Ruthenium(II) Complexes Coupled by Erianin via a Flexible Carbon Chain as a Potential Stabilizer of G-Quadruplex DNA.

Herein, two novel ruthenium(II) complexes coupled by erianin a flexible carbon chain, Ru(phen)(L-(CH)-erianin) (L = 2-(2-(tri-fluoromethyphenyl))-imidazo [4,5][1-10]phenanthroline (1) and Ru(phen)(L-(CH)-eria) (L = 2-(4-(tri-fluoromethyphenyl))-imidazo [4,5][1,10]phenanthroline (2), have been synthesized and investigated as a potential G-quadruplex(G4) DNA stabilizer. Both complexes, especially 2, can bind to G4 DNA with high affinity by electronic spectra, and the binding constant calculated for 1 and 2 is about 15.1 and 2.05 × 10 M, respectively. This was further confirmed by the increase in fluorescence intensity for both complexes. Moreover, the positive band at 265 nm in the CD spectra of G4 DNA decreased treated with 2, indicating that 2 may bind to G4 DNA through extern groove binding mode. Furthermore, fluorescence resonance energy transfer (FRET) assay indicated that the melting point of G4 DNA treated with 1 and 2 increased 15.5 and 16.5 °C, respectively. Finally, molecular docking showed that 1 can bind to G4 DNA in the extern groove formed by base pairs G7-G9 and G22-A24, and 2 inserts into the small groove of G4 DNA formed by base pairs T19-A24. In summary, these ruthenium(II) complexes, especially 2, can be developed as potential G4 DNA stabilizers and will be exploited as potential anticancer agents in the future.