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N-Heterocyclic Carbenes as Stabilizing Ligands for High-Valent Technetium Chemistry

English title N-Heterocyclic Carbenes as Stabilizing Ligands for High-Valent Technetium Chemistry
Applicant Braband Henrik
Number 140665
Funding scheme Project funding (Div. I-III)
Research institution Institut für Chemie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Inorganic Chemistry
Start/End 01.05.2012 - 30.04.2015
Approved amount 170'558.00
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Keywords (7)

Radiopharmaceutical Chemistry; Coordination Chemistry; Rhenium; Radiochemistry; N-Heterocyclic Carbenes; Technetium; Organometallic Chemistry

Lay Summary (English)

Lead
Lay summary

Whereas the isotope 99 of the element technetium (99Tc) is a fission product in nuclear power plants, its nuclear isomer 99mTc is the choice for the synthesis of radio probes for nuclear diagnostics. Both are important fields for society and require a fundamental understanding of the chemistry of this element.

High-valent 99(m)Tc chemistry with complexes containing the fac-{99mTcO3}+ core is a rather new field. It gained much interest, since the reactivity of fac-99mTcO3}+ complexes with alkenes ((3+2) cycloaddition) enables a new labeling strategy for radiopharmaceutical applications and is a complement to established labeling procedures. Today, this new strategy is limited to one particular type of stabilizing tripodal ligand, 1,4,7-triazacyclononane (tacn) and its monosubstituted derivatives (tacn-R), due to the sterical pre-orientation and the strong sigma-donating nature of the nitrogen atoms in the tacn ligand. N-Heterocyclic carbenes (NHCs) are an interesting alternative for the established tacn-based ligands. NHCs are versatile strong electron donors (sigma-donor) which are known to stabilize metal centers in low and high oxidation states. In this project the suitability of tripodal NHCs as stabilizing ligands for high-valent 99(m)Tc and Re chemistry will be studied, aiming at the development of a high-valent organometallic technetium chemistry suitable for clinical translation.

These studies will give a better understanding of the organometallic chemistry of technetium in comparison with rhenium and will help to close gaps in knowledge in ‘Fundamental Chemistry’. Due to the fact that the proposed class of compounds is essentially unknown, but has, according to our preliminary results, a multitude of activities and reactivities it will create new perspectives in technetium chemistry. This is essential, keeping in mind that the research with this important element is lagging behind that of its heavier congener rhenium. The synthesized Re-NHC compounds are of interest from a therapeutic point of view. Recently, NHC-complexes of copper-, silver-, gold- and palladium gained of much interest due to their promising antimicrobial and antitumor properties. In this context the evaluation of the bioactivity of the synthesized Re-NHC complexes will have an impact in the field of ‘Metals in Medicine’. Based on the fundamental research of rhenium and technetium with NHC ligands the development of an aqueous 99mTc-NHC chemistry will significantly influence the field of ‘Radiopharmacy and Nuclear Medicine’ and will widen the scope for 99mTc imaging probes in Life Science. Especially the synthesis of fac-{99mTcO3}+-NHC complexes and their application for labeling reactions following (3+2) cycloaddition strategies will paves the way for new opportunities in this upcoming field of 99mTc research. Furthermore, the impact of this project will not be limited to medicinal diagnostics or therapy; the investigation of the possibility of an aqueous organometallic chemistry (carbene chemistry) will be of general interest for the field of ‘Organometallic Chemistry’.

Finally, this project has a strong educational aspect, since the training of (young) students in radionuclide chemistry working techniques is essential to prevent society from the foreseeable lack of scientists with experience in this important field.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
Toward Organometallic 99mTc Imaging Agents: Synthesis of Water-Stable 99Tc–NHC Complexes
Benz Michael Spingler Bernhard Alberto Roger Braband Henrik (2013), Toward Organometallic 99mTc Imaging Agents: Synthesis of Water-Stable 99Tc–NHC Complexes, in J. Am. Chem. Soc., 135(46), 17566-17572.

Collaboration

Group / person Country
Types of collaboration
Prof. Dr. Gilles Gasser / Institute of Inorganic Chemistry University of Zurich Switzerland (Europe)
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Terachem 2014 Poster Synthesis of Water Stable {M(V)O2}+-N-Heterocyclic Carbene Complexes (M = Re, 99Tc) 10.09.2014 Bressanone, Italy Benz Michael;
EuroBIC 12 Talk given at a conference Synthesis of Water Stable {M(V)O2}+-NHC Complexes (M = Re, 99Tc) 24.08.2014 Zürich, Switzerland Benz Michael;
Chemiedozententagung Talk given at a conference Neue metallorganische Komplexe für die radiopharmazeutische Forschung – Wasserstabile NHC-Komplexe des Technetiums 10.03.2014 Paderborn, Germany Braband Henrik;
SCS Fall Meeting 2013 Talk given at a conference A Novel synthetic pathway for the formation of water stable 99Tc-NHC Complexes 06.09.2013 Ecole Polytechnique Fédérale de Lausanne, Switzerland Benz Michael;
RheManTec-II Symposium Talk given at a conference N-Heterocyclic Carbenes - Ligands for Water Stable Organometallic 99(m)Tc-Complexes 23.02.2013 Saas-Grund, Switzerland, Switzerland Braband Henrik; Benz Michael;


Associated projects

Number Title Start Funding scheme
159800 Target Specific Technetium and Rhenium NHC Complexes for Diagnostic and Therapeutic Applications 01.05.2015 Project funding (Div. I-III)
126414 Technetium Chemistry at High Oxidation States: New Perspectives for Nanomaterials and Polyoxometalates in Medicine and Environmental Science 01.10.2009 Ambizione
144964 Upgrade of the UZH NMR Core Facility 01.12.2012 R'EQUIP

Abstract

Whereas the isotope 99 of the element technetium (99Tc) is a fission product in nuclear power plants, its nuclear isomer 99mTc is the choice for the synthesis of radio probes for nuclear diagnostics. Both are important fields for society and require a fundamental understanding of the chemistry of this element. High-valent 99(m)Tc chemistry with complexes containing the fac-{99(m)TcO3}+ core is a rather new field. It gained much interest, since the reactivity of fac-{99(m)TcO3}+ complexes with alkenes ((3+2) cycloaddition) enables a new labeling strategy for radiopharmaceutical applications and is a complement to established labeling procedures. Today, this new strategy is limited to one particular type of stabilizing tripodal ligand, 1,4,7-triazacyclononane (tacn) and its monosubstituted derivatives (tacn-R), due to the sterical pre-orientation and the strong sigma-donating nature of the nitrogen atoms in the tacn ligand. N-Heterocyclic carbenes (NHCs) are an interesting alternative for the established tacn-based ligands. NHCs are versatile strong electron donors (sigma-donor) which are known to stabilize metal centers in low and high oxidation states. In this project the suitability of tripodal NHCs as stabilizing ligands for high-valent 99(m)Tc chemistry will be studied, aiming at the development of a high-valent organometallic technetium chemistry suitable for clinical translation. This project combines the fundamental research of the isotope 99Tc with the more applied field of 99mTc chemistry (radiopharmacy and nuclear medicine) at a molecular level, and will lead to new opportunities for the development of novel and effective imaging probes. Furthermore, this project has a strong educational aspect, since the training of (young) students in radionuclide chemistry working techniques is essential to prevent society from the foreseeable lack of scientists with experience in this important field.
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