Search Results (46)

The state of the art in the thermodynamics of calix[4]resorcinarene derivatives and its metal ion complexes is briefly discussed in the introduction. This is followed by the synthesis and characterization of a recyclable calix[4]resorcinarene amide derivative (L). The 1H NMR analyses in CD3CN and CD3OD showed solvent-dependent conformational changes with a notable downfield chemical shift in the aromatic proton (H-2) in moving from deuterated methanol to acetonitrile, indicating an interaction of the solvent within the ligand cavity as suggested by molecular dynamic simulations. 1H NMR complexation in acetonitrile revealed that L forms relatively strong 1:1 complexes with cations, with selectivity for Ca(II) and, to lesser extent, with Pb(II) over other metal cations. The composition of the complexes is corroborated by conductance measurements. The thermodynamics of these systems indicate that the complexation process is predominantly enthalpy controlled in acetonitrile, while it is entropy controlled in methanol. A remarkable outcome of fundamental studies is found in its application as new material for the removal of Ca(II) from water. The capacity of L to remove Ca(II) from water is 24 mmol/g which exceeds by far the capacity of cation exchange resins. Full article

In this study, a series of novel alkoxylated resorcinarenes were synthesized using secondary and tertiary alcohols under mild catalytic conditions involving iminodiacetic acid. Structural characterization, including single-crystal X-ray diffraction, confirmed the successful incorporation of branched alkyl chains and highlighted the influence of substitution patterns on molecular packing. Notably, detailed mass spectrometric analysis revealed that, under specific conditions, the reaction pathway may shift toward the formation of defined oligomeric species with supramolecular characteristics—an observation that adds a new dimension to the synthetic potential of this system. To complement the chemical analysis, selected derivatives were evaluated for biological activity, focusing on bacterial growth and biofilm formation. Using four clinically relevant strains (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis), we assessed both planktonic proliferation (OD₆₀₀) and biofilm biomass (crystal violet assay). Compound 2c (2-pentanol derivative) consistently promoted biofilm formation, particularly in S. aureus and B. subtilis, while having limited cytotoxic effects. In contrast, compound 2e and the DMSO control exhibited minimal impact on biofilm development. The results suggest that specific structural features of the alkoxy chains may modulate microbial responses, potentially via membrane stress or quorum sensing interference. This work highlights the dual relevance of alkoxylated resorcinarenes as both supramolecular building blocks and modulators of microbial behavior. Full article

The dichromate ion (Cr₂O₇²⁻), a highly toxic chromium VI species, is widely used in industrial processes, generating serious environmental problems when released into water bodies. This investigation proposes the use of a functionalized polymer as an adsorbent material for its removal in the aqueous phase. Poly(butyl methacrylate) (PBMA) was synthesized and modified by impregnation with resorcinarenes derived from long-chain aliphatic aldehydes. To improve the affinity for the dichromate, the resorcinarenes were functionalized with sulfomethyl groups by treatment with Na₂SO₃. The resulting matrices were characterized using IR-ATR, ¹H-NMR, and ¹³C-NMR, and their adsorbent performance was evaluated via UV-Vis spectroscopy in batch extraction assays. The results showed that the functionalized polymer exhibited a higher adsorption capacity than the base polymer, reaching up to 81.1% removal at pH 5.0 in one hour. These results highlight the potential of PBMA as an effective support and raise a promising research perspective for functionalized resorcinarenes in the development of new materials for the treatment of contaminated water. Full article

This review highlights how advances in silico techniques have shed new light on phenomena in confined supramolecular resorcinarene-based systems. Computational studies have provided detailed insights into capsule formation, their dynamic behavior, guest encapsulation and reaction mechanisms within these hosts, often revealing information that experimental methods cannot reach. The focus is placed on the self-assembly of resorcin[4]arenes, pyrogallol[4]arenes, velcrands, and octa acid systems. These computational studies complement experimental findings and, in many cases, offer new perspectives that are inaccessible using experimental techniques alone. Supramolecular architectures are growing in complexity the role of in silico approaches is becoming indispensable. They offer a way to design rationally and understand host–guest chemistry more deeply. Full article

Resorcinarenes are polyhydroxylated platforms consisting of 4, 5, 8, or more units of resorcinol. The numbers refer to the number of resorcinol units, with 4-unit platforms being the most stable. Investigation into their use in pharmaceutical applications has increased due to high versatility and functionalization. They exhibit significant flexibility due to their methylene bridges and to the interactions of hydrogen bridges and van der Waals forces. These platforms can be used in an increasing number of applications, which include the functionalization of nanoparticles and relevant materials, the synthesis of catalysts, the removal of contaminants, and analytical separations in analytes such as benzodiazepines and norepinephrine. For this last application, resorcinarenes are functionalized with specific important functional groups. Polymers were developed in the 20th century for the development of materials with significant improvements in thermal and mechanical properties. They are cross-linked polymeric structures, mainly made up of monomers such as styrene, divinylbenzene acrylate, vinylpyridine, and vinyl acetate, among others. They often have a homogeneous, porous structure, but this structure can vary significantly depending on the type of solvent used. Therefore, they have been applied in the functionalization of the polyhydroxylated platforms. In this review, the structure, properties, and synthesis of resorcinarenes, as well as the use of polymeric matrices, are analyzed, emphasizing the functionalization of organic polymers using resorcinarenes. Furthermore, the respective applications in controlled drug delivery, pharmaceutical transport, and therapeutics, which are diverse and show promising growth, will be explored. Full article

Calix[4]resorcinarenes are polyhydroxylated macrocyclic compounds with four units of resorcinol. These compounds can be derivatized through modifications at the upper rim, allowing reactivity with secondary amines to produce Mannich base derivatives via Mannich-type aminomethylation reactions. In this paper, we report the reaction of C-tetra(propyl)calix[4]resorcinarene with piperidine in acetonitrile. The aminomethylated compound C-2,8,14,20-tetra(propyl)-5,11,17,23-tetrakis(N–(piperidine)methyl)calix[4]resorcinarene was obtained with a 52% yield, with an exact mass of 1044.6994 u and a mass error of 7.6 ppm. The reaction progress and product formation were monitored by RP-HPLC, and the compound was characterized using LC ESI-TOF/MS, one- and two-dimensional ¹H and ¹³C NMR, and FTIR spectroscopy. Chromatographic and spectroscopy data are presented and discussed. Full article

The molecular interactions of water-soluble crown resorcinarenes with choline were analyzed. To this end, four sulfonated resorcinarenes were synthesized and characterized by ATR-IR, ¹H-NMR, and ¹³C-NMR spectroscopy. The molecular interaction studies with choline were carried out through FT-IR spectroscopy, ¹H-NMR titrations, and conductimetric titrations, with which it was possible to determine that the complexes formed 1:1 stoichiometries with the host, in addition to showing good interaction in the electronic cavity of the macrocycle, demonstrating great potential for host–guest systems for choline detection in aqueous media. Finally, the incidence of the structural aspects of sulfonated resorcinarenes were analyzed. Full article

The separation and purification of molecular compounds and their functionalized derivatives is a common challenge in organic synthesis. In particular, calix[4]resorcinarenes present a high potential for chemical derivatization at their upper edge by aminomethylation reactions, and these compounds and their derivatives require appropriate analytical methodologies for their analysis, separation, and purification. In this study, C-tetra(propyl)calix[4]resorcinarene was synthesized and functionalized with maleimide groups by optimized aminomethylation reactions, obtaining a mixture of mono-, di-, tri-, and tetrasubstituted compounds. Initial separation by RP-HPLC with a core-shell column showed poorly resolved peaks, indicating a loss of separation efficiency. Therefore, a monolithic C18 column was used, which significantly improved the separation, thanks to its larger pore volume and continuous structure facilitating the diffusion of these bulky molecules, notably improving efficiency. Finally, the six compounds functionalized with maleimide groups were efficiently separated and enriched by RP-SPE by analytical method transfer, and the two peptides of six and the thirteen residues derived from LfcinB (20–25): RRWQWR were synthesized by SPPS-Fmoc/tBu and purified. These were modularly linked by the Michael thiol-maleimide addition reaction obtaining six (peptide)_n-resorcinarene conjugates. The analytical method by RP-HPLC with a monolithic C18 column, the separation and purification by RP-SPE were used transversally in all the steps to obtain compounds with adequate purities and quantities. Finally, the antibacterial activities of the six conjugates were evaluated against E. coli and E. faecalis strains, and it was determined that three aminomethylated compounds and one monosubstituted conjugate showed activity against E. faecalis. Our work established a new modular conjugation strategy between calix[4]resorcinarenes and peptides by thiol-maleimide click chemistry, and a methodology of separation, purification, and enrichment for these products by RP-HPLC and RP-SPE, which permitted us to obtain quantities with purities appropriate for their characterization by NMR, LC-MS and antibacterial activity assays. Full article

The advancement of synthetic host–guest chemistry has played a pivotal role in exploring and quantifying weak non-covalent interactions, unraveling the intricacies of molecular recognition in both chemical and biological systems. Macrocycles, particularly calix[4]resorcinarene-based cavitands, have demonstrated significant utility in receptor design, facilitating the creation of intricately organized architectures. Within the realm of macrocycles, these cavitands stand out as privileged scaffolds owing to their synthetic adaptability, excellent topological structures, and unique recognition properties. So far, extensive investigations have been conducted on various applications of calix[4]resorcinarene-based cavitands. In this review, we will elaborate on their diverse functions, including catalysis, separation and purification, polymeric materials, sensing, battery materials, as well as drug delivery. This review aims to provide a holistic understanding of the multifaceted roles of calix[4]resorcinarene-based cavitands across various applications, shedding light on their contributions to advancing the field of supramolecular chemistry. Full article

Ladder oligomers containing calixarene skeletons in the main chain—calix[4]resorcinarene (CRA) ladder macromolecules with open chain and cyclic macromolecules with double ring-like (Noria-type) topologies—bring particular research attention as functional materials with various applications. However, there is still a remarkable lack of studies into the synthesis of fully water-soluble derivatives of these interesting macromolecules. Research on this topic would allow their bio-based research and application niche to be at least revealed. In the present study, a strategy for the synthesis of water-soluble polyglycidol-derivatized calix resorcinarene ladder oligomers with open chain and cyclic structures is introduced. A grafting from approach was used to build branched or linear polyglycidol chains from the ladder scaffolds. The novel structures were synthesized in quantitative yields and fully characterized by NMR, FTIR and UV–vis spectroscopy, gel permeation chromatography, MALDI-TOF mass spectrometry, analytical ultracentrifugation, and static light scattering to obtain the molar mass characteristics and composition. The biocompatibility and toxicity of the two polyglycidol-derivatized oligomers were investigated and the concentration dependence of the survival of three cell lines of human origin determined. The selective apoptosis effect at relatively low dissolve concentrations toward two kinds of cancerous cell lines was found. Full article

C-tetra(4-methoxyphenyl)calix[4]resorcinarene was synthesized by hydrochloric acid-catalysed cyclocondensation of resorcinol and 4-methoxybenzaldehyde. Under these conditions, the reaction produces a conformational mixture of crown and chair structural conformers, which were separated and characterized by chromatographic and spectroscopic techniques. The antioxidant activity of both conformers was measured by using the DPPH assay, through which it was observed that the chair conformer showed greater antioxidant activity (IC₅₀ = 47.46 ppm) than the crown conformer (IC₅₀ = 78.46 ppm). Additionally, it was observed that the mixture of both conformers presented lower antioxidant activity than either conformer in isolation. The results found suggest that the chair conformer has efficient antioxidant activity that makes it a potential target for further research. Full article

In this study, a composite film was developed for the electrochemical sensing of tryptophan (Trp). Porous reduced graphene oxide (PrGO) was utilized as the electron transfer layer, and a C-undecylcalix[4]resorcinarene Langmuir–Blodgett (CUCR-LB) film served as the molecular recognition layer. Atomic force microscopy (AFM), transmission electron microscopy (TEM), Raman spectroscopy, scanning electron microscopy (SEM), and electrochemical experiments were employed to analyze the characteristics of the CUCR-LB/PrGO composite film. The electrochemical behavior of Trp on the CUCR-LB/PrGO composite film was investigated, revealing a Trp linear response range of 1.0 × 10⁻⁷ to 3.0 × 10⁻⁵ mol L⁻¹ and a detection limit of 3.0 × 10⁻⁸ mol L⁻¹. Furthermore, the developed electroanalytical method successfully determined Trp content in an amino acid injection sample. This study not only introduces a rapid and reliable electrochemical method for the determination of Trp but also presents a new strategy for constructing high-performance electrochemical sensing platforms. Full article

We present five new sorbents for the evaluation of the pre-concentration of L-carnitine. The sorbents were obtained from copolymerization between butylmethacrylate (BuMA) and ethylene dimethacrylate (EDMA), which were physically modified on their surface by each one of the five synthetized resorcinarenes of variable chain length studied, with long-chain resorcinarenes exhibiting better fixation on the copolymer. The characterization of the synthesized resorcinarenes was done using FTIR-ATR, ¹H NMR, ¹³C NMR, and mass spectrometry, while characterization of the sorbents was done using FTIR-ATR and scanning electron micrography (SEM). The molecular interaction between L-carnitine and the synthesized resorcinarenes was studied in DMSO via ¹H-NMR spectroscopy and, in the gas phase, via electrospray ionization-mass spectrometry (ESI-MS). The results showed that the short-chain resorcinarenes underwent a stable interaction with the neurotransmitter. Once the sorption of resorcinarenes on the copolymer was accomplished, the best parameters for the evaluation of the L-carnitine preconcentration were established. The solution tests were carried out through LC/MS analysis, obtaining better results for L-carnitine absorption with the short-chain resorcinarenes such as tetra(ethyl)calix[4]resorcinarene and tetra(propyl)calix[4]resorcinarene. Full article

Supramolecular self-assembly is a powerful tool for the development of polymolecular assemblies that can form the basis of useful nanomaterials. Given the increasing popularity of RNA therapy, the extension of this concept of self-assembly to RNA is limited. Herein, a simple method for the creation of nanosized particles through the supramolecular self-assembly of RNA with a three-dimensional macrocycle from the calixarene family was reported for the first time. This self-assembly into nanoparticles was realized using cooperative supramolecular interactions under mild conditions. The obtained nanoparticles are able to bind various hydrophobic (quercetin, oleic acid) and hydrophilic (doxorubicin) drugs, as a result of which their cytotoxic properties are enhanced. This work demonstrates that intermolecular interactions between flexible RNA and rigid calixarene is a promising route to bottom-up assembly of novel supramolecular soft matter, expanding the design possibilities of nanoscale drug carriers. Full article

Antimicrobial resistance (AMR) is one of the top ten threats to public health, as reported by the World Health Organization (WHO). One of the causes of the growing AMR problem is the lack of new therapies and/or treatment agents; consequently, many infectious diseases could become uncontrollable. The need to discover new antimicrobial agents that are alternatives to the existing ones and that allow mitigating this problem has increased, due to the rapid and global expansion of AMR. Within this context, both antimicrobial peptides (AMPs) and cyclic macromolecules, such as resorcinarenes, have been proposed as alternatives to combat AMR. Resorcinarenes present multiple copies of antibacterial compounds in their structure. These conjugate molecules have exhibited antifungal and antibacterial properties and have also been used in anti-inflammatory, antineoplastic, and cardiovascular therapies, as well as being useful in drug and gene delivery systems. In this study, it was proposed to obtain conjugates that contain four copies of AMP sequences over a resorcinarene core. Specifically, obtaining (peptide)₄-resorcinarene conjugates derived from LfcinB (20–25): RRWQWR and BF (32–34): RLLR was explored. First, the synthesis routes that allowed obtaining: (a) alkynyl-resorcinarenes and (b) peptides functionalized with the azide group were established. These precursors were used to generate (c) (peptide)₄-resorcinarene conjugates by azide-alkyne cycloaddition CuAAC, a kind of click chemistry. Finally, the conjugates’ biological activity was evaluated: antimicrobial activity against reference strains and clinical isolates of bacteria and fungi, and the cytotoxic activity over erythrocytes, fibroblast, MCF-7, and HeLa cell lines. Our results allowed establishing a new synthetic route, based on click chemistry, for obtaining macromolecules derived from resorcinarenes functionalized with peptides. Moreover, it was possible to identify promising antimicrobial chimeric molecules that may lead to advances in the development of new therapeutic agents. Full article