Determination of CYP activity in precision-cut liver slices: whether to use intact slices or slice homogenate

Despite CYP induction in vitro in precision-cut liver slices (LS) is well documented, there are no standardised assays for determining CYP activity as a major end-point. In this paper, short-term assays with intact and homogenised LS from male and female rats were directly compared. We obtained similar results for 7-ethoxycoumarine O-deethylation (ECOD) with LS from both sexes: higher basal activities were measured in LS homogenate, whereas slightly stronger induction by BNF was found with intact LS. CYP3A-dependent basal and dexamethasone (Dex)-induced 2β-, 15β- and 6β-testosterone hydroxylation (TH) rates were higher in both intact and homogenised LS from male compared to female rats. CYP3A induction in vitro could likewise be detected in intact and homogenised LS preferentially by determining 2β- and 15β-TH, with higher induction factors observed in LS from females. 6β-TH seems to be less inducible in intact LS of males. In vivo pretreatment of liver donors with BNF and Dex did not substantially disturb the subsequent in vitro induction of ECOD and TH, respectively.     

Quadrupole versus dipole photomotors: Symmetry constraints and operating properties

The operating properties of different-type Brownian photomotors have been compared in relation to the symmetry interplay between their moving (particle/molecule) and immovable (substrate) units. As found, essentially different symmetry constraints and hence different motor behavior are characteristic of molecules if their electron density redistribution on excitation involves only odd-order or only even-order multipole moments. The two respective types of molecules give rise to dipole and quadrupole photomotors. Purely dipole photomotors can operate only on substrates with symmetric charge distribution and their ensemble with random molecular orientations undergoes equidirectional diffusion rather than directed motion. Contrary to this, purely quadrupole photomotors need substrates with antisymmetric charge distribution for directed motion to occur and they can move directionally in an ensemble. Also, quadrupole photomotors provide much smaller velocities of directed motion than their dipole counterparts (as a result of the much weaker interaction of quadrupoles than dipoles with an electric field). The generic distinctions between the two photomotor types are exemplified by donor-acceptor-substituted stilbenoids (dipole molecules) and symmetric squaraines (quadrupole molecules). The model used affords the rational design of photomotors by the selection of promising moving molecules and by the continuous wide-range tuning of charge-distribution symmetry in substrates.     

Synthesis,Structural Characterization,and Reductive Cleavage of an Oxygen-Containing Naphthyl Macrocycle

A small macrocycle comprising ether-bridged naphthyl units was prepared in a two-step synthesis. Single-crystal X-ray diffraction of two polymorphs are reported, one of which showed multiple C−H⋅⋅⋅π_naphthyl interactions of a solvent molecule in the cavity of the macrocycle. Chemical reduction led to C−O bond cleavages accompanied by a Z/E isomerization. The resulting twofold negatively charged (E)-1,2-bis(2-naphthyl)ethylene fragment was isolated as its potassium salts. Electronic characterization revealed a singlet ground state, and a marked distortion of the central ethylene unit was observed upon electron uptake.     

LC Method for Quantification of Lutein in Rat Plasma: Validation, and Application to a Pharmacokinetic Study

A reversed-phase LC method has been developed for quantitative analysis of lutein in rat plasma and applied to a study of the pharmacokinetics of lutein in rats. From a variety of compounds and solvents tested, astaxanthin was selected as the internal standard. n-Hexane was found to be the best solvent for extracting lutein from plasma. LC analysis of the extracts was performed on a C₁₈ column equipped with a guard pre-column. Linearity was good (r > 0.99) over the range 10–100 ng mL^?1. Recovery from plasma was 82.7–92.9% the intra-day and inter-day precision were always better than 3%. The limits of detection (LOD) and quantification (LOQ) were 2.5 and 8.3 ng mL^?1, respectively. The LC method was used to quantify lutein and zeaxanthin in rat plasma in a 36-h pharmacokinetic study in which experimental rats received a single oral dose of lutein (20 mg kg^?1). The results are presented.     

Synthesis, characterization, and sorption properties of amorphous titanium phosphate and silica-modified titanium phosphates

Amorphous titanium hydroxyphosphate with formula Ti(OH)(1.36)(HPO(4))(1.32).2.3H(2)O and a new silica-modified titanium hydroxyphosphate with a general formula Ti(OH)(2x)(HPO(4))(2-x).ySiO(2).nH(2)O are synthesized and characterized using IR, TG, XRD, SEM, solid-state NMR, and BET techniques. It is concluded that SiO(2) is evenly distributed within the titanium phosphate (TiP) agglomerates and that neither the separate silica phase nor the titanium silicates are formed during the synthesis of silica-modified titanium hydroxyphosphate. Correlations between the texture, ion-exchange properties of the amorphous titanium hydroxyphosphate, and the amount of SiO(2) present within the TiP matrix are established. Sorption properties of silica-modified titanium hydroxyphosphate toward Cs(+) and Sr(2+) are studied in a series of samples with an increasing amount of silica, at different pH, and in NaCl solutions with a varying ionic strength. It is found that sorption of Cs(+) does not depend practically on the amount of SiO(2) present, whereas the Sr(2+) uptake drastically decreases with an increase of silica amount. The effects of pH and of the electrolyte concentration on the sorption behavior of titanium phosphate are discussed in terms of ionic hydration shell and titanium phosphate structural specificity. The kinetics of sorption processes is also investigated, and the diffusion coefficients for cesium and strontium are obtained.     

Pulsed flow modulation comprehensive two-dimensional gas chromatography

Pulsed flow modulation (PFM) is based on higher flow rate time compression of the first GC column effluent, which prior to the injection into the second column is stored for a few seconds in a standard fused silica wide bore transfer line. We constructed the PFM device with two standard 1/16 in. brass compression fittings with the insertion of the two columns inside the wide bore 0.53 mm i.d. fused silica storage transfer line for the elimination of dead volumes. This simple arrangement provides a combination of flexibility in the length of the sample storage transfer line hence comprehensive two-dimensional gas chromatography (GC x GC) cycle time, inert sample path and full elimination of cooling gas consumption. A record short second column injection time of 20 ms is demonstrated. Practical injection times are the sample collection time (such as 4s) divided by the second to first column flow rate ratio (such as 20/0.7), which is typically around 150 ms. Due to the low cost of the device it can also be considered for use with non comprehensive time segmented GC x GC to remove a few accidental coelutions. PFM-GCxGC excels with high second column capacity due to the use of 0.32 mm i.d. columns with high flow rates as the second dimension GC x GC column. As a result, PFM-GCxGC can have up to two orders of magnitude higher second column sample capacity and linear dynamic range for improved reduction of adverse matrix interference effects due to column overloading.     

Hexafluorosilicates of bis(carboxypyridinium) and bis(2-carboxyquinolinium)

The preparation and characterization of three isomeric carboxypyridinium and carboxyquinolinium hexafluorosilicate salts is described. The salts of the general formulas (LH)₂[SiF₆] (I-III, L = 2-carboxypyridine, 3-carboxypyridine, 4-carboxypyridine) and (LH)₂[SiF₆]·2H₂O (IV, L = 2-carboxyquinoline) were prepared from the protonation reaction of the corresponding pyridine carbonic acid by the fluorosilicic acid. The compounds were characterized by IR, mass-spectrometry, thermogravimetric analysis, solubility data, and in the case of III by X-ray crystallography. The relationship between the salts solubility and the H-bonding system was analysed.     

Synthesis of N-substituted indole-3-carboxylic acid derivatives via Cu(I)-catalyzed intramolecular amination of aryl bromides

A variety of N-alkylated and N-arylated derivatives of methyl 1 H-indole-3-carboxylate were synthesized efficiently via Ullmann-type intramolecular arylamination, using the CuI-K 3PO 4-DMF system. This catalytic amination procedure can be performed with good to high yields under mild conditions under an air atmosphere.     

Gas phase synthesis and X-ray crystal structures of supramolecular networks with bromocorannulene: Similarities and differences with their corannulene analogs

The reactivity of bowl-shaped mono-bromocorannulene (C₂₀H₉Br) has been examined and compared with that of corannulene (C₂₀H₁₀). Although bromination of corannulene was shown to flatten the bowl and change its electronic properties, it has not affected the outcome of coordination reactions toward the avid Lewis acidic [Rh₂(O₂CCF₃)₄] complex. Two new products have the same composition [{Rh₂(O₂CCF₃)₄}_m · (C₂₀H₉Br)_n] where m:n = 1:1 (1) and 3:2 (2), as the corresponding corannulene-based analogs. The X-ray diffraction studies of 1 and 2 revealed 1D chain and 2D layered structures built on η²-coordination of rhodium(II) to rim carbon sites of the C₂₀H₉Br-bowl, similar to those of C₂₀H₁₀. While no essential difference is found in 2D structures, the local coordination environments of the [Rh₂(O₂CCF₃)₄] unit differ in their 1D complexes.