Miller–Urey Spark‐Discharge Experiments in the Deuterium World

We designed and conducted a series of primordial‐soup Miller‐Urey style experiments with deuterated gases and reagents to compare the spark‐discharge products of a “deuterated world” with the standard reaction in the “hydrogenated world”. While the deuteration of the system has little effect on the distribution of amino acid products, significant differences are seen in other regions of the product‐space. Not only do we observe about 120 new species, we also see significant differences in their distribution if the two hydrogen isotope worlds are compared. Several isotopologue matches can be identified in both, but a large proportion of products have no equivalent in the corresponding isotope world with ca. 43 new species in the D world and ca. 39 new species in the H world. This shows that isotopic exchange (the addition of only one neutron) may lead to significant additional complexity in chemical space under otherwise identical reaction conditions.     

Dynamic Cooperative Glycan Assembly Blocks the Binding of Bacterial Lectins to Epithelial Cells

Pathogens frequently rely on lectins for adhesion and cellular entry into the host. Since these interactions typically result from multimeric binding of lectins to cell‐surface glycans, novel therapeutic strategies are being developed with the use of glycomimetics as competitors of such interactions. Herein we study the benefit of nucleic acid based oligomeric assemblies with PNA–fucose conjugates. We demonstrate that the interactions of a lectin with epithelial cells can be inhibited with conjugates that do not form stable assemblies in solution but benefit from cooperativity between ligand–protein interactions and PNA hybridization to achieve high affinity. A dynamic dimeric assembly fully blocked the binding of the fucose‐binding lectin BambL of Burkholderia ambifaria , a pathogenic bacterium, to epithelial cells with an efficiency of more than 700‐fold compared to l ‐fucose.     

Individual‐Molecule Perspective Analysis of Chemical Reaction Networks: The Case of a Light‐Driven Supramolecular Pump

The first study in which stochastic simulations of a two‐component molecular machine are performed in the mass‐action regime is presented. This system is an autonomous molecular pump consisting of a photoactive axle that creates a directed flow of rings through it by exploiting light energy away from equilibrium. The investigation demonstrates that the pump can operate in two regimes, both experimentally accessible, in which light‐driven steps can be rate‐determining or not. The number of photons exploited by an individual molecular pump, as well as the precision of cycling and the overall efficiency, critically rely on the operating regime of the machine. This approach provides useful information not only to guide the chemical design of a self‐assembling molecular device with desired features, but also to elucidate the effect of the environment on its performance, thus facilitating its experimental investigation.     

Chemically Fueled Dissipative Self‐Assembly that Exploits Cooperative Catalysis

In living systems, dissipative processes are driven by the endergonic hydrolysis of chemical fuels such as nucleoside triphosphates. Now, through a simple model system, a transient self‐assembled state is realized by utilizing the catalytic effect of histidine on the formation and breaking of ester bonds. First, histidine facilitates the ester bond formation, which then rapidly co‐assembles to form a self‐supporting gel. An out‐of‐equilibrium state is realized owing to the cooperative catalysis by the proximal histidines in the assembled state, driving the second pathway and resulting in disassembly to sol. Cooperative effects that use the dual role of imidazoles as nucleophile and as proton donor is utilized to achieve transient assemblies. This simple system mimics the structural journey seen in microtubule formation where the substrate GTP facilitates the non‐covalent assembly and triggers a cooperative catalytic process, leading to substrate hydrolysis and subsequent disassembly.