Syntheses of ruthenium(II) quinonediimine complexes of cyclam and characterization of their DNA-binding activities and cytotoxicity

Inorg Chem. 2002 Jun 17;41(12):3161-71. doi: 10.1021/ic0112802.


The synthesis and characterization of ruthenium(II) complexes, [Ru(cyclam)(bqdi)] x ZnCl(4) (1 x ZnCl(4); cyclam = 1,4,8,11-tetraazacyclotetradecane, bqdi = o-benzoquinonediimine), [Ru(cyclam)(nqdi)] x (ClO(4))(2) (2 x (ClO(4))(2); nqdi = 2,3-naphthoquinonediimine), and [Ru(cyclam)(phi)] x (ClO(4))(2) (3 x (ClO(4))(2); phi = 9,10-phenanthroquinonediimine), are described. The DNA binding properties and biological activity of the Ru(II) complexes were studied by various biophysical and cytological techniques. As expected, only 3 showed significant binding with DNA. The thermodynamic profile of the binding of 3 and DNA was constructed by analyzing the experimental data of absorption titration and UV melting studies with the McGhee equation, van't Hoff's equation, and the Gibbs-Helmholtz equation. Compound 3 binds double-stranded DNA with a binding constant of 5.0 x 10(4) M(-1) at 20 degrees C, and the binding mode of the complex to DNA was proved to be intercalative. Cytotoxicity and induced type of cell death of 1-3 were also investigated. Basically, metal complexes with ligands of molecular shape closely related to the structure of DNA are more likely to bind DNA and possess higher toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Apoptosis
  • Binding Sites
  • Cattle
  • Circular Dichroism
  • DNA / metabolism*
  • Electrophoresis
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry*
  • Humans
  • KB Cells / drug effects
  • Molecular Conformation
  • Molecular Structure
  • Organometallic Compounds* / chemical synthesis
  • Organometallic Compounds* / chemistry
  • Organometallic Compounds* / pharmacology
  • Ruthenium / chemistry*
  • Spectrophotometry, Ultraviolet
  • Temperature
  • Thermodynamics
  • Thymus Gland


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Heterocyclic Compounds
  • Organometallic Compounds
  • cyclam
  • Ruthenium
  • DNA