Online solid-phase extraction based on size-controllable spherical covalent organic framework for efficient determination of polybrominated diphenyl ethers in foods.

An analytical method of microspheric brominated covalent organic framework (Br-COF)-online solid-phase extraction integrated with high-performance liquid chromatography (online SPE-HPLC) was proposed for efficiently enriching six polybrominated diphenyl ethers (PBDEs) in foods. The Br-COF microspheres were facilely prepared with uniformity and dispersion by a size-controllable synthesis at the room temperature. Attributed to multiple interactions of the halogen bonding, Van der Waals forces, hydrophobic interaction along with size-matching effect, Br-COF performed satisfactory extraction capacity for PBDEs compared with commercial adsorbents. Five primary influencing factors were optimized, including loading solvent, loading flow rate, elution solvent, elution flow rate and elution volume. Under the optimal parameters, the implement displayed excellent linear ranges (0.5-500 ng mL-1) and low detection limits (0.01-0.05 ng mL-1). The relative recoveries in six spiked food samples ranged from 87.8 to 119.7 % with relative standard deviations below 10 %. This research estabished a promising platform for quantitatively determining trace PBDEs in complex foods.

A novel near-infrared optical and redox-active receptor for the multi-model detection of Hg2+ in water and living cells.

A key issue for constructing optical and redox-active receptors is how to conjugate a specific sensing kernel with a multi-signal-responsive system to carry out multi-feature analysis. Mercury is considered to be highly toxic to human health and ecological security. In this work, we present a novel near-infrared optical and redox-active receptor that can sense Hg2+ at ppb level in aqueous media via multi-model monitors with a low detection limit of 8.4 × 10-9 M (1.68 ppb). This receptor features a visible detection, 'off-on' fluorescence response, and efficient electrochemistry assessment, as well as pH-insensitivity to Hg2+ with high sensitivity. In view of its marked near-infrared emission and fluorescence enhancement, we successfully applied this receptor to visualize Hg2+ in live cells. Furthermore, a possible sensing model was established and rationalized with theoretical studies.

New Pyridine-Bridged Ferrocene-Rhodamine Receptor for the Multifeature Detection of Hg2+ in Water and Living Cells.

A challenge in the design of optical and redox-active receptors is how to combine a specific recognition center with an efficient responsive system to facilely achieve multifeature detection in biological and environmental analyses. Herein, a novel ferrocene-rhodamine receptor conjugated with a pyridine bridge was designed and synthesized. This receptor can sensitively sense Hg2+ in aqueous media via chromogenic, fluorogenic, and electrochemical multisignal outputs with a low detection limit and fast response time. Moreover, it can be qualified as a fluorescent probe for effectively monitoring Hg2+ in living cells. A plausible recognition mode was proposed and rationalized with theoretical calculations.

Ag@S-nitrosothiol core-shell nanoparticles for chemo and photothermal synergistic tumor targeted therapy.

Along with the development of controlled delivery systems for targeted therapy, 'single-strategy' therapy often fails to achieve the desired performance in real body internal environments. In such a case, it is necessary to develop synergistic therapy strategies. Herein, for the first time, we designed and synthesized hyaluronic acid (HA) modified Ag@S-nitrosothiol core-shell nanoparticles for synergistic tumor cell targeted therapy based on photothermal therapy (PTT) and nitric oxide (NO) based chemotherapy. Triggered by near-infrared irradiation (NIR), the Ag core nanoparticle would convert the light to cytotoxic heat via a surface plasmon resonance mechanism for cancer cell apoptosis. Meanwhile, responding to NIR as well as the generated heat, the S-nitrosothiol polymeric shells would give off free NO at high concentration, inducing NO based chemotherapy. Tumor cell selective cytotoxicity assay in vitro as well as tumor bearing mouse experiments in vivo demonstrated the effective photothermal and NO based chemical synergistic tumor targeted therapy. This spatiotemporally controllable system could provide a new option and era for tumor targeted therapy in the future.

Rapid microwave synthesis of dioxin-linked covalent organic framework for efficient micro-extraction of perfluorinated alkyl substances from water.

To synthesize covalent organic framework (COF) via irreversible reactions is more challenging than by reversible ones. In this work, microwave-assisted synthesis is used to facilitate the nucleophilic substitution of 2,3,5,6-tetrafluoro-4-pyridinecarbonitrile with 2,3,6,7,10,11-hexahydroxy triphenylene. The dioxin-linked COF, named TH-COF, was efficiently synthesized with extraordinarily large surface area of 1254 m2 g-1. With its high crystallinity, excellent thermal and chemical stabilities, TH-COF is used as the coating for the solid-phase micro-extraction (SPME) of perfluorinated alkyl substances (PFASs). The adsorptive mechanism was evaluated with adsorption isotherm and kinetic adsorption. Adsorption energies are calculated based on the density functional theory. Following SPME with TH-COF-coated fibers, PFASs were eluted using 1 mL of 0.6% trifluoroacetic acid/methanol and analyzed through the ultra-performance liquid chromatography equipped with triple quadrupole mass spectrometer (UPLC-MS/MS). When applied to spiked real water samples, this method demonstrates good linearity (0.01-1000 ng L-1) with R2 ≥ 0.9945. The TH-COF-SPME-UPLC-MS/MS technique provides low limits of detection (0.0020-0.0045 ng L-1), excellent precision (≤ 7.9%), and good fiber-to-fiber reproducibility (≤ 7.1%). The TH-COF-coated fibers can be reused at least 20 times without the loss of extraction performance. In addition, the relative recoveries from spiked real water samples are 89.5%-105%.

Magnetic core-shell S-nitrosothiols nanoparticles as tumor dual-targeting theranostic platform.

The external force guided targeting strategy, as well as the in vivo active targeting strategy based on "ligands-receptors" on the targeting cells and tissues have attracted much research interest. Herein, a kind of hyaluronic acid (HA) and folic acid (FA) modified magnetic S-nitrosothiols core-shell nanoparticles for nitric oxide (NO) control release as dual-tumor targeting theranostic platform were described, combining the external guidance and internal active targeting properties. Confocal microscopy assay and cells cytotoxicity experiments confirmed the active tumor cells targeting recognition, cells uptake, and NO initiated cytotoxicity of the HA-FA external functional layer modified S-nitrosothiols nanoparticles in vitro. In vivo magnetic resonance imaging (MRI) characterization, bio-distribution assay in organs and tumor, significant tumor inhibition efficacy, survival units of the mice bearing tumor, as well as the systemic toxicity assay demonstrated the efficiency of cooperative tumor targeting diagnosis and controlled NO-releasing chemotherapy. To the best of our knowledge, this is the first time of the external magnet and HA-FA actively induced synergistic effect tumor targeting systems based on NO chemotherapy in vivo, serving as a new theranostic system.

Amino-modified covalent organic framework as solid phase extraction absorbent for determination of carboxylic acid pesticides in environmental water samples.

The amino-modified covalent organic framework (NH2@COF) was synthesized via the thiol-ene click reaction of vinyl covalent organic framework (COF) with 4-aminobenzenethiol. The introduction of amino groups can interact with the anionic headgroup of carboxylic acid pesticides. Moreover, ample hydrophilic surface area can boost absorption in the water media. The NH2@COF was fully characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. Compared with vinyl COF and four commercial absorbents, the NH2@COF shows higher extraction efficiency for carboxylic acid pesticides. The solid phase extraction (SPE) conditions, involving flow rate, ionic strength, sample pH, desorption solvent, and desorption solvent volume, were optimized in details. Under the optimized conditions, the NH2@COF was successfully applied for the enrichment and determination of six carboxylic acid pesticides in environmental water samples combined with high performance liquid chromatography. The method features wide linearity (0.2-100 ng mL-1, r > 0.999), low limits of quantification (0.04-0.20 ng mL-1), and excellent precision (RSDs ≤ 8.7%). The recoveries range from 89.6% to 102.4% with RSDs ≤ 7.1%. Therefore, the NH2@COF-SPE method is an efficient pretreatment procedure and can be utilized for the selective extraction of carboxylic acid pesticides from environmental water samples.

Molecular imprinted S-nitrosothiols nanoparticles for nitric oxide control release as cancer target chemotherapy.

It is the goal for the development of cancer target chemotherapy with specific recognition, efficient killing the tumor cells and tissues to avoid the intolerable side effects. Molecular imprinted polymer (MIPs) nanoparticles could introduce kinds of specific bio-markers (template molecules) into the nanoparticles with the subsequent removal, leaving special holes in the structure with predictable recognition specificity with cells. Herein, we design and synthesize a kind of sialic acid (SA) over-expressed tumor target hollow double-layer imprinted polymer nanoparticles with S-nitrosothiols for nitric oxide (NO)-releasing as chemotherapy. Equilibrium/selective bindings properties and probe experimental results implies that the MIPs have an intelligently selective binding to cancer cells featuring high levels of SA glyans, providing precondition for the disulfide polymer assisted cell uptake, intracellular GSH induced decomposition and rapid NO-releasing. Cytotoxicity assay with kinds of cells demonstrates the intelligent in vitro SA over-expressed tumor cells targeting recognition, intracellular delivery and cytotoxicity. In vivo bio-distribution in tumor sites and major organs, significant suppression of tumor growth, tumor-bearing mice survival unit, and the systemic toxicity investigation experiments confirm the effective chemotherapy of the S-nitrosothiols MIPs nanoparticles for the target recognition and the controlled NO release for tumor treatment comparing to the results with S-nitrosothiols CPs as delivery system. The inevitable small amount of NO leakage from S-nitrosothiols MIPs would take part in normal physiological activities and not cause serious side effects. For the first time, this kind of nitric oxide based chemotherapy and molecular-imprinting cell recognition technique both in vitro and in vivo, might provide a solution for accurate therapy to various forms of cancer with specific markers and avoid the intolerable side effects of the traditional chemotherapy treatment.

Preparation and Reactivation of Heterogeneous Palladium Catalysts and Applications in Sonogashira, Suzuki, and Heck Reactions in Aqueous Media.

A new type of heterogeneous palladium catalyst, PdMgAl-LDH, was facilely prepared by the immobilization of Pd2+ species in the layers of a Mg-Al layered double hydroxide (LDH) with co-precipitation, and then fully characterized by using powder XRD, thermogravimetric differential thermal analysis, TEM, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy techniques. These catalysts can efficiently catalyze copper-free Sonogashira, Suzuki and Heck coupling reactions of various aryl iodides, bromides, and chlorides in aqueous media under phosphine-ligand- and organic-base-free conditions. These catalysts feature easy recovery through simple filtration and could be reused at least six times without a marked loss in activity. Notably, they can be facilely reactivated by a combination of nitrolysis with co-precipitation. The basic LDH skeletons could effectively stabilize the Pd0 species created in situ and donate electron density to the Pd0 center to facilitate the oxidative addition of aryl halides, thus the PdMgAl-LDH catalysts are stable during catalysis.

Highly sensitive and selective detection of Pd2+ ions using a ferrocene-rhodamine conjugate triple channel receptor in aqueous medium and living cells.

Herein, a novel ferrocene-rhodamine receptor conjugated with an allylimine bridge was facilely synthesized. This triple channel receptor can selectively and sensitively monitor Pd2+ ions through chromogenic, fluorogenic and electrochemical assays in aqueous medium with a low detection limit (8.46 × 10-9 M) and a fast response (<8 min). It can be applied as a fluorescent probe for effective survey of Pd2+ ions in living cells. Moreover, a plausible recognition mode was proposed and rationalized by theoretical calculations.

An efficient and green synthesis of ferrocenyl-quinoline conjugates via a TsOH-catalyzed three-component reaction in water.

An efficient and green synthesis of 4-ferrocenylquinoline derivatives through a TsOH-catalyzed three-component reaction of aromatic aldehydes, amines and ferrocenylacetylene in water has been successfully developed. This strategy is a powerful method for the construction of diverse ferrocenyl-quinoline conjugates from simple available starting materials as it minimized the use of metal catalyst and organic solvent in the reaction process. The conjugates feature unique structures and excellent electronic properties. Moreover, a plausible mechanism for this TsOH-catalyzed three-component reaction was proposed and assessed.

Synthesis, Crystal Structures and Properties of Ferrocenyl Bis-Amide Derivatives Yielded via the Ugi Four-Component Reaction.

Ten ferrocenyl bis-amide derivatives were successfully synthesized via the Ugi four-component reaction by treating ferrocenecarboxylic acid with diverse aldehydes, amines, and isocyanides in methanol solution. Their chemical structures were fully characterized by IR, NMR, HR-MS, and X-ray diffraction analyses. They feature unique molecular morphologies and create a 14-membered ring motif in the centro-symmetric dimers generated in the solid state. Moreover, the electrochemical behavior of these ferrocenyl bis-amides was assessed by cyclic voltammetry.

Hollow double-layered polymer nanoparticles with S-nitrosothiols for tumor targeted therapy.

Tumor targeted hollow double-layered polymer nanoparticles (HDPNs) with S-nitrosothiols for nitric oxide (NO)-release as chemotherapy were described. Via a two-stage distillation precipitation co-polymerization, simple post-treatment and S-nitrosothiol modification, the S-nitroso HDPNs showed pH and glucose dual responsiveness. This would benefit accurate binding with the sialic acid over-expressed cancer cells, providing prerequisites for the disulfide polymer assisted cell uptake, intracellular GSH induced decomposition and rapid NO release. Confocal microscopy and cytotoxicity assay with normal versus tumor cells demonstrated in vitro recognition, intracellular delivery ability and tumor cell targeting cytotoxicity. Especially worth mentioning, the inevitable small amount of NO leakage in the transmission would take part in normal physiological activities and not cause serious side effects, providing a possible solution to avoid the intolerable side effects of traditional chemotherapy treatments for cancer.

Two novel ferrocenyl dipeptide-like compounds generated via the Ugi four-component reaction.

The Ugi four-component reaction, a powerful method for the synthesis of diverse dipeptide-like derivatives in combinatorial chemistry, was used to synthesize (S)-1'-{N-[1-(anthracen-9-yl)-2-(tert-butylamino)-2-oxoethyl]-N-(4-methoxyphenyl)carbamoyl}ferrocene-1-carboxylic acid dichloromethane disolvate, [Fe(C6H5O2)(C33H31N2O3)]·2CH2Cl2, (I), and (S)-2-(anthracen-9-yl)-N-tert-butyl-2-[N-(4-methylphenyl)ferrocenylformamido]acetamide, [Fe(C5H5)(C33H31N2O2)], (II). They adopt broadly similar molecular conformations, with near-eclipsed cyclopentadienyl rings and near-perpendicular amide planes in their dipeptide-like chains, one of which is almost coplanar with its attached cyclopentadienyl ring but perpendicular to the aromatic ring bound to the N atom. In the supramolecular structure of (I), a two-dimensional network is constructed based on molecular dimers and a combination of intermolecular O-H···O, N-H···O and C-H···O hydrogen bonds, forming R2(2)(11), R2(2)(16), R2(2)(22) and C(9) motifs. These two-dimensional networks are connected by C-H···O and C-H···Cl contacts to create a three-dimensional framework, where one dichloromethane solvent molecule acts as a bridge between two neighbouring networks. In the packing of (II), classical hydrogen bonds are absent and an infinite one-dimensional chain is generated via a combination of C-H···O hydrogen bonds and C-H···π interactions, producing a C(7) motif. This work describes a simple synthesis and the supramolecuar structures of ferrocenyl dipeptide-like compounds and is significant in the development of redox-active receptors.

Supramolecular structures in three thiouracil derivatives: 5,6-trimethylene-2-sulfanylidene-1,2-dihydropyrimidin-4(3H)-one, 2-(4-fluorobenzylsulfanyl)-5,6-trimethylenepyrimidin-4(3H)-one and methyl 2-{[2-(4-fluorobenzylsulfanyl)-5,6-trimethylenepyrimidin-4-yl]oxy}acetate.

The molecules of the title compounds, C7H8N2OS, (1), C14H13FN2OS, (2), and C17H17FN2O3S, (3), crystallize in the space groups C2/m, C2/c and Ia, respectively. Compounds (1) and (2), an S-alkylated derivative of (1), consist of only one symmetry-independent molecule, while (3), an O-alkylated derivative of (2), contains two independent molecules in the asymmetric unit. The molecules of (1) sit on crystallographic mirror planes. In the supramolecular structure of (1), a combination of N-H···O and N-H···S hydrogen bonds creates a molecular strap with C(6) and R2(2)(8) motifs, which is further stabilized by an S···S contact. In the packing of (2), a one-dimensional molecular column is made up of two kinds of dimers. One dimer, with an R2(2)(18) motif, is formed by a pair of C-H···O soft hydrogen bonds and the other, with an R2(2)(8) motif, is produced via a pair of N-H···O hard hydrogen bonds. In the packing of (3), molecules A and B form two different types of one-dimensional chain by intermolecular C-H···N hydrogen bonds, and by C···N and O···S contacts, respectively. Two such kinds of chain are connected alternately via interchain C-H···O hydrogen bonds, giving a two-dimensional sheet. Finally, a three-dimensional supramolecular structure is formed through weak intersheet C-H···F hydrogen bonds. The study of the molecular and supramolecular structures of thiouracil derivatives is significant in the development of lipoprotein-associated phospholipase A2 inhibitors.

6-Chloro-N(4),N(4)-dimethyl-pyrimidine-2,4-diamine.

The asymmetric unit of the title compound, C(6)H(9)ClN(4), contains four independent mol-ecules (A, B, C and D). Their main difference is the torsion angles, ranging from 1.6 (5) to 5.9 (5)°, between the methyl group and the pyrimidine plane. A pair of inter-molecular N-H⋯N hydrogen bonds link mol-ecules A and C into a twisted dimer with a dihedral angle of 32.9 (1)° between the two pyrimidine rings, creating an R(2) (2)(8) motif. In the packing, each two mol-ecules of B, C and D form centrosymmetric dimers through two inter-molecular N-H⋯N hydrogen bonds, locally creating R(2) (2)(8) motifs. The dimers of C and D are alternately bridged by A into an infinite zigzag strip, locally creating two different R(2) (2)(8) motifs with dihedral angles of 32.9 (1) and 63.4 (1)° between the pyrimidine rings. Finally, these strips together with the dimers of B associate into a complicated three-dimensional framework.

5,17-Dibromo-26,28-bis-[(meth-oxy-carbon-yl)meth-oxy]-25,27-diprop-oxy-2,8,14,20-tetra-thia-calix[4]arene.

The title thia-calix[4]arene derivative, C(36)H(34)Br(2)O(8)S(4), adopts an unusual pinched cone conformation with the prop-oxy-substituted benzene rings inclined inward [forming a dihedral angle of 33.4 (1)°] and with the brominated benzene rings bent outward, making a dihedral angle of 66.1 (1)°. In the crystal, the mol-ecules form chains along [001] via C-H⋯S hydrogen bonds and S⋯S contacts [S⋯S = 3.492 (3) Å]. The chains are associated into bilayers through C-H⋯O hydrogen bonds, generating an R(2) (2)(10) motif.

2-[4-(2-Hy-droxy-propan-2-yl)-1H-1,2,3-triazol-1-yl]phenol.

In the title compound, C(11)H(13)N(3)O(2), the 1,2,3-triazole ring and the phenol ring form a dihedral angle of 55.46 (5)°. In the crystal, inversion-related mol-ecules associate through pairs of hy-droxy-phenol O-H⋯O hydrogen bonds, giving centrosymmetric cyclic dimers [graph set R(2) (2)(18)]. These dimers are linked into infinite chains along [001], giving an overall two-dimensional network structure parallel to the bc plane through hy-droxy O-H⋯N and triazole C-H⋯N hydrogen bonds.

Supramolecular structures constructed by 3-(2-amino-6-chloropyrimidin-4-yl)-1,1-dimethylprop-2-yn-1-ol monohydrate and 3-[2-amino-6-(3-hydroxy-3,3-dimethylprop-1-yn-1-yl)pyrimidin-4-yl]-1,1-dimethylprop-2-yn-1-ol.

The molecule of 3-(2-amino-6-chloropyrimidin-4-yl)-1,1-dimethylprop-2-yn-1-ol monohydrate, C(9)H(10)ClN(3)O·H(2)O, (I), shows a very polarized molecular-electronic structure, while the polarization is slight for 3-[2-amino-6-(3-hydroxy-3,3-dimethylprop-1-yn-1-yl)pyrimidin-4-yl]-1,1-dimethylprop-2-yn-1-ol, C(14)H(17)N(3)O(2), (II). In the supramolecular structure of (I), a combination of hard N-H···N hydrogen bonds and soft C-H···N hydrogen bonds creates a molecular column. Aromatic π-π stackings between the pyrimidine rings stabilize the column with perpendicular and centroid-centroid distances of 3.283 (3) and 3.588 (1) Å, respectively. Short Cl···Cl contacts further link neighbouring molecular columns, creating a hydrophilic tube in which water molecules are fixed by various hydrogen bonds. In the packing of (II), a one-dimensional molecular chain is formed through several contacts involving hard N-H···O(N) and O-H···O(N) and soft C-H···O hydrogen bonds. Interchain O-H···O hydrogen bonds link the chains giving a two-dimensional stepped network. It is anticipated that study of the influence of hydrogen bonding on the patterns of base pairing and molecular packing in aminopyrimidine structures will shed significant light on nucleic acid structures as well as their functions.

5,17-Dibromo-26,28-dihy-droxy-25,27-diprop-oxy-2,8,14,20-tetra-thia-calix[4]arene.

In the title compound, C(30)H(26)Br(2)O(4)S(4), the thia-calix[4]arene unit adopts a pinched cone conformation, with one of the ether-substituted rings bent towards the calix cavity and the two phenolic rings bent outwards. The phenyl rings make dihedral angles of 27.12 (9), 36.71 (10), 75.04 (8), and 76.01 (7)° with the virtual plane defined by the four bridging S atoms. The two opposite ether-substituted rings are almost parallel to each other, with an inter-planar anagle of 2.99 (12)°, while the two phenolic rings are nearly perpendicular to each other, making a dihedral angle of 74.52 (11)° and a Br⋯Br distance of 13.17 (2) Å. Two intra-molecular O-H⋯O hydrogen bonds between the OH groups and the same ether O atom stabilize the cone conformation. In the crystal, two different chains of mol-ecules, one with alternating and the other with tail-to-tail orientations, are formed by inter-molecular offset-face-to-face π-π stacking inter-actions with distances of 3.606 (3) to 4.488 (4) Šbetween the centroids of the aromatic rings.