Itamar Willner

Hebrew University of Jerusalem, Yerushalayim, Jerusalem, Israel

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Publications (787)5498.16 Total impact

  • H. Bauke Albada · Eyal Golub · Itamar Willner
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    ABSTRACT: The rational design of a set of hemin/G-quadruplex (hGQ)-dopamine binding aptamer (DBA) conjugates, acting as nucleoapzymes, is described. The nucleoapzyme constructs consist of a hGQ DNAzyme as a catalytic unit and DBA as a substrate binding unit that are brought into spatial proximity by a duplex scaffold composed of complementary oligonucleotide strands. When the hGQ unit is linked to the duplex scaffold via a single-strand DNA tether of variable length, the resulting nucleoapzymes reveal a moderate catalytic enhancement toward the H2O2-mediated oxidation of dopamine to aminochrome as compared to the process stimulated by the separated hGQ and DBA units (5–7 fold enhancement). This limited enhancement is attributed to inappropriate spatial positioning of the hGQ in respect to the dopamine binding site, and/or to the flexibility of the tether that links the hGQ catalytic site to the double-strand scaffold. To solve this, rigidification of the hGQ/DBA conjugates by triplex oligonucleotide structures that anchor the hGQ to a duplex domain associated with the DBA units was achieved. By the sequential, programmed, triplex-controlled rigidification of the hGQ/DBA structure, a nucleoapzyme with superior catalytic activity toward the oxidation of dopamine to aminochrome is identified (30-fold catalytic enhancement). Molecular dynamics simulations reveal that in the resulting highly active rigidified nucleoapzyme structure, the hGQ catalytic site is positioned in spatial proximity to the opening of the DBA substrate binding site, thus rationalizing and supporting the enhanced catalytic functions of the system. Finally, the most active nucleoapzyme system was subjected to fuel- and anti-fuel strands that separate and re-assemble the nucleoapzyme structure, allowing “ON” and “OFF” switching of the nucleoapzyme catalytic functions.
    No preview · Article · Jan 2016 · Chemical Science
  • Tzuriel S Metzger · Ran Tel-Vered · Itamar Willner
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    ABSTRACT: Two configurations of molecularly imprinted bis-aniline-bridged Au nanoparticles (NPs) for the specific binding of the electron acceptor N,N'-dimethyl-4,4'-bipyridinium (MV(2+) ) and for the photosensitizer Zn(II)-protoporphyrin IX (Zn(II)-PP-IX) are assembled on electrodes, and the photoelectrochemical features of the two configurations are discussed. Configuration I includes the MV(2+) -imprinted Au NPs matrix as a base layer, on which the Zn(II)-PP-IX-imprinted Au NPs layer is deposited, while configuration II consists of a bilayer corresponding to the reversed imprinting order. Irradiation of the two electrodes in the presence of a benzoquinone/benzohydroquinone redox probe yields photocurrents of unique features: (i) Whereas configuration I yields an anodic photocurrent, the photocurrent generated by configuration II is cathodic. (ii) The photocurrents obtained upon irradiation of the imprinted electrodes are substantially higher as compared to the nonimprinted surfaces. The high photocurrents generated by the imprinted Au NPs-modified electrodes are attributed to the effective loading of the imprinted matrices with the MV(2+) and Zn(II)-PP-IX units and to the effective charge separation proceeding in the systems. The directional anodic/cathodic photocurrents are rationalized in terms of vectorial electron transfer processes dictated by the imprinting order and by the redox potentials of the photosensitizer/electron acceptor units associated with the imprinted sites in the two configurations.
    No preview · Article · Jan 2016 · Small
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    ABSTRACT: The hybridization chain reaction (HCR) is implemented for the development of amplified electrochemical DNA sensing platforms. The target analyte hybridizes with a probe oligonucleotide-functionalized electrode and triggers on the HCR process in the presence of the hairpins HA and HB. The formation of the analyte-triggered HCR chains is followed by Faradaic impedance spectroscopy or chronocoulometry using Fe(CN)63-/4- or Ru(NH3)63+ as redox labels, respectively. By using two different probes-functionalized electrodes and a mixture of four hairpins, HA:HB and HC:HD, the parallel analysis of two analytes is demonstrated. Through the structural design of the hairpin structures to include caged G-quadruplex subunits, the analyte/probe hybrid associated with the electrode triggers on the HCR process, leading to G-quadruplex-functionalized HCR chains. The association of hemin to the matrix yields electrocatalytic hemin/G-quadruplex units that provide a secondary amplification path for the detection of DNA through an electrocatalyzed reduction of H2O2. The system allows the detection of the analyte DNA with a detection limit corresponding to 0.2 nM.
    No preview · Article · Jan 2016 · The Journal of Physical Chemistry C
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    ABSTRACT: Nature Energy 1 , 15021 (2016); published 18 January 2016; corrected 28 January 2016. In the version of this Article originally published, an author's name contained a typographical error and should have read Sabine Alsaoub.
    Preview · Article · Jan 2016
  • Miguel Angel Aleman Garcia · Yuwei Hu · Itamar Willner
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    ABSTRACT: Switchable β-cyclodextrin (β-CD)-induced hydrolysis of m-tert-butylphenyl acetate is demonstrated in the presence of supramolecular β-CD/adamantane oligonucleotide scaffolds. In one system, a duplex between a β-CD-functionalized nucleic acid and an adamantane-nucleic acid leads to a switchable catalytic system. In a second system, a β-CD/adamantane duplex is cooperatively generated by K(+)-stabilized G-quadruplex units. The binding of hemin to the second system yields a bifunctional DNA scaffold with alternate catalytic functions.
    No preview · Article · Dec 2015 · Chemical Communications
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    ABSTRACT: ITO electrodes modified with a nano-patterned film of polystyrene-block-poly(2-vinylpyridine), PS-b-P2VP, where the P2VP domains are quaternized with iodomethane, are used for selective deposition of redox-active materials. Electrochemical studies (cyclic voltammetry, Faradaic impedance measurements) indicate that the PS domains insulate the conductive surface towards redox labels in solution. In turn, the quaternized P2VP domains electrostatically attract negatively-charged redox labels solubilized in the electrolyte solution, resulting in an effective electron transfer between the electrode and the redox label. This phenomenon is implemented for the selective deposition of the electroactive Prussian blue on the nano-patterned surface and for the electrochemical deposition of Au nanoparticles, modified with a monolayer of p-aminothiophenol/2-mercaptoethane sulfonic acid, on the quaternized P2VP domains. The patterned Prussian blue-modified surface enables controlling the wettability properties by the content of the electrochemically-deposited Prussian blue. Controlled wettability is unattainable with the homopolymer-modified surface, attesting to the role of the nano-pattern.
    Full-text · Article · Dec 2015 · ACS Applied Materials & Interfaces
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    ABSTRACT: A novel concept to improve the catalytic functions of nucleic acids (DNAzymes) is introduced. The method involves the conjugation of a DNA recognition sequence (aptamer) to the catalytic DNAzyme, yielding a hybrid structure termed "nucleoapzymes". Concentrating the substrate within the "nucleoapzyme" leads to enhanced catalytic activity, displaying saturation kinetics. Different conjugation modes of the aptamer/DNAzyme units and the availability of different aptamer sequences for a substrate provide diverse means to design improved catalysts. This is exemplified with: (i) The H2O2-mediated oxidation of dopamine to aminochrome using a series of hemin/G-quadruplex-dopamine aptamer nucleoapzymes. All nucleoapzymes reveal enhanced catalytic activities as compared to the separated DNAzyme/aptamer units, and the most active nucleoapzyme reveals a 20-fold enhanced activity. Molecular dynamics simulations provide rational assessment of the activity of the various nucleoapzymes. The hemin/G-quadruplex-aptamer nucleoapzyme also stimulates the chiroselective oxidation of L- vs. D-DOPA by H2O2. (ii) The H2O2-mediated oxidation of N-hydroxy-L-arginine to L-citrulline by a series of hemin/G-quadruplex-arginine aptamer conjugated nucleoapzymes.
    No preview · Article · Dec 2015 · Journal of the American Chemical Society
  • Chun-Hua Lu · Weiwei Guo · Yuwei Hu · Xiu-Juan Qi · Itamar Willner
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    ABSTRACT: Acrylamide-acrylamide nucleic acids are crosslinked by two cooperative functional motives to form shaped acrylamide-DNA hydrogels. One of the crosslinking motives responds to an external trigger leading to the dissociation of one of the stimuli responsive bridges, and to the transition of the stiff shaped hydrogels into soft shapeless states, where the residual bridging units, due to the chains entanglement, provide an intrinsic memory, for re-shaping of the hydrogels. Subjecting the shapeless states to counter stimuli restore the dissociated bridges, and regenerate the original shape of the hydrogels. By the cyclic dissociation and re-assembly of the stimuli-responsive bridges, the reversible switchable transitions of the hydrogels between stiff shaped hydrogel structures and soft shapeless states are demonstrated. Shaped hydrogels bridged by K(+)-stabilized G-quadruplexes/duplex units, by i-motif/duplex units or two different duplex bridges are described. The cyclic transitions of the hydrogels between shaped and shapeless states are stimulated in the presence of appropriate triggers and counter triggers (K(+)-ion/crown ether; pH = 5.0/8.0; fuel/anti-fuel strands). The shape memory hydrogels are integrated into shaped two-hydrogel or three-hydrogel hybrid structures. The cyclic programmed transitions of selective domains of the hybrid structures between shaped hydrogel and shapeless states are demonstrated. The possible applications of the shape memory hydrogels for sensing, inscription of information, and controlled release are discussed.
    No preview · Article · Nov 2015 · Journal of the American Chemical Society
  • Ran Tel-Vered · Jason S Kahn · Itamar Willner
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    ABSTRACT: Layered metal nanoparticle (NP) assemblies provide highly porous and conductive composites of unique electrical and optical (plasmonic) properties. Two methods to construct layered metal NP matrices are described, and these include the layer-by-layer deposition of NPs, or the electropolymerization of monolayer-functionalized NPs, specifically thioaniline-modified metal NPs. The layered NP composites are used as sensing matrices through the use of electrochemistry or surface plasmon resonance (SPR) as transduction signals. The crosslinking of the metal NP composites with molecular receptors, or the imprinting of molecular recognition sites into the electropolymerized NP matrices lead to selective and chiroselective sensing interfaces. Furthermore, the electrosynthesis of redox-active, imprinted, bis-aniline bridged Au NP composites yields electrochemically triggered "sponges" for the switchable uptake and release of electron-acceptor substrates, and results in conductive surfaces of electrochemically controlled wettability. Also, photosensitizer-relay-crosslinked Au NP composites, or electrochemically polymerized layered semiconductor quantum dot/metal NP matrices on electrodes, are demonstrated as functional nanostructures for photoelectrochemical applications.
    No preview · Article · Oct 2015 · Small
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    ABSTRACT: A novel method to assemble acrylamide/acrydite DNA copolymer hydrogels on surfaces, specifically gold-coated surfaces, is introduced. The method involves the synthesis of two different copolymer chains consisting of hairpin A, HA, modified acrylamide copolymer and hairpin B, HB, acrylamide copolymer. In the presence of a nucleic acid promoter monolayer associated with the surface, the hybridization chain reaction between the two hairpin-modified polymer chains is initiated, giving rise to the cross-opening of hairpins HA and HB and the formation of a crosslinked hydrogel on the surface. The co-functionalization of the HA- and HB-modified polymer chains with G-rich DNA tethers, that include the G-quadruplex subunits, hydrogels of controlled and switchable stiffness are generated. In the presence of K(+)-ions, the hydrogel associated with the surface is cooperatively crosslinked by duplex units of HA and HB, and K(+)-ion-stabilized G-quadruplex units, giving rise to a stiff hydrogel. The 18-crown-ether-stimulated elimination of the K(+)-ions dissociates the bridging G-quadruplex units, resulting in a hydrogel of reduced stiffness. The duplex/G-quadruplex cooperatively-stabilized hydrogel associated with the surface reveals switchable electrocatalytic properties. The incorporation of hemin into the G-quadruplex units of the duplex/G-quadruplex cooperatively electrocatalyzes the reduction of H2O2. The 18-crown-6-ether stimulated dissociation of the hemin/G-quadruplex bridging units leads to a catalytically-inactive hydrogel.
    No preview · Article · Oct 2015 · Nano Letters
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    ABSTRACT: Shape memory acrylamide/DNA hydrogels include two different crosslinkers as stabilizing elements. The triggered dissociation of one of the crosslinking elements transforms the shaped hydrogel into an arbitrarily shaped (or shapeless) quasi-liquid state. The remaining crosslinking element, present in the quasi-liquid, provides an internal memory that restores the original shaped hydrogel upon the stimulus-triggered regeneration of the second crosslinking element. Two pH-sensitive shape memory hydrogels, forming Hoogsten-type triplex DNA structures, are described. In one system, the shaped hydrogel is stabilized at pH = 7.0 by two different duplex crosslinkers, and the transition of the hydrogel into the shapeless quasi-liquid proceeds at pH = 5.0 by separating one of the crosslinking units into a protonated cytosine–guanine–cytosine (C–G·C+ ) triplex. The second shaped hydrogel is stabilized at pH = 7.0, by cooperative duplex and thymine–adenine–thymine triplex (T–A·T) bridges. At pH = 10.0, the triplex units separate, leading to the dissociation of the hydrogel into the quasi-liquid state. The cyclic, pH-stimulated transitions of the two systems between shaped hydrogels and shapeless states are demonstrated. Integrating the two hydrogels into a shaped “two-arrowhead” hybrid structure allows the pH-stimulated cyclic transitions of addressable domains of the hybrid between shaped and quasi-liquid states.
    No preview · Article · Oct 2015 · Advanced Functional Materials
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    Full-text · Dataset · Sep 2015
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    ABSTRACT: The electropolymerization of thioaniline-modified Au nanoparticles (NPs) on thioaniline monolayer-functionalized electrodes in the presence of Zn(II)-protoporphyrin IX yields bis aniline-crosslinked Au NPs matrices that include molecular imprinted sites for binding the Zn(II)-protoporphyrin IX photosensitizer. The binding of the photosensitizer yields photoelectrochemically active electrodes that produce anodic photocurrents in the presence of the electron donor benzohydroquinone. The efficient photocurrents formed in the presence of the imprinted electrode are attributed to the high-affinity binding of the photosensitizer to the imprinted sites, Ka = 3.2 × 106 m−1, and to the effective transport of the photoejected electrons to the bulk electrode via the bridged Au NPs matrix. Similarly, a N,N′-dialkyl-4,4′-bipyridinium-modified Zn(II)-protoporphyrin IX photosensitizer-electron acceptor dyad is imprinted in the bis aniline-crosslinked Au NPs matrix. The photocurrent generated by the imprinted matrix is approximately twofold higher as compared to the photocurrent generated by the Zn(II)-protoporphyrin IX-imprinted Au NPs matrix. The efficient photocurrents generated in the presence of the bipyridinium-modified Zn(II)-protoporphyrin IX-imprinted matrix are attributed to the effective primary charge separation of the electron–hole species in the dyad structure, followed by the effective transport of the photoejected electrons to the electrode via the bis aniline-crosslinked Au NPs matrix.
    No preview · Article · Sep 2015 · Advanced Functional Materials
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    ABSTRACT: The synthesis, purification and structure characterization of a seven-ring interlocked DNA catenane is described. The design of the seven-ring catenane allows the dynamic reconfiguration of any of the four rings (R1, R3, R4, and R6) on the catenane scaffold, or the simultaneous switching of any combination of two, three or all four rings to yield sixteen different isomeric states of the catenane. The dynamic reconfiguration across the states is achieved by implementing the strand-displacement process in the presence of appropriate fuel/anti-fuel strands, and is probed by fluorescence spectroscopy. Each of the sixteen isomers of the catenane can be transformed into any of the other isomers, thus allowing for 240 dynamic transitions within the system.
    No preview · Article · Sep 2015 · Nano Letters
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    Helmut Schwarz · Itamar Willner · Ilan Marek
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    ABSTRACT: Als vor 50 Jahren die Welt nach dem Zweiten Weltkrieg in Schutt und Asche lag, initiierten Konrad Adenauer und David Ben-Gurion diplomatische Beziehungen zwischen Deutschland und Israel. Dieses Jubiläum ist Anlass für dieses Sonderheft, in dem die fruchtbare, wechselseitig bereichernde Zusammenarbeit zwischen israelischen und deutschen Wissenschaftlern beleuchtet wird … Lesen Sie mehr im Editorial von Helmut Schwarz, Itamar Willner und Ilan Marek.
    Preview · Article · Sep 2015 · Angewandte Chemie
  • Helmut Schwarz · Itamar Willner · Ilan Marek
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    ABSTRACT: "…︁ Fifty years ago, out of the ashes of the Second World War, the German Chancellor, Konrad Adenauer, and the Israeli Prime Minister, David Ben-Gurion, initiated the establishment of diplomatic relations between Germany and Israel. This special issue commemorates the fruitful and mutually enriching long-term collaborations between Israeli and German scientists …︁ Read more in the Editorial by Helmut Schwarz, Itamar Willner, and Ilan Marek. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    No preview · Article · Sep 2015 · Angewandte Chemie International Edition
  • 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.
    No preview · Article · Aug 2015 · Angewandte Chemie International Edition
  • 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.
    No preview · Article · Aug 2015 · Angewandte Chemie
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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.
    No preview · Article · Aug 2015 · ACS Nano
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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.
    Full-text · Article · Aug 2015 · Chemical Science

Publication Stats

46k Citations
5,498.16 Total Impact Points

Institutions

  • 1977-2016
    • 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
  • 2010
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
  • 2007
    • Universität Siegen
      Siegen, North Rhine-Westphalia, Germany
  • 1993
    • Universität des Saarlandes
      • Organische Chemie II
      Saarbrücken, Saarland, Germany
  • 1992
    • National Renewable Energy Laboratory
      گلدن، کلرادو, Colorado, United States
  • 1979-1981
    • University of California, Berkeley
      • • Department of Chemistry
      • • Lawrence Berkeley Laboratory
      Berkeley, California, United States
  • 1979-1980
    • Ben-Gurion University of the Negev
      • Department of Chemistry
      Be'er Sheva`, Southern District, Israel