Organocatalysis in aqueous media van der Helm, Michelle P.; Klemm, Benjamin; Eelkema, Rienk
Nature reviews. Chemistry,
08/2019, Volume:
3, Issue:
8
Journal Article
Peer reviewed
Open access
Even though enzymes are the cornerstones of living systems, it has so far proven difficult to deploy artificial catalysts in a biological setting. Organocatalysts are arguably well-suited artificial ...catalysts for this purpose because, compared with enzymes and inorganic catalysts, they are simpler, often less toxic and widely accessible. This Review describes how organocatalysts that operate in aqueous media might enable us to selectively access new chemical transformations and provide new possibilities for chemical biology and biomedicine. Organocatalysts can be categorized according to the mechanisms by which they activate substrates, drawing comparisons with enzymes. We describe the characteristics of a catalyst that are necessary for biological compatibility and in vivo applicability, and use these to evaluate a selection of organocatalytic reactions. The attributes of the catalyst (such as functional groups and pKa values) and the reaction (such as the microenvironment surrounding intermediates) are key considerations when developing efficient organocatalysis in aqueous media. Although we only know of a limited set of organocatalytic reactions with biological potential, on the basis of recent developments we expect a bright future for organocatalysis in biology, to the benefit of chemical biology and biomedicine.The application of organocatalysis in biology is still in its infancy. In this Review, we evaluate organocatalytic reactions in terms of their applicability in biological settings, including new technologies in chemical biology and biomedicine.
The use of dissipative self-assembly driven by chemical reaction networks for the creation of unique structures is gaining in popularity. In dissipative self-assembly, precursors are converted into ...self-assembling building blocks by the conversion of a source of energy, typically a photon or a fuel molecule. The self-assembling building block is intrinsically unstable and spontaneously reverts to its original precursor, thus giving the building block a limited lifetime. As a result, its presence is kinetically controlled, which gives the associated supramolecular material unique properties. For instance, formation and properties of these materials can be controlled over space and time by the kinetics of the coupled reaction network, they are autonomously self-healing and they are highly adaptive to small changes in their environment. By means of an example of a biological dissipative self-assembled material, the unique concepts at the basis of these supramolecular materials will be discussed. We then review recent efforts towards man-made dissipative assembly of structures and how their unique material properties have been characterized. In order to help further the field, we close with loosely defined design rules that are at the basis of the discussed examples.
This tutorial review focuses on the structural and kinetic design of dissipative self-assembling systems and highlight their resulting unique properties.
Fuel-driven self-assembly of actin filaments and microtubules is a key component of cellular organization. Continuous energy supply maintains these transient biomolecular assemblies far from ...thermodynamic equilibrium, unlike typical synthetic systems that spontaneously assemble at thermodynamic equilibrium. Here, we report the transient self-assembly of synthetic molecules into active materials, driven by the consumption of a chemical fuel. In these materials, reaction rates and fuel levels, instead of equilibrium composition, determine properties such as lifetime, stiffness, and self-regeneration capability. Fibers exhibit strongly nonlinear behavior including stochastic collapse and simultaneous growth and shrinkage, reminiscent of microtubule dynamics.
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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.
Synthetic self‐assembly has long been recognized as an excellent approach for the formation of ordered structures on the nanoscale. Such self‐assembling systems are currently being applied as bioactive materials in biological environments. This up‐and‐coming field, which has the potential of becoming a key area in chemical biology and medicine, is reviewed.
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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.
Spatial control over the self‐assembly of synthetic molecular fibers through the use of light‐switchable catalysts can lead to the controlled formation of micropatterns made up of hydrogel ...structures. A photochromic switch, capable of reversibly releasing a proton upon irradiation, can act as a catalyst for in situ chemical bond formation between otherwise soluble building blocks, thereby leading to fiber formation and gelation in water. The use of a photoswitchable catalyst allows control over the distribution as well as the mechanical properties of the hydrogel material. By using homemade photomasks, spatially structured hydrogels were formed starting from bulk solutions of small molecule gelator precursors through light‐triggered local catalyst activation.
Lighting the way: The spatial distribution and mechanical properties of a low‐molecular‐weight hydrogel can be controlled by using a photoswitchable catalyst for in situ gelator formation. Upon light irradiation, the photochromic compound temporarily lowers the pH of the solution, thereby catalyzing the formation of the of hydrazone gelator. Spatial control over gel formation is accomplished by using a simple photomask to give local catalyst activation.
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While DNA sequencing is now amply available, fast, and inexpensive, protein sequencing remains a tremendous challenge. Nanopores may allow for developing a protein sequencer with single-molecule ...capabilities. As identification of 20 different amino acids currently presents an unsurmountable challenge, fingerprinting schemes are pursued, in which only a subset of amino acids is labeled and detected. This requires modification of amino acids with chemical structures that generate a distinct nanopore ionic current signal. Here, we use a model peptide and the fragaceatoxin C nanopore to characterize six potential tags for a fingerprinting approach using nanopores. We find that labeled and unlabeled proteins can be clearly distinguished and that sensitive detection is obtained for labels with a spectrum of different physicochemical properties such as mass (427–1275 Da), geometry, charge, and hydrophobicity. Additionally, information about the position of the label along the peptide chain can be obtained from individual current-blockade event features. The results represent an important advance toward the development of a single-molecule protein-fingerprinting device with nanopores.
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Transient assembled structures play an indispensable role in a wide variety of processes fundamental to living organisms including cellular transport, cell motility, and proliferation. Typically, the ...formation of these transient structures is driven by the consumption of molecular fuels via dissipative reaction networks. In these networks, building blocks are converted from inactive precursor states to active (assembling) states by (a set of) irreversible chemical reactions. Since the activated state is intrinsically unstable and can be maintained only in the presence of sufficient fuel, fuel depletion results in the spontaneous disintegration of the formed superstructures. Consequently, the properties and behavior of these assembled structures are governed by the kinetics of fuel consumption rather than by their thermodynamic stability. This fuel dependency endows biological systems with unprecedented spatiotemporal adaptability and inherent self-healing capabilities. Fascinated by these unique material characteristics, coupling the assembly behavior to molecular fuel or light-driven reaction networks was recently implemented in synthetic (supra)molecular systems. In this invited feature article, we discuss recent studies demonstrating that dissipative assembly is not limited to the molecular world but can also be translated to building blocks of colloidal dimensions. We highlight crucial guiding principles for the successful design of dissipative colloidal systems and illustrate these with the current state of the art. Finally, we present our vision on the future of the field and how marrying nonequilibrium self-assembly with the functional properties associated with colloidal building blocks presents a promising route for the development of next-generation materials.
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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.
Biomimetic strain‐stiffening hydrogels have been prepared through the self‐assembly of molecular gelators. On the basis of orthogonal self‐assembly of the molecular gelators and lipids, hydrogel networks embedded with liposomes are formed and show strain‐stiffening behavior as well, resembling both the structures and mechanical responsiveness of biological tissue.
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The amplification of molecular chirality by liquid crystalline systems is widely applied in investigations towards enantioselective solvent-solute interactions, chiral supramolecular assemblies, ...smart materials, and the development of liquid crystal displays. Here we present an overview of recent achievements in the development of new chiral dopant systems for the generation of cholesteric liquid crystalline phases. Based on a distinction between shape-persistent and bistable dopants, several dopant classes will be discussed.
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