Recognition of N‐Alkyl and N‐Aryl Acetamides by N‐Alkyl Ammonium Resorcinarene Chlorides

N‐Alkyl ammonium resorcinarene chlorides are stabilized by an intricate array of intra‐ and intermolecular hydrogen bonds that leads to cavitand‐like structures. Depending on the upper‐rim substituents, self‐inclusion was observed in solution and in the solid state. The self‐inclusion can be disrupted at higher temperatures, whereas in the presence of small guests the self‐included dimers spontaneously reorganize to 1:1 host–guest complexes. These host compounds show an interesting ability to bind a series of N‐alkyl acetamide guests through intermolecular hydrogen bonds involving the carbonyl oxygen (C?O) atoms and the amide (NH) groups of the guests, the chloride anions (Cl^?) and ammonium (NH₂⁺) cations of the hosts, and also through CH ??? π interactions between the hosts and guests. The self‐included and host–guest complexes were studied by single‐crystal X‐ray diffraction, NMR titration, and mass spectrometry.     

N‐Alkyl Ammonium Resorcinarene Salts as High‐Affinity Tetravalent Chloride Receptors

N‐Alkyl ammonium resorcinarene salts (NARYs, Y=triflate, picrate, nitrate, trifluoroacetates and NARBr) as tetravalent receptors, are shown to have a strong affinity for chlorides. The high affinity for chlorides was confirmed from a multitude of exchange experiments in solution (NMR and UV/Vis), gas phase (mass spectrometry), and solid‐state (X‐ray crystallography). A new tetra‐iodide resorcinarene salt (NARI) was isolated and fully characterized from exchange experiments in the solid‐state. Competition experiments with a known monovalent bis‐urea receptor ( 5 ) with strong affinity for chloride, reveals these receptors to have a much higher affinity for the first two chlorides, a similar affinity as 5 for the third chloride, and lower affinity for the fourth chloride. The receptors affinity toward chloride follows the trend K₁?K₂?K₃≈ 5 >K₄, with K_a=5011 m ^?1 for 5 in 9:1 CDCl₃/[D₆]DMSO.     

Light‐Triggered Capture and Release of DNA and Proteins by Host–Guest Binding and Electrostatic Interaction

The development of an effective and general delivery method that can be applied to a large variety of structurally diverse biomolecules remains a bottleneck in modern drug therapy. Herein, we present a supramolecular system for the dynamic trapping and light‐stimulated release of both DNA and proteins. Self‐assembled ternary complexes act as nanoscale carriers, comprising vesicles of amphiphilic cyclodextrin, the target biomolecules and linker molecules with an azobenzene unit and a charged functionality. The non‐covalent linker binds to the cyclodextrin by host–guest complexation with the azobenzene. Proteins or DNA are then bound to the functionalized vesicles through multivalent electrostatic attraction. The photoresponse of the host–guest complex allows a light‐induced switch from the multivalent state that can bind the biomolecules to the low‐affinity state of the free linker, thereby providing external control over the cargo release. The major advantage of this delivery approach is the wide variety of targets that can be addressed by multivalent electrostatic interaction, which we demonstrate on four types of DNA and six different proteins.     

Remote Impacts of Methyl Substituents on the Guest‐Binding Ability of Self‐Assembled Cages

We synthesized self‐assembled coordination cages in which 1,10‐phenanthroline derivatives serve as capping ligands. Substituents at the 2,9‐positions of the phenanthroline ligand covered the outside of the cage but had an impact on the guest binding inside the cage. Introduction of methyl groups at the 2,9‐positions allowed the cage to accommodate tetraphenylsilane. Bulky mesityl groups overhanging the cage framework significantly shrunk the cage cavity through π–π interactions with the aromatic panels of the cage. The p‐methyl group of the mesityl substituent was a determinant of the restricted motion of 4,4′‐dimethoxybenzil inside the cage at high temperature. Thus, the presence or absence of one methyl group, which is far from the guest‐binding site, makes a significant difference in the guest species and motions inside the cage.     

Water‐Soluble Molecular Capsules: Self‐Assembly and Binding Properties

The self‐assembly and characterization of water‐soluble calix[4]arene‐based molecular capsules ( 1?2 ) is reported. The assemblies are the result of ionic interactions between negatively charged calix[4]arenes 1 a and 1 b , functionalized at the upper rim with amino acid moieties, and a positively charged tetraamidiniumcalix[4]arene 2 . The formation of the molecular capsules is studied by ¹H NMR spectroscopy, ESI mass spectrometry (ESI‐MS), and isothermal titration calorimetry (ITC). A molecular docking protocol was used to identify potential guest molecules for the self‐assembled capsule 1 a?2 . Experimental guest encapsulation studies indicate that capsule 1 a?2 is an effective host for both charged (N‐methylquinuclidinium cation) and neutral molecules (6‐amino‐2‐methylquinoline) in water.     

Allosteric and Chelate Cooperativity in Divalent Crown Ether/Ammonium Complexes with Strong Binding Enhancement

A thorough thermodynamic analysis by isothermal titration calorimetry of allosteric and chelate cooperativity effects in divalent crown ether/ammonium complexes is combined with DFT calculations including implicit solvent on the one hand and large‐scale molecular dynamics simulations with explicit solvent molecules on the other. The complexes studied exhibit binding constants up to 2×10⁶ m ^?1 with large multivalent binding enhancements and thus strong chelate cooperativity effects. Slight structural changes in the spacers, that is, the exchange of two ether oxygen atoms by two isoelectronic methylene groups, cause significantly stronger binding and substantially increased chelate cooperativity. The analysis is complemented by the examination of solvent effects and allosteric cooperativity. Such a detailed understanding of the binding processes will help to efficiently design and construct larger supramolecular architectures with multiple multivalent building blocks.     

Dimeric Capsules Formed by Tetra‐CMPO Derivatives of (Thia)Calix[4]arenes

Thiacalix[4]arene 2 , calix[4]arene 3 a and its tetraether fixed in the cone conformation 3 b form homo‐ and heterodimeric capsules in apolar solvents, which are held together by a seam of NH???O=P hydrogen bonds between carbamoylmethyl phospine oxide functions attached to their wide rim. Their internal volume of ～370 ų requires the inclusion of a suitable guest. Although neutral molecules such as adamantane (derivatives) or tetraethylammonium cations form kinetically stable complexes (¹H‐ and ³¹P‐time scale), the included solvent is rapidly exchanged. The internal mobility of the included tetraethylammonium cation is distinctly higher (ΔG=42.5 and 49.7 kJ mol^?1 for 3 a and 3 b ) than that for similar capsules of tetraurea calix[4]arenes 1 . Mixtures of 1 with 2 , 3 a , or 3 b contain only the two homodimers but the heterodimerization occurs with the tetraloop tetraurea 6 , which cannot form homodimers. Two dimers with cationic guests ( 2? (C₅H₅)₂Co⁺ ?2 and 3 a? Et₃NH⁺ ? H₂O ?3 a ) were confirmed by single‐crystal X‐ray analysis.     

Halogen‐Bond‐Assisted Guest Inclusion in a Synthetic Cavity

The confined space inside a self‐assembled cage enhanced halogen bonding (XB) between iodoperfluorocarbons (XB donors) and NO₃^? anions or H₂O molecules (XB acceptors), as confirmed by NMR spectroscopy in solution and by X‐ray crystallography in the solid state. The cavity also bound an XB donor–acceptor pair, C₆F₃I₃ and C₆H₅NMe₂, in a selective pairwise fashion.     

A Tetraferrocenyl‐Resorcinarene Cavitand as a Redox‐Switchable Host of Ammonium Salts

Tetraannulation of a resorcinarene‐octaamino cavitand with ferrocenecarboxaldehyde allows the preparation of a tetrabenzimidazole‐resorcinarene cavitand with four ferrocenyl moieties directly linked to the C2 atom of the imidazole units. Oxidation of the four ferrocenyl moieties produces important structural modifications of the molecule, as indicated by DFT calculations performed for the neutral and tetraoxidized forms of the cavitand. By means of ¹H NMR spectroscopic analysis, the encapsulating properties of the new tetraferrocenyl‐resorcinarene cavitand toward a series of ammonium salts were evaluated, and a clear cutoff point in binding affinity with respect to size was observed. Cyclic voltammetric studies allowed us to estimate the relative association constants for the neutral and oxidized forms of the cavitand, thus indicating that the guest was bound to the neutral (reduced) state of the cavitand and was released from the oxidized form. These redox‐addressable conformational and binding properties of the resorcinarene‐tetraferrocenyl cavitand constitute all the necessary features of a redox‐switchable molecular gripper. By means of mass‐spectrometric analysis, we could unambiguously confirm the molar stoichiometry of the host–guest complex (1:1) and assess the strong guest encapsulation, as indicated by triggering the covalent coupling between host and guest in the gas phase.     

Periodic Mesoporous Organosilica with Molecular‐Scale Ordering Self‐Assembled by Hydrogen Bonds

Nanoporous materials with functional frameworks have attracted attention because of their potential for various applications. Silica‐based mesoporous materials generally consist of amorphous frameworks, whereas a molecular‐scale lamellar ordering within the pore wall has been found for periodic mesoporous organosilicas (PMOs) prepared from bridged organosilane precursors. Formation of a “crystal‐like” framework has been expected to significantly change the physical and chemical properties of PMOs. However, until now, there has been no report on other crystal‐like arrangements. Here, we report a new molecular‐scale ordering induced for a PMO. Our strategy is to form pore walls from precursors exhibiting directional H‐bonding interaction. We demonstrate that the H‐bonded organosilica columns are hexagonally packed within the pore walls. We also show that the H‐bonded pore walls can stably accommodate H‐bonding guest molecules, which represents a new method of modifying the PMO framework.     

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.     

Probing the Inner Space of Resorcinarene Molecular Capsules with Nitroxide Guests

In quarantine : Nitroxide spin probes are encapsulated by hexameric resorcinarene molecular capsules in dichloromethane solutions (see picture). A substantial reduction in the tumbling rates occurs upon encapsulation of two cationic probes and one neutral probe. As the molecular volume of the probe increases, the tumbling rate of the probe reflects the overall tumbling rate of the entire supramolecular assembly.

     

Controlled Self‐Assembly by Mono‐p‐sulfonatocalix[n]arenes and Bis‐p‐sulfonatocalix[n]arenes

The complexation‐induced critical aggregation concentrations of 1‐pyrenemethylaminium by mono‐p‐sulfonatocalix[n]arenes and bis‐p‐sulfonatocalix[n]arenes (n=4, 5) were systemically measured by fluorescence spectroscopy. In all cases, the complexation‐induced critical aggregation concentration decreases by about 3 times upon addition of p‐sulfonatocalix[n]arenes. However, the optimal molar ratios for the aggregation of 1‐pyrenemethylaminium by mono‐p‐sulfonatocalix[n]arenes and bis‐p‐sulfonatocalix[n]arenes are distinctly different: For mono‐p‐sulfonatocalix[n]arenes, the optimum mixing ratio for the aggregation of 1‐pyrenemethylaminium is 1:4 mono‐p‐sulfonatocalix[n]arenes/1‐pyrenemethylaminium, whereas only 2.5 molecules of 1‐pyrenemethylaminium can be bound by one cavity of bis‐p‐sulfonatocalix[n]arenes. The intermolecular complexation of mono‐p‐sulfonatocalix[n]arenes and bis‐p‐sulfonatocalix[n]arenes with 1‐pyrenemethylaminium led to the formation of two distinctly different nanoarchitectures, which were shown to be nanoscale vesicle and rod aggregates, respectively, by using dynamic laser scattering, TEM, and SEM. This behavior is also different from the fiber‐like aggregates with lengths of several micrometers that were formed by 1‐pyrenemethylaminium itself above its critical aggregation concentration. Furthermore, the obtained nanoaggregates exhibit benign water solubility, self‐labeled fluorescence, and, more importantly, temperature responsiveness.     

Development of C3‐Symmetric Tris‐Urea Low‐Molecular‐Weight Gelators

This article describes recent developments in C₃‐symmetric tris‐urea low‐molecular‐weight gelators and their applications. The C₃‐symmetric tris‐ureas are excellent frameworks to form supramolecular polymers through noncovalent interactions. In organic solvents, hydrophobic tris‐ureas form supramolecular gels. Amphiphilic tris‐ureas form supramolecular gels in aqueous media. Functional supramolecular gels were prepared by introducing appropriate functional groups into the outer sphere of tris‐ureas. Supramolecular hydrogels obtained from amphiphilic tris‐ureas were used in the electrophoresis of proteins. These electrophoreses results showed several unique characteristics compared to typical electrophoreses results obtained using polyacrylamide matrices.

     

Solvent‐Driven Chiral‐Interaction Reversion for Organogel Formation

For chiral gels and related applications, one of the critical issues is how to modulate the stereoselective interaction between the gel and the chiral guest precisely, as well as how to translate this information into the macroscopic properties of materials. Herein, we report that this process can also be modulated by nonchiral solvents, which can induce a chiral‐interaction reversion for organogel formation. This process could be observed through the clear difference in gelation speed and the morphology of the resulting self‐assembly. This chiral effect was successfully applied in the selective separation of quinine enantiomers and imparts “smart” merits to the gel materials.     

A Hollow Foldecture with Truncated Trigonal Bipyramid Shape from the Self‐Assembly of an 11‐Helical Foldamer

The creation of self‐assembling microscale architectures that possess new and useful physical properties remains a significant challenge. Herein we report that an 11‐helical foldamer self‐assembles in a controlled manner to form a series of 3D foldectures with unusual three‐fold symmetrical shapes that are distinct from those generated from 12‐helical foldamers. The foldamer packing motif was revealed by powder X‐ray diffraction technique, and provides an important link between the molecular‐level symmetry and the microscale morphologies. The utility of foldectures with hollow interiors as robust and well‐defined supramolecular hosts was demonstrated for inorganic, organic, and even protein guests. This work will pave the way for the design of functional foldectures with greater 3D shape diversity and for the development of biocompatible delivery vehicles and containment vessels.