The Role of Singlet Oxygen in Photoreactivity and Phototoxicity of Curcumin

Curcumin is a plant-derived yellow-orange compound widely used as a spice, dye and food additive. It is also believed to have therapeutic effects against different disorders. On the other hand, there are data showing its phototoxicity against bacteria, fungi and various mammalian cells. Since the mechanism of its phototoxic action is not fully understood, we investigated here the phototoxic potential of curcumin in liposomal model membranes and in HaCaT cells. First, detection of singlet oxygen (¹O₂) luminescence proved that curcumin generates ¹O₂ upon blue light irradiation in organic solvent and in liposomes. Then, HPLC-EC(Hg) measurements revealed that liposomal and cellular cholesterol is oxidized by ¹O₂ photogenerated by curcumin. Enrichment of liposome membranes with curcumin significantly increased the oxygen photo-consumption rate compared to the control liposomes as determined by EPR oximetry. Cytotoxicity measurements, mitochondrial membrane potential analyses and protein hydroperoxides detection confirmed strong phototoxic effects of curcumin in irradiated HaCaT cells. These data show that since curcumin is advertised as a valuable dietary supplement, or a component of cosmetics for topical use, caution should be recommended especially when skin is exposed to light.     

Relativistic model core potential study of the Au+ Xe system

A computational study of the Au(+)Xe ionic system has been performed using newly developed coupled-cluster methods and relativistic model core potentials, with extra basis functions optimized to afford superior polarizabilities. Potential energy curves for the dissociation of Au(+)Xe were studied at different levels of theory, and molecular properties (bond length and harmonic vibrational frequency) were calculated. Wave functions were analyzed using the natural bond orbital method. The nature of bonding in this system is discussed.     

Properties of polyethylene glycol supported tetraarylporphyrin in aqueous solution and its interaction with liposomal membranes

5,10,15,20-Tetrakis(4-hydroxyphenyl)porphyrin was functionalized by covalent attachment of poly(ethylene glycol) (PEG) chains of various molecular weights, 350, 2000, and 5000 Da. The properties of PEG-functionalized tetraarylporphyrins in aqueous solution and their interactions with liposomes have been studied. Electronic absorption spectroscopy, dynamic light scattering, atomic force microscopy, and fluorescence quenching were used to monitor aggregation of porphyrin chromophores and behavior of the attached PEG chains in the aqueous solution. The tendency for aggregation of porphyrin chromophores in aqueous solution and the efficiency of fluorescence quenching by KI decrease with increasing length of PEG chain linked to the porphyrin ring. The experimental results indicate that polymer clusters are present in aqueous solution of all pegylated porphyrins. The interactions between the pegylated porphyrins and phosphatidylcholine liposomes in the aqueous solution were studied using the fluorescence methods. The apparent binding constants of porphyrin chromophores to liposomes were determined. The degree of binding was found to be dependent on the molecular weight of the attached polymer.     

Highly stereoselective synthesis of para-substituted (E)-N-styrylcarbazoles via sequential silylative coupling-Hiyama coupling reaction

A series of new para-substituted (E)-(N)-styrylcarbazoles, i.e., eight (E)-9-[2-(aryl)ethenyl]-9H-carbazoles (5-12) and 1,4-bis[(E)-2-(9H-carbazol-9-yl)vinyl]benzene (13), have been synthesized in high yield and stereoselectively by a sequential silylative coupling-Hiyama coupling reaction, i.e., coupling of commercially available 9-vinylcarbazole with vinyltriethoxysilane or divinyltetramethyldisiloxane in the presence of [RuHCl(CO)(PCy₃)₂] (I), followed by Pd (II) catalyzed cross-coupling with para-substituted iodobenzenes.The tandem procedure has facilitated the synthesis of 13. X-ray structures of the intermediate silylvinylcarbazole (4), as well as products 12 and 13 have been obtained.     

Revised model core potentials of s-block elements

We developed new model core potentials (MCPs) for s-block elements from Na to Ra, in which the outer core (n-1)s and (n-1)p electrons are treated explicitly together with the ns electrons. By adding suitable correlating functions, we demonstrated that the present MCP basis sets show excellent performance in describing the electronic structures of atoms and molecules, bringing about accurate ionization potentials of atoms and very good spectroscopic constants of ionic and covalent molecules. The results obtained with the new MCPs are very close to the ones obtained using the all-electron correlation consistent basis sets of Dunning.     

Photobleaching of melanosomes from retinal pigment epithelium: II. Effects on the response of living cells to photic stress

Melanosomes of the retinal pigment epithelium (RPE) are long lived organelles that may undergo photobleaching with aging, which can diminish the antioxidant efficiency of melanin. Here, isolated porcine RPE melanosomes were experimentally photobleached with visible light to simulate aging and compared with untreated granules or control particles (black latex beads) for their effects on the survival of photically stressed ARPE-19 cultures. Particles were delivered to cultures for uptake by phagocytosis then cells were exposed to violet light and analyzed by a new live cell imaging method to identify the time of apoptotic blebbing as a dynamic measure of reduced cell survival. Results indicated that untreated melanosomes did not decrease photic injury to ARPE-19 cells when compared with cells lacking particles or with cells containing control particles, as might be expected if melanin performed an antioxidant function. Instead cells with untreated melanosomes showed reduced survival indicated by an earlier onset of blebbing and a lower fraction of surviving cells after photic stress. Cell survival was reduced even further in stressed cells containing melanosomes that were photobleached, and survival decreased with increasing photobleaching time. Photobleaching of RPE melanosomes therefore makes cells containing them more sensitive to light-induced cytotoxicity. This observation raises the possibility that aged melanosomes increase RPE cell photic stress in situ, perhaps contributing to reduced tissue function and to degeneration of the adjacent retina that the RPE supports. How melanosomes (photobleached or not) interact with their local subcellular environment to modify RPE cell survival is poorly understood and is likely determined by the physicochemical state of the granule and its constituent melanin. The live cell imaging method introduced here, which permitted detection of a graded effect of photobleaching, provides a sensitive bioassay for probing the effects of melanosome modifications.     

Simple physics-based analytical formulas for the potentials of mean force for the interaction of amino acid side chains in water. 1. Approximate expression for the free energy of hydrophobic association based on a Gaussian-overlap model

A physics-based model is proposed to derive approximate analytical expressions for the cavity component of the free energy of hydrophobic association of spherical and spheroidal solutes in water. The model is based on the difference between the number and context of the water molecules in the hydration sphere of a hydrophobic dimer and of two isolated hydrophobic solutes. It is assumed that the water molecules touching the convex part of the molecular surface of the dimer and those in the hydration spheres of the monomers contribute equally to the free energy of solvation, and those touching the saddle part of the molecular surface of the dimer result in a more pronounced increase in free energy because of their more restricted mobility (entropy loss) and fewer favorable electrostatic interactions with other water molecules. The density of water in the hydration sphere around a single solute particle is approximated by the derivative of a Gaussian centered on the solute molecule with respect to its standard deviation. On the basis of this approximation, the number of water molecules in different parts of the hydration sphere of the dimer is expressed in terms of the first and the second mixed derivatives of the two Gaussians centered on the first and second solute molecules, respectively, with respect to the standard deviations of these Gaussians, and plausible analytical expressions for the cavity component of the hydrophobic-association energy of spherical and spheroidal solutes are introduced. As opposed to earlier hydration-shell models, our expressions reproduce the desolvation maxima in the potentials of mean force of pairs of nonpolar solutes in water, and their advantage over the models based on molecular-surface area is that they have continuous gradients in the coordinates of solute centers.