Host-guest Assembly Research Articles

A Promising Approach for Controlling the Second Coordination Sphere of Biomimetic Metal Complexes: Encapsulation in a Dynamic Hydrogen-Bonded Capsule.

The design of biomimetic models of metalloenzymes needs to take into account many factors and is therefore a challenging task. We propose in this work an original strategy to control the second coordination sphere of a metal centre and its distal environment. A biomimetic complex, reproducing the first coordination sphere, is encapsulated in a self-assembled hydrogen-bonded capsule. The cationic complex is co-encapsulated with its counter-anion or with solvent molecules. The capsule is dynamic, allowing a fast in/out exchange of the co-encapsulated species. It also provides both a hydrogen-bonding site in the second coordination sphere and a source of proton as it can be deprotonated in the presence of the complex, providing a globally neutral host-guest assembly. This simple and broad scope strategy is unprecedented in biomimetic studies. The approach appears to be a very promising method for the stabilisation of reactive species and for the study of their reactivity.

Metal-Free White Light-Emitting Fluorescent Material Based on Simple Pillar[5]arene-tripodal Amide System and Theoretical Insights on Its Assembly and Fluorescent Properties.

The booming of host-guest assembly-based supramolecular chemistry provides abundant ways to construct functional systems and materials. Attracted by the important application prospect of white light emission and aggregation-induced emission (AIE) materials, herein, we report an efficient way for fabricating metal-free white light-emitting AIE materials through the supramolecular assembly of simple organic compounds: methoxyl pillar[5]arene (MP5) and tri-(pyridine-4-ylamido)benzene (TAP). By host-guest assembly, MP5 and TAP formed a supramolecular polymer (MP5-T); meanwhile, the MP5-T xerogel powder emitted white light at CIE coordinates (0.29 and 0.29). The supramolecular assembly and white light-emitting mechanisms were carefully investigated by experiments as well as quantum chemical calculations including density functional theory (DFT), reduced density gradient, electrostatic surface potential, independent gradient model, and frontier molecular orbital (highest-occupied molecular orbital-lowest-unoccupied molecular orbital) analyses. Interestingly, according to the experiments and calculations, the supramolecular assembly is critical in the white light-emitting phenomenon. Moreover, in this work, the quantum chemical calculations could not only support experimental phenomena but also provide deep understanding and visualized presentation of the assembly and emission mechanism. In addition, the obtained MP5-T solid powder could serve as a novel and easy means to make material for white light-emitting devices.

A bioinspired mineral-organic composite hydrogel as a self-healable and mechanically robust bone graft for promoting bone regeneration

Despite advances in the development of osteo-regenerative biomaterials, current products are vulnerable to stress-induced formation of cracks, resulting in the loss of functionality and a limited lifespan. In the present study, a strategy based on host-guest assembly was developed to fabricate a silk fibroin-based inorganic-organic hybrid hydrogel (termed SF@HG@HA) in which silk fibroin was used as a polymer template to tether host (β-cyclodextrin) and guest (cholesterol) monomers, respectively. Due to dynamic host-guest interactions, the prepared hydrogel could repair itself spontaneously when damaged, without the assistance of any external stimuli, mimicking the self-healing characteristics of native bone tissue. Furthermore, the efficient energy dissipation mechanism provided by the host-guest crosslinking strategy endowed the hydrogel with robust mechanical properties to bear substantial mechanical loading. SF@HG@HA was shown to support cell proliferation and osteogenic differentiation in vitro and accelerate bone regeneration in critical-size rat femoral defects in vivo. Together, the silk fibroin-based self-healing hydrogel with robust mechanical properties shows potential applications in the reconstruction of bone defects, which may provide new directions for the design of functional biomaterials for tissue regeneration.

An AIE singlet oxygen generation system based on supramolecular strategy

The design of supramolecular systems with efficient singlet oxygen generation has attracted considerable interests. Herein, an AIE-based singlet oxygen generation system with chemiluminescence properties is reported in aqueous media based on supramolecular host‒guest assembly between a water-soluble pillar[5]arene (WP5) and an AIE photosensitizer (TPEDM). The formed supramolecular nanoparticles exhibit significant singlet oxygen generation ability as well as enhanced fluorescence. In addition, by introducing catalase, this H2O2-responsive supramolecular system shows increased 1O2 generation efficiency compared with the blank nanoparticles. An efficient chemiluminescence system can also be achieved by entrapping an energy donor adamantane derivative (AMPPD). Moreover, the present system can function as nanoreactors to perform the photooxidation of dopamine to form polydopamine with visible light irradiation. This work provides a new strategy for the construction of 1O2 generation system based on supramolecular nanomaterials, which has potential applications in the fields such as chemiluminescence imaging and controlled photocatalysis.

Stimuli-responsive supramolecular hydrogel with white AIE effect for ultrasensitive detection of Fe3+ and as rewritable fluorescent materials

The development of fluorescent smart materials by introducing white light emission into supramolecular polymer hydrogels, and tuning their aggregation-induced emission (AIE) effect are essential for the manufacture of advanced functional materials. Herein, a novel bi-component supramolecular polymer hydrogel (NDG) was successfully constructed via a simple host-guest assembly process based on two easy-to-synthesize tripodal gelators (NTS and DTB). Strikingly, the NDG exhibits strong white aggregation-induced emission (WAIE), and can act as an AIE-based sensor for ultrasensitive detect Fe3+ and F−. The lowest limits of detection (LODs) are 5.33 × 10−9 M and 1.61 × 10−8 M, respectively. The xerogel of NDG exhibits nice adsorption and separation capacity for Fe3+, the adsorption rate reaches to 99.26%. In addition, the prepared NDG-based thin films can be used as rewritable fluorescent display material for the continuity detection of Fe3+ and F−. Due to the outstanding optical behavior of the NDG, it also be used as an “IMPLICATION” logic gate at the molecular level. The AIE hydrogel-guided enriches the self-assembly strategy of new supramolecular polymers, which also makes it become a good candidate for flexible optical materials.

Carbon Dots in Porous Materials: Host–Guest Synergy for Enhanced Performance

AbstractCarbon dots (CDs) are emerging as a new class of carbon nanomaterials, which have inspired growing interest for their widespread applications in anti‐counterfeiting, sensing, bioimaging, optoelectronic and energy‐related fields. In terms of the concept of host–guest assembly, immobilizing CDs into porous materials (PMs) has proven to be an effective strategy to avoid the aggregation of bare CDs in solid state, in particular, the host—guest synergy with both merits of CDs and PMs affords composites promising properties in afterglow and tunable emissions, as well as optimizes their performance in optics, catalysis, and energy storage. This Minireview summarizes the recent progress in the research of CDs@PMs, and highlights synthetic strategies of constructing composites and roles of porous matrices in boosting the applications of CDs in diverse areas. The prospect of future exploration and challenges are proposed for designing advanced CDs‐based functional nanocomposite materials.

Carbon Dots in Porous Materials: Host-Guest Synergy for Enhanced Performance.

Carbon dots (CDs) are emerging as a new class of carbon nanomaterials, which have inspired growing interest for their widespread applications in anti-counterfeiting, sensing, bioimaging, optoelectronic and energy-related fields. In terms of the concept of host-guest assembly, immobilizing CDs into porous materials (PMs) has proven to be an effective strategy to avoid the aggregation of bare CDs in solid state, in particular, the host-guest synergy with both merits of CDs and PMs affords composites promising properties in afterglow and tunable emissions, as well as optimizes their performance in optics, catalysis, and energy storage. This Minireview summarizes the recent progress in the research of CDs@PMs, and highlights synthetic strategies of constructing composites and roles of porous matrices in boosting the applications of CDs in diverse areas. The prospect of future exploration and challenges are proposed for designing advanced CDs-based functional nanocomposite materials.

Zwitterionic Ru(III) Complexes: Stability of Metal-Ligand Bond and Host-Guest Binding with Cucurbit[7]uril.

A wide range of ruthenium-based coordination compounds have been reported to possess potential as metallodrugs with anticancer or antimetastatic activity. In this work, we synthesized a set of new zwitterionic Ru(III) compounds bearing ligands derived from N-alkyl (R) systems based on pyridine, 4,4'-bipyridine, or 1,4-diazabicyclo[2.2.2]octane (DABCO). The effects of the ligand(s) and their environment on the coordination stability have been investigated. Whereas the [DABCO-R]+ ligand is shown to be easily split out of a negative [RuCl4]- core, positively charged R-pyridine and R-bipyridine ligands form somewhat more stable Ru(III) complexes and can be used as supramolecular anchors for binding with macrocycles. Therefore, supramolecular host-guest assemblies between the stable zwitterionic Ru(III) guests and the cucurbit[7]uril host were investigated and characterized in detail by using NMR spectroscopy and single-crystal X-ray diffraction. Paramagnetic 1H NMR experiments supplemented by relativistic DFT calculations of the structure and hyperfine NMR shifts were performed to determine the host-guest binding modes in solution. In contrast to the intramolecular hyperfine shifts, dominated by the through-bond Fermi-contact mechanism, supramolecular hyperfine shifts were shown to depend on the "through-space" spin-dipole contributions with structural trends being satisfactorily reproduced by a simple point-dipole approximation.

High-Performance n -Hexane Purification by Nonporous Adaptive Crystals of Leaning Pillar[6]arene

The production of high-purity n-hexane under mild conditions is of great significance in both the petrochemical industry and synthetic chemistry. Here, we report an easy-to-operate and energy-effic...

Supramolecular Self-Assembled Nanostructures for Cancer Immunotherapy.

Functional materials and nanostructures have been widely used for enhancing the therapeutic potency and safety of current cancer immunotherapy. While profound nanostructures have been developed to participate in the development of cancer immunotherapy, the construction of intricate nanostructures with easy fabrication and functionalization properties to satisfy the diversified requirements in cancer immunotherapy are highly required. Hierarchical self-assembly using supramolecular interactions to manufacture organized architectures at multiple length scales represents an interesting and promising avenue for sophisticated nanostructure construction. In this mini-review, we will outline the recent progress made in the development of supramolecular self-assembled nanostructures for cancer immunotherapy, with special focus on the supramolecular interactions including supramolecular peptide assembly, supramolecular DNA assembly, lipid hydrophobic assembly, host-guest assembly, and biomolecular recognition assembly.

Repeatedly Intrinsic Self-Healing of Millimeter-Scale Wounds in Polymer through Rapid Volume Expansion Aided Host-Guest Interaction.

Implantable and wearable materials, which are usually used in/on a biological body, are mostly needed with biomimetic self-healing function. To enable repeatable large-wound self-healing and volume/structure recovery, we verified a proof-of-concept approach in this work. We design a polymer hydrogel that combines temperature responsiveness with an intrinsic self-healing ability through host-guest orthogonal self-assembly between two types of poly(N-isopropylacrylamide) (PNIPAM) oligomers. The result is thermosensitive, capable of fast self-repair of microcracks based on reversible host-guest assembly. More importantly, when a large open wound appears, the hydrogel can first close the wound via volume swelling and then completely self-repair the damage in terms of intrinsic self-healing. Meanwhile, its original volume can be easily recovered by subsequent contraction. As demonstrated by the experimental data, such millimeter-level wound self-healing and volume recovery can be repeatedly carried out in response to the short-term cooling stimulus. With low cytotoxicity and good biocompatibility, moreover, this highly intelligent hydrogel is greatly promising for practical large-wound self-healing in wound dressing, electronic skins, wearable biosensors, and humanoid robotics, which can tolerate large-scale human motions.

Genetically multimodal therapy mediated by one polysaccharides-based supramolecular nanosystem

Multimodal therapy has been continuously explored for different diseases. Photodynamic/gene combined therapy is a promising treatment strategy of tumor. However, the limitation of traditional chemical photosensitizer and the asynchronism of the two therapies restrict the development of this technology. Herein, one genetically multimodal treatment nanosystem (HES@PGEA/pKR-p53), composed of biocompatible hydroxyethyl starch (HES), low-toxic β-cyclodextrin-based ethanolamine-functionalized poly(glycidyl methacrylate) (CD-PGEA) and combined plasmid pKR-p53, is structurally designed based on host-guest assembly and electrostatic complexing. Supramolecular assembled HES@PGEA exhibits low cytotoxicity, excellent cellular internalization and enhanced gene transfection efficiency. With the delivery of pKR-p53, p53 and KillerRed proteins could be expressed simultaneously in the same tumor cell for p53-mediated apoptosis therapy and photodynamic therapy (PDT), where the synergistic effect of KillerRed and p53 proteins is achieved. Compared with single therapy, HES@PGEA/pKR-p53 shows more remarkable antitumor effects in the 4T1 tumor model.

Superlubricity of Fullerene Derivatives Induced by Host-Guest Assembly.

Fullerenes have been recognized as good candidates for solid lubricants. In this study, the microscale superlubricity of fullerene derivatives was accomplished by the construction of regular host-guest assembly structures. Herein, the host-guest assembly structures of fullerene derivatives were successfully constructed on a highly oriented pyrolytic graphite (HOPG) surface by introducing the macrocycles as the templates and were explicitly revealed by scanning tunneling microscopy (STM). Meanwhile, the nanotribological properties of the host-guest assemblies were measured using atomic force microscopy (AFM), revealing ultralow friction coefficients of 0.003-0.008, which could be attributed to the restriction on removal of fullerene molecules after introducing the templates. The interaction energies were calculated by density functional theory (DFT) method, which indicates the correlation between friction coefficients and interaction strength in the host-guest assemblies. The effort on fullerene-related superlubricity could extend the solid superlubrication systems and provide a novel pathway to explore the friction mechanisms at the molecular level.

Probing Host-Guest inclusion complexes of Ambroxol Hydrochloride with α- & β-Cyclodextrins by physicochemical contrivance subsequently optimized by molecular modeling simulations

Herein, we report the inclusion of AMB in cyclodextrins leading to host-guest assemblies. The inclusion complexes comprised of Ambroxol Hydrochloride (AMB) with α-cyclodextrin (αCD) and β-cyclodextrin (βCD) have been confirmed by experimental (UV–vis titration, FTIR, ESI-MS, 1NMR, 2D-NMR) and computational studies (molecular docking, molecular mechanics calculation). The molecular docking studies demonstrate a better insight into geometry and inclusion mode of AMB inside αCD as well as βCD cavity. Formation of inclusion complexes with different cyclodextrins causes some structural changes of guest molecules during the encapsulation process confirmed by bond length, dihedral angle changes and dynamic simulations.

Chalcogen Bonding and Hydrophobic Effects Force Molecules into Small Spaces.

Supramolecular capsules are desirable containers for the study of molecular behavior in small spaces and offer applications in transport, catalysis, and material science. We report here the use of chalcogen bonding to form container assemblies that are stable in water. Cavitands 1-3 functionalized with 2,1,3-benzoselenadiazole walls were synthesized in good yield from resorcin[4]arenes. The solid-state single-crystal X-ray structure of 3 showed a dimeric assembly cemented together through multiple Se···N chalcogen bonds. Binding of hydrophobic and amphiphilic guests in D2O was investigated by 1H NMR methods and revealed host-guest assemblies of 1:1, 2:1, and 2:2 stoichiometries. Small guests such as n-hexane or cyclohexane assembled as 2:2 capsular complexes, larger guests like cyclohexane carboxylic acid or cyclodecane formed 1:1 cavitand complexes, and longer linear guests like n-dodecane, cyclohexane carboxylic acid anhydride, and amides created 2:1 capsular complexes. The 2:1 complex of the capsule with cyclohexane carboxylic acid anhydride was stable over 2 weeks, showing that the seam of chalcogen bonds is "waterproof". Selective uptake of cyclohexane over benzene and methyl cyclohexane over toluene was observed in aqueous solution with the capsule. Hydrophobic forces and hydrogen-bonding attractions between guest molecules such as 3-methylbutanoic acid stabilized the assemblies in the presence of the competing effects of water. The high polarizability and modest electronegativity of Se provide a capsule lining complementary to guest C-H bonds. The 2,1,3-benzoselenadiazole walls impart an unusually high magnetic anisotropy to the capsule environment, which is supported by density functional theory calculations.

Visible-Light-Excited Room-Temperature Phosphorescence in Water by Cucurbit[8]uril-Mediated Supramolecular Assembly.

Solid-state materials with efficient room-temperature phosphorescence (RTP) emissions have found widespread applications in materials science, while liquid or solution-phase pure organic RTP emission systems has been rarely reported, because of the nonradiative decay and quenchers from the liquid medium. Reported here is the first example of visible-light-excited pure organic RTP in aqueous solution by using a supramolecular host-guest assembly strategy. The unique cucurbit[8]uril-mediated quaternary stacking structure allows tunable photoluminescence and visible-light excitation, enabling the fabrication of multicolor hydrogels and cell imaging. The present assembly-induced emission approach, as a proof of concept, contributes to the construction of novel metal-free RTP systems with tunable photoluminescence in aqueous solution, providing broad opportunities for further applications in biological imaging, detection, optical sensors, and so forth.

Use of a cyclo-P4 building block - a way to networks of host-guest assemblies.

Despite the proven ability to form supramolecular assemblies via coordination to copper halides, organometallic building blocks based on four-membered cyclo-P4 ligands find only very rare application in supramolecular chemistry. To date, only three types of supramolecular aggregates were obtained based on the polyphosphorus end-deck complexes CpRTa(CO)2(η4-P4) (1a: CpR = Cp′′; 1b: CpR = Cp′′′), with none of them, however, possessing a guest-accessible void. To achieve this target, the use of silver salts of the weakly coordinating anion SbF6− was investigated as to their self-assembly in the absence and in the presence of the template molecule P3Se4. The two-component self-assembly of the building block 1a and the coinage-metal salt AgSbF6 leads to the formation of 1D or 3D coordination polymers. However, when the template-driven self-assembly was attempted in the presence of an aliphatic dinitrile, the unprecedented barrel-like supramolecular host–guest assembly P3Se4@[{(Cp′′Ta(CO)2(η4-P4))Ag}8]8+ of 2.49 nm in size was formed. Moreover, cyclo-P4-based supramolecules are connected in a 2D coordination network by dinitrile linkers. The obtained compounds were characterised by mass-spectrometry, 1H and 31P NMR spectroscopy and X-ray structure analysis.

Chain conformation transition induced host-guest assembly between triple helical curdlan and β-CD for drug delivery.

The unique conformation transition from a triple helix to single coils for the triple helical β-d-glucans has paved the way to fabricate various functional nanocomposites through the denaturing-renaturing process. This study firstly reports a novel kind of naturally derived supramolecular polymer micelle consisting of single-stranded chains of curdlan (CUR) and β-CDs. It is proposed that β-CDs as the host molecules were threaded onto single β-glucan chains (denatured triplex CUR) via the host-guest interaction, thereby forming supramolecular micelles. The results from the 1H NMR, FT-IR, XRD and 2D 1H NOESY NMR studies confirmed the formation of the inclusion complex and the existence of the core-shell structure of the supramolecular assembly. TEM images and DLS revealed that the self-organized micelles displayed a regular spherical shape with an average diameter of ∼27 nm. Furthermore, the hydrophobic anticancer drug camptothecin (CPT) was selected as a model drug and successfully encapsulated into the CUR/β-CD micelles. The drug-loaded micelles exhibited a steady sustained-release pattern regardless of the environmental pH. The flow cytometry and confocal laser scanning microscopy measurements confirmed that the CPT-loaded micelles could be well internalized into HepG 2 cells and continuously release the drug molecules inside the tumor cells. Meanwhile, the in vivo experiments demonstrated that CPT-loaded micelles could effectively inhibit tumor growth in comparison to free drugs. This concept will give a favorable platform to construct intelligent drug delivery systems for potential use.

The construction of an AIE-based controllable singlet oxygen generation system directed by a supramolecular strategy.

An aggregation-induced emission (AIE) based smart singlet oxygen (1O2) generation system has been successfully fabricated based on supramolecular host-guest assembly. The controllable 1O2 generation can be achieved by conveniently changing the molar ratio between the macrocyclic host (WP5) and the guest molecule (TPEPY). Moreover, reversible control of 1O2 generation and fluorescence emission of supramolecular nanoassemblies can be achieved via adding Fe3+ and EDTA, which allows qualitatively monitoring the singlet oxygen generation efficiency by the naked eye.

Atomic Decomposition Scheme of Noncovalent Interactions Applied to Host-Guest Assemblies.

The design of novel stimuli-responsive supramolecular systems based on host-guest chemistry implies a thorough understanding of the noncovalent interactions involved. In this regard, some computational tools enabling the extraction of the noncovalent signatures from local descriptors based on the electron density have been previously proposed. Although very useful to detect the existence of such interactions, these analyses provide only a semi-quantitative description, which represents a limitation. In this work, we present a novel computational tool based on the local atomic descriptor IGM-δginter/At, which is able to decompose the fragment interaction into atomic contributions. Then, the role played by each atom in the formation of the host-guest assembly is quantified by an integrated Δginter/At score. Herein, we apply the IGM-Δginter/At approach to some challenging systems, including multimetallic arrays, buckycatchers, and organic assemblies. These systems exhibit unique structural features that make it difficult to determine the host/guest atoms that contribute the most to the guest encapsulation. Here, the Δginter/At score proves to be an appealing tool to shed light on the guest accommodation on a per-atom basis and could be useful in the rational design of more selective target agents. We strongly believe that this novel approach will be useful for experimental teams devoted to the synthesis of supramolecular systems based on host-guest chemistry.