Designed Synthesis of a Highly Conjugated Hexaethynylbenzene‐Based Host for Supramolecular Architectures

The construction of efficient synthetic functional receptors with tunable cavities, and the self‐organization of guest molecules within these cavities through noncovalent interactions can be challenging. Here we have prepared a double‐cavity molecular cup based on hexaethynylbenzene that possesses a highly π‐conjugated interior for the binding of electron‐rich guests. X‐ray crystallography, NMR spectroscopy, UV/Vis spectroscopy, fluorescent spectroscopy, cyclic voltammetry, and SEM were used to investigate the structures and the binding behaviors. The results indicated that the binding of a guest in one cavity would affect the binding of the same or another guest in the other cavity. The effect of electron transfer in this system suggests ample opportunities for tuning the optical and electronic properties of the molecular cup and the encapsulated guest. The encapsulation of different guests would also lead to different aggregate nanostructures, which is a new way to tune their supramolecular architectures.     

Highly Efficient Supramolecular Catalysis by Endowing the Reaction Intermediate with Adaptive Reactivity

A new strategy of highly efficient supramolecular catalysis is developed by endowing the reaction intermediate with adaptive reactivity. The supramolecular catalyst, prepared by host–guest complexation between 2,2,6,6‐tetramethylpiperidin‐1‐oxyl (TEMPO) and cucurbit[7]uril (CB[7]), was used for biphasic oxidation of alcohols. Cationic TEMPO⁺, the key intermediate, was stabilized by the electrostatic effect of CB[7] in aqueous phase, thus promoting the formation of TEMPO⁺ and inhibiting side reactions. Moreover, through the migration into the organic phase, TEMPO⁺ was separated from CB[7] and recovered the high reactivity to drive a fast oxidation of substrates. The adaptive reactivity of TEMPO⁺ induced an integral optimization of the catalytic cycle and greatly improved the conversion of the reaction. This work highlights the unique advantages of dynamic noncovalent interactions on modulating the activity of reaction intermediates, which may open new horizons for supramolecular catalysis.     

Processive Catalysis

Nature’s enzymes are an ongoing source of inspiration for scientists. The complex processes behind their selectivity and efficiency is slowly being unraveled, and these findings have spawned many biomimetic catalysts. However, nearly all focus on the conversion of small molecular substrates. Nature itself is replete with inventive catalytic systems which modify, replicate, or decompose entire polymers, often in a processive fashion. Such processivity can, for example, enhance the rate of catalysis by clamping to the polymer substrate, which imparts a large effective molarity. Reviewed herein are the various strategies for processivity in nature’s arsenal and their properties. An overview of what has been achieved by chemists aiming to mimic one of nature’s greatest tricks is also included.     

Exploiting Cavities in Supramolecular Gels

Endowing supramolecular gelators with cavities opens up a number of opportunities not possible with other gel systems. The well‐established host–guest chemistry of cavitands can be utilized to build up and break down gel structures, introduce responsive functionalities, or enhance selectivity in applications such as catalysis and extraction. Cavity‐containing gelators provide an excellent case study for how different aspects of supramolecular chemistry can be used intelligently to create responsive materials.     

Supramolecular Polymerization at Low Monomer Concentrations: Enhancing Intermolecular Interactions and Suppressing Cyclization by Rational Molecular Design

We present the construction of long‐chain water‐soluble supramolecular polymers at low monomer concentrations. Naphthalene‐based host‐enhanced π–π interactions, which possess high binding constants, were used as the driving force of supramolecular polymerization. A monomer, DNDAB, with a rigid, bulky 1,4‐diazabicyclo[2.2.2]octane‐1,4‐diium linker was designed. The design of the monomer structure strongly influenced the efficiency of the supramolecular polymerization. The rigid, bulky linker in DNDAB effectively eliminates cyclization, promoting the formation of long‐chain supramolecular polymers at low monomer concentrations. In contrast, a reference monomer containing a flexible linker (DNPDN) only forms oligomers owing to cyclization.     

Solid‐State Conformational Flexibility at Work: Zipping and Unzipping within a Cyclic Peptoid Single Crystal

A peptidomimetic compound undergoes a reversible single‐crystal‐to‐single‐crystal transformation upon guest release/uptake with the transformation involving a drastic conformational change. The extensive and reversible alteration in the solid state is connected to the formation of an unprecedented “CH–π zipper” which can reversibly open and close (through the formation of CH–π interactions), thus allowing for guest sensing.     

Thermoresponsive Supramolecular Dendronized Polymers

Combining the concepts of supramolecular polymers and dendronized polymers provides the opportunity to create bulky polymers with easy structural modification and tunable properties. In the present work, a novel class of side‐chain supramolecular dendronized polymethacrylates is prepared through the host–guest interaction. The host is a linear polymethacrylate (as the backbone) attached in each repeat unit with a β‐cyclodextrin (β‐CD) moiety, and the guest is constituted with three‐fold branched oligoethylene glycol (OEG)‐based first‐ (G1) and second‐generation (G2) dendrons with an adamantyl group core. The host and guest interaction in aqueous solution leads to the formation of the supramolecular polymers, which is supported with ¹H NMR spectroscopy and dynamic light scattering measurements. The supramolecular formation was also examined at different host/guest ratios. The water solubility of hosts and guests increases upon supramolecular formation. The supramolecular polymers show good solubility in water at room temperature, but exhibit thermoresponsive behavior at elevated temperatures. Their thermoresponsiveness is thus investigated with UV/Vis and ¹H NMR spectroscopy, and compared with their counterparts formed from individual β‐CD and the OEG dendritic guest. The effect of polymer concentration and molar ratio of host/guest was examined. It is found that the polar interior of the supramolecules contribute significantly to the thermally‐induced phase transitions for the G1 polymer, but this effect is negligible for the G2 polymer. Based on the temperature‐varied proton NMR spectra, it is found that the host–guest complex starts to decompose during the aggregation process upon heating to its dehydration temperature, and this decomposition is enhanced with an increase of solution temperature.     

Supramolecular Antibiotic Switches: A Potential Strategy for Combating Drug Resistance

Bacterial infectious disease is a serious public health concern throughout the world. Pathogen drug resistance, arising from both rational use and abuse/misuse of germicides, complicates the situation. Aside from developing novel antibiotics and antimicrobial agents, molecular approaches have become another significant method to overcome the problem of pathogen drug resistance. Established supramolecular systems, the antibiotic properties of which can be switched “on” and “off” through host–guest interactions, show great potential in combating issues regarding antibiotic resistance in the long term, as indicated by several recent studies. In this Concept, recently developed strategies for antibacterial regulation are summarized and further directions for research into antibiotic switches are proposed.     

Supramolecular Drug Delivery Systems Based on Water‐Soluble Pillar[n]arenes

Supramolecular drug delivery systems (SDDSs), including various kinds of nanostructures that are assembled by reversible noncovalent interactions, have attracted considerable attention as ideal drug carriers owing to their fascinating ability to undergo dynamic switching of structure, morphology, and function in response to various external stimuli, which provides a flexible and robust platform for designing and developing functional and smart supramolecular nano‐drug carriers. Pillar[n]arenes represent a new generation of macrocyclic hosts, which have unique structures and excellent properties in host–guest chemistry. This account describes recent progress in our group to develop pillararene‐based stimuli‐responsive supramolecular nanostructures constructed by reversible host–guest interactions for controllable anticancer drug delivery. The potential applications of these supramolecular drug carriers in cancer treatment and the fundamental questions facing SDDSs are also discussed.

     

Supramolecular Interactions of Nonsteroidal Anti‐inflammatory Drug in Nanochannels of Molecular Containers: A Spectroscopic,Thermogravimetric and Microscopic Investigation

Supramolecular host–guest complexation between the nonsteroidal anti‐inflammatory drug indomethacin (IMC) and molecular containers were investigated. The weakly fluorescent drug molecule becomes highly fluorescent on complexation with different molecular containers, and time‐resolved fluorescence emission spectroscopy reveals that the lifetime components of IMC significantly increase in the presence of molecular containers, compared with the lifetimes in neat water. The respective solid host–guest complexes were synthesised and characterised by Fourier transform infrared and ¹H nuclear magnetic resonance spectroscopic analysis. Microscopy techniques were used to analyse modifications of the surface morphology, owing to the formation of supramolecular complexes. The effect of the molecular container on the optical properties of IMC has also been investigated to determine the effect of nanochannels of different size and structure.     

The Supramolecular Chemistry of Strained Carbon Nanohoops

Since 1996, a growing number of strained macrocycles, comprising only sp²‐ or sp‐hybridized carbon atoms within the ring, have become synthetically accessible, with the [n]cycloparaphenyleneacetylenes ( CPPAs ) and the [n]cycloparaphenylenes ( CPPs ) being the most prominent examples. Now that robust and relatively general synthetic routes toward a diverse range of nanohoop structures have become available, the research focus is beginning to shift towards the exploration of their properties and applications. From a supramolecular chemistry perspective, these macrocycles offer unique opportunities as a result of their near‐perfect circular shape, the unusually high degree of shape‐persistence, and the presence of both convex and concave π‐faces. In this Minireview, we give an overview on the use of strained carbon‐rich nanohoops in host–guest chemistry, the preparation of mechanically interlocked architectures, and crystal engineering.