Singlet Oxygen Delivery Through the Porous Cap of a Hollow-Core Fiber Optic Device

The development of the first photosensitizer/fiber optic device is reported. An oxygen-flowing, fiber-capped configuration is used for the application of heterogeneous, spatially confined singlet oxygen delivery in aqueous media. This is a unique device, unlike other heterogeneous photosensitizers, in which local concentrations of singlet oxygen can be delivered via introduction and withdrawal of the fiber tip

Numerical Modeling for the Prediction of Primary Blast Injury to the Lung

As explosive blasts continue to cause casualties in both civil and military environments, there is a need for increased understanding of the mechanisms of blast trauma at the organ level and a need for a more detailed predictive methodology. A fundamental understanding of blast injury will lead to the development of improved protective equipment and ultimately reduce the severity of injury. Models capable of predicting injury to varied blast loading will also reduce the emphasis on animal blast testing. To provide some historical context, this research was begun shortly after the U.S. led invasion of Iraq, and came to a close while there continues to be daily loss of life from blast injuries in the Middle East, as well as continued threats of terrorism throughout the world. In addition to industrial accidents, it is clear that blast injury is far more than just a military concern. Simplified finite element models of the human and sheep thoraces were created in order to provide practical and flexible models for the prediction of primary blast injury in simple and complex blast environments, and subsequently for the development of improved protective equipment. The models were created based on actual human and sheep geometries and published material properties. The fluid-structure interaction of the models compared well with experimental blast studies carried out during the course of the research, as shown by comparing actual and predicted overpressures in the free field and at the thorax. By comparing the models to published experimental data from simple blasts, trends in the results were verified and peak lung pressure was proposed as a trauma criterion. Local extent of injury in the lung is correlated to the peak pressure measured in each finite element, categorized as no injury ( 240 kPa). The calculation of the mean value of the peak lung pressures of all of the finite elements allows for an overall estimate of the injury level, with 35 kPa predicting threshold damage, 129 kPa for one percent lethality, and 186 kPa for fifty percent lethality. The simple blast results also compared well to the predictions of two previously validated mathematical models. Variation of predicted injury within a given loading severity was 15%, which is comparable to the model by Stuhmiller that had a variation of 20%. The model by Axelsson had very little variation (1.4%), but the differences between levels of severity were quite small, and often difficult to decipher. In addition to predicting consistent levels of injury, the finite element models were able to provide insight into the trauma mechanism, map the extent of injury through the lungs, and validate a local injury criterion. The models were then applied to predict injury under complex blast loading by subjecting the human finite element torso to a threshold level blast while located at varying distances from a wall or a corner. The results compared well to the validated mathematical models, showing a sharp increase in injury severity as the model approached the reflecting surface. When directly against the wall, the mean of the peak lung pressure values was 57 kPa, and in the corner, the mean value reached 69 kPa. Although these values did not reach the level representing one percent lethality, they do represent a significant increase in injury above threshold as a direct result of the surrounding geometry. Once again, the finite element models correctly showed injury trends and lung injury patterns reported in experiments. The models predicted the level of injury and were able to predict the time varying pattern of injury, which is something existing models cannot do. Having designed the models from physical principals, and having validated the models against published results, they can now be used in the continued development of protective equipment. Acknowledging that this model was the first iteration, the author believes that improvements in material properties, mesh refinement, and the investigation of other possible parameters for the prediction of injury will lead to substantial advances in the understanding of primary blast injury

Practical Aspects in the Study of Biological Photosensitization Including Reaction Mechanisms and Product Analyses: A Do's and Don'ts Guide

The interaction of light with natural matter leads to a plethora of photosensitized reactions. These reactions cause the degradation of biomolecules, such as DNA, lipids, proteins, being therefore detrimental to the living organisms, or they can also be beneficial by allowing the treatment of several diseases by photomedicine. Based on the molecular mechanistic understanding of the photosensitization reactions, we propose to classify them in four processes: oxygen-dependent (type I and type II processes) and oxygen-independent [triplet-triplet energy transfer (TTET) and photoadduct formation]. In here, these processes are discussed by considering a wide variety of approaches including time-resolved and steady-state techniques, together with solvent, quencher, and scavenger effects. The main aim of this survey is to provide a description of general techniques and approaches that can be used to investigate photosensitization reactions of biomolecules together with basic recommendations on good practices. Illustration of the suitability of these approaches is provided by the measurement of key biomarkers of singlet oxygen and one-electron oxidation reactions in both isolated and cellular DNA. Our work is an educational review that is mostly addressed to students and beginners.Fil: Baptista, Maurício S.. Universidade de Sao Paulo; BrasilFil: Cadet, Jean. University of Sherbrooke; CanadáFil: Greer, Alexander. City University of New York; Estados UnidosFil: Thomas, Andrés Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentin

Kinetic Control in the Regioselective Alkylation of Pterin Sensitizers: A Synthetic, Photochemical, and Theoretical Study

Alkylation patterns and excited-state properties of pterins were examined both experimentally and theoretically. 2D NMR spectroscopy was used to characterize the pterin derivatives, revealing undoubtedly that the decyl chains were coupled to either the O4 or N3 sites on the pterin. At a temperature of 70°C, the pterin alkylation regioselectively favored the O4 over the N3. The O4 was also favored when using solvents, in which the reactants had increased solubility, namely N,N-dimethylformamide and N,N-dimethylacetamide, rather than solvents in which the reactants had very low solubility (tetrahydrofuran and dichloromethane). Density functional theory (DFT) computed enthalpies correlate to regioselectivity being kinetically driven because the less stable O-isomer forms in higher yield than the more stable N-isomer. Once formed these compounds did not interconvert thermally or undergo a unimolecular ?walk? rearrangement. Mechanistic rationale for the factors underlying the regioselective alkylation of pterins is suggested, where kinetic rather than thermodynamic factors are key in the higher yield of the O-isomer. Computations also predicted greater solubility and reduced triplet state energetics thereby improving the properties of the alkylated pterins as 1 O 2 sensitizers. Insight on thermal and photostability of the alkylated pterins is also provided.Fil: Walalawela, Niluksha. City University of New York; Estados UnidosFil: Vignoni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. City University of New York; Estados UnidosFil: Urrutia, María Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Belh, Sarah J.. City University of New York; Estados UnidosFil: Greer, Edyta M.. City University of New York; Estados UnidosFil: Thomas, Andrés Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Greer, Alexander. City University of New York; Estados Unido

Highlight Article Photoactive Chitosan: A Step Toward a Green Strategy for Pollutant Degradation

ABSTRACT This article is a highlight of the paper by Ferrari et al. in this issue of Photochemistry and Photobiology. It describes the innovative use of rose bengal-conjugated chitosan as a reusable green catalyst that photo-degrades phenolic compounds in aqueous media, and thereby has decontamination potential of polluted waters. Whether a next-generation photoactive polymer that produces singlet oxygen is a solution to pollutant degradation can be argued. It is as yet unclear what polymeric sensitizer would be practical on a large scale. Nonetheless pursuing this goal is worthwhile

Articles An Adjacent Thioester Provides Apical-Directed Stabilization to 3-Isothiazolidinone 1-Oxide Heterocycles

The structural and energetic features of the attractive intramolecular through-space S-X interaction [X being oxygen (O) or sulfur (S)] of thioester containing 3-isothiazolidinone 1-oxide heterocycles are described. Density functional theoretical and semiempirical calculations are used to explain the previous X-ray data on 3-isothiazolidinone 1-oxides 5 and 6 [Kanda, Y., Ashizawa, T., Kakita, S., Takahashi, Y., Kono, M., Yoshida, M., Saitoh, Y., and Okabe, M. (1999) J. Med. Chem. 42, 1330-1332 and implicate a mechanism where the adjacent thioester participates in an apical-directed stabilization of the sulfur heterocycle. A key factor that distinguishes the S-O interaction from the S-S interaction is the stronger through-space interaction of the former, which is a consequence of the greater electronegativity of apical O compared to apical S. Reaction field theory reveals that the conversion of the S-O interaction to the S-S interaction is more facile compared to gas phase computations, which suggest a reduced importance of the 1,5-S-X interactions in solution. The conversion of the S-O interaction to the S-S interaction gives an isothiazolidinone oxide that places the reacting sulfurs in proximity with an orientation presumably suitable for bond formation and access to the dithiolanone oxide surface. Factors that influence the through-space S-X interactions may represent important issues in identifying target 3-isothiazolidinone 1-oxide prodrugs capable of rearranging to 1,2-dithiolan-3-one 1-oxide drugs

Singlet Oxygen Chemistry in Water. 2. Photoexcited Sensitizer Quenching by O2 at the Water−Porous Glass Interface

Insight into the O2 quenching mechanism of a photosensitizer (static or dynamic) would be useful for the design of heterogeneous systems to control the mode of generation of 1O2 in water. Here, we describe the use of a photosensitizer, meso-tetra(N-methyl-4-pyridyl)porphine (1), which was adsorbed onto porous Vycor glass (PVG). A maximum loading of 1.1 × 10−6 mol 1 per g PVG was achieved. Less than 1% of the PVG surface was covered with photosensitizer 1, and the penetration of 1 reaches a depth of 0.32 mm along all faces of the glass. Time-resolved measurements showed that the lifetime of triplet 1*-ads was 57 μs in water. Triplet O2 quenched the transient absorption of triplet 1*-ads; for samples containing 0.9 × 10−6−0.9 × 10−8 mol 1 adsorbed per g PVG, the Stern−Volmer constant, KD, ranged from 23 700 to 32 100 M−1. The adduct formation constant, KS, ranged from 1310 to 510 M−1. The amplitude of the absorption at 470 nm decreased slightly (by about 0.1) with increased O2 concentrations. Thus, the quenching behavior of triplet 1*-ads by O2 was proposed to be strongly dependent on dynamic quenching. Only ∼10% of the quenching was attributed to the static quenching mechanism. The quenching of triplet 1*-ads was similar to that observed for photosensitizers in homogeneous solution which are often quenched dynamically by O2

Combination Treatment with Sublethal Ionizing Radiation and the Proteasome Inhibitor, Bortezomib, Enhances Death-Receptor Mediated Apoptosis and Anti-Tumor Immune Attack

Sub-lethal doses of radiation can modulate gene expression, making tumor cells more susceptible to T-cell-mediated immune attack. Proteasome inhibitors demonstrate broad anti-tumor activity in clinical and pre-clinical cancer models. Here, we use a combination treatment of proteasome inhibition and irradiation to further induce immunomodulation of tumor cells that could enhance tumor-specific immune responses. We investigate the effects of the 26S proteasome inhibitor, bortezomib, alone or in combination with radiotherapy, on the expression of immunogenic genes in normal colon and colorectal cancer cell lines. We examined cells for changes in the expression of several death receptors (DR4, DR5 and Fas) commonly used by T cells for killing of target cells. Our results indicate that the combination treatment resulted in increased cell surface expression of death receptors by increasing their transcript levels. The combination treatment further increases the sensitivity of carcinoma cells to apoptosis through FAS and TRAIL receptors but does not change the sensitivity of normal non-malignant epithelial cells. Furthermore, the combination treatment significantly enhances tumor cell killing by tumor specific CD8+ T cells. This study suggests that combining radiotherapy and proteasome inhibition may simultaneously enhance tumor immunogenicity and the induction of antitumor immunity by enhancing tumor-specific T-cell activity