Syntheses of ruthenium(II) quinonediimine complexes of cyclam and characterization of their DNA-binding activities and cytotoxicity.
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.
Chan
Hing-Leung
HL
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong.
Liu
Heng-Qian
HQ
Tzeng
Biing-Chiau
BC
You
Yuan-Shyane
YS
Peng
Shie-Ming
SM
Yang
Mengsu
M
Che
Chi-Ming
CM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D004586:Electrophoresis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D008968:Molecular Conformation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D013816:Thermodynamics; D013950:Thymus Gland
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C024560:cyclam; D012428:Ruthenium; D004247:DNA