Host-guest Molecular Recognition Research Articles

Cucurbit[6]uril functionalized gold nanoparticles and electrode for the detection of metformin drug

Based on the host-guest molecular recognition capability of cucurbit[6]uril (CB[6]) modified on the gold surface, sensitive spectrophotometric and electrochemical methods for the detection of metformin (MET) have been developed. The molecular recognition between cucurbit[7]uril (CB[7]) or CB[6] and MET is initially demonstrated and the related recognition mechanism is further deliberated. First, CB[6]-modified gold nanoparticles (AuNPs/CB[6]) were synthesized and then characterized by ultraviolet visible light spectrum (UV–vis) and transmission electron microscopy (TEM). The aggregation of AuNPs/CB[6] prompted by MET triggered changes of color and the absorption spectrum, that explored for the visual identification and spectrophotometric determination of MET. Under the optimized detection conditions, the UV–vis spectrometry had a good linear relationship in the range of 6–700 µmol/L, and the detection limit was 2 µmol/L. In addition, a single-layer CB[6]-modified gold electrode (GE-CB[6]) detection system for MET was constructed. As the concentration of MET in the solution continues to increase, the charge transfer resistance (Rct) in the Nyquist diagram of the electrochemical impedance method (EIS) continues to increase. In the concentration range from 10 pmol/L to 20 nmol/L, the logarithm of the MET concentration has a good linear relationship with Rct, and the detection limit of this method is 1.35 pmol/L. Both methods have good concentration sensitivity to MET in different concentration ranges, providing a powerful tool for the detection of MET.

A General Supramolecular Approach to Regulate Protein Functions by Cucurbit[7]uril and Unnatural Amino Acid Recognition

AbstractRegulation of specific protein function is of great importance for both research and therapeutic development. Many small or large molecules have been developed to control specific protein function, but there is a lack of a universal approach to regulate the function of any given protein. We report a general host–guest molecular recognition approach involving modification of the protein functional surfaces with genetically encoded unnatural amino acids bearing guest side chains that can be specifically recognized by cucurbit[7]uril. Using two enzymes and a cytokine as models, we showed that the activity of proteins bearing unnatural amino acid could be turned off by host molecule binding, which blocked its functional binding surface. Protein activity can be switched back by treatment with a competitive guest molecule. Our approach provides a general tool for reversibly regulating protein function through molecular recognition and can be expected to be valuable for studying protein functions.

A General Supramolecular Approach to Regulate Protein Functions by Cucurbit[7]uril and Unnatural Amino Acid Recognition.

Regulation of specific protein function is of great importance for both research and therapeutic development. Many small or large molecules have been developed to control specific protein function, but there is a lack of a universal approach to regulate the function of any given protein. We report a general host-guest molecular recognition approach involving modification of the protein functional surfaces with genetically encoded unnatural amino acids bearing guest side chains that can be specifically recognized by cucurbit[7]uril. Using two enzymes and a cytokine as models, we showed that the activity of proteins bearing unnatural amino acid could be turned off by host molecule binding, which blocked its functional binding surface. Protein activity can be switched back by treatment with a competitive guest molecule. Our approach provides a general tool for reversibly regulating protein function through molecular recognition and can be expected to be valuable for studying protein functions.

Host–Guest Molecular Recognition at Liquid–Liquid Interfaces

Host–guest molecular recognition at the liquid–liquid interface endows the interface with unique properties, including stimuli-responsiveness and self-regulation, due to the dynamic and reversible nature of non-covalent interactions. Increasing research efforts have been put into the preparation of supramolecular interfacial systems such as films and microcapsules by integrating functional components (e.g., colloidal particles, polymers) at the interface, providing tremendous opportunities in the areas of encapsulation, delivery vehicles, and biphasic reaction systems. In this review, we summarize recent progress in supramolecular interfacial systems assembled by host–guest chemistry, and provide an overview of the fabrication process, functions, and promising applications of the resultant constructs.

Reversible regulation of esterase activity via host–guest molecular recognition at the nanoparticle surface

Precise and controlled regulation of enzymes is an important aspect to understand their fundamental complex biological molecular mechanism. While many synthetic receptors were developed to inhibit enzymatic activity, they lack reversible control over their function. Herein, we present an engineered nanoparticle (NP) surface that synergistically combines host–guest assembly with protein surface targeting to reversibly control enzyme activity. We demonstrate the effective inhibition of anionic esterase enzyme activity upon electrostatic binding to dimethyl-benzyl ammonium terminated positively charged gold NPs. The NP surface upon threading by non-covalent host–guest interactions with CB[7] moiety has enabled the reactivation of enzyme catalysis. This reactivation has been further reversed by disrupting NP–CB[7] complex by employing a competitive orthogonal guest, hence leading to the controlled reversibility of enzyme activity. Tuning of NP surfaces by different supramolecular interactions and concomitant protein recognition on the NP surface can thus be emphasized as a significant tool for biotechnology applications.

Photoresponsive Structured Liquids Enabled by Molecular Recognition at Liquid-Liquid Interfaces.

Using host-guest molecular recognition at the oil-water interface, a new type of photoresponsive nanoparticle surfactant (NPS) was designed and prepared to structure liquids. With the help of a polymeric surfactant, the interfacial host-guest interactions can be significantly enhanced, leading to the rapid formation and assembly of a NP monolayer and offering sufficient binding energy to hold the NPs in a jammed state. The assembly of the NPSs can be reversibly manipulated via a photoswitchable jamming-to-unjamming transition, endowing the interface as well as the macroscopic assemblies with responsiveness to the external trigger (photons). This study for the first time opens a pathway for the construction of multiresponsive, structured all-liquid systems by introducing host-guest chemistry, showing promising potential applications in encapsulation, delivery systems, and unique microfluidic devices.

Supramolecular Approach to Electron Paramagnetic Resonance Distance Measurement of Spin-Labeled Proteins.

We demonstrate a host-guest molecular recognition approach to advance double electron-electron resonance (DEER) distance measurements of spin-labeled proteins. We synthesized an iodoacetamide derivative of 2,6-diazaadamantane nitroxide (DZD) spin label that could be doubly incorporated into T4 Lysozyme (T4L) by site-directed spin labeling with efficiency up to 50% per cysteine. The rigidity of the fused ring structure and absence of mobile methyl groups increase the spin echo dephasing time (Tm) at temperatures above 80 K. This enables DEER measurements of distances >4 nm in DZD-labeled T4L in glycerol/water at temperatures up to 150 K with increased sensitivity compared to that of a common spin label such as MTSL. Addition of β-cyclodextrin reduces the rotational correlation time of the label, slightly increases Tm, and most importantly, narrows (and slightly lengthens) the interspin distance distributions. The distance distributions are in good agreement with simulated distance distributions obtained by rotamer libraries. These results provide a foundation for developing supramolecular recognition to facilitate long-distance DEER measurements at near physiological temperatures.

PH/ROS Dual-Responsive Supramolecular Vesicles Fabricated by Carboxylated Pillar[6]arene-Based Host-Guest Recognition and Phenylboronic Acid Pinacol Ester Derivative.

The pH and reactive oxygen species (ROS) dual-responsive supramolecular vesicle utilizing a novel host-guest molecular recognition between a phenylboronic acid pinacol ester derivative carrying long alkyl chain (PBEC12A) and carboxylated pillar[6]arene (CP[6]) is developed. The host-guest complexation between CP[6] and PBEC12A was first studied in aqueous solution. PBEC12A was encapsulated within CP[6] forming a stable host-guest complex with a binding constant as high as 106 M-1 order of magnitude. The driving force behind such a host-guest recognition was the combination of electrostatic interaction and hydrophobic effect. Then, the self-assembly of the supra-amphiphiles of PBEC12A-CP[6] host-guest complexes was investigated in aqueous solution through high-resolution transmission electron microscope and dynamic light scattering. It was found that the supra-amphiphiles self-assembled into supramolecular vesicles and the size of the self-assembled supramolecular vesicles could be tuned from 25 to 200 nm by varying the ratio of CP[6] to PBEC12A. To demonstrate the pH- and ROS-responsive properties of the self-assembled vesicles, the supramolecular vesicles self-assembled from PBEC12A/CP[6] (5:1) were utilized. The Nile Red loading and release studies demonstrated that the supramolecular vesicles possessed good pH/ROS dual-responsive properties. This study enriches the field of supra-amphiphile based on noncovalent interactions. It is anticipated that the pH/ROS dual-responsive supramolecular vesicles have potential applications in drug-delivery systems because both the stimuli are in close relation with specific microenvironments of tumors and relevant diseases of the human body.

A Self-Cross-Linking Supramolecular Polymer Network Enabled by Crown-Ether-Based Molecular Recognition.

Supramolecular polymers based on host-guest molecular recognition have emerged as promising platforms for the development of smart materials. However, the studies on them are primarily conducted in solution and/or in the gel state. In contrast, little is known about dynamic properties and applications of supramolecular polymers in bulk. Herein, we present a self-cross-linking supramolecular polymer network (SPN) as a model system to understand the bulk properties controlled by noncovalent interactions. Specifically, the SPN monomer is composed of two benzo-21-crown-7 (B21C7) host units and two dialkylammonium salt guest moieties on a four-arm core, wherein complementary host-guest complexation drives the formation of the SPN with [2]pseudorotaxane linkages between B21C7 and ammonium motifs. The dynamic and reversible behaviors of the linkages are evaluated by measurement of viscoelasticity. The results indicate that the host-guest molecular recognition becomes highly dynamic at elevated temperature. Moreover, the relatively high activation energy of the SPN manifests itself as a new type of thermoplastic material with network topology freezing glass transition. Finally, we demonstrate how these findings provide insights into the malleability and processability of the SPN by simple demos. The fundamental understanding gained from the research on this SPN in bulk will facilitate the advancement and application of supramolecular materials.

Synthesis of a Tetracorannulene-perylenediimide That Acts as a Selective Receptor for C60 over C70.

We report the use of a tetraborylated perylenediimide as starting material for the preparation of a tetracorannulene-perylenediimide that is able to bind up to two fullerene-C60 molecules by host-guest molecular recognition with preference over C70. Titration with fullerene-C60 is followed by a dramatic shift of the aromatic signals in 1H NMR and an initial increase in the fluorescence of the system. By this simple mechanism, fluorogenic sensing of fullerene-C60 is easily accomplished by an unprecedented fluorescent turn-on mechanism.

Codeposition Modification of Cation Exchange Membranes with Dopamine and Crown Ether To Achieve High K+ Electrodialysis Selectivity.

Surface modification has been proven to be an effective approach for ion exchange membranes to achieve separation of counterions with different valences by altering interfacial construction of membranes to improve ion transfer performance. In this work, we have fabricated a series of novel cation exchange membranes (CEMs) by modifying sulfonated polysulfone (SPSF) membranes via codeposition of mussel-inspired dopamine (DA) and 4'-aminobenzo-15-crown-5 (ACE), followed by glutaraldehyde cross-linking, aiming at achieving selective separation of specific cations. The as-prepared membranes before and after modification were systematically characterized in terms of their structural, physicochemical, electrochemical, and electrodialytic properties. In the electrodialysis process, the modified membranes exhibit distinct perm selectivity to K+ ions in binary (K+/Li+, K+/Na+, K+/Mg2+) and ternary (K+/Li+/Mg2+) systems. In particular, at a constant current density of 5.0 mA·cm-2, modified membrane M-co-0.50 shows significantly prominent perm selectivity [Formula: see text] in the K+/Mg2+ system and M-co-0.75 exhibits remarkable performance in the K+/Li+ system [Formula: see text], superior to commercial monovalent-selective CEM (CIMS, [Formula: see text], [Formula: see text]). Besides, in the K+/Li+/Mg2+ ternary system, K+ flux reaches 30.8 nmol·cm-2·s-1 for M-co-0.50, while it reaches 25.8 nmol·cm-2·s-1 for CIMS. It possibly arises from the effects of pore-size sieving and the synergistic action of electric field driving and host-guest molecular recognition of ACE and K+ ions. This study can provide new insights into the separation of specific alkali metal ions, especially on reducing influence of coexisting cations K+ and Na+ on Li+ ion recovery from salt lake and seawater.

Water-soluble pillar[6]arene functionalized PdPt porous core-shell octahedral nanodendrites to construct highly sensitive and robust neuron-specific enolase immunosensor by host-guest chemistry assisted catalytic amplification

In this work, water-soluble pillar[6]arene functionalized PdPt porous core-shell octahedral nanodendrites (WP6@PdPt PCONs) were simply synthesized and used for the fabrication of NSE immunosensor. The newest generation of macrocyclic host and biomimetic nano-enzymes have been effectively integrated to achieve the robust immobilization of signal molecules by host-guest molecular recognition and sensitively catalytic amplification of electrochemical signals. The addition of Pd and the formation of WP6@PdPt PCONs unique bimetallic nanostructure are beneficial to changing Pt-based catalyst electronic structure, accelerating the electron transport, promoting the generation of synergistic catalysis effect. Compared with enzyme-based methods, the fabricated sandwich-type immunosensor demonstrates more advantages in robustness owing to the introduction of host-guest chemistry and biomimetic nano-enzymes. In the wide range from 0.0003 to 100.00 ng mL−1, a good linear relationship (R2 = 0.998) and a low LOD (0.095 pg mL−1, S/N = 3) can be obtained. The proposed immunosensor shows remarkable analytical performances in the measurements of selectivity, stability, reproducibility, and real sample analysis, which provided a promising approach for clinical detection of NSE in human serum. Besides, the successful synthesis of WP6@PdPt PCONs provides a new idea for the preparation of biosensors based on bionic materials, nanotechnology and host-guest molecule recognition.

Supramolecular nanogels fabricated via host–guest molecular recognition as penetration enhancer for dermal drug delivery

Nanogels that are assembled by supramolecular interactions as compared to covalent crosslinked nanogels, exhibit new functionalities with potential for easy processability, recycling and self-healing due to the nature of dynamic and reversible non-covalent interactions. Here we design a supramolecular polymer nanogel that utilize host–guest interactions between the groups pillar [5] arene and alkyl chains on hyperbranched polyglycerol backbone as crosslinking agents for a new dermal drug delivery system. The anti-inflammatory drug Dexamethasone (Dexa) can be efficiently loaded into the nanogels and released from the assemblies. Besides, the supramolecular polymer nanogels exhibit better drug loading capacity and skin penetration enhancement than the individual host polymer and guest polymer. In vitro skin permeation studies show that supramolecular polymer nanogels can improve the Nile red penetration through the skin by up to 9 fold, compared to the individual polymers or a conventional cream formulation on a barrier deficient skin model.

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.

Controllable and large-scale supramolecular vesicle aggregation: orthogonal light-responsive host–guest and metal–ligand interactions

On the basis of the host–guest molecular recognition interaction between β-cyclodextrin and azobenzene, two kinds of supramolecular self-assemblies (Py-CD⊃Azo-C and Py-CD⊃Azo-C3) were constructed.

Dynamic Interfacial Adhesion through Cucurbit[n]uril Molecular Recognition.

Supramolecular building blocks, such as cucurbit[n]uril (CB[n])-based host-guest complexes, have been extensively studied at the nano- and microscale as adhesion promoters. Herein, we exploit a new class of CB[n]-threaded highly branched polyrotaxanes (HBP-CB[n]) as aqueous adhesives to macroscopically bond two wet surfaces, including biological tissue, through the formation of CB[8] heteroternary complexes. The dynamic nature of these complexes gives rise to adhesion with remarkable toughness, displaying recovery and reversible adhesion upon mechanical failure at the interface. Incorporation of functional guests, such as azobenzene moieties, allows for stimuli-activated on-demand adhesion/de-adhesion. Macroscopic interfacial adhesion through dynamic host-guest molecular recognition represents an innovative strategy for designing the next generation of functional interfaces, biomedical devices, tissue adhesives, and wound dressings.

Temperature and Recognition Dual Responsive Poly(N-Isopropylacrylamide) and Poly(N,N-Dimethylacrylamide) with Adamantyl Side Group.

A series of copolymers with an adamantyl side group (poly(NIPAM-co-AdMA) and poly(DMAM-co-AdMA)) were prepared by radical copolymerization of N-isopropylacrylamide (NIPAM) and N,N-dimethylacrylamide (DMAM) with a 2-methyl-2-adamantylmethacrylate (AdMA) monomer. The structure and composition of the as-synthesized copolymers were characterized by Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, gel permeation chromatography (GPC), thermogravimetric analysis (TGA), and elemental analysis. Temperature and recognition dual responsivity of the copolymers was investigated by cloud point (Tcp) and dynamic light scattering (DLS), respectively. The results show that the as-synthesized copolymers are a kind of temperature-responsive polymer with a lower critical solution temperature (LCST). Tcp was approximately consistent with the critical temperature of intermolecular copolymer association (Tass) from DLS. For these copolymers, Tcp decreases with increasing content of AdMA unit in the copolymers. After the addition of β-cyclodextrins (β-CD), Tcp increases, and the increment of Tcp values gradually became large with increasing content of AdMA in the copolymers. It is host-guest molecular recognition of β-CD and adamantyl groups that endows the as-synthesized copolymers with recognition-tunable thermosensitivity.

Silica bonded calix[4]arene as an efficient, selective and reusable sorbent for rubber chemical additives

This study presents the adsorption behavior of chemically bonded chlorosulfonyl-calix[4]arene to silica gel (CSC[4]A–SiO2) for couples of rubber chemicals additives, diphenylguanidine (DPG), N-cyclohexyl-2-benzothiazolesulfenamide (CBS) and 2-mercaptobenzothiazole (MBT). Results of study showed that CSC[4]A–SiO2 is a selective sorbent for DPG and CBS (as ordinary accelerators in the manufacture of rubber compounds) by means of electrostatic interaction and hydrogen bonding between hydroxyl groups of calix[4]arene moiety and the NH group of DPG and CBS molecules. The batch adsorption study was carried out to evaluate the rubber chemical additives removal efficiency and selectivity of CSC[4]A–SiO2. It was observed that the percentage of DPG and CBS removal reached 49 and 55% in the presence of CSC[4]A–SiO2 respectively. In order to give evidence to the stronger interaction of DPG and CBS with CSC[4]A–SiO2, 1H-NMR studies were performed. We have also discovered that the CSC[4]A–SiO2 can be act as a new auxiliary NMR shift reagent, via a host–guest molecular recognition process.

Cucurbit[7]uril-Directed Assembly of Colloidal Membrane and Stimuli-Responsive Microcapsules at the liquid-liquid Interface.

Colloidal microcapsules based on supramolecular architectures feature attractive properties and offer new opportunities in diverse areas such as delivery, sensing, and catalysis. Herein, we report a new strategy to fabricate the colloidal membrane and stimuli-responsive microcapsules by utilizing cucurbit[7]uril-mediated interfacial host-guest molecular recognition. In contrast to the traditionally used cross-linking approach, this method exploits the engineered interaction between a nanoparticle ligand and cucurbit[7]uril to tune the interfacial energy and stabilize the colloidal assembly at the interface. These capsules provide a versatile platform for simultaneous encapsulation of dual cargos. Additionally, the dynamic nature of the supramolecular interactions allows triggered release of the encapsulated cargos through the orthogonal presentation of a high affinity guest molecule.

Multi-mode supermolecular polymerization driven by host-guest interactions.

A novel supermolecular self-assembly based on ternary host–guest interaction between cucurbit[8]uril (CB[8]), 1,1′-dimethyl-4,4′-bipyridinium dication (MV) and coumarin derivative was applied for the construction of linear supramolecular polymer with high degree of polymerization in aqueous solution. Accompanied by the introduction of azobenzene on linear ABBA type monomer the supermolecular polymerization is different and the morphology changes from linear to dendritic polymer. The successful supramolecular polymerization of linear and dendritic supramolecular polymers by non-covalent host–guest molecular recognition was confirmed by various characterization methods, such as 1H NMR spectroscopy, ROESY, transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements. Meanwhile, the supramolecular polymerization could promote the conversion of the azobenzene from cis to trans, which ultimately results in no isomerism upon UV irradiation.