Responsive organocatalysis in soft materials

Cells react to the environment by changing the activity of enzymes. Catalysts, such as enzymes, speed up reaction rates by lowering the activation energy of the reaction. Changing reaction rates by altering enzyme activity is used to temporarily increase the production of, for instance, a hormone or to change the mechanical properties of a cell. Control over enzyme activity is achieved in two different ways: by covalent modifications (e.g. phosphorylation) and by non-covalent interactions (allosteric enzymes). In this thesis we describe how we designed signal-responsive catalysts and used them to introduce signal response in artificial materials. Inspired by nature we developed a covalent and a noncovalent method to design catalysts that can react to signals from their environment. To design covalently protected catalysts we used self-immolative chemistry. A self-immolative molecule contains a signal-labile functional group. When this group reacts with the signal, the molecule fragments and releases a molecule of interest, in our case a catalyst.ChemE/Advanced Soft Matte

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

Aniline Catalysed Hydrazone Formation Reactions Show a Large Variation in Reaction Rates and Catalytic Effects

Hydrazone formation reactions from aldehydes and hydrazides have the remarkable qualities that they proceed in water and the kinetics can be controlled by organocatalysis. For these reasons, this class of reactions finds widespread use in biological as well as material settings. We recently reported a protected aniline catalyst for hydrazone formation that can be activated using a chemical signal. In our search to find a suitable hydrazone formation reaction to investigate the activation of this pro-catalyst, we found a wide variety in reaction rates and response to catalysis. Here we report an overview of hydrazone formation reactions, their reaction rates and response to aniline catalysis, their compatibility for kinetic analysis by UV/Vis spectroscopy, and their compatibility with the reaction environment and with the pro-catalyst pro-aniline.</p

Aniline Catalysed Hydrazone Formation Reactions Show a Large Variation in Reaction Rates and Catalytic Effects

Hydrazone formation reactions from aldehydes and hydrazides have the remarkable qualities that they proceed in water and the kinetics can be controlled by organocatalysis. For these reasons, this class of reactions finds widespread use in biological as well as material settings. We recently reported a protected aniline catalyst for hydrazone formation that can be activated using a chemical signal. In our search to find a suitable hydrazone formation reaction to investigate the activation of this pro-catalyst, we found a wide variety in reaction rates and response to catalysis. Here we report an overview of hydrazone formation reactions, their reaction rates and response to aniline catalysis, their compatibility for kinetic analysis by UV/Vis spectroscopy, and their compatibility with the reaction environment and with the pro-catalyst pro-aniline.ChemE/Advanced Soft Matte

Chemical signal activation of an organocatalyst enables control over soft material formation

Cells can react to their environment by changing the activity of enzymes in response to specific chemical signals. Artificial catalysts capable of being activated by chemical signals are rare, but of interest for creating autonomously responsive materials. We present an organocatalyst that is activated by a chemical signal, enabling temporal control over reaction rates and the formation of materials. Using self-immolative chemistry, we design a deactivated aniline organocatalyst that is activated by the chemical signal hydrogen peroxide and catalyses hydrazone formation. Upon activation of the catalyst, the rate of hydrazone formation increases 10-fold almost instantly. The responsive organocatalyst enables temporal control over the formation of gels featuring hydrazone bonds. The generic design should enable the use of a large range of triggers and organocatalysts, and appears a promising method for the introduction of signal response in materials, constituting a first step towards achieving communication between artificial chemical systems.ChemE/Advanced Soft Matte

Catalysis of Supramolecular Hydrogelation

ConspectusOne 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.ChemE/Advanced Soft Matte

Negatively Charged Lipid Membranes Catalyze Supramolecular Hydrogel Formation.

In this contribution we show that biological membranes can catalyze the formation of supramolecular hydrogel networks. Negatively charged lipid membranes can generate a local proton gradient, accelerating the acid-catalyzed formation of hydrazone-based supramolecular gelators near the membrane. Synthetic lipid membranes can be used to tune the physical properties of the resulting multicomponent gels as a function of lipid concentration. Moreover, the catalytic activity of lipid membranes and the formation of gel networks around these supramolecular structures are controlled by the charge and phase behavior of the lipid molecules. Finally, we show that the insights obtained from synthetic membranes can be translated to biological membranes, enabling the formation of gel fibers on living HeLa cells.</p

Negatively Charged Lipid Membranes Catalyze Supramolecular Hydrogel Formation.

In this contribution we show that biological membranes can catalyze the formation of supramolecular hydrogel networks. Negatively charged lipid membranes can generate a local proton gradient, accelerating the acid-catalyzed formation of hydrazone-based supramolecular gelators near the membrane. Synthetic lipid membranes can be used to tune the physical properties of the resulting multicomponent gels as a function of lipid concentration. Moreover, the catalytic activity of lipid membranes and the formation of gel networks around these supramolecular structures are controlled by the charge and phase behavior of the lipid molecules. Finally, we show that the insights obtained from synthetic membranes can be translated to biological membranes, enabling the formation of gel fibers on living HeLa cells

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.ChemE/Advanced Soft Matte