Multifunctional Cationic PeptoStars as siRNA Carrier: Influence of Architecture and Histidine Modification on Knockdown Potential

RNA interference provides enormous potential for the treatment of several diseases, including cancer. Nevertheless, successful therapies based on siRNA require overcoming various challenges, such as poor pharmacokinetic characteristics of the small RNA molecule and inefficient cytosolic accumulation. In this respect, the development of functional siRNA carrier systems is a major task in biomedical research. To provide such a desired system, the synthesis of 3‐arm and 6‐arm PeptoStars is aimed for. The different branched polypept(o)idic architectures share a stealth‐like polysarcosine corona for efficient shielding and a multifunctional polylysine core, which can be independently varied in size and functionality for siRNA complexation‐, transport and intra cellular release. The special feature of star‐like polypept(o)ides is in their uniform small size (<20 nm) and a core–shell structure, which implies a high stability and stealth‐like properties and thus, they may combine long circulation times and a deep penetration of cancerous tissue. Initial toxicity and complement studies demonstrate well tolerated cationic PeptoStars with high complexation capability toward siRNA (N/P ratio up to 3:1), which can lead to potent RNAi for optimized systems. Here, the synthetic development of 3‐arm and 6‐arm polypept(o)idic star polymers, their modification with endosomolytic moieties, and first in vitro insights on RNA interference are reported on.     

Tetrazole Azasydnone (C2N7O2H) And Its Salts: High-Performing Zwitterionic Energetic Materials Containing A Unique Explosophore

This work reports the first compound containing both a tetrazole and an azasydnone ring, a unique energetic material. Several energetic salts of the tetrazole azasydnone were synthesized and characterized, leading to the creation of new secondary and primary explosives. Molecular structures are confirmed by ¹H and ¹³C NMR, IR spectroscopy, and X-ray crystallographic analysis. The high heats of formation, fast detonation velocities, and straight-forward synthesis of energetic azasydnones should capture the attention of future energetics research.     

Highly Dispersible Hexagonal Carbon–MoS2–Carbon Nanoplates with Hollow Sandwich Structures for Supercapacitors

MoS₂, a typical layered transition-metal dichalcogenide, is promising as an electrode material in supercapacitors. However, its low electrical conductivity could lead to limited capacitance if applied in electrochemical devices. Herein, a new nanostructure composed of hollow carbon–MoS₂–carbon was successfully synthesized through an l -cysteine-assisted hydrothermal method by using gibbsite as a template and polydopamine as a carbon precursor. After calcination and etching of the gibbsite template, uniform hollow platelets, which were made of a sandwich-like assembly of partial graphitic carbon and two-dimensional layered MoS₂ flakes, were obtained. The platelets showed excellent dispersibility and stability in water, and good electrical conductivity due to carbon provided by the calcination of polydopamine coatings. The hollow nanoplate morphology of the material provided a high specific surface area of 543 m² g⁻¹, a total pore volume of 0.677 cm³ g⁻¹, and fairly small mesopores (≈5.3 nm). The material was applied in a symmetric supercapacitor and exhibited a specific capacitance of 248 F g⁻¹ (0.12 F cm⁻²) at a constant current density of 0.1 A g⁻¹; thus suggesting that hollow carbon–MoS₂–carbon nanoplates are promising candidate materials for supercapacitors.     

Soft hydrogen bonds to alkenes: the methanol–ethene prototype under experimental and theoretical scrutiny

An FTIR spectroscopic study of the elusive hydrogen-bonded methanol–ethene complex, the most elementary example for weak intermolecular alcohol hydrogen bonding to a π cloud, is presented. By isolating the complex in a supersonic jet, the rigorous comparability to high-level quantum chemical calculations is ensured. In stark contrast to classical hydrogen bonds, experimental overtone analysis reveals the harmonic oscillator approximation for the OH red shift to be accurate. Harmonic calculations up to explicitly correlated local coupled-cluster level are thus found to agree very well with experiment. The experimental OH values for the red shift (45 cm^–1), the small change in diagonal anharmonicity (–3 cm^–1) and the overtone intensity attenuation (2 × 10²-fold) together with theoretical predictions for the preferred structural arrangement and the zero-point-corrected dissociation energy (8 kJ mol^–1) may thus be regarded as definitive reference values for related systems and for more approximate computational methods. In particular, MP2 calculations are shown to fail for this kind of weak intermolecular interaction.     

Enantioselective Approach for Expanding the Three-Dimensional Space of Tetrahydroquinoline to Develop BET Bromodomain Inhibitors**

The pharmaceutical industry has a pervasive need for chiral specific molecules with optimal affinity for their biological targets. However, the mass production of such compounds is currently limited by conventional chemical routes, that are costly and have an environmental impact. Here, we propose an easy access to obtain new tetrahydroquinolines, a motif found in many bioactive compounds, that is rapid and cost effective. Starting from simple raw materials, the procedure uses a proline-catalyzed Mannich reaction followed by the addition of BF₃ ⋅ OEt₂, which generates a highly electrophilic aza-ortho-quinone methide intermediate capable of reacting with different nucleophiles to form the diversely functionalized tetrahydroquinoline. Moreover, this enantioselective one-pot process provides access for the first time to tetrahydroquinolines with a cis-2,3 and trans-3,4 configuration. As proof of concept, we demonstrate that a three-step reaction sequence, from simple and inexpensive starting compounds and catalysts, can generate a BD2-selective BET bromodomain inhibitor with anti-inflammatory effect.     

Dual Gold‐Catalyzed Head‐to‐Tail Coupling of Iodoalkynes

Various haloalkynes are converted in the presence of a dual activation gold catalyst. Via a dual activation process a completely atom economic head‐to‐tail coupling delivers gem‐dihalogenated conjugated enynes as valuable building blocks for organic synthesis.     

Multicomponent Self‐Assembly with a Shape‐Persistent N‐Heterotriangulene Macrocycle on Au(111)

Multicomponent network formation by using a shape‐persistent macrocycle ( MC6 ) at the interface between an organic liquid and Au(111) surface is demonstrated. MC6 serves as a versatile building block that can be coadsorbed with a variety of organic molecules based on different types of noncovalent interactions at the liquid–solid interface. Scanning tunneling microscopy (STM) reveals the formation of crystalline bicomponent networks upon codeposition of MC6 with aromatic molecules, such as fullerene (C₆₀) and coronene. Tetracyanoquinodimethane, on the other hand, was found to induce disorder into the MC6 networks by adsorbing on the rim of the macrocycle. Immobilization of MC6 itself was studied in two different noncovalently assembled host networks. MC6 assumed a rather passive role as a guest and simply occupied the host cavities in one network, whereas it induced a structural transition in the other. Finally, the central cavity of MC6 was used to capture C₆₀ in a complex three‐component system. Precise immobilization of organic molecules at discrete locations within multicomponent networks, as demonstrated here, constitutes an important step towards bottom‐up fabrication of functional surface‐based nanostructures.