The accelerated preparation of 1,4-dihydropyridines using microflow reactors

The synthesis of 1,4-dihydropyridines was performed in a continuous-flow microreactor. Elevated temperatures accelerated the reaction rate significantly allowing the reaction to be finished in minutes (6–11 min). Different 1,4-dihydropyridines were prepared in good to excellent isolated yields (45–88% yield). The method was amenable to the preparation of daropidine, a calcium channel blocker which is currently in clinical phase 3 trials.     

A round robin exercise in archaeometry: analysis of a blind sample reproducing a seventeenth century pharmaceutical ointment

Chemical analysis of ancient residues of pharmaceutical or cosmetic preparations such as balms or ointments is made problematic by the high complexity of these mixtures, composed of organic and inorganic materials. Consequently, a multi-analytical approach and special caution in the interpretation of the results are necessary. In order to contribute to the improvement of analytical strategies for the characterization of complex residues and to reconstruct ancient medical practices, a replica of a pharmaceutical formulation of the seventeenth century was prepared in the laboratory according to a historically documented recipe. In a round robin exercise, a portion of the preparation was analysed as a blind sample by 11 laboratories using various analytical techniques. These included spectroscopic, chromatographic and mass spectrometric methods. None of the laboratories was able to completely reconstruct the complex formulation, but each of them gave partial positive results. The round robin exercise has demonstrated that the application of a multi-analytical approach can permit a complete and reliable reconstruction of the composition. Finally, on the basis of the results, an analytical protocol for the study of residues of ancient medical and pharmaceutical preparations has been outlined.     

A multi-analytical approach for the characterization of powders from the Pompeii archaeological site

Nine black powders found in Pompeii houses in three different types of bronze vessels (cylindrical theca atramentaria, unguentaries, and aryballoi) were characterized in order to assess a correspondence between the composition and the type of vessel and, possibly, to verify if these powders were inks or not. For the compositional characterization, a multi-analytical approach was adopted, which involved the use of scanning electron microscopy-energy dispersive X-ray, Fourier-transformed infrared spectroscopy, Raman, X-ray diffraction, electron paramagnetic resonance spectroscopy, thermogravimetric analysis, gas chromatography coupled with mass spectrometry (GC/MS), and pyrolysis GC/MS. Powders contained in cylindrical theca atramentaria form a homogeneous group, and their organic and inorganic compositions suggest that they were writing inks, while powders contained in unguentaries and aryballoi could have had several different uses, including writing inks and cosmetics. Furthermore, the composition profile of the powders found in cylindrical cases shows that, at 79?AD: , in Pompeii, carbon-based inks were still used for writing, and iron gall inks had not been introduced yet.     

Spectroscopic analysis of Pr<Superscript>3+</Superscript> crystal-field transitions in YAl<Subscript>3</Subscript>(BO<Subscript>3</Subscript>)<Subscript>4</Subscript>

Yttrium aluminium borate single crystals, doped with 1 and 4 mol% of Pr³⁺, were analyzed in the wave number range 500–25000 cm⁻¹ and temperature range 9–300 K by means of high-resolution Fourier transform spectroscopy. In spite of the complex spectra, exhibiting broad and split lines, the energy level scheme was obtained for several excited manifolds. The careful analysis of the spectra as a function of the temperature allowed us to identify most of the sublevels of the ground manifold. The thermally induced line shift, well described by a single-phonon coupling model, could be exploited to provide information about the energy of the phonons involved. The orientation of the dielectric ellipsoid and of the dipole moments associated to a few transitions was also determined from linear dichroism measurements. The experimental data were fitted in the framework of the crystal-field theory, but the agreement was not satisfactory, as already reported for Pr³⁺ ion in other matrices. Additional discrepancies came from the dichroic spectra analysis and the line splitting, possibly associated to hyperfine interaction. Some causes which might be responsible for the difficulties encountered in the Pr³⁺ ion theoretical modelling are discussed.     

Growth and Spectroscopic Properties of Er:Yab Single Crystals

The Er-doped YAB (YAl₃(BO₃)₄) is a potential self-frequency-doubling laser material. Single crystals were grown by the top-seeded flux method. The absorption spectra of the infrared Er^3? transitions were monitored in YAB crystals in the 9–300 K temperature range by high-resolution Fourier transform spectroscopy. In the whole spectral range the energy levels and Stark components of 12 transitions were detectable. In this paper the two infrared transitions (from the ⁴I_15/2 ground state to the ⁴I_13/2 and ⁴I_11/2 levels) were analyzed in detail. The low temperature absorption spectra of Er:YAB consist of sharp lines, the number of which corresponds to the theoretical predictions. This suggests that Er^3? ions occupy one specific lattice site (yttrium positions) with negligible aggregation at the higher dopant concentrations investigated (i.e. 0.12 Fr atom/YAB mole).     

Superposition-model analysis of rare-earth doped BaY 2 F 8

The energy level schemes of four rare-earth dopants (Ce 3+ , Nd 3+ , Dy 3+ , and Er 3+ ) in BaY 2 F 8 , as determined by optical absorption spectra, were fitted with a single-ion Hamiltonian and analysed within Newman's Superposition Model for the crystal field. A unified picture for the four dopants was obtained, by assuming a distortion of the F m ligand cage around the RE site; within the framework of the Superposition Model, this distortion is found to have a marked anisotropic behaviour for heavy rare earths, while it turns into an isotropic expansion of the nearest-neighbours polyhedron for light rare earths. It is also inferred that the substituting ion may occupy an off-center position with respect to the original Y 3+ site in the crystal.     

A Series of Analogues to the AT2R Prototype Antagonist C38 Allow Fine Tuning of the Previously Reported Antagonist Binding Mode

We here report on our continued studies of ligands binding to the promising drug target angiotensin II type 2 receptor (AT₂R). Two series of compounds were synthesized and investigated. The first series explored the effects of adding small substituents to the phenyl ring of the known selective nonpeptide AT₂R antagonist C38 , generating small but significant shifts in AT₂R affinity. One compound in the first series was equipotent to C38 and showed similar kinetic solubility, and stability in both human and mouse liver microsomes. The second series was comprised of new bicyclic derivatives, amongst which one ligand exhibited a five-fold improved affinity to AT₂R as compared to C38 . The majority of the compounds in the second series, including the most potent ligand, were inferior to C38 with regard to stability in both human and mouse microsomes. In contrast to our previously reported findings, ligands with shorter carbamate alkyl chains only demonstrated slightly improved stability in microsomes. Based on data presented herein, a more adequate, tentative model of the binding modes of ligand analogues to the prototype AT₂R antagonist C38 is proposed, as deduced from docking redefined by molecular dynamic simulations.     

Synthesis of 2-(5′-substituted isoxazol-3′-yl)-4-oxo-3-thiazolidinylalkanoic acids

A series of 2-substituted 4-oxo-3-thiazolidinylalkanoic acids bearing an isoxazole nucleus in the 2-position have been prepared. None of the compounds synthesised showed antibacterial activity in vitro.     

Calculation of bound and quasi-bound energy levels of the ground state of H g H: Matrix method

Summary The bound and quasi-bound energy levels for theX ²Σ⁺ state of the H _g H molecule were calculated by sing the matrix method in the harmonic-oscillator representation. The results are in very good agreement with the experimental ones.

---

Riassunto Le energie dei livelli di legame e di quasi-legame dello statoX ²Σ⁺ dell'H _g H sono state calcolate usando il metodo matriciale nella rappresentazione dell'oscillatore aromonico. I risultati sono in ottimo accordo con quelli sperimentali.

---

Резюме Используя матричный метод в представлении гармонического осциллятора, вычисляются связанные и квази-связанные энергетические уровни для основного состояния X²Σ⁺ молекулы H _g H. Полученные результаты хорошо согласуются с экспериментальными данными.