Synthesis, characterization, cellular uptake and interaction with native DNA of a bis(pyridyl)-1,2,4-oxadiazole copper(II) complex

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 39; no. 38; pp. 9140 - 9145
• Main Authors: Terenzi, Alessio, Barone, Giampaolo, Piccionello, Antonio Palumbo, Giorgi, Gianluca, Guarcello, Annalisa, Portanova, Patrizia, Calvaruso, Giuseppe, Buscemi, Silvestre, Vivona, Nicolò, Pace, Andrea
• Format: Journal Article
• Language: English
• Published: England 14.10.2010
• Subjects: Cell Line, Tumor; Cell Survival - drug effects; Copper - chemistry; DNA - chemistry; Humans; Ligands; Models, Molecular; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Oxadiazoles - chemistry; Pyridines - chemistry
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c0dt00266f

The copper(II) complex of 3,5-bis(2'-pyridyl)-1,2,4-oxadiazole was synthesized and characterized. X-Ray crystallography revealed that the complex consists of a discrete [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)(2)(H(2)O)(2)](2+) cation and two ClO(4)(-) anions. The Cu(II) coordination sphere has a distorted octahedral geometry and each ligand chelates the copper ion through the N(4) nitrogen of the oxadiazole ring and the nitrogen of one pyridine moiety. The coordinated water molecules are in cis position and each of them is H-bonded to the 5-pyridyl nitrogen of the oxadiazole ligand and to an oxygen of the perchlorate anion. Biological assays showed that, despite the free ligand not being effective, [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)(2)(H(2)O)(2)](2+) reduced the vitality of human hepatoblastoma HepG2 and colorectal carcinoma HT29 cells in a dose- and time-dependent manner. The interaction of the cationic copper complex with native DNA was investigated by variable-temperature UV-vis spectroscopy, circular dichroism, viscosity and gel electrophoresis, indicating that it is a groove binder with binding constant K(b) = 2.2 × 10(4) M(-1).