@article{CroneAschnerSchwerdtleetal.2015, author = {Crone, Barbara and Aschner, Michael A. and Schwerdtle, Tanja and Karst, Uwe and Bornhorst, Julia}, title = {Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS}, series = {Metallomics}, volume = {2015}, journal = {Metallomics}, number = {7}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-591X}, doi = {10.1039/c5mt00096c}, pages = {1189 -- 1195}, year = {2015}, abstract = {cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 μm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.}, language = {en} } @article{GhoshCherstvyMetzler2014, author = {Ghosh, Surya K. and Cherstvy, Andrey G. and Metzler, Ralf}, title = {Non-universal tracer diffusion in crowded media of non-inert obstacles}, series = {Physical Chemistry Chemical Physics}, volume = {3}, journal = {Physical Chemistry Chemical Physics}, number = {17}, editor = {Metzler, Ralf}, publisher = {The Royal Society of Chemistry}, address = {Cambridge}, issn = {1463-9076}, pages = {1847 -- 1858}, year = {2014}, abstract = {We study the diffusion of a tracer particle, which moves in continuum space between a lattice of excluded volume, immobile non-inert obstacles. In particular, we analyse how the strength of the tracer-obstacle interactions and the volume occupancy of the crowders alter the diffusive motion of the tracer. From the details of partitioning of the tracer diffusion modes between trapping states when bound to obstacles and bulk diffusion, we examine the degree of localisation of the tracer in the lattice of crowders. We study the properties of the tracer diffusion in terms of the ensemble and time averaged mean squared displacements, the trapping time distributions, the amplitude variation of the time averaged mean squared displacements, and the non-Gaussianity parameter of the diffusing tracer. We conclude that tracer-obstacle adsorption and binding triggers a transient anomalous diffusion. From a very narrow spread of recorded individual time averaged trajectories we exclude continuous type random walk processes as the underlying physical model of the tracer diffusion in our system. For moderate tracer-crowder attraction the motion is found to be fully ergodic, while at stronger attraction strength a transient disparity between ensemble and time averaged mean squared displacements occurs. We also put our results into perspective with findings from experimental single-particle tracking and simulations of the diffusion of tagged tracers in dense crowded suspensions. Our results have implications for the diffusion, transport, and spreading of chemical components in highly crowded environments inside living cells and other structured liquids.}, language = {en} } @article{ShinCherstvyMetzler2014, author = {Shin, Jaeoh and Cherstvy, Andrey G. and Metzler, Ralf}, title = {Kinetics of polymer looping with macromolecular crowding: effects of volume fraction and crowder size}, series = {Soft Matter}, journal = {Soft Matter}, editor = {Metzler, Ralf}, publisher = {The Royal Society of Chemistry}, address = {Cambridge}, issn = {1744-683X}, pages = {472 -- 488}, year = {2014}, abstract = {The looping of polymers such as DNA is a fundamental process in the molecular biology of living cells, whose interior is characterised by a high degree of molecular crowding. We here investigate in detail the looping dynamics of flexible polymer chains in the presence of different degrees of crowding. From the analysis of the looping-unlooping rates and the looping probabilities of the chain ends we show that the presence of small crowders typically slows down the chain dynamics but larger crowders may in fact facilitate the looping. We rationalise these non-trivial and often counterintuitive effects of the crowder size on the looping kinetics in terms of an effective solution viscosity and standard excluded volume. It is shown that for small crowders the effect of an increased viscosity dominates, while for big crowders we argue that confinement effects (caging) prevail. The tradeoff between both trends can thus result in the impediment or facilitation of polymer looping, depending on the crowder size. We also examine how the crowding volume fraction, chain length, and the attraction strength of the contact groups of the polymer chain affect the looping kinetics and hairpin formation dynamics. Our results are relevant for DNA looping in the absence and presence of protein mediation, DNA hairpin formation, RNA folding, and the folding of polypeptide chains under biologically relevant high-crowding conditions.}, language = {en} } @article{RoderHille2014, author = {Roder, Phillip and Hille, Carsten}, title = {ANG-2 for quantitative Na+ determination in living cells by time-resolved fluorescence microscopy}, series = {Photochemical \& Photobiological Sciences}, volume = {12}, journal = {Photochemical \& Photobiological Sciences}, number = {13}, editor = {Hille, Carsten}, publisher = {The Royal Society of Chemistry}, address = {Cambridge}, issn = {1474-905X}, pages = {1699 -- 1710}, year = {2014}, abstract = {Sodium ions (Na+) play an important role in a plethora of cellular processes, which are complex and partly still unexplored. For the investigation of these processes and quantification of intracellular Na+ concentrations ([Na+]i), two-photon coupled fluorescence lifetime imaging microscopy (2P-FLIM) was performed in the salivary glands of the cockroach Periplaneta americana. For this, the novel Na+-sensitive fluorescent dye Asante NaTRIUM Green-2 (ANG-2) was evaluated, both in vitro and in situ. In this context, absorption coefficients, fluorescence quantum yields and 2P action cross-sections were determined for the first time. ANG-2 was 2P-excitable over a broad spectral range and displayed fluorescence in the visible spectral range. Although the fluorescence decay behaviour of ANG-2 was triexponential in vitro, its analysis indicates a Na+-sensitivity appropriate for recordings in living cells. The Na+-sensitivity was reduced in situ, but the biexponential fluorescence decay behaviour could be successfully analysed in terms of quantitative [Na+]i recordings. Thus, physiological 2P-FLIM measurements revealed a dopamine-induced [Na+]i rise in cockroach salivary gland cells, which was dependent on a Na+-K+-2Cl- cotransporter (NKCC) activity. It was concluded that ANG-2 is a promising new sodium indicator applicable for diverse biological systems.}, language = {en} } @article{MeyerSchulzJeibmannetal.2014, author = {Meyer, S{\"o}ren and Schulz, Jacqueline and Jeibmann, Astrid and Taleshi, Mojtaba S. and Ebert, Franziska and Francesconi, Kevin and Schwerdtle, Tanja}, title = {Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster}, series = {Metallomics}, journal = {Metallomics}, editor = {Schwerdtle, Tanja}, publisher = {The Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, pages = {2010 -- 2014}, year = {2014}, abstract = {Arsenic-containing hydrocarbons (AsHC) constitute one group of arsenolipids that have been identified in seafood. In this first in vivo toxicity study for AsHCs, we show that AsHCs exert toxic effects in Drosophila melanogaster in a concentration range similar to that of arsenite. In contrast to arsenite, however, AsHCs cause developmental toxicity in the late developmental stages of Drosophila melanogaster. This work illustrates the need for a full characterisation of the toxicity of AsHCs in experimental animals to finally assess the risk to human health related to the presence of arsenolipids in seafood.}, language = {en} } @article{SchwarzeMuellerAstetal.2014, author = {Schwarze, Thomas and M{\"u}ller, Holger and Ast, Sandra and Steinbr{\"u}ck, D{\"o}rte and Eidner, Sascha and Geißler, Felix and Kumke, Michael Uwe and Holdt, Hans-J{\"u}rgen}, title = {Fluorescence lifetime-based sensing of sodium by an optode}, series = {Chemical Communications}, journal = {Chemical Communications}, editor = {Kumke, Michael Uwe}, publisher = {The Royal Society Chemistry}, address = {Cambridge}, issn = {0022-4936}, pages = {14167 -- 14170}, year = {2014}, abstract = {We report a 1,2,3-triazol fluoroionophore for detecting Na+ that shows in vitro enhancement in the Na+-induced fluorescence intensity and decay time. The Na+-selective molecule 1 was incorporated into a hydrogel as a part of a fiber optical sensor. This sensor allows the direct determination of Na+ in the range of 1-10 mM by measuring reversible fluorescence decay time changes.}, language = {en} } @article{UnterbergLeffersHuebneretal.2014, author = {Unterberg, Marlies and Leffers, Larissa and H{\"u}bner, Florian and Humpf, Hans-Ulrich and Lepikhov, Konstantin and Walter, J{\"o}rn and Ebert, Franziska and Schwerdtle, Tanja}, title = {Toxicity of arsenite and thio-DMAV after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics}, series = {Toxicology Research}, volume = {3}, journal = {Toxicology Research}, number = {6}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {2045-4538}, pages = {456 -- 464}, year = {2014}, abstract = {This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAsIII and its metabolite thio-DMAV were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAsIII and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMAV. Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAsIII and thio-DMAV caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMAV; iAsIII induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies.}, language = {en} } @article{WirthNeumannAntoniettietal.2014, author = {Wirth, Jonas and Neumann, Rainer and Antonietti, Markus and Saalfrank, Peter}, title = {Adsorption and photocatalytic splitting of water on graphitic carbon nitride}, series = {physical chemistry, chemical physics : PCCP}, volume = {2014}, journal = {physical chemistry, chemical physics : PCCP}, number = {16}, issn = {1463-9076}, doi = {10.1039/c4cp02021a}, pages = {15917 -- 15926}, year = {2014}, abstract = {Graphitic carbon nitride, g-C₃N₄, is a promising organic photo-catalyst for a variety of redox reactions. In order to improve its efficiency in a systematic manner, however, a fundamental understanding of the microscopic interaction between catalyst, reactants and products is crucial. Here we present a systematic study of water adsorption on g-C₃N₄ by means of density functional theory and the density functional based tight-binding method as a prerequisite for understanding photocatalytic water splitting. We then analyze this prototypical redox reaction on the basis of a thermodynamic model providing an estimate of the overpotential for both water oxidation and H⁺ reduction. While the latter is found to occur readily upon irradiation with visible light, we derive a prohibitive overpotential of 1.56 eV for the water oxidation half reaction, comparing well with the experimental finding that in contrast to H₂ production O₂ evolution is only possible in the presence of oxidation cocatalysts.}, language = {en} } @article{ZamponiPenfoldNachtegaaletal.2014, author = {Zamponi, Flavio and Penfold, Thomas J. and Nachtegaal, Maarten and L{\"u}bcke, Andrea and Rittmann, Jochen and Milne, Chris J. and Chergui, Majed and van Bokhoven, Jeroen A.}, title = {Probing the dynamics of plasmon-excited hexanethiol-capped gold nanoparticles by picosecond X-ray absorption spectroscopy}, series = {physical chemistry, chemical physics : PCCP}, volume = {2014}, journal = {physical chemistry, chemical physics : PCCP}, number = {16}, issn = {1463-9076}, doi = {10.1039/c4cp03301a}, pages = {23157 -- 23163}, year = {2014}, abstract = {Picosecond X-ray absorption spectroscopy (XAS) is used to investigate the electronic and structural dynamics initiated by plasmon excitation of 1.8 nm diameter Au nanoparticles (NPs) functionalised with 1-hexanethiol. We show that 100 ps after photoexcitation the transient XAS spectrum is consistent with an 8\% expansion of the Au-Au bond length and a large increase in disorder associated with melting of the NPs. Recovery of the ground state occurs with a time constant of ∼1.8 ns, arising from thermalisation with the environment. Simulations reveal that the transient spectrum exhibits no signature of charge separation at 100 ps and allows us to estimate an upper limit for the quantum yield (QY) of this process to be <0.1.}, language = {en} } @article{WessigGerngrossPapeetal.2014, author = {Wessig, Pablo and Gerngroß, Maik and Pape, Simon and Bruhns, Philipp and Weber, Jens}, title = {Novel porous materials based on oligospiroketals (OSK)}, series = {RSC Advances : an international journal to further the chemical sciences}, volume = {2014}, journal = {RSC Advances : an international journal to further the chemical sciences}, number = {4}, issn = {2046-2069}, doi = {10.1039/c4ra04437a}, pages = {31123 -- 31129}, year = {2014}, abstract = {New porous materials based on covalently connected monomers are presented. The key step of the synthesis is an acetalisation reaction. In previous years we used acetalisation reactions extensively to build up various molecular rods. Based on this approach, investigations towards porous polymeric materials were conducted by us. Here we wish to present the results of these studies in the synthesis of 1D polyacetals and porous 3D polyacetals. By scrambling experiments with 1D acetals we could prove that exchange reactions occur between different building blocks (evidenced by MALDI-TOF mass spectrometry). Based on these results we synthesized porous 3D polyacetals under the same mild conditions.}, language = {en} }