Transcript Слайд 1 - SCIENCE & TECHNOLOGY CENTER IN UKRAINE

CALIXARENE RECEPTORS FOR
RADIOWASTE PARTITION,
CHEMOSENSORS,
DRUG DESIGN
HANNOVER MESSE-2007
16-20 April, 2007
Hannover
Iurii MATVIEIEV
+38 044 551-1628
+38 050 501-1393
[email protected]
National Academy of Sciences of Ukraine
Institute of Organic Chemistry
Kiev
Calix[4]arenes are available
macrocycles
Upper rim modification
HCHO
NaOH
O
H
O O
H H
O O
H
H
Lower rim modification
C.D.Gutsche. Org. Synth., Coll. Vol. 1993, 8, 75
2
CALIXARENE EXTRACTANTS FOR
RADIOWASTE PARTITION
CALIXARENE BASED CHEMOSENSORS
CALIXARENES FOR DRUG DESIGN
RADIOWASTE PARTITION
Problem Description & Market Need
• Efficient reprocessing of wastes arising from nuclear
power remains one of the most complicated problems of
radiochemical
industry.
Long-lived
radionuclides,
especially actinides, are the most hazardous
components of the high level waste (HLW) of nuclear
power stations.
• Their separation from the total waste mass and disposal
should enable significantly to raise the ecological safety
and efficiency of nuclear fuel cycle. A combined
approach to HLW reprocessing, i.e. the recovery of
several radionuclide groups immediately in one cycle,
seems to be promising.
RADIOWASTE PARTITION
Brief technology description
•
•
The HLW partitioning problem can
be solved by the extraction
technology with the use of
organophosphorus extractants
recovering TRU, technetium and
platinides. The widely used
extractants like trialkylphosphine
oxide possess low efficiency and
insufficient selectivity.
We propose a new class of
perspective extractants on the base
of calixarenes functionalized with
phosphine oxide,
carbamoylphosphine oxide or
diphosphine dioxide groups. In
such compounds the binding
groups may be best located around
a metal cation, increasing the
extraction efficiency and selectivity
to a great extent.
Am3+ / Eu3+ separation by Calixarene-CMPO
Distribution D between nitrobenzotrifluoride and HNO3
Bu2N
O
Ph
P O
12
Eu
10
O-Pr
4
Am
8
D 6
4
2
0
0,1
0,3
1
3
6
[HNO3]
J. Supramol. Chem. 2002. 2. 421-427
Extraction and stripping of radionuclides of the real High Level
Waste
RADIOWASTE PARTITION
Extraction of radionuclides (% of initial) by CIP-67
from the Real High Level Waste
Real HLW
E1
Pr
P
Pr
E2
Am – 47
Cm – 27
Eu – 20
Ce – 70
 gross – 28
O
4
O
Extractant CIP-67
0,04 M CIP-67
2% n-octanol
NBTF
Solvent
E3
E4
Eu < 0,1
Ce – 12
gross – 0,14
EXTRACT,
radionuclides, 100%
RADIOWASTE PARTITION
Advantages
• Calix[4]arene alkylphosphine oxides,
carbamoylphosphine oxides or diphosphine
dioxides extract simultaneously actinides,
lanthanides, technetium and palladium from real
HLW hundred times more efficient than the
industrial extractants.
• In three contacts almoust 100% of gross activity, more than 98 % of Tc and Pd were
recovered from real HLW.
RADIOWASTE PARTITION
Stage of development
• The Institute of Organic Chemistry of the
National Academy of Sciences of Ukraine is
enable to product the calixarene extractants in
kilo scale quantities
• The testing of the calixarene extractants has
being successfully performed with the real HLW
on the “MAYAK” plant by specialists of the
Khlopin Radium Institute (St.-Petersburg,
Russia)
RADIOWASTE PARTITION
Opportunities
We offer:
• Calix[4]arene alkylphosphine oxides,
carbamoylphosphine oxides or diphosphine dioxides for
radiowaste partition (Institute of Organic Chemistry
NASU, Kiev, Ukraine www.ioch.kiev.ua/calix)
• the extraction technology with the use of
organophosphorus extractants recovering TRU,
technetium and platinides (Khlopin Radium Institute, St.
Petersburg, Russia www………)
Targeted Market Segment
• Any Atomic Power Station
• Radiochemical Enterprizes
CALIXARENE BASED CHEMOSENSORS
 Easy to use
 Flexible in application
 High sensitivity
 Multi-purpose
CHEMOSENSORS
Problem Description & Market Need
• Calixarene based Electronic Nose was
developed for monitoring of organic compounds
in environment.
• Application of traditional methods for monitoring
of
hazardous
substances
in
variable
environment (air, water, waste, etc.) is not often
effective and has a range of drawbacks, mainly
complicity and long-term exposure.
• The main problem in developing of sensor
systems is to supply them with the exceptional
selectivity towards a different analytes.
CHEMOSENSORS
Basic operation principles
-Array of quartz crystal resonators are covered with
calixarenecontaining receptors which have different
sensitivity towards different volatile organic molecules.
-Due to adsorption of analyte molecules onto sensitive
surfaces of sensors frequency of quartz resonators is
reducing. This frequency shift is considered as a sensor
response.
-Obtained array of sensors responses to pulse of analyte
vapor is used for “teaching” system and after that – for
recognition of chemical image of analyte by means of
special mathematical apparatus for statistical treatment.
CHEMOSENSORS
Schematic view of ELECTRONIC NOSE
4
1.
3
2
Exhaust
8
5
«Purification»
9
«Sampling»
1
11
7
PC
10
6
8-element
Teflon gas cell
2. QCM-sensor
array
3. air pump
4. filter-desiccant
5. two-positioned
gas flow control
valve
6. syringe–filler
7. analyte vapor
8. analyte
container
9. analyte probe
10. end injection
sensor
CHEMOSENSORS
Stage of development
• The series of calixarene based receptors of ions
and neutral molecules were synthesized in the
Institute of Organic Chemistry NASU
(www.ioch.kiev.ua/calix)
• The sensitive calixarene based polymer films
were prepared in the Institute of
Macromolecular Chemistry NASU
• The chemosensor pilot model ELECTRONIC
NOSE is constructed in the Institute of
Semiconductor Physics NASU
(www.isp.kiev.ua)
CHEMOSENSORS
Opportunities
We offer the ELECTRONIC NOSE for:
Targeted Market Segment
• monitoring of hazardous pollutants in
environment;
• quality control in food industry and
agriculture;
• quality control of perfumes and beverages.
CALIXARENES FOR DRUG DESIGN
• Calix[4]arenes
substituted
with
different
pharmacophoric groups have shown multifarious
biological activity.
• Highly diverse biomedical applications of these
molecules now include antiviral, anti-thrombotic
activities, enzyme blocking and protein
complexation.
• Calixarenes are promising scaffolds for design of
inhibitors containing of bioisosteric groups – the
medicine-relevant molecules.
DRUG DESIGN
• The calixarene-methylene-bis-phosphonic acid is one of
the most efficient substance among the alkaline
phosphatase inhibitors described in the literature.
Enantioselective Inhibition
of Porcine Kidney Alkaline Phosphatase
by the Chiral Aminophosphonous Acids
Inhibition
Constants, μM
Inhibitor
O
HO
P
HO
R
H
73
NH 2
H
H
O O
Pr
O
2.28
O
H
Pr
O
P(OH)2
O
(HO)2P
NH 2
S
32
RR
1.7
H
H 2N
O O
H Pr
Selectivity
O
50.5
O
Pr
H
SS
Organic Lett. 2006. 8. 549-552
86
DRUG DESIGN
• Calix[4]arenesulfonylamidine is a single inhibitor of Mg2+, ATPdependent calcium pump of the myometrial plasma membrane.
• Calixarene-phosphonic acids are 200-500 times more efficient than
ouabaine in suppressing activity of the sodium pump.
Calixarene Selective Inhibition
of Calcium Membrane Pumps
Inhibition, %
80
60
O
O
N
40
F3 C
O
S
OO
S
N
N
NH
NH
F3 C
O
O
CF3
NH
S
O
N
CF3
NH
20
0
-20
1.
2.
3.
4.
5.
S
O
1
2
3
4
O
O
O
5
Mg2+,ATP-dependent Ca2+ accumulation in the miometrial sarcoplasmic reticulum.
Mg2+, ATP-dependent Ca2+ accumulation in the plasma membrane.
Ouabaine-suppressed Na+,K+-ATPase.
Mg2+,ATP-dependent Ca2+ accumulation in the mitochondria.
Ca2+-independent Mg2+-ATPase (“basal” Mg2+-ATPase).
Tetrahedron Lett. 2005. P.7459-7462
DRUG DESIGN
Stage of development
• A series of calixarene based alkaline phosphatase
inhibitors and Ca2+ exchange regulators were
synthesized in the Institute of Organic Chemistry
NASU (www.ioch.kiev.ua/calix).
• The high phosphatase inhibition activity and Ca2+
exchange regulation properties of the calixarenes
were studied in the Institute of Bioorganic &
Petrochemistry NASU (www………………….) and in
the Institute of Biochemistry NASU (www……………..)
•
Org. Lett., Vol. 8, No. 4, 2006, p.549-552; Tetrahedron Letters 46 (2005) 7459–7462
DRUG DESIGN
Opportunities
We offer:
• Design of new biologically active
compounds by means of attaching of
pharmacophoric groups to the calixarene
platform.
Targeted Market Segment
• Bio-medicine Industry
• Pharmacology
Contact information
Iurii MATVIEIEV
+38 044 551-1628
+38 050 501-1393
[email protected]
www.ioch.kiev.ua/calix
Institute of Organic Chemistry
National Academy of Sciences of Ukraine
Kiev