Novel methyl helianthrones as photosensitizers: synthesis and biological evaluation

A combination of light, oxygen and a photosensitizer is used to induce death of cancer cells by photodynamic therapy. In this study, we have synthesized several new methyl helianthrone derivatives and compared their phototoxicity with that of hypericin. In contrast to hypericin, methyl helianthrones are soluble in aqueous solutions and have a broad range of light absorbance, which allows the use of polychromatic light. Structural modifications of methyl helianthrone demonstrated that substitution of hydrogen atoms of methyl helianthrone at Positions 2 and 5 with Br atoms or methylation of its phenolic hydroxyls, significantly increases the corresponding singlet oxygen quantum yield and their phototoxicity toward alphaT3-1, M2R and LNCaP cells. The phototoxicity of some of these compounds was similar to that of hypericin. Methyl helianthrones, like hypericin, accumulated mainly in the perinuclear region as evident by confocal microscopy. Irradiation of cells pretreated with methyl helianthrone derivatives generates intracellular reactive oxygen species and lipid free radicals, as shown by a fluorescentic probe and electron paramagnetic resonance methods, respectively. The phototoxicity of these methyl helianthrones as well as their ability to oxidize membrane lipids were significantly decreased on addition of specific Type-II inhibitors, suggesting the involvement of singlet oxygen as the main oxidant.     

Electron paramagnetic resonance investigation of molecular bond rupture due to ozone in deformed rubber

Electron paramagnetic resonance (EPR) provides a sensitive tool by which microscopic bond rupture can be monitored simultaneously with observations of macroscopic deformation and failure. Past techniques for studying fracture in semicrystalline polymers have been extended to investigate degradation of unfilled ruber in the presence of ozone. It was found that the rate of free radical production was linearly proportional to stretch ratio and ozone concentration and that stress relaxation and creep were not directly proportional to this production rate. The latter behavior was attributed to the particular dependence of crack density and growth on stress. It was concluded that at low strains, comparatively few surface cracks form; however, at higher strains, many more crack centers become active. Although many more surface cracks are present, they do not progress into the material as rapidly. Therefore, although more bonds were broken at higher strains and stresses, the stress relaxation rate and creep rates were not significantly increased.     

Ge掺杂n型Sn基VIII型单晶笼合物的制备及热电传输特性

采用Sn自熔剂法制备了具有n型传导的VIII型Ba8Ga16 xGexSn30(0 x 1.0)单晶笼合物,并对其结构和热电特性进行研究.研究结果表明:Ge在单晶中的实际含量较少,随着掺杂量的增加样品的晶格常数略有减小,Ge掺杂后样品的载流子浓度较掺杂前低,迁移率增加;所有样品的Seebeck系数均为负值,且绝对值较未掺杂样品低,但Ge掺杂后样品的电导率提高了62%;x=0.5的样品在500 K附近取得最大ZT值1.25.     

Isotope effects in water as investigated by neutron diffraction and path integral molecular dynamics

The structures of heavy and light water at 300?K were investigated by using a joint approach in which the method of neutron diffraction with oxygen isotope substitution was complemented by path integral molecular dynamics simulations. The diffraction results, which give intra-molecular O-D and O-H bond distances of 0.985(5) and 0.990(5)??, were found to be in best agreement with those obtained by using the flexible anharmonic TTM3-F water model. Both techniques show a difference of ??0.5% between the O-D and O-H intra-molecular bond lengths, and the results support a competing quantum effects model for water in which its structural and dynamical properties are governed by an offset between intra-molecular and inter-molecular quantum contributions. Further consideration of the O-O correlations is needed in order to improve agreement with experiment.     

The two-cardinals transfer property and resurrection of supercompactness

We show that the transfer property for singular does not imply (even) the existence of a non-reflecting stationary subset of . The result assumes the consistency of ZFC with the existence of infinitely many supercompact cardinals. We employ a technique of ``resurrection of supercompactness'. Our forcing extension destroys the supercompactness of some cardinals; to show that in the extended model they still carry some of their compactness properties (such as reflection of stationary sets), we show that their supercompactness can be resurrected via a tame forcing extension.

     

Limited path percolation in complex networks

We study the stability of network communication after removal of a fraction q=1-p of links under the assumption that communication is effective only if the shortest path between nodes i and j after removal is shorter than al(ij)(a> or =1) where l(ij) is the shortest path before removal. For a large class of networks, we find analytically and numerically a new percolation transition at p(c)=(kappa(0)-1)((1-a)/a), where kappa(0) [triple bond] / and k is the node degree. Above p(c), order N nodes can communicate within the limited path length al(ij), while below p(c), N(delta) (delta<1) nodes can communicate. We expect our results to influence network design, routing algorithms, and immunization strategies, where short paths are most relevant.     

Oxygen as a site specific probe of the structure of water and oxide materials

The method of oxygen isotope substitution in neutron diffraction is introduced as a site specific structural probe. It is employed to measure the structure of light versus heavy water, thus circumventing the assumption of isomorphism between H and D as used in more traditional neutron diffraction methods. The intramolecular and intermolecular O-H and O-D pair correlations are in excellent agreement with path integral molecular dynamics simulations, both techniques showing a difference of ?0.5% between the O-H and O-D intramolecular bond distances. The results support the validity of a competing quantum effects model for water in which its structural and dynamical properties are governed by an offset between intramolecular and intermolecular quantum contributions.     

Current development of analytical affinity chromatography: Design and biotechnological uses of molecular recognition surfaces

Analytical high performance liquid affinity chromatography (analytical HPLAC) has been investigated as an experimental guide to both synthetic design and affinity technological use of peptide and protein recognition surfaces. This work has progressed from the ongoing use of analytical affinity chromatography to study interaction mechanisms of naturally-occurring peptides and proteins, including enzyme fragment complexes and neuroendocrine biosynthetic precursors. We recently initiated a study to use analytical HPLAC for de novo design of recognition peptides called “anti-sense peptides”. Present data suggest the potential to use anti-sense peptides as “synthetic antibodies”, in immobilized forms, for biomolecular separation and analysis. Analogous studies have been started with immobilized natural antibodies in analytical immuno HPLAC. Our present data typify the growing usefulness of analytical HPLAC when designing recognition molecules, analyzing their interaction characteristics, and devising ways to use them in affinity technology.     

Proton binding to proteins: pK(a) calculations with explicit and implicit solvent models

Ionizable residues play important roles in protein structure and activity, and proton binding is a valuable reporter of electrostatic interactions in these systems. We use molecular dynamics free energy simulations (MDFE) to compute proton pKa shifts, relative to a model compound in solution, for three aspartate side chains in two proteins. Simulations with explicit solvent and with an implicit, dielectric continuum solvent are reported. The implicit solvent simulations use the generalized Born (GB) model, which provides an approximate, analytical solution to Poisson's equation. With explicit solvent, the direction of the pKa shifts is correct in all three cases with one force field (AMBER) and in two out of three cases with another (CHARMM). For two aspartates, the dielectric response to ionization is found to be linear, even though the separate protein and solvent responses can be nonlinear. For thioredoxin Asp26, nonlinearity arises from the presence of two substates that correspond to the two possible orientations of the protonated carboxylate. For this side chain, which is partly buried and has a large pKa upshift, very long simulations are needed to correctly sample several slow degrees of freedom that reorganize in response to the ionization. Thus, nearby Lys57 rotates to form a salt bridge and becomes buried, while three waters intercalate along the opposite edge of Asp26. Such strong and anisotropic reorganization is very difficult to predict with Poisson-Boltzmann methods that only consider electrostatic interactions and employ a single protein structure. In contrast, MDFE with a GB dielectric continuum solvent, used for the first time for pKa calculations, can describe protein reorganization accurately and gives encouraging agreement with experiment and with the explicit solvent simulations.