Constructing Adaptive Photosensitizers via Supramolecular Modification Based on Pillararene Host–Guest Interactions

In order to promote the development of photodynamic therapy (PDT), undesired side effects like low tumor specificity and the “always-on” phenomenon should be avoided. An effective solution is to construct an adaptive photosensitizer that can be activated to generate reactive oxygen species (ROS) in the tumor microenvironment. Herein, we design and synthesize a supramolecular switch based on a host–guest complex containing a water-soluble pillar[5]arene ( WP5 ) and an AIEgen photosensitizer ( G ). The formation of the host–guest complex WP5 ⊃ G quenches the fluorescence and inhibits ROS generation of G . Benefitting from the pH-responsiveness of WP5 , the binding site between G and WP5 changes in an acidic environment through a shuttle movement. Consequently, fluorescence and ROS generation of the host–guest complex can be switched on at pH 5.0. This work offers a new paradigm for the construction of adaptive photosensitizers by using a supramolecular method.     

Guest–Host Interactions in Hofmann-Td-type Aniline Clathrates: IR Spectral Study

Synthesis and IR spectra of novel Hofmann-T _d -type aniline clathrates, M(NH₃)₂Zn(CN)₄· 2C₆H₅NH₂ (M = Zn or Cd) are reported for the first time. All the vibrational modes of aniline are characterised. The shifts in _a (NH₂) and _s (NH₂) reveal hydrogen bonding between the NH₂ group of aniline and the cyanide group of the host lattice to be stronger than in Hofmann-type aniline clathrates. However, the out of plane deformation mode of aniline indicates absence of hydrogen bonding between ammonia and the -cloud of the aniline ring. The related aniline clathrates with bridging Cd(CN)₄ M(NH₃)₂Cd(CN)₄· 2C₆H₅NH₂ (M=Zn or Cd), exhibit similar behaviour.     

Electrochemical Detection of Host–Guest Interactions of Dicarboximide Pesticides with Cyclodextrins

Electrochemical methods sensitively detect the formation of host–guest complexes of cyclodextrins and three redox-active pesticides: vinclozoline (3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione), iprodione (3-(3,5-dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-imidazolidinecarboxamide), and procymidone (3-(3,5-dichloro-phenyl)-1,5-dimethyl-3-azabicyclo[3.1.0]hexane-2,4-dione). The protecting environment of the CD cavity allows a four-electron heterogeneous reaction leading to a preferential cleavage of the C–Cl bonds and conservation of the heterocycle structure for a further second electron transfer step. This interpretation is supported by numerical simulation of the voltammetric curves and by quantum-chemical calculations of the LUMO changes of vinclozoline. Electrochemical detection of these host–guest interactions is far superior to the spectral methods.     

Ultra-High to Ultra-Low Drug-Loaded Micelles: Probing Host–Guest Interactions by Fluorescence Spectroscopy

Polymer micelles are an attractive means to solubilize water insoluble compounds such as drugs. Drug loading, formulations stability and control over drug release are crucial factors for drug-loaded polymer micelles. The interactions between the polymeric host and the guest molecules are considered critical to control these factors but typically barely understood. Here, we compare two isomeric polymer micelles, one of which enables ultra-high curcumin loading exceeding 50 wt.%, while the other allows a drug loading of only 25 wt.%. In the low capacity micelles, steady-state fluorescence revealed a very unusual feature of curcumin fluorescence, a high energy emission at 510 nm. Time-resolved fluorescence upconversion showed that the fluorescence life time of the corresponding species is too short in the high-capacity micelles, preventing an observable emission in steady-state. Therefore, contrary to common perception, stronger interactions between host and guest can be detrimental to the drug loading in polymer micelles.     

Dual Responsive Regulation of Host–Guest Complexation in Aqueous Media to Control Partial Release of the Host

The regulation of the concentration of a wide range of small molecules is ubiquitous in biological systems because it enables them to adapt to the continuous changes in the environmental conditions. Herein, we report an aqueous synthetic system that provides an orchestrated, temperature and pH controlled regulation of the complexation between the cyclobis(paraquat-p-phenylene) host ( BBox ) and a 1,5-dialkyloxynaphthalene ( DNP ) guest attached to a well-defined dual responsive copolymer composed of N-isopropylacrylamide as thermoresponsive monomer and acrylic acid as pH-responsive monomer. Controlled, partial release of the BBox , enabling control over its concentration, is based on the tunable partial collapse of the copolymer. This colored supramolecular assembly is one of the first synthetic systems providing control over the concentration of a small molecule, providing great potential as both T and pH chromic materials and as a basis to develop more complex systems with molecular communication.     

Photoregulation of Gene Expression with Amantadine-Modified Caged siRNAs through Host–Guest Interactions

RNA interference is an essential and powerful tool for targeting and verifying specific gene functions. Conditional control of small interfering RNA (siRNA) activity, especially using light activation, is a potential method for regulating target gene expression and functions. In this study, a series of photolabile siRNAs with amantadine modification have been rationally designed and developed through host–guest interactions between amantadine and β-cyclodextrin derivatives to enhance the blocking effect of siRNA binding and/or RNA-induced silencing complex processing. These caged siRNAs with amantadine modification at the 5′ end of antisense-strand RNA were efficiently inactivated through the host–guest interactions between amantadine and β-cyclodextrin. Photomodulation of the gene silencing activity of these amantadine-modified caged siRNAs targeting both exogenous and endogenous genes was successfully achieved, which indicates that host–guest interactions could be a new strategy for developing new caged siRNAs for gene photoregulation with low leaking activity.     

Toward Expanded Diversity of Host–Guest Interactions via Synthesis and Characterization of Cyclodextrin Derivatives

Researchers developing software to predict the binding constants of small molecules for proteins have, in recent years, turned to host–guest systems as simple, computationally tractable model systems to test and improve these computational methods. However, taking full advantage of this strategy requires aqueous host–guest systems that probe a greater diversity of chemical interactions. Here, we advance the development of an experimental platform to generate such systems by building on the cyclodextrin (CD) class of hosts. The secondary face derivative mono-3-carboxypropionamido-β-cyclodextrin (CP-β-CD) was synthesized in a one-pot strategy with 87% yield, and proved to have much greater aqueous solubility than native β-CD. The complexation of anionic CP-β-CD with the cationic drug rimantadine hydrochloride was explored using one- and two-dimensional nuclear magnetic resonance; NOESY analysis showed secondary face binding of the ammonium moiety of the guest, based on cross-correlations between the amic acid functionality and the side-chain of rimantadine. Isothermal titration calorimetry was furthermore used to determine the standard Gibbs energy and enthalpy for this binding reaction, and the results were compared with those of rimantadine with native β-CD.     

Mixed Micelles in the Presence of Macrocyclic Additives: A Host–Guest Conductometric Study

The conductances of sodium dodecylsulphate (SDS) + sodium decylsulfate (SDeS) and decyltrimethylammonium bromide (DeTAB) + tetradecyltrimethylammonium bromide (TTAB) over the entire mole fraction range of SDS (_SDS) or DeTAB (_DeTAB) were measured in water, 18-crown-6 ether + water (CR + W) and -cyclodextrin + water (CYC + W) mixtures at fixed 4 mM and 8 mM of CR or CYC in their respective binary mixtures at 30 °C. The conductivity plots for SDS + SDeS mixtures show a single break whereas two breaks are observed at most of the _DeTAB for DeTAB + TTAB mixtures. From the break in the conductivity data, the mixed critical micellar concentration (cmc) and degree of counter-ion association () were computed. The first break corresponds to the classical cmc of TTAB is termed as the first cmc (C₁) and the second break which is observed at concentrations about 4 times the first one, corresponding to the classical cmc of DeTAB and is considered to be the second cmc (C₂). The non-ideality in SDS + SDeS mixtures has been evaluated by using the regular solution theory and it has been observed that the mixture is close to ideal in the absence and presence of additives. The variation in C₁, C₂ and ₁, ₂ for DeTAB + TTAB has been discussed in terms of the mixed micelle formation which are predominantly rich in the TTAB and DeTAB monomers respectively.     

Voltammetric Investigation of Host–Guest Systems in the Absence of a Supporting Electrolyte

Journal of Inclusion Phenomena and Macrocyclic Chemistry - In the classic voltammetric approach to host--guest systems the investigations are carried out in excess of a supporting electrolyte,...     

Using Gas-Phase Guest–Host Chemistry to Probe the Structures of b Ions of Peptides

Middle-sized b _n (n????5) fragments of protonated peptides undergo selective complex formation with ammonia under experimental conditions typically used to probe hydrogen?Cdeuterium exchange in Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Other usual peptide fragments like y, a, a*, etc., and small b _n (n????4) fragments do not form stable ammonia adducts. We propose that complex formation of b _n ions with ammonia is characteristic to macrocyclic isomers of these fragments. Experiments on a protonated cyclic peptide and N-terminal acetylated peptides fully support this hypothesis; the protonated cyclic peptide does form ammonia adducts while linear b _n ions of acetylated peptides do not undergo complexation. Density functional theory (DFT) calculations on the proton-bound dimers of all-Ala b ₄ , b ₅ , and b ₇ ions and ammonia indicate that the ionizing proton initially located on the peptide fragment transfers to ammonia upon adduct formation. The ammonium ion is then solvated by N⁺-H??O H-bonds; this stabilization is much stronger for macrocyclic b _n isomers due to the stable cage-like structure formed and entropy effects. The present study demonstrates that gas-phase guest?Chost chemistry can be used to selectively probe structural features (i.e., macrocyclic or linear) of fragments of protonated peptides. Stable ammonia adducts of b ₉ , b ₉ -A, and b ₉ -2A of A₈YA, and b ₁₃ of A₂₀YVFL are observed indicating that even these large b-type ions form macrocyclic structures.     

Interaction Study of Guest with Host in Clathrate Hydrate

Lattice dynamical simulations of noble gas hydrate structuresⅠandⅡhave been performed. Potential energies were investigated to study the influence of guest species on the stability of the hydrate structure.Results show that when the diameter of inclusion molecules is between 3(?)and 4.2(?),such as Ar and Kr,the critical role of the 5~(12)cage in the stabilization of hydrates becomes effective.For Xe hydrates SⅠand SⅡ,with the help of lattice dynamical calcnlations,the modes attributions are identified directly.We proposed the resonant effect of the fingerprint frequency at about 7 meV and 10 meV which arise from the coupling of Xe molecules in the 5~(12)cage with the host lattice.     

Smart Materials Based on Synthetic Host Molecules: The Role of Host–Guest Chemistry in the Fabrication and Application

Stimuli-responsive or smart materials have recently shown a significant impact on the frontier of material science and engineering. The exponential development of synthetic host molecules (SHMs) over the last decades and their corresponding host–guest chemistry, have empowered researchers with new opportunities to design and construct tailored or guest-specific smart materials. In this Minireview, we present the recent advancements in synthetic host based smart materials, ranging from the fabrication strategies to the state-of-art applications including adsorption, separation, luminescence, self-healing and actuation. The role that the host–guest chemistry plays in these systems is highlighted throughout to give a better prospective of the available possibilities for emerging materials of future economies.     

Carbon Dots in Porous Materials: Host–Guest Synergy for Enhanced Performance

Carbon dots (CDs) are emerging as a new class of carbon nanomaterials, which have inspired growing interest for their widespread applications in anti-counterfeiting, sensing, bioimaging, optoelectronic and energy-related fields. In terms of the concept of host–guest assembly, immobilizing CDs into porous materials (PMs) has proven to be an effective strategy to avoid the aggregation of bare CDs in solid state, in particular, the host—guest synergy with both merits of CDs and PMs affords composites promising properties in afterglow and tunable emissions, as well as optimizes their performance in optics, catalysis, and energy storage. This Minireview summarizes the recent progress in the research of CDs@PMs, and highlights synthetic strategies of constructing composites and roles of porous matrices in boosting the applications of CDs in diverse areas. The prospect of future exploration and challenges are proposed for designing advanced CDs-based functional nanocomposite materials.     

Cyclodextrins in Polymer Synthesis: Free Radical Polymerization of a tert-Butylmethacrylate-Cyclodextrin Host–Guest System in Aqueous Medium

The homopolymerization of methylated-β-cyclodextrin (me-β-CD) host–guest compound of tert-butyl methacrylate (1a) is described. We investigated the free radical polymerization of the complexed monomer (1a) and of the free monomer (1) at ambient and high temperature. Poly(tert-butylmethacrylate) synthesized via the cyclodextrin mediated method exhibited number-average molecular weights ranging from 12,000–60,000 g/mol with polydispersities from 1.9–3.1. The polymerizations without cyclodextrin show significantly lower yields in comparison with the cyclodextrin mediated polymerizations. Here, the polymer obtained is colloidal dispersed. At ambient temperature (20°C) no polymerization occurs in the absence of cyclodextrin, whereas, under the same conditions, the homopolymerization of the complexed monomer (1a) leads to polymerization with yields around 75%.     

Structural Analysis of Host–Guest Systems. Methyl-substituted Phenols in beta;-Cyclodextrin

Complexation trajectories and the variation ofinduced circular dichroism are calculated for thedocking of phenol and 2,4,6-trimethyl-phenol with-cyclodextrin. The results are compared toexperimental chirality data to elucidate themechanism of nonspecific molecular recognitionprocesses in aqueous solution. Large geometricalchanges along nearly isoenergetic Dynamic Monte Carlotrajectories show the conformational flexibility ofsuch host–guest systems. This proves diffuseintermolecular interactions, van der Waals orelectrostatic in nature, as the main contributions to thebinding energy. The number and position of the methylsubstituents of the guest reduces the complexityof the conformational space as the guests positionbecomes fixed by steric constraints.The solvation free energy is calculated from thesolvent accessible surface area weighted byrespective atomic solvation parameters. Consideringthe solvation term in the dynamic simulationsrestricts the conformational flexibility of themacromolecular system. The relative importance ofvarious contributions to the solvation energy isdiscussed and it is shown that those terms arisingfrom the interaction of hydrophobic groups with theaqueous environment are essential for thedetermination of the complex structure. Consideringthese terms in the dynamic simulation model, the signand strength of the calculated rotatory strength isin perfect agreement with induced circular dichroismobtained from experimentally determined averagedspectra. The results demonstrate the accuracy of thegeometrical properties of host–guest systems obtainedfrom these simulations.     

Fluorescent Metallacycle-Cored Amphiphilic Nanoparticles Formed by β-Cyclodextrin-Based Host–Guest Interactions towards Cancer Theranostics

Theranostic agents, taking the advantages of both imaging and therapeutic functions, are anticipated to be key components in the development of personalized medicine in which the therapeutic response can be real-time monitored. Herein, three metallacycles with pendent adamantane groups are prepared by coordination-driven self-assembly of Pt^II ligands with anticancer activities and tetraphenylethylene derivatives with emission. β-Cyclodextrin, which shows good host–guest interactions with adamantane moieties, was added to form amphiphilic supramolecular nanoparticles with the aim to enhance the aqueous solubilities and bioactivities of these metallacycles. Moreover, when rhodamine-modified β-cyclodextrin was used as the carrier, the release of the metallacycles from the nanoparticles could be monitored in situ through the fluorescence changes owing to the efficient fluorescence resonance energy transfer from the metallacycles to rhodamine-modified β-cyclodextrin. In vitro and in vivo studies showed that these nanoparticles not only served as cell imaging contrast agents but also displayed improved anticancer activities, allowing them to serve as potential candidates for cancer theranostics. This study provides a simple and efficient method to prepare theranostic agents by hierarchical supramolecular self-assembly, which will pave the way for image-guided cancer therapy, targeted cancer therapy, and related biomedical fields.     

Anion Binding Properties of Alkynylplatinum(II) Complexes with Amide-Functionalized Terpyridine: Host–Guest Interactions and Fluoride Ion-Induced Deprotonation

Molecular sensors able to detect ions are of interest due to their potential application in areas such as pollutant sequestration. Alkynylplatinum(II) terpyridine complexes with an amide-based receptor moiety have been synthesized and characterized. Their anion binding properties based on host–guest interactions have been examined with the use of UV-vis absorption and emission spectral titration studies. Spectral changes were observed for both complexes upon the addition of spherical and nonspherical anions. Their titration profiles were shown to be in good agreement with theoretical results predicting a 1:1 binding model, and the binding constants were determined from the experimental data. Drastic color changes from yellow to orange–red were observed for one of the complexes upon titration with fluoride (F⁻) ion in acetone. These changes were ascribed to the deprotonation of the amide functionalities induced by F⁻ ion, and this was confirmed by the restoration of spectral changes upon addition of trifluoroacetic acid to the F⁻ ion–complex mixture as well as by electrospray ionization mass spectrometry (ESI-MS) data.     

Host–Guest Recognition and Fluorescence of a Tetraphenylethene-Based Octacationic Cage

We report the synthesis and characterization of a three-dimensional tetraphenylethene-based octacationic cage that shows host–guest recognition of polycyclic aromatic hydrocarbons (e.g. coronene) in organic media and water-soluble dyes (e.g. sulforhodamine 101) in aqueous media through CH⋅⋅⋅π, π–π, and/or electrostatic interactions. The cage⊃coronene exhibits a cuboid internal cavity with a size of approximately 17.2×11.0×6.96 ų and a “hamburger”-type host–guest complex, which is hierarchically stacked into 1D nanotubes and a 3D supramolecular framework. The free cage possesses a similar cavity in the crystalline state. Furthermore, a host–guest complex formed between the octacationic cage and sulforhodamine 101 had a higher absolute quantum yield (Φ_F=28.5 %), larger excitation–emission gap (Δλ_ex-em=211 nm), and longer emission lifetime (τ=7.0 ns) as compared to the guest (Φ_F=10.5 %; Δλ_ex-em=11 nm; τ=4.9 ns), and purer emission (Δλ_FWHM=38 nm) as compared to the host (Δλ_FWHM=111 nm).