Supramolecular Host-guest Systems Research Articles

Encapsulated Dye in Coordination-Assembled Octahedron for Visible-Light-Driven Proton Reduction and Nitroaromatic Hydrogenation.

To mimic the finely tuned natural photosynthetic systems, a large metal-organic octahedron was synthesized by one-pot self-assembly with modified triphenylamine ligands and redox-active cobalt ions. By encapsulating an organic dye, fluorescein (Fl), within the inner cavity of the octahedron, the host-guest supramolecular system was provided for light-driven hydrogen production. The intimate distance between the redox site and the photosensitizer in the supramolecular metal-organic cage allowed the photoinduced electrons to transfer from the excited state Fl* to the redox cobalt center in a pseudo-intramolecular pathway. The supramolecular system showed good performance in light-driven hydrogen production and the reduction of nitroaromatic compounds. Control experiments based on a mononuclear compound resembling a cobalt corner of the octahedron and inhibitor competition provided evidence of enzyme-like catalytic behavior. The supramolecular reaction pathways within confined spaces contribute to the superior activity of the host-guest system.

Voltammetric Sensing of Chloride Based on a Redox-Active Complex: A Terpyridine-Co(II)-Dipyrromethene Functionalized Anion Receptor Deposited on a Gold Electrode.

A redox-active complex containing Co(II) connected to a terpyridine (TPY) and dipyrromethene functionalized anion receptor (DPM-AR) was created on a gold electrode surface. This host-guest supramolecular system based on a redox-active layer was used for voltammetric detection of chloride anions in aqueous solutions. The sensing mechanism was based on the changes in the redox activity of the complex observed upon binding of the anion to the receptor. The electron transfer coefficient (α) and electron transfer rate constant (k0) for the modified gold electrodes were calculated based on Cyclic Voltammetry (CV) experiments results. On the other hand, the sensing abilities were examined using Square Wave Voltammetry (SWV). More importantly, the anion receptor was selective to chloride, resulting in the highest change in Co(II) current intensity and allowing to distinguish chloride, sulfate and bromide. The proposed system displayed the highest sensitivity to Cl- with a limit of detection of 0.50 fM. The order of selectivity was: Cl- > SO42- > Br-, which was confirmed by the binding constants (K) and reaction coupling efficiencies (RCE).

Overcoming barriers with non-covalent interactions: supramolecular recognition of adamantyl cucurbit[n]uril assemblies for medical applications.

Adamantane, a staple in medicinal chemistry, recently became a cornerstone of a supramolecular host-guest drug delivery system, ADA/CB[n]. Owing to a good fit between the adamantane cage and the host cavity of the cucurbit[n]uril macrocycle, formed strong inclusion complexes find applications in drug delivery and controlled drug release. Note that the cucurbit[n]uril host is not solely a delivery vehicle of the ADA/CB[n] system but rather influences the bioactivity and bioavailability of drug molecules and can tune drug properties. Namely, as host-guest interactions are capable of changing the intrinsic properties of the guest molecule, inclusion complexes can become more soluble, bioavailable and more resistant to metabolic conditions compared to individual non-complexed molecules. Such synergistic effects have implications for practical bioapplicability of this complex system and provide a new viewpoint to therapy, beyond the traditional single drug molecule approach. By achieving a balance between guest encapsulation and release, the ADA/CB[n] system has also found use beyond just drug delivery, in fields like bioanalytics, sensing assays, bioimaging, etc. Thus, chemosensing in physiological conditions, indicator displacement assays, in vivo diagnostics and hybrid nanostructures are just some recent examples of the ADA/CB[n] applicability, be it for displacements purposes or as cargo vehicles.

Dynamic host-guest interfacial recognition of alginate-based β-cyclodextrin/cholic acid supra-amphiphiles for stabilizing multi-type Pickering emulsion

The multi-type Pickering emulsions were formed by macromolecule-based soft colloidal emulsifiers due to its great architectural tailorability. Herein, the supramolecular β-cyclodextrin-modified alginate/cholic acid-grafted alkyl chain (SA-CD/CA-C12) system was designed by β-CD/CA-engineered host-guest molecular recognition at oil-water interface. Especially, supra-amphiphilic SA-CD/CA-C12 self-assemblies acted as excellent colloidal surfactant with high interfacial activity (0.74 mN/m), and the interfacial adsorption films exhibited higher coverages and thickness in contrast to that of alone amphiphilic SA-CD, and CA-C12 system, further preventing interdroplets aggregation, collision, and coalescence. Furthermore, the W/O, bicontinuous, and O/W emulsions were generated by altering the oil/water volume ratio due to the dynamical host-guest recognition-induced self-regulated flexibility of macromolecular architectonics. Additionally, the microstructures of supramolecular host-guest emulsion-templated aerogel were regulated by tuning the aggregation behaviors of supramolecular host-guest interfacial system, providing a new strategy for engineering soft materials.

Supramolecular Chemotherapy with Cucurbit[n]urils as Encapsulating Hosts.

The cucurbit[n]urils (CB[n]) belong to the field of relatively young supramolecules which act as containers for a large variety of guests and are being explored extensively for their numerous biomedical applications. This includes drug formulation and delivery, controlled drug release, photodynamic therapy, sensing for bioanalytical purposes, etc. These supramolecular host-guest systems have distinctive recognition properties and have successfully been shown to enhance the in vitro and in vivo utility of various chemotherapeutic agents. The CB[n]s are tailored to optimize their application in payload delivery and diagnostics and in lowering the toxicity of existing drugs. This review has listed the recent studies on working mechanisms and host-guest complexation of the biologically vital molecules with CB[n] and highlighted their implementation in anticancer therapeutics. Various modifications in CB-drug inclusion compounds like CB supramolecular nanoarchitectures along with application in photodynamic therapy, which has shown potential as targeted drug delivery vehicles in cancer chemotherapy, have also been discussed.

Supramolecular Cucurbit[7]uril@Ferrocene Complexation on Surface: From Nanostructure Differentiation to Guest Quantitation

ConspectusCucurbit[7]uril (CB[7]), an important member of the macrocyclic cucurbit[n]uril host family, has attracted much attention due to its ability to form ultrastable inclusion complexes with aromatic or “ring”-structured compounds. In particular, for the CB[7]@ferrocene (Fc) host–guest complex, its exceptionally high binding affinity, ideal redox activity, and extreme stability against biological media have promoted its potential to substitute traditional natural binding pairs (antigen/antibody and biotin/avidin complexes as examples) in many biochemical applications, such as purification, labeling, and biomolecular assembly. In recent years, the immobilization of CB[7]@Fc host–guest complex on electrode surface via various strategies has expanded its use for fabricating electroactive biofunctional devices, such as electrochemical biosensors and switches, where the redox response of Fc/Fc+ can be used as both characterization and sensing signal. These applications require in-depth understanding of the interfacial CB[7]@Fc host–guest binding behavior, which is different from that in a homogeneous solution phase; such studies, in turn, will facilitate the design and development of more efficient interfacial host–guest binding systems.With the advantages of easy preparation, high stability, and reversible redox response, ferrocenyl alkanethiolate self-assembled monolayers (SAMs) on gold have been widely employed as an electroanalytical platform for studying electron transfer behavior and molecular interactions (i.e., ion pairing) and probing microenvironmental changes. In order to achieve an “ideal” redox response for these applications (e.g., a single pair of redox peaks), mixed Fc-alkanethiolate SAMs with low Fc coverage are usually prepared, where the influences from different structural domains and nonuniform distribution of Fc terminal groups in the SAM are minimized.In the past decade, our team has been exploring the renewed applications of Fc-alkanethiolate SAMs, while performing characterizations of their structural properties by electrochemistry and other surface techniques. In particular, we employed redox-active Fc-alkanethiolate SAMs to quantitatively study the interfacial CB[7]@Fc host–guest binding and explored a range of applications for nanostructure differentiation, long-range electron transfer regulation, and quantitation of non-redox-active guests. Besides, we have extended our electrochemical study of interfacial CB[7]@Fc host–guest binding with CB[7]-terminated alkanethiolate SAMs, where the electrochemical quantitation of the CB[7]@Fc host–guest complex formed on an electrode surface becomes straightforward.In this Account, we first provide a brief literature review of the CB[7]@Fc host–guest chemistry, including fundamental studies in solution as well as the challenges for its application on surfaces. Subsequently, we describe our studies of interfacial CB[7]@Fc host–guest complexation on binary SAMs on gold, including fundamental voltammetric evaluation of binding thermodynamics and kinetics, as well as its applications. Lastly, we introduce our recent electrochemical study on interfacial CB[7]@Fc complexation by tethering CB[7] on alkanethiolate SAMs (via click chemistry). These research accomplishments shed light on the profound ability of forming interfacial CB[7]@Fc host–guest binding systems for both fundamental studies and practical applications; the knowledge obtained herein paves the way to further understanding of surface-immobilized supramolecular host–guest systems.

Single-Crystal X-ray Diffraction Analysis of Inclusion Complexes of Triflate-Functionalized Pillar[5]arenes with 1,4-Dibromobutane and n-Hexane Guests

Herein, we report the single-crystal X-ray diffraction analysis of supramolecular host–guest systems based on triflate-functionalized pillar[5]arenes and 1,4-dibromobutane or n-hexane. The guest molecule was stabilized inside the pillar[5]arene cavity by C–H⋯π and C–H⋯O interactions. These inclusion complexes were further self-assembled into supramolecular networks by various non-bonding interactions such as C-H⋯O, C-H⋯F, Br⋯Br, F⋯F, etc. The intermolecular interactions present in these systems were investigated in detail. One of the supramolecular systems analyzed in this study exhibited intermolecular F⋯F interactions which were operative between the adjacent pillararene rims. It was observed that the type of guest molecule considerably influenced the mutual interactions of pillararene macrocycles and their networking pattern in the crystal. The inclusion complexes were further studied by Hirshfeld surface analysis which not only provided a visual representation of the intermolecular interactions experienced by the systems but gave a quantitative account of these various interactions.

Supramolecular Coordination Cages for Artificial Photosynthesis and Synthetic Photocatalysis.

Because sunlight is the most abundant energy source on earth, it has huge potential for practical applications ranging from sustainable energy supply to light driven chemistry. From a chemical perspective, excited states generated by light make thermodynamically uphill reactions possible, which forms the basis for energy storage into fuels. In addition, with light, open-shell species can be generated which open up new reaction pathways in organic synthesis. Crucial are photosensitizers, which absorb light and transfer energy to substrates by various mechanisms, processes that highly depend on the distance between the molecules involved. Supramolecular coordination cages are well studied and synthetically accessible reaction vessels with single cavities for guest binding, ensuring close proximity of different components. Due to high modularity of their size, shape, and the nature of metal centers and ligands, cages are ideal platforms to exploit preorganization in photocatalysis. Herein we focus on the application of supramolecular cages for photocatalysis in artificial photosynthesis and in organic photo(redox) catalysis. Finally, a brief overview of immobilization strategies for supramolecular cages provides tools for implementing cages into devices. This review provides inspiration for future design of photocatalytic supramolecular host-guest systems and their application in producing solar fuels and complex organic molecules.

Exploring π-π interactions and electron transport in complexes involving a hexacationic host and PAH guest: a promising avenue for molecular devices.

Single isolated molecules and supramolecular host-guest systems, which consist of π-π stacking interactions, are emerging as promising building blocks for creating molecular electronic devices. In this article, we have investigated the noncovalent π-π interaction and intermolecular electron charge transport involved in a series of host-guest complexes formed between a cage-like host (H6+) and polycyclic aromatic hydrocarbon (PAH) guests (G1-G7) using different quantum chemical approaches. The host (H6+) consists of two triscationic π-electron-deficient trispyridiniumtriazine (TPZ3+) units that are bridged face-to-face by three ethylene-triazole-ethylene. Our theoretical calculations show that the perylene and naphthalene inclusion complexes G7⊂H and G1⊂H have the highest and lowest interaction energies, respectively. In addition, energy decomposition analysis (EDA) indicated that the dispersion interaction term, ΔEdisp, significantly contributes to the host-guest interaction and is correlated with the existence of π-π van der Waals interaction. Using the nonequilibrium Greens function (NEGF) method in combination with density functional theory (DFT), the current-voltage (I-V) curves of the complexes were estimated. The conductance values increased when the guests were embedded inside the host cavity. Notably, the complex G7⊂H has the maximum conductance value. Overall, this study provided the electron transport of the PAH inclusion host-guest complex through π-π interaction and provided a direction for the fabrication of future supramolecular molecular devices.

Light-responsive nanochannels based on the supramolecular host-guest system.

The light-responsive nanochannel of rhodopsin gained wider research interest from its crucial roles in light-induced biological functions, such as visual signal transduction and energy conversion, though its poor stability and susceptibility to inactivation in vitro have limited its exploration. However, the fabrication of artificial nanochannels with the properties of physical stability, controllable structure, and easy functional modification becomes a biomimetic system to study the stimulus-responsive gating properties. Typically, light-responsive molecules of azobenzene (Azo), retinal, and spiropyran were introduced into nanochannels as photo-switches, which can change the inner surface wettability of nanochannels under the influence of light; this ultimately results in the photoresponsive nature of biomimetic nanochannels. Furthermore, the fine-tuning of their stimulus-responsive properties can be achieved through the introduction of host–guest systems generally combined with a non-covalent bond, and the assembling process is reversible. These host–guest systems have been introduced into the nanochannels to form different functions. Based on the host–guest system of light-responsive reversible interaction, it can not only change the internal surface properties of the nanochannel and control the recognition and transmission behaviors but also realize the controlled release of a specific host or guest molecules in the nanochannel. At present, macrocyclic host molecules have been introduced into nanochannels including pillararenes, cyclodextrin (CD), and metal–organic frameworks (MOFs). They are introduced into the nanochannel through chemical modification or host–guest assemble methods. Based on the changes in the light-responsive structure of azobenzene, spiropyran, retinal, and others with macrocycle host molecules, the surface charge and hydrophilic and hydrophobic properties of the nanochannel were changed to regulate the ionic and molecular transport. In this study, the development of photoresponsive host and guest-assembled nanochannel systems from design to application is reviewed, and the research prospects and problems of this photo-responsive nanochannel membrane are presented.

Solvent‐Dependent Supramolecular Host–Guest Assemblies of Platinum(II) Tweezers and a Guest System: From Discrete Molecules to High‐Ordered Oligomers

AbstractA series of platinum(II) calix[4]arene‐based molecular tweezers was synthesized. The studies of the host–guest association with a charge‐neutral cyclometalated platinum(II) complex showed a drastic color change and the turning on of near‐infrared emission resulting from Pt⋅⋅⋅Pt and π–π interactions. Control of the host–guest assembly process by varying the solvent composition can lead to a change from discrete host and guest molecules to high‐ordered host–guest oligomers with the formation of sheet‐like nanostructures, demonstrating a rare example of three‐state supramolecular host–guest system with high solubility in solvents of diverse polarity. The change in host–guest assembly behaviors could be probed by drastic color changes from yellow to orange to green. The present study provides insights into the systematic design of solvent‐responsive molecular materials using molecular tweezers‐directed host–guest assembly, with potential applications in colorimetric sensing of changes in the micro‐environment.

Self-assembled cyclodextrins-based nanostructures on indium-tin-oxide for a detection of catecholamine neurotransmitters

Host-guest supramolecular systems are the leading technology to mimic biological systems. The current rapid development of non-enzymatic electrochemical sensors of neurotransmitters urges a focus towards the host-guest system on electrode that enables to selectively bind these analytes with an electrochemical response. In this study, novel method to deposit β- and γ-cyclodextrin-based self-assembled nanostructures with the sub-nanometer scale size cavities on the indium-tin-oxide glass surface was developed. The surfaces were characterized using the electrochemical, vibrational spectroscopy, and atomic force microscopy methods. We have demonstrated that these nanostructures can be easily prepared and regenerated. Our performed theoretical computations demonstrated that neutral and protonated forms of the neurotransmitters can be assembled into the cavities and reduce the ionization potential of the analytes. The electrodes with these nanostructures showed the electrochemical response to dopamine and adrenaline as the catecholamine neurotransmitters. These electrodes provide the low limit of detections in nM level, display good selectivity for these catecholamines over co-existing interferential compounds in living cells. The key advantages of the presented electrochemical systems are their simple and cheap preparation, and the ability to achieve the low levels of catecholamine concentration detections.

Flow-induced-crystallization: tailoring host-guest supramolecular co-assemblies at the liquid-solid interface.

Here, we report that using the method of simply contacting a sample solution droplet with a piece of tissue paper can create a solvent flow (capillary force). During this process, the dynamics and solvent removal can promote the formation and stabilization of a meta-stable linear quasi-crystal composed of p-terphenyl-3,5,3′,5′-tetracarboxylic acid (TPTC) molecules, which would otherwise pack into thermodynamically favored random tiling. The tailored quasi-crystal (linear) template allows atop it higher-efficiency accommodation of fullerene molecules (C60) from 40.1% to 97.5%, compared with that obtained in the random-tiling (porous) case. Overall, the result of this study presents an unusual yet remarkably simple strategy for tailoring complex host–guest supramolecular systems at the liquid–solid interface.

Crystal structure prediction of host–guest supramolecular systems based on β-cyclodextrin dimers and trimers with luminescent probes

A theoretical method is proposed for constructing new crystals consisting of β-cyclodextrin inclusion complexes with luminescent probes and determining their structural parameters.

Surfactant-induced chirality transfer, amplification and inversion in a cucurbit[8]uril–viologen host–guest supramolecular system

The L4 molecular chirality can be amplified to a supramolecular scale by coassembling with SDS. Further incorporation of the CB[8] leads to a chirality inversion via a change from lamellar structure of L4/SDS to rectangular stacking in L4/SDS/CB[8].

Supramolecular Coronation of Platinum(II) Complexes by Macrocycles: Structure, Relativistic DFT Calculations, and Biological Effects.

Platinum-based anticancer drugs are actively developed utilizing lipophilic ligands or drug carriers for the efficient penetration of biomembranes, reduction of side effects, and tumor targeting. We report the development of a supramolecular host-guest system built on cationic platinum(II) compounds bearing ligands anchored in the cavity of the macrocyclic host. The host-guest binding and hydrolysis process on the platinum core were investigated in detail by using NMR, MS, X-ray diffraction, and relativistic DFT calculations. The encapsulation process in cucurbit[7]uril unequivocally promotes the stability of hydrolyzed dicationic cis-[PtII(NH3)2(H2O)(NH2-R)]2+ compared to its trans isomer. Biological screening on the ovarian cancer lines A2780 and A2780/CP shows time-dependent toxicity. Notably, the reported complex and its β-cyclodextrin (β-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@β-CD, respectively, while maintaining a significantly lower toxicity profile.

A host\u2013guest semibiological photosynthesis system coupling artificial and natural enzymes for solar alcohol splitting

Development of a versatile, sustainable and efficient photosynthesis system that integrates intricate catalytic networks and energy modules at the same location is of considerable future value to energy transformation. In the present study, we develop a coenzyme-mediated supramolecular host-guest semibiological system that combines artificial and enzymatic catalysis for photocatalytic hydrogen evolution from alcohol dehydrogenation. This approach involves modification of the microenvironment of a dithiolene-embedded metal-organic cage to trap an organic dye and NADH molecule simultaneously, serving as a hydrogenase analogue to induce effective proton reduction inside the artificial host. This abiotic photocatalytic system is further embedded into the pocket of the alcohol dehydrogenase to couple enzymatic alcohol dehydrogenation. This host-guest approach allows in situ regeneration of NAD+/NADH couple to transfer protons and electrons between the two catalytic cycles, thereby paving a unique avenue for a synergic combination of abiotic and biotic synthetic sequences for photocatalytic fuel and chemical transformation.

A supramolecular host-guest interaction-mediated injectable hydrogel system with enhanced stability and sustained protein release

Injectable hydrogels have been studied as drug delivery systems because of their minimal invasiveness and sustained drug release properties. Pluronic F127, consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers, exhibits thermo-responsive properties and hence is injectable due to its rapid sol-gel transition. Unmodified Pluronic F127-based hydrogels, however, have limited long-term stability and controllable release of drugs entrapped within them. In this study, host-guest interactions between adamantane-conjugated Pluronic F127 (F127-Ad) and polymerized β-cyclodextrin (CDP) were employed to develop a hydrogel-based protein delivery system. Single or multiple adamantane units were successfully introduced at the termini of Pluronic F127 with a 100% conversion yield, and the synthesized F127-Ad polymer produced a physically crosslinked micelle-packing structure when mixed with CDP. As the number of adamantanes at the terminal ends of Pluronic F127 increased, the critical gelation concentration of F127-Ad/CDP hydrogel decreased from 15 to 6% (w/v). The F127/CDP hydrogel was able to maintain its structure even with lower polymer content, and its injectability improved with a reduction of the hydrogel viscosity. The long-term stability of F127/CDP hydrogels was evaluated in vitro and in vivo, and it was demonstrated that the subcutaneously injected hydrogel did not disintegrate for up to 30 d. Throughout the drug release test using gelatin and insulin as model drugs, it was demonstrated that their release rates could be regulated via complexation between the protein drugs and the β-cyclodextrin molecules inside the hydrogel. In conclusion, the F127-Ad/CDP hydrogel is expected to be a versatile protein delivery system with controllable durability and drug release characteristics. Statement of significancePluronic F127 is one of the widely studied polymeric materials for thermo-sensitive injectable hydrogels due to its high biocompatibility and rapid sol-gel transition. Since the Pluronic F127-based hydrogel has some limitations in its long-term stability and mechanical property, it is inevitable to modify its structure for the application to drug delivery. In this study, mono- or multi- adamantane-conjugated Pluronic F127s were synthesized and mixed with β-cyclodextrin polymers to form hydrogels with host-guest interaction-mediated micelle-packing structures. The host-guest interaction introduced into the hydrogel system endowed it a sustained protein drug release behavior as well as high durability in vitro and in vivo. By increasing the number of adamantane molecules at the end of the Pluronic F127, both the stability and injectability of the hydrogel could be also modulated.

Nonviral DNA Delivery System with Supramolecular PEGylation Formed by Host-Guest Pseudo-Block Copolymers.

A cationic supramolecular system based on host-guest pseudoblock copolymers was developed for nonviral DNA delivery. In this system, the macromolecular host was a cationic star-shaped polymer composed of a β-cyclodextrin (β-CD) core and multiple poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) chains grafted on the core, while the macromolecular guest was a linear adamantyl-ended poly(ethylene glycol) (mPEG-Ad). Pseudoblock copolymers were self-assembled from the polymeric host-guest pairs (typically, 1:1 molar ratio) in aqueous media through the inclusion of an adamantyl group at the end of guest polymer into the β-CD cavity of host polymers. Through such an approach, the resultant supramolecular system was integrated with not only a superior DNA condensing ability due to the host polymer but also an outstanding polyplex-stabilizing ability as well as biocompatibility due to the guest polymer. The cationic star-shaped host polymers alone were capable of condensing plasmid DNA efficiently into nanoparticles (70-100 nm) with positive surface charge. They showed obviously lower cytotoxicity than PEI 25K (commercial branched polyethylenimine with a molecular weight around 25 kDa) in cell lines of L929, MB231, and Hela under high dose. In serum-free or serum-containing culture conditions, these host polymers exhibited either higher or lower in vitro DNA transfection efficiency as compared with PEI 25K in the three cell lines under study, which was dependent on the N/P ratios and PDMAEMA arm length. Upon incorporation of the PEG block through host-guest complexation with mPEG-Ad (i.e., supramolecular PEGylation), the resulting host-guest supramolecular systems exhibited even lower cytotoxicity than the host polymers alone. The polyplexes between plasmid DNA (pDNA) and the host-guest systems showed significantly improved stability in BSA-PBS buffer solution (pH 7.4) and enhanced in vitro DNA transfection efficiency in the cases of higher N/P ratios or longer PDMAEMA arms in all tested cell lines under both serum-free and serum-containing culture conditions, as compared with the corresponding polyplexes without supramolecular PEGylation. Further, through forming pseudoblock copolymer, the DNA transfection ability of the supramolecular system can be easily modulated and optimized either by changing the ratio between the guest and host or by using different hosts with varied PDMAEMA arm lengths.

Dynamic Macro- and Microgels Driven by Adenosine Triphosphate-Fueled Competitive Host–Guest Interaction

Supramolecular host–guest systems are generally at thermodynamic equilibrium states or in kinetically trapped states. Herein, we demonstrate the concept of a chemical fuel-driven competitive host–g...