Nature uses catalysis as an indispensable tool to control assembly and reaction cycles in vital non-equilibrium supramolecular processes. For instance, enzymatic methionine oxidation regulates actin (dis)assembly, and catalytic guanosine triphosphate hydrolysis is found in tubulin (dis)assembly. Here we present a completely artificial reaction cycle which is driven by a chemical fuel that is catalytically obtained from a 'pre-fuel'. The reaction cycle controls the disassembly and re-assembly of a hydrogel, where the rate of pre-fuel turnover dictates the morphology as well as the mechanical properties. By adding additional fresh aliquots of fuel and removing waste, the hydrogels can be reprogrammed time after time. Overall, we show how catalysis can control fuel generation to control reaction / assembly kinetics and materials properties in lifelike non-equilibrium systems. File list (4) download file view on ChemRxiv REV_SachCHO_20191221_Chemrxiv.pdf (1.38 MiB) download file view on ChemRxiv REV_SI_SachCHO_20191221_GF_v2.pdf (1.37 MiB) download file view on ChemRxiv Video1_gel-sol-gel_vial.mp4 (109.69 MiB) download file view on ChemRxiv Video2_microscopy.mp4 (62.71 MiB)

Fuel‐driven reaction cycles are found in biological systems to control the assembly and disassembly of supramolecular materials such as the cytoskeleton. Fuel molecules can bind noncovalently to a self‐assembling building block or they can react with it, resulting in covalent modifications. Overall the fuel can either switch the self‐assembly process on or off. Here, a closer look is taken at artificial systems that mimic biological systems by making and breaking covalent bonds in a self‐assembling motif. The different chemistries used so far are highlighted in chronological order and the pros and cons of each system are discussed. Moreover, the desired traits of future reaction cycles, their fuels, and waste management are outlined, and two chemistries that have not been explored up to now in chemically fueled dissipative self‐assembly are suggested.

Supramolecular polymerization can be controlled in space and time by chemical fuels. A nonassembled monomer is activated by the fuel and subsequently self-assembles into a polymer. Deactivation of the molecule either in solution or inside the polymer leads to disassembly. Whereas biology has already mastered this approach, fully artificial examples have only appeared in the past decade. Here, we map the available literature examples into four distinct regimes depending on their activation/deactivation rates and the equivalents of deactivating fuel. We present increasingly complex mathematical models, first considering only the chemical activation/deactivation rates (i.e., transient activation) and later including the full details of the isodesmic or cooperative supramolecular processes (i.e., transient self-assembly). We finish by showing that sustained oscillations are possible in chemically fueled cooperative supramolecular polymerization and provide mechanistic insights. We hope our models encourage the quantification of activation, deactivation, assembly, and disassembly kinetics in future studies.

Nature uses catalysis as an indispensable tool to control assembly and reaction cycles in vital non-equilibrium supramolecular processes. For instance, enzymatic methionine oxidation regulates actin (dis)assembly, and catalytic guanosine triphosphate hydrolysis is found in tubulin (dis)assembly. Here we present a completely artificial reaction cycle which is driven by a chemical fuel that is catalytically obtained from a ‘pre-fuel’. The reaction cycle controls the disassembly and re-assembly of a hydrogel, where the rate of pre-fuel turnover dictates the morphology as well as the mechanical properties. By adding additional fresh aliquots of fuel and removing waste, the hydrogels can be re-programmed time after time. Overall, we show how catalysis can control fuel generation to control reaction / assembly kinetics and materials properties in life-like non-equilibrium systems.

Nature uses catalysis as an indispensable tool to control assembly and reaction cycles in vital non-equilibrium supramolecular processes. For instance, enzymatic methionine oxidation regulates actin (dis)assembly, and catalytic guanosine triphosphate hydrolysis is found in tubulin (dis)assembly. Here we present a completely artificial reaction cycle which is driven by a chemical fuel that is catalytically obtained from a ‘pre-fuel’. The reaction cycle controls the disassembly and re-assembly of a hydrogel, where the rate of pre-fuel turnover dictates the morphology as well as the mechanical properties. By adding additional fresh aliquots of fuel and removing waste, the hydrogels can be re-programmed time after time. Overall, we show how catalysis can control fuel generation to control reaction / assembly kinetics and materials properties in life-like non-equilibrium systems.

Supramolecular polymerization can be controlled in space and time by chemical fuels. A non-assembled monomer is activated by the fuel and subsequently self-assembles into a polymer. Deactivation of the molecule either in solution or inside the polymer leads to disassembly. Whereas biology has already mastered this approach, fully artificial examples have only appeared in the past decade. Here, we map the available literature examples into four distinct regimes depending on their activation/deactivation rates and the equivalents of deactivating fuel. We present increasingly complex mathematical models, first considering only the chemical activation/deactivation rates (i.e., Transient Activation), and later including the full details of the isodesmic or cooperative supramolecular processes (i.e., Transient Self-assembly). We finish by showing that sustained oscillations are possible in chemically fueled cooperative supramolecular polymerization and provide mechanistic insights. We hope our models encourage the exact quantification of activation, deactivation, assembly, and disassembly kinetics in future studies.

Nature uses catalysis as an indispensable tool to control assembly and reaction cycles in vital non-equilibrium supramolecular processes. For instance, enzymatic methionine oxidation regulates actin (dis)assembly, and catalytic guanosine triphosphate hydrolysis is found in tubulin (dis)assembly. Here we present a completely artificial reaction cycle which is driven by a chemical fuel that is catalytically obtained from a ‘pre-fuel’. The reaction cycle controls the disassembly and re-assembly of a hydrogel, where the rate of pre-fuel turnover dictates the morphology as well as the mechanical properties. By adding additional fresh aliquots of fuel and removing waste, the hydrogels can be re-programmed time after time. Overall, we show how catalysis can control fuel generation to control reaction / assembly kinetics and materials properties in life-like non-equilibrium systems.

Targeting RNA using small molecules is now established as a very promising strategy for many therapeutic applications since coding and non‐coding RNAs bear a pivotal role both in viral and bacterial infections as well as in diseases such as cancer. Here, we focused on HIV‐1 TAR RNA as a promising target for the development of new anti‐HIV therapies but also as an ideal model to validate the discovery of original RNA ligands. First, we performed an initial screening of a library of compounds against TAR that led to the discovery of verapamil, a marketed calcium‐channel blocker, as a promising chemical structure for the development of new RNA ligands. The synthesis of a series of analogs of verapamil led to promising structure activity relationships and to the discovery of a conjugate between verapamil and an indole fragment, as an efficient and selective TAR binder able to inhibit Tat/TAR interaction with an IC50 of 18.8 μM. This work supports the potential of library screening for the discovery of original and selective RNA ligands and illustrates how existing drugs directed against protein targets still need to be studied for RNA binding as a promising strategy in the field of RNA targeting by small molecules.