Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives.

In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, 4b and 4c showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC50) values of 4b were 4.42 ± 0.24 µM (NCI-H1299), 3.94 ± 0.01 µM (A549) and 1.56 ± 0.06 µM (NCI-1437). The IC50 values of 4c were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 µM (A549) and 3.51 ± 0.05 µM (NCI-H1437). Furthermore, our results showed that 4b and 4c could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, 4b and 4c exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that 4b and 4c be developed as potential new drugs for lung cancer treatment.

A Redox-Active Phenothiazine-based Pd2L4-Type Coordination Cage and Its Isolable Crystalline Polyradical Cations.

Polyradical cages are of great interest because they show very fascinating physical and chemical properties, but many challenges remain, especially for their synthesis and characterization. Herein, we present the synthesis of a polyradical cation cage 14⋅+ through post-synthetic oxidation of a redox-active phenothiazine-based Pd2L4-type coordination cage 1. It's worth noting that 1 exhibits excellent reversible electrochemical and chemical redox activity due to the introduction of a bulky 3,5-di-tert-butyl-4-methoxyphenyl substituent. The generation of 14⋅+ through reversible electrochemical oxidation is investigated by in situ UV/Vis-NIR and EPR spectroelectrochemistry. Meanwhile, chemical oxidation of 1 can also produce 14⋅+ which can be reversibly reduced back to the original cage 1, and the process is monitored by EPR and NMR spectroscopies. Eventually, we succeed in the isolation and single crystal X-ray diffraction analysis of 14⋅+, whose electronic structure and conformation are distinct to original 1. The magnetic susceptibility measurements indicate the predominantly antiferromagnetic interactions between the four phenothiazine radical cations in 14⋅+. We believe that our study including the facile synthesis methodology and in situ spectroelectrochemistry will shed some light on the synthesis and characterization of novel polyradical systems, opening more perspectives for developing functional supramolecular cages.

Anion-Afforded Functions of Ionic Metal-Organic Frameworks: Ionochromism, Anion Conduction, and Catalysis.

The exchangeable counterions in ionic metal-organic frameworks (IMOFs) provide facile and versatile handles to manipulate functions associated with the ionic guests themselves and host-guest interactions. However, anion-exchangeable stable IMOFs combining multiple anion-related functions are still undeveloped. In this work, a novel porous IMOF featuring unique self-penetration was constructed from an electron-deficient tris(pyridinium)-tricarboxylate zwitterionic ligand. The water-stable IMOF undergoes reversible and single-crystal-to-single-crystal anion exchange and shows selective and discriminative ionochromic behaviors toward electron-rich anions owing to donor-acceptor interactions. The IMOFs with different anions are good ionic conductors with low activation energy, the highest conductivity being observed with chloride. Furthermore, integrating Lewis acidic sites and nucleophilic guest anions in solid state, the IMOFs act as heterogeneous and recyclable catalysts to efficiently catalyze the cycloaddition of CO2 to epoxides without needing the use of halide cocatalysts. The catalytic activity is strongly dependent upon the guest anions, and the iodide shows the highest activity. The results demonstrate the great potential of developing IMOFs with various functions related to the guest ions included in the porous matrices.

Positive Cooperative Protonation of a Metal-Organic Framework: pH-Responsive Fluorescence and Proton Conduction.

Positive cooperative binding, a phenomenon prevalent in biological processes, holds great appeal for the design of highly sensitive responsive molecules and materials. It has been demonstrated that metal-organic frameworks (MOFs) can show positive cooperative adsorption to the benefit of gas separation, but potential binding cooperativity is largely ignored in the study of sensory MOFs. Here, we report the first demonstration of positive cooperative protonation of a MOF and the relevant pH response in fluorescence and proton conduction. The MOF is built of Zr-O clusters and bipyridyl-based tetracarboxylate linkers and has excellent hydrolytic stability. It shows a unique pH response that features two synchronous abrupt turn-off and turn-on fluorescent transitions. The abrupt transitions, which afford high sensitivity to small pH fluctuations, are due to cooperative protonation of the pyridyl sites with a Hill coefficient of 1.6. The synchronous dual-emission response, which leads to visual color change, is ascribable to proton-triggered switching between (n, π*) and (π, π*) emissions. The latter emission can be quenched by electron donating anion-dependent through photoinduced electron transfer and ground-state charge transfer. Associated with cooperative protonation, the proton conductivity of the MOF is abruptly enhanced at low pH by two orders, but overhigh acid concentration is adverse because excessive anions can interrupt the conducting networks. Our work shows new perspectives of binding cooperativity in MOFs and should shed new light on the development of responsive fluorescent MOFs and proton conductive materials.

Metal-Organic Frameworks with Novel Catenane-like Interlocking: Metal-Determined Photoresponse and Uranyl Sensing.

The assembly of two tripyridinium-tricarboxylate ligands and different metal ions leads to seven isostructural MOFs, which show novel 2D→2D supramolecular entanglement featuring catenane-like interlocking of tricyclic cages. The MOFs show tripyridinium-afforded and metal-modulated photoresponsive properties. The MOFs with d10 metal centers (1-Cd, 1-Zn, 2-Cd, 2-Zn) show fast and reversible photochromism and concomitant fluorescence quenching, 1-Ni displays slower photochromism but does not fluoresce, and 1-Co and 2-Co are neither photochromic nor fluorescent. It is shown here that the network entanglement dictates donor-acceptor close contacts, which enable fluorescence originated from interligand charge transfer. The contacts also allow photoinduced electron transfer, which underlies photochromism and concomitant fluorescence response. The metal dependence in fluorescence and photochromism can be related to energy transfer through metal-centered d-d transitions. In addition, 1-Cd is demonstrated to be a potential fluorescence sensor for sensitive and selective detection of UO2 2+ in water.

Bioassay-Guided Isolation of Two Eudesmane Sesquiterpenes from Lindera strychnifolia Using Centrifugal Partition Chromatography.

In this study, a centrifugal partition chromatography (CPC) separation was applied to identify antioxidant-responsive element (ARE) induction molecules from the crude extract of Lindera strychnifolia roots. CPC was operated with a two-phase solvent system composed of n-hexane-methanol-water (10:8.5:1.5, v/v/v) in dual mode (descending to ascending), which provided a high recovery rate (>95.5%) with high resolution. Then, ARE induction activity of obtained CPC fractions was examined in ARE-transfected HepG2 cells according to the weight ratios of the obtained fractions. The fraction exhibiting ARE-inducing activity was further purified by preparative HPLC that led to isolation of two eudesmane type sesquiterpenes as active compounds. The chemical structures were elucidated as linderolide U (1) and a new sesquiterpene named as linderolide V (2) by spectroscopic data. Further bioactivity test demonstrated that compounds 1 and 2 enhanced ARE activity by 22.4-fold and 7.6-fold, respectively, at 100 µM concentration while 5 µM of sulforaphane induced ARE activity 24.8-fold compared to the control.

A pH-Sensing Fluorescent Metal-Organic Framework: pH-Triggered Fluorescence Transition and Detection of Mycotoxin.

Due to its great relevance to environmental, biological, and chemical processes, the precise detection of pH or acidic/basic species is an ongoing and imperative need. In this context, pH-sensitive luminescent systems are highly desired. We reported a three-dimensional Zn(II) MOF synthesized from a bipyridyl-tetracarboxylic ligand and composed of 4-fold interpenetrated diamond frameworks. Because the steric hindrance in the ligand prevents metal coordination with the pyridyl group, the MOF features free basic N sites accessible to the small H+ ions, which renders pH responsivity. The aqueous dispersion exhibits an abrupt, high-contrast, and reversible on-off fluorescence transition in the narrow pH range of 5.4-6.2. The sensitive bistable system can be used for the precise monitoring of pH within the range and for use as a pH-triggered optical switch. The responsive mechanism through pyridyl protonation is collaboratively supported by data fitting, absorption spectra, and molecular orbital calculations. In particular, spectral and theoretical analyses reveal the destruction of n → π* transitions and the appearance of intramolecular charge-transfer transitions upon pyridyl protonation. Moreover, by virtue of the pH-responsive fluorescence, the MOF shows appealing sensing performance for the detection of 3-nitropropionic acid, a major mycotoxin in moldy sugar cane.

Bioassay-Guided Separation of Centipeda minima Using Comprehensive Linear Gradient Centrifugal Partition Chromatography.

A comprehensive linear gradient solvent system for centrifugal partition chromatography (CPC) was developed for the bioassay-guided isolation of natural compounds. The gradient solvent system consisted of three different ternary biphasic solvents types: n-hexane-acetonitrile-water (10:2:8, v/v), ethyl acetate-acetonitrile-water (10:2:8, v/v), and water-saturated n-butanol-acetonitrile-water (10:2:8, v/v). The lower phase of the n-hexane-acetonitrile-water (10:2:8, v/v) was used as the stationary phase, while its upper phase, as well as ethyl acetate-acetonitrile-water (10:2:8), and water-saturated n-butanol-acetonitrile-water (10:2:8, v/v) were pumped to generate a linear gradient elution, increasing the mobile phase polarity. We used the gradient CPC to identify antioxidant response elements (AREs), inducing compounds from Centipeda minima, using an ARE-luciferase assay in HepG2 cells, which led to the purification of the active molecules 3-methoxyquercetin and brevilin A. The developed CPC solvent systems allow the separation and isolation of compounds with a wide polarity range, allowing active molecule identification in the complex crude extract of natural products.

Versatile and Switchable Responsive Properties of a Lanthanide-Viologen Metal-Organic Framework.

Metal-organic frameworks (MOFs) provide intriguing platforms for the design of responsive materials. It is challenging to mobilize as many components as possible of a MOF to collaboratively accomplish multiple responsive properties. Here, reversible photochromism, piezochromism, hydrochromism, ionochromism, and luminescence modulation of an ionic Eu(III) MOF is reported furnished by cationic electron-deficient viologen units and exchangeable guest anions. Mechanistically, the extraordinarily versatile responsive properties are owed to electron transfer (ET), charge transfer (CT), and energy transfer, involving viologen as electron acceptor, anion as electron donor, luminescing Eu(III) as energy donor, and anion-viologen CT complex or ET-generated radical as energy acceptor (luminescence quencher). Moreover, guest anions and waters provide flexible handles to control the ET-based responsive properties. Water release/reuptake or exchange with organic solvents can switch on/off the response to light, while reversible anion exchange can disenable or awaken the responses to pressure, light, and water release/reuptake. The impacts of water and anions on ET are justified by the high polarity and hydrogen-bonding capability of water, the different electron donor strength of anions, and the strong I- -viologen CT interactions. The rich responsive behaviors have great implications for applications such as pressure sensors, iodide detection, and chemical logic gates.

Interpenetration-Enabled Photochromism and Fluorescence Photomodulation in a Metal-Organic Framework with the Thiazolothiazole Extended Viologen Fluorophore.

A novel metal-organic framework (MOF), formulated as [Cd2(TTVTC)Cl2(H2O)3]·2H2O (1), was synthesized from a tetracarboxylate ligand ([TTVTC]2-) functionalized with the thiazolothiazole extended viologen (TTV2+) fluorophore. The MOF features three-dimensional (10,3)-d frameworks with 6-fold interpenetration. The MOF exhibits reversible photochromism, due to photoinduced electron transfer from carboxylate to TTV2+. The photoactivity benefits from the electron donor-acceptor contacts enabled by mutual interpenetration of the frameworks. This is the first demonstration of photochromism in TTV2+ derivatives. In addition, the fluorescence arising from the TTV2+ fluorophore can be reversibly modulated during the photochromic process. The work demonstrates the great potential of extended viologen based ligands in the construction of MOFs with dual photomodulable optical properties, which could find future applications in photoelectronics.

Graphite paste electrodes modified with a sulfo-functionalized metal-organic framework (type MIL-101) for voltammetric sensing of dopamine.

The metal-organic frameworks MIL-101 and sulfo-MIL-101 were used to modify graphite paste electrodes (GPEs) to obtain sensors for determination of dopamine (DA). Taking advantage of the catalytic activity of metal-organic frameworks (MOFs) and of the electrical conductivity of graphite, the modified GPEs show enhanced voltammetric responses, and the GPE modified with the sulfo-MOF displays superior sensitivity when operated at a working potential of -0.4 to 0.8 V (vs. Ag/AgCl). The sensor works in the 0.07 to100 µM DA concentration range and has a 43 nM detection limit. It is concluded that the sulfo group provides open sites for efficient electrostatic and hydrogen bonding interactions, which facilitates electron transfer. Graphical abstractSchematic representation of the structure of the sulfo-functionalized MOF (sulfo-MIL-101) and the different voltammetric signals of dopamine at the graphite paste electrodes (GPEs) modified with sulfo-MIL-101 and the parent MOF (MIL-101).

Random Co(II)-Ni(II) Ferromagnetic Chains Showing Coexistent Antiferromagnetism, Metamagnetism, and Single-Chain Magnetism.

A series of isomorphous compounds of general formula [Co1- xNi x(tzpo)(N3)(H2O)2] n· nH2O ( x = 0, 0.19, 0.38, 0.53, 0.68, 0.84, and 1; tzpo = 4-(5-tetrazolate)pyridine- N-oxide) was prepared. The compounds consist of homometallic or heterometallic chains with simultaneous azide-tetrazolate bridges. The heterometallic systems feature random distribution of metal ions. All compounds across the series exhibit intrachain ferromagnetic coupling, interchain antiferromagnetic (AF) ordering, field-induced metamagnetic transition, and, except the Ni-only compound, single-chain magnetic dynamics. The AF ordering temperature, the metamagnetic critical field, and the relaxation parameters show different composition dependence. Notably, the blocking temperature for the Co-rich materials is higher than the Co-only compound, suggesting synergy between the randomly distributed Co(II) and Ni(II) ions in promoting slow relaxation. The results imply rich physics in the random mixed-metal systems and demonstrate the possibility of improving single-chain relaxation properties by blending metal ions.

Switchable Ferro-, Ferri-, and Antiferromagnetic States in a Piezo- and Hydrochromic Metal-Organic Framework.

The Mn(II) metal-organic framework with a viologen-based tetracarboxylate ligand exhibits reversible optical (color) and magnetic changes concomitant with stimuli-induced electron transfer from carboxylate to viologen. Compression causes a magnetic transformation from ferro- to ferrimagnetic, while water release/reuptake switches the magnetic behavior between ferro- and antiferromagnetic.

Effects of Metal Blending in Random Bimetallic Single-Chain Magnets: Synergetic, Antagonistic, or Innocent.

A family of isomorphous three-dimensional metal-organic frameworks based on bimetallic (FeCo, FeNi, and CoNi) chains with random metal sites have been prepared and magnetically characterized. The solid-solution-type bimetallic materials inherit intrachain ferromagnetic interactions and single-chain-magnet (SCM) behaviors from the homometallic parent materials. Interestingly, different composition dependence of magnetic behaviors has been found. The FeII1-x NiIIx series (0≤x≤1) show an innocent composition dependence, where the blocking temperature of slow relaxation decreases monotonically as FeII is replaced by less anisotropic NiII . The FeII1-x CoIIx series show an unexpected antagonistic blending effect on slow relaxation: blending FeII and CoII tends to depress the spin dynamics, and the bimetallic materials with intermediate composition show significantly lower blocking temperature than both FeII and CoII materials. This is quite the opposite of what happens in the Co1-x Nix series, where CoII and NiII seem to have a synergetic effect so that slow relaxation in bimetallic systems can be promoted to higher temperature than both CoII and NiII materials.

Bioactive Asarone-Derived Phenylpropanoids from the Rhizome of Acorus tatarinowii Schott.

Eight new (1a/1b, 2a, 3a, 4a/4b, and 5a/5b) and seven known (2b, 3b, and 6-10) asarone-derived phenylpropanoids, a known asarone-derived lignan (12), and four known lignan analogues (11 and 13-15) were isolated from the rhizome of Acorus tatarinowii Schott. The structures were elucidated via comprehensive spectroscopic analyses, modified Mosher's method, and quantum chemical calculations. Compounds 1-8 were present as enantiomers, and 1-5 were successfully resolved via chiral-phase HPLC. Compounds 1a/1b were the first cases of asarone-derived phenylpropanoids with an isopropyl C-3 side-chain tethered to a benzene core from nature. Hypoglycemic, antioxidant, and AChE inhibitory activities of 1-15 were assessed by the α-glucosidase inhibitory, ORAC, DPPH radical scavenging, and AChE inhibitory assays, respectively. All compounds except 3a showed α-glucosidase inhibitory activity. Compound 3b has the highest α-glucosidase inhibitory effect with an IC50 of 80.6 µM (positive drug acarbose IC50 of 442.4 µM). In the antioxidant assays, compounds 13-15 exhibited ORAC and DPPH radical scavenging activities. The results of the AChE inhibitory assay indicated that all compounds exhibited weak AChE inhibitory activities.

Aldehyde-Tagged Zirconium Metal-Organic Frameworks: a Versatile Platform for Postsynthetic Modification.

Aldehyde-tagged UiO-67-type metal-organic frameworks (MOFs) have been synthesized via the direct solvothermal method or postsynthetic ligand exchange. Various functionalities have been introduced into the MOFs via postsynthetic modification (PSM) employing C-N and C-C coupling reactions of the aldehyde tag. Tandem PSM has also been demonstrated. An amino-functionalized MOF obtained by PSM is shown to be an efficient, heterogeneous, and recyclable catalyst for Knoevenagel condensation.

Amino- and Sulfo-Bifunctionalized Metal-Organic Frameworks: One-Pot Tandem Catalysis and the Catalytic Sites.

New MIL-101 metal-organic frameworks (MOFs) dually functionalized with amino and sulfo groups were fabricated by postsynthetic modification and used to catalyze one-pot deacetalization-Knoevenagel condensation. We proved that the MOFs take the zwitterionic form, with the catalytic acid site being the ammonium group rather than the sulfo one. The acid and base concentrations in the materials are correlated, and the ratio can be readily tuned to achieve optimal catalytic performance.

Magnetic and Photochromic Properties of a Manganese(II) Metal-Zwitterionic Coordination Polymer.

The solvothermal reaction of Mn(ClO4)2, NaN3, and a rigid viologen-tethered tetracarboxylic acid (1,1'-bis(3,5-dicarboxyphenyl)-4,4'-bipyridinium chloride, [H4L]Cl2) led to a coordination polymer of formula [Mn4(L)(N3)6(H2O)2]n. X-ray analysis revealed a 3D coordination structure. The Mn(II) ions are connected by mixed azide and carboxylate bridges to give 2D layers, which are pillared by the viologen tether of the zwitterionic ligand. Magnetic analyses suggested that the compound features antiferromagnetism and field-induced metamagnetism. The compound also shows photochromic and photomagnetic properties. The long-range magnetic ordering is owed to the spin-canting structure of the Mn(II)-azide-carboxylate layer; the photochromism involves the formation of viologen radicals via photoinduced electron transfer, and the photomagnetism is related to the interactions between the metal ion and the photogenerated radicals. The study demonstrates a strategy for the design of new multifunctional materials with photoresponsive properties.

The Syntheses, Structures, Fluorescence Properties and Biological Activity of two Novel Zinc(II) Complexes Controlled by the Tripodal Imidazole Ligand.

Two new zinc complexes, namely Zn(L(1))ClCH2NO(1) and {Zn(L(2))CH2NO}n▪N(CH3)3▪ClO4(2) (L(1) = 3,5-di(1H-imidazol-1-yl)pyridine L(2) = 1,3,5-tris(1-imidazolyl) benzene), have been synthesized, and characterized by IR spectra, elemental analysis, and a single crystal X-ray diffraction. Fluorescence spectroscopy indicated that two complexes presented strong DNA binding affinity constants to fish sperm DNA (FS-DNA). Gel electrophoresis assay demonstrated the ability of the complex to cleave the HL-60 DNA. Apoptotic study showed the complex exhibited significant cancer cell(KB) inhibitory rate.

Magnetic coupling and slow relaxation of magnetization in chain-based Mn(II), Co(II), and Ni(II) coordination frameworks.

Three isomorphous coordination polymers based on the chain with triple (µ-1,1-N3)(µ-1,3-COO)2 bridges have been synthesized from a new zwitterionic dicarboxylate ligand [L(-) = 1-(4-carboxylatobenzyl)pyridinium-4-carboxylate]. They are of formula [M(L)(N3)]n·3nH2O [M = Mn(II), Co(II), and Ni(II)]. In these compounds, the mixed-bridge chains are linked into 2D coordination networks by the N-benzylpyridinium spacers. The magnetic properties depend strongly on the nature of the metal center. The magnetic coupling through (µ-1,1-N3)(µ-1,3-COO)2 is antiferromagnetic in the Mn(II) compound but ferromagnetic in the Co(II) and Ni(II) analogues. Magnetostructural analyses indicate that the magnitude of the magnetic coupling can be correlated to the M-N-M angle of the azide bridge and the average M-O-C-O torsion angle of the carboxylate bridge. As the values of these parameters increase, the antiferromagnetic coupling for Mn(II) decreases while the ferromagnetic coupling for Co(II) increases. With strong magnetic anisotropy, the Co(II) compound behaves as a single-chain magnet showing hysteresis and Glauber-type slow dynamics probably in the infinite-chain region, with Δ(τ)/k = 86 K, Δ(ξ)/k = 26 K, and Δ(A)/k = 34 K. With weaker anisotropy, the Ni(II) species shows slow relaxation of magnetization at much lower temperature.