Covalent connection of individualized, neutral, dendronized polymers on a solid substrate using a scanning force microscope

The synthesis of a neutral, high-molar-mass, acrylamide-based, third-generation dendronized polymer (denpol) with a defined number of azide groups at its periphery is reported. An attach-to route is used in which a first-generation denpol is reacted with second-generation (G2) dendrons. The degree of structure perfection of the resulting denpol is quantified as 99.8 %. This value was obtained after the introduction of a fluorescence label at the sites that remained unaffected by the dendronization. The high coverage was independently confirmed for the dendronization of another first-generation polymer and a closely related G2 dendron. The third-generation denpol resulting from the first dendronization experiment was spin-coated as a sub-monolayer onto highly oriented graphite precoated with an ultrathin layer of C12H25NH2, which was introduced to provide a well-defined substrate for denpol adsorption and manipulation. Scanning force microscopy revealed single denpols, which could be moved across the surface and "welded" by covalent cross-linking induced by photochemical decomposition of the azides into highly reactive nitrenes. The successful formation of covalent bonds between two denpols was confirmed by mechanically challenging the link with the scanning force microscope (SFM) tip. This is the second reported case of a move-connect-prove sequence using polymers and the SFM, which for the first time employs noncharged denpols, thus widening the applicability of this method significantly.     

Thermoresponsive Supramolecular Dendronized Polymers

Combining the concepts of supramolecular polymers and dendronized polymers provides the opportunity to create bulky polymers with easy structural modification and tunable properties. In the present work, a novel class of side‐chain supramolecular dendronized polymethacrylates is prepared through the host–guest interaction. The host is a linear polymethacrylate (as the backbone) attached in each repeat unit with a β‐cyclodextrin (β‐CD) moiety, and the guest is constituted with three‐fold branched oligoethylene glycol (OEG)‐based first‐ (G1) and second‐generation (G2) dendrons with an adamantyl group core. The host and guest interaction in aqueous solution leads to the formation of the supramolecular polymers, which is supported with ¹H NMR spectroscopy and dynamic light scattering measurements. The supramolecular formation was also examined at different host/guest ratios. The water solubility of hosts and guests increases upon supramolecular formation. The supramolecular polymers show good solubility in water at room temperature, but exhibit thermoresponsive behavior at elevated temperatures. Their thermoresponsiveness is thus investigated with UV/Vis and ¹H NMR spectroscopy, and compared with their counterparts formed from individual β‐CD and the OEG dendritic guest. The effect of polymer concentration and molar ratio of host/guest was examined. It is found that the polar interior of the supramolecules contribute significantly to the thermally‐induced phase transitions for the G1 polymer, but this effect is negligible for the G2 polymer. Based on the temperature‐varied proton NMR spectra, it is found that the host–guest complex starts to decompose during the aggregation process upon heating to its dehydration temperature, and this decomposition is enhanced with an increase of solution temperature.     

Synthesis and encapsulation properties of dendronized polymer with Fréchet‐type dendrons peripherally decorated by carboxylic acid functionalization

A new carboxylic acid‐terminated dendronized polymer (denpol), constructed with linear chain attaching Fréchet‐type dendrons at each repeat unit, has been designed and synthesized through a combination of macromonomer route and hydrolysis reaction. The resulting denpol exhibits excellent solubility in aqueous solution for pH ≥ 6, and significantly the denpol also encapsulates various aromatic molecules efficiently. The results of UV–vis and fluorescence spectra indicate that hydrophobic and π‐π interactions bring into effect between the water‐insoluble organic molecules and the denpol. Moreover, the photoisomerization of azobenzene solubilized in denpol aqueous solution was investigated, which indicated that trans‐to‐cis and cis‐to‐trans conversions were first‐order reactions. The enhancement of photoisomerization property may attribute to the proper microenvironment in the denpol. Therefore, the denpol is expected to be a potential candidate as amphiphilic unimolecular container. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4564–4574, 2008     

Modular Assembly of Host–Guest Metal–Phenolic Networks Using Macrocyclic Building Blocks

The manipulation of interfacial properties has broad implications for the development of high‐performance coatings. Metal–phenolic networks (MPNs) are an emerging class of responsive, adherent materials. Herein, host–guest chemistry is integrated with MPNs to modulate their surface chemistry and interfacial properties. Macrocyclic cyclodextrins (host) are conjugated to catechol or galloyl groups and subsequently used as components for the assembly of functional MPNs. The assembled cyclodextrin‐based MPNs are highly permeable (even to high molecular weight polymers: 250–500 kDa), yet they specifically and noncovalently interact with various functional guests (including small molecules, polymers, and carbon nanomaterials), allowing for modular and reversible control over interfacial properties. Specifically, by using either hydrophobic or hydrophilic guest molecules, the wettability of the MPNs can be readily tuned between superrepellency (>150°) and superwetting (ca. 0°).     

Size‐Tunable Micron‐Bubbles Based on Fluorous–Fluorous Interactions of Perfluorinated Dendritic Polyglycerols

This paper describes the behavior of various generations of polyglycerol dendrimers that contain a perfluorinated shell. The aggregation in organic solvents is based on supramolecular fluorous–fluorous interactions, which can be described by means of ¹⁹F NMR spectroscopy. In order to study the interaction and aggregation phenomena of dendrimers with perfluorinated shell and perfluoro‐tagged guest molecules we investigated [G3.5]‐dendrimer with a perfluorinated shell in the presence of perfluoro‐tagged disperse red. Noteworthy, the interaction intensities varied in an unexpected manner depending on the equivalents of perfluoro‐tagged guest molecules added to the dendrimers in solution which then formed supramolecular complexes based on fluorous–fluorous interactions. We found that these complexes aggregated around residual air in the solvent to form stable micron‐sized bubbles. Their sizes correlated with the interaction intensities measured for certain dendrimer–guest molecule ratios. Degassing of the solutions led to a quasi phase separation between organic and fluorous phase, whereby the dendrimers formed the fluorous phases. Regassing the sample with air afforded bubbles of the initial size again.     

Dendronized copolymers functionalized with crown ethers and their reversible modification through host–guest interaction

Crown ether‐functionalized dendronized copolymers with an alternating structure were synthesized by free radical copolymerization of styrene derivatives pendent with Percec‐type polyether dendron of two generations and maleimide pendent with dibenzo[24]crown‐8 (24C8). Novel dendronized copolymers bearing tremendous host molecular cavities have been characterized by ¹H NMR, ¹³C NMR spectroscopy, static light scattering (SLS), and differential scanning calorimetry (DSC) analysis as well as atomic force microscopy (AFM) techniques. Host–guest interactions between 24C8 units dispersed along the dendronized copolymers and organic ammonium salts of pyrene, anthracene, and phenol have been explored. These molecular recognition processes can be monitored by ¹H NMR spectroscopy and fluorescence excitation spectroscopy. These results showed that the supramolecular polymer systems are acid–base controllable, demonstrating that dendronized copolymers may be modified reversibly via host–guest interaction. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Host–Guest Chemistry between Perylene Diimide (PDI) Derivatives and 18‐Crown‐6: Enhancement in Luminescence Quantum Yield and Electrical Conductivity

Perylene diimide (PDI) derivatives exhibit a high propensity for aggregation, which causes the aggregation‐induced quenching of emission from the system. Host–guest chemistry is one of the best‐known methods for preventing aggregation through the encapsulation of guest molecules. Herein we report the use of 18‐crown‐6 (18‐C‐6) as a host system to disaggregate suitably substituted PDI derivatives in methanol. 18‐C‐6 formed complexes with amino‐substituted PDIs in methanol, which led to disaggregation and enhanced emission from the systems. Furthermore, the embedding of the PDI ? 18‐C‐6 complexes in poly(vinyl alcohol) (PVA) films generated remarkably high emission quantum yields (60–70 %) from the PDI derivatives. More importantly, the host–guest systems were tested for their ability to conduct electricity in PVA films. The electrical conductivities of the self‐assembled systems in PVA were measured by electrochemical impedance spectroscopy (EIS) and the highest conductivity observed was 2.42×10^?5 S cm^?1.     

Acid–Base Controllable Recognition Properties of a Highly Versatile Calix[6]crypturea

Versatile concave receptors with binding properties that can be controlled by external stimuli are rare. Herein, we report on a calix[6]crypturea ( 1 ) that features two different binding sites in close proximity, that is, a tris(2‐aminoethyl)amine (tren)‐based tris‐ureido cap that provides convergent hydrogen‐bond‐donor sites and a hydrophobic cavity suitable for the inclusion of organic guests. The binding properties of this heteroditopic receptor have been evaluated by NMR spectroscopic studies. Compound 1 behaves as a remarkably versatile host that strongly binds neutral molecules, anions, or contact ion pairs. Within each family of guests, compound 1 is able to discriminate between different guests with a high degree of selectivity. Indeed, neutral molecules that possess hydrogen‐bond donor and acceptor groups, chloride anions, and linear ammonium ions associated to F^? or Cl^? are particularly well recognized. In comparison with all the related receptors, compound 1 displays several unique features: 1) charged or neutral species are also recognized in polar or protic solvents, 2) thanks to the flexibility of the calixarene structure, induced‐fit processes allow the binding of large, biologically relevant ammonium salts such as neurotransmitters, and 3) the protonation of the basic cap leads to a positively charged receptor, 1? H⁺, which is reluctant to host anions and in which host properties are now governed by strong charge–dipole interactions with the guests. In other words, compound 1 presents an acid–base controllable tris‐ureido recognition site protected by a hydrophobic corridor that can select guests through induced‐fit processes. Thus, its versatile host properties can be allosterically controlled by protonation and selective guest‐switching processes are possible. To illustrate all these remarkable features, a sophisticated three‐pole supramolecular switch, based on the interconversion of host–guest systems displaying either charged or neutral guests, is described.     

Retarded Solid‐State Rotations of an Oval‐Shaped Guest in a Deformed Cylinder with CH–π Arrays

Upon encapsulating an oval‐shaped hydrocarbon guest, a cylindrical host deforms its shape to maximize intermolecular contacts. Structure–assembly relationship studies with a series of hydrocarbon guests disclosed the importance of molecular shapes and CH–π contacts. Multiple contacts and weak CH–π hydrogen bonds resulted in an optimal assembly; however, the shape deformation resulted in severe retardation of rotational motions in the crystal. Thus, unlike a circular guest, the oval‐shaped guest did not change its orientation in the host. Unexpectedly, the planar guest did not affect the packing structure to form a double helix in intertwined host arrays.     

Guest Binding with Sulfated Cyclodextrins: Does the Size of Cavity Matter?

Sulfated cyclodextrins have recently emerged as potential candidates for producing host–induced guest aggregation with properties better than p-sulfonatocalixarenes that have previously shown numerous applications involving the phenomena of host-induced guest aggregation. In the class of sulfated cyclodextrins (SCD), sulfated β-cyclodextrin (β-SCD) remains the most extensively investigated host molecule. Although it is assumed that the host-induced guest aggregation is predominantly an outcome of interaction of the guest molecule with the charges on the exterior of SCD cavity, it has not been deciphered whether the variation in the cavity size will make a difference in the efficiency of host-induced guest-aggregation process. In this investigation, we present a systematic study of host–induced guest aggregation of a cationic molecular rotor dye, Thioflavin T (ThT) with three different sulfated cyclodextrin molecules, α-SCD, β-SCD and γ-SCD, which differ in their cavity size, using steady-state emission, ground-state absorption and time-resolved emission measurements. The obtained photophysical properties of ThT, upon interaction with different SCD molecules, indicate that the binding strength of ThT with different SCD molecules correlate with the cavity size of the host molecule, giving rise to the strongest complexation of ThT with the largest host molecule (γ-SCD). The binding affinity of ThT towards different host molecules has been supported by molecular docking calculations. The results obtained are further supported with the temperature and ionic strength dependent studies performed on the host-guest complex. Our results indicate that for host–induced guest aggregation, involving oppositely charged molecules, the size of the cavity also plays a crucial role beside the charge density on the exterior of host cavity.     

Supramolecular Porphyrin Copolymer Assembled through Host–Guest Interactions and Metal–Ligand Coordination

Bisporphyrin cleft molecule 1 Zn possessing a guest moiety assembled to form supramolecular polymers through host–guest interactions. Bispyridine cross‐linkers created interchain connections among the supramolecular polymers to form networked polymers in solution. Solution viscometry confirmed that the cross‐linked supramolecular polymers were highly entangled. Frequency‐dependent linear viscoelastic spectroscopy revealed that the supramolecular polymers generated well‐entangled solutions with associating and networking polymers, whereas the solid‐like aggregates moved individually without breaking and reforming structures below the transition temperature of 9.6 °C. Morphological transition of the supramolecular polymers was evidenced by AFM images; the non‐cross‐linked polymer resulted in wide‐spread thin networks, while the cross‐linked networks produced thicker worm‐like nanostructures. The supramolecular networks gelled in 1,1,2,2‐tetrachloroethane, and an elastic free‐standing film was fabricated with a Young’s modulus of 1 GPa.     

Stepwise Evolution of Molecular Nanoaggregates Inside the Pores of a Highly Flexible Metal–Organic Framework

The crystalline sponge method (CSM) is primarily used for structural determination by single‐crystal X‐ray diffraction of a single analyte encapsulated inside a porous MOF. As the host–guest systems often show severe disorder, reliable crystallographic determination is demanding; thus the dynamics of the guest entering and the formation of nanoconfined molecular aggregates has not been in the spotlight. Now, the concept is investigated of the CSM for monitoring the structural evolution of nanoconfined supramolecular aggregates of eugenol guests with displacement of DMF inside the cavities of the flexible MOF, PUM168. The interpretation of the electron density provides a series of unique detailed snapshots depicting the supramolecular guest aggregation, thus showing the tight interplay between the host flexible skeleton and the molecular guests through the DMF‐to‐eugenol exchange process.     

A Rapidly Self‐Healing Host–Guest Supramolecular Hydrogel with High Mechanical Strength and Excellent Biocompatibility

It is still a challenge to achieve both excellent mechanical strength and biocompatibility in hydrogels. In this study, we exploited two interactions to form a novel biocompatible, slicing‐resistant, and self‐healing hydrogel. The first was molecular host–guest recognition between a host (isocyanatoethyl acrylate modified β‐cyclodextrin) and a guest (2‐(2‐(2‐(2‐(adamantyl‐1‐oxy)ethoxy)ethoxy)ethoxy)ethanol acrylate) to form “three‐arm” host–guest supramolecules (HGSMs), and the second was covalent bonding between HGSMs (achieved by UV‐initiated polymerization) to form strong cross‐links in the hydrogel. The host–guest interaction enabled the hydrogel to rapidly self‐heal. When it was cut, fresh surfaces were formed with dangling host and guest molecules (due to the breaking of host–guest recognition), which rapidly recognized each other again to heal the hydrogel by recombination of the cut surfaces. The smart hydrogels hold promise for use as biomaterials for soft‐tissue repair.     

A Solid‐State Fluorescent Host System with a 21‐Helical Column Consisting of Chiral (1R,2S)‐2‐Amino‐1,2‐diphenylethanol and Fluorescent 1‐Pyrenecarboxylic Acid

A solid‐state fluorescent host system was created by self‐assembly of a 2₁‐helical columnar organic fluorophore composed of (1R,2S)‐2‐amino‐1,2‐diphenylethanol and fluorescent 1‐pyrenecarboxylic acid. This host system has a characteristic 2₁‐helical columnar hydrogen‐ and ionic‐bonded network. Channel‐like cavities are formed by self‐assembly of this column, and various guest molecules can be included by tuning the packing of this column. Moreover, the solid‐state fluorescence of this host system can change according to the included guest molecules. This occurs because of the change in the relative arrangement of the pyrene rings as they adjust to the tuning of the packing of the shared 2₁‐helical column, according to the size of the included guest molecules. Therefore, this host system can recognize slight differences in molecular size and shape.     

Synthesis,optical properties,and spectral stability of chiral dendronized binaphthyl‐containing polyfluorene derivatives

A new kind of chiral dendronized binaphthyl‐containing random polyfluorene derivatives bearing different contents (3.2–14.9 mol %) of Fréchet's polyether dendritic wedges have been designed and synthesized through a versatile Pd‐catalyzed Suzuki polycondensation. Their properties have been investigated by NMR, TGA, DSC, CD, UV–vis, and photoluminescence and compared to those of poly(9,9‐dihexylfluorene) ( PF ). It was found that attachment of Fréchet's dendritic wedges into the main chain enhanced the emission efficiency and thermal stability of the copolymers. Furthermore, different from PF , good to excellent spectral stabilities in the solid state were proven for all the dendronized chiral copolymers after a thermal annealing under air at 200 °C. The second‐generation dendronized polymer P3 bearing about 15 mol % of dendritic pendants exhibited high quantum yields in both solutions and films, and excellent thermal oxidative stability. These results demonstrated that the combination of the twisted nonplanar binaphthyl and the sterically demanding dendron could efficiently suppress the intermolecular packing and aggregation at much lower dendron contents compared to other reported dendronized polyfluorenes. Additionally, the investigation of circular dichroism spectra of these chiral dendronized polymers showed a strong Cotton effect at long wavelength (378–384 nm), indicating that the chirality of binaphthyl unit was transferred to the whole polyfluorene backbone. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 886–896, 2008     

Metal–Organic Cyclohelicates as Optical Receptors for Glutathione: Syntheses,Structures, and Host–Guest Behaviors

Two trinuclear zinc‐based cyclohelicates, Zn–PDB (PDB=[5‐(dibenzylamino)‐N1′,N3′‐bis(pyridin‐2‐ylmethylene)isophthalohydrazide]) and Zn–PMB (PMB=[5‐(bodipy‐oxy)‐N1′,N3′‐bis(pyridin‐2‐ylmethylene)isophthalohydrazide]) containing dibenzylamino and BODIPY groups, respectively, were generated by incorporating two amide‐containing tridentate chelators into meta‐positions of a substituted phenyl ring. Single‐crystal structure analysis and related spectroscopic characterizations demonstrated the formation of macrocyclic helicals both in the solid state and in solution. The host–guest behavior of the cyclohelical hosts towards γ‐glutamyl‐cysteinyl‐glycine (GSH) and its component amino acids was investigated by spectroscopic titrations. UV/Vis absorption titration and NMR titrations of Zn–PDB and Zn–PMB upon addition of the above‐mentioned guests suggested that the Glu residue of GSH was positioned within the cavity. The COO⁻ groups interacted with metal ions through static interactions. The Cys moiety of GSH interacted with the amide groups sited in host molecules through hydrogen‐bonding interactions to produce measurable spectral changes. Fluorescent titrations of Zn–PMB upon the addition of GSH and ESI‐MS investigations of the titration solutions confirmed the host–guest interaction modes and revealed the possible 1:1 complexation stoichiometry. These results showed that the recognition of a substrate within the cavity of functionalized metal–organic cage‐like receptors could be a useful method to produce supramolecular sensors for biomolecules.     

Exploring the Loading Capacity of Generation Six to Eight Dendronized Polymers in Aqueous Solution

Aspects of size, structural (im)perfection, inner density, and guest molecule loading capacity of dendronized polymers (DPs) of high generation (6≤g≤8) in aqueous solution are studied using electron paramagnetic resonance spectroscopy on amphiphilic, spin‐labeled guest molecules. The results show that the interior of the charged DPs is strongly polar, especially in comparison to their lower generation (1–4) analogues. This is a direct sign that large amounts of water penetrate the DP surface, reflecting the structural (im)perfections of these high‐generation DPs and much lower segmental densities than theoretically achievable. Images obtained with atomic force microscopy reveal that the high‐generation DPs do not aggregate and give further insights into the structural imperfections. Electron paramagnetic resonance spectroscopic data further show that despite their structural imperfections, these DPs can bind and release large numbers of amphiphilic molecules. It is concluded that attention should be paid to their synthesis, for which a protocol needs to be developed that avoids the relatively large amount of defects generated in the direct conversion of a generation g=4 DP to a generation g=6 DP, which had to be used here.     

Metalla‐Assembled Electron‐Rich Tweezers: Redox‐Controlled Guest Release Through Supramolecular Dimerization

Developing methodologies for on‐demand control of the release of a molecular guest requires the rational design of stimuli‐responsive hosts with functional cavities. While a substantial number of responsive metallacages have already been described, the case of coordination‐tweezers has been less explored. Herein, we report the first example of a redox‐triggered guest release from a metalla‐assembled tweezer. This tweezer incorporates two redox‐active panels constructed from the electron‐rich 9‐(1,3‐dithiol‐2‐ylidene)fluorene unit that are facing each other. It dimerizes spontaneously in solution and the resulting interpenetrated supramolecular structure can dissociate in the presence of an electron‐poor planar unit, forming a 1:1 host–guest complex. This complex dissociates upon tweezer oxidation/dimerization, offering an original redox‐triggered molecular delivery pathway.     

Light‐Triggered Capture and Release of DNA and Proteins by Host–Guest Binding and Electrostatic Interaction

The development of an effective and general delivery method that can be applied to a large variety of structurally diverse biomolecules remains a bottleneck in modern drug therapy. Herein, we present a supramolecular system for the dynamic trapping and light‐stimulated release of both DNA and proteins. Self‐assembled ternary complexes act as nanoscale carriers, comprising vesicles of amphiphilic cyclodextrin, the target biomolecules and linker molecules with an azobenzene unit and a charged functionality. The non‐covalent linker binds to the cyclodextrin by host–guest complexation with the azobenzene. Proteins or DNA are then bound to the functionalized vesicles through multivalent electrostatic attraction. The photoresponse of the host–guest complex allows a light‐induced switch from the multivalent state that can bind the biomolecules to the low‐affinity state of the free linker, thereby providing external control over the cargo release. The major advantage of this delivery approach is the wide variety of targets that can be addressed by multivalent electrostatic interaction, which we demonstrate on four types of DNA and six different proteins.     

Propagation of Enzyme‐Induced Surface Events inside Polymer Nanoassemblies for a Fast and Tunable Response

We report a new molecular design strategy that allows for the propagation of surface enzymatic events inside a supramolecular assembly for accelerated molecular release. The approach addresses a key shortcoming encountered with many of the currently available enzyme‐induced disassembly strategies, which rely on the unimer–aggregate equilibria of amphiphilic assemblies. The enzymatic response of the host to predictably tune the kinetics of guest‐molecule release can be programmed by controlling substrate accessibility through electrostatic complexation with a complementary polymer. Accelerated guest release in response to the enzyme is shown to be accomplished by a cooperative mechanism of enzyme‐triggered supramolecular host disassembly and host reorganization.