Tuneable Control of Organocatalytic Activity through Host-Guest Chemistry.

Dynamic regulation of chemical reactivity is important in many complex chemical reaction networks, such as cascade reactions and signal transduction processes. Signal responsive catalysts could play a crucial role in regulating these reaction pathways. Recently, supramolecular encapsulation was reported to regulate the activities of artificial catalysts. We present a host-guest chemistry strategy to modulate the activity of commercially available synthetic organocatalysts. The molecular container cucurbit[7]uril was successfully applied to change the activity of four different organocatalysts and one initiator, enabling up- or down-regulation of the reaction rates of four different classes of chemical reactions. In most cases CB[7] encapsulation results in catalyst inhibition, however in one case catalyst activation by binding to CB[7] was observed. The mechanism behind this unexpected behavior was explored by NMR binding studies and pKa measurements. The catalytic activity can be instantaneously switched during operation, by addition of either supramolecular host or competitive binding molecules, and the reaction rate can be predicted with a kinetic model. Overall, this signal responsive system proves a promising tool to control catalytic activity.

Biomimetic Strain-Stiffening Self-Assembled Hydrogels.

Supramolecular structures with strain-stiffening properties are ubiquitous in nature but remain rare in the lab. Herein, we report on strain-stiffening supramolecular hydrogels that are entirely produced through the self-assembly of synthetic molecular gelators. The involved gelators self-assemble into semi-flexible fibers, which thereby crosslink into hydrogels. Interestingly, these hydrogels are capable of stiffening in response to applied stress, resembling biological intermediate filaments system. Furthermore, strain-stiffening hydrogel networks embedded with liposomes are constructed through orthogonal self-assembly of gelators and phospholipids, mimicking biological tissues in both architecture and mechanical properties. This work furthers the development of biomimetic soft materials with mechanical responsiveness and presents potentially enticing applications in diverse fields, such as tissue engineering, artificial life, and strain sensors.

Hierarchically Compartmentalized Supramolecular Gels through Multilevel Self-Sorting.

Hierarchical compartmentalization through the bottom-up approach is ubiquitous in living cells but remains a formidable task in synthetic systems. Here we report on hierarchically compartmentalized supramolecular gels that are spontaneously formed by multilevel self-sorting. Two types of molecular gelators are formed in situ from nonassembling building blocks and self-assemble into distinct gel fibers through a kinetic self-sorting process; interestingly, these distinct fibers further self-sort into separated microdomains, leading to microscale compartmentalized gel networks. Such spontaneously multilevel self-sorting systems provide a "bottom-up" approach toward hierarchically structured functional materials and may play a role in intracellular organization.

Control over the formation of supramolecular material objects using reaction-diffusion.

Controlled diffusion, reaction and assembly of hydrogelator precursors can be used to create soft hydrogel objects of defined shape and size. In this study we show that controlling local reaction kinetics by means of pH, diffusion length and the concentrations of reactants allows control over the dimensions of formed supramolecular structures. By correlating a reaction diffusion model to experimental results, we show that the influence of all these control parameters can be unified using the Damköhler number, thus providing an easy-to-use relation between experimental parameters and structure dimensions. Finally, our study suggests that control over concentration gradients and chemical reactivity in combination with supramolecular chemistry is a promising platform for the design of soft matter objects of defined sizes, a concept that has received little attention up until now.

Access to Metastable Gel States Using Seeded Self-Assembly of Low-Molecular-Weight Gelators.

Here we report on how metastable supramolecular gels can be formed through seeded self-assembly of multicomponent gelators. Hydrazone-based gelators decorated with non-ionic and anionic groups are formed in situ from hydrazide and aldehyde building blocks, and lead through multiple self-sorting processes to the formation of heterogeneous gels approaching thermodynamic equilibrium. Interestingly, the addition of seeds composing of oligomers of gelators bypasses the self-sorting processes and accelerates the self-assembly along a kinetically favored pathway, resulting in homogeneous gels of which the network morphologies and gel stiffness are markedly different from the thermodynamically more stable gel products. Importantly, over time, these metastable homogeneous gel networks are capable of converting into the thermodynamically more stable state. This seeding-driven formation of out-of-equilibrium supramolecular structures is expected to serve as a simple approach towards functional materials with pathway-dependent properties.

Catalysis of Supramolecular Hydrogelation.

One often thinks of catalysts as chemical tools to accelerate a reaction or to have a reaction run under more benign conditions. As such, catalysis has a role to play in the chemical industry and in lab scale synthesis that is not to be underestimated. Still, the role of catalysis in living systems (cells, organisms) is much more extensive, ranging from the formation and breakdown of small molecules and biopolymers to controlling signal transduction cascades and feedback processes, motility, and mechanical action. Such phenomena are only recently starting to receive attention in synthetic materials and chemical systems. "Smart" soft materials could find many important applications ranging from personalized therapeutics to soft robotics to name but a few. Until recently, approaches to control the properties of such materials were largely dominated by thermodynamics, for instance, looking at phase behavior and interaction strength. However, kinetics plays a large role in determining the behavior of such soft materials, for instance, in the formation of kinetically trapped (metastable) states or the dynamics of component exchange. As catalysts can change the rate of a chemical reaction, catalysis could be used to control the formation, dynamics, and fate of supramolecular structures when the molecules making up these structures contain chemical bonds whose formation or exchange are susceptible to catalysis. In this Account, we describe our efforts to use synthetic catalysts to control the properties of supramolecular hydrogels. Building on the concept of synthesizing the assembling molecule in the self-assembly medium from nonassembling precursors, we will introduce the use of catalysis to change the kinetics of assembler formation and thereby the properties of the resulting material. In particular, we will focus on the synthesis of supramolecular hydrogels where the use of a catalyst provides access to gel materials with vastly different appearance and mechanical properties or controls localized gel formation and the growth of gel objects. As such, catalysis will be applied to create molecular materials that exist outside of chemical equilibrium. In all, using catalysts to control the properties of soft materials constitutes a new avenue for catalysis far beyond the traditional use in industrial and lab scale synthesis.

An Implantable Artificial Atherosclerotic Plaque as a Novel Approach for Drug Transport Studies on Drug-Eluting Stents.

Atherosclerotic arteries are commonly treated using drug-eluting stents (DES). However, it remains unclear whether and how the properties of atherosclerotic plaque affect drug transport in the arterial wall. A limitation of the currently used atherosclerotic animal models to study arterial drug distribution is the unpredictability of plaque size, composition, and location. In the present study, the aim is to create an artificial atherosclerotic plaque-of reproducible and controllable complexity and implantable at specific locations-to enable systematic studies on transport phenomena of drugs in stented atherosclerosis-mimicking arteries. For this purpose, mixtures of relevant lipids at concentrations mimicking atherosclerotic plaque are incorporated in gelatin/alginate hydrogels. Lipid-free (control) and lipid-rich hydrogels (artificial plaque) are created, mounted on DES and successfully implanted in porcine coronary arteries ex-vivo. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is used to measure local drug distribution in the arterial wall behind the prepared hydrogels, showing that the lipid-rich hydrogel significantly hampers drug transport as compared to the lipid-free hydrogel. This observation confirms the importance of studying drug transport phenomena in the presence of lipids and of having an experimental model in which lipids and other plaque constituents can be precisely controlled and systematically studied.

Transient Supramolecular Hydrogels Formed by Aging-Induced Seeded Self-Assembly of Molecular Hydrogelators.

Here, transient supramolecular hydrogels that are formed through simple aging-induced seeded self-assembly of molecular gelators are reported. In the involved molecular self-assembly system, multicomponent gelators are formed from a mixture of precursor molecules and, typically, can spontaneously self-assemble into thermodynamically more stable hydrogels through a multilevel self-sorting process. In the present work, it is surprisingly found that one of the precursor molecules is capable of self-assembling into nano-sized aggregates upon a gentle aging treatment. Importantly, these tiny aggregates can serve as seeds to force the self-assembly of gelators along a kinetically controlled pathway, leading to transient hydrogels that eventually spontaneously convert into thermodynamically more stable hydrogels over time. Such an aging-induced seeded self-assembly process is not only a new route toward synthetic out-of-equilibrium supramolecular systems, but also suggests the necessity of reporting the age of self-assembling building block solutions in other self-assembly systems.

Erratum: Free-standing supramolecular hydrogel objects by reaction-diffusion.

This corrects the article DOI: 10.1038/ncomms15317.

Real-time volumetric lipid imaging in vivo by intravascular photoacoustics at 20 frames per second.

Lipid deposition can be assessed with combined intravascular photoacoustic/ultrasound (IVPA/US) imaging. To date, the clinical translation of IVPA/US imaging has been stalled by a low imaging speed and catheter complexity. In this paper, we demonstrate imaging of lipid targets in swine coronary arteries in vivo, at a clinically useful frame rate of 20 s-1. We confirmed image contrast for atherosclerotic plaque in human samples ex vivo. The system is on a mobile platform and provides real-time data visualization during acquisition. We achieved an IVPA signal-to-noise ratio of 20 dB. These data show that clinical translation of IVPA is possible in principle.

Free-standing supramolecular hydrogel objects by reaction-diffusion.

Self-assembly provides access to a variety of molecular materials, yet spatial control over structure formation remains difficult to achieve. Here we show how reaction-diffusion (RD) can be coupled to a molecular self-assembly process to generate macroscopic free-standing objects with control over shape, size, and functionality. In RD, two or more reactants diffuse from different positions to give rise to spatially defined structures on reaction. We demonstrate that RD can be used to locally control formation and self-assembly of hydrazone molecular gelators from their non-assembling precursors, leading to soft, free-standing hydrogel objects with sizes ranging from several hundred micrometres up to centimeters. Different chemical functionalities and gradients can easily be integrated in the hydrogel objects by using different reactants. Our methodology, together with the vast range of organic reactions and self-assembling building blocks, provides a general approach towards the programmed fabrication of soft microscale objects with controlled functionality and shape.