Sensitive determination of verticine and verticinone in Bulbus Fritillariae by ionic liquid assisted capillary electrophoresis-electrochemiluminescence system

CE/Ru(bpy)₃²⁺ electrochemiluminescence (ECL) system with the assistance of ionic liquids (ILs) was successfully established for sensitive determination of verticine and verticinone in Bulbus Fritillariae for the first time. Migration behavior of alkaloid largely relies on the hydrogen bonding interactions between alkyl imidazolium cations in ILs and the alkaloids. Running buffer containing 40 mmol/L 1-butyl-3-methylimidazolium tetrafluoroborate (BMImBF₄) IL-8 mmol/L phosphate resulted in significant changes in separation selectivity for alkaloids with similar structures. The highest sensitivity of the detection was obtained by maintaining the detection potential at 1.2 V. Under the optimized conditions, relative standard derivations of the ECL intensity and the migration time were 3.27 and 2.84% for verticine and 4.42 and 1.69% for verticinone, respectively. The standard curves were linear between 1 × 10⁻⁸ and 1 × 10⁻⁶ mol/L for verticine and between 5 × 10⁻⁸ and 1 × 10⁻⁶ mol/L for verticinone, respectively. Detection limits of 1.25 × 10⁻¹⁰ mol/L for verticine and 1 × 10⁻¹⁰ mol/L for verticinone were obtained (S/N = 3). Developed method was successfully applied to determine the amounts of alkaloids in Bulbus Fritillariae.     

Excess enthalpies of alkane-1-amines {CnH2n+1NH2, n = 3-8} + methyl methylthiomethyl sulfoxide and +dimethyl sulfoxide at 298.15 K

Excess enthalpies of binary mixtures between each of alkane-1-amines {C_nH_2n+1NH₂, n=3-8} and methyl methylthiomethyl sulfoxide (MMTSO) or dimethyl sulfoxide (DMSO) have been determined at 298.15 K. All mixtures showed positive enthalpy changes over the whole range of mole fractions.The limiting excess partial molar enthalpies of the aliphatic amines, H₁^E,∞, of all the mixtures with MMTSO or DMSO studied were smaller than those of MMTSO or DMSO, H₂^E,∞, respectively. Linear relations are obtained between limiting excess partial molar enthalpies and number of methylene groups.     

Galanthamine analogs: 6H-benzofuro[3a,3,2,-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3]benzazepine

The known cholinesterase inhibitory capability of the Amarylidaceae alkaloid galanthamine prompted preparation of analogs in which the position of the nitrogen within the azepine ring is altered. The analogs 6H-benzofuro[3a,3,2-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3]benzazepine were prepared in 19 and 2.5%, respectively, following Kametani and Shimizu approaches, respectively. The aniline derivative 6H-benzofuro[3a,3,2-e,f][1]benzazepine failed to undergo most of the reactions typical for galanthamine. Thus, it neither oxidized to the analogous narwedine, nor epimerized to the analogous epigalanthamine, nor reduced to the lycoramine analog, under the conditions used for galanthamine.     

Application of cyclic-1,3-diketones in domino and multicomponent reactions: facile route to highly functionalized chromeno[2,3-d]pyrimidinones and diazabenzo[b]fluorenones under solvent-free conditions

A facile and efficient protocol for the synthesis of chromeno[2,3-d]pyrimidinones and diazabenzo[b]fluorenones has been developed by one-pot three-component cyclocondensation of aldehydes, cyclic-1,3-diketones and 1,3-dimethylbarbituric acid in the presence of InCl₃ or P₂O₅ under solvent-free conditions.     

Synthesis and characterization of metal substituted AlxCr1−x(acetylacetonate)3 single-source precursors for their application to MOCVD of thin films

A detailed study, involving the synthesis of a single-source precursor containing two metal ions sharing the same crystallographic site, has been undertaken to elucidate the use of such a single-source precursor in a CVD process for growing thin films of oxides comprising these two metals, ensuring a uniform composition and distribution of metal ions. The substituted complexes Cr_1−xAl_x(acac)₃, where acac = acetylacetonate, have been prepared by a co-synthesis method, and characterized using UV–Vis spectroscopy, TGA/DTA measurements, and single crystal X-ray diffraction at low temperature. All the studied compositions crystallize in the monoclinic space group P2₁/c with Z = 4 in the unit cell. It was observed that the ratio (Al:Cr) of the site occupancy for the metal ions, obtained from single crystal refinement, is in agreement with the results obtained from complexometric titrations. All the solid state structures have the metal in an octahedral environment forming six-membered chelate rings. M–O acac bond lengths and disorder in the terminal carbon have been studied in detail for these substituted metal–organic complexes. One composition among these was chosen to evaluate their suitability as a single-source precursor in a LPMOCVD process (low-pressure metal–organic chemical vapour deposition) for the deposition of a substituted binary metal oxide thin film. The resulting thin films were characterized by X-ray diffraction, scanning electron microscopy, and infrared spectroscopy.     

Simple test system for single molecule recognition force microscopy

We have established an easy-to-use test system for detecting receptor-ligand interactions on the single molecule level using atomic force microscopy (AFM). For this, avidin-biotin, probably the best characterized receptor-ligand pair, was chosen. AFM sensors were prepared containing tethered biotin molecules at sufficiently low surface concentrations appropriate for single molecule studies. A biotin tether, consisting of a 6 nm poly(ethylene glycol) (PEG) chain and a functional succinimide group at the other end, was newly synthesized and covalently coupled to amine-functionalized AFM tips. In particular, PEG₈₀₀ diamine was glutarylated, the mono-adduct NH₂-PEG-COOH was isolated by ion exchange chromatography and reacted with biotin succinimidylester to give biotin-PEG-COOH which was then activated as N-hydroxysuccinimide (NHS) ester to give the biotin-PEG-NHS conjugate which was coupled to the aminofunctionalized AFM tip. The motional freedom provided by PEG allows for free rotation of the biotin molecule on the AFM sensor and for specific binding to avidin which had been adsorbed to mica surfaces via electrostatic interactions. Specific avidin-biotin recognition events were discriminated from nonspecific tip-mica adhesion by their typical unbinding force (∼40 pN at 1.4 nN/s loading rate), unbinding length (<13 nm), the characteristic nonlinear force-distance relation of the PEG linker, and by specific block with excess of free d-biotin. The convenience of the test system allowed to evaluate, and compare, different methods and conditions of tip aminofunctionalization with respect to specific binding and nonspecific adhesion. It is concluded that this system is well suited as calibration or start-up kit for single molecule recognition force microscopy.     

Locked nucleic acid/DNA chimeric aptamer probe for tumor diagnosis with improved serum stability and extended imaging window in vivo

As promising molecular probes for in vivo tumor imaging, aptamers without modification remain problematic due to insufficient serum stability and unabiding imaging window. To address this problem, a novel locked nucleic acid (LNA)/DNA chimeric aptamer probe was developed through proper LNA incorporation and supplemented 3′-3′-thymidine (3′-3′-T) capping. TD05, a DNA aptamer against lymphoma Ramos cells, being used as the model, a series of modification strategies were designed and optimized with different positions, numbers and combinations. It was revealed that the combined use of LNA and 3′-3′-T had a synergistic effect, and with the increase of LNA substitution in stem region, the serum stability of TD05 was gradually enhanced while its affinity and specificity were perfectly maintained to Ramos cells. Particularly, TD05.6 with 7-base pair-LNA substitution exhibited the significantly elevated detection stability half-life from ∼0.5 h of TD05 to 5–6 h of TD05.6 for target cells in serum. Moreover, a much slower clearance rate in tumor-bearing mice was also observed for TD05.6, thus leading to the greatly extended tumor imaging window from <150 min of TD05 to >600 min of TD05.6. This strategy might be of great potentials to generate more aptamer probes that are stable and nuclease-resistant for tumor diagnosis in real biological systems.     

Facile generation of vicinal bromoazides from olefins using TMSN3 and TsNBr2 without any catalyst

A very rapid and efficient method has been developed for the synthesis of vicinal bromoazides directly from olefin using N,N-dibromo-p-toluenesulfonamide (TsNBr₂) without any catalyst. The reaction is extremely fast which goes into completion instantaneously to produce bromoazides. This procedure is applicable to various olefins such as cinnamates, chalcone, styrenes, and acrylate to give the corresponding 1,2-bromoazide in an excellent yield.     

The pyrochlore to ‘defect fluorite’ transition in the Y2(ZryTi1−y)2O7 system and its underlying crystal chemistry

A careful investigation of the previously reported single phase, pyrochlore structure type Y₂(Zr_yTi_1−y)₂O₇, 0?y?0.9, (YZT) solid solution has been carried out. Given the known slow rate of diffusion of cations in fluorite-related stabilized zirconia systems and the consequent difficulty in achieving equilibrium, careful attention was paid to synthesis procedures while Guinier XRD and electron diffraction were used to investigate the synthesized materials. As a consequence, a subtle but nonetheless clear two-phase region separating a pyrochlore-type solid solution field (from 0?y?∼0.54) from a “defect fluorite” type solid solution field (from ∼0.68?y?1) has been found. The underlying crystal chemistry of the system has been investigated using the bond valence sum approach. The dielectric properties have also been measured as a function of composition. The dielectric constant and dielectric loss of the lowest y compounds are potentially quite useful but deteriorate rapidly with increasing Zr content.     

一种检测CO32-比率荧光探针的合成及其在细胞成像中的应用

本文设计开发了一种以2,6-二甲酰基对甲苯酚为母体的新型荧光探针HMI,可用于高效识别EtOH-H₂O (8/2, v/v, HEPES 10 mM, pH =7.4)体系中的CO_3^2-。HMI在660 nm处显示发射带,加入CO_3^2-后,在600 nm的等吸收点激发时,原来在660 nm处的荧光淬灭,而以540 nm为中心的新发射带荧光显着增加,为比率型荧光探针。HMI对CO_3^2-表现出高选择性且具有较强的抗干扰能力。此外,荧光探针HMI对CO_3^2-荧光响应的检测限较低,可达到3.938×10^_-6 M。更具有意义的是,HMI探针对CO_3^2-的检测能够在实际水样中起到很好的应用,而且细胞成像研究表明,HMI可用于活体MCF-7细胞中CO_3^2-的成像。     

Pheromone synthesis. Part 244: Synthesis of the racemate and enantiomers of (11Z,19Z)-CH503 (3-acetoxy-11,19-octacosadien-1-ol), a new sex pheromone of male Drosophila melanogaster to show its (S)-isomer and racemate as bioactive

The enantiomers of (11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol were synthesized from the enantiomers of 3,4-epoxy-1-butanol PMB ether. Its racemate was also synthesized. Its (S)-isomer and racemate were shown to possess the same pheromone activity as CH503, a long-lived inhibitor of male courtship in Drosophila melanogaster, although the racemate was less active.     

Capillary electrophoresis procedure for the simultaneous analysis and stoichiometry determination of a drug and its counter-ion by using dual-opposite end injection and contactless conductivity detection: Application to labetalol hydrochloride

In this work, a capillary electrophoresis (CE) procedure was developed for the simultaneous determination of a pharmaceutical drug and its counter-ion, namely labetalol hydrochloride. For this purpose, an uncoated fused-silica capillary, a low conductivity background electrolyte (BGE) and a capacitively coupled contactless conductivity detector (C⁴D) were employed. This detection system is highly sensitive and enables detection of inorganic as well as organic ions unlike with direct UV detection. Moreover, to be able to simultaneously analyze the cationic drug (labetalol⁺) and its anionic counter-ion (Cl⁻) in the same electrophoretic run without the need of a coated capillary, a dual-opposite end injection was performed. In this technique, the sample is hydrodynamically injected into both ends of the capillary. This method is simple and easy to perform since the different injection steps are automated by the CE software.This novel CE-C⁴D procedure with dual-opposite end injection has been successfully validated and applied for the analysis of chloride content in an adrenergic antagonist (labetalol hydrochloride). Thus, the hereby developed method has been shown to enable fast (analysis time < 10 min), precise (repeatability of migration times < 0.7% and of corrected-peak areas < 3.3%; n = 6) and rugged analyses for the simultaneous determination of a pharmaceutical drug and its counter-ion.     

Hepatobiliary excretion and brain distribution of caffeine in rats using microdialysis

To investigate the pharmacokinetic mechanism of hepatobiliary excretion and brain distribution of caffeine, this study uses a method based on microdialysis technique and liquid chromatography that allows continuous and concurrent in vivo monitoring of extracellular caffeine in the blood, brain and bile of anesthetized rats following the administration of caffeine (3 or 10 mg/kg, i.v.) through the femoral vein. Dialysates of the blood, brain and bile were directly injected onto the liquid chromatographic system and no further clean-up procedures were required. The study design consisted of two groups of six rats in parallel: the rats of the control group received caffeine (3 or 10 mg/kg, i.v.) alone and those of the cyclosporine treated-group were injected cyclosporine (10 mg/kg, i.v.) 10 min prior to caffeine administration (3 or 10 mg/kg, i.v.). The decline of caffeine in the blood, brain striatum and bile suggested that caffeine had rapid exchange and equilibration between the peripheral compartment and the central nervous system. In addition, the results indicated that caffeine underwent hepatobiliary excretion and was distributed into brain. When cyclosporine was co-administered, the pharmacokinetic parameters were not significantly altered. The results of this study reveal that the pharmacokinetic mechanism of hepatobiliary excretion and brain distribution of caffeine might not relate to P-glycoprotein.     

A Generalized Method for the Synthesis of Carbon-Encapsulated Fe3O4 Composites and Its Application in Water Treatment

In this paper, a simple and environmentally friendly method was developed for the preparation of highly stable C@Fe₃O₄ composites with controllable morphologies using sodium alginate as the carbon source and the easily obtained α-Fe₂O₃ as the precursors. The morphologies of the as-prepared C@Fe₃O₄ composites, inherited from their corresponding precursors of α-Fe₂O₃, survived from the annealing treatments, were characterized by the field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The C@Fe₃O₄ composites resisted to oxidation, acidification and aggregation, exhibiting porous structures and ferromagnetic properties at room temperature. Moreover, the adsorption performance of the C@Fe₃O₄ composites was evaluated by absorbing MB (methylene blue) in liquid environment. Experiments indicated that the C@Fe₃O₄ composites exhibited highly enhanced adsorption capacities and efficiencies as compared with their corresponding precursors of α-Fe₂O₃. This generalized method for the synthesis of C@Fe₃O₄ composites provides promising applications for the highly efficient removal of MB from industrial effluents.     

Synthesis and properties of novel 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-triones: methodology for synthesizing cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates

Novel condensation reaction of tropone with N-substituted and N,N′-disubstitued barbituric acids in Ac₂O afforded 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (8a-f) in moderate to good yields. The ¹³C NMR spectral study of 8a-f revealed that the contribution of zwitterionic resonance structures is less important as compared with that of 8,8-dicyanoheptafulvene. The rotational barriers (ΔG^‡) around the exocyclic double bond of mono-substituted derivatives 8a-c were obtained to be 14.51-15.03 kcal mol⁻¹ by the variable temperature ¹H NMR measurements. The electrochemical properties of 8a-f were also studied by CV measurement. Upon treatment with DDQ, 8a-c underwent oxidative cyclization to give two products, 7 and 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates (11a-c·BF₄⁻ and 12a-c·BF₄⁻) in various ratios, while that of disubstituted derivatives 8d-f afforded 7,9-disubstituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (11d-f·BF₄⁻) in good yields. Similarly, preparation of known 5-(1′-oxocycloheptatrien-2′-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (14a-d) and novel derivatives 14e,f was carried out. Treatment of 14a-c with aq. HBF₄/Ac₂O afforded two kinds of novel products 11a-c·BF₄⁻ and 12a,c·BF₄⁻ in various ratios, respectively, while that of 14d-f afforded 11d-f. The product ratios of 11a-c·BF₄⁻ and 12a-c·BF₄⁻ observed in two kinds of cyclization reactions were rationalized on the basis of MO calculations of model compounds 20a and 21a. The spectroscopic and electrochemical properties of 11a-f·BF₄⁻ and 12a-c·BF₄⁻ were studied, and structural characterization of 11c·BF₄⁻ based on the X-ray crystal analysis and MO calculation was also performed.     

The Crystal Chemistry of Lithium in the Alluaudite Structure: A Study of the (Na1−xLix)CdIn2(PO4)3 Solid Solution (x=0 to 1)

Several compounds of the (Na_1−xLi_x)CdIn₂(PO₄)₃ solid solution were synthesized by a solid-state reaction in air, and pure alluaudite-like compounds were obtained for x=0.00, 0.25, and 0.50. X-ray Rietveld refinements indicate the occurrence of Cd²⁺ in the M(1) site, and of In³⁺ in the M(2) site of the alluaudite structure. This non-disordered cationic distribution is confirmed by the sharpness of the infrared absorption bands. The distribution of Na⁺ and Li⁺ on the A(1) and A(2)′ crystallographic sites cannot be accurately assessed by the Rietvled method, probably because the electronic densities involved in the Na⁺→Li⁺ substitution are very small. A comparison with the synthetic alluaudite-like compounds, (Na_1−xLi_x)MnFe₂(PO₄)₃, indicates the influence of the cations occupying the M(1) and M(2) sites on the coordination polyhedra morphologies of the A(1) and A(2)′ crystallographic sites.     

Synthesis and properties of 4,9-methanoundecafulvenes and their transformation to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones: photo-induced autorecycling oxidizing reaction toward amines

The synthesis and properties of 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-trione] derivatives 8a,b were studied. Their structural characteristics were investigated on the basis of the ¹H and ¹³C NMR and UV-vis spectra. The rotational barrier (ΔG^‡) around the exocyclic double bond of 8a was found to be 12.55 kcal mol⁻¹ by the variable temperature ¹H NMR measurement. The electrochemical properties of 8a,b were also studied by CV measurement. Furthermore, the transformation of 8a,b to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones 16a,b was accomplished by oxidative cyclization using DDQ and subsequent ring-opening and ring-closure. The structural details and chemical properties of 16a,b were clarified. Reaction of 16a with deuteride afforded C13-adduct 19 as the single product, and thus, the methano-bridge controls the nucleophilic attack to prefer endo-selectivity. The photo-induced oxidation reaction of 16a and a vinylogous compound, 3-methylcyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(3H)-dione 2a, toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 6.1-64.0 (for 16a) and 2.7-17.2 (for 2a), respectively.     

CuFe2O4 nanoparticles: a magnetically recoverable and reusable catalyst for the synthesis of 5-substituted 1H-tetrazoles

An efficient and economical protocol for the synthesis of 5-substituted 1H-tetrazoles from various nitriles and sodium azide is described using magnetically recoverable and reusable CuFe₂O₄ nanoparticles. A wide variety of aryl nitriles underwent [2+3] cycloaddition under mild reaction conditions to afford tetrazoles in good to excellent yields. The catalyst was magnetically separated and reused five times without significant loss of catalytic activity.