1

Poster Session A Monday, February 13, 2017

2

PA-1

Enhancing the Stability and Selectivity of Nanocarriers by Dimerization of

their Building Blocks

Ido Rosenbaum, Roey J. Amir

Organic Chemistry, Tel Aviv University, Tel Aviv, Israel

Enzyme-responsive micelles have a great potential as drug delivery systems due to the high selectivity and

overexpression of disease-associated enzymes. Recently we have reported on enzyme-responsive amphiphilic

block copolymers composed of a hydrophilic PEG block and a dendron with enzymatically cleavable lipophilic

end-groups as the hydrophobic block. These amphiphilic hybrids formed micellar structures in aqueous

environment and enzymatic activation led to their disassembly. However, when examining micelles and their

properties, it is clear that one of the biggest challenges is the the risk of their fast dilution and disassembly in

the body. By cross-linking the micelles we can increase their stability and decrease their spontaneous

disassembly in the body. By choosing a reversible cross-linker such as disulfide bonds, we will also benefit the

introduction of another stimuli-responsive group. This will open the way for smart nanocarriers with improved

micellar stabilities that require activation by both types of stimuli for their disassembly.

Keywords:

Block copolymer micelles, Enzyme responsive materials, Nanocarriers.

3

PA-2

Proof of Hydrogen Spillover by Product-Distribution Analysis in Solid Phase

Hydrogenations

Adi Mary Akiva Moyal1,2, Ofra Paz-Tal1, Eyal Ben-Yehuda1, Michael Gozin2,

Svetlana Pevzner1 1Chemistry Department, Nuclear Research Centre Negev, Beer-Sheva, Israel

2School of Chemistry, Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel

Hydrogenation in the solid-phase is important in green-chemistry for the limited use of solvents and use of

solid, recyclable catalysts and, in the field of hydrogen-scavenging, preventing risks of explosion, or hydrogen-

induced metal corrosion or embrittlement.

In solid-phase hydrogenations the reaction progress is believed to involve hydrogen-spillover, where the

activated hydrogen migrates across the catalyst’s carbon-support. The study of solid-phase hydrogenation of

1,4-bis(phenylethynyl)benzene (PEB) was used to demonstrate the effect of different parameters on the solid-

phase hydrogenation mechanism.

The samples of PEB containing a Pd/C catalyst were hydrogenated to various degrees at different initial

pressures and with the addition of carbon-nanotubes (CNTs) or C60 fullerenes; the partially hydrogenated

samples were then analyzed by gas-chromatography, for product quantification.

Comparison of the products distribution at different reaction-conditions gives insight into the nature of the

spillover-mechanism of hydrogenation in the solid-phase.

The results of this study show that the product-distribution is greatly affected by the hydrogen pressure.

Addition of CNTs, known to accelerate solid-phase hydrogenations, gives the same effect on product-

distribution trend as a hydrogen pressure increase. We suppose that CNTs facilitate and increase the distance of

the hydrogen’s migration from the metal catalyst to the substrate.

C60 addition has the opposite effect. The reaction-rate substantially diminishes; and the product-distribution

trend resembles that of decreased hydrogen pressure. We suppose that the mechanism of C60 inhibition is by

recombination of hydrogen-atoms into molecular hydrogen and subsequent H2 release to the gas-phase. Thus,

we can presume that the nature of the spilled-over hydrogen is radical.

In summary, by studying the product-distribution of the solid-phase hydrogenation at different pressures with

the addition of additives, we gain insight into the reaction mechanism.

4

PA-3

Facile and Highly Chemoselective N-Difluoromethylation of Functionalized

Tertiary Amines

Dafna Amir, Lea Yehezkel, Naama Karton-Lifshin, Moran Madmon, Sigal Saphier,

Eytan Gershonov, Yossi Zafrani

Organic Chemistry, Israel Institute for Biological Research, Ness-Ziona, Israel

Synthesis of organic compounds containing fluorine atoms has become one of the more important issues in the

field of organic synthesis because of the central role fluorinated functions play as bioisosteres in agrochemicals

and drugs, leading to changes in affinity, metabolic stability, hydrophobicity and bioavailability of various

bioactive compounds. In the world of organic synthesis, the incorporation of a fluorine atom/s is also frequently

employed for various other applications to modify both chemical and physical properties of molecules. Among

various fluorinated moieties, difluoromethyl (-CF2H) is one of the most promising. Quaternary ammonium salts

are a well-known and abundant family of compounds used in medical applications, cosmetics, agriculture, and

chemical catalysis. Since the charged moiety is responsible for the unique properties of these compounds, the

influence of a difluoromethyl group adjacent to the cationic center may be of interest. In this work, we present a

practical, convenient and general method for the difluoromethylation of tertiary amines, using diethyl

bromodifluoromethylphosphonate and fluoride. We found that this commercially available phosphonate

smoothly reacts with a fluoride ion to liberate a difluorocarbene intermediate that in the presence of a proton

source and a tertiary amine generates the corresponding a-difluoromethyl ammonium compound in good to

excellent yields. Despite the involvement of a difluorocarbene intermediate, this difluoromethylation occurs

almost exclusively on the nitrogen atom with diverse molecular structures (e.g. drugs, ionic liquids, polymers).

Combining the two highly important issues of fluorinated organic compounds and quaternary ammonium salts

may lead to interesting changes in chemical and physical properties. A preliminary assessment of the effects an

a-difluoromethyl group has on hydrogen bonding and log P of quaternary ammonium salts is also described.

5

PA-4

Design and Synthesis of Highly Branched Organocatalysts

for Site–Selective Acylation

Natali Ashush, Ramesh Palakuri, Moshe Portnoy

School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences,

Tel Aviv University, Tel Aviv, Israel

Site-selective acylation organocatalysts are a promising approach for preparing derivatives of polyhydroxylated

natural products. Working toward this goal, we synthesized a molecular probe for acylation reaction that

includes two reactive sites, which are situated in different environment (polar and a-polar). Such design allows

examining the tendency of various catalysts to perform acylation at a specific site (Scheme 1).

We envisaged using the dendritic architecture in order to create a catalytic pocket of a specified polarity. Thus,

we conceived a catalytic system composed of a dendrimer that incorporates a polar imidazole active site in the

interior and an a-polar periphery that will create a hydrophobic envelopment of this catalytic site. We presume

that the polarity differences between the dendrimer regions will impact the probe access path into the catalytic

pocket and, consequently, allow a preferred reaction at a particular site.

The designed catalysts (Figure 1) were synthesized, examined under several standard sets of conditions and

compared to a simple non-dendritic analogue. The catalytic experiments revealed several trends, reflecting the

effects of the probe concentration, solvent polarity and the nature of the acylation reagent. Based on these

findings, preference for the desired site of the proe can be achieved by providing specific conditions and a

specific catalyst.

6

PA-5

Enzymatically Degradable Self-Reporting Micelles

Marina Buzhor, Roey J. Amir

Department of Organic Chemistry, Faculty of Exact Sciences, Tel Aviv University, Tel Aviv,

Israel

Enzyme responsive micelles have gained increased interest in recent years due to their high potential in

different field`s ranging from smart materials to drug delivery. Our group has recently developed a highly

modular platform of enzymatically degradable polymeric micelles. These micelles are composed of self-

assembled amphiphilic hybrids of hydrophilic polyethyleneglycol (PEG) block and a dendron functionalized

with enzymatically cleavable hydrophobic end-groups. The need for new methods for drug delivery and

imaging probes led us to develop the next generation of labeled smart micelles that can self-report their

structural changes by spectral response. Here we present a novel design of covalently labeled enzyme-

responsive amphiphilic hybrids that can report the self-assembly and disassembly of the micelles by changes in

the dyes` spectral properties. These spectral changes occur due to alteration of dye-dye interactions caused by

the supramolecular structural changes of the micelles. By simply changing the labeling dyes, we demonstrate

different spectral activities (turn-On or spectral-switch of the spectral signal [1]) that are generated due to

different dye-dye interactions, such as, excimer formation, self-quenching or FRET. This highly modular

approach opens the way for new delivery platforms that allow advanced methods for imaging and tracking the

degree and location of drug released.

[1] “Supramolecular translation of enzymatically triggered disassembly of micelles into tunable

fluorescent responses”, Buzhor, Marina; Harnoy, Assaf J.; Tirosh, Einat; Barak, Ayana; Schwartz, Tal; Amir,

Roey J. Chemistry–A European Journal 21.44 (2015): 15633-15638.

7

PA-6

Metal-free Catalytic Chlorination of Silanes and Silylation of Ethers

Karina Chulsky, Roman Dobrovetsky

Chemistry, Tel Aviv University, Tel Aviv, Israel

Silyl chlorides play an important role in organic synthesis, they are used to protect hydroxyl functional groups.

They are also important precursors in organosilicon chemistry and are used for the synthesis of branched

organosilanes and sol-gel materials. Various procedures were developed for chlorination of silanes, however,

most of these methods suffer from poor selectivity and the use of toxic materials. Herein we present a new

selective method for Lewis acid (B(C6F5)3) catalyzed chlorination of silanes by HCl. In addition, we developed

a B(C6F5)3 catalyzed method for activation of ethers in presence of silanes, forming silylethers and

corresponding alkanes. This method can be potentially used to replace a very robust alkyl ethereal protecting

groups to more labile silyl protecting group, this chemistry is currently under investigation. Detailed protocols,

the most recent results and the mechanisms supported both by experiment and by theoretical calculations are

shown.

8

PA-7

Thioxobimanes: Structural and Chelating Studies

Partha J. Das1, Ankana Roy1, Yael Diskin-Posner2, Iddo Pinkas2, Ashim Nandi3,

Sebastian Kozuch3, Michael Firer4, Michael Montag1, Flavio Grynszpan1 1Department of Chemical Sciences, Ariel University, Ariel, Israel

2Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel 3Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

4Department of Chemical Engineering and Biotechnology, Ariel University, Ariel, Israel

syn-(Me,Me)Bimane (1) bears the heterocyclic molecular core of a well-known class of biologically relevant

fluorescent dyes. Despite their intrinsic characteristics as chelating agents (O-donors and sterically available π

system) the coordination chemistry of bimanes has not been explored. Recently, we reported the first example

of a cationic Pd(II) complex containing syn-(Me,Me)bimane as an O-donor chelating ligand.[1]

In order to expand the scope of bimanes by accessing derivatives with different chelating and fluorescence

properties while keeping the low number of atoms in their basic structure, we reasoned that the carbonyl

oxygen atoms could be replaced by sulfur ones. We applied traditional thionating chemistry (Lawesson’s

reagent and P4S10) in the preparation of syn-monothioxobimane (2), syn-dithioxobimane (3) and anti-

dithioxobimane (4). Our preliminary results indicate that the introduction of sulfur atoms to the bimane core

results in significant depression of the original fluorescence intensity, in the UV-vis region.

X-ray data and computational quantum mechanical modeling methods were used to shed light on the topology

and dynamics of the bimane core structure. Our latest results describing syn-thioxobimanes as ligands in metal

complexes as well as their structural and spectroscopic implications will be presented.

[1] Das, P. J.; Diskin-Posner, Y.; Firer, M.; Montag, M.; Grynszpan, F., Dalton Trans. 2016, 45, 17123-17131.

9

PA-8

Olefination of N-Sulfinylimines under Mild Conditions

Shubhendu Dhara, Charles E. Diesendruck

Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

Olefins are ubiquitous building blocks in many naturally occurring bioactive molecules and important reactive

intermediates in numerous organic transformations.1A plethora of organic transformations have been invented

for the stereo-controlled construction of substituted alkenes.2 Importantly, new approaches for the synthesis of

olefins are still being investigated, as transformation of different functional groups into olefins may be key in

the total synthesis of natural compounds, drugs etc. Sulfinyl groups have an important role as chiral auxiliaries

in nucleophilic addition reactions. Therefore, N-sulfinylimines have been attracting much interest owing to their

simple preparation and inherent reactivity. Here, we demonstrate a simple and efficient diastereoselective

transformation of this chiral directing group into useful 1,2-disubstituted alkenes, which can be further

functionalized as required. Different aryl phosphonates reacted with a range of electronically diverse N-

sulfinylimines to afford in greater than 99:1 E-alkenes in almost every case. The most important feature of this

protocol is that the reaction can be performed at room temperature using inexpensive sodium hydride as the

most effective base to generate the reactive phosphonate ylide producing E- alkenes in high yields.

Reference:

1)Comprehensive Natural Products Chemistry, vol. 1–9 (Eds.: D. Barton, K. Nakanishi), Elsevier, New York,

1999.

2)Williams, J. M. J. Preparation of Alkenes: A Practical Approach; Oxford University Press: Oxford, UK,

1996. (c) Kelly, S. E. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,

UK, 1991; Vol. 1, p 729.

10

PA-9

Asymmetric Copper-Catalyzed Carbomagnesiation of Cyclopropenes

Longyang Dian, Daniel S. Müller, Ilan Marek

Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

In the last few years, we have been interested in the selective ring-opening of cyclopropanes for the preparation

of quaternary carbon stereocenter in acyclic systems.1 However, for this approach to be reliable and efficient,

one needs to have an easy access to the preparation of diastereo- and enantiomerically enriched polysubstituted

cyclopropanes from a common and easily accessible precursor. In this context and in continuation of our

previous effort on the preparation of diastereo and enantiomerically enriched polysubstituted cyclopropanes,2

we demonstrate herein a highly enantio- and diastereoselective Cu-catalyzed carbomagnesiation reaction of

unfunctionalized cyclopropenes with a great variety of alkyl Grignard reagents. The flexibility and easily

availability of both partners (cyclopropenes and Grignard reagents) provide a novel, mild and convenient

approach to a variety of polysubstituted cyclopropanes. The carbometalated species generated in situ readily

undergo C-C and C-X bond forming reactions with various electrophiles with retention of configuration.

Reference:

[1] For our recent works on the C-C bond cleavage of cyclopropanes, see: a) S. Simaan, I. Marek, J. Am. Chem.

Soc. 2010, 132, 4066; b) P.-O. Delaye, D. Didier, I. Marek, Angew. Chem. Int. Ed. 2013, 52, 5333; c) A.

Masarwa, D. Didier, T. Zabrodski, M. Schinkel, L. Ackermann, I. Marek, Nature 2014, 505, 199; d) A.

Vasseur, L. Perrin, O. Eisenstein, I. Marek, Chem. Sci. 2015, 6, 2770; e) A. Masarwa, D. Gerbig, L. O., A.

Loewenstein, H. P. Reisenauer, P. Lesot, P. R. Schreiner, I. Marek, Angew. Chem. Int. Ed. 2015, 54, 13106; f)

M. Simaan, P.-O. Delaye, M. Shi, I. Marek, Angew. Chem. Int. Ed. 2015, 54, 12345; g) S. R. Roy, D. Didier, A.

Kleiner, I. Marek, Chem. Sci. 2016, 7, 5989; h) F.-G. Zhang, G. Eppe, I. Marek, Angew. Chem. Int. Ed. 2016,

55, 714.

[2] D. S. Müller, I. Marek, J. Am. Chem. Soc. 2015, 137, 15414. For previous works on the asymmetric

carbozincation of cyclopropens by other groups, see: b) M. Nakamura, A. Hirai, E. Nakamura, J. Am. Chem.

Soc. 2000, 122, 978; c) K. Krämer, P. Leong, M. Lautens, Org. Lett. 2011, 13, 819.

11

PA-10

Selective Synthesis of Polyaryls by Iron Catalyzed Consecutive Oxidative

Cross-Coupling of biphenols

Alina Dyadyuk, Vlada Vershinin

Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

An Iron catalysed consecutive oxidative cross-coupling reactions between single biphenolic units and

nucleophilic arenes is presented, offering a direct entry to complex phenolic oligomers. The direct impact of

different types of substituents on each phenol ring of the biphenolic unit on the reaction regioselectivity (ortho,

para or meta) and chemoselectivity (C-coupling or O-coupling) was examined.

References:

1] Alina Dyadyuk, Kavitha Sudheendran, Yulia Vainer, Vlada Vershinin, Alexander I. Shames and

Doron Pappo, Lett.,2016, 18 (17), pp 4324–4327

2] Eden Gaster, Yulia Vainer, Almog Regev, Sachin Narute, Kavitha Sudheendran, Aviya Werbeloff,

Hadas Shalit, and Doron Pappo, Chem. Int.Ed., 2015, 54, pp 4198 –4202

3] Anna Libman, Hadas Shalit, Yulia Vainer, Sachin Narute, Sebastian Kozuch, and Doron Pappo, Am.

Chem. Soc.,2015, 137 (35), pp 11453–11460

12

PA-11

Tuning Mechanical and Thermomechanical Properties by Intramolecular

Cross-Linking

Or Galant, Feng Wang, Charles E. Diesendruck

Shulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

The thermomechanical response of a solid polymer is a function of the forces between the polymer chains,

which, above the entanglement limit, depends almost exclusively on the monomer chemistry. In this research,

we exploit intramolecular cross-links to physically limit entanglement between chains and study the effect of

the thermomechanical and mechanical properties independently of the monomer chemistry. The synthetic

strategy involves a two-step approach; first a linear chain is prepared; then, intramolecular cross-linking is

carried out under high dilution to inhibit intermolecular reactions. In my research, I have been using RAFT

polymerization to prepare a linear random copolymer containing a mixture of methyl methacrylate (MMA) and

(2-acetoacetoxy) ethyl methacrylate (AEMA). Cross-linking is performed by Michael addition using

trimethylolpropane triacrylate as the Michael acceptor.[1] This project expands the possibilities in bottom-up

materials design, in which the architecture of the polymer chains on the nanoscale is specifically tailored

towards desired final material properties. This research will lead to a better understanding of how polymer

architecture, in addition to chemistry, affects the form and entanglement of chains, and therefore solid-state

bulk thermomechanical and mechanical properties.

[1] “Michael” Nanocarriers Mimicking Transient-Binding Disordered. Ana Sanchez-Sanchez, Somayeh

Akbari. ACS Macro Letters, p. 2013.

13

PA-12

Direct Selective Aerobic Catalyzed Oxidation of Methylarenes to

Benzaldehyde Derivatives in HFIP as Hydrogen Bond Donor Medium

Eden Gaster, Doron Pappo

Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Hydrogen Bond Donor (HBD) medium can be used to control reaction selectivity by stabilizing Hydrogen

Bond Acceptor (HBA) products. This concept is applied in the aerobic catalyzed Co(II)/N-Hydroxyphthalimide

(NHPI) oxidation of methylarenes to selectively form benzaldehyde derivatives at ambient temperature with no

trace of benzoic acid using 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) as the reaction medium.

14

PA-13

Stimuli-responsive Self-immolative Chemiluminescent Polymers

Samer Gnaim, Doron Shabat

Organic Chemistry, Tel Aviv University, Tel Aviv, Israel

Molecular probes based on 3-hydroxyphenyl-1,2-dioxetane chemiluminescence light emission are widely used

for various sensing and diagnostic applications (e.g., DNA, enzymatic and chemical probes). Amplification of

molecular signals is an important task for the development of sensitive diagnostic probes in the field of

chemical sensing. Recently, various approaches have been introduced to increase the signal-to-noise ratio of

chemiluminescent light emission as a molecular signal.

This work describes the design and synthesis of a new class of self-immolative chemiluminescent polymers

constructed of four complementary components: ) chemically stable 1,2-dioxatene analog incorporated an

adamantyl group (bulky substituent), ii) protected 4-hydroxybenzyl alcohol substituent (self-immolative

monomeric linker), iii) a chemical or biological responsive group (e.g., silyl protecting group), and iv) the

monomers are linked together via carbonate linkage.

Our results show that a single cleavage event of the protecting group on the phenol results in the formation of a

quinone derivative of 1,2-dioxetane, which undergoes a rapid 1,6-elimination to release the leaving group on

the benzyl alcohol. A nucleophilic attack on the benzylic-methide position initiates a chemically initiated

electron-exchange luminescence (CIEEL) process affording methyl benzoate and light emission.

Using this new class of chemiluminescent polymers introduce the ability to design a novel stimuli responsive

chemilumnescent polymers as an amplification systems.

15

PA-14

The Effect of H2 on AgOTf Catalyzed Transformations of Aldehydes

Yael Gottlieb, Roman Dobrovetsky

Organic Chemistry, Tel Aviv University, Tel Aviv, Israel

The ability to perform different chemical transformations on a molecule using the same catalyst just by varying

reaction conditions is a great challenge in synthetic organic chemistry. We report here that the reaction of

aldehydes with a catalytic amount of AgOTf leads to trimerization products (trioxanes). Interestingly, when the

same reaction is performed under 4 atmospheres of H2, the reaction changes its course and leads to aldol

condensation products. We believe that in AgOTf catalyzed aldehyde trimerization process, AgOTf acts as a

Lewis acid. However, when H2 is added to the reaction mixture, heterolytic cleavage of H2 takes place, leading

to the formation of H+ (Bronsted acid) species that selectively catalyze the aldol condensation reaction. The

mechanism, supported by DFT calculations, for these transformations is proposed.

16

PA-15

Synthesis and Catalytic Activity of Dicationic Zn Complexes

Kristina Groutchik, Arseni Kostenko, Roman Dobrovetsky

Organic Chemistry, Tel Aviv University, Tel Aviv, Israel

Hydrogenation and hydroelementation of C=E bonds (E = O, N, C) are among the most important organic

reactions. Most catalytic methods involve the use of noble transition metal-based catalysts, which are

expensive, scarce or toxic. Hence, the focus of today’s research is their replacement by cheaper and less toxic

transition metal-free catalysts. The use of zinc in this perspective is of a great interest, because of its abundance,

biological relevance and distinct abilities. Here we report the synthesis of dicationic Zn complexes embedded in

tri and tetra dentate ligands, and their use in catalysis. By changing the ligand`s strategic centers we will able to

fine-tune the properties of zinc center i.e. its Lewis acidity, which will have a direct impact on the reactivity and

catalytic activity of these new Zn-based compounds.

17

PA-16

Structure and Activity of Ikarugamycin Derivatives Isolated from the Extracts

of Actinomyctes Bacteria Cultures

Ohad Hasin1, Ohad Hasin1, Dhaneesha Mohandas2, Sajeevan Thavarool2, Shmuel Carmeli1 1Raymond and Beverly Sackler School of Chemistry and Faculty of Exact Sciences,

Tel Aviv University, Tel Aviv, Israel 2National Centre for Aquatic Animal Health, Cochin University of Science and Technology,

Cochin, India

As part of our continues study on marine derived organisms and bacteria we studied the extracts of marine

Actinomyctes. Four natural products, presenting cytotoxic properties, were isolated from extracts of the

Streptomyces sp. MCCB267 cultures. The cells were freeze-dried, extracted with ethyl acetate and separated by

different chromatographic methods, including Sephadex LH-20 and HPLC chromatography. The anticancer

activity of the extracts were screened during the purification process against the NCI - H460 Lung cancer Cell

line using Sulforhodamine B (SRB) assay. The structure of the isolated compounds was determined by analysis

of the 1D and 2D NMR spectra, high-resolution mass spectroscopy, UV spectra, IR spectra and optic rotation

(αD). Ikarugamycin and 28-N-methyl ikarugamycin were isolated from samples DMS-21, DMA-37-WD and

DMA-37-D. 30-oxo-28-N-methyl ikarugamycin and clifednamide A were isolated from sample DMS-21. The

structure elucidation and biological activity of the compounds will be presented.

18

PA-17

Aminomethylene-Phosphonate Analogues as Zn(II)-Chelators: Synthesis and

Characterization

Thomas Jantz, Bosmat Levi Hevroni, Hugo Gottlieb, Bilha Fischer

Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel

series of aminomethylene(ethylene)-phosphonate (AMP, 1, AEP, 2) analogues, 3-9, bearing one or two

eterocyclic moieties (imidazolyl, pyridyl, and thiazolyl) on the aminomethylene group, were synthesized

aspotential agents for Zn(II)-chelation therapy. The complexes of analogues 3-9 with Zn(II)-ions were

characterized by their stoichiometry, geometry, coordination-sites, acid-base equilibria, and stability constants.

Analogues 3-9 form stable water-soluble 2:1 L:Zn(II) complexes, as established by Zn(II)-titration, monitored

by UV and by 1H- and 31P-NMR spectroscopy. Acidity and stability constants were established for each

derivative by potentiometric pH-titrations. ML2-type Zn(II)-complexes of AMP, bearing either an imidazolyl or

pyridyl moiety, 3, 4, and 5, exhibit high log values – 17.68, 16.92, and 16.65, respectively, while for the

AMP-thiazolyl, 6, -Zn(II) complex, log is 12.53. Generally, ligands 7, 8, and 9, bearing two heterocyclic

moieties, present higher log values (22.25, 21.00, and 18.28, respectively) vs. analogues bearing one

heterocyclic moiety. Additionally, based on 1H-,13C-, and 31P-NMR data, we propose a structure of AMP-

(Im)2-Zn(II) complex in solution, where the Zn(II)-coordination sites involve the phosphonate moiety and

both imidazolyl rings of the two binding molecules, forming an octahedral geometry around the Zn(II)-

ion. In summary, we propose a novel family of water-soluble high-affinity Zn(II)-chelators, potentially

useful for Zn(II)-chelation therapy, and in particular we suggest using AMP-(Im)2.

19

PA-18

Synthesis, Characterization and Reactivity of Thermally Stable Anhydrous

Quaternary Ammonium Fluorides

Naama Karton-Lifshin, Lea Yehezkel, Nissan Ashkenazi, Ishay Columbus, Shlomi Elias,

Yossi Zafrani

Organic Chemistry, Israel Institute for Biological Research, Ness-Ziona, Israel

Anhydrous Quaternary ammonium fluorides have been widely documented as very strong nucleophiles/bases

and are of significant interest in inorganic and organic synthesis. However, when trying to prepare such

compounds by hydrate removal conditions (heating under dynamic vacuum), they show instability and easily

undergo Hoffmann elimination (E2) by the fluoride counter ion. For example, anhydrous TBAF decomposes

even at room temperature, and therefore, it can only be prepared and used “in situ” at low temperatures. The

present work describes the synthesis and properties of a new class of anhydrous quaternary ammonium

fluorides based on the rigid skeleton of [2.2.2] azabicyclooctane, in which the Hoffmann elimination is

structurally prevented even at temperatures up to 120oC. Four such structures were easily prepared by passing

the corresponding ammonium iodides over a fluoride-based resin followed by drying under heating and reduced

pressure. The stability (experimental and theoretical study), solubility, reactivity and characterization by

solution and solid-state MAS NMR are discussed.

20

PA-19

Ru‑Catalyzed Chelation-Assisted Alkenylation of Heteroatom Substituted Aromatics and Heteroaromatics with Alkenes and Alkynes

Kishor Padala1, Masilamani Jeganmohan2 1Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

2Department of Chemistry, IISER-Pune, Pune, India

Transition-metal-catalyzed chelation-assisted ortho C‑ H bond activation of hetero-atom substituted aromatic followed by alkenylation with alkenes or alkynes is one of the powerful methods for synthesizing di- and

trisubstituted alkene derivatives in a highly regio- and stereoselective manner.1 It is important to mention that

the alkene derivatives found widespread application in organic materials, natural products and drug molecules.

The selection of directing group is highly important in order to success this type of alkenylation reaction. While

the C‑ H bond activation reaction in the presence of strong directing groups is well documented in the literature. But, activation in the presence of weak directing groups such as aldehydes, esters, cyano, sulfoxide

and ketones are still a challenging task.

In this presentation, we would like to discuss a ruthenium‑ catalyzed ortho-alkenylation of hetero-atom substituted aromatics such as aromatics and heteroaromatic carbonyl compounds with alkenes. In the reaction,

we have prepared disubstituted alkene derivatives in a highly regio- and stereoselective manner.2a-c It is

interesting to note that this catalytic reaction was conducted under the air atmosphere and only catalytic amount

of terminal oxidant Cu(OAc)2 has been used, the remaining amount of copper source being reoxidized by air. In

addition, we would like to discuss a weakly coordinating S=O assisted hydroarylation of aromatic sulfoxides

with alkynes in the presence of ruthenium catalyst leading to trisubstituted alkenes in good to excellent yields in

a highly regio- and stereoselective manner.2d

References

1. (a) Arokiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev., 2012, 112, 5879. (b) Ackermann, L. Acc. Chem.

Res., 2014, 47, 281.

2. (a) Kishor, P.; Jeganmohan, M. Org. Lett. 2011, 13, 6144. (b) Kishor, P.; Jeganmohan, M. Org. Lett. 2012,

14, 1134. (c) Kishor, P.; Pimparkar, S.; Padmaja, M.; Jeganmohan, M. Chem. Commun. 2012, 48, 7140. (d)

Kishor, P.; Jeganmohan, M. Chem. Commun. 2014, in press. (e) Kishor, P.; Jeganmohan, M. Chem. Commun.

2013, 49, 9651. (g) Kishor, P.; Jeganmohan,Chem. Eur. J. 2014, 20, 4092.

21

PA-20

Synthesis and folding of Seleno-Insulin

Orit Ktorza Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

Insulin has been the premier drug for improving the quality of life for diabetes mellitus patients. Since the early

1960s, chain A and chain B of insulin were successfully synthesized; however the recombination of these

chains to form mature native insulin remains ineffective due to the numerous non-native disulfide links, and

peptide precipitation. Many research groups have showed total chemical synthesis of fully active insulin, or

analogs that show higher stability. Our Research project proposes an alternative approach for the preparation of

human insulin analogs by substitution of pair of cysteine residues by selenocysteine, the 21st encoded amino

acid. Since it has been shown that selenium enhances the oxidative folding and diselenide bonds are more stable

that disulfide bonds, we expect to obtain an improvement of stability and recombination of the chains in higher

yields. Here we show preliminary data on our design and synthesis of seleno-insulin.

22

PA-21

Enhanced Mechanical Endurance of Internally Cross-Linked Polymers

Avishai Levy, Feng Wang, Sinai Aharonovich, Charles E. Diesendruck

Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

Understanding how materials are affected by mechanical stress is central for developing novel and robust

materials with extended lifetimes. In this regard, the most fundamental process is the effect of mechanical stress

on molecules, where mechanical energy is transduced into chemical energy by scission of chemical bonds, a

process called mechanochemistry1,2. The accumulation of stress at specific locations in the polymer chain is

known mainly for two polymeric architectures - linear and cross-linked. In our research we exploit a novel

architecture in which linear polymers are intramolecularly cross-linked, forming Single Chain Polymer

Nanoparticle (SCPN). Our study shows that whereas linear polymer chains undergo fast degradation under the

influence of mechanical force, SCPNs derived from the same linear chains demonstrate high endurance. In

addition, we studied how different parameters affect the mechanical stability such as molecular weight, cross-

link density and side-chain length, and with the help of ultra-high Mw polymers, are able to observe the

scission of intramolecular cross-links and therefore redirection of the mechanical force from the polymer main

chain.

(1) Caruso, M. M.; Davis, D. A.; Shen, Q.; Odom, S. A.; Sottos, N. R.; White, S. R.; Moore, J. S. Chemical

Reviews 2009, 109, 5755.

(2) May, P. A.; Moore, J. S. Chemical Society Reviews 2013, 42, 7497.

23

PA-22

Enolonium Species – Umpoled Enolates

Shimon Maksymenko1, Shlomy Arava1, Keshaba Parida1, Mark A. Iron1,3, Peter Fristrup1,2,

Alex Szpilman1, Jayprakash Kumar1 1Ariel University, Department of Natural Sciences, Ariel, Israel

2Technical University of Denmark, Department of Chemistry, Kgs. Lyngby, Denmark 3Weizmann Institute of Science, Department of Chemical Research Support, Rehovot, Israel

Nature has determined the roles of chemical reagents in organic synthesis as either electrophiles or

nucleophiles. Umpolung or Polarity Reversal is a powerful concept that allows these roles to be switched

thereby enabling a much larger array of methods to assemble complex organic molecules.

Umpolung of enolates mediated by hypervalent iodine reagents has shown itself to be the method of choice for

functionalizing of carbonyl compounds. This is amply illustrated by numerous papers describing halogenations,

oxygenations, aminations, and many other applications.[1] Recently we reported the use of this concept in C-C

bond forming reactions.[2,3] These reactions are widely believed to proceed through a iodo(III)-enolate like

structure named Enolonium Species.[1] However due to their high reactivity they are difficult to characterize

and they have consequently been researched mainly through computational studies.[2,4] We have now

characterized the Enolonium Species and shown determined their structure React-IR and NMR. A particular

point of discussion in the community and a scientific challenge was to determine whether the hypervalent

iodine is attached to the O of the enolate or to the C of its keto-form. The application of the Enolonium Species

in various reactions, including chlorination, amination, enol ether coupling and allylation (including examples

that lead to the formation of quaternary carbons), will be discussed.[5]

[1] a) V. V. Zhdankin, “Hypervalent Iodine Chemistry: Preparation, Structure, and Synthetic Applications of

Polyvalent Iodine Compounds”, Wiley, 2014; b) F. V. Singh, T. Wirth in: Comprehensive Organic Synthesis,

2nd ed., Vol 7, (Eds: G. A. Molander, P. Knochel P.), Oxford: Elsevier, 2014.

[2] O. S. Shneider, E. Pisarevsky, P. Fristrup, A. M. Szpilman, Org. Lett., 2015, 17, 282.

[3] T. A. Targel, J. N. Kumar, O. S. Shneider, S. Bar, N. Fridman, S. Maximenko, A. M. Szpilman Org.

Biomol. Chem., 2015, 13, 2546.

[4] a) S. Beaulieu, C. Y. Legault, Chem. Eur. J. 2015, 21, 11206; b) P.-O. Norrby, T. B. Petersen, M.

Bielawski, B. Olofsson, Chem. Eur. J. 2010, 16, 8251.

[5] S. Arava, J. N. Kumar, S. Maksymenko, M. A. Iron, K. N. Parida, P. Fristrup, A. M. Szpilman Submitted for

Publication.

24

PA-23

Catalytic Mechanochemistry

Iris Melnik, Charles E. Diesendruck

Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

Mechanochemistry is a process in which chemical reactions are driven by mechanical stress;1 however, up to

date, mechanochemical transformations were shown to occur only on polymers.2 Importantly, some

mechanochemical transformations could be very useful in the synthesis of small molecules such as natural

products and drugs, as the mechanical force changes the energy potential of different chemical processes,

directing the reaction to different products from the ones obtained by classical thermal, electro and

photochemistry. Here, we present an approach to use semi-telechelic polymers capable of reversibly binding

small molecule substrates and induce mechanochemical transformations catalytically.

We synthesized boronic ester terminated polymers, capable of binding 1,2- or 1,3-diols reversibly through

transesterification reaction. The general catalytic reaction is depicted in Scheme 1. Mechanochemically stable

polymers a boronic acid end group (P) and a small molecule (M1-M2) containing two 1,2-diols connect to form

a mechanochemically sensitive polymer chain with the substrate at its center (P-M1-M2-P). Under

solvodynamic shear, the substrate breaks into two substances (M1 and M2) and is released by trans-

esterification with a new substrate.

1] Philippe Lavalle, Fouzia Boulmedais, Pierre Schaaf and Loïc Jierry, Langmuir, 2016, 32(29), 7265–

7276.

2] Jun Li, Jeffrey S. Moore, Chem. Res., 2015, 48, 2181-2190.

25

PA-24

Methodology of the C(sp2)-Н Bond Functionalization in the Synthesis of Novel

Imidazole Derivatives

Timofey Moseev1, Mikhail Varaksin1,2, Oleg Chupakhin1,2, Valery Charushin1,2 1Department of Organic and Biomolecular Chemistry, Ural Federal University, Ekaterinburg,

Russia 2Laboratory of Heterocyclic Compounds, Institute of Organic Synthesis, Ekaterinburg, Russia

The C(sp2)-H Functionalization methodology is known to be an atom- and stage-efficient synthetic approach

for the synthesis of novel imidazole derivatives. It has been found that cyclic aldonitrones do react with both

azoles (i,ii) and azines (iii-v) to give the novel heterocyclic systems in good yields.1-3

The synthesized imidazole derivatives are of interest as promising polymer stabilizers, free radical trapping

agents, biologically active compounds, and nitroxide radical precursors.

1] Varaksin, M.V., Utepova I.A., Chupakhin O.N., Charushin V.N. J. Org. Chem., 2012, 77, 9087.

2] Varaksin, M.V., Utepova I.A., Chupakhin. Chem. Heterocycl. Comp., 2012, 48, 1213.

3] Varaksin, M.V., Utepova I.A., Chupakhin O.N., Charushin V.N. Tetrahedron, 2015, 71, 7077.

The study was supported by the Russian Science Foundation (Project № 14-13-01177) and the Russian

Foundation for Basic Research (Project № 16-03-00958)

26

PA-25

Synthesis of Highly Functionalized Alkenylfluorides by Silver-Mediated

Fluorodestannation

Heiko Sommer1,2, Alois Fürstner1 1Organometallic Chemistry, Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr,

Germany 2Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

The role of fluorine in synthetic and medicinal chemistry receives an ever-increasing attention as fluorine plays

a unique role in influencing the conformation, solubility, potency, permeability or degradability of small

molecules. The late-stage introduction of fluorine is of great interest as it allows the modification of complex

molecules without significantly changing the synthetic route.

In conjunction with our previously reported ruthenium-catalyzed directed trans-hydrostannation of internal

alkynes[1], an efficient method for the synthesis of highly elaborate alkenyl fluorides could be implemented

(Scheme 1).[2]

Scheme 1. Hydrostannation/fluorodestannation for the synthesis of fluoroolefins

During our studies, we developed a mild protocol that allowed us to transform a plethora of alkenylstannanes

into the corresponding fluorides while overcoming competing protodestannation.[3] Key to success is the

utilization of the non-hygroscopic salt silver(I) diphenyl phosphinate (AgDPP) as a mediator.

We applied this new protocol to the synthesis of highly functionalized, biologically relevant compounds,

consisting among others of a polyketide derivative, a peptide bioisoster and a prostaglandin derivative (Scheme

2).

Scheme 2. Selected examples of the silver-mediated fluorodestannation

Literature

[1] a) S. M. Rummelt, A. Fürstner, Angew. Chem. Int. Ed. 2014, 53, 3626-3630; b) S. M. Rummelt, K.

Radkowski, D.-A. Roşca, A. Fürstner, J. Am. Chem. Soc. 2015, 137, 5506-5519.

[2] H. Sommer, A. Fürstner, submitted manuscript, 2016.

[3] M. A. Tius, J. K. Kawakami, Tetrahedron 1995, 51, 3997-4010.

27

PA-26

Mechanisms of Reactions of Ce(III)DOTA with Radicals in Aqueous Solutions

Elad Avraham1,2, Inna Popivker1, Israel Zilbermann1,2, Eric Maimon1,2, Guy Yardeni1,

Philippe Moisy3, Laurence Berthon3, Laurent Venault3, Dan Meyerstein2,4 1Chemistry, Nuclear Research Center Negev, Beer-Sheva, Israel

2Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel 3Nuclear Energy Division, Radiochemistry & Processes, CEA, Bagnols-Sur-Ceze, France

4Chemical Sciences Department and the Schlesinger Family Center for Compact Accelerators,

Radiation Sources and Applications, Ariel University, Ariel, Israel

Recent studies have shown that DOTA stabilizes thermodynamically both Ce(III) (log K= 23.4)1 and Ce(IV)

(log K= 35.9)2, shifting cathodically the CeIV/III couple to +0.65V vs. SCE , a stabilization of ~ 13 orders of

magnitude compared to its aqueous analogue2.

As such we decided to study the reactions of Ce(III)DOTA with several radicals, oxidizing agents: .OH; .CH3; .OOCH3 (given in the exact order of the redox potentials, .OH –the strongest), analyze the products –compare to

the reported electrochemical and chemical oxidized cerium complex.

The radicals were produced by continuous radiolysis in aqueous N2O saturated solutions (DMSO present for .CH3; .OOCH3 and 50% v/v O2 present for .OOCH3.). The spectra of the products clearly show the formation of

long lived Ce(IV)DOTA(pH dependent) species in the case of .OH and .OOCH3. In the case of peroxyl radicals

the main organic product is methanol, different of the main product of the reactions of DOTA and DyDOTA

(not redox active) with the same radical, where formaldehyde is the main product. In the case of methyl radicals

the ratio CH4/C2H6 is similar for Ce(III)DOTA, DyDOTA and DOTA indicating an H abstraction mechanism

from DOTA as the main path. Detailed data will be presented.

1] Burai et al., J.Chem.Soc.Dalton Trans. 1998, 443.

2] Y. Moiseev et al., J.Coord.Chem. 2016, 69(19),2895

28

PA-27

Expanding the Toolbox for the Synthesis of Organometallic Nanoparticles via

the Single-Chain Collapse Approach

Inbal Berkovich, Gabriel N. Lemcoff

Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Organic nanoparticles (ONPs) prepared via the intramolecular cross-linking of single polymer chains pose

promising prospects for various applications.1-4 We have recently developed an intramolecular single chain

collapse approach for the synthesis of organometallic nanoparticles using ROMP-derived polycyclooctadiene

(PCOD) and the direct ligand exchange of Rh(I), Ir(I) and Ni(0) complexes.5-6 This methodology was further

expanded for the preparation of high MW ONPs from commercially available polybutadiene.7 Herein, the use of

commercial polyisoprene as an alternative precursor for the preparation of ONPs will be examined. In addition,

we present our current efforts towards the preparation of catalytically active Rh(II)-ONPs by the exchange of

trifluoroacetate ligands in Rh2[TFA]4 with the -COOH groups of ROMP- derived polymers.

References:

1] T. Ashai, T. Sugiyama, H. Masuhara, Acc. Chem. Res. 2008, 41, 1790-1798.

2] S. Mavila, O. Eivgi, I. Berkovich, N. G. Lemcoff, Chem. Rev. 2016, 116, 878-961

3] A. Sanchez-Sanchez, A. Arbe, J. Colmenero, J. A. Pomposo, ACS Macro Lett., 2014, 5, 439-443.

4] N.G. Lemcoff, T. A. Spurlin, A. A. Gewirth, S. C. Zimmerman, J. B. Beil, S. L. Elmer, G.

Vandeveer, J. Am. Chem. Soc. 2004, 126, 11420-11421.

5] S. Mavila, C. E. Diesendruck, S. Linde, L. Amir, R. Shikler, N.G. Lemcoff, Angew. Chem. Int. ed.

2013, 52, 5767-5770.

6] S. Mavila, I. Rozenberg, N.G. Lemcoff, Chem. Sci. 2014, 5, 4196-4203.

7] I. Berkovich, S. Mavila, O. Iliashevsky, S. Kozuch, N. G. Lemcoff, Chem. Sci. 2016, 7, 1773-1778.

29

PA-28

Jojoba Oil Olefin Metathesis: A Valuable Source for Bio-Renewable Materials

Danielle Butilkov, Gabriel N. Lemcoff

Chemistry Department, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Jojoba oil is a diene composed of two monounsaturated hydrocarbon chains linked by an ester moiety.

Ruthenium catalysed cross-metathesis reactions (CM) of the oil produced ADMET oligomers and hydrocarbon

by-products under various conditions.1 Both the polyester oligomers and the hydrocarbon distillates were

analysed by several analytical techniques. The oligomers were also hydrolysed under basic conditions to assess

potential degradability. Oligomerisation of the starting material by an alternative thiol-ene ‘click’ reaction was

also probed. A high atom economy is expected for this catalytic process given that all products obtained may be

used either as sources for bio-fuel (hydrocarbons), or as potential renewable and degradable materials

(polyester chains). In addition, a novel methodology for a concise preparation of synthetic jojoba oil will be

presented.

Cyclic alkyl amino carbene (CAAC) ligands are a class of σ-donor ligands which was introduced first by

Bertrand et al. in 2005.2 Ruthenium catalysts bearing this type of ligands showed high reactivity towards

ethenolysis3 (TON = 340,000) and CM4 (TON = 315,000) reactions. Reactions of Jojoba oil and CAAC bearing

ruthenium catalysts were conducted in different conditions in order to make the reaction more efficient and

achieve better materials. Results will be presented.

Reference

1] Butilkov, and N. G. Lemcoff, Green Chem., 2014, 16, 4728-4733.

2] Lavallo, Y. Canac, C. Prasang, B. Donnadieu, G. Bertrand, Angew. Chem. Int. Ed., 2005, 44, 5705 –

5709.

3] M. Marx, A. H. Sullivan, M. Melaimi, S. C. Virgil, B. K. Keitz, D. S. Weinberger, G. Bertrand, and

R. H. Grubbs, Angew. Chem. Int. Ed., 2015, 54, 1919 –1923.

4] Gawin, A. Kozakiewicz, P. A. Guńka, P. Dąbrowski, and K. Skowerski, Angew. Chem. Int. Ed.,

2016, DOI: 10.1002/anie.201609009.

30

PA-29

Sunscreen and Ruthenium Olefin Metathesis Catalysts: A One-Pot, Two-Step

Photochemical Synthesis of Coumarins

Or Eivgi, Gabriel N. Lemcoff

Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

We have recently demonstrated a novel type of chromatic selectivity by exploiting differences in molar

absorption coefficients. Thus, selective removal of photolabile protecting groups (PPGs) using internal or

external "sunscreens" was achieved using a single light source.1 Herein, the sunscreen methodology is applied

to the catalytic photo-induced cross metathesis (CM) reaction of 2-vinyl phenol derivatives protected with 2-

nitrobenzyl PPG. 2-vinyl phenols are impractical for olefin metathesis reactions due to stable chelate formation

with the ruthenium catalyst.2-4 By protection of the phenol moiety with a 2-nitrobenzyl PPG we can exploit the

large difference in the molar absorption coefficients at 380 nm UV light between the ruthenium catalysts

developed by our group5-7 and the 2-nitrobenzyl chromophore, to selectively activate the ruthenium catalyst

without removal of the 2-nitrobenzyl PPG in the presence of an external sunscreen solution. Thus, we can now

carry out a light triggered cross metathesis (CM) reaction of the acrylate esters and 2-nitrobenzyl protected 2-

vinyl phenols in 380 nm light, in the presence of an external solution of pyrene carboxaldehyde as a sunscreen.

While subsequent irradiation of the reaction vessel with 254 nm light after removal of the external sunscreen

prompts a chain of three reactions to yield the coumarin derivatives.

References:

(1)Eivgi, O. et al. Org. Lett. 2015, 17, 740

(2)Kozłowska, A. et al. Chem. Eur. J. 2014, 20, 14120

(3)Garber, S. B. et al. J. Am. Chem. Soc. 2000, 122,8168

(4)Kingsbury, J. S. et al. J. Am. Chem. Soc. 1999, 121, 791

(5)Ben-Asuly, A. et al. Organometallics 2009, 28, 4652

(6)Diesendruck, C. E. et al. Inorg. Chem. 2009, 48, 10819.

(7)Ginzburg, Y. et al. Organometallics 2011, 30, 3430.

31

PA-30

Cobalt Porphyrin-Graphene Systems for the Electrocatalytic Reduction of

Oxygen

Meital Eliyahu, Eli Korin, Armand Bettelheim

Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Oxygen reduction reaction occurs on the cathode of fuel cells. This reaction is considered to be very sluggish

and therefore it is a necessity to use catalysts to improve the kinetics. Electrocatalytic reduction of oxygen

occurs in 2 main pathways: direct reduction of the oxygen to water by a four-electron pathway and indirect

reduction of oxygen by a two-electron pathway, forming hydrogen peroxide as an intermediate.

Although catalysts for oxygen reduction reaction that exhibit a very good activity exist, most of them are based

on noble metal catalysts, which are considered to be very expensive. Developing efficient non-noble metal

catalysts for the oxygen reduction reaction is one of the main keys to the production of commercially durable

fuel cell devices for future renewable energy applications. Porphyrins have been extensively studied and

demonstrated a good catalytic activity for oxygen reduction reaction, but most of them show activity only for

the two-electron pathway to yield H2O2. The present study deals with interactions, such as π-π stacking,

occurring between metalloporphyrin and graphene derivatives and their effect on the activity of the systems

towards O2 reduction.

Stable suspensions were obtained from 5,10,15,20-tetrakis(1-methyl-4-pyridinio) porphyrin (CoTMPyP) and

graphene oxide (GO) in a wide range of pH. UV/Vis spectroscopy measurements for suspensions of CoTMPyP-

GO at pH 7.2 showed a 9 nm red shift for the CoTMPyP Soret band observed around 433 nm, thus indicating π-

π stacking. Cyclic voltammetry measurements for glassy carbon electrode coated with CoTMPyP-GO showed

that the O2 catalytic reduction peak is shifted 200 mV anodically in comparison to that observed for CoTMPyP

(-0.09 and -0.29 V vs. Ag/AgCl, respectively).

32

PA-31

Synthesis of Heavier Analogues Af alkenes, R2E=CR’2 (E= Si, Ge, Sn),

via Lithium Silanolate Elimination

Yuliya Goldshtein, Lieby Zborovsky, Victoria Molev, Dmitry Bravo-Zhivotovskii,

Yitzhak Apeloig

Schulich Faculty of Chemistry and the Lise Meitner-Minerva Center for Computational

Quantum Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

We report here the study of the reaction of tri-silyl-substituted lithium anions (R3Si)3ELi•nTHF 1, 3, 5, 6 (E =

Si, Ge, Sn) with 2-adamantanone, in order to prepare stable heavier analogues of alkenes (R3Si)2E=CR’2 (E=

Si, Ge, Sn). We find that larger silyl-substituents on (R3Si)3ELi facilitate their reduction, but at the same time

provide stability to the desired product. In this work we aimed to find the best combination of silyl-substituents,

to obtain stable heavier analogues of alkenes.

The reaction of the most bulky silyl-branched (R3Si)3ELi 1 with 2-adamantanone leads to the corresponding E-

radicals 2 i.e., only electron-transfer occurs. Decrease in the size of the silyl-substituents, e.g., 3a and 5a leads

to formation of a stable silene 4a. In contrast, the reaction of analogous stannyl lithium 3b leads to

corresponding radical. Reaction of silyl-branched stannyl lithium 5b with 2-adamantanone yields the stable

stannene 4c. Reaction of smallest silyl-branched (t-BuMe2Si)3E-Li 6 with 2-adamantanone leads to the

corresponding stable silene 7a and germene 7b, but to a transient stannene 7c, trapped by reaction with p-

quinone. The obtained products 2, 4, 7, 8 were characterized by NMR, EPR spectroscopy and some by X-ray

crystallography.

33

PA-32

Photochemical Reduction of CO2 with Visible Light using a Polyoxometalate

as Photoreductant

Eynat Haviv1, Ronny Neumann1, Linda J. W. Shimon2 1Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel

2Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel

The reduction of CO2 to a higher energy species such as CO is a key transformation and by and large an

important missing link towards the development of carbon-based solar fuels to remediate increasing amount of

CO2 in the atmosphere and replace finite amounts of fossil fuels. Both photochemical and electrochemical

pathways are being studied. The present state of the art teaches that the CO2 to CO reduction by

a photochemical pathway requires sacrificial tertiary amines as the source of electrons and protons needed for the transformation and either low wavelength light or photosensitizers based on Ir

and Ru compounds.1

an electrochemical pathway that still requires prohibitively high potentials, typically higher than 1.7 V versus Ag/AgNO3.

2

In order to overcome these two basic deficiencies, we combine a new di-rhenium molecular catalyst

active for CO2 photoreduction that also has a tether to bind a polyoxometalate via a simple acid-base

interaction. The polyoxometalate is an electron reservoir that can shuttle electrons from an electrode to

the molecular catalyst.

Now, in a cascade of transformations a new photoelectrochemical pathway is presented wherein a

polyoxometalate, the commercially available phosphotungstic acid, H3PW12O40, is electrochemically reduced at

low potential (1.3 V versus Ag/AgNO3), and low intensity visible light (60 W tungsten lamp) is used to

transfer electrons from the polyoxometalate to the catalyst that is active for selective reduction of CO2 to CO.

1] a)Ziessel, R., Hawecker, J., Lehn, J.-M., Chim. Acta, 69, 1990–2012 (1986). (b) Fujita, E., Coord.

Chem. Rev., 185-186, 373-384 (1999). (c) Takeda H., Koike K., Inoue H., Ishitani O., J. Am. Chem.

Soc., 130, 2023-2031 (2008).

2] Kumar, B., Llorente, M., Froehlich, J., Dang, T., Sathrum, A., Kubiak, C. P., Rev. Phys. Chem., 63,

541-569 (2102).

34

PA-33

Exploration of the Nature of the Anionic Ligands in Ruthenium Pre-Catalysts

Designed for Asymmetric Olefin Metathesis

Elisa Ivry, Gabriel N. Lemcoff

Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Ruthenium alkylidenes complexes are key components in the promotion of the highly important metathesis

reaction. Throughout the years there have been extensive studies discussing the nature and impact of the

surrounding ligands within the catalytic sphere of these complexes. Replacement of the commonly used

chloride ligands in the known ruthenium alkylidenes by different halides and pseudo-halides showed that fine-

tuning of the anionic ligands can lead to different reactivity and selectivity of the pre-catalysts.1 We have

recently demonstrated that asymmetric metathesis can be achieved by the facile installation of amino acids as

chiral anionic ligands.2 The use of readily available amino acids enables a simple protocol as well as easily

tuned properties. Nonetheless, due to the dynamic nature of the anionic position,3 reduction of the lability of the

carboxylate ligands was found to be crucial in improving the observed enantioselectivity. Therefore we are

currently focusing on probing the dynamic nature of the anionic position and its role in the stability and

reactivity of a variety of ruthenium complexes. Better understanding of the processes in which the anionic

ligands are involved, will lead to the synthesis of a stable, enantioselective ruthenium complex bearing amino

acid anionic ligands as chiral inducers.

References:

1 Anderson, E. B.; Buchmeiser, M. R. Synlett 2012, 2, 185.

2 Ivry, E.; Ben-Asuly, A.; Goldbergb, I.; Lemcoff, N. G. Chem. Commun. 2015, 51, 3870.

3 Tanaka, K.; Böhm, V. P. W.; Chadwick, D.; Roeper, M.; Braddock, D. C. Organometallics. 2006, 25, 5696.

35

PA-34

Towards Silanone via Bromosilanols and Bromosiloxanes

Alexander Kaushansky, Dmitry Bravo-Zhivotovskii, Yitzhak Apeloig

Schulich Faculty of Chemistry and the Lise Meitner-Minerva Center for Computational

Quantum Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

Stable isolable silanones, R2Si=O, the silicon analogue of ketones, are not yet known.

Here, we report the synthesis and X-Ray structural analysis of lithium bromosilanolate 3 and the reaction of

bromosiloxane 5 with silyllithium in hexane and in THF, which we believe yields a transient silanone.

Reaction of 2 with )Me3Si(2NLi yields trimer 3. X-Ray structural analysis of 3 reveals significant Li-Br

interactions, i.e. r(Li--Br) = 2.20 Å (shorter than the sum of their ionic radii), a very short r(Si-O) = 1.58 Å and

a relatively long r(Si-Br) = 2.29 Å.(see Figure 1) These structural features point to a major contribution of a

R2Si=O···LiBr complex character in 3. The structural features of 3 resemble those of dialkyl substituted dimeric

R2Si=O-LiBr complex recently published by Iwamoto.2 Hydrolysis of 3 yields diol 4. Disappointingly, heating

3 to 70°C in hexane or THF does not lead to LiBr elimination, indicating strong intermolecular bonding in 3.1

To prevent aggregation through strong O-Li-O interactions as in 3, the hydroxyl group in 2 was replaced by a

siloxy group, i.e., 5. Interestingly, reaction of 5 with tBu2MeSiLi is solvent dependent. In hexane this reaction

yields tris(silyl)silyllithium 7. However, in THF disilane 8 is produced together with what we believe is the

transient silanone 9. As expected, hydrolysis of 9 yields diol 4. We continue efforts to isolate silanone 9.

[1] A. Kaushansky, M.Sc. Thesis, Technion, Haifa, Israel, 2013.

[2] S. Ishida, T. Abe, F. Hirakawa, T. Kosai, K. Sato, M. Kira, T. Iwamoto, Chemistry – A European Journal

2015, 21, 15100-15103.

36

PA-35

Studying the Role of Anion Ligands in Organometallic Nanoparticles

Victoria Kobernik, Gabriel N. Lemcoff

Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

In recent years the field of single chain organic nanoparticles has attracted the interest of the scientific

community due to their promising applications and ease of synthesis.1 By coordinating metals to a binding

polymer matrix under dilute conditions, intramolecular cross-linking could be achieved, leading to single chain

collapse and the formation of organometallic nanoparticles (ONPs).2

Polycyclooctadiene (PCOD) can coordinate rhodium chloride dimer complexes, leading to a change in the

polymer`s properties; e.g. its conductivity.2 The current study focuses on the possible role of the anion bridging

ligand in the ONPs with different anions made from PCOD and polybutadiene (PBD).3 This study may enable a

better understanding of the conductivity mechanism and will furnish a series of new ONPs with potential novel

properties.

References:

1.Mavila, S.; Eivgi, O.; Berkovich, I.; Lemcoff, N.G., Intramolecular Cross- Linking Methodologies for the

Synthesis of Polymer Nanoparticles, Chem. Rev., 2016, 116, 878–961.

2.a) Mavila S.; Diesendruck C.E.; Linde S.; Amir L.; Shikler R.; Lemcoff N.G., Polycyclooctadiene complexes

of rhodium (I): direct access to organometallic nanoparticles, Angew. Chem. Int. Ed., 2013, 52, 5767-5770. b)

Mavila S.; Rozenberg I.; Lemcoff N.G., A General Approach to Mono- and Bimetallic Organometallic

Nanoparticles, Chem. Sci., 2014, 5, 4196-4203.

3.Berkovich I.; Mavila S.; Iliashevsky O.; Kozuch S.; Lemcoff N.G., Single chain polybutadiene

organometallic nanoparticles: an experimental and theoretical study, Chem. Sci. 2016, 7, 1773-1778.

37

PA-36

Synthesis of Sila-Grignard Reagents Via Radical Activation of Si-H Bonds by

RMgX or R2Mg

Yosi Kratish, Yevgeni Mashin, Yuliya Goldshtein, Alexander Kaushansky,

Dmitry Bravo-Zhivotovskii, Yitzhak Apeloig

Schulich Faculty of Chemistry and the Lise Meitner Minerva Center for Computational

Quantum Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

Organomagnesium compounds play an important role in both organic and organometallic chemistry. In

contrast, the chemistry of silylmagnesium compounds is very limited, most probably due to the fact that

reactions of elemental magnesium with silyl halides do not lead to the formation of silylmagnesium compounds

but rather to Wurtz-type silicon-silicon coupling products. Reaction of silyllithium compounds with magnesium

halides is currently the most useful method for preparation of silylmagnesium compounds. However the limited

number of silyllithium reagents available is a major drawback.

Previously, we reported that organozinc reagents can activate Si-H bonds via a radical mechanism producing

silylzinc compounds [1]. Here, we report the first examples of radical activation of Si-H bonds in silyl

substituted hydridosilanes R(4-n)SiHn (n=1-3) by tBuMgCl and R`2Mg (R` = nBu, tBu, R``3Si) leading to a direct

sila-metalation reaction. Using this reaction we synthesized mono and bis magnesium substituted silanes from

the di-hydrido silane 1 (Eq. 1). Moreover, reaction of the tri-hydrido silane 2 with tBu2Mg yields the novel

trifunctional mono magnesium silane 3 which was then reacted with several electrophiles (Scheme 1). Addition

of tBu2Hg (radical initiator) increased the reaction yield significantly. Addition of 1,4-cyclohexadiene (radical

inhibitor) inhibited the reaction completely. These results support a radical mechanism similar to reactions of

silanes with organozinc reagents [1].

[1] R. Dobrovetsky, Y. Kratish, B. Tumanskii, M. Botoshansky, D. Bravo-Zhivotovskii, Y. Apeloig, Angew.

Chem. Int. Ed. 2012, 51, 4671.

38

PA-37

Self-Assembly of Peptide-Oligonucleotide Nanostructures

Agata Chotera, Gonen Ashkenasy

Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Systems chemistry attempts to mimic the complex biological networks within synthetic chemical framework.

Analysis of their dynamic self-organization, as well as self-replication and catalytic properties, can help us to

better understand the bottom-up organization of supramolecular architectures. Thus, we investigate self-

assembly of synthetic peptide-oligonucleotide conjugates. Although peptide- and nucleic acids- based self-

organizing systems are well documented in the literature, artificially synthesized hybrid molecules present a

unique family of compounds. Studying such conjugates will offer new superior soft matter suitable for many

applications and might even shed light on bottom-up scenarios related to the origin of life. Here, we present a

set of self-assembling peptide-DNA hybrids that have been designed and synthesized. Short nucleic acid

segments have been attached to amphiphilic replicating peptides previously explored in our lab1-3. The basic

system consists of two conjugates, for which the oligonucleotide segment of one is complementary to the other

(Scheme 1). We demonstrate the self-assembly of our system into different morphologies: fibers and sphere-

like structures. To the best of our knowledge, this study proposes the first systematic analysis of structural and

functional characteristics of small peptide-DNA assemblies.

REFERENCES

1] B. Rubinov, N. Wagner, H. Rapaport and G. Ashkenasy, Angew Chem Int Ed Engl, 2009, 48, 6683-

6686.

2] B. Rubinov, N. Wagner, M. Matmor, O. Regev, N. Ashkenasy and G. Ashkenasy, ACS nano, 2012,

6, 7893-7901.

3] M. Tena-Solsona, J. Nanda, S. Díaz-Oltra, A. Chotera, G. Ashkenasy, B. Escuder, Chem. Eur. J.,

2016 (DOI: 10.1002/chem.201600344).

39

PA-38

Total Chemical Synthesis of SUMO-2-Lys63-linked diUbiquitin Hybrid

Chains Assisted by Removable Solubilizing Tags

Emad Eid1, Somasekhar Bondalapati1, Patrick Lombardi2, Cynthia Wolberger2, Ashraf Brik1 1Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

2Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of

Medicine, Baltimore, USA

Along with the known posttranslational modification by ubiquitin, known as ubiquitination, there are many

ubiquitin like modifiers such as the Small Ubiquitin Like Modifier (SUMO) proteins, which are know to

regulate many important cellular processes. Like ubiquitination, SUMOlytion is also mediated by E1, E2, and

E3 enzymes linked via an isopeptide bond to the C-terminal Gly of SUMO to a Lys residue from a target

protein. Recently, the hybrid chains of SUMO-ubiquitin and specifically SUMO-2 linked to Lys63-di-ubiquitin

were found to play major role in DNA repair. Despite some progress in understanding the role of the hybrid

chains in DNA repair, there are various fundamental questions remained to be answered. To farther investigate

the importance of hybrid SUMO-ubiquitin chains in DNA repair, homogenous material of the hybrid chains and

their unique analogs are needed in workable quantities. For the first time and by applying advanced chemical

strategies in protein synthesis we report the total chemical synthesis of four different SUMO-2-Lys63-linked di-

ubiquitin hybrid chains. In this synthesis, the usefulness of removable solubilizing tags is demonstrated and

new lessons were learned for future studies where peptide fragments are difficult to handle and purify. The

availability of these chains open new opportunities in studying the role of these chains in DNA repair and other

cellular processes, which we are currently pursuing.

40

PA-39

Coiled Coil Protein Based Smart Surfaces Implementing Orthogonal Logic

Operations

Chiara Glionna1, Nurit Ashkenasy2, Gonen Ashkenasy1 1Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

2Materials Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Recently, the gap facilitating the utility of molecular logic systems for application in technological fields was

reduced after the implementation of molecular logics on solid surfaces, where molecules functionalizing the

surface are designed to respond to specific inputs. Coiled coil protein assemblies are suggested here as new

candidates for this task, due to their versatile properties and functionalities.[1] Here, we present reversible

surface attachment-detachment processes involving coiled coil proteins and describing orthogonal logic

operations. Coiled coil peptides have been designed, synthesized and characterized in solution by circular

dichroism and fluorescence spectroscopies. Several reversible binding and releasing, folding and unfolding

processes of heterodimeric coiled coil proteins have been performed on silicon nitride and gold surfaces. The

surface layer was characterized by ellipsometry, fluorescence and contact angle after each step. These

programmable reactions have been performed demonstrating Boolean logic operation. The coiled coil peptides

were labelled with a FRET couple, allowing the parallel implementation of two- and three-input logic gates,

NOR-OR and AND-ANH-NAND, following monolayer thickness, donor quenching, and wettability as readout.

The experiments accomplished demonstrated the feasibility of this system for reversible protein self-assembly

on solid surfaces. Surface properties can be dynamically dictated by functionalization with appropriate designed

proteins depending on the targeted device application. This new approach of programmable manipulation of

synthetic proteins on solid surface can pave the way to the development of more effective and flexible

biosensing devices.

[1] C. Shlizerman, A. Atanassov, I. Berkovich, G. Ashkenasy and N. Ashkenasy, J. Am. Chem. Soc., 2010, 132,

5070-5076.

41

PA-40

Dual Enzymatic Activation of Polymeric Micelles

Assaf J. Harnoy, Tamir Forsht, Sabina Panfilov, Einat Tirosh, Roey J. Amir

School of Chemistry, Tel Aviv University, Tel Aviv, Israel

Synthetic self-assembled nano structures and their interactions with enzymes have been drawing increased

attention as part of the growing interest in biocompatible and biodegradable stimuli-responsive polymeric

platforms. Utilization of enzymes as triggers that can modify the structural properties of polymeric assemblies

can be highly relevant for biological applications such as controlled drug delivery, tissue engineering, etc. The

key factors that grant enzymes the potential to act as stimuli are their catalytic efficiency, high selectivity

towards their substrates and vast natural abundance in biological tissues. Furthermore, many disease states are

frequently associated with a unique enzymatic over-expression, which could be exploited to stimulate cleverly

designed platforms in order to induce a site specific-response. Our research group recently developed a simple

synthetic approach for preparation of enzyme-responsive PEG-dendron hybrids. Our molecular design included

PEG as the hydrophilic backbone, while the enzyme-responsive functionalities were attached to the terminal

positions of a dendron unit. These amphiphilic hybrids were shown to self-assemble in aqueous media into

nano-sized polymeric micelles and to disassemble in response to the designed enzymatic stimulus. In this work,

we wished to expand the enzymatic trigger from a single enzyme into two activating enzymes by attaching two

different kinds of dendrons to the block copolymer junction. Each dendron unit was functionalized with

different substrates and activation by either one of the enzymes was shown to cause the micelles to disassemble

and release their encapsulated molecular cargo. In addition, simultaneous activation with both enzymes caused

the micelles to disassemble even faster, granting a much wider range of activation rates.

42

PA-41

Analyzing Amyloid Beta Aggregates with a Combinatorial Fluorescent

Molecular Sensor

Joydev Hatai, Leila Motiei, David Margulies

Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel

The self-assembly of amyloid beta (Aβ) peptides into insoluble aggregates is thought to play a major role in the

progression of various neurodegenerative diseases, including Alzheimer`s disease (AD). Although various

studies have shown that subtle variations in the dynamics and compositions of Aβ aggregates could have a

significant impact on their physicochemical and pathological properties,1 currently there is no effective means

to straightforwardly characterize the Aβ aggregation state. Fluorescent assays, which mainly rely on the ‘turn-

on’ properties of a thioflavin T (ThT) molecule, can only detect the fibril formation, whereas other techniques

that can determine the content of these assemblies require special expertise and are not high-throughput. To

improve the ability to analyze Aβ aggregates, we have developed a combinatorial fluorescent molecular sensor

that generate a wide range of unique emission ‘fingerprints’ upon binding to distinct Aβ aggregate species. The

molecular sensor has been used to discriminate among aggregates generated from different alloforms (i.e., Aβ40

and Aβ42) or through distinct pathways, and it has also been used to track dynamic changes that occur in Aβ

aggregation states, which result from the formation of low molecular weight (LMW) oligomers, high molecular

weight (HMW), oligomers, protofibrils, and fibrils (Figure 1).

Figure 1. (a) Schematic representation of the Aβ aggregation process. (b) Chemical structure of a combinatorial

fluorescent molecular sensor 1. (c) Linear discriminating analysis (LDA) showed the ability of sensor to

discriminate among the various aggregates.

References.

1.Bitan, G.; Kirkitadze, M. D.; Lomakin, A.; Vollers, S. S.; Benedek, G. B.; Teplow, D. B., Proc. Natl. Acad.

Sci. 2003, 100, 330; (b) Benilova, I.; Karran, E.; De Strooper, B., Nat. Neurosci. 2012, 15, 349.

43

PA-42

Overcoming the Lack of Stereocomplementarity within Ene-reductases: The

Chemoenzymatic Synthesis of all four Stereoisomers of 2-Methylbutane-1,3-

diol

Marvin Rafael Mantel1, Elisabeth Rüthlein1, Thomas Classen2, Jörg Pietruszka1,2 1Institute for Bioorganic Chemistry, Heinrich-Heine-University Düsseldorf at the Research

Center Jülich, Jülich, Germany 2Institute of Bio - and Geosciences, Research Center Jülich, Jülich, Germany

The chemoenzymatic synthesis of small molecules can provide perfect stereoselectivity where organic methods

only supply a certain level of enantiopurity. However, enantiocomplementary enzymes are not always

accessible, preventing chemoenzymatic synthesis from becoming a versatile tool in accessing all stereoisomers

of a desired product. [1]

Herein we present an approach to overcome this problem by dexterous substrate-design instead of exhausting

catalyst-engineering. Two different substrates converted by the same ene-reductase enable access to

enantiocomplementary products. Next to the original substrate, ‘mirrored’ starting material can be converted in

a similar stereospecific fashion. Afterwards chemical modification of the residues following the enzymatic

reaction causes a priority-switch of the residues granting access to the missing isomers.

All remaining stereogenic information is installed by ADHs, matching the advantages of classic organic

methods and biocatalysis within a truly chemoenzymatic synthesis to all possible stereoisomers perfectly.

[1] (a) E. Rüthlein, T. Classen, L. Dobnikar, M. Schölzel, J. Pietruszka Adv. Synth. Catal. 2015, 375, 1775-

1786 (b) Enzyme Catalysis in Organic Synthesis, Vol. 1, Wiley-VCH Verlag & Co. KGaA, Weinheim,

Germany, 2012.

44

PA-43

Identifying Small Protein Populations by a Combinatorial

Fluorescent Molecular Sensor

Zohar Pode1, Ronny Peri-Naor1, Joseph Georgeson2, Tal Ilani2, Vladimir Kiss3,

Tamar Unger4, Leila Motiei1, David Margulies1 1Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel 2Structural Biology, Weizmann Institute of Science, Rehovot, Israel

3Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel 4Israel Structural Proteomics Center, Weizmann Institute of Science, Rehovot, Israel

In recent years, a growing number of cross-reactive sensor arrays that can recognize proteins in a non-selective

manner have emerged. Although various differential sensors of this class have been developed and used to

discriminate among proteins, these systems are less suitable for analyzing specific populations of proteins in

their native environment. Cell-penetrating unimolecular sensors, on the other hand, are very specific and can

only detect one target at a time. In this study, we developed a unimolecular sensor that can detect different

proteins by generating unique identification patterns, similarly to cross-reactive arrays. We have shown that its

unimolecular scaffold and selective binding enable the combinatorial sensor to identify combinations of

proteins within complex biological mixtures and track several binding interactions simultaneously.

45

PA-44

Chemo-Enzymatic Labelling of the Epigenetic DNA Modification

5-Hydroxymethylcytosine

Gil Nifker, Micha Fridman, Yuval Ebenstein

Chemistry, Tel Aviv University, Tel Aviv, Israel

The field of Epigenetics focuses on DNA and chromatin modifications not encoded in the DNA sequence.

5-Methylcytosine (5-mC), DNA methylation, is known to play a key role in diseases and differentiation

mechanisms. It recently has been shown that 5-mC is oxidized to 5-hydroxymethylcytosine (5-hmC) in an

endogenous enzymatic reaction. 5-hmC, displays tissue specific distribution and has been related to gene

expression. For labeling purpose, 5-hmC can be selectively glycosylated by the β-glucosyltransferase enzyme

(β-GT), originated from the T4 bacteriophage; using a synthetic substrate that enables fluorescent tagging of

5-hmC residues via click chemistry. This approach has not been broadly adopted due to the challenging

synthesis and limited commercial availability of the glycosylation substrate 6-N3-UDPG. This work focused on

finding a solution for this problem.

46

PA-45

Strategy for the Development of Non-toxic Antimicrobial Cationic

Amphiphiles

Kfir B. Steinbuch Department of Organic Chemistry, Tel Aviv University, Tel Aviv, Israel

Fungal infections are an increasing problem both in Western medicine and in regions with limited healthcare

availability. Mortality due to invasive fungal diseases likely exceeds that of tuberculosis or malaria with

Candida albicans and Candida glabrata as the most frequently treated opportunistic fungal pathogens. Inspired

by antimicrobial cationic peptides, we have developed several families of synthetic antimicrobial cationic

amphiphiles. We demonstrated that by manipulating structural motifs it is possible to enhance their selectivity

for microbial rather than mammalian red blood cell membranes. To date, none of the reported cationic

amphiphiles exhibited membrane selectivity sufficient to be considered for development of membrane-

disrupting antifungal agents.

Here in we report that the incorporation of cis-double bonds into the lipids of cationic amphiphile significantly

decrease their hemolysis and toxicity against mammalian cells. We demonstrated that increasing the degree of

cis-unsaturation in the lipid of antifungal cationic amphiphiles does not affect their antifungal activity against

Candida and decreases their hemolytic activity as well as their mammalian cell toxicity. One of the cationic

amphiphiles with a linolenic acid lipid residue, containing three cis-double bonds, displayed no cytotoxicity

against a panel of mammalian cell lines and primary cells. This compound selectively eradicated C. albicans

cells while not affecting the viability of human cells in co-culture experiments. Our findings offer a new

promising strategy for the development of non-toxic antimicrobial cationic amphiphiles safe for systemic

antifungal treatment.

47

PA-46

Characterizing Mineral-Bearing Vesicles in Sea Urchin Embryos

Keren Kahil1, Netta Vidavsky1, Eyal Shimoni2, Ifat Kaplan-Ashiri2, Lia Addadi1, Steve

Weiner1 1Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel

2Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel

Sea urchin embryos have endoskeletons comprised of two calcitic spicules. Spicule growth takes place by the

initial deposition of amorphous calcium carbonate (ACC)[1] in vesicles inside the spicule forming

cells[2](PMCs). The calcium in the mineral bearing vesicles was recently reported to originate from body fluid

internalization and in part from calcium channels[3]. Using cryo-scanning electron microscopy to image high

pressure frozen and cryo-sectioned samples of embryos, we were able to detect several types of vesicles inside

the PMCs. Some vesicles have granulated texture, some appear smooth, some have backscattered electrons

signal, and some contain lipids or proteins. Performing EDS measurements under cryogenic conditions revealed

that some of these vesicles are rich in sodium, while others give signals for potassium and calcium. We

conclude that the compositional landscape of the vesicles in the PMCs is complex. Some of these vesicles fulfil

a fundamental role in the mineralization of the spicules.

Figure 1 – Sea urchin embryo spicule (S) with its adjacent spicule forming cells. Red asterisks mark vesicles

with granulated texture suspected to be ACC.

[1] E. Beniash, J. Aizenberg, L. Addadi, S. Weiner, P Roy Soc B-Biol Sci 1997, 264, 461-465.

[2] N. Vidavsky, S. Addadi, J. Mahamid, E. Shimoni, D. Ben-Ezra, M. Shpigel, S. Weiner, L. Addadi, P Natl

Acad Sci USA 2014, 111, 39-44.

[3] N. Vidavsky, S. Addadi, A. Schertel, D. Ben-Ezra, M. Shpigel, L. Addadi, S. Weiner, Proc. Natl. Acad. Sci.

U.S.A 2016, 201612017, 201610027-201618424.

48

PA-47

One-Pot Conversion of Fluorophores to Phosphorophores

Sudhakar Kolanu, Matan Soll, Zeev Gross

Department of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

The porphyrinoids shows quite significant chemical and photophysical properties.1-3 Development of simple

and efficient procedures for corrole synthesis, combined with facile tuning of physical and chemical characteristics by changing substituents on either the macrocycle or the chelate metal, has elevated in various

extensive applications.4,5

We have introduced a very efficient and facile one-pot conversion of free base 5,10,15-

tris(pentafluorophenyl)corrole, (H3)tpfc, into the coinage metal complexes of 2,3,17,18-tetraiodo-5-10-15-

tris(pentafluorophenyl)corrole, (I4-tpfc)M (M = Cu, Ag, Au). The iodoniation/metallation procedures provide

much higher yields and larger selectivity than both conceivable stepwise syntheses. Photophysical analysis

discloses that the gold(III) complex (I4-tpfc)Au displays phosphorescence at room temperature and a substantial

quantum yield for singlet oxygen formation. We trust the conclusions deduced from this research to be of large

utility for structure/activity tuning of other corroles and related ligands. We are presenting now our results on

the facile one-pot synthesis of group 11 metals with tetraiodinated-corroles, as well as some functionalization of

the C-I bonds therein.6

References:

1] Lemon, C. M.; Brothers, P. J. Porphyrins Phthalocyanines 2011, 15, 809.

2] Flamigni, L. The Chemical Rec. 2016, 47, 32.

3] Sudhakar, K; Giribabu, L; D’Souza, F. etc. –An Asian J. 2015, 10, 2708.

4] Vestfrid, J.; Goldberg, I.; Gross, Z. Chem. 2014, 53, 10536.

5] Vestfrid, J.; Kothari, R.; Kostenko, A.; Goldberg, I.; Tumanskii, B.; Gross, Z. Chem. 2016, 55, 6