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| Ursula Roethlisberger, Swiss Federal Institute of Technology, Lausanne |
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Ursula Röthlisberger was born in Solothurn (Switzerland). In 1988 she obtained her diploma in Physical Chemistry in the group of Prof. Ernst Schumacher at the University of Berne (Switzerland). Her Ph.D. thesis was done in collaboration with Dr. Wanda Andreoni at the IBM Zurich Research Laboratory in Rüschlikon. After finishing her Ph.D in 1991 she spent some time as a postdoctoral research assistant at the IBM Research Lab. From 1992-1995 she was a postdoctoral research assistant in the group of Prof. Michael L. Klein at the University of Pennsylvania in Philadelphia (USA). In 1994 she was awarded an advanced researcher fellowship (Profile 2) from the Swiss National Science Foundation. Before starting her Profile 2-fellowship she spent another year as postdoctoral research assistant in the group of Prof. Michele Parrinello at the Max-Planck-Institute for Solid State Physics in Stuttgart, Germany. In 1996 she moved as Profile 2-fellow to the ETH in Zurich, hosted by the group of Prof. Wilfred F. van Gunsteren. In 1997 she became Assistant Professor of Computer-Aided Inorganic Chemistry at the ETH Zurich. She is currently a Professor at the Laboratory of Computational Chemistry and Biochemistry at the Swiss Federal Institute of Technology EPF Lausanne, Switzerland.
Her research interests are concentrated on ab initio MD methods based on density functional theory (Car-Parrinello simulations) and their application, adaption and extension to systems of chemical and/or biological interest; this includes the following research topics:
(i) Development of Hybrid QM/MM Methods for Combined Quantum/Classical Car-Parrinello Simulations.
(ii) Development of Long-Time Scale Techniques for ab initio MD Simulations.
(iii) In situ Simulations of Chemical Reactions in Gas Phase and in Solution.
(iv) Ab initio Simulations of Biological Systems.
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Organoruthenium Compounds as Potential Anticancer Drugs
Christian Gossens, Ivano Tavernelli, and Ursula Rothlisberger, Laboratory of Computational Chemistry and Biochemistry, Federal Institute of Technology, 1015 Lausanne, Switzerland
Organometallic ruthenium(II) arene complexes are currently attracting increasing interest as anti-cancer compounds with the potential to overcome drawbacks of traditional drugs like cisplatin with respect to resistance, selectivity and toxicity. Rational design of new potential pharmaceutical compounds requires a detailed understanding of structure-property relationships at an atomistic level.
We performed in vacuo density functional theory (DFT) calculations, classical MD and mixed QM/MM Car-Parrinello MD explicit solvent simulations to rationalize the binding mode of two series of anti-cancer ruthenium(II) arene complexes to double-stranded (ds)DNA. Binding energies between the metal centres and the surrounding ligands as well as proton affinities were calculated using DFT. Our results support a pH dependent mechanism for the activity of the RAPTA [Ru(eta6-arene)X2(pta)] (pta=1,3,5-triaza-7-phospha-tricyclo [3.3.1.1] decane) compounds. Adducts of the bifunctional RAPTA and the monofunctional [Ru(eta6-p-cymene)Xen]+ series of compounds with the DNA sequence d(CCTCTG*G*TCTCC)/d(GGAGACCAGAGG), where G* are guanosine bases that bind to the ruthenium compounds through their N7 atom have been investigated. The resulting binding sites were characterized in QM/MM molecular dynamics simulations showing that DNA can easily adapt to accommodate the ruthenium compounds.
References
[1] A. Dorcier, P.J. Dyson, C. Gossens, U. Rothlisberger, and R. Scopelliti, Binding of organometallic ruthenium(II) and osmium(II) complexes to an oligonucleotide: a combined mass spectrometric and theoretical study, Organometallics 24, 2114-2123 (2005)
[2] C. Gossens, I. Tavernelli, and U. Rothlisberger, Rational Design of Organoruthenium Anticancer Compound, CHIMIA 59, 81-84(2005)
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Organoruthenium Complex
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