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Systematic Approach to Rhenium (II) Building Blocks via Ligand-Mediated Decarbonylation: Prospective and Applications in Medicinal Inorganic Chemistry and for Single-Molecule Magnets

Applicant Zobi Fabio
Number 121989
Funding scheme Ambizione
Research institution Institut für Chemie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Inorganic Chemistry
Start/End 01.01.2009 - 31.12.2011
Approved amount 366'657.00
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All Disciplines (2)

Discipline
Inorganic Chemistry
Physical Chemistry

Keywords (4)

Cancer; Single-Molecule Magnets; Chemotherapy; Quantum-Based Computing

Lay Summary (English)

Lead
Lay summary
In our modern society two of the most pressing needs are: in medicine, the development of new therapeutic agents for the treatment of malignant neoplasms (cancer) and: in technology, the search of more efficient ways to store and process digital information.

With the term "cancer" is indicated a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Cancer may affect people at all ages, even fetuses, but the risk for most varieties increases with age. Cancer causes about 13 % of all deaths in western society and according to the American Cancer Society, 7.6 million people died from cancer in the world during 2007.

For more efficient ways to store and process digital information there are a couple of possibilities: One is to squeeze more data onto storage devices by making currently used magnetic nanoparticles even smaller. Another is to develop fundamentally different ways to process information, such as quantum-based computing. That's where single-molecule magnets (SMMs) may fit in. Conventional magnets rely on the collective behavior of the unpaired electrons of hundreds of thousands or millions of individual metal centers in a particle or bulk material. SMMs, on the other hand, are metal-based molecules that individually exhibit the classical properties of a magnet below a critical temperature called the blocking temperature, which is currrently limited to about 4 K. Because of their small size, SMMs also have been shown to exhibit quantum tunneling of magnetization and quantum phase interference, key properties needed for materials to function as quantum bits.

For both of these needs, the use of chemistry to develop new drugs and materials is crucial. Interestingly, the natural occurring metal Rhenium (Re) shows chemical and physical properties which make the element useful for applications both in medicine (as a chemotherapeutic agent) and in technology (for the development of SMMs).

This research program intends to synthesize, investigate, develop and apply new Re-based paramagnetic molecules for application in the two fields described above.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
17 e− rhenium dicarbonyl CO-releasing molecules on a cobalamin scaffold for biological application
Zobi Fabio Blacque Olivier Jacobs Robert A. Schaub Marcus C. Bogdanova Anna Yu. (2012), 17 e− rhenium dicarbonyl CO-releasing molecules on a cobalamin scaffold for biological application, in Dalton Transactions, 41, 370-378.
Post-Protein-Binding Reactivity and Modifications of the fac-[Re(CO)3]+ Core
Zobi Fabio Splingler Bernhard (2012), Post-Protein-Binding Reactivity and Modifications of the fac-[Re(CO)3]+ Core, in Inorganic Chemistry, Article ASAP (available online), ASAP-ASAP.
Reactivity of 17e- Complex [ReIIBr4(CO)2]2- with Bridging Aromatic Ligands. Characterization and CO-Releasing Properties
Zobi Fabio Blacque Olivier (2011), Reactivity of 17e- Complex [ReIIBr4(CO)2]2- with Bridging Aromatic Ligands. Characterization and CO-Releasing Properties, in Dalton Transactions, 40, 4994-5001.
A Different ‘Spin’ on Rhenium Chemistry. Synthetic Approaches and Perspectives of 17-Electron Rhenium Complexes
Zobi Fabio (2010), A Different ‘Spin’ on Rhenium Chemistry. Synthetic Approaches and Perspectives of 17-Electron Rhenium Complexes, in Chimia, 64, 259-265.
CO Releasing Properties and Cytoprotective Effect of cis-trans-[ReII(CO)2Br2L2]n Complexes
Zobi Fabio Degonda Alois Schaub Marcus C. Bogdanova Anna Yu. (2010), CO Releasing Properties and Cytoprotective Effect of cis-trans-[ReII(CO)2Br2L2]n Complexes, in Inorganic Chemistry, 49, 7313-7322.
CO Releasing Properties of cis-trans-[ReII(CO)2Br2L2]n Complexes
Zobi Fabio Degonda Alois (2010), CO Releasing Properties of cis-trans-[ReII(CO)2Br2L2]n Complexes, in Nuclear Medicine and Biology, 37, 712-712.
Ligand Electronic Parameters as a Measure of the Polarization of C≡O Bond in [M(CO)xLy]n Complexes and of the Relative Stabilization of [M(CO)xLy]n/n+1 Species
Zobi Fabio (2010), Ligand Electronic Parameters as a Measure of the Polarization of C≡O Bond in [M(CO)xLy]n Complexes and of the Relative Stabilization of [M(CO)xLy]n/n+1 Species, in Inorganic Chemistry, 49, 10370-10377.
Redox Induced Binding of [(tacn)ReIIBr(CO)2]+ to Guanine, Oligonucleotides and Peptides
Zobi Fabio Alberto Roger (2010), Redox Induced Binding of [(tacn)ReIIBr(CO)2]+ to Guanine, Oligonucleotides and Peptides, in Chemistry a European Journal, 16, 2710-2713.
Formation and Reactivity of [(tacn)-N-CO-ReIIIBr(CO)2]+ in Water: a Theoretical and Experimental Study
Zobi Fabio Spingler Bernhard Alberto Roger (2009), Formation and Reactivity of [(tacn)-N-CO-ReIIIBr(CO)2]+ in Water: a Theoretical and Experimental Study, in Inorganic Chemistry, 48, 4963-4970.
Parametrization of the Contribution of Mono- and Bidentate Ligands on the Symmetric C=O Stretching Frequency of fac-[Re(CO)3]+ Complexes
Zobi Fabio (2009), Parametrization of the Contribution of Mono- and Bidentate Ligands on the Symmetric C=O Stretching Frequency of fac-[Re(CO)3]+ Complexes, in Inorganic Chemistry, 48, 10845-10855.
Synthesis and Reactivity of the 17 e- Complex [ReIIBr4(CO)2]2-: A Convenient Entry into Rhenium(II) Chemistry
Zobi Fabio Kromer Lukas Spingler Bernhard Alberto Roger (2009), Synthesis and Reactivity of the 17 e- Complex [ReIIBr4(CO)2]2-: A Convenient Entry into Rhenium(II) Chemistry, in Inorganic Chemistry, 48, 8965-8970.
Post-Protein-Binding Metal-Mediated Coupling of an Acridine Orange-Based Fluorophore
Santoro Giuseppe Blacque Olivier Zobi Fabio, Post-Protein-Binding Metal-Mediated Coupling of an Acridine Orange-Based Fluorophore, in Metallomics.

Collaboration

Group / person Country
Types of collaboration
Dr. Luca Quaroni, Infrared Beamline, Swiss Light Source, Paul Scherrer Institut Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Prof. Dr. Marcus C. Schaub, Institute of Pharmacology, University of Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
MD Prof. Claude Piantadosi, Duke University Medical Hospital United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Dr. Anna Yu. Bogdanova, Institute of Veterinary Physiology, University of Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
11th International Symposium on Applied Bioinorganic Chemistry (ISABC11) Individual talk Discussion on the Therapeutic Potentials of Carbon Monoxide Releasing Molecules 02.12.2011 Barcelona, Spain, Spain Zobi Fabio;
Swiss Chemical Society fall meeting 2011 Talk given at a conference 17 e– Rhenium CO-Releasing Molecules on a Cobalamin Scaffold 09.09.2011 EPFL, Lausanne, Switzerland Zobi Fabio;
Exploiting the therapeutic effects of carbon monoxide Talk given at a conference 17 e- rhenium dicarbonyl CO-releasing molecules on a cobalamin scaffold for biological application 08.05.2011 Chicheley, UK , Great Britain and Northern Ireland Zobi Fabio;
Swiss Chemical Society fall meeting 2010 Talk given at a conference CO Releasing Properties of cis-trans-[ReII(CO)2Br2L2]n Complexes: A Feature Modulated by Ligand Variation. 16.09.2010 ETH Zurich, Switzerland Zobi Fabio;
5th International Symposium on Bioorganometallic Chemistry (ISBOMC’10) Talk given at a conference CO Releasing Properties of cis-trans-[ReII(CO)2Br2L2]n Complexes: A Feature Modulated by Ligand Variation for a True Chance at Medicinal Applications 05.07.2010 Bochum, Germany, Germany Zobi Fabio;
10th International Symposium on Applied Bioinorganic Chemistry (ISABC10) Talk given at a conference Ligand-Mediated Decarbonylation (LMD ) as a General Synthetic Route to Rhenium(II) Dicarbonyl Complexes Acting as Bio-Inducible Redox Switches 25.09.2009 Debrecen, Hungary, Hungary Zobi Fabio;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Towards Pharmaceutically Acceptable CO-RMs Talk 28.01.2011 Instituto De Tecnologia Quimica E Biologica (ITBQ), Oeiras, Portugal, Portugal Zobi Fabio;


Patents

Title Date Number Inventor Owner
CARBON MONOXIDE RELEASING RHENIUM COMPOUNDS FOR MEDICAL USE 08.03.2010 EP 2545064 A1

Associated projects

Number Title Start Funding scheme
139424 Biocompatible 17 e- Rhenium Dicarbonyl CO-Releasing Molecules on Natural Heme and Cobalamin Scaffolds 01.01.2012 Ambizione

Abstract

Rhenium (II) chemistry is rare. There is no systematic synthetic strategy to Re(II) precursors. Rhenium (II) compounds, however, are particularly attractive from a medicinal inorganic chemistry point of view (specially as Tc congeners) and (as recently demonstrated) as precursors for single-molecule magnetic clusters. Besides our compounds to be described later in this proposal, our research group has recently introduced substitution labile Re(II) compounds of the form [ReBr3(NCCH3)(CO)2]-. These compounds enable a systematic study of complexes comprising the cis-[ReII(CO)2]2+ core with various ligands for medicinal and supramolecular studies. Furthermore and of high relevance for this proposal, we recently discovered a synthetic method (henceforth called “ligand-mediated decarbonylation” LMD) which allowed the systematic synthesis of rare Re(II)-based complexes starting from common and easily accessible fac-ReI(CO)3 species in high yields.On this base, the objectives of this proposal can be summarized as follows:1.Explore Re(II) chemistry starting from synthons comprising the “fac-[(N3)Re]2+“ or the cis-[ReII(CO)2]2+ core.2.Generalize the LMD reaction to other amine-based ligands3.Investigate the action of specially designed Re(II) complexes with biologically relevant molecules such as DNA 4.Introduce bridging ligands such as cyanide into the building blocks received under 1 for building up supramolecular structures for single molecular magnetsWe argue that systematic synthetic methods to Re(II) complexes represent an important leap forward in the field of rhenium chemistry, opening new horizons in basic chemistry, technology, application and scholarship. The proposal describes an undisclosed synthetic method to unique Re(II) complexes and the directions we intend to pursue for applications of these species.
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