Search Results (88)

Dacarbazine (DTIC) is a clinically important anticancer drug whose photosensitivity poses challenges for its stability and interactions with supramolecular hosts. Here, we investigate its complexation with the host 1,10-N,N′-bis-(β-D-ureidocellobiosyl)-4,7,13,16-tetraoxa-1,10-diazacyclooctadecane (TN), a hybrid urea–carbohydrate–diazacrown system, using combined experimental and computational approaches. While TN has been studied as a host molecule, its specific interactions with DTIC and the associated thermodynamic characteristics had not been characterized. Computational results (obtained at the density functional theory level (DFT)) indicate that TN primarily forms non-inclusion complexes, with DTIC engaging in hydrogen bonding with sugar units, urea bridges, and diazacrown ether moieties. Experimental ¹H NMR studies in D₂O confirmed these interaction patterns, showing notable chemical shifts for sugar protons. Conductometric measurements between 293 and 313 K allowed for the determination of formation constants and thermodynamic parameters. The results demonstrate that TN:DTIC complexation is spontaneous, exothermic, and enthalpy-driven, accompanied by decreased system entropy. Comparison with previous studies on cyclodextrin complexes shows that TN forms strong associations with DTIC, owing to its abundant donor–acceptor groups, which facilitate extensive hydrogen-bonding networks. These findings provide new insights into DTIC stabilization and highlight TN’s potential as a multifunctional platform for drug delivery. Full article

The escalating crisis of multidrug resistance, together with the persistence of antibiotic residues in clinical and environmental matrices, demands integrated strategies that couple sensitive detection, efficient decontamination, and controlled delivery. However, current techniques for quantifying avibactam (AVI)—a broad-spectrum β-lactamase inhibitor—such as HPLC-UV lack the sensitivity and specificity required for both therapeutic drug monitoring and environmental surveillance. Encapsulation of AVI within cyclodextrins (CDs) may simultaneously enhance its stability, bioavailability, and detectability, while the high binding affinities of CDs position them as molecular traps capable of scavenging residual AVI. In this study, the inclusion complexation of AVI with various CDs was examined through molecular dynamics (MD) simulations, experimental isothermal titration calorimetry (ITC), and non-covalent interaction (NCI) analysis. Stable 1:1 inclusion complexes were observed between AVI and β-cyclodextrin (β-CD), 2,6-dimethyl-β-cyclodextrin (DM-β-CD), and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), with standard Gibbs free energies of binding (ΔG°) of –3.64, –3.24, and –3.11 kcal/mol, respectively. In contrast, γ-cyclodextrin (γ-CD) exhibited significantly weaker binding (ΔG° = –2.25 kcal/mol). DFT-based NCI analysis revealed that cooperative interaction topology and cavity complementarity, rather than the sheer number of localized contacts, govern complex stability. Combined computational and experimental data establish β-CD derivatives as effective supramolecular hosts for AVI, despite an entropic penalty in the DM-β-CD/AVI complex. These CD–AVI affinities support the development of improved analytical methodologies and pharmaceutical formulations, and they also open avenues for decontamination strategies based on molecular trapping of AVI. Full article

In this study, supramolecular inclusion complexes composed of komecosanol (Ko), a lipophilic compound derived from rice bran, and α-cyclodextrin (αCD) were prepared using a solvent-free three-dimensional (3D) ball milling method. Their physicochemical properties were examined using various techniques. Powder X-ray diffraction analysis of the ground mixture at a Ko/αCD ratio of 1/8 revealed the disappearance of diffraction peaks characteristic of Ko and the emergence of new peaks, indicating the formation of a distinct crystalline phase. Moreover, differential scanning calorimetry analysis showed the disappearance of the endothermic peaks corresponding to Ko, indicating molecular-level interactions with αCD. Near-infrared spectroscopy results suggested the formation of hydrogen bonds between the C–H groups of Ko and the O–H groups of αCD. Solid-state ¹³C CP/MAS NMR and T₁ relaxation time measurements indicated the formation of a pseudopolyrotaxane structure, while scanning electron microscopy images confirmed distinct morphological changes consistent with complex formation. These findings demonstrate that 3D ball milling facilitates the formation of Ko/αCD inclusion complexes with a supramolecular architecture, providing a novel approach to improve the formulation and bioavailability of poorly water-soluble lipophilic compounds. Full article

The cationic chloro-P-{[4-(diphenylphosphanyl)phenyl]-N,N-dimethylmethanammonio(norbornadiene)rhodium(I) complex was encapsulated inside a self-assembled hexameric capsule. This capsule was obtained through a reaction involving 2,8,14,20-tetra-undecyl-resorcin[4]arene and water in chloroform. The formation of an inclusion complex was deduced from a combination of spectral measurements (UV-visible spectroscopy, ¹H, ³¹P{¹H} NMR and DOSY). The rhodium complex was evaluated in the [2+2+2] cycloaddition between N,N-dipropargyl-p-toluenesulfonamide and arylacetylene derivatives. In the presence of two equivalents of arylacetylenes in water-saturated chloroform at 60 °C for 24 h, the 4-methyl-N-(prop-2-yn-1-yl)-N-((2-tosylisoindolin-5-yl)methyl)benzenesulfonamide, the homocycloaddition product of 1,6-diyne is predominantly formed. In the presence of the supramolecular capsule, a selectivity inversion in favor of 5-aryl-2-tosylisoindoline is observed, with heterocycloaddition products formed in proportions between 53 and 69%. Full article

Background/Objectives: In order to enhance the biological activity, novel complexes of N-(2-bromo-phenyl)-2-hydroxy-benzamide derivatives and β-cyclodextrin were obtained. Methods: The inclusion complexes were characterized using spectral and thermal analyses. The antimicrobial activity was determined using the disk diffusion agar method, and completed with the minimum inhibitory concentration (MIC) values obtained by the broth microdilution method. The in vitro anti-inflammatory activity was evaluated using the protease inhibition assay. Results: The computed supramolecular architectures of the inclusion complexes showed that the most stable molecular arrangements correspond to the models in which the N-(2-bromo-phenyl)-2-hydroxy-benzamide derivatives are partially included in the cyclodextrin cavity. The antimicrobial screening showed that the compounds were active against Gram-positive bacteria (MIC = 2.5–5.0 mg/mL). Also, the evaluation of the proteinase inhibitory activity showed that the IC₅₀ values of the title compounds (0.04–0.07 mg/mL) were much lower than that of the acetylsalicylic acid (0.4051 ± 0.0026 mg/mL) used as positive control, proving their superior efficiency in inhibiting trypsin activity. Conclusions: The complexation proved to be beneficial for both antimicrobial and anti-inflammatory effects. Full article

Background/Objectives: Increasing the solid-state landscape of an active pharmaceutical ingredient (API) by generating new crystalline forms (e.g., polymorphs, cyclodextrin (CD) inclusion complexes, co-crystals, and salts) can yield products with significantly enhanced biopharmaceutical properties (especially increased water solubility), thereby improving API delivery and extending its lifetime. The aim of this study was the isolation of new solid forms of the poorly water-soluble non-steroidal anti-inflammatory drug fenbufen (FBF), for which relatively few solid phases have been reported to date. Further motivation for the study is the recent finding that it has potential for repurposing to treat acute pancreatitis. Methods: Interventions for generating new solid forms of FBF included (a) polymorph screening with a variety of solvent media, (b) attempts to form solid inclusion complexes with the native cyclodextrins α-, β-, and γ-CD using various preparative methods, and (c) co-crystallization with a series of coformers to produce co-crystals and/or molecular salts. Results: No new polymorphic forms of FBF were identified, but screening with CDs resulted in isolation and characterization of a new solid inclusion complex with γ-CD. However, co-crystallization of FBF with the water-soluble coformer isonicotinamide yielded two new products, namely a 1:1 co-crystal and an unusual multi-component ionic co-crystal, whose aqueous solubility indicated significant enhancement of FBF solubility. Conclusions: Due to its extremely low water solubility, FBF presented challenges during the study aimed at modifying its crystalline form. However, two new supramolecular forms, a co-crystal and an ionic co-crystal, were isolated, the latter phase having potential for further formulation owing to its significantly enhanced solubility. 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

Receptors capable of binding both positive and negative ions are an important domain of supramolecular chemistry with valuable application potential. A Complete thermodynamic description of the equilibria related to ion pair recognition is beneficial in developing the optimized receptor systems, although it represents a difficult task that is rarely resolved due to various coupled processes. Here, we present a comprehensive study of ion pair (NaCl, NaHSO₄, and NaH₂PO₄) binding by a ureido–amide calix[4]arene host in acetonitrile using a series of experimental techniques and molecular dynamics simulations. We devoted particular attention to characterizing the side processes (ion association and salt precipitation) and included them in the models describing ion pair complex formation. For this purpose, a multimethod approach (potentiometry, conductometry, ITC, flame AES) was employed, generating reliable data which provided insight into the thermodynamic effect of each included equilibrium. Positive cooperativity was observed in the context of NaCl and NaHSO₄ binding by the studied calixarene. Computational results related to the NaCl complex in acetonitrile revealed that favorable Coulombic interactions, changes in affinity for solvent molecule inclusion, and intramolecular hydrogen bonding contributed to cation-induced cooperativity. Full article

This study investigated the influence of β-cyclodextrin (βCD) on the micellization behavior of two bile salt surfactants, sodium deoxycholate (NaDC) and sodium cholate (NaC), in aqueous solutions. Tensiometry, conductometric, and spectrofluorimetric techniques were employed to determine critical micelle concentrations (CMCs) in the presence of varying concentrations of βCD, as well as in the presence of inorganic salts (NaCl and CsCl). The results showed that βCD forms inclusion complexes with both bile salts, leading to an increase in their CMCs, consistent with a competitive interaction between micelle formation and complexation. The inclusion constants, determined graphically, revealed stronger complexation for NaDC than NaC, attributed to differences in hydrophobic surface area. Salt addition decreased the CMC of both surfactants, with CsCl having a more pronounced effect. However, salt presence also modulated the inclusion complex formation, suggesting specific ion effects influence the availability and behavior of βCD. These findings contribute to the understanding of bile salt–cyclodextrin interactions and their modulation by electrolytes, with implications for drug delivery and supramolecular chemistry. Full article

We demonstrate a rapid and sensitive boron detection method through current amplification mediated by supramolecular interaction. Oxidation peak currents obtained by cyclic voltammetry (CV) measurements of a ferrocene/catechol-functionalized β-cyclodextrin inclusion complex were amplified through an EC’ reaction (where EC’ denotes an electrochemical step followed by a catalytic chemical step). However, the amplified current was decreased by boric acid (the primary form of boron in water) addition at pH 8.6 owing to interactions of boron with the cis-diol structure of dihydroxybenzoic acid-β-cyclodextrin and ferrocene for ester formation. We determined the optimum CyD functionalization sites and measurement conditions and obtained a limit of detection of 0.16 mg B L⁻¹ for ferrocene/3,4-dihydroxybenzoic acid-β-cyclodextrin (Fc/3,4-DHBA-β-CyD). The binding constant (assuming a 1:1 binding model) for the interaction between Fc/3,4-DHBA-β-CyD and boric acid was estimated to be approximately 1500 M⁻¹. Boron concentrations in spiked real samples showed good recoveries and linear calibration curves. The electrochemical response of this system was not significantly affected by the presence of other anions or cations. We also found that an aqueous solution of 3,4-DHBA-β-CyD remained stable for at least 112 days. Full article

The discovery of efficient and stable nanopesticides with improved water solubility and sustained release effects has become particularly important. Pyrimethanil (Pyr) as a low toxicity fungicide of an aniline pyrimidine group is widely used for the prevention and control of gray mold in crops and ornamental plants, however, poor water solubility hinders its further development. Herein, we use a supramolecular self-assembly process to encapsulate a pyrimethanil in a hydroxypropyl-gamma-cyclodextrin (HPγCD) via electrostatic interactions, thereby constructing the inclusion complex nanofibers. The HPγCD as an environmentally friendly carrier material for pesticide delivery is favorable for facilitating the control efficacy, water solubility, and thermostability with Pyr. The diameter of the prepared inclusion nanofiber is 426.6 ± 82.1 nm. Pyr/HPγCD inclusion complex nanofibers could be completely dissolved in water within 3 s. As predicted, the fungicidal activity of Pyr/HPγCD inclusion complex nanofibers is much higher than that of either Pyr, and the EC₅₀ value of Pyr/HPγCD inclusion nanofibers is 0.437 μg/mL, which is about half of that of Pyr (0.840 μg/mL). The inclusion strategy achieved by Pyr and HPγCD is important for improving the safety of nanopesticides. This work provides a versatile insight to promote the development of water-based pesticide dosage forms and reduce pesticide losses in agricultural production. Full article

In this present study, we developed and characterized a series of supramolecular G4 hydrogels by integrating β-cyclodextrin (β-CD) and boronic acid linkers into a supramolecular matrix to enhance antibacterial activity against Staphylococcus aureus (S. aureus). We systematically investigated how varying the number of free boronic acid moieties (ranging from two to six), along with guanosine and β-CD content, influences both the structural integrity and antimicrobial efficacy of these materials. Comprehensive characterization using FTIR, circular dichroism, X-ray diffraction, SEM, AFM, and rheological measurements confirmed successful synthesis and revealed that higher boronic acid content correlated with a stronger, more organized network. The most effective hydrogel displayed an inhibition zone of 25 mm in disk diffusion assays, and was further explored as a drug delivery platform, with the aim to exploit the capacity of the free β-CD cavity of the hydrogels to incorporate hydrophobic drugs. Norfloxacin (Nfx), a poorly water-soluble antibiotic, was successfully encapsulated within the hydrogel matrix through the inclusion of complex formation with β-CD, improving its solubility and enabling sustained, targeted release. The Nfx-loaded hydrogel expanded the inhibition zone to 49 mm and completely eradicated S. aureus cells within 24 h, outperforming both the unloaded hydrogel and free Nfx. These results highlight the synergistic effect of boronic acid moieties and controlled drug release, underlining the potential of these hydrogels as versatile platforms for localized antimicrobial therapy, such as in wound dressings or implant coatings. Nevertheless, further in vivo studies and long-term stability assessments are needed to fully establish clinical relevance, safety, and scalability before these systems can be translated into routine healthcare applications. Full article

Cisplatin (DDP), a platinum-chelated compound renowned for its antitumor activity, is often utilized in cancer therapy. However, its real-world clinical efficacy is compromised by poor solubility and low stability, which impedes wider clinical application. Our study aimed to address these limitations of DDP through host–guest supramolecular chemistry approaches. We explored the potential of 18-crown-6 as the host molecule to solubilize and stabilize DDP, the guest molecule. Utilizing techniques such as UV–visible spectroscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, and molecular docking, we conducted a comprehensive analysis on the physical state and inclusion mode of the DDP@18-crown-6 complex. Phase solubility studies and Job’s plot confirmed that the DDP@18-crown-6 complex significantly enhanced the aqueous solubility of DDP, with an optimal 1:1 binding ratio. Stability analyses revealed that this complex markedly improved the stability of DDP in pure water. Meanwhile, the stabilization effects of DDP@18-crown-6 were remarkably elevated when combined with 0.9% sodium chloride. In vitro antitumor assays in A549 cell lines demonstrated that the DDP@18-crown-6 complex outperformed raw DDP in cytotoxicity, showing a significantly lower IC₅₀ value. This research offered a promising strategy for DDP solubilization and stabilization, facilitating its anticancer therapeutic efficacy. Full article

Background/Objectives: Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery results is a powerful tool to control Dox release only in cancer cells. For this reason, supramolecular self-assembly was performed between a poly(amidoamine) (PAMAM) dendrimer decorated with four β-cyclodextrin (βCD) units (PAMAM-βCD) and an adamantane–hydrazone–doxorubicin (Ad-h-Dox) prodrug. Methods: The formation of inclusion complexes (ICs) between the prodrug and all the βCD cavities present on the surface of the PAMAM-βCD dendrimer was followed by ¹H-NMR titration and corroborated by 2D NOESY experiments. A full characterization of the supramolecular assembly was performed in the solid state by thermal analysis (DSC/TGA) and scanning electron microscopy (SEM) and in solution by the DOSY NMR technique in D₂O. Furthermore, the Dox release profiles from the PAMAM-βCD/Ad-h-Dox assembly at different pH values was studied by comparing the efficiency against a native βCD/Ad-h-Dox IC. Additionally, in vitro cytotoxic activity assays were performed for the nanocarrier alone and the two supramolecular assemblies in different carcinogenic cell lines. Results: The PAMAM-βCD/Ad-h-Dox assembly was adequately characterized, and the cytotoxic activity results demonstrate that the nanocarrier alone and its hydrolysis product are innocuous compared to the PAMAM-βCD/Ad-h-Dox nanocarrier that showed cytotoxicity equivalent to free Dox in the tested cancer cell lines. The in vitro drug release assays for the PAMAM-βCD/Ad-h-Dox system showed an acidic pH-dependent behavior and a prolonged profile of up to more than 72 h. Conclusions: The design of PAMAM-βCD/Ad-h-Dox consists of a new controlled and prolonged Dox release system for potential use in cancer treatment. Full article

Cyclodextrins (CDs) have garnered significant attention in various scientific and industrial fields due to their unique ability to form inclusion complexes with a wide range of guest molecules. This review comprehensively explores the latest advancements in cyclodextrin chemistry, focusing on the synthesis and characterization of cyclodextrin derivatives and their inclusion complexes. This review examines the biological activities of cyclodextrins, highlighting their pharmacological properties and pharmacokinetics, and discussing their promising applications in drug delivery systems. Furthermore, the industrial utilization of cyclodextrins, including their role in nanomaterials and nanostructured coatings, as well as their potential in environmental remediation, are explored. The present research also addresses the critical aspect of toxicity, particularly concerning cyclodextrin inclusion complexes, providing an overview of the current understanding and safety considerations. Through a multidisciplinary approach, the aim is to present a complete view of cyclodextrins, underscoring their versatility and impact across various domains. Full article