Direct HPLC resolution of beta-aminoalcohol (tazifylline,ranolazine, sotalol) enantiomers

Summary A routine chiral analysis has been developed to control the optical purity of chiral drugs and to monitor their asymmetric synthesis. The recent advent of new chiral stationary phases for HPLC enabled us to achieve the direct resolution of chiral drugs without any derivatization. The factors affecting chiral resolution on a new alpha₁-acid glycoprotein column (EnantioPac, LKB) were assessed with three beta-aminoalcohols.     

高效液相色谱用标样——多缩乙二醇二甲基丙烯酸酯的研制

本工作对多缩乙二醇二甲基丙烯酸酯标样的制备条件进行了研究。结果表明,应用经典柱色谱及制各级高效液相色谱两步分离,能方便地从合成反应所得粗试样制取纯样品,但是合成反应所用阻聚剂(包括贮存时所用阻聚剂)需要选择易分离的化合物,例如对苯二酚。结果还表明,对于已经过经典色谱柱预分离的二缩三乙二醇二甲基丙烯酸酯试样,硅胶/含0.25%(体积比)甲醇的二氯甲烷二元溶剂,是制备级HPLC比较理想的分离体系,可高效率地制备标样。     

La matrice eau de mer et le signal du cuivre en spectrometrie d'adsorption atomique sans flamme : Partie 1: Etude de l'influence des principaux composants

(Copper signals from seawater matrices in electrothermal atomic absorption spectrometry. Part 1: study of the effects of principal inorganic ions.)The effects of the main inorganic ions of seawater (Na⁺, Mg²⁺, Ca²⁺, Cl^?, SO^2?₄), and of nitrate as modifier, on the electrothermal atomic absorption spectrometric signal of copper are studied. Sodium chloride, sulfate or nitrate, magnesium chloride or nitrate, and calcium chloride can cause serious interferences. Thermal treatment at about 700°C prevents the interference of MgCl₂ by its hydrolysis. Ashing can be done without loss of copper at higher temperatures in the presence of sulfate salts (1300°C) and nitrate salts (1200°C) than in the presence of chloride salts (1100°C). This is ascribed to the stabilising effect of oxides and sulfides. A study of the influence of two-component matrices, MCl-MNO₃ or MCl-MSO₄, on the atomization signal of copper confirms this stabilizing effect which adds to the decrease in interference connected with removal of chloride in acidic medium.     

Versatile reactions of a para-bromophenylacetylide iron(II) derivative and X-ray structure of the fluoro analogue. Synthesis of new redox-active organoiron(II) synthons

The synthesis of the new (η²-dppe)(η⁵-C₅Me₅)Fe---CC---1,3-(C₆H₄X) (m-2a/2b; X=F/Br) and (η²-dppe)(η⁵-C₅Me₅)Fe---CC---1,4-(C₆H₄I) (2c) complexes, as well as the solid-state structure of the known (η²-dppe)(η⁵-C₅Me₅)Fe---CC---1,4-(C₆H₄F) (2a) complex are described. The catalytic coupling reactions of the bromo complexes with various alkynes were next investigated. Starting from the known (η²-dppe)(η⁵-C₅Me₅)Fe---CC---1,4-(C₆H₄Br) complex (2b), the synthesis of the (η²-dppe)(η⁵-C₅Me₅)Fe---CC---1,4-(C₆H₄)---CC---H complex (6d) and of the corresponding silyl-protected precursors (η²-dppe)(η⁵-C₅Me₅)Fe---CC---1,4-(C₆H₄)CC---SiR₃ (6b/6c; R=ⁱPr/Me) are reported. By use of lithium---bromine exchange reactions on 2b, the silyl- (7a; E=Si; R=Me) and tin- (7b–7d; E=Sn; R=Me, Bu, Ph) substituted analogues (η²-dppe)(η⁵-C₅Me₅)Fe---CC---1,4-(C₆H₄)ER₃ are also isolated. The spectroscopic and electrochemical characterisations of all these new Fe(II)/Fe(III) redox-active building blocks are presented and the electronic substituent parameters for the “(η²-dppe)(η⁵-C₅Me₅)Fe---CC” group are determined by means of ¹⁹F-NMR.     

Magnetic properties on holmium iron garnet in high magnetic field. Optical absorption spectra in the infra-red region

On single crystals of holmium iron garnet (HoIG), magnetic properties have been studied in magnetic field up to 150kOe applied parallel to the main crystallographic directions in the 4.2–300K temperature range. Above 130 K, the magnetization is isotropic and linear magnetic field dependent as previously found in polycrystals and predicted by Néel's ferrimagnetic theory. Nevertheless the paramagnetic Curie temperature is much higher than the polycrystal value. Below 130K, due to the onset of the umbrella structure, the ferrite magnetization presents a non linear field variation with [111] as easy direction. The field evolutions of the anisotropy constants (K ₁ andK ₂) were calculated. Optical absorption measurements of both 5₈5I ₆ and 5I ₈5I ₇ transitions are reported and compared to the results of the literature in terms of inequivalent magnetic sites.     

Influence de l'oxygene adsorbe sur la sulfatation de l'oxyde de nickel par le dioxyde de soufre

The interactions between gaseous sulfur dioxide and nickel oxide at 250° have been investigated by means of temperature-programmed desorption (TPD) and microcalorimetric techniques. Depending on the thermal treatment of the oxide, different NiO samples were prepared containing chemisorbed oxygen species, O¹, O², O³ and O⁴, with different energies. The calorimetric data indicated that the weakly-bound species O¹ is the most reactive of the oxygen forms towards sulfur dioxide. In this case, the TPD curves (m/e=48 andm/e=32) show a new peak at 710°; this may be correlated with the desorption of a sulfur-containing compound, probably NiSO₄, created by oxidation of sulfur according to the reaction S^IVS^VI. The regeneration of the species O¹ has been studied as a function of the temperature of oxygen adsorption; the most favourable temperature for the sulfation of nickel oxide appears to be about 400°.

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Zusammenfassung Die Wechselwirkung zwischen gasförmigen Schwefeldioxid und Nickeloxid bei 250° wurde mittels temperaturprogrammierter Desorption (TPD) und mikrokalorimetrischer Techniken untersucht. Abhängig von der thermischen Behandlung der Proben wurden verschiedene, die Sauerstoffspecies O¹, O², O³ und O⁴ mit unterschiedlichen Energien enthaltenden NiO-Proben hergestellt. Die kalorimetrischen Daten weisen darauf hin, dass die schwach gebundene Species O¹ gegenüber Schwefeldioxid die reaktivste von diesen Sauerstoffarmen ist. In diesem Falle zeigt die TPD-Kurve (m/e=48 undm/e=32) einen neuen Peak bei 710°; das kann mit der Desorption einer schwefelhaltigen Verbindung, wahrscheinlich NiSO₄, erklärt werden, die durch Oxydation von Schwefel entsprechend der Reaktion S^IVS^VI gebildet wird. Die Regeneration der Species O¹ wurde in Abhängigkeit von der Temperatur der Sauerstoffadsorption untersucht; die günstigste Temperatur für die Überführung von Nickeloxid in das Sulfat scheint etwa 400° zu sein.

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- 250° . , NiO, O¹, O², O³ O⁴ . , , O¹ - . , - (/=48 32) 710°, , NiSO₄ . O¹ . , 400°.

     

New Syntheses of Retinal and Its Acyclic Analog γ‐Retinal by an Extended Aldol Reaction with a C6 Building Block That Incorporates a C5 Unit after Decarboxylation. A Formal Route to Lycopene and β‐Carotene

Since the C₁₅ β‐end‐group aldehyde 10 ((β‐ionylidene)acetaldehyde), an excellent intermediate in the syntheses of retinoids, can be synthesized in many ways from β‐ionone, and since the corresponding acyclic C₁₅ ψ‐end‐group aldehyde 5 can easily be synthesized from citral ( 1 ) (Scheme 3), we applied the C₁₅+C₅ route to the syntheses of γ‐retinal ((all‐E)‐ 8 ) (Scheme 3) and retinal ((all‐E)‐ 13 ) (Scheme 4), and therefore, by coupling (2×C₂₀→C₄₀), to the preparation of lycopene ( 14 ) and β‐carotene ( 15 ) (Scheme 5). Our new syntheses of retinal ((all‐E)‐ 13 ) and γ‐retinal ((all‐E)‐ 8 use an extended aldol reaction with a C₆ building block that incorporates a C₅ unit after decarboxylation.     

Density functional calculation of the electronic circular dichroism spectra of the transition metal complexes [M(phen)3]2+ (M = Fe, Ru, Os)

The circular dichroism spectra of the tris-bidentate metal complexes Lambda-[M(phen)3]2+, with M = Fe, Ru, Os and phen = 1,10-tris-phenanthroline, are investigated computationally, employing time-dependent density functional theory. Good agreement with experimental spectra is obtained for Ru and Os. The Lambda-[Os(phen)3]2+ spectrum is analyzed in detail. It is shown how relativistic effects red shift CD bands where the Os 5d-orbital participates to a large extent in the excitations. Further, the participation of the metal in the ligand pi --> pi exciton CD is determined to be of the order of 10%. Though solvent effects can have a noticeable effect on individual transitions and rotatory strengths, they are demonstrated to have only a very small overall effect on the resulting simulated CD spectra. For Lambda-[Fe(phen)3]2+, the results are shown to be rather sensitive to the choice of the applied hybrid and nonhybrid density functionals, and the optimized geometries based thereupon. In particular, the sign pattern of the lower-energy part (up to 33 x 10(3) cm(-1)) of the Lambda-[Fe(phen)3]2+ CD spectrum is difficult to reproduce. Some combinations of functionals and geometries yield good agreement with experiment, but no "best" approach can be devised based on the available results. Possible sources of errors in the spectrum of Lambda-[Fe(phen)3]2+ due to deficiencies in the functionals and the exchange-correlation kernels are investigated.     

Detection of DNA adducts of benzo[a]pyrene using immunoelectrophoresis with laser-induced fluorescence. Analysis of A549 cells

Detection of benzo[a]pyrene diol epoxide (BPDE)-damaged DNA in a human lung carcinoma cell line (A549) has been performed using free zone affinity capillary electrophoresis with laser-induced fluorescence (LIF). Using BPDE as a model carcinogenic compound, the speed, sensitivity and specificity of this technique was demonstrated. Under free zone conditions, an antibody bound adduct was baseline-resolved from an unbound adduct in less than 2 min. The efficiencies of separation were in excess of 6 x 10(5) and 1 x 10(6) plates per meter for the antibody-bound and unbound adducts, respectively. Separation using a low ionic strength buffer permitted the use of a high electric field (830 V/cm) without the loss of resolving power. Using LIF detection, a concentration detection limit of roughly 3 x 10(-10) M was achieved for a 90-mer oligonuleotide containing a single BDPE. The use of formamide in the incubation buffer to enhance denaturing of DNA did not affect the stability of the complex between the antibody and the adducts. Using a fluorescently labeled BPDE-modified DNA adduct probe, a competitive assay was established to determine the levels of BPDE-DNA adducts in A549 cells.     

Evaluation of a high-performance thin-layer chromatographic technique for the determination of salbutamol serum levels in clinical trials.

Salbutamol concentrations were determined by high-performance thin-layer chromatography in the sera of two sets of ten volunteers at hourly intervals for 6 h after taking one 8-mg slow-release tablet. The influence of time lapse in processing of serum samples, i.e. centrifugation, extraction and chromatography, was studied. A statistical significant instability of salbutamol in the sera of patients was found which was not present in standard drug-free serum samples spiked with salbutamol and used for construction of standard curves.