Quantification methods of amorphous/crystalline fractions in high-energy ball milled pharmaceutical products

In this work, thermoanalytical, diffractometry, and microscopy measurements have been performed in order to characterize the effect of high energy milling on a drug active in the migraine prophylaxis and smoke cessation. We can assert that the mechanical treatment induces only a partial amorphisation of the solid phase, in particular it reduces the crystal order by producing lattice defects which propagate from the surface to the bulk crystal. For this reason, the DSC is able to detect the presence of ordered solid, while the powder X-ray diffractometry, because of its low penetration depth, does not reach the crystalline core of the particles.     

Adsorption isotherms for the system n-heptane/ethanol/HDPE

The equilibrium isotherms for the adsorption of n-heptane and ethanol on high density polyethylene (HDPE) are reported at 27–110°C and at 20–100 mmHg.

The experimental apparatus and procedures are described for three methods, namely flow, static and chromatographic.

The obtained results are discussed on the basis of the Henry law for adsorbates at low coverage on solids.     

On the Effect of the Aglycon Structure of Three Aryl β-D-Galactosides on the Yield and the Regioselectivity of the Transglycolytic Synthesis of N-Acetyllactosamine

ABSTRACT

We examined the effect as donors of three aryl β-D-galactosides (i.e. p-nitrophenyl β-D-galactopyranoside, o-nitrophenyl β-D-galactopyranoside and phenyl β-D-galacto-pyranoside) on the regioselectivity and the yield of the synthesis of N-acetyllactosamine obtained from the transglycosylation reaction catalyzed by a crude preparation of β-D-galactosidase from Bacillus circulans at 25 °C, 37 °C and 55 °C, respectively. Using p-nitrophenyl β-D-galactopyranoside the reaction results were fully regiospecific at all the temperatures considered: the maximum molar yield (74%) was obtained at an incubation temperature of 55 °C. Using o-nitrophenyl β-D-galactopyranoside as the donor the reaction was still highly regioselective and the maximum molar yield (50%) was achieved at an incubation temperature also of 55 °C. Using phenyl β-D-galactopyranoside transglycolytic products appear only at an incubation temperature of 55 °C but at very low molar yield (about 14%) and lower regioselectivity.     

Effect of metal ions in organic synthesis. Part XXXI. Synthesis of new 3-carbonyl- and 3-carboxy-1-heterocyclaminopyrroles by copper(II) chloride-catalyzed reaction of heterocyclic azoalkenes

The direct synthesis of a new class of unknown 1-heterocyclamino-3-carbonylpyrroles and 1-heterocyclamino-3-carboxypyrroles by copper(II) chloride-catalyzed reaction of heterocyclic conjugated azoalkene derivatives with β-diketones and β-ketoesters is reported.     

1,3-Cycloaddition of nitrones in ionic liquids catalyzed by Er(III): an easy access to isoxazolidines

1,3-Dipolar cycloadditions of nitrones with alkenes afforded the corresponding isoxazolidines in ionic liquids in the presence of Er(OTf)₃. The ionic liquid and the catalyst are recycled up to five times without any specific treatment or loss of activity. Extension of the procedure to the synthesis of isoxazolidinyl nucleosides has been investigated.     

Reactivity of β-aluminas with water

The reactivity with air moisture of finely divided crystals of Na β and Li⁺-containing β-aluminas is analyzed with thermogravimetric and X-ray techniques. For Na β-alumina two distinct water intake processes are evident: 1) a fast one, controlled by the elastic interactions among water molecules near the crystal boundaries; 2) a slow one, driven by water diffusion away from the boundaries. For finely divided crystals of Li β-alumina the two processes cannot be distinguished but the slow one is observable in crystals of macroscopic dimensions. The water intake is generally accompanied by an expansion of the c-axis. However, the relationship between water content and c-parameter is highly non-linear and the c-axis length at room temperature depends upon the thermal history of the sample. Our results confirm previous reports suggesting that β-aluminas absorb about one water molecule per cation of the conducting plane.     

In silico discovery of beta-secretase inhibitors

Alzheimer's disease, the most common amyloid-associated disorder, accounts for the majority of the dementia diagnosed after the age of 60. The cleavage of the beta-amyloid precursor protein is initiated by beta-secretase (BACE-1), a membrane-bound aspartic protease, which has emerged as an important but difficult protein target. Here, an in silico screening approach consisting of fragment-based docking, ligand conformational search by a genetic algorithm, and evaluation of free energy of binding was used to identify low-molecular-weight inhibitors of BACE-1. More than 300,000 small molecules were docked and about 15,000 prioritized according to a linear interaction energy model with evaluation of solvation by continuum electrostatics. Eighty-eight compounds were tested in vitro, and 10 of them showed an IC(50) value lower than 100 microM in a BACE-1 enzymatic assay. Interestingly, the 10 active compounds shared a triazine scaffold. Moreover, four of them were active in an assay with mammalian cells (EC(50) < 20 microM), indicating that they are cell-permeable. Therefore, these triazine derivatives are very promising lead candidates for BACE-1 inhibition. The discoveries of this series and two other series of nonpeptidic BACE-1 inhibitors demonstrate the usefulness of our in silico high-throughput screening approach.