Search

Shape-persistent macrocycles enable superior control on molecular self-assembly, allowing the preparation of well-defined nanostructures with new functions. Here, we report on anionic amphiphilic calixarenes of conic shape and their self-assembly behavior in aqueous media for application in intracellular delivery of peptides. Newly synthesized calixarenes bearing four phosphonate groups and two or four long alkyl chains were found to form micelles of ∼ 10 nm diameter, in contrast to an analogue with short alkyl chains. These amphiphilic calixarenes are able to complex model (oligo-lysine) and biologically relevant (HIV-1 nucleocapsid peptide) cationic peptides into small nanoparticles (20-40 nm). By contrast, a control anionic calixarene with short alkyl chains fails to form small nanoparticles with peptides, highlighting the importance of micellar assembly of amphiphilic calixarenes for peptide complexation. Cellular studies reveal that anionic amphiphilic calixarenes exhibit low cytotoxicity and enable internalization of fluorescently labelled peptides into live cells. These findings suggest anionic amphiphilic macrocycles as promising building blocks for the preparation of peptide delivery vehicles.

A molecular capsule (

A preparative method for the synthesis of optically pure N-(1-phenylethyl)amides of inherently chiral (cR)- and (cS)-dibenzoyloxy-calix[4]arene acetic acids has been developed. Their absolute stereochemical configuration was determined by X-ray diffraction analysis.

Gold nanoparticles (AuNPs) are currently intensively exploited in the biomedical field as they possess interesting chemical and optical properties. Although their synthesis is well-known, their controlled surface modification with defined densities of ligands such as peptides, DNA, or antibodies remains challenging and has generally to be optimized case by case. This is particularly true for applications like in vivo drug delivery that require AuNPs with multiple ligands, for example a targeting ligand and a drug in well-defined proportions. In this context, we aimed to develop a calixarene-modification strategy that would allow the controlled orthogonal conjugation of AuNPs, respectively, via amide bond formation and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). To do this, we synthesized a calix[4]arene-tetradiazonium salt bearing four PEG chains ended by an alkyne group (

ConspectusThis Account summarizes the progress in protein-calixarene complexation, tracing the developments from binary recognition to the

Artificial supramolecular light-harvesting systems have expanded various properties on photoluminescence, enabling promising applications on cell imaging, especially for imaging in organelles. Supramolecular light-harvesting systems have been used for imaging in some organelles such as lysosome, Golgi apparatus, and mitochondrion, but developing a supramolecular light-harvesting platform for imaging two organelles synchronously still remains a great challenge. Here, we report a series of lower-rim dodecyl-modified sulfonato-calix[4]arene-mediated supramolecular light-harvesting platforms for efficient light-harvesting from three naphthalene diphenylvinylpyridiniums containing acceptors, Nile Red, and Nile Blue. All of the constructed supramolecular light-harvesting systems possess high light-harvesting efficiency. Furthermore, when the two acceptors are loaded simultaneously in a single light-harvesting donor system for imaging in human prostate cancer cells, organelle imaging in lysosome and Golgi apparatus can be realized at the same time with distinctive wavelength emission. Nile Red receives the light-harvesting energy from the donors, reaching orange emissions (625 nm) in lysosome while Nile Blue shows a near-infrared light-harvesting emission at 675 nm in Golgi apparatus in the same cells. Thus, the light harvesting system provides a pathway for synchronously efficient cell imaging in two distinct organelles with a single type of photoluminescent supramolecular nanoparticles.

Triazolated calix[4]semitubes comprising two or three calixarene cores and crownether loop(s) form (hetero)multinuclear Ag+/K+ complexes or operate as molecular switches depending on the mutual arrangement of the receptor sites in the molecules.

By combining the precisely sized cavity of pillar[5]arene and photodynamic properties of porphyrin derivatives, novel COMs (P5COMs) as an efficient cancer therapy platform from aldehyde-modified pillar[5]arene (P5CHO) and tetra-(4-aminophenyl)porphyrin (TAPP) were fabricated successfully.

Ammonium ion/carboxylate ion pairing is a key interaction ubiquitous in biological systems, but amine recognition by ionizable molecular receptors, mediated by host-to-guest proton transfer, has too often been overlooked as a design element for molecular recognition. This survey will show that proton transfer mediated recognition is a powerful and versatile tool that can be made to work with different amines and diverse macrocyclic scaffolds, such as crown ethers, calixarenes or pillararenes. We will trace the history of this recognition motif since Cram's first report half a century ago down to the latest applications in supramolecular sensing, drug-delivery and materials science, highlighting along the way the impact of host-to-guest proton transfer on self-assembly and molecular recognition.

Supramolecular chemistry focuses on the molecular recognition and self-assembly of various building blocks through weak non-covalent interactions, including anion-π interactions, hydrogen bonding (HB) interactions, hydrophobic interactions, van der Waals (vdW) interactions

We report a solid-state structural investigation of diametric calix[6]arene-based phosphine gold(I) cavitands which are characterised by two specific, different 1,2,3-alternate conformations in solution and in the solid state. The effect of the specific orientation of phosphines, with respect to macrocycles, was studied in intramolecular cyclopropanation of 1,6-dienynes. The general applicability of these catalysts was disclosed, delivering a family of polycycles with high yields and functional group tolerance.

Calix[4]arene scaffold, blocked in the cone conformation through alkylation with long alkyl chains, and decorated at the upper rim with four guanidine or arginine units, effectively catalyzes the cleavage of the phosphodiester bond of DNA and RNA model compounds in water. An exhaustive kinetic investigation unequivocally points to the existence of spontaneous aggregation phenomena, driven by hydrophobic interactions, occurring at different critical concentrations that depend on the identity of the compound. A pronounced superiority of the assembled structures compared with the monomers in solution was observed. Moreover, the catalytically active units, clustered on the macrocyclic tetrafunctional scaffold, were proved to efficiently cooperate in the catalytic mechanism and result in improved reaction rates compared to those of the monofunctional model compounds. The kinetic analysis is also integrated and corroborated with further experiments based on fluorescence spectroscopy and light scattering. The advantage of the supramolecular assemblies based on tetrafunctional calixarenes leads to believe that the active units can cooperate not only intramolecularly but also intermolecularly. The molecules in the aggregates can probably mold, flex and rearrange but, at the same time, keep an ordered structure that favor phosphodiester bond cleavage. This dynamic preorganization can allow the catalytic units to reach a better fitting with the substrates and perform a superior catalytic activity.

N-Nitrosamines are found in food, drugs, air, water, and soil. They pose a significant risk to human health because of their carcinogenicity; consequently, materials that can be used to selectively and sensitively detect nitrosamines are needed. In this work, we designed and synthesized two polymers bearing calix[4]arene or 4-tert-butylcalix[4]arene tungsten−imido complexes (PCalixH and PCalixtBu) as N-nitrosodimethylamine (NDMA) receptors. The interaction between metallocalix[4]arene monomers/polymers and NDMA was confirmed by (1)H NMR and IR spectroscopy. Single-crystal X-ray analysis further revealed that the host−guest interaction is based on binding of the terminal oxygen of NDMA to tungsten within the calixarene cavity. Gravimetric detection of NDMA was performed on a quartz crystal microbalance (QCM) in air. Both polymers show responses to NDMA, with PCalixtBu exhibiting a low theoretical limit of detection of 5 ppb for NDMA. The sensor also shows high selectivity toward NDMA and moderate humidity tolerance. This work provides a sensitive sensor for detection of NDMA and also offers a class of new, selective, and efficient NDMA receptors for the future design of NDMA sensors and NDMA extraction materials.

Carbohydrate–lectin interactions and glycol-molecule-driven self-assembly are powerful yet challenging strategies to create supramolecular nanostructures for biomedical applications. Herein, we develop a modular approach of micellization with a small molecular mannosylated-calix[4]arene synthetic core, CA4-Man3, to generate nano-micelles, CA4-Man3-NPs, which can target cancer cell surface receptors and facilitate the delivery of hydrophobic cargo. The oligomeric nature of the calix[4]arene enables the dynamic self-assembly of calix[4]arene (CA4), where an amphiphile, functionalized with mannose units (CA-glycoconjugates) in the upper rim and alkylated lower rim, afforded the CA4-Man3-NPs in a controllable manner. The presence of thiourea units between calixarene and tri-mannose moiety facilitated the formation of a stable core with bidentate hydrogen bonds, which in turn promoted mannose receptor targeted uptake and helped in the intracellular pH-responsive release of antineoplastic doxorubicin (Dox). Physiochemical features including the stability of the nanomicelle could circumvent the undesirable leakage of the cargoes, ensuring maximum therapeutic output with minimum off-targeted toxicity. Most importantly, surface-enhanced Raman scattering (SERS) was utilized for the first time to evaluate the critical micelle concentration during the formation, cellular uptake and intracellular drug release. The present study not only provides an architectural design of a new class of organic small molecular nanomicelles but also unveils a robust self-assembly approach that paves the way for the delivery of a wide range of hydrophobic chemotherapeutic drugs.

Cone-shaped calix[4]arene-tetrol 3 has the ability to form open structures due to the presence of four OH groups at the upper rim, which allows the construction of H-bonded supramolecular organic frameworks (SOFs). In the presence of water, SOF-1 is formed, which contains hydrophilic channels (mean diameter of 8.5 Å) contoured by the p-phenolic OH groups. In the presence of acetonitrile, SOF-2 is formed, which contains smaller hydrophobic channels (mean diameter of 6.6 Å) delimited by aromatic walls. The Na+@3 complex, which hosts acetonitrile molecules in the calixarene cavities, and dibromo-calix[4]arene-diol 5 give rise to more compact SOFs not containing channels. The H-bond network formed by all four p-phenolic OH groups in a pinched cone conformation of the calixarene is a determinant for the porosity of SOFs based on calix[4]arene-tetrol.

Inspired by the nuclear pore complex (NPC), herein we have established a biomimetic high-flux protein delivery system via the selective introduction of pillar[5]arene-based host-guest system into one side of an artificial concave (hour-glass) shaped nanochannels. With a transport flux of 660 lysozymes per minute, the system provides efficient high-flux protein transport at a rate which is significantly higher than that of an unmodified nanochannel and conventional bilateral symmetrical modified nanochannels. In view of these promising results, the use of artificial nanochannels to improve protein transport not only provides a new potential chemical model for biological research and better understanding of protein transport behavior in the living systems, but also provides a high-flux protein transporter device, which may have applications in the design of protein drug release systems, protein separation systems and microfluidics in the near future.

Bioinspired artificial nanochannels for molecular and ionic transport have extensive applications. However, it is still a huge challenge to achieve an intelligent transport system with high selectivity/efficiency and controllability. Inspired by glutathione transport across the plasma membrane via redox regulation, we herein designed and fabricated a redox-reactive artificial nanochannel based on the host-guest chemical strategy. The nanochannel platform achieved high selectivity/efficiency for the identification and transmission of glutathione in the confined space. In addition, this nanochannel can switch between the ON and OFF states through the redox reaction. This redox-regulated system can provide a potential application for detection/binding of biological analytes and redox-controlled drug release.

Owing to their remarkable features, calix[n]arenes are being exploited to study different aspects of molecular recognition, including protein complexation. Different complexation modes have been described, depending on the moieties that complement the aromatic cavity, allowing for function regulation and/or controlled assembly of the protein target. Here, a rigid cone calix[4]arene, bearing four anionic alanine units at the upper rim, was tested as a ligand for cytochrome

We present a supramolecular sensor array based on a series of heteromultivalent macrocyclic coassemblies using amphiphilic calixarenes and cyclodextrin as the building blocks for cell recognition. The corresponding cross-reactivity between the coassemblies and cells served as the unique fingerprint for cell classification, and successfully identified the normal cell lines, cancerous cell lines, and cross-contaminated cells.

Artificial gene delivery systems are in great demand from both scientific and practical biomedical points of view. In this paper, we present the synthesis of a new click chemistry calix[4]arene precursor with free lower rim and new water-soluble calixarene triazoles with 12 amino-groups on the upper rim (one with free phenol hydroxyl groups and two another containing four butyl or tetradecyl fragments). Aggregation in the series of amino-triazole calixarenes of different lipophilicity (calixarene with free phenol hydroxyl groups or butyl and tetradecyl fragments on the lower rim) was studied using dynamic light scattering and fluorescent pyrene probe. It was found that calix[4]arene with a free lower rim, like alkyl-substituted butyl calix[4]arene, forms stable submicron aggregates 150–200 nm in size, while the more lipophilic tetradecyl –substituted calix[4]arene forms micellar aggregates19 nm in size. Using UV-Vis spectroscopy, fluorimetry and CD, it was shown that amino-triazole calix[4]arenes bind to calf thymus DNA by classical intercalation. According to DLS and TEM data, all studied macrocycles cause significant DNA compaction, forming stable nanoparticles 50–20 nm in size. Among all studied calix[4]arenes the most lipophilic tetradecyl one proved to be the best for both binding and compaction of DNA.

Calix[4]arene 1, with two lower-rim isoxazolylchloroanthracene groups, is shown to be not only a chromogenic but also a fluorogenic chemodosimeter for the selective sensing of Cu

A novel composite was fabricated by hybridizing terbium 1,3,5-benzenetricarboxylic MOF (TB-MOF) with Cx[6]. The obtained composite TB-Cx[6] possessed long-term stability and dispersion stability and was used for on-site analysis of the anti-COVID-19 disinfection product

The regulation of surface wettability and cell adhesion behavior in a mild and unperturbed state at the interface remains a challenging task. To address this task, we adopt a strategy, based on bridging the host-guest recognition capacities of pillar[5]arene and good attachment for cell adhesion abilities of graphene oxide, to construct a smart pillar[5]arene triazole-linked naphthalene-modified graphene oxide interface. The hybrid surface exhibited a good stimuli-responsive selectivity toward arginine, as demonstrated by the wettability and cell adhesion behavior. Further studies at molecular levels indicated that the recognition mechanism of arginine was probably due to the formation of a host-guest complex driven by π-π stacking interactions between the cavity of pillar[5]arenes and arginine, which eventually resulted in the change in surface wettability and cellular adhesion behavior. It not only signifies a host-guest interaction strategy for the design of smart devices via the host-guest effect but also inspires the design of high-performance biointerface for affinity-adherent cells without exposing cells to harsh physical and chemical conditions.

Inherently chiral dialkyloxy-calix[4]arene acetic acids with asymmetric placement of substituents on the lower rim of the macrocycle were first studied as enantiodiscriminating additives to the mobile phase MeCN/H2 O/HCOOH (75/25/0.02 by volume) in the high-performance liquid chromatography (HPLC) separation of d,l-alanine and d,l-valine on the achiral stationary phase ZORBAX Original CN. The dependence of enantio-binding properties on the position of alkyl groups is demonstrated. The highest resolution (1.65) and enantioselectivity (1.80) were obtained for the 1,2-dipropyloxy-calix[4]arene acetic acid.

Reaction of Co(OAc)

Developing hierarchical ordered systems is challenging. Using organo-macrocycles to construct metal-organic frameworks (MOFs) and porous coordination cages (PCCs) provides an efficient way to obtain hierarchical assemblies. Macrocycles, such as crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillararenes, can be incorporated within MOFs/PCCs and they also endow the resultant composites with enhanced properties and functionalities. This review summarizes recent developments of organo-macrocycle-containing hierarchical MOFs/PCCs, emphasizing applications and structure-property relationships of these hierarchically porous materials. This review provides insights for future research on hierarchical self-assembly using macrocycles as building blocks and functional ligands to extend the applications of the composites.

A supramolecular nano-delivery system GP5⊃Pro-ANI based on the host-guest complex of glycosylated pillar[5]arene (GP5) and an amide linked fluorescent PARP inhibitor (4-amino-1,8-naphthimide, ANI) was constructed. The PARP inhibitor ANI, capable of inhibiting the ability of DNA damage repair, was modified into an AIE prodrug (Pro-ANI), which allows for the visualization of real-time cancer cellular drug uptake tracing and selective drug release.

Traditional drugs have the disadvantages of poor permeability and low solubility, which makes the utilization of pesticides lower and brings many side effects. With the continuous development of supramolecular chemistry in recent years, it has also played an irreplaceable role in the field of pharmaceutical science. Supramolecular macrocycles, such as crown ethers, cyclodextrins, calixarenes, pillararenes and cucurbiturils, are potentially good candidates for drug carriers due to their biocompatibility, hydrophobic cavity and ease of derivatization. The encapsulation of drugs based on host-guest interaction has the advantage of being adjustable and reversible as well as improving the low availability of drugs. Here, the recent advances in methods and strategies for drug encapsulation and release based on supramolecular macrocycles with host-guest interactions have been systematically summarized, laying a bright foundation for the development of novel nanopesticide preparations in the future and pointing out future directions of novel biopesticide research.

Calixarenes represent very popular building blocks in supramolecular chemistry. Compared to other macrocyclic families, they exhibit an almost infinite possibility of derivatization of the basic skeleton, which makes them ideal candidates for the design of new receptors or other functional systems. Although the chemistry of calixarenes is well established, there are still some substitution patterns that are unavailable or require a very lengthy synthetic approach. Among such synthetic challenges is the

Two pillar[5]arene-based [1]rotaxanes with salicylaldimine as the stopper were synthesized and characterized fully, and could be further applied in the fluorescence turn-on sensing of Zn

We report the synthesis and dynamic covalent chemistry (DCvC) of an A1/A2-dimercapto-functionalized pillar[5]arene (Di-SH-P5). The introduction of thiol moieties into this macrocyclic host makes it an effective building block for making a dynamic combinatorial library (DCL), giving rise to a set of cyclic trimers with intriguing host-guest properties as the dominant constituents.

In recent years, supramolecular systems for nano-medicine, and in particular for photodynamic therapy, have gained great attention for their uses as smart and engineered therapeutic agents. We proposed a collection of very recent articles on supramolecular complexes for photodynamic therapy based on different photosensitizers assembled with cyclodextrins, cucurbiturils, calixarenes, pillararenes, or involved in nanobox and tweezer structures, nanoparticles, aggregates and micelles, that are dynamic assemblies inspired to biological systems. Despite the advantages of traditional Photodynamic therapy (PDT), which is a non-invasive, reliable and highly selective clinical treatment for several pathological conditions, different drawbacks are still smothering the applicability of this clinical treatment. In this contest, a new supramolecular approach is emerging, in fact, the reversible formation of these supramolecular assemblies, combined with the possibility to modify their dimensions and shapes in the presence of a guest make them similar to biological macromolecules, such as proteins and enzymes. Furthermore, due to the relatively weak and dynamic nature of supramolecular assemblies, they can undergo assembly and disassembly very fast as well as responses to external stimuli, such as biological (e.g. enzyme activation), chemical (e.g. redox potential or pH), and physical (e.g. temperature, light or magnetic fields). Therefore, the responsiveness of these supramolecular assemblies represents a highly promising approach to obtain potentially personalized PDT.

Traditional macrocyclic hosts have finite cavity sizes, generally 5-10 A, which are commonly adaptive to recognize small guests rather than biological macromolecules. Here two water-soluble large-sized quaterphen[n]arenes (WQPns, n=3, 4) were designed and synthesized. These two hosts present significantly distinct recognition abilities. Specifically, they could strongly complex an antimicrobial peptide, pexiganan (PXG) with the association constants (Ka ) of (4.20±0.23)×104 M-1 for PXG/WQP3 and (2.46±0.44)×105 M-1 for PXG/WQP4. Complexation of PXG by WQP3 and WQP4 served to decrease the hemolysis of PXG in rabbit red blood cells in a statistically significant way. Furthermore, host-guest complexation was shown to substantially enhance metabolic stability of PXG in presence of proteinase K, rat plasma and liver or kidney homogenates.

Metal organic frameworks (MOFs) are hybrid organic inorganic materials with unique properties such as well-defined pore structure, extremely high surface area, excellent chemical-thermal stability. MOFs-based constructs have been extensively engineered and used for applications, such as enzyme immobilization for bio-catalysis. To obtained a zeolitic imidazole framework-8 (ZIF-8) for enzyme immobilization, Candida rugosa lipase (CRL) was pretreated with calix [4]arene tetracarboxylic acid (Calix) and reacted with Zn and imidazole by co-precipitation method. The prepared biocomposite was characterized by SEM, EDX, FT-IR, and XRD. The prepared CRL@Calix-ZIF-8 with high encapsulation efficiency showed improved resistance to alkali and thermal conditions. The CRL@Calix-ZIF-8 with the biocatalytic activity was 2-folds higher than that of the CRL@ZIF-8 (without Calix). The free lipase lost its catalytic activity completely at 60 °C after 100 min, while the CRL@Calix-ZIF-8 and CRL@ZIF-8 retained about 84% and 73%. It was found that CRL@Calix-ZIF-8 and CRL@ZIF-8 still retained ~83 and 67% of catalytic activity after its 6th use, respectively. The kinetic resolution of the immobilized lipases was examined for enantioselective hydrolysis of racemic naproxen methyl ester. CRL@Calix-ZIF-8 showed enantioselectivity against the racemic naproxen methyl ester, with E = 183 and 131 compared to the CRL@ZIF-8.

Fluorescently labeled calix[4]arene glycoconjugates demonstrate multifunctional potential in both Warburg effect mediated tumor imaging and GLUT1 targeted drug delivery. Nitrobenzoxadiazole and mannose conjugated NBD-Man-CA was found to be selectively recognized by GLUT1 and act as a "molecular carrier" for selective tumor targeting.

A galactose-targeting supramolecular photosensitizer system DOX@GP5⊃NBSPD was constructed based on a host-guest inclusion complex. The supramolecular system could achieve efficient delivery of DOX/NBS and selective release under GSH stimulation. In vitro studies revealed that this supramolecular DOX/NBS co-delivery system exhibited high ROS production and excellent cancer cell damage capability in a hypoxic environment. This strategy can therefore achieve enhanced hypoxic-tumor therapeutic effectiveness by chemo-photodynamic combination.

Calixarenes are reportedly excellent activators that can remarkably improve the transport efficiencies of cell penetrating peptides. We employed eight calixarenes to systematically study the influence of structure on activation efficiency, which revealed that the scaffold, head group, and alkyl chain are all significant factors for activation efficiency by affecting affinities with the peptide and membrane.

This Review introduces the research directions for the synthesis of supramolecular fullerene polymers. First, the discovery of host-guest complexes of pristine fullerenes is briefly outlined. We focus on progress in supramolecular fullerene polymers directed by the use of calix[5]arene-fullerene interactions, which comprise linear, networked, helical arrays of fullerenes in supramolecular ensembles. The unique self-sorting behavior of right-handed and left-handed helical supramolecular fullerene arrays is discussed. Thereafter, an extensive investigation of the calix[5]arene-fullerene interaction for control over the chain structures of covalent polymers is introduced.

Developing a water-soluble supramolecular system for the detection and removal of Hg

A switchable fluorescence sensor based on a calix (Monapathi et al., 2021) [4]arene:Cu

Dipstick assays using silver nanoparticles (AgNPs) stabilized by a thin calix[4]arene-based coating were developed and used for the detection of Anti-SARS-CoV-2 IgG in clinical samples. The calixarene-based coating enabled the covalent bioconjugation of the SARS-CoV-2 Spike Protein via the classical EDC/sulfo-NHS procedure. It further conferred remarkable stability to the resulting bioconjugated AgNPs, as no degradation was observed over several months. In comparison with lateral-flow immunoassays (LFIAs) based on classical gold nanoparticles, our AgNP-based system constitutes a clear step forward, as the limit of detection for Anti-SARS-CoV-2 IgG was reduced by 1 order of magnitude and similar signals were observed with 10 times fewer particles. In real clinical samples, the AgNP-based dipstick assays showed impressive results: 100% specificity was observed for negative samples, while a sensitivity of 73% was determined for positive samples. These values match the typical sensitivities obtained for reported LFIAs based on gold nanoparticles. These results (i) represent one of the first examples of the use of AgNP-based dipstick assays in the case of real clinical samples, (ii) demonstrate that ultrastable calixarene-coated AgNPs could advantageously replace AuNPs in LFIAs, and thus (iii) open new perspectives in the field of rapid diagnostic tests.

Host-guest chemistry, particularly of supramolecules, has been an intriguing topic for researchers for a long time due to its multiplicative applications ranging from chemical to biological to materials science. Supramolecules, such as calixarenes, are excellent host molecular systems due to their controllable cavity along with the ease of functionalization both at the lower and upper rims. The host-guest interactions involving calixarenes have been primarily studied using physical methods, such as absorption, fluorescence and nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and mass spectrometry. The corresponding literature as disseminated through review articles triggered broadening of the spectrum of research. Depending upon the nature of the derivatization, the supramolecular conjugates of calixarenes have been shown to form different morphologies of micro and nanometric size as reported in the literature. Pertinent research performed in our own group was based on atomic force microscopy, transmission electron microscopy and scanning electron microscopy studies. The literature reveals that such morphologies are modified in the presence of guest species. Thus, the supramolecular host-guest complexation of calixarenes leading to the formation of various architectures has been studied using both spectroscopy and microscopy techniques to obtain complimentary data. However, there are no review articles that provide discussions on this exciting area of supramolecular science involving microscopy. Therefore, in the present article, for the first time, we have brought together the research reported in the literature during the past decade, including ours, in demonstrating the supramolecular architectures formed from the host-guest interactions extended by the conjugates of calixarenes, and their applications using microscopy. The scope of this article spans across various features of interaction in these systems: (i) in solution, (ii) at the air-water interface and (iii) on solid surfaces. The application domain includes sensing of organic explosives and drugs, exhibiting antibacterial activity, supramolecular self-assembly or co-assembly resulting in gels, micelles and vesicles, and the consequent aggregation-induced emission and a few others.

Kynurenic acid is a by-product of tryptophan metabolism in humans, with abnormal levels indicative of disease. There is a need for water-soluble receptors that selectively bind kynurenic acid, allowing for detection and quantification. We report here the high-affinity binding of kynurenic acid in aqueous media to a resorcinarene salt receptor decorated with four flexible naphthalene groups at the upper rim. Experimental results from

Supramolecular prodrug vesicles with efficient property for dual chemotherapy have been successfully constructed based on the orthogonal self-assembly between a water-soluble pillar[5]arene host (

In the recent decade, macrocycle-surfaced polymer nanocapsules have been developed and studied as potential drug carriers. In particular, a unique group of these nanocapsules were constructed from a covalently self-assembled polymer network based on several classic macrocycles including cucurbituril, pillararene, and calixarene. The unique structure of these nanocapsules consists of a liquid or solid core and a shell laced with macrocycles in which the macrocycles not only act as the shell matrix of the nanocapsules but also allow further facile, modular functionalization via host-guest interactions with guest-tagged molecules. More interestingly, when a responsive cross-linker was introduced between the macrocycles, the payload inside the nanocapsules could be selectively released in the presence of typical hallmarks of certain diseases, which is of great interest for biomedical applications. In this Topical Review, macrocycle-surfaced polymer nanocapsules derived from covalently self-assembled polymer networks are introduced systemically with a focus on the molecular design and biomedical applications.

We review here the use of container molecules known as cavitands for performing organic reactions in water. Central to these endeavors are binding forces found in water, and among the strongest of these is the hydrophobic effect. We describe how the hydrophobic effect can be used to drive organic molecule guests into the confined space of cavitand hosts. Other forces participating in guest binding include cation-π interactions, chalcogen bonding and even hydrogen bonding to water involved in the host structure. The reactions of guests take advantage of their contortions in the limited space of the cavitands which enhance macrocyclic and site-selective processes. The cavitands are applied to the removal of organic pollutants from water and to the separation of isomeric guests. Progress is described on maneuvering the containers from stoichiometric participation to roles as catalysts.

Metallic amphiphiles are used as building blocks in the construction of nanoscale superstructures, where the hydrophobic effects induce the self-assembly of the nanoparticles of interest. However, the influence of synergizing multiple chemical interactions on an effective design of these structures mostly remains an open question. In this regard, supraamphiphilic systems based on flexible surfactant molecules and rigid macrocycles are being actively developed, but there are few works on the interaction between metallosurfactants and macrocycles. In the present work, the self-assembly and biological properties of a metallosurfactant with calixarene were studied for the first time. The metallosurfactant, a complex between lanthanum nitrate and two 4-aza-1-hexadecylazoniabicyclo[2.2.2]octane bromide units, and calix[4]resorcinol containing sulfonate groups on the upper rim were used to form a novel supraamphiphilic composition. The system formed was studied using a variety of physicochemical methods, including spectrophotometry, NMR, XRF, and dynamic and electrophoretic light scattering. It was found that the most optimal tetraanionic calix[4]resorcinol to dicationic metallosurfactant molar ratio, leading to mixed aggregation upon ion pair complexation, is 2:3. The mixed aggregates formed in the pentamolar concentration range were able to encapsulate hydrophilic substrates, including the anticancer drug cisplatin, the pure form of which is more cytotoxic toward healthy cells than toward diseased cells. Interestingly, the drug loaded into the macrocycle-metallosurfactant particles was less cytotoxic to a healthy Chang liver cell line and more cytotoxic to tumor M-HeLa cells. This selectivity depends on the amount of cisplatin added. The more drug is added to the macrocycle-metallosurfactant composition, the greater the biological activity against cancer cells. Taking into account that the appearance of resistance of cancer cells to drugs, especially to cisplatin, is one of the most important problems in treatment, the results of this work envisage the potential application of a mixed macrocycle-metallosurfactant system for the design of therapeutic cisplatin compositions.

Background: One of the possible ways of improving the activity and selectivity profile of anticancer agents is to design drug carrier systems employing nanomolecules. Calix[4]arene derivatives and chlorambucil and ibuprofen are important compounds that exhibit interesting anticancer properties. Objective: The objective of this article is the synthesis of new calix[4]arene-derivative conjugates of chlorambucil or ibuprofen with potential anticancer activity. Methods: Cytotoxicity assays were determined using the protein-binding dye sulforhodamine B (SRB) in microculture to measure cell growth as described [19, 20]. Conjugates of chlorambucil and resorcinarene-dendrimers were prepared in 2% DMSO and added into the culture medium immediately before use. Control cells were treated with 2% DMSO. Results: Thus, calix[4]arene-derivative conjugates of chlorambucil or ibuprofen showed good stability of the chemical link between drug and spacer. Evaluation of the cytotoxicity of the calix[4]arene chlorambucil or ibuprofen conjugates employing a sulforhodamine B (SRB) assay in K-562 (human chronic myelogenous leukemia cells) and U-251 (human glioblastoma cells) demonstrated that the conjugate was more potent as an antiproliferative agent than free chlorambucil and ibuprofen. The conjugates did not show any activity against the COS-7 African green monkey kidney fibroblast cell line. Conclusion: In the paper, we report the synthesis and spectroscopic analyses of new calix[4]arene derivative conjugates of chlorambucil or ibuprofen. Cytotoxicity assays revealed that at 10 μM, the conjugates were very active against K-562 (human chronic myelogenous leukemia cells) and U- 251 (human glioblastoma cells) cancer cells' proliferation. In order to explain the molecular mechanisms involved in the anticancer activity of calix[4]arene chlorambucil or ibuprofen conjugates, our research will be continued.

Calixarenes (CAs), representing the third generation of supramolecular hosts and one of the most widely studied macrocyclic scaffolds, offer (almost) unlimited structure and application possibilities due to their ease of modification, which allows one to establish a large molecular library as a material basis for diverse biomedical applications. Moreover, CAs and their derivatives engage in various noncovalent interactions for the facile recognition of guests including bioactive molecules and are also important building blocks for the fabrication of supramolecular architectures. In view of their molecular recognition and self-assembly properties, CAs are extensively applied in biosensing, bioimaging, and drug/gene delivery. Additionally, some CA derivatives exhibit biological activities and can therefore be used as new therapeutic agents. Herein, we summarize the diverse biomedical applications of CAs including in vitro diagnosis (biosensing), in vivo diagnosis (bioimaging), and therapy.

A stoichiometry-controlled chirality induction was successfully achieved through coassemblies of amphiphilic tetraphenylethylene derivative TPEA, γ-cyclodextrin (γ-CD), and water-soluble pillar[5]a...