Enzymes from the histone deacetylase (HDAC) family are highly regulated by different mechanisms. However, only very limited knowledge exists about the regulation of HDAC8, an established target in multiple types of cancer. A previous dedicated study of HDAC class I enzymes identified no redox-sensitive cysteinyl thiol in HDAC8. This is in contrast to the observation that HDAC8 preparations show different enzyme activities depending on the addition of reducing agents. In the light of the importance of HDAC8 in tumorigenesis a possible regulation by redox signaling was investigated using biochemical and biophysical methods combined with site directed mutagenesis. The occurrence of a characteristic disulfide bond under oxidizing conditions is associated with a complete but reversible loss of enzyme activity. Cysteines 102 and 153 are the integral components of the redox-switch. A possible regulation of HDAC8 by redox signal transduction is suggested by the observed relationship between inhibition of reactive oxygen species generating NOX and concomitant increased HDAC8 activity in neuroblastoma tumor cells. The slow kinetics for direct oxidation of HDAC8 by hydrogen peroxide suggests that transmitters of oxidative equivalents are required to transfer the H2O2 signal to HDAC8.

Human histoned eacetylase 8i saw ell-recognized target forT-cell lymphomaa nd particularly childhoodn euroblastoma. PD-404,182 was shown to be as elective covalent inhibitor of HDAC8t hat formsm ixed disulfides with several cysteine residues and is also able to transform thiol groups to thiocyanates. Moreover,H DAC8 was shown to be regulated by ar edox switch based on the reversible formation of a disulfideb ond between cysteines Cys 102 andC ys 153 .T his study on the distinct effects of PD-404,182 on HDAC8 reveals that this compound induces the dose-dependent formationo fi ntramolecular disulfide bridges. Therefore,t he inhibition mechanism of HDAC8b yP D-404,182 involves both, covalentmodification of thiols as well as ligand mediated disulfide formation. Moreover,t his study provides ad eep moleculari nsighti ntot he regulation mechanismo fH DAC8i nvolvings everal cysteines with graduated capability to form reversible disulfide bridges.

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Photochemical reactions typically proceed via multiple reaction pathways, yielding a variety of isomers and products. Enhancing the selectivity is challenging. Now, the potential of supramolecular control for oxidative photocyclization of a tetraarylethylene, containing a stereogenic -C=C- bond, is demonstrated. In solution, this photochemical reaction produces three constitutional isomers (substituted phenanthrenes), with slow kinetics. When the reactant is assembled into a crystalline framework, only one product forms with accelerated kinetics. Key to this selectivity enhancement is the integration into a surface grown metal-organic framework (SURMOF); the dramatic gain in selectivity is ascribed to the hindrance of the rotational freedom of the -C=C- double bond. The structure of the MOF is key; the corresponding reaction in the solid does not result in such a high increase in selectivity. A striking change of luminescence properties after photocyclization is observed.

Background and objectives Red blood cells that are stored for transfusions as red cell concentrates (RCCs) undergo changes during the storage period, culminating in the lysis of the cells. The goal of this work is to find markers that are linked to high haemolysis, in order to explain the inter-donor variability that is known to occur in storage quality, and also the known differences between RCCs from male and female donors. Materials and methods The relative amounts of lipids at the end of the storage period were compared for one group of low haemolysis samples (24 units, all ≤0Á15% haemolysis), and one group of high haemolysis samples (26 units, all ≥0Á5% haemolysis). Representative lipids were analysed from different lipid classes, including cholesterol, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin and ceramide. Whole membrane preparations were analysed with one mass spectrometry technique, and lipid extracts were analysed with a second mass spectrometry technique. Results The ratio of palmitoyl-oleoyl phosphatidylcholine (POPC) to sphingomyelin was different for the high and low haemolysis groups (P = 0Á0001) and for the RCCs from male and female donors (P = 0Á0009). The ratio of cholesterol to phospholipids showed only minimal links to haemolysis. Higher relative amounts of sphingomyelin were associated with lower haemolysis, and higher relative amounts of ceramides were associated with increased haemolysis. Conclusion The level of sphingomyelinase activity and the resulting ratio of sphingomyelin to POPC is proposed as a possible marker for RCC storage quality.

Metal–organic frameworks (MOFs) built from different building units offer functionalities going far beyond gas storage and separation. In connection with advanced applications, e.g., in optoelectronics, hierarchical MOF-on-MOF structures fabricated using sophisticated methodologies have recently become particularly attractive. Here, we demonstrate that the structural complexity of MOF-based architectures can be further increased by employing highly spatioselective photochemistry. Using a layer-by-layer, quasi-epitaxial synthesis method, we realized a photoactive MOF-on-MOF hetero-bilayer consisting of a porphyrinic bottom layer and a tetraphenylethylene (TPE)-based top layer. Illumination of the monolithic thin film with visible light in the presence of oxygen gas results in the generation of reactive oxygen species (1O2) in the porphyrinic bottom layer, which lead to a photocleavage of the TPE units at the internal interface. We demonstrate that this spatioselective photochemistry can be utilized to delaminate the top layers, yielding two-dimensional (2D) MOF sheets with well-defined thickness. Experiments using atomic force microscopy (AFM) demonstrate that these platelets can be transferred onto other substrates, thus opening up the possibility of fabricating planar MOF structures using photolithography.

Photochemische Reaktionen verlaufen typischerweise über mehrere Reaktionswege und führen zu einer Vielfalt von Produkten. Die Verbesserung ihrer Selektivität ist anspruchsvoll. Hier wird das Potential einer supramolekularen Steuerung für die photooxidative Zyklisierung eines Tetraaryleethylens (oder substituierten Stilbens) mit stereogener C=C‐Bindung demonstriert. In Lösung führt diese langsame photochemische Reaktion zu drei Phenantren‐Konstitutionsisomeren. Wird die Startverbindung in einen kristallinen Rahmen gesetzt, bildet sich nur ein Reaktionsprodukt, und die Reaktion wird erheblich beschleunigt. Entscheidend ist hier die Integration in ein SURMOF; die drastische Selektivitätszunahme wird auf die Einschränkung der Rotationsfreiheit der C=C‐Bindung zurückgeführt. Die Struktur des MOF ist verantwortlich für diesen Erfolg; die entsprechende Reaktion im Festkörper führt nicht zu einem solch starken Selektivitätsanstieg. Außerdem ist nach der photooxidativen Zyklisierung eine erhebliche Veränderung der Lumineszenzeigenschaften zu beobachten.

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