PHOTOCYTOTOXICITY OF CURCUMIN

Curcumin, bis (4-hydroxy-3-methoxyphenyl)-l,6-diene-3,5-dione, is a yellow-orange dye derived from the rhizome of the plant Curcuma longa. Curcumin has demonstrated phototoxicity to several species of bacteria under aerobic conditions (Dahl, T. A., et al. , 1989, Arch. Microbiol. 151 183), denoting photodynamic inactivation. We have now found that curcumin is also phototoxic to mammalian cells, using a rat basophilic leukemia cell model, and that this phototoxicity again requires the presence of oxygen. The spectral and photochemical properties of curcumin vary with environment, resulting in the potential for multiple or alternate pathways for the exertion of photodynamic effects. For example, curcumin photogenerates singlet oxygen and reduced forms of molecular oxygen under several conditions relevant to cellular environments. In addition, we detected carbon-centered radicals, which may lead to oxidation products (see accompanying paper). Such products may be important reactants in curcumin's phototoxicity since singlet oxygen and reduced oxygen species alone could not explain the biological results, such as the relatively long lifetime (t¹²= 27 s) of the toxicant responsible for decreased cell viability.     

Electron-stimulated desorption from ionic crystal surfaces

Inelastic interactions of electrons with surfaces of ionic crystals result in emission of various particles such as ions, atoms and molecules. We will review such electron-stimulated desorption processes for the particular class of ionic crystals, namely for alkali halides. In this case, a dominant fraction of the emission is in the form of halogen and alkali atoms characterized by a thermal (Maxwellian) spectrum of translational energies. For several alkali halides (potassium and rubidium chlorides, bromides, and iodides), however, a significant part of the halogen atoms is ejected with nonthermal energies, i.e. energies of the order of 0.1 eV. The results of recent systematic studies of angular-resolved kinetic energy distributions of the emitted particles will be reported and current views on the electronic mechanisms of desorption will be described. In particular, it will be shown that the ESD mechanism can be understood in terms of the model involving a surface localisation of the so called “hot-holes” created by electron bombardment of alkali halides. A role of hot holes in ESD processes will further be discussed in relation to very recent experimental results obtained for the KBr crystals doped with In impurities which act as efficient hole traps.     

Thermal properties of fats extracted from powdered baby formulas

The aim of this research was to analyse composition, fatty acids distribution and oxidative stability of fats extracted from four samples of baby formulas. The fats were oxidized in a differential scanning calorimeter (DSC) under polythermal (dynamic) conditions and at normal pressure. The DSC experiments were carried out in an oxygen flow atmosphere using different, linearly programmed, heating rates in the range of 4?C12.5?°C/min. The extrapolated onset temperatures were determined using DSC exotherms and used for the assessment of the thermal oxidative stabilities of the samples. Activation energies (E _a), pre-exponential factors (Z) and reaction rate constants (k) for oil oxidation under DSC conditions were calculated using the Ozawa?CFlynn?CWall method and the Arrhenius equation. The melting characteristics of the studied fats were obtained. The fats extracted from the agglomerated samples with higher onset temperatures were more stable than the fats extracted from the initial samples of baby formulas.     

Monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent

Chemical exchange saturation transfer (CEST) is a new approach for generating magnetic resonance imaging (MRI) contrast that allows monitoring of protein properties in vivo. In this method, a radiofrequency pulse is used to saturate the magnetization of specific protons on a target molecule, which is then transferred to water protons via chemical exchange and detected using MRI. One advantage of CEST imaging is that the magnetizations of different protons can be specifically saturated at different resonance frequencies. This enables the detection of multiple targets simultaneously in living tissue. We present here a CEST MRI approach for detecting the activity of cytosine deaminase (CDase), an enzyme that catalyzes the deamination of cytosine to uracil. Our findings suggest that metabolism of two substrates of the enzyme, cytosine and 5-fluorocytosine (5FC), can be detected using saturation pulses targeted specifically to protons at +2 ppm and +2.4 ppm (with respect to water), respectively. Indeed, after deamination by recombinant CDase, the CEST contrast disappears. In addition, expression of the enzyme in three different cell lines exhibiting different expression levels of CDase shows good agreement with the CDase activity measured with CEST MRI. Consequently, CDase activity was imaged with high-resolution CEST MRI. These data demonstrate the ability to detect enzyme activity based on proton exchange. Consequently, CEST MRI has the potential to follow the kinetics of multiple enzymes in real time in living tissue.     

One-pot synthesis of (E)-styryl ketones from styrenes

A new, efficient protocol for the highly stereoselective one-pot synthesis of (E)-styryl ketones from styrenes based on sequential ruthenium-catalyzed silylative coupling-rhodium-catalyzed desilylative acylation reactions is reported.     

Geometric and magnetic properties of Pt clusters supported on graphene: relativistic density-functional calculations

The geometric and magnetic structures of small Pt(n) clusters (n = 1 - 5) supported on a graphene layer have been investigated using ab initio density functional calculations including spin-orbit coupling. Pt-Pt interactions were found to be much stronger than the Pt-C interactions promoting the binding to the support. As a consequence, the equilibrium structure of the gas-phase clusters is preserved if they are deposited on graphene. However, the clusters bind to graphene only via at most two Pt-C bonds: A Pt(2) dumbbell prefers an upright position, the larger clusters are bound to graphene only via one edge of the planar cluster (Pt(3) and Pt(5)) or via two terminal Pt atoms of a bent Pt(4) rhombus. Evidently, the strong buckling of the graphene layer induced by the Pt-C bonds prevents the formation of a larger number of cluster-support bonds. As the local spin and orbital magnetic moments are quenched on the Pt atoms forming Pt-C bonds, the magnetic structure of the supported clusters is much more inhomogeneous as in the gas-phase. This leads to noncollinear magnetic structures and a strongly reduced magnetic anisotropy energy.     

Sugar-derived cyclic imines: one-pot synthesis and direct functionalization

A simple method for the synthesis of sugar-derived imines by a Schwartz's reagent reduction of easily available sugar lactams has been described. A direct addition of nucleophiles to the generated in situ cyclic imines and subsequent deprotection of hydroxyl function allows to convert sugar lactams in polyhydroxylated pyrrolidines and piperidines.     

Synthesis and structure–activity relationship study of cytotoxic lupane-type 3β-O-monodesmosidic saponins with an extended C-28 side chain

A concise synthesis of lupane triterpenes with an elongated carbon chain at the C-28 position, as well as saponins containing d-mannose, l-arabinose, and l-rhamnose moieties at the C-3 position is described. The overall synthesis of the new triterpenes involved seven linear steps starting from natural betulin: selective protection of a hydroxyl group, oxidation, elongation of the carbon chain by Grignard reaction, and deoxygenation. O-Glycosides were obtained by glycosylation of triterpenes with classical Schmidt's donors. Additionally, all new compounds were evaluated in vitro for their cytotoxic activities. Several triterpenes and the corresponding saponins exhibited an interesting cytotoxic activity profile against human cancer cell lines. The therapeutical index of active triterpenes is very high, since almost none of them were cytotoxic for normal BJ fibroblasts. These results open the way to the synthesis of various lupane-type saponin derivatives as potentially bioactive compounds.     

Modeling of diffusive transport of benzoic acid through a liquid membrane

A model of diffusive transport of benzoic acid through a liquid membrane (LM) separating two aqueous solutions, based on diffusion layers and the assumption of a steady state, has been developed and tested using experimental results. It has been found that a model with the apparent partition coefficient dependent on the concentration is able to describe the time dependence of acid concentration in LM with and without a maximum on that dependence. The quality of the model fit with the single apparent diffusion coefficient of benzoic acid is the same as the one which takes into account the diffusion of benzoic acid in different forms (undissociated and dissociated form in aqueous phase, monomer and dimer in organic phase); however, in the second case, the model becomes overparameterized. Assuming that the partition and diffusion coefficients are constant, the diffusion layer model corresponds to the model of reversible consecutive reactions. Analytical solution for such case is given. Apart from the partition equilibrium, also kinetics of partitioning was considered. It was shown that in some basic situations both cases yield identical results.