Synthesis, characterization, photocleavage, cytotoxicity in vitro, apoptosis, and cell cycle arrest of ruthenium(II) complexes

Abstract

Two new ruthenium(II) complexes, [Ru(dmp)₂(BHIP)]²⁺ (1) and [Ru(dmb)₂(BHIP)]²⁺ (2), were synthesized and characterized by elemental analysis, ESI-MS, and ¹H NMR. DNA-binding constants of these complexes with calf-thymus DNA (ct-DNA) were determined to be 2.09 (±0.18) × 10⁴ (mol L⁻¹)⁻¹ (s = 2.58) and 1.48 (±0.17) × 10⁵ (mol L⁻¹)⁻¹ (s = 1.57), respectively. Viscosity measurements show that 1 and 2 interact with ct-DNA by intercalation. Upon irradiation at 365 nm, 1 and 2 induce cleavage of pBR322 DNA. The cytotoxicity of these complexes was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis induced by the complexes was studied by flow cytometry. The results of the cell cycle arrest show that 2 can inhibit the proliferation of BEL-7402 cells in the G0/G1 phase.

Keywords:

• Ruthenium(II) complexes
• Photocleavage
• Cytotoxicity
• Apoptosis
• Cell cycle arrest

Acknowledgments

This work was supported by the Science and Technology Foundation of Guangdong Province (No. 2010B31500005), Science and Technology Planning Project Pillar Program of Guangzhou Municipality (No. 2010 J-E021-1), and Medical Scientific Research Foundation of Guangzhou Municipality (201102A212029) of China.