Structural diversity in dinuclear copper(I) halide complexes of 2, 4-dithiouracil: Synthesis, crystal structures, induction of DNA damage and oxidative stress mediated by ROS. (9th March 2015) - Varna, D.
Graphical abstract: Three dinuclear copper(I) halide complexes containing 2, 4-dithiouracil and triphenylphosphine with different bridging motifs, namely doubly bridged [Cu2 (μ-Cl)(μ-S, S-dtucH)(PPh3 )4 ], single bridged [Cu2 Br2 (μ-S, S-dtucH2 )(PPh3 )4 ] and triply bridged [Cu2 (μ-I)2 (μ-S, S-dtucH2 )(PPh3 )2 ] were isolated and structurally characterized. The compounds were also screened for their ability to interact with CT-DNA in vitro and to produce reactive oxygen species (ROS). Abstract: 2, 4-Dithiouracil (dtucH2 ) reacts with [CuX(PPh3 )]4 (X = Cl, Br, I) to give dinuclear complexes with different bridging motifs, namely doubly bridged [Cu2 (μ-Cl)(μ-S, S-dtucH)(PPh3 )4 ] (1 ), single bridged [Cu2 Br2 (μ-S, S-dtucH2 )(PPh3 )4 ] (2 ) and triply bridged [Cu2 (μ-I)2 (μ-S, S-dtucH2 )(PPh3 )2 ] (3 ). In the structure of1 the two copper(I) centers are joined by one bridging chlorine atom as well as a 2, 4-dithiouracil anion acting as an S, S-donor, while compound3 contains two bridging iodine atoms besides the neutral bridging 2, 4-dithiouracil ligand. The structure of2 consists of two CuBr(PPh3 )2 sub-units joined by the S-atoms of a neutral dtucH2 . The biological properties of the new complexes were evaluated in relevance to their binding with calf-thymus double stranded DNA (dsCTDNA) in vitro monitored by mobility shift experiments in agarose gel electrophoresis, and their ability to induce oxidative stress in bacteria Escherichia coli . The experiments showed that these complexes are able to interact with dsCTDNA and to cause DNA damage, and are also able to induce oxidative stress in bacteria. Because of the relevance of these properties, these complexes are regarded as a very promising starting point for biological studies in living systems.