Warfarin Sodium Stability in Oral Formulations

Warfarin sodium is a low-dose pharmaceutical blood thinner that exists in two forms: the clathrate form and the amorphous form. In commercially available warfarin sodium oral suspension, the active pharmaceutical ingredient (API) is added in the amorphous state. This study investigates the apparent instability of the commercially available warfarin liquid oral formulation using Raman and IR spectroscopy, X-ray diffraction, differential scanning calorimetry, UV spectroscopy, and optical microscopy. Warfarin, not its sodium salt, was identified as the undissolved solid existing in the suspension. This was found to be due to the dissociation of sodium salt and the protonation of the warfarin ion in the liquid phase, which triggered the crystallization of the sparingly soluble unsalted form. The coexistence of protonated and unprotonated warfarin ions in the supernatant, as detected by Raman and UV spectroscopy, confirmed this assumption. Study of the dissolution of warfarin sodium amorphous salt and crystalline sodium clathrate in the placebo and pure water verified the results. The effect of pH and temperature on warfarin precipitation was also explored.     

Synthesis of symmetrical 1,3-diynes via homocoupling reaction of n-butyl alkynyltellurides

An ultrasound-assisted synthesis of symmetrical 1,3-diyne compounds with electron-withdrawing or -donating substituents is described and illustrated by the palladium-catalyzed homocoupling reaction of n-butyl alkynyltellurides. This procedure offers easy access to 1,3-diynes in very short reaction times, and the products are achieved in good to excellent yields.     

Computational analysis and in vivo validation of a microRNA encoded by the IBTK gene,a regulator of B-lymphocytes differentiation and survival

MicroRNAs (miRNAs) are small single-stranded RNA molecules that play an essential role in the regulation of gene expression and cell physiology. Gene rearrangements occurring in the miRNA sequence are associated with cancer. The IBTK genetic locus is located in the genomic sequence 6q14.1 that undergoes chromosomal aberration in lymphoproliferative disorders. The IBTK gene encodes the proteins IBtk-α, β and γ that regulate the B cell receptor signalling through Bruton's tyrosine kinase, which promotes B cell survival and differentiation. Pro-MirII-based analysis predicted four precursors of microRNAs (pre-miR) encoded by introns 17, 21, 26 and the 3′ un-translated region of the IBTK gene. Pre-miR-IBTK3, which was encoded by intron 26, was the effective substrate of RNase III Dicer in vitro as well as the precursor of an IBtk miRNA generated in vivo. By CLUSTALW-based analysis, pre-miR-IBTK3 homologues were found in Pan troglodytes, Pongo pygmaeus and Macaca mulatta, suggesting an evolutionary conserved function in primates.     

Automatic identification of terpenoid skeletons by feed-forward neural networks

Feed-forward neural networks (FFNNs) were used to predict the skeletal type of molecules belonging to six classes of terpenoids. A database that contains the ¹³C NMR spectra of about 5000 compounds was used to train the FFNNs. An efficient representation of the spectra was designed and the constitution of the best FFNN input vector format resorted from an heuristic approach. The latter was derived from general considerations on terpenoid structures.     

Photoluminescent behavior of SrB4O7:RE (RE=Sm and Eu) prepared by Pechini, combustion and ceramic methods

This work reports the preparation of system containing RE²⁺ ions (RE=Sm and Eu)-doped in SrB₄O₇ matrix by ceramic, Pechini and combustion methods. These compounds were prepared by reduction of RE³⁺ to RE²⁺ in air, which exhibit some different features according to the preparation method. Photoluminescent properties of these systems were investigated based on the emission and excitation spectral data. The emission spectra of SrB₄O₇:Eu²⁺ system prepared by combustion and Pechini methods are characterized by a broad band assigned to interconfigurational 4f⁶5d→4f⁷ transition, while SrB₄O₇:Sm²⁺ compound exhibit narrow emission bands arising from intraconfigurational-4f⁶ also shows ⁴G_5/2→⁶H_J′ transitions ( and ) arising from Sm³⁺ ion, transitions. SrB₄O₇:RE system prepared by combustion method presents emission bands from RE³⁺ ions as intense as that arising from RE²⁺, suggesting that the preparation route is not efficient for the reduction RE³⁺→RE²⁺ process. Emission quantum efficiency and radiative emission rates of Sm²⁺ ion are determined and discussed.     

Synthesis of 1,2,3-triazolylpyranosides through click chemistry reaction

We have developed an efficient method for the synthesis of functionalized C-glycosyl 1,2,3-triazoles through a Cu(I)-promoted azide–alkyne 1,3-dipolar cycloaddition between a TMS-protected C-alkynyl-glycoside and organic azides. The reaction was accelerated by ultrasound irradiation and the addition of a base was not necessary to obtain the 1,2,3-triazole product. Moreover, further manipulation of the products led to chiral molecules with a C-glycoside linkage.     

Synthesis of α-alkenyl-α-amino esters via addition of potassium Alkenyltrifluoroborate salts to imine in the presence of Yb(OTf)3

A simple protocol which led to an effective construction of α-alkenyl-α-amino esters was achieved under mild conditions. This transformation proceeded by Yb-catalyzed addition of alkenyltrifluoroborates across the imine double bond. A variety of functional groups could be applicable to both partners.     

Negishi cross-coupling of organotellurium compounds: synthesis of biaryls, aryl-, and diaryl acetylenes

A functional group tolerant palladium-catalyzed Negishi coupling of diaryl tellurides with organozinc has been developed. This methodology permits efficient preparation of biaryls, aryl acetylenes and diaryl acetylenes in moderate to good yields. A preliminary study to gain further insight into the reaction was performed using in situ ReactIR technology.     

Expression of AMPA and NMDA receptor subunits in the cervical spinal cord of wobbler mice

Background  

The localisation of AMPA and NMDA receptor subunits was studied in a model of degeneration of cervical spinal motoneurons, the wobbler mouse. Cervical regions from early or late symptomatic wobbler mice (4 or 12 weeks of age) were compared to lumbar tracts (unaffected) and to those of healthy mice.