On the G‐Quadruplex Binding of a New Class of Nickel(II), Copper(II), and Zinc(II) Salphen‐Like Complexes
Gianluca Farine, Claudio Migliore, Alessio Terenzi, Fabrizio Lo Celso, A. Santoro, Giuseppe Brunò, Riccardo Bonsignore, Giampaolo Barone
Abstract
Abstract The involvement of non‐canonical DNA structures, such as G‐quadruplex (G4) DNA, in cancer development and progression has set the pace towards the renaissance of DNA‐binding metal complexes. In this work, we report the DNA‐binding of three Ni(II), Cu(II), Zn(II) complexes of a salphen‐like N 4 ‐donor ligand, bearing two imidazole groups condensed with a phenylenediamine moiety. Both duplex and G4 DNAs derived from human telomeres (hTelo), and a sequence mimicking the promoter of the oncogene myc ( c‐myc ) were studied. UV‐Vis and circular dichroism spectroscopic binding studies pointed out that, while all the three complexes bind the selected oligonucleotides, the Cu(II) derivative is the strongest and G4‐selective compound of the series. Lastly, FRET DNA melting assay results on the Cu(II) complex/hTelo G4 system were interpreted by a loop‐binding mechanism of interaction, as corroborated by molecular dynamics (MD) simulations.