Micromechanics and damage in slide-ring networks.

We explore the mechanics and damage of slide-ring gels by developing a discrete model for the mechanics of chain-ring polymer systems that accounts for both crosslink motion and internal chain sliding. The proposed framework utilizes an extendable Langevin chain model to describe the constitutive behavior of polymer chains undergoing large deformation and includes a rupture criterion to innately capture damage. Similarly, crosslinked rings are described as large molecules that also store enthalpic energy during deformation and thus have their own rupture criterion. Using this formalism, we show that the realized mode of damage in a slide-ring unit is a function of the loading rate, distribution of segments, and inclusion ratio (number of rings per chain). After analyzing an ensemble of representative units under different loading conditions, we find that failure is driven by damage to crosslinked rings at slow loading rates, but polymer chain scission at fast loading rates. Our results indicate that increasing the strength of the crosslinked rings may improve the toughness of the material.

Pressure-Sensitive Supramolecular Adhesives Based on Lipoic Acid and Biofriendly Dynamic Cyclodextrin and Polyrotaxane Cross-Linkers.

Slide-ring materials are polymer networks with mobile cross-links that exhibit impressive stress dissipation and fracture resistance owing to the pulley effect. On account of their remarkable ability to dissipate the energy of deformation, these materials have found their way into advanced materials such as abrasion-resistant coatings and elastic battery electrode binders. In this work, we explore the role of mobile cross-links on the properties of a biofriendly pressure-sensitive adhesive made using composites of cyclodextrin-based macromolecules and poly(lipoic acid). We modify cyclodextrin-based hosts and polyrotaxanes with pendant groups of lipoic acid (a commonly ingested antioxidant) to incorporate them as cross-links in poly(lipoic acid) networks obtained by simple heating in open air. By systematically varying the adhesive formulations while probing their mechanical and adhesive properties, we uncover trends in structure-property relationships that enable one to tune network properties and access biofriendly, high-tack adhesives.

A Transient Printed Soil Decomposition Sensor Based on a Biopolymer Composite Conductor.

Soil health is one of the key factors in determining the sustainability of global agricultural systems and the stability of natural ecosystems. Microbial decomposition activity plays an important role in soil health; and gaining spatiotemporal insights into this attribute is critical for understanding soil function as well as for managing soils to ensure agricultural supply, stem biodiversity loss, and mitigate climate change. Here, a novel in situ electronic soil decomposition sensor that relies on the degradation of a printed conductive composite trace utilizing the biopolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) as a binder is presented. This material responds selectively to microbially active environments with a continuously varying resistive signal that can be readily instrumented with low-cost electronics to enable wide spatial distribution. In soil, a correlation between sensor response and intensity of microbial decomposition activity is observed and quantified by comparison with respiration rates over 14 days, showing that devices respond predictably to both static conditions and perturbations in general decomposition activity.

Redox-switchable host-guest complexes of metallocenes and [8]cycloparaphenylene.

The cycloparaphenylene (CPP) nanocarbons are an appealing family of macrocyclic organic semiconductors with size-tunable structures and unique optoelectronic properties, which can be further modulated by complexation with guest molecules. While many π-π-stabilized CPP-fullerene host-guest complexes are known, CPPs can also host polycyclic guests stabilized by aromatic CH-π interactions. Here we combine experimental and computational results to report that CH-π interactions can also be tapped to include redox-active metallocene guests in [8]cycloparaphenylene ([8]CPP). Oxidation of a metallocene guest is accompanied by an increase in binding affinity and tilt angle. Crystallographically determined solid-state structures reveal CH-π interactions in the ferrocene complex (Fc⊂[8]CPP) and additional π-π interactions in the cobaltocenium complex (CoCp2+⊂[8]CPP). Functionalizing Fc with oxygen-bearing side chains also improves complex stability to a similar extent as oxidation, due to the formation of CH-O hydrogen bonds with the host's p-phenylene units. This work shows that CH-π bonding can be generalized as a driving force for CPP host-guest complexes and combined with other supramolecular forces to enhance stability. Owing to their semiconducting nature, amenability to functionalization, and reversible redox-dependent behavior, the [8]CPP-metallocene host-guest complexes may expand the library of synthons available for designing bespoke nanoelectronics and artificial molecular machines.

Chemorheological Monitoring of Cross-Linking in Slide-ring Gels Derived From α-cyclodextrin Polyrotaxanes.

Despite hundreds of studies involving slide-ring gels derived from cyclodextrin (CD)-based polyrotaxanes (PRs), their covalent cross-linking kinetics are not well characterized. We employ chemorheology as a tool to measure the gelation kinetics of a model slide-ring organogel derived from α-cyclodextrin/poly (ethylene glycol) PRs cross-linked with hexamethylenediisocyanate (HMDI) in DMSO. The viscoelastic properties of the gels were monitored in situ by small-amplitude oscillatory shear (SAOS) rheology, enabling us to estimate the activation barrier and rate law for cross-linking while mapping experimental parameters to kinetics and mechanical properties. Gelation time, gel point, and final gel elasticity depend on cross-linker concentration, but polyrotaxane concentration only affects gelation time and elasticity (not gel point), while temperature only affects gelation time and gel point (not final elasticity). These measurements facilitate the rational design of slide-ring networks by simple parameter selection (temperature, cross-linker concentration, PR concentration, reaction time).

Scalable synthesis of [8]cycloparaphenyleneacetylene carbon nanohoop using alkyne metathesis.

Large scale synthesis of cycloparaphenyleneacetylenes has been challenging due to low macrocyclization yields and harsh aromatization methods that often decompose strained alkynes. Herein, a cis-stilbene-based building block is subjected to alkyne metathesis macrocylization. The following sequence of alkene-selective bromination and dehydrobromination afforded a [8]cycloparaphenyleneacetylene derivative in high yield with good scalability. X-Ray crystal structure and computational analysis revealed a unique same-rim conformation for the eight methyl groups on the nanohoop.

Post-synthesis modification of slide-ring gels for thermal and mechanical reconfiguration.

Ring-sliding behavior in polyrotaxanes imbues gels, elastomers, and glasses with remarkable stress-dissipation and actuation properties. Since these properties can be modulated and tuned by structural parameters, many efforts have been devoted to developing synthetic protocols that define the structures and properties of slide-ring materials. We introduce post-synthetic modifications of slide-ring gels derived from unmodified α-cyclodextrin and poly(ethylene glycol) polyrotaxanes that enable (i) actuation and control of the thermo-responsive lower critical solution temperature (LCST) behavior of ring-modified slide-ring hydrogels, and (ii) chemically bonding separate gels into hybrid or shape-reconfigured macro-structures with a slide-ring adhesive solution. The mechanical properties of the post-modified gels have been characterized by shear rheology and uniaxial tensile tests, while the corresponding xerogels were characterized by wide-angle X-ray scattering. These demonstrations show that post-synthetic modification offers a practical solution for re-configuring the properties and shapes of slide-ring gels.

Mechanochemistry Activated Covalent Conjugation Reactions in Soft Hydrogels Induced by Interfacial Failure.

This work reports the development of a mechanochemistry activated covalent conjugation (MACC) reaction that shows areas of interfacial failure in soft hydrogels. Hydrogels are prone to delamination from rigid substrates due to the competition between swelling and adhesion, which can lead to bonding failure in a mechanism similar to crack propagation in harder materials. In this work, reductive amination was shown to occur when a ketone-bearing fluorescein derivative was bonded to an amine-functionalized hydrogel, as both of these moieties were found to be necessary for covalent conjugation into the gel network. For thin, circular polyacrylamide hydrogels, wrinkle patterns and regions of subsequent delamination at the edge of the gel were found to be selectively tagged by the dye. This reaction was then used to explore the effect of gel properties on patterns of interfacial failure. As cross-linker loading increased, the propagation of the delamination front and the area fraction of delamination were both found to increase, as shown by fluorescence images of gels. Increasing the thickness of the gel increased the fraction of delaminated area but did not change its propagation toward the center of the gel. This MACC reaction shows how mechanochemical reactions can be used for fluorescence tagging without incorporating mechanophores into the polymer gel matrix.

Solar Freckles: Long-Term Photochromic Tattoos for Intradermal Ultraviolet Radiometry.

While tattooable nanotechnology for in-skin sensing and communication has been a popular concept in science fiction since the 1990s, the first tattooable intradermal nanosensors have only emerged in the past few years, and none have been demonstrated in human skin. We developed a photochromic tattoo that serves as an intradermal ultraviolet (UV) radiometer that provides naked-eye feedback about UV exposure in real time. These small tattoos, or "solar freckles", comprise dermally implanted colorimetric UV sensors in the form of nanoencapsulated leuco dyes that become more blue in color with increasing UV irradiance. We demonstrate the tattoos' functionality for both quantitative and naked-eye UV sensing in porcine skin ex vivo, as well as in human skin in vivo. Solar freckles offer an alternative and complementary approach to self-monitoring UV exposure for the sake of skin cancer prevention. Activated solar freckles provide a visual reminder to protect the skin, and their color disappears rapidly upon removal of UV exposure or application of topical sunscreen. The sensors are implanted in a minimally invasive procedure that lasts only a few seconds, yet remain functional for months to years. These semipermanent tattoos provide an early proof-of-concept for long-term intradermal sensing nanomaterials that provide users with biomedically relevant information in the form of an observable color change.

Synthetic oligorotaxanes exert high forces when folding under mechanical load.

Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems 1,2 . Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts 3-5 . Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure 6-8 . Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 µs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

Dynamic force spectroscopy of synthetic oligorotaxane foldamers.

Wholly synthetic molecules involving both mechanical bonds and a folded secondary structure are one of the most promising architectures for the design of functional molecular machines with unprecedented properties. Here, we report dynamic single-molecule force spectroscopy experiments that explore the energetic details of donor-acceptor oligorotaxane foldamers, a class of molecular switches. The mechanical breaking of the donor-acceptor interactions responsible for the folded structure shows a high constant rupture force over a broad range of loading rates, covering three orders of magnitude. In comparison with dynamic force spectroscopy performed during the past 20 y on various (bio)molecules, the near-equilibrium regime of oligorotaxanes persists at much higher loading rates, at which biomolecules have reached their kinetic regime, illustrating the very fast dynamics and remarkable rebinding capabilities of the intramolecular donor-acceptor interactions. We focused on one single interaction at a time and probed the stochastic rupture and rebinding paths. Using the Crooks fluctuation theorem, we measured the mechanical work produced during the breaking and rebinding to determine a free-energy difference, ΔG, of 6 kcal·mol-1 between the two local conformations around a single bond.

Rotaxane probes for protease detection by 129Xe hyperCEST NMR.

We report a CB6 rotaxane for the 129Xe hyperCEST NMR detection of matrix metalloprotease 2 (MMP-2) activity. MMP-2 is overexpressed in cancer tissue, and hence is a cancer marker. A peptide containing an MMP-2 recognition sequence was incorporated into the rotaxane, synthesized via CB6-promoted click chemistry. Upon cleavage of the rotaxane by MMP-2, CB6 became accessible for 129Xe@CB6 interactions, leading to protease-responsive hyperCEST activation.

Near-Quantitative Aqueous Synthesis of Rotaxanes via Bioconjugation to Oligopeptides and Proteins.

In spite of widespread interest in rotaxane-based molecular machines and materials, rotaxanes have not been attached covalently to proteins. We describe the near-quantitative aqueous synthesis of [2]rotaxanes based on neutral and charged aqueous hosts-cucurbit[7]uril (CB7) and cyclobis(paraquat-p-phenylene) (CBPQT4+), respectively-using the thiol-ene addition of cysteine and maleimide as a stoppering protocol. After verifying the high efficiency of the reaction using glutathione (GSH) as an oligopeptide stopper, we have employed cytochrome C (CytC) as a protein stopper to produce the first well-characterized protein-rotaxane bioconjugates. We anticipate that this methodology will enable the preparation of novel materials that combine the unique properties of proteins and mechanical bonds.

Rotaxane-mediated suppression and activation of cucurbit[6]uril for molecular detection by (129)Xe hyperCEST NMR.

We report a method for blocking interactions between (129)Xe and cucurbit[6]uril (CB6) until activation by a specific chemical event. We synthesized a CB6-rotaxane that allowed no (129)Xe interaction with the CB6 macrocycle component until a cleavage event released the CB6, which then produced a (129)Xe@CB6 NMR signal. This contrast-upon-activation (129)Xe NMR platform allows for modular synthesis and can be expanded to applications in detection and disease imaging.

Tunable solid-state fluorescent materials for supramolecular encryption.

Tunable solid-state fluorescent materials are ideal for applications in security printing technologies. A document possesses a high level of security if its encrypted information can be authenticated without being decoded, while also being resistant to counterfeiting. Herein, we describe a heterorotaxane with tunable solid-state fluorescent emissions enabled through reversible manipulation of its aggregation by supramolecular encapsulation. The dynamic nature of this fluorescent material is based on a complex set of equilibria, whose fluorescence output depends non-linearly on the chemical inputs and the composition of the paper. By applying this system in fluorescent security inks, the information encoded in polychromic images can be protected in such a way that it is close to impossible to reverse engineer, as well as being easy to verify. This system constitutes a unique application of responsive complex equilibria in the form of a cryptographic algorithm that protects valuable information printed using tunable solid-state fluorescent materials.

Emergent ion-gated binding of cationic host-guest complexes within cationic M12L24 molecular flasks.

"Molecular flasks" are well-defined supramolecular cages that can encapsulate one or more molecular guests within their cavities and, in so doing, change the physical properties and reactivities of the guests. Although molecular flasks are powerful tools for manipulating matter on the nanoscale, most of them are limited in their scope because of size restrictions. Recently, however, increasingly large and diverse supramolecular cages have become available with enough space in their cavities for larger chemical systems such as polymers, nanoparticles, and biomolecules. Here we report how a class of metallosupramolecular cages known as M12L24 polyhedra have been adapted to serve as nanometer-scale containers for solutions of a pseudorotaxane host-guest complex based on a tetracationic cyclophane host, cyclobis(paraquat-p-phenylene) (CBPQT(4+)), and a 1,5-dioxynaphthalene (DNP) guest. Remarkably, the hierarchical integration of pseudorotaxanes and M12L24 superhosts causes the system to express stimulus-responsive behavior, a property which can be described as emergent because neither the DNP⊂CBPQT(4+) nor the M12L24 assemblies exhibit this behavior independently. The DNP-containing M12L24 molecular flasks are effectively "sealed off" to CBPQT(4+) until ions are added as a stimulus to "open" them. The electrolyte stimulus reduces the electrostatic screening distance in solution, allowing favorable DNP⊂CBPQT(4+) host-guest interactions to overcome repulsive Coulombic interactions between the cationic M12L24 cages and CBPQT(4+) rings. This unusual example of ion-gated transport into chemical nanocontainers is reminiscent of transmembrane ion channels which act as gates to the cell, with the important difference that this system is reversible and operates at equilibrium.

Rotaxane-based molecular muscles.

CONSPECTUS: More than two decades of investigating the chemistry of bistable mechanically interlocked molecules (MIMs), such as rotaxanes and catenanes, has led to the advent of numerous molecular switches that express controlled translational or circumrotational movement on the nanoscale. Directed motion at this scale is an essential feature of many biomolecular assemblies known as molecular machines, which carry out essential life-sustaining functions of the cell. It follows that the use of bistable MIMs as artificial molecular machines (AMMs) has been long anticipated. This objective is rarely achieved, however, because of challenges associated with coupling the directed motions of mechanical switches with other systems on which they can perform work. A natural source of inspiration for designing AMMs is muscle tissue, since it is a material that relies on the hierarchical organization of molecular machines (myosin) and filaments (actin) to produce the force and motion that underpin locomotion, circulation, digestion, and many other essential life processes in humans and other animals. Muscle is characterized at both microscopic and macroscopic length scales by its ability to generate forces that vary the distance between two points at the expense of chemical energy. Artificial muscles that mimic this ability are highly sought for applications involving the transduction of mechanical energy. Rotaxane-based molecular switches are excellent candidates for artificial muscles because their architectures intrinsically possess movable filamentous molecular components. In this Account, we describe (i) the different types of rotaxane "molecular muscle" architectures that express contractile and extensile motion, (ii) the molecular recognition motifs and corresponding stimuli that have been used to actuate them, and (iii) the progress made on integrating and scaling up these motions for potential applications. We identify three types of rotaxane muscles, namely, "daisy chain", "press", and "cage" rotaxanes, and discuss their mechanical actuation driven by ions, pH, light, solvents, and redox stimuli. Different applications of these rotaxane-based molecular muscles are possible at various length scales. On a molecular level, they have been harnessed to create adjustable receptors and to control electronic communication between chemical species. On the mesoscale, they have been incorporated into artificial muscle materials that amplify their concerted motions and forces, making future applications at macroscopic length scales look feasible. We emphasize how rotaxanes constitute a remarkably versatile platform for directing force and motion, owing to the wide range of stimuli that can be used to actuate them and their diverse modes of mechanical switching as dictated by the stereochemistry of their mechanical bonds, that is, their mechanostereochemistry. We hope that this Account will serve as an exposition that sets the stage for new applications and materials that exploit the capabilities of rotaxanes to transduce mechanical energy and help in paving the path going forward to genuine AMMs.

Redox switchable daisy chain rotaxanes driven by radical-radical interactions.

We report the one-pot synthesis and electrochemical switching mechanism of a family of electrochemically bistable 'daisy chain' rotaxane switches based on a derivative of the so-called 'blue box' (BB(4+)) tetracationic cyclophane cyclobis(paraquat-p-phenylene). These mechanically interlocked molecules are prepared by stoppering kinetically the solution-state assemblies of a self-complementary monomer comprising a BB(4+) ring appended with viologen (V(2+)) and 1,5-dioxynaphthalene (DNP) recognition units using click chemistry. Six daisy chains are isolated from a single reaction: two monomers (which are not formally 'chains'), two dimers, and two trimers, each pair of which contains a cyclic and an acyclic isomer. The products have been characterized in detail by high-field (1)H NMR spectroscopy in CD3CN-made possible in large part by the high symmetry of the novel BB(4+) functionality-and the energies associated with certain aspects of their dynamics in solution are quantified. Cyclic voltammetry and spectroelectrochemistry have been used to elucidate the electrochemical switching mechanism of the major cyclic daisy chain products, which relies on spin-pairing interactions between V(•+) and BB(2(•+)) radical cations under reductive conditions. These daisy chains are of particular interest as electrochemically addressable molecular switches because, in contrast with more conventional bistable catenanes and rotaxanes, the mechanical movement of the ring between recognition units is accompanied by significant changes in molecular dimensions. Whereas the self-complexed cyclic monomer-known as a [c1]daisy chain or molecular 'ouroboros'-conveys sphincter-like constriction and dilation of its ultramacrocyclic cavity, the cyclic dimer ([c2]daisy chain) expresses muscle-like contraction and expansion along its molecular length.