2014 proceed-istr version 0

La Baule - Pornichet, France 29th sept. - 3rd oct. 2014

8th International Symposium on Technetium and

Rhenium: Science and Utilization

1

8th

International Symposium on Technetium and Rhenium: Science and Utilization.

September 29th

to October 3rd

2014. Proceedings and selected lectures. La Baule -

Pornichet, France. Eds. K.German, F.Poineau, M. Fattahi., Ya. Obruchnikova, A.

Safonov. Nantes Moscow Las Vegas : Granica Publishing Group, 2014. 561 p.

IPCE RAS 2014

SUBATEC 2014

GRANICA PUBLISHING GROUP 2014

UNLV 2014

UDK 546.718 : 548.736

ISBN 978-5-94691-703-2

Nantes Moscow Las Vegas

Granica Publishing Group 2014

2

German

Table of Contents

Chemistry of Technetium in the nuclear fuel cycle

Multiple Facets of Technetium and Rhenium Chemistry in Molecular

Imaging and Therapy. Roger Alberto, Samer Ursillo, Henrik

Braband, Michael Benz, Michael Felber, Sebastian Imstepf 10

Techntium behavior in the PUREX process. P. Baron 47

The role of a choice of the target form for 99

Tc transmutation. ..Kozar, K.E. German, V.F. Peretrukhin

61

Complexation and extraction of Pu(IV) in the presence of

pertechnetic acid. L. Venault, L. Abiad and Ph. Moisy 74

The ways of technetium localization at the SNF reprocessing. N.D.

Goletsky, B.Ya. Zilberman, Yu.S. Fedorov, A.S. Kudinov, A.A.

Timoshuk, L.V., Sytniuk, E.A. Puzikov, S.A. Rodionov, A.P.

Krinitsyn, V.I. Ryasantsev, D.V. Ryabkov, T.A. Boytsova

85

The nature of the technetium volatile species formed during

vitrification in borosilicate glass. Bradley Childs, Frederic Poineau,

Kenneth R. Czerwinski, and Alfred P Sattelberger.

102

Electrochemical studies of technetium-ruthenium and rhenium-

ruthenium alloys in nitric acid: implications for the long term

behavior of metallic technetium waste forms. Romina Farmand,

Frederic Poineau, Daniel J. Koury, David G. Kolman, Gordon D.

Jarvinen and Kenneth R. Czerwinski

114

Fundamental chemistry of Technetium and Rhenium

Review on the Tc Chemistry at SUBATECH in Inorganic Media

(Chloride, Sulfate, Carbonate) with or without Radiation Effect.

J. Vandenborre, M. Fattahi

128

Speciation of technetium in acidic media (CF3SO3H, H2SO4): Effect

of alpha radiations. Ibtihel Denden, Jrme Roques, Frdric Poineau, Massoud Fattahi

141

Study induced oxidation/reduction of Tc in carbonate media by and radiolysis. M. Ghalei, J.Vandenborre, G. Blain, F. Haddad, M. Fattahi-Vanani

159

Speciation of Technetium in Sulfuric Acid/Hydrogen Sulfide

Solutions. Maryline Ferrier, Frederic Poineau, Jerome Roques, 176

33

Alfred P. Satteleberger and Kenneth R. Czerwinski

Electrochemical properties of technetium species in acidic media. M.

Chotkowski 190

Aquatic chemistry and thermodynamics of Tc in dilute to

concentrated saline systems. E. Yalcintas, X. Gaona, A. C. Scheinost,

M. Altmaier, H. Geckeis

204

Density and activity of perrhenic and pertechnetic acid aqueous

solutions at 25C. P. Moeyaert, L. Abiad, C. Sorel, J.-F. Dufrche, M. Miguirditchian and P. Moisy

218

Comparative study of several supramolecular TcO4- and ReO4

-

receptors. K.E. German, Ya.A. Obruchnikova, G.V. Kolesnikov,

G.A. Kirakosyan, I.G. Tananaev, B.F. Myasoedov

229

The Chemistry of Technetium Chlorides. A. Sattelberger. 245

Synthesis and Characterization of Binary Technetium Bromides and

Iodides. Erik Johnstone, Frederic Poineau, Paul M. Forster, Alfred P.

Sattelberger and Kenneth R. Czerwinski

258

Dinuclear Technetium complexes with multiple metal-metal bonds.

Poineau F., Forster P.M., Todorova T.K., Johnstone E.V., Kerlin

W.M., Gagliardi L., Czerwinski K.R., Sattelberger A.P.

272

Polynuclear Technetium Iodides Compounds with Multiple Metal-

metal Bonds. W.M. Kerlin, F. Poineau, C. Malliakas, P.M. Forster,

A.P. Sattelberger, K.R. Czerwinski .

284

In-Situ Study Of Minor And Major Phase Formation And

Transformation In Tc Bearing Mineral Analogues with Carbonate

Starting Components. Gordon Thorogood, Brendan Kennedy, Emily

Reynolds, Massey De Los Reyes and Helen Brand.

302

Spectroscopic and Photophysical Properties of

Tetracyanidonitridorhenium(V) and -technetium(V) Complexes.

Takashi Yoshimura, Hayato Ikeda, Akitaka Ito, Eri Sakuda, Noboru

Kitamura, Tsutomu Takayama, Tsutomu Sekine and Atsushi

Shinohara

328

Educational Opportunities Within the UNLV Radiochemistry PhD

Program, J. Wendee. 344

Rhenium complexes of benzothiazoles as models for the diagnosis of

Alzheimer`s disease. T.I.A._Gerber,_X._Schoultz 356

44

Nitrosyltechnetium Complexes with Various P,N Ligands. Janine Ackermann, Adelheid Hagenbach, Ulrich Abram

374

Fluorido Complexes of Low-valent Technetium. Samundeeswari Mariappan Balasekaran, Adelheid Hagenbach, Ulrich Abram

390

Formation of nitrosyl-containing o-phenanthroline complex of iron in presence of TcO4- and HNO3. Tatiana Boytsova, V.A. Babain, A.A. Lumpov, A.A. Murzin

403

A new method for rapid extraction of rhenium from raw vegetation with subsequent determination of the metal under field conditions. Ognyan Bozhkov and Christina Tzvetkova

414

Rhenium in the industry

Sorption separation of Rhenium and associated components of polymetallic raw materials. I. Troshkina, N.V. Balanovskyi, A.V. Shilyaev, V.A. Moiseenko, Nway Shwan Oo, A.P. Grekhov

424

Ionosilicas for Ion Exchange Reaction. P. Hesemann, M. Gigue, P. Moisy, B. Prelot, U. D. Thach

442

Study on Rhenium sorption at high rate from washing acid of the sulphuric acid plant at balkhash copper plant. Sergey Zakharyan, A.B. Yun, E.I. Gedgagov, I.V.Terentieva

464

Study on Rhenium desorption at high rate from macroporous low base ionites. S. Zakharyan, A.B. Yun, E.I. Gedgagov, V.A. Chen

467

Technetium and Rhenium in nuclear medicine

Molybdenum-99 production from a thorium target irradiated by light charged particles up to 70 MeV. C. Duchemin, Arnaud Guertin, Ferid Haddad, Vincent Mtivier, Nathalie Michel

472

Rhenium-188: application for glioblastoma internal radiotherapy. Annabelle Cikankowitz

473

Starch based microparticles radiolabelling with 99mTc and 188Re for diagnostic and therapy of Hepatocellular carcinoma. E.Verger, A. Cikankowitz, A. Bouvier, N. Lepareur, J. Benoit, J. Deloye, C. Aub, O. Couturier, F. Lacoeuille, R. Hustinx, F. Hindr

474

Rhenium-tricarbonyl with a new tripodal N2O ligand: from structural investigations to a therapeutic radiopharmaceutical. Romain

475

5

Echeynne, Sihem Guizani, Mariusz Wolff, Eric Benoist, Nicolas

Lepareur

Interdisciplinary consortium collaboration for the development of

radiopharmaceutical approach for effective diagnostics and therapy of

prostate cancer in Russia. K. German, O. Vlasova, V. Petriev, V.

Skvortsov, G. Kodina, A. Maruk, N. Airapetova, N. Epshtein, N.

Nerozin, A. Safonov, V. Lebedev, Ya. Obruchnikova, Yu. Shevko

476

Influence of oxygen isotopes on the NMR parameters of the

pertechnetate anion TcO4- . Use of technetium-99g in PET nuclear

chemistry technology: application of 99gTc-NMR for analysis of O-

18 content in water. K. German, G. Kirakosyan, V. Tarasov

491

Poster session

Technetium and Rhenium sulfides formation: kinetics, structure and properties, K. E. German, A.V. Safonov A.A. Shiryaev, Ya. A.

Obruchnikova, V.A. Ilin, V.P. Tarasov, A. V. Afanasiev, V.E.

Tregubova, S.N. Kalmykov

494

Supramolecular interactions of caffeine molecules with each other,

water molecules and oxygen atoms of tetraoxidoanions in the three

new different compounds Me(H2O)6[ReO4]2.caffeine (Me = Co, Cd,

Mg ). K. German, M.N. Glazkova, M.S. Grigoriev, Ya.A.

Obruchnikova, G.V. Kolesnikov, Yu.A. Ustynyuk, F. Poineau, O.S.

Kryzhovets

503

Biological reduction of pertechnetate ion in the implementation of

technology biobarrer into aquifers contaminated with radioactive

waste. A. Safonov T. Khijniak, V. Ilin, K. German

510

Development of Bio filtration system for cleaning solutions from

uranyl and pertechnetate anions. A. Safonov, O. Gorbunova, T.

Khijniak, K. German

511

Platinum And Rhenium Recovery From PtRe Reforming Catalysts via Plasma Arc Technology. Peter Keeley, Neil Rowson, David

Deegan

512

Technetium and Rhenium Complexes with Heavy

Arylchalcogenolates. Bruno N. Cabral, Ernesto S. Lang, Adelheid

Hagenbach, Lars Kirsten, Ulrich Abram

516

Solvent extraction separation of Rhenium and Molybdenum using

octanols and mixtures of trisooctilamine 2-octanone in acid media. A. 523

66

Petrova, A. Kasikov

Evaluation of Rhenium Production Rates in Tungsten Irradiated in

Fast Reactors by Using Continuous Energy Monte Carlo Code MVP.

Tsugio Yokoyama, Atsunori Terashima and Masaki Ozawa

526

Application of Solvent Extraction Preconcentration methods for

Spectrophotometric Determination of Traces of Molybdenum in

Radiopharmaceutical Preparation using 1,5-Diphenylcarbazide.

Nafisa H. Gmati and M. A. Abuzwida

533

Biosorption processes for radioactive waste purification from Tc, U, Sr and Cs. Alexey Safonov, Varvara Tregubova, Olga Gorbunova,

Kjnstantin German, T. Nazina

537

Measurement of 99

Tc via Cherenkov counting. Mojmr Nmec,Kateina ubov

539

Tc(V) and Re(V) oxido complexes with tetradentate

thiocarbamoylbenzamidines for bioconjugation. Adelhei Hagenbach,

U.Abram

540

Review on Chemical Separation of Tc with Extraction

Chromatographic Resins. A. Bombard, S. Happel 544

Microorganisms from extreme habitats for use in biological

technologies to LRW treatment. A. Safonov, S. Gavrilov, T.

Khijniak, K. German, I. Troshkina

545

Octahedral chalcogenide rhenium cluster complexes with phosphine

and pyridine derivatives : synthesis, structure and properties. A.A.

Ivanov, V.K. Khlestkin, M.. Shestopalov, K.A.Brylev, Y.V. Mironov

550

Prospects of octahedral rhenium cluster complexes in biology and

medicine. Michael A. Shestopalov, Anna A. Krasilnikova, Kristina

E. Zubareva, Konstantin A. Brylev, Yuri V. Mironov

551

Rhenium recovery from secondary raw material. Anna Petrova,

Aleksandr Kasikov 552

77

The 8th

International

Symposium

on Technetium and Rhenium:

Science and Utilization, September 29th to October 3rd 2014

La Baule - Pornichet, France.

The 8th

ISTR aimed at continuing 20 years of tradition on Technetium and Rhenium conferences

and the symposium happening every 3 years. It was originally created in 1993 and has been

successively held in 1993 (Sendai, Japan), 1996 (Moscow, Russia), 1999 (Shizuoka, Japan),

2002 (Dubna, Russia), 2005 (Oarai-Ibaraki, Japan), 2008 (Port-Elizabeth, South Africa) and

2011 (Moscow, Russia).

The aims of the 8th

ISTR was to cover all aspects of Technetium and Rhenium chemistry. The

conference was organized around plenary lectures (30-40 minutes), short lectures (15-20)

minutes and poster sessions. The technical program has covered the following topics :

Chemistry of Technetium in the nuclear fuel cycle (separation, disposal, waste form) Technetium and Rhenium in nuclear medicine (isotopes production, labeling,

coordination chemistry) Radioanalytical chemistry (Measure of Tc an Re in biosphere) Fundamental chemistry of Technetium and Rhenium (synthetic, materials and

coordination chemistry, inorganic and organometallic complexes, properties...)

Rhenium in the industry (mining, metallurgy, catalysis)

88

Committees

International Advisory Committee

R. Alberto (Switzerland)

J. Barbet (France)

B. Bryskin (USA)

K. Czerwinski (USA)

J. R. Dilworth (England)

Y. Fujii (Japan)

T.I.A. Gerber (South Africa)

K.E. German (Russia)

G.E. Kodina (Russia)

Ph. Moisy (France)

M. Ozawa (Japan)

V.F. Peretrukhin (Russia)

A. Sattelberger (USA)

T. Sekine (Japan)

I.D. Troshkina (Russia)

A.Yu. Tsivadze (Russia)

F. Poineau (USA)

Yuezhou WEI (China)

Shuao Wang (China)

Local committee

Massoud Fattahi - Chair, Laboratoire SUBATECH - Ecole des Mines de Nantes La Chantrerie - 4 rue Alfred Kastler - BP 20722

44307 NANTES Cedex 3 - France - together with

:

Sverine Gadeyne Sophie Girault

Bernard Kubica

Tanja Pierret

Pascaline Rtout,

Philippe Moisy Co-chair, CEA MARCOULE - DEN/DRCP/SERA/LCAR - Bt 399,BP17171 30207 BAGNOLS-SUR-CEZE Cedex

Frdric Poineau Co-Chair, Department of Chemistry / University of Nevada, Las Vegas - 4505 S. Maryland Pkwy - Las Vegas, NV 89154

Contact : [email protected]

Sponsored by :

99

Multiple Facets of Technetium and Rhenium Chemistry in Molecular

Imaging and Therapy

Roger Alberto, Samer Ursillo, Henrik Braband, Michael Benz, Michael Felber, Sebastian Imstepf

Department of Chemistry, University of Zurich, Winterthurerstr. 190, CH-8057 Zurich

PET is becoming more and more important, but 99mTc as a radionuclide for Single Photon Emission Computed Tomography (SPECT) has still the strongest impact on diagnostic health care. Whereas SPECT cameras can compete with PET cameras, chemical research efforts are required for keeping the role of Tc alive. Complementing diagnosis with 99mTc by therapeutic modalities is a clear asset over PET strategies (with 18F). Adapting the theranostic concept, we aim at synthesizing 99mTc complexes which mimic pharmacophores (imaging) with cold Re homologues (therapy), the 99mTc complex is a structural moiety in pharmaceutically active lead structures. This strategy requires demanding organometallic reactions. The preparation of cyclopentadienyl based bioorganometallic compounds is a focus since the Cp-ring can mimic phenyls in pharmaceuticals. Complexes of the type [(Cp-R)99mTc(CO)3] opened the so-called Cp-phenyl analogy.1 The Cp complex can be a tag, as will be shown with peptides (A),2 but also an integral part of structure in which it plays an essential role for receptor recognition. Examples with CA and HDAC inhibitors will be presented.3 Replacing Tc by Re will yield homologues with almost identical, pharmacological properties but with therapeutic potential.

We have extended the approach to cyclopentadienyl derivatives with two carboxylato groups (B) allowing to couple two bioactive functionalities to one 99mTc or Re complex. Finally, for replacing a phenyl ring in a pharmaceutical by a "true" phenyl ring, first insights in arene chemistry will be given. These aspects from low valent, organometallic chemistry will be rounded up by insights from high valent 99mTc and Re chemistry.4

1. Liu, Y.; Spingler, B.; Alberto, R. et al., J. Am. Chem. Soc., 2008, 130, 1554.2. Nadeem, Q.; Can, D.; Alberto, R. et al., Org. & Biomol. Chem., 2014, 12, 1966.3. Can, D.; Spingler, B.; Alberto, R.; et al., Angew. Chem. Int. Edit., 2012, 51, 3354.4. Braband, H., Benz, M., Tooyama, Y. Alberto, R. Chem. Commun., 2014, 50, 4126.

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MultipleFacetsofTechnetiumandRhenium

Chemistry in Molecular Imaging and Therapy

MultipleFacetsofTechnetiumandRhenium

Chemistry in Molecular Imaging and TherapyChemistryinMolecularImagingandTherapyChemistryinMolecularImagingandTherapy

RogerAlberto

D f Ch i

RogerAlberto

D f Ch iDepartmentofChemistryUniversityofZrich

DepartmentofChemistryUniversityofZrich

LaBaule Pornichet,France,September29,2014LaBaule Pornichet,France,September29,2014

OutlineOutline

Abitofhistory

Organometallic Chemistry and Coordination Chemistry

Abitofhistory

Organometallic Chemistry and Coordination ChemistryOrganometallicChemistryandCoordinationChemistry

OrganometallicChemistry andCoordinationChemistry

WhatcanwelearnfromMetalsinMedicine

IntegratedMolecularImagingAgents:Theranostics

Phenyl Cyclopentadienyl Analogy

OrganometallicChemistryandCoordinationChemistry

OrganometallicChemistry andCoordinationChemistry

WhatcanwelearnfromMetalsinMedicine

IntegratedMolecularImagingAgents:Theranostics

Phenyl Cyclopentadienyl Analogy

2

Functionalized Cyclopentadienylcomplexes

MissedOpportunities

Functionalized Cyclopentadienylcomplexes

MissedOpportunities

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Duringthepastfiveyears,therehasbeenadramaticsurgeofactivityintechnetiumchemistry,thisactivityhasbeendriventoalargeextentbythedesireofinorganicchemiststoobtainabasicunderstandingofthislargelyunexploredelement.AnevengreaterdrivingforcehasbeenprovidedbytheextensiveuseofTc99mindiagnosticnuclear

AbitofHistory..AbitofHistory..

e e g eate d g o ce as bee p o ded by t e e te s e use o c 99 d ag ost c uc eamedicineproceduresandthegrowingrealizationthatsignificantadvanceinthisappliedfieldwilldependuponbasicresearchinthefieldofinorganicTechnetiumchemistry

the several oxidation states of technetium exhibit diverse chemistries which will allow Tc99m

E.Deutsch,K.Libson andS.Jurisson,L.F.Lindoy inProgressinInorganicChemistry,1983,30,75

3

theseveraloxidationstatesoftechnetiumexhibitdiversechemistrieswhichwillallowTc 99mtobeincorporatedintoavarietyofformulationsthatarespecificfordifferentorgans,thus,variouschemicalformsofthesingleisotope

E.Deutsch,K.Libson andS.Jurisson,L.F.Lindoy inProgressinInorganicChemistry,1983,30,75

Oneofthereasonsfortheincreasedinterestintechnetiumchemistryduringthelastfewyearsisthewidespreaduseofradiopharmaceuticallabelledwith99mTc.{..}However,Fig.2showsthatthenumberofstudiesreportedonnew99mTcradiopharmaceuticalshasdecreasedfrom1977to1980.Thisfactevidencesastall

i i i di h i l h h ill l b ll i d b h


positioninradiopharmaceuticalresearchthatwillonlybealleviatedbyFurtherdevelopmentoftechnetiumchemistry.Fortunatelystudiesonthecoordinationchemistryareexpanding.

JACS,1952

G.Bandoli,U,Mazzi,E.Roncari,Coord.Chem.Rev.1982,44,191

TechnetiumandChemistry

4

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Duringthisperiodoftime*,thecoordinationchemistryoftechnetiumplayedasignificantrole.Thesuccessfuldevelopmentof99mTcimagingagentswastotallydependentonthedesignoftechnetiumcomplexes sincethebiodistributionandtargeting capability depend exclusively on their lipophilicity, size and charge.


targetingcapabilitydependexclusivelyontheirlipophilicity,sizeandcharge.

Theroleofcoordinationchemistryinthedevelopmentoftargetspecificradiopharmaceuticals

Althoughthefocusofradiopharmaceuticalresearchhasshiftedtowardsbiologicalcharacterizationofradiolabeledreceptorligandsinthelastseveralyears,coordination chemistrystillplaysasignificantroleinthedesignanddevelopmentofnewtargetspecificradiopharmaceuticals.

5

S.Liu, Chem.Soc.Rev.2004,33,445

Muchofthisworkhasbeendirectedtowardtheinvestigationofkineticallyinertcomplexesformedinoxidationstatesthatarereadilyaccessibleinaqueousmediab th d ti f th t h t t i Th t di h d t t d th t


bythereductionofthepertechnetateion.ThesestudieshavedemonstratedthatitispossibletoprepareclassesofstablecomplexesinboththeVandtheIIIoxidationstateswiththeappropriatechoiceofligand.

Thisinturnhasenabledus(a)tosynthesizethisclassofair andwaterstablecomplexesattracerconcentrations(ca.108109 M)withmetastable 99mTc(b,)tobegintoevaluatethebiologicaldistributionsofthesecomplexesinanimals,and( )

6

(c)toestablishstructurefunctioncorrelationsonapotentiallylargeclassofwellcharacterizedcomplexes.

SynthesisandCharacterizationofHexakis(alkylisocyanide)andHexakis(arylisocyanide)ComplexesofTechnetium(I)M.J.Abrams,A.Davison,A.G.Jones,C.E.Costello,H.Pang,Inorg.Chem.,1983,22,2798

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Forthesynthesisofspecificradiopharmaceuticals,theversatilechemistryofthistransitionelement,apparentfromtheexistenceofcompoundsinalargenumberoftechnetiumoxidationstates,isanadvantage.However the labeling requires the complexing of 99mTc with suitable functional groups


However.thelabelingrequiresthecomplexing of99mTcwithsuitablefunctionalgroups.

K.Schwochau,Angew.Chem.Int.Ed.,1994,33,2258

TheearlyhistoryoftechnetiumandtechnetiumradiopharmaceuticalsisbestcharacterizedbythequotefromLouisPasteur:Inthefieldsofobservations,chancefavors onlythepreparedmind

7

UnparalleledcontributionsofTechentium99mtoMedicineover5decadesW.C.Eckelman,CardiovascularImaging,2009,2,364

OrganometallicchemistryandCoordinationchemistryOrganometallicchemistryandCoordinationchemistry

Complexes;noMCbondsCoordinationcompoundsaregenerallythermodynamicallyverystableChelateeffectplaysanimportantrole;entropiccontrolpH dependencies; competition metalbindingH+

Complexes;noMCbondsCoordinationcompoundsaregenerallythermodynamicallyverystableChelateeffectplaysanimportantrole;entropiccontrolpH dependencies; competition metalbindingH+

InTechnetiumcoordinationchemistry:afewbasicligandtypesInTechnetiumcoordinationchemistry:afewbasicligandtypes

pHdependencies;competitionmetal binding HpHdependencies;competitionmetal binding H

8

PnAO,MAMA,MAGs,DADTetcandderivativesPnAO,MAMA,MAGs,DADTetcandderivatives

Designedforthe{Tc=O}3+ andthe{TcN}2+ coreDesignedforthe{Tc=O}3+ andthe{TcN}2+ core

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DTPA

Ligandsforthe3+family,Ga3+,Lu3+,In3+,Gd3+ etcLigandsforthe3+family,Ga3+,Lu3+,In3+,Gd3+ etc


DOTA TETA

NOTA

YDOTAYDOTA YDOTAYDOTA

9

HYNIC,awonderfulcoordinationchemistryapproach..HYNIC,awonderfulcoordinationchemistryapproach..


terminaldiazenidoterminaldiazenido

zwitterionicdiazenidozwitterionicdiazenido

bidentatediazenidobidentatediazenido

monodentatediazene

monodentatediazene

bentdiazenidobent

diazenido

O NH

R..butrequiresmultidentatecoligands..butrequiresmultidentatecoligands

10

N

N

N

TcLO

NHN

O

O

H

OH

COOH

tricine tricine tricine +LEDDA

J.Dilworthetal.

115

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HYNIC,awonderfulcoordinationchemistryapproach..HYNIC,awonderfulcoordinationchemistryapproach..


Modelcomplexes

TcNCl

NH

Cl

Cl

NN

N

N

H

11J.Dilworth J.etal., J.Chem.Soc.DaltonT. 1994,1251;T.Nicholson,J.Zubieta,J.Babich etal., Inorg.Chim.Acta, 1996,252,421;Inorg.Chem., 1998,37,2701.

Organometallicchemistry andCoordinationchemistryOrganometallicchemistry andCoordinationchemistry

oneormoreMCbondsbondsessentiallycovalentstabilityratherkineticthanthermodynamicchelate effect plays a minor role (robustness)

oneormoreMCbondsbondsessentiallycovalentstabilityratherkineticthanthermodynamicchelate effect plays a minor role (robustness)chelateeffectplaysaminorrole(robustness)closedshellcomplexes,diamagnetic,oftenredoxinertrarelypHdependenciesduetocovalentbonds

chelateeffectplaysaminorrole(robustness)closedshellcomplexes,diamagnetic,oftenredoxinertrarelypHdependenciesduetocovalentbonds

OrganometalliccompoundsrelyonafewbasicligandclassesOrganometalliccompoundsrelyonafewbasicligandclasses

OR

R'

12

[Tc2(CO)10]

J.C.Hileman etal.,JACS,1961,83,2953W.Hieber etal.ANIE,1961,73,579

[Tc(5C5H5)(CO)3]Carbonmonoxide Cyclopentadienyl Carbene

[Tc2(CO)9(=C(COMe)R)]

E.O.Fischeretal.,Chem.Ber.,1972,105,3027

Ch.Palmetal.Naturwissenschaften,1962,49,279

areneF.Baumgrtner etal.

Chem.Ber.,1961,94,2198

[Tc(C6H6)2]+

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oneormoreMCbondsbondsessentiallycovalentstabilityratherkineticthanthermodynamicchelate effect plays a minor role (robustness)

oneormoreMCbondsbondsessentiallycovalentstabilityratherkineticthanthermodynamicchelate effect plays a minor role (robustness)chelateeffectplaysaminorrole(robustness)closedshellcomplexes,diamagnetic,oftenredoxinertrarelypHdependenciesduetocovalentbonds

chelateeffectplaysaminorrole(robustness)closedshellcomplexes,diamagnetic,oftenredoxinertrarelypHdependenciesduetocovalentbonds

OrganometalliccompoundsrelyonafewbasicligandclassesOrganometalliccompoundsrelyonafewbasicligandclasses

otherligands

13

[Tc(CNtBu)6]+

isonitrileM.J.Abrams etal.

J.LabelledComp.Radiopharm.,1982,14,1596

alkyle

[Tc2O4(CH3)4]

W.A.Herrmannetal.ANIE.,1990,29,189

alkenealkine

? ?


Difficultieswithorganometallic(technetium)compoundsDifficultieswithorganometallic(technetium)compoundslowoxidationsstates;reductionpronetobackoxidationsolubilitiesofligandsinwaterhydrolytic stability of complexes

lowoxidationsstates;reductionpronetobackoxidationsolubilitiesofligandsinwaterhydrolytic stability of complexeshydrolyticstability ofcomplexesStabilityofligandsinwateraccessibilityofligands andderivativesligandcentredreactivities

hydrolyticstability ofcomplexesStabilityofligandsinwateraccessibilityofligands andderivativesligandcentredreactivities

notveryattractiveconditionsforradiopharmaceuticalapproaches!notveryattractiveconditionsforradiopharmaceuticalapproaches!

14

CN-R

Tc

CN-RR-NC CN-R

CN-RR-NC[99mTcO4]-[S2O4]2- Cu+

H2O / 10min 98o C

yield >98%

M.J.Abrams etal. Inorg.Chem.1983,22,2798

arock!!

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Organometallicchemistry/MetalsinMedicineOrganometallicchemistry/MetalsinMedicine

OrganometalliccompoundsinotherfieldsoflifesciencesOrganometalliccompoundsinotherfieldsoflifesciences

BioorganometallicChemistry:TherapyBioorganometallicChemistry:Therapy

Cyclopentadienyls Carbenes Arenes

15P.J.Dysonetal.J.Med.Chem. 2011,54,3895/G.Savaetal.DaltonT. 2011,40,9069/C.Hartinger etal.Organometallics,2012,31,5677G.Jaouenetal.Chem.Brit.,2001,37,36;J.Med.Chem.2006,48, 3937,M.Tackeetal.Metallomics,2011,3,74.


BioorganometallicChemistry:TherapyBioorganometallicChemistry:Therapy


NH2O

N Peptide

cyclopentadienyl alkines /alkyls arenes

16

Mo

COCO

ONH2N N Peptide

P.KpfMaieretal.,ANIE. 1984,23,456/D.R.vanStaveren etal.Chem.Commun. 2002,1406.G.Jaouen(ed)inBioorganometallics,WileyVCH,2004

carbonyls 3allyl

EssentiallyallorganometallicligandsarefoundinMetalsinMedicineEssentiallyallorganometallicligandsarefoundinMetalsinMedicine

118

10/7/2014

9


MetalsinMedicineMetalsinMedicine

C M F C Ni CC M F C Ni C


Cr Mn Fe Co Ni CuMo Tc Ru Rh Pd Ag

Re Os Ir Pt Au

Cr Mn Fe Co Ni CuMo Tc Ru Rh Pd Ag

Re Os Ir Pt Au

Essentiallynothingwithrhenium, notwithcoldandscarcelywith186/188ReEssentiallynothingwithrhenium, notwithcoldandscarcelywith186/188Re

T h ti Rh i th t h d i diT h ti Rh i th t h d i di

17

didwemisssomething?didwemisssomething?

Technetium Rhenium,thematchedpairparadigmTechnetium Rhenium,thematchedpairparadigm

OrganometalliccompoundsinotherfieldsoflifesciencesOrganometalliccompoundsinotherfieldsoflifesciencesUnderestimatedPotentialofOrganometallicRheniumComplexesasAnticancerAgents*


18

*GillesGasseretal.ACSChem.Biol.2014,inpress

ManyRecomplexesshowlowmicromolar cytotoxicity againstvarietiesofcancercelllines!ManyRecomplexesshowlowmicromolar cytotoxicity againstvarietiesofcancercelllines!

Rheniumastherapeuticcomplexes areessentiallynotexploredRheniumastherapeuticcomplexes areessentiallynotexplored

119

10/7/2014

10

RecentdevelopmentsinbioorganometallicchemistryRecentdevelopmentsinbioorganometallicchemistry

mostcomplexesinbomc arenontargeting,cisplatinlikemostcomplexesinbomc arenontargeting,cisplatinlike

ExtensionoftheconceptExtensionoftheconcept


pp

A

D CB

10/7/2014

11

MetalsinMedicine:ComplexmediatedactivityMetalsinMedicine:Complexmediatedactivity


IC50=130nMPAK1

IC50=130nMPAK1

IC50=70nMMSK1

IC50=70nMMSK1

IC50=40nMPi3K

IC50=40nMPi3K

IC50=0.5nMPim1

IC50=0.5nMPim1

IC50=0.4nMGSK3

IC50=0.4nMGSK3

ProteinKinase InhibitorProteinKinase Inhibitor MLCKinhibitor4.4nMMLCKinhibitor4.4nM Pim1inhibitor0.07nMPim1inhibitor0.07nM

E.Meggersetal., Chem.Commun.2009,1001; JACS.2011,133,5976;ANIE 2011,50,2442

21Rhenium fortherapy Technetium fordiagnosisRhenium fortherapy Technetium fordiagnosis

FinetuningofmetalcomplexguidesaffinityandselectivityFinetuningofmetalcomplexguidesaffinityandselectivity

canweestablishsimilarformatchedpairelementscanweestablishsimilarformatchedpairelements

MetalsinMedicine:ComplexmediatedactivityMetalsinMedicine:Complexmediatedactivity

Structuralmimics ofsteroidhormonesStructuralmimics ofsteroidhormones


22

J.A.Katzenellenbogen etal.,JACS,1993,115,7045;J.Med.Chem.,1994,37,928; J.Org.Chem.,1997,62,6290;J.Org.Chem.,1996, 61,2624

Denovoinhibitors forreceptorsDenovoinhibitors forreceptors

Challengingfor99mTcchemistrywithcoordinationcompoundsChallengingfor99mTcchemistrywithcoordinationcompounds

2121

10/7/2014

12

Tc vectorTc

bioinactivebioinactive bioactivebioactive bioactivebioactive

M

IntegratedMolecularImagingAgentsIntegratedMolecularImagingAgents

TcessentialperfusionTcessentialperfusion

Tcpendent/BFCtargeting

Tcpendent/BFCtargeting

integratedimagingagentsintegrated

imagingagents

M receptorreceptorvectorvector

lead M

TherapyTherapy

TheranosticsTheranostics

inactiveinactive activeactive Tc receptorreceptorvectorvector

DiagnosisDiagnosisstructuralrecognitionbymetalcomplex

structuralrecognitionbymetalcomplex

23

OrganometallicComplexesarewellsuitedfortheconcept

bioactivebioactive

M

i t t di t t d

IntegratedMolecularImagingAgentsIntegratedMolecularImagingAgents

integratedimagingagentsintegrated

imagingagents

TechnetiumforimaginganditsRheniumhomologuefortherapyTechnetiumforimaginganditsRheniumhomologuefortherapy

since..since..

OrganometallicComplexesarewellsuitedfortheconceptOrganometallicComplexesarewellsuitedfortheconcept

24

..manyleadstructurescompriseorganometallicstructuralmotives..manyleadstructurescompriseorganometallicstructuralmotives

2222

10/7/2014

13

HN OO

TherapyandImagingwithMetalComplexesTherapyandImagingwithMetalComplexes

PracticallimitationsPracticallimitations

Optimizedstructurerecognizingcomplexesb th i d b

Optimizedstructurerecognizingcomplexesb th i d b

N N

OO

ReCORHN

O

inaccessible

25

canbesynthesizedbyanymeanscanbesynthesizedbyanymeans

[99mTcO4] productssaline

3060min/r.t.or100Csaline

3060min/r.t.or100C

TrueTcRe(andMn)homologyonlyinlowoxidationstatesTrueTcRe(andMn)homologyonlyinlowoxidationstates

TherapyandImagingwithMetalComplexesTherapyandImagingwithMetalComplexes

OrganicleadstructureOrganicleadstructure ImagingImaging TherapyTherapy

Aminoacids

Aminoacids

Inhibitor

Inhibitor

Aminoacids

Aminoacids

Inhibitor

Inhibitor

Re

CONH

SOC

OCO

O

SO2NH2

HDAC

HD

AC

CAInhibitor

CAInhibitor

HDAC

HD

AC

CAInhibitor

CAInhibitor

2626

2323

10/7/2014

14

TheCyclopentadienyl PhenylAnalogyTheCyclopentadienyl PhenylAnalogy

Thieles acidThieles acidDielsAlder:DielsAlder:

Synthesisof[(5CpR)99mTc(CO)3]+ complexesfromwaterSynthesisof[(5CpR)99mTc(CO)3]+ complexesfromwater

dienophiledienophiledienedieneT>160 CT>160 C

[(HCpCOOH)2][(HCpCOOH)2]

H2O/95 C/3060minH2O/95 C/3060min[99mTcO4][99mTcO4]allinoneallinone

>97%>97%

27

Liu,Y.etal.J.Am.Chem.Soc.2008, 130,155


ReCO

COOH

NH2


OC COCO

therapytherapy diagnosisdiagnosis

OTc

O OO Isolink

98C/30 min

OH2

Tc

COOC CO

OH2H2O

28

2424

10/7/2014

15

OTc

O OO Isolink

98C/30 min

OH2

TcOC CO

OH2H2O

60 min / 90C



O 98 C/30 minCO

insituBoc deprotection

60min/90 C

D.Canetal,.Organometallics,2012,31,6880

29



0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0

Inte

nsity

22.30

17.10

UV-trace

labelling

30

Minutes

0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0

Inte

nsity

UV-trace -trace

22.1921.71

0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0 UV trace -trace

Inte

nsity

15.67 16.77

99mTcReneutralize

2525

10/7/2014

16


Whichisthelabelingsite?Whichisthelabelingsite?


R1R1R2R2

31

D.Canetall,Chem.Biodivers.2012,9,1849

Tworadiopharmaceuticalsfromonesingleprecursor!Tworadiopharmaceuticalsfromonesingleprecursor!

CarbonicAnhydrase(CA)InhibitorsCarbonicAnhydrase(CA)Inhibitors

1 01 0

Labeling

[99mTcO4]Isolink

0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0

0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0

32

C.Supuran,Nature,2008,7,168181

Re

99mTc

Ligand

26

10/7/2014

17

IC50 valuesIC50 values


HC I II III IV VA VB VI VII IX XII XIII XIV XV

BA

CAinhibition (nM affinities)CAinhibition (nM affinities)

AZA

33

A 50 49 5217 624 658 556 647 470 57 69 727 29 585

B 39 15 4600 467 481 305 497 360 43 7 482 20 313

AZA 250 12 20000 74 63 54 11 2 25 6 17 41 72


IC50 valuesIC50 values

HC I II IV VA VB VI VII IX XII XIII XIV XV

CC DD EE

CAinhibition (nM affinities)CAinhibition (nM affinities)

34

HC I II IV VA VB VI VII IX XII XIII XIV XV

C 4590 35.5 41.1 124 104 22.1 21.3 5.2 6.9 78.5 7.9 36.8

D 2570 25.3 32.9 113 105 10.6 7.6 3.7 4.5 62.1 4.1 28.4

E 2775 27.4 33.8 109 102 14.5 10.1 7.0 4.4 56.8 85.4 12.5

AZA 250 12 74 63 54 11 2 25 6 17 41 72

27

10/7/2014

18

ReceptorSubtypeSpecificitiesReceptorSubtypeSpecificities


FC5

HN

OSO

ONH2

Re

COOC

OC

DCB40

H

FC5

35

HN

OSO

ONH2

Re

COOC

OC

O

HN

ORe

COOC

OC

SO

O

NH2

DCB41

DCB43

CocrystallizationwithCAIICocrystallizationwithCAII


36

D.Canetal.Angew.Chem.Int.Ed.2012,51,3354

28

10/7/2014

19

HDACInhibitor,SAHA VorinostatHDACInhibitor,SAHA Vorinostat

IC50 (M)MCF-7 A431 HeLa A375 B16F1

Re-(i7)SAHA 9.47 13.7 14.4 14.7 9.82

IntegratedapproachIntegratedapproach

Re-(i6)SAHA 15.2 17.1 13.3 23.3 12.6Re-SAHA 11.4 17.3 8.34 12.5 15.2(i7)SAHA 1.71 2.51 1.65 2.63 3.10(i6)SAHA 7.19 5.22 5.83 4.85 8.88

SAHA 3.74 4.44 4.45 4.58 3.67

37

ReSAHA Re(i6)SAHA Re(i7)SAHA

(i7)SAHA (i6)SAHA

verylowaffinitywithout phenylorCpringverylowaffinitywithout phenylorCpring

HDACInhibitor,SAHA VorinostatHDACInhibitor,SAHA Vorinostat

IntegratedapproachIntegratedapproach

99mTc(i7)SAHA99mTc(i7)SAHA

[99mTc(OH2)3(CO)3]+[99mTc(OH2)3(CO)3]+

[99mTcO4][99mTcO4]Nr.9

38

Smallyieldonly,oxidationtopertechnetate!!Smallyieldonly,oxidationtopertechnetate!!

Systemlimited bychemicalstabilityof[99mTc(OH2)3(CO)3]+ towardsfunctionalgroupsSystemlimited bychemicalstabilityof[99mTc(OH2)3(CO)3]+ towardsfunctionalgroups

29

10/7/2014

20

Cyclopentadienyl PeptidesCyclopentadienyl Peptides

Pendentvs integratedapproachPendentvs integratedapproach

PeptideTransporter2(PEP2)inhibitors:smalltripeptidesPeptideTransporter2(PEP2)inhibitors:smalltripeptides

Cl

PClCl

Cl

39

Q.Nadeem etal.,Org.&Biomol.Chem.,2014,12,1966;Y.Liuetal.,BioconjugateChem.,2013,24,26

Cyclopentadienyl PeptidesCyclopentadienyl Peptides

Pendentvs.integratedapproachPendentvs.integratedapproach

from[99mTcO4]from[99mTcO4]microwave30 120min3080%yield

microwave30 120min3080%yield

40

30

10/7/2014

21

ExtendingthecyclopentadienylscaffoldExtendingthecyclopentadienylscaffold

dimerizessolubilitydimerizessolubility

FunctionalizedCpDerivativesFunctionalizedCpDerivatives

spacerpK

spacerpKsolubility

derivatizationssolubility

derivatizations dimerizevery slowlydimerizevery slowly

Labeling,30min60C

pKapKa

41

faster,moreefficientthanC0faster,moreefficientthanC0

nolabelingatall!!nolabelingatall!!

IntroducingatargetingfunctionIntroducingatargetingfunction

onepottwopotonepottwopot


rearrangement!rearrangement!

activationactivation peptideformationpeptideformation

42

31

10/7/2014

22

IntroducingasecondfunctionalityIntroducingasecondfunctionality


Pharmaceuticallyactiveleadstructuresoftencompriseanintegrated andnotaterminalphenylgroup

Pharmaceuticallyactiveleadstructuresoftencompriseanintegrated andnotaterminalphenylgroup

twodifferentfunctionscanbeconjugatedviathemetalcomplex..twodifferentfunctionscanbeconjugatedviathemetalcomplex..

..oronlyasingleoneindifferentmodalities..oronlyasingleoneindifferentmodalities

O

O

N function 1


IntroducingasecondfunctionalityIntroducingasecondfunctionality

baseexc.Cpp

isomersisomers

+isomers+isomers

sideproductsideproduct

44

alternativeroutealternativeroute 8MNaOH80C/3d

ca.30%

32

10/7/2014

23

pKa =5pKa =5

existsatpH=7.4inwaterasmonoanionexistsatpH=7.4inwaterasmonoanion


Introducingasecondfunctionality:RheniumIntroducingasecondfunctionality:Rhenium

+H++H+aa

tautomerstautomers

1,2and1,3CpasaWernertypeligands?1,2and1,3CpasaWernertypeligands?

45Cpchemistryinwaterwithanyelement?Cpchemistryinwaterwithanyelement?

30 C/120min

Na+

>90%

1,2

>90%

1,3

R

OOCH3

OH3CO


Introducingasecondfunctionality:RheniumIntroducingasecondfunctionality:Rhenium

Re

COCOOC

waternoradrenalinwaternoradrenalin HBTUamineHBTUamine

46

HBTUamineHBTUamine

33

10/7/2014

24

LabelinginsalineLabelinginsaline

Na+


Introducingasecondfunctionality:TechnetiumIntroducingasecondfunctionality:Technetium

standard conditionspH=10,30min70Cstandard conditionspH=10,30min70C BA

CAC

D

47

D

A

B

OOCH3

OH3CO

Na+

LabelingLabeling

O OH2


Introducingasecondfunctionality:TechnetiumIntroducingasecondfunctionality:Technetium

pH=5,15min60CpH=5,15min60C

Tc

COCOOC

OTc

O OO Isolink

98C/30 min

OH2

Tc

COOC CO

OH2H2O

trace(99mTc)

48StartingcompoundformultifunctionalityimagingagentsStartingcompoundformultifunctionalityimagingagents

UVtrace(Re)

34

10/7/2014

25

Rhenium:stepwiseintroductionofbiofunctionsRhenium:stepwiseintroductionofbiofunctions


OOCH3

OH3CO

NaOH /H2ONaOH /H2O NaOH /H2ONaOH /H2ORe

COCOOC

HBTU

HBTUHBTU

HBTU

HNNH

49

Re

COCOOC

OO

symmetricsymmetricasymmetricasymmetric


Technetium:directlabelingwithaminesinwaterTechnetium:directlabelingwithaminesinwater

Buildingblockfor mono and homo difunctionalized complexes

Buildingblockfor mono and homo difunctionalized complexes R

OOCH3

OH3CO

anyaminewater

formonoandhomodi functionalizedcomplexesformonoandhomodi functionalizedcomplexes Re

COCOOC

anyaminewater

35

10/7/2014

26

TargetingtheNucleusTargetingtheNucleus

NuclearTargetingwithAugerEmittersNuclearTargetingwithAugerEmitters

Doxorubicin,anucleustargeting,fluorescentmoleculeDoxorubicin,anucleustargeting,fluorescentmolecule

51Radiotoxic Doxorubicin Tc99mConjugatesImstepf etal. inpreparation

Nucleus Targeting Bifunctional Tc99mComplexesBioconjugateChem.,2011,22,958.


NuclearTargetingwithAugerEmittersNuclearTargetingwithAugerEmittersAsystematicapproach:Synthesis,PropertiesandinvitroProfilAsystematicapproach:Synthesis,PropertiesandinvitroProfil

ctDNA Titration:DNABinding

5252

IC50:Cytotoxicity

36

10/7/2014

27



OHOOH

O

OH

OHO OO

O

HN

OH

N

O99mTc

N

N

O

OO

S1

Surviving Fraction @50CiHeLa: 74.5 2.0%A431: 70 0 5 5%

IC50:~14Ci (500kBq)

53

A431: 70.0 5.5%B16F1: 22.5 1.4%

IC50 of coldRecomplex:>100M

Exhibits most significant killingability inmurine melanoma (B16F1)cells.

Radiosensitivity:B16F1>A431>HeLa



Maxuptake 4hrs:~610%

Maxuptake 4hrs:~3%

54

Maxuptake 4hrs:~67%

Maxuptake 4hrs:~4%

Cellularinternalizationisnotcompleteafter4hrsSomewhathigheruptakeforS1Nosignificantdifferencesbetweencelllines

37

10/7/2014

28


M Nucleus Mitochondria Nucleus MitochondriaRe185 (ICPMS) 71% 1.6% 74% 2.1%Tc99m (activity meter) 81% 1.2% 76% 1.8%

55

majoraccumulationofcompoundsinthenucleus~7080%minoraccumulationinmitochondria~12%good(excellent)agreementbetweenquantificationmodalities

M Nucleus Mitochondria Nucleus MitochondriaRe185 (ICPMS) 80% 1.6% 66% 1.8%Tc99m (activity meter) 82% 1.4% 79% 3.2%

Values:Nuclearandmitochondrialinternalization,respectively,asthepercentageofactivityorRecontentwithrespecttowholecell uptake.


NuclearTargetingwithAugerEmittersNuclearTargetingwithAugerEmittersOHO

OHO OO

OHO

OH

HN

N N

OOH

N

O99mTc

N

N

O

OO

S1

M Nucleus Mitochondria

Re185 (ICPMS) 71% 1.6%Tc99m (activity meter) 81% 1.2%

R di t i it ( 80 M) Ch t i it ( 100 M)

56

Radiotoxicity ( 80nM)>>Chemotoxicity(>100M)ComplexS1 exhibitedmarkedlyradiotoxiceffect:IC50 500kBq (B16F1)Majoraccumulationofallderivativesinnucleus:notvisiblewithfluorescenceimaging

FluorescenceQuenchingbyintercalation!!

Verificationwithtwoquantificationmodalities

38

10/7/2014

29

FromCyclopentadienyltoArenesFromCyclopentadienyltoArenes

Chromocene:FischerHafner Synthesis

attractivesinceitcontainsPhenyls

arenescanbesubstituted

arenesareactivated




arenesareactivated




arenesareactivated

metalcentredactivity(Dyson,Sadleretal.)

areneringtendstobelost

introductionoffunctionalities

Multivariationsatmetal(X,Y,Z)









S th i d b E O Fi h t l f 99MS th i d b E O Fi h t l f 99M

57

SynthesizedbyE.O.Fischeretal.from99Mo

Chemistryessentiallynotinvestigated

Sourceforhigheroxidationstates

Precursorforlabeling

Rheniumanalogues

SynthesizedbyE.O.Fischeretal.from99Mo

Chemistryessentiallynotinvestigated

Sourceforhigheroxidationstates

Precursorforlabeling

Rheniumanalogues

F.Baumgrtner etal.TetrahedronLett.1962,6,253;Chem.Ber.1961,94,2198

MissedOpportunities(Terachem 2010)MissedOpportunities(Terachem 2010)

Tc

[TcCl4]

Al/AlCl3 C6H6 /135 C

5858FischerE.O.etal.Tetrahedron Lett.,1962

it is water stable

39

10/7/2014

30

Radiopharmaceuticalchemistrybranch4methodsforthepreparationoftheanalogues99mTccomplex

[99mTcO4] (dry)

Basicchemistry branchTc

MissedOpportunities(Terachem 2010)MissedOpportunities(Terachem 2010)

orultrasoundr.t.

Purification HPLC50 95%

Moderatemyocardialuptake

[TcCl4]

Al/AlCl3 C6H6 /135 C

Al/AlCl3 /C6H6135 C60min

59

Wester,D.W.etal.J.Med.Chem. 1991 and this conference

it is water stable

FischerE.O.etal.Tetrahedron Lett. 1962

monocationic99mTcbisarenecomplexesformyocardialimagingmonocationic99mTcbisarenecomplexesformyocardialimaging

[99mTcO4][99mTcO4] Al /AlCl3Al /AlCl3


arenearene

notenoughheartuptake discarded stableinwaterunderphysiologicalconditions

notenoughheartuptake discarded stableinwaterunderphysiologicalconditions

[99TcCl4][99TcCl4]

R3 E05

[Re(C6H6)2 ]PF6

60

D.W.Wester etal.J.Med.Chem.1991,34,3284D.W.Wester etal.J.Med.Chem.1991,34,3284

[ReO4]Zn /AlCl3arene/810hZn /AlCl3arene/810h

Re

R

2030%4,E05

3,E05

2,E05

1,E05

0,E+00

1,E05

2,E05

3,E05

2,50 2,00 1,50 1,00 0,50 0,00 0,50 1,00 1,50 2,00

40

10/7/2014

31


ExtendingthechemistrywithRheniummodelcomplexesExtendingthechemistrywithRheniummodelcomplexes

[R O ] Zn / AlCl3Zn / AlCl3BuLi Re

H

Bu

[ReO4]Zn /AlCl3benzene/810hZn /AlCl3benzene/810h

70%

Re

80%

COOH

LDACO2

COOH

61

ReRe

COOH

introductionoftargetingfunctionsintroductionoftargetingfunctions

Technetiumcomplexes?Technetiumcomplexes?

[99T O ][99T O ]Zn /AlCl3Zn /AlCl3

R

Modelcomplexeswith99TcModelcomplexeswith99Tc


[99TcO4][99TcO4]3

arene/810h3

arene/810hTc

R

2030%2030%

99TcNMR(benzene)99TcNMR(benzene)

62

41

10/7/2014

32

[99T O ][99T O ]Zn /AlCl3Zn /AlCl3

R

Modelcomplexeswith99TcModelcomplexeswith99Tc

XX


[99TcO4][99TcO4]3

arene/810h3

arene/810hTc

R

XXFriedelCraftsconditionsFriedelCraftsconditions

63

99TcNMR99TcNMR

From99Tcto99mTcFrom99Tcto99mTc

Na[99mTcO4]insaline(0.9%NaCl):Howtotransferintoarenes?Na[99mTcO4]insaline(0.9%NaCl):Howtotransferintoarenes?

ILIL


[99mTcO4] /0.9%saline[99mTcO4] /0.9%salinefewmgILfewmgIL [99mTcO4] inIL[99mTcO4] inIL

arenearene >95%99mTcdissolvedinarene>95%99mTcdissolvedinarene

[99mTcO4] /arene[99mTcO4] /areneZn /AlCl31h/95 CZn /AlCl31h/95 C

extractintobufferextractintobuffer

64

20 80%yield20 80%yield

stablefrompH=2 12at37C

notairsensitiveatall

stablefrompH=2 12at37C

notairsensitiveatall

arenecomplexesareanoptionformolecularimaging!arenecomplexesareanoptionformolecularimaging!H.Brabandetal.Chem.Sci. 2014,inpress

42

10/7/2014

33

ConclusionsConclusions

imagingneedstobecombinedwiththerapy,orviceversaimagingneedstobecombinedwiththerapy,orviceversa

Forthefuture..Forthefuture..

ClassicalMetalsinMedicineconceptshaverelevancetomolecularimagingClassicalMetalsinMedicineconceptshaverelevancetomolecularimaging

65

cytotoxic,fluorescent imaging,metabolism

Technetium(andRhenium)chemistry....isstillanexcitingfieldforresearchwithimpactforotherelements

Technetium(andRhenium)chemistry....isstillanexcitingfieldforresearchwithimpactforotherelements

ConclusionsConclusions

TheinertnessoflowvalentReandTc complexes enablesnewconceptsintheranosticsTheinertnessoflowvalentReandTc complexes enablesnewconceptsintheranostics

[99mTcO4] /0.9%saline[99mTcO4] /0.9%saline

66

Nothingisimpossible!Nothingisimpossible!

43

10/7/2014

34

AcknowledgmentsAcknowledgments

99(m)Tc Chemistry99(m)Tc Chemistry

Henrik BrabandMichaelBenz

Sebastian Imstepf

Henrik BrabandMichaelBenz

Sebastian Imstepf

UniversityofZrichUniversityofZrich

ITN,LisbonPortugalITN,LisbonPortugalI.Santos

P.RaposinhoF.Mendes

I.SantosP.RaposinhoF.Mendes

TU MunichTU MunichSebastianImstepfMichaelFelberQaisar NadeemSamer SuliemanAngeloFrei

Guiseppe Meola

SebastianImstepfMichaelFelberQaisar NadeemSamer SuliemanAngeloFrei

Guiseppe Meola

BildungundForschungSBFBildungundForschungSBF

UniversityofFlorence,ItalyUniversityofFlorence,ItalyProf.C.SupuranProf.C.Supuran

SSAJRP JRPSSAJRP JRP0101SSAJRP JRPSSAJRP JRP0101

TUMunichTUMunich

M.SchotteliusH.J.WesterM.SchotteliusH.J.Wester

67

SSAJRPJRPSSAJRPJRP 0101SSAJRPJRPSSAJRPJRP 0101

68

44

10/7/2014

35

SolutionstoProblemsSolutionstoProblems

Nr.1B.Noll,P.Leibnitz,H.Spies,ForschungszentRossendorf(Ber.)1999,270,153

Nr.2N.Bryson,J.ListerJames,A.G.Jones,W.M.Davis,A.Davison,Inorg.Chem.1990,29,2948.

6969Nr.3U.Mazzi,D.A.Clemente,G.Bandoli,L.Magon,A.A.Orio,Inorg.Chem. 1977,16,1042.


C.K.Fair,D.E.Troutner,E.O.Schlemper,R.K.Murmann,M.L.Hoppe,Acta Crystallogr.,Sect.C:Cryst.Struct.Commun.1984,40,1544.Nr.5

Nr.4J.L.Vanderheyden,A.R.Ketring,K.Libson,M.J.Heeg,L.Roecker,P.Motz,R.Whittle,R.C.Elder,E.Deutsch, Inorg.Chem.1984,23,3184.

70Nr.6W.A.Herrmann,R.Alberto,J.C.Bryan,A.P.Sattelberger, Chem.Ber.1991,124,1107.

Nr.7F.A.Cotton,L.Daniels,A.Davison,C.Orvig,Inorg.Chem.1981,20,3051.F.Poineau,E.V.Johnstone,P.M.Forster,Longzou Ma,A.P.Sattelberger,K.R.Czerwinski,Inorg.Chem.2012,51,9563.

45

10/7/2014

36


Nr.8C.Bolzati,A.Boschi,L.Uccelli,F.Tisato,F.Refosco,A.Cagnolini,A.Duatti,S.Prakash,G.Bandoli,A.Vittadini,JACS,2002,124,11468

71

Nr.9R.Alberto,R.Schibli,D.Angst,P.A.Schubiger,U.Abram,S.Abram,T.A.Kaden,Trans.Met.Chem. 1997,22,597

46

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1

TECHNETIUMBEHAVIORINTHEPUREX PROCESS

PascalBARONCurrentFuelCycleBackEndProgramy g

CEA,NuclearEnergyDivision

| PAGE 1

ISTR2014 8th INTERNATIONALSYMPOSIUMONTECHNETIUM ANDRHENIUM29th SEPTEMBER 3rd OCTOBER 2014,Pornichet LABAULEFRANCE

THE PUREX PROCESS

SPENT FUEL HNO3

TBPU

Pu

U, Pu, FPs,MAssolution

3 Pu

DISSOLUTION EXTRACTION

HULLS FPs, MAs

47

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2

1ST CYCLE U-Pu WITH U/Pu PARTITIONING

EXTRACTANTCLEANING

TBP

stripping stripping

RaffinateFP, MA

FEEDU,Pu,FP,MA

UPu

RductorU(IV)

Scrubbingstripping. stripping.

INTRODUCTION

Tc is just one FP among many othersYES, BUT:

Tc production yield in reactor is high

on the contrary than most of the others, Tc is

able to be extracted by TBP (multiple mechanisms)

Tc can have deleterious impact on U/Pu REDOX

chemistry in the PUREX process (multiple oxydation

state)

4

48

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3

FISSION PRODUCTS YIELD

Tc 99

INTRODUCTION

Tc is just one FP among many othersYES, BUT:

Tc production yield in reactor is high

on the contrary than most of the others, Tc is

able to be extracted by TBP (multiple mechanisms)

Tc can have deleterious impact on U/Pu REDOX

chemistry in the PUREX process (multiple oxydation

state)

6

49

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4

TECHNETIUM BEHAVIOR IN THE DISSOLUTION STEP

AMOUNT:About 1kg / ton (burn up dependent)not cooling-time dependent ( 99Tc , half-life= 2,1.105years),

SPECIESTcO2 and poly mtallic compounds

(undissolved species)

TcO4- in the dissolution solution

DISSOLUTION YIELDDISSOLUTION YIELDFuel type dependent at lab scale: UOX ~ 90 %, MOX ~ 60 %, SFR ~ 20 %

Lower yield at industrial scale (rotating dissolver): ~50% for UOX and MOX

7

TECHNETIUM EXTRACTION BY TBP

SIMPLIFIED EXTRACTION MECHANISMS [ ]+ ++ 44 ,3TBPHTcO3TBPTcOH

( )[ ] ( )( )[ ]( )[ ] ( )( )[ ]

++

++

3334443

33424232

NO,2TBPNOTcOPuTcO,2TBPNOPu

NO,2TBPNOTcOUOTcO,2TBPNOUO

( )[ ] ( )( )[ ] ++ 3334443 NO,2TBPNOTcOZrTcO,2TBPNOZrCo-extraction:

Higher for Zr >> Pu > U Reduced at high [NO3-] (competition)

50

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5

TECHNETIUM BEHAVIOR IN EXTRACTION STEP

ExtractionU + Pu

scrubbingFP

TBP-dodecane ZrTc +U UTc

Zr AcidHNO3Zr, FP

U, Pu, Tc

U u

ZrTc

Zr +Tc

FeedU, Pu, Tc, Zr, FP

HNO3

TECHNETIUM BEHAVIOR IN EXTRACTION STEPOPTIONS TO LIMIT THE IMPACT

CHEMICAL ADJUSTMENTIntroduction of Zr complexing agent: carboxylic acids

Oxalic acid (forgiven / Pu leakage risk)( g g )Other acids (ex.: KMA)

NOT READY FOR UP3

OPERATING ADJUSTMENT / TOPOLOGYAdjunction of a complementary operation the "Tc scrubbing"(allow separate management of Tc / others FPs)( p g )

SOLUTION CHOOSEN FOR UP3 AND UP2-800

10

51

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6

TECHNETIUM BEHAVIOR IN EXTRACTION STEP

TBP 30 %

Main FPs U, Pu, Tcextraction

sscrubbing

FeedU, Pu, FPs HNO3 3 M

HNO3 2 M

Secondaryextraction

Tc scrubbing

FPs, ,

TBP 30 %

U, Pu

TcHNO3 10 M HNO3 1,5 M

TECHNETIUM SCRUBBING FOR LA HAGUE

PRINCIPLES:Zr scrubbing at first stepTc back extraction (high acidity)( g y)

DESIGN CONSTRAINT (1985, active start of UP3 1989)Minimization of the impact on upstream/downstream steps(mainly acid effluents)

OPTIMISATION USING PAREX CODE:DF Tc = 2,8 UP3 (1989), ( )

(validated at lab scale on genuine solution and confirmed by UP3)

Today DF > 30 routinely performed at UP2800 and UP3

12

52

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7

1

10

Zr(IV)

Concent

0.001

0.01

0.1

FP scrubbing sectionMain extraction section

Tc(VII)

ration

g/l

N of stage

0.0001

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

FP scrubbing sectionMain extraction section

Aqueous technetium profile: experimental ( ), calculated ( )

Aqueous zirconium profile: experimental ( ), calculated ( .....)

1

T (VII)

Concent

0.1

Secondaryextraction

Technetiumscrubbing

Tc(VII)

section section

ration

g/l

N of stage

0.01

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Profils techntium aqueux: experimental ( ), calcul ( )

53

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8

U/Pu SPLITTING STEP

FUNCTIONAL REACTION : Pu(IV) Reduction

U4+ + 2Pu4+ + 2H2O UO22+ + 2Pu3+ + 4H+U + 2Pu + 2H2O UO2 + 2Pu + 4H

PARASISTIC REACTION : Pu(III) Oxydation

Pu3+ + HNO2 + H+ + 0,5HNO3 Pu4+ + 0,5H2O + 1,5HNO2

USEFULL or STABILIZING REACTION : HNO Destruction USEFULL or STABILIZING REACTION : HNO2 Destruction

N2H5NO3 + HNO2 HN3 + HNO3 + 2H2O

U/Pu SPLITTING STEP

Pu(IV)

Pu(IV)Pu(III)

TBP 30%Loaded solvent

U(VI), Pu(IV) U(VI)

Pu(III)

HNO3 0.2 M hydrazineU(IV), hydrazine

Pu(III)

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9

TECHNETIUM BEHAVIOR IN URANIUM/PLUTONIUM SPLITTING STEP

SIMPLIFIED REDOX MECHANISM

fast)(very ...UOTc...UTc(VII) 22ox4 ++++ ++ ww

reaction) (limiting...HNOTc...HNOTc

fast)(very ...UOTc...UTc

(fast)...Tc...HNTc

2ox3red

22red

4ox

red52ox

++++++++

+++++

+

zz

yy

x

Tcox is for Tc(V) and/or Tc(VI)Tcred is for Tc(IV) (ou Tc(III) ?)

where

Globally Kinetic of first-order versus [ Tc ]With relatively high activation energy (22 kcal/mol)

DELETERIOUS IMPACT OF Tc ON PUREX PROCESS

Pu(IV)

Pu(IV)Pu(III)

TBP 30%Loaded solvent

U(VI), Pu(IV) U(VI)

Pu(IV)

Pu(III)Pu(IV)

HNO3 0.2 M hydrazineU(IV), hydrazine

Pu(III) HNO2

N2H4

Tc

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10


NHPu

Pu(IV)Pu(III)Pu(III) NHx Pu

Pu(IV)


Pu(IV)Pu(III)Pu(III)x Pu

Pu

Pu(IV)

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11

TECHNETIUM BEHAVIORARRANGEMENT TAKEN FOR U/Pu SPLITTING STEP

OPERATING CONDITIONS Increase excess of hydrazineyLimiting operating temperatureNeutrons on line monitoring

UP3 - UP2 800 RESULTS Outstanding stable operationOutstanding stable operationDF of uranium vs plutonium > 106Good agreement with model predictions

IN CONCLUSION

Tc is just one FP among many others

YES BUT:YES, BUT:

It has an atypical behavior in the PUREX process

That must be taken into account in the fl h t d i tflowsheet design step

Its chemistry needs to be deepen in the frame of FR fuel reprocessing (high Pu)

22

57

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12

ISTR2014

THANK YOUFOR YOUR ATTENTION !

| PAGE 23

Pornichet LABAULE,FRANCE29TH SEPTEMBER,3RD OCTOBER2014

PascalBARON

58

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13

____________________________________Family Amount (kg/t)____________________________________

R G (K X ) K 96 Nd 3 (0 3 PB )

FISSION PRODUCTS :AVERAGEDISTRIBUTION (1 ton UOX, 3,5 % 235U ,33 GWj/t)

Rare Gas (Kr, Xe) Kr : 96 Ndm3 (0,3 PBq) Xe : 736 Ndm3

3T & Alkali (Cs, Rb) 3T = 16 TBq ; 3,977Alkaline earth (Sr, Ba) 2,407Yttrium & Lanthanides 10,198Zirconium 3,586Chalcogens (Se, Te) 0,527Molybdenum 3 335Molybdenum 3,335

Technetium 0,814Platinoids (Ru, Rh, Pd) 3,892Ag, Cd, Sn, Sb, etc... 0,216____________________________________

TECHNETIUM BEHAVIOR OF IN NITRIC ACID

INITIATION INDUCTION FAST REACTIONh d i hydrazine hydrazine

Tc(VII) Tc(VI).Tc(V) Tc(IV) Tc(VI)

hydrazine

very slow

hydrazine

fast

hydrazine

fast

slow

NO3-slow

NO3-

very

fast

TERMINATION3NO3

Tc(VII)

J. Garraway and P.D. Wilson, Journal of Less-Common Metals, 97(1984) 191-203

59

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14

CINTIQUE DE DCOMPOSITION DE L'HYDRAZINE EN PRSENCE DE TECHNTIUM

0,5

0,6

(mol

/L/h

)

0,1

0,2

0,3

0,4

-d[N

2H5+

]/dt

40C

30C

00 100 200 300 400 500

[Tc] (mg/L)

TECHNETIUM BEHAVIOR IN URANIUM/PLUTONIUM SPLITTING STEP

J. Garraway and P.D. Wilson, Journal of Less-Common Metals, 97(1984) 191-203

60

THE ROLE OF A CHOICE OF THE TARGET FORM FOR 99

Tc TRANSMUTATION

.. Kozar, V.F. Peretrukhin, K.E. German

Frumkin Institute of Physical Chemistry and Electrochemistry of RAS, 31/4 Leninsky

prosp., Moscow, 119071, Russia, [email protected]

99Tc transmutation can be the source of artificial stable ruthenium

100102Ru. Such

ruthenium has been received as a result of a neutron irradiation of Tc targets up to 20 70 % burn-up (for 3 different groups of Tc targets) in experiments on SM high-flux reactor. Metal

homogeneous Tc targets had the form of disks in diameter 6 and with thickness of 0.3 mm [1, 2]. They have been irradiated in geometry of a thin plate and consequently occupied

irradiated volume corresponding to the cylinder in diameter and with height of 6 mm.

Artificial ruthenium demanded exposure during 8 10 years for application without restrictions, as it contained fission fragment

106Ru (T1/2 = 369 days) which can not be

removed from this material by chemical methods.

Application of heterogeneous targets with nuclear-inert stuff to reduce a 106

Ru

radioactivity in artificial Ru and to lower its exposure time before application or to exclude a

technological step on additional preliminary purification of commercial Tc from actinide

impurities [3]. Hence, the target form has effect on the artificial ruthenium purity at equal Tc

nuclear density in irradiated volume.

Transformation of disks in cylinders in the conditions of identical irradiated volume

could allow to lower 106

Ru concentration in artificial ruthenium. The minimum fission-

fragment path length in Tc metal makes about 5 microns (average fission-fragment path

length is about 8 microns). The corresponding form of a heterogeneous target is a tablet

consisting of a mix of spherical Tc metal particle in diameter of 5 microns and a nuclear-inert

stuff with Tc average density which in 20 times is less, than Tc metal. In this case all fission-

fragments, including 106

Ru, escape the Tc (Tc-Ru) grains to stuff. The average distance

between Tc spherical grains is about 23 microns, between their surfaces is about 18 microns

at regular distribution of Tc particles in a target.

Fission-fragment path length in the most applicable nuclear-inert materials (such as

ZrO2, Y2O3, MgAl2O4, MgO, Y3Al5O12, SiC, Al2O3, ZrO2-Y2O3, ZrO2-CaO and many others)

makes 12 15 microns, hence hit probability of 106Ru fission-fragments in the next Tc grainis negligibly small. Artificial ruthenium from such target would be almost free from

106Ru

nuclei. Additional purification of commercial Tc from actinide impurities would be not

necessary at a choice of such target form instead of metal disks. In this case artificial

ruthenium could be applied in non-nuclear field through 3 3.5 years after an irradiation, necessary to decay of transmutation product

103Ru (T1/2 = 39.3 days).

References

1. V. Peretroukhine, V. Radchenko, A. Kozar et al. Technetium transmutation andproduction of artifical stable ruthenium. // Comptes Rendus. Ser. Chimie. 2004. Tome 7. Fascicule 12. P. 1215 1218.

2. .. Kozar, V.F. Peretroukhin, K.V. Rotmanov, V.A. Tarasov. The elaboration oftechnology bases for the artificial stable ruthenium preparation from technetium-99

transmutation products. // 7th

International Symposium on Technetium and Rhenium Science and Utilization. Moscow, Russia, July 4 8, 2011. Book of Proceedings. P. 113. Publishing House GRANITSA, Moscow, 2011. 460 p.

3. .. Kozar, V.F. Peretroukhin, K.V. Rotmanov, V.A. Tarasov. The elaboration oftechnology bases for the artificial stable ruthenium preparation from technetium-99

transmutation products. // Ibid. P. 113.

4/73 61

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1

THEROLEOFACHOICEOF THE TARGET FORMOFTHETARGETFORM

FOR99TcTRANSMUTATION

..Kozar, V.F.Peretrukhin, K.E.German FrumkinInstituteofPhysical

ChemistryandElectrochemistryofRAS,

31/4Leninskyprosp.,Moscow,119071,Russia,

[email protected] [email protected]

ITSWELLKNOWN(SINCE2000) 99Tctransmutationcanbethesourceof

artificialstableruthenium100102Ru,thesecondofthemjst interestingelementsj g

ofthePeriodictable.SuchrutheniumhasbeensynthesizedasaresultofaneutronirradiationofTc

targetsupto20 70%burnup(for3differentgroupsofTctargets)

inexperimentsatSMhighfluxreactorin1999 2003.

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2

Russian Tc - Transmutation program (1992-2003)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

99Tc(n,)100Tc()100Ru75,00%

%

P tt (NL)

Dimitrovgrad (Russia)

IPC RAS - NIIAR 65%

2

25,00%

50,00%

netiu

m-9

9 Bu

rnup

, %

Hanford (USA) 1989

Wootan WJordheim DP

Matsumoto WY

Petten (NL) 1994-1998

Konings RJMFranken WMP

Conrad RP et al.

1999 - 2000Kozar AA

Peretroukhine VFTarasov VA et al.

18%

34%

0,00%1 2 3 4 5

Irradiation time, days

Tech

n

6%

10.5 days 193 days 579 days 72 days 260 days

0,67 % = Pessimistic

Tc transmutationexperiment(IPCERAS NIIAR,19992008)InIPCRASasetofmetaldisctargets(10x10x0.3mm)preparedandassembledintwobatcheswithtotalweightupto5g.Transmutationexperimentwascarriedoutathighflux

SM3reactor(NIIAR,Dimitrovgrad )

2nd2nd batchbatch: F: F > 2> 2 10101155 cmcm--22ss--11 1

2

2nd2nd batchbatch: F: Ftt > 2> 2 10101155 cmcm 22ss 111st batch1st batch: F: Ftt=1.3=1.3 10101155 cmcm--22ss--119999TcTc burnupsburnups havemade:havemade:

34 34 6 % and 65 6 % and 65 11 %11 %forthe1stand2ndtargetsbatchesforthe1stand2ndtargetsbatches

TheThe highhigh 9999TcTc burnburnupupss werewerereachedreached andand aboutabout 22 55 gg ofof newnew

1

-3 -1

9 12

465666768696

6575 45558595

425262728292

4151617181

44548494

43538393

43

1912

-2

2

6

3

7

816

-4

-5

17

-6

-10

-9

13

-8

1

19

4

10-7

5

20

11 2118

reachedreached andand aboutabout 22..55 gg ofof newnewmattermatter transmutationtransmutation rutheniumrutheniumwerewere accumulatedaccumulated asas aa resultresult ofofexperimentsexperiments onon SMSM33 reactorreactor

TheseThese valuesvalues areare significantlysignificantlyhigherhigher ofof burnupsburnups 66 andand 1616 %%achievedachieved onon HFRHFR inin PettenPetten earlierearlier

1 ; 2 ;3 ; 4

7 -2 81

91-

4 3

2

6

1415

7

.5.

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3

IRRADIATIONOF99TcMETALTARGETSINNUCLEARHIGHFLUXREACTORS

Petten transmutationexperiment99 l l d d h h h

3

Dimitrovgrad transmutationexperimentonSMhigh

99Tctargets:metalcylinders4.8mmandwithheightof25mm99Tc burnupinPetten reactorare6% (T1) and 1618% (T2).

fluxreactor99Tc targets:metaldisks 6.0 0.3mmandwiththickness of 0.3 0.02mmTotal targetsmassis 10g

99Tc BURNUPANDHALFCONVERSIONPERIOD

of group

Burn-up, % Irradiation time,

eff. days

Half-conversion period ,

eff. days measured calculated 1 192 202 72 7 240

Measured and calculated 99Tc burnup and halfconversion periods in SM reactor.

burnT 2/1

4

1 192 202 72.7 2402 453 505 262.7 305 3 705 707 424.8 245

99Tc burnupinPetten reactorare6% (T1)and 16 18% (T2).99Tchalfconversionperiodb 2160eff.days.burnT 2/1

Fig. 2. Calculated dependence of 99Tc burnup onirradiation time () and its experimental values() for 3 groups of targets.

64

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4

ARTIFICIALRuACTIVITYDECAY

Activityof 106Ru+106Rh inartificialRu ,371.6days ,29.8 sec

ActinidecontentinTc:5108gAnpergofTc(bettervaluesareexpensive!)Actinidefission product 106Ru(T1/2=371.6days)cantbeseparatedfromartificialRubychemical methods.

5

106Ru(pure radiator, isabsent) 106Rh 106Pd (stable)106Rhhas 2 main lineswithenergies511.8keV and 621.8keVIn 2006106RhactivityinRufrom20%burnuptargetslater 2100days{5.7T1/2 (106Ru)}after irradiationstop:

15 2 Bk/g of Ru total activity of pair 106Ru + 106Rh 30 Bk/g of RuLater10yearsafterirradiationstop: =3.2 0.4Bk/gof Ru

11/23/2014

5

Transformationofdisks6mm 0.3mmincylindricaltargets6mm 6mm

7

Fig.4.RelativepositionofTc(TcRu)grainsinheterogeneoustarget.

Possibletargetchemicalsubstances8

TcMetal Tc

TcCarbide Tc6C TcDioxide TcO2 Tc Disulfide TcS TcDisulfide TcS2

anditsmixtureswithinertmatter

66

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6

Targetsubstances1. Metal

InstrumentationSample type : Starting

9

Instrumentation Furnaces 6%H2|Arindusturialballoonmixture

Sampletype: OrdinaryPowdermetal

Fusedmetal

Startingmaterial:

TcO2 NH4TcO4 R NTcO

Ingots Rollingmill etcetera

Singlecrystal

Foil

R4NTcO4

1. BulkTcmetal

SetupusedforfusionandcastingofTcmetal

11

SinglecrystalTcmetal

67

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7

1. Tcmetal foil,Xraystudy12

d:20micrometers SystematicabsenceofXrayreflex =PreferentialorientationofcrystalliteswithCaxeperpendiculartothefoilsurface

1. Tcmetal foil,assembling13

Spacer gridbushwith99Tctargets(1)andaluminium core (2)ofcapsule forloadinginreactor.

68

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8

1. Tcmetal foilchemicalconsequences

DissolutioninHNO3 dramaticallysloweddowni f 20% T R i

12

startingfrom20%TctoRuconversion

Possibletoincreasethedissolutionratebyaggressiveagentsaddition(Ag2+,IO4)butcorrosionproblemsarises

PossiblythebestreprocessingprocedureburninginO2 notapprovedbyindustrytodate

Targetsubstances2. TcCarbide

OrthorhombicTcmetalisformedatlowCcontent

50

75

100

Grey bars : ref. hcp Tc metalCurves : exp. spectra

%

30 40 50 60 70 80 900

25

50

75

100

30 40 50 60 70 80 900

25B

I, %

2Theta, deg

A

I, %

69

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9

Targetsubstances2. TcCarbide

Tc6C nonstoechiometry6 y Tc6C+nCexcesscarbonforno slowingdown

Tc6C formedby: Tc+Creaction Tc+C6H6 R4NTcO4 thermaldecompositioninAr

Targetsubstances Tccarbide2. Tc6C+nCexcesscarbon

EXAFSstudyofTc6C+nC[1]

waveletpresentation

[1]K.German,Ya.Zubavichus ISTR2011

70

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10

1. Tccarbidechemicalconsequences

Dissolution of Tc is more active as no RuC is known

12

DissolutionofTcismoreactiveasnoRuC isknownandsoitisnt formedduringtransmutationofTccarbidetoRu TcandRubeingstabilizedinseparatephases

Drawback:PossiblemechanicalinclusionsofTcinRu residue at high burnupsRuresidueathighburnups

MixtureswithCexcesscouldbethebestchoicebecauseresonanceenergyneutronsareparticipatingintransmutationduetoenhancedthermolisation insidethetarget

1. Tcdioxidechemicalconsequences

12

Preparationbychemicalreduction highimpuritycontent

PreparationfromNH4TcO4 similartoTcmetal TargetinstabilityduetoexcessOreleased(Ruisstabilised asmetal))

SomeTc2O7formedathighburnup Thistargetmaterialisnotrecommended

71

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11

PreparationofartificialstableRutheniumbytransmutationofTechnetium

NewRutheniumisalmostz Tctargetmaterial:monoisotopic Ru100,ithasdifferentspectralproperties

Itisavailableonlytoseveralcountriesthatdevelopnuclearindustry

z Tcmetalpowder/Kozar(2008)

z Tc CcompositeTccarbide/German(2005)

z Rotmanov K.etall.Radiochemistry, 50(2008)408:

99Tctransmutationcanbethesourceofartificialstableruthenium100102Ru.

Conclusions

MetalhomogeneousTctargetsarepossible Tccarbidetargetsarefavorabale Artificialrutheniumdemandedexposureduring810yearsforapplicationwithoutrestrictions

Application of heterogeneous targets with nuclear Applicationofheterogeneoustargetswithnuclearinertstufftoreducea106RuradioactivityinartificialRu

ThetargetformeffecttheartificialrutheniumpurityatequalTcnucleardensityinirradiatedvolume.

72

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12

Transformationofdisksincylindersintheconditionsofidenticalirradiatedvolumecouldallowtolower106Ruconcentrationinartificialruthenium.TheminimumfissionfragmentpathlengthinTcmetalmakesabout5microns(averagefissionfragmentpathlengthisabout8microns).ThecorrespondingformofaheterogeneoustargetisatabletconsistingofamixofsphericalTcmetalparticleindiameterof5micronsandanuclearinertstuffwithTcaveragedensitywhichin20times is less than Tc metal In this case all fission fragments includingtimesisless,thanTcmetal.Inthiscaseallfissionfragments,including106Ru,escapetheTc(TcRu)grainstostuff.TheaveragedistancebetweenTcsphericalgrainsisabout23microns,betweentheirsurfacesisabout18micronsatregulardistributionofTcparticlesinatarget.

Fissionfragmentpathlengthinthemostapplicablenuclearinertmaterials(suchasZrO2,Y2O3,MgAl2O4,MgO,Y3Al5O12,SiC,Al2O3,ZrO2Y2O3,ZrO2CaOandmanyothers)makes12 15microns,hencehitprobabilityof106RufissionfragmentsinthenextTcgrainisnegligiblysmall. Artificial ruthenium from such target would be almost free fromsmall.Artificialrutheniumfromsuchtargetwouldbealmostfreefrom106Runuclei.AdditionalpurificationofcommercialTcfromactinideimpuritieswouldbenotnecessaryatachoiceofsuchtargetforminsteadofmetaldisks.Inthiscaseartificialrutheniumcouldbeappliedinnonnuclearfieldthrough3 3.5yearsafteranirradiation,necessarytodecayoftransmutationproduct103Ru(T1/2 =39.3days).

References 1.V.Peretroukhine,V.Radchenko,A.Kozaretal.Technetium

transmutationandproductionofartificalstableruthenium.//ComptesRendus. Ser.Chimie. 2004. Tome7. Fascicule12. P.12151218.

2 Kozar V F Peretroukhin K V 2...Kozar ,V.F.Peretroukhin,K.V, ,, .Rotmanov,V.A.Tarasov.Theelaborationoftechnologybasesfortheartificialstablerutheniumpreparationfromtechnetium99transmutationproducts.//7th InternationalSymposiumonTechnetiumandRhenium ScienceandUtilization.Moscow,Russia,July4 8,2011. BookofProceedings. P.113. PublishingHouseGRANITSA,Moscow,2011. 460p.

3. .. Kozar, V.F. Peretroukhin, K.V , 3...Kozar ,V.F.Peretroukhin,K.V, ,, .Rotmanov,V.A.Tarasov.Theelaborationoftechnologybasesfortheartificialstablerutheniumpreparationfromtechnetium99transmutationproducts.//Ibid. P.113.

73

Complexation and extraction of Pu(IV) in the presence of pertechnetic acid

L. Abiad, L. Venault and Ph. Moisy

CEA Marcoule, DEN/DRCP, BP 17171, 30207 Bagnols-sur-Cze Cedex, France

The hypothesis that pertechnetate ion can form extractible complexes with actinides at the +IV or

+VI oxidation state in nitric acid is quite commonly pointed out. Therefore, in nitric acid, the

pertechnetate anion could act as a co-ligand with the nitrate ion and then could replace it in the

extracted species. It can be noticed that in the absence of nitric acid a complex of U(VI) with the

pertechnetate anion 2(4)2 . 2 has already been identified in an organic phase made of

TBP. However, even in the presence of nitric acid, a mixed complex can be formed by replacing a

nitrate anion by a pertechnetate one:

2(3)2 . 2 + 4 2 3 4 . 2 + 3

To check the ability of pertechnetate ions to give rise to complexes with actinides, the study of the

complexation of Pu(IV) by TcO4- was carried out by spectrophotometry in perchloric acid media.

Absorption spectra of Pu(IV)-Tc(VII) mixtures, according to the temperature, enable the calculation of

the complexation constant i of the complex present in solution by chemometric treatment. It was

found that for [Tc]/[Pu] ratio up to 1300, two species are present in solution: the aquo ion Pu4+ and a

complex which could either be Pu(TcO4)3+ or Pu(TcO4)4.The complexation constants have been

respectively estimated to 3 ~ 2.3 0.1 and 4 ~ 3.5 0.2 at T = 298 K.

Onthe other hand, some measurements of the distribution of Tc(VII) and Pu(IV) in biphasic system

(HClO4 TBP 30%/cyclohexane) were carried out. Firstly, it has been shown that the extraction of

pertechnetic acid alone involves 2.5 molecules of TBP perpertechnetic acid, indicating that the

extracted species are both 4 . 2and 4 . 3.Secondly, in the presence of Pu(IV), this

latter is highly extracted when the ratio [Tc]/[Pu] is close to 2500 with DPu 10. Therefore, two

extraction equilibria for the extracted neutral complex Pu(TcO4)4 in organic phase are proposed:

84 + 24+ + 3 (4)4 . + (4)4 . 2

84 + 24+ + 3 ((4)4)2. + (4)4. 2

Nevertheless, as the [Tc]/[Pu] ratio becomes lower than 1400, Pu(IV) is then poorly extracted with D-

values not higher than 1. It is in accordance with the spectrophotometric observations and

chemometric calculations assuming that, in these conditions the complex formed is Pu(TcO4)3+. The

thermodynamic characteristics of this complex have thenbeen calculated.

6/73 74

23/11/2014

8thISTR,LaBaule(FRANCE),Spet.29th,Oct.3rd,2014 1

PPuu(IV(IV))COMPLEXATIONCOMPLEXATION ANDANDEXTRACTIONEXTRACTION

INPRESENCEOFINPRESENCEOFPERTECHNETICPERTECHNETIC ACIDACID

L.ABIAD,L.VENAULT,Ph.MOISY

CEAMarcoule

| PAGE 1

NuclearEnergyDivision

RadiochemistryandProcessDepartment

9 Main GoalGoalTo improve knowledge about Tc complexation chemistry with

GOALS & CONTEXT

o p o e o edge about c co p e at o c e st y tactinides

99 IndustrialIndustrial interestinterest:: PUREX process Disturbances in actinide extraction due to Tc Specific Tc scrubbing step

Nuclear Energy DivisionRadioChemistry and Process Department 2

Chemistry of Tc in the process still not well described

75

23/11/2014


Chemical behavior of Tc(VII) with metallic cations (U, Th, Zr, Pu)

LITTERATURE DATA

Many studies only on the distribution of metallic cations between an aqueous and an organic solutions

Sole identified complex in organic phaseQuoted in litterature (but not identified)

Co-extraction of TcO4- with nitrate ion

[ ]TBP2,)TcO(UO 242[Macasek, 1983]

[ ]TBP2),TcO()NO(Th 433[Pruett, 1984]

[ ]TBP2),TcO()NO(Zr 433[Jassim, 1984]


No studies about the complexation Pu(IV) Tc(VII)Can Pu(IV) be complexed by Tc(VII) alone ? ++ + )4(444 )( nnTcOPunTcOPu

Complexation Complexation reactionreaction

EXPERIMENTAL

++ + )4(444 )( nnTcOPunTcOPu[ ][ ][ ]n

nn

nTcOPu

TcOPu+

+=

44

)4(4

.)(

9 Inert acidic medium towards Pu(IV) chemistry : HClO4 Limitation : radiolysis - competiting extraction of HClO4 and HTcO4

9 Preparation of about 50 samples Tc(VII) Pu(IV)


9 R = 0 to 1400 where

9 Temperatures vary from T = 10 C to T = 50 C

[ ][ ]init.

init.

Pu(IV)Tc(VII)R =

8th ISTR,LaBaule(FRANCE),Sept.29th,Oct.3rd,2014

76

23/11/2014


Experimental absorption spectra for 5 mixtures Pu(IV)-Tc(VII)

I = 2 (HClO4 2 M), [Pu]total = 2.10-3M 25C

RESULTS

9 No Pu(VI) at = 830 nm9 No band for HTcO49 Increase and changes in UV bands at < 500 nm as R 9 Pu(III) at = 600 nm due to radiolysis in Pu(IV) sol. subtraction of Pu(III) spectra

Abs

.

0,04

0,06

0,08

0,10

0,12

0,14 HTcO4 2MR = 1308R = 677R = 500R = 346R = 144

[Tc]

830 nm600 nm


Longueur d'onde (nm)

400 500 600 700 800-0,02

0,00

0,02

,


cm/m

ol)

30

40

50

For For everyevery spectrumspectrum, at , at everyevery TT subtraction of Pu(III) spectrumA() = Atot.() Pu()()

RESULTS

0,14

HTcO4 2M 680 nm

475 nm

Longueur d'onde (nm)400 450 500 550 600 650 700 750 800

(L/

c

0

10

20

Extinction coefficient for a 10-3 M Pu(III) solution in HClO4 2 M at 25C

Increase of Abs. / Changes in bands complexation of Pu(IV) ?

Abs

.

0 02

0,04

0,06

0,08

0,10

0,12 R = 1308R = 677R = 500R = 346R = 144R = 0

655 nm

550 nm


Absorption spectra of Pu(IV)-Tc(VII) mixtures corrected fromPu(III) contribution

I = 2 (HClO4 2 M, [Pu]total = 2.10-3M 35C

p ( )

Changes in hydratation sphere ?

aw and [H+] kept constant Complexation of Pu(IV) withTc(VII)

Longueur d'onde (nm)350 400 450 500 550 600 650 700 750 800

0,00

0,02


77

23/11/2014


RESULTS

Qualitative Qualitative studystudy9 Changes in spectra Existence of one or several complexes Pu(TcO4)i(4-i)+9 Effect of T determination of thermodynamic data

Quantitative Quantitative studystudy9 Spectrum = 520 760 nm 9 Small changes in spectrum9 Free Pu(IV) & complexes in the same wavelength range9 No reference spectra for the complexes

Direct treatment of spectra impossible Chimiometric method


Chimiometric method Treatment of a lot of data Few hypothesis about the chemical composition


ProgramRECONS

11stst stepstep:: Principal Component Analysis Number of species

ProgramNBESPECE

CHIMIOMETRIC METHOD

Hypothesis :2species Reconstructionofspectra reconstructed spectra similar to

experimental ones

statistical &empirical tests 2species T

Number of spectra

[Tc]

1st species

Apparitionofa2nd


At T = 40CWavelength (nm)

ln (

i/ i)

species

background

2species


78

23/11/2014


22ndnd stepstep:: Modeling Factors Analysis (MFA) Complexation constants & reference spectra

Comparison

CHIMIOMETRIC METHOD

Estimationof n

ExperimentalabsorbanceExperimental

conditions

Hypothesis aboutchemical species

EstimationofabsorbanceAbsestim

Comparison


Estimationofn EstimationofconcentrationsCestim IfAbsestim =Absexper Estimated concentrations=real Criterion :calculated reference spectra &relativedeviation


22ndnd stepstep:: Modeling Factor Analysis (MFA)

Reference spectra for the two Relative deviation

CHIMIOMETRIC METHOD

+3%

on c

oeff

icie

nt

/mol

/cm

)

4050607080 R maximum upper complex

R = 0 [Pu4+] libre 0.002 M

Reference spectra for the twospecies

Relative deviation

Absexp - Absest


-3%

Wavelength (nm)400 450 500 550 600 650 700 750 800

Extin

ctio

(L/

0102030


79

23/11/2014


Results from MFA calculations[Pu4+]o = 0.002 M, I = 2, et [TcO4-] = 0 to 2 M)

MFA calculations areT 3 4

CHIMIOMETRIC METHOD

( )( )4444

344

4

TcOPuPuTcO4

TcOPuPuTcO3

4

3

+

+

+

++

or

consistent with ML3 & ML410C 2,8 5% 7,3 16%18C 4,8 21% 9,5 21%25C 2,3 4% 3,4 5%35C 3,5 2% 6,2 2%40C 4,5 2% 8,3 4%


50C 7,9 14% 19,1 14%


Pu(IVPu(IV) Distribution Ration in ) Distribution Ration in presencepresence of of Tc(VII)Tc(VII)