Biomedical Applications of Sulfonylcalix[4]arene-Based Metal-Organic Supercontainers.

Coordination cages sustained by metal-ligand interactions feature polyhedral architectures and well-defined hollow structures, which have attracted significant attention in recent years due to a variety of structure-guided promising applications. Sulfonylcalix[4]arenes-based coordination cages, termed metal-organic supercontainers (MOSCs), that possess unique multi-pore architectures containing an endo cavity and multiple exo cavities, are emerging as a new family of coordination cages. The well-defined built-in multiple binding domains of MOSCs allow the efficient encapsulation of guest molecules, especially for drug delivery. Here, we critically discuss the design strategy, and, most importantly, the recent advances in research surrounding cavity-specified host-guest chemistry and biomedical applications of MOSCs.

Triphenylamine-Functionalized Coordination Cage as a Supramolecular Fluorescence Sensor for Sequential Detection of Aluminum Ions and Nitrofurantoin.

Coordination cages with a well-defined nanocavity are a class of promising supramolecular materials for molecular recognition and sensing. However, their applications in sequential sensing of multiple types of pollutants are highly desirable yet extremely limiting and challenging. Herein, we demonstrate a convenient strategy to develop a supramolecular fluorescence sensor for sequentially detecting environmental pollutants of aluminum ions and nitrofurantoin. A coordination cage (Ni-NTB), adopting an octahedral structure with triphenylamine chromophores occupying on the faces, is weakly emissive in solution due to the intramolecular rotations of the phenyl rings. Ni-NTB exhibits sensitive and selective fluorescence "off-on-off" processes during consecutive sensing of Al3+ and nitrofurantoin, an antibacterial drug. These sequential detection processes are highly interference-tolerant and visually observable with the naked eye. Mechanism studies reveal that the fluorescence switch is controllable by tuning the degree of intramolecular rotations of the phenyl rings and the pathway of intermolecular charge transfer, which is associated with the host-guest interaction. Moreover, the fabrication of Ni-NTB on test strips enabled a quick naked-eye sequential sensing of Al3+ and nitrofurantoin in seconds. Hence, this novel supramolecular fluorescence "off-on-off" sensing platform provides a new approach to developing supramolecular functional materials for monitoring environmental pollution.

Ultrasmall PtAu2 nanoclusters activate endogenous anti-inflammatory and anti-oxidative systems to prevent inflammatory osteolysis.

Rationale: Inflammatory osteolysis, characterized by abundant immune cell infiltration and osteoclast (OC) formation, is a common complication induced by bacterial products and/or wear particles at the bone-prosthesis interface that severely reduces long-term stability after implantation. Molecular nanoclusters are ultrasmall particles with unique physicochemical and biological properties that have great potential as theranostic agents for treating inflammatory diseases. Methods: In this study, heterometallic PtAu2 nanoclusters with sensitive nitric oxide-responsive phosphorescence turn-on characteristics and strong binding interactions with cysteine were designed, making them desirable candidates for the treatment of inflammatory osteolysis. Results: PtAu2 clusters exhibited satisfactory biocompatibility and cellular uptake behavior, with potent anti-inflammatory and anti-OC activities in vitro. In addition, PtAu2 clusters alleviated lipopolysaccharide-induced calvarial osteolysis in vivo and activated nuclear factor erythroid 2-related factor 2 (Nrf2) expression by disrupting its association with Kelch-like ECH-associated protein 1 (Keap1), thereby upregulating the expression of endogenous anti-inflammatory and anti-oxidative products. Conclusion: Through the rational design of novel heterometallic nanoclusters that activate the endogenous anti-inflammatory system, this study provides new insights into the development of multifunctional molecular therapeutic agents for inflammatory osteolysis and other inflammatory diseases.

Mitochondria-targeted supramolecular coordination container encapsulated with exogenous itaconate for synergistic therapy of joint inflammation.

Rationale: Inflammatory macrophages and osteoclasts (OCs) play critical roles in joint inflammation, which feature the excessive production of reactive oxygen species (ROS), resulting in synovial inflammation and bone erosion. Scavenging ROS, especially by modulating mitochondrial metabolic activity, could be a desirable strategy for the management of inflammatory joints. This study aimed to develop a mitochondria-targeted supramolecular drug delivery system with exogenous and endogenous ROS-scavenging activities for the treatment of joint inflammation. Methods: In this study, we utilized a zinc-based metal-organic supercontainer (MOSC) as a proton sponge and electron reservoir with outstanding proton binding capacity, extracellular ROS-scavenging ability, and biocompatibility to establish an efficient supramolecular nanocarrier for endo/lysosomal escape and mitochondrial targeting. 4-Octyl itaconate (4-OI), an itaconate derivative, served as the loaded guest for the construction of a synergistic therapeutic system for inflammatory macrophages and OCs. Results: After the effective encapsulation of 4-OI, 4-OI@Zn-NH-pyr not only exhibited potent ROS-scavenging capacity, but also reduced ROS production by mediating mitochondrial respiration in inflammatory macrophages. Regarding its anti-inflammatory efficacy, 4-OI@Zn-NH-pyr ameliorated the inflammatory reaction by activating nuclear factor erythroid 2-related factor 2 (Nrf2), thus increasing the production of antioxidants, apart from the inhibition of NF-κB pathways. Additionally, receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and function was remarkably suppressed by 4-OI@Zn-NH-pyr. Consistent with in vitro observations, 4-OI@Zn-NH-pyr efficiently inhibited synovial inflammation and subchondral bone destruction in an acute arthritis model. Conclusion: By using MOSCs that are highly reactive to ROS as drug-loaded matrices for the first time, this study provides an avenue for the management of severe joint inflammation by designing synergistic supramolecular drug-delivery systems with subcellular targeting and ROS-scavenging capacity.

Decahexanuclear Zinc(II) Coordination Container Featuring a Flexible Tetracarboxylate Ligand: A Self-Assembly Supermolecule for Highly Efficient Drug Delivery of Anti-Inflammatory Agents.

The application of a coordination container in biomedicine is hindered by single binding domains and unsatisfactory biostability and biocompatibility. Herein, we designed a sulfonylcalix[4]arene-based decahexanuclear zinc(II) coordination container employing a flexible tetracarboxylate ligand as a linker and utilized it as a novel drug delivery system. The coordination container consisting of one endo and four exo cavities provides multiple binding domains for efficient encapsulation of drug molecules as clearly revealed by systematic host-guest studies using NMR techniques of 1H NMR titration experiments and 2D NOESY and diffusion-ordered NMR spectroscopy studies. Incorporation of a flexible p-phenylene-bis(methanamino) spacer into the container via the carboxylate linker allowed a stepwise drug loading process through sequential binding at endo and exo cavities, as well as enabling pH-responsive stepwise drug release. The drug-loaded coordination container not only exhibits excellent biostability and biocompatibility but also provides encouraging therapeutic efficiency toward inflammatory macrophages as revealed by in vitro studies. The novel strategy for engineering the endo cavity of a coordination container provides a new approach to achieving controlled drug delivery and opens up new opportunities for designing novel functional supramolecular materials.

Cooperative Binding and Stepwise Encapsulation of Drug Molecules by Sulfonylcalixarene-Based Metal-Organic Supercontainers.

The cooperative binding behavior of a face-directed octahedral metal-organic supercontainer featuring one endo cavity and six exo cavities was thoroughly examined in chloroform solution through ultraviolet-visible (UV-Vis) titration technique using two representative drug molecules as the guests. The titration curves and their nonlinear fit to Hill equation strongly suggest the efficient encapsulation of the guest molecules by the synthetic host, which exhibit interesting cooperative and stepwise binding behavior. Based on the control experiments using tetranuclear complex as a reference, it is clear that two equivalents of the guest molecules are initially encapsulated inside the endo cavity, followed by the trapping of six additional equivalents of the drug molecules through six exo cavities (1 eq. per exo cavity), and the remaining guests are entrapped by the external pockets. The results provide an in-depth understanding of the cooperative binding behavior of metal-organic supercontainers, which opens up new opportunities for designing synthetic receptors for truly biomimetic functional applications.

Aggregation-induced emission enhancement and reversible mechanochromic luminescence of quinoline-based zinc(ii)-Schiff base complexes.

Three quinoline-based zinc(ii)-Schiff base complexes were synthesized and characterized by X-ray crystallography. They exhibit remarkable aggregation-induced emission enhancement (AIEE) in acetonitrile/diethyl ether mixtures due to the conversion of weak luminescence in homogeneous solution into strong emission in the nano-aggregated phase after increasing the fractions of diethyl ether. Interestingly, the AIEE performance can be significantly promoted by joining the two quinoline units through an alkoxy chain. Moreover, they show reversible mechanochromic luminescence behavior between dark and bright states during the grinding-fuming cycles, due to the modulation of morphologies between amorphous and crystalline states. Introducing an electron donating group in the para-position of aniline significantly improves the mechanochromic luminescence effect with a more accessible and distinct emission colour contrast. The molecular packing in the crystalline phase and time-dependent density functional theory (TD-DFT) calculations demonstrate that multiple intermolecular C-Hπ and π-π interactions significantly strengthen the molecular rigidity and enhance the intramolecular charge-transfer (ICT) characteristics, leading to the effective emission enhancement in crystalline/nano-aggregated states. The novel AIEE and reversible mechanochromic luminescence properties point to the promising potential applications of these complexes in smart fluorescent materials.

Stimuli-responsive metal-organic supercontainers as synthetic proton receptors.

We demonstrate a proof-of-concept design of a new platform for proton recognition and modulation. The new proton receptors are derived from a unique class of synthetic supercontainers that exhibit exceptional proton binding capacity (over 50 equiv.) and intriguing proton-dependent fluorescent switching behavior. Experimental and computational studies suggest that the proton-responsive event involves a two-step mechanism pertaining to proton binding by both amino and pyrenyl moieties of the supercontainer constructs. The high proton binding capacity of the supercontainers can be further modulated via small-molecule "regulators" that compete for the proton-binding sites, opening exiting new opportunities for proton manipulation in both chemistry and biology.

Sensitive and selective urinary 1-hydroxypyrene detection by dinuclear terbium-sulfonylcalixarene complex.

A new sulfonylcalix[4]arene-based dinuclear terbium molecular container (1) was conveniently synthesized and utilized as a fluorescence probe for the detection of a well-known biomarker 1-hydroxypyrene (1-OHP), which is used for the evaluation of polycyclic aromatic hydrocarbons (PAHs). The sulfonylcalix[4]arene ligand could not only serve as an efficient antenna ligand to promote the ligand-to-metal energy transfer but also provide a suitable cavity to accommodate 1-OHP. Promising fluorescence quenching effects were well established during the titration of the compound 1 with 1-OHP, and these effects were due to the enhancement in the host-guest intermolecular charge transfer and the decrease in the ligand-to-metal energy transfer after the formation of the stable host-guest complex. The fluorescence sensing mechanism was clearly understood through the titration experiments, and the data could be fit with the Benesi-Hildebrand and Stern-Volmer models. The TbIII-TBSC-based luminescent sensor exhibited quick response, high sensitivity, and specific selectivity to 1-OHP, even in the presence of other constituents in urine, thus providing a new sensing platform for the clinical diagnosis of human exposure to PAHs.

Sensitive and Specific Guest Recognition through Pyridinium-Modification in Spindle-Like Coordination Containers.

An elaborately designed pyridinium-functionalized octanuclear zinc(II) coordination container 1-Zn was prepared through the self-assembly of Zn2+ , p-tert-butylsulfonylcalix[4]arene, and pyridinium-functionalized angular flexible dicarboxylate linker (H2 BrL1). The structure was determined by a single-crystal X-ray diffractometer. 1-Zn displays highly sensitive and specific recognition to 2-picolylamine as revealed by drastic blueshifts of the absorption and emission spectra, ascribed to the decrease of intramolecular charge transfer (ICT) character of the container and the occurrence of intermolecular charge transfer between the host and guest molecules. The intramolecular charge transfer plays a key role in the modulation of the electronic properties and is tunable through endo-encapsulation of specific guest molecules.

Organic donor materials based on Bis(arylene ethynylene)s for bulk heterojunction organic solar cells with high V(oc) values.

A series of purely organic small molecules 1-4 based on bis(arylene ethynylene)s with various electron-rich aromatic bridges, such as benzene, cyclopentadithiophene (CDT), and diphenyl(p-tolyl)amine, were synthesized by a Sonogashira coupling reaction. Their optical, electronic, and electrochemical properties were fully characterized. The photovoltaic properties of these molecules as donor materials and [6,6]-phenyl-C71 -butyric acid methyl ester as an acceptor material in solution-processed bulk heterojunction devices were studied. Among them, CDT-bridged molecule 2 exhibited the best photovoltaic performance and achieved a power conversion efficiency of 3.28 %. In addition, the photovoltaic efficiencies of these molecules are higher than their corresponding platinum-containing counterparts, probably owing to their stronger light absorption and improved open-circuit voltage.

pH-modulated molecular assemblies and surface properties of metal-organic supercontainers at the air-water interface.

The orientation of metal-organic supercontainer (MOSC) molecules in Langmuir films was systematically studied at the air-water interface. The acidity of the aqueous subphases plays a significant role in tuning the orientation of MOSC molecules in the Langmuir films. Furthermore, Langmuir-Blodgett films of MOSCs were prepared and the uniform multilayer structures demonstrated various surface properties, depending on their conditions of fabrication. Our use of Langmuir films provides a novel approach to access tunable assemblies of MOSC molecules in two-dimensional thin films.

Synthetic supercontainers exhibit distinct solution versus solid state guest-binding behavior.

The phase-dependent host-guest binding behavior of a new family of synthetic supercontainers has been probed in homogeneous solution and at liquid-liquid, solid-liquid, and solid-gas interfaces. The synthetic hosts, namely, type II metal-organic supercontainers (MOSCs), are constructed from the assembly of divalent metal ions, 1,4-benzenedicarboxylate (BDC) linker, and sulfonylcalix[4]arene-based container precursors. One member of the MOSCs, MOSC-II-tBu-Ni, which is derived from Ni(II), BDC, and p-tert-butylsulfonylcalix[4]arene (TBSC), crystallizes in the space group R3 and adopts pseudo face-centered cubic (fcc) packing, whereas other MOSCs, including TBSC analogue MOSC-II-tBu-Co, p-tert-pentylsulfonylcalix[4]arene (TPSC) analogues MOSC-II-tPen-Ni/Co, and p-tert-octylsulfonylcalix[4]arene (TOSC) analogues MOSC-II-tOc-Ni/Mg/Co, all crystallize in the space group I4/m and assume a pseudo body-centered cubic (bcc) packing mode. This solid-state structural diversity is nevertheless not reflected in their solution host-guest chemistry, as evidenced by the similar binding properties of MOSC-II-tBu-Ni and MOSC-II-tBu-Co in solution. Both MOSCs show comparable binding constants and adsorb ca. 7 equiv of methylene blue (MB) and ca. 30 equiv of aspirin in chloroform. In contrast, the guest-binding behavior of the MOSCs in solid state reveals much more variations. At the solid-liquid interface, MOSC-II-tBu-Co adsorb ca. 5 equiv of MB from an aqueous solution at a substantially faster rate than MOSC-II-tBu-Ni does. However, at the solid-gas interface, MOSC-II-tBu-Ni has higher gas uptake than MOSC-II-tBu-Co, contradicting their overall porosity inferred from the crystal structures. This discrepancy is attributed to the partial collapse of the solid-state packing of the MOSCs upon solvent evacuation. It is postulated that the degree of porosity collapse correlates with the molecular size of the MOSCs, i.e., the larger the MOSCs, the more severe they suffer from the loss of porosity. The same principle can rationalize the negligible N2 and O2 adsorption seen in the larger MOSC-II-tPen-Co and MOSC-II-tOC-Ni/Mg/Co molecules. MOSC-II-tPen-Ni features an intermediate molecular size and endures a partial structural collapse in such a way that the resulting pore dimension permits the inclusion of kinetically smaller O2 (3.46 Å) but excludes larger N2 (3.64 Å), explaining the observed remarkable O2/N2 adsorption selectivity.

(BMI)3LnCl6 crystals as models for the coordination environment of LnCl3 (Ln = Sm, Eu, Dy, Er, Yb) in 1-butyl-3-methylimidazolium chloride ionic-liquid solution.

A series of (BMI)3LnCl6 (Ln = Sm, Eu, Dy, Er, Yb) crystals was prepared from solutions of LnCl3 dissolved in the ionic liquid, 1-butyl-3-methylimidazolium chloride (BMICl). Crystals with Ln = 5% Sm + 95% Gd and with Ln = 5% Dy + 95% Gd were also grown to assess the importance of cross-relaxation in the Sm and Dy samples. The crystals are isostructural, with monoclinic space group P21/c and four formula units per unit cell. The first coordination sphere of Ln(3+) consists of six Cl(-) anions forming a slightly distorted octahedral LnCl6(3-) center. The second coordination sphere is composed of nine BMI(+) cations. The emission spectra and luminescence lifetimes of both (BMI)3LnCl6 crystals and LnCl3 in BMICl solution were measured. The spectroscopic similarities suggest that crystalline (BMI)3LnCl6 provides a good model of the Ln(3+) coordination environment in BMICl solution.

Modulating guest binding in sulfonylcalixarene-based metal-organic supercontainers.

Metal-organic supercontainers (MOSCs) represent a new family of synthetic receptors derived from container precursors and featuring both endo and exo cavities. A neutral MOSC has been functionalized into an anionic container by incorporating sulfo groups. The anionic MOSC exhibits cavity-specific binding properties in both solid state and solution.

Oligothiophene-bridged bis(arylene ethynylene) small molecules for solution-processible organic solar cells with high open-circuit voltage.

A new series of conjugated oligothiophene-bridged bis(arylene ethynylene) small molecules have been designed, synthesized, and characterized by photophysical, electrochemical and computational methods. These compounds were found to have optimal LUMO levels that ensure effective charge transfer from these compounds to [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM). They were utilized as good electron-donor materials that can be blended with electron-acceptor PC70BM in the fabrication of solution-processed molecular bulk heterojunction (BHJ) solar cells. All of these BHJ devices showed very high open-circuit voltage (V(oc)) of 0.90-0.97 V, and the best power conversion efficiency achieved was 3.68%. The high V(oc) is consistent with the deeper low-lying HOMO level and is relatively insensitive to the donor : acceptor blend ratio. The spin-coated thin films of these small molecules showed p-channel field-effect charge transport with the hole mobilities of up to 2.04×10(-4) cm(2) V(-1) s(-1). These compounds illuminate the potential of solution-processible small-molecular aryl acetylide compounds for efficient power generation in photovoltaic implementation.

Heterometallic cerium(IV) perrhenate, permanganate, and molybdate complexes supported by the imidodiphosphinate ligand [N(i-Pr2PO)2]-.

Heterometallic cerium(IV) perrhenate, permanganate, and molybdate complexes containing the imidodiphosphinate ligand [N(i-Pr2PO)2](-) have been synthesized, and their reactivity was investigated. Treatment of Ce[N(i-Pr2PO)2]3Cl (1) with AgMO4 (M = Re, Mn) afforded Ce[N(i-Pr2PO)2]3(ReO4) (2) or Ce2[N(i-Pr2PO)2]6(MnO4)2 (3). In the solid state, 3 is composed of a [Ce2{N(i-Pr2PO)2}6(MnO4)](+) moiety featuring a weak Ce-OMn interaction [Ce-OMn distance = 2.528(8) Å] and a noncoordinating MnO4(-) counteranion. While 3 is stable in the solid state and acetonitrile solution, it decomposes readily in other organic solvents, such as CH2Cl2. 3 can oxidize ethylbenzene to acetophenone at room temperature. Treatment of 1 with AgBF4, followed by reaction with [n-Bu4N]2[MoO4], afforded [Ce{N(i-Pr2PO)2}3]2(µ-MoO4) (4). Reaction of trans-Ce[N(i-Pr2PO)2]2(NO3)2 (5), which was prepared from (NH4)2Ce(NO3)6 and K[N(i-Pr2PO)2], with 2 equiv of [n-Bu4N][Cp*MoO3] yielded trans-Ce[N(i-Pr2PO)2]2(Cp*MoO3)2 (6). 4 can catalyze the oxidation of methyl phenyl sulfide with tert-butyl hydroperoxide with high selectivity. The crystal structures of complexes 3-6 have been determined.

Modular assembly of metal-organic supercontainers incorporating sulfonylcalixarenes.

A new strategy for the design of container molecules is presented. Sulfonylcalix[4]arenes, which are synthetic macrocyclic containers, are used as building blocks that are combined with various metal ions and tricarboxylate ligands to construct metal-organic "supercontainers" (MOSCs). These MOSCs possess both endo and exo cavities and thus mimic the structure of viruses. The synthesis of MOSCs is highly modular, robust, and predictable. The unique features of MOSCs are expected to provide exciting new opportunities for the exploration of their functional applications.

Unsymmetric platinum(II) bis(aryleneethynylene) complexes as photosensitizers for dye-sensitized solar cells.

Four new unsymmetric platinum(II) bis(aryleneethynylene) derivatives have been designed and synthesized, which showed good light-harvesting capabilities for application as photosensitizers in dye-sensitized solar cells (DSSCs). The absorption, electrochemical, time-dependent density functional theory (TD-DFT), impedance spectroscopic, and photovoltaic properties of these platinum(II)-based sensitizers have been fully characterized. The optical and TD-DFT studies show that the incorporation of a strongly electron-donating group significantly enhances the absorption abilities of the complexes. The maximum absorption wavelength of these four organometallic dyes can be tuned by various structural modifications of the triphenylamine and/or thiophene electron donor, improving the light absorption range up to 650 nm. The photovoltaic performance of these dyes as photosensitizers in mesoporous TiO(2) solar cells was investigated, and a power conversion efficiency as high as 1.57% was achieved, with an open-circuit voltage of 0.59 V, short-circuit current density of 3.63 mA cm(-2), and fill factor of 0.73 under simulated AM 1.5G solar illumination.

catena-Poly[1-butyl-3-methyl-imidazolium [[dichlorido(methanol-κO)(propan-2-ol-κO)lanthanate(III)]-di-µ-chlorido]].

The title compound, (C(8)H(15)N(2))[LaCl(4)(CH(3)OH)(C(3)H(7)OH)], consists of one 1-butyl-3-methyl-imidazolium (BMI(+)) cation and one hexa-hedral tetra-chlorido(methanol)(propan-2-ol)lanthanate anion. The La(III) ion is eight-coordinate, with the La(III) ion bridged by a pair of Cl atoms, so forming chains propagating along the a-axis direction. Each La(III) ion is further coordinated by two isolated Cl atoms, one methanol and one propan-2-ol mol-ecule. The coordinated methanol and propan-2-ol mol-ecules of the anion form O-H⋯Cl hydrogen bonds with the Cl atoms of inversion-related anions. The BMI(+) cation froms C-H⋯Cl hydrogen bonds with the Cl atoms of the anion. The anions are located in the C faces of the triclinic unit cell, with an inversion center in the middle of the La(2)Cl(2) ring of the polymeric chain.