“Dynamical Docking” of Cyclic Dinuclear Au(I) Bis-N-heterocyclic Complexes Facilitates Their Binding to G-Quadruplexes
Clemens Kaußler, Darren Wragg, Claudia Schmidt, Guillermo Moreno‐Alcántar, Christian Jandl, Johannes Stephan, Roland A. Fischer, Stefano Leoni, Angela Casini, Riccardo Bonsignore
Abstract
have been studied by metadynamics. The atomistic simulations evidenced that the Au(I) compound interacts noncovalently with the top G4 tetrad. The theoretical results on the Au(I) complex/DNA Gibbs free energy of binding were experimentally validated by FRET DNA melting assays. The compounds have also been tested for their antiproliferative properties in human cancer cells in vitro, showing generally moderate activity. This study provides further insights into the biological activity of Au(I) organometallics acting via noncovalent interactions and underlines their promise for tunable targeted applications by appropriate chemical modifications.