Structure and Thermochromic Property of a Silver(I) Complex Based on Dicyanamide and Phosphine Ligands

A new silver(I) complex {Ag_2(dppm)_2[N(CN)_2]}_2[μ-N(CN)_2]_2(1) with chelate ligand bis(diphenylphosphino)methane(dppm) and bridging ligand dicyanamide(N(CN)_2) was carefully synthesized and fully characterized by single-crystal X-ray crystallography, IR spectrometry, high-resolution mass spectrometry, thermal analysis and ~1H NMR. According to the crystal structure analysis, this complex could be considered as two binucleate moieties {Ag_2(dppm)_2[N(CN)_2]}~+ linked by two bridging anionic ligands N(CN)_2~-. It exhibits thermochromic property in solid state. The dependence of color or emission of substance on temperature is known as thermochromism. Various temperature luminescences of complex 1 are tested. Along with the reduction of temperature from 298 K to 77 K, a noticeable emission enhancement as well as lifetime extension is observed.     

Solvent-driven reversible transformation between electrically neutral thiolate protected Ag_(25) and Ag_(26) clusters

Two atom-precise silver nanoclusters[Ag_(25)Cl_2(Tab)_(14)(Ph COO)_(11)(DMF)_4](PF_6)_(12)(Ag_(25),DMF=N,N-dimethylformamide) and[Ag_(26)Cl_2(Tab)_(14)(Ph COO)_(13)(DMAc)_4](PF_6)_(11)(Ag_(26),DMAc=N,N-dimethylacetamide) were synthesized based on the electrically neutral thiolate protective ligand,4-(trimethylammonio)benzenethiolate (Tab).The weak Ag–S interaction in Tab-protected silver nanoclusters allows to insert or leave a single silver atom in the Ag–S skeleton through solvent-trigger core fragmentation and re-arrangement,thereby realizing the reversible conversion of Ag_(25) and Ag_(26) for the first time.     

Synthesis and Structural Study of a N-Heterocyclic Carbene Trinuclear Silver(Ⅰ) Complex

The bis-benzimidazolium salt bis[2-(N-ethylbenzimidazoliumyl)ethyl]amine hexafluorophosphate(LH_2·(PF_6)_2) and its N-heterocyclic carbene silver(Ⅰ) complex[L_2Ag_3](PF_6)_3(1)have been prepared and characterized.In complex 1,a trinuclear silver(Ⅰ) architecture is formed by two tridentate ligands and three silver(I) atoms,in which one 12- and two 7-membered rings are contained.In the crystal packing of 1,1D chain and 2D supramolecular layer are formed via intermolecular weak interactions,including π…π interactions and C-H…π contacts.Additionally,the fluorescence emission spectra of LH_2-(PF_6)2 and 1 are described.     

Synthesis,Crystal Structure and Antitumor Activity of a Na(Ⅰ) Coordination Polymer Based on 2-Propyl-4,5-imidazoledicarboxylic Acid and 1,10-Phenanthroline Ligands

A new Na(I) coordination polymer, [Na2(Hpimdc)(H2 pimdc)(phen)2]n(1), has been synthesized by the reaction of NaOH with 2-propyl-4,5-imidazoledicarboxylic acid(H3 pimdc)and 1,10-phenanthroline(phen). The Na(I) coordination polymer 1 was characterized by single-crystal X-ray diffraction analysis and elemental analysis. In 1, the bridged ligand H3 pimdc adopts two modes(singly deprotonated and doubly deprotonated) to coordinate with the Na(I) ion.The Na(1) ion is six-coordinated with three N atoms from a phen ligand and a H2 pimdc ligand,three O atoms from a Hpimdc ligand and two other different H2 pimdc ligands. The Na(2) ion is also six-coordinated with three N atoms from a phen ligand and a Hpimdc ligand, three O atoms from a H2 pimdc ligand and other two different Hpimdc ligands. Complex 1 exhibits a 1 D chain structure built up by μ-H2 pimdc-and μ-Hpimdc2-ligands. The antitumor activities of complex 1 against human SGC7901, A549 and H08910 cells have been tested.     

Folic Acid Modified Polymeric Micelles for Intravesical Instilled Chemotherapy

In this study,a targeting micellar drug delivery system was developed for intravesical instilled chemotherapy of bladder cancer.The amphiphilic diblock copolymer poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEO) with functional amino group (NH2) at the end of PEO block was synthesized.Then the copolymer was conjugated with folic acid (FA) and fluorescein isothiocyannate (FITC) via the PEO-NH2 terminus,and then assembled into micelles with the target moiety and fluorescence labeling.In addition,drug loaded micelles were also fabricated with anticancer drug doxorubicin (DOX) encapsulated in the hydrophobic core.The micelles were characterized in terms of size,drug loaded efficiency and critical micellization concentration (CMC) by means ofDLS,UV and fluorescence spectra.In vitro cellular uptake and cytotoxicity studies showed that FA modified PCL-b-PEO-FA micelles have a greater targeting efficiency to human bladder cancer cell (T-24 cell) compared to PCL-b-PEO-NH2 micelles due to the conjugation of FA on the surface,while no targeting effect to normal tissue originated human embryonic kidney 293 (HEK-293) cells was observed,enabling the micelles a promising drug carrier for intravesical instilled chemotherapy of bladder cancer.     

Chemical and structural biology of nucleic acids and protein-nucleic acid complexes for novel drug discovery

Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic agents.Targeting nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the ...     

Synthesis, Crystal Structure and Photoluminescent Property of a Novel Disilver Complex with Pyrazinyl Oxime Ligand

<正>A novel binuclear Ag(I) complex [Ag_2(C_6H_6N_3O)_2(C_6H_7N_3O)_2]·2CH_3CN (1) was synthesized by the evaporation reaction of silver nitrate and (E)-1-(pyrazin-2-yl)ethanone oxime (HL). The complex was characterized by elemental analysis, IR spectrum and X-ray single-crystal diffraction analysis. It crystallizes in the monoclinic space group C2/c with a = 22.7089(3), b = 11.5443(7), c = 16.1468(4) , β = 127.7150(10)°, V = 3348.6(2) ~3, D_c = 1.675 g/cm~3, M_r = 844.42, Z = 4, F(000) = 1696.0, μ = 1.226 mm~(-1), the final R =0.0250 and wR = 0.070. The coordination around the silver(I) atom is a distorted trigonal-bipyramidal geometry involving one protonated pyrazinyl oxime ligand (HL), one deprotonated oxime ligand (L~-) and one CH_3CN solvate molecule in the asymmetric unit of complex 1.     

Self-assembled thermosensitive luminescent nanoparticles with peptide-Au conjugates for cellular imaging and drug delivery

A facile and efficient strategy has been developed to fabricate a multifunctional,theranostic anticancer drug delivery platform featuring active targeting,controlled drug release and fluorescence imaging for real-time control of delivery.To this end,thermo sensitive poly(N-isopropyl acrylamide)(PNIPAM)nanospheres are decorated with peptide-Au cluster conjugates as a smart nanomedicine platform.A sophisticated trifunctional peptide is designed to release the anticancer drug doxorubicin(DOX),target cells and reduce Au^3+ions to form luminescent Au cluste rs.Importantly,the peptide-Au cluster moieties are attached to the PNIPAM nanospheres via amide bonds rather than noncovalent interactions,significantly improving their stability in biological medium and drug release efficiency.The in vitro experiments showed that DOX was released in an efficient and controlled manner under physiological conditions.     

Hypoxia-activatable nano-prodrug for fluorescently tracking drug release in mice

Chemotherapy is one of the commonly used methods to treat various types of cancers in clinic by virtue of its high efficiency and universality. However, strong side effects and low concentration of conventional drugs at the tumor site have always been important factors that plague the chemotherapy effects of patients, further precluding their practical applications. Thereof, to solve the above dilemma, by integration of anticancer drug(nitrogen mustard, NM) into an NIR fluorophore(a dicyanoisophorone derivative), an intelligent prodrug NIR-NM was developed via molecular engineering strategy. Prodrug NIR-NM stimulated in hypoxia condition exhibits significantly higher toxicity to cancer cells than normal cells, essentially reducing the collateral damage to healthy cells and tissues of nitrogen mustard. More importantly, the nanoparticle prodrug FA-lip@NIR-NM showed the advantages of the high accumulation of drug at tumor site and long-circulation capacity in vivo, which endowed it the ability to track the release of the active chemotherapeutic drug and further treat solid tumors.     

An on-chip intestine-liver model for multiple drugs absorption and metabolism behavior simulation

A double-layer microfluidic chip integrated with a hollow fiber(HF)was developed to reconstitute the intestine-liver functionality for studying the absorption and metabolism of combination drugs.Caco-2 cells were inoculated in the HF cavity at the top of the serpentine channel to simulate the intestinal tissue for drug absorption and transport studied,and Hep G2 cells,seeded in the bottom chamber,were used to mimic the liver for metabolism-related studies.Genistein and dacarbazine were selected for combination drug therapy and its effects on cell viability,hepatotoxicity,and cell cycle arrest under drug-conditioned culture were investigated.The results suggested that the combined concentration below-100μg/m L had no significant inhibitory effect on Hep G2 cell viability,and therefore Hep G2 cells maintained their drug metabolism ability.When the drug concentration was increased above 250μg/m L,Hep G2 cells underwent apoptosis.Detection of metabolites by mass spectrometry proved the effective metabolism in the microchip model.This dynamic,co-culture microchip successfully provided a podium for long-term observation of absorption,transport,and metabolism of combination drugs,and could be an effective in vitro simulation model for further clinical research.     

Dinuclear Silver（Ⅰ） Complex Based on 1-Picolyl-3-propylbenzimidazolium Salt： Crystal Structure and Weak Interactions

1-Picolyl-3-propylbenzimidazolium bromide (LBr) was prepared from benzimida- zole by alkylation with 2-chloromethyl-pyridine in the presence of NaH, followed by quaternization with 1-bromopropane. Ligand LBr was treated with AgBr in CH2Cl2 to afford a dinuclear silver(I) complex L2Ag2Br4 (1). In complex 1, a 2-D supramolecular layer is formed through two types of π-π stacking interactions. Fluorescent emission spectra of ligand LBr and complex 1 are described.     

Development of LC–MS method for analysis of paclitaxel-inhibited growth and enhanced therapeutic response in human glioblastoma cells

Glioma stem cells are considered responsible for drug resistance and glioma relapse resulting in poor prognosis in glioblastoma multiforme. SU3 glioma cell is a highly invasive glioma stem cell line from the patients with glioblastoma multifrome. It is of great significance to study the efficacy and molecular mechanism for anticancer drug effects on SU3 glioma cells. In this work, we develop a liquid chromatography–mass spectrometry(LC–MS) method for direct analysis of the role of drugs(paclitaxel)on SU3 glioma cells at the molecular level. We use the specific fluorescence dyes to evaluate cell viability,the levels of ROS and GSH when the cells were treated with drugs. In addition, the LC–MS platform was successfully employed to detect the amount of 6-O-methylguanine, demonstrating that it is effective to induce cell apoptosis and enhance the cytotoxic response of SU3 glioma cells. The analytical linear equals are Y = 9.49 ? 105 X + 2.42 ? 104 for 6-O-methylguanine(R2= 0.9998) and Y = 4.72 ? 104 X + 2.21 ? 103(R2= 0.9996) for 7-methylguanine. Thus, the combination of cell-specific fluorescence dyes and LC–MS method enables us to reveal the molecular mechanism of paclitaxel-inhibited growth and enhanced therapeutic response in the chemotherapy for glioma multiforme.     

液/液界面电子转移研究苯甲酰吡啶-缩氨基硫脲的亲脂性

The ion transfer reaction of 2-benzoylpyridine-thiosemicarbazone (HL), which has antimicrobial and antifungal properties and anticancer activity, has been studied to determine its lipophilicity by cyclic voltammetry at the water/1,2-dichloroethane (1,2-DCE) interface. The physicochemical parameters such as standard partition coefficient (IgP1) and the standard Gibbs energy of transfer (△G0,w→otr,I) of the protonated form of the ligand were measured as a function of pH in aqueous phase. The protonated form of the ligand exhibited reversible or quasi-reversible voltammograms at the 1,2-DCE in the range of pH 1-5. The protonation constants of the ligand, pKal, and pK? were determined spectrophotometrically and were found to be 12.14 and 3.24, respectively. The standard Gibbs energy of transfer (△G0,w→otr,N) and the partition coefficient of neutral species (IgPN) were also determined by the shake-flask method. The standard Gibbs energy of transfer of this compound across the water/1,2-DCE interface was evaluated as the quantitative measure of its lipophilicity. The difference between lgP1 and lgPN was related to the degree of charge delocalization and was used to evaluate qualitatively the lipophilicity of the ligand.     

Preparation, Release-control and Cell Apoptosis of C6 Glioma Cells in PEG-PLGA-Rg3 Nanoparticles

With biodegradable material poly(ethylene glycol)-poly(lactide-co-glycolide) (PEG-PLGA) as substrate, the size distribution of Rg3-NPs was approved by the scanning electron microscopy. MTT assay was used to detect the effects of Rg3-NPs on the growth rate of C 6 cells at various concentrations and flow cytometry(FCM) was applied to assay the cell cycle and cell apoptosis of C 6 glioma cells. Western blot analysis was used to measure the protein level of PCNA. The results show that Rg3-NPs are slick and uniformity, the average diameter of the nanoparticles is about 75―90 nm, entrapment efficiency is (89.7±1.7)%. MTT assay shows the growth of C 6 Glioma Cells can be significantly inhibited by Rg3-NPs in a dose-dependence manner. FCM and Western blot analysis show Rg3 can be released from the conjugated nanoparticles to function in the cell nuclei so as to lead to the changes in the growth cycle of the cells, which results in the arrest of G 0-G 1 cell cycle and induces the apoptosis of C 6 cells. Therefore, Rg3-NPs may be used for the auxiliary therapy of brain glioma.     

Design, synthesis and anti-tumoractivity of novel amidine derivatives of doxifluridine

<正>A series of novel amidine derivatives of doxifluridine were synthesized using acid amide as the starting material,and their antitumor activity was evaluated in A549 cells.Compounds 10 and 11 demonstrated were more potent than 5-Fu,which was used as a positive control.Compound 10,which were found to be the most potent one with IC_(50) of 3.2μmol/L,was 16 times more potent than 5-Fu with IC_(50) of 52μmol/L to the A549 cells.A new route was designed to synthesize 5'-deoxy-5-fluorocytidine.All compounds were characterized by ~1H NMR,MS and X-ray spectras in detail.     

Design,Synthesis and Anticancer Activity Evaluation of Novel Quinazoline Derivatives as EFGR Inhibitors

Malignant tumor is one of the major diseases that seriously threaten human health today. Compared with traditional chemotherapy, targeted drug therapy has become a new idea of tumor therapy. And EGFR(epidermal growth factor receptor) is highly expressed in many human tumor cell lines, which is a biomarker of tumor proliferation. In this paper, small molecule tyrosine kinase inhibitors with quinazoline structure aiming at EGFR were studied. A series of novel quinazoline derivatives(4 a～4 l) have been designed and synthesized from 4-hydroxyquinazoline as the parent core. Structures of target compounds were characterized by ~1H NMR and ~(13)C NMR spectra. The in vitro anticancer activity of compounds 4 a～4 l was evaluated by MTT assay against Hela,MCF-7 and A549 tumor cell lines, and apoptosis-inducing capacity was investigated by Annexin-V/PI staining assay.The results showed that all compounds had good antitumor activity against the test tumor cell lines. Especially,compound 4 a exhibited the best anticancer activity(IC_(50) = 10.23 μM) against Hela cell lines, remarkable ability to induce apoptosis, and low toxicity, which identified 4 a as a promising anticancer drug aiming at EFGR.     

Lipase-catalyzed synthesis of novel galactosylated cholesterol

In an organic phase system,an enzymes lipase was used as a catalyst to synthesize galactosylated cholesterol,(5-cholesten-3b-yl)[(4-O-β-D-galactopyranosyl)D-glucitol-6]sebacate(CHS-SE-LA),which contains galactose residues.Its chemical structure was characterized by ESI-MS,and NMR.For HepG2 cells,the cellular fluorescence intensities of liposomes modified with CHS-SE-LA(GAL-FL) were as much as 2.6-fold(p 0.01) control liposomes(FL).Moreover,the presence of excess galactose significantly inhibited the uptake of GAL-FL suggesting ASGPR mediated uptake.In conclusion,the novel galactosylated ligand CHS-SE-LA was synthesized by lipase-catalyzation and revealed a great potential as drug carrier materials for hepatocyte-selective targeting.     

Metal complexes of anthranilic acid derivatives: A new class of noncompetitive α-glucosidase inhibitors

Metal complexes of anthranilic acid derivatives that constitute a novel class of non-sugar-type aglucosidase inhibitors were synthesized and assessed in vitro for inhibitory activity. All of the Ag(I)complexes(9–16) inhibited a-glucosidase at the nanomolar scale, while 3,5-dichloroanthranilic acid silver(I)(9) was the most potent(IC_(50)= 3.21 nmol/L). Analysis of the kinetics of enzyme inhibition indicated that the mechanism of the newly prepared silver complexes was noncompetitive. The structure-activity relationships were also analyzed, and they are discussed in this report.     

Molecular-scale drug delivery systems loaded with oxaliplatin for supramolecular chemotherapy

Smart strategies that can decrease the side effect and enhance the therapeutic efficacy of chemotherapy are in urgent need to meet the special demands of cance r therapy.Herein,two wate r-soluble macrocyclic hosts,i.e.,a carboxylated leaning tower[6]arene(CLT6) and a carboxylated [2]biphenyl-extended pillar[6]arene(CBpP6),are used to load chemotherapy drug oxaliplatin(OxPt) by forming inclusion complexes(OxPt■CLT6 and OxPt■CBpP6) through host-guest interactions.Interestingly,OxPt can be released from the macrocyclic cavities of these drug delivery systems(DDSs) via the competitive binding effect of spermine(SPM) because of the stronger binding abilities of CLT6/CBpP6 toward SPM as compared with OxPt,leading to enhanced cytotoxicity on SPM-overexpressed cancer cells,such as breast cancer MCF-7 cells.Moreover,compared to free OxPt,due to the low concentration of SPM in normal cells,OxPt■CGT6 and OxPt■CBpP6 demonstrated a decreased cytotoxicity on liver L02 cells,which is beneficial fo r reducing the side effect of anticancer drug during chemotherapy.Such a strategy might be extended to other antitumor drugs and water-soluble macrocycles with suitable cavity sizes to achieve controllable drug delivery and enhanced anticancer ability in supramolecular chemotherapy     

Studies on solid state reactions of coordination compounds LI.Solid state syntheses of a family of Ag-Mo(W)-S cubane-like cluster compounds:Crystal structures of{Ag_3MoS_3I}(PPh_3)_3S and{Ag_3WS_3Cl}(PPh_3)_3S·0.5P(S)Ph_3·3H_2O~+

Reactions of[NH_4]_2[MS_4](M=Mo,W),AgX(X=Cl,Br,I,CN,SCN)and PPh_3in the solid state produced six new mixed-metal sulfur containing cluster compounds,two ofwhich,{Ag_3MoS_3I}(PPh_3)_3S(1)and{Ag_3WS_3Cl}(PPh_3)_3S·0.5P(S)Ph_3·3H_2O(2),were determinedby single crystal X-ray analysis.The crystal data:1,triclinic,P,a=12.114(2),b=13.420(2),c=20.346(3),α=74.53(1),β=86.73(1),γ=63.74(1)°,Z=2,R=0.043 for 4805 independentdata;2,hexagonal,R3,a=b=16.201(3),c=45.091(10),Z=6,R=0.042 for 2729 independentdata.The central unit{Ag_3MS_3X}(M=Mo,W;X=Cl,I)of the two compounds can be des-cribed as a slightly distorted cube,four corners being formed by the MS_4~(2-) ligand(with a ter-minal S atom).The remaining corners are occupied by one X(Cl or I)atom and three Agatoms(with one PPh_3 ligand bound to each of the latter).The generation of different types ofAg-Mo(W)-S cluster compounds prepared from solid state reactions under different reactiontemperatues is discussed.