Bernd Jastorff

Publications of Bernd Jastorff

• Thinking in Terms of Structure-Activity-Relationships (T-SAR): A Tool to Better Understand Nanofiltration Membranes

  Authors: José F. Fernández, Bernd Jastorff, Reinhold Störmann, Stefan Stolte, Jorg Thöming

  Membranes. 01/2011; 1:162-183.

  A frontier to be conquered in the field of membrane technology is related to the very limited scientific base for the rational and task-specific design of membranes. This is especially true forA frontier to be conquered in the field of membrane technology is related to the very limited scientific base for the rational and task-specific design of membranes. This is especially true for nanofiltration membranes with properties that are based on several solute-membrane interaction mechanisms. “Thinking in terms of Structure-Activity-Relationships” (T-SAR) is a methodology which applies a systematic analysis of a chemical entity based on its structural formula. However, the analysis become more complex with increasing size of the molecules considered. In this study, T-SAR was combined with classical membrane characterization methods, resulting in a new methodology which allowed us not only to explain membrane characteristics, but also provides evidence for the importance of the chemical structure for separation performance. We demonstrate an application of the combined approach and its potential to discover stereochemistry, molecular interaction potentials, and reactivity of two FilmTec nanofiltration membranes (NF-90 and NF-270). Based on these results, it was possible to predict both properties and performance in the recovery of hydrophobic ionic liquids from aqueous solution.

• Analyzing Cytotoxic Effects of Selected Isothiazol-3-one Biocides Using the Toxic Ratio Concept and Structure-Activity Relationship Considerations.

  Authors: Jürgen Arning, Marianne Matzke, Stefan Stolte, Frauke Nehen, Ulrike Bottin-Weber, Andrea Böschen, Salha Abdulkarim, Bernd Jastorff, Johannes Ranke

  Chemical research in toxicology. 11/2009;

  To demonstrate how baseline toxicity can be separated from other more specific modes of toxic action and to address possible pitfals when dealing with hydrophobic substances, the fourTo demonstrate how baseline toxicity can be separated from other more specific modes of toxic action and to address possible pitfals when dealing with hydrophobic substances, the four isothiazol-3-one biocides N-methylisothiazol-3-one (MIT), 5-chloro-N-methylisothiazol-3-one (CIT), N-octylisothiazol-3-one (OIT), and 4,5-dichloro-N-octylisothiazol-3-one (DCOIT) as an example for reactive electrophilic xenobiotics were tested for their cytotoxic effects on the human hepatoblastoma cell line Hep G2, on the marine bacterium Vibrio fischeri, and on the limnic green alga Scenedesmus vacuolatus. In each of the three test systems, toxic effects were observed in a consistent pattern. The two chlorinated compounds and OIT were found to be significantly more toxic than MIT. As compared to baseline toxicants, the small and polar MIT and CIT exhibited pronounced excess toxicity in each of the three test systems that is presumably triggered by their intrinsic reactivity toward cellular thiols. In contrast, OIT and DCOIT showed mainly toxicities that could be explained by their hydrophobicity. Analyzing and comparing these results using the toxic ratio concept and with data that indicate a dramatic depletion of cellular glutathione levels after incubation with DCOIT reveals that for highly hydrophobic substances, baseline level toxicity in an assay for acute toxicity can lead to an oversight of other more specific modes of toxic action that may cause significant effects that might be less reversible than those caused by unreactive baseline toxicants. This possibility should be taken into account in the hazard assessment of chemicals that are both hydrophobic and reactive.

• Structure-activity relationships for the impact of selected isothiazol-3-one biocides on glutathione metabolism and glutathione reductase of the human liver cell line Hep G2.

  Authors: Jürgen Arning, Ralf Dringen, Maike Schmidt, Anette Thiessen, Stefan Stolte, Marianne Matzke, Ulrike Bottin-Weber, Birgit Caesar-Geertz, Bernd Jastorff, Johannes Ranke

  Toxicology. 05/2008; 246(2-3):203-12.

  To investigate the toxic mode of action of isothiazol-3-one biocides the four compounds N-methylisothiazol-3-one (MIT), 5-chloro-N-methylisothiazol-3-one (CIT), N-octylisothiazol-3-one (OIT) andTo investigate the toxic mode of action of isothiazol-3-one biocides the four compounds N-methylisothiazol-3-one (MIT), 5-chloro-N-methylisothiazol-3-one (CIT), N-octylisothiazol-3-one (OIT) and 4,5-dichloro-N-octylisothiazol-3-one (DCOIT) were purified and tested as single chemical entities for their effects on the human hepatoblastoma cell line Hep G2 and on isolated and cellular glutathione reductase GR). The two chlorinated substances CIT and DCOIT significantly decreased the amount of total cellular glutathione (GSx) in a dose and time dependent manner. Concomitantly, an increase in the level of oxidised glutathione (GSSG) was observed. The resulting shift in the GSH/GSSG ratio entailing the breakdown of the cellular thiol reduction potential was accompanied by necrotic morphological changes like swelling of the plasma membrane and subsequent lysis of the cells. Additionally, CIT and DCOIT were found to inhibit cellular GR in the cells in a concentration dependent manner. The T-SAR-based (thinking in terms of structure-activity relationships) comparison of the chlorine-substituted structures CIT and DCOIT with their non-chlorinated and less active analogues MIT and OIT identified the chlorine substituents and the resulting reaction mechanisms to be the key structural mediators of the observed toxic effects. Furthermore, differences in the activity of both chlorinated substances could be explained using the T-SAR approach to link the lipophilicity and the intrinsic glutathione-reactivity of the compounds to the expected target site concentrations inside the cells.

• Lipophilicity parameters for ionic liquid cations and their correlation to in vitro cytotoxicity.

  Authors: Johannes Ranke, Anja Müller, Ulrike Bottin-Weber, Frauke Stock, Stefan Stolte, Jürgen Arning, Reinhold Störmann, Bernd Jastorff

  Ecotoxicology and environmental safety. 08/2007; 67(3):430-8.

  Regarding the great structural variability of the currently expanding group of ionic liquids, it is highly desirable to understand the basic factors affecting their toxicity in different biologicalRegarding the great structural variability of the currently expanding group of ionic liquids, it is highly desirable to understand the basic factors affecting their toxicity in different biological systems. The present study of a set of 74 ionic liquids with imidazolium, pyrrolidinium, pyridinium, quinolinium, quaternary phosphonium and quaternary ammonium cations and the comparatively small anions Cl(-), Br(-), BF(4)(-), or PF(6)(-) demonstrates the influence of the cation lipophilicity on the cytotoxicity in IPC-81 leukemia cells from rats. The scope of this correlation is limited to ionic liquids with these or similarly small anions that are sufficiently nonreactive under physiological and chromatographic conditions and whose cation lipophilicity does not exceed a certain threshold.

• Progress in evaluation of risk potential of ionic liquids—basis for an eco-design of sustainable products

  Authors: Bernd Jastorff, Kerstin Mölter, Peter Behrend, Ulrike Bottin-Weber, Juliane Filser, Anna Heimers, Bernd Ondruschka, Johannes Ranke, Maike Schaefer, Heike Schröder, Annegret Stark, Piotr Stepnowski, Frauke Stock, Reinhold Störmann, Stefan Stolte ...

  Green Chemistry. 01/2005; 7:362-372.

  Motivated by the prevailing need for a sustainable development and taking the principles of Green Chemistry as a starting point, the present paper describes new and updated findings regarding aMotivated by the prevailing need for a sustainable development and taking the principles of Green Chemistry as a starting point, the present paper describes new and updated findings regarding a sustainable product design for ionic liquids. The focus is on environmental risk. Nevertheless, cytotoxicity testing and first indicative results from a genotoxicity study extend present knowledge also with regard to possible effects on humans. The structural variability of commercially available ionic liquids as well as the abundance of theoretically accessible ionic liquids is illustrated and the consequences for an integrated risk assessment accompanying the development process are discussed. The side chain effect on toxicity for imidazolium type ionic liquids was confounded by more complex biological testing. Also, an influence of an anion on cytotoxicity is shown for the first time. Testing of presumed metabolites of the imidazolium type cations showed a significantly lower biological activity in cytotoxicity studies than their parent compounds. The importance of a purity assessment for ionic liquids is pointed out and a collection of methods that is believed to be adequate is presented. In addition to risk analysis, the use of life cycle analysis for the multi-objective problem of designing ionic liquids is sketched and an eco-design scheme for ionic liquids is proposed. In conclusion, the paper illustrates the complex nature of the development processes ionic liquids are currently undergoing and provides guidance on which aspects have to be kept in mind.

• Chromatographic behavior of pyrithiones.

  Authors: Caren Anja Doose, Maciej Szaleniec, Peter Behrend, Anja Müller, Bernd Jastorff

  Journal of chromatography. A. 11/2004; 1052(1-2):103-10.

  Pyrithione biocides are currently viewed as a major prospect for the replacement of tributyltin antifoulants in ship paints. The chromatographic behavior of 1-hydroxy-2-pyridinethione (pyrithione,Pyrithione biocides are currently viewed as a major prospect for the replacement of tributyltin antifoulants in ship paints. The chromatographic behavior of 1-hydroxy-2-pyridinethione (pyrithione, PT), bis(2-pyridinyl)disulfide 1,1'-dioxide (PT2), and the metal complexes zinc [Zn(PT)2], iron [Fe(PT)3] and copper [Cu(PT)2] pyrithione, were investigated by means of UV-vis spectroscopy, ESI-MSn, HPLC-DAD and HPLC-ESI-MSnD. This revealed transformations of the analytes, which affect the development of adequate methods for species or environmental analysis of pyrithiones. PT transforms into copper- or iron- containing complexes and/or the oxidation product PT2, depending on the type of the stationary phase used in chromatographic analysis. Speciation complicates direct chromatography of [Zn(PT)2] and [Fe(PT)3].

• Bioactivatable, membrane-permeant analogs of cyclic nucleotides as biological tools for growth control of C6 glioma cells.

  Authors: Martin Bartsch, Michaela Zorn-Kruppa, Nicole Kühl, Hans-Gottfried Genieser, Frank Schwede, Bernd Jastorff

  Biological chemistry. 10/2003; 384(9):1321-6.

  In the present study, the cAMP analogs 8-bromo-cAMP (8-Br-cAMP), N6-2'O-dibutyryl-cAMP (DBcAMP) and 8-para-chlorophenylthio-cAMP (8-CPT-cAMP), as well as the corresponding cAMP-acetoxymethylIn the present study, the cAMP analogs 8-bromo-cAMP (8-Br-cAMP), N6-2'O-dibutyryl-cAMP (DBcAMP) and 8-para-chlorophenylthio-cAMP (8-CPT-cAMP), as well as the corresponding cAMP-acetoxymethyl (AM)-ester-prodrugs were tested in a HPLC study for their membrane permeability, intracellular accumulation and biotransformation. Antiproliferative activities of these compounds were studied in the rat C6 glioma cell line. Chromatographic analysis revealed that the AM-ester analogs of the cyclic nucleotides penetrate quantitatively into rat C6 glioma cells and generate high amounts of their parent cyclic nucleotides intracellularly within 60 min; however, long-term growth inhibition tested in C6 cells is only slightly enhanced with the AM-ester prodrugs of 8-Br-cAMP or DBcAMP.

• Reversed-phase liquid chromatographic method for the determination of selected room-temperature ionic liquid cations.

  Authors: Piotr Stepnowski, Anja Müller, Peter Behrend, Johannes Ranke, Jens Hoffmann, Bernd Jastorff

  Journal of chromatography. A. 05/2003; 993(1-2):173-8.

  The separation of selected 1-alkyl- and 1-aryl-3-methylimidazolium-based room temperature ionic liquid cations has been performed using reversed-phase high-performance liquid chromatography withThe separation of selected 1-alkyl- and 1-aryl-3-methylimidazolium-based room temperature ionic liquid cations has been performed using reversed-phase high-performance liquid chromatography with electrospray ionization mass detection. The RP-HPLC method development started with the selection of a column taking into account especially the resolution of low molecular congeners of the selected group. Mobile phase composition was optimized for peak resolution, sensitivity and high reproducibility of retention values. The results of the method development were applied to the determination of exemplary ionic liquid species present in the medium used in cytotoxicity studies.

• How hazardous are ionic liquids? Structure–activity relationships and biological testing as important elements for sustainability evaluation

  Authors: Bernd Jastorff, Reinhold Störmann, Johannes Ranke, Kerstin Mölter, Frauke Stock, Boris Oberheitmann, Wolfgang Hoffmann, Jens Hoffmann, Matthias Nüchter, Bernd Ondruschka, Juliane Filser

  Green Chemistry. 01/2003; 5:136-142.

  For ionic liquids only few toxicological and/or ecotoxicological data are available until now. A strategy is presented which aims at an environmental risk assessment of chemicals, using a combinationFor ionic liquids only few toxicological and/or ecotoxicological data are available until now. A strategy is presented which aims at an environmental risk assessment of chemicals, using a combination of structure–activity relationships (SAR), toxicological and ecotoxicological tests and modelling. The parts “test-kit-concept” and “multidimensional risk analysis” are described in detail by means of selected imidazolium ionic liquids. The iterative process of this strategy offers a tool for sustainable product design.

• Applied waste-free recovery of methanol: a sustainable solution for chromatography laboratories.

  Authors: Piotr Stepnowski, Karl-Heinz Blotevogel, Bernd Jastorff

  Environmental science and pollution research international. 01/2002; Spec No 1:34-8.

  In this paper, we present appliedmethanol recycling technology utilising chromatographic applications, which has been designed for an academic-size institution. The procedure is combined out ofIn this paper, we present appliedmethanol recycling technology utilising chromatographic applications, which has been designed for an academic-size institution. The procedure is combined out of proper recovery technique and the biodegradation method intended for postprocessing residues. Additionally, analytical methods controlling the quality of the process are described in detail in order to enable full transfer of the proposed methodology to the analogous institution. The recovered solvent is of relatively high purity (> 99.92%), containing traces of water and volatile compounds. The spectral purity is sufficient to employ recycled methanol in HPLC applications where low wavelength detection is necessary. Biodegradation of distillation first-cuts and still bottoms is implemented using isolated strains of Methylobacterium organophilum. During the biodegradation process, a series of carotenoids are biosynthesized, which are of a high commercial value. The proposed application, therefore, offers not only a sustainable, waste-free solution in handling methanol waste, but can also serve as a potential source of value.

• Cyclic Nucleotide Analogs as Prospective Drugs

  Authors: Frank Schwede, Hans-Gottfried Genieser, Bernd Jastorff

  Cellular and Molecular Biology Letters. 01/1999; 4:466.

• Synthesis of the 3`, 5` Cyclic Phosphates from Unprotected Nucleosides

  Authors: Hans - Gottfried Genieser, Elke Butt, Ulrike Bottin, Wolfgang Dostmann, Bernd Jastorff

  Synthesis. 01/1989;

• Synthesis of Nucleoside - 3', 5' - Cyclic Phosphorothioates by Cyclothiophosphorylation of Unprotected Nucleosides

  Authors: Hans-Gottfried Genieser, Wolfgang Dostmann, Ulrike Bottin, Elke Butt, Bernd Jastorff

  Tetrahedron Letters. 01/1988; 29:2803 - 2804.

• Determination of Hydrophobic Parameters by Reversed - Phase High - Performance Liquid Chromatography. Effect of Stationary Phase

  Authors: Thomas Braumann, Hans-Gottfried Genieser, Cord Lüllmann, Bernd Jastorff

  Chromatographia. 01/1987; 24:777 - 782.

• Structural Investigations on Reversed Phase Silicas II. The Proof of Endcapping Trimethylsilyl Groups

  Authors: Cord Lüllmann, Hans - Gottfried Genieser, Bernd Jastorff

  Journal of Chromatography. 01/1986; 354:434 - 437.

• Structural Investigations on Reversed Phase Silicas - Determination of Ligand Functionality

  Authors: Cord Lüllmann, Hans - Gottfried Genieser, Bernd Jastorff

  Journal of Chromatography. 01/1985; 323:273 - 280.

• Characterization of Silica Bonded Stationary Phases

  Authors: Hans - Gottfried Genieser, Detlef Gabel, Bernd Jastorff

  Journal of Chromatography. 01/1983; 269:127 - 152.

• Gas Chromatographic Adsorption Effect Arising from Boron Trihalides

  Authors: Hans - Gottfried Genieser, Detlef Gabel, Bernd Jastorff

  Journal of High Resolution Chromatography, Chromatographic Commununications. 01/1983; 6:515.

• Determination of Ligand Contents of Octadecyl - Modified Silicas

  Authors: Hans - Gottfried Genieser, Detlef Gabel, Bernd Jastorff

  Journal of Chromatography. 01/1982; 244:368 - 372.

• Cell-permeable Non-hydrolyzable cAMP Derivatives as Tools for Analysis of Signaling Pathways Controlling Gene Regulation in Dictyostelium

  Authors: Pauline Schaap, Martine van Ments-Cohen, Ron D.M. Soede, Raymond Brandt, Richard A Firtel, Wolfgang Dostmann, Hans-Gottfried Genieser, Bernd Jastorff, Peter J.M. van Haastert

  A novel class of cAMP derivatives were tested for binding to surface cAMP receptors (CAR), protein kinase A (PKA), and cAMP-phosphodiesterase (PDE) and for induction of three classes of cAMPA novel class of cAMP derivatives were tested for binding to surface cAMP receptors (CAR), protein kinase A (PKA), and cAMP-phosphodiesterase (PDE) and for induction of three classes of cAMP regulated genes in Dictyostelium discoideum. These derivatives carry sulfur substitutions for either the axial (Sp) or equatorial (Rp) exocyclic oxygen atoms, while further modifications were introduced to provide specificity for binding to either CAR or PKA, and/or to increase lipophilicity and render the derivatives membrane-permeable. All derivatives bind weakly to PDE and are almost not degraded during incubation with Dictyostelium cells. One cAMP derivative, 6-thioethylpurineriboside 3',5‘-monophosphorothioate, Sp-isomer (Sp-6SEtcPuMPS), fulfills the criteria for selective activation of PKA in vivo. The compound enters Dictyostelium cells and reaches an intracellular concentration of 1 µM, sufficient to activate PKA, at an extracellular concentration of 30 µM, which is insufficient to activate CAR. Expression of cAMP-regulated prespore and prestalk genes and the aggregative PDE gene are effectively induced by CAR agonists and very poorly by PKA agonists. Even Sp-6SEtcPuMPS is ineffective to induce gene expression. These data not only indicate that surface cAMP receptors are the first targets for cAMP-induced gene expression, but argue against direct induction of expression of these genes by cAMP-induced PKA activation.