Synthesis,crystal structure and magnetic properties of (acetato‐κ2O,O′)bis(5,5′‐dimethyl‐2,2′‐bipyridine‐κ2N,N′)nickel(II) perchlorate monohydrate

The title hydrated ionic complex, [Ni(CH₃COO)(C₁₂H₁₂N₂)₂]ClO₄·H₂O or [Ni(ac)(5,5′‐dmbpy)₂]ClO₄·H₂O (where 5,5′‐dmbpy is 5,5′‐dimethyl‐2,2′‐bipyridine and ac is acetate), (1), was isolated as violet crystals from the aqueous ethanolic nickel acetate–5,5′‐dmbpy–KClO₄ system. Within the complex cation, the Ni^II atom is hexacoordinated by two chelating 5,5′‐dmbpy ligands and one chelating ac ligand. The mean Ni—N and Ni—O bond lengths are 2.0628 (17) and 2.1341 (15) Å, respectively. The water solvent molecule is disordered over two partially occupied positions and links two complex cations and two perchlorate anions into hydrogen‐bonded centrosymmetric dimers, which are further connected by π–π interactions. The magnetic properties of (1) at low temperatures are governed by the action of single‐ion anisotropy, D, which arises from the reduced local symmetry of the cis‐NiO₂N₄ chromophore. The fitting of the variable‐temperature magnetic data (2–300 K) gives g_iso = 2.134 and D/hc = 3.13 cm⁻¹.     

Synthesis and polymerization reactions of cyclic imino ethers. VI. Polymers with biphenyl structure

A monomer of the AB‐type and a bifunctional comonomer of the AA‐type containing two 2‐oxazoline rings and a biphenyl structural unit were prepared from the corresponding carboxylic acids via their esterification and subsequent amidation with an aminoalcohol. The cyclization of an amide to 2‐oxazoline structure was achieved by treatment with thionyl chloride followed by liberation of the free base with sodium hydrocarbonate in an aqueous solution. The prepared monomers were used for the polyaddition polymerization of the AB‐type monomer having a 2‐oxazoline and phenol group bound on adjacent rings of the biphenyl structure in solution. The monomer of the AA‐type was used for AA+BB‐type polyaddition reactions with aliphatic dicarboxylic acids. Both types of polymerizations have been performed in melt and in solution. The structures of the polymers were determined, and the thermal properties of the polymers were evaluated. Liquid‐crystalline (LC) structures of the prepared polymers were observed by DSC measurements and optical microscopy. The polyaddition reactions of the monomers containing a 2‐oxazoline ring and a biphenyl unit represent a new efficient way for the preparation of a biphenyl unit containing poly(ether amide)s and poly(ester amide)s. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Enantiomeric purity control of <Emphasis Type="Italic">R</Emphasis>-cinacalcet in pharmaceutical product by capillary electrophoresis

The capillary zone electrophoresis method was developed for the chiral separation of R,S-cinacalcet. Cyclodextrins with different substituents were tested in both acidic and alkaline background electrolytes. The non-ionic cyclodextrin, 2-hydroxypropyl-γ-cyclodextrin, was selected as the best chiral selector. The separation was performed using a positive voltage in a phosphate buffer at pH 2.5. The analytes studied were separated within 12 min. The proposed method was applied to the analysis of tablets containing R-cinalcalcet as the active substance. The enantiopurity of R-cinacalcet in the tablets studied was confirmed. Subsequently, the analysis of tablets spiked with S-cinacalcet (chiral impurity) was also performed. The method here presented makes possible the determination of 0.1 % of S-cinacalcet in tablets. The analytical characteristics of the method, such as linearity, recovery and RSD values of the peak area and the migration time, were evaluated. The inter-day RSD values of the peak area and the migration time were lower than 3.71 % and 1.3 %, respectively.     

19F NMR Spectroscopy as a Highly Sensitive Method for the Direct Monitoring of Confined Crystallization within Nanoporous Materials

The introduction of fluorine into the structure of pharmaceuticals has been an effective strategy for tuning their pharmacodynamic properties, with more than 40 new drugs entering the market in the last 15 years. In this context, ¹⁹F NMR spectroscopy can be viewed as a useful method for investigating the host–guest chemistry of pharmaceuticals in nanosized drug‐delivery systems. Although the interest in confined crystallization, nanosized devices, and porous catalysts is gradually increasing, understanding of the complex phase behavior of organic molecules confined within nanochambers or nanoreactors is still lacking. Using ¹⁹F magic‐angle‐spinning NMR spectroscopy, we obtained detailed mechanistic insight into the crystallization of flufenamic acid (FFA) in a confined environment of mesoporous silica materials with different pore diameters (3.2–29 nm), providing direct experimental evidence for the formation of a molecular‐liquid‐like layer besides crystalline confined FFA form I.     

A high-throughput liquid chromatography-tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma

Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non-compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra-high-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one-step extraction procedure in 96-well formate for phospholipid and protein removal was used for sample pre-treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0–1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.     

Preparation of trisodium O-monoalkyl and O-monoaryl diphosphates

Trisodium O-methyl, O-butyl, O-phenyl, and O-(4-nitrophenyl) diphosphates were synthesized from sodium dimethylamido-O-(2-cyanoethyl) phosphate and O-alkyl-and O-aryl phosphoric acids. While in the previously described method, sodium hydroxide was used for the preparation of O-phenyl diphosphate, in our current work, we present an improved protocol, where sodium methoxide is used to increase the yields of O-alkyl and O-aryl diphosphates. The structures of final compounds were determined by ¹H NMR, ³¹P NMR, and IR spectroscopy. The sodium O-alkyl- and O-aryl diphosphate salts prepared by this method may be used for the study of biological activity of diphosphate analogues.     

Transport and Reaction Characteristics of Reconstructed Polyolefin Particles

The 3D spatial structure of porous polyethylene particles was reconstructed from their X‐ray micro‐tomography images. Several polyolefin particles with an artificial granular structure were generated. Transport in reconstructed particles was calculated for the case of a monomer diffusing through both the pores and the polymer. The calculated degassing characteristics of reconstructed polyolefin particles can be compared to experiments. Monomer mass transport limitations are important not only in the early stage of particle growth, but also in fully‐developed polyolefin particles. The problems and limitations of the developed method are discussed. The method developed allows prediction of the effect of particle structure on mass transport limitations for real particle structures.

     

A theoretical study of AmOn and CmOn (n = 1, 2)

Americium and curium oxides AmOn and CmOn (n = 1, 2) were studied using state-of-the-art multiconfigurational, relativistic, quantum chemical methods. Spectroscopic properties for the ground state and several excited states of the four target compounds were determined. The computed dissociation energy of AmO (4.6 eV) agrees fairly well with estimates derived from experimental studies (5.73 +/- 0.37 eV) while the computed dissociation energy of CmO (7.1 eV) agrees well with the experimental value (7.5 eV). The computed ionization energy of AmO (6.3 eV) is in good agreement with the current experimental value (5.9 +/- 0.2 eV).