Cytotoxic Activity of Unique Synthesized Five-membered Heterocyclic Compounds Coordinated with Tiopronin Monovalent.

BACKGROUND: We recently synthesized a compound in which 5-mercapto-1-methyltetrazole (MM4) was coordinated to tiopronin monovalent (TPN-Au(I)) and reported its cytotoxic activity against human leukemia cells in vitro. OBJECTIVE: We further synthesized other heterocyclic compounds coordinated with TPN-Au(I) and assessed their cytotoxic activity against hepatocellular carcinoma HepG2 and lung cancer cell line H1299 in vitro. METHODS: Seven kinds of compounds were synthesized by introducing a five-membered heterocyclic compound into TPN-Au(I). The number of viable cells was counted by a trypan blue dye exclusion assay. Fluorescence conjugated-Annexin V and propidium iodide were used for the apoptosis analysis. RESULTS: Seven compounds were successfully synthesized. Among these compounds, TPN-Au(I)-MTZ (3- mercapto-1,2,4-triazole), TPN-Au(I)-MMT (2-mercapto-5-methyl-1,3,4-thiadiazole), and TPN-Au(I)-MMTT (2-mercapto-5-methylthio-1,3,4-thiadiazole) effectively suppressed the proliferation and induced apoptosis in HepG2 cells. In addition, TPN-Au(I)-MMTT and TPN-Au(I)-MMT also showed effective cytotoxicity against H1299 cells. CONCLUSION: The present results showed that introduction of some five-membered heterocyclic compounds, especially MMT and MMTT, to TPN-Au(I) improved the cytotoxicity against solid cancer cells.

Cytotoxic Activity of a Unique Monomeric Heterogeneous Two-Coordinate Ligand Monovalent Gold Complex with Tiopronin and a Heterocyclic Mercapto-Tetrazole Compound.

BACKGROUND: The importance of the role of NF-κB is recognized in situations such as malignant transformation and metastasis of cancer, and it has been suggested that inhibiting this role can be one of the cancer treatment strategies. Gold preparations such as auranofin are known to have an indirect NF-κB inhibitory effect. OBJECTIVE: We synthesized a novel gold complex [tiopronin monovalent gold-5-mercapto- 1-methyl tetrazole, abbreviated as TPN-Au(I)-MM4], with different physical properties and chemical structure from auranofin, and evaluated its cytotoxic activity and radiation sensitizing effect on human THP1 cells. METHODS: The number of viable cells was counted by the trypan blue dye exclusion method. The cell death evaluation was performed by FITC-Annexin V+ and PI staining. In investigating the radiation sensitizing effect of TPN-Au(I)-MM4, this compound [10 or 25 µM] was added into the culture medium 1 h before X-ray irradiation. RESULTS: In the cells treated with 25 µM TPN-Au(I)-MM4 for 72 h, a decrease in the proliferation of THP1 cells was observed [The relative values of viable cells in the control group and the 25 µM treatment group were approximately 6.8 and 4.2, respectively]. In the combination of 25 µM of the compound treatment and X-ray irradiation, an increase of approximately 3.0-fold was observed in 2 Gy irradiation and approximately 1.4-fold in 4 Gy irradiation as in comparison to the case of irradiation alone. CONCLUSION: These results suggest that TPN-Au(I)-MM4 reduces the proliferation of THP1 cells through the induction of cell death, and the combined use of TPN-Au(I)-MM4 and X-ray irradiation shows effective cytotoxicity against THP1 cells.

Tailored cell sheet engineering using microstereolithography and electrochemical cell transfer.

Postoperative adhesion and occlusion remain a serious issue associated with various surgeries, including endoscopic surgery, in which proliferated fibrous tissues stick to adjacent tissues and often cause severe complications. Cell sheet engineering has emerged as an effective approach not only for cell transplantation but also for the treatment of postoperative adhesion and occlusion. However, as the tissues in the body, such as middle ear and small intestine, and typical operative sites are non-flat and spatially complicated, tailored cell sheets with three-dimensional (3D) configurations may lead to widespread use of this approach. In the present study, we used microstereolithography, biocompatible gold plating, and electrochemical cell detachment to achieve this purpose. Various objects with dimensions ranging from millimeter- to micrometer-scale were fabricated with photocurable resin using lab-made equipment for microstereolithography. To coat the fabricated objects with a thin gold layer, conventional cyanide-based gold plating was unusable because it severely damaged almost all cells. Electroless non-cyanide gold plating we prepared was cytocompatible and suitable for electrochemical cell detachment. Cell sheets on the gold-plated substrate could be directly transplanted into a mouse intraperitoneally using electrochemical cell detachment. We further demonstrated that cell sheets grown on gold-coated 3D objects were rapidly detached along with the desorption of electroactive-oligopeptide monolayer and transferred to a surrounding hydrogel. This approach may provide a promising strategy to prepare and directly transplant tailor-made cell sheets with suitable configurations.

Formation of Micrometer Scale Metal Structures on Glass by Selective Electroless Plating on Photopatterned Titanium and Copper Containing Films.

A procedure for formation of catalytic SiO2 substrate adhesive layer patterns and selective electrochemical metal deposition on the catalyst images was investigated. A photoreactive solution containing a diazonaphthoquinone sulfonate ester and Ti and Cu complexes was developed to deposit Cu catalyst-TiO2 adhesive layer latent images on glass. Sub-micrometer/micrometer scale positive tone photoactive TiCu complex film patterns were formed using a conventional photolithography technique. The Cu ions in 40-50 nm thick Ti and Cu oxide layers formed by pyrolysis of the TiCu complex films were reduced, residual Cu displaced with Pd then the porous Ti oxide structure filled and plated with Cu by selective electroless then electrolytic plating. Annealing the Cu plating filled TiO2 layers on glass resulted in formation of a smooth Ti3+/Cu1+ oxide interface that enabled formation of 20 µm thick Cu deposits on glass substrate with up to 1 kN/m adhesion strength. The adhesion strength was attributed to chemical bonding of Ti3+ and Cu1+ oxides to the glass and Ti4+ oxide to the Cu plating that was formed upon annealing the Cu filled TiO2 interlayer. Furthermore, a dip coating procedure was adapted that allowed copper film deposition on the entire surface of a 300 µm thick glass substrate with 50 µm in diameter holes enabling formation of electrically conductive through glass substrate interconnects.

Metallic film formation using direct micropatterning with photoreactive metal complexes.

Palladium, cobalt, and nickel in complex with photoacid-generating ligands, 4-(2-nitrobenzyloxycarbonyl)catechol and 4-(6-nitroveratryloxycarbonyl)catechol, were prepared in solution. Films formed from the metal complex solutions perform as positive-tone, directly photopatternable palladium, cobalt, nickel oxide, or composite film precursors. After exposure, acid-bearing selectively soluble complexes could be removed to give patterned films upon developing in aqueous base, which were transformable to the corresponding pattern-preserving metal/metal oxide film. The photodynamics of photoinduced solubility and direct micropatterning of palladium, cobalt, nickel, and palladium/nickel oxide composite films were investigated. Employing palladium as the initiator for autocatalytic chemical plating, selective direct copper plating on palladium film on polyethylene naphthalate and palladium/nickel oxide composite film on glass was accomplished.

Simultaneous Patterning of Independent Metal/Metal Oxide Multi-Layer Films Using Two-Tone Photo-Acid Generating Compound Systems.

(1) The photo-induced solubility and positive-tone direct photo-patterning of iron, copper and lanthanides chelated with 4-(2-nitrobenzyloxycarbonyl)catechol (NBOC) or 4-(6-nitroveratryloxycarbonyl)catechol (NVOC) was investigated. Photo-patterning of iron, copper, cerium, samarium, europium, terbium, dysprosium, holmium, erbium and lutetium complexes was accomplished. Continuous films were formed by the pyrolysis of metal complex films at 500 °C. (2) Based on the difference in the photo-reaction excitation wavelength profile of NBOC and NVOC complexes, a short and simple method for simultaneous micro-patterning of two independent films on each side of a transparent glass substrate was developed. Using the developed procedure, indium tin oxide and/or titanium oxide films were formed on each side of a quartz substrate without use of resist or etching.

Photoacid generating ligands for development of positive-tone directly photopatternable metal complexes.

Photoacid generating ligands, 4-(2-nitrobenzy-loxycarbonyl)catechol and 4-(6-nitroveratryloxycarbonyl)catechol, and indium tin and titanium complexes thereof, were synthesized. These metal complexes perform as positive-tone, directly photopatternable indium tin oxide (ITO) or titanium oxide film precursors. After exposure, acid-bearing selectively soluble complexes could be removed to give patterned films upon developing in aqueous base, which were transformable to the corresponding pattern-preserving metal oxide film. Micropatterning of ITO and titanium oxide films was accomplished with the photoreactivity of the 2-nitrobenzyloxycarbonyl (NBOC) and 6-nitroveratryloxycarbonyl (NVOC) moiety bearing ligands.

Preparation and characterization of self-cleaning glass for vehicle with niobia nanosheets.

Self-cleaning glasses were prepared by coating niobia nanosheets and investigated on the performance. The coated glass heated at >450 degrees C had very low turbidity, high hardness, and excellent adhesion properties. Niobia nanosheets ([Nb(3)O(8)](-)) reacted with sodium ions (Na(+)) diffused from the glass into the films to form a crystalline phase of NaNb(3)O(8) and this phase was converted to NaNbO(3) at >450 degrees C. The films exhibited photoinduced hydrophilicity under UV irradiation but low photocatalytic oxidation activity. Excellent self-cleaning ability of the niobia nanosheet coated glass was confirmed by the Taber abrasion test, which is thought to be a candidate as self-cleaning glasses for vehicles.

Photocatalytic activity of NaNbO(3) thin films.

NaNbO(3) thin films prepared by the sol-gel method had homogeneous microstructure with an average grain size of 15-25 nm and exhibited photoinduced hydrophilic conversion under UV irradiation. However, the films had little photocatalytic oxidation activity under UV irradiation. This is the first observation that NaNbO(3) undergoes photoinduced hydrophilicity under UV irradiation.

Reaction of 2-methoxy-3H-azepine with NBS: efficient synthesis of 2-substituted 2H-azepines.

[reaction: see text] The reaction of 2-methoxy-3H-azepines, in the presence or absence of a nucleophile, with N-bromosuccinimide (NBS) gave a regioselective 1,4-adduct from which the corresponding 2H-azepine derivatives were formed via base-promoted hydrogen bromide elimination, generally in moderate to quantitative yield. Competitive formation of 4-bromo-2-methoxy-3H-azepine by electrophilic substitutuion or 3H-azepin-2-yl 2H-azepin-2-yl ether by transetherification was minimized at lower reaction temperatures. Quantitative substitution of 2-(2',4',6'-trichlorophenoxy)-2H-azepine derivatives, formed in moderate yield from the respective 3H-azepine and NBS in the presence of 2,4,6-trichlorophenol (TCP), by various nucleophiles gave the corresponding 2-substituted 2H-azepine. Among these nucleophiles were alkanethiol and alkylamine that are not tolerated in the reaction of 3H-azepine and NBS.