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CALIXARENE RECEPTORS FOR CALIXARENE RECEPTORS FOR RADIOWASTE PARTITION, RADIOWASTE PARTITION,
CHEMOSENSORS, CHEMOSENSORS, DRUG DESIGNDRUG DESIGN
HANNOVER MESSE-2007 16-20 April, 2007
Hannover
Iurii MATVIEIEV
+38 044 551-1628+38 050 501-1393
National Academy of Sciences of UkraineInstitute of Organic Chemistry
Kiev
OH
HCHO
NaOH
O OOOH H H H
C.D.Gutsche. Org. Synth., Coll. Vol. 1993, 8, 75
Calix[4]arenes are available macrocycles
Upper rim modification
Lower rim modification
2
CALIXARENE EXTRACTANTS FOR CALIXARENE EXTRACTANTS FOR RADIOWASTE PARTITIONRADIOWASTE PARTITION
CALIXARENE BASED CHEMOSENSORSCALIXARENE BASED CHEMOSENSORS
CALIXARENES FOR DRUG DESIGNCALIXARENES FOR DRUG DESIGN
RADIOWASTE PARTITIONRADIOWASTE 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 PARTITIONRADIOWASTE 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.
0
2
4
6
8
10
12
D
0,1 0,3 1 3 6
[HNO3]
Eu
Am
P
O-Pr
O
Ph
4
OBu2N
Am3+ / Eu3+ separation by Calixarene-CMPODistribution D between nitrobenzotrifluoride and HNO3
J. Supramol. Chem. 2002. 2. 421-427
Extraction and stripping of radionuclides of the real High Level Waste
RADIOWASTE PARTITIONRADIOWASTE PARTITION
Extraction of radionuclides (% of initial) by CIP-67
from the Real High Level Waste
E1 E2
Real HLW
0,04 M CIP-672% n-octanolNBTFSolvent
EXTRACT,radionuclides, 100%
E3
E4
Am – 47Cm – 27Eu – 20Ce – 70 gross – 28
Eu < 0,1Ce – 12gross – 0,14
O
PO
PrPr
4
Extractant CIP-67
RADIOWASTE PARTITIONRADIOWASTE 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 PARTITIONRADIOWASTE 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 PARTITIONRADIOWASTE PARTITION
OpportunitiesWe 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 CHEMOSENSORSCALIXARENE BASED CHEMOSENSORS
Easy to useEasy to use Flexible inFlexible in aapplicationpplication High sensitivityHigh sensitivity Multi-purposeMulti-purpose
CHEMOSENSORSCHEMOSENSORS 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.
CHEMOSENSORSCHEMOSENSORS
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.
CHEMOSENSORSCHEMOSENSORS
Schematic view of ELECTRONIC NOSE
«Purification»
«Sampling»
PC
1
2 5
4
3
8
7
9
610
11
Exhaust
1. 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 vapor8. analyte
container9. analyte probe 10. end injection
sensor
CHEMOSENSORSCHEMOSENSORS 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)
CHEMOSENSORSCHEMOSENSORS 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 DESIGNCALIXARENES 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 DESIGNDRUG DESIGN
• The calixarene-methylene-bis-phosphonic acid is one of the most efficient substance among the alkaline phosphatase inhibitors described in the literature.
Enantioselective Inhibitionof Porcine Kidney Alkaline Phosphataseby the Chiral Aminophosphonous Acids
50.5
SS
RR
S
R
2.28
Selectivity
86
1.7
32
73
Inhibition Constants, μMInhibitor
OO O OH Pr Pr H
P H
NH2
OH
OOH
(HO)2P
O(OH)2
NH2
OO
P
O
O O
H Pr Pr H
NH2H
H
Organic Lett. 2006. 8. 549-552
DRUG DESIGNDRUG DESIGN• Calix[4]arenesulfonylamidine is a single inhibitor of Mg2+, ATP-
dependent 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.
-20
0
20
40
60
80
1 2 3 4 5
NS OO
CF3
NH
NSO O
F3CNH
O O
NH NH
OO
N N
F3C CF3
S SO O O O
1. Mg2+,ATP-dependent Ca2+ accumulation in the miometrial sarcoplasmic reticulum.2. Mg2+, ATP-dependent Ca2+ accumulation in the plasma membrane.3. Ouabaine-suppressed Na+,K+-ATPase.4. Mg2+,ATP-dependent Ca2+ accumulation in the mitochondria.5. Ca2+-independent Mg2+-ATPase (“basal” Mg2+-ATPase).
Calixarene Selective Inhibition
of Calcium Membrane Pumps
Tetrahedron Lett. 2005. P.7459-7462
Inhib
itio
n, %
DRUG DESIGNDRUG 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 DESIGNDRUG 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]/calix
Institute of Organic Chemistry National Academy of Sciences of Ukraine
Kiev
