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

Abstract

The synthesis and characterization of ruthenium(II) complexes, [Ru(cyclam)(bqdi)]·ZnCl4 (1·ZnCl 4; cyclam = 1,4,8,11-tetraazacyclotetradecane, bqdi = o-benzoquinonediimine), [Ru(cyclam)(nqdi)l·(ClO 4) 2 (2·(ClO 4) 2 nqdi = 2,3- naphthoquinonediimine), and [Ru(cyclam)(phi)]·(ClO 4) 2 (3·(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 × 10 4 M -1 at 20 °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.