Optochemically Responsive 2D Nanosheets of a 3D Metal–Organic Framework Material

Outstanding functional tunability underpinning metal–organic framework (MOF) confers a versatile platform to contrive next‐generation chemical sensors, optoelectronics, energy harvesters, and converters. A rare exemplar of a porous 2D nanosheet material constructed from an extended 3D MOF structure is reported. A rapid supramolecular self‐assembly methodology at ambient conditions to synthesize readily exfoliatable MOF nanosheets, functionalized in situ by adopting the guest@MOF (host) strategy, is developed. Nanoscale confinement of light‐emitting molecules (as functional guest) inside the MOF pores generates unusual combination of optical, electronic, and chemical properties, arising from the strong host–guest coupling effects. Highly promising photonics‐based chemical sensing opened up by the new guest@MOF composite systems is shown. By harnessing host–guest optochemical interactions of functionalized MOF nanosheets, detection of an extensive range of volatile organic compounds and small molecules important for many practical applications has been accomplished.     

主客体微观复合作用导致的凝胶宏观聚集效应

利用分子链上α-环糊精(α-CD)与苯基、丁基和十二烷基的微观复合作用,实现了毫米/厘米尺寸主、客体凝胶在水溶液中的聚集。实验显示,主、客体凝胶之间的聚集是选择性的,其与空白凝胶,或主体凝胶、客体凝胶自身之间都没有观察到任何相互作用产生。自由α-CD对凝胶聚集体的离解作用进一步证明了主、客体凝胶的宏观自聚集是由接枝于聚合物大分子链上的α-CD与客体基团的微观相互作用引起的。在此过程中,凝胶表面层的充分溶胀对于主、客体凝胶表面官能团能够相互接近,并发生复合起到了关键作用。     

Pillar[n]arene-Based Supramolecular Switches in Solution and on Surfaces

The design and synthesis of new synthetic macrocycles has driven the rapid development of supramolecular chemistry and materials. Pillar[n]arenes, as a new type of macrocyclic compounds, are used as a promising type of building blocks for switchable supramolecular systems due to their versatile functionalization and the ability of binding toward various guest molecules. A number of guests can form inclusion complexes with pillar[n]arenes and their derivatives in solution, which are sensitive to different external triggers. Interestingly, the pursuit of complex stimuli-responsive functional materials and devices has largely motivated the shift of pillar[n]arene-based switches from solution media to surfaces for controllable macroscopic motions on solid platforms. Facilitated by the facile modification of pillar[n]arenes on various solid supports and the dynamic binding of host–guest complexes, numerous functional hybrid materials with adjustable physical or chemical properties and integrated functionalities have been reported in the last decade. Here, the advance of supramolecular switches in solution and on surfaces based on pillar[n]arenes and derivatives with an emphasis on the efforts and the latest contributions from the field is discussed.     

Cyclodextrin-Based Multistimuli-Responsive Supramolecular Assemblies and Their Biological Functions

Cyclodextrins (CDs), which are a class of cyclic oligosaccharides extracted from the enzymatic degradation of starch, are often utilized in molecular recognition and assembly constructs, primarily via host–guest interactions in water. In this review, recent progress in CD-based supramolecular nanoassemblies that are sensitive to chemical, biological, and physical stimuli is updated and reviewed, and intriguing examples of the biological functions of these nanoassemblies are presented, including pH- and redox-responsive drug and gene delivery, enzyme-activated specific cargo release, photoswitchable morphological interconversion, microtubular aggregation, and cell–cell communication, as well as a geomagnetism-controlled nanosystem for the suppression of tumor invasion and metastasis. Moreover, future perspectives and challenges in the fabrication of intelligent CD-based biofunctional materials are also discussed at the end of this review, which is expected to promote the translational development of these nanomaterials in the biomedical field.     

Chemical selectivity of self-assembled monolayers of calix[4]resorcinarene

Selective molecular interactions at an interface formed by self-assembly of a macrocyclic synthetic host, calix[4]resorcinarene with four thiol groups (R4SH), are investigated. The recognition of guest adsorbates from aqueous solutions is monitored using surface plasmon resonance (SPR) and the orientation of the guest-molecule is probed using polarization modulation infrared absorption spectroscopy (PM-IRRAS). The experiments reported here demonstrate that the chemical selectivity of self-assembled monolayers (SAMs) of host molecules such as calix[4]resorcinarenes extends to isomers of several different guest molecules. By using structural isomers of guest molecules such as bipyridine and nitrophenol that are multidentate hydrogen bond acceptors, it is shown that geometric match between guest and host molecules is an integral aspect of the recognition phenomena. Results from SPR and PM-IRRAS experiments reported here highlight the interplay between steric size and forces such as hydrogen bonding and hydrophobic interactions. Competitive and sequential adsorption of guest molecules such as -hydroxy-γ-butyrolactone and 4,4′-bipyridine shows that these guests compete for the same binding sites on the surface and that the interplay between steric size and molecular forces underlies the preferential selectivity of one guest molecule over another.     

Nanomaterials with Supramolecular Assembly Based on AIE Luminogens for Theranostic Applications

One of the major pursuits of biomedical science is to develop advanced strategies for theranostics, which is expected to be an effective approach for achieving the transition from conventional medicine to precision medicine. Supramolecular assembly can serve as a powerful tool in the development of nanotheranostics with accurate imaging of tumors and real-time monitoring of the therapeutic process upon the incorporation of aggregation-induced emission (AIE) ability. AIE luminogens (AIEgens) will not only enable fluorescence imaging but will also aid in improving the efficacy of therapies. Furthermore, the fluorescent signals and therapeutic performance of these nanomaterials can be manipulated precisely owing to the reversible and stimuli-responsive characteristics of the supramolecular systems. Inspired by rapid advances in this field, recent research conducted on nanotheranostics with the AIE effect based on supramolecular assembly is summarized. Here, three representative strategies for supramolecular nanomaterials are presented as follows: a) supramolecular self-assembly of AIEgens, b) the loading of AIEgens within nanocarriers with supramolecular assembly, and c) supramolecular macrocycle-guided assembly via host–guest interactions. Meanwhile, the diverse applications of such nanomaterials in diagnostics and therapeutics have also been discussed in detail. Finally, the challenges of this field are listed in this review.     

25th Anniversary Article: Reversible and Adaptive Functional Supramolecular Materials: “Noncovalent Interaction” Matters

Supramolecular materials held together by noncovalent interactions, such as hydrogen bonding, host–guest interactions, and electrostatic interactions, have great potential in material science. The unique reversibility and adaptivity of noncovalent intreractions have brought about fascinating new functions that are not available by their covalent counterparts and have greatly enriched the realm of functional materials. This review article aims to highlight the very recent and important progresses in the area of functional supramoleuclar materials, focusing on adaptive mechanical materials, smart sensors with enhanced selectivity, soft luminescent and electronic nanomaterials, and biomimetic and biomedical materials with tailored structures and functions. We cannot write a complete account of all the interesting work in this area in one article, but we hope that it can in a way reflect the current situation and future trends in this prosperously developing area of functional supramolecular materials.     

A Supramolecular Approach to Enzyme Immobilization in Micro‐Channels

A supramolecular assembly scheme is developed to enable the facile in‐situ immobilization of enzymes in a microfluidic channel system. A combination of orthogonal supramolecular interactions of host (β‐cyclodextrin)–guest (adamantane) and biotin–Streptavidin (SAv) interactions are employed to generate reusable homogeneous enzyme layers in microchannels. The structural integrity and catalytic activity of the immobilized enzyme calf‐intestine alkaline phosphatase (AlkPh) is demonstrated. From the kinetic analysis of a dephosphorylation reaction, the specificity constant k_cat/K_M for immobilized alkaline phosphatase in the channels is on the order of 10⁵ M^?1s^?1 and comparable to known literature values in other environments. These observations are ascribed to the good access of the substrate to favorably oriented enzymes across the microchannel. Therefore, this study demonstrates the great potential for adopting a supramolecular assembly scheme to immobilize enzymes in microfluidic devices.     

Reversible Ion‐Conducting Switch in a Novel Single‐Ion Supramolecular Hydrogel Enabled by Photoresponsive Host–Guest Molecular Recognition

A novel ion‐conducting supramolecular hydrogel with reversible photoconductive properties in which the azobenzene motif, α‐cyclodextrin (α‐CD), and ionic liquid are grafted onto the gel matrix is reported. Host–guest interactions with different association constants between α‐CD and azobenzene or the anionic part of the ionic liquid can be readily tuned by photoinduced trans–cis isomerization of the azobenzene unit. When irradiated by 365 nm light, α‐CD prefers to form a complex with the anionic part of the ionic liquid, resulting in decreased ionic mobility and thus high resistance of the hydrogel. However, under 420 nm light irradiation, a more stable complex is again formed between α‐CD and trans‐azobenzene, thereby releasing the bound anions to regenerate the low‐resistive hydrogel. As such, remote control of the ionic conductivity of the hydrogel is realized by simple host–guest chemistry. With the incorporation of a logic gate, this hydrogel is able to reversibly switch an electric circuit on and off by light irradiation with certain wavelengths. The concept of photoswitchable ionic conductivity of a hydrogel mediated by competitive molecular recognition is potentially promising toward the fabrication of optoelectronic devices and applications in bioelectronic technology.     

Bioadhesive Polymersome for Localized and Sustained Drug Delivery at Pathological Sites with Harsh Enzymatic and Fluidic Environment via Supramolecular Host–Guest Complexation

Targeted and sustained delivery of drugs to diseased tissues/organs, where body fluid exchange and catabolic activity are substantial, is challenging due to the fast cleansing and degradation of the drugs by these harsh environmental factors. Herein, a multifunctional and bioadhesive polycaprolactone‐β‐cyclodextrin (PCL‐CD) polymersome is developed for localized and sustained co‐delivery of hydrophilic and hydrophobic drug molecules. This PCL‐CD polymersome affords multivalent crosslinking action via surface CD‐mediated host–guest interactions to generate a supramolecular hydrogel that exhibits evident shear thinning and efficient self‐healing behavior. The co‐delivery of small molecule and proteinaceous agents by the encapsulated PCL‐CD polymersomes enhances the differentiation of stem cells seeded in the hydrogel. Furthermore, the PCL‐CD polymersomes are capable of in situ grafting to biological tissues via host–guest complexation between surface CD and native guest groups in the tissue matrix both in vitro and in vivo, thereby effectively extending the retention of loaded cargo in the grafted tissue. It is further demonstrated that the co‐delivery of small molecule and proteinaceous drugs via PCL‐CD polymersomes averts cartilage degeneration in animal osteoarthritic (OA) knee joints, which are known for their biochemically harsh and fluidically dynamic environment.     

Characterization of chiral host-guest complexation in fast atom bombardment mass spectrometry

A new method has been developed for the characterization of complexion between host and guest molecules. Adduct formation between chiral crown ethers 1 and 2 and enantiomeric ammonium ions 4 and 5 was examined. The reference compound 3 (achiral host) was chosen to be similar in structure to the chiral crown ethers for quantitative measurements. Our approach is based on a formalism assuming an equilibrium: [chiral host + H](+) + [achiral host + chiral guest](+) ? [chiral host + chiral guest](+) + [achiral host + H](+). The equlibrium constant for this process was calculated using the relative peak intensities of the corresponding species in the FAB mass spectra. It was found that these provide significantly better reproducibility and more reliable results than the relative peak intensity method described before (Sawada, M.; et al. J. Am. Chem. Soc. 1992, 114, 4405; 1993, 115, 7381; Org. Mass Spectrom. 1993, 28, 1525).(1)(-)(3) In the examples studied, the equilibrium constants corresponding to the formation of heterochiral adducts (S,S-R or R,R-S) were higher than those for the formation of homochiral aggregates (S,S-S or R,R-R).     

Rodlike Supramolecular Nanoassemblies of Degradable Poly(Aspartic Acid) Derivatives and Hydroxyl‐Rich Polycations for Effective Delivery of Versatile Tumor‐Suppressive ncRNAs

The delivery of tumor‐suppressive noncoding RNAs (ncRNAs) including short ncRNAs (i.e., miRNAs) and long ncRNAs (lncRNAs) is put forward to treat tumors. In this work, novel rodlike supramolecular nanoassemblies (CNC @CB[8] @ PGEA) of degradable poly(aspartic acid) (PAsp) derivatives‐grafted cellulose nanocrystals (CNCs) and hydroxyl‐rich polycations (ethanolamine‐functionalized poly(glycidyl methacrylate), PGEA) are proposed via typical cucurbit[8]uril (CB[8])‐based host–guest interactions for delivery of different ncRNAs to treat hepatocellular carcinoma (HCC). Spindly CNCs, one kind of natural polysaccharide nanoparticles, possess good biocompatibility and unique physico‐chemical properties. PGEA with abundant hydroxyl groups is one promising gene carrier with low cytotoxicity. PAsp can benefit the disassembly and degradability of nanoassemblies within cells. CNC @ CB[8]@PGEA combines the different unique properties of CNC, PGEA, and PAsp. CNC @ CB[8] @ PGEA effectively complexes the expression constructs of miR‐101 (plasmid pc3.0‐miR‐101) and lncRNA MEG3 (plasmid pc3.0‐MEG3). CNC @ CB[8] @ PGEA produces much better transfection performances than PGEA‐containing assembly units. In addition, the codelivery system of CNC @ CB[8] @ PGEA/(pc3.0‐MEG3+pc3.0‐miR‐101) nanocomplexes demonstrates better efficacy in suppressing HCC than CNC @ CB[8] @ PGEA/pc3.0‐MEG3 or CNC @ CB[8] @ PGEA/pc3.0‐miR‐101 nanocomplexes alone. Such rodlike supramolecular nanoassemblies will provide a promising means to produce efficient delivery vectors of versatile tumor‐suppressive nucleic acids.     

Cross-platform method for identifying candidate network biomarkers for prostate cancer

Discovering biomarkers using mass spectrometry (MS) and microarray expression profiles is a promising strategy in molecular diagnosis. Here, the authors proposed a new pipeline for biomarker discovery that integrates disease information for proteins and genes, expression profiles in both genomic and proteomic levels, and protein?protein interactions (PPIs) to discover high confidence network biomarkers. Using this pipeline, a total of 474 molecules (genes and proteins) related to prostate cancer were identified and a prostate-cancer-related network (PCRN) was derived from the integrative information. Thus, a set of candidate network biomarkers were identified from multiple expression profiles composed by eight microarray datasets and one proteomics dataset. The network biomarkers with PPIs can accurately distinguish the prostate patients from the normal ones, which potentially provide more reliable hits of biomarker candidates than conventional biomarker discovery methods.     

Organic nanoporous structures

Research on microporous materials, hollow solids with channels and cavities that include small guest molecules, has advanced in fundamental and applied aspects during 1999–2000. The retrosynthesis of crystal structures in terms of robust supramolecular synthons (recognition motifs) and functionalised organic molecules (building blocks) has led to the design of new porous architectures and modification in the properties of existing host materials. Even as conventional O–H⋯O and N–H⋯O hydrogen bonds continue to be used to attain these goals, weak hydrogen bonds and heteroatom interactions, such as C–H⋯O, halogen⋯halogen, strengthened by multi-point recognition and cooperativity effects, have emerged in new design strategies. A proper understanding of pseudopolymorphism, the phenomenon of solvent inclusion in crystals, will promote the next phase of host–guest research.     

Photoresponsive Cucurbit[8]uril‐Mediated Adhesion of Bacteria on Supported Lipid Bilayers

In this work, the development of a photoresponsive platform for the presentation of bioactive ligands to study receptor–ligand interactions has been described. For this purpose, supramolecular host–guest chemistry and supported lipid bilayers (SLBs) have been combined in a microfluidic device. Quartz crystal microbalance with dissipation monitoring (QCM‐D) studies on methyl viologen (MV)‐functionalized oligo ethylene glycol‐based self‐assembled monolayers, gel and liquid‐state SLBs have been compared for their nonfouling properties in the case of ConA and bacteria. In combination with bacterial adhesion test, negligible nonspecific bacterial adhesion is observed only in the case of methyl‐viologen‐modified liquid‐state SLBs. Therefore, liquid‐state SLBs have been identified as most suitable for studying specific cell interactions when MV is incorporated as a guest on the surface. The photoswitchable supramolecular ternary complex is formed by assembling cucurbit[8]uril (CB[8]) and an azobenzene–mannose conjugate (Azo–Man) onto MV‐functionalized liquid‐state SLBs and the assembly process has been characterized using QCM‐D and fluorescence techniques. Mannose has been found to enable binding of E. coli via cell‐surface receptors on the nonfouling supramolecular SLBs. Optical switching of the azobenzene moiety allows us to “erase” the bioactive surface after bacterial binding, providing the potential to develop reusable sensors. Localized photorelease of bacterial cells has also been shown indicating the possibility of optically guiding cellular growth, migration, and intercellular interactions.     

Recent Advances of Using Hybrid Nanocarriers in Remotely Controlled Therapeutic Delivery

The development of hybrid biomaterials has been attracting great attention in the design of materials for biomedicine. The nanosized level of inorganic and organic or even bioactive components can be combined into a single material by this approach, which has created entirely new advanced compositions with truly unique properties for drug delivery. The recent advances in using hybrid nanovehicles as remotely controlled therapeutic delivery carriers are summarized with respect to different nanostructures, including hybrid host–guest nanoconjugates, micelles, nanogels, core–shell nanoparticles, liposomes, mesoporous silica, and hollow nanoconstructions. In addition, the controlled release of guest molecules from these hybrid nanovehicles in response to various remote stimuli such as alternating magnetic field, near infrared, or ultrasound triggers is further summarized to introduce the different mechanisms of remotely triggered release behavior. Through proper chemical functionalization, the hybrid nanovehicle system can be further endowed with many new properties toward specific biomedical applications.     

Freestanding 3D Supramolecular Particle Bridges: Fabrication and Mechanical Behavior

Freestanding particle bridges with controlled composition and macroscopic robustness are demonstrated by the use of supramolecular nanoparticle assembly. Self‐assembly of nanoparticles, templating, and supramolecular glue infiltration are combined to form stable and ordered three‐dimensional polystyrene particle composites on a polydimethylsiloxane stamp. Freestanding hybrid polystyrene nanoparticle bridges are obtained by transfer printing of the hybrid structures onto topographically patterned substrates via host–guest interactions. The mechanical robustness and rigidity of the particle bridges can be controlled by manipulating the layer‐by‐layer cycles of supramolecular glues of gold nanoparticles and dendrimers. Atomic force microscopy‐based microbending results, in particular the location and force‐dependent deflection behavior, confirm that the particle bridge fulfills the classical supported‐beam characteristics. As estimated from classical beam theory, the bending moduli of the particle bridges vary between 0.8 and 1.1 GPa, depending on the degree of filling by the supramolecular glues. Failure analysis on the particle structure indicates linear elastic behavior and a plastic deformation upon failure.     

Efficient Aggregation‐Induced Emission Manipulated by Polymer Host Materials

Linear copolymer hosts bearing a number of pillar[5]arene dangling side chains are synthesized for the facile construction of highly emissive supramolecular polymer networks (SPNs) upon noncovalently cross‐linking with a series of tetraphenyethylene (TPE)‐based tetratopic guests terminated with different functional groups through supramolecular host–guest interactions. An extremely high fluorescence quantum yield (98.22%) of the SPNs materials is obtained in tetrahydrofuran (THF) by fine‐tuning the parameters, and meanwhile supramolecular light‐harvesting systems based on spherical supramolecular nanoparticles are constructed by interweaving 9,10‐distyrylanthracene (DSA) and TPE‐based guest molecules of aggregation‐induced emission (AIE) with the copolymer hosts in the mixed solvent of THF/H₂O. The present study not only illustrates the restriction of the intramolecular rotations (RIR)‐ruled emission enhancement mechanism regulated particularly by macrocyclic arene‐containing copolymer hosts, but also suggests a new self‐assembly approach to construct high‐performance light‐harvesting materials.     

Lipid bilayer regulation of membrane protein function: gramicidin channels as molecular force probes

Membrane protein function is regulated by the host lipid bilayer composition. This regulation may depend on specific chemical interactions between proteins and individual molecules in the bilayer, as well as on non-specific interactions between proteins and the bilayer behaving as a physical entity with collective physical properties (e.g. thickness, intrinsic monolayer curvature or elastic moduli). Studies in physico-chemical model systems have demonstrated that changes in bilayer physical properties can regulate membrane protein function by altering the energetic cost of the bilayer deformation associated with a protein conformational change. This type of regulation is well characterized, and its mechanistic elucidation is an interdisciplinary field bordering on physics, chemistry and biology. Changes in lipid composition that alter bilayer physical properties (including cholesterol, polyunsaturated fatty acids, other lipid metabolites and amphiphiles) regulate a wide range of membrane proteins in a seemingly non-specific manner. The commonality of the changes in protein function suggests an underlying physical mechanism, and recent studies show that at least some of the changes are caused by altered bilayer physical properties. This advance is because of the introduction of new tools for studying lipid bilayer regulation of protein function. The present review provides an introduction to the regulation of membrane protein function by the bilayer physical properties. We further describe the use of gramicidin channels as molecular force probes for studying this mechanism, with a unique ability to discriminate between consequences of changes in monolayer curvature and bilayer elastic moduli.