PRIMARY DNA DAMAGE, HPRT MUTATION AND CELL INACTIVATION PHOTOINDUCED WITH VARIOUS SENSITIZERS IN V79 CELLS

DNA strand breaks and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutants were measured in parallel in photochemically treated (PCT) cells and compared at the same level of cell survival. Chinese hamster fibroblasts (V79 cells) were either incubated with the lipophilic dyes tetra(3—hydroxyphenyl)porphyrin (3THPP) and Photofrin II (PII), the anionic dye meso -tetra(4—sulfonatophenyl)porphine (TPPS₄) or the cationic dye meso -tetra( N -methyl-4-pyridyl)porphine ( p -TMPyPH₂ before light exposure. In the cells, the lipophilic dyes were localized in membranes, including the nuclear membrane, while the hydrophilic dyes were taken up primarily into spots in the cytoplasm. In addition, the hydrophilic TPPS₄ was distributed homogeneously throughout the whole cytoplasm and nucleoplasm. According to the HPRT mutation test, the mutagenicity of light doses survived by 10% of the cells was a factor of six higher in the presence of 3THPP than of PII, whereas for X-rays it was a factor of three higher than for PCT with 3THPP. Light exposure in the presence of the hydrophilic dyes TPPS₄ and p -TMPyPH₂ was not significantly mutagenic. There was no correlation between the induced rates of HPRT mutants and of DNA strand breaks. Thus, TPPS₄ was the most efficient sensitizer with regard to DNA strand breaks when compared at the same level of cell survival, followed by 3THPP, PII and p -TMPyPH₂. Hence, the rate of DNA strand breaks cannot be used to predict the mutagenicity of PCT.     

Absorption Spectra of 4‐Nitrophenolate Ions Measured in Vacuo and in Solution

From blue to red: While four π‐conjugated nitrophenolates absorb within a relatively narrow region in solution, they cover the entire visible spectrum when isolated in vacuo (see picture). The work combines gas‐ and solution‐phase spectroscopy and provides the first benchmark of theoretical excitation energies for nitrophenolates.

     

Chemical ionization of phenyl n-propyl ether and methyl substituted analogs: Propene loss initiated by competing proton transfer to the oxygen atom and the aromatic ring

The mechanism of propene loss from protonated phenyl n-propyl ether and a series of mono-, di-, and trimethylphenyl n-propyl ethers has been examined by chemical ionization (CI) mass spectrometry in combination with tandem mass spectrometry experiments. The role of initial proton transfer to the oxygen atom and the aromatic ring, respectively, has been probed with the use of deuterated CI reagents, D₂O, CD₃OD, and CD₃CN (given in order of increasing proton affinity), in combination with deuterium labeling of the β position of the n-propyl group or the phenyl ring. The metastable [M + D]⁺ ions of phenyl n-propyl ether—formed with D₂O as the CI reagent—eliminate C₃H₅D and C₃H₆ in a ratio of 10:90, which indicates that the added deuteron is incorporated to a minor extent in the expelled neutral species. In the experiments with CD₃OD as the CI reagent, the ratio between the losses of C₃H₅D and C₃H₆ from the metastable [M + D]⁺ ions of phenyl n-propyl ether is 18:82, whereas the ratio becomes 27:73 with CD₃CN as the reagent. A similar trend in the tendency to expel a propene molecule that contains the added deuteron is observed for the metastable [M + D]⁺ ions of phenyl n-propyl ether labeled at the β position of the alkyl group. Incorporation of a hydrogen atom that originates from the aromatic ring in the expelled propene molecule is of negligible importance as revealed by the minor loss of C₃H₅D from the metastable [M + H]⁺ ions of C₆D₅OCH₂CH₂CH₃ irrespective of whether H₂O, CH₃OH, or CH₃CN is the CI reagent. The combined results for the [M + D]⁺ ions of phenyl n-propyl ether and deuterium-labeled analogs are suggested to be in line with a model that assumes that propene loss occurs not only from species formed by deuteron transfer to the oxygen atom, but also from ions generated by deuteron transfer to the ring. This is substantiated by the results for the methyl-substituted ethers, which reveal that the position as well as the number of methyl groups bonded to the ring exert a marked effect on the relative importances of the losses of C₃H₅D and C₃H₆ from the metastable [M + D]⁺ ions of the unlabeled methyl-substituted species.     

Photophysical and Redox Properties of a Series of Phthalocyanines: Relation with Their Photodynamic Activities on TF-1 and Daudi Leukemic Cells

Abstract— The photodynamic therapy (PDT) efficiency of five phthalocyanines, chloroaluminum phthalocyanine (AlPc), dichlorosilicon phthalocyanine (SiPc), bis (tri- n -hexylsi-loxy)silicon phthalocyanine (PcHEX), bis (triphenyl-siloxy)silicon phthalocyanine (PcPHE) and nickel phthalocyanine (NiPc), was assessed on two leukemic cell lines TF-1 and erythroieukemic and B lymphoblastic cell lines, Daudi, respectively. AlPc showed the best photocytotox-icity leading to 0.008 surviving fraction at 2 × 10⁻⁹ M for TF-1 and 4 × 10⁻⁹ M for Daudi. At 5 × 10⁻⁷ M , SiPc and PcHEX induced a significant photokilling, whereas NiPc and PcPHE were inactive. Laser flash photolysis and photoredox properties of the phthalocyanines were investigated to try to relate these parameters with the biological effects. AlPc showed the longest triplet lifetime: 484 fis in dimethyl sulfoxide/H₂O. This value was increased up to 820 u.s when AlPc was complexed with human serum albumin used as a membrane model. Such an enhancement was not observed with the silicon phthalocyanines. Upon irradiation, all the phthalocyanines generated singlet oxygen with 0.29–0.37 quantum yield values. The reduction potentials of the excited states obtained from measurement in the ground state and energy of the excited triplets show that AlPc is the best electron acceptor. The in vitro photocytotoxicity observed and the measured parameters are in agreement with a key role of electron transfer in PDT assays involving these phthalocyanines.     

α-Distonic ions as transient species in the reactions of metastable alkyl benzoate radical cations

The key intermediates to the fragmentation of metastable methyl and ethyl benzoate radical cations are α- and β-distonic isomers of the molecular ions. The α-distocic isomers are also formed by fragmentation of longer chain alkyl benzoates, but may not be long-lived, stable species. Rearrangement of the α-distonic ions prior to fragmentation can take place, but (re)formation of the benzoate molecular ions does not occur.     

Minimal webs in Riemannian manifolds

For a given combinatorial graph G a geometrization (G, g) of the graph is obtained by considering each edge of the graph as a 1-dimensional manifold with an associated metric g. In this paper we are concerned with minimal isometric immersions of geometrized graphs (G, g) into Riemannian manifolds (N ⁿ , h). Such immersions we call minimal webs. They admit a natural ‘geometric’ extension of the intrinsic combinatorial discrete Laplacian. The geometric Laplacian on minimal webs enjoys standard properties such as the maximum principle and the divergence theorems, which are of instrumental importance for the applications. We apply these properties to show that minimal webs in ambient Riemannian spaces share several analytic and geometric properties with their smooth (minimal submanifold) counterparts in such spaces. In particular we use appropriate versions of the divergence theorems together with the comparison techniques for distance functions in Riemannian geometry and obtain bounds for the first Dirichlet eigenvalues, the exit times and the capacities as well as isoperimetric type inequalities for so-called extrinsic R-webs of minimal webs in ambient Riemannian manifolds with bounded curvature.      

Intravascular photoacoustic imaging of human coronary atherosclerosis

We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. The data was obtained from two fresh human coronary arteries ex vivo, showing different stages of disease. A 1.25?mm diameter intravascular imaging catheter was built, comprising an angle-polished optical fiber adjacent to a 30?MHz ultrasound transducer. Specific photoacoustic imaging of lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230?nm. Simultaneous imaging with intravascular ultrasound was performed.