Supramolecular Host Research Articles

Polyoxometalate-Organic Hybrid "Calixarenes" as Supramolecular Hosts.

Calixarenes are among the most useful and versatile macrocycles in supramolecular chemistry. The one thing that has not changed in the 80 years since their discovery, despite numerous derivatizations, is their fully organic, covalent scaffolds. Here, we report a new type of organic-inorganic hybrid "calixarenes" constructed by means of coordination-driven assembly. Replacing acetate ligands on the {SiW10 Cr2 (OAc)2 } clusters with 5-hydroxyisophthalates allows these 95° inorganic building blocks to be linked into bowl-shaped, hybrid "calix[n]arenes" (n=3, 4). With a large concave cavity, the metal-organic calix[4]arene can accommodate nanometer-sized polyoxoanions in an entropically driven process. The development of hybrid variants of calixarenes is expected to expand the scope of their physicochemical properties, guest/substrate binding, and applications on multiple fronts.

An Overview on Cyclodextrin and Its Derivatives Encapsulated Inclusion Complex: Preparation Methods and Influencing Factors

Inclusion Complex formation is supported by non-covalent interaction between host and guest molecules. Cyclodextrins are supramolecular hosts with distinct structural characteristics that can enclose a diverse spectrum of viable compounds. The toroidal shape of CD offers the hydrophobic environment in the cavity where the guest moieties are entrapped which undergoes the physicochemical transformation and results into a superior physical, chemical and biological profiles. This review describes the chemical behavior of pharmaceuticals, both natural and synthetic, as well as other related compounds complexed with cyclodextrins. The study focuses on the commonly employed preparation methods of inclusion complexes and influencing factors to demonstrate host-guest interaction. The study demonstrates the possible stoichiometric combinations of cyclodextrins with the active pharmaceutical and organic molecules. The review also provides instances of synthetic pharmaceuticals that have combined with cyclodextrin to create inclusion products, demonstrating how cyclodextrins can be exploited to create biological substances with novel features and advance therapeutic research.

Triplet Exciton Harvesting in Water by a Structurally Simple Organic Phosphor with Sustained Afterglow and Lifetime Tunability

AbstractUltra‐long room temperature phosphorescence (URTP) materials are extremely promising for applications in organic electronics. Creating materials with controlled photophysics to achieve this, however, is difficult due to the challenges in filling up and stabilizing the sensitive triplet excited states at ambient temperature. Herein, triplet excitons are harvested by an intuitively designed structurally simple organic phosphor in water under ambient conditions by using supramolecular host–guest chemistry with cucurbituril‐7 (CB7) and sodium dodecyl sulphate (SDS), a negatively charged surfactant, with high photoluminescence (PL) quantum yields (PLQYs) (69% and 73% for CB7 and SDS, respectively) and phosphorescence lifetimes (12.52 and 12.42 ms for CB7 and SDS, respectively). A protective polyvinyl alcohol (PVA) film successfully controls the afterglow emission, excited state lifetime as well as PLQY in a single organic phosphor (CzPy24+). While a 1% concentration of CzPy24+ in the PVA film shows blue phosphorescence with 78.82% PLQY having a lifetime of 1.9 s, a 5% of CzPy24+ addition shows a green afterglow with 67.52% PLQY and a lifetime of 1.3 s. Similarly, yellow afterglow is achieved on adding 20% CzPy24+ to the PVA film with a PLQY of 40.88%. The findings are promising and helpful in constructing tunable phosphors for suitable applications.

Fullerene-Functionalized Halogen-Bonding Heteroditopic Hosts for Ion-Pair Recognition.

Despite their hydrophobic surfaces with localized π-holes and rigid well-defined architectures providing a scaffold for preorganizing binding motifs, fullerenes remain unexplored as potential supramolecular host platforms for the recognition of anions. Herein, we present the first example of the rational design, synthesis, and unique recognition properties of novel fullerene-functionalized halogen-bonding (XB) heteroditopic ion-pair receptors containing cation and anion binding domains spatially separated by C60. Fullerene spatial separation of the XB donors and the crown ether complexed potassium cation resulted in a rare example of an artificial receptor containing two anion binding sites with opposing preferences for hard and soft halides. Importantly, the incorporation of the C60 motif into the heteroditopic receptor structure has a significant effect on the halide binding selectivity, which is further amplified upon K+ cation binding. The potassium cation complexed fullerene-based receptors exhibit enhanced selectivity for the soft polarizable iodide ion which is assisted by the C60 scaffold preorganizing the potent XB-based binding domains, anion-π interactions, and the exceptional polarizability of the fullerene moiety, as evidenced from DFT calculations. These observations serve to highlight the unique properties of fullerene surfaces for proximal charged guest binding with potential applications in construction of selective molecular sensors and modulating the properties of solar cell devices.

Orthogonal Three‐Wavelength‐Controlled Two‐Stage Supramolecular Self‐Assemblies

AbstractPhotoswitchable supramolecular self‐assemblies are promising candidates for intelligent recognition because of their noninvasive and spatial precision. However, the manipulation of the self‐assembly and disintegration of multicomponent mixtures with light of different wavelengths remain difficult. Here, an orthogonal three‐wavelength‐controlled two‐stage supramolecular self‐assembly consisting of two photoswitches, diarylethene, and protonated merocyanine is designed, mediated by supramolecular macrocyclic host. Owing to the reversible photo‐transformation of the switches, an optimized approach including three wavelengths irradiation and a thermal relaxation process is developed without mutual interference, realizing interconversion among four self‐assembled states. These self‐assemblies are photodeformable with reversibility, which can be operated in a cellular environment. Taking advantage of the photochromism in both absorption and fluorescence of these self‐assemblies in different behaviors, a visual pattern that can simultaneously display multiple hidden information under dual‐signal emission is created. This work signifies a promising strategy in improving the ability of information encryption and anti‐counterfeiting.

Modulating Aryl Azide Photolysis: Synthesis of a Room-Temperature Phosphorescent Carboline in Cucurbit[7]uril Host.

Cucurbit[7]uril (CB7), a supramolecular host, is employed to control the pathway of photolysis of an aryl azide in an aqueous medium. Normally, photolysis of aryl azides in bulk water culminates predominantly in the formation of azepine derivatives via intramolecular rearrangement. Remarkably, however, when this process unfolds within the protective confinement of the CB7 cavity, it results in a carboline derivative, as a consequence of a C─H amination reaction. The resulting carboline caged by CB7 reveals long-lived room temperature phosphorescence (RTP) in the solid state, with lifetimes extending up to 2.1 s. These findings underscore the potential of supramolecular hosts to modulate the photolysis of aryl azides and to facilitate novel phosphorescent materials.

Bifunctional drug delivery system with carbonic anhydrase IX targeting and glutathione-responsivity driven by host-guest amphiphiles for effective tumor therapy

It remains a critical issue to deliver anticancer drugs to tumor tissues and reducing the toxic effects on normal tissues. The drug delivery system (DDS) based on self-assembly provides a multi-functional way for drug delivery. In this work, a supramolecular host (L-CD) with targeting function based on a β-cyclodextrin (β-CD) backbone was synthesized with carbonic anhydrase IX (CAIX) overexpressed on tumor cells as a target, and the methotrexate prodrug (MTX-SS-Ad) modified by adamantane and disulfide bond was prepared to be used as the guest. The amphiphilic complex was prepared between L-CD and MTX-SS-Ad through host-guest interactions and could further self-assemble into supramolecular nanoparticles (SNPs) with active targeting and stimulus release functions. The interaction between host and guest was investigated by UV, NMR, IR, XRD and TGA. The characteristic of SNPs was observed by DLS and TEM. Throng the study of molecular docking, in vitro inhibition, cell uptake experiments, and western blotting, SNPs have showed CAIX inhibitory effects both inside and outside the cells. The in vitro release experiments indicated that SNPs can undergo disintegration and release drugs under acidic and GSH conditions. Moreover, SNP can effectively inhibit the proliferation of cancer cells without generating additional toxic side effects on normal cells. So, we provide a strategy of bifunctional drug delivery system with targeting and glutathione-responsivity for effective tumor therapy.

Tunable Electrochemical Entropy through Solvent Ordering by a Supramolecular Host.

An aqueous electrochemically controlled host-guest encapsulation system demonstrates a large and synthetically tunable redox entropy change. Electrochemical entropy is the basis for thermally regenerative electrochemical cycles (TRECs), which utilize reversible electrochemical processes with large molar entropy changes for thermogalvanic waste-heat harvesting and electrochemical cooling, among other potential applications. A supramolecular host-guest system demonstrates a molar entropy change of 4 times that of the state-of-the-art aqueous TREC electrolyte potassium ferricyanide. Upon encapsulation of a guest, water molecules that structurally resemble amorphous ice are displaced from the host cavity, leveraging a change in the degrees of freedom and ordering of the solvent rather than the solvation of the redox-active species to increase entropy. The synthetic tunability of the host allows rational optimization of the system's ΔS, showing a range of -51 to -101 cal mol-1 K-1 (-2.2 to -4.4 mV K-1) depending on ligand and metal vertex modifications, demonstrating the potential for rational design of high-entropy electrolytes and a new strategy to overcome theoretical limits on ion solvation reorganization entropy.

Pushing the Boundaries of Covalent Organic Frameworks through Postsynthetic Linker Exchange

AbstractCovalent organic frameworks (COFs) are a fast‐developing family of porous organic materials that have received substantial research interest during the last two decades. Dynamic covalent chemistry (DCC) is the cornerstone of COF fabrication. DCC is a process that entails reversible bond breaking‐reforming under equilibrium to attain the thermodynamically most stable structure. Due to the reversible nature of the covalent linkages, the building blocks of pre‐synthesized COF or pre‐assembled chemical entities, like network polymers and supramolecular hosts, can be replaced postsynthetically under appropriate reaction conditions. The technique is known as postsynthetic linker exchange (PLE). PLE provides an easy way to introduce functional building blocks into the COF backbone and control its chemical and physical properties. In this article, we have highlighted the recent advancements (from 2017 to 2023) in the postsynthetic linker exchange strategy for constructing highly crystalline and porous COFs that are often unattainable via de novo fabrication. The mechanistic insights of the linker exchange process for transforming various parent entities, such as COFs, amorphous covalent organic networks, linear polymers, and molecular cages to daughter COFs, have been deliberated with fascinating examples. We have also outlined some future avenues for applying the PLE process for the large‐scale fabrication of highly crystalline COFs for real‐time applications.

Supramolecular Enhancement of BODIPY Singlet Oxygen Generation Using Bile Salt Micelles

Singlet Oxygen (SO) generation is the core chemical process of many medical and industrial applications. Designing efficient SO-Generating (SOG) agents is a major research focus for its utility in photodynamic therapy, wastewater treatment, material science, and organic synthesis. Photosensitization of ambient oxygen using organic dyes is an efficient approach to generating SO, though their efficiency is often severely hampered due to aggregation-induced deactivation. In this manuscript, we present the utility of bile salt micelle as supramolecular host for promoting SOG in aqueous media for a BODIPY dye, which was otherwise highly inactive. The SOG efficiency in test media was probed by monitoring the oxidation of 1,5-Dihydroxy Naphthalene (DHN) to corresponding quinone (juglone) through spectroscopic and chromatographic methods. In this study, we investigated the use of bile salt micelles as a supramolecular platform for enhancing the SOG efficiency of a BODIPY dye in aqueous media through complexation. Our results show that sodium cholate micelles can solubilize the hydrophobic dye and enhance its ability to generate singlet oxygen, while traditionally used macrocyclic hosts such as Β- and γ-cyclodextrin complexation was found to be far less efficient. Computational modeling revealed that the bile salt micelles form an aggregated complex structure with the dye, leading to improved supramolecular interactions and photophysical properties. This work demonstrates the potential of bile salt micelles as a natural and safe platform for enhancing the activity of nonpolar dyes for PDT applications.

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

Cobalt-Centered Supramolecular Nanoensemble for Regulated Aerobic Oxidation of Alcohols and "One-Pot" Synthesis of Quinazolin-4(3H)-ones.

The supramolecular assemblies of the donor-acceptor (D-A) system Im-Tpy, having phenanthro[9,10-d]imidazole as the donor and terpyridyl group as the acceptor unit, have been developed, which serve as supramolecular host to stabilize Co(II) in its nanoform. The as-prepared supramolecular nanoensemble Im-Tpy@Co in DMSO:water (7:3) shows high thermal stability and photostability. Even in the case of solvent mismatch, i.e., on dilution with cosolvent THF/DMSO, insignificant changes were observed in the size/morphology of the nanoensemble. The as-prepared Im-Tpy@Co nanoensemble in low catalytic loading (0.1 mol % of Co) catalyzes the oxidation of a wide variety of alcohols to aromatic aldehydes/ketones using visible light radiations as the source of energy without the need of any additive at room temperature. In comparison to already reported systems, the Im-Tpy@Co nanoensemble exhibits high turnover numbers (TONs) and turnover frequencies (TOFs). The practical application of the catalytic system has also been demonstrated in the gram-scale synthesis of 4-chlorobenzaldehyde. The Im-Tpy@Co nanoensemble exhibits recyclability up to four catalytic cycles with insignificant leaching and morphological changes. The present study also demonstrates the catalytic activity of the Im-Tpy@Co nanoensemble in "one-pot" synthesis of quinazolin-4(3H)-ones from 2-aminobenzamide and primary alcohols with better efficiency in comparison to other transition-metal-based catalytic systems.

Fluorescence and Phosphorescence Energy Transfer in Cucurbituril‐Based Supramolecular Systems

AbstractSupramolecular systems demonstrating resonance energy transfer have recently became a topical area on the borderline of supramolecular chemistry, photochemistry, photophysics and biology. The modularity of supramolecular interactions is a prerequisite for fine tuning of optical properties, which is difficult to achieve by other means. As a component of such systems, cucurbit[n]uril (CB[n]) macrocycles can play a wide spectrum of roles from anchoring of FRET pairs and modulation of the optical output to providing biocompatibility of FRET stains for cell imaging. The aim of this Review is to outline the development of the CB[n]‐based systems with fluorescence (FRET) and phosphorescence (TS‐FRET) energy transfer and to highlight achievements, challenges and perspectives of this fascinating combination of a classical photophysical process and a classical supramolecular host. Particular attention in this Review is given to the current and potential applications of the reviewed systems.

Motorized Photomodulator: Making A Non‐photoresponsive Supramolecular Gel Switchable by Light

AbstractIntroducing photo‐responsive molecules offers an attractive approach for remote and selective control and dynamic manipulation of material properties. However, it remains highly challenging how to use a minimal amount of photo‐responsive units to optically modulate materials that are inherently inert to light irradiation. Here we show the application of a light‐driven rotary molecular motor as a “motorized photo‐modulator” to endow a typical H‐bond‐based gel system with the ability to respond to light irradiation and create a reversible sol‐gel transition. The key molecular design feature is the introduction of a minimal amount (2 mol %) of molecular motors into the supramolecular network as photo‐switchable non‐covalent crosslinkers. Advantage is taken of the subtle interplay of the large geometry change during photo‐isomerization of the molecular motor guest and the dynamic nature of a supramolecular gel host system. As a result, a tiny amount of molecular motors is enough to switch the mechanical modulus of the entire supramolecular systems. This study proves the concept of designing photo‐responsive materials with minimum use of non‐covalent light‐absorbing units.

Motorized Photomodulator: Making A Non-photoresponsive Supramolecular Gel Switchable by Light.

Introducing photo-responsive molecules offers an attractive approach for remote and selective control and dynamic manipulation of material properties. However, it remains highly challenging how to use a minimal amount of photo-responsive units to optically modulate materials that are inherently inert to light irradiation. Here we show the application of a light-driven rotary molecular motor as a "motorized photo-modulator" to endow a typical H-bond-based gel system with the ability to respond to light irradiation and create a reversible sol-gel transition. The key molecular design feature is the introduction of a minimal amount (2 mol %) of molecular motors into the supramolecular network as photo-switchable non-covalent crosslinkers. Advantage is taken of the subtle interplay of the large geometry change during photo-isomerization of the molecular motor guest and the dynamic nature of a supramolecular gel host system. As a result, a tiny amount of molecular motors is enough to switch the mechanical modulus of the entire supramolecular systems. This study proves the concept of designing photo-responsive materials with minimum use of non-covalent light-absorbing units.

Deciphering conformational changes in human serum albumin induced by bile salts using spectroscopic and molecular modeling approaches

Bile salts are physiologically-important natural amphiphilic biosurfactants synthesized in the liver and play a vital role in the solubilization and digestion of dietary lipids, cholesterol, and other fat-soluble compounds in the body. Bile salts also exhibit pharmacological and biological uses as carriers for transporting scarce water-soluble drugs and other chemicals owing to their unique emulsifying, solubilizing capacities and micelle forming ability. In this context, we present an endeavor towards the possibilities underlying the interaction and binding between the most abundant plasma protein namely, human serum albumin (HSA) and bile salts to demonstrate an intriguing interplay of hydrophobic, electrostatic and hydrogen bonding effects using steady state absorption, fluorescence emission, anisotropy, time-resolved emission, and molecular modelling approaches. The outcome illuminates how amphiphilic interfaces of bile salts under various physico-chemical conditions trigger the conformational changes and binding affinities of native and molten-globule forms of HSA. To elucidate non-covalent interactions during HSA-bile salt supramolecular host–guest complex formation, changes in intrinsic (tryptophan) and extrinsic (ANS) fluorescence have been investigated. The results reveal upon binding of bile salts in subdomain IIA of HSA, the protein undergoes conformational changes mediated primarily by hydrophobic interactions. Furthermore, time-resolved fluorescence measurements provide important structural and dynamical insights into the protein-bile salt supramolecular complexes. Additionally, molecular docking studies on these complexes clearly reveal spontaneous binding of bile salts into subdomain IIA of HSA while suggesting that the binding affinity decreases with the decreasing order of hydrophobicity of the bile salts (NaDC > NaC > NaTC) (ΔGdock = −29.64 kJ mol−1, −26.15 kJ mol−1, −14.35 kJ mol−1), respectively. This study exclusively highlights the molecular mechanism of conformational perturbation in the native (pH 7) and molten-globule (pH 3) forms of HSA, induced by bile salts. We believe that the results reported herein will be helpful in the design and formulation of protein-bile salt-based pharmacological carriers suitable for drug delivery.

Sequence-Responsive Multifunctional Supramolecular Nanomicelles Act on the Regression of TNBC and Its Lung Metastasis via Synergic Pyroptosis-Mediated Immune Activation.

Design of effective nanodrugs to modulate the immunosuppression of tumor microenvironment is a desirable approach to boost the clinical tumor-therapeutic effect. Supramolecular nanomicelles PolyMN-TO-8, which are constructed by self-assembling supramolecular host MTX-MPEG2000, guest NPX-2S, and TO-8 through hydrophobic forces, have excellent stability and responsiveness to carboxylesterase and glutathione in turn. In vivo studies validate that PolyMN-TO-8 enable to trigger pyroptosis-mediated immunogenic cell death under laser, avoiding the occurrence of immune dysregulation simultaneously. This therapeutic mode strengthens dendritic cells' maturation and accelerates the infiltration of CD8+ T cells into tumors through moderate activation of pro-inflammatory factors with elimination of immune-escape, ultimately making the tumor inhibition rate as high as 87.44% via synergistic functions of photodynamic therapy, photothermal therapy, chemotherapy, etc. The loss of immune-escape quickens the infiltration of CD8+ T cells into lungs, and further eschews the generation of tumor nodules in it. Chemotherapy, the release of interferon-γ, and immune memory effect also strengthen the defense against metastasis. The generation of O2 catalyzed by PolyMN-TO-8 under laser is indispensable for tumor metastasis inhibition undoubtedly.

Complexation of AAPH (2,2′-azobis(2-methylpropionamidine) dihydrochloride) with cucurbit[7]uril enhances the yield of AAPH-derived radicals

AAPH (2,2′-azobis(2-methylpropionamidine) dihydrochloride), a water-soluble azo compound is widely employed to produce peroxyl radicals for chemical and biological studies. This compound is shown herein to form a stable inclusion complex with cucurbit[7]uril (CB7), a well-established supramolecular host. Competitive binding assays using berberine dye, isothermal titration calorimetry (ITC), and nuclear magnetic resonance (1H NMR) experiments, provided evidence for the inclusion of AAPH inside the CB7 cavity with a binding constant of 2.51 ± 0.76 × 105 M−1 (determined by ITC). Computational analysis at B3LYP-D3BJ/6-311G(d,p) of the complex (AAPH@CB7) showed interactions of the positively-charged amino groups of AAPH with carbonyl functions at the CB7 entrances. Photolysis of AAPH@CB7 by illumination at 365 nm, gave a higher yield of carbon-centered radicals when compared to the absence of CB7, as evidenced by electron paramagnetic resonance spin trapping using α-phenyl-N-t-butylnitrone. Enhanced radical formation was corroborated by increased consumption of pyrogallol red, free Trp and Trp-containing peptides when these were exposed to AAPH@CB7 in the presence of light. The increased yield of radicals generated by AAPH@CB7 is believed to arise from a pull effect of CB7 portals on initial AAPH-derived carbon-centered radicals generated by photolysis. It is proposed that these radicals are exposed and released to the bulk solution and react with O2 to give peroxyl radicals. These results suggest that the AAPH@CB7 complex can be used to generate high yields of peroxyl radicals for their use in studying these species in material, environmental and biomedical sciences amongst others.

Modifying and Taming Photoactive Compounds Using Synthetic Macrocycles as Supramolecular Hosts

AbstractPhotoactives have a wide variety of applications that can benefit human health including the prevention of melanoma and in photodynamic therapy. However, they have also been implicated in potential adverse impacts on the aquatic environment. Hence, several efforts have been made to either synthesize or to modulate properties of existing photoactives. Supramolecular modification is one of the ways in which photoactives are complexed with macrocycles to yield unique physical and chemical properties. Confined cavities of macrocycles have the potential to alter the life span of photoactive intermediates and thereby their applications. In this review, we have discussed the complexation of photoactives within select macrocycles, including calixarenes, curcurbit[n]urils, cyclodextrins, bis‐urea and octa‐acid. The comprehensive review gives an overview of how self‐assembly through non‐covalent interactions have enabled formation of inclusion complexes with improved photo stability and reduced phototoxicity. It also discusses how this technology may be leveraged in the future to counter the possible negative effects of photoactives.

Chiral Adaptive Induction of an Achiral Cucurbit[8]uril-Based Supramolecular Organic Framework by Dipeptides in Water.

Chiral induction by natural biomolecules can reveal the indispensable role of chiral structures in life and can be used to develop the chirality-sensing biomolecular recognition. Here, we present the synthesis and characterization of an achiral supramolecular organic framework (SOF-1) constructed from cucurbit[8]uril (CB[8]) and hexaphenylbenzene (HPB) derivative (1) in water. Due to the propeller-like rotational chiral conformation of HPB units and the specific recognition properties of CB[8], SOF-1 demonstrates chiral adaptive induction in water when interacting with the N-terminal Trp-/Phe-containing dipeptides including L-TrpX and L-PheX (X is an amino acid residue), respectively, exhibiting contrasting circular dichroism (CD) and circularly polarized luminescence (CPL) spectra. Consequently, SOF-1 has been developed as a supramolecular host and chiroptical sensor capable of recognizing and distinguishing the sequence-opposite Trp-/Phe-containing dipeptide pairs including L-TrpX/L-XTrp and L-PheX/L-XPhe based on the sequence-selective CD responses.