Guest Complexes Research Articles

A Terrylene Bisimide based Universal Host for Aromatic Guests to Derive Contact Surface-Dependent Dispersion Energies.

π-π interactions are among the most important intermolecular interactions in supramolecular systems. Here we determine experimentally a universal parameter for their strength that is simply based on the size of the interacting contact surfaces. Toward this goal we designed a new cyclophane based on terrylene bisimide (TBI) π-walls connected by para-xylylene spacer units. With its extended π-surface this cyclophane proved to be an excellent and universal host for the complexation of π-conjugated guests, including small and large polycyclic aromatic hydrocarbons (PAHs) as well as dye molecules. The observed binding constants range up to 108 M-1 and show a linear dependence on the 2D area size of the guest molecules. This correlation can be used for the prediction of binding constants and for the design of new host-guest systems based on the herewith derived universal Gibbs interaction energy parameter of 0.31 kJ/molÅ2 in chloroform.

Determination of pesticide residue in soil samples by molecularly imprinted solid-phase extraction method

Abstract Porous molecularly imprinted polymer (MIP) microspheres were synthesized via iniferter-suspension polymerization method, employing lenacil (LA) as the template molecule and methacrylic acid (MAA) as the functional monomer. The host–guest complexes formed using LA and MAA were characterized by hydrogen nuclear magnetic resonance and ultraviolet–visible absorption spectroscopy. The obtained results showed that the interaction between LA and MAA mainly relied on hydrogen bonding. The surface morphologies and chemical structures of the MIPs were characterized by scanning electron microscopy. MIPs were spherical in shape with a relatively regular sphericity, rough surface structure, and numerous small holes, which significantly reduced the mass transfer resistance of the template molecules and exhibited excellent recognition performance for template molecules. In addition, soil samples were pretreated with solid-phase extraction columns molecularly imprinted with LA, and analyzed by high-performance liquid chromatography. The recoveries of LA, bromacil, and terbacil were up to 89.65%, 53.17%, and 44.63%, respectively. The developed method showed a minimum detection limit of 10–50 µg·mL−1. In view of the continuous increase of public requirements for pesticide residue detection, a versatile pretreatment method was developed that is green, rapid, simple, and can be miniaturized.

Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis

Hypothesis: Poloxamines are amphiphilic block copolymers that self-assemble forming polymeric micelles (PMs) and hydrogels. They have emerged as promising colloidal carriers for their potential in improving drug delivery and controlled release through their multi-responsive properties. Tetronic® 1307 (T1307) PMs and gels have been used herein as vehicles of host–guest complexes of cyclodextrins (CDs) and miltefosine (MF), an amphiphilic, anti-parasitic drug effective against leishmaniasis.Experiments: The association of MF to αCD, βCD, and HPβCD and the topology of the complexes have been fully characterized by NMR spectroscopy. Then, the structure of the complex-loaded PMs and hydrogels investigated using diffusion nuclear magnetic resonance (DOSY), small angle neutron scattering (SANS), and dynamic light scattering (DLS). The antileishmanial activity of the constructs was evaluated against Leishmania major promastigotes and amastigotes, as well as their cytotoxicity in macrophages.Findings: All the CDs investigated form highly stable inclusion complexes with MF in a 2CD:1MF stoichiometry that lead to considerable proportions of complexed drug at high dilution, the HPβCD providing the highest stability and compatibility with the poloxamine. The complex incorporates preferentially into the hydrophilic shell of the PMs, inducing the elongation of the aggregates and the dehydration of the micellar core, formed mainly by the PPO blocks. At high concentration of polymer and physiological temperature, the complex-loaded PMs pack in a BCC-type paracrystal network. The micellar formulations of the CD-complexed MF reduced the cytotoxicity of the drug, while enhancing its antileishmanial activity. This approach could improve the currently available treatments, facilitating the administration of MF at lower concentrations and achieving relevant therapeutic effects, not only through the intravenous route, but also as topical formulations through injectable thermogels for the treatment of the cutaneous and mucocutaneous forms of the disease.

Synthesis, characterization, molecular modeling, binding energies of β-cyclodextrin-inclusion complexes of quercetin: Modification of photo physical behavior upon β-CD complexation

We prepared a naturally occurring flavanoid namely quercetin from tea leaves and analyzed by Absorption, Emission, FT-IR, 1H, 13C nmr spectra and ESI-MS analysis. The inclusion behavior of quercetin in cyclodextrins like α-, β-, γ-, per-6-ABCD and mono-6-ABCD cavities were supported such as UV–vis., Emission, FT-IR and ICD spectra and energy minimization studies. From the absorption and emission results, the type of complexes formed were found to depend on stoichiometry of Host:Guest. FT-IR data of CD complexes of quercetin supported inclusion complex formation of the substrate with α-, β- and γ-CDs. The inclusion of host–guest complexation of quercetin with α-, β-, γ-CDs, per-6-ABCD and mono-6-ABCDs provides very valuable information about the CD:quercetin complexes, the study also shows that β-CD complexation improves water solubility, chemical stability and bioavailability of quercetin. Besides, phase solubility studies also supported the formation of 1:1 drug-CD soluble complexes. All these spectral results provide insight into the binding behavior of substrate into CD cavity in the order per-6-ABCD > Mono-6-ABCD > γ-CD > β-CD > α-CD. The proposed model also finds strong support from the fact with excess CD this exciton coupling disappears indicates the formation of only 1:1 complex.

Constructing [2.2]Paracyclophane‐Based Ultrasensitive Optical Fluorescent‐Phosphorescent Thermometer with Cucurbit[8]uril Supramolecular Assembly

AbstractThe pursuit of developing novel approaches to fully organic and efficient phosphorescent materials is in high demand. The optical activity of such functional, organic phosphorescent/fluorescent materials may exhibit great temperature dependence, allowing their application as advanced, highly sensitive molecular thermometers. In this study, a rational strategy involving host–guest complexation and polymerization of [2.2]paracyclophane (PCP) based molecules with cucurbit[8]uril (CB8) to suppress the molecular motion and promote temperature‐dependent phosphorescence is presented. The rigid cavity of CB8 provides an ideal microenvironment to host PCP molecules 1 and 2, significantly enhancing the photophysical performance after complexation. Co‐polymerizing phosphors 1 and 2 with acrylamide is an efficient method for improving phosphorescence. Incorporating CB8 into the resulting P‐1 and P‐2 polymers enhances phosphorescence performance. Importantly, the obtained materials exhibit a big structure‐dependent spectral shift and change of phosphorescence lifetimes with temperature, allowing novel, phosphorescence‐based, and purely organic optical thermometers to be developed. The practical applications of PCP‐based luminescent materials in temperature sensing via a multi‐parameter approach are showcased, i.e., using fluorescence spectral shift and changes in bandwidth, as well as phosphorescence lifetimes, exhibiting thermal sensitivity of ≈17.7 cm−1 °C−1, 47.8 cm−1 °C, and 5.2% °C−1, respectively.

Evaluation of the Immunosafety of Cucurbit[n]uril In Vivo.

Cucurbiturils are a family of macrocyclic oligomers capable of forming host-guest complexes with various molecules. Due to noncovalent binding to drug molecules and low toxicity, cucurbiturils has been extensively investigated as potential carriers for drug delivery. However, the immune system's interactions with different drug carriers, including cucurbiturils, are still under investigation. In this study, we focused on cucurbiturils' immunosafety and immunomodulation properties in vivo. We measured blood counts and lymphocyte subpopulations in blood, spleen, and bone marrow, and assessed the in vivo toxicity to spleen and bone marrow cells after intraperitoneal administration to BALB/c mice. When assessing the effect of cucurbit[6]uril on blood parameters after three intraperitoneal injections within a week in laboratory animals, a decrease in white blood cells was found in mice after injections of cucurbit[6]util, but the observed decrease in the number of white blood cells was within the normal range. At the same time, cucurbit[7]uril and cucurbit[8]uril did not affect the leukocyte counts of mice after three injections. Changes in the number of platelets, erythrocytes, and monocytes, as well as in several other indicators, such as hematocrit or erythrocyte volumetric dispersion, were not detected. We show that cucurbiturils do not have immunotoxicity in vivo, with the exception of a cytotoxic effect on spleen cells after сucurbit[7]uril administration at a high dosage. We also evaluated the effect of cucurbiturils on cellular and humoral immune responses. We founded that cucurbiturils in high concentrations affect the immune system in vivo, and the action of various cucurbiturils differs in different homologues, which is apparently associated with different interactions in the internal environment of the body.

Stimuli‐responsive fluorescent hydrogels: Strategies and applications

AbstractStimuli‐responsive fluorescent hydrogels are three‐dimensional networked polymeric materials with tunable luminescence and dynamic properties, which play an important role as a water‐rich soft material in the fields of information encryption, bionic actuation, bioimaging, environmental monitoring, and luminescent materials. Compared with conventional hydrogels, their unique luminescent properties allow the visualization of microscopic dynamics within the polymer network. By rational inclusion of dynamic motifs, such as photoswitches, AIEgens, lanthanide complexes, and host–guest complexes, these materials are endowed with tunability of emission, shape, and phase in time and space in response to environmental effectors. In this review, we summarize the fabrication strategies that are mainly used by recently reported stimuli‐responsive fluorescent hydrogels and the applications of these materials.

Structural connectivity of 18‐Crown‐6/H+/L‐tryptophan noncovalent complexes in gas phase and in solution: Delineating host–guest–solvent interactions in solution from gas phase structures

AbstractWe investigate the structural correlation of noncovalent crown ether/H+/L‐tryptophan (CR/TrpH+) host–guest complexes in the solution phase with those in the gas phase generated through electrospray ionization/mass spectrometry (ESI/MS) techniques. We perform quantum chemical calculations to determine their structures, relative Gibbs free energies, and infrared spectra. We compare the calculated infrared (IR) spectra with the IR multiphoton dissociation (IRMPD) spectra observed for the 18‐Crown‐6/TrpH+ complex by Polfer and co‐workers [J. Phys. Chem. A 2013, 117, 1181–1188] for assigning the IR bands. We observe that the carboxyl group remains “naked,” lacking hydrogen bonding with the CR unit in the gas phase, and that this most stable conformer originates from the corresponding lowest Gibbs free energy structure in solution. Based on these findings, we propose that gas phase host–guest complexes directly correlate with those in solution, reinforcing the possibility of obtaining invaluable information about host–guest–solvent interactions in solution from the structure of the host–guest pair in the gas phase.

Fluorescent Nile blue‐functionalized poly (N‐isopropylacrylamide) microgels responsive to temperature and polyamines

AbstractFluorescent poly(N‐isopropylacrylamide‐co‐Nile blue) (pNIPAm‐co‐NB) microgels were synthesized that exhibited fluorescence intensity changes in a water temperature‐dependent fashion. NB is well known to exhibit fluorescence intensity that depends on the hydrophobicity of the environment, while pNIPAm‐based microgels are well known to transition from swollen (hydrophilic) to collapsed (relatively hydrophobic) at temperatures greater than 32 °C; hence, we attribute the above behavior to the hydrophobicity changes of the microgels with increasing temperature. This phenomenon is ultimately due to NB dimers (relatively quenched fluorescence) being broken in the hydrophobic environment of the microgels leading to relatively enhanced fluorescence. We went on to show that the introduction of cucurbit[7]uril (CB[7]) into the pNIPAm‐co‐NB microgels enhanced their fluorescence allowing them to be used for polyamine (e.g., spermine [SPM]) detection. Specifically, CB[7] forms a host–guest interaction with NB in the microgels, which prevents NB dimerization and enhances their fluorescence. When SPM is present, it forms a host–guest complex that is favored over the CB[7]‐NB host–guest interaction, which frees the NB for dimerization and leads to fluorescence quenching. As a result, we could generate an SPM sensor capable of SPM detection down to ~0.5 µmol/L in complicated matrixes such as serum and urine.

Confined Lewis Pairs: Investigation of the X−→Si20 Interaction in Halogen‐Encapsulating Silafulleranes

AbstractA joint theoretical and experimental study on 32 endohedral silafullerane derivatives [X@Si20Y20]− (X=F‐I; Y=F‐I, H, Me, Et) and ‐[Cl@Si20H12Y8]− (Y=F‐I) is presented. First, we evaluated the structure‐determining template effect of Cl− in a systematic series of concave silapolyquinane model systems. Second, we investigated the X−→Si20 interaction energy ( ) as a function of X− and Y and found the largest values for electron‐withdrawing exohedral substituents Y. Given that X− ions can be considered as Lewis bases and empty Si20Y20 clusters as Lewis acids, we classify our inseparable host–guest complexes [X@Si20Y20]− as “confined Lewis pairs”. Third, 35Cl NMR spectroscopy proved to be highly diagnostic for an experimental assessment of the Cl−→Si20 interaction as the paramagnetic shielding and, in turn, (35Cl) of the endohedral Cl− ion correlate inversely with . Finally, we disclose the synthesis of [PPN][Cl@Si20Y20] (Y=Me, Et, Br) and provide a thorough characterization of these new silafulleranes.

A cucurbit[8]uril-mediated host–guest complex for red-light photocatalysis

Two-step host–guest complexation can occur between an elongated dye and CB[8], leading to the formation of CB[8]@2TPP and 3CB[8]@2TPP sequentially. Of these species, 3CB[8]@2TPP in particular can act as an efficient red-light photocatalyst.

Host–Guest Complexation in Wide Bandgap Perovskite Solar Cells

Host–Guest Complexation in Wide Bandgap Perovskite Solar Cells

Cucurbit[8]uril-based host–guest complexation enhancing afterglow of a naphthalimide derivative for anti-counterfeiting printing

The host–guest complexation strategy was introduced to enhance afterglow of a bromophenoxy-substituted naphthalimide derivative and its polymer. The host–guest complex with humidity response was used as an encryption ink.

Host–guest complexes of perylene bisimide-based metallacage and fullerenes for efficient photoinduced charge separation

Fast photoinduced charge separation was predicted in non-covalent complexes of Pt6PBI3 metallacage and endohedral metallofullenes.

Responsive pillar[n]arene materials

AbstractIntelligent materials with responsive behaviors toward external stimuli, such as light, temperature, pH, redox, and solvent have been increasingly fascinating. Reversible noncovalent interactions provide an efficient way to construct stimuli‐responsive materials. Macrocyclic compounds, such as cyclodextrins, cucurbit[n]urils, calix[n]arenes, crown ethers, and related macrocycles, are useful skeletons for constructing such materials through host–guest interactions. Pillar[n]arenes are pillar‐shaped macrocyclic hosts developed by our groups in 2008, in which the repeated 1,4‐dialkoxybenzene units are connected by methylene bridges at the para position. The versatile functionality, easy modification, excellent size‐dependent host–guest complexation, and adjustable electron density of the cavity endow pillar[n]arenes with excellent properties compared with other cyclic host molecules. Moreover, the unique planar chirality and chirality inversion generated by unit rotation make pillar[n]arenes ideal platforms for investigating chirality inversion, induction, and transformation. In this review, we describe stimuli‐responsive topological, optical, chiroptical, supramolecular assemblies, and solid‐state materials based on the host–guest complexation and structural regulation of pillar[n]arenes.

Experimental and theoretical study on supramolecular encapsulation of molnupiravir by Cucurbit[7]uril: A potential formulating agent for COVID-19

Global propagation of the Novel Coronavirus Diseases-2019 (COVID-19) outbreak threatens the scientific community's ability to develop and learn effective SARS-CoV-2 treatment methods. Most of the current therapeutics have some form of side effects to treat COVID-19. The requirement for new medications emerges as a consequence of the evolution of new strain such as EG.5.1. Remdesivir, Molnupiravir, Favipiravir, Ribavirin, Baricitinib, Camostat, and other pharmaceuticals have been used to treat patients with COVID-19, among which only Molnupiravir was a novel synthesized agent while the rest were all repurposed medications. However, the side effects from these medications, such as vomiting, diarrhea, dizziness etc., necessitate immediate medical attention. To decrease the toxicity of some medications and increase their efficacy, cyclic macromolecules such as α/β-Cyclodextrin or Cucurbit[n]uril (n = 6–8) can play an important role by forming host–guest complexes. The drugs were coupled with several host molecules in the current investigation to examine their effectiveness against SARS-CoV-2 proteins via a molecular docking study, which revealed that Cucurbit[7]uril-molnupiravir had superior performance against SARS-CoV-2. The inclusion complex was synthesized and characterized via different characterization techniques to prove the formation of stable 1:1 complex. Furthermore, DFT studies also validate our experimental observations.

Modulation of excimer formation and photostability of avobenzone inside the nanocavities of cyclodextrins

Avobenzone (AVZ), a UVA filter, is extensively used in sunscreen lotion and protects the skin from harmful UVA radiation. Despite their importance in sunscreen formulation, less attention has been given to its light induced excited state properties. Herein, we have explored the photophysical properties of AVZ in aqueous solutions and cyclodextrins (CDs) complexes by employing steady-state, time-resolved fluorescence, and molecular modelling tools followed by photostability analysis. AVZ exhibits dual emission from monomer and excimer forms in aqueous solutions. Spectroscopic studies revealed that AVZ forms multiple inclusion complexes with β-CD and γ-CD depending upon the host’s cavity size. These versatile host–guest complexes resulted in the modulation of the excimer formation of AVZ. The presence of α-CD and β-CD complexes with AVZ inhibited the excimer forms. In contrast, γ-CD facilitated excimer formation because its larger cavity could encapsulate the AVZ dimer. Stoichiometry and association constants for multiple host–guest complexes were determined using Benesi-Hildebrand (BH) plot. Job’s plot was used to confirm the stoichiometry of complexes. Time correlated single photon counting (TCSPC) technique was used to depict the excited state lifetime values of AVZ:CD inclusion complexes. Furthermore, these inclusion complexes were characterized by Fourier transform-infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. Molecular docking followed by semiempirical calculations confirm the experimental results on stoichiometries and binding constants of host–guest complexes. UV light-induced absorption kinetics revealed that the photostability of AVZ inside the β-CD cavity is much better than other inclusion complexes of CDs. Overall, the present study helps us in further understanding of excited state behavior of AVZ inside hydrophobic nanocavities.

Ordered nanoassemblies from self‐assembly of amphiphilic molecule containing pillar[5]arene and azobenzene groups

AbstractThe derivatization of pillar[n]arenes is a prerequisite for endowing them with functions, as well as enriching the application of pillar[n]arene materials in advanced material science. Herein, we report the self‐assembly of amphiphilic rim‐differentiated pillar[5]arene (H1). One side of the pillar[5]arene is composed of hydrophilic poly(ethylene oxide) chains, benzene and azobenzene groups connected with ether bonds, and the other side is composed of ethoxy groups. In CHCl3 solvent, the amphiphile H1 self‐assembled into spherical micelles, while in H2O/THF mixed solvent H1 self‐assembled into nanorod‐like assemblies. Interestingly, addition of a guest molecule composed of tetraphenylethene and hexanenitrile groups (G1) to the CHCl3 solution of H1 produces large sheet aggregates via the strong π–π stacking of rod segments. The reversible transformation between the nanosheet assemblies of host–guest complexes and nanoparticles is achieved by addition of the guest molecule 1,4‐butylamine (G2) and pillar[5]arene with ethoxy groups as competitive molecules. Notably, worm‐like and nanorod micelles of H1 were constructed in H2O/THF solution triggered by light irradiation, which assemblies can be used as photosensitive erasable writing materials. © 2023 Society of Industrial Chemistry.

Luteolin, a flavone ingredient: Anticancer mechanisms, combined medication strategy, pharmacokinetics, clinical trials, and pharmaceutical researches.

Current pharmaceutical research is energetically excavating the pharmacotherapeutic role of herb-derived ingredients in multiple malignancies' targeting. Luteolin is one of the major phytochemical components that exist in various traditional Chinese medicine or medical herbs. Mounting evidence reveals that this phytoconstituent endows prominent therapeutic actions on diverse malignancies, with the underlying mechanisms, combined medication strategy, and pharmacokinetics elusive. Additionally, the clinical trial and pharmaceutical investigation of luteolin remain to be systematically delineated. The present review aimed to comprehensively summarize the updated information with regard to the anticancer mechanism, combined medication strategies, pharmacokinetics, clinical trials, and pharmaceutical researches of luteolin. The survey corroborates that luteolin executes multiple anticancer effects mainly by dampening proliferation and invasion, spurring apoptosis, intercepting cell cycle, regulating autophagy and immune, inhibiting inflammatory response, inducing ferroptosis, and pyroptosis, as well as epigenetic modification, and so on. Luteolin can be applied in combination with numerous clinical anticarcinogens and natural ingredients to synergistically enhance the therapeutic efficacy of malignancies while reducing adverse reactions. For pharmacokinetics, luteolin has an unfavorable oral bioavailability, it mainly persists in plasma as glucuronides and sulfate-conjugates after being metabolized, and is regarded as potent inhibitors of OATP1B1 and OATP2B1, which may be messed with the pharmacokinetic interactions of miscellaneous bioactive substances in vivo. Besides, pharmaceutical innovation of luteolin with leading-edge drug delivery systems such as host-guest complexes, nanoparticles, liposomes, nanoemulsion, microspheres, and hydrogels are beneficial to the exploitation of luteolin-based products. Moreover, some registered clinical trials on luteolin are being carried out, yet clinical research on anticancer effects should be continuously promoted.

Ditopic Covalent Cage for Ion-Pair Binding: Influence of Anion Complexation on the Cation Exchange Rate.

A new hemicryptophane host with a ditopic molecular cavity combining a cyclotriveratrylene (CTV) unit with a tris-urea moiety was synthesized. The complexation of halides, tetramethylammonium (TMA+) cation, and ion pairs was investigated. A positive cooperativity was observed, since halides display a higher binding constant when a TMA+ cation is already present inside the cage. When TMA+ was complexed alone, a decrease of temperature from 298 K to 230 K was required to switch from a fast to a slow exchange regime on the NMR time scale. Nevertheless, the prior complexation of a halide guest in the lower part of the host resulted in significant decrease of the exchange rate of the subsequent complexation of the TMA+ cation. Under these conditions, the 1H NMR signals characteristic of a slow exchange regime were observed at 298 K. Addition of an excess of salts, increases the ionic strength of the solution, restoring the fast exchange dynamics. This result provides insight on how the exchange rate of a cation guest can be modulated by the complexation of a co-guest anion.