Ruthenium(II) polypyridyl complexes: synthesis and studies of DNA binding, photocleavage, cytotoxicity, apoptosis, cellular uptake, and antioxidant activity

DNA Cell Biol. 2011 Oct;30(10):829-38. doi: 10.1089/dna.2010.1170. Epub 2011 Mar 13.

Abstract

Two ruthenium (II) complexes [Ru(dmb)2(APIP)](ClO4)2 (APIP=2-(2-aminophenyl)imidazo[4,5-f ][1,10]phenanthroline, dmb=4,4'-dimethyl-2,2'-bipyridine; 1) and [Ru(dmb)2(HAPIP)](ClO4)2 (HAPIP=2-(2-hydroxyl-4-aminophenyl)imidazo[4,5-f ][1,10]phenanthroline; 2) were synthesized and characterized. DNA binding was investigated by electronic absorption titration, luminescence spectra, thermal denaturation, viscosity measurements, and photocleavage. The DNA binding constants for complexes 1 and 2 were 4.20 (±0.14)×10(4) and 5.45 (±0.15)×10(4) M(-1). The results suggest that these complexes partially intercalate between the base pairs. The cytotoxicity of complexes 1 and 2 was evaluated by MTT assay. Cellular uptake was observed under fluorescence microscopy; complexes 1 and 2 can enter into the cytoplasm and accumulate in the nuclei. Apoptosis and the antioxidant activity against hydroxyl radicals (•OH) were also explored.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / chemistry
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • DNA / chemistry
  • DNA / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Female
  • Fluorescence
  • Humans
  • Hydroxyl Radical / antagonists & inhibitors
  • Hydroxyl Radical / metabolism
  • Intercalating Agents / chemical synthesis
  • Intercalating Agents / pharmacology*
  • Kinetics
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / pharmacology*
  • Oxidation-Reduction / drug effects
  • Oxidation-Reduction / radiation effects
  • Phenanthrolines / chemistry
  • Photolysis / radiation effects
  • Plasmids / metabolism
  • Ruthenium / chemistry
  • Ruthenium / metabolism*
  • Spectrum Analysis
  • Ultraviolet Rays

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Intercalating Agents
  • Organometallic Compounds
  • Phenanthrolines
  • Hydroxyl Radical
  • 2,2'-Dipyridyl
  • Ruthenium
  • DNA
  • calf thymus DNA