A new cloud-point preconcentration approach for the spectrophotometric determination of p-aminophenol in the presence of paracetamol with 2-(2-Hydroxyphenyl)-1H-benzimidazole as a coupling reagent

A preconcentration and determination method for trace p-aminophenol (PAP) in paracetamol was developed. Cloud-point extraction (CPE) was employed for the preconcentration of p-aminophenol prior to spectrophotometric determination using Triton X-100 (TX-100) as an extractant. The determination is based on the reaction of p-aminophenol with 2-(2-hydroxyphenyl)-1H-benzimidazole (HPBI) at room temperature in the presence of an oxidant to produce indophenol blue dye. The dye formed is subsequently entrapped in micelles of the surfactant TX-100. The surfactant-rich phase shows maximum absorbance at 650 nm and the proposed method is linear in the 0.1 to 5.0 mg mL⁻¹ concentration range. By preconcentrating 10 mL of the sample solution, a detection limit as low as 55 ng/mL was obtained after a single-step extraction and the experimental concentration factor achieved for this method was found to be 10. The stoichiometric composition of the dye is 1: 1 (PAP: HPBI). Some parameters such as HPBI, KIO₄, Na₂CO₃, and TX-100 concentration, extraction temperature, incubation, and centrifugation time, and the sample volume were investigated in detail. The established procedure was successfully adopted for the determination of p-aminophenol in the presence of paracetamol in various pharmaceutical preparations. The text was submitted by the authors in English.     

新型吡咯并三嗪酮类PARP-1抑制剂的设计、合成及生物活性

分别以5-溴-2-氟苯甲腈(1a)和3-溴苯甲腈(1b)为原料,经Sonogashira偶联,脱三甲基硅基保护基,三分子偶联及水解等5步反应制得中间体2-氟-5-［(4-氧代-3,4-二氢吡咯［1,2-d］［1,2,4］三嗪-1-基)甲基］苯甲酸（6a)和3-[(4-氧代-3,4-二氢吡咯［1,2-d］［1,2,4］三嗪-1-基)甲基］苯甲酸（6b）。环烷基甲酸经酰氯化,缩合和脱Boc保护基3步反应制得环烷基哌嗪-1-基甲酮(7a~7c)。 6a与NCS（1 eq.）反应制得5-［(6-氯-4氧代-3,4二氢吡咯［1,2-d］［1,2,4］三嗪-1-基)甲基］-2氟 苯甲酸(6c); 6a与NCS(2 eq.)反应制得5-［(6,7-二氯-4氧代-3,4二氢吡咯［1,2-d］［1,2,4］三嗪-1-基)甲基］-2氟-苯甲酸(6d)。 6a~6d, 6a~6c分别与7a~7c和1-（2-嘧啶基）哌嗪在TBTU（缩合剂）,DIPEA（碱）的作用下合成了13个新型吡咯并三嗪酮类PARP-1抑制剂(8a~8m),其结构经¹HNMR和MS(ESI)表征。采用Alarm blue法研究了8a~8m对肿瘤细胞MDA-MB-436的抑制活性(IC₅₀)。结果表明：8f, 8g, 8i和8j对MDA-MB-436有较强的抑制活性（IC₅₀=30.5~69.3 nmol·L^-1）。     

Spectrophotometric determination of phenol and resorcinol by reaction with p-aminophenol

Based on the reaction with p-aminophenol, a series of procedures have been developed for the spectrophotometric determination of phenol and resorcinol. Three basic approaches have been studied: (i) a batch procedure, using the dissolved oxygen as oxidant, (ii) a stopped-flow procedure by use of KIO(4) as oxidant and (iii) a flow injection (FI) procedure developed in the presence of KIO(4). Phenol can be accurately determined at 626 nm, in the stopped-flow mode, after a reaction time of 45 min in 0.005M NaOH, 0.004M KIO(4) and 500 mug/ml of PAP. The development of a manifold, which incorporates a sample parking, is a convenient approach which makes it possible to measure, in the stopped-flow mode, four solutions in one hour. The limit of detection of this method corresponds to 64 ng/ml of phenol Resorcinol can be determined by FI at 540 nm in 0.006M NaOH, 0.0002M KIO(4) and 50 mug/ml PAP with a limit of detection of 6.6 ng/ml and a sample throughput of 300 injections per hour. A combination between the FI procedure for the determination of resorcinol and the stopped-flow procedure for phenol determination provides accurate results in the analysis of spiked samples containing both phenol and resorcinol.     

Investigations in the imidazole series LXXII. Synthesis of naphth[1,2-d]imidazo[3,2-b]-3-thiazolidone and its derivatives

Naphth[1,2-d]imidazo[3,2-b]-3-thiazolidone and its methyl homolog were synthesized by the reaction of 2-mercaptonaphth[1,2-d]imidazole with chloroacetic and -chloropropionic acids with subsequent cyclization of the naphth[1,2-d]imidazole-2-mercaptoacetic acids. The reactions of the first of them at the methylene group with aldehydes, nitroso compounds, and benzenediazonium salts were studied; the corresponding arylidene and azomethine derivatives of naphthimidazo-3-thiazolidone and the arylhydrazones of naphth[1,2-d]imidazo[3,2-b]thiazoline-2,3-dione were obtained. The arylidene derivatives of naphthimidazo-3-thiazolidone were also obtained by the reaction of naphthimidazole-2-mercaptoacetic acid or its methyl ester with aldehydes or (in one step) by the reaction of 2-mercaptonaphth[1,2-d]imidazole with chloroacetic acid and carbonyl compounds.See [1] for communication LXXI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 399–402, March, 1972.     

Liquid chromatography-electrospray tandem mass spectrometric assay suitable for quantitation of YM155, a novel small-molecule survivin suppressant, in dog plasma

This paper describes a sensitive and selective liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for determination of the novel survivin suppressant YM155, 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazolium, which is developed for the treatment of solid tumors. This method uses a liquid-liquid extraction from 0.25 mL of dog plasma. LC separation was carried out on a Genesis Silica column (50 mm x 3.0 mm i.d.) at a flow-rate of 0.5 mL/min. Compounds were eluted using a mobile phase of 5 mm ammonium acetate and 0.1% formic acid in water-0.1% formic acid in acetonitrile, 17:83 (v/v). MS/MS detection was carried out with an MDS-Sciex API3000 triple quadrupole mass spectrometer in positive electrospray ionization mode. The standard curve was linear from 0.05 to 50 ng/mL (r > or = 0.9968). The lower limit of quantitation was 0.05 ng/mL. Good intra- and inter-day assay precision (within 7.4% RSD) and accuracy (within +/-12.3%) were obtained. The extraction recovery was 66.2%. The method was successfully applied to preclinical pharmacokinetic studies in dogs.     

An improved ELISA for the determination of tobacco mosaic virus with linear sweep voltammetry detection based on a new system of PAP-H2O2-HRP

An improved ELISA for the determination of tobacco mosaic virus (TMV) with linear sweep voltammetry based on a new system of p-aminophenol (PAP)- H₂O₂- horseradish peroxidase (HRP) has been developed. The enzymatic product 3-[(4-hydroxyphenyl)amino]-4-(2-amino-5-hydroxyphenyl)-6-[(4-hydroxyphenyl)imino]-2,4-cyclohexadiene-1-one, produced from HRP catalyzing the oxidation of PAP with H₂O₂, yields a sensitive linear sweep voltammetric response at a potential of –0.45 V (vs. SCE) in Britton-Robinson (BR) buffer solution. By using this voltammetric peak, HRP can be measured with a detection limit of 0.4 mU/L and a linear range of 1.0 ～ 1.0 × 10² mU/ L. The detection limit for the clarified TMV is 4.0 ng/mL and the highest dilution ratio detected for the infected leaf sap is 1?:?3.9 × 10⁶. The processes of the enzyme-catalyzed reaction and the electro-reduction of the product of the enzyme-catalyzed reaction have been investigated.     

Quantitative determination of fluvastatin in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry using [18O2]-fluvastatin as an internal standard

A sensitive and specific method for the quantitative determination of fluvastatin in human plasma is presented. The drug was isolated from plasma by extractive alkylation with pentafluorobenzyl bromide and further derivatized to the bis-trimethylsilyl derivative. [18O2]-Fluvastatin was prepared from unlabelled fluvastatin and used as an internal standard. Gas chromatography/mass spectrometry under negative ion chemical ionization conditions was used for quantitative measurement of the drug, using m/z 554.26 and 558.26 for target and internal standard, respectively. Calibration graphs were linear within a range of 2 and 512 ng mL(-1) plasma. Intra-day precision was 0.94% (2 ng mL(-1)), 2.53% (8.2 ng mL(-1)), 2.16% (81.9 ng mL(-1)) and 3.26% (409.6 ng mL(-1)); inter-day variability was found to be 1.64% (2 ng mL(-1)), 0.97% (8.2 ng mL(-1)), 1.97% (81.9 ng mL(-1)) and 2.01% (409.6 ng mL(-1)). Intra-day accuracy showed deviations of 0.6% (2 ng mL(-1)), 0.37% (8.2 ng mL(-1)), -1.52% (81.9 ng mL(-1)) and -1.67% (409.6 ng mL(-1)); inter-day accuracy was of -1.64% (2 ng mL(-1)), -1.13% (8.2 ng mL(-1)), -2.28% (81.9 ng mL(-1)) and -0.46% (409.6 ng mL(-1)). The stable isotope labelled standard was found to be stable under the analytical conditions.     

Determination of saterinone enantiomers in plasma samples with an internal standard using a Chiralcel OD column, fractionation and reversed-phase chromatography

A specific and validated high-performance liquid chromatographic method was developed for the determination of the S-(-) and R-(+) enantiomers of saterinone. 1-[(4-cyano-1,2-dihydro-6-methyl-2-oxopyridin-5-yl)phenoxyl] -3-[4-(2- methoxyphenyl)piperazin-1-yl]propan-2-ol, in plasma at the low ng/ml level. The enantiomers of saterinone and an internal standard, 1-[(4-cyano-1,2-dihydro-6-methyl-2-oxo-pyridin-5-yl)phenoxy]-3-[4-(2- ethoxyphenyl)piperazin-1-yl]propan-2-ol, were chromatographed on a chiral Chiralcel OD stationary phase. However, the S-(-) enantiomers of saterinone and the internal standard were unresolved, as were the R-(+) enantiomers of both substances. Therefore, the two fractions were collected and each was separately resolved on an achiral Polyencap A reversed-phase column and quantified. The detection limit was 0.5 ng/ml of enantiomer, allowing the determination of plasma levels up to 36 h after oral administration of 90, 150 and 180 mg of saterinone to twelve subjects.     

An improved ELISA for the determination of tobacco mosaic virus with linear sweep voltammetry detection based on a new system of PAP-H2O2-HRP

An improved ELISA for the determination of tobacco mosaic virus (TMV) with linear sweep voltammetry based on a new system of p-aminophenol (PAP)- H₂O₂- horseradish peroxidase (HRP) has been developed. The enzymatic product 3-[(4-hydroxyphenyl)amino]-4-(2-amino-5-hydroxyphenyl)-6-[(4-hydroxyphenyl)imino]-2,4-cyclohexadiene-1-one, produced from HRP catalyzing the oxidation of PAP with H₂O₂, yields a sensitive linear sweep voltammetric response at a potential of –0.45 V (vs. SCE) in Britton-Robinson (BR) buffer solution. By using this voltammetric peak, HRP can be measured with a detection limit of 0.4 mU/L and a linear range of 1.0 ∼ 1.0 × 10² mU/ L. The detection limit for the clarified TMV is 4.0 ng/mL and the highest dilution ratio detected for the infected leaf sap is 1 : 3.9 × 10⁶. The processes of the enzyme-catalyzed reaction and the electro-reduction of the product of the enzyme-catalyzed reaction have been investigated. Received: 17 November 1998 / Revised: 17 March 1999 / Accepted: 20 March 1999     

Synthesis and properties of some derivatives of 2-thionoindeno [1,2-d]-pyrimidine and indeno [1,2-d] [3,1] thiazine

Derivatives of 2-thiono-5-oxo-2,3,4,5-tetrahydroindeno[1,2-d] pyrimidine and 5-oxo-1,2,4,5-tetrahydroindeno [1,2-d] [3,1] thiazine are formed in the cyclocondensation of 2-arylideneindan-1,3-diones with thiourea and N-monomethylthiourea, while only derivatives of indeno [1,2-d]-pyrimidine are formed in the reaction with N,N-di-methylthiourea. S- and N(₃)-Alkylation occur in the alkylation of 2-thiono-4-pheny1-5-oxo-2,3,4,5-tetrahydroindeno[1,2-d]pyrimidine, while only the N-methyl derivative is formed in the alkylation of 2,5-dioxo-4-phenyl-1,2,4,5-tetrahydroindeno [1,2-d] [3,1]thiazine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1136–1141, August, 1988.     

A novel amphiphilic chiral ligand derived from D-glucosamine. Application to palladium-catalyzed asymmetric allylic substitution reaction in an aqueous or an organic medium, allowing for catalyst recycling

A novel amphiphilic phosphinite-oxazoline chiral compound, 2-methyl-4,5-[4,6-O-benzylidene-3-O-bis[4-((diethylamino)methyl)phenyl]phosphino-1,2-dideoxy-alpha-D-glucopyranosyl]-[2,1-d]-2-oxazoline (1), has been prepared from natural D-glucosamine hydrochloride. The newly prepared complex, [Pd(2-methyl-4,5-[4,6-O-benzylidene-3-O-bis[(4-((diethylmethylammonium)methyl)phenyl)]phosphino-1,2-dideoxy-alpha-D-glucopyranosyl]-[2,1-d]-2-oxazoline)(eta3-C3H5)]3+ x 3BF4- (3), is soluble in water and an efficient catalyst for asymmetric allylic substitution reaction in water or an aqueous/organic biphasic medium (up to 85% ee). This catalytic system offers an easy separation of the aqueous catalyst phase from the product phase and allows recycling of the catalyst phase. In addition, compound 1 also works as an effective ligand for the palladium-catalyzed reaction under conventional homogeneous conditions in an organic medium, in which the catalyst (Pd-1 complex) can be recovered by simple acid/base extraction and reused in the second reaction.     

Fluorimetric determination of ultratraces of lead by ion-pair extraction with cryptand 2.2.1 and eosin

A spectrofluorimetric study of the extraction of lead into 1,2-dichloroethane, as an ion-pair formed between the cryptand 2.2.1-lead complex and the eosinate counter-ion is described. Optimum conditions for the extraction have been established and a new spectrofluorimetric determination of ultratraces of lead is proposed (detection limit 0.8 ng/ml; relative standard deviation 2.4% at the 60 ng/ml level). The metal:ligand:counter-ion molecular ratio in the extracted mononuclear ion-pair is 1:1:1. The equilibrium constants involved in the extraction have been estimated and refined by the Letagrop-DISTR program.     

Development of a quantitative method for the analysis of total L-ascorbic acid in foods by high-performance liquid chromatography

A new method has been developed for the determination of total vitamin C in foods. The method requires less time than the traditional methodologies and uses a radical oxidation of L-ascorbic acid (AA) to obtain dehydro-L-ascorbic acid (DHAA) by means of a peroxyl radical generated in situ by thermal decomposition of an azo-compound, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). The dehydro-L-ascorbic acid is condensed with benzene-1,2-diamine (o-phenylenediamine, OPDA) to form its highly fluorescent quinoxaline derivative, 3-(1,2-dihydroxyethyl)furo[3,4-b]quinoxaline-1-one (DFQ), which is then separated on a C(18) column eluted with a mobile phase of 80 mM phosphate buffer and methanol at pH=7.8 and detected fluorometrically at lambda(ex)=355 nm and lambda(em)=425 nm. The reaction conditions for the complete conversion of AA to DFQ were 56 degrees C, 36 min and a mumol AAPH/AA ratio of 60. The sample, extracted with an aqueous metaphosphoric acid solution, was analyzed after being filtered through a 0.45 microm membrane. The method has shown good repeatability, sensitivity and accuracy compared to the results obtained with the reference method. The response of the detection system was linear within a range of 0.5-8.0 microg/mL with a correlation coefficient of 0.9997. The limit of detection was 0.27 microg/mL and the limit of quantification was 0.83 microg/mL. The AA contents of some selected foods were analyzed.     

新型环烷烯并嘧啶并噻唑-3-酮类化合物的合成

以环戊酮、环庚酮为起始原料合成的环烷烯并[1,2-d]嘧啶-2-硫酮(2)与氯乙酸、芳香醛反应, 合成具有潜在抗癌活性的稠合杂环化合物5-芳基-2,8-二芳亚甲基-2,3,6,7-四氢-5H,8H-环戊烯并[1,2-d]噻唑并[3,2-a]嘧啶-3-酮(3)以及5-芳基-2,10-二芳亚甲基-2,3,6,7,8,9-六氢-5H,10H-环庚烯并[1,2-d]噻唑并[3,2-a]嘧啶-3-酮(4). 3和4的结构经¹H NMR, IR, MS分析确认.     

Synthesis of Fluoroalkylated Heterocycles via the Reaction of 3-(1-Hydropolyfluoroalkenyl)-1-oxo-2,4,1-benzoxazines with Dinucleophilic Reagents

The reaction of 3-(1-hydropolyfluoroalkenyl)-1-oxo-2,4,1-benzoxazines 1 with some dinucleophiles was inves-tigated.7-Fluoroalkyl-2,3-dihydro-1,4-diazepine[1,2-d]quinazolin-11-ones 2,2-fluoroalkylisoxazolo[3,2-b]quin-azolin-9-ones 3 and 2-fluoroalkylbenzoimidazoles 4 were obtained from the reaction of 1 with 1,2-diaminoethane,hydroxylamine hydrochloride and 1,2-diaminobenzene respectively.     

荧光动力学法测定唾液中痕量硫氰根

人体内的SCN-主要分布于人体体液及代谢物中,如唾液、血浆、尿液等。其来源主要有两种途径:一是烟草中氰化物的代谢产物,人体内硫氰酸盐的含量是区别吸烟者和不吸烟者的重要标志[1,2];二是某些食物的代谢产物,如卷心菜等。硫氰酸盐可作为药物用于治疗甲状腺疾病,但体液中SCN-含     

Capillary electrophoretic separation between Fe(II) and Ni(II) precomplexed with 1,10-phenanthroline in a high concentration buffer of n-butyric acid/ n-butyrate and its application

The capillary electrophoretic separation was accomplished for Fe(II) and Ni(II) precomplexed with 1,10-phenanthroline (phen) in 2 M n-butyric acid/ n-butyrate buffer at pH 4.5 with direct UV detection at 260 nm. The applied voltage was 5 kV. The high concentration buffer of the n-butyrate resulted in a similar separation mechanism to that of ion-pair reversed-phase high-performance liquid chromatography. The separation would be due to the hydrophobic interaction between the ionic associates, [Fe(phen)(3)]( n-butyrate)(+) and [Ni(phen)(3)]( n-butyrate)(+), with the n-butyrate ion and n-butyric acid as background electrolyte. Linear calibration ranges were obtained for Fe(II) and Ni(II) from 100 to 500 ng ml(-1). The relative standard deviations ( n=10) for 3 g mL(-1) Fe(II) and Ni(II) were 0.090 and 0.086, respectively. Detection limits ( S/ N=3) for Fe(II) and Ni(II) were 20 ng mL(-1). The method was applied to the determination of nickel in aluminium and duralumin alloys.     

Synthesis and reactivity of 2-(benzothiazol-2-yl)-1-bromo-1,2-ethanedione-1-arylhydrazones

The novel, highly versatile 2-(benzothiazol-2-yl)-1-bromo-1,2-ethanedione-1-arylhydrazones 3 were prepared and their behavior toward some nucleophiles was investigated. Thus, reaction of 3 with the sodium salt of malononitrile afforded the aminopyrazolecarbonitriles 5 that undergo cyclocondensation with hydrazine, formic acid, and formamide to give the corresponding pyrazolo[3,4-d]pyridazine 6, pyrazolo[3,4-d]pyrimidinone 7, and pyrazolo[3,4-d]pyrimidine 8 derivatives, respectively. Similarly, reactions of 3 with each of acetylacetone, dibenzoylmethane, and benzoylacetonitrile afforded the corresponding pyrazole derivatives 9, 10, and 11, respectively. The latter products undergo cyclocondensation with hydrazine to afford the corresponding pyrazolo[3,4-d]pyridazines 12, 13, and 14, respectively. © 1997 John Wiley & Sons, Inc.     

Triazolobenzodiazepine Derivative (III): Synthesis of s-Triazolo-[4,3-a]-benzimidazolo-[1,2-d][1,4]-benzodiazepines

A 7H-benzimidazolo-[1,2-d] [1,4]-benzodiazepin-6(5H)-one was isolated in high yield from a condensation reaction of 2-(o-aminophenyl)benzimidazole with bromoacetyl bromide. The reactivity of 7H-benzimidazolo-[1,2-d] [1,4]-benzodiazepin-6(5H)-one have been studied.     

Investigations in the imidazole series

2,3-Dihydro derivatives of naphth[1,2-d]imidazo[3,2-b]imidazole were synthesized by the reaction of 2-chloro-3-(-haloalkyl)naphth[1,2-d]imidazole with ammonia and primary amines and by the reaction of 2-chloro-3-(-hydroxyaIkyl)naphth[1,2-d]imidazole with ammonia and amines with subsequent cyclization of the resulting 2-amino(alkylamino, arylamino)-3-(-hydroxyalkyl)naphth[1,2-d]imidazoles under the influence of thionyl chloride or phosphorus oxychloride. Dihydro derivatives of the condensed naphth[1,2-d]imidazo[3,2-b]imidazole system have not been described in the literature.See [1] for communication LX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1125–1127, August, 1971.