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

Herein, two novel ruthenium(II) complexes coupled by erianinviaa flexible carbon chain, [Ru(phen)2(L1-(CH2)4-erianin)](ClO4)2(L1= 2-(2-(tri-fluoromethyphenyl))-imidazo [4,5f][1–10]phenanthroline (1) and [Ru(phen)2(L2-(CH2)4-eria)](ClO4)2(L2= 2-(4-(tri-fluoromethyphenyl))-imidazo [4,5f][1,10]phenanthroline (2), have been synthesized and investigated as a potential G-quadruplex(G4) DNA stabilizer. Both complexes, especially 2, can bind toc-mycG4 DNA with high affinity by electronic spectra, and the binding constant calculated for 1 and 2 is about 15.1 and 2.05 × 107M−1, 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 ofc-mycG4 DNA decreased treated with 2, indicating that 2 may bind toc-mycG4 DNA through extern groove binding mode. Furthermore, fluorescence resonance energy transfer (FRET) assay indicated that the melting point ofc-mycG4 DNA treated with 1 and 2 increased 15.5 and 16.5 °C, respectively. Finally, molecular docking showed that 1 can bind toc-mycG4 DNA in the extern groove formed by base pairs G7–G9 and G22–A24, and 2 inserts into the small groove ofc-mycG4 DNA formed by base pairs T19–A24. In summary, these ruthenium(II) complexes, especially 2, can be developed as potentialc-mycG4 DNA stabilizers and will be exploited as potential anticancer agents in the future.Keywords:ruthenium(II) complexes;erianin;c-mycG-quadruplex DNA;stabilizer