caa a22 4500 60550766X CHVBK 20210128100633.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00775-015-1270-6 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1270-6 Insights into the structure-activity relationships of chiral 1,2-diaminophenylalkane platinum(II) anticancer derivatives [Elektronische Daten] [Gilles Berger, Luca Fusaro, Michel Luhmer, Joanna Czapla-Masztafiak, Ewelina Lipiec, Jakub Szlachetko, Yves Kayser, Daniel Fernandes, Jacinto Sá, François Dufrasne, Sophie Bombard] The structure-activity relationships of chiral 1,2-diaminophenylalkane platinum(II) anticancer derivatives are studied, including interactions with telomeric- and genomic-like DNA sequences, the pKa of their diaqua species, structural properties obtained from DFT calculations and resonant X-ray emission spectroscopy. The binding modes of the compounds to telomeric sequences were elucidated, showing no major differences with conventional cis-platinum(II) complexes like cisplatin, supporting that the cis-square planar geometry governs the binding of small Pt(II) complexes to G4 structures. Double-stranded DNA platination kinetics and acid-base constants of the diaqua species of the compounds were measured and compared, highlighting a strong steric dependence of the DNA-binding kinetics, but independent to stereoisomerism. Structural features of the compounds are discussed on the basis of dispersion-corrected DFT, showing that the most active series presents conformers for which the platinum atom is well devoid of steric hindrance. If reactivity indices derived from conceptual DFT do not show evidences for different reactivity between the compounds, RXES experiments provide new insight into the availability of platinum orbitals for binding to nucleophiles. SBIC, 2015 Cancer nationallicence Platinum nationallicence G-quadruplex nationallicence Conceptual DFT nationallicence RXES nationallicence Berger Gilles Laboratoire de Chimie Pharmaceutique Organique, Université Libre de Bruxelles, Campus Plaine CP205/5, Bd du Triomphe, 1050, Brussels, Belgium aut Fusaro Luca Laboratoire de Résonance Magnétique Nucléaire Haute Résolution, Université Libre de Bruxelles (ULB), Avenue F.D. Roosevelt 50, CP160/08, 1050, Brussels, Belgium aut Luhmer Michel Laboratoire de Résonance Magnétique Nucléaire Haute Résolution, Université Libre de Bruxelles (ULB), Avenue F.D. Roosevelt 50, CP160/08, 1050, Brussels, Belgium aut Czapla-Masztafiak Joanna The Henryk Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland aut Lipiec Ewelina The Henryk Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland aut Szlachetko Jakub Paul Scherrer Institute (PSI), Villigen, Switzerland aut Kayser Yves Paul Scherrer Institute (PSI), Villigen, Switzerland aut Fernandes Daniel Ångström Laboratory, Department of Chemistry, Uppsala University, Uppsala, Sweden aut Sá Jacinto Ångström Laboratory, Department of Chemistry, Uppsala University, Uppsala, Sweden aut Dufrasne François Laboratoire de Chimie Pharmaceutique Organique, Université Libre de Bruxelles, Campus Plaine CP205/5, Bd du Triomphe, 1050, Brussels, Belgium aut Bombard Sophie Homéostasie Cellulaire et Cancer, UMR-S INSERM 1007, Université Paris Descartes, 45 rue des Saint-Pères, 75006, Paris, France aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 841-853 0949-8257 20:5<841 2015 20 775 https://doi.org/10.1007/s00775-015-1270-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1270-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Berger Gilles Laboratoire de Chimie Pharmaceutique Organique, Université Libre de Bruxelles, Campus Plaine CP205/5, Bd du Triomphe, 1050, Brussels, Belgium aut NATIONALLICENCE 700 1- Fusaro Luca Laboratoire de Résonance Magnétique Nucléaire Haute Résolution, Université Libre de Bruxelles (ULB), Avenue F.D. Roosevelt 50, CP160/08, 1050, Brussels, Belgium aut NATIONALLICENCE 700 1- Luhmer Michel Laboratoire de Résonance Magnétique Nucléaire Haute Résolution, Université Libre de Bruxelles (ULB), Avenue F.D. Roosevelt 50, CP160/08, 1050, Brussels, Belgium aut NATIONALLICENCE 700 1- Czapla-Masztafiak Joanna The Henryk Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland aut NATIONALLICENCE 700 1- Lipiec Ewelina The Henryk Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland aut NATIONALLICENCE 700 1- Szlachetko Jakub Paul Scherrer Institute (PSI), Villigen, Switzerland aut NATIONALLICENCE 700 1- Kayser Yves Paul Scherrer Institute (PSI), Villigen, Switzerland aut NATIONALLICENCE 700 1- Fernandes Daniel Ångström Laboratory, Department of Chemistry, Uppsala University, Uppsala, Sweden aut NATIONALLICENCE 700 1- Sá Jacinto Ångström Laboratory, Department of Chemistry, Uppsala University, Uppsala, Sweden aut NATIONALLICENCE 700 1- Dufrasne François Laboratoire de Chimie Pharmaceutique Organique, Université Libre de Bruxelles, Campus Plaine CP205/5, Bd du Triomphe, 1050, Brussels, Belgium aut NATIONALLICENCE 700 1- Bombard Sophie Homéostasie Cellulaire et Cancer, UMR-S INSERM 1007, Université Paris Descartes, 45 rue des Saint-Pères, 75006, Paris, France aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 841-853 0949-8257 20:5<841 2015 20 775