Host-guest Interactions Research Articles

Shrinkable Hydrogels through Host–Guest Interactions: A Robust Approach to Obtain Tubular Cell‐Laden Scaffolds with Small Diameters

AbstractThe availability of realistic in vitro models is crucial for tissue engineering, disease modeling, and drug screening assays. However, reproducing the complex shapes and intricate structures of naturally occurring tissues or organs in the presence of functional cells remains a challenge. For example, it is still not trivial to obtain cell‐laden tubular structures on a micrometer scale present in the nephrons of the human kidney. Here, a unique hydrogel‐based shrinking approach making use of host–guest interactions to decrease the diameters of the preformed hydrogel tubules seeded with cells is proposed as a tool to overcome the abovementioned challenge. The hydrogels are composed of covalently crosslinked methacrylated hyaluronic acid and methacrylated dextran modified with either cyclodextrin or adamantane groups that can form dynamic bonds. The hydrogels are initially formed in the presence of small‐molecule competitors that block any interpolymer host–guest interactions, and the shrinking process is triggered by the release of these competitor molecules. The high shrinking efficiency with a shrinking factor up to eight times in volume and robust cytocompatibility make the host‐guest‐based shrinking approach an appealing tool to obtain hydrogel tubular in vitro models with the desired dimensions on demand.

A Ni4O4-cubane-squarate coordination framework for molecular recognition.

Molecular recognition is a fundamental function of natural systems that ensures biological activity. This is achieved through the sieving effect, host-guest interactions, or both in biological environments. Recent advancements in multifunctional proteins reveal a new dimension of functional organization that goes beyond single-function molecular recognition, emphasizing the need for artificial multifunctional materials in industrial applications. Herein, we have designed a porous Ni4O4-cubane squarate coordination polymer as an artificial molecular recognition host, drawing inspiration from the structural and functional features of natural enzymes. A comprehensive assessment of the material's ability to distinguish target species under different operating conditions was carried out. The results confirm its sieving function through hexane isomers separation, host-guest interaction function via xenon/krypton separation, and dual presence of sieving and interaction through carbon dioxide/nitrogen separation. Additionally, the material demonstrates good stability and feasibility for large-scale production, indicating its practical potential. Our findings provide a bio-inspired multifunctional recognition material for chemical separations as proof-of-concept while offering solutions to advance artificial multifunctional materials adaptable to other applications beyond chemical separations.

Pore configuration control in hybrid azolate ultra-microporous frameworks for sieving propylene from propane.

Developing porous adsorbents for the complete sieving of propylene/propane mixtures represents an alternative method to energy-intensive cryogenic distillation processes. However, the similar physical properties of these molecules and the inherent trade-off among adsorption capacity, selectivity, diffusion kinetic and host-guest binding interactions in molecular sieving adsorbents makes their separation challenging. Here we report the separation of propylene/propane mixtures through a crystalline porous material (HAF-1) that features channels and shrinkage throats-the latter defined as narrower channels that connect the main channels and a molecular pocket-where the throat aperture is between the kinetic diameters of propylene and propane. Single-crystal X-ray diffraction and computational simulation reveal that the shrinkage channels and hanging molecular pockets are key to ensure high sieving efficiency and high propylene adsorption capacity. Dynamic breakthrough experiments show that HAF-1 enables the achievement of high-purity (≥99.7%) propylene with a productivity of 33.9 l kg-1 by just one adsorption-desorption circle from propylene/propane mixtures.

A Supramolecular Self-Assembled Nanoprodrug for Enhanced Ferroptosis Therapy.

Ferroptosis can induce cell death that leverages Fe2+-triggered Fenton reactions within living organisms, leading to an excessive accumulation of lipid peroxides (LPOs) and inducing cell death. Ferroptosis can effectively circumvent the inevitable drug resistance encountered with traditional apoptotic therapies. However, several issues remain in the clinical application of ferroptosis anticancer therapy, primarily due to the poor efficiency of intracellular Fenton reaction. To address this issue, we developed a supramolecular self-assembled codelivery nanoprodrug (DOX@C18Fc-Q[7] NPs) composed of ferrocene (Fc)-based supramolecular amphiphiles (C18Fc-Q[7]) and a nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) activator (doxorubicin, DOX). The C18Fc-Q[7] is based on Fc linked to a hydrophobic long-chain alkane via a disulfide linkage, which interacts with hydrophilic Q[7] to form self-assembled amphiphiles. Importantly, the host-guest interaction between Q[7] and Fc effectively enhances the solubility of Fc while maintaining the stability of the Fe2+ source. Moreover, C18Fc-Q[7] also acts as a good carrier for loading DOX due to its good self-assembly. In cancer cells, elevated glutathione (GSH) triggers the disassembly of nanoprodrug, leading to the release of DOX, which upregulates NOX4 expression and increases H2O2 level, thereby promoting an efficient Fenton reaction for Fc-induced ferroptosis. Moreover, DOX induces cell death through apoptosis, providing a synergistic effect to further enhance the ferroptosis therapy. In vivo studies have demonstrated that this enhanced ferroptosis therapy effectively inhibits tumor growth and metastasis while maintaining good biosafety.

Self-Healing, Electrically Conductive, Antibacterial, and Adhesive Eutectogel Containing Polymerizable Deep Eutectic Solvent for Human Motion Sensing and Wound Healing.

Flexible electronic devices such as wearable sensors are essential to advance human-machine interactions. Conductive eutectogels are promising for wearable sensors, despite their challenges in self-healing and adhesion properties. This study introduces a multifunctional eutectogel based on a novel polymerizable deep eutectic solvent (PDES) prepared by the incorporation of diallyldimethylammonium chloride (DADMAC) and glycerol in the presence of polycyclodextrin (PCD)/dopamine-grafted gelatin (Gel-DOP)/oxidized sodium alginate (OSA). The synthesized eutectogel has reversible Schiff-base bonds, hydrogen bonds, and host-guest interactions, which enable rapid self-healing upon network disruption. GPDO-15 eutectogel has significant tissue adhesion, high stretchability (419%), good ionic conductivity (0.79 mS·cm-1), and favorable antibacterial and self-healing properties. These eutectogels achieve 90% antibacterial effect, show excellent biocompatibility, and can be used as sensors to monitor human activities with strong stability and durability. The in vivo studies indicate that the eutectogels can improve the wound healing process which makes them an effective option for biological dressings.

Solvent-Controlled Separation of Integratively Self-Sorted Pd2LA 2LB 2 Coordination Cages.

The integrative implementation of multiple different components into metallosupramolecular self-assemblies requires sophisticated strategies to avoid the formation of statistical mixtures. Previously, the key focus was set on thermodynamically driven reactions of simple homoleptic into complex heteroleptic structures. Using Pd2LA 2LB 2-type coordination cages, we herein show that integrative self-sorting can be reversed by a change of solvent (from DMSO to MeCN) to favor narcissistic re-segregation into coexisting homoleptic species Pd2LA 4 and Pd3LB 6. Full separation ("unsorting") back to a mixture of the homoleptic precursors was finally achieved by selective precipitation of Pd3LB 6 with anionic guest G1 from MeCN, keeping pure Pd2LA 4 in solution. When a mixture of homoleptic Pd3LB 6 and heteroleptic Pd2LA 2LB 2 is exposed to a combination of two different di-anions (G1 and G2) in DMSO, selective guest uptake gives rise to two defined coexisting host-guest complexes. A joint experimental and deep theoretical investigation via liquid-state integral equation theory of the reaction thermodynamics on a molecular level accompanied by solvent distribution analysis hints at solvent expulsion from Pd2LA 4 to favor the formation of Pd2LA 2LB 2 in DMSO as the key entropic factor for determining the solvent-specific modulation of the cage conversion equilibrium.

Host-Guest Assemblies of Polyoxovanadate Clusters as Supramolecular Catalysts.

Supramolecular functional materials can be used to overcome some of the most challenging tasks in materials science, where the dynamic nature of supramolecular interactions can be leveraged to fine-tune the properties of the material. The Lindqvist hexavanadate family of polyoxometalates are interesting candidates for supramolecular materials due to their redox and Lewis acid properties that enable their application inenergy conversion or catalysis. Despite their promising potential, hexavanadate clusters are underrepresented in supramolecular materials, mainly due to the synthetic challenges related to their inherent reactivity. In this work, pillar[5]arene was successfully grafted onto a Lindqvist hexavanadate and the resulting structure was confirmed by single crystal X-ray diffraction, presenting the first example of a crystal structure of a polyoxometalate covalently functionalized with a pillar[5]arene. By introducing a ditopic guest molecule that could interlink pillar[5]arene moieties, host-guest interactions were leveraged as the driving force for the formation of supramolecular assemblies incorporating hexavanadate clusters in a controlled manner. The enhanced catalytic performance of the resulting aggregates confirmed their potential application as functional catalytic materials. This novel approach for developing hexavanadate-based catalysts reported here showcases the potential of using host-guest interactions as a means to introduce catalytically active metal-oxo clusters into supramolecular frameworks.

Interfacial Charge Transfer in One-Dimensional AgBr Encapsulated inside Single-Walled Carbon Nanotube Heterostructures.

The advent of one-dimensional van der Waals heterostructure (1D vdWH) nanomaterials has provided valuable opportunities for the advancement of electronic or optical devices, as well as for exploring various condensed matter phenomena. Electron transfer is a fundamental process in host-guest interactions, significantly influencing nanoscale physicochemical processes. Elucidating the mechanism by which the host influences the electronic structure of the guest is essential for elucidating these interactions. This study reports the successful synthesis of a material system consisting of precisely resolved AgBr nanowires encapsulated within single-walled carbon nanotubes (SWCNTs) that has been successfully synthesized and utilized to investigate the intrinsic electron transfer across 1D vdWHs. Cyclic voltammetry (CV) was employed to investigate the 1D vdWH interaction between AgBr and SWCNTs, which provided a more intuitive and accurate characterization of the charge transfer from SWCNTs to AgBr. Furthermore, Kelvin probe force microscopy showed a 149 mV reduction in the average surface potential of carbon nanotubes after AgBr filling, supporting the efficacy of CV in probing electron dynamics in 1D vdWHs. Finally, theoretical calculations indicated a charge transfer of 0.11 e- per simulation cell, reinforcing the effectiveness of CV in assessing the interactions within 1D vdWHs.

Single Molecular Dispersion of Crown Ether-Decorated Cobalt Phthalocyanine on Carbon Nanotubes for Robust CO2 Reduction through Host-Guest Interactions.

Immobilizing molecular catalysts on electro-conductive supports (for example, multi-walled carbon nanotubes, CNTs) represent a promising way to well-defined catalyst/support interfaces, which has shown appreciable performance for catalytic transformation. However, their full potential is far from achieved due to insufficient utilization of the intrinsic activity for each immobilized molecular catalyst, especially at loadings that should allow decent current densities. In the present work, we discover host-guest interaction between tetra-crown ether substituted cobalt phthalocyanine and metal ions, for example K+ ions, not only eliminate catalyst aggregation at immobilization procedures but also reinforce catalyst/support interactions by additional electrostatic attractions under operational conditions. Through simple dip-coating procedures, a successful single molecular dispersion is achieved. Such a catalyst/electrode interface is stable and can selectively catalyze CO2-to-CO conversion with Faradaic efficiency over 96%. Importantly, this interface maintains an almost unchanged turnover frequency (TOF) across all loading conditions, implying a full utilization of the intrinsic activity of supported molecular catalysts. Therefore, a simultaneous achievement of high TOF and high current density (TOF of 111 s-1 at 38 mA cm-2) is achieved, in an aqueous H-type electrolyzer at an overpotential of 570 mV.

Single Molecular Dispersion of Crown Ether‐Decorated Cobalt Phthalocyanine on Carbon Nanotubes for Robust CO2 Reduction through Host‐Guest Interactions

AbstractImmobilizing molecular catalysts on electro‐conductive supports (for example, multi‐walled carbon nanotubes, CNTs) represent a promising way to well‐defined catalyst/support interfaces, which has shown appreciable performance for catalytic transformation. However, their full potential is far from achieved due to insufficient utilization of the intrinsic activity for each immobilized molecular catalyst, especially at loadings that should allow decent current densities. In the present work, we discover host–guest interaction between tetra‐crown ether substituted cobalt phthalocyanine and metal ions, for example K+ ions, not only eliminate catalyst aggregation at immobilization procedures but also reinforce catalyst/support interactions by additional electrostatic attractions under operational conditions. Through simple dip‐coating procedures, a successful single molecular dispersion is achieved. Such a catalyst/electrode interface is stable and can selectively catalyze CO2‐to‐CO conversion with Faradaic efficiency over 96%. Importantly, this interface maintains an almost unchanged turnover frequency (TOF) across all loading conditions, implying a full utilization of the intrinsic activity of supported molecular catalysts. Therefore, a simultaneous achievement of high TOF and high current density (TOF of 111 s−1 at 38 mA cm−2) is achieved, in an aqueous H‐type electrolyzer at an overpotential of 570 mV.

Encapsulation of an Au25 Nanocluster inside a Porphyrin Nanoring Enhances Singlet Oxygen Generation and Photo‐Electrocatalytic CO2 Reduction

AbstractThe synthesis of molecular host–guest complexes with enhanced performance, relative to those of their components, is a central theme in supramolecular chemistry. Here we explore a host‐guest system consisting of an atomically precise gold nanocluster bound inside a zinc porphyrin nanoring. UV/Vis absorption and fluorescence titrations with different sized nanorings revealed strong binding between a pyridinethiol‐coated Au25 nanocluster and a nanoring consisting of six zinc porphyrin units, and complexation is confirmed by mass spectrometry. Formation of this assembly enhances the stability of the gold nanocluster. The host‐guest complex also exhibits remarkable activity and selectivity for photochemical CO2 to CO conversion and singlet oxygen generation.

Proximity Effects and Aggregation of Hamilton-Receptor Barbiturate Host-Guest Complexes Probed by Cross-Metathesis and ESI MS Analysis.

The molecular environment around supramolecular bonding systems significantly affects their stability and the assembly of host-guest complexes, most prominent for hydrogen bonds (H-bonds). Hamilton receptor-barbiturate host-guest complexes are well-known in solution, typically forming a 1:1 molar ratio complex. However, within a polymer matrix, these complexes can form higher-order assemblies, deviating from the standard 1:1 complex, which are challenging to characterize and often require lab-intensive methods. In this study, a novel Hamilton receptor (H) was equipped with cyclopentene moieties and used as a host to form host-guest complexes (H-B) with allobarbital (B), followed by covalent crosslinking. UV-Vis spectroscopy titration experiments in different solvents and at various temperatures revealed that polar solvents containing additional H-bonding sites significantly reduce the formation of the 1:1 H-B complex, as indicated by a reduced association constant. Higher-order aggregates (HH-dimer, HHH-trimer) were subsequently detected via an alkene cross-metathesis (CM) reaction to fix the assemblies covalently, followed by analysis via electrospray ionization mass spectrometry (ESI MS). This two-step method, firstly via CM fixation followed by ESI MS, was extended to study the H-B model complex within a polyisobutylene (PIB) matrix, presenting a direct method to analyze the complex host-guest assembly in solvent-free (polymer) environments.

Construction of Slide-Ring Polymers Based on Pillar[5]Arene/Alkyl Chain Host-Guest Interactions.

Slide-ring polymers exhibit distinctive mechanical properties, making them highly promising for applications in emerging fields such as energy storage devices and smart sensing. However, existing slide-ring polymer systems primarily rely on hydrophilic-hydrophobic interactions to achieve ring-axle interlocking in aqueous phases. This reliance limits the construction of slide-ring networks mainly to water-soluble polymers, excluding a diverse range of lipophilic polymers. Therefore, it is crucial to introduce efficient construction strategies that facilitate interpenetration in organic solvents, enabling the development of diverse slide-ring polymers and expanding their range and applications. Herein, by utilizing the pillar[5]arene/alkyl chain host-guest interactions, we successfully facilitated the interpenetration of a pillar[5]arene and poly(caprolactone), enabling the efficient construction of two slide-ring polymer networks in organic solvents. One of these two slide-ring polymers demonstrates a unique network deformation mechanism along with outstanding mechanical properties compared with the control covalently cross-linked polymer network, including maximum stress (4.43 vs 1.98 MPa), maximum strain (1285 vs 330 %), and toughness (35.4 vs 3.92 MJ/m3). More importantly, this strategy of making slide-ring polymers is highly versatile, given the wide range of macrocyclic arenes and alkyl chain-containing polymers it can accommodate.

Bimodal Array-Based Fluorescence Sensor and Microfluidic Technology for Protein Fingerprinting and Clinical Diagnosis.

Proteins play a crucial role in determining disease states in humans, making them prime targets for the development of diagnostic sensors. The developed sensor array is used to investigate global proteomic changes by fingerprinting multifactorial disease states in model urine simulating phenylketonuria and in serum from preeclamptic pregnant women. Here, we report a fluorescence-based chemical sensing array that exploits the host-guest interaction between cucurbit[7]uril (CB[7]) and fluorescent triphenylamine derivatives (TPA) to detect a range of proteins. Using linear discriminant analysis, we identify fluorescence fingerprints of 14 proteins with over 98% accuracy in buffer and human serum. The array is optimized on an automated droplet microfluidic-based platform, for high-throughput sensing with controlled composition and lower sample volumes. This sensor enables the discrimination of proteins in physiological buffer and human serum, with promising applications in disease diagnosis.

Organic Room Temperature Phosphorescence from BN‐Substituted Xanthene Derivatives

AbstractEmissive organic materials are predominantly fluorescent and there is significant interest in realizing and understanding examples that defy this paradigm and exhibit phosphorescence under ambient conditions. Organic room temperature phosphorescence (ORTP) offers the long‐lived excited states and bathochromically‐shifted emission maxima of phosphorescence without the use of potentially toxic and expensive transition metals. Most ORTP materials rely on well‐studied structural motifs that include aryl carbonyls, sulfones, and heavy main group elements. We report the unexpected ORTP of a series of heavy atom‐free BN‐substituted xanthene derivatives. The creation of heteroatom‐rich scaffolds, combined with stabilizing C−H⋅⋅⋅F interactions in the solid‐state, resulted in oxygen‐tolerant heavy atom‐free organic phosphorescence without relying on the use of cryogenic temperatures, polymer matrices, or host–guest interactions. The observation of ORTP in these simple systems sets a blueprint for the further development of heavy atom‐free organic phosphors.

Short-Range Coulomb Interaction Is a Key to Switch the Utilization of Higher Triplet Excitons in Multiresonance Thermally Activated Delayed Fluorescence Doped Film.

Multiresonance thermally activated delayed fluorescence (MR-TADF) materials have attracted widespread attention due to ultrahigh definition display standards. However, many MR-TADF materials lack TADF properties in both the solution and solid states. Interestingly, the TADF characteristics appear once these MR-TADF compounds are doped in a suitable host film, but the precise mechanism involved in the host-guest interaction remains uncertain. Herein, we systematically investigated the role of host-guest interactions employing doped films (DABNA-1@mCBP and DABNA-1@DPEPO) with opposite phenomena. The results indicate that mCBP with a V-shape and enhanced rigidity could facilitate the formation of an energy spacing layer by employing short-range Coulomb energy through the MR luminescent core, which could offset the sensitivity of the stacking distance, enhancing the coupling between T1 and T2, and thus switch the reverse internal conversion and the higher T2 reverse intersystem crossing process. This work is a further development of luminescence mechanisms and an update of the host-guest interaction criteria for the targeted design of doped films.

Crown Ether-Magnesium Ion Complexes: A Reliable Theoretical Estimation of Host-Guest Interaction and Binding Energies in a Solvent.

Metal ion detection is of a paramount importance for health monitoring. The host should properly accommodate the desired ion and be selective with respect to other potential guests, which makes devising ion sensors a demanding task. Recently (Phys. Chem. Chem. Phys. 2023, 25, 32656), we suggested a procedure for a computational design of crown ethers that can capture magnesium ions. In the present contribution we apply the same approach to search for Mg2+ trap with thiophene units, in accord with proposed hosts for Na+ and K+ ions (Adv. Funct. Mater., 2016, 26, 514). Additionally, we present a procedure based on the combination of Density Functional Theory based Molecular Dynamics and the Interacting Quantum Fragments methodology for determination of host-guest interaction and binding energies in a model with a large number of explicit solvent molecules. The presented strategy could be applied for identification of the right host for an arbitrary guest.

Structural insights into 1,4-bis(neopentyloxy)pillar[5]arene and the pyridine host–guest system

The crystal structure of 1,4-bis(neopentyloxy)pillar[5]arene, C95H140N2O10 (TbuP), featuring two encapsulated pyridine molecules, reveals significant host–guest interactions. Interestingly, the pyridine guests are positioned near the neopentyloxy substituents instead of the electron-rich aromatic core of the pillar[5]arene. This spatial arrangement suggests a preference for the pyridine molecules to engage with the aliphatic regions of the host. Detailed analysis of the structural characteristics of this host–guest system (TbuP·2Py), as well as its packing pattern within the crystal network, is presented and discussed.

Single-molecule profiling of per- and polyfluoroalkyl substances by cyclodextrin mediated host-guest interactions within a biological nanopore.

Biological nanopores are increasingly used in molecular sensing due to their single-molecule sensitivity. The detection of per- and polyfluoroalkyl substances (PFAS) like perfluorooctanoic acid and perfluorooctane sulfonic acid is critical due to their environmental prevalence and toxicity. Here, we investigate selective interactions between PFAS and four cyclodextrin (CD) variants (α-, β-, γ-, and 2-hydroxypropyl-γ-CD) within an α-hemolysin nanopore. We demonstrate that PFAS molecules can be electrochemically sensed by interacting with a γ-CD in a nanopore. Using HP-γ-CDs with increased steric resistance, we can identify homologs of the perfluoroalkyl carboxylic acid and the perfluoroalkyl sulfonic acid families and detect common PFAS in drinking water at 0.4 to 2 parts per million levels, which are further lowered to 400 parts per trillion by sample preconcentration. Molecular dynamics simulations reveal the underlying chemical mechanism of PFAS-CD interactions. These insights pave the way toward nanopore-based in situ detection with promises in environmental protection against PFAS pollution.

Pillar[5]arene stabilized gold nanoparticles for the enhanced light-triggered nitric oxide release with antibacterial and antibiofilm activities

The reactivity of guests confined in well-defined host cavities act significantly different from that in bulk systems. In this work, pillar[5]arene not only works as a stabilizer for the fabrication of gold nanoparticles, but also act as an accelerator for the enhanced photo-triggered release of gaseous nitric oxide (NO) from encapsulated NO donor. The host–guest complex can dramatically improve the photoactivity of loaded guest molecule to generate antibacterial NO molecules through the confinement effect of pillar[5]arene cavity. The synergistic photo-triggered localized NO release and photo-thermal effect of host–guest complex demonstrated impressive antibacterial behaviors against Gram-negative bacterial strain Escherichia coli, Gram-positive bacterial strain Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. Moreover, this biocompatible photo-responsive complex can also inhibit bacterial biofilm formation and disrupt the pre-existing biofilms.