Guest Inclusion Complexes Research Articles

Supramolecular Materials Cross-Linked by Host–Guest Inclusion Complexes: The Effect of Side Chain Molecules on Mechanical Properties

Functional polymeric materials constructed by noncovalent bonds have attracted considerable attention due to their beneficial stretching and self-healing properties. We chose host–guest interactions using cyclodextrins (CDs) as host molecules to realize supramolecular materials with stretching and self-healing properties. Notably, an inclusion complex of a CD and a guest molecule functions as a reversible bond in a material. Herein, we studied the relationship between the mechanical properties of the materials and host–guest interactions based on the association constants of CDs with guest molecules and molecular structures of the guest molecules. A chemically cross-linked poly(acrylamide) gel showed high rupture stress, although the rupture strain was noticeably low. However, the host–guest hydrogels (CDAAmMe-R hydrogels) exhibited a higher rupture stress and strain of approximately 1000%. These rupture stress and strain values were related to the association constants of the CDs with guest units on the ...

Host–guest inclusion complex of quercetin and hydroxypropyl-β-cyclodextrin

Quercetin (QCT), a flavonoid derived from many fruits and vegetables, is endowed with manifold biological properties, such as the ability to elicit a strong inhibitory effect on the growth of several tumor cell lines. Unfortunately, the pharmacological application of QCT is severely restricted by its inherent hydrophobicity and consequent low in vivo bioavailability. The therapeutic potential of QCT can be unraveled by enhancing its solubility through the formation of a host–guest complex with hydroxypropyl-β-cyclodextrin (HPβCD). In this study, HPβCD·QCT complex has been obtained in liquid phase, at 37 °C and under a prolonged mixing (72 h), and using two buffers at pH = 3.6 and pH = 8.0. Phase solubility and differential scanning calorimetry (DSC) studies revealed that, at pH = 8.0, the complex was obtained with a 1:1 stoichiometric ratio and a strong enhancement of QCT solubility, while in acidic buffer complex formation was significantly thwarted. The affinity constant was calculated by isothermal calorimetry at pH = 8 and was found to be 489 ± 38 M−1, in good agreement with the value indirectly obtained from phase solubility tests 394 ± 101 M−1. The results confirmed the formation of the inclusion complex between QCT and HPβCD and highlight the importance of the choice of the appropriate solvent, pH, temperature and mixing time on the formation of host guest inclusion complex with active ingredient(s) and HPβCD.

Synthesis of stimuli-responsive support material for pectinase immobilization and investigation of its controllable tailoring of enzymatic activity

In this study, a novel type of stimuli-responsive support materials was synthesized successfully by atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP) of N-isopropylacrylamide (NIPAAm), tert-butyl methacrylate (tBMA) and ε-caprolactone (CL). β-Cyclodextrin (β-CD) and azobenzene (Azo) were employed as the starting groups to form PCL-hv-PNIPAAm by host–guest inclusion complexation, while PCL-PMAA was converted by simple hydrolysis of PCL-PtBMA with trifluoroacetic acid. Both PCL-PMAA and PCL-hv-PNIPAAm formed the microspheres by self-assembly. Their characteristics were confirmed by NMR, TEM, GPC, DLS, etc. Then, the microspheres were used for the immobilization of pectinase by electrostatic interaction. The optimal immobilization reaction parameters were 10U/mL for pectinase at 25°C for 4h at pH=6. Compared with free pectinase, the immobilized enzymes were found to exhibit better tolerance of variations in pH and temperature, as well as improved storage stability. Furthermore, the relative activity of the immobilized pectinase was controlled at approximately 13% when the temperature was higher than the LCST of PNIPAAm. With different light irradiation, there is approximately a 15% influence on the relative activity of the immobilized pectinase. This new enzyme support material has good environmental adaptability and can make the activity of immobilized enzymes be tailored predictably and enable the enzyme to be used as a biocatalyst for various applications in the food industry.

A mitochondria-targeting supramolecular photosensitizer based on pillar[5]arene for photodynamic therapy

A mitochondria-targeting supramolecular photosensitizer system TPP-QAS/WP5/DTAB was constructed based on a host-guest inclusion complex. The supramolecular system could efficiently release and activate TPP-QASs in an acidic environment, which have been demonstrated to preferentially accumulate in mitochondria. Singlet oxygen (1O2) could be in situ generated in mitochondria under light irradiation, further enhancing the PDT efficacy.

Fabrication of multi-stimuli responsive supramolecular hydrogels based on host–guest inclusion complexation of a tadpole-shaped cyclodextrin derivative with the azobenzene dimer

Multi-responsive supramolecular hydrogels, based on host–guest complexation of tadpole-shaped cyclodextrin with the azobenzene dimer, possess reversible sol–gel transition behaviors and better biocompatibility.

Study to explore the mechanism to form inclusion complexes of β-cyclodextrin with vitamin molecules.

Host–guest inclusion complexes of β-cyclodextrin with two vitamins viz., nicotinic acid and ascorbic acid in aqueous medium have been explored by reliable spectroscopic, physicochemical and calorimetric methods as stabilizer, carrier and regulatory releaser of the guest molecules. Job’s plots have been drawn by UV-visible spectroscopy to confirm the 1:1 stoichiometry of the host-guest assembly. Stereo-chemical nature of the inclusion complexes has been explained by 2D NMR spectroscopy. Surface tension and conductivity studies further support the inclusion process. Association constants for the vitamin-β-CD inclusion complexes have been calculated by UV-visible spectroscopy using both Benesi–Hildebrand method and non-linear programme, while the thermodynamic parameters have been estimated with the help of van’t Hoff equation. Isothermal titration calorimetric studies have been performed to determine the stoichiometry, association constant and thermodynamic parameters with high accuracy. The outcomes reveal that there is a drop in ΔSo, which is overcome by higher negative value of ΔHo, making the overall inclusion process thermodynamically favorable. The association constant is found to be higher for ascorbic acid than that for nicotinic acid, which has been explained on the basis of their molecular structures.

Bromination of N-phenyloxypropyl-N′-ethyl-4,4′-bipyridium in cucurbit[8]uril molecular reactor

CB[n] (n=6–8) is a family of synthetic macrocyclic host molecules composed of n glycoluril units, which can be employed as molecular reactor. N-Phenyloxypropyl-N′-ethyl-4,4′-bipyridium (1) was designed to form a host–guest inclusion complex with CB[n] (n=6–8), subsequently, the bromination reaction of 1 and its corresponding inclusion complexes was investigated in this work. In the case of 1/CB[8], the folded including mode is quite helpful to acquire 1-bormination product completely through intramolecular charge transfer (ICT), and CB[8] can provide a safe bromination environment for 1.

Host–guest inclusion system of rhein with polyamine-modified β-cyclodextrins: characterization and cytotoxicity

We report the preparation of inclusion complexes between rhein and four polyamine-modified β-cyclodextrins, namely amino-β-cyclodextrins (NH2-βCD), ethylenediamine-β-cyclodextrins (EN-βCD), diethylenetriamine-β-cyclodextrins (DETA-βCD) and triethylenetetramine-β-cyclodextrins (TETA-βCD) using suspension method. The solution and solid state forms of the inclusion complexes of rhein with polyamine-β-cyclodextrins were characterized by multiple techniques. Additionally, saturated solution and MTT methods were implemented to assess the water solubilization and in vitro cytotoxicity of the inclusion complexes, respectively. The results suggested that rhein was encapsulated within the CD cavity to form a 1:1 host–guest inclusion complex. Notably, a significant enhancement of the water solubility and in vitro cytotoxicity of rhein was found in the form of inclusion complex with polyamine-β-cyclodextrin.

Host–guest inclusion complexation of β-cyclodextrin and hecogenin acetate to enhance anti-hyperalgesic effect in an animal model of musculoskeletal pain

Abstract Hecogenin acetate (HA), a steroidal acetylated-sapogenin, has an analgesic profile already assigned, but its low water solubility and short half-life limit its use in chronic conditions. β-cyclodextrin (β-CD) can improve the chemical and pharmacological property of nonpolar compounds such as HA. Therefore, a HA complexed with β-CD (HA-CD) was prepared and characterized by thermal, morphological and spectroscopic analysis. A model of chronic musculoskeletal pain was induced by means of two injections of pH 4.0 saline (20 μL) into the left gastrocnemius 5 days apart was used. After confirming hyperalgesia, male mice were treated with HA, HA-CD (20 mg/kg; p.o.) or vehicle (saline 0.9%, p.o.). Motor coordination tests, substance P (SP) levels in a lumbosacral (L4-S2) spinal cord sample and a docking study were equally assessed to check for a possible action on the opioid receptors. Oral pretreatment with HA or HA-CD produced a significant antinociceptive (p

An ultra-sensitive sensor based on β-cyclodextrin modified magnetic graphene oxide for detection of tryptophan

A novel, ultra-sensitive and selective sensing platform was fabricated for detection of tryptophan (Trp) based on β-cyclodextrin modified magnetic graphene oxide (MGO-CD) nanocomposites. Magnetic Fe3O4 modified graphene oxide (MGO) was prepared by a simple coprecipitation method, then β-CD was conjugated on the surface of MGO through strong hydrogen bond and hydrophobic interaction. The sensitivity was obviously improved due to the synergistic effects between Fe3O4 and graphene oxide (GO), which would enhance the electron transfer rate as well as increase the surface area to capture a large amount of β-CD. Furthermore, the graft of β-CD had strong recognition capability for Trp to form stable host–guest inclusion complexes leading to the promotion of selectivity. The MGO-CD modified glassy carbon electrode (MGO-CD/GCE) was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV), and it revealed extraordinary electrochemical response towards the determination of Trp. Under the optimized conditions, the electrochemical sensor showed a wide linear range from 5.0×10−7M to 7.5×10−4M with a low detection limit of 3.1×10−7M (S/N=3). The proposed method displayed good reproducibility and excellent stability, which could be validated for commercial amino acid preparation sample, and satisfactory results were received. This strategy might provide the new clue for the clinic application.

NMR, surface tension and conductance study to investigate host–guest inclusion complexes of three sequential ionic liquids with β-cyclodextrin in aqueous media

Host–guest inclusion complexes of three sequential cationic room temperature surface active ionic liquids, benzyltrialkylammonium chloride [(C6H5CH2)N(CnH2n+1)3Cl; where n=1,2,4] with β-cyclodextrin in aqueous media have been studied using surface tension, conductance and NMR spectroscopy. All the studies have suggested that the hydrophobic benzyl group of ionic liquids is encapsulated inside into the cavity of β-cyclodextrin and played a crucial role in supporting the formation of inclusion complexes. The variation of the thermodynamic parameters with guest size, shape is used to draw inferences about contributions to the overall binding by means of the driving forces, viz., hydrophobic effect, steric hindrance, van der Waal force, and electrostatic force.

Controllable Construction of Biocompatible Supramolecular Micelles and Vesicles by Water-Soluble Phosphate Pillar[5,6]arenes for Selective Anti-Cancer Drug Delivery

The controllable construction of biocompatible supramolecular nanocarriers with different morphologies based on dynamic noncovalent interactions to achieve selective delivery of drugs with different properties remains highly challenging. We herein report controllable construction of two types of supramolecular nanocarriers based on biocompatible water-soluble phosphate-based pillar[5]arene (WP5P) or pillar[6]arene (WP6P) with pyridinium bromide guest G for the selective anticancer drug delivery. Solid supramolecular micelles could be obtained by the amphiphilic host–guest inclusion complex formed from WP5P and G, whereas hollow supramolecular vesicles were acquired from WP6P and G. Both of them showed pH- and Zn2+-responsiveness. Furthermore, the resulting solid micelles were able to encapsulate hydrophobic anticancer drug doxorubicin (DOX) to achieve DOX-loaded micelles, while hydrophilic anticancer drug mitoxantrone (MTZ) could be successfully loaded into the hollow vesicles. Additionally, the encapsula...

Exploration of inclusion complexes of neurotransmitters with β-cyclodextrin by physicochemical techniques

Molecular assemblies of β-cyclodextrin with few of the most important neurotransmitters, viz., dopamine hydrochloride, tyramine hydrochloride and (±)-epinephrine hydrochloride in aqueous medium have been explored by reliable spectroscopic and physicochemical techniques as potential drug delivery systems. Job plots confirm the 1:1 host–guest inclusion complexes, while surface tension and conductivity studies illustrate the inclusion process. The inclusion complexes were characterized by 1H NMR spectroscopy and association constants have been calculated by using Benesi–Hildebrand method. Thermodynamic parameters for the formation of inclusion complexes have been derived by van’t Hoff equation, which demonstrate that the overall inclusion processes are thermodynamically favorable.

ChemInform Abstract: Metal Complexes Based on Native Cyclodextrins: Synthesis and Structural Diversity

AbstractReview: 44 refs.

Host–guest inclusion complexes derived heteroatom-doped porous carbon materials

A facile and efficient strategy for the synthesis of heteroatom-doped carbon materials was developed, in which host–guest inclusion complexes were employed as versatile precursors. Inclusion of heteroatom containing guest molecules in the cavity of host molecules (such as cyclodextrins and cucurbit[n]urils) not only doped the carbon frameworks with heteroatoms (for instance, nitrogen, sulfur, boron, fluorine and iron), but also highly improved the carbonization yield. Since the chemical structure (composition) of host–guest inclusion complexes can be finely tuned at molecular level, they are ideal small molecular precursors for heteroatoms doped carbon materials. A nitrogen-doped porous carbon material derived from inclusion complexes exhibited a high performance as supercapacitors electrode with a high specific capacitance (348 F g−1) at a current density of 1 A g−1 in 6 M KOH aqueous solution and good cycling stability over 5000 cycles, demonstrating its potential application in energy storage.

Structural investigation of the β-cyclodextrin complexes with linalool and isopinocampheol – Influence of monoterpenes cyclicity on the host–guest stoichiometry

The crystal structures of the complexes of β-cyclodextrin with two chiral terpene alcohols are presented. (−)-Linalool forms the complex of a 2:2 host–guest stoichiometry, while the complex with (−)-isopinocampheol exhibits a 2:3 stoichiometry. The comparison of the crystal structures with the data for other complexes of β-cyclodextrin with chiral monoterpene alcohols obtained from Cambridge Structural Database (CSD) highlights the tendency of linear and monocyclic alcohols to form complexes of 2:2 stoichiometry whereas bicyclic alcohols prefer to form 2:3 host–guest inclusion complexes.

Host-Guest Inclusion Complexation of α-Cyclodextrin and Triiodide Examined Using UV-Vis Spectrophotometry.

The historically relevant host-guest complexation of α-cyclodextrin (α-CD) and triiodide (I3(-)) in aqueous solution was examined using a systematic UV-vis spectrophotometric approach. This particular system is experimentally challenging because of the coupled equilibria, namely, I2 + I(-) ⇌ I3(-) and α-CD + I3(-) ⇌ α-CD·I3(-). We therefore developed a unique experimental approach that allowed us to determine the concentration of all iodine species. This enabled us to unequivocally demonstrate that the large increase in the UV absorbance with added α-cyclodextrin is due to an increase in the overall triiodide concentration as α-CD essentially converts iodine to triiodide according to the coupled equilibria. Herein we report (a) the complexation stoichiometry is 1:1 (i.e., the host-guest complex is α-CD·I3(-)), (b) the binding constant is KH-G = (1.35 ± 0.05) × 10(5) M(-1) at room temperature, and

A hybrid hydrogel based on clay nanoplatelets and host–guest inclusion complexes

Abstract In this work, a monomer with double bond was introduced to the surface of clay nanosheets via inclusion complexation between cyclodextrin (CD) host and azobenzene (Azo) guest, as well as electrostatic interaction between clay nanoplatelets and cations of azobenzene derivatives. The obtained supra-structure acts as a supramolecular cross-linker in its copolymerization with macromonomer PEG resulting in a hybrid supramolecular hydrogel. Only viscous liquid was obtained in the absence of clay nanoplatelets, revealing the supramolecular cross-linker played an important role in the hydrogel formation. Such hybrid supramolecular hydrogel exhibited good stability and shear thinning property.

Host–guest inclusion complexes of RNA nucleosides inside aqueous cyclodextrins explored by physicochemical and spectroscopic methods

Spectroscopic and physicochemical studies reveal formation of host–guest inclusion complexes of RNA nucleosides inside hydrophobic cavity of α and β-cyclodextrins.

Insertion behavior of imidazolium and pyrrolidinium based ionic liquids into α and β-cyclodextrins: mechanism and factors leading to host–guest inclusion complexes

The encapsulation of [BMIm]Cl and [BMP]Cl within α and β-cyclodextrin in both the solid state and aqueous solution with 1 : 1 supramolecular assembly.