Supramolecular Host Guest Interactions Research Articles

Calix[6]arene-Functionalized Photonic Hydrogel Biosensor for Naked-Eye Cholesterol Detection Based on Supramolecular Host-Guest Interactions.

Cholesterol (CHO) is an essential constituent of human cellular tissues and a crucial activity indicator for the clinical diagnosis and prevention of various diseases. Abnormal CHO levels can lead to various cardiovascular diseases, including coronary heart disease, cerebral thrombosis, and atherosclerosis. Thus, developing simple and effective methods for CHO detection is of great significance. Herein, a novel calix[6]arene-modified photonic hydrogel biosensor (PAAH@SCX6) was developed for naked-eye monitoring of CHO based on supramolecular host-guest interactions between 4-sulfocalix[6]arene (SCX6) and CHO molecules. This sensor was constructed by embedding Fe3O4 colloidal nanocrystal cluster chains into a poly(acrylamide-co-acrylic acid) smart hydrogel (PAAH), followed by incorporation of plentiful SCX6 units into the PAAH via hydrogen bonding interactions. The specific recognition of SCX6 to CHO leads to the volume expansion of the hydrogel, causing a shift in the photonic band gap and a change in the hydrogel's structural color. The sensor demonstrated a linear detection range of 2.83-5.20 mM, covering the typical CHO levels in the human body. Importantly, the PAAH@SCX6 biosensor showed high selectivity and satisfactory stability, making it highly suitable for practical applications. Such a photonic hydrogel-based biosensor provides a convenient, simple, and efficient strategy for visual CHO detection.

Advanced electrochemical detection of pyrophosphatase activity in LNCaP cells utilizing in-situ redox of copper

The necessity for precise delineation and quantitation of pyrophosphatase (PPase) activities is underscored, especially in aggressive prostate cancer, driving the demand for more refined analytical techniques due to challenges associated with inadequate sensitivity and poor signal amplification. In response, a novel electrochemical method utilizing in-situ copper(II) (Cu(II))-based Fast Scan Cyclic Voltammetry (FSCV) is introduced for the advanced detection of PPase in LNCaP prostate cancer cells. This technique is characterized by the exploitation of competitive binding between Cu(II) and L-Phenylalanine (L-Phe) versus pyrophosphate (PPi), with FSCV technology enhanced by ohmic drop compensation to improve detection sensitivity and signal reliability. Through the application of the FSCV technique transitioned to Current(I)-Voltage(V) analysis, the signal generation is facilitated by an L-Phe-Cu(II) complex, driven by the redox reaction of in-situ Cu(II), specifically its rapid transition from the Cu(0) state back to the Cu(II) state. When this complex is anchored onto a gold substrate modified with cucurbit[7]uril (CB[7]) through supramolecular host–guest interactions, a significant FSCV signal is elicited. A detection limit of 0.05 mU/mL (S/N = 3) is subsequently achieved when the method is applied to the quantification of PPase concentration. Leveraging the FSCV method, we have effectively analyzed PPase activity in LNCaP cells, offering a fresh perspective on tumor marker analysis and fostering advancements in drug development.

In Situ Photoreversible Tuning of Chemical Interface Damping in Single Gold Nanorods Through Cucurbit[8]uril-Based Host-Guest Interactions.

Chemical interface damping (CID) is a recently proposed plasmon-damping pathway based on the interfacial hot-electron transfer from metal to adsorbate molecules. However, the in situ reversible tuning of CID in single gold nanorods (AuNRs) has remained a considerable challenge. In this study, we used total internal reflection scattering microscopy and spectroscopy to investigate the CID induced by p-aminoazobenzene (p-AAB), which has fast photoisomerization characteristics, attached to single AuNRs. We demonstrated the in situ reversible tuning of CID in single AuNRs by switching between ultraviolet (UV, 365 nm) and visible (vis, 465 nm) irradiation to induce photoresponsive structural conversions between the cis and trans forms of p-AAB in ethanol, leading to different lowest unoccupied molecular orbital (LUMO) energies for both forms. The localized surface plasmon resonance (LSPR) line width was wide under vis irradiation but narrow under UV irradiation, indicating that hot electrons are more efficiently transferred to trans-p-AAB with a low LUMO energy level. We further investigated the in situ photoreversible tuning of CID by manipulating supramolecular host-guest interactions between cucurbit[8]uril (CB[8]) and p-AAB in the single AuNRs. Additionally, real-time in situ reversible tuning of CID in single AuNRs was achieved through photonic switching of the cis-trans forms of p-AAB inside CB[8]. The LSPR line width was narrow under vis irradiation but gradually widened under UV irradiation before narrowing again upon returning to vis irradiation, unlike the case with p-AAB only. These results can be ascribed to the fact that cis-p-AAB completely encapsulated within CB[8] in water is thermodynamically more favorable than trans-p-AAB. Therefore, we have discovered a new strategy for tuning the CID by performing p-AAB photoisomerization and adjusting the wavelength of incident light in single AuNRs. In addition, this study demonstrates that CID can be effectively applied to the development of biosensors to detect guest molecules and their structural changes inside the cavity of CB[8] in single AuNRs.

Enhancing interfacial elasticity via supramolecular microgel assembly for improved Pickering emulsions stability

We propose a new method to improve the interfacial elasticity of microgel-stabilised Pickering emulsions (PEs) by introducing supramolecular host-guest interactions to promote clustering among microgel particles. To this aim, microgels based on poly(N-isopropylacrylamide) (pNIPAM) are modified with 1-benzyl-3-vinylimidazolium bromide (BVI) to create pNIPAM-co-BVI microgels (MG). Cucurbit[8]uril (CB[8]) are introduced to form supramolecular BVI/CB[8] host-guest complexes. The introduction of CB[8] affects microgel spatial distribution at the interface of Pickering droplets, promoting the formation of monolayers of microgel clusters. These structures alter the interfacial viscoelasticity of the microgel monolayers, enhancing the resistance of (MG+CB[8])-stabilised interfaces to lateral and dilational deformations. PEs stabilised by microgels with the presence of CB[8] host-guest interactions exhibit improved stability over time. These results show the possibility of tuning the interfacial properties of microgel-laden interfaces by introducing supramolecular ternary complexes that can solely alter the interparticle interactions among microgels without significantly changing their morphology and deformability at the interface, thus providing a new route for improved emulsion stabilisation.

Preparation of a Fluorescent Polymer Sensing System with an Oxidation-Electric Dual-Mode Response Based on the Supramolecular Host–Guest Interaction

Preparation of a Fluorescent Polymer Sensing System with an Oxidation-Electric Dual-Mode Response Based on the Supramolecular Host–Guest Interaction

Supramolecular self‐assembled nanoparticles for targeted therapy of myocardial infarction by enhancing cardiomyocyte mitophagy

AbstractMyocardial infarction accompanied by diabetes mellitus is accepted as the most serious type of coronary heart disease, and among the current treatment strategies, the precise delivery of protective drugs for inhibiting cardiomyocyte apoptosis is still a challenge. In this study, we developed a biodegradable nanoparticles‐based delivery system with excellent macrophage escape, cardiac targeting, and drug release properties to achieve targeted therapy of myocardial infarction. Specifically, a copolymer of p(DMA–MPC–CD) combining self‐adhesion, hydration lubrication, and targeting peptide binding site was successfully prepared by free radical copolymerization, and it was self‐assembled on the surface of melatonin‐loaded dendritic mesoporous silica nanoparticles (bMSNs) following the integration of adamantane‐modified cardiac homing peptide (CHP) based on supramolecular host–guest interaction. Importantly, a hydration layer formed around the zwitterionic phosphorylcholine groups of the multifunctional nanoparticles, which was confirmed by the enhancement in hydration lubrication and reduction in coefficient of friction, prevented the nanoparticles from phagocytosis by the macrophages. The in vivo bioluminescence imaging test indicated that the nanoparticles were endowed with satisfied cardiac targeting capability, and the in vivo mice study demonstrated that the intravenous injection of drug‐loaded nanoparticles (namely bMSNs–Mel@PDMC–CHP) effectively reduced cardiomyocyte apoptosis, alleviated myocardial interstitial fibrosis, and enhanced cardiac function.

Cephalopod-Inspired Chemical-Gated Hydrogel Actuation Systems for Information 3D-Encoding Display.

Cephalopods evolve the acetylcholine-gated actuation control function of their skin muscles, which enables their dynamic/static multimode display capacities for achieving perfectly spatial control over the colors/patterns on every inch of skin. Reproduction of artificial analogs that exhibit similar multimodal display is essential to reach advanced information three-dimensional (3D) encoding with higher security than the classic 2D-encoding strategy, but remains underdeveloped. The core difficulty is how to replicate such chemical-gated actuation control function into artificial soft actuating systems. Herein, this work proposes to develop azobenzene-functionalized poly(acrylamide) (PAAm) hydrogel systems, whose upper critical solution temperature (UCST) type actuation responsiveness can be intelligently programmed or even gated by the addition of hydrophilic α-cyclodextrin (α-CD) molecules for reversible association with pendant azobenzene moieties via supramolecular host-guest interactions. By employing such α-CD-gated hydrogel actuator as an analogue of cephalopods' skin muscle, biomimetic mechanically modulated multicolor fluorescent display systems are designed, which demonstrate a conceptually new α-CD-gated "thermal stimulation-hydrogel actuation-fluorescence output" display mechanism. Consequently, high-security 3D-encoding information carriers with an unprecedented combination of single-input multiple-output, dynamic/static dual-mode and spatially controlled display capacities are achieved. This bioinspired strategy brings functional-integrated features for artificial display systems and opens previously unidentified avenues for information security.

Mechanically interlocked [c2]daisy chain backbone enabling advanced shape-memory polymeric materials

The incorporation of mechanically interlocked structures into polymer backbones has been shown to confer remarkable functionalities to materials. In this work, a [c2]daisy chain unit based on dibenzo-24-crown-8 is covalently embedded into the backbone of a polymer network, resulting in a synthetic material possessing remarkable shape-memory properties under thermal control. By decoupling the molecular structure into three control groups, we demonstrate the essential role of the [c2]daisy chain crosslinks in driving the shape memory function. The mechanically interlocked topology is found to be an essential element for the increase of glass transition temperature and consequent gain of shape memory function. The supramolecular host-guest interactions within the [c2]daisy chain topology not only ensure robust mechanical strength and good network stability of the polymer, but also impart the shape memory polymer with remarkable shape recovery properties and fatigue resistance ability. The incorporation of the [c2]daisy chain unit as a building block has the potential to lay the groundwork for the development of a wide range of shape-memory polymer materials.

Photo-Controlled Reversible Uptake and Release of a Modified Sulfamethoxazole Antibiotic Drug from a Pillar[5]arene Cross-Linked Gelatin Hydrogel.

Pillararene cross-linked gelatin hydrogels were designed and synthesized to control the uptake and release of antibiotics using light. A suite of characterization techniques ranging from spectroscopy (FT-IR, 1H and 13C NMR, and MAS NMR), X-ray crystallographic analysis, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA) was employed to investigate the physicochemical properties of hydrogels. The azobenzene-modified sulfamethoxazole (Azo-SMX) antibiotic was noncovalently incorporated into the hydrogel via supramolecular host-guest interactions to afford the A-hydrogel. While in its ground state, the Azo-SMX guest has a trans configuration structure and forms a thermodynamically stable inclusion complex with the pillar[5]arene motif in the hydrogel matrix. When the A-hydrogel was exposed to 365 nm UV light, Azo-SMX underwent a photoisomerization reaction. This changed the structure of Azo-SMX from trans to cis, and the material was released into the environment. The Azo-SMX released from the hydrogel was effective against both Gram-positive and Gram-negative bacteria. Importantly, the A-hydrogel exhibited a striking difference in antibacterial activity when applied to bacterial colonies in the presence and absence of UV light, highlighting the switchable antibacterial activity of A-hydrogel aided by light. In addition, all hydrogels containing pillar[5]arenes have demonstrated biocompatibility and effectiveness as scaffolds for biological and medical purposes.

Tuning of chemical interface damping in single gold nanorods through pH-dependent host-guest interactions using cucurbit[6]uril.

Chemical interface damping (CID) in gold nanorods (AuNRs) arises from direct hot electron transfer from Au to adsorbed molecules. Despite recent studies on CID, its tunability in single AuNRs remains challenging. Herein, we present a method for in situ control of CID in single AuNRs using pH-dependent host-guest supramolecular interactions. We employ cucurbit[6]uril (CB[6]), a well-known host molecule capable of encapsulating and releasing guest molecules, along with bis(3-aminopropyl)amine (BAPA) as guest molecules forming a complex with CB[6] (CB[6]-BAPA). CID is induced by attaching the CB[6]-BAPA complex on AuNR surfaces through a strong Au-amine interaction. In addition, in situ tuning of CID is achieved by releasing CB[6] from the complex using a NaOH solution. Successful CB[6]-BAPA complex formation, their attachment onto AuNRs, and CB[6] release from the complex are confirmed through changes in the localized surface plasmon resonance (LSPR) peak and LSPR linewidth, alongside mass analysis. Therefore, this study offers a new method for in situ CID tuning using CB[6]-based pH-sensitive host-guest interactions in individual AuNRs. This study can be further used in CB[6]-based photochemical processes and biosensing studies.

Supramolecular host-guest interaction triggered dye extraction from metal-organic framework for dual-mode ATP sensing from serum

Adenosine triphosphate (ATP) universally exists in all living organisms and holds a paramount role as a fundamental energy molecule in daily life. The abnormal concentration of ATP is closely related to many diseases, making the highly efficient detection of ATP very urgent. In this study, a dual-mode sensing system was developed to detect ATP sensitively and selectively via both DPV and fluorescence (FL) techniques, based on the strong interaction of ATP and Zn (II) nodes of zeolitic imidazolate framework-90 (ZIF-90). The disassembly of ZIF-90 further induced the subsequent release of pre-loaded rhodamine B (RhB). Benefitting from the robust host-guest recognition of β-cyclodextrin (β-CD) towards RhB, an enzyme-free and highly specific DPV detection strategy was established with the linear detecting range of 10.0–1.0 × 108 pM and the limit of detection (LOD) as low as 0.13 pM. Meanwhile, the FL sensing mode based on RhB exhibits comparable sensing performance with the linearity range of 10.0–1.0 × 107 pM and the LOD of 0.29 pM. Furthermore, the enzyme-free ATP sensing system exhibit outstanding long-term storage stability. The two-mode sensing platform was successfully applied to detect the ATP in human serum samples with the yielded result highly agree with the results of commercial ELISA kits. This dual-mode sensing platform is inspiring and paves the road for developing high-performance biosensor, demonstrating enormous potential for vitro diagnosis and practice clinic.

PH Sensor Based on Supramolecular Host–Guest Interactions and an Organic Field-Effect Transistor with a Magnetic Carbon Gate Electrode

pH Sensor Based on Supramolecular Host–Guest Interactions and an Organic Field-Effect Transistor with a Magnetic Carbon Gate Electrode

Supramolecular self-assembly between cyclopentanocucurbit[6]uril and 1H-benzotriazole

In this paper, the host-guest supramolecular interactions between cyclopentanocucurbit[6]uril with 1H-benzotriazole (BTA) have been investigated using 1H NMR spectroscopy, isothermal titration calorimetry (ITC), HPLC-QTOF mass spectrometry, IR spectroscopy, thermogravimetric analysis and single crystal X-ray diffraction. The results show that there is a 1:1 mode of inclusion in BTA@CyP6Q[6], which forms a supramolecular framework through hydrogen bonds and dipole interactions. In addition, the benzene ring of the BTA molecule entered the cavity of CyP6Q[6], while the triazole part resided at the port of the CyP6Q[6]. According to the ITC data, the complexation process for BTA with CyP6Q[6] is mainly driven by enthalpy.

Promoting the Recruitment, Engagement, and Reinvigoration of Effector T Cells via an Injectable Hydrogel with a Supramolecular Binding Capability for Cancer Immunotherapy.

T cells play a basic and key role in immunotherapy against solid tumors, and efficiently recruiting them into neoplastic foci and sustaining long-term effector function are consistent goals that remain a critical challenge. Here, an injectable alginate-based hydrogel with abundant β-cyclodextrin (ALG-βCD) sites is developed and intratumorally injected to recruit CCR9+ CD8+ T cells (a subset of T cells with robust antitumor activity) via the trapped chemokine CCL25. In the meantime, an intravenously injected adamantane-decorated anti-PD1 antibody (Ad-aPD1) would hitchhike on recruited CCR9+ CD8+ T cells to achieve the improved intratumoral accumulation of Ad-aPD1. Moreover, the Ad-PD1 and Ad-PDL1 antibodies are immobilized in the ALG-βCD hydrogel through supramolecular host-guest interactions of Ad and βCD, which facilitate engagement between CD8+ T cells and tumor cells and reinvigorate CD8+ T cells to avoid exhaustion. Based on this treatment strategy, T cell-mediated anticancer activity is promoted at multiple levels, eventually achieving superior antitumor efficacy in both orthotopic and postsurgical B16-F10 tumor models.

A strained π-extended [10]cycloparaphenylene carbon nanoring

Herein, we report the facile synthesis of a highly strained hexabenzocoronene-containing carbon nanoring, cyclo[4]-paraphenylene[2]-2,11-hexabenzocoronenylene ([4,2]CPHBC), as the segment of a [10,10] single-walled carbon nanotube ([10,10]SWNT). [4,2]CPHBC was synthesized based on the platinum-mediated assembly of diborylbiphenyl and diborylhexabenzocoronene, forming a tetranuclear platinum complex, followed by reductive elimination. This nanoring molecule was confirmed by NMR and HR-MS, and its photophysical properties were studied using steady-state and time-resolved spectroscopies. Moreover, the selective supramolecular host-guest interaction between [4,2]CPHBC and C60 was also investigated.

Bioinspired Redox-Responsive Graphene Oxide Membrane Based on Supramolecular Host–Guest Interaction for Tunable Molecular Separation

Intelligent and controllable water and molecule transport through a membrane is of crucial significance for broadening membrane applications in smart-gating filtration. Herein, inspired by the extensive redox reactions in living systems, we report a redox-responsive graphene oxide (GO) membrane assembled by introducing a supramolecular host–guest complex between ferrocene (Fc) and β-cyclodextrin (CD) into the interlayer of GO. The well-designed intelligent responsive membrane, which was composed of Fc-modified GO and CD-modified GO, possessed fascinating redox-response property. Utilizing the reversible deformation and restoration of the Fc/CD complex, the size of the interlayer nanochannel between adjacent GO nanosheets was tunable by changing the membrane redox state. The water permeance and molecular separation performance of the membrane could be reversibly regulated with a high gating ratio (5.6) by virtue of the redox-responsive interlayer nanochannel. In addition, the obtained membrane also demonstrated superior cyclic response performance, excellent antifouling ability, and satisfactory stability in harsh environments. This work provides an innovative strategy for the fabrication of redox-responsive membranes, showing promising applications in intelligent and controllable gating and controllable water-contaminant removal process.

Switchable Separation Strategy via Host–Guest Locks

Universal separation strategies are the ultimate goal in separation science. However, there is always a tradeoff between universality and selectivity due to the negative influence among different recognition domains. With the goal of universal separation in mind, an unprecedented, switchable, and versatile separation strategy using reversible supramolecular host-guest interactions has been developed. These adjustable separation mediums were prepared using surface-grafted cationic cyclodextrin to firmly bind negatively charged adamantane derivatives. By changing guest structures, the surface functionality of the separation medium can be precisely regulated to be selective for a variety of substrates including chiral or achiral molecules, thus producing satisfactory single-column universality. This method offers a new approach to move beyond conventional separation methodologies and should stimulate the design of switchable functional materials.

A supramolecular cucurbit[8]uril-based rotaxane chemosensor for the optical tryptophan detection in human serum and urine

Sensing small biomolecules in biofluids remains challenging for many optical chemosensors based on supramolecular host-guest interactions due to adverse interplays with salts, proteins, and other biofluid components. Instead of following the established strategy of developing alternative synthetic binders with improved affinities and selectivity, we report a molecular engineering approach that addresses this biofluid challenge. Here we introduce a cucurbit[8]uril-based rotaxane chemosensor feasible for sensing the health-relevant biomarker tryptophan at physiologically relevant concentrations, even in protein- and lipid-containing human blood serum and urine. Moreover, this chemosensor enables emission-based high-throughput screening in a microwell plate format and can be used for label-free enzymatic reaction monitoring and chirality sensing. Printed sensor chips with surface-immobilized rotaxane-microarrays are used for fluorescence microscopy imaging of tryptophan. Our system overcomes the limitations of current supramolecular host-guest chemosensors and will foster future applications of supramolecular sensors for molecular diagnostics.

Transient and Dissipative Host–Guest Hydrogels Regulated by Consumption of a Reactive Chemical Fuel

AbstractThe transient self‐assembly of molecules under the direction of a consumable fuel source is fundamental to biological processes such as cellular organization and motility. Such biomolecular assemblies exist in an out‐of‐equilibrium state, requiring continuous consumption of high energy molecules. At the same time, the creation of bioinspired supramolecular hydrogels has traditionally focused on associations occurring at the thermodynamic equilibrium state. Here, hydrogels are prepared from cucurbit[7]uril host–guest supramolecular interactions through transient physical crosslinking driven by the consumption of a reactive chemical fuel. Upon action from this fuel, the affinity and dynamics of CB[7]–guest recognition are altered. In this way, the lifetime of transient hydrogel formation and the dynamic modulus obtained are governed by fuel consumption, rather than being directed by equilibrium complex formation.

Transient and Dissipative Host-Guest Hydrogels Regulated by Consumption of a Reactive Chemical Fuel.

The transient self-assembly of molecules under the direction of a consumable fuel source is fundamental to biological processes such as cellular organization and motility. Such biomolecular assemblies exist in an out-of-equilibrium state, requiring continuous consumption of high energy molecules. At the same time, the creation of bioinspired supramolecular hydrogels has traditionally focused on associations occurring at the thermodynamic equilibrium state. Here, hydrogels are prepared from cucurbit[7]uril host-guest supramolecular interactions through transient physical crosslinking driven by the consumption of a reactive chemical fuel. Upon action from this fuel, the affinity and dynamics of CB[7]-guest recognition are altered. In this way, the lifetime of transient hydrogel formation and the dynamic modulus obtained are governed by fuel consumption, rather than being directed by equilibrium complex formation.