Synthetic organic chemistry, Synthesis and Chemistry of Pheromones,
Organobromine compounds, Organic Flame Retardants, Heterocyclic Compounds.
In a joint nine-year project with Bromine Compounds Ltd. on the synthesis of flame
retardants for engineering plastics, a number of topics were investigated. The main
subjects were the synthesis of a series of new polybrominated aliphatic, aromatic, alkyl
aromatic compounds and polybrominated reactive monomers as potential flame
retardants. The research included the determination of their heat stability, compatibility
with a series of engineering polymers, flammability of the new compounded substances,
and polymerization parameters of the reactive monomers. A secondary topic comprised
testing of a new class of non-halogenated flame retardants. These were based on
heterocyclic compounds containing an -N=N- bond in the ring, which included
tetrazoles and urazoles and their derivatives, and a series of aliphatic compounds derived
from carbohydrazide. A third, minor topic was the bromination of aromatic phosphates
to produce new phosphorous bromine-containing flame retardants.
Additional projects performed with Bromine Compounds Ltd. :
Facile Neopentyl Halide Exchange of Tribromopivalamides.
Bromine Chloride as a Selective Brominating Agent.
Benzylic Bromination Reactions.
Synthesis and Physiochemical Study of Monomeric and Polymeric Phthalocyanines.
Synthesis of ketoconazole. (Industry)
Polybrominated Organic Peroxides. ( Harry Stern fund for Applied Research)
Synthesis of novel polynitrogen Heterocyclic Systems.
Novel Hybrid Supramolecular Systems: Langmuir-Blodgett Films of
Nanoparticles and Functionalized Organics
Nonlinear optical materials, especially those possessing high second- and third-order
nonlinearities, are invaluable building blocks for optoelectronic devices. In particular,
Langmuir-Blodgett multilayered films are attractive materials that are suitable for a
variety of potential applications: integrated optics and sensors, piezoelectric films,
photovoltaic cells, and micro-optomechanical structures. Optomechanics is a new
field of technological interest that can be approached by means of Langmuir-Blodgett
film growth techniques. The general idea is to develop microscopic structures that can
couple light to a mechanical function. Langmuir-Blodgett films give nanometer-scale
structural variability in the vertical direction. Additional processing by techniques
such as photolithography can lead to further structuring within the plane to produce
three-dimensional complex structures. In an interdisciplinary program, which has
been conducted in cooperation with research groups in the Department of Chemistry
and at the Nuclear Research Center Soreq, our group in The Institutes for Applied
Research has synthesized functionalized surface active molecules such as long chain
functionalized akyl thiols, dithiols, xanthates, dithiocarbonates, thiophosphates and
thiocarbamates, with emphasis on the attachment of these surface active parts to the
specially designed chromophores. These molecules can then be used as building
blocks for optoelectronic devices.
H. Schwartz, R. Mazor, V. Khodorkovsky, L. Shapiro, J. T. Klug, E. Kovalev, G.
Meshulam, G. Berkovic, Zvi Kotler, S. Efrima, Langmuir and Langmuir Blodgett
films of NLO active 2-(p-N-alkyl-N-methylamino)benzylidene-1,3-indandione – /A
curves, UV-Vis spectra and SHG behavior, J. Phys. Chem., B 105, 5914 (2001).
Functionalized Capping agents for Nanoparticles
There is a growing interest in nanoparticles of metals such as cobalt, copper, gold,
silver and platinum , as well as in semiconductor nanoparticles (quantum dots). Metal,
metal oxide and semiconductor colloids are inherently unstable with respect to
aggregation and subsequent precipitation from the suspension. Capping, coating these
nanoparticles by a strongly adsorbed monolayer of (usually organic) molecules is
often being used in order to stabilize them not only with respect to aggregation, but
also against corrosive chemical reactions. Functionalizing the capping agents allows
one to impart to the particles a variety of additional useful properties (molecular and
biological recognition, special linear and nonlinear optical behavior, specific packing
and assembly capabilities). Capped colloids find potential uses in science and in
technological applications such as microelectronics, optoelectronics, chemical
sensors, and biosensors, lubrication, catalysis, colloid modified electrodes, contrast
agents for electron and visible microscopy, colloidal immunoassays, and hollow
Cooperating with the research group of Professor S. Efrima from the Department of
Chemistry a series of alklylxanthates (alkyldithiocabonates) were prepared and
studied. It was found that xanthates can serve as efficient capping agents producing
transferable colloids with considerable resistance to heat and chemical oxidation.
P. Sawant, E. Kovalev, J. T. Klug, S. Efrima,
“Alkyl xanthates - New capping Agents for Metal Colloids: Capping of
Platinum Nanoparticles”, Langmuir 17 (10), 2913 (2001)
O. Tzhayik, P. Sawant, S. Efrima, E. Kovalev, J. T. Klug,
“Xanthate Capping of Silver, Copper and Gold Colloids”, Langmuir
2001, in press.
Chemistry of Tetrazine
J. Klug, E. Kovalev, Dr. X. Zhou,
In an ongoing investigation on the chemistry of 1,2,4,5-tetrazines, emphasis was
placed on the inverse [4+2] cycloaddition of dienophiles to these compounds.
Unstable dienophiles were prepared in situ in the presence of the tetrazine and the
reaction products were analyzed. In contrast to the usual C,C cycloaddition reactions
observed so far an unusual N,N cycloaddition has been observed and reported. This
new course of the reaction is being investigated
Zhou, Xiaojian; Kovalev, Efim; Klug, Jacob T.; Khodorkovsky, Vladimir.
An Alternative Route for Carboni-Lindsey Reaction: N,N Cycloaddition of an Alkene
to s-Tetrazine. Org. Lett. 2001, 3(11), 1725-1727.
Development of new fluorescent probes for investigation of the folding and
of globular proteins by means of protein engineering and ultrafast dynamics
(Bar-Ilan University & Israel Academy of Sciences) 2001 - 2002.
A long term goal of a world wide research effort is to be able to predict the structures and
functions of gene products based solely on sequence information. The human genome
project, produce excessive genetic information that accumulates in databases, but cannot
yet be interpreted in terms of the structure and function of the gene products. In principle, it
should be possible to predict the structure of proteins encoded in genomes, provided the
rules of the folding transition were known. The future of rational protein design for
technological applications (bio-chips, bio-sensors, etc.), rational drug design, and molecular
medicine depends to a large extent on the knowledge of the “folding code”. The protein
engineering techniques are available, but our understanding of the mechanism of protein
folding is still very limited.
The folding transition of many globular proteins involves transient intermediate states.
Their characterization might provide an answer to some major questions.
To follow these transitions to their native state is a very a difficult task due to their
complexity, their very short lifetimes and very low population.
Determination of intramolecular distances and rates of their fast changes by time resolved
fluorescence resonance energy transfer (FRET) measurements, can be a powerful method
for characterization of the structures of partially folded proteins and their transitions. The
strength of this experimental approach derives from the ability to determine distributions of
intramolecular distances and rates of fluctuations under equilibrium and fast kinetics
refolding experiments. Applications of this powerful approach depend on availability of
organic reagents with appropriate spectroscopic characteristics for site specific modification
of protein molecules. The spectroscopic characteristics of the probes to be used in the
preparation of protein samples for time resolved FRET experiments determine the temporal
and spatial resolution of the experiments.To this aim our group is angaged in development
of new organic fluorescent reagents with desired chemical and spectral characteristics.
The probes will be based on pyrene molecule substituted by polar groups, which are
characterized by long lifetimes of the excited states and fast rotational averaging, feature
maximum photo stability and high extinction coefficient (for pyrene max=34000 M-1cm-1)
and can form pairs with matching acceptor reagents with desired critical distance (Ro)