Search

A direct arylation of pyrazolo[1,5-a]pyridines with aryl iodides selectively occurring at the C-3 and C-7 positions via palladium-catalyzed C–H activation is described. In these reactions, (a) cesium(I) fluoride and (b) silver(I) carbonate were employed as the additive to afford 3- and 7-arylated pyrazolo[1,5-a]pyridines, respectively, in modest to good yields. These reactions showed good compatibility with functional groups, and the catalytic mechanisms of these reactions were proposed. Finally, the synthetic application on the potent p38 kinase inhibitors was demonstrated.

This paper reports the first successful preparation of biotechnological grade agarose from Gelidium amansii found in Taiwan. The scale-efficiency preparation was achieved by shortening EDTA treatment time through dispersing G. amansii agar in water in the presence of heat and EDTA, removing agaropectin impurity with a heat-compatible and strong-anion exchange resin, and precipitating agarose with a cost-effective isopropanol method. The yield of agarose from prepared G. amansii agar was 11.3%. The acquired agarose has a gel strength of 853 g cm −2 , a sulfate content of 0.14%, a pyruvate content of 1.03%, a degree of electroendosmosis of 0.16 and very limited binding affinity to DNA. The excellent properties of agarose from G. amansii of Taiwan confirm its potential diverse biotechnological applications. This innovative agarose preparation method with the significantly improved scale-efficiency can be modified for large-scale preparation of agarose for use in biotechnological industry and biochemical research.

Here we present the in vitro selection of a novel ribozyme specific for Zn2+-dependent catalysis on hydrolysis of a phosphorothiolate thiolester bond. The ribozyme, called the TW17 ribozyme, was evolved and selected from an artificial RNA pool covalently linked to a biotin-containing substrate through the phosphorothiolate thiolester bond. The secondary structure for the evolved ribozyme consisted of three major helices and three loops. Biochemical and chemical studies of ribozyme-catalyzed reaction products provided evidence that the ribozyme specifically catalyzes hydrolysis of the phosphorothiolate thiolester linkage. A successful ribozyme construct with active catalysis in trans further supported the determined ribozyme structure and indicated the potential of the ribozyme for multiple-substrate turnover. The ribozyme also requires Zn2+ and Mg2+ for maximal catalysis. The TW17 ribozyme, in the presence of Zn2+ and Mg2+, conferred a rate enhancement of at least 5 orders of magnitude when compared to the estimated rate of the uncatalyzed reaction. The ribozyme completely lost catalytic activity in the absence of Zn2+, like Zn2+-dependent protein hydrolases. The discovery and characterization of the TW17 ribozyme suggest additional roles for Zn2+ in ribozyme catalysts.

Room temperature luminescence in a CuI/AgI glass system is investigated by irradiating the system at 410 nm (3.02 eV). The spectrum peaks at 635 nm (1.95 eV) and 700 nm (1.77 eV), while the intensity is significantly enhanced (centered at 635 nm) by increasing the amount of AgI. We propose a model based on an increase in the AgI:Cu + species at higher AgI concentration at which the red emission is attributed to the radiative recombination from carriers trapped at the donor sites (e.g., interstitial silver ions) and the acceptor sites (e.g., a vacancy-compensated divalent cation). The PL efficiency is also estimated by comparison with a standard rhodamine B solution.

The present study was designed to investigate the proteomic alteration of hepatic mitochondria during sepsis and to explore the possible effects induced by heat shock treatment. Sepsis was induced by cecal ligation and puncture in Sprague-Dawley rats. Liver mitochondrial proteins were isolated and evaluated by 2-dimensional electrophoresis with broad pH-ranged (pH 3 - 10) immobile DryStrip and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein spots were visualized with silver stain and analyzed by Bio-2D software. Results showed that around 120 dominant spots could be separated and visualized distinctly by 2-dimensional electrophoresis analysis. Among them, three spots with the same molecular weight (56.4 kd), mitochondrial protein 1 (MP1), MP2, and MP3, were significantly altered in septic specimens. When analyzed by liquid chromatography-tandem mass spectrometry, the three spots all revealed to be an identical enzyme: aldehyde dehydrogenase 2 (ALDH2, EC 1.2.1.3). During sepsis, MP1 and MP2 were downregulated, whereas MP3 was upregulated concomitantly. Interestingly, heat shock treatment could reverse this phenomenon. Phosphoprotein staining showed that the degree of phosphorylation is higher in MP1 and MP2 than that in MP3. The enzyme activity assay showed that ALDH2 activity was downregulated in nonheated septic rats of 18 h after cecal ligation and puncture operation, and preserved in heated septic rats. The results of this study suggest that posttranslation modification, highly possible the phosphorylation, in ALDH2 may play a functional role in the pathogenesis of sepsis and provide a novel protective mechanism of heat shock treatment.

The photoluminescence (PL) properties of CuBr and CuBr/AgBr semiconductor nanocrystals (NCs) embedded in borosilicate glasses are measured under band-to-band excitation by a 355-nm Nd YAG laser. We observed emission from CuBr (peaked at 520 nm) doped glass, which is associated with deep states in CuBr NCs. We also observed the sensitized blue to orange-red emission in CuBr/AgBr-glass systems (peaked at 520 and 570 nm), in which the luminescence intensity of CuBr decreases with increasing AgBr concentrations, while it is enhanced significantly around 570 nm. The results are discussed by the possible energy transfer between them, or by the multi-exitonic recombination process which ejects an excited carrier from CuBr to AgBr NCs.

The cyclization mechanism for the title compound (2) reacting with one-carbon fragment reagents or nitrous acid to afford heterobicyclic compounds 6-amino-3-substituted-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-ones (3a∼d) or 6-amino-1,2,3,4-tetrazolo[5,1-f][1,2,4]triazin-8(7H)-one (4), respectively, is explored in this paper. When 3-amino-2-benzyl-6-hydrazino-1,2,4-triazin-5(2H)-one (10), the N-2 benzylated derivative of 2, is treated under the same conditions, ring cyclization does not occur; instead, 3-amino-2-benzyl-6-substituted-1,2,4-triazin-5(2H)-ones (11,12,14) and 2-N-(2-amino-1-benzyl-4-oxo-1,2,4-triazin-5-yl)semicarbazide (13) are formed. Alternatively, when 3-amino-6-hydrazino-2-[(2-hydroxyethoxy)methyl]-1,2,4-triazin-5(2H)-one (16), a compound bearing the 2-[(2-hydroxyethoxy)methyl] side-chain at N-2 of 2 by an NCO bond, reacts with glacial acetic acid or nitrous acid, the side-chain is cleaved through acidolysis to affford the ring-closed compound 6-amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (3b) or compound 4, respectively. From these results, we suggest a cyclization mechanism that the ring cyclization is dependent on the aromatization of the 1,2,4-triazine ring, which influence the reactivity and reaction behavior of the π-deficient 1,2,4-triazine.

1-Allyl- (2) and 7-allyl-6-amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (3) were obtained via the 18-crown-6-ether catalyzed room temperature reaction of 6-amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (1) with potassium carbonate and allyl bromide in dry acetone. The structures of these two derivatives were verified by 2D-NMR measurements, including gHSQC and gHMBC measurements. The minor compound 2 may possess aromatic character. A single crystal X-ray diffraction experiment indicated that the major compound 3 crystallizes from dimethyl sulfoxide in the monoclinic space group P2(1)/n and its molecular structure includes an attached dimethylsulfoxide molecule, resulting in the molecular formula C(10)H(16)N(6)O(2)S. Molecular structures of 3 are linked by extensive intermolecular N-H...N hydrogen bonding [graph set C(1)(1)(7)]. 1 Each molecule is attached to the dimethyl sulfoxide oxygen via N-H...O intermolecular hydrogen bonding. The structure is further stabilized by pi-pi stacking interactions.

CuI embedded in borosilicate glasses are prepared by a melt and heat-treatment method. We obtain the free carrier absorption cross section σ ≈ 1.0 × 10−17 cm2 and the two-photon absorption coefficient β ≈ 0.14 cm/GW by means of the Z-scan method using 6-ns laser pulses at 532 nm, with an irradiation I0 ≈ 16 MW/cm2. Upon excitation with 355 nm laser pulses at room temperature, very bright luminescence is observed, while the peak position shifts to lower energy as the band gap of CuI decreased by crystal growth. We also observed that the peak intensity varies linearly with the input intensity. The results could be attributed to the radiative recombination associated with traps or defects from impurities in the CuI microcrystallites.

In this paper we report that the title compound (3) reacts with excess N,N-dimethylformamide (DMF) containing two equivalents of acetic acid to afford 6-amino-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (1). When 3-amino-2-benzyl-6-hydrazino-1,2,4-triazin-5(2H)-one (6), the N-2 benzylated derivative of 3, is treated under the same conditions, ring cyclization does not occur; instead, 3-amino-2-benzyl-6-(2-formyl-hydrazino)-1,2,4-triazin-5(2H)-one (7) is formed. Single-crystal X-ray analysis of a 3-ethyl derivative of compound 1 reveals the predominant tautomeric structure to be the 7H-tautomer (7H-1). From these results, we propose a reasonable cyclization mechanism that incorporates two important points: (1) the tautomerism of the N-2 hydrogen with the C-5 oxo group aromatizes the 1,2,4-triazine ring, and (2) the DMF is proto-nated by acetic acid on the nitrogen atom, then deamination occurs where DMF is attacked by the 6-hydrazino group of 3 or 6.

We investigate the nonlinear properties of several PbO–B2O3 glasses and their composites using 6-ns laser pulses. The nonlinear index of refraction n2 are measured with Z-scan method at 532 nm for these samples, which are all an order larger than a CS2 solution (n2=0.98×10−11 esu) determined here; the composite materials with silver or copper metal particle dispersions exhibit larger nonlinear refractive index than the related lead glasses. These samples exhibit saturation absorption property at 532 nm under the input irradiance I0 levels from 1.02 to 7.09 × 10−2 GW/cm2; the estimated saturation absorption coefficient β s (=α 0 /I s ) decreases with increasing I0. The enhancement of nonlinear absorption coefficient β at 355 nm can be attended by either increasing the lead oxide contained in glass matrix or by doping with silver or copper metal particles.

The nonlinear absorption of five metal TMPPs (TMPP: tetrakis-(3,4,5-trimethoxyphenyl)porphyrin) doped in boric acid glass are measured with the linear polarized nanosecond laser pulses at different wavelengths by Z-scan; the two-photon absorption (TPA) is dominant in the near infrared, while the characteristic of saturation absorption (SA) is observed close to the Q(0,0) band of porphyrin. The symmetry allowed two-photon π*←π transitions are suggested to be 1 B 1 g * ← S 0 and 1 B 2 g * ← S 0 , with the cross-sections δ ranging from 25×10−50 to 114×10 −50 cm 4 s / photon . We analyze the property of SA with a four-level system, and find that the magnitudes of excited-state absorptivity and saturation intensity are not affected by changing the central metal ion in these experiments.

The non lin ear ab sorp tion prop er ties of GaClTMPP, InClTMPP and TlClTMPP (TMPP: tetrakis- (3,4,5trimethoxyphenyl)por phy rins) doped in bo ric acid glass are probed us ing the Z-scan tech nique at dif fer ent wave lengths. The characteristc of re verse sat u ra ble ab sorp tion (RSA) is ob served at 532 nm, while the two pho ton ab sorp tion (TPA) is dom i nated at sev eral wave lengths from 840 to 1350 nm. We find that the ex cited state ab sorp tion cross sec tion ex at 532 nm is en larged along a se ries of the cen tral metal ions: Ga(III)Cl < In(III)Cl < Tl(III)Cl, and the two-photon al lowed tran si tions at near in fra red are pro posed to be 1 B * 1g S0 and 1 B * 2g S0.

The X-ray structural investigations has been carried out for the title compound, 2-[(2-acetoxyethoxy)methyl]-3-amino-1,2,4-triazin-5(2 H )-one (1-[(2-acetoxyethoxy)methyl]-6-azaisocytosine), molecular formula C 8 H 12 N 4 O 4 , crystallizes in a monoclinic space group P -1 with a = 5.3124(3) A, b = 7.3635(3) A, c = 14.0170(8) A, α = 81.5265(19)°, β = 85.852(2)°, γ = 76.760(2)°, V = 527.49(5) A 3 and Z = 2, resulting in a density, D calc , of 1.437 g/cm 3 . The hydrogen-bonding systems assemble with N-H···O [graph set C (6)], N-H···N [graph set R (8)], and N-H···N combine with N-H···O [graph set R (12)]. The side chain of the molecular structure is further stabilized by short contacts formed by intermolecular C-H···O interactions.

2,7-Disubstituted pyrazolo[1,5-a]pyridines were synthesized in good chemical yields by the reaction of enediynones with hydrazine, followed by addition of copper chloride. This reaction can tolerate many functional groups.

Pyrazolo[1,5-a]pyridines and 6-iodopyrazolo[1,5-a]pyridines were synthesized by gold-catalyzed and iodine-mediated cyclization of enynylpyrazoles in good to excellent yields, respectively. The iodinated adducts were further converted to 6-arylpyrazolo[1,5-a]pyridines via Suzuki–Miyaura coupling reaction and 6-cyanopyrazolo[1,5-a]pyridine by Ullmann condensation reaction. One of the cyclization adducts, 2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine, was converted to a p38 kinase inhibitor, 2-(4-fluorophenyl)-3-(4-pyridinyl)pyrazolo[1,5-a]pyridine, in two steps.

The nonlinear absorption and refraction of soluble phthalocyanines and naphthalocyanines have been measured with z-scan technique using 8 ns, 532 nm laser pulses. The excited-state absorption cross-section and the excited-state refractive-index cross section have been estimated under the consideration of laser induced thermal effect. The excited state absorption induced n2 and Re χ(3) values are in the range of 10−12 esu. These observed data are enhanced by the concentrations of both metal substituted Pc's and Nc's, but this increment became very small for the metal free phthalocyanine. During the optical limiting experiments, a 25% linear transmitted solution of R8PcH2 can limit laser pulses to ≤ 120 μJ from incident energies as high as 2.0 mJ, and this limitation moved down to ≤ 50 μJ when replacing R8PcCu from P8PcH2. A similar property has also been observed for the metal substituted naphthalocyanines. The results indicate that both the nonlinear refraction and optical limiting properties should be strongly affected by the metal induced triplet-state nonlinear absorption in both Pc's and Nc's. Moreover, the laser pulses created a self trapped filament inside the solution of this optical limiter, while emitting time-resolved, concentric rings on a projection screen, which could be induced by the thermal lensing effect. The various optical nonlinear properties observed from these materials should make them valuable as an optical limiter.

Acyclic nucleoside analogues of antiviral DHPA and HPMPA have been prepared. Coupling of silylated 6-azauracils with benzyl glycidyl ether and stannic chloride followed by the deprotection with boron trichloride gave 1-(2,3-dihydroxypropyl)-6-azauracils (3) in good overall yields. Reaction of silylated 6-azauracil and epichlorohydrin with or without catalytic stannic chloride afforded 1-(2-chloro-3-hydroxypropyl)-6-azauracil (4a) and 1-(3-chloro-2-hydroxypropyl)-6-azauracil (6a) respectively. Coupling of silylated 6-azaisocytosine under the same reaction conditions provided 1-(2,3-dihydroxypropyl)-6-azaisocytosine (9) and 1-(2-chloro-3-hydroxypropyl)-6-azaisocytosine (10) respectively. None of the compounds exhibited significant antiviral activity against herpes simplex viruses.

2,7-Disubstituted pyrazolopyridines (II) and (IV) are synthesized in moderate to good yields by a cascade cyclization reaction of enediynones (I) and (III) with hydrazine, promoted by copper chloride.

A number of 5-benzyl-5H-imidazo[4,5-e]-1, 2, 4-triazine 1-oxides, bioisosteric isomers of antiviral 9-benzylpurines, have been prepared. Oxidation of 6-amino-5-benzylamino-3-methylsulfanyl-1, 2, 4-triazine 1 with excess of m-chloroperbenzoic acid afforded 6-amino-5-benzylamino-3-methylsulfonyl-1, 2, 4-triazine 1-oxide 2 in 75% yield. The 3-methylsulfonyl group, which is a good leaving group, has been replaced with various nucleophiles to give 3-amino 4, 3-methoxy 5 and 3-hydrazino 8 derivatives. Oxidative dehydrazination of 8 with mercury(II) oxide (HgO) in ethanol gave 6-amino-5-benzylamino-1, 2, 4-triazine 1-oxide 9 in a moderate yield. The 1, 2, 4-triazine 1-oxides were then cyclized with triethyl orthoformate (TEOF) to afford the title compounds in 28–88% yields.

Acyclic nucleoside analogues of antiviral DHPA and HPMPA have been prepared. Coupling of silylated 6-azauracils with benzyl glycidyl ether and stannic chloride followed by the deprotection with boron trichloride gave 1-(2,3-dihydroxypropyl)-6-azauracils (3) in good overall yields. Reaction of silylated 6-azauracil and epichlorohydrin with or without catalytic stannic chloride afforded 1-(2-chloro-3-hydroxypropyl)-6-azauracil (4a) and 1-(3-chloro-2-hydroxypropyl)-6-azauracil (6a) respectively. Coupling of silylated 6-azaisocytosine under the same reaction conditions provided 1-(2,3-dihydroxypropyl)-6-azaisocytosine (9) and 1-(2-chloro-3-hydroxypropyl)-6-azaisocytosine (10) respectively. None of the compounds exhibited significant antiviral activity against herpes simplex viruses.

Objective The objective of this study was to investigate whether exposure to aluminum, gallium, indium, arsenic, and antimony induces lipid peroxidation in humans. Methods Whole blood and urine levels of 103 exposed electronic industry workers and 67 referents were analyzed by use of inductively coupled plasma mass spectrometry. Malondialdehyde (MDA), the product of lipid peroxidation, was determined by high-performance liquid chromatography. Results The mean plasma MDA level in the 103 workers was significantly higher than that in 67 referents. The levels of MDA in the exposed workers were correlated significantly with the levels of urinary gallium and arsenic. Conclusions Malondialdehyde as an index of lipid peroxidation can be induced by gallium and arsenic exposure. By reducing exposure to these metals, biologic effects such as lipid peroxidation may also be diminished.

The title compound 6-amino-3-benzylmercapto-1,2,4-triazolo[3,4-f][1,2,4]-triazin-8(7H)-one (4), molecular formula C11H10N6OS, was obtained by the reaction of3-amino-2-benzyl-6-hydrazino-1,2,4-triazin-5(2H)-one (3) with carbon disulfide in awater/pyridine mixture. Compound 4 can also be synthesized by reacting6-amino-3(2H)mercapto-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (7) with benzylbromide in methanolic ammonia water. The compound crystallizes in the monoclinicspace group P21/c with a = 7.2926(15), b = 14.456(2), c = 11.436(2) Ã¥, β = 105.30(2)°, V= 1162.9(4) Ã¥3 and Z = 4, resulting in a density Dcalc of 1.567 g/cm3. Molecules of 4 arelinked by extensive intermolecular N-H···N and N-H···O hydrogen bonding [graph set R22 (9)]. The structure is further stabilized by À-À stacking interactions. 2

In this study, the authors attempted to determine factors associated with earthquake deaths in the great Chi-Chi Earthquake that occurred on September 21, 1999, in Taiwan. An isoseismal map was used to identify life-threatening hazards. The vertical peak ground acceleration of ground motion intensity was deemed the most appropriate index for the evaluation of building collapse and mortality. Mortality increased with the increase in earthquake intensity, and building collapse, approaching the epicenter. The greatest number of collapsed buildings and human deaths occurred between the Chelungpu Fault and the Shuantun Fault. Individuals 65 yr of age and older were the most vulnerable to the impact. The authors' findings suggest that improvements in earthquake-resistant building design and construction, as well as improved medical rescue for the elderly, could reduce the level of exposure to earthquake hazards.

X-ray structural investigations have been carried out for the title compound, 3-amino-2-benzyl-6-bromo-1,2,4-triazin-5(2H)-one (1-benzyl-5-bromo-6-azaisocytosine), molecular formula C10H9BrN4O, which crystallizes in the monoclinic space group P21/n with a = 12.3645(1)A, b = 6.9011(1)A, c = 14.0685(2)A, β = 111.947(1)°, V = 1113.45(2)A3 and Z = 4, resulting in a density, Dcalc, of 1.677 g/cm3. The title compound is linked by extensive intermolecular N-H…N hydrogen bonding [graph set R22(8)] and N-H…O hydrogen bonding [graph set C11(6)].

The title compound, C3H2BrN3O2, bearing an H2O molecule, crystallizes in the monoclinic space group P21/c with a = 11.3794(7), b = 6.7248(6), c = 8.6383(10)A, β = 98.792(5)°, V = 653.27(10)A3 and Z = 4, resulting in a density, Dcalc, of 2.135 g/cm3. Each 1,2,4-triazine molecule is linked with seven adjacent molecules, including three H2O molecules. The molecules of the title compound are linked by a combination of extensive N-H…O, O-H…O intermolecular hydrogen bonds and N…Br interactions, leading to a continuous wave framework structure. The framework layers are further stabilized by intermolecular short contacts: N…O, C…O and Br…C.

The crystal structure of 3-amino-1,2,4-triazine was determined with single-crystal XRD data. The double bond sites are at C(2)-N(2) and C(3)-N(3) positions. The 3-amino group donates the unpaired electrons and resonates through C(1)-N(1) with the 1,2,4-triazine ring. There are two intermolecular hydrogen bonds stabilizing the crystal structure.

Pyrazolo[1,5-a]pyridines and 6-iodopyrazolo[1,5-a]pyridines were synthesized by gold-catalyzed and iodine-mediated cyclization of enynylpyrazoles in good to excellent yields, respectively. The iodinated adducts were further converted to 6-arylpyrazolo[1,5-a]pyridines via Suzuki-Miyaura coupling reaction and 6-cyanopyrazolo[1,5-a]pyridine by Ullmann condensation reaction. One of the cyclization adducts, 2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine, was converted to a p38 kinase inhibitor, 2-(4-fluorophenyl)-3-(4-pyridinyl)pyrazolo[1,5-a]pyridine, in two steps.

Imidazo[4,5-e]-as-triazine 1-oxides (6-azapurine 6-oxides), structurally related to guanine and hypoxanthine, have been prepared. Reaction of 5,6-diamino-3-methylsulfonyl-as-triazine 1-oxide(1) with hydrazine afforded 5,6-diamino-3-hydrazino-as-triazine 1-oxide(2) which was then oxidized with mercuric oxide to give 5,6-diamino-as-triazine 1-oxide(3). The 3-methylsulfonyl group of 1 was also replaced with liquid ammonia and methanolic ammonia respectively to give 3-amino (5) and 3-methoxy (6) derivatives. as-Triazine N-oxides were then cyclized with triethyl orthoformate (TEOF) to afford the title compounds

A number of 5-benzyl-5H-imidazo[4,5-e]-1, 2, 4-triazine 1-oxides, bioisosteric isomers of antiviral 9-benzylpurines, have been prepared. Oxidation of 6-amino-5-benzylamino-3-methylsulfanyl-1, 2, 4-triazine 1 with excess of m-chloroperbenzoic acid afforded 6-amino-5-benzylamino-3-methylsulfonyl-1, 2, 4-triazine 1-oxide 2 in 75% yield. The 3-methylsulfonyl group, which is a good leaving group, has been replaced with various nucleophiles to give 3-amino 4, 3-methoxy 5 and 3-hydrazino 8 derivatives. Oxidative dehydrazination of 8 with mercury(II) oxide (HgO) in ethanol gave 6-amino-5-benzylamino-1, 2, 4-triazine 1-oxide 9 in a moderate yield. The 1, 2, 4-triazine 1-oxides were then cyclized with triethyl orthoformate (TEOF) to afford the title compounds in 28–88% yields.