereochemical concepts arising from a combination of the topological and Euclidean stereochemistry of covalently bonded component parts that share mechanical bonds. These emergent concepts constitute one of the most intellectually challenging and unprecedented lines of fundamental research in contemporary stereochemistry.
6. Molecular Switches and Machines with Mechanical Bonds
Mechanically interlocked molecules (MIMs) which contain two or more different recognition sites in the shape of noncovalent bonds between their component parts provide the perfect prototypes for the design and synthesis of molecular switches and machines. In some of the best known examples, namely bistable catenanes and rotaxanes, it is convenient to identify a ground state co-conformation (GSCC) and a higher energy metastable state co-conformation (MSCC) where the GSCC:MSCC ratio at room temperature in solution is ideally for most purposes in the range of at least 10:1. Many different ways can then be sought to perturb temporarily this equilibrium by applying, usually to the recognition site associated with the GSCC, stimuli which are routinely provided (i) physically by (a) light – including photoinduced electron transfer (PET) processes, (b) heat (e.g., noncovalent bond interactions which stabilize the GSCC of a polyrotaxane, for example, and are enthalpically favorable at low temperatures whereas increased ring mobility becomes entropically favorable with rising temperatures), (c) pressure, (d) solvent polarity, etc., (ii) chemically by (a) using acid/base (pH changes), often in order to influence hydrogen bonding, (b) employing reductants and oxidants to change redox states which control donor-acceptor and radical-radical interactions, (c) altering coordination numbers and geometries between ligands and transition metal ions, (d) probing competitive recognition processes triggered by cations, anions and small molecules, including allosteric effects, (e) promoting photoisomerizations (e.g., between cis and trans configurations of double bonds) and photoreactions, etc., and (iii) electrochemically by controlling interactions all the way from electrostatic and hydrogen bonding to π–π stacking and hydrophobic bonding in aqueous solutions. Different classes of mechanically interlocked molecular switches operate at very different speeds, e.g., donor-acceptor based switches are a lot slower than benzylic amide based ones, for example, while different ligands associated with transition metal cations control kinetics that span several orders of magnitude. In addition, molecular switches based on bistable MIMs continue to perform in condensed phases with very similar thermodynamic characteristics, although their performance is invariably dampened considerably when it comes to their rate of relaxation from the MSCC back to the GSCC.
While artificial molecular switches based on bistable MIMs have been well-explored and have found applications in the fabrication of nanoelectromechanical systems capable of storing memory and momentum, as well as in executing logic and truth statements, artificial molecular machines which perform work on their surroundings are few and far between. Aside from their performing work, designing and developing machines requires that they circumvent microscopic reversibility (the principle that the mechanism of a reversible process in the forward direction is exactly the reverse of that in the backward direction) either by means of non-reciprocating cycles where the forward and backward pathways are different, and/or by a motion constrained by a mechanical bond that is biased in a particular direction—call it mechanostereoselective motion. Molecular machines employ ratchet mechanisms: in an information ratchet, the position of a microscopic entity is employed to pump a system away from equilibrium: in an energy ratchet, the biased movement of an energy form is attained by raising and lowering energy minima and maxima asymmetrically. Making the transition from switches to machines is challenging at both the level of conceptualization and in the realization of the concepts. It requires the coupling of mechanical motions in settings where symmetry is broken or the scaling of mechanical motion at the molecular level with those on the nano-, micro- and macroscopic scales in order to produce chemo-, electro- and photomechanical devices and functional materials that exhibit responsive behavior over multiple length scales. The challenge of creating these highly integrated systems in which operating molecular machines are interfaced with complex networks that are programmed to fulfill particular tasks is one that promises to be transformative in more ways than one. The mechanical bond is poised to play a major role in this potpourri of systems chemistry without borders.
Carson J. Bruns, Associate Professor, ATLAS Institute and the Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder.