Chemical reaction networks based on conjugate additions on β′-substituted Michael acceptors

Over the last few decades, the study of more complex, chemical systems closer to those found in nature, and the interactions within those systems, has grown immensely. Despite great efforts, the need for new, versatile, and robust chemistry to apply in CRNs remains. In this Feature Article, we give a brief overview over previous developments in the field of systems chemistry and how β′-substituted Michael acceptors (MAs) can be a great addition to the systems chemist's toolbox. We illustrate their versatility by showcasing a range of examples of applying β′-substituted MAs in CRNs, both as chemical signals and as substrates, to open up the path to many applications ranging from responsive materials, to pathway control in CRNs, drug delivery, analyte detection, and beyond.ChemE/Advanced Soft Matte

On-Demand Release of Secondary Amine Bases for the Activation of Catalysts and Crosslinkers

Dynamic covalent (DCv) ureas have been used abundantly to design self-healing materials. We demonstrate that apart from self-healing materials, the species present in the equilibrium of DCv ureas can be employed as responsive organocatalysts. Easily controllable stimuli like heat or addition of water shift the equilibrium towards isocyanate and free base which can function as an in situ released reagent. We demonstrate this application of DCv ureas with two examples. Firstly, we use the liberated base to catalytically activate a latent organocatalyst for acylhydrazone formation. Secondly, this base can be employed in an equimolar manner to trigger the release of nitrile-N-oxides from chlorooximes, which react with acrylate-terminated polymers to form an isoxazoline polymer gel.ChemE/Advanced Soft Matte

Catalytic control over the formation of supramolecular materials

In this Perspective, we will discuss how the rate of formation of supramolecular materials can be drastically enhanced by catalytically controlling the rate of formation of their molecular building blocks, resulting in the formation of out-of-equilibrium soft materials with enhanced mechanical properties. Also, the use of surface confined, patterned catalysts allows spatial control over self-assembly, which can be applied to the formation of regular, micrometer sized hydrogel patterns. Catalysis has been applied for decades as an indispensable tool in the synthesis of both simple and highly complex molecules and polymers, ranging from milligram lab-scale to multi-ton industrial processes. However, despite being widespread in nature, until recently the use of catalysis to control the formation of supramolecular materials has remained limited. We will demonstrate the large potential of using catalysis as a tool in the construction of soft materials, illustrated by recent developments.Chemical EngineeringApplied Science

Selective activation of organocatalysts by specific signals

Reminiscent of signal transduction in biological systems, artificial catalysts whose activity can be controlled by physical or chemical signals would be of high interest in the design of chemical systems that can respond to their environment. Self-immolative chemistry offers a generic method for the development of catalysts that can be activated by different signals. To demonstrate the versatility of that concept, we synthesized organocatalysts that can be activated by three different signals and that can be used to control two different reactions. In this way the organocatalyst proline is designed as a pro-catalyst that is activated either by the chemical signal H2O2, by light or by the enzyme penicillin acylase. The pro-catalysts were used to exert temporal control over the rate of an aldol reaction and a Michael reaction.ChemE/Advanced Soft Matte

Out-of-Equilibrium Assembly Based on Host–Guest Interactions

The field of supramolecular chemistry is rapidly progressing, transitioning from the creation of thermodynamically stable systems found in local or global minima on the free energy landscape to the development of out-of-equilibrium systems that rely on chemical reactions to establish and maintain their structures. Over the past decade, numerous artificial out-of-equilibrium systems have been devised in various domains of supramolecular chemistry, many of which have been extensively reviewed. However, one area that has received limited attention thus far is the use of out-of-equilibrium processes to regulate host–guest interactions. This minireview aims to address this gap by exploring the construction of out-of-equilibrium systems based on host–guest complexation, which likely employs similar strategies to those employed in analogous noncovalent interactions. The review begins with a summary of these shared strategies. Subsequently, it discusses representative publications that exemplify these strategies and classifies them based on which component is being modulated–host, guest, or competitive molecules. Through this examination, our objective is to shed light on the design of out-of-equilibrium systems relying on host–guest interactions and provide valuable insights into the preparation strategies for various transient materials.ChemE/Advanced Soft Matte

Synthetic Self-Assembled Materials in Biological Environments

Synthetic self-assembly has long been recognized as an excellent approach for the formation of ordered structures on the nanoscale. Although the development of synthetic self-assembling materials has often been inspired by principles observed in nature (e.g., the assembly of lipids, DNA, proteins), until recently the self-assembly of synthetic molecules has mainly been investigated ex vivo. The past few years however, have witnessed the emergence of a research field in which synthetic, self-assembling systems are used that are capable of operating as bioactive materials in biological environments. Here, this up-and-coming field, which has the potential of becoming a key area in chemical biology and medicine, is reviewed. Two main categories of applications of self-assembly in biological environments are identified and discussed, namely therapeutic and imaging agents. Within these categories key concepts, such as triggers and molecular constraints for in vitro/in vivo self-assembly and the mode of interaction between the assemblies and the biological materials will be discussed.ChemE/Advanced Soft Matte

Fuel-driven macromolecular coacervation in complex coacervate core micelles

Fuel-driven macromolecular coacervation is an entry into the transient formation of highly charged, responsive material phases. In this work, we used a chemical reaction network (CRN) to drive the coacervation of macromolecular species readily produced using radical polymerisation methods. The CRN enables transient quaternization of tertiary amine substrates, driven by the conversion of electron deficient allyl acetates and thiol or amine nucleophiles. By incorporating tertiary amine functionality into block copolymers, we demonstrate chemical triggered complex coacervate core micelle (C3M) assembly and disassembly. In contrast to most dynamic coacervate systems, this CRN operates at constant physiological pH without the need for complex biomolecules. By varying the allyl acetate fuel, deactivating nucleophile and reagent ratios, we achieved both sequential signal-induced C3M (dis)assembly, as well as transient non-equilibrium (dis)assembly. We expect that timed and signal-responsive control over coacervate phase formation at physiological pH will find application in nucleic acid delivery, nano reactors and protocell research.ChemE/Advanced Soft Matte

Self-Healing Injectable Polymer Hydrogel via Dynamic Thiol-Alkynone Double Addition Cross-Links

Introduction of dynamic thiol-alkynone double addition cross-links in a polymer network enable the formation of a self-healing injectable polymer hydrogel. A four-arm polyethylene glycol (PEG) tetra-thiol star polymer is cross-linked by a small molecule alkynone via the thiol-alkynone double adduct to generate a hydrogel network under ambient aqueous conditions (buffer pH = 7.4 or 8.2, room temperature). The mechanical properties of these hydrogels can be easily tuned by varying the concentration of polymer precursors. Through the dynamic thiol-alkynone double addition cross-link, these hydrogels are self-healing and shear thinning, as demonstrated by rheological measurements, macroscopic self-healing, and injection tests. These hydrogels can be injected through a 20G syringe needle and recover after extrusion. In addition, good cytocompatibility of these hydrogels is confirmed by cytotoxicity test. This work shows the application of the thiol-alkynone double addition dynamic covalent chemistry in the straightforward preparation of self-healing injectable hydrogels, which may find future biomedical applications such as tissue engineering and drug delivery.ChemE/Advanced Soft MatterChemE/Product and Process Engineerin

Temporally programmed polymer – solvent interactions using a chemical reaction network

Out of equilibrium operation of chemical reaction networks (CRNs) enables artificial materials to autonomously respond to their environment by activation and deactivation of intermolecular interactions. Generally, their activation can be driven by various chemical conversions, yet their deactivation to non-interacting building blocks remains largely limited to hydrolysis and internal pH change. To achieve control over deactivation, we present a new, modular CRN that enables reversible formation of positive charges on a tertiary amine substrate, which are removed using nucleophilic signals that control the deactivation kinetics. The modular nature of the CRN enables incorporation in diverse polymer materials, leading to a temporally programmed transition from collapsed and hydrophobic to solvated, hydrophilic polymer chains by controlling polymer-solvent interactions. Depending on the layout of the CRN, we can create stimuli-responsive or autonomously responding materials. This concept will not only offer new opportunities in molecular cargo delivery but also pave the way for next-generation interactive materials.ChemE/Advanced Soft Matte

Gamma Radiation Induced Contraction of Alkyne Modified Polymer Hydrogels

Gamma radiation triggered secondary crosslinking of dextran hydrogels leads to macroscopic hydrogel contraction. The authors use stable polymer hydrogels, prepared through azide-alkyne crosslinking, containing surplus alkyne groups. γ-irradiation of these gels leads to more alkyne crosslinking, enabling controlled increase of crosslink density, which in turn leads to an increase of hydrogel stiffness and macroscopic hydrogel contraction. Gel contraction scales linearly with the applied radiation dose. The same mechanism is applied to achieve γ-radiation triggered release of the small molecule cargo, akin to wringing out a sponge. γ-irradiation of touching hydrogel objects leads to gel fusion and the formation of a self-supporting gel connection, demonstrating the reactivity of the excess alkyne groups. They envision applications in gel gluing and the construction of complex gel architectures, as well as in responsive materials for controlled release.ChemE/Advanced Soft MatterRST/Applied Radiation & Isotope