Spectroscopic and magnetic properties of Cu(II) complexes with selected biologically important ligands

The aim of this work was to study the spectroscopic and magnetic properties of copper(II) o-, m-, p-aminobenzoates, o-, m-, p-methoxybenzoates and o-, m- and p-nitrobenzoates. The complexes were synthesized and their compositions were evaluated by elementary analysis. The infrared and Raman spectra for Cu(II) aminobenzoates, methoxybenzoates and nitrobenzoates were recorded and assigned. The obtained data were compared with those previously published for aminobenzoic, methoxybenzoic and nitrobenzoic acids and their sodium salts. The structures of Cu(II) o-, m-, p-aminobenzoates, o-, m-, p-methoxybenzoates and o-, m- and p-nitrobenzoates as well as the change in the electronic charges distribution caused by Cu(II) complex formation were discussed.     

Synthesis and antimicrobial activity of a series of optically active quaternary ammonium salts derived from phenylalanine

We synthesized nine quaternary ammonium compounds (QUATs) starting from phenylalanine, N-alkyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromides, which were prepared as optically pure substances. Five compounds were prepared as S-enantiomers and four compounds as R-enantiomers. These compounds were evaluated by their activities against bacteria and fungi. Three microbial strains were used in the study: the gram-negative bacteria Escherichia coli, the gram-positive bacteria Staphylococcus aureus and the fungi Candida albicans. The activities were expressed as minimum bactericidal or fungicidal concentrations (MBC). The most active compounds were (2S)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide and (2R)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide, with MBC values exceeding those of commercial benzalkoniumbromide (BAB) used as standard. The relationships between structure and biological activity of the tested QUATs were quantified by the bilinear model (QSAR) and are discussed.     

Antimicrobial activity of amino acid,imidazole, and sulfonamide derivatives of pyrazolo[3,4-d]pyrimidine

Derivatives of pyrazolo[3,4-d]pyrimidine with amino acid 3a–d , imidazole 4a–d , carbonyl 6–9 , pyrazole 10 , pyrazolone 11 , and sulfonamide 12–17 moieties were synthesized. Structure of the new compounds were established by their elemental analyses and spectral data. Some of the synthesized compounds were tested in vitro for their antimicrobial activity. Compounds 4b, 12 , and 16 were almost as potent as the standard antibiotic Chloramphenicol as positive control. Also, compounds 3b, 3c, 12 , and 16 were nearly as active as Terbinafine as positive control. © 2003 Wiley Periodicals, Inc. 15:57–62, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10212     

The oxidative cyclization of n-phenyl-3-methylthiopropylamines to form N-phenyl-s-methylisothiazolidinium salts

A series of N-phenyl-3-methylthiopropylamine hydrochlorides were prepared by reacting a series of anilines with methional and sodium cyanoborohydride. These were cyclized upon oxidation by N-chloro-succinimide to the corresponding N-phenyl-S-methylisothiazolidinium derivatives which were isolated as the tetraphenylborate salts. Compounds successfully prepared included the m-methyl, p-methyl, m-methoxy, and p-methoxyphenyl derivatives.     

A Novel Synthesis of 2-Alkylthiobenzothiazoles and 2-Alkylthiobenzoxazoles

Abstract

3H-Benzothiazole-2-thione and 3H-benzoxazole-2-thione were selectively S-alkylated by use of O-alkylisoureas as the alkylating reagents. The reactions could be performed under mild reaction conditions in short reaction times, and high yields were obtained using O-primary-alkylisoureas, whereas low yields were obtained with sec- and tert-alkylisoureas.     

Spectroscopic studies on some phenylethylamine drugs: Molecular orbital calculations

The electronic absorption spectra of some phenylethylamine drugs, namely, d-pseudoepherine, l-pseudoephedrine, l-ephedrine, dl-ephedrine dl-norephedrine, phenylethylamine, methoxyphenamine, and l-noradrenaline were investigated in polar and nonpolar solvents. The observed transitions were interpreted, and the role of σ-π interaction was explored. Molecular orbital calculations were performed on representatives of the above group of compounds, namely, d-pseudoephedrine, l-ephedrine, and l-noradrenaline using the INDO procedures and adopting the best conformer of the molecule. The transition energy, band intensity, and dipole moments were calculated and corresponded satisfactorily with the experimental values.     

Synthesis of a series of diaminobenzo[f]- and diaminobenzo[h]pyrimido[4,5-b]quinolines as 5-deaza tetracyclic nonclassical antifolates

A series of diaminobenzo[f]- and diaminobenzo[h]pyrimido[4,5-b]quinolines 1–11 were designed as 5-deaza tetracyclic nonclassical, lipophilic antifolates. The compounds were designed as conformationally semi-rigid and rigid analogs of 2,4-diamino-6-phenyl- 12 and 2,4-diamino-7-phenylpyrido[2,3-d]pyrimidines 13 and 14 . The target compounds were synthesized by cyclocondensation of chlorovinyl aldehydes obtained from appropriately substituted 1- or 2-tetralone, with 2,4,6-friaminopyrimidine. Compounds 1–11 were evaluated as inhibitors of P. carinii and T. gondii dihydrofolate reductases. These pathogens cause fatal opportunistic infections in AIDS patients. In addition, the selectivity of these agents was evaluated using rat liver dihydrofolate reductase as the mammalian source. In general the benzo[f]pyrimido[4,5-b]quinolines 1–5 were more potent than the corresponding benzo[h]pyrimido[4,5-b]quinoline analogues 6–11 against P. carinii and rat liver dihydrofolate reductase and were equipotent against T. gondii dihydrofolate reductase. Compounds 6–11 were moderately selective towards T. gondii dihydrofolate reductase with IC₅₀S in the 10⁻⁷ M range. In contrast analogues 1–5 lacked selectivity against P. carinii or T. gondii dihydrofolate reductase and were, in general, potent inhibitors of rat liver dihydrofolate reductase with IC₅₀S in the 10⁻⁸ M range. Analogues 1 and 4 were evaluated against a series of tumor cell lines in vitro and were found to have moderate antitumor activity (IC50 10⁻⁶ M). The structure activity/selectivity relationships suggest that benzo[f]pyrimido analogues 1–5 with the phenyl ring substitution in the “upper” portion of the tetracyclic ring are better accommodated within the rat liver (mammalian) dihydrofolate reductase and P. carinii dihydrofolate reductase active sites compared to the benzo[h]pyrimido analogues 6–11 which have the phenyl ring substitution in the “lower” portion of the tetracyclic ring. In contrast T. gondii dihydrofolate reductase does not discriminate between the isomers and binds to both series of compounds with similar affinities.     

Isolation and Partial Characterization of Halotolerant Lactic Acid Bacteria from Two Mexican Cheeses

Isolated strains of halotolerant or halophilic lactic acid bacteria (HALAB) from Cotija and doble crema cheeses were identified and partially characterized by phenotypic and genotypic methods, and their technological abilities were studied in order to test their potential use as dairy starter components. Humidity, a_w, pH, and salt concentration of cheeses were determined. Genotypic diversity was evaluated by randomly amplified polymorphic DNA-polymerase chain reaction. Molecular identification and phylogenetic reconstructions based on 16S rRNA gene sequences were performed. Additional technological abilities such as salt tolerance, acidifying, and proteolytic and lipolytic activities were also investigated. The differences among strains reflected the biodiversity of HALAB in both types of cheeses. Lactobacillus acidipiscis, Tetragenococcus halophilus, Weissella thailandensis, and Lactobacillus pentosus from Cotija cheese, and L. acidipiscis, Enterococcus faecium, Lactobacillus plantarum, Lactobacillus farciminis, and Lactobacillus rhamnosus from doble crema cheese were identified based on 16S rRNA. Quantitative and qualitative assessments showed strains of T. halophilus and L. plantarum to be proteolytic, along with E. faecium, L. farciminis, and L. pentosus to a lesser extent. Lipolytic activity could be demonstrated in strains of E. faecium, L. pentosus, L. plantarum, and T. halophilus. Strains belonging to the species L. pentosus, L. plantarum, and E. faecium were able to acidify the milk media. This study evidences the presence of HALAB that may play a role in the ripening of cheeses.     

The synthesis,configuration, and conformation of cis- and trans-3-amino-3,4-dihydro-1-hydroxy-4-methylcarbostyrils and other configurationally related compounds

The cis- and trans-3-amino-3,4-dihydro-1-hydroxy-4-methylcarbostyrils (Ia and Ib) were synthesized by catalytic hydrogenation of erythro- and threo-α-amino-β-(o-nitrophenyl)butyric acid hydrochlorides, IIIa and IIIb, respectively, under acidic conditions. The free bases of IIIa and IIIb were catalytically hydrogenated under neutral conditions to yield the erythro- and threo-α-amino-β-(o-aminophenyl)butyric acids (VIa and VIb), which were converted by acidification to their corresponding lactams, cis- and trans-3-amino-3,4-dihydro-4-methylcarbostyrils, IIa and IIb. The erythro and threo isomers of α-amino-β-(o-nitrophenyl)-butyric acid were prepared and separated by liquid chromatography via a diastereomeric mixture of (V) of methyl α-acetamido-β-(o-nitrophenyl)butyrates. The configurations and conformational assignments of the cyclic hydroxamic acids Ia and Ib were first established by analysis of the proton nmr spectra. In turn, the configurations of the o-nitroaromatic amino acids IIIa and IIIb were assigned as well as the other structurally related compounds (VIa, VIb, IIa and IIb) derived therefrom.     

Determination of Retention Factors of s-Triazines Homologous Series in Water Using a Numerical Method Basing on Ościk's Equation

The retention factors in pure water for a homologous series of s-triazines were calculated by a numerical method basing on Ościk's equation and were correlated with log k _w values obtained by linear and parabolic extrapolation. Chromatographic data (log k _w ) were compared with the software-calculated partition coefficients in the n-octanol/water system (Alog P, IAlog P, clog P, log P _Kowin , xlog P, log P _ACD and log P _Chem.Off.) as alternative hydrophobicity indices. The effect of organic modifier (methanol and acetonitrile) and its concentration in the mobile phase used for log k _w evaluation were investigated. Very good linear correlations were found between log k _w values calculated by the numerical method and log P _ACD , log P _Chem.Off . and clog P values, independent of organic modifier type.

     

Thiomethylation of aromatic amines: efficient method for the synthesis of heterocyclic compounds

Primary aromatic amines were thiomethylated by formaldehyde and hydrogen sulfide. N-Substituted 1,3-thiazetidines, 4,5-dihydro-1,3,5-dithiazines, 3,4,5,6-tetrahydro-2H-1,3,5-thiadiazines, and 4,5-dihydro-1,3,5-oxathiazines were prepared for the first time starting from meta- and para-toluidines, meta-, para-, and ortho-anisidines, and para-xylidine. Amines characterized by higher mobility of hydrogen atoms produced previously unknown four-membered thiazetidines, whereas amines characterized by lower mobility of hydrogen atoms gave six-membered thiadiazines. The sorption properties with respect to silver were studied for the compounds, which were prepared from p-toluidine and p-anisidine.     

The synthesis of the monomethyl isomers of benzo[b]naphth[2,1-d]thiophene

All isomers of the monomethylbenzo[b]naphth[2,1-d]thiophenes were synthesized using photocyclization of 3-styrylbenzo[b]thiophenes. The 1-, 3-, 4-, and 5-methylbenzo[b]naphtho[2,1-d]thiophenes were synthesized by irradiation of the corresponding methylated 3-styrylbenzo[b]thiophenes which were prepared by the Wadsworth-Emmons reaction of diethyl benzo[b]thenylphosphonate with o-, m-, p-tolualdehyde and acetophenone. The 7-, 8-, 9- and 10-methylbenzo[b]naphtho[2,1-d]thiophenes were synthesized by decarboxylation of 7-, 8-, 9- and 10-methylbenzo[b]naphtho[2,1-d]thiophene-6-carboxylic acid with copper in quinoline. These carboxylic acids were prepared by photocyclization of the corresponding 2-(benzo[b]thiophen-3-yl)-3-phenylpropenoic acids which were prepared by the condensation of the methylated benzo[b]thiophene-3-ylacetic acids with benzaldehyde in the presence of triethylamine in acetic anhydride.     

Lipid Production by Culturing Oleaginous Yeast and Algae with Food Waste and Municipal Wastewater in an Integrated Process

Food waste and municipal wastewater are promising feedstocks for microbial lipid biofuel production, and corresponding production process is to be developed. In this study, different oleaginous yeast strains were tested to grow in hydrolyzed food waste, and growths of Cryptococcus curvatus, Yarrowia lipolytica, and Rhodotorula glutinis in this condition were at same level as in glucose culture as control. These strains were further tested to grow in municipal primary wastewater. C. curvatus and R. glutinis had higher production than Y. lipolytica in media made from primary wastewater, both with and without glucose supplemented. Finally, a process was tested to grow C. curvatus and R. glutinis in media made from food waste and municipal wastewater, and the effluents from these processes were further treated with yeast culture and phototrophic algae culture; 1.1 g/L C. curvatus and 1.5 g/L R. glutinis biomass were further produced in second-step yeast cultures, as well as 1.53 and 0.58 g/L Chlorella sorokiniana biomass in phototrophic cultures. The residual nitrogen concentrations in final effluents were 33 mg/L and 34 mg/L, respectively, and the residual phosphorus concentrations were 1.5 and 0.6 mg/L, respectively. The lipid contents in the produced biomass were from 18.7% to 28.6%.     

Metabolic profiles and pharmacokinetics of goitrin in rats through liquid chromatography combined with electrospray ionization–tandem mass spectrometry

Several chemical and biological studies have revealed R,S‐goitrin as the main bioactive constituent of Isatis indigotica Fort., responsible for antiviral antiendotoxin activity; however, few pharmacokinetic studies have been conducted. To comprehend the kinetics of R,S‐goitrin and promote its curative application, a rapid and sensitive UHPLC–MS/MS method was developed. The selected reaction monitoring transitions were m/z 130.0 → 70.0 for R,S‐goitrin and m/z 181.1 → 124.0 for the internal standard in a positive‐ion mode. The established UHPLC–MS/MS method achieved good linearity for R,S‐goitrin at 10–2000 ng/mL. The intra‐ and interday accuracy levels were within ±9.7%, whereas the intraday and interday precision levels were <11.3%. The extraction recovery, stability and matrix effect were within acceptable limits. The validated method was successfully applied for the pharmacokinetic analysis of R,S‐goitrin in rats after oral administration. Moreover, a total of six metabolites were structurally identified through UHPLC–Q/TOF–MS. The proposed metabolic pathways of R,S‐goitrin in rats involve demethylation, acetylation, glutathionylation and oxygenation.     

The preparation of N-(1H-pyrazol-3-yl)arylamides and 1H-pyrazol-3-amines from polylithiated C(α),N-thiosemicarbazones and C(α),N-semicarbazones

C(α),N-Thiosemicarbazones or C(α),N-semicarbazones were polylithiated with excess lithium diiso-propylamide, and the resulting cyclized intermediates were condensed with aromatic esters to afford N-(1H-pyrazol-3-yl)arylamides. The polylithiated intermediates were also quenched with aqueous acid to give 5-substituted, 1H-pyrazol-3-amines.     

Homo‐ and Copolymerization of Styrene and Alkylstyrenes with the Highly Active Catalyst System CpTiF3/MAO

Syndiotactic copolymers with p‐methylstyrene, p‐tert‐butylstyrene and α‐methylstyrene were obtained using fluorinated half‐sandwich catalyst systems. In the presence of p‐alkylstyrenes the activities were high. The incorporation of p‐alkylstyrenes is nearly as good as it is for styrene. Molar masses increase using p‐alkylstyrene comonomers. The steric hindrance of the α‐methyl group in α‐methylstyrene results in low activities and poor incorporation rates. Since the melting points of the copolymers are lower than the melting point of the styrene homopolymer the products are easier to process. Crystalline p‐tert‐butylstyrene‐rich copolymers were obtained if appropriate crystallization procedures were carried out.     

Benzimidazole condensed ring systems. 7. An entry to substituted 1h,6h-2,6a,10b-triazafluoranthene-1,3,6-(2h)-triones and related systems as possible chemotherapeutic agents

The syntheses of some derivatives of three new benzimidazole condensed ring systems; namely, 1H,6H-2,6a,10b-triazafluoranthene-1,3,6(2H)-trione ( 3 ), 1H,8H,11H-12-oxa-2,3a,7b-triazabenz[e]acephenanthrylene-1,3,8,11(2H)-tetrone ( 4 ) and 1H,4H-2,5,6a,10b-tetrazafluoranthene-1,3,4,6(2H,5H)-tetrone ( 10 ) are described. Two compounds exhibited in vitro antibacterial activity. Four compounds were screened for in vitro anti-HIV activity and three compounds were evaluated for antileukemic potency but were inactive.     

Herstellung enantiomerenreiner cis- oder trans-konfigurierter 2-(tert-Butyl)-3-methylimidazolidin-4-one aus den Aminosäuren (S)-Alanin, (S)-Phenylalanin, (R)-Phenylglycin, (S)-Methionin und (S)-Valin

Preparation of the Enantiomerically Pure cis- and trans-Configurated 2-(tert-Butyl)-3-methylimidazolidin-4-ones from the Amino Acids (S)-Alanine, (S)-Phenylalanine, (R)-Phenylglycine, (S)-Methionine, and (S)-Valine In contrast to α-hydroxy and α-mercapto carboxylic acids, simple α-amino acids do not form acetal-type derivatives ( 2 , X = NH) with pivalaldehyde. For the generation of amino-acid-derived chiral, nonracemic enolates (cf. 3 ), and hence, for the α-alkylation of amino acids without racemization and without an external chiral auxiliary, the imidazolidinones 12–14 were prepared diastereoselectively. To this end, the methyl or ethyl esters of amino-acid hydrochlorides were first converted to N-methylamides of amino acids which in turn were condensed with pivalaldehyde to give (neopentylidenamino)amides ( 11 ). These Schiff bases could be cyclized either to trans-or to cis-imidazolidinones ( 12, 14 and 13 , respectively), which were obtained in enantiomerically pure form after recrystallization. The enantiomeric purities were confirmed by HPLC with chiral stationary phases or by ¹H-NMR spectroscopy in the presence of chiral shift reagents. The configurations (cis, trans) were assigned by NOE measurements on 300- or 360-MHz ¹H-NMR spectrometers.     

Synthesis and anticonvulsant activity of 3H-imidazo[4,5-c]-pyridazine, 1H-imidazo[4,5-d]pyridazine and 1H-benzimidazole analogues of 9-(2-fluorobenzyl)-6-methylamino-9H-purine

The 3H-imidazo[4,5-c]pyridazine, 1H-imidazo[4,5-d]pyridazine, and 1H-benzimidazole analogues of the potent anticonvulsant purine 9-(2-fluorobenzyl)-6-methylamino-9H-purine (1, 78U79) were synthesized and tested for anticonvulsant activity. The 3H-imidazo[4,5-c]pyridazines 8 and 9 were prepared in five stages from 3,4,5-trichloropyridazine (2) . The 1H-imidazolo[4,5-d]pyridazine 15 was synthesized in four stages from 5-[(benzyloxy)methyl]-1,5-dihydro-4H-imidazo[4,5-d] pyridazin-4-one (10a) . The benz-imidazole analogues 18 and 20 were prepared from 2,6-dinitroaniline in three stages. These compounds were one-tenth or less as active as 1 in protecting rats against maximal electroshock-induced seizures.     

Comparison of the active components of Aster tataricus from different regions and related processed products by ultra‐high performance liquid chromatography with tandem mass spectrometry

We investigated crude Aster tataricus, vinegar‐processed Aster tataricus, honey‐processed Aster tataricus, and steamed Aster tataricus as a case study and developed a comprehensive strategy integrating quantitative analysis and chemical pattern recognition methods for the evaluation and differentiation of Aster tataricus from different regions, as well as related processed products. In the study, 15 batches of raw Aster tataricus collected from seven provinces were analyzed. A sensitive and rapid ultra‐high performance liquid chromatography with tandem mass spectrometry method for simultaneous determination of 15 compounds was established to evaluate the quality of raw and processed Aster tataricus. Furthermore, multivariate statistical techniques were applied to compare the differences among Aster tataricus samples. As a result, the herbs collected from seven provinces were divided into two categories, and chlorogenic acid was the most important component distinguishing between the regions. Moreover, all of the raw and processed samples were classified by partial least squares discriminant analysis based on the 15 analyzed compounds. Results showed that raw Aster tataricus, vinegar‐processed Aster tataricus, honey‐processed Aster tataricus, and steamed Aster tataricus were clustered in four different areas. Shionone, chlorogenic acid and kaempferol were the significant constituents differentiating the raw and differently processed Aster tataricus samples.