G-quadruplex vs. duplex-DNA binding of nickel(II) and zinc(II) Schiff base complexes

Novel nickel(II) (1) and zinc(II) (2) complexes of a Salen-like ligand, carrying a pyrimidine ring on the N,N′ bridge, were synthesized and characterized. Their interaction with duplex and G-quadruplex DNA was investigated in aqueous solution through UV–visible absorption, circular dichroism and viscometry measurements. The results obtained point out that, while the zinc(II) complex does not interact with both duplex and G-quadruplex DNA, the nickel(II) complex 1 binds preferentially to G-quadruplex respect to duplex-DNA, with values of the DNA-binding constants, Kb, 2.6×105M−1 and 3.5×104M−1, respectively. Molecular dynamics simulations provided an atomic level model of the top-stacking binding occurring between 1 and hTelo (a 22-mer sequence oligonucleotide) in G-quadruplex conformation. The right choice of the metal ion deeply influences the DNA-binding ability of Schiff base complexes: while the zinc(II) complex does not bind to DNA, the nickel(II) complex intercalates duplex-DNA and selectively binds G-quadruplex, by top-stacking. [Display omitted] •NiII (1) and ZnII (2) Schiff base complexes were synthesized and characterized.•1 binds to both G-quadruplex and duplex-DNA, by top-stacking and intercalation.•2 does not possess DNA-binding properties.•1 has G-quadruplex binding 10 fold stronger than duplex-DNA binding.•The binding of 1 with G-quadruplex was mimicked by molecular dynamics simulations.