Carson J. Bruns
Associate Professor, ATLAS Institute and the Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder. Director of the SEAM Lab.
Freeskating Tricks
Two inline wheels per foot, nothing in between, and the whole thing fits in a bag.
A freeskate is a small platform carrying two inline wheels, one under each foot, with nothing connecting them. No boot, no binding, no board. Each foot steers on its own, which is what makes everything else possible.
You do not push off. You pump: a continuous sine wave carved into the pavement, the two skates tracing opposing arcs while your weight rolls through them. The speed comes out of the motion itself. It is the closest thing I have found to swimming on land.
I think this is the perfect skate. It is the most portable one ever made, small enough to fit in a purse, so it comes with you rather than waiting at home. It fits anywhere a shoe fits. And because each foot is free, the trick vocabulary is enormous and still being invented.
Hardly anyone rides them, which I mostly find puzzling and occasionally a little lonely. So here is my pitch: the tricks below are the fastest way to understand what these things can do that nothing else can. Watch a few. Then go get a pair from JMKRIDE and find me.
Fourteen tricks
Treenets
Shelters built in trees from whatever the site provided.
I spent my honeymoon taking a treenet weaving master class with Treenet Willy, a pioneer of the art.
A treenet is woven from nylon and polyester paracord, strung between living trees and tensioned against them so the trees carry the load. Somewhere between a hammock, a floor and a trampoline.
The form was born in the redwoods, where activists wove nets high in old-growth canopy and lived in them so the trees could not be cut down. The first treenets were built to keep something alive. I am glad to be a small part of that lineage.
There is something in the tension that I keep turning over. You spend a day pulling every line taut, building stored energy into the thing on purpose, so that later somebody can lie down in it and let all of theirs go. The net holds its tension so the body does not have to.
Teaching Color
Half science, half art. A semester spent on one subject from every direction at once.
Color belongs to nobody. A physicist will tell you it is a wavelength, a chemist that it is what a molecule does with a photon, a biologist that it is three cone cells and a nerve, a psychologist that it does not exist until a brain says so, and a painter that none of this helps at the easel. Each of them is right and none of them is enough.
The course takes color from all of those directions at once and refuses to pick. Half the semester is theory: the physics of light and optics, the chemistry of dyes and pigments, the biology of vision, the psychology of perception, then the theory of color and color spaces, which finally make sense once you know why the rules exist. The other half is studio. Students work across acrylic, oil and watercolor paint, tattoo, resin, and a medium of their own choosing, and finish with a project of their own design.
What students take away is a way of thinking that outlives the subject. They arrive having only ever been taught to see color as a choice from a menu, and leave able to reason about it from the electron up and from the eye down, and to make something with it. Engineers discover that aesthetic decisions have technical content. Designers discover that the technical content is theirs to control.
That is the argument for teaching it this way. Almost nothing worth understanding sits inside one discipline, and color is the most vivid proof of it I know.
Coverage
What happened when the work left the building.
Smart tattoos turned out to be the kind of science people want to read about. The coverage has run from chemistry trade press to CNN, NPR, and an unlikely afternoon with the History Channel.
Collected here because it is the clearest evidence that the work reaches past the people who cite it.
Can a Tattoo Help You Stay Healthy?
The TEDx talk that took smart tattoos to a very large audience.
TEDxMileHigh, Denver, December 2018.
Anatomy of the (Future) Wet Lab
Dissecting what a chemist actually does, task by task, before deciding what a robot should take over.
Before deciding what a robot in a chemistry laboratory should do, we studied what the humans in one actually do: a task typology for synthetic chemistry, then a workload analysis of the people doing it.
The harder question came next. Not can this be automated, but should it be, and how. We are building a task allocation framework that sorts wet-lab work four ways: automate it outright, augment it so the robot carries the burden while the chemist keeps the judgement, defer it because the burden is too low to be worth the engineering, or preserve it because the work is valuable to the person doing it.
This is the part of automation research that usually gets skipped, and skipping it is how you build a robot nobody wants.
Robo-Chemistry
Mobile robots that assist chemists at the bench instead of replacing them.
Organic synthesis has barely changed in a century. It is still manual, still hazardous, and still the bottleneck between an idea for a molecule and the molecule itself. Most laboratory robotics has answered this with bespoke auto-synthesizers designed to remove the chemist.
RoboChemistry takes the opposite position. We build mobile collaborative robots that offer real-time physical and cognitive assistance to human chemists, reducing workload and exposure while leaving the science where it belongs. Doing that requires three things at once: a general schema for describing chemical procedures, task planning that gives a robot enough chemical understanding to generate its own assistance policies, and physical human-robot interaction safe enough for a room that is not built for robots.
An NSF Future of Work award, run with Daniel Szafir and Alessandro Roncone. The robot-assisted dialysis platform is the first published piece of it.
Spirit Animals
Wildlife rendered in the colors they don't have.
I have always seen animals in colors they do not have. In dreams, in imagination, and in altered states, forms arrive saturated past anything the eye receives, shimmering and pulsing across their own surfaces. I have been chasing that since childhood.
The rule is simple. Every color on the canvas must be as high in saturation and value as acrylic will go. No neutrals, nothing shaded down. The method is divisionist, the intent expressionist.
Each painting begins in control and ends in surrender. I outline the animal precisely, in the brightest yellow I have, then add colors one at a time in descending value, taking a little less care with each. By the time the form holds, instinct is choosing. The distribution of color is mostly unplanned, which is the point: the finished painting surprises me the way the original vision did.
I call them spirit animals because the animal in the painting is the one that showed up in my head, not the one that exists. A spirit animal is a creature you are given rather than one you find. These arrived that way.
Paintings
Murals
Animations
Every animation starts from a photograph of a finished work. Nothing is generated. The color is already there; the motion only does what the color was doing in my head.
Chemistry Is Interdisciplinary
One of twelve scientists in the ACS 150th-anniversary film series.
The American Chemical Society chose twelve scientists to represent the themes of its 150th anniversary. I was asked to represent interdisciplinary, which is either a compliment or a diagnosis.
Permanent Sun Protection
A permanent sunscreen that lives in the skin instead of on it.
Sunscreen is the only sun protection available for skin that has to be uncovered, and it fails in every direction: it lasts an hour or two, it pollutes reefs, it feels unpleasant, it looks wrong, and almost nobody applies it correctly. Skin cancer still occurs more often than all other cancers combined.
Skin already solved this problem once. The three rows below are the same job done three ways, and the third is ours.
Invelanin uses the same encapsulation chemistry as Magic Ink with the pigment swapped for an ultra-stable absorber, so the particles stay where they are placed and the absorber never leaves. Because dermal sun damage is what drives visible aging as well as cancer risk, protection sitting in the dermis addresses both at the depth where they happen. One treatment, no reapplication, nothing to wash into a reef.
Mouse studies are underway and the early results are encouraging: the implants appear to be doing what they should in living skin, which is the finding we needed before taking the idea toward people. Jesse Butterfield’s doctoral thesis reports the first of this data. It is preliminary, and we are treating it that way.
In development in my lab. HYPRSKN Inc. licenses the technology.
“Side Reactions”
The products I wasn’t trying to make.
A side reaction is what forms while you are busy making something else. Not a mistake, exactly. Just not the target. Every one of these started that way, and none of them has anything to do with the others, so I have stopped pretending they add up to a body of work. They add up to a person.
The Wall is the one that explains the rest, so it goes first.
In my office, I have a wall. On the wall I paste notes I have written to myself during periods of self-reflection and self-isolation. Some of the words are playful, some are serious. Messy and raw, they represent my psyche in its most naked and vulnerable state.
There is wisdom in this soup of nonsense. The wall helps me remember who I am and who I want to be. The pages land somewhere between zen koan, poetry, and art: hand-lettered, declarative, and not interested in being argued with.
It is also, I think, the honest version of what the rest of this panel is doing: making something with no audience in mind and finding out later that it meant something.
Pigmented epoxy resin, poured and left to find its own arrangement. I set the initial conditions and the fluid does the composition, which is the same bargain I make in the laboratory: choose the starting conditions carefully, then get out of the way and see what the physics wants. Here the answer arrives in an afternoon, and it arrives in color.
On a screen I can do the things the physical world charges too much for. Zoom in past what any lens would resolve. Give a molecule a nebula to sit in. Repeat a line ten thousand times without my hand getting tired, until repetition stops reading as pattern and starts reading as motion. Most of these are the same impulse as everything else here, which is to render something at a scale or in a palette that it does not get in life, and then look at it.
I built a trail, right up the side of my neck of Fourmile Canyon. Construction at the scale of a landscape, done with hand tools and time, and the only project here whose output you can walk on.
I probably stacked 10,000 rocks to make this trail, which I find 10,000 times better than a gym membership.
The Wall
Flow Art
Digital Art
The Trail
Lab Automation with LEGO®
Research instruments built from toy bricks, for a twentieth of the price.
Laboratory automation is gated by price, bench space and the assumption that an instrument does one job forever. We built three research tools out of LEGO® Technic™ and MINDSTORMS® EV3 parts: a syringe pump, an orbital shaker and a microcentrifuge. They share 384 pieces. Build them one at a time and the whole set costs under $83.
Then we made them do real work. We synthesized calcium carbonate microparticles using the brick-built machines and the commercial instruments side by side, and the results came out comparably. The shaker went further than parity: because its motion is programmed rather than dialed in, we could write shake profiles the commercial unit has no way to produce, and reach particles it could not make.
The argument is sustainability as much as cost. A commercial centrifuge is a centrifuge until it is landfill. A pile of bricks is a centrifuge this week and a syringe pump next week, which is exactly the property that makes LEGO® worth taking seriously outside a classroom.
Then it went back to the classroom on purpose. We ran a three-day workshop for middle schoolers who assembled all three machines, used them to automate the chemistry, and finished by redesigning their equipment for jobs we had not assigned. The chemistry drew the strongest engagement. The building humbled the students who had never met a Technic™ beam, which is a finding worth publishing rather than hiding.
Assembly instructions and timelapse builds for all three machines are behind the doors above.
Syringe pump
A motor drives a threaded rod that advances a syringe plunger at a set speed, which is how you add a reagent slowly and evenly instead of dumping it in. The commercial version costs hundreds of dollars and does one thing.
Orbital shaker
A platform driven in a circular orbit keeps a reaction mixed and suspended. Because ours is programmed rather than dialed in, the shake profile itself becomes an experimental variable, and that turned out to matter: custom profiles gave us particle characteristics the commercial shaker could not reach.
Microcentrifuge
Spin a sample fast enough and the solids collect at the bottom, which is how you separate a product from the liquid it formed in. This is the smallest of the three builds and the fastest to put together.
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.
Electriflow
A book whose illustrations move.
Soft electrohydraulic actuators, thin and quiet enough to be bound into paper, turning a printed page into something that animates as you read it.
Real Tattoos I Made
Mostly on myself, occasionally on a volunteer.
Most of my tattoos exist because something needed testing and I was the nearest available substrate. A single-subject study, unblinded, with the investigator as the only volunteer.
A few other people have let me tattoo them, which I consider an act of considerable trust!
The tattoos
Tattoo a Fruit Workshop
Hand someone a tattoo machine and a banana, and the lecture becomes unnecessary.
Citrus peel takes a needle in almost the same way skin does. That accident of anatomy is the whole workshop: give a person two minutes of instruction, a real tattoo machine and a grapefruit, and they learn more about depositing pigment under a living surface than an hour of slides could teach them. Nobody has to be told it is engineering. They work it out while holding the needle.
What happens next is always the same and never gets old. The questions arrive unprompted, because a person mid-tattoo has to solve a real problem: how deep, how fast, what happens when the fruit fights back. Art, chemistry and biomedical engineering stop being separate subjects for as long as the machine is running. Then they take the fruit home.
It started in 2019 as a teen science café at a public library, ten students and a talk about color-changing tattoos. Since then it has run as an open pop-up ambushing passers-by in the engineering center, and four times through CU Science Discovery’s Biotechnology Bootcamp. Fourteen offerings, more than two hundred people, middle school through undergraduate.
The pop-up was formally assessed with the CU Center for STEM Learning. Thirty participants, seventeen minutes each on average, and of twenty-two who filled out the survey, twenty-one reported feeling significantly better afterward and twenty said it had improved their day. Good numbers. But the one that decided I would keep doing this came from a survey form at that first library café, and it was a sample size of one.
Magic Ink
The world's first rewritable tattoo ink, taken through clinical studies and onto the market.
Point a flashlight at your arm and a tattoo appears. Point a different one at it and the tattoo goes away. The ink stays in the skin the whole time, doing what tattoo ink has always done, except that the image it holds is now yours to change.
The pigment is photochromic: a molecule that changes shape, and therefore color, when it absorbs light. We seal it inside a shell of medical-grade polymer, the same material already trusted inside the body in dermatology, dentistry and bone surgery. The shell keeps the particles where the artist put them and keeps the chemistry doing only what it should. Ultraviolet light switches the design on, visible light switches it off, and it happens fast enough to watch. In the dish it survives more than ten thousand cycles without fading.
So the tattoo becomes editable. Draw it, wear it, erase it, draw something else in the same skin next year, with a light pen rather than a laser and a dermatologist. What is permanent is the canvas, not the picture.
With tattoo artist Keith “Bang Bang” McCurdy we took it out of the laboratory: through first-in-human clinical studies, where it healed and performed comparably to conventional inks across a range of skin types with no adverse effects, and onto the market in May 2025. The activation device is patented and the clinical data are published.
The same chemistry has a quieter application we care about just as much. Radiotherapy patients receive small permanent tattoos to align the beam, and those marks outlast the illness by decades as a daily reminder of it. A mark that can be switched on for treatment and switched off afterward does the clinical job and then gets out of the way.
Robo-Tattooing
Teaching a machine to tattoo.
A tattoo machine is a needle oscillating at a few hundred hertz, a depth tolerance of a fraction of a millimetre, and a substrate that moves, bleeds and flinches. Automating it is a hard robotics problem and a hard skin problem at the same time.
Underway in the lab. More here soon.
Programmable Pigments
Nanoparticles that turn skin into a full-color rewritable display.
Multicolor photochromic nanoparticle inks, each channel addressable by a different wavelength, so a pattern can be written, erased and rewritten in living skin.
Shape-Changing Interfaces
Origami-inspired soft actuators that fold themselves.
Folding is a way of getting large motion out of flat, thin material. Driving the folds electrostatically makes a surface that reconfigures itself on command.
Fingertip Haptics
A wearable that puts texture on your fingertip.
A high-resolution electrohydraulic array small enough to sit on a fingertip. Sixteen miniature actuators delivering multi-modal tactile sensation over about a square centimetre.
93% Water Elastomer
A rubber that is almost entirely water and still won't tear.
Two toughening mechanisms in one network, sliding crosslinks and dense entanglement, producing a hydrogel that stretches enormously and refuses to break, while being almost all water.
The property we did not expect is the elasticity. Stretch it hard and let go and it returns to very nearly where it started, recovering about 99.7% of its original shape. Near-perfect recoverability is unusual in any hydrogel, because water-swollen networks normally dissipate energy by breaking something and stay slightly deformed. At 93% water it should be worse, not better.
Smart Tattoos as Personal Radiation Sensors
Tattoos that read UV and gamma dose from inside the skin.
Every wearable dosimeter shares one flaw: it can be taken off. Badges get forgotten, left in a locker, or removed by whoever least wants the reading. A sensor implanted in the skin cannot be misplaced, does not chafe, and is still there years later. A single one is a millimetre or two across. The particles that make it work are a thousand times smaller than that.
Three of them exist so far, each answering a different question.
Solar Freckles came first, and were the first intradermal nanosensors demonstrated in living human skin rather than a model. They are ultraviolet radiometers: dermally implanted colorimetric sensors that turn bluer the harder the sun is hitting you, in real time and readable by naked eye. The color fades again within minutes of stepping into shade or applying sunscreen, which makes them a nagging visual reminder rather than a number in an app. The implantation takes seconds and the sensors keep working for months to years. Tattooable in-skin sensing had been a science fiction premise since the 1990s; this was the version that worked in a person.
The gamma dosimeter takes the same idea somewhere more consequential. Radiation workers, first responders and patients need to know their ionizing dose, and that is precisely the setting where a removable badge is least trustworthy. We doped polystyrene nanoparticles with photoresponsive dithienylethenes to make a colorimetric gamma-ray dosimeter that is reversible: it darkens with dose and is reset with red light, so the same implant can be read and reused. It is a proof of concept, and it points at personal dosimetry that cannot be forgotten or tampered with.
The dosimeters answer the other half of the ultraviolet question. A radiometer tells you how strong the sun is now; a dosimeter counts what you have accumulated, which is what actually determines whether you got enough light for vitamin D or too much for your skin. A redesigned generation of UV-photochromic pigments gave us better tunability, stability and biocompatibility, and the same chemistry can be formulated to behave as a dosimeter or as a plain sunscreen-efficacy monitor. They stay functional and re-usable in the dermis for years, which is the part that makes daily use realistic where a disposable sticker is not.
Skin cancer is the most common malignancy in North America, Europe and Australia. The argument running through all three is the same: the information that helps you avoid it should live where you cannot leave it behind.
Microgels That Assemble Themselves
Shape-complementary hydrogel blocks that find their partners in water, and take microplastics with them.
Hydrogels can be made to recognize each other. Give two populations complementary shapes and opposite surface charges and they will find one another in water and lock together, a mesoscale echo of host–guest chemistry.
We photopolymerize acrylic acid and dimethylaminoethyl acrylate through shape-defined photomasks, producing microgels with matching geometry and opposing charge. Electrostatic attraction between deprotonated carboxylates and protonated amines then drives selective lock-and-key assembly, tuned by pH, ionic strength and how the mixing is done.
Loading the gels with magnetic nanoparticles turns the assembly into a tool: the blocks capture polystyrene, polycarbonate and PVC microplastics out of contaminated water, and a magnet pulls the whole assembly back out. Assembled pairs remove more than the same gels working alone, which is the part we did not expect.
Unpublished. Manuscript in preparation.
Blue Energy
Electricity from nothing but salt and water, and it composts.
Where fresh water meets salt water there is free energy, and the only thing standing between us and it is a membrane tough enough and selective enough to harvest it.
Ours is a slide-ring hydrogel, asymmetrically doped with a polyelectrolyte network, and it composts.
Eco-Friendly Ultra-Sticky Adhesives
Ultra-sticky glue from lipoic acid and threaded sugar rings.
Pressure-sensitive adhesives built on dynamic cyclodextrin and polyrotaxane crosslinkers. The pulley effect applied to stickiness, from feedstocks that are bio-friendly rather than petrochemical.
Photochromic Particles
Particles that switch color under ultraviolet light, and remember.
Each particle holds a photochromic dye that flips between two stable forms. Ultraviolet light writes one state; visible light erases it. Nothing moves and nothing is consumed. The molecule simply reshapes and stays reshaped.
Implanted in the dermis by the million, they are what makes a tattoo able to sense.
Electrodeposited Lamellae
Growing striped nanostructures by pushing current through a solution.
Run a current through the right solution of small molecules and they will assemble on the electrode into anisotropic lamellar nanostructures: stripes, grown rather than fabricated.
Doctoral work with Samuel Stupp, and the first time I designed a molecule for what the bulk material would do rather than for what the molecule itself was.
Printable Power
Matter taught to absorb light and move charge.
Small-molecule donors for solution-processed organic solar cells, designed so the way they self-assemble determines how well the device works.
The oldest thread here, and the first time I cared what a molecule did after it left the flask.
Rotaxane–Protein Bioconjugates
A mechanical bond tied directly onto a protein, in water.
Rotaxanes are made in organic solvent by chemists who like organic solvent. Making them in water, on a peptide or a protein, was the moment my chemistry stopped being only chemistry.
Done during a Miller Fellowship at Berkeley with Matthew Francis. It is why almost everything since has had biology in it.
Slide-Ring Actuators
Gels that move because the crosslinks can slide.
Polyrotaxane “molecular necklaces”: rings threaded onto a polymer chain, free to slide, used as crosslinks, then chemically reconfigured after synthesis to tune how the material moves.
Why Slide-Ring Networks Don't Break
The theory of how sliding crosslinks redistribute stress instead of failing.
With Franck Vernerey: a micromechanical account of what sliding crosslinks actually do to stress and damage, so the properties can be predicted rather than discovered.
Switch-On MRI Contrast Agents
A mechanical bond that turns a magnetic resonance signal on when it finds what it is looking for.
Hyperpolarized xenon can be made to report on its surroundings, but only if something gates its access to a molecular cage. We used a rotaxane to do the gating: thread the axle and the cage is silenced, cut the thread and the signal switches on.
Because the thread can be a peptide, the switch becomes a detector. An enzyme cuts it, and the contrast agent announces that the enzyme was there. A molecular machine doing diagnostics.
Switchable Host–Guest Assemblies
Molecules built to recognize, trap and release other molecules.
A self-assembled M12L24 cage whose charged interior gates what may bind inside it. Rigid boxes that scavenge polycyclic aromatic hydrocarbons out of solution. Rings threaded through rings. Recognition that flips with a change in redox state.
Different molecules, one preoccupation: designing the conditions under which molecules decide to hold on to each other, and what it takes to make them let go.
Carbon Nanohoop Machinery
Rings of benzene that grip whatever fits inside them.
A cycloparaphenylene is a loop of benzene rings, the shortest possible slice of a carbon nanotube. Because the loop is curved, its inner surface is electron-rich in a way a flat aromatic never is, and it will hold a guest by CH–π contact alone.
Hyejin Kwon’s work in my lab showed these hoops binding polycyclic aromatics with no covalent chemistry at all, and binding metallocenes in a way that switches with redox state, so the hoop can be told when to let go.
Folding Under Load
Interlocked molecules that pull hard when they fold.
Single-molecule force spectroscopy on oligorotaxane foldamers, showing they generate substantial force as they fold against mechanical load. The closest synthetic analogue yet to what a muscle protein does.
Molecular Muscles
Interlocked rings that contract and extend on command.
Daisy-chain rotaxanes: two molecules threaded through one another so they can slide apart and back together, driven electrochemically or thermally.
This is where the whole thing starts. Matter taught to move.
What Is a Molecular Machine?
Nobody agrees, so I chair the committee deciding.
The field grew faster than its vocabulary. “Machine”, “motor”, “switch” and “pump” are used to mean incompatible things by people who then talk past each other in the literature.
I argued the case in Nature Nanotechnology, and now chair the IUPAC task group writing the definitions, which turns out to be less a chemistry problem than a philosophy-of-language one.