Quantum yields of triplet and O2(1 delta g) formation of 4-thiouridine in water and acetonitrile

The quantum yield of triplet formation, phi T, and that of the photosensitized formation of singlet molecular oxygen, phi delta, were determined for a rare nucleoside, 4-thiouridine (4t-Urd), in water and in acetonitrile, using singlet molecular oxygen phosphorescence, laser-induced optoacoustics and time-resolved thermal lensing. These yields, phi T and phi delta, the latter in aerated solutions, were found to be, respectively, in water: 0.67 +/- 0.17 and 0.18 +/- 0.04 and in acetonitrile: 0.61 +/- 0.15 and 0.50 +/- 0.20. The fraction of the 4t-Urd triplet molecules quenched by oxygen leading to singlet molecular oxygen, S delta, was calculated to be between 0.7 and unity in both solvents, this value being indicative of a pi pi*character for the lowest triplet state of 4t-Urd.     

MEROCYANINE DYES: EFFECT OF STRUCTURAL MODIFICATIONS ON PHOTOPHYSICAL PROPERTIES AND BIOLOGICAL ACTIVITY

Abstract Merocyanine derivatives were prepared by structural alterations at the barbituric acid or chalcogenazole moieties. The photophysical properties of the dyes were markedly influenced by the presence of selenium rather than sulfur as a substituent at position 2 of the barbiturate. In methanol, quantum yields of both triplet state (φ_τ) and singlet oxygen sensitization (φ_Δ) were increased by over an order of magnitude, with a concomitant decrease in fluorescence, when selenium was present in the molecule. Photoisomerization, one of the dominant deactivation pathways in the sulfur- or oxygen-containing analogues, was completely absent in the selenium-containing derivatives. Efficient triplet state formation was observed for selenium-containing derivatives incorporated into L1210 cells by diffuse reflectance laser flash photolysis. Cytotoxicity studies, camed out using clonogenic assays on L1210 leukemia cells, showed a good correlation with φ_τ and φ_Δ, measured in solution. Experimental evidence provided by this paper supports a triplet state-, and probably singlet oxygen-, mediated phototoxic mechanism. Photoisomerization or singlet state mechanisms can be discounted.     

Environmental Effects on Cellular Photosensitization: Correlation of Phototoxicity Mechanism with Transient Absorption Spectroscopy Measurements

Abstract— Little is directly known about the influence of the local environment experienced by a photosensitizer in a biological system on its photophysics and photochemistry. In this paper, we have addressed this issue by correlating mechanistic studies using laser flash photolysis with cellular phototoxicity data, obtained under the same experimental conditions. In particular, we have focused on the interaction between local concentrations of photosensitizer (deuteroporphyrin) and oxygen in determining the mechanism of phototoxicity in L1210 cells. In cells, as well as in models such as liposomes and red blood cell ghosts, hypochromicity and a reduction in fluorescence and intersystem crossing yields are observed on increasing the photosensitizer concentration between 0.5 and 20 μM, which illustrates the onset of a self-association. In aerated cellular preparations, the phototoxicity is predominantly type II (singlet oxygen) for all concentrations studied but an oxygen-independent mechanism occurs at the higher concentrations in deaerated samples. These observations are readily explained by consideration of triplet state kinetics as a function of oxygen and photosensitizer concentrations in cells. The rate constant for quenching of the photosensitizer triplet state by oxygen in cells was measured as 6.6 × 10⁸ M^?1 s^?1 and by photosensitizer ground state as -10⁶M^?1s^?1 (in terms of local concentration). The latter reaction gave rise to a long-lived species that is presumably responsible for the oxygen-independent phototoxicity observed at the higher photosensitizer concentrations used. This self-quenching of the triplet state is postulated to arise from electron transfer resulting in radical ion formation. Under conditions where no self-quenching contributes, the phototoxicity measured as a function of oxygen concentration correlates well with a model based on the determined kinetic parameters, thus, unambiguously proving the intermediacy of singlet oxygen. These effects should be borne in mind when interpreting phototoxicity mechanisms from in vitro cell studies. The excellent correlation achieved between laser flash photolysis data and measured phototoxicity gives credence to the direct use of photophysical techniques to elucidate photochemical mechanisms in biological media.     

Can Cellular Phototoxicity be Accurately Predicted on the Basis of Sensitizer Photophysics?

The phototoxicity of three structurally related photosensitizers (PS), deuteroporphyrin IX (DP) and monobromo (Br-DP) and dibromo (Br2-DP) derivatives, was studied in murine L1210 leukemia cells. These compounds were chosen on the basis of heavy-atom-induced differences in triplet yield, phi T, and lifetime, tau T, and used as tools to test a model for phototoxicity based on photophysical parameters. All three porphyrins were found to localize preferentially in the plasma membrane of L1210 cells by confocal fluorescence microscopy. A poor correlation was observed between the measured photodynamic efficacies of these PS and a model using photophysical parameters determined by laser flash photolysis in homogeneous solution. However, an excellent correlation was obtained when the same parameters measured directly in the cells were used. The biological microenvironment of the porphyrins in cells induces significant changes in the photophysics of the PS. Reduction in fluorescence yield, phi F, and phi T observed for Br2-DP in cell suspensions arises from self association of the molecule due to increased hydrophobicity and high local concentrations. The photophysical model was also tested for its ability to handle variations in the oxygen dependence of cellular phototoxicity of these PS. The good correlation achieved between laser flash photolysis data determined in cells and the measured phototoxicity under air, 1.5% and 0.5% O2-saturated conditions, proves the intermediacy of singlet oxygen. This study gives further credence to the direct use of photophysical techniques to elucidate photochemical mechanisms in biological media while highlighting the potential pitfalls of using solution data to predict photosensitizing potential.     

Self-assembly of a functional electronic circuit directed by capillary interactions

We report on the use of capillary interactions to drive the self-assembly of an electronic circuit based on mesoscale building blocks. The specific target structure is a linear heterotetramer comprising non-identical millimetre-scale cubic blocks that, following assembly, forms a functioning astable multivibrator circuit. Importantly, the self-assembly process is designed to be unconstrained, i.e., each of the blocks are free to move in any way during assembly. To this end, solder droplets are selectively patterned on the block faces. On contact, capillary interactions between shape complimentary solder patterns on the blocks cause the molten solder droplets to coalesce and the blocks to self-assemble. In this way, capillary forces direct the alignment, registration, linking and electrical interconnection of each block during the assembly process. This demonstration of mesoscale self-assembly mediated by capillary interactions illustrates that the application of unconventional assembly paradigms to complex structure fabrication is feasible and that these approaches may yet yield viable strategies for fabrication of highly integrated systems.     

An Analysis of Drug Dissolution Rates in the USP 24 Type 2 Apparatus

This paper applies boundary layer theory to the process of drug dissolution in the USP 24, Type 2 Apparatus. The mass transfer rate from the top flat surface of a compact in various positions within the device is evaluated by means of a Pohlhausen integral method. (© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Intrinsic chromatic switching of visible luminescence in Yb3+,Er3+:CsCdBr3

Bistability is reported in sensitized Er3+ luminescence driven by an Yb3+ transition that previously revealed an Yb3+ luminescent instability. To our knowledge this is the first report of bistable energy transfer between different rare-earth ions.     

Application of covering techniques to families of curves

Much success in finding rational points on curves has been obtained by using Chabauty's Theorem, which applies when the genus of a curve is greater than the rank of the Mordell-Weil group of the Jacobian. When Chabauty's Theorem does not directly apply to a curve , a recent modification has been to cover the rational points on by those on a covering collection of curves , obtained by pullbacks along an isogeny to the Jacobian; one then hopes that Chabauty's Theorem applies to each . So far, this latter technique has been applied to isolated examples. We apply, for the first time, certain covering techniques to infinite families of curves. We find an infinite family of curves to which Chabauty's Theorem is not applicable, but which can be solved using bielliptic covers, and other infinite families of curves which even resist solution by bielliptic covers. A fringe benefit is an infinite family of Abelian surfaces with non-trivial elements of the Tate-Shafarevich group killed by a bielliptic isogeny.     

Transform-Limited Pulses Are Not Optimal for Resonant Multiphoton Transitions

Maximizing nonlinear light-matter interactions is a primary motive for compressing laser pulses to achieve ultrashort transform limited pulses. Here we show how, by appropriately shaping the pulses, resonant multiphoton transitions can be enhanced significantly beyond the level achieved by maximizing the pulse's peak intensity. We demonstrate the counterintuitive nature of this effect with an experiment in a resonant two-photon absorption, in which, by selectively removing certain spectral bands, the peak intensity of the pulse is reduced by a factor of 40, yet the absorption rate is doubled. Furthermore, by suitably designing the spectral phase of the pulse, we increase the absorption rate by a factor of 7.