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Updated: Aug 29, 2026

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
Unlocking G4 DNA affinity through aromatic side chains: a comparative study of nickel(II), copper(II), and zinc(II)
Luisa D'Anna1, Riccardo Rozza2, Aurane Froux1
1Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università degli Studi di Palermo, Palermo 90128, Italy. riccardo.bonsignore@unipa.it.
Abstract:
Three nickel(II), copper(II), and zinc(II) salnaphen complexes, bearing structurally related charged side chains, were designed to elucidate the role of substituent size and shape in determining their binding strength and affinity for G-quadruplex (G4) DNA structures. Solution DNA-binding studies revealed that aromatic complexes exhibited enhanced G4 stabilization compared to non-aromatic analogues, with copper(II) complexes displaying the strongest affinity and a marked sequence-dependent DNA-binding profile. Molecular dynamics simulations provide a structural rationale for these observations, revealing for the first time that aromatic substituents foster more persistent end-stacking interactions and enhanced stability of the metal complex-G4 system, bridging ligand design, G4 recognition, and biological response. Consistently, the most effective G4 stabilizer also exhibits measurable antiproliferative activity in vitro, associated with pronounced reactive oxygen species (ROS) generation, highlighting how G4 targeting and redox-mediated cytotoxicity-two features only rarely addressed together-can be effectively combined within a single molecular framework.
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