A hydroxyquinoline-appended ruthenium(II)-polypyridyl complex that induces and stabilizes G-quadruplex DNA

Abstract

A polypyridyl ruthenium(II) complex with hydroxyquinoline-derived ligand has been synthesized and characterized. The ability to act as telomeric quadruplex inducer and stabilizer, and quadruplex-binding properties of the complex have been evaluated by absorption and emission analyses, fluorescent intercalator displacement (FID) titrations, circular dichroism (CD) spectroscopy, polymerase chain reaction (PCR) stop assay, color reaction studies, fluorescence resonance energy transfer (FRET) melting assay, Job plot, and molecular modeling. Observations revealed that the complex could well induce and stabilize the formation of antiparallel G-quadruplex of telomeric DNA in the presence or absence of metal cations, and showed superior G-quadruplex selectivity over duplex DNA with remarkable ΔT_m value of 18.0 °C even at 50-fold excessive supplies of calf thymus (ct) DNA. The complex exhibited high interaction affinity of 2.56 × 10⁶ M⁻¹ with G-quadruplex DNA and evident luminescence enhancements of 3.1 and 4.2 times for quadruplex binding in Na⁺ and K⁺ buffer, respectively. In addition, the 1:1 [quadruplex]/[complex] binding mode ratio was determined. The results suggest that the complex can be developed as potential anticancer reagent through binding and stabilization of G-quadruplex DNA.

Keywords:

• Ruthenium
• G-Quadruplex
• luminescence

Acknowledgements

The authors thank the National Natural Science Foundation (No. 21401038), Natural Science Foundation of Hebei Province (No. B2016201122), the Science and Technology Research and Development Plan Project of Baoding City (No. 14ZF009), the Science and Technology Development Plan Project in Tai’an City (No. 2015GX2048), and the Scientific Research Foundation of Taishan University (No. Y-01-2014017).

Disclosure statement

No potential conflict of interest was reported by the authors.