Search Results (396)

Two metallacyclic tetranuclear Fe(III) complexes, [{Fe₂(μ-O)(μ-RCOO)₂(tpon)}₂](BPh₄)₄ [R = Me (1), Ph (2)], where the flexible ditopic ligand tpon (N,N,N′,N′-tetrakis(2-pyridylmethyl)octane-1,8-diamine) links two μ-oxo-bis(μ-carboxylato) triple-bridged dinuclear units, have been prepared. Single-crystal X-ray diffraction establishes that both complexes adopt a 26-membered macrocyclic framework featuring an internal cavity capable of guest inclusion. Notably, incorporation of a monoatomic μ-oxo bridge enforces an outward orientation of the ligand alkyl chains, thereby suppressing the “zipper effect” observed in the previously reported Mn(II) analogue and facilitating the encapsulation of an acetone molecule. UV–vis absorption and diffuse-reflectance spectra confirm that the tetranuclear scaffold remains intact in both the solid state and in solution. These results demonstrate that modulating local coordination directionality via μ-oxo bridging is an effective strategy for controlling the global conformation and host–guest properties of large metallasupramolecular architectures. Full article

Ionotropic alginate-based hydrogelation by divalent metal interaction has been employed to study the effect that different types of ions might have on gel formation. In this regard, EPR and IR spectroscopies, as well as rheology techniques, have been used to evaluate the influence of divalent cations on gel formation, and at the same time to assess host–guest interactions. Alginate was functionalized with TEMPO moieties; therefore, TEMPO-alginate system was taken as a reference. The novelty of this study consists of using a mixture of adamantyl-TEMPO-functionalized alginate and β-cyclodextrin linked through 1,3-diaminopropane to assess the host–guest interactions in functionalized gels. The properties of divalent cations considered in this study (Ba²⁺, Ca²⁺, Sr²⁺, Zn²⁺) were proven by changes in spectral parameters of paramagnetic moieties, while the viscoelastic moduli as functions of shear strain and frequency were evaluated through rheology measurements. Overall, the information obtained from these investigations has shown that the properties of the alginate gels are influenced both by the type of divalent cation used for complexation and by the host–guest interactions. The results show that the type of the cation significantly affects gel strength; therefore, Ba²⁺ forms the strongest gel, while Zn²⁺ the least resistant. Additionally, a high immobilization of the spin-labeled probes has been obtained by the addition of tosylated β-cyclodextrin in the alginate gel network containing Ba²⁺ ions. Full article

Allyl isothiocyanate (AITC) is a potent natural antimicrobial agent; however, its practical application is severely hindered by its extreme volatility and pungent, irritating odor. In this study, AITC inclusion complexes (AITC@β-CD) were successfully fabricated via a co-precipitation strategy using β-cyclodextrin (β-CD) as the host matrix. Physicochemical characterizations, including FTIR, SEM, and XRD, confirmed the successful integration of AITC into the β-CD framework, inducing a crystalline phase transition from a cage-type to a channel-type structure. TGA demonstrated a substantial enhancement in thermal stability, with the maximum decomposition temperature shifting to 330 °C. This indicates that the spatial confinement within the channel-type lattice acts as a robust molecular shield that minimizes premature volatilization. Notably, water contact angle measurements revealed that the complexes attained a modulated surface wettability (89.0°), attributed to the structural rearrangement of surface hydroxyl groups. This modification ensures that the material remains compatible with aqueous food matrices while notably masking the unpleasant sensory attributes of pure AITC. Antibacterial assays against the standard indicator strain Escherichia coli (E. coli) confirmed that the encapsulation process preserved the intrinsic bioactivity of the guest, exhibiting comparable inhibitory zones to free AITC. Furthermore, the complexes maintained high inhibitory efficacy against indigenous microbial populations from spoiled fruits. These findings suggest that β-CD encapsulation effectively stabilizes AITC through guest-induced co-crystallization and enhances its consumer acceptability, providing a versatile and efficient strategy for sustainable food preservation. Full article

Conventional electrochemical mechanisms for electrical energy storage face fundamental limitations in achieving ultra-high energy density and high-power output. These constraints arise from the intrinsic nature of the electrochemical processes themselves. Overcoming this challenge requires a paradigm shift—from electrochemical to quantum mechanisms of energy storage. As shown by theoretical models, this concept can be implemented in nanostructured materials consisting of clusters with tunnel-transparent shells. It is possible to build such a structure using supramolecular complexes and clathrate organization of matter. For this purpose, we synthesized a supramolecular clathrate with a hierarchical sub-host<host<guest>> architecture and investigated its conductive and polarization properties using impedance spectroscopy. As shown by the results of the research, in this structure it was possible to combine a high value of the dielectric permittivity with a dielectric loss tangent below unity in the ultra-low-frequency range. This was facilitated by the presumably specific energy structure of the clathrate, as evidenced by the measured spectra of thermally stimulated discharge currents. The ability of the clathrate to accumulate an electric charge is evidenced by the measured hysteresis current-voltage characteristic. The value of the specific capacitance of this clathrate reaches the value that arises from the theoretical model of a quantum supercapacitor. Full article

The functionalization of molecules on C₆₀ is a promising engineering approach, as non-covalently governed fullerene surfaces facilitate reversible host–guest recognition, tunable electronic communication, and conformationally adaptive molecular adsorption. In this work, spin-resolved simulations using density functional theory (DFT) were conducted to examine the interaction between a newly identified arylalkanone isolated from the medicinal species Myristica ceylanica and the nanocarbon framework of C₆₀ fullerene, including doped configurations incorporating group III elements (B, Al, Ga, In and Tl). The results indicate that the arylalkanone binds to pristine C₆₀ through an exothermic, energetically favourable binding process, supporting thermodynamically viable molecular uptake. Among the doped models, B substitution exhibits the greatest overall thermodynamic preference; however, Al doping produces the most pronounced enhancement in binding energy, identifying the Al-doped configuration as the most effective surface-uptake architecture in relative terms. Across all complexes, a small amount of charge transfer is noted, signifying weak yet persistent electronic coupling between the ligand and the carbon carrier. Additionally, all doped fullerenes demonstrate induced magnetic behaviour, a property of increasing relevance in spintronics research, suggesting that these complexes may hold future value in spin-dependent electronic and molecular-recognition-guided nanoscale biomedical engineering. Full article

The widespread occurrence of pharmaceutical residues in aquatic environments necessitates the development of advanced porous materials for efficient remediation. This study investigates the adsorption mechanisms of ibuprofen and atenolol within the high-silica zeolite Y. Batch adsorption experiments demonstrated significant uptake, with loading capacities of 191.6 mg/g for ibuprofen and 273.0 mg/g for atenolol, confirming the material’s effectiveness. Using a combination of neutron and X-ray powder diffraction, complemented by Rietveld refinement and simulated annealing algorithms, we achieved the exact localization of the guest molecules. While the pristine zeolite maintains cubic symmetry $Fd\overline{3}$, the incorporation of pharmaceutical molecules induces significant residual nuclear density and anisotropic lattice distortions. To accurately model these perturbations, a systematic symmetry reduction to the acentric triclinic space group F1 was implemented. This approach enabled an ab initio refinement of the structure, revealing that drug uptake of each guest is governed by distinct chemical drivers. Ibuprofen is stabilized via steric confinement and long-range dispersive interactions. In contrast, atenolol stability is governed by electrostatic charge compensation within the zeolitic voids. Our results suggest that the final adsorption geometry is dictated by the spatial orientation of functional groups and host–guest proximity rather than molecular chirality. These results provide a microscopic model describing the fundamental host–guest interactions in FAU zeolites. This structural understanding is an essential step towards the potential use of zeolitic materials in environmental remediation and complex guest sequestration. Full article

The principal challenge in the development of efficient porphyrin-based photosensitizers is the intrinsic aggregation-induced quenching effect, which significantly impairs the generation efficiency of singlet oxygen (¹O₂) in photodynamic therapy (PDT). This study addresses this limitation through a supramolecular approach grounded in host-guest chemistry. Partially methyl-substituted cucurbit[6]uril (HMeQ[6]) was selected as the macrocyclic host owing to its smaller portal size and larger outer diameter, features that facilitate both strong binding affinity and effective spatial isolation. A porphyrin derivative functionalized with two cationic arms (DPPY) was designed and synthesized as the guest molecule. The results derived from ¹H NMR titration and UV spectroscopy analyses demonstrate that, in aqueous solution, these components self-assemble via host-guest interactions to form a 2:1 stoichiometric supramolecular complex (DPPY@HMeQ[6]) with a binding constant of 2.11 × 10⁵ M⁻¹. TEM, AFM, and DLS analyses indicate that this complex further assembles into nanosheet structures with dimensions of approximately 100 nm. Spectroscopic analyses reveal that encapsulation by HMeQ[6] effectively inhibits π-π stacking aggregation of DPPY molecules, resulting in an approximate threefold increase in fluorescence intensity and an extension of fluorescence lifetime from 3.2 ns to 6.2 ns. Relative to free DPPY, the complex demonstrates a sixfold enhancement in ¹O₂ generation efficiency. Subsequently, 4T1 cells, derived from mouse triple-negative breast tumors, were selected as the experimental model. These cells exhibit high invasiveness and metastatic potential, thereby effectively recapitulating the pathological progression of human triple-negative breast cancer. In vitro cellular assays indicate efficient internalization of the complex by 4T1 cells, inducing a concentration-dependent increase in reactive oxygen species (ROS) and oxidative stress following light irradiation. The in vitro cytotoxicity of the supramolecular photosensitizer was assessed employing the CCK-8 assay and flow cytometry techniques. The half-maximal inhibitory concentration (IC₅₀) against cancer cells is 1.8 μM, with apoptosis rates reaching up to 65.3%, while exhibiting minimal dark toxicity. This study expands the potential applications of methyl-substituted cucurbiturils within functional supramolecular assemblies and proposes a viable approach for the development of efficient and activatable supramolecular photosensitizers. Full article

In this study, we review the use of cyclodextrin-based formulations to develop oral tablets of cladribine by enhancing its bioavailability and to improve the solubility and stability of retrometabolic chemical delivery systems (CDSs) in general and estredox, a brain-targeting estradiol-CDS, in particular. Cyclodextrins (CDs), cyclic oligosaccharides that can form host–guest inclusion complexes with a variety of molecules, are widely utilized in pharmaceuticals to increase drug solubility, stability, bioavailability, etc. The stability of the complex depends on how well the guest fits within the cavity of the CD host; a model connecting this to the size of the guest molecules is briefly discussed. Modified CDs, and particularly 2-hydroxypropyl-β-cyclodextrin (HPβCD), provided dramatically increased water solubility and oxidative stability for estredox (estradiol-CDS, E₂-CDS), making its clinical development possible and highlighting the potential of our brain-targeted CDS approach for CNS-targeted delivery with minimal peripheral exposure. A unique HPβCD-based formulation also provided an innovative solution for the development of orally administrable cladribine. The corresponding complex dual CD-complex formed by an amorphous admixture of inclusion- and non-inclusion cladribine–HPβCD complexes led to the development of tablets that provide adequate oral bioavailability for cladribine, as demonstrated in both preclinical and clinical studies. Cladribine–HPβCD tablets (Mavenclad) offer a convenient, effective, and well-tolerated oral therapy for multiple sclerosis, achieving worldwide approval and significant clinical success. Overall, the developments summarized here underscore the importance of tailored cyclodextrin-based approaches for overcoming barriers in drug formulation for compounds with challenging physicochemical properties, and demonstrate the versatility and clinical impact of CD inclusion complexes in modern pharmaceutical development. Full article

This study reports measurements of density, viscosity, and ternary mutual diffusion coefficients (D₁₁, D₁₂, D₂₁, D₂₂) for aqueous solutions containing two antibiotics—sulfamethoxazole (SMX) or trimethoprim (TMP) (component 1)—in the presence of various cyclodextrins (α–CD, β–CD, and γ–CD) (component 2) at 298.15 K. The relative viscosity data were analyzed by fitting to a second-order Jones-Dole equation via a least-squares regression to obtain the viscosity B coefficients. Apparent molar volumes (V_ϕ) were derived from the measured densities (ρ) for SMX and TMP in aqueous media. Furthermore, partial molar volumes of transfer at infinite dilution, ΔV_ϕ⁰, were evaluated to elucidate solute–solvent interactions within the ternary systems investigated. Nonzero ΔV_ϕ⁰ values, positive viscosity B coefficients, and negative cross-diffusion coefficients (D₁₂ and D₂₁), evidencing significant coupled diffusion, collectively indicate strong interactions between the antibiotics and cyclodextrins, consistent with host–guest complex formation. Full article

Background/Objectives: Lipid nanoparticles (LNPs) have demonstrated notable clinical success as advanced drug delivery systems. However, the development of novel covalently bonded ionizable lipids faces substantial technical challenges, as their modification is difficult and they have a high molecular weight. To address this issue, we report the use of host–guest complexes in supramolecular chemistry as functional lipid motifs for constructing LNPs. Methods: Ionizable amine β-cyclodextrin (amine β-CD)-derived host–guest amphiphilic lipid molecules (HGLs) were designed for the construction of multi-stage assembly supramolecular LNPs (MSLNPs). The structure–function relationships and stability of MSLNPs were explored by screening eight types of amine β-CDs and varying the ratio of HGL to yolk phosphatidylcholine. Stability screening and molecular dynamics simulations were performed to clarify the self-assembly mechanisms and optimal formulations, followed by a systematic evaluation of delivery performance. Results: MSLNPs showed a high drug-loading efficiency (> 30%), a rapid-response release in acidic environments, and multi-pathway cellular uptake. In vivo delivery experiments using ethylenediamine β-CD-based MSLNPs in mice revealed no significant immunogenicity, no significant abnormalities in organs/tissues or their functions, a unique biodistribution pattern, and pronounced renal targeting. The successful development of MSLNPs with acidic pH-responsive control, a high delivery efficiency, and renal-targeting properties simplifies LNP preparation. Conclusions: This study offers novel insights into the design of simplified LNPs and the optimization of targeted delivery, with potential applications in renal disease therapy. Full article

Apixaban (APX) is a direct oral anticoagulant with low aqueous solubility and limited bioavailability. This study aimed to improve APX solubility by forming spray-dried inclusion complexes (ICs) with β-cyclodextrin (β-CD) derivatives. ICs were prepared using hydroxypropyl-β-CD (HP-β-CD), sulfobutylether-β-CD (SBE-β-CD), randomly methylated-β-CD (RM-β-CD), and heptakis(2,6-di-O-methyl)-β-CD (DM-β-CD). Complex formation (1:1 stoichiometry) was confirmed by phase solubility studies and Job’s plots. The ICs were characterized by SEM, PXRD, DSC, and FTIR, and their saturated solubility was evaluated. Molecular docking assessed host–guest interactions. Among the tested carriers, DM-β-CD exhibited the highest stability constant (K_C = 371.92 M⁻¹) and produced amorphous ICs. DM-ICs achieved the greatest solubility enhancement at all pH conditions, with a maximum solubility of 1968.7 μg/mL at pH 1.2 and ~78.7-fold increase in water compared with pure APX. Docking results supported stable inclusion with the lowest binding free energy (−8.01 kcal/mol). These findings indicate that DM-β-CD-based ICs effectively enhance APX dissolution and show potential as solubilizing carriers for oral dosage forms. Full article

A novel inclusion complex of a fluorinated pyrazolopiperidine derivative (5-benzyl-7-(2-fluorobenzylidene)-2,3-bis(2-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo [4,3-c]pyridine hydrochloride, PP·HCl) with β-cyclodextrin (PPβCD) was designed, synthesized, and characterized as a potential therapeutic agent for chemotherapy-induced myelosuppression and lymphopenia. Encapsulation of PP within β-cyclodextrin increased aqueous solubility by approximately 3.4-fold and improved dissolution rate by 2.8-fold compared with the free compound. Structural analysis using IR, ^1H/^13C NMR, and TLC confirmed the formation of a stable 1:1 host–guest complex, and the disappearance of free PP signals further supported complete encapsulation. In vivo evaluation in a cyclophosphamide-induced myelosuppression model demonstrated that PPβCD accelerated hematopoietic recovery, restoring leukocyte and erythrocyte counts 35–40% faster than methyluracil, without any signs of systemic toxicity. These findings indicate that β-cyclodextrin complexation significantly enhances solubility, dissolution, and biological efficacy of the pyrazolopiperidine scaffold, supporting further preclinical development of PPβCD as a supportive therapy for chemotherapy-related hematological complications. Full article

Carmustine (BCNU) is a powerful alkylating agent primarily used in the chemotherapeutic treatment of malignant brain tumors. However, its clinical application faces significant constraints due to its lipophilicity, low thermal stability, and rapid degradation in physiological environments. To tackle these challenges, our research aimed at the development and detailed characterization of α-cyclodextrin (α-CD) inclusion complexes (ICs) with BCNU employing three different synthesis techniques: co-grinding, cryomilling, and co-precipitation. The selected synthetic methods displayed variations dependent on the technique used, affecting the efficiency, inclusion ratios, and drug-loading capacities, with co-precipitation achieving the most favorable complexation parameters. Structural elucidation through ¹H NMR chemical shifts analysis indicated that only partial inclusion of BCNU occurred within α-CD in ICs produced via co-grinding, while cryomilling and co-precipitation allowed for complete inclusion. Multimodal spectroscopic analyses (FT-IR, UV-Vis, ¹³C CP MAS NMR, and ESI-MS) further substantiated the effective encapsulation of BCNU within α-CD, and systematic solubility assessments via Job’s continuous variation and the Benesi-Hildebrand method revealed a 1:1 host-guest stoichiometry. The ICs obtained were evaluated for BCNU release in vitro at pH levels of 4, 5, 6.5, and 7.4. The mechanism of BCNU drug release was determined to be Fickian diffusion, with the highest cumulative release noted in the acidic microenvironment. These findings collectively validate the effectiveness of α-CD as a functional excipient for the modulation of BCNU’s physicochemical properties through non-covalent complexation. This strategy shows potential for increasing the stability and solubility of BCNU, which may enhance its therapeutic effectiveness in the treatment of brain tumors. Full article

Nerolidol (REL), a sesquiterpene with cis and trans isomers, exhibits diverse bioactive and sensory properties. In this study, we integrate single-crystal X-ray diffraction (SC-XRD), molecular docking, molecular dynamics (MD) simulations, and MM/GBSA binding free energy calculations to investigate its inclusion behavior in β-cyclodextrin (β-CD). Crystallization from a cis/trans mixture yielded a complex containing exclusively the trans isomer, forming a 2:1 host–guest assembly where a head-to-head β-CD dimer encapsulates one trans-REL molecule in an extended conformation. Computational models of cis-REL (bent c1 and extended c8 conformers) also stabilized within the β-CD cavity, with the extended conformer showing the most favorable dynamics. The computed binding affinities for all complexes differed by less than the estimated MM/GBSA uncertainty, indicating no statistically significant preference. Since cis/trans separation of nerolidol and related long-chain terpenoids is of considerable interest, our findings suggest that crystallization selectivity in β-CD inclusion complexes cannot be rationalized solely by binding affinity; instead, it likely arises from crystal packing forces and conformational preferences that govern the solid-state assembly. Full article

Methicillin-resistant S. aureus is a problematic pathogen due to its high-risk infections and resistance mechanisms. To fight against this bacterium, novel antimicrobial sources and new delivery systems must be developed. Antimicrobial polyurethanes for developing biomaterials can function as preventive strategies. In this study, we explore the synthesis of partially renewable polyurethanes as biomaterial carriers of novel antimicrobials. An antibacterial extract from a Streptomyces sp. strain and its inclusion complexes with β-cyclodextrin, used as an additional protective approach, were incorporated into castor oil-based polyurethane films through bulk or surface loading. The inclusion complexes were characterized to confirm host–guest interactions. The films were characterized by FTIR, XRD spectra, surface SEM images, hydrophilicity, thermal stability, and mechanical performance. FTIR suggested successful polyurethane synthesis. The polymers were semicrystalline and thermally stable until 260 °C, and Tg ranged between −16.9 and −9 °C. Bulk modification decreased the mechanical performance of the films. Surface modification promoted good antibacterial performance but cytotoxic potential against HDFa cells. However, PU active films showed favorable properties and hemocompatibility, making them a promising alternative for applications such as short-term dressings, serving as an antimicrobial delivery system and a preventive strategy against methicillin-resistant S. aureus. Full article