Reversible Host-guest Interactions Research Articles

β-cyclodextrin/spiropyran-functionalized optical-driven hydrogel film for bisphenol A detection in food packaging

Bisphenol A (BPA), an endocrine disruptor, is widely used in food packaging materials, including drink containers. Sensitive detection of BPA is crucial to food safety. Herein, we have developed a novel optical-driven hydrogel film sensor for sensitive BPA detection based on the displacement of spiropyran (SP) from β-cyclodextrin (β-CD) cavity by BPA followed by the photochromism of the released SP. The released SP converts to the ring-opened merocyanine form which shows an enhanced red fluorescence in the dark. The sensor demonstrates a linear detection range from 0.1 to 20 μg mL−1 with a limit of detection at 0.027 μg mL−1 and a limit of quantification at 0.089 μg mL−1. Notably, the proposed β-CD/SP hydrogel can be reused due to the reversible isomerization of SP and the reversible host–guest interaction. This sensor also shows good performance for BPA determination in real samples, indicating its great potential for food safety monitoring.

A strong and tough supramolecular assembled β-cyclodextrin and chitin nanocrystals protein adhesive: Synthesis, characterization, bonding performance on three-layer plywood

The development of a biomass adhesive as a substitute for petroleum-derived adhesives has been considered a viable option. However, achieving both superior bonding strength and toughness in biomass adhesives remains a significant challenge. Inspired by the human skeletal muscles structure, this study reveals a promising supramolecular structure using tannin acid (TA) functionalized poly-β-cyclodextrin (PCD) (TA@PCD) as elastic tissues and chitin nanocrystals (ChNCs) as green reinforcements to strengthen the soybean meal (SM) adhesive crosslinking network. TA@PCD acts as a dynamic crosslinker that facilitates reversible host-guest interactions, hydrogen bonds, and electrostatic interactions between adjacent stiff ChNCs and SM matrix, resulting in satisfactory strength and toughness. The resulting SM/TA@PCD/ChNCs-2 adhesive has demonstrated satisfactory wet and dry shear strength (1.25 MPa and 2.57 MPa, respectively), toughness (0.69 J), and long-term solvents resistance (80 d). Furthermore, the adhesive can exhibit desirable antimildew characteristics owing to the phenol hydroxyl groups of TA and amino groups of ChNCs. This work showcases an effective supramolecular chemistry strategy for fabricating high-performance biomass adhesives with great potential for practical applications.

Structurally dynamic self-healable hydrogel cooperatively inhibits intestinal inflammation and promotes mucosal repair for enhanced ulcerative colitis treatment

Hydrogels are a class of biocompatible materials with versatile functions that have been increasing explored for the localized treatment of ulcerative colitis (UC), but various mechanical stimuli may cause premature hydrogel breakage and detachment, impeding their further clinical translation. Here we report a multifunctional mechanically-resilient self-healing hydrogel for effective UC treatment, which is synthesized through the host-guest interaction between dopamine/β-cyclodextrin-modified hyaluronic acid (HA-CD-DA) and amantadine-modified carboxymethyl chitosan (CMCS-AD). The excessive β-CD cavities allow the incorporation of dexamethasone (DEX), while the porous hydrogel network potentiates the encapsulation of basic fibroblast growth factor (bFGF) and L-alanyl-l-glutamine (ALG). DA moieties in HA components allow firm adhesion of the hydrogel to the ulcerative lesions after in-situ implantation, while the reversible host-guest interaction between CD and AD could enhance the persistence of hydrogel. The hydrogel demonstrated favorable biocompatibility and could continuously release DEX to induce M1-to-M2 repolarization of mucosal macrophages through inhibiting the toll-like receptor 4 (TLR4)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) axis. Furthermore, the co-delivered bFGF and ALG facilitates the regeneration of ulcerative mucosa and restore its barrier functions to ameliorate UC symptoms. The mechanically resilient hydrogel offers an integrative approach for UC therapy in the clinics.

A hierarchical supramolecular nanozyme platform for programming tumor-specific PDT and catalytic therapy

Supramolecular chemistry as a promising tool bridges the gap between conveniently synthetic processes and multifunction through reversible noncovalent interactions. Herein, a supramolecular nanoplatform, AuP-PS, is built by flexible and reversible supramolecular interactions between pillar[5]arene-capped gold nanoparticles (AuPs) and porphyrin-containing “V” shape block copolymers (PS). The biosafety of AuP-PS was greatly improved by the formation of supramolecular complexes. Taking advantage of gradient pH changes in the tumor microenvironment (TME), AuP-PS can first disassemble into single AuP-PS nanoparticles due to the pH-sensitive DPA units of PS under pH = 6.5 and enter into the in-depth tumor sites. Whereafter, single AuP-PS nanoparticles completely dissociate, release PS and expose AuPs due to the reversible host-guest interaction at pH = 5.4, where photodynamic therapy and catalytic therapy were sufficiently activated to combat against the in-depth tumor. In vitro results indicate that the singlet oxygen yield of supramolecular AuP-PS nanoplatform was amplified 5.6 times under pH = 5.4 than that under pH = 7.4, and the nanozyme activity of AuP-PS nanoplatform was dramatically boosted 6.7 times than that of the control sample without reversible linkers under pH = 5.4. In vivo data further reveal that the supramolecular AuP-PS nanoplatform displayed superb therapeutic efficacy. Hence, this supramolecular AuP-PS nanoplatform may provide a programmed and complementary synergistic therapy strategy for in-depth and efficient treatment for solid tumors.

Facile synthesis of self-dispersed β-cyclodextrin-coupled cellulose microgel for sustained release of vanillin

A self-dispersed β-cyclodextrin-coupled cellulose (β-CD-Cel) microgel was firstly synthesized via chemically coupling cellulose and β-CD in NaOH/urea aqueous solution. Following, after encapsulating the hydrophobic vanillin molecules into the cavities of β-CD-Cel microgel through host-guest interaction, cellulose-based long-lasting fragrance-released complex was obtained. β-CD was mainly bonded onto the hydroxyl groups at C6 in the AGU units of cellulose, and about 0.5 β-CD molecule were introduced into the AGU unit when cellulose skeleton contained the β-CD content of 19.33%. FTIR, 1H NMR, XRD, and UV–Vis provided evidences for the encapsulation of vanillin in the cavity of β-CD-Cel, and the encapsulating efficiency of vanillin for the β-CD-Cel inclusion complex was upped to 86.9%, which exceeded that of single β-CD small molecule encapsulating fragrance. Benefiting from the reversible host-guest interaction between β-CD and vanillin molecule, the continuous fragrance release time could exceed 196 h, and the sustained release behavior of β-CD-Cel complex could be adjusted by temperature. Also, the fragrance-released β-CD-Cel composite film showed high transparency, strong water resistance, and good flexibility. The vanillin retention of the composite film can keep 40% after soaking in ethanol solution for 96 h. This study will provide a new approach for the development of biomass functional coating.

Supramolecular Radiosensitizer Based on Hypoxia-Responsive Macrocycle.

Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia‐responsive macrocycle with small‐molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host–guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4A•AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation‐mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent‐based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation.

High capacity ammonia adsorption in a robust metal-organic framework mediated by reversible host-guest interactions.

To understand the exceptional adsorption of ammonia (NH3) in MFM-300(Sc) (19.5 mmol g−1 at 273 K and 1 bar without hysteresis), we report a systematic investigation of the mechanism of adsorption by a combination of in situ neutron powder diffraction, inelastic neutron scattering, synchrotron infrared microspectroscopy, and solid-state 45Sc NMR spectroscopy. These complementary techniques reveal the formation of reversible host–guest supramolecular interactions, which explains directly the observed excellent reversibility of this material over 90 adsorption–desorption cycles.

Injectable supramolecular hydrogels based on host–guest interactions with cell encapsulation capabilities

Injectable hydrogels, which can deliver cells or drugs directly to tissue sites by minimally invasive injection methods, have attracted considerable attention. In this work, using β-cyclodextrin-grafted alginate as the host polymer and adamantane-grafted polyacrylamide as the guest polymer, an injectable supramolecular hydrogel system was developed based on the host–guest interaction between β-cyclodextrin (βCD) and adamantane (Ad). Simple physical mixing and stirring methods allowed the hydrogels to be prepared in a short time (<1 min). The rheological and mechanical properties and microscopic morphology of the hydrogels were conveniently regulated by changing the grafting degree of βCD and Ad in alginate or polyacrylamide. The shear-thinning and self-healing properties induced by reversible host–guest interactions and a natural, plant-based polysaccharide endow the developed hydrogels with good injectability and biocompatibility, respectively. Experiments showed that the hydrogels effectively adhered to pork tissue. Moreover, human umbilical vein endothelial cells and human ovarian cancer cells encapsulated in the hydrogels showed good viability and three-dimensional distribution after being cultured for three days. Overall, the rapid preparation method and the advantages of injectability, self-healing and cytocompatibility endow the proposed injectable hydrogel system with great potential as a tissue engineering material.

Mechanical stimulation of single cells by reversible host-guest interactions in 3D microscaffolds.

Many essential cellular processes are regulated by mechanical properties of their microenvironment. Here, we introduce stimuli-responsive composite scaffolds fabricated by three-dimensional (3D) laser lithography to simultaneously stretch large numbers of single cells in tailored 3D microenvironments. The key material is a stimuli-responsive photoresist containing cross-links formed by noncovalent, directional interactions between β-cyclodextrin (host) and adamantane (guest). This allows reversible actuation under physiological conditions by application of soluble competitive guests. Cells adhering in these scaffolds build up initial traction forces of ~80 nN. After application of an equibiaxial stretch of up to 25%, cells remodel their actin cytoskeleton, double their traction forces, and equilibrate at a new dynamic set point within 30 min. When the stretch is released, traction forces gradually decrease until the initial set point is retrieved. Pharmacological inhibition or knockout of nonmuscle myosin 2A prevents these adjustments, suggesting that cellular tensional homeostasis strongly depends on functional myosin motors.

High-Strength and High-Toughness Silk Fibroin Hydrogels: A Strategy Using Dynamic Host-Guest Interactions.

Natural polymer-based hydrogels attract great attention because of their inherent biocompatibility and controllable biodegradability. However, the broad applications of these hydrogels require a combination of high mechanical strength, high toughness, fatigue resistance, as well as self-healing. The integration of this combination into one natural polymer-based hydrogel remains challenging. Here, a molecular design strategy was proposed to fabricate mechanically robust silk fibroin-based hydrogels using host-guest interactions. Silk fibroin molecules was chemically modified with cholesterol (Chol, guest) or β-cyclodextrin (β-CD, host), and host-guest interaction between Chol and β-CD moieties drove the supramolecular assemblies of hydrogels. The dissociation/reassociation behavior of host-guest complexation, serving as sacrificial bonds, endowed hydrogels with effective energy dissipation and rapid self-healing ability. The prepared silk fibroin-based hydrogels exhibited high mechanical strength, high toughness, and remarkable fatigue resistance, superior to conventional silk fibroin hydrogels. Moreover, due to reversible host-guest interactions, hydrogels achieved facile functional recovery after damage without any external stimuli. This design strategy provides an avenue to develop natural polymer-based materials with robust mechanical properties, thus broadening current hydrogel applications.

Pillar[5]arene‐Stabilized Silver Nanoclusters: Extraordinary Stability and Luminescence Enhancement Induced by Host–Guest Interactions

AbstractHerein, we report the synthesis of a new class of functional silver nanoclusters (AgNCs) capped with pillar[5]arene (P5)‐based host ligands. These NCs are readily prepared through direct synthesis or ligand exchange synthesis and are stable at room temperature for over 4 months. The pillar[5]arene‐stabilized NCs (Ag29(LA‐P5)12(TPP)2) endorse reversible host–guest interactions with neutral alkylamines and cationic quaternary ammonium guests. This results in the formation of spherical assemblies with unparalleled changes in their optical properties including an astonishing circa 2000‐fold luminescence enhancement. This is the highest luminescence enhancement ratio reported so far for such atomically precise NCs. Our synthetic protocol paves the way for the preparation of a new generation of metal nanoclusters protected by macrocyclic ligands with molecular recognition and selectivity toward specific guests.

Pillar[5]arene-Stabilized Silver Nanoclusters: Extraordinary Stability and Luminescence Enhancement Induced by Host-Guest Interactions.

Herein, we report the synthesis of a new class of functional silver nanoclusters (AgNCs) capped with pillar[5]arene (P5)-based host ligands. These NCs are readily prepared through direct synthesis or ligand exchange synthesis and are stable at room temperature for over 4 months. The pillar[5]arene-stabilized NCs (Ag29 (LA-P5)12 (TPP)2 ) endorse reversible host-guest interactions with neutral alkylamines and cationic quaternary ammonium guests. This results in the formation of spherical assemblies with unparalleled changes in their optical properties including an astonishing circa 2000-fold luminescence enhancement. This is the highest luminescence enhancement ratio reported so far for such atomically precise NCs. Our synthetic protocol paves the way for the preparation of a new generation of metal nanoclusters protected by macrocyclic ligands with molecular recognition and selectivity toward specific guests.

Recent Progress in Metal-Organic Framework (MOF) Based Luminescent Chemodosimeters.

Metal–organic frameworks (MOFs), as a class of crystalline hybrid architectures, consist of metal ions and organic ligands and have displayed great potential in luminescent sensing applications due to their tunable structures and unique photophysical properties. Until now, many studies have been reported on the development of MOF-based luminescent sensors, which can be classified into two major categories: MOF chemosensors based on reversible host–guest interactions and MOF chemodosimeters based on the irreversible reactions between targets with a probe. In this review, we summarize the recently developed luminescent MOF-based chemodosimeters for various analytes, including H2S, HClO, biothiols, fluoride ions, redox-active biomolecules, Hg2+, and CN−. In addition, some remaining challenges and future perspectives in this area are also discussed.

Cyclodextrin-/photoisomerization-modulated assembly and disassembly of an azobenzene-grafted polyoxometalate cluster.

Herein, a mono-lacunary Keggin-type polyoxometalate (POM), [SiW11O39]8-, grafted with an azobenzene group through Sn ion bridging was prepared, and the formed organic-inorganic hybrid cluster was characterized via elemental analysis, NMR, TGA, and IR techniques. A vesicular structure of the hybrid cluster assembly in aqueous media was observed in the TEM image, and it dissociated in the presence of α-/β-, γ-cyclodextrins (α-/β-, γ-CDs); this dissociation was driven by the host-guest interactions. The monodispersed inclusion complex further reassembled into smaller micelles under irradiation with 365 nm light, and this transformation was reversibly controlled by alternating the irradiation with 450 nm light. Moreover, in the case of the POM-Azo/β-CD system, reassembly from the monodispersed state to the vesicular state was achieved by the addition of a competitive guest molecule. Thus, the reversible host-guest interactions combining reversible photoisomerization of the azobenzene group provided multiple ways to modulate the assembly and disassembly of the POM hybrid as well as the changes between different assemblies. The present study inspires the potential use of these kind of hybrid POMs in enhanced catalytic reactions and recycling.

Preparation of light-sensitive polymer/graphene composite via molecular recognition by β-cyclodextrin

The dispersion of graphene in water has generally been considered an insurmountable challenge owing to its hydrophobic nature. In this study, a new type of light-sensitive polymer/graphene composite (AzoPEO/β-CD–RGO) was synthesized by the reversible host–guest interaction between azobenzene-terminal poly(ethylene oxide) (AzoPEO) and a β-cyclodextrin (β-CD) host attached to the surface of graphene via hydrogen bonding. In water, the AzoPEO/β-CD–RGO composite not only is well dispersed, but also exhibits reversible dispersion/aggregation behavior triggered by UV and visible light. Moreover, the graphene composite can be used to fabricate a light-responsive graphene-based drug delivery system. This kind of light-responsive graphene composite, which efficiently allows the control of graphene dispersion/aggregation, may find wide applications in the preparation of intelligent drug delivery systems, smart sensors, and switching devices.

Recent Advances in Cyclodextrin-Based Light-Responsive Supramolecular Systems.

Cyclodextrins (CDs), one of the host molecules in supramolecular chemistry, can host guest molecules to form inclusion complexes via non-covalent and reversible host-guest interactions. CD-based light-responsive supramolecular systems are typically constructed using CDs and guest molecules with light-responsive moieties, including azobenzene, arylazopyrazole, o-nitrobenzyl ester, pyrenylmethyl ester, coumarin, and anthracene. To date, numerous efforts have been reported on the topic of CD-based light-responsive supramolecular systems, but these have not yet been highlighted in a separated review. This review summarizes the efforts reported over the past ten years. The main text of this review is divided into five sections (vesicles, micelles, gels, capturers, and nanovalves) according to the formation of self-assemblies. This feature article aims to afford a comprehensive understanding of the light-responsive moieties used in the construction of CD-based light-responsive supramolecular systems and to provide a helpful guide for the further design of CD-based light-responsive supramolecular systems.

Dynamic Mechano-Regulation of Myoblast Cells on Supramolecular Hydrogels Cross-Linked by Reversible Host-Guest Interactions

A new class of supramolecular hydrogels, cross-linked by host-guest interactions between β-cyclodextrin (βCD) and adamantane, were designed for the dynamic regulation of cell-substrate interactions. The initial substrate elasticity can be optimized by selecting the molar fraction of host- and guest monomers for the target cells. Moreover, owing to the reversible nature of host-guest interactions, the magnitude of softening and stiffening of the substrate can be modulated by varying the concentrations of free, competing host molecules (βCD) in solutions. By changing the substrate elasticity at a desired time point, it is possible to switch the micromechanical environments of cells. We demonstrated that the Young’s modulus of our “host-guest gels”, 4–11 kPa, lies in an optimal range not only for static (ex situ) but also for dynamic (in situ) regulation of cell morphology and cytoskeletal ordering of myoblasts. Compared to other stimulus-responsive materials that can either change the elasticity only in one direction or rely on less biocompatible stimuli such as UV light and temperature change, our supramolecular hydrogel enables to reversibly apply mechanical cues to various cell types in vitro without interfering cell viability.

Construction of a Repairable Fixed Porous Catalytic Bed Loaded with Gold Nanoparticles via Multivalent Host–Guest Interactions

The reversible combination between gold nanoparticles (AuNPs) and carriers is crucial for the preparation of a recycle system. Here, a repairable catalytic system was constructed on the basis of AuNPs and porous nickel (PNi) which were combined through the multivalent host–guest interactions between βCD-AuNPs and PNi@IPTS-Azo [β-CD, β-cyclodextrin; IPTS, (3-isocyanatopropyl) triethoxysilane; Azo, azobenzene]. The large specific surface area and connected porous structure of PNi provide a good opportunity to achieve the multivalent interactions between βCD-AuNPs and PNi@IPTS-Azo in the nickel. Additionally, the reaction solution could be catalyzed by flowing over the PNi@IPTS-Azo@βCD-AuNPs substrates. This catalytic model showed a high efficiency close to 95%. Because of the reversible host–guest interactions between β-cyclodextrin and azobenzene, the catalytic system could be regenerated by removing the deactivated AuNPs with UV-light irradiation and recombining new ones through multivalent interactions in situ. This type of catalytic system is regenerative, material-saving, and effective. This system could be expected to be constructed as catalytic fixed beds and applied in industry.

Reduced Graphene Oxide-Reinforced Polymeric Films with Excellent Mechanical Robustness and Rapid and Highly Efficient Healing Properties.

The fabrication of nanofiller-reinforced intrinsic healable polymer composite films with both excellent mechanical robustness and highly efficient healability is challenging because the mobility of the polymer chains is suppressed by the incorporated nanofillers. In this study, we exploit the reversible host-guest interactions between nanofillers and the matrix polymer films and report the fabrication of intrinsically healable, reduced graphene oxide (RGO)-reinforced polymer composite films capable of conveniently and repeatedly healing cuts of several tens of micrometers wide. The healable films can be prepared via layer-by-layer assembly of poly(acrylic acid) (PAA) with complexes of branched poly(ethylenimine) grafted with ferrocene (bPEI-Fc) and RGO nanosheets modified with β-cyclodextrin (RGO-CD) (denoted as bPEI-Fc&RGO-CD). The as-prepared PAA/bPEI-Fc&RGO-CD films are mechanically robust with a Young's modulus of 17.2 ± 1.9 GPa and a hardness of 1.00 ± 0.30 GPa. The healing process involves two steps: (i) healing of cuts in an oxidation condition in which the host-guest interactions between bPEI-Fc and RGO-CD nanosheets are broken and the cuts on the films are healed; and (ii) reconstruction of host-guest interactions between bPEI-Fc and RGO-CD nanosheets via reduction to restore the original mechanical robustness of the films.

Novel highly-flexible, acid-resistant and self-healing host-guest transparent multilayer films

The integration of self-healing ability and mechanical robustness is a challenge in the fabrication of the highly transparent films which are based on host-guest interactions. Beta-cyclodextrin (β-CD) bound with poly (ethylenimine) (PEI) and adamantane (AD) linked with poly (acrylic acid) (PAA) were employed to form a multilayer film based on host-guest interactions via the layer-by-layer (LbL) self-assembly technique. The obtained highly flexible, acid-resistant, self-healing host-guest transparent multilayer film can easily and repeatedly heal external mechanical damage. The PAA-AD/PEI-β-CD multilayer film enhances the transmittance and mechanical properties of PAA/PEI. The average transmittance was approximately 98.6%, and the pre-crack length was approximately 163mm. The multilayer film can be self-healing because of the rearrangement and reversible host-guest interactions between β-CD and AD, and its practical utility as curable coatings have been demonstrated.