Multifunctional Polyoxometalate Platforms for Supramolecular Light-Driven Hydrogen Evolution

Multifunctional supramolecular systems are a central research topic in light-driven solar energy conversion. Here, we report a polyoxometalate (POM)-based supramolecular dyad, where two platinum-complex hydrogen evolution catalysts are covalently anchored to an Anderson polyoxomolybdate anion. Supramolecular electrostatic coupling of the system to an iridium photosensitizer enables visible light-driven hydrogen evolution. Combined theory and experiment demonstrate the multifunctionality of the POM, which acts as photosensitizer/catalyst-binding-site[1] and facilitates light-induced charge-transfer and catalytic turnover. Chemical modification of the Pt-catalyst site leads to increased hydrogen evolution reactivity. Mechanistic studies shed light on the role of the individual components and provide a molecular understanding of the interactions which govern stability and reactivity. The system could serve as a blueprint for multifunctional polyoxometalates in energy conversion and storage

Pyrimidoquinazolinophenanthroline Opens Next Chapter in Design of Bridging Ligands for Artificial Photosynthesis **

The synthesis and detailed characterization of a new Ru polypyridine complex containing a heteroditopic bridging ligand with previously unexplored metal‐metal distances is presented. Due to the twisted geometry of the novel ligand, the resultant division of the ligand in two distinct subunits leads to steady state as well as excited state properties of the corresponding mononuclear Ru(II) polypyridine complex resembling those of prototype [Ru(bpy) 3 ] 2+ (bpy=2,2'‐bipyridine). The localization of the initially optically excited and the nature of the long‐lived excited states on the Ru‐facing ligand spheres is evaluated by resonance Raman and fs‐TA spectroscopy, respectively, and supported by DFT and TDDFT calculations. Coordination of a second metal (Zn or Rh) to the available bis‐pyrimidyl‐like coordination sphere strongly influences the frontier orbitals, apparent by, for example, luminescence quenching. Thus, the new bridging ligand motif offers electronic properties, which can be adjusted by the nature of the second metal center. Using the heterodinuclear Ru−Rh complex, visible light‐driven reduction of NAD + to NADH was achieved, highlighting the potential of this system for photocatalytic applications

Induction of plasminogen activator inhibitor type-1 (PAI-1) by hypoxia and irradiation in human head and neck carcinoma cell lines

Contains fulltext : 53187.pdf ( ) (Open Access)BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) often contain highly radioresistant hypoxic regions, nonetheless, radiotherapy is a common treatment modality for these tumours. Reoxygenation during fractionated radiotherapy is desired to render these hypoxic tumour regions more radiosensitive. Hypoxia additionally leads to up-regulation of PAI-1, a protein involved in tumour progression and an established prognostic marker for poor outcome. However, the impact of reoxygenation and radiation on PAI-1 levels is not yet clear. Therefore, we investigated the kinetics of PAI-1 expression and secretion after hypoxia and reoxygenation, and determined the influence of ionizing radiation on PAI-1 levels in the two human SCCHN cell lines, BHY and FaDu. METHODS: HIF-1alpha immunoblot was used to visualize the degree of hypoxia in the two cell lines. Cellular PAI-1 expression was investigated by immunofluorescence microscopy. ELISA was used to quantify relative changes in PAI-1 expression (cell lysates) and secretion (cell culture supernatants) in response to various lengths (2-4 h) of hypoxic exposure (< 0.66% O2), reoxygenation (24 h, 20% O2), and radiation (0, 2, 5 and 10 Gy). RESULTS: HIF-1alpha expression was induced between 2 and 24 h of hypoxic exposure. Intracellular PAI-1 expression was significantly increased in BHY and FaDu cells as early as 4 h after hypoxic exposure. A significant induction in secreted PAI-1 was seen after 12 to 24 h (BHY) and 8 to 24 h (FaDu) hypoxia, as compared to the normoxic control. A 24 h reoxygenation period caused significantly less PAI-1 secretion than a 24 h hypoxia period in FaDu cells. Irradiation led to an up-regulation of PAI-1 expression and secretion in both, BHY and FaDu cells. CONCLUSION: Our data suggest that both, short-term (approximately 4-8 h) and long-term (approximately 20-24 h) hypoxic exposure could increase PAI-1 levels in SCCHN in vivo. Importantly, radiation itself could lead to PAI-1 up-regulation in head and neck tumours, whereas reoxygenation of hypoxic tumour cells during fractionated radiotherapy could counteract the increased PAI-1 levels

Cobaloxime complex salts : synthesis, patterning on carbon nanomembranes and heterogeneous hydrogen evolution studies

Cobaloximes are promising, earth-abundant catalysts for the light-driven hydrogen evolution reaction. Typically, these cobalt(III) complexes are prepared in situ or employed in their neutral form, e.g. [Co(dmgH 2 )(py)Cl], even though related complex salts have been reported previously and could in principle offer improved catalytic activity as well as more efficient immobilization on solid support. Here we report an interdisciplinary investigation into complex salts [Co(dmgH) 2 (py) 2 ] + [Co(dmgBPh 2 ) 2 Cl 2 ] - , TBA + [Co(dmgBPh 2 ) 2 Cl 2 ] - and [Co(dmgH) 2 (py) 2 ] + BArF - . We describe their strategic syntheses from commercially available complex [Co(dmgH) 2 (py)Cl] and demonstrate that these double and single complex salts are potent catalysts for the light-driven hydrogen evolution reaction. We also show that scanning electrochemical cell microscopy can be used to deposit arrays of catalysts [Co(dmgH) 2 (py) 2 ] + [Co(dmgBPh 2 ) 2 Cl 2 ] - and [Co(dmgH) 2 (py)Cl] on supported and free-standing amino-terminated ~ 1 nm thick carbon nanomembranes (CNMs). Photocatalytic H 2 evolution at such arrays was quantified with Pd microsensors using scanning electrochemical microscopy, thus providing a new approach for catalytic evaluation and opening up novel routes for the creation and analysis of “designer catalyst arrays”, nano-printed in a desired pattern on a solid support

Combined mRNA expression levels of members of the urokinase plasminogen activator (uPA) system correlate with disease-associated survival of soft-tissue sarcoma patients

<p>Abstract</p> <p>Background</p> <p>Members of the urokinase-type plasminogen activator (uPA) system are up-regulated in various solid malignant tumors. High antigen levels of uPA, its inhibitor PAI-1 and its receptor uPAR have recently been shown to be associated with poor prognosis in soft-tissue sarcoma (STS) patients. However, the mRNA expression of uPA system components has not yet been comprehensively investigated in STS patients.</p> <p>Methods</p> <p>The mRNA expression level of uPA, PAI-1, uPAR and an uPAR splice variant, uPAR-del4/5, was analyzed in tumor tissue from 78 STS patients by quantitative PCR.</p> <p>Results</p> <p>Elevated mRNA expression levels of PAI-1 and uPAR-del4/5 were significantly associated with clinical parameters such as histological subtype (<it>P </it>= 0.037 and <it>P </it>< 0.001, respectively) and higher tumor grade (<it>P </it>= 0.017 and <it>P </it>= 0.003, respectively). In addition, high uPAR-del4/5 mRNA values were significantly related to higher tumor stage of STS patients (<it>P </it>= 0.031). On the other hand, mRNA expression of uPA system components was not significantly associated with patients' survival. However, in STS patients with complete tumor resection (R0), high PAI-1 and uPAR-del4/5 mRNA levels were associated with a distinctly increased risk of tumor-related death (RR = 6.55, <it>P </it>= 0.054 and RR = 6.00, <it>P </it>= 0.088, respectively). Strikingly, R0 patients with both high PAI-1 and uPAR-del4/5 mRNA expression levels showed a significant, 19-fold increased risk of tumor-related death (<it>P </it>= 0.044) compared to the low expression group.</p> <p>Conclusion</p> <p>Our results suggest that PAI-1 and uPAR-del4/5 mRNA levels may add prognostic information in STS patients with R0 status and distinguish a subgroup of R0 patients with low PAI-1 and/or low uPAR-del4/5 values who have a better outcome compared to patients with high marker levels.</p

Characteristics of the level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1.

Item does not contain fulltextIn cancer, the serine protease urokinase-type plasminogen activator, its inhibitor (plasminogen activator inhibitor type-1) and the receptor (CD87), among other proteolytic factors, are involved in tumor cell dissemination and turnover of the extracellular matrix. Unsurprisingly, a battery of very uniform data, amassed since the end of the 1990s, has put these members of the plasminogen activation system into the forefront of prognostic/predictive cancer biomarkers relevant to predict the clinical course of cancer patients and their response to cancer therapy. The present review focuses on the molecular characteristics of the disease forecast biomarkers urokinase-type plasminogen activator and plasminogen activator inhibitor type-1, and techniques to quantitatively assess these cancer biomarkers, in the context of potential clinical application and personalized disease management.1 oktober 201