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Protein–calixarenes binding plays an increasingly central role in many applications, spanning from molecular recognition to drug delivery strategies and protein inhibition. These ligands obey a specific bio-supramolecular chemistry, which can be revealed by computational approaches, such as molecular dynamics simulations. In this paper, we rely on all-atom, explicit-solvent molecular dynamics simulations to capture the electrostatically driven association of a phosphonated calix-[4]-arene with cytochome-C, which critically relies on surface-exposed paired lysines. Beyond two binding sites identified in direct agreement with the x-ray structure, the association has a larger structural impact on the protein dynamics. Then, our simulations allow a direct comparison to analogous calixarenes, namely, sulfonato, similarly reported as "molecular glue." Our work can contribute to a robust in silico predictive tool to assess binding sites for any given protein of interest for crystallization, with the specificity of a macromolecular cage whose endo/exo orientation plays a role in the binding. [ABSTRACT FROM AUTHOR]

Due to their structural features, macrocyclic compounds such as calixarenes, conjugated with a variety of fluorophores have led to the development of fluorescent probes for numerous applications. This review covers the recent advances (from 2009 to date) made in calixarene-based fluorescent sensors and their biological applications. In addition to the fluorescence mechanisms used to signal the analyte binding, this article focuses mainly on the detection of biological relevant ions, on the selective sensing of biomolecules, such as amino acids, enzymes, drugs and other organic compounds, and on intracellular imaging. Calixarene-containing fluorescent nanoparticles and nanoaggregates for imaging and drug delivery are also described. Finally, this review presents some conclusions and future perspectives in this field. [ABSTRACT FROM AUTHOR]

This review explores calixarenes, a prominent family of third-generation supramolecules celebrated for their distinct hollow, cavity-shaped structures. These macrocycles are intricately assembled by linking multiple phenolic units orthogonally through methylene (–CH2–), sulfur (–S–), or sulfonyl (–SO2–) bridges. This structural framework plays a pivotal role in the intricate assembly of nanoclusters, significantly advancing the field of cluster chemistry. A key focus of current research is the remarkable ability of calixarenes to stabilize titanium-oxo clusters. Our review details the application of calixarenes in constructing titanium-oxo cluster structures, emphasizing how these clusters, when encapsulated within calixarenes, exploit flexible coordination sites for structural modifications and serve as foundational units for more complex assemblies. Additionally, we investigate how these calixarene-stabilized metal-oxo clusters function as versatile scaffolds for catalytically active metal ions, facilitating the creation of bimetallic nanoclusters. These clusters not only exhibit unique structural diversity but also demonstrate exceptional catalytic efficiency. This review aims to inspire ongoing exploration and innovation in the use of calixarenes for the synthesis and application of advanced cluster materials. [ABSTRACT FROM AUTHOR]

In current chemistry, supramolecular materials that respond to a wide variety of external stimuli, such as solvents, temperature, light excitation, pH, and mechanical forces (pressure, stress, strain, and tension), have attracted considerable attention; for example, we have developed cyclodextrins, cucurbiturils, pillararenes, calixarenes, crown ether-based chemical sensors, or chemosensors. These supramolecular chemosensors have potential applications in imaging, probing, and cancer detection. Recently, we focused on pressure, particularly solution-state hydrostatic pressure, from the viewpoint of cancer therapy. This Mini Review summarizes (i) why hydrostatic pressure is important, particularly in biology, and (ii) what we can do using hydrostatic pressure stimulation. [ABSTRACT FROM AUTHOR]

Inherently chiral calixarenes are known to exhibit versatile functions due to their delicate three-dimensional macrocyclic frameworks. However, the catalytic asymmetric synthesis of these compounds remains largely unexplored and poses a significant challenge. Herein, we report an unprecedented enantioselective electrochemical synthesis of inherently chiral calix[4]arenes. Our approach is based on a 3d metal cobalt-catalyzed asymmetric C–H acyloxylation of the prochiral macrocyclic frameworks. The easily accessible and modifiable chiral salicyloxazoline (Salox) was used as the ligand to efficiently regulate the enantioselectivity. This protocol proceeded smoothly under electrochemically mild conditions and was compatible with a wide range of carboxylic acids, including aryl carboxylic acids and tertiary, secondary, primary aliphatic carboxylic acids, yielding a variety of acyloxylated calix[4]arenes with good yields (up to 94% yield) and excellent enantioselectivities (95–99% ee). The synthetic practicability of this method was demonstrated by the scale-up reaction and the divergent derivatizations of the inherently chiral macrocyclic products. [ABSTRACT FROM AUTHOR]

The calixarene‐templated synthesis of new cyclo(meta‐ polyphenylenes (CMPs) is described. These compounds are functionalized with added aromatic units, that are suitably oriented for oxidative aromatization to be envisioned. This could pave the way towards the synthesis of elongated segments of zigzag‐type single‐walled carbon nanotubes (SWCNTs). [ABSTRACT FROM AUTHOR]

Inherently chiral calixarenes have garnered significant attention due to their distinctive properties, yet the development of efficient catalytic asymmetric synthesis methods remains a critical challenge. Herein, we report the asymmetric synthesis of calix[4]arenes featuring inherent or both inherent and axial chirality via a cobalt‐catalyzed C−H activation/annulation strategy in high yield with excellent enantio‐ and diastereoselectivity (up to >99 % ee and >20 : 1 dr). Electrooxidation was also suitable for this transformation to obviate the sacrificial metal oxidants, underscoring the environmentally friendly potential of this approach. A key octahedral cobaltacycle intermediate was synthesized and characterized, providing valuable insights into the mode of enantio‐ and diastereocontrol of this protocol. Noteworthy photoluminescence quantum yields of up to 0.94 were measured, underscoring the potential of these compounds in the domain of organic fluorescent materials. [ABSTRACT FROM AUTHOR]

AbstractThe emergence of calixarenes as versatile compounds in recent years marks a significant advancement in scientific research. In the area of analytical chemistry, calixarenes have garnered attention for their utility as selective chemosensors, enabling the sensitive and specific detection of metal ions through colorimetric and fluorimetric methods. Moreover, calixarenes have found applications in bioimaging, where they serve as effective probes for visualizing biological structures and processes with high resolution and sensitivity. Additionally, recent studies have explored the anticancer properties of calixarenes, unveiling their potential as therapeutic agents for cancer treatment. This comprehensive review explores recent advancements in calixarenes chemistry, emphasizing their significance in the colorimetric and fluorimetric detection of metal ions. Additionally, it highlights the mechanisms involved in chemosensor design, providing insights into the underlying principles driving their efficacy. Furthermore, the application of calixarenes in bioimaging, particularly for visualizing cellular structures and processes, is discussed, showing their potential in biomedical research and diagnostics. The anticancer activity of calixarenes and their derivatives is also explored, shedding light on their promising role as therapeutic agents. Through an extensive examination of recent literature, this review provides valuable insights into the multifaceted applications of calixarenes and offers perspectives for future research directions. [ABSTRACT FROM AUTHOR]

Calix[n]arenes, macrocycles constituted of 4–8 phenol moieties linked through methylene bridges, are stable molecules that can be selectively functionalised at the upper or lower rim. It has already been demonstrated that calixarene derivatives can be biologically or pharmacologically active compounds. More recently, suitably functionalised calixarenes and calixarene analogues (dihomooxacalixarenes, thiacalixarenes, calix[4]resorcinols, azacalixarenes, calixpyrroles, and pillarenes) were found to act as anticancer agents, at least in in vitro assays. We are reporting on the latest progress in this research field. [ABSTRACT FROM AUTHOR]

The purpose of this study was to synthesize and structurally characterize ketocalixarenes (i.e., calixarenes where the bridging methylene bridges are replaced by carbonyl groups) derived from the largest "major" calixarene, namely p-tert-butylcalix[8]arene 3a. Ketocalix[8]arenes were synthesized by the oxidation of protected p-tert-butylcalix[8]arene derivatives. Octamethoxy-p-tert-butylketocalix[8]arene 6b was prepared by the photochemical reaction of the calixarene 3b with NBS in a CHCl3/H2O mixture. The oxidation of the methylene groups of octaacetoxy-p-tert-butylcalix[8]arene 3c was conducted by a reaction with CrO3 in Ac2O/AcOH. The basic hydrolysis of the acetate groups of the oxidation product yielded octahydroxy-p-tert-butylketocalix[8]arene 6a. In the crystal, the molecule adopts a saddle-like conformation of crystallographic C2 and idealized S4 symmetry. Strikingly, the array of OH/OH intramolecular hydrogen bonds present in the parent 3a is completely disrupted in 6a. [ABSTRACT FROM AUTHOR]

Biomembranes function as hydrophobic barriers for hydrophilic substances enabling compartmentalization in biological systems. This poses, however, a problem for the targeted introduction of cargo into cells. The result is a high demand for delivery pathways into cells with the goal to investigate biological processes or to treat diseases by improved delivery. Polycationic cell‐penetrating peptides (CPPs) are interesting as they can cross cell membranes and transport attached cargos directly into the cytosol. Their efficiency can be improved by anionic amphiphilic counterion activators, which bind to the CPPs to form charge‐neutralized counterion‐CPP complexes with sufficient hydrophobicity to cross the lipid bilayer membrane. This review summarizes recent results, which establish amphiphilic calixarenes as a new class of biocompatible and non‐cytotoxic counterion activators with very high transport activities at nanomolar concentrations. We also include a brief summary of fluorescence‐based assays with large unilamellar vesicles (LUVs) to investigate counterion‐activated transport. Current methods use liposome‐encapsulated, supramolecular host‐dye reporter pairs including calixarenes, which provide new mechanistic insights and enable rapid in vitro identification of suitable activators. Taken together, amphiphilic calixarenes are currently emerging as prime candidates for counterion activation of membrane transport, which are highly modifiable and can be specifically tailored towards different cargoes and membrane types. [ABSTRACT FROM AUTHOR]

Transition metal catalysts with modified second‐coordination sphere employed in the electrocatalytic CO2 can result in increased activity or directed product selectivity. Calixarenes can form metal complexes and potentially catalyze reactions within its cavity, taking advantage of the surrounding phenols groups to tune the reactivity by second‐coordination sphere effects. Here, we present a Mn(I) bromotricarbonyl complex with phenanthroline‐functionalized calix[8]arene ligands capable of electrocatalytically reducing CO2 into different products with 2,2,2‐trifluoroethanol as proton donor. The selectivity of the reaction seems to be affected by the calixarene cavity: two calixarene‐free analogous complexes reduce CO2 to CO almost exclusively, while the calixarene complexes produce primarily CO, H2. Interestingly, in some cases the less frequently observed CH4 was also detected, albeit with low Faradaic efficiency. Thus, the manganese center placed within the calixarene cavity promotes the formation of reduced CO2 products by more than two electrons and two protons, affording CH4 in some cases. [ABSTRACT FROM AUTHOR]

Self‐folding cavitands represent the quintessential form of bioinspired synthetic receptors, featuring deep hydrophobic cavities that engage in host‐guest chemistry reminiscent of that operating in biomolecules. Although remarkable proof‐of‐concept applications have been reported, the narrow and rigid spaces of the legacy resorcin[4]arene derived hosts constitute a liability towards the development of specific applications in catalysis, sensing or sequestration. While notable efforts to expand the size of the cavities have been reported, the development of confined spaces reproducing the highly adaptable nature of biological receptors is a largely unaddressed issue. This review summarizes the development of a new family of calix[5]arene derived self‐folding cavitands displaying enhanced induced fit and conformational selection phenomena. Our approach capitalizes on hydrogen bonding preorganization rather than the covalent restriction approaches customary of conventional supramolecular chemistry. [ABSTRACT FROM AUTHOR]

Calix[4]arenes and calix[4]resorcinarenes are well‐known macrocyclic hosts that can be tailored to bind guests of very different natures, including anions, cations, and various neutral molecules. The molecular architectures of the hosts can be altered in many ways: by attaching polar or hydrophilic groups, extending inner cavities with enlarged aromatic side walls, and adding H‐bonding sites to promote the formation of molecular capsules. The attachment of different types of redox‐active moieties renders calix[4]arene and calix[4]resorcinarene derivatives electrochemically active, enabling them to either control the guest‐binding properties of the receptors or be used as electrochemical sensors. This review will focus on calix[4]arene and calix[4]resorcinarene macrocyclic hosts with appended redox‐active groups, such as ferrocene, tetrathiafulvalene, and quinone. We will discuss molecular receptors that can serve as redox sensors for cations or electron‐deficient molecules or can bind and release their guests controlled by redox or electrochemical stimuli. [ABSTRACT FROM AUTHOR]

Herbal medicines (HMs) are gaining increasing popularity and recognition worldwide due to their eco‐friendliness and efficacy. With their multi‐compounds, multi‐targets, and multi‐pathways characteristics, HMs have been used in treatment of various diseases. However, the clinical applications of preparations containing HMs have been limited due to their inherent physicochemical properties, including low water solubility, poor stability, and unsatisfactory bioavailability of bioactive compounds. Supramolecular macrocyclic hosts, like cyclodextrins, calixarenes, cucurbiturils, and pillararenes, are important objects of researches in supramolecular chemistry. These hosts have been utilized to encapsulate the ingredients, improve the solubility of poorly water‐soluble components, enhance the stability of the tested compounds, increase the bioavailability of bioactive compounds, and ensure the safety of HMs. Herein, we provide a brief introduction to the theories of supramolecular chemistry and summarize the extensive applications of supramolecular macrocyclic hosts in the field of HMs. These applications encompass the screening of bioactive compounds in HMs and the enhancement of druggability for HMs. We hope this review can provide a strategy for dealing with the challenges of HMs, thereby enabling their better applications and development. [ABSTRACT FROM AUTHOR]

The research of molecular capsules offers high application potential and numerous benefits in various fields. With the aim of forming supramolecular capsules which can be reversibly assembled and dissociated by simple external stimuli, we studied interactions between calixarenes containing urea and carboxylate moieties. To this end two ureido‐derivatives of p‐tert‐butylcalix[4]arene comprising phenylureido‐moieties and diacetate‐calix[4]arenes were prepared. The binding of acetate by ureido‐derivatives of calixarene in acetonitrile was characterized, revealing high affinity of ureido‐calixarenes for carboxylates. This suggested high potential for uniting the complementary calix[4]arenes via H‐bonds between carboxylic groups and urea moieties. The assembly of calixarenes was examined in detail by means of UV, 1H NMR, ITC, DOSY, MS, and conductometry providing insight in the structure‐stability relationship. The tetraureido‐calixarene derivative formed the most stable heterodimers with diacetate‐calix[4]arenes featuring practically quantitative association upon mixing the two calixarene counterparts. The possibility of controlling the formation of the heterodimer by protonating the carboxylates, thereby hindering the interactions critical for capsule assembly, was investigated. Indeed, the reversibility of breaking and re‐forming the heterodimer by addition of an acid and base to the solution containing urea‐ and carboxylate‐derivative calix[4]arene was demonstrated using NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Biomembranes function as hydrophobic barriers for hydrophilic substances enabling compartmentalization in biological systems. This poses, however, a problem for the targeted introduction of cargo into cells. The result is a high demand for delivery pathways into cells with the goal to investigate biological processes or to treat diseases by improved delivery. Polycationic cell‐penetrating peptides (CPPs) are interesting as they can cross cell membranes and transport attached cargos directly into the cytosol. Their efficiency can be improved by anionic amphiphilic counterion activators, which bind to the CPPs to form charge‐neutralized counterion‐CPP complexes with sufficient hydrophobicity to cross the lipid bilayer membrane. This review summarizes recent results, which establish amphiphilic calixarenes as a new class of biocompatible and non‐cytotoxic counterion activators with very high transport activities at nanomolar concentrations. We also include a brief summary of fluorescence‐based assays with large unilamellar vesicles (LUVs) to investigate counterion‐activated transport. Current methods use liposome‐encapsulated, supramolecular host‐dye reporter pairs including calixarenes, which provide new mechanistic insights and enable rapid in vitro identification of suitable activators. Taken together, amphiphilic calixarenes are currently emerging as prime candidates for counterion activation of membrane transport, which are highly modifiable and can be specifically tailored towards different cargoes and membrane types. [ABSTRACT FROM AUTHOR]

Herbal medicines (HMs) are gaining increasing popularity and recognition worldwide due to their eco‐friendliness and efficacy. With their multi‐compounds, multi‐targets, and multi‐pathways characteristics, HMs have been used in treatment of various diseases. However, the clinical applications of preparations containing HMs have been limited due to their inherent physicochemical properties, including low water solubility, poor stability, and unsatisfactory bioavailability of bioactive compounds. Supramolecular macrocyclic hosts, like cyclodextrins, calixarenes, cucurbiturils, and pillararenes, are important objects of researches in supramolecular chemistry. These hosts have been utilized to encapsulate the ingredients, improve the solubility of poorly water‐soluble components, enhance the stability of the tested compounds, increase the bioavailability of bioactive compounds, and ensure the safety of HMs. Herein, we provide a brief introduction to the theories of supramolecular chemistry and summarize the extensive applications of supramolecular macrocyclic hosts in the field of HMs. These applications encompass the screening of bioactive compounds in HMs and the enhancement of druggability for HMs. We hope this review can provide a strategy for dealing with the challenges of HMs, thereby enabling their better applications and development. [ABSTRACT FROM AUTHOR]

Self‐folding cavitands represent the quintessential form of bioinspired synthetic receptors, featuring deep hydrophobic cavities that engage in host‐guest chemistry reminiscent of that operating in biomolecules. Although remarkable proof‐of‐concept applications have been reported, the narrow and rigid spaces of the legacy resorcin[4]arene derived hosts constitute a liability towards the development of specific applications in catalysis, sensing or sequestration. While notable efforts to expand the size of the cavities have been reported, the development of confined spaces reproducing the highly adaptable nature of biological receptors is a largely unaddressed issue. This review summarizes the development of a new family of calix[5]arene derived self‐folding cavitands displaying enhanced induced fit and conformational selection phenomena. Our approach capitalizes on hydrogen bonding preorganization rather than the covalent restriction approaches customary of conventional supramolecular chemistry. [ABSTRACT FROM AUTHOR]

Transition metal catalysts with modified second‐coordination sphere employed in the electrocatalytic CO2 can result in increased activity or directed product selectivity. Calixarenes can form metal complexes and potentially catalyze reactions within its cavity, taking advantage of the surrounding phenols groups to tune the reactivity by second‐coordination sphere effects. Here, we present a Mn(I) bromotricarbonyl complex with phenanthroline‐functionalized calix[8]arene ligands capable of electrocatalytically reducing CO2 into different products with 2,2,2‐trifluoroethanol as proton donor. The selectivity of the reaction seems to be affected by the calixarene cavity: two calixarene‐free analogous complexes reduce CO2 to CO almost exclusively, while the calixarene complexes produce primarily CO, H2. Interestingly, in some cases the less frequently observed CH4 was also detected, albeit with low Faradaic efficiency. Thus, the manganese center placed within the calixarene cavity promotes the formation of reduced CO2 products by more than two electrons and two protons, affording CH4 in some cases. [ABSTRACT FROM AUTHOR]

Calix[4]arenes and calix[4]resorcinarenes are well‐known macrocyclic hosts that can be tailored to bind guests of very different natures, including anions, cations, and various neutral molecules. The molecular architectures of the hosts can be altered in many ways: by attaching polar or hydrophilic groups, extending inner cavities with enlarged aromatic side walls, and adding H‐bonding sites to promote the formation of molecular capsules. The attachment of different types of redox‐active moieties renders calix[4]arene and calix[4]resorcinarene derivatives electrochemically active, enabling them to either control the guest‐binding properties of the receptors or be used as electrochemical sensors. This review will focus on calix[4]arene and calix[4]resorcinarene macrocyclic hosts with appended redox‐active groups, such as ferrocene, tetrathiafulvalene, and quinone. We will discuss molecular receptors that can serve as redox sensors for cations or electron‐deficient molecules or can bind and release their guests controlled by redox or electrochemical stimuli. [ABSTRACT FROM AUTHOR]

Macrocycles composed of diverse aromatic or nonaromatic structures, such as cyclodextrins (CDs), calixarenes (CAs), cucurbiturils (CBs), and pillararenes (PAs), have garnered significant attention due to their inherent advantages of possessing cavity structures, unique functional groups, and facile modification. Due to these distinctive features enabling them to facilitate ion insertion and extraction, form crosslinked porous structures, offer multiple redox-active sites, and engage in host–guest interactions, macrocycles have made huge contributions to electrochemical energy storage and conversion (EES/EEC). Here, we have summarized the recent advancements and challenges in the utilization of CDs, CAs, CBs, and PAs as well as other novel macrocycles applied in EES/EEC devices. The molecular structure, properties, and modification strategies are discussed along with the corresponding energy density, specific capacity, and cycling life properties in detail. Finally, crucial limitations and future research directions pertaining to these macrocycles in electrochemical energy storage and conversion are addressed. It is hoped that this review is able to inspire interest and enthusiasm in researchers to investigate macrocycles and promote their applications in EES/EEC. [ABSTRACT FROM AUTHOR]

The calixarenes, 5,17-di­bromo-26,28-dihy­droxy-25,27-dipropynyloxycalix[4]arene (C34H26Br2O4, 1), 5,17-di­bromo-26,28-dipropoxy-25,27-dipropynyloxycalix[4]arene (C40H38Br2O4, 2) and 25,27-bis­(2-azido­eth­oxy)-5,17-di­bromo-26,28-di­hydroxy­calix[4]arene (C32H28Br2N6O4, 3) possess a pinched cone mol­ecular shape for 1 and 3, and a 1,3-alternate shape for compound 2. In calixarenes 1 and 3, the cone conformations are additionally stabilized by intra­molecular O—H⋯O hydrogen bonds, while in calixarene 2 intra­molecular Br⋯Br inter­actions consolidate the 1,3-alternate mol­ecular conformation. The dense crystal packing of the cone dialkyne 1 is a consequence of π–π, C—H⋯π and C—H⋯O inter­actions. In the crystal of the diazide 3, there are large channels extending parallel to the c axis, which are filled by highly disordered CH2Cl2 solvent mol­ecules. Their contribution to the intensity data was removed by the SQUEEZE procedure that showed an accessible void volume of 585 ų where there is room for 4.5 CH2Cl2 solvent mol­ecules per unit cell. Rigid mol­ecules of the 1,3-alternate calixarene 2 form a columnar head-to-tail packing parallel to [010] via van der Waals inter­actions, and the resulting columns are held together by weak C—H⋯π contacts. [ABSTRACT FROM AUTHOR]

1,3-Alternate calix[4]arenes were prepared, having bulky adamantyl groups in the p-positions of all four aromatic units of the macrocycles and pairs of propargyl or 2-azidoethyl groups alternating with n-propyl groups at the phenol oxygen atoms. The step-wise syntheses were carried out through a selective distal alkylation of the parent p-adamantylcalix[4]arene with propargyl bromide or 1,2-dibromoethane, resulting in calix[4]arenes bearing pairs of propargyl or 2-bromoethyl groups at their narrow rims. The bromine atoms were replaced by azide groups, and then both calix[4]arene diethers were exhaustively alkylated at the remaining OH-groups with 1-iodopropane under stereoselective conditions to fix the macrocycles in an 1,3-alternate shape. The structures of the prepared p-adamantylcalix[4]arenes were confirmed by NMR and HRMS data, and, for the 1,3-alternate dipropargyl ether, the X-ray diffraction data were also collected. Preliminary data on the reactivity of the prepared calixarenes under the CuAAC conditions suggested a strong steric hampering created by the adamantane units nearby the reacting alkyne or azide groups that affected the outcome of the two-fold cycloaddition involving the calixarene bis(azides) or bis(alkynes) as complementary partners. [ABSTRACT FROM AUTHOR]

We report the synthesis of a series of amphiphilic p‐sulfonatocalix[4]arenes with varying alkyl chain lengths (CX4‐Cn) and their application as efficient counterion activators for membrane transport of cell‐penetrating peptides (CPPs). The enhanced membrane activity is confirmed with the carboxyfluorescein (CF) assay in vesicles and by the direct cytosolic delivery of CPPs into CHO−K1, HCT 116, and KTC‐1 cells enabling excellent cellular uptake of the CPPs into two cancer cell lines. Intracellular delivery was confirmed by fluorescence microscopy after CPP entry into live cells mediated by CX4‐Cn, which was also quantified after cell lysis by fluorescence spectroscopy. The results present the first systematic exploration of structure‐activity relationships for calixarene‐based counterion activators and show that CX4‐Cn are exceptionally effective in cellular delivery of CPPs. The dodecyl derivative, CX4‐C12, serves as best activator. A first mechanistic insight is provided by efficient CPP uptake at 4 °C and in the presence of the endocytosis inhibitor dynasore, which indicates a direct translocation of the CPP‐counterion complexes into the cytosol and highlights the potential benefits of CX4‐Cn for efficient and direct translocation of CPPs and CPP‐conjugated cargo molecules into the cytosol of live cells. [ABSTRACT FROM AUTHOR]

The highly strained, phenylene‐derived organic cages are typically regarded as very rigid entities, yet their deformation potential and supramolecular properties remain underexplored. Herein, we report a pliable conjugated phenylene nanocage by synergistically merging rigid and flexible building blocks. The anisotropic cage molecule contains branched phenylene chains capped by a calix[6]arene moiety, the delicate conformational changes of which endow the cage with a remarkably deformable cavity. When complexing with fullerene guests, the cage showcases excellent guest‐adaptivity, with its cavity volume capable of swelling by as much as 85 %. [ABSTRACT FROM AUTHOR]

The highly strained, phenylene‐derived organic cages are typically regarded as very rigid entities, yet their deformation potential and supramolecular properties remain underexplored. Herein, we report a pliable conjugated phenylene nanocage by synergistically merging rigid and flexible building blocks. The anisotropic cage molecule contains branched phenylene chains capped by a calix[6]arene moiety, the delicate conformational changes of which endow the cage with a remarkably deformable cavity. When complexing with fullerene guests, the cage showcases excellent guest‐adaptivity, with its cavity volume capable of swelling by as much as 85 %. [ABSTRACT FROM AUTHOR]

The calixarenes, 5,17-dibromo-26,28-dihydroxy-25,27-dipropynyloxycalix[4]- arene (C34H26Br2O4, 1), 5,17-dibromo-26,28-dipropoxy-25,27-dipropynyloxycalix[4]arene (C40H38Br2O4, 2) and 25,27-bis(2-azidoethoxy)-5,17-dibromo-26,28-dihydroxycalix[4]arene (C32H28Br2N6O4, 3) possess a pinched cone molecular shape for 1 and 3, and a 1,3-alternate shape for compound 2. In calixarenes 1 and 3, the cone conformations are additionally stabilized by intra-molecular O-H⋯O hydrogen bonds, while in calixarene 2 intra-molecular Br⋯Br inter-actions consolidate the 1,3-alternate mol-ecular conformation. The dense crystal packing of the cone dialkyne 1 is a consequence of π-π, C-H⋯π and C-H⋯O inter-actions. In the crystal of the diazide 3, there are large channels extending parallel to the c axis, which are filled by highly disordered CH2Cl2 solvent mol-ecules. Their contribution to the intensity data was removed by the SQUEEZE procedure that showed an accessible void volume of 585 Å3 where there is room for 4.5 CH2Cl2 solvent mol-ecules per unit cell. Rigid mol-ecules of the 1,3-alternate calixarene 2 form a columnar head-to-tail packing parallel to [010] via van der Waals inter-actions, and the resulting columns are held together by weak C-H⋯π contacts. [ABSTRACT FROM AUTHOR]

As drug carriers, calixarenes are often investigated and employed in numerous sectors as host molecules. The use of calixarenes in drug delivery systems is a relatively new notion, despite the fact that countless studies have been conducted on calixarenes and their various applications. It is worthwhile to research the computational investigation of the host-guest interaction between calixarenes and para-aminobenzoic acid (PABA) in terms of their binding energy and band gap. The first principles study of PABA sensing by calix [4] arene (C4) and calix [6] arene (C6) based on density functional theory (DFT) was carried out in this study using Quantum ESPRESSO software. By using the coCalixarenes, Band gap, Binding energy, Density functional theory, PABAmputational method, the binding energy, as well as the band gap of C4, C6, PABA, and the novel complexes, C4-PABA, and C6-PABA, were calculated. Different interaction distances were used in the formation of complexes. Our results demonstrate the reduction of the band gap for both complexes. Furthermore, the calculated binding energy shows the promising stability of the complexes. This demonstrates the sensing ability of calixarenes towards PABA and the potential anti-cancer properties of calixarene-PABA in sunscreens. [ABSTRACT FROM AUTHOR]

Diamond nanoparticles are an extremely promising class of carbon‐based nanomaterials. Because of their versatility, they have an interest in a large variety of applications, however, their use in the fabrication of enzyme mimics was not previously investigated. In this study, we realized hybrid systems based on guanidinium derivatives and diamond nanoparticles by simple adsorption of the organic material on their surface. The guanidinium derivatives chosen for this study are calix[4]arenes, blocked in the cone conformation via functionalization at the lower rim with alkyl chains, and decorated with guanidinium or arginine units at the upper rim. The corresponding monofunctional counterparts were also investigated as model compounds. These materials were characterized with different experimental techniques, i. e. thermogravimetric analysis, dynamic light scattering, ζ‐potential measurements and IR/Raman spectroscopy. Their catalytic properties in the cleavage of phosphodiesters were investigated by an in‐depth kinetic analysis. The whole experimental picture points to conclude that these compounds are stably adsorbed onto the nanodiamonds surface and are active in the transesterification reaction of the RNA model compound 2‐hydroxypropyl p‐nitrophenyl phosphate in water, with a notable advantage over their catalytic performances at the same concentration in solution. [ABSTRACT FROM AUTHOR]

Polyimides are a polymer class that has been extensively investigated as a membrane material for gas separation owing to its interesting permselective properties in a wide range of operation temperatures and pressures. In order to improve their properties, the addition of different filler types is currently studied. p-tert-Butylcalix[n]arene macrocycles (PTBCs) with different cavity sizes (PTBC4, PTBC6, PTBC8) were used as fillers in a commercial thermoplastic polyimide, with a concentration in the range 1–9 wt%, to develop nanocomposite membranes for gas separation. The selected macrocycles are attractive organic compounds owing to their porous structure and affinity with organic polymers. The nanocomposite membranes were prepared in the form of films in which the polymeric matrix is a continuous phase incorporating the dispersed additives. The preparation was carried out according to a pre-mixing approach in a mutual solvent, and the solution casting was followed by a controlled solvent evaporation. The films were characterized by investigating their miscibility, morphology, thermal and spectral properties. The gas transport through these films was examined as a function of the temperature and also time. The results evidenced that the incorporation of the chosen nanoporous fillers can be exploited to enhance molecular transport, offering additional pathways and promoting rearrangements of the polymeric chains. [ABSTRACT FROM AUTHOR]

A series of tetraaza‐expanded calix[4]arene analogues (2–4), in which two of the four aryl groups are ethylene‐protected thiophenol components were prepared from tetraaldehyde 1. Two of these strapped macrocycles were characterized crystallographically, as well as the dipalladium complex of 4. The same tetraaldehyde had been previously used for the synthesis of a macrotricycle (5) and a macropentacycle (6), the coordination properties of which have been investigated. In particular, ligand 6 was shown to be able to encapsulate a Cu+ or a Ag+ ion in the tetrahedral coordination pocket offered by a bridgehead nitrogen atom and the three proximal thioether sulfur atoms. [ABSTRACT FROM AUTHOR]

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 {SiW10Cr2(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. [ABSTRACT FROM AUTHOR]

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 {SiW10Cr2(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. [ABSTRACT FROM AUTHOR]

This review article focuses on the supramolecular assemblies fabricated through host-guest interaction using macrocycles such as cyclodextrins, calixarenes and cucurbiturils as hosts. Though several review articles have appeared on such host-guest assemblies having importance in controlled drug-delivery, fluorescence on-off sensors, catalysis etc., not much attention has been given to collect their potential applications in antibacterial activity. In this article we have mainly discussed the concepts, strategies and applications to enhance the antibacterial activity of different assemblies with some of the well-established antibacterial drugs/agents. The enhanced antibacterial activity of hydrogel, gelatin composite film, bismuth oxide nanoparticles and sanguinarine drug in the presence of cyclodextrins have been described in detail. The mechanism for the improved antibacterial activity of calixarene-capped nanoparticles, calixarene-complexed antibiotics and stimuli-responsive calixarene-based nanoassemblies for NO release was discussed. The enhanced photosensitizing effect of cucurbituril (CB) complexed porphyrins and their stimuli-responsive control over its antibacterial activity and the photothermal therapy has been elaborated. The effect of augmented antibacterial activity of CB-encapsulated drugs have also been given emphasis as they are promising for long-acting antibiotics. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A highly selective palladium‐catalyzed carbonylation of 2‐alkynylanilines bearing an amide moiety to condensed six‐membered heterocyclic structures has been developed under mild conditions (room temperature and atmospheric pressure of CO). The carbonylative protocol is also compatible with CO surrogates, such as benzene‐1,3,5‐triyl triformate (TFBen) or the newly developed calix[6]arenes functionalized with six formate groups (CLX[6]CO), which are both capable to release CO in situ. A series of tricyclic fused heterocycles containing the important oxazino‐quinolinone scaffold have been selectively obtained (only the 6‐endo‐dig cyclization mode has been observed) in good to excellent yields (up to 99%). [ABSTRACT FROM AUTHOR]

Supramolecular chemistry enables the manipulation of functional components on a molecular scale, facilitating a "bottom-up" approach to govern the sizes and structures of supramolecular materials. Using dynamic non-covalent interactions, supramolecular polymers can create materials with reversible and degradable characteristics and the abilities to self-heal and respond to external stimuli. Pillar[n]arene represents a novel class of macrocyclic hosts, emerging after cyclodextrins, crown ethers, calixarenes, and cucurbiturils. Its significance lies in its distinctive structure, comparing an electron-rich cavity and two finely adjustable rims, which has sparked considerable interest. Furthermore, the straightforward synthesis, uncomplicated functionalization, and remarkable properties of pillar[n]arene based on supramolecular interactions make it an excellent candidate for material construction, particularly in generating interpenetrating supramolecular polymers. Polymers resulting from supramolecular interactions involving pillar[n]arene find potential in various applications, including fluorescence sensors, substance adsorption and separation, catalysis, light-harvesting systems, artificial nanochannels, and drug delivery. In this context, we provide an overview of these recent frontier research fields in the use of pillar[n]arene-based supramolecular polymers, which serves as a source of inspiration for the creation of innovative functional polymer materials derived from pillar[n]arene derivatives. [ABSTRACT FROM AUTHOR]

Copper(I)-catalyzed azide-alkyne cycloaddition was employed to construct biscalixarene assemblies from the calix[4]arene dipropargyl ethers and 4,4′-bis-azidomethylated azobenzene or stilbene. Three bis(calixarenes) having the calix[4]arene cores linked to each other by pairs of (E)-azobenzene/stilbene units through four triazole groups were obtained as confirmed by NMR, HRMS and X-ray diffraction data. Nevertheless, the formation of larger macrocycles and polymeric/oligomeric products was found to be the major competing process that seriously limited the applicability of the one-step macrocyclization approach for the construction of photoresponsive biscalixarene assemblies linked by pairs of azobenzene/stilbene units. [ABSTRACT FROM AUTHOR]

A calix[4]arene‐based gelator 1, with lower‐rim mono triazolylpyridine group, capable of spontaneous self‐assembly into microspheres in different ethanol/H2O mixtures, is synthesized. The concentration‐dependent 1H NMR spectra and X‐ray single‐crystal structure of 1 provided evidence for self‐assembly of gelator 1 via cooperative interactions of intermolecular noncovalent forces. Furthermore, metallogels by self‐assembly of 1 was found to exhibit remarkable selectivity toward Hg2+ ions. 1H NMR spectra support that Hg2+ ion was bound to the nitrogen atoms of two coordination sites of 1, which composed of triazole and pyridine. Moreover, the results of field emission scanning electron microscopy and rheology experiments indicated that Hg2+ ions not only enhanced the gelling ability of gelator 1 in ethanol but also led to morphological change of its self‐assembly through metal‐ligand interactions. Finally, the in situ gelation, triggered by mixing a gelator solution of 1 in ethanol with water samples such as deionized (DI), tap, and lake water, leads to the effective removal of Hg(II) from a water sample which reduced from 400 to 1.6 ppm. [ABSTRACT FROM AUTHOR]

Inherent chirality represents a distinct category of molecular chirality that does not fall within the traditional classification of four chiral elements: central, axial, planar, and helical chirality. While extensive research has been conducted on the catalytic enantioselective construction of these conventional chiralities, the corresponding synthesis of inherently chiral molecules has remained largely unexplored. This minireview provides a comprehensive summary of recent advancements in this field, focusing on the catalytic asymmetric synthesis of inherently chiral calixarenes, saddle‐shaped tetraphenylenes and their heterocycle derivatives, mechanically planar chiral rotaxanes and chiral multilayer 3D frameworks, as well as our perspective in this field. [ABSTRACT FROM AUTHOR]

Molecular differentiation by supramolecular sensors is typically achieved through sensor arrays, relying on the pattern recognition responses of large panels of isolated sensing elements. Here we report a new one‐pot systems chemistry approach to differential sensing in biological solutions. We constructed an adaptive network of three cross‐assembling sensor elements with diverse analyte‐binding and photophysical properties. This robust sensing approach exploits complex interconnected sensor‐sensor and sensor‐analyte equilibria, producing emergent supramolecular and photophysical responses unique to each analyte. We characterize the basic mechanisms by which an adaptive network responds to analytes. The inherently data‐rich responses of an adaptive network discriminate among very closely related proteins and protein mixtures without relying on designed protein recognition elements. We show that a single adaptive sensing solution provides better analyte discrimination using fewer response observations than a sensor array built from the same components. We also show the network's ability to adapt and respond to changing biological solutions over time. [ABSTRACT FROM AUTHOR]

Molecular differentiation by supramolecular sensors is typically achieved through sensor arrays, relying on the pattern recognition responses of large panels of isolated sensing elements. Here we report a new one‐pot systems chemistry approach to differential sensing in biological solutions. We constructed an adaptive network of three cross‐assembling sensor elements with diverse analyte‐binding and photophysical properties. This robust sensing approach exploits complex interconnected sensor‐sensor and sensor‐analyte equilibria, producing emergent supramolecular and photophysical responses unique to each analyte. We characterize the basic mechanisms by which an adaptive network responds to analytes. The inherently data‐rich responses of an adaptive network discriminate among very closely related proteins and protein mixtures without relying on designed protein recognition elements. We show that a single adaptive sensing solution provides better analyte discrimination using fewer response observations than a sensor array built from the same components. We also show the network's ability to adapt and respond to changing biological solutions over time. [ABSTRACT FROM AUTHOR]

Since the discovery of polyphenolic resins 150 years ago, the study of polymeric compounds named calix[n]arene has continued to progress, and those skilled in the art perfectly know now how to modulate this phenolic ring. Consequently, calix[n]arenes are now used in a large range of applications and notably in therapeutic fields. In particular, the calix[4]arene exhibits multiple possibilities for regioselective polyfunctionalization on both of its rims and offers researchers the possibility of precisely tuning the geometry of their structures. Thus, in the crucial research of new antibacterial active ingredients, the design of calixarenes finds its place perfectly. This review provides an overview of the work carried out in this aim towards the development of intrinsically active prodrogues or metallic calixarene complexes. Out of all the work of the community, there are some excellent activities emerging that could potentially place these original structures in a very good position for the development of new active ingredients. [ABSTRACT FROM AUTHOR]

Precise and efficient separation of molecules and ions is important in many fields, including the chemical industry, textiles, and medicine. Two-dimensional (2D) materials with high specific surface areas and atomic thickness are an excellent choice for membrane building blocks. However, stacking nanosheets face-to-face usually prevents the transport of molecules or ions across such 2D membranes, thereby reducing their flux. Supramolecular macrocyclic hosts contain cucurbiturils, cyclodextrins, pillararenes, crown ethers, and calixarenes, which afford macrocyclic cavities with rigid structures that are easy to be functionalized. Thus, it is possible to construct membranes using 2D materials as "beams" and supramolecular macrocyclic compounds as "columns". This strategy has been applied to overcome challenges related to the permeability–selectivity trade-off. Supramolecular 2D membranes have been widely used in a wide range of critical separations, including water purification, enantiomer separation, ion extraction and separation, and gas separation. This review provides a new perspective to inspire researchers to develop promising 2D supramolecular membranes with high selectivity, mild flux, and appreciable reversibility. [ABSTRACT FROM AUTHOR]

One pot sequential reactions of silica gel with tetrachlorosilane/triethylamine mixture and after with the conical upper rim tetraphosphorylated tetrahydroxy(thia)calixarenes yielded porous organo-inorganic sorbents modified by spatially ordered phosphonate, phosphinate or phosphine oxide groups capable of co-operative binding of metal cations. The grafting improves efficacy of europium(III) sorption by the silica gels. DFT calculations of the calixarene-Eu3+ complexes predict a calixarene flattened cone conformation with the coordination of Eu3+ cation to three of four P = O oxygen atoms and one of the aromatic systems. Adding three water molecules excludes completely cation–π interactions. [ABSTRACT FROM AUTHOR]

Photoactives 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. [ABSTRACT FROM AUTHOR]

A series of cationic p-tert-butylcalix[4]arenes, with side-arms that are functionalized with imidazolium groups, have been synthesized in good yields. The parent tetrahydroxy para-t-butyl-calix[4]arene was dialkylated at the phenolic hydrogen atoms using α,ω-dibromo-alkanes to yield bis(mono-brominated) alkoxy-chains of variable length. The brominated side-arms in these compounds were then further alkylated with substituted imidazoles (N-methylimidazole, N-(2,4,6-trimethyl-phenyl)imidazole, or N-(2,6-di-isopropylphenyl)imidazole) to yield a series of dicationic calixarenes with two imidazolium groups tethered, via different numbers of methylene spacers (n = 2–4), to the calixarene moiety. Related tetracationic compounds, which contain four imidazolium units linked to the calix[4]arene backbone, were also prepared. In all of these compounds, the NMR data show that the calixarenes adopted a cone configuration. All molecules were characterized by NMR spectroscopy and by MS studies. Single crystal X-ray diffraction studies were attempted on many mono-crystals of these cations, but significant disorder problems, partly caused by occluded solvent in the lattice, and lack of crystallinity resulting from partial solvent loss, precluded the good resolution of most X-ray structures. Eventually, good structural data were obtained from an unusually disordered single crystal of 5a, (1,3)-Cone-5,11,17,23-tetra-t-butyl-25,27-di-hydroxy-26,28-di-[2-(N-2,6-diisopropylphenyl-imidazolium)ethoxy]calix[4]arene dibromide and its presumed structure was confirmed. The structure revealed the presence of H-bonded interactions and some evidence of π-stacking. Some of these imidazolium salts were reacted with nickelocene to form the nickel N-heterocyclic carbene (NHC) complexes 7a–7d. A bis-carbene nickel complex 8 was also isolated and its structure was established by single crystal X-ray diffraction studies. The structure was disordered and not of high quality, but the structural data corroborated the spectroscopic data. [ABSTRACT FROM AUTHOR]

This study aims to investigate the adsorption characteristics of tetracycline from polluted waters using C-4- hydroxyphenylcalix[4]resorcinarene as an adsorbent. The adsorptive efficiency of C-4-hydroxyphenylcalix[4]resorcinarene is optimized by adjusting various operational parameters such as the adsorbent dosage, the pH, the contact time, the temperature, and the initial adsorbate concentration. The most efficient remediation is 96% at 10.0 mg/L tetracycline as the initial concentration, 0.05 mg/L C-4-hydroxyphenylcalix[4]resorcinarene, a contact time of 30 min, pH 5.6, and ambient temperature. The adsorption ability of C-4-hydroxyphenylcalix[4]resorcinarene toward tetracycline is also investigated in water with different characteristics, including solutions with and without the addition of background salts. The results show that C-4-hydroxyphenylcalix[4]resorcinarene can effectively remove tetracycline from aqueous solutions with an adsorption capacity of ca. 36.9 mg/g. The study also finds that the removal process followed pseudo-second order kinetics and Freundlich isotherm models. Moreover, the adsorption is spontaneous and exothermic, suggesting a thermodynamically favorable chemisorption process. In addition, the optimized method is successfully applied to remove tetracycline from various real natural water systems. [ABSTRACT FROM AUTHOR]

Controlled protein assembly and crystallization is necessary as a means of generating diffraction‐quality crystals as well as providing a basis for new types of biomaterials. Water‐soluble calixarenes are useful mediators of protein crystallization. Recently, it was demonstrated that Ralstonia solanacearum lectin (RSL) co‐crystallizes with anionic sulfonato‐calix[8]arene (sclx8) in three space groups. Two of these co‐crystals only grow at pH ≤ 4 where the protein is cationic, and the crystal packing is dominated by the calixarene. This paper describes a fourth RSL–sclx8 co‐crystal, which was discovered while working with a cation‐enriched mutant. Crystal form IV grows at high ionic strength in the pH range 5–6. While possessing some features in common with the previous forms, the new structure reveals alternative calixarene binding modes. The occurrence of C2‐symmetric assemblies, with the calixarene at special positions, appears to be an important result for framework fabrication. Questions arise regarding crystal screening and exhaustive searching for polymorphs. [ABSTRACT FROM AUTHOR]

The effect of the platinum content (3–10 wt %) in the Pt/SnO2(Sb)-based working-electrode material on the properties (sensitivity, high-speed performance, recovery time) of solid-state potentiometric gas sensors for hydrogen and carbon monoxide including their simultaneous presence in air is studied. Sensors with 5% Pt demonstrate the best characteristics: the efficient carbon-monoxide detection for its concentration from 0.01 to 1 vol %; no effect of hydrogen present in the CO + air mixture in concentrations comparable with the CO concentration; the shortest relaxation time (~30 s at 1% CO). [ABSTRACT FROM AUTHOR]