Itamar Willner

Hebrew University of Jerusalem, Yerushalayim, Jerusalem, Israel

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Publications (727)5248.85 Total impact

  • Chun‐Hua Lu · Itamar Willner
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    ABSTRACT: Stimuli-responsive DNA-functionalized nano- and microcontainers composed of mesoporous SiO2 nanoparticles (MP SiO2 NPs), microcapsules, or micelles/vesicles act as carriers for the transport and release of drugs. The information encoded in the DNA sequences provides instructive information for the gating of drug-loaded pores of MP SiO2 NPs, for the assembly and degradation of microcapsules or lipid-DNA micelles/vesicles, and for the targeting of nano-/microcontainers to cancer cells. Different triggers are applied to release the drugs loaded in the nano-/microcontainers by unlocking the pores of the MP SiO2 NPs or by degradation of the containers. These include the use of switchable DNA nanostructures (nucleic acid hairpins, i-motif, G-quadruplexes) and the implementation of chemical, thermal, or photonic stimuli. Also, catalytic processes stimulated by DNAzymes or enzymes are used to release drugs from the nano-/microcontainers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Angewandte Chemie International Edition 08/2015; DOI:10.1002/anie.201503054 · 11.26 Impact Factor
  • Chun‐Hua Lu · Itamar Willner
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    ABSTRACT: Stimuliresponsive DNA-funktionalisierte Nano- und Mikrocontainer, die aus mesoporösen SiO2-Nanopartikeln (SiO2-NPs), Mikrokapseln oder Micellen/Vesikeln bestehen, fungieren als Träger zur Freisetzung von Wirkstoffen. Die in den DNA-Sequenzen gespeicherte Information liefert den Code für die Ver- und Entriegelung der wirkstoffbeladenen Poren mesoporöser SiO2-NPs, für den Auf- und Abbau von Mikrokapseln oder Lipid-DNA-Micellen bzw. Lipid-DNA-Vesikeln und für den gezielten Transport von Nano- und Mikrocontainern zu Krebszellen. Es werden verschiedene Trigger eingesetzt, um die in den Nano- und Mikrocontainern enthaltenen Wirkstoffe durch Entriegelung der Poren der mesoporösen SiO2-NPs oder durch Abbau der Container freizusetzen. Hierzu gehören schaltbare DNA-Nanostrukturen (Nukleinsäure-Haarnadeln, i-Motive, G-Quadruplexe) und die Anwendung chemischer, thermischer oder photonischer Stimuli. Außerdem werden durch DNAzyme oder Enzyme stimulierte katalytische Prozesse genutzt, um die Wirkstoffe aus den Nano- und Mikrocontainern freizusetzen.
    Angewandte Chemie 08/2015; DOI:10.1002/ange.201503054
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    ABSTRACT: The synthesis of stimuli-responsive DNA microcapsules acting as carriers for different payloads, and being dissociated through the formation of aptamer-ligand complexes are described. Specifically, stimuli-responsive anti-adenosine triphosphate (ATP) aptamer-crosslinked DNA-stabilized microcapsules loaded with tetramethylrhodamine-modified dextran (TMR-D), CdSe/ZnS quantum dots (QDs) or microperoxidase-11 (MP-11), are presented. In the presence of ATP as trigger, the microcapsules are dissociated through the formation of aptamer-ATP complexes, resulting in the release of the respective loads. Selective unlocking of the capsules is demonstrated, and CTP, GTP or TTP do not unlock the pores. The ATP-triggered release of MP-11 from the microcapsules enables the MP-11 catalyzed oxidation of Amplex UltraRed by H2O2 to the fluorescent product resorufin.
    ACS Nano 08/2015; DOI:10.1021/acsnano.5b03223 · 12.88 Impact Factor
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    ABSTRACT: A G-rich nucleic acid tethered acrylamide/N-isopropylacrylamide (NIPAM) copolymer is prepared. The nucleic acid modified pNIPAM chains assemble, in the presence of K+ ions, into the stimuli-responsive G-quadruplex-crosslinked pNIPAM hydrogel undergoing cyclic and reversible solution/hydrogel/solid transitions. Addition of kryptofix [2.2.2] to the K+-stabilized G-quadruplex-crosslinked hydrogel eliminates the K+ ions from the crosslinking units resulting in the transition of the hydrogel into a pNIPAM solution. In turn, heating the pNIPAM hydrogel from 25˚C to 40˚C results in the transition of the hydrogel into a solid state, and cooling the solid to 25˚C restores the hydrogel state. Incorporation of hemin into the G-quadruplex-crosslinked hydrogel results in a catalytic hydrogel that catalyses the oxidation of aniline by H2O2 to form polyaniline. The polyaniline/pNIPAM hydrogel hybrid doped by 2M HCl forms the emeraldine salt, exhibiting electrical conductivity, 9 × 10-4 [cm•Ω]-1.
    Chemical Science 08/2015; DOI:10.1039/C5SC02203G · 9.21 Impact Factor
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    ABSTRACT: We demonstrate the single-molecule imaging of the catalytic reaction of a Zn(2+) -dependent DNAzyme in a DNA origami nanostructure. The single-molecule catalytic activity of the DNAzyme was examined in the designed nanostructure, a DNA frame. The DNAzyme and a substrate strand attached to two supported dsDNA molecules were assembled in the DNA frame in two different configurations. The reaction was monitored by observing the configurational changes of the incorporated DNA strands in the DNA frame. This configurational changes were clearly observed in accordance with the progress of the reaction. The separation processes of the dsDNA molecules, as induced by the cleavage by the DNAzyme, were directly visualized by high-speed atomic force microscopy (AFM). This nanostructure-based AFM imaging technique is suitable for the monitoring of various chemical and biochemical catalytic reactions at the single-molecule level. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Angewandte Chemie International Edition 07/2015; DOI:10.1002/anie.201504656 · 11.26 Impact Factor
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    ABSTRACT: DNAzyme-capped mesoporous SiO2 nanoparticles (MP SiO2 NPs) are applied as stimuli-responsive containers for programmed synthesis. Three types of MP SiO2 NPs are prepared by loading the NPs with Cy3-DBCO (DBCO=dibenzocyclooctyl), Cy5-N3, and Cy7-N3, and capping the NP containers with the Mg2+, Zn2+, and histidine-dependent DNAzyme sequences, respectively. In the presence of Mg2+ and Zn2+ ions as triggers, the respective DNAzyme-capped NPs are unlocked, leading to the “click” reaction product Cy3-Cy5. In turn, in the presence of Mg2+ ions and histidine as triggers the second set of DNAzyme-capped NPs is unlocked leading to the Cy3-Cy7 conjugated product. The unloading of the respective NPs and the time-dependent formation of the products are followed by fluorescence spectroscopy (FRET). A detailed kinetic model for the formation of the different products is formulated and it correlates nicely with the experimental results.
    Angewandte Chemie 05/2015; DOI:10.1002/ange.201501777
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    ABSTRACT: DNAzyme-capped mesoporous SiO2 nanoparticles (MP SiO2 NPs) are applied as stimuli-responsive containers for programmed synthesis. Three types of MP SiO2 NPs are prepared by loading the NPs with Cy3-DBCO (DBCO=dibenzocyclooctyl), Cy5-N3 , and Cy7-N3 , and capping the NP containers with the Mg(2+) , Zn(2+) , and histidine-dependent DNAzyme sequences, respectively. In the presence of Mg(2+) and Zn(2+) ions as triggers, the respective DNAzyme-capped NPs are unlocked, leading to the "click" reaction product Cy3-Cy5. In turn, in the presence of Mg(2+) ions and histidine as triggers the second set of DNAzyme-capped NPs is unlocked leading to the Cy3-Cy7 conjugated product. The unloading of the respective NPs and the time-dependent formation of the products are followed by fluorescence spectroscopy (FRET). A detailed kinetic model for the formation of the different products is formulated and it correlates nicely with the experimental results. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Angewandte Chemie International Edition 05/2015; DOI:10.1002/anie.201501777 · 11.26 Impact Factor
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    ABSTRACT: The stabilization of G-quadruplexes by means of K+ ions, and the separation of the nanostructures by 18-crown-6 or [2.2.2] cryptand, provide means to assemble switchable photonic or electrocatalytic molecular systems. On page 3654, this is exemplified with the construction of a G-quadruplex-based photonic "DNA spring" by I. Willner and co-workers, and by the assembly of a switchable hemin/G-quadruplex nanostructure on an electrode, acting as an electrocatalytic "ON"/"OFF" switch towards the reduction of H2 O2 . Image designed by Guoyuan Tan. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Small 04/2015; 11(30). DOI:10.1002/smll.201403794 · 8.37 Impact Factor
  • H Bauke Albada · Eyal Golub · Itamar Willner
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    ABSTRACT: The binding properties of sequence-specific nucleic acids (aptamers) to low-molecular-weight ligands, macromolecules and even cells attract substantial scientific interest. These ligand-DNA complexes found different applications for sensing, nanomedicine, and DNA nanotechnology. Structural information on the aptamer-ligand complexes is, however, scarce, even though it would open-up the possibilities to design novel features in the complexes. In the present study we apply molecular docking simulations to probe the features of an experimentally documented L-argininamide aptamer complex. The docking simulations were performed using AutoDock 4.0 and YASARA Structure software, a well-suited program for following intermolecular interactions and structures of biomolecules, including DNA. We explored the binding features of a DNA aptamer to L-argininamide and to a series of arginine derivatives or arginine-like ligands. We find that the best docking results are obtained after an energy-minimization of the parent ligand-aptamer complexes. The calculated binding energies of all mono-substituted guanidine-containing ligands show a good correlation with the experimentally determined binding constants. The results provide valuable guidelines for the application of docking simulations for the prediction of aptamer-ligand structures, and for the design of novel features of ligand-aptamer complexes.
    Journal of Computer-Aided Molecular Design 04/2015; 29(7). DOI:10.1007/s10822-015-9844-5 · 2.78 Impact Factor
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    ABSTRACT: The design of artificial cells, mimicking functions of native cellular cells, is a continuous scientific goal. The development of stimuli-responsive chemical systems that stimulate cascaded catalytic transformations, trigger chemical networks, and control vectorial branched transformation and dose-controlled processes, provides minimal elements for mimicking cell functions. We report on the electrochemical addressing of electrodes that results in the programmed release of ions that trigger selective DNAzyme-driven chemical reactions, cascaded reactions that self-assemble catalytic DNAzyme polymers, and the ON-OFF switching and dose-controlled operation of the catalytic reactions. The addressable and potential-controlled release of Pb2+ or Ag+ ions into an electrolyte that includes a mixture of nucleic acids results in the metal ion-guided selection of nucleic acids that yield the formation of dictated DNAzymes stimulating orthogonal reactions or activating DNAzyme cascades.
    Chemical Science 04/2015; 6(6). DOI:10.1039/C5SC00744E · 9.21 Impact Factor
  • Source
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    ABSTRACT: The capping of electron relay units in mesoporous carbon nanoparticles (MPC NPs) by crosslinking of different enzymes on MPC NPs matrices leads to integrated electrically contacted bienzyme electrodes acting as dual biosensors or as functional bienzyme anodes and cathodes for biofuel cells. The capping of ferrocene methanol and methylene blue in MPC NPs by the crosslinking of glucose oxidase (GOx) and horseradish peroxidase (HRP) yields a functional sensing electrode for both glucose and H2O2, which also acts as a bienzyme cascaded system for the indirect detection of glucose. A MPC NP matrix, loaded with ferrocene methanol and capped by GOx/lactate oxidase (LOx), is implemented for the oxidation and detection of both glucose and lactate. Similarly, MPC NPs, loaded with 2,2′-azino-bis(3-ethylbenzo­thiazoline-6-sulphonic acid), are capped with bilirubin oxidase (BOD) and catalase (Cat), to yield a bienzyme O2 reduction cathode. A biofuel cell that uses the bienzyme GOx/LOx anode and the BOD/Cat cathode, glucose and/or lactate as fuels, and O2 and/or H2O2 as oxidizers is assembled, revealing a power efficiency of ≈90 μW cm−2 in the presence of the two fuels. The study demonstrates that multienzyme MPC NP electrodes may improve the performance of biofuel cells by oxidizing mixtures of fuels in biomass.
    Advanced Energy Materials 04/2015; 5(8). DOI:10.1002/aenm.201401853 · 16.15 Impact Factor
  • Sivan Lilienthal · Zohar Shpilt · Fuan Wang · Ron Orbach · Itamar Willner
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    ABSTRACT: Acrylamide-acrylamide modified nucleic acid copolymer chains provide building units for the construction of acrylamide/DNA hydrogels. Three different hydrogels are prepared by the crosslinking of the acrylamide-DNA chains with metal-ion dependent DNAzyme sequences and their substrates. The metal-ion dependent DNAzyme sequences used in the study include the Cu2+-, Mg2+- and Zn2+-dependent DNAzymes. In the presence of the respective metal ions the substrates of the respective DNAzymes are cleaved, leading to the separation of the crosslinking units and to the dissolution of the hydrogel. The different hydrogels were loaded with a fluorophore-modified dextrane or with a fluorophore-functionalized glucose oxidase. Treatment of the different hydrogels with the respective ions led to the release of the loaded dextrane or the enzyme, and the rates of releasing of the loaded macromolecules followed the order Cu2+ > Mg2+ > Zn2+. Also, the different hydrogels were loaded with the enzymes β-galactosidase (β-Gal), glucose oxidase (GOx) or horseradish peroxidase (HRP). In the presence of the appropriate metal-ions, the respective hydrogels were dissolved, resulting in the activation of the β-Gal/GOx or GOx/HRP bi-enzyme cascades and of the β-Gal/GOx/HRP tri-enzyme cascade.
    ACS Applied Materials & Interfaces 03/2015; 7(16). DOI:10.1021/acsami.5b02156 · 6.72 Impact Factor
  • Source
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    ABSTRACT: Anticancer drug gossypol cross-links phenylboronic acid-modified acrylamide copolymer chains to form a hydrogel matrix. The hydrogel is dissociated in an acidic environment (pH 4.5), and its dissociation is enhanced in the presence of lactic acid (an α-hydroxy carboxylic acid) as compared to formic acid. The enhanced dissociation of the hydrogel by lactic acid is attributed to the effective separation of the boronate ester bridging groups through the formation of a stabilized complex between the boronic acid substituent and the lactic acid. Because lactic acid exists in cancer cells in elevated amounts and the cancer cells' environment is acidic, the cross-linked hydrogel represents a stimuli-responsive matrix for the controlled release of gossypol. The functionality is demonstrated and characterized by rheology and other spectroscopic means.
    Langmuir 02/2015; 31(7). DOI:10.1021/la504959d · 4.46 Impact Factor
  • Lianzhe Hu · Chun-Hua Lu · Itamar Willner
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    ABSTRACT: Two-ring interlocked DNA catenanes are synthesized and characterized. The supramolecular catenanes show switchable cyclic catalytic properties. In one system, the catenane structure is switched between a hemin/G-quadruplex catalytic structure and a catalytically-inactive state. In the second catenane structure the catenane is switched between a catalytically active Mg(2+)-dependent-DNAzyme-containing catenane and an inactive catenane state. In the third system, the interlocked catenane structure is switched between two distinct catalytic structures that include the Mg(2+)- and the Zn(2+)-dependent DNAzymes.
    Nano Letters 02/2015; 15(3). DOI:10.1021/nl504997q · 13.59 Impact Factor
  • Ron Orbach · Bilha Willner · Itamar Willner
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    ABSTRACT: This feature article addresses the implementation of catalytic nucleic acids as functional units for the construction of logic gates and computing circuits, and discusses the future applications of these systems. The assembly of computational modules composed of DNAzymes has led to the operation of a universal set of logic gates, to field programmable logic gates and computing circuits, to the development of multiplexers/demultiplexers, and to full-adder systems. Also, DNAzyme cascades operating as logic gates and computing circuits were demonstrated. DNAzyme logic systems find important practical applications. These include the use of DNAzyme-based systems for sensing and multiplexed analyses, for the development of controlled release and drug delivery systems, for regulating intracellular biosynthetic pathways, and for the programmed synthesis and operation of cascades.
    Chemical Communications 01/2015; 51(20). DOI:10.1039/c4cc09874a · 6.83 Impact Factor
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    ABSTRACT: Nucleic acid-functionalized polyacrylamide chains that are cooperatively cross-linked by i-motif and nucleic acid duplex units yield, at pH 5.0, DNA hydrogels exhibiting shape-memory properties. Separation of the i-motif units at pH 8.0 dissolves the hydrogel into a quasi-liquid phase. The residual duplex units provide, however, a memory code in the quasi-liquid allowing the regeneration of the hydrogel shape at pH 5.0.
    Advanced Materials 01/2015; 27(1). DOI:10.1002/adma.201403702 · 17.49 Impact Factor
  • Eyal Golub · Chun-Hua Lu · Itamar Willner
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    ABSTRACT: Guanine-rich single-stranded nucleic acids self-assemble into G-quadruplex nanostructures (predominately in the presence of K+-ions). Metalloporphyrins bind to the G-quadruplex nanostructures to form supramolecular assemblies exhibiting unique catalytic, electrocatalytic and photophysical properties. This paper addresses the advances in the characterization and the implementation of the metalloporphyrin/G-quadruplexes complexes for various applications. Out of the different complexes, the most extensively studied complexes are the hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme and the Zn(II)-protoporphyrin IX-functionalized G-quadruplex. Specifically, the hemin/G-quadruplex was found to act as a catalyst for driving different chemical transformations that mimic the native horseradish peroxidase enzyme, and, also, to function as an electrocatalyst for the reduction of H2O2. Also, the hemin/G-quadruplex stimulates interesting photophysical and photocatalytic processes such as the electron-transfer quenching of semiconductor quantum dots or the chemiluminescence resonance energy transfer to semiconductor quantum dots. Alternatively, Zn(II)-protoporphyrin IX associated with G-quadruplexes exhibit intensified fluorescence properties. Beyond the straight forward application of the metalloporphyrin/G-quadruplexes as catalysts that stimulate different chemical transformations, the specific catalytic, electrocatalytic and photocatalytic functions of hemin/G-quadruplexes are heavily implemented to develop sophisticated colorimetric, electrochemical, and optical sensing platforms. Also, the unique fluorescence properties of Zn(II)-protoporphyrin IX-functionalized G-quadruplexes are applied to develop fluorescence sensing platforms. The article exemplifies different sensing assays for analyzing DNA, ligand-aptamer complexes and telomerase activity using the metalloporphyrins/G-quadruplexes as transducing labels. Also, the use of the hemin/G-quadruplex as a probe to follow the operations of DNA machines is discussed.
    Journal of Porphyrins and Phthalocyanines 01/2015; 19(01n03):65-91. DOI:10.1142/S1088424615300025 · 1.36 Impact Factor
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    ABSTRACT: A new method to incorporate metal nanoparticles, NPs, into pores of mesoporous carbon nanoparticles, MPC NPs, is presented. MPC NPs loaded with metal ion solutions are capped with protein units. The electrochemical reduction of the pore-entrapped ions, followed by digestion of the protein caps, yields metal NPs-loaded MPC NPs electrodes. Pt NPs/MPC NPs electrodes are used for the electrocatalyzed reduction of O2 or H2O2. Furthermore, the metal NPs electrically contact enzymes with the bulk electrodes, as demonstrated for glucose oxidase-capped Pt NPs/MPC NPs electrodes that electrocatalyze glucose oxidation, and for horseradish peroxidase-capped Au NPs/MPC NPs electrodes, which electrocatalyze H2O2 reduction.
    Electroanalysis 01/2015; DOI:10.1002/elan.201500183 · 2.50 Impact Factor
  • Fuan Wang · Xiaoqing Liu · Itamar Willner
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    ABSTRACT: The base sequence of nucleic acid encodes structural and functional properties into the biopolymer. Structural information includes the formation of duplexes, G-quadruplexes, i-motif, and cooperatively stabilized assemblies. Functional information encoded in the base sequence involves the strand-displacement process, the recognition properties by aptamers, and the catalytic functions of DNAzymes. This Review addresses the implementation of the information encoded in nucleic acids to develop DNA switches. A DNA switch is a supramolecular nucleic acid assembly that undergoes cyclic, switchable, transitions between two distinct states in the presence of appropriate triggers and counter triggers, such as pH value, metal ions/ligands, photonic and electrical stimuli. Applications of switchable DNA systems to tailor switchable DNA hydrogels, for the controlled drug-release and for the activation of switchable enzyme cascades, are described, and future perspectives of the systems are addressed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Angewandte Chemie International Edition in English 12/2014; 54(4). DOI:10.1002/anie.201404652 · 13.45 Impact Factor
  • Fuan Wang · Xiaoqing Liu · Itamar Willner
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    ABSTRACT: Die Basensequenz der Nukleinsäuren verschlüsselt strukturelle und funktionelle Eigenschaften in einem Biopolymer. Strukturelle Informationen beinhalten die Bildung von Duplexen, G-Quadruplexen, i-Motiven und kooperativ stabilisierten Anordnungen. Funktionelle Informationen betreffen z. B. den Prozess der Strangverdrängung, Erkennungseigenschaften von Aptameren und die katalytische Funktion von DNAzymen. Dieser Aufsatz befasst sich mit der Implementierung der in Nukleinsäuren kodierten Informationen zur Entwicklung von DNA-Schaltern. Ein DNA-Schalter ist eine supramolekulare Nukleinsäureanordnung, die in Gegenwart geeigneter Auslöser und Gegenauslöser wie pH, Metallionen/Liganden, photonischen und elektrischen Stimuli zyklische, schaltbare Übergänge zwischen zwei Zuständen eingeht. Anwendungen von schaltbaren DNA-Systemen umfassen maßgeschneiderte DNA-Hydrogele für die kontrollierte Wirkstofffreisetzung und die Aktivierung schaltbarer Enzymkaskaden.
    Angewandte Chemie 12/2014; 127(4). DOI:10.1002/ange.201404652

Publication Stats

35k Citations
5,248.85 Total Impact Points

Institutions

  • 1977–2015
    • Hebrew University of Jerusalem
      • • Institute of Chemistry
      • • Farkas Center for Light-Induced Processes
      • • Department of Organic Chemistry
      • • Fritz Haber Center for Molecular Dynamics Research
      Yerushalayim, Jerusalem, Israel
  • 2008
    • University of Bologna
      Bologna, Emilia-Romagna, Italy
  • 2007
    • Universität Siegen
      Siegen, North Rhine-Westphalia, Germany
  • 1992
    • National Renewable Energy Laboratory
      گلدن، کلرادو, Colorado, United States
  • 1987
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany
  • 1979–1980
    • Ben-Gurion University of the Negev
      • Department of Chemistry
      Be'er Sheva`, Southern District, Israel