Leyong Wang

pH-Responsive Supramolecular Vesicles Based on Water-Soluble Pillar[6]arene and Ferrocene Derivative for Drug Delivery

The drug delivery system based on supramolecular vesicles that were self-assembled by a novel host-guest inclusion complex between a water-soluble pillar[6]arene (WP6) and hydrophobic ferrocene derivative in water has been developed. The inclusion complexation between WP6 and ferrocene derivative in water was studied by (1)H NMR, UV-vis, and fluorescence spectroscopy, which showed a high binding constant of (1.27 ± 0.42) × 10(5) M(-1) with 1:1 binding stoichiometry. This resulting inclusion complex could self-assemble into supramolecular vesicles that displayed a significant pH-responsive behavior in aqueous solution, which were investigated by fluorescent probe technique, dynamic laser scattering, and transmission electron microscopy. Furthermore, the drug loading and in vitro drug release studies demonstrated that these supramolecular vesicles were able to encapsulate mitoxantrone (MTZ) to achieve MTZ-loaded vesicles, which particularly showed rapid MTZ release at low-pH environment. More importantly, the cellular uptake of these pH-responsive MTZ-loaded vesicles by cancer cells was observed by living cell imaging techniques, and their cytotoxicity assay indicated that unloaded vesicles had low toxicity to normal cells, which could dramatically reduce the toxicity of MTZ upon loading of MTZ. Meanwhile, MTZ-loaded vesicles exhibited comparable anticancer activity in vitro as free MTZ to cancer cells under examined conditions. This study suggests that such supramolecular vesicles have great potential as controlled drug delivery systems.

Multistimuli-Responsive Supramolecular Vesicles Based on Water-Soluble Pillar[6]arene and SAINT Complexation for Controllable Drug Release

Supramolecular binary vesicles based on the host-guest complexation of water-soluble pillar[6]arene (WP6) and SAINT molecule have been successfully constructed, which showed pH-, Ca(2+)-, and thermal-responsiveness. These supramolecular vesicles can efficiently encapsulate model substrate calcein, which then can be efficiently released either by adjusting the solution pH to acidic condition due to the complete disruption of vesicular structure, or particularly, by adding a certain amount of Ca(2+) due to the Ca(2+)-induced vesicle fusion and accompanied by the structure disruption. More importantly, drug loading and releasing experiments demonstrate that an anticancer drug, DOX, can be successfully encapsulated by the supramolecular vesicles, and the resulting DOX-loaded vesicles exhibit efficient release of the encapsulated DOX with the pH adjustment or the introduction of Ca(2+). Cytotoxicity experiments suggest that the resulting DOX-loaded supramolecular vesicles exhibit comparable therapeutic effect for cancer cells as free DOX and the remarkably reduced damage for normal cells as well. The present multistimuli-responsive supramolecular vesicles have great potential applications in the field of controlled drug delivery. In addition, giant supramolecular vesicles (~3 μm) with large internal volume and good stability can be achieved by increasing the temperature of WP6 ⊃ SAINT vesicular solution, and they might have potential applications for bioimaging.

Pillar[5]arene-based polymeric architectures constructed by orthogonal supramolecular interactions

Ureidopyrimidinone functionalized pillar[5]arene (UPyP5) was synthesized and employed to complex with a bisparaquat derivative (G) to form supramolecular polymers at relatively high concentration. The orthogonal binding interactions including quadruple hydrogen bonding and host-guest interaction should play vital roles in the construction of this linear assembly.

Dynamic Supramolecular Complexes Constructed by Orthogonal Self-Assembly

CONSPECTUS: Supramolecular complexes, including various low-molecular-mass structures and large molecular aggregates that are assembled by reversible and highly directional noncovalent interactions, have attracted more and more attention due to their fascinating and unconventional chemical and physical properties that are different from those of traditional architectures encountered by covalently linked backbones. Supramolecular complexes are by nature dynamic architectures considering the reversibility of noncovalent interactions by which small molecular monomers can assemble into specific architectures that are able to be repeatably reorganized through the assembly/disassembly processes under certain environmental factors such as temperature, concentration, and solvent conditions. The construction of supramolecular complexes by orthogonal self-assembly with different types of highly specific, noninterfering interactions is currently attracting considerable interest since they not only can dynamically self-assemble, but also can be tuned by various external stimuli through addressing each type of noncovalent interaction separately. Therefore, these dynamic supramolecular complexes, especially with external responsiveness, represent the most outstanding candidates for the future development of functional and smart materials, and even mimic the assembling process of natural systems. In this Account, we will summarize the recent advances of dynamic supramolecular complexes constructed by orthogonal self-assembly in soluiton in two sections: (1) Construction strategies for supramolecular complexes based on orthogonal self-assembly, whose dynamic behaviors with external responsiveness were not experimentally investigated but potentially existed due to the intrinsic reversibility of noncovalent bonds; (2) dynamic behaviors of multiresponsive supramolecular complexes, which were experimentally reported to exhibit reversible multi-responsiveness to external stimuli. Dynamic nature is one of intrinsic properties of supramolecular complexes constructed by self-assembly. Therefore, in the first section, we will describe the dynamic self-assembly in the construction of supramolecular complexes, but will focus on their external responsive dynamic behaviors in the second section. In addition, considering that an increasing number of supramolecular complexes constructed by biological building blocks through bio-orthogonal assembly as mimics of biological systems have been reported in recent years, in the second section we will also present some typical examples on such special dynamic biological supramolecular complexes. The final part of this Account is devoted to foreseeing the rapid development of dynamic supramolecular complexes toward applications in functional and smart materials and fundamental questions facing dynamic supramolecular complexes in the future.

A novel redox-responsive pillar[6]arene-based inclusion complex with a ferrocenium guest

A novel and highly stable inclusion complex was formed between per-butylated pillar[6]arene and a ferrocenium cation, while the reduced form ferrocene only showed extremely weak binding affinity with per-butylated pillar[6]arene in organic solvents.

Pillar[5]arene-based supramolecular polypseudorotaxanes constructed from quadruple hydrogen bonding

Novel linear supramolecular polypseudorotaxanes constructed from bifunctional ureidopyrimidinone (UPy) pillar[5]arene as the wheel and alkyl diamine as the axle were successfully prepared. This supramolecular polymer was stabilized by the combination of two different non-covalent interactions: quadruple hydrogen bonding and pillararene-based host–guest interactions.

Late transition metal complexes bearing 2,9-bis(imino)-1,10-phenanthrolinyl ligands: synthesis, characterization and their ethylene activity

Abstract A series of iron, cobalt and nickel halide complexes, LMX2 (M=Fe, X=Cl; M=Co, X=Cl; M=Ni, X=Br) bearing 2,9-bis(imino)-1,10-phenanthrolinyl ligands [L=2,9-(ArNCH)2C12H6N2] were synthesized. The solid-state structures of 4 and 7 have been determined by single-crystal X-ray diffraction study. Treatment of the complexes LMX2 with methylaluminoxane (MAO) leaded to activate ethylene as oligomerization catalysts.

Cu-Catalyzed Cross-Dehydrogenative Coupling Reactions of (Benzo)thiazoles with Cyclic Ethers

Copper-catalyzed cross-dehydrogenative coupling (CDC) reactions of (benzo)thiazoles with cyclic ethers were developed under mild conditions. In particular, the formation of C-C bonds via the CDC reactions between non-benzo-fused azoles and ethers are reported for the first time. In addition, the acetals, known as the masked 2-thiazolecarboxaldehydes, could be successfully obtained by this CDC reaction. The preliminary mechanism and supportive DFT calculations are discussed as well.

Dramatically Promoted Swelling of a Hydrogel by Pillar[6]arene–Ferrocene Complexation with Multistimuli Responsiveness

The swelling-shrinking transition of hydrogels is crucial for their wide applications such as actuators and drug delivery. We hereby fabricated a smart hydrogel with ferrocene groups on pendant of polymer networks. While it was immersed in the water-soluble pillar[6]arene (WP6) aqueous solution, the hydrogel was dramatically swollen, which was an approximately 11-fold promotion in weight compared with that in pure water, due to the formation of the inclusion complexes between WP6 and ferrocene groups in the hydrogel. In particular, the well-swollen hydrogel exhibited good responsiveness to multistimuli including temperature, pH, redox, and competitive guests by tuning the dissociation/formation of WP6-ferrocene inclusion complexes or the strength of their charges. Meanwhile, potential application of such a smart hydrogel in pH-responsive drug release was demonstrated as well.

Cobalt and nickel complexes bearing 2,6-bis (imino) phenoxy ligands: syntheses, structures and oligomerization studies

Abstract A series of new cobalt and nickel complexes LMX2 (M=Co, X=Cl; M=Ni, X=Br) bearing 2, 6-bis(imino)phenoxy ligands were synthesized. The solid-state structures of 1 and 4 have been determined by single-crystal X-ray diffraction study. Treatment of the complexes LMX2 with methylaluminoxane (MAO) leads to active catalysts for oligomerization of ethylene with catalytic activities in the range of 1.2×105–2.1×105 g mol−1 h−1 atm−1 for Ni complexes, and ∼103 g mol−1 h−1 atm−1 for Co complexes. The oligomers were olefins from C4 to C16.