Non–symmetrically p–nitrobenzyl–substituted N–heterocyclic carbene–silver(I) complexes as metallopharmaceutical agents

In the present work, a series of eight new imidazole, 4,5–dichloroimidazole, 4,5–diphenylimidazole and benzimidazole based nitro–functionalized mono–N –heterocyclic carbene (NHC)–silver(I) acetate ( 7a–d ) and bis–NHC–silver(I) hexafluorophosphate complexes ( 8a–d ) were synthesised by the reaction of the corresponding azolium hexafluorophosphate salts ( 6a–d ) with silver(I) acetate and silver(I) oxide in methanol and acetonitrile, respectively. All the synthesised compounds were fully characterized by various spectroscopic techniques and elemental analyses. Additionally, the structure of bis–(1–benzyl–3–(p –nitrobenzyl)–4,5–dichloroimidazole–2–ylidene)silver(I) hexafluorophosphate complex ( 8b ) was confirmed by single crystal X–ray diffraction analysis. Preliminary in vitro antibacterial evaluation was conducted for all the compounds ( 6a–d) , ( 7a–d) , and ( 8a–d) by Kirby–Bauer's disc diffusion method followed by the determination of Minimum Inhibitory Concentration (MIC) from broth macrodilution method against five standard bacteria; two Gram–positive bacterial strains (Staphylococcus aureus and Bacillus subtilis) and three Gram–negative bacterial strains ( Escherichia coli , Shigella sonnei, and Salmonella typhi). All the hexafluorophosphate salts ( 6a – d) were found inactive against the tested bacterial strains and their corresponding mono– and bis–NHC–silver(I) complexes ( 7a–d and 8a–d ) exhibited moderate to high antibacterial activity with MIC value in the range 8–128 μg/mL. In addition, preliminary in vitro anticancer potential of all the silver(I) complexes ( 7a–d and 8a–d ) was determined against the human derived breast adenocarcinoma cells (MCF 7) by MTT assay. All the mono– and bis–NHC–silver(I) complexes ( 7a–d and 8a–d ) orchestrated high anticancer potential with IC₅₀ values ranging from 10.39 to 59.56 nM. In comparison, mono– NHC–silver(I) complexes performed better than the bis–NHC–silver(I) complexes.     

3‐Aryl‐5‐furylpyrazolines and their biological activities

Aryl‐furyl substituted pyrazolines 2a–c and 4a–c were prepared by the reaction of α,β‐unsaturated carbonyl compounds with hydrazine or phenyl hydrazine. N‐chloroacetyl derivatives 3a–c were obtained by the N‐acetylation of 2a–c . The antibacterial activities of synthesized pyrazolines were examined by employing the disk‐diffusion technique. All synthesized compounds showed antibacterial effects in 1200 μg concentration. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:345–347, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10159     

Stereocomplex formation of isotactic poly(methyl methacrylate) with a wide variety of syndiotactic polymethacrylates

Syndiotactic (st–) polymers of methacrylates with primary and secondary ester groups, prepared by the syndiotactic-specific living polymerization with t-C₄H₉Li/R₃Al, were found to form stereocomplexes with isotactic (it–) poly(methyl methacrylate) (PMMA) by annealing in the solid state or by mixing in certain solvents such as acetone and toluene. Melting points of the complexes depend on the structure of the ester group and can be changed in a wide range of temperature. st–Polymers of tertiary esters did not form the complex. Effects of anneal conditions, molecular weight, and tacticity on the melting point of the complex were studied in some detail for the combination of st–poly(benzyl methacrylate) and it–PMMA. st–Random copolymers of MMA with several alkyl methacrylates also formed stereocomplexes with it–PMMA, whose melting point could be changed continuously by changing the composition in a certain range of temperature. st–Block copolymers of PMMA and poly(benzyl methacrylate) formed stereocomplexes with it–PMMA which showed two melting points, provided the block lengths are long enough for the two types of the com plexes to form independently. Stereoblock PMMA, it–PMMA–block–st–PMMA, and stereoblock copolymer, it–PMMA–block–st–poly(butyl methacrylate), were found to form stereocomplexes more easily than the corresponding mixtures. The stereoregular uniform PMMAs were used for elucidating the process of stereocomplex formation and its stoichiometry by means of gelpermeation chromatography (GPC). The preliminary results clearly indicated that the complexation occurs mainly in 1:1 stoichiometry in the beginning, while a small fraction of 1:2 (it–: st–) complex was also formed concomitantly. By similar GPC experiments using a series of uniform PMMAs, the minimum length of PMMA chains for the complex formation was found to be in the range of degrees of polymerization from 42 to 46.     

Development of a Special Two-Dimensional Fingerprint for the Quality Evaluation of Euonymus Alatu by HPLC with Diode Array Detector Coupled with Chemiluminescence Detection

A special two-dimensional fingerprint developed by a hyphenated method, HPLC–DAD coupled with flow injection analysis and chemiluminescence detection (HPLC–DAD–FIA–CL), was applied to evaluate the quality of Euonymus alatu. Chromatographic fingerprint and active characteristics of Euonymus alatu from different habitats were investigated by HPLC–DAD–FIA–CL method. The similarity of two-dimensional fingerprint obtained by a vectorial angle method was used to evaluate the quality of Euonymus alatu. The results suggested that the two-dimensional fingerprint could reveal more objective conclusions for the quality of Euonymus alatu, and might be helpful to improve the quality control ability of herbal medicines.     

Determination of Six Resorcylic Acid Lactones in Feed by GC–MS

A method was developed to simultaneously detect six resorcylic acid lactones in feed by GC–MS. Samples were extracted with methanol followed by a two step liquid–liquid extraction and an HLB SPE clean-up. The samples were derivatized with BSTFA + TMCS (99/1; v/v) and determined by GC–MS. For all analytes, the ranges of recoveries were 81.2–98.2%, with RSDs of 3.2–15.2%, and the LODs were 0.2–0.6 μg kg⁻¹.

     

Formation of 1,1,2,3,3-pentakis(arylthio)-1-propenes from tris(arylthio)cyclopropenyl cations and their conversion into 1,1,2,5,6,6-hexakis(arylthio)-(3E)-1,3,5-hexatriene

The reaction of tetrachlorocyclopropene (1) with arenethiols (2a–e), followed by treatmentwith perchloric acid, gave tris(arylthio)cyclopropenylium perchlorates (3a–c and e), 1,1,2,3,3-pentakis(arylthio)-1-propenes (4a–d), and 2,3,3-tris(arylthio)propenals (5a–d). The structures of tris(phenylthio)cyclopropenylium perchlorate (3a), 1,1,2,3,3-pentakis(phenylthio)-1-propene (4a), and 2,3,3-tris(o-tolylthio)propenal (5b) were analyzed by single-crystal X-ray diffraction studies. The yields depended significantly on the electron-withdrawing property of the substituents of the arenethiols and the molar ratio of 2 to 1. The reaction with 2,6-dimethylbenzenethiol (2e) gave only tris(2,6-dimethylphenylthio)cyclopropenylium perchlorate (3e) without the formation of 4e and 5e. Compounds 5a–d were produced by acid hydrolysis of 4a–d. Pyrolysis of 4a–d gave (3R,4S)-1,1,2,3,4,5,6,6-octakis(arylthio)-1,5-hexadienes (9a–d) and 1,1,2,5,6,6-hexakis(arylthio)-(3E)-1,3,5-hexatrienes (10a–d) together with diaryl disulfides (11a–d). Compound 10a was also produced by photolysis. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:387–397, 1998     

Synthesis and Reactions of Some New Thieno[2,3-C]pyridazine Derivatives

The alkylation of 4-cyano-5,6-dimethylpyridazin-3(2H)-thione 3 with some halo compounds gave the S-alkylated products 4a–c , which upon treatment with ethanolic sodium ethoxide afforded the cyclized thienopyridazines 5a–c as products. Pyridazothienotriazines 6a–c were prepared by the treatment of compounds 5a–c with nitrous acid, while their reaction with triethyl orthoformate and with carbon disulfide gave the corresponding pyrimidothienopyridazines 7a–c , and 8a–c , respectively. S-alkylated products 9a–o were obtained by the reaction of 8a–c with some halo compounds.     

Glycosylidene Carbenes. Part 14. Glycosidation of partially protected galactopyranose-, glucopyranose-, and mannopyranose-derived vicinal diols

The relation between H-bonding in diequatorial trans-1,2 and axial, equatorial cis-1,2-diols and the regioselectivity of glycosidation by the diazirine 1 was examined. H-Bonds were assigned on the basis of FT-IR and ¹H-NMR spectra (Fig. 1). Glycosidation by 1 of the gluco-configurated diequatorial trans-2,3-diols 4–7 yielded the mono-glucosylated products 16/17/20/21 (69–89%); 1,2-/1,3-linked products (37–46:63–54), 24/25/28/29 (60–63%; 1,2-/1,3-linked products 46–51:54–49), 32–35 (69–94%; 1,2-/1,3-linked products 45–52:55–48), and 36/37/40/41 (59–63%; 1,2-/1,3-linked products 52–59:48–41), respectively (Scheme 1, Table 3). The disaccharides derived from 4, 5 , and 7 were characterized as their acetates 18/19/22/23, 26/27/30/31 , and 38/39/42/43 , respectively. Glycosidation of the galacto-configurated diequatorial 2,3-diols 8 and 9 and the manno-configurated diequatorial 3,4-diol 10 by 1 (Scheme 2, Table 3) also proceeded in fair yields to give the disaccharides 44–47 (69–80%;1,2-/1,3-linked products ca. 1:1), 48–51 (51–61%;1,2/-1,3-linked products 54–56:56–54), and 56/57/60/61 (71–80%; 1,3-/1,4-linked products 49–54:51–46), respectively. The 1,3-linked disaccharides 56/57 derived from the diol 10 were characterized as the acetates 58/59 . The regio- and stereoselectivities of the glycosidation by 1 were much better for the α-D -manno-configurated axial, equatorial cis-2,3-diol 11 and the galacto-configurated axial, equatorial cis-3,4-diol 13 (1,2-/1,3-linked disaccharides ca. 3:7 for 11 and 1,3-/1,4-linked disaccharides ca. 4:1 for 13 ; Scheme 3, Table 4). The regio- and stereoselectivity for the β-D -manno-configurated cis-2,3-diol 12 were, however, rather poor (1,2-/1,3-linked products 48:52). The 1,2-linked disaccharides 66/67 derived from 12 were characterized as the acetates 70/71 . Koenigs-Knorr-type glycosidation of the cis-diols 11–13 by 2 or 3 proceeded with a similar regio- and a higher stereoselectivity (α-D > β-D with the donor 2 and α-D < β-D with the donor 3 ) than with 1 , with the exception of 12 which did not react with 2 . The regioselectivity of the glycosidations by 1 agrees fully with the H-bonding scheme of the diols and with the hypothesis that the intermediate carbene is preferentially protonated by the most weakly H-bonded OH group. The regioselectivity of the glycosidation by 2 and by 3 is determined by a higher reactivity of the equatorial OH groups and by H-bonding. Several H-bonded and equilibrating isomers of a given diol may intervene in the glycosidation by 1 , or by 2 and 3 , resulting in the same regioselectivity. The low nucleophilicity of 12 and the low degree of regioselectivity in its reaction with 3 show that stereoelectronic effects may also profoundly influence the nucleophilicity of OH groups.     

Synthesis and characterization of new poly(amide–imide)s from 1,4-bis(4-trimellitimidophenoxy)-2-tert-butylbenzene with various diamines

New poly(amide–imide)s were prepared from a diimide–dicarboxylic acid, 1,4-bis(4-trimellitimidophenoxy)-2-tert-butylbenzene ( BTTB ), with various diamines by the direct polycondensation in N-methyl-2-pyrrolidinone (NMP) using triphenyl phosphite and pyridine as condensing agents. The new diimide–dicarboxylic acid BTTB containing an ether linkage and tert-butyl substituent was synthesized by the condensation reaction of 1,4-bis(4-aminophenoxy)-2-tert-butylbenzene with trimellitic anhydride. All the polymers were obtained in quantitative yields with inherent viscosities of 0.62–1.06 dL g⁻¹. The polymers were amorphous, and most of them were readily soluble in aprotic polar solvents such as NMP, N,N-dimethylacetamide (DMAc), and N,N-dimethylformamide (DMF), as well as in less polar solvents such as dimethyl sulfoxide (DMSO), m-cresol, pyridine, and γ-butyrolactone, and also even in tetrahydrofuran. The glass transition temperatures of the polymers were determined by DSC method, and they were in the range of 238–279°C. These polymers were stable up to 408–449°C in air and 451–483°C in nitrogen and lose 10% weight in the range of 479–525°C in air and 480–528°C in nitrogen atmosphere. The polymer films had a tensile strength range of 71–115 MPa, an elongation at break range of 4–14%, and a tensile modulus range of 2.3–3.1 GPa. © 1998 John Wiley & Sons, Inc. J. Polym. Sci. A Polym. Chem. 36: 2301–2307, 1998     

SPME-GC-MS analysis of commercial henna samples (Lawsonia inermis L.)

The aim of this work was to provide a characterisation of volatile constituents from different commercial batches of henna (Lawsonia inermis) leaves of different geographic origin. Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry (GC–MS) was used for the purpose. A total of 72 components were identified by GC–MS in the headspace of different henna samples which proved to differ considerably from each other, because they were characterised by different classes of components, mainly aliphatic compounds (9.0–64.7%), terpenoids (5.8–45.5%) and aromatics (7.9–45.2%), with alkanes (0.9–18.5%), aldehydes (2.1–18.8%) and carboxylic acids (3.1–29.3%), monoterpenes (3.4–30.0%) and sesquiterpenes (0.8–23.7%) and phenyl propanoids (0.6–43.1%), being the most abundant, respectively. Major representatives of these groups were n-hexadecane (0.5–4.7%), (2E)-hexenal (0.5–11.7%) and acetic acid (2.8–24.5%), limonene (0.8–14.7%), carvol (3.8–7.1%), geranyl acetone (1.4–7.9%) and (E)-caryophyllene (3.3–8.4%), and (E)-anethole (0.6–35.0%), respectively. We assume that factors such as the manufacturing process, the storage conditions and the different geographic origin of the samples may contribute to such variability.     

Synthesis of hindered hydrazones and their reaction with thionyl chloride

Hydrazones 12a–c and ketazines 13a–c were prepared by the reaction of ketones 11a–c with hydrazine hydrate depending on the temperature and the reaction time. Some ketone (aryl)hydrazone derivatives 14a,c,e reacted with thionyl chloride to afford the chlorothiadiazoline derivatives 15a–c . Surprisingly, the chlorine atom in the latter compounds was found to undergo smooth nucleophilic substitution, and by boiling these compounds in absolute ethanol gave the corresponding ethoxythiadiazoline derivatives 16a–c . The structure of the ethoxythiadiazoline 16b was confirmed by single crystal X‐ray determination. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:223–228, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10125     

Molecular Reorientational Dynamics of the Neat Ionic Liquid 1‐Butyl‐3‐methylimidazolium Hexafluorophosphate by Measurement of 13C Nuclear Magnetic Relaxation Data

The reorientational dynamics of the ionic liquid 1butyl‐3‐methylimidazolium hexafluorophosphate ([BMIM]PF₆) were studied over a wide range of temperatures by measurement of ¹³C spin–lattice relaxation rates and NOE factors. The reorientational dynamics were evaluated by performing fits to the experimental relaxation data. Thus, the overall reorientational motion was described by a Cole–Davidson spectral density with a Vogel–Fulcher–Tammann temperature dependence of the correlation times. The reorientational motion of the butyl chain was modelled by a combination of the latter model for the overall motion with a Bloembergen–Purcell–Pound spectral density and an Arrhenius temperature dependence for the internal motion. Except for C2 in the aromatic ring, an additional reduction of the spectral density by the Lipari–Szabo model had to be employed. This reduction is a consequence of fast molecular motions before the rotational diffusion process becomes effective. The C2 atom did not exhibit this reduction, because the librational motion of the corresponding C2? H vector is severely hindered due to hydrogen bonding with the hexafluorophosphate anion. The observed dynamic features of the [BMIM]⁺ cation confirm quantum‐chemical structures obtained in a former study.     

Quorum sensing inhibitors from marine bacteria Oceanobacillus sp. XC22919

In this study, three active compounds isolated from Oceanobacillus sp. XC22919 were identified as 2-methyl-N-(2′-phenylethyl) butyramide (1), 3-methyl-N-(2′-phenylethyl)-butyramide (2) and benzyl benzoate (3), and were first reported to exhibit the apparent quorum sensing inhibitory activities against C. violaceum 026 and P. aeruginosa. Compounds 1–3 inhibited violacein production of C. violaceum 026 by 10.5–55.7, 11.2–55.7, and 27.2%–95.7%, respectively, and inhibited pyocyanin production of P. aeruginosa by 1.7–50.8, 39.1–90.7, and 57.2%–98.7%, respectively. The azocasein-degrading proteolytic rates of P. aeruginosa were observed by 13.4–31.5, 13.4–28.8, and 11.3%–21.1%, respectively. With respect to elastase, the range of inhibition of activity of compounds 1–3 was 2.1–30.3, 4.2–18.2, and 8.9%–15.7%, respectively. Compounds 1 and 3 also showed a concentration-dependent attenuation in biofilm formation, with the maximum of 50.6% inhibition, and 37.7% inhibition at 100 μg/mL, respectively.     

Preparative isolation of ganoderic acid S,ganoderic acid T and ganoderol B from Ganoderma lucidum mycelia by high‐speed counter‐current chromatography

Ganoderic acid S, ganoderic acid T and ganoderal B are the main bioactive triterpenes of Ganoderma lucidum. In this study, mycelia of G. lucidum were obtained by two‐stage fermentation and then extracted by ethanol and petroleum ether sequentially to obtain crude triterpenes. The crude sample was further purified by recycling high‐speed counter‐current chromatography with n‐hexane–ethyl acetate–methanol–water (7:12:11:5, v/v/v/v) as the optimized two‐phase solvent system. A 16.4 mg aliquot of ganoderol B with a purity of 90.4% was separated from 300 mg of the crude sample in a single run. After employing the recycling elution mode of HSCCC with n‐hexane–ethyl acetate–methanol–water (6:10:8:4.5, v/v/v/v) for five cycles, 25.7 mg ganoderic acid T and 3.7 mg ganoderic acid S with purities of 97.8 and 83.0%, respectively, were obtained. The purities of three compounds were determined by high‐performance liquid chromatography and their chemical structures were identified by NMR and MS data.     

Synthesis,Crystal Structure,and Ultraviolet–Visible Spectrum of 8–Substituted–10,10–Dimethyl–10H–pyrido[1,2–a]indolium Perchlorates–Containing Thienyl Moiety

Two novel compounds, 8–[2–(2–thienyl)vinyl]–10,10–dimethyl–10H–pyrido[1,2–a] indolium perchlorate ( 3a ) and 8–[2–(5–phenyl–2–thienyl)vinyl]–10,10–dimethyl–10H–pyrido[1,2–a]indolium perchlorate ( 3b ) were synthesized and characterized by IR, ¹H–NMR, elemental analyses, and X–ray diffraction. Crystal structural analysis suggested that either 3a or 3b exhibited good coplanarity and rings and vinyl in the target molecule could make up a large conjugated system. Ultraviolet–visible absorption analysis indicated both 3a and 3b possessed large maximum absorptions, and 3b underwent a significant redshift (43.0 nm) in comparison with 3a .     

Synthesis and characterization of novel poly(amide-imide)s containing hexafluoroisopropylidene linkage

A series of novel soluble poly(amide-imide)s were prepared from the diimide-dicarboxylic acid, 2,2-bis[N-(4-carboxyphenyl)-phthalimidyl]hexafluoropropane, with various diamines by the direct polycondensation in N-methyl-2-pyrrolidinone containing CaCl₂ using triphenyl phosphite and pyridine as condensing agents. All the polymers were obtained in quantitative yields with inherent viscosities of 0.78–1.63 dL g⁻¹. The polymers were amorphous and readily soluble in aprotic polar solvents such as N-methyl-2-pyrrolidinone, N,N-dimethylacetamide, N,N-dimethylformamide, and dimethyl sulfoxide as well as in less polar solvents such as pyridine and γ-butyrolactone, and also in tetrahydrofuran. The polymer films had tensile strength of 84–129 MPa, an elongation at break range of 6–22%, and a tensile modulus range of 2.0–2.7 GPa. The glass transition temperatures of the polymers were determined by DSC method and they were in the range of 240–282°C. These polymers were fairly stable up to a temperature around or above 400°C, and lose 10% weight in the range of 450–514°C and 440–506°C in nitrogen and air, respectively. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2629–2635, 1999     

Chromophoric macrocycles from the oxidation of bis(aminofurazanylic) ethers of 1,2-diols

A series of chromophoric azofurazan-containing macrocycles 6a–c and 7a–d were synthesized from bis(aminofurazanylic) ethers of 1,2-diols 4a–d by dibromoisocyanurate oxidation. The macrocycle closure is a result of NN bond formation. An ion-binding ability of these compounds was tested. The macrocycles were characterized by NMR, MS, IR, and UV spectroscopy. The X-ray crystal structures of the macrocycles 6a, 7c , and linear counterpart 12 are reported. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:131–145, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10226     

Synthesis and characterization of novel thermotropic liquid crystalline copoly(ester imide)s

Novel liquid crystalline copoly(ester imide)s were synthesized via polyesterification of triethyleneglycol bis(4-carboxyphenyl) ether ( 1e ), diacetoxybiphenyl, and diacids with imide moieties. The effects of composition on the changes of T_g, T_m, and T_i were examined by global TSC and DSC. Thermal gravimetric analyses (TGA) found that 4a–d and 5a–g possess higher thermal stability. Strong stir opalescence phenomenon and observations from polarized optical microscopy identified that 2b–e and 3a–d possess the typical schlieren texture of an enantiotropic nematic mesophase. The birefrigent melts of 4a–d and 5a–g, however, displayed particular liquid crystalline behavior. Copolymers with higher aromatic imide ring content ( 4a–d, 5a–g ) form a layered structure and an enantiotropic smectic mesophase in the melting state. The melt viscosity of the semetic mesophase was higher than the nematic mesophase which was observed by capillary rheometer. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1791–1803, 1998     

Synthesis of Novel Substituted Indazoles via Nucleophilic Substitution of Hydrogen (SNH)

New four‐substituted indazoles 4a–e were synthesized by regioselective nucleophilic substitution of hydrogen of N‐alkyl‐7‐nitroindazoles 2a,b with arylacetonitriles 3a–c . Compounds 4a–e were reacted with arylsulfonyl chloride in pyridine to give some new indazole linked sulfonamides with good yields. The S_NH at position C‐4 of 7‐nitroindazole with arylacetonitrile is confirmed by X‐ray diffraction analysis of compounds 4e and 6a .     

Electrical properties of polypyrrole/p‐InP structure

The polypyrrole/p‐InP structure has been fabricated by the electrochemical polymerization of the organic polypyrrole onto the p‐InP substrate. The current–voltage (I–V), capacitance–voltage (C–V), and capacitance–frequency (C–f) characteristics of the PPy/p‐InP structure have been determined at room temperature. The structure showed nonideal I–V behavior with the ideality factor and the barrier height 1.48 and 0.69 eV respectively. C–f measurements of the structure have been carried out using the Schottky capacitance spectroscopy technique and it has been seen that there is a good agreement between the experimental and theoretical values. Also, it has been seen that capacitance almost show a plateau up to a certain value of frequency, after which, the capacitance decreases. The higher values of capacitance at low frequencies were attributed to the excess capacitance resulting from the interface states in equilibrium with the p‐InP that can follow the a.c. signal. The interface state density N_ss and relaxation time τ of the structure were determined from C–f characteristics. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1572–1579, 2006