Dual pH and Ca2+-Responsive PEG-Modified Pillar[5]arene-Based Supramolecular Nanodrug Delivery System: Excellent Cargo Encapsulation and Minimal Drug Toxicity.

Chemotherapy is one of the most employed strategies in clinical treatment of cancer. However, reducing medication adverse effects and improving the biological activity remains a significant issue for chemotherapy. We developed a pH and Ca2+-responsive pillar[5]arene-based supramolecular nanodrug delivery system (NDDS) WP5⊃EV@DOX to address the aforementioned challenges. The formation of this NDDS began with the spontaneous formation of supramolecular nanodrug carrier WP5⊃EV in water from PEG-modified pillar[5]arene and the bipyridilium salt derivative EV through simple host-guest interaction. Then the antitumor drug doxorubicin DOX was efficiently loaded with a high encapsulation rate of 84.6 %. Cytotoxicity results indicated that the constructed nanoplatform not only reduced DOX toxicity and side effects on normal cell (293T), but also significantly enhanced the antitumor activity on cancer cell (HepG2). Moreover, in vivo experiments showed that WP5⊃EV@DOX had a longer half-life and higher bioavailability in the blood of mice compared to the nake drug DOX, with increases to 212 % and 179 %, respectively. Therefore, WP5⊃EV@DOX has great potential in tumor therapy and provides a new idea for host-guest drug delivery system.

Construction of a pillar[5]arene-based supramolecular chiral polymer linked to aminophosphine salt for chiral recognition of enantiomers of mandelic acid.

In recent years, supramolecular chirality has been greatly developed in asymmetric synthesis, chiral sensing and other research fields, but its application in molecular chiral recognition has not been extensively studied. In this paper, L-Boc-tyrosine methoxyester and phosphorus chloride salts were introduced into the framework of pillar[n]arene, and a pillar[5]arene-based supramolecular chiral polymer L-TPP-P was constructed. The supramolecular polymer had stable supramolecular chiral properties and could be used as a chiral solvation reagent for chiral recognition of mandelic acid MA. The molar ratio method and Scatchard plot showed that the complexation ratio of L-TPP-P (pillar[5]arene monomer as the reference object) and MA was 1 : 1, and the complexation constants of L-TPP-P with R-MA and S-MA were 4.51 × 105 M-1 and 6.5 × 104 M-1, respectively. The significant affinity difference of L-TPP-P for different enantiomers of MA showed the excellent chiral recognition and stereoselectivity of pillar[5]arene-based supramolecular polymers for MA. This study provides a new idea for a novel supramolecular polymer chiral recognition reagent or chiral recognition method.

A Nanoplatform Based on Pillar[5]arene Nanovalves for Combined Drug Delivery and Enhanced Antitumor Activity.

Modern nanodrug delivery technologies offer new approaches in the fight against cancer. However, due to the heterogeneity of tumors and side effects of anticancer drugs, monotherapies are less effective. Herein, we report a novel pH and light dual-responsive nanodrug delivery platform. The platform was formed by sulfonate-modified gold nanoparticles loaded with the anticancer drugs doxorubicin (DOX) and glucose oxidase (GOx) and then covered by water-soluble pillar[5]arene as a nanovalve. The nanovalve formed by the host-guest interaction between pillar[5]arene and the sulfonic acid group grafted onto the gold nanoparticle increased the drug loading capacity of the nanoplatform and enabled sustained release of the drug in a simulated weakly acidic tumor environment. The released GOx can consume intracellular glucose, namely, starvation therapy, while the generated hydrogen peroxide can further kill tumor cells, complementing DOX chemotherapy. Gold nanoparticles have good photothermal conversion ability and can enhance the drugs release rate under specific wavelengths of light irradiation. The results of in vitro and in vivo experiments showed that this novel nanodrug delivery platform has good biocompatibility and better therapeutic efficacy relative to monotherapy. This study successfully developed a combined chemo/starvation therapy strategy with good tumor suppression, providing a new approach for cancer treatment.

Transition Metal Phosphides: The Rising Star of Lithium-Sulfur Battery Cathode Host.

Lithium-sulfur batteries (LSBs) with ultra-high energy density (2600 W h kg-1 ) and readily available raw materials are emerging as a potential alternative device with low cost for lithium-ion batteries. However, the insulation of sulfur and the unavoidable shuttle effect leads to slow reaction kinetics of LSBs, which in turn cause various roadblocks including poor rate capability, inferior cycling stability, and low coulombic efficiency. The most effective way to solve the issues mentioned above is to rationally design and control the synthesis of the cathode host for LSBs. Transition metal phosphides (TMPs) with good electrical conductivity and dual adsorption-conversion capabilities for polysulfide (PS) are regarded as promising cathode hosts for new-generation LSBs. In this review, the main obstacles to commercializing the LSBs and the development processes of their cathode host are first elaborated. Then, the sulfur fixation principles, and synthesis methods of the TMPs are briefly summarized and the recent progress of TMPs in LSBs is reviewed in detail. Finally, a perspective on the future research directions of LSBs is provided.

Supramolecular Polymer Polymorphism: Spontaneous Helix-Helicoid Transition through Dislocation of Hydrogen-Bonded π-Rosettes.

Polymorphism, a phenomenon whereby disparate self-assembled products can be formed from identical molecules, has incited interest in the field of supramolecular polymers. Conventionally, the monomers that constitute supramolecular polymers are engineered to facilitate one-dimensional aggregation and, consequently, their polymorphism surfaces primarily when the states of assembly differ significantly. This engenders polymorphs of divergent dimensionalities such as one- and two-dimensional aggregates. Notwithstanding, realizing supramolecular polymer polymorphism, wherein polymorphs maintain one-dimensional aggregation, persists as a daunting challenge. In this work, we expound upon the manifestation of two supramolecular polymer polymorphs formed from a large discotic supramolecular monomer (rosette), which consists of six hydrogen-bonded molecules with an extended π-conjugated core. These polymorphs are generated in mixtures of chloroform and methylcyclohexane, attributable to distinctly different disc stacking arrangements. The face-to-face (minimal displacement) and offset (large displacement) stacking arrangements can be predicated on their distinctive photophysical properties. The face-to-face stacking results in a twisted helix structure. Conversely, the offset stacking induces inherent curvature in the supramolecular fiber, thereby culminating in a hollow helical coil (helicoid). While both polymorphs exhibit bistability in nonpolar solvent compositions, the face-to-face stacking attains stability purely in a kinetic sense within a polar solvent composition and undergoes conversion into offset stacking through a dislocation of stacked rosettes. This occurs without the dissociation and nucleation of monomers, leading to unprecedented helicoidal folding of supramolecular polymers. Our findings augment our understanding of supramolecular polymer polymorphism, but they also highlight a distinctive method for achieving helicoidal folding in supramolecular polymers.

A pH-Responsive Supramolecular Drug Delivery System Constructed by Cationic Pillar[5]arene for Enhancing Antitumor Activity.

Drug delivery systems have good biocompatibiliy and low side effects for cancer treatment, but overcoming high efficiency of drug-loading and the drug-targeting controlled release still remains challenging. In this work, supramolecular vesicles, with pH-triggering effect, have been successfully constructed for drug delivery, which are fabricated by the complexation between a cationic pillar[5]arene (DAWP5) and a sodium dodecyl sulfonate (SDS) in aqueous solution. Drug-loading and releasing results demonstrated that anticancer drug doxorubicin (DOX) could be loaded efficiently by such cationic vesicles in neutral condition, and the drug release could be controlled in the simulated weak acid environment of tumor cells. Moreover, the vesicles had low cytotoxicity to normal human cell (L02), while the DOX-loaded vesicles could significantly enhance the cytotoxicity of free DOX for normal cell L02 and four tested tumor cells (Hela, HepG2, MGC-803 and T24). Especially for HepG2, after 24 h incubation time, IC50 of DOX-loaded vesicles was only 0.79 µM, about 23% of that of DOX (3.43 µM). These results suggested that such novel vesicles have promising potential to construct nano-drug delivery systems for various biomedical applications.

Recognition Selectivities of Lasso-Type Pseudo[1]rotaxane Based on a Mono-Ester-Functionalized Pillar[5]arene.

Two types of mono-ester-functionalized pillar[5]arenes, P1 and P2, bearing different side-chain groups, were synthesized. Their host-guest complexation and self-inclusion properties were studied by 1H NMR and 2D nuclear overhauser effect spectroscopy (NOESY) NMR measurements. The results showed that the substituents on their phenolic units have a great influence on the self-assembly of both pillar[5]arenes, although they both could form stable pseudo[1]rotaxanes at room temperature. When eight bulky 4-brombutyloxy groups were capped on the cavity, instead of methoxy groups, pseudo[1]rotaxane P1 became less stable and its locked ester group in the inner space of cavity was not as deep as P2, leading to distinctly different host-guest properties between P1 and P2 with 1,6-dibromohexane. Moreover, pillar[5]arene P1 displayed effective molecular recognition toward 1,6-dichlorohexane and 1,2-bromoethane among the guest dihalides. In addition, the self-complex models and stabilities between P1 and P2 were also studied by computational modeling and experimental calculations.

Synthesis and antifungal activity of dehydroabietic acid-based 1,3,4-thiadiazole-thiazolidinone compounds.

In an attempt to search for new natural products-based antifungal agents, a series of novel dehydroabietic acid derivatives bearing a 1,3,4-thiadiazole-thiazolidinone moiety were designed and synthesized. The primary bioassay used showed that at a concentration of [Formula: see text], the target compounds 3c, 3f, and 3n exhibited excellent antifungal activity (91.3 % inhibition) against Gibberella zeae, which was equivalent to the commercial antifungal drug azoxystrobin (positive control).

Dimerization control in the self-assembly behavior of copillar[5]arenes bearing ω-hydroxyalkoxy groups.

Two novel copillar[5]arenes bearing ω-hydroxyalkoxy groups are synthesized and their self-assembly properties are studied by (1)H NMR spectroscopy, specific viscosity, and X-ray measurements. The copillar[5]arene 2b bearing a 6-hydroxyhexyloxy group exhibits a reversible self-assembly behavior, leading to the formation of the self-inclusion monomer and hugging dimers. The reversible self-assembly behavior can be controlled by tuning solvent, temperature, guest, and H-bond interaction. However, the copillar[5]arene 2a bearing a short 4-hydroxybutyloxy group does not show such a self-assembly behavior to the formation of the self-inclusion monomer and hugging dimers.

Efficient synthesis of copillar[5]arenes and their host-guest properties with dibromoalkanes.

An efficient method for the synthesis of copillar[5]arenes was developed with FeCl(3) as catalyst and different 1,4-dialkoxybenzenes and paraformaldehyde as reactants (yields: 50-85%). The host-guest property of (co)pillar[5]arenes and terminal dibromoalkanes was investigated by (1)H NMR measurements and an X-ray study. The complexation behavior of the copillar[5]arenes can be tuned by changing the substituents on the host. A complete complexation selectivity was found between pillar[5]- and pillar[6]arenes, which is an interesting aspect for sensor techniques.

Synthesis of a dehydroabietyl derivative bearing a 2-(2'-hydroxyphenyl)benzimidazole unit and its selective Cu²+ chemosensing.

A dehydroabietyl derivative 2 bearing a 2-(2'-hydroxyphenyl)benzimidazole unit was synthesized and its sensing behaviors toward metal ions were investigated by UV-Vis and fluorescence spectroscopy methods. In THF solution, compound 2 exhibited excellent selectivity for CuII over miscellaneous other metal ions including CrII, MnII, CoII, NiII, ZnII, CdII, AlIII, MgII, PbII, HgII, NaI, LiI and KI evidenced through the quenching of the fluorescence of the benzimidazole fragment. The reaction between 2 and Cu²+ was found to be stoichiometric with the formation of a 1:1 complex.

Syntheses, characterization and fluorescent properties of two series of dehydroabietic acid C-ring derivatives.

Two series of dehydroabietic acid C-ring derivatives, nitrogen-containing heterocycles (6a-9b) and C-12 substituted compounds (10a-11b), were synthesized and characterized by element analysis, IR, NMR and MS. The UV-vis absorption and fluorescence spectral characteristics of these compounds have been comparatively investigated, and their fluorescence quantum yields were further evaluated. Compared to dehydroabietic acid 1, the absorption and emission spectra of these compounds were bathochromically shifted due to the multiple aromatic rings with rigid planar structures or the larger conjugation of benzene moiety.