Synthesis of ruthenium(II) N-heterocyclic carbene complexes and their catalytic activities in transfer hydrogenation of ketones

Three RuCl₂(η⁶-arene, η¹-carbene) and two RuCl₂(NHC)(arene) complexes have been prepared by the reaction of bis(1,3-dialkylperhydrobenzimidazol-2-ylidene) (1) and bis(1,3-dialkyl-4-methylzimidazolin-2-ylidene) (3) with [RuCl₂(arene)]₂ in toluene and characterized by elemental analysis, ¹H NMR, ¹³C NMR and IR spectroscopy. The catalytic activities of these complexes were examined in the transfer hydrogenation of aromatic ketones using 2-propanol as hydrogen source.     

Portfolio selection in stochastic markets with exponential utility functions

We consider the optimal portfolio selection problem in a multiple period setting where the investor maximizes the expected utility of the terminal wealth in a stochastic market. The utility function has an exponential structure and the market states change according to a Markov chain. The states of the market describe the prevailing economic, financial, social and other conditions that affect the deterministic and probabilistic parameters of the model. This includes the distributions of the random asset returns as well as the utility function. The problem is solved using the dynamic programming approach to obtain the optimal solution and an explicit characterization of the optimal policy. We also discuss the stochastic structure of the wealth process under the optimal policy and determine various quantities of interest including its Fourier transform. The exponential return-risk frontier of the terminal wealth is shown to have a linear form. Special cases of multivariate normal and exponential returns are disussed together with a numerical illustration.     

Synthesis,Crystal Structure and Spectroscopic Characterization of {6-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]-2-oxo-1,3-benzothiazol-3(2<Emphasis Type="Italic">H</Emphasis>)-yl}acetic acid

Abstract  

The title compound {6-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]-2-oxo-1,3-benzothiazol-3(2H)-yl}acetic acid was prepared and characterized by elemental analyses, FT-IR, ¹H NMR spectroscopy, X-ray diffraction. A quantum-chemical calculation was performed using the CNDO method. In the title compound, C₁₈H₁₁ClN₂O₃S₂, the crystal structure is stabilized by intermolecular hydrogen bonds (C–H···O=C) to form centrosymmetric R₂² R_{2}^{2} (16) dimers and the C–H···O, O–H···N, and C–H···N interactions generating the graph set motifs R₂² R_{2}^{2} (9) and R₂² R_{2}^{2} (22).     

Determination of ivacaftor by liquid chromatography techniques in pharmaceutical formulation with interlaboratory comparison and characterization of five novel degradation products by high-performance liquid chromatography ion trap time-of-flight mass spectrometry

Cystic fibrosis is a life-threatening genetic disease that causes damage to the lungs. Ivacaftor, the first drug to target the underlying defect of the disease caused by specific mutations, improves outcomes and reduces hospitalizations. In this study, quantitative determination of ivacaftor was performed by liquid chromatography, while high-resolution mass spectrometric analyses were performed for qualitative determination. The validation studies of the developed methods were performed according to International Conference on Harmonisation Q2(R1) guideline. Ivacaftor was separated from its degradation product by using Phenomenex Kinetex C₁₈ (150 × 3 mm, 2.6 µm) column. The isocratic mobile phase for binary pump configuration was 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in acetonitrile (27:63) (v/v), pH = 2.5; the flow rate of 0.25 mL/min was used in all methods. In the degradation studies, five degradation products were identified using high-performance liquid chromatography ion trap time-of-flight mass spectrometric analyses: three of them have never been reported up to date; whereas the other two were existing in the literature and they were having Chemical Abstracts Services registry numbers since they were synthesized before for various other purposes. Also, analysis of an in-lab prepared chemical equivalent of Kalydeco^® and interlaboratory comparison were performed.     

Liquid chromatographic determination of lumacaftor in the presence of ivacaftor and identification of five novel degradation products using high-performance liquid chromatography ion trap time-of-flight mass spectrometry

Lumacaftor is a transmembrane conductance regulator potentiator drug, prescribed for the treatment of cystic fibrosis in patients who are homozygous for the F508del mutation. Quantitation of lumacaftor besides its degradation products and ivacaftor was achieved on a fused-core silica particle column packed with pentafluorophenylpropyl stationary phase (Ascentis Express F5, 2.7 μm particle size 100 mm × 4.6 mm; Supelco) using gradient elution (A: 0.1% [v/v] formic acid in water, B: 0.1% [v/v] formic acid in acetonitrile [the mobile phase pH 2.5]). A constant flow rate at 1 mL/min was applied, and the detection was realized using a photodiode array detector set at 216 nm. The pseudo tablet formulation of the lumacaftor/ivacaftor fixed-dose combination preparation, namely, Orkambi®, was prepared in vitro and used for the analytical performance validation and method application studies. In addition, five novel degradation products, four of which even have no Chemical Abstracts Services registry number, were identified using high-resolution mass spectrometry instrument, and their possible mechanisms of formation were proposed. According to current literature, this paper can be regarded as the most comprehensive liquid chromatographic study on lumacaftor determination, among its counterparts.