Interaction of isomeric forms of xanthophyll pigment zeaxanthin with dipalmitoylphosphatidylcholine studied in monomolecular layers

Two-component monomolecular layers were formed with DPPC and two stereoisomers of zeaxanthin 9-cis and 13-cis at the argon-water interface. Very distinct over-additivity which represents affection of a lipid arrangement in the membrane has been observed in the case of zeaxanthin 9-cis (maximum at 20 mol%) but not in the case of zeaxanthin 13-cis. The differences in the organization of the isomers of zeaxanthin-DPPC monolayers are interpreted in terms of the different orientation of both xanthophylls at the interface observed at relatively high surface pressures (>25 mN/m) comparable to the surface pressures of biomembranes. The results are consistent with the model according to which zeaxanthin 9-cis adopts a vertical orientation at the polar-nonpolar interface in contrast to zeaxanthin 13-cis, which is oriented horizontally owing to the fact that it interacts by two hydroxyl groups with the same hydrophobic-hydrophilic interface in the monolayer. The findings are discussed in comparison with the behavior of zeaxanthin in the conformation all-trans in the same system. Zeaxanthin all-trans forms efficiently molecular aggregates in the mixed monolayers in contrast to cis isomers. Circular dichroism measurements show the formation of molecular structures by zeaxanthin 13-cis that are interpreted as dimers. FTIR measurements show that these dimers are stabilized by van der Waals interactions unlike aggregated structures formed by all-trans zeaxanthin that are stabilized by hydrogen bonding. Physiological importance of the differences in aggregation and orientation of stereoisomers of zeaxanthin in lipid environment is discussed.     

A systematic SAR study of C10 modified paclitaxel analogues using a combinatorial approach

A library with 63 paclitaxel analogues modified at the C10 position of paclitaxel has been prepared using parallel solution phase synthesis. Most of the C10 analogues were slightly less active than paclitaxel in the tubulin assembly assay and had reduced potency in the B16 melanoma and MCF-7 cell line cytotoxicity assays. These modifications at C10, however, did not lead to the total loss of activity, indicating that the C10 moiety of paclitaxel may not be directly involved in the drug-microtubule interactions, but could influence its binding affinity to P-glycoprotein. Approximately 50% of the analogues demonstrated better activity against the drug resistant cell line MCF7-ADR. However, the increase in activity was 10-fold at most. This result demonstrates that the cytotoxicity against this drug resistant cancer cell line is sensitive to structural changes at the C10 position of paclitaxel. It was also found that the presence of a nitrogen atom in the C10 substituent might play a role in the interaction of analogues with microtubules.     

Dynamic mechanical properties of epoxy/novolac system modified with reactive liquid rubber and carbon filler

This paper reports on the work carried out to evaluate the frequency dependent viscoelastic properties of epoxy/novolac compositons modified with a liquid reactive rubber and carbon filler. For epoxy systems modified with elastomer, three typical transitions were observed: the α-relaxation deeply related to the glass transition of epoxy, the β-transition of epoxy, and the glass transition of rubber appeared near to the β-relaxation of epoxy resin. Considering an Arrhenius equation, the activation energies of β-relaxation were estimated. In the region of glass transition and rubbery state the temperature dependence of the shift factor (α_T) was determined through Williams-Landel-Ferry (WLF) equation.     

Synthesis,characterization and antibacterial studies of Tm(III), Yb(III) and Lu(III) complexes of morin

New solid amorphous compounds of Tm(III), Yb(III) and Lu(III) with morin have been synthesized. Their composition and some physicochemical properties have been studied by elemental analysis, thermogravimetric analysis, IR spectroscopy as well as by conductivity, UV/Vis, MS, and NMR spectroscopies in solution. The spectroscopic studies have indicated that the 3-OH hydroxyl group and the carbonyl oxygen of morin were involved in the coordination of metal ion. The antibacterial activity of the synthesized compounds has been determined by the cylinder-plate diffusion and dilution methods (determination of minimum inhibitory concentration).     

Inspecting the structure-activity relationship of protein kinase CK2 inhibitors derived from tetrabromo-benzimidazole

CK2 is a very pleiotropic protein kinase whose high constitutive activity is suspected to cooperate to neoplasia. Here, the crystal structure of the complexes between CK2 and three selective tetrabromo-benzimidazole derivatives inhibiting CK2 with Ki values between 40 and 400 nM are presented. The ligands bind to the CK2 active site in a different way with respect to the parent compound TBB. They enter more deeply into the cavity, establishing halogen bonds with the backbone of Glu114 and Val116 in the hinge region. A detailed analysis of the interactions highlights a major role of the hydrophobic effect in establishing the rank of potency within this class of inhibitors and shows that polar interactions are responsible for the different orientation of the molecules in the active site.     

New SRDN-3 probes with a semi-conductor detector for measuring radon activity concentration in underground spaces

The article presents new Polish probes SRDN-3, developed at the Institute of Nuclear Chemistry and Technology in Warsaw, equipped with a semi-conductor detector used for continuous measurements of ²²²Rn activity concentration. Due to a relatively high lower detection limit, the device is dedicated for use in underground spaces—caves, adits, mines, tourist routes in strongholds, pyramids, etc. Its structure allows for difficult conditions in which the device is transported to the measurement site, as well as hard operating conditions caused chiefly by large ambient relative humidity, reaching up to 100%. The authors present calibration results of these appliances, as well as the results of their work in a cave and an adit in the Sudetes (SW Poland). After almost 2 years of working in difficult conditions, the probes displayed high reliability. No defects of the semi-conductor detectors or the electronics were observed, which ensured problem-free communication of the probe-programmer-PC set. Thanks to this, the authors have a 2 year stock of data, recorded hourly by five probes, at their disposal. The only element that did not withstand the test of extreme operating conditions was one of the combined relative humidity and temperature sensors. No powering problems were observed either, and the batteries were replaced once a year, before the winter season. Also the programmer functioned faultlessly, enabling data transmission to a PC, which, being much more sensitive to operating conditions, had been placed away from the site of probe exposure. After using more sensitive temperature, relative humidity and pressure sensors, SRDN-3 probes will certainly prove an excellent tool for microclimate measurements (including measurement of air-atmosphere exchange) in caves and other underground sites. Even nowadays they are already a satisfactory tool for monitoring ²²²Rn concentration in underground spaces.     

Simple Analytical Method for the Determination of Paclitaxel (Taxol ® ) Levels in Human Plasma

Paclitaxel has been widely used for tumor chemotherapy in recent years and it would be useful to assess occupational exposure to the drug, if only to confirm that the procedures and measures for prevention and protection applied in health care structures are effective against this kind of risk. This study is to establish a simple, robust analytical method for routine use in biological monitoring of health workers exposed to taxanes, and extendable to patients receiving these drugs. HPLC equipped with a diode array detector was used. The assay was validated. Intra- and inter-day accuracy and reproducibility were good. Recovery of paclitaxel spiked in drug-free plasma was higher than 87% with SPE using extract-clean normal phase cyanopropyl silica cartridges for plasma clean-up. The calibration curve was linear in the range 10–500 ng mL^?1. The method was applied to plasma samples of nurses occupationally exposed to paclitaxel. The experimental analytical method performed well, detecting paclitaxel in plasma at a concentrations down to 10 ng mL^?1. This straightforward method for analytical determination of paclitaxel in human plasma is rapid and can measure up to 36 plasma samples per day. It uses more economical equipment than other methods proposed in the literature and its validation parameters are highly satisfactory.     

Influence of the Helical Backbone in the Behavior of a Simple Model for Dimeric Coiled‐Coil Proteins

Using computer simulations as a tool for thought experiments, we investigate the influence of the helical backbone geometry in the association process and the final structures of a simple model which mimics parallel, two‐stranded coiled‐coil proteins. We define three types of helices: two of them have straight helical axes and 3.5 or 3.6 residues per helical turn; the third type presents a coiled helical axis, according to the canonical scheme defined by Crick. By using a Monte Carlo simulation algorithm, we observe that the three models exhibit different transition temperatures for the formation of the dimeric structure from two independent peptides, and a different behavior concerning the appearance of out‐of‐register structures. The energy minimized dimer structures present strong deviations from the correct association for straight helices with 3.6 residues/turn, especially for long peptides, deviations which are absent for the other two types when only the burial of hydrophobic residues is considered. A careful analysis of the energies for the out‐of‐register configurations and the contact maps reveals also differences between dimers resulting from the model with Crick parameterization and with 3.5 residues/turn. The results presented in this paper may be relevant for the design of simple models which use rigid α‐helices built from predicted elements of secondary structure.

Top views of the helical models used in this work.     

Dinuclear gold(I) Complexes with Bidentate NHC Ligands as Precursors for Alkynyl Complexes via Mechanochemistry

The use of alkynyl gold(I) complexes covers different research fields, such as bioinorganic chemistry, catalysis, and material science, considering the luminescent properties of the complexes. Regarding this last application, we report here the synthesis of three novel dinuclear gold(I) complexes of the general formula [(diNHC)(Au-C≡CPh)₂]: two Au-C≡CPh units are connected by a bridging di(N-heterocyclic carbene) ligand, which should favor the establishment of semi-supported aurophilic interactions. The complexes can be easily synthesized through mechanochemistry upon reacting the pristine dibromido complexes [(diNHC)(AuBr)₂] with phenylacetylene and KOH. Interestingly, we were also able to isolate the monosubstituted complex [(diNHC)(Au-C≡CPh)(AuBr)]. The gold(I) species were fully characterized by multinuclear NMR spectroscopy and mass spectrometry. The emission properties were also evaluated, and the salient data are comparable to those of analogous compounds reported in the literature.