Tissue distribution and in vivo photosensitizing activity of 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester

Photosensitizers 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 (HPC) and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester (MMC) absorb at 711 nm and possess high photoinduced cytotoxicity in vitro. Here we report, that photodynamic therapy with HPC and MMC provide considerable antitumor effect in mice bearing subcutaneous P338 lymphoma. The highest antitumor effect was achieved at a dose of 4 micromol/kg when 1.5 h delay between dye injection and light irradiation (drug-light interval) was used. According to the confocal spectral imaging studies of tissue sections this drug-light interval corresponds to a maximum of tumor accumulation of MMC and HPC (tumor to skin accumulation ratio is 8-10). Short (15 min) drug-light interval can be used for efficient vasculature-targeted photodynamic therapy with HPC at a dose of 1 micromol/kg, whereas MMC is ineffective at the short drug-light interval. Relationships between the features of tissue distribution and efficacy of photodynamic therapy at different drug-light intervals are discussed for HPC and MMC.     

Ab initio studies on nanoscale friction between fluorinated diamond surfaces: effect of model size and level of theory

Interactions between two fluorinated diamond surfaces placed in contact with each other were investigated with quantum chemical Hartree-Fock and M?ller-Plesset perturbation theory and basis sets def-SV(P), def-TZVP, and 6-31G. Two models, C(6)H(6)F(3)-C(24)H(24)F(12) and C(13)H(16)F(6)-C(22)H(24)F(10), were used to examine how model size and level of theory affect the atomic-scale friction, especially the coefficient of friction. Also of interest was a comparison of the interaction energies of the two models with different stacking configurations. The averages of the calculated friction coefficients fell within the range of values 0.28-0.43.     

Magnetic and luminescent properties of manganese-doped ZnSe crystals

Magnetic and photoluminescent properties of manganese-doped ZnSe crystals with different impurity concentrations were investigated. The concentration of Mn²⁺ ions in ZnSe crystals has been varied from 0.01 to 0.3 at%. Magnetic and photoluminescent studies have confirmed the introduction of Mn in ZnSe crystals. It was established that Mn²⁺ ions are responsible for the emission bands with maximum at 616 nm and 633 nm, which correspond to ⁴T₂→⁶A₁ and ⁴T₁→⁶A₁ intracentre transitions of Mn²⁺ ions respectively. It was found that the concentration quenching of the photoluminescent bands is associated with Mn²⁺ ions, which are due to the formation of Mn–Mn clusters. Magnetic properties studies have shown that at high doping levels the manganese atoms form Mn–Mn clusters in ZnSe. From the temperature dependence of magnetic susceptibility of ZnSe:Mn crystals that follows the Curie–Weiss law, it was possible to estimate the Curie–Weiss temperature Θ(x) and the effective Mn–Mn antiferromagnetic exchange constant (J₁).     

The role of the alien proton acceptor on the formation of LC structure in H-bonded monomeric and polymeric derivatives of alkoxybenzoic acids

The formation of the complex between 4-cyanopyridine and 4-(6-acryloyloxy-hexyloxy) benzoic acid and its polymeric analog proceeds due to the proton transfer with the H-bond formation. The presence of two proton acceptor groups within one molecule provides a strong shift of the electron density along the complex molecule due to the conjugation within the proton acceptor molecule. The dielectric relaxation process in a symmetric associate experimentally observed is explained as a kinetic effect related to the formation and destruction of the associate.

Transition from a monomer to a polymer proton donor leads to the formation of the characteristic 1:1 complex with SmC layered structure different from that of a polymer itself.     

Near-infrared photosensitizer based on a cycloimide derivative of chlorin p6: 13,15-N-(3'-hydroxypropyl)cycloimide chlorin p6

The 13,15-N-(3'-hydroxypropylcycloimide) chlorin p6 (CIC), which absorbs at 711 nm, possesses considerable photoinduced cell-killing activity. It is 43-, 61- and 110-fold more active than chlorin p6, 3-formyl-3-devinyl chlorin p6 and Photogem, respectively, and has no cytotoxicity without irradiation as estimated on A549 human adenocarcinoma cells. To attain the highest intracellular penetration and activity the monomeric form of CIC should be stabilized. This stabilization in an aqueous environment can be achieved using 0.002-0.005% of Cremophor EL emulsion (polyoxyethylene derivative of hydrogenated castor oil). The intracellular accumulation of CIC occurs in cytoplasm in a monomeric form bound to cellular membranes. This form of the dye is characterized by a high quantum yield of singlet oxygen generation (0.66 +/- 0.02). Besides diffuse staining of intracellular membranous structures, CIC accumulates 3- to 4-fold more intensely in mitochondria and Golgi apparatus, thus indicating these organelles to be the initial targets of its photodynamic action. The incubation time providing 50% accumulation level of CIC in cells is 30 +/- 5 min. The time for 50% release of CIC from the cells is 60 +/- 10 min. A 10-fold decrease in CIC intracellular penetration at 22 degrees C proves that temperature-sensitive mechanisms of transport, rather than diffusion, are responsible for the dye uptake. The average cytoplasmic concentration of CIC was seven times the extracellular concentration in the 0.2-1.6 microM range, used for the photodynamic activity measurements. The concentration of CIC and the light dose that correspond to ca 50% level of phototoxicity induce predominantly an apoptotic-type of cell death, whereas the conditions providing 100% level of phototoxicity induced necrosis. The results obtained indicate that cycloimide derivatives of chlorin p6 may serve as a base for the development of an efficient near-IR photosensitizer.     

Chelation with metal is not essential for antitumor photodynamic activity of sulfonated phthalocyanines

It is generally assumed that a central metal is essential for the efficiency of phthalocyanines in photodynamic therapy (PDT) of cancer. Contrary to the set opinion, the results of the present study indicate that the metal-free sulfonated phthalocyanines (H2PcSn, where n is the number of sulfonate groups per molecule) possess a considerable photoactivity. The relative phototoxicities of H2PcS1.5, H2PcS2.4, H2PcS3.1 and H2PcS3.8 on HEp2 human epidermoid carcinoma cells were 3.3, 20, 3.3 and 1, respectively, thus demonstrating dependence of the activity on the sulfonation degree, known for metallo-PcSn. A significant delay in tumor growth and a decrease in tumor regrowth rate were observed in mice after PDT with H2PcS2.4. The antitumor effect declined in the order H2PcS2.4 > H2PcS3.1 > H2PcS1.5 and vanished for H2PcS3.8. We demonstrate here that the high photodynamic activity of H2PcS2.4 can be explained by its physicochemical properties in living cells and tissues. Thus, H2PcSn (n is about 2) can be considered as a new alternative in PDT of light-accessible neoplasms and further clinic-oriented studies are warranted.     

Ab initio studies on nanoscale friction between graphite layers: effect of model size and level of theory

Ab initio methods were used to investigate the nanoscale friction between two graphite layers placed in contact. The interaction energies were calculated for four two-layer models in series, C(6(n+1))2H(6n+1))-C(6)(n)2H(6)(n) with n = 1, 2, 3, and 4, and additionally for C(54)H(18)-C(6)H(6) and C(150)H(30)-C(6)H(6). The study was done with the Hartree-Fock method using basis sets 3-21G and 6-31G and with the second-order M?ller-Plesset theory using basis set 6-31G. A density functional method (B3PW91) was also tested for reference purposes. The main interest was how the model size and level of theory affect the nanoscale friction coefficient. Most of the calculated friction coefficients fell within the range of values of 0.07-0.14.