Enantiomeric analysis of rivastigmine in pharmaceuticals by cyclodextrin-modified capillary zone electrophoresis

Chiral separation method development is usually very time-consuming due to the diversity in chemical structures of pharmaceutical drug substances as well as the suitable separation conditions and the problem to choose the appropriate chiral selector. This paper shows capillary zone electrophoresis (CZE) which was developed for chiral separation of a basic compound - rivastigmine (RIV) using 30 cm × 50 μm i.d. polyacrylamide (PAA)-coated fused-silica capillary (effective length 20 cm), amine-modified phosphate buffer of pH 2.5 and sulfated-β-CD (S-β-CD) as chiral selector. Other selected native or derivatized cyclodextrins (CDs) were also tested: β-CD (5, 30 mM), carboxymethyl-β-CD (5, 30 mM), dimethyl-β-CD (15 mM), hydroxypropyl-β-CD (5, 30 mM), hydroxypropyl-α-CD (5, 30 mM) and hydroxypropyl-γ-CD (5, 30 mM). Complete enantiomeric separation of RIV was achieved at 20 kV, 18 °C and detection at 200 nm within 8 min with R.S.D. for the absolute migration time reproducibility of less than 2.1%. Rectilinear calibration range was 5.0-500.0 μM of each enantiomer (r = 0.9994-0.9995). The CZE method proposed was used for the control of chiral purity of pharmaceutically active S-RIV and for the analysis of Exelon caps preparation.     

A ring-fission/C–C bond cleavage reaction with an N-alkyl-N-methyl-N-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]amine

The reaction of N-(3,4-dichlorophenethyl)-N-methylamine (1) with 3-chloromethyl-5-phenyl-1,2,4-oxadiazole (2) was investigated. Employment of an equimolar amount of 1 and 2 in the presence of potassium carbonate led to the expected tertiary amine 3 (N-[(3,4-dichlorophenyl)ethyl]-N-methyl-N-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]amine), whereas an excess of 1 and prolonged reaction time resulted in ring fission of the oxadiazole system in 3 and finally in the formation of N′-benzoyl-N-[(3,4-dichlorophenyl)ethyl]-N-methylguanidine (4) and N,N′-bis[(3,4-dichlorophenyl)ethyl]-N,N′-dimethylmethanediamine (5). The structures of products 3–5 were determined by means of ¹H and ¹³C NMR-spectroscopy, mass spectrometry and IR-spectroscopy, for 3 (as picrate) and 4 also X-ray structure analysis was employed. A possible mechanism of the reaction pathway leading to compounds 4 and 5 is proposed.     

Synthesis of new derivatives of 4-amino-2,4-dihydro-1,2,4-triazol-3-one as potential antibacterial agents

Thirty new 2-substituted-4-amino-5-alkyl or aryl-2,4-dihydro-1,2,4-triazol-3-ones and ten 2-substituted-5-alkyl or aryl-4-(5-nitro-2-furfurylidene)amino-2,4-dihydro-1,2,4-triazol-3-ones were synthesized and characterised by their sharp melting points, elemental analysis, ir and ¹H nmr spectra. These new derivatives of 5-nitro-2-furaldehyde were screened for their antibacterial activities. Most of the compounds showed good activity against one test organism, Staphylococcus aureus. For a few compounds, C.M.I. ranged from 4 to 8 μg/ml (higher results than nitrofurantoin).     

New compounds obtained by enzymatic oxidation of phloridzin

Oxidation of phloridzin was studied in a model system in the presence of apple polyphenol oxidase. In addition to 3-hydroxy phloridzin, two major oxidation products were purified by reversed phase HPLC at the semi-preparative scale. Their structures were elucidated by UV, ESI-MSⁿ and NMR spectroscopies. The first compound was a colourless product, whose novel structure strongly differs from its precursor showing a biphenyl moiety and a propionic acid chain. The second product was an oxidised form of the first one and corresponded to a stable yellow pigment with two isomeric forms. A mechanism of formation of these products, which implied successive oxidation and nucleophilic addition steps was proposed.     

Die Gadoliniumcarbidhalogenide Gd4C2X3 (X = Cl,Br)

The Gadolinium Carbide Halides, Gd₄C₂X₃ (X = Cl, Br) The compounds Gd₄C₂X₃ (X = Cl, Br) and Tb₄C₂Br₃ have been prepared by reaction of the metals (RE), REX₃, and C in sealed Ta capsules at 1 100° and 1 300°C, respectively. Monophasic samples of Gd₄C₂Br₃ and Tb₄C₂Br₃ were obtained by reacting stoichiometric mixtures of the starting materials for five days. The needle shaped crystals are bronze-coloured and sensitive to air and moisture. Gd₄C₂X₃ crystallizes in the space group Pnma (No. 62) with lattice constants a = 1 059.6(4), b = 368.4(1), c = 1 962.7(8) pm (Gd₄C₂Cl₃), a = 1 084.4(1), b = 373.0(1), c = 2 036.1(1) pm (Gd₄C₂Br₃). According to Guinier photographs, Tb₄C₂Br₃ is isotypic (a = 1 074.3(2), b = 370.6(1), c = 2 019.4(1) pm). In the crystal structure C is octahedrally coordinated by Gd. The Gd₆ octahedra are linked via common edges to form corrugated layers. The X-anions coordinate all free edges and corners of these layers and connect them via Xⁱ? Xⁱ contacts parallel [001]. Gd₄C₂Br₃ shows metallic conductivity. The magnetic susceptibility follows at high temperatures a Curie Weiss law with an effective moment of 7.95 μ_B. At temperatures below 50 K antiferromagnetic order is observed.     

Preparation of 3-methyl-4-vinyl-1,2,5-oxadiazole and 3-methyl-4-vinyl-1,2,5-thiadiazole

Short and high yielding preparations of 3-Methyl-4-vinyl-1,2,5-oxadiazole ( 6a ) and 3-Methyl-4-vinyl-1,2,5-thiadiazole ( 6b ) are described.     

Settling of paraffin crystals in cooled middle distillate fuels

The mechanism of action of additives that control the sedimentation of paraffin crystals after their crystallization in model diesel oil has been studied by means of a new experimental approach. The chemical analysis of the crystals and detailed measurements of the sedimentation phenomenon give new insights into this complex process. Thus, the wax antisettling additives used for preventing wax crystal sedimentation adsorb at the surfaces of wax particles and provide them with enhanced colloidal stability. The settling rate is not related to the size of the crystals or the viscosity of the liquid medium, but to the ability of the additives to prevent the aggregation of wax crystals. The reported methodology makes it possible to investigate the fundamental mechanisms, but also to evaluate structure-activity relationships of the various additives used in the petroleum industry.     

Sol-gel phase transition of brucine-appended porphyrin gelator: a study by vibrational circular dichroism spectroscopy

A novel approach to study the sol-gel phase transition of a brucine–porphyrin based gelator, which uses vibrational circular dichroism (VCD) spectroscopy, is described. The gelation process leading to highly ordered chiral supramolecular assemblies was investigated in various solvents at the different temperatures and concentrations. The VCD spectra sensitively reveal the specific parts of molecule whose configuration is influenced by a sol-gel phase transition and chiral supramolecular aggregation and therefore indicate the parts of the molecule responsible for the chiral self-assembly formation. Temperature stability of the organogel studied is discussed on the basis of the VCD and IR absorption spectra. The scanning electron microscopy was used to visualize the structure of brucine–porphyrin conjugate in the gel phase.