Oxidative DNA Strand Scission Induced by a Trinuclear Copper(II) Complex

Abstract

A novel trinuclear copper(II) complex, Cu3-L (L = N,N,N',N',N' ',N' '-hexakis(2-pyridyl)-1,3,5-tris(aminomethyl)benzene), exhibited efficient oxidative strand scission of plasmid DNA. The solution behavior of the complex has been studied by potentiometric titration, UV spectroscopy, and cyclic voltammetry. The data showed that there are three redox-active copper ions in the complex with three types of bound water. The complex demonstrated a moderate binding ability for DNA. Cu3-L readily cleaves plasmid DNA in the presence of ascorbate to give nicked (form II) and then linear (form III) products, while the cleavage efficiency using H2O2 is less than by ascorbate, suggesting that the cleavage mode of the trinuclear complex is somewhat different from the traditional Fenton-like catalysis. Meanwhile, Cu3-L is far more efficient than its mononuclear analogue Cu-DPA (DPA = 2,2'-dipyridylamine) at the same [Cu2+] concentration, which suggests a possible synergy between the three or at least two Cu(II) centers in Cu3-L that contributes to its relatively high nucleolytic efficiency. Furthermore, the presence of standard radical scavengers does not have clear effect on the cleavage efficiency, suggesting the reactive intermediates leading to DNA cleavage are not freely diffusible radicals.

Antiproliferative effects of copper(II)–polypyridyl complexes in breast cancer cells through inducing apoptosis

“…As the nuclease activity of the complex is not completely halted in the presence of a hydroxyl radical scavenger, a small part of the DNA is probably cleaved by other active intermediates, such as cupric hydroperoxo (Cu(II)-OOH). These may induce DNA strand scission through the abstraction of a hydrogen atom from deoxyribose and subsequently sugar fragmentation, base release and then DNA cleavage as proposed in the literature (García-Giménez et al 2009;Ghosh et al 2011;Klinman 1996;Tu et al 2004). Note that the nuclease activity of the complex 2 was studied under anaerobic conditions, which exhibited DNA cleavage to some extent (data not shown).…”

Binding Studies of Asymmetric Pentacoordinate Copper(II) Complexes Containing Phenanthroline and Ethane‐1,2‐diamine Ligands with Calf‐Thymus DNA

“…5). On addition of CT-DNA, the absorption spectra of these complexes exhibit hyperchromism [36] with a red shift of 2 and 4 nm, respectively, in intraligand transitions. The hyperchromic and hypochromic effect are the spectral features of DNA concerning its double-helix structure [37].…”

Fabrication of Anchored Complexes as Electrodes for Sensing Heavy Metal Ions by Electrochemical Method

“…Referred to miscellaneous sensors, electrochemical sensors have dominant position owing to their significant sensibility, tentative easiness, minimum expenditure and its relevances in various disciplines. Because of the non-biodegradability and proliferation of heavy metal ions in tissues, they are observed as the fundamental basis to fade the biosphere and affect the physical well-being of human kind [1][2][3] . Diverse systems such as electrochemical 4 , mass spectrometric 5 and optical methods 6 have been exaggerated for the exposition of the ions.…”