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Bridged Dinuclear Arene Ruthenium Complexes: Cellular Targets and Mechanistic Profiles Investigated by NMR

English title Bridged Dinuclear Arene Ruthenium Complexes: Cellular Targets and Mechanistic Profiles Investigated by NMR
Applicant Furrer Julien
Number 144420
Funding scheme Project funding (Div. I-III)
Research institution Departement für Chemie und Biochemie Universität Bern
Institution of higher education University of Berne - BE
Main discipline Inorganic Chemistry
Start/End 01.01.2013 - 31.12.2014
Approved amount 148'204.00
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All Disciplines (2)

Discipline
Inorganic Chemistry
Physical Chemistry

Keywords (5)

Structural studies; cytotoxicity; mechanisms of action; Ruthenium complexes; NMR

Lay Summary (English)

Lead
Lay summary

The present research project focuses on the investigation of the cellular targets and mechanistic profiles of water-soluble arene ruthenium complexes using NMR Spectroscopy as a main tool. Another part will be devoted to the synthesis, characterization and biological evaluation of new ruthenium complexes containing modified arene ligands and of new ruthenium complexes containing selenium atoms. Ruthenium complexes and especially water-soluble arene ruthenium complexes, a domain pioneered in Switzerland, has undoubtedly opened new perspectives as potential anticancer drugs. In these systems, however, the mode of action, uptake and the biological processes are not yet fully understood. As such, our aims in this project is to define cellular targets of the compounds and elucidate some of their mechanistic profiles by various analytical techniques, but especially by NMR Spectroscopy.

 

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
Cytotoxic peptide conjugates of dinuclear arene ruthenium trithiolato complexes
Giannini Federico, Bartoloni Marco, Paul Lydia EH, Süss-Fink Georg, Reymond Jean-Louis, Furrer Julien (2015), Cytotoxic peptide conjugates of dinuclear arene ruthenium trithiolato complexes, in MedChemComm, 6(2), 347-350.
Tuning the in vitro cell cytotoxicity of dinuclear arene ruthenium trithiolato complexes: Influence of the arene ligand
Giannini Federico, Geiser Lennart, Paul Lydia EH, Roder Thomas, Therrien Bruno, Süss-Fink Georg, Furrer Julien (2015), Tuning the in vitro cell cytotoxicity of dinuclear arene ruthenium trithiolato complexes: Influence of the arene ligand, in Journal of Organometallic Chemistry, 783, 40-45.
Monothiolato-Bridged Dinuclear Arene Ruthenium Complexes: The Missing Link in the Reaction of Arene Ruthenium Dichloride Dimers with Thiols
Stibal David, Therrien Bruno, Giannini Federico, Paul Lydia E. H., Furrer Julien, Suess-Fink Georg (2014), Monothiolato-Bridged Dinuclear Arene Ruthenium Complexes: The Missing Link in the Reaction of Arene Ruthenium Dichloride Dimers with Thiols, in EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, (34), 5925-5931.
Trithiolato-Bridged Dinuclear p-Cymene Ruthenium Complexes: A Study of their High in vitro Anticancer Activity
Giannini F., Furrer J., Suess-Fink G. (2014), Trithiolato-Bridged Dinuclear p-Cymene Ruthenium Complexes: A Study of their High in vitro Anticancer Activity, in JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, 19, 439-439.
Tuning the in vitro cell cytotoxicity of dinuclear arene ruthenium trithiolato complexes: influence of the arene ligand
Giannini Federico, Geiser Lennart, Paul Lydia E. H., Roder Thomas, Suess-Fink Georg, Furrer Julien (2014), Tuning the in vitro cell cytotoxicity of dinuclear arene ruthenium trithiolato complexes: influence of the arene ligand, in JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, 19, 788-788.
Highly cytotoxic diruthenium trithiolato complexes of the type [(eta(6)-p-MeC6H4Pri)(2)Ru-2(mu(2)-SR)(3)](+): synthesis, characterization, molecular structure and in vitro anticancer activity
Giannini Federico, Paul Lydia E. H., Furrer Julien, Therrien Bruno, Suess-Fink Georg (2013), Highly cytotoxic diruthenium trithiolato complexes of the type [(eta(6)-p-MeC6H4Pri)(2)Ru-2(mu(2)-SR)(3)](+): synthesis, characterization, molecular structure and in vitro anticancer activity, in NEW JOURNAL OF CHEMISTRY, 37(11), 3503-3511.
Synthesis, characterization and in vitro anticancer activity of highly cytotoxic trithiolato diruthenium complexes of the type [(eta(6)-p-(MeC6H4Pr)-Pr-i)(2)Ru-2(mu(2)-SR1)(2)(mu(2)-SR2)](+) containing different thiolato bridges
Giannini Federico, Furrer Julien, Suess-Fink Georg, Clavel Catherine M., Dyson Paul J. (2013), Synthesis, characterization and in vitro anticancer activity of highly cytotoxic trithiolato diruthenium complexes of the type [(eta(6)-p-(MeC6H4Pr)-Pr-i)(2)Ru-2(mu(2)-SR1)(2)(mu(2)-SR2)](+) containing different thiolato bridges, in JOURNAL OF ORGANOMETALLIC CHEMISTRY, 744, 41-48.
Synthesis, molecular structure, computational study and in vitro anticancer activity of dinuclear thiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes
Gupta Gajendra, Garci Amine, Murray Benjamin S., Dyson Paul J., Fabre Gabin, Trouillas Patrick, Giannini Federico, Furrer Julien, Suess-Fink Georg, Therrien Bruno (2013), Synthesis, molecular structure, computational study and in vitro anticancer activity of dinuclear thiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes, in DALTON TRANSACTIONS, 42(43), 15457-15463.

Collaboration

Group / person Country
Types of collaboration
EPF Lausanne, PJ Dyson Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
SCS Fall Meeting 2014 Talk given at a conference .... 11.09.2014 Zürich, Switzerland Giannini Federico; Furrer Julien;
SCS Fall Meeting 2014 Talk given at a conference ... 11.09.2014 Zürich, Switzerland Giannini Federico; Furrer Julien;
EuroBIC Poster ... 25.08.2014 Zürich, Switzerland Furrer Julien; Giannini Federico;
ISBOMC Talk given at a conference ... 22.07.2014 Vienna, Austria Giannini Federico;
ISABC Talk given at a conference ... 01.12.2013 Guangzhou, China Giannini Federico;
ISABC Talk given at a conference ... 01.12.2013 Guangzhou, China Furrer Julien;
SCS Fall Meeting 2013 Poster Ru complexes 12.09.2013 Lausanne, Switzerland Furrer Julien; Giannini Federico;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions metal complexes as anticancer agents German-speaking Switzerland 2015

Associated projects

Number Title Start Funding scheme
173718 Ruthenium Complexes for the Treatment of Protozoan Diseases of Medical and Veterinary Importance 01.09.2017 Sinergia
139078 1.7 mm Micro-Probehead for small volume NMR Spectroscopic Investigations 01.03.2012 R'EQUIP
131867 NMR investigation of cellular targets and mechanistic profiles of ruthenium-based drugs 01.01.2011 Project funding (Div. I-III)

Abstract

The main part of the present research project focuses on the investigation of the cellular targets and mechanistic profiles of water-soluble arene ruthenium complexes using NMR Spectroscopy as a main tool. Another part will be devoted to the synthesis, characterization and biological evaluation of new ruthenium complexes containing modified arene ligands and of new ruthenium complexes containing selenium atoms. Ruthenium complexes and especially water-soluble arene ruthenium complexes, a domain pioneered in Switzerland, has undoubtedly opened new perspectives as potential anticancer drugs. In these systems, however, the mode of action, uptake and the biological processes are not yet fully understood. As such, our aims in this follow-up project remain to define cellular targets of the compounds and elucidate some of their mechanistic profiles by various analytical techniques, but especially by NMR Spectroscopy. This research proposal is a follow-up of the ongoing project No 200021-131867, which has proven to be successful and promising, and has in addition raised a lot of questions that shall be answered in this project. It is laid out for two years (01.01.2013 - 31.12.2014). Within this project, we propose to work on the topics presented subsequently involving Federico Giannini, who started his Ph.D. (01.01.2011), in close collaboration with the group of Prof. Georg Süss-Fink. Prof. Süss-Fink will continue his support as co-Ph.D. supervisor of Federico Giannini, and most of the complexes that will be studied will be provided by his group. This project will also occasionally involve the group of Prof. Dr. Oliver Mühlemann, and the group of PD Dr. Stefan Schürch, both from the Department of Chemistry and Biochemistry, University Bern, which host respectively the facilities required for cell lines cultures and cytotoxicity assessments, and dedicated mass spectrometers.
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