Synthesis, characterization, in vitro antitumor activity, DNA-binding properties and electronic structure (DFT) of the new complex cis-(Cl,Cl)[RuIICl2(NO+)(terpy)]Cl.
The complex cis-(Cl,Cl)-[RuCl2(terpy)(NO)]Cl (1) has been synthesized by the reaction of [RuCl3(H2O)2(NO)] with terpyridine (terpy) and characterized by various spectroscopic, analytical techniques and using electronic structure calculation (DFT) methods. The cytotoxic activity and the DNA-binding properties of have also been studied using biochemical techniques. The results establish unequivocally that corresponds to a so-called [RuNO]6 species, which readily releases the nitrosyl ligand upon irradiation with a mercury lamp in acetonitrile solution. DFT calculations provided a satisfactory description of structural, bonding, electronic and related properties of the new compound and throw light on the mechanism of the photo-induced NO release. Screening on A2780 (human ovarian carcinoma) cell lines showed significant cytotoxicity with an IC50 value of 0.49 microM. 31P and 23Na NMR spectroscopy along with electrophoretic mobility studies illustrated that complex primarily binds by coordination to DNA without any pi-interaction between the planar terpy ligand and the DNA bases, while weak electrostatic interactions could not be excluded. Studies on the inhibition of the restriction enzymes DraI and SmaI revealed that prefers the guanine and cytosine bases of DNA.
Karidi
Konstantina
K
Laboratory of Inorganic and General Chemistry, Department of Chemistry, University of Ioannina, Greece.
Garoufis
Achilleas
A
Tsipis
Athanassios
A
Hadjiliadis
Nick
N
den Dulk
Hans
H
Reedijk
Jan
J
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009691:Nucleic Acid Denaturation; D017975:Ruthenium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
D000970:Antineoplastic Agents; D017975:Ruthenium Compounds; D004247:DNA