Combination of Nitrogen-Rich Skeleton and Coordination Group:Synthesis of a High-Energy Primary Explosive Based on 1H-Tetrazole-5-Carbohydrazide

The high energy coordination compounds Cu(TZCA)_(2)(ClO_(4))_(2)(ECCs-1) was prepared by 1H-tetrazole-5-carbohydrazide(TZCA) with a high energy skeleton and a strong coordination ability group.At the same time,the reaction activity of the ligand was explored,and the single crystal structure of it and intermediate were obtained.The structures of all substances were characterized by IR and EA.And the structure and composition of ECCs-1 are confirmed by ESP,AC,SEM and ICP-OES.Physical and chemical properties tests show that ECCs-1 has an acceptable thermal stability(T_(d)=177℃) and extremely sensitive mechanical stimulation(IS=1 J,FS=5 N).The comprehensive performance test results show that ECCs-1 has excellent initiation ability.In addition,the decomposition mechanism of ECCs-1 is explored from two aspects of experiment and theoretical calculation.

Synthesis, Structural Characterization and Antimicrobial Activity of a Novel Cobalt(II) Complex Based on 3-Methyl-1-Phenyl-4-(2-Thienoyl)-Pyrazol-5-One

New cobalt(II) complex, [Co(O2C15H11N2S)2(OH2)2]∙2H2O (1∙2H2O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)2∙6H2O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H2O. Compound 1∙2H2O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H2O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H2O displayed moderate activity (10 ∙2H2O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).

Synthesis, Structural Characterization and Antimicrobial Activity of a Novel Cobalt(II) Complex Based on 3-Methyl-1-Phenyl-4-(2-Thienoyl)-Pyrazol-5-One

New cobalt(II) complex, [Co(O2C15H11N2S)2(OH2)2]∙2H2O (1∙2H2O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)2∙6H2O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H2O. Compound 1∙2H2O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H2O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H2O displayed moderate activity (10 ∙2H2O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).

Synthesis and Crystal Structure of Trans-4-[(5-(2,4-Dichlorophenoxy)-3-methyl-1-phenyl-1H-pyrazol-4-yl)methyleneamino]-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one

The title compound trans-4-[（5-（2,4-dichlorophenoxy）-3-methyl- 1-phenyl-1H-pyrazol-4-yl）methyleneamino]- 1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 3 （C28H23Cl2N5O2, Mr = 532.41） has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in triclinic, space group P1- with a = 8.9438（4）, b = 11.6065（5）, c = 14.2215（6）A, α = 112.566（1）, β = 92.324（2）, γ = 102.91（1）°, V= 1315.65（10） A^3, Z = 2, Dc = 1.344 g/cm^3,μ（MoKa） = 0.282 mm^-1, λ = 0.71073 A, F（000） = 552, the final R = 0.0587 and wR = 0.1578 for 5071 observed reflections （I 〉 2σ（I））. X-ray analysis reveals that the product is a thermodynamically stable trans isomer. Intra- and intermolecular C（ 12）-H（12）…O（1） and C（28）-H（28）...O（1）# 1 hydrogen bonds were observed in the title compound.

Extraction Behavior of Rare Earths with 1-phenyl-3-methyl-4-benzoyl-pyrazolone-5 Using Solid-liquid Extraction Technique

The extraction behavior of rare earths was studied by using paraffin with ceresin as a diluent containing 1-phenyl-3-methyl-4-benzoyl-pyrazolone-5.In solid phase,the composition of complexes is REP_3.The equilib- rium extraction constants and pH_(1/2) values of solid-liquid extraction are higher than those of normal liquid-liquid extraction.The extraction efficiency tends to maximum when the ratio of phases is 1:1.When the extraction temperature is higher than the melting point of paraffin and the extraction time is over 10 min,the extraction efficiency keeps constant.Moreover,the relationship among separation factor,equilibrium extrac- tion constant,pH_(1/2) value and atomic number was obtained.The mechanism of solid-liquid extraction is analogous to that of liquid-liquid extraction.

Synthesis and <i>in Vitro</i>Biological Activities of 4,5-Disubstituted 1,2,4-Triazole-3-Thiols

Purpose: The triazole nucleus is an important part of the therapeutically interesting drug candidate as antimicrobial, analgesic, anticancer, anticonvulsant and anti-inflammatory agents. Methods: Therefore, in this study, twelve 4,5-disubstituted-1,2,4-triazole-3-thiols were synthesized by the reaction of substituted isothiocyanates and hydrazides using the common method of base catalysed intramolecular dehydrative cyclization of substituted thiosemicarbazides 3(a-f) and 4(a-f). The structures of these compounds were characterized by means of FT-IR, 1H-NMR, and elemental analysis data. All these compounds were screened for antibacterial, antioxidant, antitumor and cytotoxic activities. Results: Among these compounds: 5c, 5f and 6f were found active against gram positive cocci, the compounds 5a, 5b, 5d, 6a and 6f showed 85% free radical scavenging effect at 3 ppm when tested for antioxidant activity, 75% tumors inhibition was recorded using 5c, 5d and 6a and brine shrimps lethality assay declared 5a, 5b and 6d was 129.62 μg/ml, 161.577 μg/ml and 81.56 μg/ml respectively. Conclusion: Compounds carrying significant bioactivity can be further studied using animal models to establish their safety profile prior to initiating clinical trials.

Two New Schiff Bases Based on 5-Chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde: Syntheses, Crystal Structures and Properties

Two new Schiff bases based on 5-chloro-3-methyl-1-phenyl-1 H-pyrazole-4-carbaldehyde, namely, N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-4-morpholinoaniline(Ⅲa) and N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-3-fluoro-4-morpholinoaniline(Ⅲb), were synthesized and characterized by IR, LC-MS, 1 H NMR and 13 C NMR spectroscopy. Meanwhile, the three-dimensional configurations of the two title compounds were further characterized by single-crystal X-ray diffraction analyses. Both the compounds are thermodynamically stable trans-isomers. Moreover, the fluorescence properties and antioxidant activities against DPPH of the two target compounds have been investigated, and the results showed that the title compounds both have fluorescence performance and certain antioxidant activities against DPPH radical.

Synthesis and Crystal Structure of Methyl 2-(Diphenylamino)-4-phenyl-1,3-thiazole-5-carboxylate

The title compound, methyl 2-（diphenylamino）-4-phenyl-1,3-thiazole-5-carboxylate, was synthesized and studied by single-crystal X-ray diffraction method. The structure of the product was confirmed by IR, 1H- and 13C-NMR spectroscopy and elemental analysis. These experimental studies were supported by quantum mechanical calculations. The structure was solved in monoclinic, space group P21/c with a = 9.573（3）, b = 19.533（7）, c = 9.876（3）, β = 92.35（4）°, V = 1845.2（10）3, T = 85（2） K, Z = 4, R = 0.040 and wR = 0.089 for 6424 observed reflections with I2σ（I）.

Effects of Two Anti-TNF-α Compounds: Etanercept and 5-Ethyl-1-Phenyl-2-(1H)-Pyridone on Secreted and Cell-Associated TNF-α <i>In Vitro</i>

Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine and its exaggerated production has been implicated in acute, chronic and autoimmune inflammatory diseases. Proteinaceous and non-proteinaceous anti-TNF-α agents have been developed to reduce its circulating levels either by neutralizing, binding or inhibiting the de novo synthesis with the aim of achieving desirable therapeutic effects. In the present study, we compared the effects of a protein-based anti-TNF-α drug, etanercept, and a non-protein-based anti-TNF-α small molecule, 5-ethyl-1-phenyl-2-(1H) pyridone (5-EPP), on the LPS-stimulated secretion of TNF-α in the medium and TNF-α associated with the THP-1 cells in vitro. Both drugs had marked concentration-dependent inhibitory effects on the LPS-stimulated secretion of TNF-α. However, their effects on the LPS-stimulated cell-associated TNF-α were diametrically opposed to each other. For instance, etanercept further increased the level by up to 12-fold, whereas 5-EPP inhibited the level in a dose dependent manner. In addition, 5-EPP caused a significant reduction in the elevated level of cell associated TNF-α caused by LPS + etanercept. The differences in the levels of cell-associated TNF-α as reported in the present study may partly explain the adverse effects of some protein-based anti-TNF-α drugs including etanercept as opposed to a non-protein-based anti-TNF-α drug such as pirfenidone, a structural analogue of 5-EPP, for treatment of some TNF-α mediated diseases. It was concluded from the findings of this study that drugs which elevate the levels of cell associated-TNF-α will potentially have more adverse events even after reducing the secreted levels of TNF-α than the drugs which reduce both the secreted and cell-associated TNF-α levels.

1-苯基-3-(2-羟基苯基-5-芳基)-2-吡唑啉的合成与生物活性

研究1-苯基吡唑啉类化合物的合成及其EcMetAP酶活抑制活性。以查尔酮衍生物与苯肼为原料合成啉类化合物。利用IR、1 H NMR和MS对它们进行表征。利用分光光度法测试化合物的EcMetAP酶活性抑制作用,利用生物分子结构分析软件FieldTemplater和FieldAlign计算化合物和已知的EcMetAP酶抑制剂的空间作用力场的相似性。共合成了6个1-苯基-3-(2-羟基苯基-5-芳基)-2-吡唑啉类化合物,但只有化合物5对EcMetAP酶活性有抑制作用,抑制率为31.62%,空间作用力场的相似度为0.615。说明化合物5可作为先导化合物进行结构优化,得到优良的EcMetAP酶抑制活性化合物。

Aspects on the Mechanism of the 1-Phenyl-1<i>H</i>-pyrazolo[3,4-<i>b</i>]quinoxaline Formation

Condensation of D-glucose, o-phenylenediamine and N,N-benzylphenylhydrazine hydrochloride (NNBPHH) in a one-pot reaction, or condensation of 2-(D-arabino-tetritol-1-yl) quinoxaline and NNBPHH, gave 3-(D-erythro-glycerol-1- yl)-1-phenyl-1H-pyrazolo[3,4-b]quinoxaline. The structure of the latter was determined by 1H NMR spectroscopy and by synthesis using phenylhydrazine hydrochloride instead of NNBPHH. Condensation of D-glucose and 4,5-dichloro-o-phenylenediamine gave 6,7-dichloro-2-(D-arabino-tetritol-1-yl)quinoxaline, which upon condensation with NNBPHH gave the corresponding 6,7-dichloro-3-(D-erythro-glycerol-1-yl)-1-phenyl-1H-pyrazolo[3,4-b]quinoxaline. The structure and mechanism of formation of these compounds are discussed.

Solid State Synthesis and Crystal Structure of 3—Methly—1—phenyl—4—phe

The solid state thermal reaction of benzil with 3-methyl-1-phenyl-5-pyrazolone gave the title compound 1 (C_24H_18N_2O_2) and its isomer 2. The crystal structure of the title compound has been determined by X-ray analysis. The crystal belongs to monoclinic system, space group P2_1/n, with cell parameters a = 7. 479 ( 1 ), b =16. 992(1), c=15. 165(1) A , β= 100. 99(1)°, V= 1891. 9 A￣3, M_r=366. 42, Z=4, D_c= 1. 286 g/cm￣3, μ= 6. 236 cm￣-1, F(000) = 768. In the molecule of 1, benzoyl group and CO group of five-member ring are in cis-positions, the interaction of oxygen atoms leads to the noncoplanarity.

Synthesis and biological evaluation of 5'-phenyl-3'H-spiro-[indoline-3,2'-[1,3,4]oxadiazol]-2-one analogs

A series of 5＇-phenyl-3＇H-spiro[indoline-3,2＇-[l,3,4]thiadiazol]-2-one analogs were synthesized and their Bcl-2 protein inhibitory activities were studied. The lead compound was originally identified using a fluorescence polarization-based competitive binding assay. Among the 10 compounds investigated, I k showed good binding affinities to Bcl-xL and Mcl-l, with inhibition constants of 8.9 μmol/L and 3.4 μmol/L, respectively. While compound lc achieved tight binding affinities to Bcl-xL （Ki= 0.16 μmol/L）, has the potential to be a new lead compound.

Syntheses and Crystal Structure of Six-coordinated Diorgnotin Complexes with 2,5-Dimercapto-4-phenyl-1,3,4-thiodiazole

The reactions of diorganotin dichloride [Ph2SnCl2, (PhCH2)2-SnCl2 or (n-Bu)2SnCl2] with potassium salt of 2,5-dimercapto-4-phenyl-1, 3,4-thiodiazole gave complexes R2Sn (S3N2C8H5)2 (4: R = Ph; 5: R = PhCH2 and 6: R = n-Bu), respectively. Characterizations were carried out for all complexes by IR, 'H NMR spectra and X-ray crystallography analysis. Including the Sn…N interaction, the three complexes all have six-coordinated distorted octahedral geometry. Based on the requence of stereo-chemical constraint sequence, phenyl≈benzyl > n-butyl, the less the effect of the stereochemical constraint of R groups, the shorter the Sn…N length. In complexes 5 and 6, there exist S…S weak intra-molecular interactions, through which the complexes are dissociated into loose 2D polymers. All three complexes show antitumour activity in bioactivity measurements.

Extraction and Separation of Rare Earths from Nitrate Medium by Mixtures of p-Phosphorylated Calixarene and 1-Phenyl-3-methyl-4-benzoyl-pyrazalone-5

The gadolinium extraction by the mixtures of p-phosphorylated calixarene and 1-phenyl-3-methyl-4-benzoylpyrazalone-5 from nitrate medium was studied,which indicated an obvious synergistic effect between these two extractants.The extractants exhibit no interaction with each other before the metal extraction.Gadolinium(Ⅲ)was extracted by the species of Ln(PMBP)_(2)L_(2)(NO_(3))instead of Ln(PMBP)_(3)•(HPMBP)or Ln(NO_(3))_(3)•2L which are extracted by HPMBP or L alone.Thermodynamic functions(ΔG,ΔH,ΔS)were calculated.The extraction of other rare earths was also investigated and compared.Possible single rare earth separation was discussed.

Un-catalyzed tandem Knoevenagel-Michael reaction for the synthesis of 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols)in aqueous medium

An environmentally benign un-catalyzed one-pot synthesis of 4,4＇-（arylmethylene）bis（1H-pyrazol-5-ols） has been reported via tandem Knoevenagel-Michael reaction of aldehydes with two equivalents of 3-methyl-1-phenyl-1H-pyrazol-5（4H）-one in aqueous medium.

An environmentally friendly synthesis of 1,4-dihydropyrano[2,3-c]pyrazole derivatives catalyzed by tungstate sulfuric acid

An efficient three-component synthesis of 6-amino-4-aryl-5-cyano-3-metriyl-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazoles via a reaction between 3-methyl-1-phenyl-2-pyrazolin-5-one,aromatic aldehydes and malononitrile using tungstate sulfuric acid as a catalyst was described.Mild conditions,good to excellent yields,easily available catalyst and easy work-up are the key features of this method.

Determination of ergocalciferol in human plasma after Diels-Alder derivatization by LC-MS/MS and its application to a bioequivalence study

An accurate, sensitive and selective method is developed for determination of ergoealeiferol （vitamin D2） in human plasma using LC-MS/MS. After liquid-liquid extraction with n-hexane, ergoealeiferol was derivatized by reacting with 4-phenyl-l,2,4-triazoline-3,5-dione （PTAD）, a strong dienophile based on Diels-Alder reaction. Ergocalciferol and its deuterated internal standard, ergocalciferol-d6, were analyzed on X Select CSH Cls （100 mmx4.6 mm, 2.5 lam） column using acetonitrile and 0.1% （v/v） formic acid in water containing 0.14% methylamine within 6.0 min under gradient elution mode. Tandem mass spectrometry in positive ionization mode was used to quantify ergocalciferol by multiple reaction monitoring （MRM）. Entire data processing was done using Watson LIMSTM software which provided excellent data integrity and high throughput with improved operational efficiency. The major advantage of this method includes higher sensitivity （0.10 ng/mL）, superior extraction efficiency （〉83%） and small sample volume （100 ~tL） for processing. The method was linear in the concentration range of 0.10-100 ng/mL for ergoealciferol. The intra-batch and inter-batch accuracy and precision （% CV） values varied from 97.3% to 109.0% and 1.01% to 5.16%, respectively. The method was successfully applied to support a bioequivalence study of 1.25 mg ergoealciferol capsules in 12 healthy subjects.

Synthesis, Crystal Structure and Luminescence Property of [Co(hmz)_2(H_2O)_4]·2H_2O

A new mononuclear Co（Ⅱ） complex, [Co（hmz）2（H2O）4]·2H2O, has been synthesized by the reaction of Co（CH3COO）2·4H2O with 1-（4-hydroxyphenyl）-5-mercaptotetrazole （Hhmz）. It crystallizes in the monoclinic system, space group P21/n with a = 13.502（5）, b = 6.718（3）, c = 13.972（6） A, β = 117.532（4）°, V = 1123.9（8） A^3, Z = 2, M r = 553.45, F（000） = 570, Dc = 1.635 g/cm^3, μ = 1.008 mm^-1, the final R = 0.0272 and wR = 0.0684 for 2194 observed reflections （Ⅰ〉 2σ（Ⅰ））. The Co（Ⅱ） is six-coordinated by two nitrogen atoms from two hmz^-1 ligands and four water molecules, forming an octahedral geometry. The intermolecular hydrogen bonding and offset-panel π-π stacking interactions between the adjacent molecules extend the compound into a three- dimensional supramolecular framework. The title compound emits strong blue fluorescent light （λem（max） = 427 nm） at room temperature and is red-shifted compared with free ligand Hhmz （λem（max） = 342 nm）.