Assembly-enhanced molecular recognition of calix[6]arene

<p>We comparatively investigated the molecular recognition of the amphiphilic derivatives of <i>p</i>-sulfonatocalix[<i>n</i>]arenes (SC<i>n</i>A-Rs, <i>n</i> = 4 and 6) both in aqueous solution and at the interface of liposome. When the recognition events transfer from aqueous solution to the self-assembled interface, the binding capability of SC6A-R increases drastically, but not for SC4A-R. It originates from the conformational regulation that the complicated conformation of SC6A-R in aqueous solution was immobilized to the cone shape upon embedding SC6A-R into the liposome. The resulting cone shape is privileged to accommodate guests into its cavity. Such an assembly-enhanced molecular recognition strategy could be transferable to other macrocyclic, acyclic, artificial, and natural receptors with conformational flexibility.</p

Cholinesterase-Responsive Supramolecular Vesicle

Enzyme-responsive, amphiphilic self-assembly represents one of the increasingly significant topics in biomaterials research and finds feasible applications to the controlled release of therapeutic agents at specific sites where the target enzyme is located. The supramolecular approach, using “superamphiphiles”, provides a smart way to fabricate drug delivery systems responsive to enzymatic catalysis. In this work based on the concept of supramolecular chemistry, we report an enzyme-responsive vesicle using <i>p</i>-sulfonatocalix­[4]­arene as the macrocyclic host and natural enzyme-cleavable myristoylcholine as the guest molecule. The complexation of <i>p</i>-sulfonatocalix­[4]­arene with myristoylcholine directs the formation of a supramolecular binary vesicle, which is dissipated by cholinesterase with high specificity and efficiency. Cholinesterase is a key protein overexpressed in Alzheimer’s disease, and therefore, the present system may have potential for the delivery of Alzheimer’s disease drugs

Controlling the Isomerization Rate of an Azo-BF₂ Switch Using Aggregation

A novel visible-light activated azo-BF₂ switch possessing a phenanthridinyl π-system has been synthesized, and its switching properties have been characterized as a function of concentration. The switch self-aggregates through π–π interactions, and the degree of aggregation modulates the <i>Z</i> → <i>E</i> thermal isomerization rate. This property allows for the active tuning of the thermal relaxation half-life of the same switch from seconds to days

Molecular recognition of amphiphilic <i>p</i>-sulfonatocalix[4]arene with organic ammoniums

<div><p>The binding abilities and thermodynamic origin for the intermolecular complexation of two water-soluble calixarenes, <i>p</i><b>-</b>sulfonatocalix[4]arene (SC4A) and 5,11,17,23<b>-</b>tetrasulfonato<b>-</b>25,26,27,28<b>-</b>tetrakis(<i>n</i><b>-</b>butyl)<b>-</b>calix[4]arene (SC4A<b>-</b>Bu), with six organic cations: 1,4<b>-</b>diazabicyclo[2,2,2]octane (G1), 3,5,6,8,<b>-</b>tetrahydropyrazino[1,2,3,4<b>-</b>Imn][1,10]phenanthroline (G2), diquat (G3), paraquat (G4), 1<b>-</b>methylpyridin-1-ium (G5) and 1,3<b>-</b>dimethylimidazolium (G6), have been determined by means of isothermal titration calorimetry in aqueous solutions at pH 7.0, 298.15 K, and their binding modes have been investigated by NMR spectroscopy. The obtained results indicate that the binding modes of SC4A-Bu and SC4A change a little but their binding affinities show great difference, resulting from the distinguishable binding thermodynamics. The binding selectivity of G1 is up to 688 times for the SC4A/SC4A<b>-</b>Bu hosts, and SC4A<b>-</b>Bu prefers to include planer molecules of large π system with low electron density. The aggregation behaviours of SC4A-Bu before and after complexation with G3 were then investigated, showing that G3 is able to induce the aggregation of SC4A-Bu.</p></div

Photomodulated Fluorescence of Supramolecular Assemblies of Sulfonatocalixarenes and Tetraphenylethene

Self-assembled fluorescent nanoparticles responding to specific stimuli are highly appealing for applications such as labels, probes, memory devices, and logic gates. However, organic analogues are challenging to prepare, due to unfavorable aggregation-caused quenching. We herein report the preparation of self-assembled fluorescent organic nanoparticles in water by means of calixarene-induced aggregation of a tetraphenyl­ethene derivative (QA-TPE) mediated by <i>p</i>-sulfonato­calix[4]arenes. The self-assembled nanoparticles showed interesting photoswitching behaviors, and the fluorescence output of the generated nanoparticles was opposite to that of free QA-TPE both before and after irradiation. Free QA-TPE is nonfluorescent, owing to intramolecular rotations of the phenyl rings. In contrast, the self-assembled nanoparticles that formed upon complexation of QA-TPE with <i>p</i>-sulfonato­calix[4]arene exhibited aggregation-induced emission fluorescence (λ_em = 480 nm, Φ = 14%), as a result of the inhibition of rotations. Upon UV light irradiation, free QA-TPE was cyclized to the corresponding diphenyl­phenanthrene, which showed typical fluorescence of a π-conjugated system (λ_em = 385 nm, Φ = 9.3%), whereas the nanoparticles were nonfluorescent upon irradiation due to the aggregation-caused quenching. In effect, this system allows programmed modulation of TPE fluorescence at two different emission wavelengths by means of host–guest complexation and irradiation. Relative to a single-mode stimulus-responsive system, our new developed system of highly integrated modes into a single molecular unit that can exhibit modulation of fluorescence by multiple stimulus is expected to be more adaptable for practical applications and to show enhanced multifunctionality

Inclusion of neutral guests by water-soluble macrocyclic hosts – a comparative thermodynamic investigation with cyclodextrins, calixarenes and cucurbiturils

<p>The driving forces of association between three different families of macrocycles as hosts, namely cyclodextrins (<i>α</i>-, <i>β</i>-, and <i>γ</i>-), <i>p</i>-sulfonatocalix[<i>n</i>]arenes (<i>n</i> = 4–6) as well as cucurbit[<i>n</i>]urils (<i>n</i> = 6–8), and three different bicyclic azoalkane homologues as guests, namely 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH), 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) as well as 2,3-diazabicyclo[2.2.3]non-2-ene (DBN), were examined by means of calorimetric titrations, NMR spectroscopy and molecular dynamics simulation, all in aqueous solution. The small, spherical and uncharged guests preferably bind inside the cavities of the medium sized hosts. The inclusion complexation by <i>β</i>-cyclodextrin and <i>p</i>-sulfonatocalix[4]arene shows medium binding affinities (millimolar), while cucurbit[7]uril macrocycle shows very strong binding (micromolar). For all types of macrocycles, the complex formation is enthalpically driven (Δ<i>H</i>° < 0), accompanied by slightly unfavourable entropy changes (Δ<i>S</i>° < 0). The results are discussed in terms of the flexibility of the hosts, the hydrophobic character of their cavities and the release of high-energy water upon binding, and generalised by including two additional guests, the ketones cyclopentanone and (+)-camphor.</p

Biomarker Displacement Activation: A General Host–Guest Strategy for Targeted Phototheranostics in Vivo

Activatable phototheranostics is highly appealing to meet the demand of precision medicine. However, although it displays efficacy in the construction of activatable photosensitizers (PSs), direct covalent decoration still shows some inevitable issues, such as complex molecular design, tedious synthesis, possible photoactivity changes, and potential toxicity. Herein, we propose a novel concept of biomarker displacement activation (BDA) using host–guest strategy. To exemplify BDA, we engineered a PS-loaded nanocarrier by utilizing a macrocyclic amphiphile, where the fluorescence and photoactivity of PS were completely annihilated by the complexation of macrocyclic receptor (OFF state). When nanocarriers were accumulated into tumor tissues via the enhanced permeability and retention effect, the overexpressed biomarker adenosine triphosphates displaced PSs, accompanied by their fluorescence and photoactivity recovered (ON state). These reinstallations are unattainable in normal tissues, allowing us to concurrently achieve selective tumor imaging and targeted therapy in vivo. Compared with widely used covalent approach, the present BDA strategy provides the following advantages: (1) employment of approved PSs without custom covalent decoration; (2) traceless release of PSs with high fidelity by biomarker displacement; (3) adaptability to different PSs for establishing a universal platform and promised facile combination of diverse PSs to enhance photon utility in light window. Such a host–guest BDA strategy is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged