Mono- and dinuclear molybdenum complexes with sterically demanding cycloheptatrienyl ligands

Sterically demanding cycloheptatrienylium (tropylium) salts of the type (1,3,5-C7H4R3)BF4 [R = t-Bu, (3a)BF4; R = SiMe3, (3b)BF4] have been prepared from the corresponding 1,3,5-trisubstituted benzene derivatives 1 by ring expansion with diazomethane followed by hydride abstraction with triphenylcarbenium tetrafluoroborate, (Ph3C)BF4. Complexation can be achieved by arene exchange and Mo(CO)3 group transfer employing [(eta6-p-xylene)Mo(CO)3] (4) to yield the cationic complexes (5)BF4. In refluxing mesitylene, [(eta7-C7H4t-Bu3)Mo(CO)3]BF4, (5a)BF4, undergoes CO substitution to furnish the mesitylene sandwich complex (6a)BF4. A cyclic voltammetric study reveals that this complex exhibits a reversible one-electron oxidation to the dicationic 17e complex 6a2+, which can also be accessed by chemical oxidation with AgBF4. On the contrary, the reduction of 6a+ is irreversible and does not yield a stable 19e complex 6a. To study the fate of the reduced 19e form, (5a)BF4 was treated with Na2Hg to diastereoselectively afford the C-C coupled bicycloheptatriene complex 7a. Paramagnetic, dinuclear complexes of the type [(eta7-C7H4R3)Mo(mu-Cl)3Mo(eta7-C7H4R3)] (8) have been obtained from the reaction of (5)BF4 with Me3SiCl. These can be regarded as mixed-valence Mo(0)/Mo(+I) compounds with a metal-metal bond order of 0.5. Cyclic voltammetric studies reveal that both complexes 8a and 8b undergo reversible one-electron oxidation as well as reduction. Treatment with one equivalent of ferrocenium hexafluorophosphate leads to removal of the unpaired electron and formation of the diamagnetic complexes (8)PF6. Theoretical DFT calculations have been carried out to further elucidate the bonding in these systems. In addition, the X-ray crystal structures of (5b)BF4, (6a)BF4 x CH2Cl2, (6a)(BF4)2 x (acetone)2, 7a x CH2Cl2, 8a x 0.5C6H14, and (8a)PF6 x Et2O are reported.     

Influence of Test Specimen Geometry and Water Soaking on the In Vitro Cytotoxicity of Orthocryl®, Orthocryl® LC,Loctite® EA 9483 and Polypropylene

Depending on their composition, plastics have a cytotoxic potential that needs to be evaluated before they are used in dentistry, e.g., as orthodontic removable appliances. Relevant guidelines set out requirements that a potential new resin in the medical field must meet, with a wide scope for experimental design. In the present study, test specimens of different geometries consisting of varying polymers (Orthocryl^®, Orthocryl^® LC, Loctite^® EA 9483, Polypropylene) were soaked for different periods of time, then transferred to cell culture medium for 24 h, which was subsequently used for 24-h cultivation of A549 cells, followed by cytotoxicity assays (WST-1, Annexin V-FITC-propidium iodide (PI) flow cytometry). In this context, a reduction in the cytotoxic effect of the eluates of test specimens prepared from Orthocryl^® LC and Loctite^® EA 9483 was particularly evident in the Annexin V-FITC-PI assay when the soaking time was extended to 48 h and 168 h, respectively. Consistent with this, a reduced release of potentially toxic monomers into the cell culture medium, as measured by gas chromatography-mass spectrometry, was observed when the prior soaking time of test specimens of all geometries was extended. Remarkably, a significant increase in cytotoxic effect was observed in the WST-1 assay, which was accompanied by a higher release of monomers when the thickness of the test sample was increased from 0.5 to 1.0 mm, although an elution volume adapted to the surface area was used. However, further increasing the thickness to 3.0 mm did not lead to an increase in the observed cytotoxicity or monomer release. Test specimens made of polypropylene showed no toxicity under all test specimen sizes and soaking time conditions. Overall, it is recommended to perform toxicity studies of test specimens using different geometries and soaking times. Thereby, the influence of the different specimen thicknesses should also be considered. Finally, an extension of the test protocols proposed in ISO 10993-5:2009 should be considered, e.g., by flow cytometry or monomer analysis as well as fixed soaking times.     

Metal/Metal Redox Isomerism Governed by Configuration

A pair of diastereomeric dinuclear complexes, [Tp′(CO)BrW{μ-η²-C,C′-κ²-S,P-C₂(PPh₂)S}Ru(η⁵-C₅H₅)(PPh₃)], in which W and Ru are bridged by a phosphinyl(thiolato)alkyne in a side-on carbon P,S-chelate coordination mode, were synthesized, separated and fully characterized. Even though the isomers are similar in their spectroscopic properties and redox potentials, the like-isomer is oxidized at W while the unlike-isomer is oxidized at Ru, which is proven by IR, NIR and EPR-spectroscopy supported by spectro-electrochemistry and computational methods. The second oxidation of the complexes was shown to take place at the metal left unaffected in the first redox step. Finally, the tipping point could be realized in the unlike isomer of the electronically tuned thiophenolate congener [Tp′(CO)(PhS)W{μ-η²-C,C′-κ²-S,P-C₂(PPh₂)S}Ru(η⁵-C₅H₅)-(PPh₃)], in which valence trapped W^III/Ru^II and W^II/Ru^III cationic species are at equilibrium.     

Synthesis of pyrazine-bridged diimidazolium salts and their application in palladium catalyzed Heck-type coupling reactions

Reaction of imidazole derivatives with 2,3-di(bromomethyl)pyrazine results in the formation of the new pyrazine-bridged diimidazolium salts 1-8. These salts proved to be valuable precursors for dinuclear complexes with mixed NHC/pyrazine ligands. Two of the pyrazine-bridged diimidazolium salts 3·H₂O and 8·2H₂O have been characterized by X-ray diffraction. Furthermore, the first catalytic studies with mixtures of palladium acetate and the imidazolium salts have been carried out. The in situ prepared palladium complexes derived from the diimidazolium salts 1-8 exhibit a modest catalytic activity in Heck-type coupling reactions between 4-bromo benzaldehyde and styrene or n-butyl acrylate.     

Activity of AC electrokinetically immobilized horseradish peroxidase

Dielectrophoresis (DEP) is an AC electrokinetic effect mainly used to manipulate cells. Smaller particles, like virions, antibodies, enzymes, and even dye molecules can be immobilized by DEP as well. In principle, it was shown that enzymes are active after immobilization by DEP, but no quantification of the retained activity was reported so far. In this study, the activity of the enzyme horseradish peroxidase (HRP) is quantified after immobilization by DEP. For this, HRP is immobilized on regular arrays of titanium nitride ring electrodes of 500 nm diameter and 20 nm widths. The activity of HRP on the electrode chip is measured with a limit of detection of 60 fg HRP by observing the enzymatic turnover of Amplex Red and H₂O₂ to fluorescent resorufin by fluorescence microscopy. The initial activity of the permanently immobilized HRP equals up to 45% of the activity that can be expected for an ideal monolayer of HRP molecules on all electrodes of the array. Localization of the immobilizate on the electrodes is accomplished by staining with the fluorescent product of the enzyme reaction. The high residual activity of enzymes after AC field induced immobilization shows the method's suitability for biosensing and research applications.     

Potential of the dietary antioxidants resveratrol and curcumin in prevention and treatment of hematologic malignancies

Despite considerable improvements in the tolerance and efficacy of novel chemotherapeutic agents, the mortality of hematological malignancies is still high due to therapy relapse, which is associated with bad prognosis. Dietary polyphenolic compounds are of growing interest as an alternative approach, especially in cancer treatment, as they have been proven to be safe and display strong antioxidant properties. Here, we provide evidence that both resveratrol and curcumin possess huge potential for application as both chemopreventive agents and anticancer drugs and might represent promising candidates for future treatment of leukemia. Both polyphenols are currently being tested in clinical trials. We describe the underlying mechanisms, but also focus on possible limitations and how they might be overcome in future clinical use--either by chemically synthesized derivatives or special formulations that improve bioavailability and pharmacokinetics.     

Creating Space for Large Acceptors: Rational Biocatalyst Design for Resveratrol Glycosylation in an Aqueous System

Polyphenols display a number of interesting properties but their low solubility limits practical applications. In that respect, glycosylation offers a solution for which sucrose phosphorylase has been proposed as a cost‐effective biocatalyst. However, its activity on alternative acceptor substrates is too low for synthetic purposes and typically requires the addition of organic (co‐)solvents. Here, we describe the engineering of the enzyme from Thermoanaerobacterium thermosaccharolyticum to enable glycosylation of resveratrol as test case. Based on docking and modeling studies, an active‐site loop was predicted to hinder binding. Indeed, the unbolted loop variant R134A showed useful affinity for resveratrol (K_m=185 mM ) and could be used for the quantitative production of resveratrol 3‐α‐glucoside in an aqueous system. Improved activity was also shown for other acceptors, introducing variant R134A as promising new biocatalyst for glycosylation reactions on bulky phenolic acceptors.     

Series resonance circuit with ferroelectric capacitor

A series resonance circuit under sinuousoidal driving is investigated experimentally. The inductance consists of an air coil. The capacitance is made up of a ferroelectric material that introduces its nonlinear dielectric properties into the circuit. The dynamical system linear coil-nonlinear capacaitor shows an interesting behaviour. The phase portrait differs in general from the ellipse of the harmonic oscillator. For appropriate external conditions period doubling sequences, chaos and therein enclosed periodic windows might occur. Starting from a cubic nonlinearity of the dielectric properties a Duffing equation is proposed as a model for periodic behaviour of the series resonance circuit. Simulations of experimentally recorded phase portraits yield good agreement between experiment and model.