Supramolecular Host-guest Complexes Research Articles

Dynamically Self-Assembled Supramolecular Probes in Liposomes

Liposomes are artificial vesicles, in which an aqueous inner compartment is separated from its environment by a phospholipid membrane. They have been extensively studied as cell membrane models and offer the possibility to confine molecules and chemical reactions to a small sub-micrometer-sized volume. This short review provides an overview of liposome-encapsulated, dynamically self-assembled, supramolecular structures, in which the assembly and disassembly of the supramolecular structures can be followed by optical spectroscopic methods. This includes self-quenched fluorescent dyes and dye/quencher pairs, helical stacks of guanosine nucleotides, dynamic covalent boronate esters, and supramolecular host–guest complexes. The resulting liposomes are typically used to study membrane transport processes, but the results summarized herein also serve as a potential blueprint for studying dynamic self-assembly in confined spaces by optical spectroscopic methods.Table of content:1 Introduction2 Probes Based on Fluorescence Quenching3 Chirogenic G-Quartet Probes4 Chromogenic Probes Using Dynamic Covalent Bonds5 Self-Assembled Host–Dye Reporter Pairs6 Conclusions and Outlook

A crown ether supramolecular host-guest complex with Keggin polyoxometalate: Synthesis, crystal structure and electrocatalytic performance for hydrogen evolution reaction

A new crown ether–polyoxometalate assembly [K(H24C12O6)]3[K(H24C12O6)(CH3CN)][SiMo12O40] (1) based on the Keggin-type polyanion [SiMo12O40]4− was successfully synthesized through one-pot strategy in acetonitrile solution. The polyanion is coordinated to two [K([18]-crown-6)]+ supramolecular cations via crown–K–O(POM) coordinate-covalent bonds, leading to the formation of a spindle-shaped discrete structure. Complex 1 exhibited good hydrogen evolution reaction (HER) activity in an acidic medium. Moreover, a small overpotential η10 of 120 mV and a Tafel slope of 112 mV dec−1 were obtained. This crown ether–polyoxometalate hybrid electrocatalyst also presented excellent HER stability even after 2000 cycles of operation.

Supramolecular Nanohelix Fabricated by Pillararene-Based Host–Guest System for Chirality Amplification, Transfer, and Circularly Polarized Luminescence in Water

Supramolecular Nanohelix Fabricated by Pillararene-Based Host–Guest System for Chirality Amplification, Transfer, and Circularly Polarized Luminescence in Water

Host-guest supramolecular interaction behavior at the interface between anode and electrolyte for long life Zn anode

The hydrogen evolution reaction (HER) and dendrite growth associated with Zn anode have become the main bottlenecks for the further development of zinc ion batteries (ZIBs). In this work, the electrochemical activity of H3O+ is inhibited by the supramolecular host–guest complex composed of H3O+ as guest and 18-crown-6 as host. The even Zn plating is induced by the host–guest complex electrostatic shielding layer on Zn anode, as detected by in-situ optical microscopy. The lamellar Zn is plated which profits from the improved Zn plating behavior. Density functional theory (DFT) calculation presents the stable structure of complex. The less produced H2 content is monitored online by a mass spectrometer during Zn plating/stripping, which indicates HER can be hampered by the host–guest behavior. Thus, the ZIBs with long life and high Coulombic efficiency are achieved via introducing 18-crown-6. The proposed host–guest supramolecular interaction is expected to facilitate the furthermore development of Zn batteries.

β-Cyclodextrin-Derivative-Functionalized Graphene Oxide/Graphitic Carbon Nitride Composites with a Synergistic Effect for Rapid and Efficient Sterilization.

The nonselectivity of phototherapy and the hydrophobicity of phototherapy agents limit their application in the treatment of antibiotic-resistant bacteria. In this work, β-cyclodextrin-derivative-functionalized graphene oxide (GO)/graphitic carbon nitride (g-C3N4) antibacterial materials (CDM/GO/CN) were designed and synthesized. CN is used as a photosensitizer for photodynamic therapy (PDT) and GO as a photothermal agent for photothermal therapy (PTT). In addition, the supramolecular host-guest complex on the substrate can not only increase the inherent water solubility of the substrate and reduce the aggregation of the photosensitizer/photothermal agent but also manipulate the interaction between the photosensitizer/photothermal agent and bacteria to capture specific bacteria. The hyperthermia caused by PTT denatures proteins on the cell membrane, allowing reactive oxygen species (ROS) to enter the cell better and kill bacteria. The specific capture of Escherichia coli CICC 20091 by mannose significantly improves the sterilization efficiency and reduces side effects. The synergistic antibacterial agent shows excellent antibacterial efficacy of over 99.25% against E. coli CICC 20091 after 10 min of 635 + 808 nm dual-light irradiation. Moreover, cell proliferation experiments show that the composite material has good biocompatibility, expected to have applications in bacterial infections.

Cucurbit[n]uril-based host-guest interaction enhancing organic room-temperature phosphorescence of phthalic anhydride derivatives in aqueous solution

A cyan RTP in aqueous solution was enhanced by supramolecular host–guest complexation of water-soluble halogen-substituted phthalic anhydride (PA) derivatives with cucurbit[n]urils (CB[n]s).

Supramolecularly regulated artificial transmembrane signal transduction for 'ON/OFF'-switchable enzyme catalysis.

An artificial signal transduction model with a supramolecular recognition headgroup, a membrane anchoring group, and a pro-enzyme catalysis endgroup was constructed. The transmembrane translocation of the transducer can be reversibly regulated by competitive host-guest complexations as an input signal to control an enzyme reaction inside the lipid vesicles.

VCD spectroscopy reveals conformational changes of chiral crown ethers upon complexation of potassium and ammonium cations.

Two chiral derivatives of 18-crown-6, namely the host molecules 2,3-diphenyl- and 2-phenyl-18c6, serve as model systems to investigate whether VCD spectroscopy can be used to monitor conformational changes occurring upon complexation of guests. Host-guest complexes of both crown ethers were prepared by addition of KNO3. The more bulky 2,3-diphenyl-18c6 is found to undergo major conformational changes upon encapsulation of K+, which are revealed as characteristic changes of the VCD spectral signatures. In contrast, while 2-phenyl-18c6 also incorporates K+ into the macrocycle, strong conformational changes are not occurring and thus spectral changes are negligible. With an octyl ammonium cation as guest molecule, 2,3-diphenyl-18c6 shows the same conformational and spectral changes that were observed for K+-complexes. In addition, the asymmetric NH3-deformation modes are found to gain VCD intensity through an induced VCD process. An analysis of the vibrational spectra enables a differentiation of VCD active and inactive guest modes: There appears to be a correlation between the symmetry of the vibrational mode and the induced VCD intensity. While this finding makes the host-guest complexes interesting systems for future theoretical studies on the origin of induced VCD signatures, the observations described in this study demonstrate that VCD spectroscopy is indeed a suitable technique for the characterization of supramolecular host-guest complexes.

Inclusion complex of thymol and hydroxypropyl-β-cyclodextrin (HP-β-CD) in polymeric hydrogel for topical application: Physicochemical characterization, molecular docking, and stability evaluation

The current investigation aimed to prepare and characterize the inclusion complex of thymol with hydroxypropyl-β-cyclodextrin (HP-β-CD) to uniformly incorporate in hydrogel system for its topical application. An inclusion complex of thymol with HP-β-CD was formulated through different methods viz. physical mixture, kneading, and co-precipitation. Phase solubility study was carried out to find the stability constant of complex. Further, the inclusion complex of thymol with HP-β-CD was characterized by DSC, FT-IR, and 1H NMR spectroscopy. The molecular docking studies were also performed to understand the molecular interactions of stable supra-molecular host-guest inclusion complex of thymol with HP-β-CD. After that inclusion complex was incorporated in carbopol 940 hydrogel and evaluated for its drug content, pH, homogeneity, rheological behavior, and in-vitro release. The phase solubility graph demonstrated AL type correlation with apparent stability constant (K1:1) of 370 M−1. The inclusion complex formulated by the co-precipitation technique exhibited the highest dissolution rate (98.73%) of thymol as compared to kneading and physical methods. The DSC, FT-IR and 1H NMR spectroscopic analysis confirmed the formation of inclusion complex between thymol and HP-β-CD. The molecular docking study has confirmed that the binding affinity of thymol with the HP-β-CD was −9.6 kcal/mol, indicating desirable stability of the prepared inclusion complex. The diffusion flux of thymol in a form of inclusion complex was found to be approximately 4.4 folds higher as compared to that of thymol in the hydrogel system for topical administration. The in vitro release of thymol from carbopol 940 hydrogel system exhibited a sustained release profile with thixotropic behaviour. The thymol in a form of inclusion complex was found to be stable in the developed hydrogel system according to ICH guidelines. Therefore, incorporation of thymol in form of inclusion complex in hydrogel system is an effective approach to improve its biopharmaceutical performance for topical administration.

Cyclodextrin/Adamantane-Mediated Targeting of Inoculated Bacteria in Mice.

Cyclodextrin (CD)-based host–guest interactions with adamantane (Ad) have demonstrated use for functionalizing living cells in vitro. The next step in this supramolecular functionalization approach is to explore the concept to deliver chemical cargo to living cells in vivo, e.g., inoculated bacteria, in order to study their dissemination. We validated this concept in two rodent Staphylococcus aureus models. Bacteria (1 × 108 viable S. aureus) were inoculated by (1) intramuscular injection or (2) intrasplenic injection followed by dissemination throughout the liver. The bacteria were prefunctionalized with 99mTc-UBI29–41-Ad2 (primary vector), which allowed us to both determine the bacterial load and create an in vivo target for the secondary host-vector (24 h post-inoculation). The secondary vector, i.e., chemical cargo delivery system, made use of a 111In-Cy50.5CD9PIBMA39 polymer that was administered intravenously. Bacteria-specific cargo delivery as a result of vector complexation was evaluated by dual-isotope SPECT imaging and biodistribution studies (111In), and by fluorescence (Cy5); these evaluations were performed 4 h post-injection of the secondary vector. Mice inoculated with nonfunctionalized S. aureus and mice without an infection served as controls. Dual-isotope SPECT imaging demonstrated that 111In-Cy50.5CD9PIBMA39 colocalized with 99mTc-UBI29–41-Ad2-labeled bacteria in both muscle and liver. In inoculated muscle, a 2-fold higher uptake level (3.2 ± 1.0%ID/g) was noted compared to inoculation with nonfunctionalized bacteria (1.9 ± 0.4%ID/g), and a 16-fold higher uptake level compared to noninfected muscle (0.2 ± 0.1%ID/g). The hepatic accumulation of the host-vector was nearly 10-fold higher (27.1 ± 11.1%ID/g) compared to the noninfected control (2.7 ± 0.3%ID/g; p < 0.05). Fluorescence imaging of the secondary vector corroborated SPECT-imaging and biodistribution findings. We have demonstrated that supramolecular host–guest complexation can be harnessed to achieve an in vivo cargo delivery strategy, using two different bacterial models in soft tissue and liver. This proof-of-principle study paves a path toward developing innovative drug delivery concepts via cell functionalization techniques.

Supramolecular Hydrogels with Tunable Swelling by Host Complexation with Cyclobis(paraquat-p-phenylene)

Controlling the swelling properties of hydrogels is of primary importance for many applications ranging from actuators and valves to tissue engineering and drug delivery. Herein, we report the use of cyclobis(paraquat-p-phenylene) (CBPQT4+,4X–) as a versatile host to fine-tune the swelling behavior of 1,5-dialkyloxynaphthalene guest containing poly(N,N-dimethylacrylamide) hydrogels (NaphtGelz) through supramolecular host–guest complexation. While the equilibrium swelling of NaphtGelz in water decreases with increasing amount of hydrophobic naphthalene groups, the opposite behavior is observed with superabsorbing behavior (up to 180 times their initial dry mass) upon immersion in aqueous solutions containing the macrocyclic CBPQT4+,4X– due to formation of tetracationic host–guest complexes. In this case, the swelling amplitude could be conveniently programmed either by variation of the naphthalene content of the hydrogels or by controlling the stoichiometry of the host–guest binding events. Furthermore, by modifying the nature of the counterions (X = Cl–, Br–, and I–) of the tetracationic CBPQT4+ macrocyclic host, the swelling of the hydrogels could be tuned in line with Pearson’s absolute hardness scale of X–. The swelling behavior of these supramolecular hydrogels could be successfully described by a theoretical model, taking into account the hydrophobic association of the naphthalene groups and their screening by host–guest complexation. Finally, addition of sodium dodecyl sulfate as a surfactant to the supramolecularly swollen hydrogels led to a large decrease in hydrogel size due to dissociation of the host–guest complexes and the formation of CBPQT4+,4DS– within the hydrogel.

Dynamics of Anthracene Excimer Formation within a Water-Soluble Nanocavity at Room Temperature.

Excited anthracene is well-known to photodimerize and not to exhibit excimer emission in isotropic organic solvents. Anthracene (AN) forms two types of supramolecular host-guest complexes (2:1 and 2:2, H:G) with the synthetic host octa acid in aqueous medium. Excitation of the 2:2 complex results in intense excimer emission, as reported previously, while the 2:1 complex, as expected, yields only monomer emission. This study includes confirming of host-guest complexation by NMR, probing the host-guest structure by molecular dynamics simulation, following the dynamics AN molecules in the excited state by ultrafast time-resolved experiments, and mapping of the excited surface through quantum chemical calculations (QM/MM-TDDFT method). Importantly, time-resolved emission experiments revealed the excimer emission maximum to be time dependent. This observation is unique and is not in line with the textbook examples of time-independent monomer-excimer emission maxima of aromatics in solution. The presence of at least one intermediate between the monomer and the excimer is inferred from time-resolved area normalized emission spectra. Potential energy curves calculated for the ground and excited states of two adjacent anthracene molecules via the QM/MM-TDDFT method support the model proposed on the basis of time-resolved experiments. The results presented here on the excited-state behavior of a well-investigated aromatic molecule, namely the parent anthracene, establish that the behavior of a molecule drastically changes under confinement. The results presented here have implications on the behavior of molecules in biological systems.

Supramolecular host-guest complex of methylated β-cyclodextrin with polymerized ionic liquid ([vbim]TFSI)n as highly effective and energy-efficient thermo-regenerable draw solutes in forward osmosis

Supramolecular inclusion complexes with lower critical solution temperature (LCST) properties were investigated for the first time as forward osmosis (FO) draw solutes. Randomly methylated-β-cyclodextrin (Rm-β-CD) host molecules accommodate polymerized ionic liquids (([vbim]TFSI)n PILs) through their hydrophobic TFSI− anions as guests. LCST properties were tuned by varying the chain lengths of ([vbim]TFSI)n, from which, short-chain oligo([vbim]TFSI) was found most suitable. Draw solutions (DS) of Rm-β-CD/oligo([vbim]TFSI) complex have highly tunable cloud-point temperatures (Tc), fast LCST kinetics and sufficient osmotic properties for an efficient FO. Under PRO mode, 0.5 M Rm-β-CD/0.078 M oligo([vbim]TFSI) induced competitive FO water flux (Jv ~13.73 L m−2h−1) and negligible reverse solute flux (Js ~4.41 × 10−3 mol m−2h−1) against DI water feed. It successfully processed different saline feeds (0.034 M and 0.6 M NaCl) with reasonable FO performance and superior Js/JV ~0.001 mol m−2h−1, demonstrating its competence for FO desalination. When heated slightly above its Tc = 29 °C (TTP = 30 °C), thermal precipitation (TP) is ensued with the release of TFSI− anions in oligo([vbim]TFSI) from Rm-β-CD. Due to its hydrophobicity, oligo([vbim]TFSI) precipitates while entrapping the suspended Rm-β-CDs between its chains causing flocculation and sedimentation. Thus, with only +5 °C heating above FO temperature (25 °C), 95% of draw solutes are effectively recovered from the spent DS after settling. Residual (~5%) Rm-β-CD in the DS supernatant is subsequently removed via nanofiltration at 99.33% rejection, producing non-toxic water effluent based on in vitro cytotoxicity results. Energy consumption estimates reveal the feasibility of Rm-β-CD/oligo([vbim]TFSI) as it requires minimal heat energy for recovery. This study offers new insights on the potential of host-guest complexes as a new class of energy-efficient draw solutes for FO desalination technology.

Single-crystal structures of cucurbituril-based supramolecular host-guest complexes for bioimaging.

Two single-crystal structures of cucurbit[n]uril mediated supramolecular complexes were obtained in which [1+3] and [2+3] self-assembly modes are adopted due to the different sizes of cucurbit[7]uril and cucurbit[8]uril. An obvious red-shift in absorption and emission was observed compared to the guest molecule itself which makes them good biolabels.

Highly Stable and Fine-Textured Hybrid Microspheres for Entrapment of Cosmetic Active Ingredients.

This study details the preparation and application of supramolecular host–guest inclusion complexes entrapping biomineralized microspheres for long-term storage and their pH-responsive behavior. The microspheres were assembled using a CaCO3 synthesis process coupled with cyclodextrin–tetrahydrocurcumin (CD–THC) inclusion complexes, forming fine-textured and mechanically stable hybrid materials. The products were successfully characterized using field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and particle size analysis (PSA). Various parameters such as the Brunauer–Emmett–Teller (BET) surface area, single point total pore volume, and pore size via adsorption/desorption analysis were also determined. The obtained THC-entrapped hybrid microspheres contained as high as 20 wt % THC loading and were very stable, preserving 90% of the initial concentration over four weeks of storage at different temperatures, largely limiting THC leaching and indicating high stability in a physiological environment. In addition, the pH-responsive release of THC from the hybrid microspheres was observed, showing potential use for application to weakly acidic skin surfaces. To our knowledge, this is the first demonstration of antiaging cosmetic formulation technology using biomineralization based on the co-synthesis of CaCO3 and CD–THC complexes.

Water-soluble host-guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres.

A sugar-functionalized water-soluble tribenzotriquinacene derivative bearing six glucose residues, TBTQ-(OG)6, was synthesized and its interaction with C60 and C70-fullerene in co-organic solvents and aqueous solution was investigated by fluorescence spectroscopy and ultraviolet-visible spectroscopy. The association stoichiometry of the complexes TBTQ-(OG)6 with C60 and TBTQ-(OG)6 with C70 was found to be 1:1 with binding constants of Ka = (1.50 ± 0.10) × 105 M−1 and Ka = (2.20 ± 0.16) × 105 M−1, respectively. The binding affinity between TBTQ-(OG)6 and C60 was further verified by Raman spectroscopy. The geometry of the complex of TBTQ-(OG)6 with C60 deduced from DFT calculations indicates that the driving force of the complexation is mainly due to the hydrophobic effect and to host–guest π–π interactions. Hydrophobic surface simulations showed that TBTQ-(OG)6 and C60 forms an amphiphilic supramolecular host–guest complex, which further assembles to microspheres with diameters of 0.3–3.5 μm, as determined by scanning electron microscopy.

The supramolecular host-guest complexation of Vemurafenib with β-cyclodextrin and cucurbit[7]uril as drug photoprotecting systems: A DFT/TD-DFT study

The supramolecular host-guest complexation of the first-line anticancer drug Vemurafenib (VFB) with β-cyclodextrin (β-CD) and cucurbit[7]uril (CB7) is computationally investigated employing the DFT/TD-DFT method in implicit aqueous solutions. The structures of the 1:1 complexes of VFB:β-CD and VFB:CB7 are stabilized by intermolecular hydrogen bonds (HB) that are oriented at the rims of the host molecules with an average length of 2.00 Å. The results of the thermodynamic quantities revealed Δ G° values of −15.3 and −6.2 kcal/mol associated with the formation of VFB:β-CD-I and VFB:CB7-I complexes, respectively. These results suggest that the supramolecular host-guest complexation of VFB with β-CD is favored over CB7, which in turn can be attributed to the formation of cooperative HBs. The stability of the examined complexes was verified as revealed by molecular dynamics analyses, where these complexes exhibited changes of only ±0.02 kcal/mol and ±0.06 Å in their total energy and length of key HBs, respectively.

A thermo and photoresponsive dual performing hydrogel for multiple controlled release mechanisms

A hydrogel with dual thermo and photoresponsive characteristics was developed. Using poly(N-isopropylacrylamide) (PNIPAM) as the thermosensitive unit, the hydrogel network can undergo reversible swelling/shrinking behavior under different temperatures (20 °C and 37 °C) stimulation. A supramolecular host–guest complex composed of azobenzene (Azo) and α-cyclodextrin (α-CD) was used as the photosensitive unit. Azo and α-CD can undergo reversible recombination/dissociation behavior under the stimulation of different wavelengths of light (365 nm and 430 nm). Methylene blue (MB) was selected as the model drug to measure the controlled release behavior of the hydrogel under different temperatures and photoirradiations. The experimental results showed that the hydrogel containing the thermosensitive component (PNIPAM) and the photosensitive component (α-CD/Azo) released 69.3% and 47.2% of MB at 20 °C and 37 °C, respectively. Under the condition of light wavelengths at 430 nm and 365 nm, 73.2% and 65.6% of MB were released, respectively. The results showed that α-CD and Azo formed a supramolecular host–guest complex, which could undergo reversible binding/dissociation under the action of light stimulation, thereby controlling MB to enter and exit CD cavity. In addition, when the ambient temperature was lower or higher than the lower critical solution temperature of PNIPAM (LCST, 32 °C), the hydrogel underwent a responsive volume change to control the loading and release of MB molecules. So, combining the dual thermo and photoresponsibility, this smart hydrogel could be applied for multiple controlled release mechanisms.

Host-guest complexes - Boosting the performance of photosensitizers.

In this review, we will show the diversity of supramolecular host-guest complexes of cyclodextrins, cucurbit[n]urils, calix[n]- and pillar[n]arenes with photosensitizers, like porphyrins and phthalocyanines. Host-guest complexes are one of the main building blocks in supramolecular chemistry. For example, they have been widely used to encapsulate hydrophobic drug molecules to enhance the bioavailability in the human body. In these days of multiresistant bacteria and difficulties in cancer therapy, supramolecular host-guest systems with photosensitizers for the photodynamic therapy(PDT) gain more and more interest. In general, photosensitizers with a (large) conjugated aromatic π-system are used, which tend to π-πstacking in aqueous media suppressing the cell toxicity by singletoxygen production quenching. This can be overcome by the formation of host-guest complexes. Besides that, encapsulation of the photosensitizers in host molecules can enhance the solubility, increase cellular uptake, lead to hydrogels, rotaxanes, and switchable systems.

Threading Different Rings on X-Shaped Block Copolymers: Hybrid Pseudopolyrotaxanes of Cyclodextrins and Tetronics

Pseudopolyrotaxanes (PPRs) are supramolecular host–guest complexes constituted by the reversible threading of macrocycles along a polymer chain. We report the formation of hybrid PPRs (hPPRs), wher...