Beiträge zur Chemie des Phosphors. 221 [1]. Stannylsubstituierte Bicyclo [1.1.0]tetraphosphane: Bildung und Eigenschaften von R3Sn(H)P4 (R  CH3, C6H5, c-C6H11, o-C7H7)

Contributions to the Chemistry of Phosphorus. 221. Stannyl-Substituted Bicyclo[1.1.0]tetraphosphanes: Formation and properties of R₃Sn(H)P₄ (R ? CH₃, C₆H₅, c-C₆H₁₁, o-C₇H₇) The unsymmetrically substituted bicyclo[1.1.0]tetraphosphanes Me₃Sn(H)P₄ ( 1 ), Ph₃Sn(H)P₄ ( 2 ), (c-Hex)₃Sn(H)P₄ ( 3 ) and (o-Tol)₃Sn(H)P₄ ( 4 ) have been obtained by reaction of a solution of (Na/K) HP₄ with R₃ SnCl (R ? Me, Ph, c-Hex, o-Tol) under proper conditions. The structure of the compounds 1 – 4 , which are only stable in solution, has been elucidated by means of ³¹P-NMR-spectroscopy. Whereas 3 exists at ?60°C as the exo,endo isomer, 1, 2 and 4 are fluctuating molecules at room temperature and probably invert between the three possible configurational isomers (exo,exo-, exo,endo- and endo,endo-form).     

Stress degradation studies and kinetic determinations of duloxetine enteric-coated pellets by HPLC

A stability-indicating HPLC assay method was developed for the quantitative determination of duloxetine (DLX) in a pharmaceutical dosage form in the presence of its degradation products, and kinetic determinations were evaluated in acid conditions and UV-C radiation exposure. Chromatographic separation was achieved by use of an ACE C18 column (250 x 4.0 mm id, 5 microm particle size). The mobile phase was prepared by mixing aqueous 50 mM potassium phosphate buffer (pH 6.0 containing 0.3% triethylamine) and acetonitrile (60 + 40, v/v). DLX was rapidly degraded in an acid medium and in the presence of hydrogen peroxide and UV-C radiation; it was more stable in alkaline medium. The described method was linear over a range of 4.0-14.0 microg/mL for determination of DLX (r = 0.9998). The precision was demonstrated by the RSD of intraday (0.79-1.07%) and interday (0.85%) studies. The mean recovery was found to be 100.56%. The acid degradation of DLX in 0.1 M HCI solution showed an apparent zero-order kinetics (k = 0.177 microg/mL/min), and the photodegradation demonstrated an apparent first-order kinetics (k = 0.082 microg/mL/min). The developed method was found to be simple, specific, robust, linear, precise, and accurate for the determination of DLX in enteric-coated pellets.     

Development and validation of capillary zone electrophoresis and high-performance liquid chromatography methods for the determination of oral anticoagulant edoxaban in pharmaceutical tablets

The incidence of thrombotic complications in SARS-CoV-2 infections has become a global concern; thus, anticoagulants are an integral part of the treatment. Edoxaban (EDX) is an oral anticoagulant suitable for pharmacologic thromboprophylaxis. Herein, two novel analytical methods for EDX determination in tablets are developed and validated using capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC). Operating conditions such as the electrolyte's concentration and pH value, injection time, volume, and the capillary temperature, were optimized. The methods were successfully validated by establishing the linearity, intra- and inter-day precisions (relative standard deviation [%]), accuracy, and robustness. Adequate separation of excipients and degradation products of EDX generated by stress degradation conditions demonstrated the stability-indicating capability of the methods. The analytical procedures were linear in the range of 25–125 µg/ml (r > 0.999), with the limits of detection and quantification of 3.26 and 10.87 µg/ml for CZE and 0.740 and 2.78 µg/ml for HPLC. Although both methodologies are suitable for determining EDX in tablets, CZE provides a greener alternative due to low-cost analysis using less organic solvents and minimizing waste generation.     

Beiträge zur Chemie des Phosphors. 227. HP4º als Komplexligand: Bildung und Eigenschaften von [(η5-C5H5)2ZrCl(P4H)], [(η5-C5Me5)2ZrCl(P4H)] und [(η5-C5H5)3Zr(P4H)]

Contributions to the Chemistry of Phosphorus. 227. HP₄º as a Complex Ligand: Formation and Properties of [(η⁵-C₅H₅)₂ZrCl(P₄H)], [(η⁵-C₅Me₅)₂ZrCl(P₄H)], and [(η⁵-C₅H₅)₃Zr(P₄H)] The novel complexes [(η⁵-C₅H₅)₂ZrCl(P₄H)] ( 1 ), [(η⁵-C₅Me₅)₂ZrCl(P₄H)] ( 2 ), and [(η⁵-C₅H₅)₃Zr(P₄H)] ( 3 ) have been obtained by reaction of a solution of (Na/K)HP₄ with the zirconocen derivatives [(η⁵-C₅H₅)₂ZrCl₂], [(η⁵-C₅Me₅)₂ZrCl₂], and [(η⁵-C₅H₅)₃(η¹-C₅ H₅)Zr] under suitable conditions. The structure of the compounds 1 – 3 , which are only stable in solution, has been elucidated by means of ³¹P-NMR spectroscopy. It is highly probable that the exo,endo isomer exists in each case. In addition, further isomers of lower relative abundancies have been observed, in which the ligands presumably exhibit a different spatial orientation relatively to each other.     

Intrinsic metrics for non-local symmetric Dirichlet forms and applications to spectral theory

We present a study of what may be called an intrinsic metric for a general regular Dirichlet form. For such forms we then prove a Rademacher type theorem. For strongly local forms we show existence of a maximal intrinsic metric (under a weak continuity condition) and for Dirichlet forms with an absolutely continuous jump kernel we characterize intrinsic metrics by bounds on certain integrals. We then turn to applications on spectral theory and provide for (measure perturbation of) general regular Dirichlet forms an Allegretto–Piepenbrink type theorem, which is based on a ground state transform, and a Shnol' type theorem. Our setting includes Laplacian on manifolds, on graphs and α-stable processes.     

Steady vortical flow around a finite plate

An explicit solution for a layer of fluid with constant vorticitysurrounding a thin plate of finite length is obtained usingelementary conformal mapping methods. In the limit of largeplate length the behaviour of the solution near the ends ofthe plate tends to that of the previously known solution fora semi-infinite plate. Contour dynamics is used to investigatethe stability of the steady solutions.     

Penetration by water of polyhydroxy amphiphiles in the crystalline versus the liquid crystalline states

The penetration of water in contact preparations with polyhydroxy amphiphiles in different aggregation states is compared. The onset of penetration is found at much higher temperatures when the samples are in the solid state than when they are in a super-cooled liquid-crystalline state in the case of the smectic A_d and smectic B₂phases, but not the columnar hexagonal (D_hd) mesophase. The enhanced accessibility of the bilayer smectic phases can be explained by assuming that the molecular arrangement in the layers is similar to that found in the lamellar lyotropic phase, where the polar groups are on the outside and the (partially intercalated) alkyl chains are in the core of the layers.     

Oxidation of p-aminophenols and formal radical cyclization onto benzene rings: formation of benzo-fused nitrogen heterocycles

p-Iodophenol and its O-MOM-protected ether can be converted into iodoamines 2. These give cross-conjugated ketones 3 on oxidation with hypervalent iodides in the presence of methanol, and the ketones undergo radical cyclization. Exposure of the products to acid or sequential treatment with a Grignard reagent and acid effects rearomatization to produce benzo-fused nitrogen heterocycles 4.     

Optimal strategies for virtual screening of induced-fit and flexible target in the 2015 D3R Grand Challenge

Induced fit or protein flexibility can make a given structure less useful for docking and/or scoring. The 2015 Drug Design Data Resource (D3R) Grand Challenge provided a unique opportunity to prospectively test optimal strategies for virtual screening in these type of targets: heat shock protein 90 (HSP90), a protein with multiple ligand-induced binding modes; and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), a kinase with a large flexible pocket. Using previously known co-crystal structures, we tested predictions from methods that keep the receptor structure fixed and used (a) multiple receptor/ligand co-crystals as binding templates for minimization or docking (“close”), (b) methods that align or dock to a single receptor (“cross”), and (c) a hybrid approach that chose from multiple bound ligands as initial templates for minimization to a single receptor (“min-cross”). Pose prediction using our “close” models resulted in average ligand RMSDs of 0.32 and 1.6 Å for HSP90 and MAP4K4, respectively, the most accurate models of the community-wide challenge. On the other hand, affinity ranking using our “cross” methods performed well overall despite the fact that a fixed receptor cannot model ligand-induced structural changes,. In addition, “close” methods that leverage the co-crystals of the different binding modes of HSP90 also predicted the best affinity ranking. Our studies suggest that analysis of changes on the receptor structure upon ligand binding can help select an optimal virtual screening strategy.