Three-in-One: Dye-Volatile Cocrystals Exhibiting Intensity-Dependent Photochromic, Photomechanical, and Photocarving Response.

Cocrystallization of a cis-azobenzene dye with volatile molecules, such as pyrazine and dioxane, leads to materials that exhibit at least three different light-intensity-dependent responses upon irradiation with low-power visible light. The halogen-bond-driven assembly of the dye cis-(p-iodoperfluorophenyl)azobenzene with volatile halogen bond acceptors produces cocrystals whose light-induced behavior varies significantly depending on the intensity of the light applied. Low-intensity (<1 mW·cm-2) light irradiation leads to a color change associated with low levels of cis → trans isomerization. Irradiation at higher intensities (150 mW·mm-2) produces photomechanical bending, caused by more extensive isomerization of the dye. At still higher irradiation intensities (2.25 W·mm-2) the cocrystals undergo cold photocarving; i.e., they can be cut and written on with micrometer precision using laser light without a major thermal effect. Real-time Raman spectroscopy shows that this novel photochemical behavior differs from what would be expected from thermal energy input alone. Overall, this work introduces a rational blueprint, based on supramolecular chemistry in the solid state, for new types of crystalline light-responsive materials, which not only respond to being exposed to light but also change their response based on the light intensity.

The "η-sweet-spot" (ηmax) in liquid-assisted mechanochemistry: polymorph control and the role of a liquid additive as either a catalyst or an inhibitor in resonant acoustic mixing (RAM).

Resonant acoustic mixing (RAM) offers a simple, efficient route for mechanochemical synthesis in the absence of milling media or bulk solvents. Here, we show the use of RAM to conduct the copper-catalysed coupling of sulfonamides and carbodiimides. This coupling was previously reported to take place only by mechanochemical ball milling, while in conventional solution environments it is not efficient, or does not take place at all. The results demonstrate RAM as a suitable methodology to conduct reactions previously accessed only by ball milling and provide a detailed, systematic overview of how the amount of liquid additive, measured by the ratio of liquid volume to weight of reactants (η, in µL mg-1), can affect the course of a mechanochemical reaction and the polymorphic composition of its product. Switching from ball milling to RAM allowed for the discovery of a new polymorph of the model sulfonylguanidine obtained by catalytic coupling of di(cyclohexyl)carbodiimide (DCC) and p-toluenesulfonamide, and the ability to control reaction temperature in RAM enabled in situ control of the polymorphic behaviour of this nascent product. We show that the reaction conversion for a given reaction time does not change monotonically but, instead, achieves a maximum for a well-defined η-value. This "η-sweet-spot" of conversion is herein designated ηmax. The herein explored reactions demonstrate sensitivity to η on the order of 0.01 µL mg-1, which corresponds to an amount of liquid additive below 5 mol% compared to the reactants, and is at least one to two orders of magnitude lower than the η-value typically considered in the design of liquid-assisted ball milling mechanochemical reactions. Such sensitivity suggests that strategies to optimise liquid-assisted mechanochemical reactions should systematically evaluate η-values at increments of 0.01 µL mg-1, or even finer. At η-values other than ηmax the reaction conversion drops off, demonstrating that the same liquid additive can act either as a catalyst or an inhibitor of a mechanochemical reaction, depending on the amount.

Optical and computational study of the trans ↔ cis reversible isomerization of the commercial bis-azo dye Bismarck Brown Y.

The trans-cis-trans isomerization behaviour of Bismarck Brown Y (BBY) during and after irradiation with visible light, was characterized in detail for the first time by means of optical pump-probe experiments, to study the geometric inter-conversion of bis-azobenzene both in solution and embedded in multi-layered polymeric thin films. The rate constants observed for the thermal cis-trans back isomerization permit a determination of how the thermal isomerization is influenced by its local environment. In both solution and when incorporated into multi-layered thin films, the thermal relaxation observed for the commercial azo dye BBY showed a highly unusual biexponential decay, which clearly demonstrates two distinct isomerization processes. The cis decay showed an anomalous fast isomerization process on the timescale of milliseconds, followed by a slower isomerization process with a cis lifetime on the order of seconds. It was further observed that the faster isomerization process was influenced more by its local environment than was the slower process. The faster isomerization process also displayed a higher rate constant in aprotic solvents such as THF and DMF compared to that observed in protic solvents such as ethanol and water. Additionally, a higher rate constant was observed in solution compared to the multi-layered thin films where motion of the azo molecules was likely more restricted. Following recrystallization of the BBY azo dye, the more expected monoexponential decay was observed for the cis isomer in solution, with a single cis lifetime calculated on the timescale of seconds. This timescale corresponded well to values predicted by density functional theory calculations.

Electrospun Azo-Cellulose Fabric: A Smart Polysaccharidic Photo-Actuator.

A natural polysaccharide-based smart photo-actuator is fabricated via electrospinning of cellulose 4-phenyl azobenzoate (Azo-Cel) from its organic solution in a mixture of high-volatile acetone, a poor solvent of Azo-Cel, and low-volatile N,N-dimethylacetamide (DMAc), a good solvent of Azo-Cel. At an optimal polymer concentration (17 wt%) and solvent mixing ratio (acetone/DMAc = 3/2 (v/v)), stable electrified polymer jets are formed and continuous nanofibers and their nonwoven fabric can be drawn on a cylinder-shaped rotating drum electrode under a high electric field (25 kV). Scanning electron microscopic observation of the Azo-Cel fabric confirms that the fabric consists of uniaxially aligned nanofibers with a mean diameter of 207 nm. The water contact angle of the Azo-Cel fabric reversibly decreases and increases in response to alternate irradiation with UV and visible light to induce geometric deformation of the azobenzene moiety between the trans and cis isomers, which lead to lower and higher surface free energies, respectively. In addition, self-standing Azo-Cel fabric exhibits a UV-driven photo-mechanical asymmetric bending deformation toward the light source.

Theory and experiment of chain length effects on the adsorption of polyelectrolytes onto spherical particles: the long and the short of it.

We study here the role of polyelectrolyte chain length, that is number of repeat units (mers), in the competitive adsorption of a simple model polyanion, poly(acrylic acid), onto 85 nm spherical silica particles capped with a model polycation, poly(allylamine hydrochloride). Performing fluorescence spectroscopy experiments, we measured chain-length dependence of dilute aqueous polyelectrolyte adsorption, at full surface coverage, onto an oppositely charged polyelectrolyte overtop spherical silica nanoparticles (10-3 g L-1). Preferential adsorption was determined by comparing the characteristic fluorescence intensities of the two fluorophore-labeled and narrowly disperse polyacrylic acid samples (NMA-PAA450k and Dan-PAA2k) of 450k- and 2k-molecular weight (6250- and 28-mers), respectively. To compare and validate experimental results, a lattice model was developed for computing the probabilities of the different arrangements of two polymer chain lengths of polyacrylic acid on the surface of the silica nanosphere. We then determined which numbers of long and short adsorbed chains corresponded to the most configurations in our model. Both spectroscopic experiment results and the combinatorial model demonstrated that there is an entropic preference for complete adsorption of the longer 450k polyacrylic acid chain vs. 2k. This study provides insights on entropy driven chain-length dependence of polyelectrolyte adsorption onto spherical nanoparticle surfaces for directing and optimizing their layer-by-layer self-assembly in organic films.

After 200 Years: The Structure of Bleach and Characterization of Hypohalite Ions by Single-Crystal X-Ray Diffraction*.

We report the first X-ray single crystal structures of hypochlorite (ClO- ) and hypobromite (BrO- ) salts, including hydrated sodium hypochlorite, a staple of the chlorine industry and ubiquitous bleaching and disinfection agent for almost 200 years. The structures, supported by variable-temperature Raman spectroscopy on individual crystals and periodic density-functional theory (DFT) calculations, provide insight into solid-state geometry and supramolecular chemistry of hypohalite ions.

Layers and Multilayers of Self-Assembled Polymers: Tunable Engineered Extracellular Matrix Coatings for Neural Cell Growth.

Growing primary cells and tissue in long-term cultures, such as primary neural cell culture, presents many challenges. A critical component of any environment that supports neural cell growth in vivo is an appropriate 2-D surface or 3-D scaffold, typically in the form of a thin polymer layer that coats an underlying plastic or glass substrate and aims to mimic critical aspects of the extracellular matrix. A fundamental challenge to mimicking a hydrophilic, soft natural cell environment is that materials with these properties are typically fragile and are difficult to adhere to and stabilize on an underlying plastic or glass cell culture substrate. In this review, we highlight the current state of the art and overview recent developments of new artificial extracellular matrix (ECM) surfaces for in vitro neural cell culture. Notably, these materials aim to strike a balance between being hydrophilic and soft while also being thick, stable, robust, and bound well to the underlying surface to provide an effective surface to support long-term cell growth. We focus on improved surface and scaffold coating systems that can mimic the natural physicochemical properties that enhance neuronal survival and growth, applied as soft hydrophilic polymer coatings for both in vitro cell culture and for implantable neural probes and 3-D matrixes that aim to enhance stability and longevity to promote neural biocompatibility in vivo. With respect to future developments, we outline four emerging principles that serve to guide the development of polymer assemblies that function well as artificial ECMs: (a) design inspired by biological systems and (b) the employment of principles of aqueous soft bonding and self-assembly to achieve (c) a high-water-content gel-like coating that is stable over time in a biological environment and possesses (d) a low modulus to more closely mimic soft, compliant real biological tissue. We then highlight two emerging classes of thick material coatings that have successfully captured these guiding principles: layer-by-layer deposited water-soluble polymers (LbL) and silk fibroin (SF) materials. Both materials can be deposited from aqueous solution yet transition to a water-insoluble coating for long-term stability while retaining a softness and water content similar to those of biological materials. These materials hold great promise as next-generation biocompatible coatings for tissue engineers and for chemists and biologists within the biomedical field.

Shape-Shifting Azo Dye Polymers: Towards Sunlight-Driven Molecular Devices.

The development of stimuli-responsive polymers is among the key goals of modern materials science. The structure and properties of such switchable materials can be designed to be controlled via various stimuli, among which light is frequently the most powerful trigger. Light is a gentle energy source that can target materials remotely, and with extremely high spatial and temporal resolution easily and cheaply. Reversible light-control over molecular mechanical properties in particular has in recent years attracted great interest due to potential applications as optical-to-mechanical conversion actuators and 'devices', enabling 'molecular robotic machines'. In this review, some recent examples and emerging trends in this exciting field of research are highlighted, covering a wide variety of polymer hosts that contain azobenzene photo-reversible switches. It is hoped that this review will help stimulate more interest towards the development of light-reversible materials for energy harvesting and conversion, and their successful incorporation into a wide variety of current and future high-tech applications in devices.

Rapid Mechanically Controlled Rewiring of Neuronal Circuits.

CNS injury may lead to permanent functional deficits because it is still not possible to regenerate axons over long distances and accurately reconnect them with an appropriate target. Using rat neurons, microtools, and nanotools, we show that new, functional neurites can be created and precisely positioned to directly (re)wire neuronal networks. We show that an adhesive contact made onto an axon or dendrite can be pulled to initiate a new neurite that can be mechanically guided to form new synapses at up to 0.8 mm distance in <1 h. Our findings challenge current understanding of the limits of neuronal growth and have direct implications for the development of new therapies and surgical techniques to achieve functional regeneration. Significance statement: Brain and spinal cord injury may lead to permanent disability and death because it is still not possible to regenerate neurons over long distances and accurately reconnect them with an appropriate target. Using microtools and nanotools we have developed a new method to rapidly initiate, elongate, and precisely connect new functional neuronal circuits over long distances. The extension rates achieved are ≥60 times faster than previously reported. Our findings have direct implications for the development of new therapies and surgical techniques to achieve functional regeneration after trauma and in neurodegenerative diseases. It also opens the door for the direct wiring of robust brain-machine interfaces as well as for investigations of fundamental aspects of neuronal signal processing and neuronal function.

Assembly and dichroism of a four-component halogen-bonded metal-organic cocrystal salt solvate involving dicyanoaurate(I) acceptors.

We describe the use of dicyanoaurate ions as linear ditopic metal-organic acceptors for the halogen bond-driven assembly of a dichroic metal-organic cocrystal based on azobenzene chromophores. Structural analysis by single crystal X-ray diffraction revealed that the material is a four-component solid, consisting of anticipated anionic metal-organic halogen-bonded chains based on dicyanoaurate ions, as well as complex potassium-based cations and discrete molecules of the crown ether 15-crown-5. Importantly, the structural analysis revealed the parallel alignment of the halogen-bonded chains required for dichroic behaviour, confirming that crystal engineering principles developed for the design of halogen-bonded dichroic organic cocrystals are also applicable to metal-based structures. In the broader context of crystal engineering, the structure of the herein reported dichroic material is additionally interesting as the presence of an ion pair, a neutral azobenzene and a molecule of a room-temperature liquid make it an example of a solid that simultaneously conforms to definitions of a salt, a cocrystal, and a solvate.

Photo-induced structural modification of silk gels containing azobenzene side groups.

Azobenzene modification of Bombyx mori silkworm silk creates a photo-responsive 'azosilk' biomaterial, allowing for 3D laser patterning. Written regions fluoresce, and become fluid-filled raised 'micro-blisters' with a 10-fold photo-softening effect of the modulus. Patterning is facile and versatile, with potential applications as soft tunable materials for dynamic cell guidance and microfluidics.

The Orange Side of Disperse Red 1: Humidity-Driven Color Switching in Supramolecular Azo-Polymer Materials Based on Reversible Dye Aggregation.

Humidity detection, and the quest for low-cost facile humidity-sensitive indicator materials is of great interest for many fields, including semi-conductor processing, food transport and storage, and pharmaceuticals. Ideal humidity-detection materials for a these applications might be based on simple clear optical readout with no power supply, i.e.: a clear color change observed by the naked eye of any untrained observer, since it doesn't require any extra instrumentation or interpretation. Here, the introduction of a synthesis-free one-step procedure, based on physical mixing of easily available commercial materials, for producing a humidity memory material which can be easily painted onto a wide variety of surfaces and undergoes a remarkable color change (approximately 100 nm blue-shift of λMAX ) upon exposure to various thresholds of levels of ambient humidity is reported. This strong color change, easily visible to as a red-to-orange color switch, is locked in until inspection, but can then be restored reversibly if desired, after moderate heating. By taking advantage of spontaneously-forming reversible 'soft' supramolecular bonds between a red-colored azo dye and a host polymer matrix, a reversible dye 'migration' aggregation appearing orange, and dis-aggregation back to red can be achieved, to function as the sensor.

Planar multilayer assemblies containing block copolymer aggregates.

The design, preparation, and properties of planar multilayer structures composed of various combinations of sequentially deposited polyelectrolyte (PE) chains and self-assembled layers of individual block copolymer aggregates (vesicles, micelles, or large compound micelles (LCMs)) are described. The aggregates contain negatively or positively charged corona chains while the PE multilayers contain alternating polyanionic or polycationic chains deposited on silicon wafers. The final structures consist of combinations of layers of various charged species: multilayers of alternating PEs of poly(allyl hydrochloride) (PAH) and poly(acrylic acid) (PAA) as well as vesicles, micelles, or large compound micelles of ionized poly(styrene)-b-poly(4-vinylpyridine) (PS-b-P4VP) or of poly(styrene)-b-poly(acrylic acid) (PS-b-PAA). Two types of layer-by-layer (LbL) multilayer structures were studied: individual aggregate layers sandwiched between PE multilayers and layers of individual aggregates of various morphologies and of different corona chain charges, deposited on top of each other without intermediate multilayers or individual layers of PEs. The strong interactions between the successive layers are achieved mainly by electrostatic attraction between the oppositely charged layers. The planar LbL multilayers containing block copolymer aggregates could, potentially, be used as carriers for multiple functional components; each aggregate layer could be loaded with hydrophobic (in the core of the micelles, LCMs, or vesicle walls) or hydrophilic functional molecules (in the vesicular cavities). The overall thickness of such planar LbL multilayers can be controlled precisely and can vary from tens of nanometers to several micrometers depending on the number of layers, the sizes of the aggregates, and the complexity of the structure.

Photo-tuning of highly selective wetting in inverse opals.

Crack-free inverse opals exhibit a sharply defined threshold wettability for infiltration that has enabled their use as colourimetric indicators for liquid identification. Here we demonstrate direct and continuous photo-tuning of this wetting threshold in inverse opals whose surfaces are functionalized with a polymer doped with azobenzene chromophores.

Shaping crystals with light: crystal-to-crystal isomerization and photomechanical effect in fluorinated azobenzenes.

Unusually long thermal half-lives of perhalogenated cis-azobenzenes enabled their structural characterization and the first evidence of a crystal-to-crystal cis → trans azobenzene isomerization. Irradiation with visible light transforms a perhalogenated cis-azobenzene single crystal into a polycrystalline aggregate of its trans-isomer in a photomechanical transformation that involves a significant, controllable, and thermally irreversible change of crystal shape. This is the first demonstration of permanent photomechanical modification of crystal shape in an azobenzene.

High levels of molecular orientation of surface azo chromophores can be optically induced even in a wet biological environment.

We have developed polyelectrolyte multilayer bio-films containing azobenzene chromophores that enhance reversible photo-orientation upon irradiation with linearly polarized light, to effect surface photo-switching of adjacent biological systems. When conditions of film preparation and irradiation were optimized, we could observe the highest measured birefringence to date in amorphous systems (Δn > 0.2). This birefringence change to probe orientation was also for the first time measured and determined to be stable completely underwater, permitting optimization for in situ applications immersed in biological conditions.

Production of dimethylfuran for liquid fuels from biomass-derived carbohydrates.

Diminishing fossil fuel reserves and growing concerns about global warming indicate that sustainable sources of energy are needed in the near future. For fuels to be useful in the transportation sector, they must have specific physical properties that allow for efficient distribution, storage and combustion; these properties are currently fulfilled by non-renewable petroleum-derived liquid fuels. Ethanol, the only renewable liquid fuel currently produced in large quantities, suffers from several limitations, including low energy density, high volatility, and contamination by the absorption of water from the atmosphere. Here we present a catalytic strategy for the production of 2,5-dimethylfuran from fructose (a carbohydrate obtained directly from biomass or by the isomerization of glucose) for use as a liquid transportation fuel. Compared to ethanol, 2,5-dimethylfuran has a higher energy density (by 40 per cent), a higher boiling point (by 20 K), and is not soluble in water. This catalytic strategy creates a route for transforming abundant renewable biomass resources into a liquid fuel suitable for the transportation sector, and may diminish our reliance on petroleum.

Direct mechanocatalysis by resonant acoustic mixing (RAM).

We demonstrate the use of a metal surface to directly catalyse copper-catalysed alkyne-azide click-coupling (CuAAC) reactions under the conditions of Resonant Acoustic Mixing (RAM) - a recently introduced and scalable mechanochemical methodology that uniquely eliminates the need for bulk solvent, as well as milling media. By using a simple copper coil as a catalyst, this work shows that direct mechanocatalysis can occur in an impact-free environment, relying solely on high-speed mixing of reagents against a metal surface, without the need for specially designed milling containers and media. By introducing an experimental setup that enables real-time Raman spectroscopy monitoring of RAM processes, we demonstrate 0th-order reaction kinetics for several selected CuAAC reactions, supporting surface-based catalysis. The herein presented RAM-based direct mechanocatalysis methodology is simple, enables the effective one-pot, two-step synthesis of triazoles via a combination of benzyl azide formation and CuAAC reactions on a wide scope of reagents, provides control over reaction stoichiometry that is herein shown to be superior to that seen in solution or by using more conventional CuCl catalyst, and is applied for simple gram-scale synthesis of the anticonvulsant drug Rufinamide.

Halogen bonding with carbon: directional assembly of non-derivatised aromatic carbon systems into robust supramolecular ladder architectures.

Carbon, although the central element in organic chemistry, has been traditionally neglected as a target for directional supramolecular interactions. The design of supramolecular structures involving carbon-rich molecules, such as arene hydrocarbons, has been limited almost exclusively to non-directional π-stacking, or derivatisation with heteroatoms to introduce molecular assembly recognition sites. As a result, the predictable assembly of non-derivatised, carbon-only π-systems using directional non-covalent interactions remains an unsolved fundamental challenge of solid-state supramolecular chemistry. Here, we propose and validate a different paradigm for the reliable assembly of carbon-only aromatic systems into predictable supramolecular architectures: not through non-directional π-stacking, but via specific and directional halogen bonding. We present a systematic experimental, theoretical and database study of halogen bonds to carbon-only π-systems (C-I⋯πC bonds), focusing on the synthesis and structural analysis of cocrystals with diversely-sized and -shaped non-derivatised arenes, from one-ring (benzene) to 15-ring (dicoronylene) polycyclic atomatic hydrocarbons (PAHs), and fullerene C60, along with theoretical calculations and a systematic analysis of the Cambridge Structural Database. This study establishes C-I⋯πC bonds as directional interactions to arrange planar and curved carbon-only aromatic systems into predictable supramolecular motifs. In >90% of herein presented structures, the C-I⋯πC bonds to PAHs lead to a general ladder motif, in which the arenes act as the rungs and halogen bond donors as the rails, establishing a unique example of a supramolecular synthon based on carbon-only molecules. Besides fundamental importance in the solid-state and supramolecular chemistry of arenes, this synthon enables access to materials with exciting properties based on simple, non-derivatised aromatic systems, as seen from large red and blue shifts in solid-state luminescence and room-temperature phosphorescence upon cocrystallisation.

Photoreversible surfaces to regulate cell adhesion.

We report the development of a photoreversible cell culture substrate. We demonstrate the capacity to modify the adhesivity of the substrate using light, altering its capacity to support cell growth. Polyelectrolyte multilayers (PEMs) were used to produce tunable substrates of different thickness and matrix stiffness, which have different intrinsic capacities to support cell adhesion and survival. Surfaces were top-coated with a poly(acrylic acid)-poly(allylamine hydrochloride) polyelectrolyte bilayer functionalized with a small fraction (<1%) of an azobenzene-based photoswitchable sidegroup, which included the cell-adhesive three-amino-acid peptide RGD. Irradiation with light-induced geometric switching of the azo bond, resulting in changes to RGD exposure and consequently to cell adhesion and survival, was investigated on a variety of surfaces of different thickness and stiffness. Substrate stiffness, as modified by the thickness, had a significant influence on the adhesion of NIH 3T3 cells, consistent with previous studies. However, by disrupting the isomerization state of the azobenzene-linked RGD and exposing it to the surface, cell adhesion and survival could be enhanced up to 40% when the positioning of the RGD peptide was manipulated on the softest substrates. These findings identify permissive, yet less-than-optimal, cell culture substrate conditions that can be substantially enhanced using noninvasive modification of the substrate triggered by light. Indeed, where cell adhesion was tuned to be suboptimal under baseline conditions, the light-induced triggers displayed the most enhanced effect, and identification of this 'Goldilocks zone' was key to enabling light triggering.