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.     

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.     

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.     

Enriching Science and Math Through Engineering

This case study reviewed the collaborative efforts of university engineers, teacher educators, and middle school teachers to advance sixth‐ and seventh‐grade students' learning through a series of project‐based engineering activities. This two‐year project enriched regular school curricula by introducing real‐world applications of science and mathematics concepts that expanded opportunities for creativity and problem‐solving, introduced problem‐based learning, and provided after‐school programming (for girls only) led by engineering students from the local university. This engineering education initiative showed significant impact on students' (1) confidence in science and mathematics; (2) effort toward science and mathematics; (3) awareness of engineering; and (4) interest in engineering as a potential career. With regard to gender, there were no significant differences between boys' and girls' responses. The girls' confidence in their own skills and potential, however, was significantly more positive than the boys' confidence in the girls. These results gave rise to new questions regarding mentor/mentee relationships and the overall effect of “girls only” mentoring.     

Evaluation of a quantitative structure-property relationship (QSPR) for predicting mid-visible refractive index of secondary organic aerosol (SOA)

In this work we describe and evaluate a simple scheme by which the refractive index (λ = 589 nm) of non-absorbing components common to secondary organic aerosols (SOA) may be predicted from molecular formula and density (g cm(-3)). The QSPR approach described is based on three parameters linked to refractive index-molecular polarizability, the ratio of mass density to molecular weight, and degree of unsaturation. After computing these quantities for a training set of 111 compounds common to atmospheric aerosols, multi-linear regression analysis was conducted to establish a quantitative relationship between the parameters and accepted value of refractive index. The resulting quantitative relationship can often estimate refractive index to ±0.01 when averaged across a variety of compound classes. A notable exception is for alcohols for which the model consistently underestimates refractive index. Homogenous internal mixtures can conceivably be addressed through use of either the volume or mole fraction mixing rules commonly used in the aerosol community. Predicted refractive indices reconstructed from chemical composition data presented in the literature generally agree with previous reports of SOA refractive index. Additionally, the predicted refractive indices lie near measured values we report for λ = 532 nm for SOA generated from vapors of α-pinene (R.I. 1.49-1.51) and toluene (R.I. 1.49-1.50). We envision the QSPR method may find use in reconstructing optical scattering of organic aerosols if mass composition data is known. Alternatively, the method described could be incorporated into in models of organic aerosol formation/phase partitioning to better constrain organic aerosol optical properties.     

Optical probing and imaging of live cells using SERS labels

During surface‐enhanced Raman scattering (SERS), molecules exhibit a significant increase in their Raman signals when attached, or in very close vicinity, to gold or silver nanostructures. This effect is exploited as the basis of a new class of optical labels. Here we demonstrate robust and sensitive SERS labels as probes for imaging live cells. These hybrid labels consist of gold nanoparticles with Rose Bengal or Crystal Violet attached as reporter molecules. These new labels are stable and nontoxic, do not suffer from photobleaching, and can be excited at any excitation wavelength, even in the near infrared. SERS labels can be detected and imaged through the specific Raman signatures of the reporters. In addition, surface‐enhanced Raman spectroscopy in the local optical fields of the gold nanoparticles also provides sensitive information on the immediate molecular environment of the label in the cell and allows imaging of the native constituents of the cell. This is demonstrated by images based on a characteristic Raman line of the reporter as well as by displaying lipids based on the SERS signal of the C H deformation/bending modes at ∼1470 cm⁻¹. Copyright © 2008 John Wiley & Sons, Ltd.