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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.

Background Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). Results In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4β1 and αLβ2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. Conclusion This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs. Graphical Abstract

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.

With a view to establishing molecular recognition rules, the host p-tert-butyl­calix[6]arene was crystallized with different guest molecules. The ratio between the apolar surface area and the volume was used to predict the formation of inclusion versus exclusion complexes, with inclusion complexes observed at ratios, Calixarenes are host molecules that can form complexes with one or more guest molecules, and molecular recognition in calixarenes can be affected by many factors. With a view to establishing molecular recognition rules, the host p-tert-butyl­calix[6]arene (TBC6) was crystallized with different guest molecules (cyclo­hexane, anisole, heptane, toluene, benzene, methyl acetate, ethyl acetate, di­chloro­methane, tetra­hydro­furan and pyridine) and the obtained structures were characterized by X-ray diffraction. With most solvents, 1:1 and/or 1:3 host–guest complexes were formed, although other stoichiometries were also observed with small guest molecules, and crystallization from ethyl acetate produced the unsolvated form. The calculated fill percentage of the TBC6 cavity was ∼55% for apolar guests and significantly lower for polar solvents, indicating that polar molecules can bind to apolar cavities with significantly lower packing coefficients. The most stable crystals were formed by 1:1 host–guest inclusion complexes. The ratio between the apolar surface area and the volume was used to predict the formation of inclusion versus exclusion complexes, with inclusion complexes observed at ratios

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.

The hexameric undecyl-resorcin[4]arene capsule (C11R6) features eight discrete structural water molecules located at the vertices of its cubic suprastructure. Combining NMR spectroscopy with classical molecular dynamics (MD), we identified and characterized two distinct species of this capsule, C11R6-A and C11R6-B, respectively featuring 8 and 15 water molecules incorporated into their respective hydrogen-bonded networks. Furthermore, we found that the ratio of the C11R6-A and C11R6-B found in solution can be modulated by controlling the water content of the sample. The importance of this supramolecular modulation in C11R6 capsules is highlighted by its ability to perform acid-catalyzed transformations, which is an emergent property arising from the hydrogen bonding within the suprastructure. We show that the conversion of C11R6-A to C11R6-B enhances the catalytic rate of a model Diels–Alder cyclization by 10-fold, demonstrating the cofactor-derived control of a supramolecular catalytic process that emulates natural enzymatic systems.

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.

S ciljem procjene potencijala primjene derivata kaliksarena 5,11,17,23-tetra-tert-butil-25,27- dimetoksi-26,28-bis-((fenantridin-6-il)metoksi)kaliks[4]aren (D) u teranostici, u ovom su radu istražena njegova kompleksacijska svojstva s bojama rodaminom B, auraminom O i fluoresceinom te lijekom timokinonom pri čemu je zbog slabe topljivosti liganda korišten sustav otapala acetonitril/diklormetan. Konstante stabilnosti određene su na temelju provedenih spektrofotometrijskih titracija. Za kompleks [D- rodaminB] lg(K/dm 3 mol -1 ) = 4,55 + 0,01 te lg(K/dm 3 mol -1 ) = 5,61 + 0,05 za kompleks [D-auraminO]. Za kompleks [D-fluorescein] nije bilo moguće odrediti vrijednost konstante stabilnosti iako su eksperimentalni podaci upućivali na to da do stvaranja kompleksa dolazi. Upravo suprotno, s timokinonom kompleksiranje nije opaženo, vjerojatno zbog njegove strukturne nekomplementarnosti s veznim mjestom liganda. Proučavani derivat kaliksarena D dobar je receptor za istraživane boje, pri čemu je najveći afinitet pokazao prema auraminu O. Iako je ustanovljeno da ovaj derivat kaliksarena ima jako dobra receptorska svojstva, on nije topljiv u vodi, što je nužno za primjenu u teranostici, ali se očekuje da bi njegov vodotopivi analog koji bi iskoristio potencijal fenantridinskih skupina u veznom mjestu, mogao pokazati velik potencijal u teranostičkoj primjeni. With the aim of evaluating the application potential of calixarene derivatives 5,11,17,23-tetra-tert- butyl-25,27-dimethoxy-26,28-bis-((phenanthridin-6-yl)methoxy)calix[4]arene (D), in this thesis, its complexation properties with the dyes rhodamine B, auramine O and fluorescein and the drug thymoquinone were investigated. The stability constants were determined based on spectrophotometric titrations and the obtained values were lg(K/dm 3 mol -1 ) = 4.55 + 0.01 for [D-rhodamineB], and for complex [D-auramineO] lg(K/dm 3 mol -1 ) = 5.61 + 0.05. The value of the stability constant for [D-fluorescein] could not be determined, only estimated based on experimental data, while the formation of the complex with thymoquinone was not observed. The results indicate good binding of the studied dyes by the studied calixarene derivative. At the same time, the highest affinity of ligand D towards the formation of a complex was shown for auramine O. Although it was shown that this calixarene derivative has very good receptor properties, it is not soluble in water, which is necessary for its application in theranostics, but it is espected that its water-soluble analogue, that would exploit the potential of phenantridine groups at the binding site, could have great potential in theranostic applications.

S ciljem da se ispita kompleksacijski afinitet nesimetrično supstrituiranog amidnog difenilantracenskog derivata kaliksarena 5,11,17,23-tetra-tert-butil-25-(9,10-difenilantracen-2-iloksietoksi)- 26,27,28-tris(N,N-dietil-karbamoilmetoksi)kaliks[4]arena, L, prema organskim bojama - rodaminu B, auraminu O i fluoresceinu te aktivnoj tvari – timokinonu, proveden je niz spektrofotometrijskih titracija u acetonitrilu. Određene su i konstante stabilnosti odgovarajuć ih kompleksa koje ukazuju na nastanak relativno stabilnih kompleksa derivata kaliks[4]arena L s istraživanim bojama, pri čemu je spoj L pokazao najveći afinitet prema auraminu O. S druge strane, s timokinonom nije došlo do vezanja zbog njegove strukturne nekomplementarnosti s veznim mjestom liganda. Iako kompleksu [L- fluorescein] nije bilo moguće odrediti konstantu stabilnosti, iz eksperimentalnih je podataka bio vidljiv nastanak kompleksa, te je njena vrijednost procijenjena kao niža u odnosu na odgovarajuće konstante za rodamin B i auramin O. Ispitani derivat kaliksarena demonstrirao je dobre receptorske sposobnosti veznog mjesta koje se sastoji od tercijarnih amidnih skupina i difenilantracenske skupine, pa je za očekivati da bi njegov vodotopivi analog imao velik potencijal u teranostici. In order to investigate the complexation affinity of the asymmetrically substituted amide diphenylanthracene derivative of calixarene 5,11,17,23-tetra-tert-butyl-25-(9,10-diphenylanthracene-2- yloxyethoxy)-26,27,28-tris(N,N-diethyl-carbamoylmethoxy) calix[4]arene, L, towards the organic dyes – rhodamine B, auramine O and fluorescein and the active compound – thymoquinone, a series of spectrophotometric titrations in acetonitrile were carried out. The stability constants of the corresponding complexes were determined and their values indicated that relatively stable complexes of calix[4]arene derivatives L with the studied dyes were formed, with compound L showing the highest affinity for the binding of auramine O. On the other hand, the complex with thymoquinone did not form under the experimental conditions used, due to its structural incompatibility with the ligand's binding site. Although the value of the stability constant for [L-fluorescein] complex could not be determined, there was experimental evidence of the complex formation and its value was estimated to be lower than the corresponding constants for rhodamine B and auramine O. Since the studied calixarene derivative demonstrated good receptor properties of the binding site composed of tertiary amide groups and a diphenylanthracene group, it can be expected that its water-soluble analogue should have great potential for applications in theranostics.

U ovom radu dan je teoretski uvid u supramolekulsku kemiju, teranostiku i kaliksarene, te njihovu primjenu. Eksperimentalno je spektrofotometrijskim titracijama istraživano veže li tetrasupstituirani fenantridinski derivat kaliks[4]arena: 5,11,17,23-tetra-tert-butil-25,26,27,28-tetrakis-((fenantridin-6- il)metoksi)kaliks[4]aren (L), odabrane boje: rodamin B, auramin O i fluorescein, s ciljem primjene dobivenih kompleksa za molekulsko označavanje u teranostici i kemoterapeutike: timokinon i paklitaksel, također za primjenu u teranostici. Pokazano je da L kompleksira navedene boje i farmakološki aktivnu tvar timokinon, međutim za paklitaksel nije opažen nastanak kompleksa. Na temelju eksperimentalnih podataka, izračunate su konstante stabilnosti odgovarajućih kompleksa. Prema dobivenim vrijednostima, u korištenim eksperimentalnim uvjetima, afinitet kaliksarenskog derivata L bio je najveći prema vezanju auramina O. Nadalje, vezanje istraživanih boja bilo je efikasnije od vezanja istraživanih lijekova, što je i očekivano s obzirom na njihove strukturne karakteristike i komplementarnost sa strukturom samog liganda Iz svega navedenog zaključeno je da se ovaj kaliksaren, unatoč dobrim receptorskim svojstvima njegovog veznog mjesta kojeg čine fenantridinske podjedinice na donjem obodu, ne može koristiti u teranostici jer nije topljiv u vodi. Međutim, njegov bi analog, s mogućnošću otapanja u vodi, mogao imati izniman potencijal primjene u teranostici. This paper provides a theoretical insight into supermolecural chemistry, theranostics and calixarene and their application. It was experimentally investigated, by means of spectrophotometric titrations, whether the tetrasubstituted phenanthridine derivative of calix[4]arene: 5,11,17,23-tetra-tert- butyl-25,26,27,28-tetrakis-((phenanthridin-6-yl)methoxy)calix[4]arene (L) binds selected dyes: rhodamine B, auramine O and fluorescein, with the aim of applying the resulting complexes for molecular labeling in theranostics and chemotherapeutic drugs: thymoquinone and paclitaxel, also for use in theranostics. It was shown that L forms complexes with these dyes and the pharmacologically active substance thymoquinone, however, the formation of complexwith paclitaxel was not observed. Based on experimental data, the stability constants of the corresponding complexes were calculated. According to the obtained values, under the experimental conditions applied, the affinity of the calixarene derivative L was the highest for the binding of auramine O. Furthermore, the binding of the three studied dyes were generally more efficient than the binding of the investigated drugs, which was expected considering their structural characteristics and complementarity with the structure of ligand itself. Keeping all of the above in mind, it is concluded that this calixarene derivative, despite of good receptor properties of its binding site formed by phenantridin substituents at the lower rim, cannot be used in theranostics because of its insolubility in water. Nevertheless, its water-soluble analog could have exeptional potential of application in theranostics.

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

1H NMR measurements are reported for the CD2Cl2/CDCl3 solutions of the Co(II) calix[4]arenetetraphosphineoxide complex (I). Temperature dependences of the 1H NMR spectra of I have been analyzed using the line shape analysis, taking into account the temperature variation of paramagnetic chemical shifts, within the frame of the dynamic NMR method. Conformational dynamics of the 2:1 Co(II) calix[4]arene complexes was conditioned by the pinched cone ↔pinched cone interconversion of I (with activation Gibbs energy ΔG≠(298K) = 40 ± 3 kJ/mol. Due to substantial temperature dependence of paramagnetic shifts, complex I can be used as model compound for designing an NMR thermosensor reagent for local temperature monitoring.

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.

The present work describes the reaction of triplet dioxygen with the porphyrinogenic calix[4]pyrrolato aluminates to alkylperoxido aluminates in high selectivity. Multiconfigurational quantum chemical computations disclose the mechanism for this spin‐forbidden process. Despite a negligible spin–orbit coupling constant, the intersystem crossing (ISC) is facilitated by singlet and triplet state degeneracy and spin–vibronic coupling. The formed peroxides are stable toward external substrates but undergo an unprecedented oxidative pyrrole α‐cleavage by ligand aromatization/dearomatization‐initiated O−O σ‐bond scission. A detailed comparison of the calix[4]pyrrolato aluminates with dioxygen‐related enzymology provides insights into the ISC of metal‐ or cofactor‐free enzymes. It substantiates the importance of structural constraint and element–ligand cooperativity for the functions of aerobic life., The reaction of triplet dioxygen with closed shell molecules is formally spin‐forbidden. Nature overcomes this prohibition by a variety of enzymes. The surprising reactivity of calix[4]pyrrolato aluminate with O2 is described and the spin‐inversion process is analyzed. The square‐planar aluminates transpire as enzyme models that substantiate the critical role of metal–ligand cooperativity and structural constraint for the functions of aerobic life.

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

Fluorescent receptors (4a–4c) based on (thio)ureido-functionalized hexahomotrioxacalix[3]arenes were synthesised and obtained in the partial cone conformation in solution. Naphthyl or pyrenyl fluorogenic units were introduced at the lower rim of the calixarene skeleton via a butyl spacer. The binding of biologically and environmentally relevant anions was studied with NMR, UV–vis absorption, and fluorescence titrations. Fluorescence of the pyrenyl receptor 4c displays both monomer and excimer fluorescence. The thermodynamics of complexation was determined in acetonitrile and was entropy-driven. Computational studies were also performed to bring further insight into the binding process. The data showed that association constants increase with the anion basicity, and AcO−, BzO− and F− were the best bound anions for all receptors. Pyrenylurea 4c is a slightly better receptor than naphthylurea 4a, and both are more efficient than naphthyl thiourea 4b. In addition, ureas 4a and 4c were also tested as ditopic receptors in the recognition of alkylammonium salts.

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.