2-(3,5-Dibromo-4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthrolinoruthenium(II) complexes: synthesis, characterization, cytotoxicity, apoptosis, DNA-binding and antioxidant activity

• Published in: Biometals 2010-08, Vol.23 (4), p.739-752
• Main Authors: Liu, Yun-Jun, Liang, Zhen-Hua, Li, Zheng-Zheng, Zeng, Cheng-Hui, Yao, Jun-Hua, Huang, Hong-Liang, Wu, Fu-Hai
• Format: Article
• Language: English
• Subjects: Animals; antioxidant activity; Antioxidants; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Binding sites; Biochemistry; Biomedical and Life Sciences; Cattle; Cell Biology; Cell Line; Chemical synthesis; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - drug effects; DNA - metabolism; DNA Cleavage - drug effects; Hydroxyl radicals; Life Sciences; Ligands; Medicine/Public Health; Microbiology; Molecular Structure; Nucleic Acid Denaturation; Pharmacology/Toxicology; Phenanthrolines - chemistry; Plant Physiology; Ruthenium; Ruthenium Compounds - chemical synthesis; Ruthenium Compounds - chemistry; Ruthenium Compounds - pharmacology; Ruthenium(II) complexes; Viscosity
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-010-9340-2

A new ligand DBHIP and its two ruthenium(II) complexes [Ru(dmb)₂(DBHIP)](ClO₄)₂ (1) and [Ru(dmp)₂(DBHIP)](ClO₄)₂ (2) have been synthesized and characterized. The cytotoxicity of DBHIP and complexes 1 and 2 has been assessed by MTT assay. The apoptosis studies were carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were studied by absorption titration, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants of complexes 1 and 2 were determined to be 8.64 ± 0.16 × 10⁴ (s = 1.34) and 2.79 ± 0.21 × 10⁴ (s = 2.17) M⁻¹. The results suggest that these complexes interact with DNA through intercalative mode. The studies on the mechanism of photocleavage demonstrate that superoxide anion radical (O₂ •⁻) and singlet oxygen (¹O₂) may play an important role in the DNA cleavage. The experiments on antioxidant activity show that these compounds also exhibit good antioxidant activity against hydroxyl radical (OH•).