Silylation Improves the Photodynamic Activity of Tetraphenylporphyrin Derivatives In Vitro and In Vivo

The effects of silyl and hydrophilic groups on the photodynamic properties of tetraphenylporphyrin (TPP) derivatives have been studied in vitro and in vivo. Silylation led to an improvement in the quantum yield of singlet oxygen sensitization for both sulfo and carboxy derivatives, although the silylation did not affect other photophysical properties. Silylation also improved the cellular uptake efficiency for both sulfo and carboxy derivatives, enhancing the in vitro photodynamic activity of the photosensitizer in U251 human glioma cells. The carboxy derivative (SiTPPC₄) was found to show higher cellular uptake efficiency and in vitro photodynamic activity than the corresponding sulfo derivative (SiTPPS₄), which indicates that the carboxy group is a more promising hydrophilic group than the sulfo group in the silylated porphyrin. SiTPPC₄ was found to show high selective accumulation efficiency in tumors, although almost no tumor selectivity was observed for the nonsilylated porphyrin. The concentration of SiTPPC₄ in tumors was 13 times higher than that in muscle 12 h after drug administration. We also studied tumor response after treatment and found that silylation enhanced in vivo photodynamic activity significantly. SiTPPC₄ shows higher photodynamic activity than NPe6 with white light irradiation.     

Efficient Synthesis of Eight‐Membered Nitrogen Heterocycles from O‐Propargylic Oximes by Rhodium‐Catalyzed Cascade Reactions

Azocine derivatives were successfully synthesized from O‐propargylic oximes by means of a Rh‐catalyzed 2,3‐rearrangement/heterocyclization cascade reaction. Moreover, the chirality of the substrate was maintained throughout the cascade process to afford the corresponding optically active azocines.     

In vitro and In vivo Antiproliferative Effect of a Combination of Ultraviolet‐A and Alkoxy Furocoumarins Isolated from Umbelliferae Medicinal Plants,in Melanoma Cells

We examined the effects of six furocoumarins with alkoxy groups at the C‐5 or C‐8 position isolated from Umbelliferae medicinal plants on cell proliferation, and their mechanisms of action against B16F10 melanoma cells or in melanin‐possessing hairless mice implanted with B16F10 cells, under UVA irradiation. Three furocoumarins with an alkoxy group at C‐5, isoimperatorin (1), oxypeucedanin (2) and oxypeucedanin hydrate (3), showed antiproliferative activity and caused G₂/M arrest at concentrations of 0.1–10.0 μm . Furthermore, three furocoumarins with an alkoxy group at C‐8, imperatorin (4), heraclenin (5) and heraclenol (6), inhibited the proliferation of melanoma cells and cell cycle at G₂/M at concentrations of 0.1–1.0 μm . UVA plus 1, 2, 3, 4 and 6 reduced tumor growth and final tumor weight in B16F10‐bearing mice at a dose of 0.3, 0.5 or 1.0 mg kg^?1 (intraperitoneal injection). UVA plus 1, 3 and 6 increased Chk1 phosphorylation and reduced cdc2 (Thr 161) phosphorylation in melanoma cells. We suggest that the antitumor actions of UVA plus furocoumarins with an alkoxy group at C‐5 or C‐8 were due to G₂/M arrest of the cell cycle by an increase in phosphor‐Chk1 and decrease in phospho‐cdc2.     

First Catenane‐Containing Phosphino Groups: A Step toward a Catenane Ligand

A novel [2] catenane containing a diphenylphosphino group on each ring was prepared. Synthesis of the new catenane involved the use of tetraamide rings to form an efficient pseudorotaxane intermediate. The catenane was found to be applicable as a ligand for metal-catalyzed reactions such as Suzuki-Miyaura coupling.     

Clarification of the role of protein in carbonmonoxy myoglobin by investigating electronic states

This article reports the proton tautomerization effects of distal histidine residues in carbonmonoxy myoglobin according to the density functional calculations of the whole protein. The electron eigenstates and electrostatic potential (ESP) distributed around heme and its pocket vary significantly depending on the protonation positions of the distal histidine residues. To investigate the range over which the electronic structures are affected by the proton tautomerization, the quantum mechanics/molecular mechanics (QM/MM) method is applied to probe the QM size to reproduce the atomic partial charges and ESP around the active center. Consequently, we show that these properties converged for the 300 pm QM/MM system in this study. During the analysis, we also find that amino residues such as Phe43, Val68, and Phe138 interact strongly with heme through orbital mixing, indicating that the protein is a medium not only interacting with the reaction center, but also buffering on electrons. © 2013 Wiley Periodicals, Inc.     

Molecular dynamics simulation of the mixed anion glasses Li4SiO4---Li3BO3

The structure and the mixed anion effect in the conductivity have been examined for the mixed anion glasses Li₄SiO₄---Li₃BO₃ by molecular dynamics (MD) simulation and X-ray diffraction (XRD) analysis. Structure factors derived from the MD simulation are in good agreement with those from derived from the XRD analysis of the actual glasses, showing that the MD simulation successfully reproduces the actual glass structure. Moreover, the enhancement of the diffusion coefficients of the Li⁺ ions in the middle of the composition range in the system Li₄SiO₄---Li₃BO₃ is simulated by the MD calculation. Structural analysis of the glasses derived from the MD simulation revealed that the increase in the halfwidth of the modified radial distribution function of the Li---O pairs due to the mixing of two ortho-oxoanions is one of the factors in the origin of the mixed anion effect in the conductivity.     

ACCESSORY CELL ABILITY OF LANGERHANS CELLS FOR SUPERANTIGEN IS RESISTANT TO ULTRAVIOLET-B LIGHT

Abstract We examined the effects of ultraviolet-B (UVB) irradiation on the accessory cell ability of Langerhans cells (LC) to induce a T-cell response to a superantigen, staphylococcal enterotoxin B (SEB). The ability of LC-enriched epidermal cells (LC-EC) to evoke a T-cell response to SEB was retained at the doses of UVB (up to 40 mJ/ cm²) that profoundly affected the antigen-presenting function of LC-EC for a hapten, trinitrophenyl (TNP), and a protein antigen, conalbumin. Thus, the LC accessory function for superantigens is more resistant to UVB irradiation than that for ordinary antigens. This UVB resistance is presumably due to no requirement of antigen processing for superantigens as chemically fixed or chloroquine-treated LC-EC still retained their ability to induce T-cell responses to SEB. Higher doses of UVB (more than 60 mJ/cm²) reduced the accessory cell ability of LC-EC for SEB up to 50% of control. The addition of monoclonal antibodies against adhesion molecules between LC and T cells to the culture resulted in substantial suppression of the T-cell response to SEB induced by nonirradiated LC-EC, while the U VB-irradiated LC-EC-induced T-cell response was not significantly blocked with these monoclonal antibodies. This suggested that the reduction of LC ability for superantigen by high doses of UVB is at least partly due to impairment of adhesion molecules on LC by UVB irradiation.     

Synthesis of 2,5-diaryloxazoles through van Leusen reaction and copper-mediated direct arylation

The direct arylation of 5-aryloxazoles, prepared by the van Leusen reaction, with various aryl iodides is effectively promoted by a system of CuI combined with PPh₃ and Na₂CO₃ as a ligand and a base, respectively, in DMF to produce the corresponding 2,5-diaryloxazoles in good yields.